1

OKURA Frontier Hotel Tsukuba

8th Floor, Health and Medical
Science Innovation Laboratory
bldg

Venue

Sep 27 (Sat)8th Floor, Health and Medical
Science Innovation Laboratory
bldg

International Conference
Room

Venue

Sep 26 (Fri)

9:00

9:00

:30

:30

10:00

10:00

:30

:30

:30

:30

12:00

12:00

:30

:30

:30

14:00

:30

15:00

:30

16:00

:30

Conference for International Baccalaureate

17:00

13:00

:30

14:00

:30

15:00

:30

16:00

:30

17:00

The 13th National Taiwan University, Kyoto University, and University of Tsukuba Joint Mini-Symposium on Long Distance Lecture Course 2014

13:00

The 13th National Taiwan University, Kyoto University, and University of Tsukuba Joint Mini-Symposium on Long Distance Lecture Course 2014

11:00

11:00

:30

:30

18:00

18:00

19:00

19:00

:30

:30

Banquet for the 2nd NTU-UT joint-conference

:30

:30

20:00

20:00

:30

:30

21:00

21:00

2

:30

10:00

Opening Session:30

Opening Session: Global Initiatives in Higher Education
and Research

9:00

Coﬀee
Break

:30

12:00

Systems Biology Interest Group

Joint Faculty Conference of UT and NTU -Synergy,
Alliance and a Better Future II-

Optimization and Design of Medical Services

11:00*Lunch or Coﬀee Break time is diﬀerent in each session. Please see each session program for details.
*Please check with each session program exact session time.

5C506

5C216

Annex HallMultimedia Room

Exchange Hall

Hall

International Conference
RoomSpecial Conference Room

Meeting Room 6

Meeting Room 5

Meeting Room 3

Common Schedule

Venue

Sep 28 (Sun)
13:00
Lunch

:30
Coﬀee Break

:30

16:00

:30

Spiritual and Physical Exercises in Eastern and Western Philosophies

15:00

Aging Sciences

Colloid and Interface in Bio-resources and Environment

14:00

17:00

:30

Japan and the World after 3.11

Optimization and Design of Medical Services (Panel
Discussion)

Frontier Studies of Policy and Planning Sciences (Students
Presentations)

The Second Research University Symposium - Leading-edge Researches and System/Research-ethics to Support Trusted Ones - in conjunction with The
Fourth Tsukuba URA Forum:30

Poster Display (Students Presentations, Global Aging Center Tsukuba)

:30

18:00

19:00

:30

Welcome Reception at University Hall restaurant

:30

20:00

:30

21:00

3

10:00

11:00

:30

Risk, Technology and Anthropology (Poster Display)

12:00

Risk, Technology andAnthropology (Poster Session)

13:00
Lunch

Broadening your horizonsinternational collaboration in thelife sciences

:30

:30

14:00

:30

16:00

Risk, Agent x, Science & Technology

Coﬀee Break

:30

:30

17:00

Student Presentations -The 9th Tsukuba Medical Science Research Meeting-

Universe Evolution and Matter Origin

Life and Medical Sciences in South East Asia

15:00

:30

18:00

Information Schools in Asia-Paciﬁc and their Collaboration (TGSW Satellite Session)

Symposium for Food Security and Sustainable Agriculture

Risk, Technology and Anthropology (Poster Display)

Poster Display (Students Presentations, Global Aging Center Tsukuba)

Exhibition for University of Tsukuba Overseas Oﬃces*Lunch or Coﬀee Break time is diﬀerent in each session. Please see each session program for details.
*Please check with each session program exact session time.

8th Floor, Health and Medical
Science Innovation Laboratory
bldg

Joint Research Conference
Room 1, 3F, Union of Libraryan Information-media Studios,
Kasuga Area

5C506

5C216

Annex HallMultimedia Room

Exchange Hall

Foyer of Hall

Aging Sciences

Hall

Global Aging: Emerging Challenges and Opportunities -CGAT Oral Session-

Coﬀee Break:30

Risk, Agent x, Science & Technology:30Student Presentations -The 9th Tsukuba Medical Science Research Meeting-

9:00

International Conference
RoomSpecial Conference Room

Meeting Room 6

Meeting Room 5

Meeting Room 3

Common Schedule

Venue

Sep 29 (Mon)
:30

19:00

20:00

Evening Session at Medical Campus

:30

:30

21:00

4

:30

10:00

Coﬀee Break

:30

11:00

:30

12:00

Symposium on Health and Sport Sciences

Aging Sciences

Global Aging: Emerging Challenges and Opportunities

Initiatives of Research, Preservation and Management for Granting UNESCO World Heritage Status at the Pyu and Bagan
Monument

9:00*Lunch or Coﬀee Break time is diﬀerent in each session. Please see each session program for details.
*Please check with each session program exact session time.

5C506

5C216

Annex HallMultimedia Room

Exchange Hall

Hall

International Conference
RoomSpecial Conference Room

Meeting Room 6

Meeting Room 5

Meeting Room 3

Common Schedule

Venue

Sep 30 (Tue)
:30

:30

:30

15:00
Coﬀee Break

:30

16:00

:30

17:00

Information Schools in Asia-Paciﬁc and their Collaboration

Symposium for International Collaboration of Science & Technology, and Innovative Development in Central and East Asia

14:00

G30 Joint Seminar Borderless Challenge towards Global Aging by Young Power: Comparative
Analysis of Long Term Care in the World

Aging Sciences

Innovative Approaches to Natural Resources for Development of North African and Mediterranean Regions

Symposium for expanding application of new power semiconductor devices

13:00
Lunch

:30

18:00

:30

19:00

:30

20:00

:30

Closing Session : Farewell Reception at University Hall restaurant

21:00

Dear Colleagues and Friends
It is my great pleasure to welcome guests from all over the world to the 5th Annual Tsukuba
Global Science Week (TGSW2014). Last year, a variety of study fields including not only
natural and social sciences, but Arts and sports sciences, participated in the TGSW2013 tocelebrate the 40th + 101st anniversary of University of Tsukuba. This year, all of our ten faculties
participate in the TGSW2014 as an official university-wide event to tighten international
networks and to enhance interdisciplinary collaborations.
University of Tsukuba was established in 1973, evolving from our predecessor, the Tokyo
University of Education, whose establishment dates back to 1872. During 41 years of thehistory of University of Tsukuba, we have produced not only multiple Nobel Laureates but also
61 medals in Olympic games. Ultimate achievements in both academic and sport activities
stem from a legacy of our founding president, Jigoro Kano, the father of Judo, who highly
valued the combination of sound ‘body and mind.’
To advance this tradition and to evolve further in innovative research and education,
we decided to create a new and unique program, “Campus-in-Campus.” Bilateral top-levelagreements between our partner universities and us enable our students to attend classes in ourpartner universities and vice versa. Students and researchers at each university can travel toand work at a partner university under the supervision of a partner professor most efficiently.
This new program will surely strengthen the bond among partner universities.
Today, the human beings face numerous global issues such as food crisis, energy issues,environmental risks, never-ending wars, and poverty. To address these critical issues, weneed to collaborate internationally as well as in an interdisciplinary manner, by bringing
together the fields of public health, medical science, biological science, sports science, foodscience, information science, politics, economics, humanities, arts, and more. TGSW2014 is
an excellent opportunity for international and interdisciplinary discussion, sharing cuttingedge research and creative activities.
Lastly, I would like to thank all of you for your participation and sincerely hope that you
will enjoy this invaluable three-day event. I look forward to meeting with each of you during
the week to tighten our friendship.

Kyosuke Nagata
President
University of Tsukuba

5

Dear All Participants,
I would like to extend my warmest welcome to all delegates attending Tsukuba Global
Science Week (TGSW) 2014. The University of Tsukuba will celebrate its 41th anniversary
this week. We continue to spearhead internationalization of Japanese higher education andbridge different research areas. It would be my distinct pleasure if TGSW2014 can provide
an opportunity for all participants to expand their research activities and strengthen theirinternational networks.
Interdisciplinary research is known to be one of the powerful approaches towards new
discoveries. It propels us to fearlessly confront challenges against the global issues such asaging of population, energy shortage and environmental destruction. TGSW2014 covers awide range of fields including public health, medical science, sports science, food science,
information science, politics and economics, humanities, arts, and more.
Each participant is very welcome to join the sessions of totally different fields. I believethat such mixture of participants provides the opportunity to learn from different perspectives.
This year, we expect students, researchers, professors, and administrators coming from allover the world. Guests come from Bahrain, Brazil, Canada, Chile, China, France, Germany,
Greek, Hungary, India, Indonesia, Jordan, Morocco, Myanmar, Nepal, Netherlands, Russia,
South Korea, Taiwan, Thailand, Tunisia, United Kingdom, United States, Viet Nam, and ofcourse Japan. With our university slogan, “Imagine the Future.”, in mind, we would like todiscuss the concrete steps toward resolving global issues and creating a better world for all.
I would like to thank all of you for coming and hope that you will enjoy the conference.
I hope you will find a hint for improving the world in this forum where people from different
academic fields, and backgrounds have come together to discuss cutting-edge ideas.

Yasuo Miake
Vice President
University of Tsukuba

6

Opening Session
Global Initiatives in Higher Education andResearch7

8Sep 28 (Sun)Hall
Opening Session: Global Initiatives in Higher Education and Research

9:00-9:05

Yasuo Miake

University of Tsukuba

Opening Remark

9:05-9:20

Kyosuke Nagata

University of Tsukuba

University of Tsukuba:
A Bold Action Plan for the Next Decade on a Tradition of Innovation

9:20-9:40

Pan-Chyr Yang

National Taiwan University

Translational Research and Precision Cancer Therapy in Taiwan

9:40-10:00

Vincent Dousset

University of Bordeaux

The 2014 Launch of the University of Bordeaux

10:00-10:20

Jacob E. Levin

University of California, Irvine Leveraging Global Partnerships in the Face of an Uncertain Future

10:20-10:40

Arthur (J. A. A.) Stockwin

Formerly Nissan Professor ofModern Japanese Studies,
University of Oxford

The Progress of Japanese Studies with Particular Reference to the UK
and Australia

93 / 26 ページ

University of Tsukuba:
A Bold Action Plan for the Next Decade on a Tradition of Innovation
Kyosuke Nagata
President, University of Tsukuba

The University of Tsukuba has a 40 year history of innovation. All major domestic league
tables point to the fact that we are one of the top research-oriented universities in Japan. We
count among our graduates and faculty members three Nobel Laureates, seventy Olympic
medalists, countless educators, researchers, athletes and artists who have helped make Japan
what it is today. As you can see, we have a vast and beautifully conceived campus not foundanywhere else in Japan. We occupy a strategically advantageous position in the heart of
Tsukuba Science City, which hosts over 300 research institutions with researchers from allover the world engaged in cutting edge research. Thus, we have a number of unique featuresthat can be used to good effect to successfully collaborate with world-class universities. How
can we contribute to building a next generation earth?
To fully explore our potential in the global arena, we shall invest substantial human andfinancial resources over the next decade in international exchange and collaboration. A
range of new ideas are now being materialized. The most exciting of all is what we call the
CAMPUS-in-CAMPUS project – an ambitious project whereby we seek to create a series ofminiature off-shore campuses in our partner institutions, and to invite our overseas partners
to establish their miniature off-shore campuses in Tsukuba. Once the CAMPUS-in-CAMPUS
scheme is in place, our and your students, together with students of our closest allies, will beable to study together physically as well as on-line. You, students, can find and take classes
held in not only your campus but also in the campuses of your partners. This is also the casefor researchers and university staff members. You, researchers, may carry out experiments inyour partner campuses.
All these schemes cannot be done without the help of our partner institutions. TGSW
is a good chance not only as a great showcase of our individual and collective scientificachievements, but also for incubation of our ties with partner institutions in and outside Japan.

10Translational Research and Precision Cancer Therapy in Taiwan
Pan-Chyr Yang MD, PhD
President, National Taiwan University
Professor, College of Medicine

Clinical trials are critical for translating scientific discoveries from the laboratory into
useful products for the prevention, diagnosis and treatment of human diseases. The National
Science Council funded the National Research Program for Biopharmaceuticals (NRPB) since2011 to promote the translational and clinical research in Taiwan, including the establishmentof Taiwan national bio-specimen banks and clinical trial consortiums. The NRPB diseasespecific national bio-specimen banks facilitate multi-center, high quality, bio-specimen deposit
and retrieval, with patients’ complete clinical and epidemiological data and bio-informatics
to promote translational research. The NRPB Taiwan Clinical Trial Consortiums consist oflung cancer, liver cancer/diseases, Helicobacter pylori and GI malignencies, oncology phase- I consortium, breast cancer, gynecological cancers, chronic obstructive pulmonary disease,
hypertension, lipid and atherosclerosis, pediatric infectious diseases and mental disorderconsortiums. We established central IRB to facilitate the review process are participatingin many global new drug clinical trials of major international pharmaceutical companies as
their preferred partners. We also take leadership in international clinical trials as chairmen
or advisory board members of the studies for the sponsors or to perform first-in-humanphase - I new drug clinical trials. NRPB is building up the translational research and clinicalinfrastructures in Taiwan and establish Taiwan as a center of excellence for clinical researchand clinical trial in Asia-Pacific.
To implement the precision therapy for cancer patients, we have established a nationalreference laboratory to provide high quality and standardized gene testing for all lung cancer
patients. The clinicians could treat the patients based on the genetic alterations to select themost effective therapy; including the EGFR (50%, response to Gefitnib, Erlotinib, Afatinib),
EML4-ALK (3-5%, Crizotinib), KRAS (5%, Sorafenib, chemotherapy), MET (3-5%, ARQ197, others), BRAF(3%, Sorafenib, others), ERBB2 (3%, Afatinib or Trastuzumab), etc.. Our
National Health Insurance reimbursed the Gefitnib and Erlotinib as first line therapy for EGFR
mutant lung cancer patients since 2011. The Genetic Epidemiology of Lung Cancer in Taiwan(GELAC) collaborated with NIH and identified 5 specific susceptibility loci (TERT, TP63, HLAClasss II, POS1-DCBLD1 and VTI1A) in never-smoking women in Asia. The risk genetic locimay be useful to identify high-risk group of patients who can benefit from low dose CT for
early detection of lung cancer. We also develop new strategy to overcome drug resistance andtargeting cancer stem cells. With the implementation of nation-wide gene testing and precision
therapy, the overall 5-year survival for NSCLC has been improved from 15.8% to 31.6% from2009 to 2013.

11

The 2014 Launch of the University of Bordeaux
Vincent Dousset
Vice-President, University of Bordeaux – International Affairs
Professor of Medical Imaging, University of Bordeaux & University Hospital of Bordeaux

Following national reforms and incentives for creating ten major international universities
in France (2008), several universities of Bordeaux has decided to merge and to launch in 2014
the University of Bordeaux. Historically, the first University of Bordeaux has been createdin 1441 by the bishop Pey Berland. Over time, the University has been divided up in several
ones or in independent faculties behind political issues like in 1968 to lower the role ofstudents obstructing the national policies. The fragmentation led to three major drawbacks:
1) a reduction in the capability to create bridges between disciplines, which are recognized
as having a positive impact in student education and creativity; 2) a difficulty to manage theresearch activities at a sufficient scale and to support financially and materially research of highquality; 3) to appear on the international scenery by the quality of diplomas, the excellence of
research and in the numerous rankings.
The presentation will focus on the steps that brought to the new University of Bordeaux,
the new organization chart, the ambitions in education and research, the process of recognition
that made the University of Bordeaux laureate of the French national award “initiative of
excellence” and the new management of international affairs which is at the heart of its politicalissues.

12

Leveraging Global Partnerships
in the Face of an Uncertain Future
Jacob E. Levin, PhD
Office of Research, University of California, Irvine

The problems that plague modern society and the questions that arouse human curiosity
are universal – largely independent of our country of origin or what language we speak. It
stands to reason that insight into these fundamental mysteries, and solutions to these complex
and challenging problems, will come through the joint efforts of a diverse and global team– of scientists and engineers, physicians and humanists, artists and educators, and with the
involvement of universities, government, private organizations and industry. For the largest
and most intractable of these problems, people, resources and funding will need to be
mobilized from across the world, tools employed from all fields and sectors. Especially inthese financially uncertain times, multi-pronged interdisciplinary international partnerships
must be forged, strengthened, and managed, using all the capabilities at our disposal, in order
to effectively synthesize and leverage our unique individual strengths and capabilities.
Broadly representative cross-sector partnerships are being formed to address everythingfrom the greening of college campuses to the development of new drugs and medical therapies
to preparing our athletes for the Olympics. Modern technologies and communication tools areaiding the formation of these international collaborations, as is an ever-increasing viewpointof global engagement, and responsibility for creating a sustainable future, being adopted by
Universities, research funding agencies and the government.
A few examples of these partnerships will be discussed, in the context of the multi-national
multi-disciplinary collaborative environment that is Tsukuba Global Science Week itself.

13

The Progress of Japanese Studies
with Particular Reference to the UK and Australia
Arthur (J.A.A.) Stockwin
Formerly Nissan Professor of Japanese Studies andDirector, Nissan Institute of Japanese Studies;
Emeritus Fellow, St. Antony’s College, University of Oxford
Order of the Rising Sun, Gold Rays with Neck Ribbon

Serious study of Japan, and teaching about Japan, scarcely existed at university level in the
UK and Australia before the end of the Second World War. One estimate puts the number ofAustralians fluent in Japanese in the 1930s at seven. There were a few exceptions (a JapaneseStudies Fellow at the University of Oxford around 1910, a Japanese Studies Professor at the
University of Sydney for some years after the First World War), but it was not until militaryrun Japanese language courses in the early 1940s produced numbers of fluent Japanese speakers that some universities began to regard Japan as a possible area for study. But not until theJapanese ‘economic miracle’ began to attract international attention in the 1960s did Japanesestudies really come into its own. This continued into the late 1980s and beyond, with someuniversities in both the UK and Australia reporting an ‘enrolment tsunami’ in courses relating to Japan (including language courses). In Australia in particular, Japanese became amajor language taught in schools as well. With the Japanese economy stagnant in the 1990s,
what had been over-expansion was corrected by retrenchment, but from the new millennium
Japanese studies had become consolidated and achieved both quality and depth. Even though
Chinese studies have by some measures overtaken those of Japan, both the UK and Australia
contribute extensively to research and teaching on many aspects of Japan, both historical andcontemporary, and in an increasing range of disciplines, principally but not exclusively in thehumanities and the social sciences.

14

NOTE

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NOTE

16

Joint Faculty Conference of UT and NTU– Synergy, Alliance and a Better Future II –Research Administration Office
University of Tsukuba&
Office of International Affairs
National Taiwan University

17

18

Sep 28 (Sun)Hall
Joint Faculty Conference of UT and NTU ―Synergy, Alliance and a better Future II―

11:00-11:20

Caroline F. Benton

University of Tsukuba

Transforming Higher Education in an Increasingly Globalized World

11:20-11:40

Bennett Yu-Hsiang Fu

National Taiwan University

Beyond the Student Exchange: NTU Plus Academy

11:40-12:00

Toshiyuki Inagaki

University of Tsukuba

Automated Driving: Where Are We Headed?

12:00-12:20

Pei-Chun Lin

National Taiwan University

Locomotion and manipulation: Motion generation from bio-inspired
engineering aspects

19

4 / 26 ページ

Transforming Higher Education in an Increasingly Globalized
World
Caroline F. Benton
University of Tsukuba
Vice President, Global Affairs

Today’s globalized world is characterized by accelerating levels of complexity,interdependency and change. Twenty, thirty years from now will look nothing like today.
New types of jobs will replace current ones and new manners of interaction among people
across organizations and national borders will emerge. Issues such as resource scarcity,
continued deterioration of the environment, and regional conflict will have even wider ranging
consequences with greater global impact, and will require transborder collaboration to resolve.
Such a future requires efforts from not only a limited number of global leaders, but also
from persons in all areas of society who can work across cultures and have the ability andcompetency to flexibly navigate a continuously evolving world. As educators of young people
and custodians of the present state of academia, it is our responsibility to ensure that our youth
are equipped to handle the coming future. To this end, we must rethink not only what we teachand research, but also why and how we do so. With ever-increasing change and complexity,
it is not enough to transfer knowledge from a single static field of knowledge or discipline.
We must nurture our students to be leaders of change with the competence to look past statusquos, to recognize the connections among the various issues and stakeholders of society, andto negotiate across diverse value sets and paradigms. This talk will address the emerging
challenges that the future generation will face and the competencies they will need, and how
our university will help prepare them through continuous innovation in education, researchand university governance. By spearheading reform in higher education, we aim to transform
our university into a truly transborder institution.

20

Beyond the Student Exchange: NTU Plus Academy
Dr. Bennett Yu-Hsiang Fu
Associate Dean, Office of International Affairs
Professor of English, Department of Foreign Languages and Literatures
National Taiwan University

With the promise of diverse academic opportunities, awareness of cultural differences,and personality development, international student mobility has become a popular andimportant trend amongst higher education institutions. From the development of student
exchange programs, many institutions are constantly looking for more dynamic ways toattract international students to their campus. In this talk, National Taiwan University will
share the insights into and experiences of spinning or adding on to the standard exchange
program to accommodate different student needs. The talk will focus on how NTU expands
its international opportunities on campus by developing a series of Summer+ programs,
Spring+ programs, and customized programs for partner universities. The University is now
moving forward to integrate these successful tailor-made programs in a new concept “NTU
Plus Academy” to cater to diverse needs of international students at NTU.

21

Automated Driving: Where Are We Headed?
Toshiyuki Inagaki1,2
Faculty of Engineering, Systems and Information, University of Tsukuba
Provost, Graduate School of Systems and Information Engineering, University of Tsukuba
1

2

Today’s machine can sense and analyze a situation, decide what must be done, andimplement control actions. Such smart machines can be seen at many places in our society.
Aircraft have been highly automated for more than two decades. Although human pilots haveto take care of the takeoff phase for several minutes, the rest of the flight phases from the initial
climb to the final approach and landing can be dealt with by the computers for around 10 hours
in cases of international flights.
Now autonomous cars have become part of everyday conversation. People make up theirown mental models of the autonomous cars. Some may expect that they would be freed fromstressful driving tasks and that they can enjoy using smartphones on their whole way to thedestination. Some others may assume that autonomous cars should be accident-free, because
human errors can never happen. However, it is not clear what type of automated driving weshould implement.
Several levels can be distinguished for automated driving: (1) Driver assisted, (2) partial
automation, (3) conditional automation, (4) high automation, and (5) full automation. Humandriver’s role differs from level to level. For instance, in some of these levels, control authority
is traded from automation to the human driver based on the automation’s decision. It is
well known that automation sometimes bring negative effects, such as the out-of-the-loop
performance problem, loss of situation awareness, complacency or overtrust, automation
surprises. Can the human driver cope with the trading of authority appropriately when he or
she has not monitored the driving environment? What kind of advantages can the driver have,
if we ask him or her to monitor the driving environment all the time? Can automated driving berealized under the Convention of Road Traffic that states that “Every driver of a vehicle shallin all circumstances have his vehicle under control so as to be able to exercise due and propercare and to be at all times in a position to perform all maneuvers required of him”? There arestill many issues to be solved technologically as well as legally.

22

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Optimization and Design ofMedical Services
Division of Policy and Planning Sciences,
Faculty of Engineering, Information and Systems,
University of Tsukuba

25

26

Sep 28 (Sun)International Conference Room
Optimization and Design of Medical Services

Chair

Morimitsu Kurino

University of Tsukuba

10:45-11:00

Morimitsu Kurino

University of Tsukuba

Introduction

11:00-11:20

Tayfun Sönmez

Boston College

Living Donor Lobar Liver/Lung Exchange

11:20-11:40

Takahiro Oto

Okayama University

Current status of lung transplantation in Japan

11:40-12:00

Utku Ünver

Boston College

Efficiency and Equity Consequences of Live-Donor Organ Exchange
Policies: The Case for Kidneys and Livers

12:00-12:20

Takahito Yagi

Okayama University

Liver transplantation for liver cancer in Japan -Differences between
adults and children-

12:20-12:40

Kenji Yuzawa

Mito Medical Center

Present status of organ transplantation in JapanSep 28 (Sun)Multimedia Room
Optimization and Design of Medical Services (Panel Discussion)

14:15-15:45

Panel Discussion

15：45-16：00

Coffee Break27

7 / 26 ページ

Living Donor Lobar Liver/Lung Exchange
Haluk Ergin1, Tayfun Sönmez2 and Utku Ünver3
Department of Economics, University of California, Berkeley
2
Department of Economics, Boston College
3
Department of Economics, Boston College

1Live donor transplants are carried out both for livers and lungs, where a lobe of theseorgans from a donor is transplanted to the patient. Since 2010, a handful of live donor liver
exchanges have been conducted in South Korea and Hong Kong. In addition to blood-typecompatibility, size-compatibility is also essential for a successful transplant for both organs.
Furthermore, live donor lung transplanta-tion requires two donors for each patient where eachdonor donates a lung lobe to the patient. Live donor lung exchange is proposed as a new lungtransplan-tation modality. Models of liver exchange and lung exchange are introduced andanalyzed. Welfare gains of these organ exchanges will be simulated.

28

Current status of lung transplantation in Japan
Takahiro Oto1
Department of Thoracic Surgery, Okayama University Graduate School of Medicine,
Dentistry and Pharmacological Sciences

1

To overcome severe donor shortage, maximizing organs transplanted per brain death donor
and expanded the donor pool using living donors are mandatory. Successful uses of marginallungs with ex-vivo lung re-conditioning contribute to increase the number of available lunggraft.
Utilization of adult living donor middle-lobe can save critically ill small children andinfant who otherwise cannot survive size-matched brain-dead donor organs. Overall, thestrategies Japan has adopted to overcome donor shortage can provide useful insights on how
to increase organ transplantations.

29Efficiency and Equity Consequences of Live-Donor Organ
Exchange Policies: The Case for Kidneys and Livers
Haluk Ergin1, Tayfun Sönmez2, M. Utku Ünver2
UC Berkeley ,2Boston College

1(presented by M. Utku Ünver)

Live-donor kidney exchanges have become commonplace in many countries within thelast decade. We give a summary of what has been done, referring to our and others’ earlier
work, and what still needs to be addressed for achieving higher gains from kidney exchange
from an economic organization point of view. We show that incentivizing compatible pairs toparticipate in an ethically acceptable manner will help more incompatible pairs in exchange,
and can lead to the creation of a single large clearinghouse instead of multiple small ones
which will in turn help highly sensitized patients.
Live-donor liver exchange has been a relatively new modality in organ transplantationand some exchanges have been conducted primarily in South Korea. Different from kidneys,
it requires strict size compatibility considerations and tissue incompatibility does not playa major role. In this paper we explore the structure of optimal liver-exchanges and showthat although the friction caused by size incompatibility decreases direct donations, throughutilization of exchanges it caqn increase the total number of transplants.

30

Liver transplantation for liver cancer in Japan- Differences between adults and children Takahito Yagi
Hepato-Biliary & Pancreatic Surgery, Okayama University Hospital

Liver transplantation (LT) is the only acceptable therapeutic arm for cancer therapy insolid organ transplantation. In adults, LT is used for relatively early hepatocellular carcinoma(HCC). This criteria of LT for HCC has been named as Milan Criteria by Mazzaferro et al. MCmeans a single nodule smaller than 5cm in diameter or multiple nodules fewer than three andsmaller than 3cm in diameter each. As long as met Milan Criteria, four year survival of LT for
HCC was 75%, just same as those of LT for chronic hepatic failure without HCC. LT for HCC
occupied 20.5% (1131/5510 cases) in Japanese LT registry 2007 and 24.5% in our institute. But
multi-armed intensive pretreatment including hepatectomy, ablation and chemoembolization
is able to make over Milan HCCs into met Milan HCCs. Such down staging pretreatment iscalled “intention to treat”, and will increase met Milan population.
In children, histo-pathological subtype of liver cancer is hepatoblastoma (HBT), and quite
different from that of adult. Therefore, clinic-pathological nature and LT indication of HBT
are not same as adult liver cancer (HCC). Indication of LT for HBT is unresectable advanced
tumor in Stage III or IV. Even HBT with distant metastasis, LT is acceptable when metastatic
nodule are surgically removed or not viable by intensive chemotherapy. In such advanced
HBT, primary LT has better survival than that of rescue LT after in compete hepatectomy.
I herein presents these 2 types of LC in Japan and our institute.

31

Present status of organ transplantation in Japan
Kenji Yuzawa
Director, Department of Transplantation Surgery, National Hospital Organization Mito Medical Center
Chair, Case Registration Committee, The Japan Society for Transplantation

Japan is a developed country in many medical field. But, only in organ transplantation,
Japan is a developing country. Many Japanese transplant surgeons had training in the
United States and Europe. Many basic science articles on transplantation were described by
Japanese. More than 80% recipients after organ transplantation had the immunosuppressive
drug developed in Tsukuba, Japan. Japan has a leadership in organ transplantation in theworld. After the organ transplantation law was established in 1997, the number of brain death
donors was limited, because the written consent of the donor was necessary. So many patients
who needed organ transplantation went abroad. In 2008, the Declaration of Istanbul by theinternational transplantation society and WHO stated organs for transplantation should be
equitably allocated within own countries. Many Japanese patients became unable to go abroadfor organ transplantation. In 2009, the law was revised, and the written consent was unnecessary.
But the numbers of deceased donors were remained about 110 per year. Surprisingly, in 2013,
the number of deceased donor was decreased to 84. In these circumstances, in Japan, thespecial fields in living organ transplantation were developed. These are ABO blood group
incompatible organ transplantation and living liver transplantation. The organ transplantation
between ABO blood incompatible pair was contra-indication 20 years ago. But now it’s about
27% in living renal transplantation in Japan. Using strong immunosuppressive drugs, after
removal of ABO group antibody by plasma exchange, we can perform it easily and safely.
For living liver transplantation, the high technic for donor liver operation is necessary. Of
course, Japanese transplant surgeon can perform it safely. Both are not so popular in the othercountries except for Japan, because the numbers of deceased donors were enough. I reportthese special situation of Japan in organ transplantation.

32

NOTE

33

NOTE

34

Colloid and Interface in Bio-resources
and Environment
Research unit colloid engineering in bio-resources
Auspices
Faculty of Life and Environmental Science
International cooperative Educational Program for
Creation of a Harmonious Asian Community
Electrokinetic kinetic society of Japan

35

36

Sep 28 (Sun)Special Conference Room
Colloid and Interface in Bio-resources and Environment

Chair

Wenｇfeng Tan

Huazhong Agricultural
University

11:00-11:20

Yasuhisa Adachi

University of Tsukuba

Flocculation dynamics of PSL particles with polyelectrolytes - Bridging
vs. charge neutralization-

11:20-11:40

Munehide Ishiguro

Hokkaido University

Surfactant Adsorption and Transport in a Humic Soil

11:40-12:00

Yuji Yamashita

University of Tsukuba

Colloidal properties of humic substances

12:00-12:15

Tien Duc Pham

University of Tsukuba

Adsorption of polyanion and anionic surfactant onto large alphaalumina beads with positively charged surface

12:15-12:30

Wan Khairunnisa

Malaysia-Japan International
Institute of Technology

The Effect of Extraction Process on the Effectiveness of Moringa
oleifera as a Coagulant

12:30-13:30

Lunch

Chair

Munehide Ishiguro

Hokkaido University

13:30-14:15

Alexander Zezin

Moscow State University

Interpolyelectrolyte complexes for ecology

14:15-14:35

Noriyuki Kumazawa

Ibaraki University

Development of the radioactive decontamination techniques using
polymer materials

14:35-14:55

Motoyoshi Kobayashi

University of Tsukuba

Aggregation and deposition kinetics of model colloidal particles under
the influence of attractive electric double layer force

14:55-15:10

Kenta Yamada

University of Tsukuba

Amendment Effect of Polyion Complex against Raindrop Erosion

15：10-15：30

Coffee BreakChair

Yasuhisa Adachi

University of Tsukuba

15:30-16:00

Alexander Yaroslavov

Moscow State University

Complexes of cationic polymers with anionic liposomes

16:00-16:20

Sosaku Ichikawa

University of Tsukuba

Layer-by-layer multi-coating of large oil droplets by polyelectrolytic
dietary fibers for the stability control

16:20-16:40

Kazuyoshi Ogawa

University of Tsukuba

Intermolecular Interaction observed in Polyelectrolyte Complex
Formation Using Microgel

16:40-17:00

Wenfeng Tan

Huazhong Agricultural
University

The complexation of protein and Humic substances

17:00-17:30

Hiroyuki Ohshima

Tokyo University of Science

Electrostatic interaction between soft particles

17:30-17:50

Floor discussion

37

2 / 26 ページ

Flocculation dynamics of PSL particles with polyelectrolytes- Bridging vs. charge neutralization Lili Feng and Yasuhisa Adachi
Faculty and Graduate school of Life and Environmental Sciences, University of Tsukuba

Flocculation kinetics of negatively charged polystyrene latex particles with high molecularweight linear polyelectrolytes were investigated to identify the mechanism of bridging andcharge neutralization, and also steric effects and electrostatic effects. Polyelectrolyte chainsof different charge density were applied on purpose. The two mechanisms are confirmed totake places simultaneously under the condition of hydrodynamic mixing. However, under thecondition without hydrodynamic mixing, we can identify the feature of two mechanisms. For
high charge density polymer, the mechanism of charge neutralization is more important for thesystem close to practical application. It was confirmed bridging takes places with relatively
low charge density polymers near isoelectric point. These results characterized the picture ofpolyelectrolyte dynamics at colloid interface just after incubation.

38

Surfactant Adsorption and Transport in a Humic Soil
Munehide Ishiguro
Research Faculty of Agriculture, Hokkaido University

Sodium dodecylbenzene sulfonate (DBS) is a very useful and widely used anionicsurfactant. This surfactant sometimes creates environmental problems when it is released into
the environment. However, the factors influencing the adsorption and transport of DBS in soil
have not been studied well. In this study, the influence of the potential at the adsorption site on
the adsorption of DBS in a soil was first elucidated by using a theoretical adsorption equationand its transport with adsorption and desorption was evaluated experimentally. The soil was ahighly humic soil with a negative charge. The amount of DBS adsorbed was measured with abatch method for different electrolyte concentrations of NaCl at pH 4.5 and 6.5. The adsorption
site potential of the soil was obtained with the modified Langmuir adsorption equation. The
adsorption of DBS decreased as the electrolyte concentration decreased and as the pH increased
because the repulsive electric potential between DBS and the soil increased. These results
were confirmed by the obtained adsorption site potential and the measured zeta potential. The
difference between the adsorption of DBS with a linear and with a branched carbon chain
was also detected, and this difference was related to the free energy of micellization. DBS
transport delayed with adsorption. The delay was evaluated by the distribution ratio, R=Q/
θC; C is the surfactant concentration of influent, Q is the adsorption amount per soil volume
at C and θ is the volumetric water content. At lower electrolyte and DBS concentrations,
DBS decomposition during the transport was observed. Because DBS adsorption is strongly
affected by electrolyte concentration and pH, these two factors must be carefully considered to
predict the fate of DBS in environmental applications.

39Colloidal properties of humic substances
Yuji Yamashita
Faculty of Life and Environmental Sciences, University of Tsukuba

Humic substances (HS) are natural organic matter that is commonly found in surface andsubsurface water as well as in sediments and soils. As secondary products from the microbial
decomposition of plant and animal remains, HS are organic polymeric composites that haveno particular set of elemental composition or chemical structure. It has generally beenrecognized that HS can easily be associated with other chemicals such as hazardous materials
and nutrient salts in the natural environment and consequently can influence their chemical
speciation and transport behavior. In order to better understand such mediating roles of HS
in natural environments, its property and transport behavior should be totally understood. As
secondary products from the microbial decomposition of plant and animal remains, HS areorganic polymeric composites that have no particular set of elemental composition or chemical
structure. Nevertheless, principles of the colloid and surface chemistry have successfully been
applied to elucidate the function of HS. HS is negatively charged as a result of the dissociationof its acidic functional groups; therefore, its polyelectrolyte properties including protonation
behavior, electrostatic potential and binding affinity to metal ions have been studied in great
detail. The aggregation and dispersion behavior of HA has also been investigated over theyears. Several studies have been conducted to understand the transport behavior of HS, which
be interpreted in relation to their colloidal properties. The aim of the present study was toreview researches of HS in the viewpoint of colloid and surface chemistry and to enhance theimportance of the development of study on the physicochemical function of HS.

40

Adsorption of polyanion and anionic surfactant onto
large alpha alumina beads with positively charged surface
Tien Duc Pham*, Motoyoshi Kobayashi, Yasuhisa Adachi
Graduate School of Life and Environmental Sciences, University of Tsukuba, Japan

Adsorption of strong polyanion poly(styrene sulfonate), PSS and anionic surfactant, sodium
dodecyl sulfate (SDS) onto α-alumina beads with large size was systematically investigatedas functions of pH and NaCl concentration. The calculated curves from two-step model canreasonably represent experimental results of PSS and SDS adsorption isotherms onto α-Al2O3.
The adsorption amounts of PSS and SDS onto α-Al2O3 reduce with increasing pH due to thedecrease in the initial surface charge of α-Al2O3. The proton adsorption isotherms at low salt
concentrations upon surfactant adsorption can also be described well by two-step model, but thiscannot be applicable for proton adsorption upon polyelectrolyte adsorption. The adsorption
amount of PSS increases with an increase in molecular weight of PSS from 70 to 1000 kg/
mol. It suggested that a more flat conformation for absorbed PSS70 than that of PSS1000. The
adsorption amount of PSS increases with increasing salt concentration for both PSS70 and
PSS1000, demonstrating that not only electrostatic but also non-electrostatic interactions
induce PSS adsorption. The SDS adsorption isotherms at three salt concentrations have acommon intersection point (CIP) corresponding to charge neutralization and the adsorption
density of SDS onto α-Al2O3 decreases with increasing electrolyte concentration below CIP.
Such phenomena, on the contrary, cannot be observed for PSS adsorption. The SDS uptake
onto α-Al2O3 in the presence of hemimicelles or admicelles can prevent the adsorption of PSS
so that the adsorption of PSS decreases significantly with pre-adsorption of SDS. Furthermore,
SDS is able to enhance desorption of PSS dramatically, suggesting that the adsorption of SDS
onto α-Al2O3 is stronger than PSS adsorption.

41

The Effect of Extraction Process on the Effectiveness ofMoringa oleifera as a Coagulant
Wan Khairunnisa
Malaysia-Japan International Institute of Technology (MJIIT)The most effective organic coagulant is Moringa oleifera, a multipurpose plant that can be
fully utilizes for other purpose as well. The active ingredient inside of M. oleifera seed is themain focus for high performance coagulation process. It is reported that active ingredient also
known as coagulant protein. Protein extracted M. oleifera can reduce sludge production andsafe towards the operator since the organic sludge is biodegradable, compared to aluminium
sulphate, a chemical coagulant. Aluminium sulphate (alum) has greatly used in wastewater
treatment of most countries, except rural country such as Africa. Furthermore, Malaysia
is known to the high usage of alum in wastewater treatment, same with other developing
countries. However, the problem causes by alum has not yet been solved even a new invented
chemical coagulant was introduced last 2007. Several methods on protein extraction haveestablished by earlier researcher since 1988, and still in investigation till today. Pressurizedwater extractor (PWE) is a new instrument that uses green chemical approach, where the water
is the main solvent and no chemical is involve. PWE can extract a 100% protein with suitableparameters but unfortunately, no information of PWE had been use on M. oleifera. The main
purpose of study is to investigate the effect of extraction process using PWE with coagulation
performance of M. oleifera. The temperature ranges from 40°C to 180°C of PWE will be used
for optimization of the extraction. The coagulation performances between extraction using
PWE and conventional method will be compared. The extraction using PWE is expected to
produce extracted protein in high quantity and quality compared to other conventional methods
used. Organic coagulant promises better environment compared to chemical coagulant.

42Interpolyelectrolyte complexes for ecology
A.B.Zezin, V.B.Rogacheva, M.F.Zansokhova, A.A.Yaroslavov
Department of Chemistry, M.V.Lomonosov Moscow State University, Moscow, Russia

There are so many sources of dust of different nature which consists of highly dispersed
particles. They form the air sols that are very dangerous for people. The extremely dangerous
are those one which contain the toxic substances such as heavy metals or radionuclide’s. The
last one is formed in the huge amount as a result of accidents such as at Chernobyl in 1986 andFukushima in 2011 AER. So it is necessary to suppress the secondary contamination of the
top soil via the wind and water erosion.
Because of the complex and nonuniform character of the natural dispersed particles surface it is natural to search the effective binders for the dispersed systems among the amphiphilic compounds such as interpolyelectrolyte complexes (IPC). They are formed as a resultof coupling of oppositely charged polyions. IPC particles are known to contain the coupledhydrophobic blocks and hydrophilic charged entities. They actually proved to be the effective
binders of soil particles also for the ability of different kind of units to exchange their positions
so that to find the optimal configurations. It was established in the course of fundamental studies of IPC structure and properties.
The IPC working compositions are created on the base of water-salt (mineral fertilizers)
solutions of various IPC. The technology of IPC formulations usage is that they are depositedon the top soil with the already existing technique such as watering machinery, helicoptersand so on. As a result the soil is soaked at the depth of 2-5 mm. The layer formed is the soilpolymer crust which is solid in the dry state and plastic in the wet state. The typical composition successfully used in Chernobyl contained 1-2 % wt. of oppositely charged polyelectrolytes
with the consumption 1-2 liters per 1 m2 (10-20 ton per 1 hectare). The same formulations were
found to be the effective flocculants for various aqueous mineral highly dispersed systems.
The addition of ~ 1 % wt. of anionic microgel to the typical formulation proved to increasesignificantly the strength of soil-IPC crust. The IPC hydrogels were studied especially andthey were shown to form the core-shell type of structures with IPC shell.
The study was supported by the RSF project № 12-03-00705-а

43

Development of the radioactive decontamination techniques
using polymer materials
Noriyuki Kumazawa
Department of Biomolecular Functional Engineering,College of Engineering, Ibaraki University

Cesium contamination due to the accident of the Fukushima Daiichi nuclear power plantin 2011 has not yet been resolved today. In this study, we carried out (i) development of
the novel remover film made of polyvinyl alcohol (PVA) for radioactive decontamination,(ii) development of the flocculation-precipitation (FP) reagent for the recovery of cesium
contaminated clay particles.
For the decontamination in low-polluted area, high-pressure water cleaning method havebeen widely used so far. In this method, however, the scattering of the splashing contaminatedwater should be avoided. In the decontamination of the building surface, the shot blast method
is sometimes used to scrape off the contaminated surface. However, the usage of this technique
is limited and the diffusion of polluted dust should be carefully controlled. In this study, wedeveloped a novel film-forming remover solution for the radioactive decontamination by using
PVA, surfactant and bentonite, and its performance was investigated. The prepared solution
was applied to the building surface such as rooftops. After natural drying, a strippable film
was formed which was then peeled off with sticking the surface contaminants. The cesium
removal ratio (CRR) was evaluated from the measurement using the surface dosimeter. In
the case of concrete surface (Date, Fukushima), the CRR was 40-50%. In the case of acrylic
rubber surface (Fukushima University), the CRR was as high as 90%.
The radioactive cesium is mostly sorbed to the clay particles in the soil. The clay particles
may move from the forest to the city area due to rainfall, which leads to a serious problem ofrepetitive recontamination. A new FP reagent was developed to realize effective prevention of
the recontamination and effective cesium recovery. A new FP reagent made of 3:1 molar ratioof polydiallyldimethylammonium chloride (PDADMAC) and sodium polyacrylate (PAANa)
was found to precipitate the clay particles of 57.5g per 1g, which is more than ten times effective
compared to the commercially available inorganic FP reagent.

44

Aggregation and deposition kinetics of model colloidal particles
under the influence of attractive electric double layer force
Motoyoshi Kobayashi
Faculty of Life and Environmental Sciences, University of Tsukuba

Understanding of aggregation and deposition kinetics of colloidal particles is important
to control solid-liquid separation processes and to predict the fate of substances sorbed withnatural particles in soil and water environments. Colloidal particles usually have surface charge
and form electric double layer (EDL). While the kinetics without EDL force is controlled
by the collision frequency as well as hydrodynamic and the van der Waals interactions, theaggregation/deposition rate with EDL force is affected by surface charge and ionic strength as
expressed by the theory of Derjaguin, Landau, Verwey, and Overbeek (DLVO).
Many studies so far have focused on the effect of repulsive EDL force on the kinetics.
In the presence of repulsive EDL force, the rate of aggregation/deposition sharply decreases
with decreasing electrolyte concentration and increases with decreasing the magnitude of thesurface potential. Such behaviors can be qualitatively described by rate theories with the
DLVO force. However, theoretical values quantitatively differ from experimental ones.
On one hand, less studies have been carried out for the aggregation/deposition kinetics
in the presence of attractive EDL force, which acts between oppositely charged surfaces. In
order to improve current knowledge of the rate theories of aggregation/deposition including
the DLVO force, we have performed the experimental and theoretical studies on aggregationand deposition of spherical model particles under the influence of attractive EDL. In our
experiments, rates of Brownian aggregation between silica and amidine latex and turbulent
aggregation rates between sulfate latex and amidine latex were obtained. Experiments ofdeposition of latex particles were conducted in the packed bed of zirconia beads. Using thesematerials allows us to examine the influence of surface potential on aggregation/deposition.
Experimental results demonstrate that aggregation and deposition rates increase slowly withdecrease of salt concentration and the effect of the magnitude of surface potential is weak. The
DLVO theory reasonably describes experimental trends.

45

Amendment Effect of Polyion Complex against Raindrop
ErosionKenta YAMADA1, Motoyoshi KOBAYASHI2, Haruyuki FUJIMAKI3
Graduate School of Life and Environmental Sciences, University of Tsukuba
2Faculty of Life and Environmental Sciences, University of Tsukuba
3
Arid Land Research Center, Tottori University, Japan1

We examined the preventing effect of polyion complex (PIC) against raindrop erosion
on soil surface using the rainfall simulator and a compact soil box. The used PIC solution
was composed of polycation (Polydiallyldimethylammonium chloride), polyanion (polyacrylicacid) electrolyte (KNO3) and pH adjuster (KOH). The Tottori masa soil was packed into anacrylic box. Upper and lower bottoms of the box had 40 holes of 5 mm in diameter so that
infiltrated water can be drained through the holes.
The soil in a box was saturated with tap water from the bottom. Then, the mixed solution
was applied to the soil surface under three different of PIC solution doses 0, 1, 3 L m-2. The
runoff was collected from an outlet port located at the downstream edge every 10 minutes.
The volume of runoff and the mass of washed soil were measured.
The rainfall duration was 120 minutes, and the rainfall intensity was about 70 mm h-1.
This intensity was very low compared with the hydraulic conductivity of the saturated soil.
Therefore the occurrence of runoff means the change of soil structure; a crust layer forms.
The experimental results clearly show that the cumulative runoff and the cumulative soil
loss were affected by the applied amount of the mixed solution. That is, the runoff and thesoil loss decrease with increasing the amount of applied mixed solution. It is said that runoff
is brought about by decreased hydraulic conductivity resulted from crust formation on soil
surface, and soil loss is generated by soil detachment and subsequent transport of soil particles
by raindrop impact and surface runoff flow. Therefore our results suggest that insoluble PICs,
which are formed by decreasing of salt concentration due to rainfall, act as a binding agent
between the soil particles, then stabilize soil structure.

46

Complexes of cationic polymers with anionic liposomes
A.Yaroslavov, A.Sybachin, O.Zaborova, A.Efimova, E.Yaroslavova, A.Rakhnyanskaya
Department of Chemistry, M.V.Lomonosov Moscow State University, Russia

Composition and properties of complexes are discussed, formed by cationic polymers
and anionic lipid vesicles (liposomes). The complexation can be accompanied by structural
re-arrangements in the liposomal membranes: lateral lipid segregation, highly accelerated
transmembrane migration of lipid molecules, incorporation of adsorbed polymers into the liposomal membrane, etc., and morphological changes in liposomes: their aggregation, fusionand disruption. Electrostatically adsorbed polycations can be completely removed from themembrane surface in water-salt solutions or in the presence of an anionic polymer. The above
mentioned phenomena have been examined depending on the cationic polymer architecture,content of charged lipids, vesicle phase state and size; as well as ionic strength of solution. It
is likely that the observations we made might be useful to interpret biological effects of polyelectrolytes and multicharged polymeric constructs and to fabricate functional multiliposomal
containers.

47

Layer-by-layer multi-coating of large oil dropletsby polyelectrolytic dietary fibers for the stability control
Sosaku Ichikawa
Faculty and Graduate school of Life and Environmental Sciences, University of Tsukuba

Oil-in-water (O/W) emulsion is a dispersion system, in which oil droplets are dispersed in
an aqueous dispersion medium. It has been widely used in food and pharmaceutical industries.
However, it is desirable to control the stability of oil droplets for the protection of bioactive
lipophilic components during the storage and their targeted release in a gastrointestinal
tract. In this study, we modified the surface properties of large oil droplets larger than 10
micrometer in size by electrostatic layer-by-layer multi-coating using polyelectrolytic dietaryfibers, aiming to control their stability. Monodisperse O/W emulsion was by microchannel
emulsification. The mean droplet diameter and coefficient of variation were 26.9 micrometerand 6.5%, respectively. Chitosan (CHI) as a cationic dietary fiber and carboxymethyl cellulose(CMC) as an anionic fiber were alternately coated onto oil droplet surface. The zeta-potentialof oil droplets was alternately changed, depending on the net charge of droplets dominated by
the electrostatic property of the outer fiber layer. Multi-coated oil droplets did not aggregate or
coalescence in an emulsifier-free aqueous medium after two weeks storage at room temperature.
When CHI was modified outer layer, oil droplets were unstable at high pH value (pH > 6), due
to loss of CHI charge. When CMC was outer layer, the oil droplets showed good stability toaggregation in between pH 5 and 9, but aggregated at lower pH value (pH < 5), due to lossof CMC charge. These findings indicated that large oil droplet stability can be controlled bylayer-by-layer coating using food grade polyelectrolytes.

48

Intermolecular Interaction observed in Polyelectrolyte Complex
Formation Using Microgel
Kazuyoshi Ogawa
Faculty of Life and Environmental Sciences, University of Tsukuba

Polyelectrolyte complexes are formed by the interaction between oppositely chargepolyelectrolytes. Considering that biopolymers such as protein and DNA are polyelectrolytes,
interpolyelectrolyte complex (IPEC) formation could be regarded as a simple model of assemblyphenomena of molecules observed in biological system. In the self assembly-phenomena ofmolecules, intermolecular interaction such as electrostatic interaction, hydrophobic interaction,and hydrogen bonding plays an important role. The various materials of polyelectrolyte havebeen used in order to investigate the mechanism of IPEC. In our studies on IPEC, responsive
polymer microgel has been used as sample (or material). Responsive polymer microgel
demonstrates not only swelling-deswelling behavior but also aggregation-dispersion one in
response to the change of solution pH, temperature, salt concentration etc. These behaviors
occur due to change of intra- and inter particle interaction. Through these behavior of microgelobserved by light scattering, we investigated how salt concentration effect on electrostaticinteraction and hydrophobic one. In addition we investigated intermolecular interaction
during IPEC in which charged polymers interact with oppositely charged microgels. The
resulting complexes are then divided into three types: (i) water-soluble intraparticle complexes
consisting of a microgel to which linear polyelectrolytes bind (ii) complex coacervates, and (iii)
insoluble amorphous precipitates. The type of resulting complex depends on ionic strength
as well as mixing ratio, which affects on intermolecular interaction in IPEC. These results
obtained would help not only understanding self assembly-phenomena of molecules observedin bio-system but also the technology of layer-by-layer, microencapsulation, and design ofnanoparticle for drug delivery system using intermolecular interaction.

49

The complexation of protein and Humic substances
Wenfeng Tan1, Yan Li1, Mingxia Wang1 and Luuk Koopal2
College of Resources and Environment, Huazhong Agricultural University, China
Department of Physical Chemistry and Colloid Science, Wageningen University, the Netherlands
1

2

Humic substances (HS), including humic acids (HA) and fulvic acids (FA), are importantcomponents of soil systems. The reaction between enzymes and soluble humic matter has
been attributed to co-polymerisation, adsorption and encapsulation of enzymes into the inner
structure of humic matter. The importance of electrostatic and hydrophobic interactions
between humic acids and proteins concluded that parameters like mixing ratio of HA andprotein, pH and ionic strength determined the extent of HA-protein complexation andaggregation of the complexes. Complexation of oppositely charged HS and protein is a formof ‘complex coacervation’ or ‘associative phase separation’, a well-known liquid-liquid phaseseparation driven by the association of two oppositely charged macromolecules. HS form
strong complexes with oppositely charged proteins, which will lead to changes in the enzyme
activity. The effect of soil HS on the activity and stability of two enzymes was investigatedas a function of pH, ionic strength and mass ratio HS/enzyme. Humic acid (JGHA) and fulvic
acid (JGFA) are negatively charged, lysozyme is net positive at pH values below 10.4 andurease is net positive below pH 5.2 or net negative above pH 5.2. The enzyme activities in the
HS-enzyme complexes were suppressed when the enzymes were oppositely charged to the
HS. The largest activity suppression was observed around the mass ratio HS/enzyme where
the HS-protein complex was at its isoelectric point (IEP). At the IEP strong aggregation of thecomplexes led to encapsulation of the enzyme. The ionic strength was important; an increase
decreased complex formation, but increased aggregation. Due to the larger hydrophobicityof JGHA than JGFA, the reduction in enzyme activity was stronger for JGHA. The enzyme
stability decreased also maximally at mass ratio around the IEP of the complex when HS
and protein were oppositely charged. When urease and HS were both negatively charged nocomplexes were formed, but the presence of JGHA or JGFA improved the activity and stabilityof the enzyme (Tan WF et al., J Colloid Interface Sci, 2014, 430: 40-46; Li Y et al., Environ Sci
Technol, 2013, 47: 5050-5056).

50

Electrostatic interaction between soft particles
Hiroyuki Ohshima
Faculty of Pharmaceutical Sciences, Tokyo University of Science

Electrostatic interactions between soft particles (i.e., hard particles covered with an ionpenetrable surface layer of polyelectrolytes) in an electrolyte solution are quite different fromthose for hard particles without surface structures. The remarkable difference is that the electrostatic interactions between soft particles are governed by their space-charges distributed
within the particles or the Donnan potentials, while those for hard particles are determined bytheir surface charges or surface potentials. Theoretical studies on the interaction between soft
particles so far have focused mostly on the interactions before contact of the surface layers ofinteracting soft particles (Ohshima H., Theory of Colloid and Interfacial Electric Phenomena.
Elsevier, 2006; Ohshima, H., Biophysical Chemistry of Biointerfaces, John Wiley & Sons,
2010). There are only a few studies on the electrostatic interaction between soft particles after
contact. Here we discuss the effects of compression and interdigitation of the polyelectrolyte
segments in the surface layers of two interacting parallel soft plates (Ohshima H., Colloid
Polym Sci 292: 431-439, 2014). In this model the interaction process consists of three stages,i.e., interaction before contact of the polyelectrolyte layers (stage 1), interdigitation (stage 2),
and compression (stage 3). We also discuss the interaction of two interpenetrating soft particles (Ohshima H., Colloids Surf. A., in press, 2014). A three-stage model of the electrostaticinteraction between two interpenetrating charged spherical soft particles with no particle core(space-charged porous spheres) in an electrolyte solution is presented. That is, (i) interaction
before contact of the two spheres, (ii) partial interpenetration, and (iii) full interpenetration,i.e., engulfing of one sphere by the other. Finally, we consider three-dimensional discrete
charge effects on the electrostatic interaction between soft particles (Ohshima H., Colloid
Polym Sci 292: 757-761, 2014).

51

NOTE

52

Aging Sciences
Faculty of Medicine, University of Tsukuba
Ph.D. Program in Human Biology, University of Tsukuba
International Institute for Integrative Sleep Medicine (WPI-IIIS),
University of Tsukuba
Faculty of Life and Environmental Sciences,
University of Tsukuba

53

54

Sep 28 (Sun)International Conference Room
Aging Sciences

Chair
Chair

Mamiko Sakata
Takahiro Kojima

University of Tsukuba
Univeristy of Tsukuba

13:10-13:35

Daniel S. Peeper

Netherlands Cancer InstituteIn vivo RNAi dropout screens for cancer drug target discovery

13:35-14:00

Mamiko SakataYanagimoto

University of Tsukuba

Premalignant and disease-specific mutations in age-related
hematologic malignancies

14:00-14:25

Liran Shlush

University Health Network

Preleukemia clonal hematopoiesis and the aging bone marrow

14:25-14:50

Yukio Nagasaki

University of Tsukuba

Development of redox polymer nanomedicine for anti-aging
treatments

14:50-15:15

Naoki Yoshimura

University of Pittsburgh School Age-related urinary bladder dysfunction: involvement of theof Medicine
angiotensin II receptor system

15:15-15:40

Hiromitsu Negoro

Kyoto University

15:40-15:55
Chair
Chair

Coffee BreakYu Hayashi
Kaspar Vogt

University of Tsukuba
University of Tsukuba

15:55-16:20

Joseph S. Takahashi

University of Texas
Molecular architecture to the circadian clock in mammals
Southwestern Medical Center

16:20-16:45

Joseph Bass

Northwestern University

Epigenetic regulation by the molecular clock-sirtuin pathway

16:45-17:10

Yu Hayashi

University of Tsukuba

How the brain generates REM sleep

17:10-17:35

Emmanuel Mignot

Stanford University

Narcolepsy and genetic predisposition

17:35-18:00

Ravi Allada

Northwestern University

A conserved bicycle model for circadian clock control of membrane
excitability

Sep 29 (Mon)

Coordination of day-night changes in urination by the circadian clock

Hall

Chair
Chair

Hisashi Oishi
Pleasantine Mill

University of Tsukuba
University of Edinburgh

9:00-9:25

Pleasantine Mill

University of Edinburgh

Genetic and biochemical characterization of mammalian cilia
compartmentalization

9:25-9:50

Hiroaki Nakano

University of Tsukuba

Strange and simple placozoans- ‘biologically immortal’ animals?

9:50-10:15

Alexander Medvinsky

University of Edinburgh

Mechanisms of haematopoietic stem cell development in mouse andhuman

10:15-10:30
Chair
Chair

Coffee BreakHiroshi Suzuki
Peter ten Dijke

University of Tsukuba
Leiden University Medical

10:30-10:55

Peter ten Dijke

Leiden University Medical
CenterTGF-β receptor signaling in breast cancer cell invasion and metastasis

10:55-11:20

Auro Nomizo

University of Sao PauloThe role of the thymus in modulating γδ T cell suppressor activity
during experimental Trypanosoma cruzi infection

11:20-11:45

Aristidis Moustakas

Uppsala University

Regulation of cancer stem cell potential by HMGA2, a chromatin
regulator of epithelial-mesenchymal transition and biological aging

11:45-12:10

Shu-Chun Teng

National Taiwan University

Telomerase activation in yeast and cancer cells

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Sep 30 (Tue)International Conference Room

Chair
Chair

Ryosuke Niwa
Tang-Long Shen

University of Tsukuba
National Taiwan University

9:00-9:25

Ryosuke Niwa

University of Tsukuba

Steroid hormones and aging: lesson from the fruit fly Drosophilamelanogaster9:25-9:50

Klaus Hartfelder

University of Sao PauloLong live the queen – the molecular and endocrine underpinnings ofthe reproduction/lifespan paradox in social insects

9:50-10:15

Yuko Shimada-Niwa

University of Tsukuba

Nutrient-dependent regulation of steroid hormone biosynthesis in the
puberty of fruit fly Drosophila melanogaster10:15-10:40

Pierre Trifilieff

University of Bordeaux

Impact of n-3 polyunsaturated fatty acid deficiency on
mesoaccumbens dopaminergic transmission and motivation: relevancefor the negative symptoms of schizophrenia

10:40-10:55
Chair
Chair

Coffee Break
Masayuki Matsumoto
Jacques Micheau

University of Tsukuba
University of Bordeaux

10:55-11:20

Andreas Zimmer

University of Bonn

Δ9-THC restores age-related changes in the brain

11:20-11:45

Jacques Micheau

University of Bordeaux

Effects of acute stress on memory processes

11:45-12:10

Masayuki Matsumoto

University of Tsukuba

Midbrain dopamine neurons are divided into anatomical subgroups
encoding distinct signals

12:10-12:35

Vincent Dousset

University of BordeauxImaging of iatrogenic dysimmunity

12:35-13:00

Elena Avignone

University of BordeauxActivation of microglia impacts their directional motility

Sep 30 (Tue)International Conference Room

Chair
Chair

Emiko Noguchi
Han-Yi E. Chou

University of Tsukua
National Taiwan University

13:30-13:55

Renata Rosito TonelliFederal University of Sao
Paulo

Post-translatinal modification by small ubiquitin-modifier SUMO in thecell biology of Giardia lamblia

13:55-14:20

Michael Kann

University of BordeauxInteraction of small viral capsids with the nuclear pore - they are noclassical cargo

14:20-14:45

Bela Gyurcsik

University of Szeged

Novel ‘in situ’ preparation of zinc finger nucleases based on Ni(II)induced specific hydrolysis of proteins

14:45-15:10

Kyoko Yokomori

University of California, Irvine Real time analyses of the DNA damage response in mammalian cells

15:10-15:35

Emiko Noguchi

Univerity of Tsukuba

15:35-15:50
Chair
Chair

Coffee BreakTakashi Mizuhiki
Erick L. Bastos

University of Tsukuba
University of Sao Paulo

15:50-16:15

Erick Leite Bastos

University of Sao Paulo

Biocompatible antiradicals inspired by fluorescent flowers

16:15-16:40

Frank Herbert Quina

University of Sao PauloThe Anthocyanins: plant pigments with multiple functions in nature

16:40-17:05

Ali Mortazavi

University of California, Irvine

Genome-wide remodeling of long-range interactions during skeletal
muscle differentiation

17:05-17:30

Fernando B. Da Costa

University of Sao Paulo,
Ribeirao Preto

Metabolomics and in silico tools in the search of natural compounds
from plants with anti-inflammatory potential

17:30-17:55

Arthur D. Lander

University of California, Irvine Design principles of biological growth control

Identification of disease-casing variants using next generation
sequencing

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In vivo RNAi dropout screens for cancer drug target discovery
Daniel S. Peeper
Netherlands Cancer Institute

In addition to oncogenic drivers, also the ‘non-oncogenome’ can be functionally mined
for specific cancer vulnerabilities. Although such screenings are commonly done in vitro, it
is evident that specific in vivo parameters influence both tumor behavior and therapeuticallyamenable dependencies. Therefore, we performed parallel in vitro and in vivo negative selection shRNA screens to identify factors preferentially necessary to drive tumor expansion.
Until recently, most advanced stage melanomas were refractory to the available therapeutic options, but there are encouraging developments. For example, BRAFV600E, a common driverin melanoma, can be targeted by specific inhibitors, which causes unprecedented melanoma
regression. However, relapse eventually occurs, necessitating the development of combinatorial therapies. Thus, we performed these function-based screens in melanoma. The results ofthese in vivo cancer drug target discovery approaches will be discussed.

57

Premalignant and disease-specific mutations in age-related
hematologic malignancies
Mamiko Sakata-Yanagimoto1 and Shigeru Chiba1,2
Department of Hematology, Faculty of Medicine, University of Tsukuba
Life Science Center, Tsukuba Advanced Research Center, University of Tsukuba
1

2Aging is associated with genetic and epigenetic dysregulation. Cause of various humandiseases is attributed to such a genetic and epigenetic predisposition by aging.
Recent sequencing technologies identified the frequent mutations in TET2, DNMT3A, andIDH1/2 genes, encoding epigenetic regulators, in various hematologic malignancies. These
gene mutations are also identified in peripheral T-cell lymphomas (PTCL), an age-related
hematologic malignancy, especially in those that the tumor cells have features of follicularhelper T cells. It has further been demonstrated that the mutations in these genes exist even inpremalignant cells as well as tumor cells both in myeloid and lymphoid malignancies.
Then, why do these gene mutations provoke various hematologic malignancies? Bycomprehensive gene-mutation analysis, we found that disease-specific mutations, co-existingwith the common gene mutations, might determine the subtypes of hematologic malignancies.
In myeloid malignancies, mutations in various genes, including N-RAS, JAK2, RUNX1, C/
EBPalpha, c-Cbl, and splicing machineries, have been identified since 1980s. We identified
novel recurrent RHOA mutations in around 60-70% of PTCL samples with features of follicularhelper T cells, in a highly disease-specific manner, together with the TET2, DNMT3A, andIDH2 gene mutations shared by various hematologic malignancies (Sakata-Yanagimoto M,
et al, Nature Genetics 2014). Myeloid-specific gene mutations were not identified in PTCL.
RHOA is a small GTPase, cycling between an active GTP-bound form and an inactive GDPbound form. Almost all the RHOA mutations found in PTCL were restricted to c.G50T,
p.G17V. The G17V RHOA mutant is not able to bind GTP and further inhibits function of thewild-type RHOA. The RHOA mutations are only found in the tumor cells and not found in
the premalignant cells, while TET2-and/or DNMT3A mutations are also found in premalignant
cells. These data suggest that the RHOA mutations finally occur in TET2-and/or DNMT3Amutated premalignant cells and provoke a specific type of cancer.

58

Preleukemia clonal hematopoiesis and the aging bone marrow
Liran Shlush
University Health Network

Recent evidence suggests that although de-novo AML presents as an acute condition, thedisease has a long evolution (probably years) as a subclinical entity. This is based on thedetection of genetic mutations in genes such as DNMT3a that are characteristic of AML, inostensibly normal hematopoietic cells. Furthermore, these phenotypically normal primitiveand mature cell populations carry only a subset of the mutations found in the patient’s leukemic
cells at diagnosis, and persist in functionally normal cells in remission. Mutant DNMT3a(DNMT3amut) has been reported at a frequency of ~1 in 1500 individuals with no known
hematologic problems, consistent with its occurrence as a preleukemic lesion. Mutations inother leukemia-associated genes such as TET2 have been reported in elderly females who haveclonal hematopoiesis but no abnormalities in blood cell production.
As humans age a decrease in the repertoire of B and T cells can be observed consistent
with decreasing number of stem cells contributing to hematopoiesis. A recent analysis ofsomatic mutations in the blood of a centenarian (115 years old) demonstrated oligoclonal
contribution to hematopoiesis. The distribution of variant allele frequencies suggested thatthe majority of the peripheral white blood cells were offspring of two related hematopoietic
stem cell (HSC) clones. Reports from young rhesus macaques estimated that during a year offollow-up at least 1000 genetically different HSCs clones contributed to hematopoiesis, namely
polyclonal contribution under steady state conditions in young non-human primates. This
process of decreased number of genetically different HSCs contributing to hematopoiesis canbe explained by loss of self-renewing primitive stem cells, or by selection of the fittest clones.
As we age HSC environment changes. MRI studies demonstrate increase in yellow marrow(inactive marrow with predominantly fat cells) that peaks in the third decade and a parallel
decline in red marrow (active marrow).
Under the changing environment stem cells can either die or get selected. HSCs thatcan maintain regenerative capacity under the changing environment will take over. Evidancesuggests that both decreased self-renewal and selection occur as human age. Self-renewal
capacity has decreased with age in mice serial transplantation and competitive assays. Human
HSCs isolated from elderly in most instances cannot engraft an immunedeficient mouse, while
stem cells from cord blood can. The outcomes of allogeneic stem cell transplantation are worse
from older donors. It is not clear whether the number of functional stem cells is decreasing or
their ability to regenerate is damaged.
The recent identification of preL-HSCs by us and others provide evidence that although formost of the aging population stem cell regenerative capacity and self-renewal are decreasing
with age, some stem cells gain a selective advantage by acquiring mutations in the epigenetic
machinery. Altogether these findings support a paradigm in which a hostile environment
59

selects for adapted stem cells that in time due to the accumulation of other traits can transform
into disease producing preleukemic cells. The mechanisms related to preleukemia progression
are closely related to the environment. Of note, a recent report describes the development ofdonor-derived leukemia in a patient 27 months after receiving allogeneic HSCs from an HLAmatched sibling, whose donated peripheral blood cells were later found to carry mutations in
IDH2 andDNMT3A at low frequency48. Interestingly, the donor remains free of leukemia 10
years after his stem-cell donation, indicating that the mechanisms underlying the progression
from subclinical pre-leukemic hematopoiesis to overt leukemia are complex and contextdependent.

60

Development of redox polymer nanomedicine for anti-aging
treatments
Yukio Nagasaki
Department of Materials Science, Graduate School of Pure and Applied Sciences,
Master’s School of Medical Sciences, Graduate School of Comprehensive Human Sciences andSatellite Laboratory, International Center for Materials Nanoarchitectonics (WPI-MANA),
National Institute of Materials Science (NIMS), University of Tsukuba, Tsukuba, Ibaraki

An oxidative stress, where excess reactive oxygen species (ROS) are produced, is wellknown to be closely related to not only aging but also development of numerous diseases suchas cancer, stroke, myocardial infarction, inflammatory bowel disease (IBD), kidney failure,arteriosclerosis, diabetes, rheumatoid arthritis, Parkinson’s disease, and Alzheimer’s disease.
ROS are produced by cellular respiration, normal metabolism, and xenobiotic exposure. Most
ROS are generated in cells by the mitochondrial respiratory chain. At the physiological low
levels of ROS, they function as important redox messengers in intracellular signaling andregulation. Living organisms consistently maintain a balance between the production of
ROS and the effectiveness of antioxidant-protective systems including vitamin C, vitamin E,
glutathione, and antioxidant enzymes such as superoxide dismutase, catalase, and glutathione
peroxidase, and so forth. However, under a state of oxidative stress, free radical production
increases remarkably, and the endogenous antioxidants fail to scavenge all ROS, resulting
in severe injury. ROS can directly damage cellular components such as lipids, DNA, andproteins by oxidation, thereby increasing the risk of potentially life-threatening disorders.
One of the most plausible ways to prevent these oxidative stress injuries is the administrationof an exogenous ROS scavenger. Currently, many ROS scavenging compounds have beenreported. Most of these compounds are synthetic and/or natural low-molecular-weight (LMW)
compounds. However, LMW antioxidants can spread entire body and eliminate important
ROS. We have recently been investigating our redox reactive polymers as “Novel Redox
Polymer Therapeutics”. Because the polymers and their self-assembles hardly internalize inhealthy cells, they scavenge excessive generated ROS selectively. So far, we have confirmedthat our redox polymer showed extremely high efficiencies to several oxidative injuries such as
Alzheimer’s disease, renal, cerebral and myocardial ischemia-reperfusion injuries, cancers andulcerative colitis. Our redox polymers can also be applied for biomaterials with low oxidative
stress.

61Age-related urinary bladder dysfunction: Involvement of theangiotensin II receptor system
Naoki Yoshimura1 and Kenichi Mori1,2
Department of Urology, University of Pittsburgh School of Medicine
2
Department of Urology, Oita University Faculty of Medicine

1

Lower urinary tract symptoms (LUTS), both storage and voiding ones that include urinary
urgency, frequency and incontinence, and a difficulty in urination with increased post-void
residual volume, respectively, increase as age progresses. Also, urodynamic studies in elderly
people often show both overactive and underactive bladder conditions, which are also called“detrusor hyperreflexia with impaired contractility (DHIC)”. Although the etiology of LUTS
is multifactorial, our recent study suggested a role of the angiotensin II receptor system in agerelated bladder dysfunction. Angiotensin II is reportedly involved in the bladder remodeling, andexerts its effects through angiotensin II type 1 (AT1) and type 2 receptors (AT2). Cystometricanalysis of 8 weeks-old (8W) and 15 months-old (15M) female SD rats revealed that pressure
threshold (PT), post-void residual volume (RV) and the number of non-voiding contractions(NVCs) were significantly increased in 15M vs. 8W rats (P<0.05) and that maximum voidingpressure (MVP) was significantly decreased in 15M rats compared to 8W rats (P<0.05). In
bladder tissues, the protein and mRNA expression of AT1, connexin 43 (Cx43), ERK-MAPK,and collagen I were significantly increased in 15M rats compared to 8W rats (P<0.05). AT2,
PPAR-γ, adiponectin and adiponectin receptor-1 were also significantly increased in 15M vs.
8W rats. Furthermore, the relative expression ratio of AT1 protein against AT2 protein in themucosa and detrusor was significantly higher in 15M vs. 8W rats. These results suggest thatthe upregulation of AT1, which overcomes AT2 upregulation, may play a significant role inbladder overactivity (i.e., NVCs) due to increased Cx43 expression via activation of MAPK
signaling pathways as well as in incomplete emptying and underactive bladder due to increased
collagen I expression during aging. Thus, the alteration in AT1-mediated angiotensin system
could contribute to age-related LUTS including storage and voiding ones, which are often seen
as DHIC in aged patients.

62

Coordination of day-night changes in urinationby the circadian clock
Hiromitsu Negoro1, Akihiro Kanematsu2 and Osamu Ogawa1
Department of Urology, Kyoto University Graduate School of Medicine
2
Department of Urology, Hyogo College of Medicine

1

Urinary frequency in mammals decreases during sleep period and increases during wake
period. This phenomenon is determined by triad factors; decreased arousal level in the brain,decreased urine production rate from the kidneys, and increased functional bladder capacity
during sleep. Recently, daily rhythms of physiology and behavior have been known to bemodulated by the circadian clock system, such as the sleep wake cycle, hormonal secretion,body temperature, blood pressures and so on. The circadian clock (‘the clock’) consists of anumber of clock genes and is driven by molecular genetic transcription-translation feedback
machinery. The clock exists in most organs and cells, termed ‘peripheral clock’, which isorchestrated by the central clock in the suprachiasmatic nucleus of the brain. Thousands ofgenes of such organs, about 5 to 15% of total genes, are oscillating in a circadian manner.
Several of these genes could be involved in generation of day-night changes in urination; in thekidney, they are genes involved in excretion and reabsorption of water and major electrolytes,
or in modulation of renal vascular tone, and in the bladder, genes associated with regulation of
biological process and response to stimulus, including connexin 43, a gap-junction protein thatenhances transmission of neural stimuli in muscle cells. In this session, the linkage between
the day-night changes in urinary frequency and the genetic rhythm maintained by the clock
system will be discussed, focusing on brain, kidney and especially bladder. Such linkagepresents a novel paradigm for investigating the pathophysiology of nocturnal enuresis (bedwetting in children), considered as immaturity in development of the rhythm, and nocturia(frequent urination at night in the elderly), considered as loss of the rhythm.
(Negoro H, Kanematsu A, Doi M et al Nat Commun 3:809 2012, Negoro H, Kanematsu A,
Yoshimura K and Osamu O J Urol 190(3):843-849 2013.

63

Molecular architecture to the circadian clock in mammals
Joseph S. Takahashi, Ph.D.
Howard Hughes Medical Institute, Department of Neuroscience,
University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA

The circadian clock mechanism in animals involves an autoregulatory transcriptional
feedback loop in which CLOCK and BMAL1 activate the transcription of the Period and
Cryptochrome genes. The PERIOD and CRYPTOCHROME proteins then feedback andrepress their own transcription by interaction with CLOCK and BMAL1. We have studied
the biochemistry of the CLOCK:BMAL1 transcriptional activator complex as well as the
genomic targets of CLOCK and BMAL1 using ChIP-seq methods. We describe the dynamics
of the core circadian clock transcriptional system. CLOCK and BMAL1 interact with theregulatory regions of thousands of genes. The gene network and dynamics of the system
will be discussed. A mechanistic description of the core circadian clock mechanism should
promote our understanding of how the circadian clock system influences behavior, physiology
and behavioral disorders.
References
1.	Bass, J. and J.S. Takahashi. 2010. Circadian integration of metabolism and energetics.
Science 330: 1349-1354. PMCID: 3756146.
2.	Huang, N., Y. Chelliah, Y. Shan, C.A. Taylor, S.-H. Yoo, C. Partch, C.B. Green, H.
Zhang and J.S. Takahashi. 2012. Crystal structure of the heterodimeric CLOCK:BMAL1
transcriptional activator complex. Science 337: 189-194. PMCID: 3694778.
3.	Koike, N., S.H. Yoo, H.C. Huang, V. Kumar, C. Lee, T.K. Kim and J.S. Takahashi. 2012.
Transcriptional architecture and chromatin landscape of the core circadian clock inmammals. Science 338: 349-354. PMCID: 3694775.

64

Epigenetic regulation by the molecular clock-sirtuin pathway
Joseph Bass
Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine,
Feinberg School of Medicine, Northwestern University

Clock proteins comprise an autonomous molecular network involved in organization andinformation processing from the genome to whole organisms across the lifespan. A central
question remains how circadian transcriptional programs integrate physiologic systems inindividual tissues and within the intact animal. A major step in understanding how the clock
is coupled to metabolism originated with discovery that the clock produces rhythmic cyclesof NAD+ turnover. Indeed, the observation that circadian mutant mice exhibit premature
death and hypoglycemia when subjected to a prolonged fast, and that they develop bothcardiomyopathy and skeletal myopathy, prompted us to examine the regulatory function of
the clock-NAD+ pathway in mitochondrial metabolism. We have investigated the effect of
NAD+ deficiency on mitochondria function in circadian mutant animals using a multi-faceted
approach including unbiased proteomics leading to the identification of abnormal acetylationof enzymes involved in lipid oxidation, amino acid catabolism, tricarboxylic acid (TCA) cycle,
electron transport chain (ETC), and superoxide dismutase pathways. Importantly, loss-offunction mutations in several of these oxidative enzymes have also been identified in the humanmetabolic myopathy syndrome and in both glioblastoma and renal cell carcinoma, indicatinga broader effect of the clock-NAD+ pathway on mitochondrial metabolism in both normal andtransformed cells. Using tissue- and cell-based bioenergetics assays, we found that abrogationof the clock impairs electron transfer from lipid to the TCA cycle, in addition to increased
mitochondrial-production of superoxide free radical, increasing sensitivity to genotoxic tress.
Our work also showed that cells exhibit an autonomous rhythm of oxygen consumption,
glucose oxidation, and mitochondrial lipid catabolism. Importantly, the oxygen consumption
cycle in muscle is directly linked to metabolism of NAD+ and activity of the mitochondrial
NAD+-dependent deacetylase SIRT3. NAD+ supplementation using the pro-drug NMN
influences both mitochondrial and transcriptional processes and improves respiration in live
animals. Collectively, our studies indicate that circadian control of NAD+ metabolism andsirtuin function plays a key role in cellular respiration and aging.

65How the brain generates REM sleep
Yu Hayashi1,2International Institute for Integrative Sleep Medicine, University of Tsukuba
2
PRESTO, Japan Science and Technology Agency

1

Sleep in mammals has evolved into a complex phenomenon composed of two distinct
states, REM (rapid eye movement) sleep and slow wave sleep. REM sleep is the major source ofdreams, whereas slow wave sleep is characterized by a synchronous brain activity called slow
waves. Both sleep states are unique to certain vertebrate species including human. Little is
known, however, about the evolutionary origin or significance of these two states. Furthermore,
the identity of the neurons responsible for generation of the two states is controversial dueto the heterogeneity and complexity of the brainstem. Here, using the latest mouse genetic
techniques, we identified neurons that robustly regulate transitions between REM and slow
wave sleep. Furthermore, we show that these neurons share a common developmental origin
with neurons that promote arousal. These results provide critical evidence about the neuralmechanism of REM and slow wave sleep, and may also provide important information about
the evolutionary origin of these sleep states.

66

Narcolepsy and genetic predisposition
Emmanuel Mignot, MD, PhD
Department of Psychiatry, School of Medicine, Stanford University

Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness,
cataplexy, hypnagonic hallucinations, sleep paralysis, and disturbed nocturnal sleep patterns.
Narcolepsy is caused by the loss of hypocretin (orexin)-producing neurons in the lateralhypothalamus. Evidence, such as a strong association with HLA DQB1*06:02, strongly suggests
an autoimmune basis targeting hypocretin neurons. Genome-wide association studies havestrengthened the association between narcolepsy and immune system gene polymorphisms,
including the identification of polymorphisms in the T cell receptor alpha locus, TNFSF4(also called OX40L), Cathepsin H (CTSH) the purinergic receptor P2RY11, and the DNA
methyltransferase DNMT1. Recently, attention has been raised regarding a spike in casesof childhood narcolepsy in 2010 following the 2009 H1N1 pandemic (pH1N1) in China andvaccination with Pandemrix, an adjuvanted H1N1 vaccine that was used in Europe. How theimmune system may be involved in disease initiation and/or progression remains a challenge
to researchers. Potential immunological pathways that could lead to the specific eliminationof hypocretin producing neurons include molecular mimicry or bystander activation, and arelikely a combination of genetic and environmental factors, such as upper airway infections.

67

A Conserved bicycle model for circadian clock control ofmembrane excitability
Ravi Allada
Department of Neurobiology, Northwestern University, USA

Clock control of membrane excitability is a property of master circadian pacemakerneurons that drive rhythms of sleep and wake. Yet the mechanisms underlying rhythms andthe extent of their conservation remain unclear. Using patch clamp analysis in Drosophila
DN1 clock neurons, we find that oscillation in resting sodium currents in the morning andpotassium currents in the evening underlie rhythms of resting membrane potential. Using
RNA-seq from DN1 neurons, we identified a novel molecular pathway linking the circadianclock to ion channel localization to control membrane excitability. Remarkably in mouse clockneurons, we find that sodium leak currents also oscillate with a peak during the day in opposite
phase to resting potassium currents. Thus, alternating resting sodium and potassium currents
act as a conserved “bicycle” mechanism for driving oscillations in membrane excitability inmaster clock neurons, suggesting an evolutionarily ancient origin to the neural mechanisms
governing daily sleep and wake behavior.

68Genetic and biochemical characterization of mammalian cilia
compartmentalization
Pleasantine MillMRC Human Genetics Unit, Institute for Genetics and Molecular Medicine, Edinburgh, UK

Patterning of the embryo is a tightly controlled process which requires the correct
integration and interpretation of key developmental signals. A cell makes a decision ofwhether to differentiate, divide or migrate in response to these environmental cues. Small
microtubule-based projections, or cilia, found on almost every mammalian cell play a criticalrole in signal transduction during development and disease. This is because cilia have a uniquecomposition that is enriched in many receptors and signalling components, analogous to anantenna for focusing signalling responses. Dysfunction of the cilium underlies a group ofhuman genetic disorders, termed ciliopathies. The inability to maintain a cilium results ina spectrum of health problems ranging from skeletal defects and cystic kidney disease, tocognitive and behavioral defects, as well as obesity. Despite a growing list of genes implicatedin cilia biology, we have very little idea what the encoded proteins actually do in cells, or how
mutations cause the disease. Consequently most of these cilia-related diseases are currently
untreatable. Using mouse as a genetic model of human disease, we aim to understand how
cilia are maintained as a specialized signalling compartments. We are also searching for celltype specific differences how traffic to the cilia, necessary for ciliary function, is regulated.
Work from our studies on pan-ciliary retrograde IFT mutants as well as factors restricted tosubset of cilia which are motile will be presented. Identifying novel ciliary components andcharacterizing their functions will lead to a better understanding for the diagnosis and clinicalmanagement within ciliopathy spectrum.

69

Strange and simple placozoans- ‘biologically immortal’ animals?
Hiroaki Nakano
Shimoda Marine Research Center, Faculty of Life and Environmental Sciences,University of Tsukuba

Placozoans are flat amoeba-like marine animals about 1mm, made up of only seven cell
types arranged in three layers. They lack neurons and muscle cells, but are not sessile orparasitic, making them the simplest extant free-living animals. Placozoa is one of the four
extant animal phyla not included within the Bilateria, together with the Ctenophora, Porifera,
and Cnidaria. Their simple morphology and phylogenetic position make them importantanimals for uncovering the origins and early radiation of multicellular animals. However, due
to their small size and lack of easily distinguishable traits, they are extremely difficult to find in
the natural environment, and research on the animal is not as active as the other non-bilaterian
phyla.
In 1969, Karl G. Grell caught a single placozoan specimen from the Red Sea, the firstreport of the animal from a wild environment. During the next 45 years, this single animal has
multiplied into millions of specimens, through several forms of vegetative reproduction such as
fission and budding. Now, this laboratory-cultured strain, known as the Grell strain, is being
studied in a number of laboratories worldwide. However, sexual reproduction has not been
observed in the Grell strain. In fact, the developmental process, from embryos to adults, has
not been reported for the phylum Placozoa. This implies that placozoans apparently possess
limitless vegetative reproductive capacity and can be considered ‘biologically immortal’.
Although placozoans may hide secrets for overcoming aging, there are few research on
their longevity. I have succeeded in collecting placozoans in multiple locations around Japan(Nakano H., Sci. Rep. 4: 5356, 2014). We are aiming to establish experimental systems for
the Japanese placozoans, and studies on these populations other than the Grell strain may be
useful to uncover important biological mysteries that still remain unsolved for the phylum,
including development and aging.

70Mechanisms of haematopoietic stem cell development in mouseand human
A. Medvinsky, S. Rybtsov, A. Ivanovs, A. Batsivari
University of Edinburgh

Definitive hematopoietic stem cells (dHSC) develop in the AGM region in a step-wisemanner. Using ex vivo modelling of HSC development in the mouse we have identified three
types of precursors sequentially developing into dHSCs. Pro-HSCs are found in E9.5 embryos
and are characterized by lack of CD43 expression, which is upregulated at later stages. PreHSCs Type I express CD41 but lack CD45 expression, which is subsequently upregulated in
pre-HSCs Type II prior to their maturation into definitive HSCs. We show that SCF, but not
IL3, is a major effector of HSC maturation during E9-10.
In the mouse, the first HSCs emerge in the AoV. Here, we demonstrate that in the humanembryo the first definitive HSCs also emerge asymmetrically and are localized to the AoV,
which thus identifies a functional niche for developing human HSCs. Using magnetic cell
separation and xenotransplantations, we show that the first human HSCs are CD34+VEcadherin+CD45+C-KIT+THY-1+Endoglin+RUNX1+CD38-/loCD45RA-. This population
harbors practically all committed hematopoietic progenitors and is under-represented in thedorsal domain of the Ao (AoD) and urogenital ridges (UGRs). The present study provides afoundation for analysis of molecular mechanisms underpinning embryonic specification ofhuman HSCs.
In conclusion, we present the hierarchical organization of the developing HSC lineage
as a differentially regulated 4-step process and demonstrate that developmental progressionof HSCs during a very short period of time is regulated by precise stage-specific molecularmechanisms. We also show some similarities and differences between mouse and humanhaematopoietic development.

71

TGF-β receptor signaling in breast cancer cell invasion andmetastasis
Peter ten Dijke
Dept. Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands

The transforming growth factor-β (TGF-β) signalling pathway plays a critical and dualrole in the progression of human cancer. During the early phase of tumour progression, TGF-β
acts as a tumour suppressor, exemplified by deletions or mutations in the core components of
the TGF-β signalling pathway. On the contrary, TGF-β also promotes processes that support
tumour progression such as tumour cell invasion, dissemination, and immune evasion.
Consequently, the functional outcome of the TGF-β response is strongly context-dependent
including cell, tissue, and cancer type. In my talk, I will describe the molecular signalling
pathways employed by TGF-β in cancer and how these, when perturbed, may lead to thedevelopment of breast cancer. Current TGF-β signalling inhibitors that are being evaluatedin clinical trials for treatment of cancer patients target TGF-β or TGF-β receptors. These
therapeutic agents are used systemically, and inhibit all TGF-β responses (bad and good).
Therefore, while effective in inhibiting metastasis, they have a high chance of unwanted ontarget side effects. With the aim to specifically target the oncogenic arm of the TGF-β and toleave the tumor suppressor arm intact, we have performed gain and loss of function genetic
screens, combined with expression profiling studies of breast cancer tissues, to identify novel
druggable regulators of pro-oncogenic TGF- β pathways in breast cancer. I will provide an
update on our results on key signalling molecules that regulate the stability of specific TGF-βsignaling components and thereby promote the TGF-β-induced breast cancer invasion andmetastasis.

72

The role of the thymus in modulating γδ T cell suppressor
activity during experimental Trypanosoma cruzi infection
Fabíola Cardillo1, José Mengel1 and Auro Nomizo2
Oswaldo Cruz Foundation, Gonçalo Moniz Research Center (FIOCRUZ-CPGM),
Rua Waldemar Falcão 121, 40295–001, Brotas, Salvador, Brazil
2
Department of Clinical Analysis, Toxicology and Bromatology, Faculty of Pharmaceutical Sciencesof Ribeirão Preto, University of São Paulo (FCFRP-USP), Ribeirão Preto, Brazil
1

We have previously shown that splenic γδ T cells from young but not aged BALB/c micepossess suppressor activity in vivo and in vitro during the acute phase of Trypanosoma cruzi
infection. The present work was undertaken to investigate the suppressor activity of γδ T cells
from T. cruzi infected euthymic or athymic mice and the role of the thymus in modulating nonadherent spleen cell suppressor activity during the acute phase of infection. Splenic γδ T cells
from aged or athymic BALB/c mice reconstituted with total spleen cells or non-reconstituted
did not exhibit suppressor activity when added to full allogeneic, mixed lymphocyte cultures.
In contrast, splenic γδ T cells from young euthymic BALB/c mice showed suppressor activity
in vitro. Thymectomy reduced the splenic γδ T cell suppressor activity of young BALB/cmice in a time-dependent manner, following a T. cruzi challenge. The continuous provisionof thymocytes to aged mice, young thymectomized mice or total spleen cell-reconstituted
athymic mice could re-establish the γδ T cell suppressor activity. Of particular significancewas the observation that the depletion of γδ T cells during the acute phase of T. cruzi infection
restored the capacity of these mice to mount a humoral immune response to a non-related
antigen such as ovalbumin. These results indicate that gd T cells of extrathymic origin cannot
mediate suppression and that the thymus has a role in the regulation of suppression during theacute phase of T. cruzi infection.

73

Regulation of cancer stem cell potential by HMGA2,a chromatin regulator of epithelial-mesenchymal transition andbiological aging
Kaoru Kahata1, E-Jean Tan1, Laia Caja2, Kalliopi Tzavlaki2 and Aristidis Moustakas1,2
Ludwig Institute for Cancer Research andDepartment of Medical Biochemistry and Microbiology, Uppsala University,
BioMedical Center, Sweden
1

2

Epithelial-mesenchymal transition (EMT) contributes to tumor cell invasiveness and thegeneration of cancer stem cells. Our laboratory aims at deciphering molecular mechanismsthat link EMT to the generation and maintenance of cancer stem cells. We study the nuclear
protein high mobility group A2 (HMGA2) that is required for the induction of EMT bytransforming growth factor β (TGFβ) (Thuault et al. J. Cell Biol. 174:175-83, 2006). HMGA2
regulates a cohort of transcriptional regulators of the EMT process, such as Snail1 and Twist1(Thuault et al. J. Biol. Chem. 283:33437-46, 2008; Tan et al. J. Biol. Chem. 287:7134-45).
HMGA2 is an embryonic chromatin factor that is gradually and steadily downregulated during
adult life with the exception of tissue stem cells, where its downregulation is induced by the
aging process. Signal transduction by TGFβ and its related polypeptides, bone morphogenetic
proteins (BMPs), coordinates physiological responses in diverse cell types. TGFβ promotes
EMT, tumor cell invasiveness and metastasis, while BMP promotes mesenchymal-epithelialtransition (MET) and suppresses tumorigenicity. The work that we will present focuses on therole of HMGA2 in breast carcinoma cell invasion and stem cell survival. Breast cancer cells
that express high or lower levels of HMGA2 present a corresponding degree of self-renewal
based on mammosphere assays. When HMGA2 is silenced from aggressive breast cancer
cells, the phenotype shifts to an epithelial, indicative of MET, and concomitantly, tumor cells
lose their self-renewing capacity. Transcriptomic analysis identified genes that are regulatedby HMGA2 and which functionally link to the processing of miRNA biogenesis. Finally, by
focusing on non-epithelial cancer stem cells, namely glioblastoma, we demonstrate that theability of BMP to suppress glioma cancer stem cell self-renewal and tumorigenic potential
depends on the transcriptional induction of Snail1, which induces differentiation of glioma
cells and promotes a dramatic invasion of these cells within the recipient brain, while depletingthe tumorigenicity from the same cells. Our work starts explaining in molecular detail how
embryonic nuclear factors like HMGA2 and Snail1, when reactivated in human cancer, provide
coordinated control of multiple genes, thus, promoting both the mesenchymal transition andtumor cell invasiveness, while, depending on the cell type of origin, they either promote or
suppress cancer stem cell self-renewal.

74

Telomerase activation in yeast and cancer cells
Shu-Chun Teng
Department of Microbiology, College of Medicine, National Taiwan University

Telomeres are dynamic DNA-protein complexes that protect the ends of linear chromosomes. Most telomeric DNA is synthesized by the enzyme telomerase. While most somatic
cells do not express telomerase and therefore have limited life span, cancer cells can bypass thecrisis either through telomerase reactivation or through an alternative recombination pathway
for telomere lengthening (ALT). We will discuss our recent findings of telomere replication on
telomerase expression, telomerase activation, and ALT progression.
We demonstrated that telomerase is mainly activated by Cdk1/Tel1/Mec1 on telomericbinding protein Cdc13 from late S to G2 phase of the cell cycle. Hypernegatively charged domain of Cdc13 contributed by Cdk1, Tel1 and Mec1 may provide an optimal interface to recruit
the potential positively charged domain near the amino acid 444 lysine residue of Est1 in thetelomerase complex. PP2A phosphatase and Aurora kinase coordinately inhibit the functionof telomerase. Differential and additive actions of PP2A phosphatase and Aurora kinase on
Cdc13 limit telomerase action by removing active telomerase from telomeres at G2/M phase.
Moreover, previous studies have indicated that yeast Sgs1 and Top3 may work together
to remove highly negative supercoils that are generated from telomere recombination. However, the mechanism by which cells eradicate highly positive supercoils during recombination
remains unclear. We demonstrate that Top2 is involved in telomere-telomere recombination,
perhaps by resolving the highly positive supercoil structure at the front of the helicase. Inhibition of topoisomerase II may be a promising therapeutic approach that can be used to prevent
cell proliferation in ALT-type cancer cells.

75

Steroid hormones and aging: Lesson from the fruit fly
Drosophila melanogaster
Ryusuke Niwa1,2, Chikana Yamamoto3 and Tomotsune Ameku4
Faculty of Life and Environmental Sciences, University of Tsukuba
2
PRESTO, JST3
College of Biological Sciences, University of Tsukuba
4
Graduate School of Life and Environmental Sciences, University of Tsukuba
1

Steroid hormones are small lipophilic chemical compounds that mediate a wide variety
of developmental and physiological events in almost all multicellular organisms. Recent
studies suggest that steroid hormones are also involved in regulating animal aging (Antebi,Exp. Gerontol. 48: 596-602, 2013), whereas detailed mechanism of steroid hormone-dependent
aging control is still unclear. To investigate a role of steroid hormone in animal aging, wehave been using the fruit fly Drosophila melanogaster as a model organism. In insects, theprincipal steroid hormones are ecdysteroids, which are synthesized from dietary cholesterol
via multiple conversion steps. In the last decade, we have identified ecdysteroidogenic
enzymes and developed genetic tools to knock-down these genes in vivo (Niwa and Niwa,
Genes Genet. Syst. 89: 27-34, 2014; Niwa and Niwa, Biosci. Biotechnol. Biochem. in press,
2014). Utilizing these tools, we succeeded in creating tissue-specific loss-of-function animalsof ecdysteroidogenic enzyme genes and examining aging phenotype. In this presentation, we
will present our most recent data and discuss an effect of ecdysteroids on aging.

76

Long live the queen – the molecular and endocrine underpinningsof the reproduction/lifespan paradox in social insects
Klaus Hartfelder
Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo

A tradeoff between reproductive output and lifespan is a basic rule in all major metazoan
clades, especially in the female sex, and the primary underlying mechanisms are the insulin/
insulin-like signaling (IIS) and TOR pathways. Though apparently tight, this tradeoff
relationship is broken in social insects, with their highly reproductive, long-lived queens andsterile, short-lived workers. Two points need to be addressed to understand this dissociation: theendocrine and genomic responses to the environmental stimuli driving caste development, andthe factors underlying the flexibility in caste lifespan. The primary switch between queen andworker development is the feeding regime of the larvae with royal jelly. This affects the larval
endocrine system, with queen larvae producing large amounts of juvenile hormone, a potent
stimulator of queen development. Other signaling systems investigated more recently throughgene expression and functional analyses are the IIS, TOR and Egfr pathways. Interestingly,
the expression patterns of insulin receptor, TOR and Egfr encoding genes all differed fromexpectation, as all were less expressed in queen than in worker larvae. Underlying this apparent
paradox seems to be an endogenous hypoxia response in the worker caste. The primary organ
affected by all these developmental signals is the larval ovary, which, in workers, is subject tomassive autophagic cell death, thus severely restricting the adult reproductive potential. In theadult honeybees, the queen fat body produces large amounts of vitellogenin, which sustains
their enormous egg laying rates. But different form other insects, vitellogenin synthesis isindependent of juvenile hormone. Rather, this hormone has taken on a repressor role forvitellogenin production in the worker caste, and this negative feedback relationship between
vitellogenin and juvenile hormone is thought to be the major lifespan determinant. Suchrewiring of ancestral signaling pathways makes honeybees a model system for eco-evo-devo
studies on aging and reproduction.

77

Nutrient-dependent regulation of steroid hormone biosynthesisin the puberty of fruit fly Drosophila melanogasterYuko Shimada-Niwa1 and Ryusuke Niwa1,2
Faculty of Life and Environmental Sciences, University of Tsukuba
2
PRESTO, JST

1

Steroid hormones play crucial roles in many aspects of development, growth, reproduction
and aging. They have a conserved role in controlling the developmental transition fromjuvenile to adult across animal phyla. For example, human steroid hormones promote thedevelopment of secondary sexual characteristics at puberty, leading to adult sex maturation.
The insect steroid hormone ecdysteroid determines the timing of molting and metamorphosis.
Interestingly, the temporal coordination of steroid hormone biosynthesis during the juvenileto-adult transition is tightly coupled to nutrient conditions in the juvenile stage, which allows
organisms to increase their survival fitness and reproductive success. However, it remains
unclear how nutrient information is reflected to control of the timing of steroid hormone
biosynthesis.
The fruit fly Drosophila melanogaster provides a suitable model for studying the regulatory
system of steroid hormone/ecdysteroid biosynthesis (Niwa and Niwa, Biosci. Biotechnol.
Biochem. in press, 2014). During the larval stages, a form of ecdysteroid, ecdysone is synthesized
in a special endocrine organ called the prothoracic gland (PG). Several ecdysteroidogenic
enzymes mediate the conversion steps from cholesterol to ecdysone in the PG. Therefore, oneof the fundamental questions is how the PG cells sense nutrient condition and then transduce
the signal to ecdysone biosynthetic pathway (Niwa and Niwa, Genes Genet. Syst. 89: 27-34,
2014). To address this question, we focus on a subset of serotonin (5-hydroxytryptamine,
5-HT)-producing neurons that directly innervate the PG. These neurons share their tracts
with enteric nervous system and are responsive to nutrient condition. Our result suggeststhat 3 pairs of serotonergic neurons are responsible for the timing in the transition of growth(the larval stage) to maturation (the pupal stage). Moreover, serotonin signaling in the PG isinvolved in the timing of ecdysteroid biosynthesis. Based on these results, we propose that
serotonergic neuronal control mediates the nutrient-dependent developmental plasticity via
modulating steroid hormone biosynthesis in the juvenile-to-adult transition.

78

Impact of n-3 polyunsaturated fatty acid deficiency on
mesoaccumbens dopaminergic transmission and motivation:
relevance for the negative symptoms of schizophrenia
Pierre Trifilieff 1,2
Nutrition and Integrative Neurobiology, INRA UMR 1286, Bordeaux, France
2
University of Bordeaux, France

1

Brain function is known to depend on genetic as well as environmental factors.
Accumulating evidence suggests that nutrition can be a main environmental factor that
influences both brain development and function and thereby participate to the etiology ofvarious psychiatric disorders. In particular, schizophrenia has been associated with a deficiency
in n-3 polyunsaturated fatty acid (PUFA) in the brain, however, the mechanisms by which n-3
PUFA deficiency could participate to the etiology of schizophrenia are unknown.
In this presentation, I will emphasize how both human and animal studies have shed light on
the implication of mesolimbic dopamine transmission in various symptoms of schizophrenia.
I will then present recent data showing that n-3 PUFA deficiency leads to neurobiological andbehavioral phenotypes that resemble those described in schizophrenia. In particular, our results
indicate that developmental n-3 PUFA deprivation leads to a selective decrease in motivationin adulthood, a main negative symptom of schizophrenia. This behavioral impairment was
accompanied by an increase in both dopamine D2 receptor expression and extracellular
dopamine levels in the nucleus accumbens a main region involved in the modulation of
motivation. Importantly, these effects were not reversed by n-3 PUFA supplementation at
weaning. These data show for the first time that developmental n-3 PUFA deficiency leads toalteration of dopaminergic transmission and motivation deficit in adulthood, and could thereby
constitute a main environmental factor for the development of motivation deficits as well as
certain psychiatric disorders such as schizophrenia.

79

Δ9-THC restores age-related changes in the brain
A. Bilkei-Gorzo1, O. Albayram1, A. Piyanova1, M. Dvir-Ginzberg3, A. Draffehn2,
I.Bab3, J. Schultze2, I. Rácz1, S. Imbeault1, A. Zimmer1
Institute of Molecular Psychiatry, University of Bonn;
Genomics and Immunoregulation, LIMES Institute, University of Bonn;
3
Institute of Dental Sciences, The Hebrew University Jerusalem
12Aging of the brain is accompanied by a progressive decline in cognitive abilities associatedwith reduced synaptic densities. This process is accelerated in mice lacking cannabinoid CB1
receptors. We have therefore wondered if an increase of the cannabinoid tone in older animals
would protect them against the loss of cognitive functions. Two age groups of animals were
therefore treated with 3 mg/kg/day Delta-9THC for 28 days through osmotic minipumps. This
treatment significantly improved spatial learning in the Morris water maze test as well as object
location recognition in the old but not in the young mice. The improved cognitive performance
was associated with increased synaptic densities and enhanced expression of synaptic marker
proteins. We next investigated the gene expression profile of control and THC treated young
and old mice. We found that THC treatment altered the expression of a number of age-related
genes in the old but not in the young mice. The CREB and Erk signaling systems were activatedin THC treated old animals shown by an enhanced phosphorylation. The beneficial effects of
THC on brain ageing was mediated by CB1 receptors, because THC treated CB1 knockout
mice failed to show any improvement in learning ability, increase in synaptic densities orchange in gene expression.

80Effects of acute stress on memory processes
J. Micheau, C. Huguet, P. Faucher, J. David & N. Mons
University of Bordeaux, CNRS UMR 5287, INCIA, Talence, France

Although the effects of acute stress on learning abilities have been investigated sincedecades data from the literature are still very confusing. The concomitant release ofnoradrenaline and corticosterone in response to stressful situation has been demonstrated tomodulate positively or negatively learning and memory processes according to many variables
such as stress intensity, the emotional valence of the learned material or the interval between
stressful episode and learning experience. In this report we have investigated in mice, theimportance of the timing of the application of the stressful event (acute restraint stress (ARS):50mn) on consolidation and encoding processes. In a first series of experiments the impact of
ARS was assessed on the consolidation of contextual fear memory which is supposed to dependon hippocampal function. We showed that when conditioning was performed 5mn or 6h after
completion of ARS long-term retention of contextual fear memory was impaired whereas
short-term memory was spared. We then, analysed the behavioural and molecular (ERK1/2CREB pathway) impact of the modulation of corticosterone status after either systemic or
intra-hippocampal treatments. In a second series of experiments, we have investigated theimportance of the inter-stress training interval (5mn and 6h) on online information processing
by using an episodic-like memory task, namely object recognition. Compared to non-stressed
mice ARS had a facilitating or an impairing influence on object recognition during testing
when completed 6h or 5mn before the task respectively.
Taken together, our results suggest that, in addition to direct corticosterone influence atentative explanation of stress effects on memory processes must consider delayed molecularand cellular mechanisms, including genomic activation. Finally, we integrate our data in afunctional model of how stress might affect memory processes in which amygdalar modulationof hippocampal function via noradrenaline input is also incorporated.

81Midbrain dopamine neurons are divided into anatomical
subgroups encoding distinct signals
Masayuki Matsumoto
Laboratory of Cognitive and Behavioral Neuroscience, Faculty of Medicine, University of Tsukuba

Dopamine neurons in the substantia nigra pars compacta (SNc) and the ventral tegmental
area (VTA) have been shown to encode a reward value signal and to play important roles inreinforcement and motivation. Our recent study reported, however, that not all dopamine
neurons encode the value-related signal uniformly. Using a classical conditioning withappetitive and aversive outcomes (liquid rewards and aversive airpuffs) in monkeys, we foundthat some dopamine neurons were excited by reward-predicting stimuli and inhibited by
airpuff-predicting stimuli, as the value-coding theory predicts. However, a greater numberof dopamine neurons were excited by both of these stimuli, inconsistent with the theory.
These data led a hypothesis that dopamine neurons are divided into multiple populations
encoding distinct signals. Consistent with this idea, the dopamine system has been reported
to be involved in a number of functions, not only in motivational functions but also in somecognitive ones. However, despite abundant studies demonstrating dopamine neuron activity
related to reward, little is known about what signals dopamine neurons convey to promote
cognitive processing. Therefore, we next examined dopamine neuron activity in monkeys
performing a delayed matching-to-sample task that required working memory and visual
search. We found that dopamine neurons responded to task events associated with cognitive
operations. A subset of dopamine neurons were excited by visual stimuli if the monkey had
to store the stimuli in working memory. These neurons were located dorsolaterally in theSNc, whereas ventromedially located dopamine neurons, some in the VTA, represented areward value signal. Furthermore, dopamine neurons monitored visual search performance,
becoming active when the monkey made an internal judgment that the search was successfullycompleted. Our findings suggest that dopamine neurons are divided into anatomical groups
suitable for distinct functions.

82

Imaging of iatrogenic dysimmunity
Vincent Dousset1,2 and Thomas Tourdias1,2
Laboratory Physiopathology of Neuronal Plasticity U INSERM 862 University of Bordeaux2
Departement of NeuroImaging University Hospital of Bordeaux1With the increasing use of monoclonal antibodies to treat patients with several central
nervous system (CNS) diseases, adverse events related to medication-induced immunity aredeveloping.
In Multiple Sclerosis, a frequent disease that destroys the myelin and neurons of young
adults, the use of Tysabri® (Natalizumab), a monoclonal antibody directed against VLA4
lymphocytes receptors has shown to be very efficient. However, due to restriction oflymphocytes trafficking through the CNS, the immune defense against infectious diseases isdecreased. An ubiquitous virus, JC virus, might developed in about 1 to 3% of treated patients.
JC virus has a strong pathogenicity to the oligodendrocyte a CNS that provides myelin sheathmaking a superimposed disease called progressive multifocal leukoencephalopathy (PML).
Early recognition of Natalizumab-induced PML by magnetic resonance imaging (MRI) is a
key factor to reduce the risk for spreading PML that might lead to patient death, occurring so
far to ¼ of affected patients. In addition, MS patients were also shown to develop a strong
brain immune reactivity called immune restoration inflammatory syndrome (IRIS) after stopping monoclonal antibodies treatment.
In Alzheimer disease (AD), use of monoclonal antibodies to remove amyloid protein or tau
proteins from the brain, is still under promising investigations. However, during the treatment
auto-immune reactivity of the CNS has been described in patients, leading to brain parenchyma
or meninges edema or hemorrhages. MRI plays an important role to an early recognition ofsuch adverse effects that might be clinically silent at the early stage. Later, strong hemorrhage
or cortical abnormalities might lead to patient clinical worsening.

83

Activation of microglia impacts their directional motility
Elena Avignone1,2
Univ. Bordeaux, Institut Interdisciplinaire de Neurosciences, UMR 5297, F-33000 Bordeaux, France
2
CNRS, Institut Interdisciplinaire de Neurosciences, UMR 5297, F-33000 Bordeaux, France

1

Microglia cells are the resident macrophages of the central nervous system and are considered its first line of defense. They are highly motile cells. During physiological conditions
they constantly move their tiny processes in an apparently random way (basal motility) to scan
the parenchyma, and in few minutes they can extend their processes towards a site of injury or
substances that represent a dangerous signal (directional motility).
In pathological conditions, microglia become activated. Activation is a multifaceted process, which may last several days and can become chronic. It depends on the stimulatory
context, and it plays a critical role in all neuropathologies associated with an inflammatory
reaction, including epilepsy.
How activation affects microglial ability to scan the brain or to respond to noxious stimuli
is still an open question.
In a previous work (Avignone et al. J. Neurosci. 2008), we show that in the model of kainate
induced status epilepticus (SE) microglial processes moved faster towards a pipette containing
an ATP analogue (2MeADP), suggesting that activation may affect directional motility. In
this work we investigated the effect SE induced activation on basal motility and two types of
directional motility: in response to acute laser lesions and to local application of 2MeADP. To
characterize the morphological dynamics of microglia we used time-lapse two-photon imaging in acute hippocampal slices from transgenically labeled mice (CX3XR1+/EGFP).
The effect of activation was strikingly different on different types of motility. It increased
the scanned territory of single processes during basal motility while, despite it increases thevelocity towards a 2MeADP containing pipette, it did not affect the directional motility towards an acute laser induced lesion.
In summary activation induced by a status epilepticus did not hamper the sentinel roleof microglia, and the heterogeneity of the effect of activation on different types of motility
strongly suggests that motility should be considered as stimulus dependent.

84

Post-translatinal modification by small ubiquitin-modifier
SUMO in the cell biology of Giardia lamblia
Renata R. Tonelli
Departamento de Ciências Biológicas, Universidade Federal de São Paulo, Diadema, Brazil

Posttranslational modifications of proteins play critical roles in the control of cellulardifferentiation, development, and environmental adaptation. In particular, the covalentattachment of the Small Ubiquitin-like Modifier (SUMO) to target proteins (sumoylation)
regulates cell cycle progression, transcription, nucleocytoplasmic transport, and stressresponses. The SUMO conjugation pathway is biochemically similar to ubiquitin conjugation,although the enzymes within the pathway act exclusively on SUMO proteins. Sumoylation,and enzymes of the sumoylation pathway, are conserved in the binucleated, flagellatedparasite, Giardia lamblia. In this work the biological role of SUMO in Giardia is examined.
G. lamblia (also called Giardia intestinalis) is one of the most common intestinal parasitesof humans and has a worldwide distribution. Giardia possesses a unique SUMO orthologue(Gl-SUMO) that shares 47% sequence identity with mammalian SUMO-1 and 17% sequence
identity with ubiquitin. Indirect fluorescence analysis using a monoclonal antibody against
SUMO showed an extra-nuclear localization reacting with the median body, ventral disc,flagella tips and cytoplasm in trophozoites. In cysts, the anti-SUMO antibody reacted with
the internalized flagella and some structures not identified, as yet. Treatment of trophozoites
with ginkgolic acid (an inhibitor of the SUMOylation pathway) resulted in reduced amountof SUMO conjugates in a dose-dependent manner. Furthermore, treated parasites displayeda round-shaped morphology in contrast to control cells, which retained their characteristic
pear-shaped structure. Finally, double confocal immunofluorescence with anti-SUMO andantibodies against modified tubulins confirmed that acetylated tubulins at the median body are
SUMOylated. Further studies are warranted to investigate how SUMOylation of cytoskeleton
proteins affects biological events in Giardia lamblia. (FAPESP #2010/15042-2).

85Interaction of small viral capsids with the nuclear pore - they are
no classical cargo
Michael Kann, Manvi Porwal, Kenza Snoussi, Ruth Popa-Wagner, Harald Wodrich,
Christiane Dinsart, Jürgen A. Kleinschmidt, Nelly Panté, André Schmitz
Microbiologie fondamentale et Pathogénicité, CNRS - Université Bordeaux, France;
Institute for Medical Virology, Giessen University, Germany; ATV, DKFZ Heidelberg,
Germany; Institute of Zoology, UBC,Vancouver, Canada

Macromolecules enter the nucleus by active transport through the nuclear pore complex(NPC). Translocation is mediated by nuclear transport receptors interacting on one hand withthe cargo and on the other hand with the proteins of the NPC, which are collectively called
nucleoporins (Nups). Within the nuclear basket, which is a cage-like structure formed by eight
filaments on the nuclear side of the NPC, the import complex is dissociated leading to releaseof the cargo and its diffusion deeper into the karyoplasm. DNA viruses have high jacked thistransport mechanism in order to translocate their genome to the site of genome multiplication. Practically all viruses (or viral capsids) have however diameters exceeding the maximaltransport diameter of the NPC, which is 39 nm, and they release their genome complexed bykaryophilic viral proteins prior to genome translocation into the karyoplasm. Hepatitis B virus(HBV) and parvoviruses (PV) are DNA viruses with capsids below the maximal NPC transport limit. Theoretically they thus allow that their genomes enter the karyoplasm in an intact
capsid as a karyophilic cargo followed by nuclear genome release. Analyzing the interactionsof both viral capsids with the nucleus we observed however entirely different strategies: HBV
capsids pass the nuclear pore and enter the nuclear basket intact where they interact specifically with one protein in the basket. This interaction causes arrest of the capsid in the basket,
which is followed by capsid dissociation and genome release. PV also interact with Nups but
instead of being arrested they activate enzymes involved in mitosis. This activation causes
local, transient nuclear envelope break-down allowing that larger structures as a viral capsid
pass.

86

Novel ‘in situ’ preparation of zinc finger nucleases based on
Ni(II)-induced specific hydrolysis of proteins
Brigitta Csipak1, Agnieszka Belczyk 2, Masamitsu Asaka3, Kyosuke Nagata3,
Wojciech Bal2, Béla Gyurcsik1
Department of Inorganic and Analytical Chemistry, MTA-SzTE Bioinorganic Chemistry ResearchGroup, University of Szeged, Hungary
2Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Poland
3
Nagata Special Laboratory, Faculty of Medicine, University of Tsukuba, Japan

1

Zinc-finger proteins recognize specific DNA sequences. With such modular proteins a
selected DNA sequence can be targeted by the proper design of the sequential finger units. In
addition, fusion of zinc-finger domains to proteins with enzymatic function can be applied for
manipulating DNA. Chimeric nucleases constructed from zinc-fingers and the nuclease domain of FokI restriction endonuclease are useful tools of targeted cleavage of genomic DNA.
Such agents can be applied in therapy of monogenetic diseases in the future (B. Gyurcsik andA. Czene, Future Med. Chem., 2011, 3, 1935–1966).
Recently, it has been recognized that nickel(II)ions promote site specific hydrolysis of peptides or proteins at the X-(S/T)-Y-H-Z sequence, where the variable X,Y and Z amino acids influence the reaction rate and efficiency (E. Kurowska, et al., Metallomics, 2011, 3, 1227–1231).
The metal complex formed upon the cleavage of the protein is able to cleave DNA. Thus, an induced specific damage to DNA can be performed by applying a specific DNA binding protein.
Based on the above considerations our research is focused on the design of novel artificial
nucleases that are created ‘in situ’ by the site-specific hydrolysis of specific DNA binding proteins, such as, e.g. zinc-fingers. These proteins can be activated by the addition of nickel(II)ions, and as such, their action can be controlled by the concentration of this metal ion. We
demonstrated the site-specific hydrolytic cleavage of a zinc-finger protein containing three
metal ion binding site, by gel electrophoresis and by mass spectrometric identification of the
HPLC separated cleavage products. In parallel, we have also applied a redesigned zinc-finger
protein with only one cleavage site. An intriguing question to be answered is, whether thesame reaction occurs in the presence of DNA and whether the DNA can be specifically cleavedby the newly formed protein complexes?

87Real time analyses of the DNA damage response in mammaliancells
Xiangduo Kong1, Elizabeth Hinde2, Barbara Alcaraz Silva3, Michelle Digman2,
Enrico Gratton2, Michael Berns3, and Kyoko Yokomori1
Department of Biological Chemistry, School of Medicine, University of California, Irvine, USA,
Laboratory for Fluorescence Dynamics, Department of Biomedical Engineering, University ofCalifornia, Irvine, USA;
3
Beckman Laser Institute and Medical Clinic, University of California, Irvine, USA

1

2

Genome integrity is continually threatened by endogenous metabolic products generated
during normal cellular respiration, by errors that arise during DNA replication and recombination,and by exogenous exposure to DNA damaging agents. The resulting DNA lesions, if not
faithfully repaired, can accumulate as mutations ranging from single nucleotide changes tochromosomal rearrangements and loss that can lead to cancer, developmental abnormalities,
and cell death. Accumulation of DNA damage is also a hallmark of cellular senescence andaging. Different insults to DNA are recognized by lesion-specific repair factors, which invoke
distinct repair pathways including base excision repair (BER) and double-strand break (DSB)
repair. The factors most critical for DNA repair, as well as the major players in the DNA
damage response (DDR), have been largely identified through genetics-based studies using
model organisms or through investigation of human diseases. However, how their activities
are coordinated in the cell nucleus is still not well understood, and we still do not have acomplete picture of the cellular signaling and chromatin responses following DNA damage.
We investigate the DDR in real time in living cells following site-specific DNA damage using
fluorescent imaging techniques including fluorescence lifetime imaging microscopy and paircorrelation function (pCF) analyses. Our recent findings on damage signaling in the cell will
be discussed.

88Identification of disease-casing variants using next generation
sequencing
Emiko Noguchi1,2, Kazumasa Kanemaru3, Satoko Tahara-Hanaoka2,3, Akira Shibuya2,3Department of Medical Genetics, Faculty of Medicine, University of Tsukuba
Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency
3
Department of Immunology, Faculty of Medicine, University of Tsukuba
1

2

Recent advances in next-generation sequencing (NGS) technologies allow the rapid
identification of disease-causing mutations. We applied the NGS technologies to identify
disease causing mutation in mice. Nc/Nga mouse is a inbred stain established from Japanesefancy mice by Kondo (Nagoya University, Nagoya, Japan) in 1957. NC/Nga mice spontaneously
develop an eczematous atopic dermatitis-like skin lesion when kept under conventional
condition. Mode of inheritance in Nc/Nga mouse was considered to be autosomal recessive.
We performed exome sequence using DNA obtained from Nc/Nga mice on SOLiD5500xl
sequencer (Life Technologies). We selected variants that satisfied all of the following (1)homozygous mutations, (2) not observed in other strains, (3) nonsense or frameshift mutations,
resulting in 10 nonsense mutations and 41 frameshift mutations. Among them, 6 for nonsenseand 23 for frameshift mutations were verified by Sanger sequence. Functional analysis of thecandidate mutation identified in Nc/Nga mouse by exome sequence and application of NGS
will be discussed.

89

Biocompatible antiradicals inspired by fluorescent flowers
Karina Kinuyo Nakashima, Nathana Barbosa Lopes, Letícia Christina Pires Gonçalves andErick Leite Bastos
Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo

Betalains are water-soluble, chiral and nontoxic natural pigments, which have gained
attention due to their high antioxidant capacity (Kanner J et al., J. Agric. Food Chem. 49:
5178-5185, 2001), applicability (Gonçalves LCP et al., Plos One 8: e53874, 2013; Gonçalves
LCP et al., Plos One 8: e73701, 2013) and occurrence in fluorescent flowers (Gandia-Herrero
F et al., Nature 437: 334-334, 2005). All betalains are biosynthesized from betalamic acid, an
α,β-unsaturated aldehyde with high antiradical capacity (Gonçalves LCP et al. J. Food. Eng.
118: 49-55, 2013). The main pigment in the red beet, betanin (Bn, betanidin 5-O-β-glucoside),
belongs to the class of betalains and has been used as a food colorant (E162, FDA) as well asa therapeutic agent. Very low concentrations of dietary betanin have been shown to inhibitskin and liver tumor formation in mice (Kapadia GJ et al., Pharmacol Res 47: 141-148, 2003)
and to protect mice from the effects of γ-radiation (Lu, X et al., Eur. J. Pharmacol. 615: 223227, 2009). The high antiradical capacity of Bn has been demonstrated in both in vitro andin vivo tests and, although the presence of the cyclo-DOPA moiety may be fundamental forthe high scavenging activity of Bn, the 1,7-diazaheptamethinic system has been assumed toplay a major role in the antioxidant response (Butera D et al., J. Agric. Food Chem. 50: 68956901, 2002). Our research group at the University of Sao Paulo (USP), Brazil, investigatesnatural fluorescent pigments to establish structure-property relationships and to create newfunctional chemicals. In this study, we investigate the mechanism of antioxidant action ofbetalains. Model phenolic betalains were semisynthesized using betalamic acid as starting
material (which was obtained from renewable sources, such as the beetroot, the pitaya fruit,and flowers from plants of most families of the Caryophyllales order) and their antiradical
capacity was studied by means of kinetic measurements, determination of isotope effects and
DFT calculation of relevant physico-chemical parameters.

90

The Anthocyanins: plant pigments with multiple functions innatureFrank H. Quina
Instituto de Química, Universidade de São Paulo, Brazil and
NAP-PhotoTech-The USP Research Consortium for Photochemical Technology

The anthocyanins are natural, water-soluble plant pigments responsible for the majority of
the red, blue and purple colors of flowers, fruits and leaves. In flowers, the colors imparted byanthocyanins serve primarily to attract pollinators. In fruits, anthocyanins attract herbivores
responsible for seed dispersal and provide the fruit with antioxidant protection. In red andpurple plant leaves, the primary function appears to be protection of the photosynthetic
apparatus from excess solar radiation. The basic chromophore responsible for the color ofanthocyanins is a 7-hydroxyflavylium cation, the color of which is determined by the typeand number of other substituents that are attached to the chromophore, by the local pH andby complexation with metal cations or with colorless co-pigment molecules. At pH > 3, water
adds to the colored cation form of anthocyanins to give a colorless hemiacetal, which can ringopen to give a cis-hydroxychalcone and subsequently isomerize to the trans-hydroxychalcone,
both of which are colorless or pale yellow, resulting in essentially complete color loss at neutral
pH. Our group is interested in understanding and predicting this rich, pH-dependent chemistryof anthocyanins and its implications for the photoprotective role and the anti-oxidant activityof anthocyanins. In addition, a deeper understanding of the mechanisms utilized by plants
to maintain the color of anthocyanins at pH > 3 in vivo should aid in the development of new
strategies for stabilizing the color of anthocyanins in vitro so that these natural plant pigments
can be successfully employed in a wider range of practical applications.

91Genome-wide remodeling of long-range interactions duringskeletal muscle differentiation
Ricardo Ramirez1,2,*, Katherine Fisher3,*, Huay Mei Poh4,Santiago V Lombeyda5,
Anthony G. Kirilusha3, Kenneth McCue3, Ana Conesa6, Yijun Ruan4, Barbara Wold3+,
Ali Mortazavi1,2+
Department of Developmental and Cell Biology, University of California, Irvine, CA, USA,
2
Center for Complex Biological Systems, University of California, Irvine, CA, USA,
3
Division of Biology, California Institute of Technology, Pasadena, California, USA
4
The Jackson Laboratory for Genomic Medicine, and Department of Genetic andDevelopment Biology, University of Connecticut, USA
5
Center for Advanced Computing Research, California Institute of Technology, Pasadena,
California, USA
6
Genomics of Gene Expression Lab, Centro de Investigaciones Principe Felipe, Valencia, Spain*
Authors contributed equally to this work+
Corresponding authors
1

Eukaryotic developmental programs require the orchestration of both transcriptional
regulatory mechanisms and chromatin architecture with acute spatial-temporal precision.
We investigated the interactome of CRMs during mouse skeletal muscle cell (C2C12)
differentiation by integratively analyzing DNase-seq with chromatin long-range interactions
using RNA Polymerase II ChIA-PET. We identified a total 215,977 candidate CRMs genomewide, of which ~50% were quantified to be differentially hypersensitive during differentiaton.
DNaseI Footprinting analysis allowed us to identify transcription factor footprints and denovo motif enrichments of key Myogenic Regulatory Factors (MRF). We integrated CRM
and DNaseI Footprinting information with ChIA-PET to generating high-resolution (1kb) andmedium-resolution (3kb) Chromatin Interaction Graphs (CIG) during cellular commitment.
We characterized a large number of interactions specific to each cell-type, with 6,567 foundin undifferentiated C2C12, 16,426 specific to differentiated C2C12, and 9,881 interactions
common to both. We quantified changes in DNaseI and gene expression activity acrosspromoters genomewide and identified distinct classes of promoters with strongly correlated
activity of DNaseI and gene expression, while explaining that uncorrelated behavior for aclass of promoters is consistent with changes in long-range chromatin control. Our results
demonstrate the power of integrating long-range interactions to understand the changes ingene expression during skeletal muscle differentiation.

92

Metabolomics and in silico tools in the search of naturalcompounds from plants with anti − inflammatory potential
Daniela A. Chagas-Paula1, Tiago B. Oliveira1, Tong Zhang2, RuAngeli Edrada − Ebel2 andFernando B. Da Costa1
University of São Paulo, School of Pharmaceutical Sciences of Ribeirão Preto, Ribeirão Preto,
SP, Brazil
2
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow,
Scotland1

The non − steroidal anti − inflammatory drugs are among the most common group of
drugs used in the world. However, side effects still occur and some inflammatory pathologies
lack efficient treatment. Cyclooxygenase (COX) and lipoxygenase (LOX) pathways are ofgreat importance in inflammatory processes and therefore inhibitors for both of them areneeded. Dual inhibitors on COX − 1 and 5 − LOX should be anti − inflammatory medicineswith high efficacy and low side effects and therefore would be useful to treat acute as wellchronic inflammatory processes, such as rheumatoid arthritis and asthma. Because the anti −inflammatory potential of Asteraceae plant species is well known world wide, several extracts
were screened in vitro against the enzymes COX − 1 and 5 − LOX and analyzed using a non −targeted LC − MS − based metabolomics approach.
Ethanol − water extracts were prepared using 2 mg of dried and powdered leaves. Amongthe 57 screened extracts, 13 of them displayed dual inhibition on COX − 1 and 5 − LOX. The
extracts were further analyzed by LC − MS and their data were processed. The Dictionary of
Natural Products and an in − house database were used for extract dereplication. The resulting
6,052 peaks of all extracts were combined with their biological activity data and selectedby genetic algorithm affording 1,261 peaks. A model using decision trees was built and 11
compounds were determined as the biomarkers for the dual inhibition on COX − 1 and 5 −LOX. Finally, using the LC − MS data of the biomarkers and the anti − inflammatory results of
selected extracts, a model to predict new anti − inflammatory extracts with no prior biologicalactivity information was built using artificial neural networks.
In summary, a new and robust approach for prediction of the activity of natural compounds
against COX − 1 and 5 − LOX was developed. Moreover, this approach can be useful to predict
the bioactivity of non − investigated extracts taking into account only their LC − MS data.
Acknowledgements: CNPq, CAPES and FAPESP.

93

Design principles of biological growth control
Arthur D. Lander, M.D, Ph.D.
Center for Complex Biological Systems, and Departments of Developmental & Cell Biology andBiomedical Engineering, University of California, Irvine, CA, USA

Our bodies arise through a process of controlled growth that can exhibit remarkable speed
and precision. That this can happen is quite amazing, given that the units of growth—cells andparts of cells—are self-reproducing, which means they increase by a process of exponential
expansion. Exponential processes are naturally unstable (bombs and nuclear reactors are good
examples) and tend to be very sensitive to external perturbations (because errors compound),making them among the most difficult processes to control. What general principles does
nature use to tackle this problem? Engineers typically exploit feedback to achieve control, andmany lines of evidence point to a critical role for molecular feedback in regulating biological
growth. But although some specific molecules and mechanisms have been implicated, we still
have a very limited understanding of what information is being fed back, and for what purpose.
Often our understanding of what is not being fed back is greater: for example, there are manyorgans or tissues whose final sizes are known to be specified in a manner independent of bodysize, independent of cellular growth rate, independent of elapsed time, and independent of cellsize. In my talk, I will discuss some insights into growth control strategies that have emerged
from modeling and experiments focused on the regulated progression of cells through lineage
stages. I will also discuss how the design principles behind these strategies may be generalized
to other types of biological growth systems, and may even relate to problems of controlled
growth in non-biological (e.g. social, economic) arenas.

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96

The Second Research University Symposium– Leading-edge Researches and System/
Research-ethics to Support Trusted Ones –In conjunction with The Fourth Tsukuba
URA Forum(The program for promoting enhancement of research universities,
Ministry of Education,Culture,Sports,Science and Technology)
Reserch Administration Office
University of Tsukuba

97

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Sep 28 (Sun)Hall

The Second Research University Symposium - Leading-edge Researches and System/Research-ethics to Support Trusted Ones in conjunction with The Fourth Tsukuba URA Forum
13:30-13:40

Yasuo Miake

University of Tsukuba

IntroductoryPart I: Introduction of Leading-edge Researches in University of Tsukuba
13:40-14:20

Masashi Yanagisawa

University of Tsukuba

Solving the mystery of sleep

14:20-15:00

Hiroyuki Kusaka

University of Tsukuba

Computational sciences empowering heat island research

15:00-15:15
BreakPart II: How to support "Trusted Researches"?
15:15-15:45

Tokie Tani

Design Division, Japan Patent Protection of intellectual property right - Focusing on design
Officeexamination system -15:45-16:15

Kaori Yamaguchi

University of Tsukuba

Coaching with integrity

16:15-16:45

Koji Okabayashi

University of Tsukuba

Research management and academic integrity

16:45-17:15

Shinya Uji

National Institute for Materials
How can research be trusted?
Science

17:15-17:45

Hajime Nagahara

ASAHI KASEI CORPORATION

An example; R&D management in industry

17:45

Tadashi Baba

University of Tsukuba

Closing* The oﬃcial language of the Symposium will be Japanese.
* The abstracts are distributed in the separate booklet at the conference room.

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100

Spiritual and Physical Exercises
in Eastern and Western Philosophies
Faculty of Humanities and Social Sciences,
University of Tsukuba
Doctoral Program in Philosophy,
Graduate School of Humanities and Social Sciences,
University of Tsukuba

101

102

Sep 28 (Sun)Meeting Room 3
Spiritual and Physical Exercises in Eastern and Western Philosophies

Chair

Yoshinori Tsuzaki

University of Tsukuba

13:30-13:40

Yoshinori Tsuzaki

University of Tsukuba

Prospectus for the Session Spiritual and Physical Exercises in Easternand Western Philosophies

13:40-14:10

Leonard Willem Johannes
van der Kuijp

Harvard University

The Spiritual Teacher in Tibet: 'Gos Lo tsā ba Gzhon nu dpal's (13921481) Assessment of His Master Vanaratna (1384-1468)

14:10-14:40

Yoshitsugu Igawa

University of Tsukuba

Chinese Theory of Mind's Transformation and Gottlieb Spizel's De reliteraria Sinensium commentarius

14:40-15:10

Martin Delhey

University of Hamburg

On the Place of Knowledge in Ancient Indian Buddhist Spiritual Practice

15:10-15:30
Chair

Break
Chizuko Yoshimizu

University of Tsukuba

15:30-16:00

Michael Zimmermann

University of Hamburg

Practicing Ethics and Purifying the Mind: the 'Four Immeasurables' - an
Early Buddhist Spiritual Exercise

16:00-16:30

Yoko Ito

University of Tsukuba

Thomas Aquinas and Dionysius the Areopagite - The Relationshipbetween the Creator and the Creature -16:30-17:00

Akio Kikai

University of Tsukuba

Diaries, Religious Experience, and Philosophical Change of Ludwig
Wittgenstein

17:00-17:10

Break

17:10-17:20

Naoki Kuwabara

University of Tsukuba

General Remark

17:20-17:50

Closing Discussion

103

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Prospectus for the Session Spiritual and Physical Exercises in
Eastern and Western Philosophies
Yoshinori Tsuzaki
Doctoral Program in Philosophy, Faculty of Humanities and Social Sciences, University of Tsukuba

In his highly praised book Philosophy as a Way of Life, Pierre Hadot, one of the most eminent
French historians of Western philosophy in the last five decades, deftly articulates the distinction
between the social function of ancient and modern philosophy in Europe. “Ancient philosophy
proposed to mankind an art of living. By contrast, modern philosophy appears above all as theconstruction of a technical jargon reserved for specialists.”1 According to him, the ultimate purposeof this “art of living” is “to transform the whole of the individual’s life.”2 Such transformation isaccomplished in everyday life by undertaking so-called spiritual exercises. As Habot notes in adifferent book:
By this term [spiritual exercises], I mean practices which could be physical, as in dietary
regimes, or discursive, as in dialogue and meditation, or intuitive, as in contemplation, butwhich were all intended to effect a modification and a transformation in the subject whopractices them.3
Whether we accept the adequacy of Hadot’s account of the history of philosophy or not4, inconsidering these exercises we may be encouraged to not only reconsider what Western philosophy
should be today, but also to further understand Eastern thoughts in which the Western way ofseparating philosophy from religion seems less easy to accomplish. From there, we are able tocriticize the distinction between religion and philosophy, since religion should be practicallyinseparable from these exercises. In other words, it is still important for today’s humanity studies,to analyze, from the diachronic and synchronic points of view using the comparative method, howpractices and discourses have developed in different types of philosophies and religions, focusing
on acts unique to mankind: spiritual and physical exercises.
Our session aims, firstly, to use philological analysis of primary sources to understand how
practices and discourses on these exercises can be characterized in each of the three cultural
spheres: India, China, and Europe. Secondly, we try to describe, by using the comparative method,
the differences and similarities between these spheres. In the process of this analysis are we able toidentify any commonalities in exercises developed, seemingly independently, in the Western andEastern spheres of influence without ignoring the specifics of each philosophy and religion? This
question will be discussed by Japanese specialists, including young researchers of Confucianism,
Christianity, and Western modern philosophy from the University of Tsukuba as well as foreignscholars of Buddhism from the University of Hamburg and Harvard University.
Pierre Hadot, Philosophy as a Way of Life, trans. by Michael Chase, Oxford: Blackwell, 1995, p. 272.
Ibid., p. 265.
3
Pierre Hadot, What is Ancient Philosophy?, trans. by Michael Chase, Cambridge, MA: Harvard UP, 2002, p. 6.
4
See one of the latest collections of critical essays on this question: Michael Chase, at al. eds., Philosophy as a Way
of Life: Ancients and Moderns: Essays in Honor of Pierre Hadot, Oxford: Wiley-Blackwell, 2013.
1
2

104

The Spiritual Teacher in Tibet: ‘Gos Lo tsā ba Gzhon nu dpal’s(1392-1481) Assessment of His Master Vanaratna (1384-1468)
Leonard W. J. van der Kuijp
Department of South Asian Studies, Harvard University

The notion of spirituality is complex and highly nuanced, being very much related to ideas
we entertain about the nature and the varieties of religious experience. Crucial in its conceptualization from a Buddhist perspective is the notion of the spiritual teacher (guru, Tib. bla ma)
and his or her [or even its role – the world (loka, Tib. ‘ jig rten) as a teacher] who functions as a
guide during one’s “spiritual cultivation” (bhavana). Towards the end of the first millenniumof the common era, an individual variously called Rta dbyangs [*Aśvaghoṣa] or Bha vi lha[*Bhavideva] wrote a little text in fifty quatrains titled the Gurupañcāsika. The complete textof this work is available in two Tibetan translations and in one Chinese translation – he is there
called Maming馬鳴 [*Aśvaghoṣa] –, and only a fragment is extant in Sanskrit. In this talk, I
will first briefly discuss this work as well as the identity of its rather mysterious author on thebasis of two rare manuscripts that deal with him. Much of the contents of this work is based on
those chapters titled “Inquiring into the Characteristics of the Spiritual Teacher” that we findin many esoteric, tantric Buddhist texts. Numerous Tibetan commentaries also exist on thiswork, but only one Indian one, namely, the one that was probably written by the great scholar
Vanaratna (1384-1468). This work was translated by his disciple ʻGos Lo tsā ba Gzhon nu dpal
(1392-1481). ʻGos Lo tsā ba was also the author of this master’s biography. He makes a pause
about two-thirds into this biography to reply to a question raised by an unknown individual tothe effect why he would write a biography of this master, given that he had so many other greatteachers. My talk will close with an analysis of his answer, since it sheds interesting light on
the ideas of spirituality and the spiritual teacher.

105

Chinese Theory of Mind’s Transformation and Gottlieb Spizel’s
De re literaria Sinensium commentarius
Yoshitsugu Igawa
Doctoral Program in Philosophy, Faculty of Humanities and Social Sciences, University of Tsukuba

The Jesuit missionaries who visited China in the 16-18th century translated the Confucianclassic four books (「四書」). The Protestant pastor Spizel in the 17th century, acquired theirinformation, wrote research document about Chinese philosophy De re literaria Sinensium
commentarius. This book introduced information of the philosophy and the religion in China,
Chinese characters and hexagrams (易卦) in Book of Changes (『易経』) as a universal sign incidentally young Leibniz read through this book when he wrote De Arte combinatoria. The
fundamental view of the world and idea of Confucianism appear in the Great Learning (『大学』) of the four books. The book asserts the change of the heart by inductive grasp of universal natural laws, and perfection of the others and the world. With reference to this, Spizel
presented the originality of Chinese philosophy as contrasted with the view of the European
philosophy. Furthermore, Spizel explained about the reason for being of all things (Ratio), theworld development by the combination of the binary multiplication (binarium multiplicatis) of
hexagrams, monad concerned with a numeration in the Chinese philosophy. In this regard,
empirical research based on the Eastern and Western literatures is expected. In this presentation is announced its preliminary research result.

106

On the Place of Knowledge in Ancient Indian Buddhist
Spiritual PracticeMartin Delhey
Centre for the Study of Manuscript Cultures, University of Hamburg

Specialists in Indian Buddhism still disagree widely on the question of which teachings
found in the oldest sources can or cannot be regarded as authentic words of the historicalfounder of Buddhism and on the problem how to interpret them. However, one general statement made by the Austrian Indologist Erich Frauwallner in his Philosophy of Buddhism (Delhi
2010, p. 12) certainly meets with relatively small resistance in the academic community:
Above all else, he [i.e. the Buddha, M.D.] is imbued with a passionate urge to find liberationfrom the suffering of existence. The philosophical teaching activities of his time, on
the other hand, repelled him. […] As far as possible, he rejects theoretical discussions,providing only the reasons for entanglement in the suffering of existence and the possibilityof liberation in a few formulaic sentences.
It is, indeed, hardly imaginable that the historical Buddha Siddhārtha Gautama would
have found anything valuable in modern philosophy as characterized by Pierre Hadot (seehis Philosophy as a Way of Life or What is Ancient Philosophy?). Instead, one can easily findmany spiritual exercises and practical instructions for living the life of a Buddhist ascetic in his
teachings that served the goal to attain final liberation from mundane existence.
The lecture will, however, not exclusively restrict itself to the earliest times. There canbe no doubt that Buddhism later in its history contributed enormously to the development ofIndian and Asian philosophy. In the present context, it is especially interesting to note that in
the centuries surrounding the beginning of the common era, highly sophisticated edifices of
Buddhist scholasticism developed. Therefore, in the second part of the lecture I would like toexamine to what extent these developments were still in line with the pronouncedly practicaland pragmatic approach taken by Siddhārtha Gautama. Moreover, I will try to answer on thebasis of select sources the question what place knowledge and theory occupied in some varieties of Buddhist systematized soteriology and religious practice.

107

Practicing Ethics and Purifying the Mind:the ‘Four Immeasurables’ ― an Early Buddhist Spiritual Exercise
Michael Zimmermann
Numata Center for Buddhist Studies, University of Hamburg

The paper will deal with a spiritual exercise from the earliest times of Buddhism in India,
called the ‘Four Immeasurables’ (Sanskrit: apramāṇa, brahmavihāra). In this exercise themeditator cultivates and radiates out the four mental/emotional states of loving-kindness,compassion, empathetic joy and equanimity/indifference in all directions. Each of these fourstates will be analyzed and an interpretation of the likely historical development of the exercise
will be attempted. It will become clear that this early exercise combines several salient pointsof the early Buddhist tradition such as the purification and protection of one’s own mind
directed towards a state of eradicating all of its limiting factors, while at the same time having
a discernible ethical dimension. The Four Immeasurables as a ‘spiritual technology’ have, indifferent forms, been employed and innovatively integrated in modern Buddhist meditative
practices and therapeutic applications. As a widely followed exercise across the Buddhist
traditions, it portrays an alternative way in which the central Buddhist philosophy of ‘NotSelf’ is manifested in a major meditative technique: here the concept of a Self is not eradicatedby plain intellectual analysis and insight, but rather through the infinite extension of one’s selfcentered emotions leading to the dispersal and ensuing evaporation of the concept of a Self.

108

Thomas Aquinas and Dionysius the Areopagite- The Relationship between the Creator and the Creature Yoko Ito
Doctoral Program in Philosophy, Graduate School of Humanities and Social Sciences,
University of Tsukuba

French Dominican theologian Gilles Emery O.P. argues that the theology of St. Thomas
Aquinas (ca. 1225–1274) is regarded as a spiritual exercise in which the practitioner of theology is a pilgrim seeking wisdom and, ultimately, a union with triune God1. Thomas, who is
one of the greatest representatives of Scholasticism, had been recognized only as the “Aristotelian” figure. However we also have to remember the name of “Dionysius the Areopagite”.
Dionysius, the early sixth-century “Christian” writer who used the name of Paul’s first convert
in Athens, eventually effected a marriage between Christianity and Neoplatonism. We canfind out one of the most important examples of this marriage in the thought of Thomas. Father Andrew Louth, a priest of the Russian Orthodox Church says: “St. Thomas Aquinas read
Denys with great care and attention: and whole areas of his theology – the doctrine of divine
attributes, angelology, to name but two – are deeply in debt to him”2. My talk aims to clarify
the understanding of Thomas about the relationship between the Creator and the Creature in
the Summa Theologiae. In order to account for this dimension I will analyze in particularquestions 3-13 in S.T. with the support of Thomas’s commentary on Dionysius’ Divine Names.

 is short presentation of this argument is found in the essay: Gilles Emery, “Trinitarian Theology
H
as Spiritual Exercise in Augustine and Aquinas,” in Aquinas the Augustinian, edited by Michael
Dauphinais, Barry David, and Matthew Levering, Washington, D.C.: Catholic University of America
Press, 2007.
2
Andrew Louth, Denys the Areopagite, London: Geoffrey Chapman, 1989, p. 126.
1

109

Diaries, Religious Experience, and Philosophical Change of
Ludwig Wittgenstein
Akio Kikai
Doctoral Program in Philosophy, Faculty of Humanities and Social Sciences,
University of Tsukuba

Ludwig Wittgenstein (1889-1951) is one of the most well-known philosophers of our age.
He was born in Vienna and acted as a philosopher in Austria and England. Throughout his
life, the major object of his philosophical interest had been logic and language. However, hisview on these subjects radically changed in the second half of his philosophical career, so
the researchers usually talk as if there were two Wittgenstein’s: early Wittgenstein and later
Wittgenstein. These two views were represented in his two major works: Tractatus Logicophilosophicus and Philosophical Investigations. In the former, which was written in his 20’s,
he tried to give a philosophical foundation for Frege’s formal logic and all scientific languages
based on it. According to it, our language is essentially a tool for describing the world and it
is possible because there is a structural parallelism between the world and our language. Thisview, which was also held by Galileo and may sound attractive to many modern scientists aswell, was to be completely thrown away by him in his later philosophy. The work in which
he described and developed his second view is Philosophical Investigations. According toit, human language including our mathematics is not something that reflects the essential
structure of the world, but a part of human mutual activities in which our actual life consists.
He calls each unit of these activities with language a “language game”. So natural sciences andmathematics are not the mirror of nature in themselves, but a system of various human language
games like chess or football. How the same philosopher can hold such radically different viewsin his life had been just a mystery for long time since there were so few materials from which
we could construct the answer for it. However, his diaries written in 1936-37, in which themost important part of Philosophical Investigations was written, were made public by the heirof his most intimate friend who had inherited some important manuscripts of Wittgenstein in
1993. These diaries are casting a completely new light onto the study of Wittgenstein. In mytalk, I, as a translator of diaries into Japanese, want to show what lay behind his philosophicalchange.

110

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Frontier Studies of Policy andPlanning Sciences
Department of Policy and Planning Sciences,
Graduate School of Systems and Information Engineering,
University of Tsukuba

113

114

Sep 28 (Sun)Multimedia Room
Frontier Studies of Policy and Planning Sciences (Students Presentations)

Chair

Stephen Turnbull

University of Tsukuba

16:00-16:15

Berdymyrat Ovezmyradov

University of Tsukuba

Traditional Turkmen Textiles: Consumer Properties and Market

16:15-16:30

Kotohumi Inaba

University of Tsukuba

A Lagrangian Relaxation Algorithm for Modularity Maximization
Problem

16:30-16:45

Kouhei Moriyama

University of Tsukuba

Packing: Distributed TDMA MAC protocol with Spatial Reuse for
Wireless Sensor Networks

16:45-17:00

Michio Matsubayashi

University of Tsukuba

Using BIM for Conversion of Design Documents into Electronic Form

17:00-17:15

Taohong Zou

University of Tsukuba

Forest cover change detection using multi-source data analysis in
Daxing’anling Mountain during 2000 to 2010

17:15-17:30

Xindi Zhang

University of Tsukuba

Considerations about the Strategy that cut down the cost to maintainsideway trees’ function

17:30-17:45

Benyan Jiang

University of Tsukuba

Beautiful city image: suggestions from the constructions of green
spaces in Qingdao (1898-1938)

17:45-18:00

Melissa Wanjiru

University of Tsukuba

Restoration of Nairobi River Basin and Creation of a Vibrant Riverfront
Development Zone
Lessons from Tokyo’s Sumida River115

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Traditional Turkmen Textiles: Consumer Properties and Market
Berdymyrat Ovezmyradov
Policy and Planning Sciences Program, Graduate School of Systems and Information Engineering,
University of Tsukuba

The purpose of this research was to evaluate traditional Turkmen textiles’ properties
which were the most important for consumers and to study the corresponding market
in Turkmenistan. The focus was on women’s clothing since, unlike males, females so far
remained the frequent users of traditional clothing. The research was implemented in asequential order. A mixed method was applied using both quantitative (physical tests and asurvey) and qualitative (interviews and observations) techniques. Interviews were conductedfirst. Then, the questionnaire was developed and distributed among respondents. Afterwards,
tests of fabric samples were conducted in textile labs according to DIN ISO standards. Finally,
the comparative analysis of garments was implemented. Functionality, durability, safety,
ease of care, image, popularity, affordability, availability, expedience and aesthetic properties
were chosen for evaluation as the most important properties for consumers. Panbarhat and
Keteni, two types of widely used dresses, were found to have both low clothing comfort andexcessively high costs for an average consumer. On the other side, popular Shtapel dresses were
found to be substantially more affordable and comfortable. The study showed how attitudes
towards wearing clothing among Turkmen consumers seemed to be constrained by social andcultural influences, specifically by ideals of modesty. A comparative analysis of consumers’
preferences for clothing was implemented comparing Germany and Turkmenistan. Overall,the comparison showed that for Turkmen consumers aesthetic properties of clothing had thehigher priority while practical aspects such as functionality and comfort had a relatively lower
significance. Those results indicated issues in consumption of textiles and clothing among
the Turkmen population and revealed an issue of changing consumption patterns in a way that
boosts acceptance of more comfortable and economic clothing.

116

A Lagrangian Relaxation Algorithm for Modularity
Maximization Problem
Kotohumi Inaba1, Yoichi Izunaga1 and Yoshitsugu Yamamoto2
Graduate School of Systems and Information Engineering, University of Tsukuba
2Faculty of Engineering, Information and Systems, University of Tsukuba

1

The modularity proposed by Newman and Girvan is one of the most common measureswhen the nodes of a graph are grouped into communities consisting of tightly connected nodes.
Due to the NP-hardness of the problem, few exact algorithms have been proposed.
Aloise et al. formulated the problem as a set partitioning problem, which has to take into
account all, exponentially many, nonempty subsets of the node set, and makes it difficult tosecure the computational resource when the number of nodes is large. Their algorithm is basedon the linear programming relaxation, LP relaxation for short, and uses the column generation
technique. Although it provides a tight upper bound of the optimal value, it can suffer a highdegeneracy due to the set partitioning constraints.
In this study, we propose an algorithm based on the Lagrangian relaxation. We relax
the set partitioning constraints and add them to the objective function as a penalty with
Lagrangian multipliers, and obtain the Lagrangian relaxation problem with only the binary
variable constraints. For a given Lagrangian multiplier vector, an optimal solution of the
Lagrangian relaxation problem can be obtained by checking the sign of coefficients, but it ishard to compute all the coefficients of variables. Then we propose to use the column generation
technique in order to alleviate the computational burden. Namely, we start the algorithm witha small number of variables and gradually add variables as the computation goes on. We also
propose some methods to accelerate the convergence.

117

Packing: Distributed TDMA MAC protocol with Spatial Reuse
for Wireless Sensor Networks
Kouhei Moriyama1 and Yongbing Zhang1,2
Master’s Program in Social System Engineering Section,
Graduate School of Systems and Information Engineering, University of Tsukuba
2Graduate School of Systems and Information Engineering, University of Tsukuba
1

A time division multiple access (TDMA) channel control approach is an efficient method
for large-scale wireless sensor networks, especially when the network is congested. However,
it is generally difficult to allocate the time slots to the nodes in a distributed way. Recently,
a distributed approach called TreeMAC (Song W-Z et al., Pervasive and Mobile Computing
5: 750-765, 2009) is proposed wherein the sink node allocates the required time slots of eachnode that is connected to the sink depending on the number of its children. Each node thenrecursively allocates the time slots to its children. The key disadvantage of TreeMAC is its low
channel efficiency. In this paper, we propose a packing (called PACK) algorithm that tries tofind the unused time slots for additional traffic demand. The proposed protocol is composedof two phases, say, information collection and free time-slot search phases. Firstly, in theinformation collection phase, each node collects the interference information within its twohop neighbors expect its grandchildren. Then, in the free time-slot search phase each node
reserves free time slot(s) incrementally. The PACK algorithm is triggered by a leaf node withthe least node identification number. The node reserves its required time slots according to
the traffic demand, and sends the results to its parent. A parent which receives the reservation
numbers from all of its children does the same process, and it sends the slot numbers of it andits children to its parent. If the number of a sensor’s available slots is less than its slot demand,the parent deletes the enough slots reserved to ensure its slot demand, or adds enough new timeslots. The simulation results show that the PACK protocol significantly improves not only thechannel efficiency but also the network throughput and the energy consumption in comparison
with TreeMAC.

118

Using BIM for Conversion of Design Documents into Electronic
FormMichio Matsubayashi1 and Shun Watanabe2
Graduate School of Systems and Information Engineering, University of Tsukuba
2Faculty of Engineering, Information and Systems, University of Tsukuba

1

The conservation of building stock constructed during the period of high economic growthis the urgent problem in Japan. Paper media had been used for the design documents to construct those buildings. Now, these design documents are often unusable for their renovationand conversion, since they are deteriorated or sometimes lost. It is urgent to convert them into
electronic form for the conservation of building stock. Building Information Modeling (BIM)
is the state of the art technology of recording design information to 3D model. As the casestudy, we have converted old drawings and specifications of University of Tsukuba to the BIM
model for saving design information.
Our previous study treated the comparison between paper media and BIM model, andexamined the difference between them. Design documents are classified into “Architecture”,“Structure” and “Mechanical/Electrical/Plumbing (MEP)”. In paper media, drawings of“MEP” are less numerous than those of “Architecture” and “Structure” in vertical section. As
for vertical section, the position of “MEP” elements are described and managed in different
forms, such as distribution diagrams of plumbing. The problem of conversion into the BIM
model was found, since the BIM model requires the exact 3D data of these elements.
On the other hand, the conversion methods from the BIM models to traditional drawings
was also confirmed. The BIM model can produce plan drawings by cutting it horizontally. It
can also produce elevation and section by cutting it perpendicularly. However, it is difficult
to grasp the connection between “MEP” elements because they are placed complexly in the
BIM model. The method of generating distribution diagram of plumbing is necessary for theeffective facility management, because we can easily grasp the placement of “MEP” elements
in traditional forms.
Creating of the program to generate a distribution diagram from the BIM model is ournext work. The challenge is to grasp the whole network by following connection information,
because attribute information about their connection is inherent and concealed in the objects of“MEP” elements. We plan to extract data by using API of the software and create a distribution diagram by repositioning these. The utility of the BIM model as the means to save design
information will improve by the conversion method of distribution diagram being realized.

119Forest cover change detection using multi-source data analysis in
Daxing’anling Mountain during 2000 to 2010
Taohong Zou and Kunihiko Yoshino
Graduate school of System and Information Engineering, University of Tsukuba

Abstract: Forest cover change is an important part of global environmental change, which
could induce a series of bad effects to the environment. And the forest cover change detection
is indispensable for sustainable forest management. Considering the Moderate Resolution
Imaging Spectro-radiometer (MODIS) can provide global vegetation condition in a large
temporal and spatial scale, it plays a significant role in monitoring the vegetation change. In
this paper, a decision tree was built based on the phenology features of vegetation extracted
from the MODIS EVI products, Land surface temperature and topographic condition to get theforest cover map in Daxing’anling Mountain in 2000 and 2010. Then the statistical analysis isconducted to detect the forest cover change in the area. Results showed that the area of needle
forest is decreasing and the portion of mixed forest and shrub is increasing, and the forest
cover change mainly happened in the southern and northern part in the area where the humanactivities are more active.
Key words: forest cover change; decision tree; MODIS; Daxing’anling Mountain120

Considerations about the Strategy that cut down the cost to
maintain sideway trees’ function
Xindi Zhang
Graduates School of System & Information Engineering,
Master’s Program in Social Systems Engineering, University of Tsukuba

Government spends large amount of budget on managing sideway trees, but these years
public work-related expenditures that can be spent on the maintenance of them are shrinking.
We can see trees be pruned badly so they won’t need any prunetrim for some years. But those
trees on the streets losing their elegant appearance makes none sense as a sideway tree. However, the tax used spent on supporting each sideway tree is limited by the decreasing population. Years later, the management of sideway trees will be a heavy burden, especially to thosesmall municipalities. The goal of this research is to find the if there is an optimum strategy
to cut down managing cost of sideway trees, in other words, to reduce the trees, but still keep
their multiple functions. One of the way to decide a tree’s necessity is to divide by functionsof sideway trees, that is to say, who can benefit from them. Sideway trees could improve theenvironment by preventing hot-island effect, absorbing noise, and eliminate Carbon dioxide
eliminating; they could contribute to urban landscape and protect walkers from the burningsun; and they could also guide direction for drivers. Another way to considering the sequence
we decrease the number of sideway trees is from the condition that they are in. First, to consider those roads whose traffic or users decreased a lot in the past years; second, to consider toplan sideway trees for those roads surrounding by green land as a background that the amountof green land had already been secured; third, to conduct the chosen of tree types depend on
its’ suitability of land development.

121Beautiful city image: suggestions from the constructions of green
spaces in Qingdao (1898-1938)
Benyan Jiang
Researcher in Graduate School of Human Comprehensive Sciences, University of Tsukuba

Qingdao, which was governed by Germany, Japan and Republic of China from 1898 to1938, was honored as “the most beautiful city in China” before WWII. This paper aims
to examine how Qingdao was constructed into such a beautiful city and try to get someinspirations from its development process. I found that first of all, the beautiful city image wasa result of accumulated ideas of different governors. Since urban planning theories started to
be widely accepted through the world, ideal city concepts such like hygienic city and park citywere gradually proposed by the German governors and Japanese governors in the first phasesof urban constructions in Qingdao. Thanks to this common goal and continuous efforts ofdifferent governors, lots of green spaces were constructed before WWII. Secondly, Qingdao
is endowed with hills and sea, which are really precious resources to create beautiful city
landscape. Fortunately, the German governors realized that since the very beginning, andstarted to create forests both on hills and along seaside rather than houses. Forestation activities
were also continued by the governors of Japan and Republic of China, which not only solved
the soil erosion and the shortage of drinking water but also provided a green background to
the whole city. As for parks, firstly, they were mainly arranged around significant public
facilities such as government office, church and railway station during the German period.
These facilities even now are often landmarks of a city and parks around helped to strengthen
their significant status and create much more beautiful landmark scape. On the other hand,colonial rule led to an unequal distribution of parks as well. The situation of no parks built
in the Chinese area was not improved until Qingdao was recovered by the Republic of China.

122

Restoration of Nairobi River Basin and Creation of a VibrantRiverfront Development Zone
Lessons from Tokyo’s Sumida River
Melissa Wanjiru1, Kosuke Matsubara2
PhD Candidate, Doctoral Program in Policy and Planning Sciences, University of Tsukuba
2
Associate Professor, Department of Policy and Planning Sciences, University of Tsukuba

1

Nairobi city has an immense potential for waterfront development owing to the fact that
it is traversed by three rivers (Mathare, Nairobi and Ngong’) which make up the Nairobi river
basin. However, there has been continued degradation of the riparian environment, principally
because of uncontrolled discharge of domestic and industrial waste into the river. In addition,
poor enforcement of the existing environmental laws such as the Environmental Management
and Co-ordination Act – EMCA (1999) and the Water Act (2002) has exacerbated the situation.
The challenge of riparian degradation notwithstanding, there is a great potential forriverfront development along this river basin. There have been notable efforts towards
restoration of Nairobi River and these include: KENSUP (Kenya Slum Upgrading Program) toalleviate slums; the Nairobi River Basin Project (1999) spearheaded by UNEP; and the current
Nairobi Rivers Rehabilitation and Restoration Programme (2010).
This paper was an attempt to highlight the Sumida River restoration programme and thesubsequent successful riverfront development as a benchmark for Nairobi river basin. Thiswas done in consideration of the local peculiarities of the two sites. This comparative analysis’
intent is to contribute to the knowledge that will enable creation of a Nairobi riverfront designthat will lead to socio-economic and environmental benefits.
Key words: Nairobi River Basin, Sumida River, restoration, riverfront design and development

123

NOTE

124

Japan and the World after 3.11
Institute for Comparative Research in Human andSocial Sciences (ICR),
University of Tsukuba
Graduate School of Business,
MBA Program in International Business,
University of Tsukuba

125

126

Sep 28 (Sun)5C216
Japan and the World after 3.11

Chair

Takafumi Ohtomo

University of Tsukuba

Yutaka Tsujinaka

University of Tsukuba

Takafumi Ohtomo

University of Tsukuba

13:10-13:30

Arthur (J. A. A.) Stockwin

Formerly Nissan Professor ofModern Japanese Studies,
University of Oxford

13:30-13:50

Kiyoshi Kurokawa

National Graduate Institute forJapan and the World After 3.11: Quo Vadis
Policy Studies

13:50-14:10

Makoto Iokibe

Prefectural University of
Kumamoto(Tentative) Japan after Great Earthquake –View from Former
Chairman of Reconstruction Design Council in Response to Great East
Japan Earthquake–

14:10-14:30

Yutaka Tsujinaka

University of Tsukuba

Japan after the Great Earthquake: Exploring Public Decision Making

14:30-16:00

Dicussion, Q&A

Chair

Remy Magnier-Watanabe

16:00-16:05

Remy Magnier-Watanabe

16:05-16:30

Caroline Tan

University of Tsukuba

Yoshinoya and It’s Cause-Related Marketing Initiative post-3.11: When
Risk and Trust Affect Consumer Behavior

16:30-16:55

Jean-Claude Maswana

University of Tsukuba

Foreign exchange and market value of Japanese firms: a threshold cointegration estimation

16:55-17:20

Hirohisa Nagai

University of Tsukuba

Developing Next Generation of the Global Leaders-Endeavor for Creating a New Global Education Program-

17:20-17:30

Short Break

17:30-18:00

Panel Discussion

13:00-13:10

Introduction

The Impact of the 3/11 Disasters on Domestic Japanese Politics

University of Tsukuba
Introduction*Order of presentation subject to change.

127

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The Impact of the 3/11 Disasters on Domestic Japanese Politics
Arthur (J.A.A.) Stockwin
Formerly Nissan Professor of Japanese Studies andDirector, Nissan Institute of Japanese Studies;
Emeritus Fellow, St. Antony’s College, University of Oxford

The triple disasters of 11th March 2011, of earthquake, tsunami and nuclear meltdown, took
an enormous toll in human lives and in a crisis of radiation near the Fukushima nuclear reactors. The aim of this presentation, however, will be to assess the impact of the crisis, both shortterm and long term, on the domestic politics of Japan.
The crisis took place around eighteen months after the long political dominance of the Liberal Democratic Party (LDP) had been broken in the elections of August 2009, which produced
a new government headed by the Democratic Party of Japan (DPJ), founded only 13 years earlier. The handling of the disasters by the DPJ leader and Prime Minister, Kan Naoto, becamea matter of acute controversy, which I shall briefly discuss. But a broader question is how far
3/11 contributed to the eventual downfall of the DPJ government in the decisive elections ofDecember 2012. This is complicated, because the government had already created doubts
about its competence under its first prime minister, Hatoyama Yukio, with his inept handlingof the Futenma Marine Base issue in Okinawa. Some weeks after the disasters Kan was replaced by a third DPJ prime minister, Noda Yoshihiko, who presided over a sharp deteriorationin relations between Japan and China over ownership of the Senkaku (Diaoyu) islands. It istherefore difficult to argue that it was 3/11 that brought down the DPJ government, though it
undoubtedly played some part.
I shall also examine the political impact, under the Abe Government, of nuclear power
plant closure and threatened reopening, and will conclude that this issue has served to revivelong moribund movements of popular political opposition, as well as enhancing conflict between central and local governments.

128

Japan and the World After 3.11: Quo Vadis
Kiyoshi Kurokawa
Academic Fellow, National Graduate Institute for Policy Studies, Tokyo.

The world is in a major historical transition in coming few decades from the Principles
built since Industrial Revolution to something quite Uncertain. Knowledge dissemination andrapid progress in science and technology have been critical elements underlying such a majorchange as our history shows. Two major factors bringing this big transition are explosion of
Human Population from 1.6 billion in year 1900 to more than 7 billion in recent years andHyper-Connectivity. The status of the world of globalization becomes rapidly changing, fragmented and fragile. Examples of major buzz words we often see these days include; Resilience,
Risks, while 'Accountability and Transparency' have become essential to the governance of
any organization, institution and government.
Fukushima Nuclear Accident of 3.11, 2011, was a 'Black Swan Event' hit by huge earthquake and tsunami; many official and independent investigation reports, books, documentaries
have been published in Japan and in abroad.
Fukushima Nuclear Accident Independent Investigation Commission (NAIIC) by the National Diet, launched 9 months after the Accident, was FIRST of such kind in Constitutional
Democratic Japan, NAIIC turned out to be a 'While Body Scan of the Governance of Japan
Inc.,’ revealing Inconvenient Truth to many in the 'Establishment' of Japan.
In this session I discuss the Change of the Status of the World and Japan and choices andopportunities ahead of you.
References for copy distribution
1. http://naiic.go.jp ; NAIIC Reports in both Japanese and English
2. naiic.net/; Easy to understand NAIIC report in animation videos, 6 x 3 minutes each.
3. kiyoshikurokawa.com/

129Yoshinoya and It’s Cause-Related Marketing Initiative post-3.11:
When Risk and Trust Affect Consumer Behavior
Caroline Tan
MBA-International Business, Graduate School of Business Sciences, University of Tsukuba

Cause-related marketing is a strategy that has appeals to corporations, as it not only responds to societal pressure for ‘corporate social responsibility’ but at the same time it also
shareholders’ pressure for profits. This practice of the advocacy of corporate social responsibility in marketing activities has witnessed a surge in corporations adopting it as offers the‘win-win’ solution to both profit and non-profit alike. Nielsen conducted a corporate social
responsibility study in 2014 and the results showed that 64% of the Asia-Pacific respondents
indicated their willingness to pay extra for products and services that are committed to positivesocial and environmental impact. In 2013, Yoshinoya announced that it will start cultivating
rice and other vegetables through a joint-venture with local farmers in Fukushima with aninvestment of ¥10 million beginning 2014. This move was aimed at lowering costs and improving the supply chain and at the same time contribute to the reconstruction of Fukushima
post 3.11. Using the Theory of Reasoned Action this study examines the consumers’ attitude
towards Yoshinoya’s cause-related marketing initiative and its impact on consumer behavior.
While cause-related marketing has been positively effective in influencing consumer behavior, the findings of this study proved otherwise. The results indicate that factors of trust andperceived risk play a major role in determining consumption and purchase decisions. Interestingly, the element of personal impact and implication influenced the consumers’ decisions andshowed that unlike the majority of cause-related marketing initiatives that proved to be successstories, Yoshinoya’s decision could bring about a negative effect.
Keywords: Cause-related marketing, Trust, Perceived Risk, Consumer Behavior, Theory
of Reasoned Action130Foreign exchange and market value of Japanese firms:
a threshold co-integration estimation
Jean-Claude Maswana
MBA-International Business, Graduate School of Business Sciences, University of Tsukuba

Measuring foreign exchange has been a critical issue both in theoretical literature related
to international financial management and in the regular operations of multinational firms,
especially Japanese ones. As major Japanese firms derive nearly half of their sales from overseas markets, impacts of foreign exchange fluctuation on their performance (in terms of market
value). While the assessment of such impacts has been theoretically well-documented, however, empirical studies have been providing conflicting evidence. This is so, in part, becauseof econometrics misspecification related to the application of linear models. Yet, it is increasingly admitted that the linear models cannot explain a number of important features common
to much financial data. Building on recent developments in nonlinear econometrics models,the present study empirically investigates exchange rate exposure of Japanese firms whose
performance (measured by aggregate market value) highly depends on exchange rate changes
using threshold cointegration estimation. The primary finding is that stock market and foreignexchange are asymmetrically cointegrated with stock prices being significantly exposed to
exchange rate changes in depreciation regimes. The result has some implication for policy inthe post-March 11 Japan, especially as the most direct way that Abenomics has helped firms isthrough lowering the value of the yen.

131

Developing Next Generation of the Global Leaders-Endeavor for Creating a New Global Education ProgramHirohisa Nagai, Ph.D.
MBA-International Business, Graduate School of Business Sciences, University of Tsukuba

Japanese society has been encountering the various aspects of challenges on dealing withthe globalization for past decade. Among those, developing competent global leaders is one of
the most demanding topics for Japanese business society. Contrary to that rapidly emerging
issue, the current status of the Japanese companies’ training and developing for global leaders
is ranked at the tail end among twelve advanced and semi-advanced countries (Tsukuba Global
HRD Research Unit, 2013). In fact, training opportunity for next generation of the global
leaders has been decreasing. For example, number of high school students studied in abroad(>3 months) has decreased by 22% between 1998 and 2011 (MEXT, 2012). Also, Japan’s
TOEFL score was ranked at #28 among 30 Asian countries in 2011. According to the survey
results on the Japan’s high school programs conducted by the Japan Institute for Social andEconomic Affairs (2013), there are eight issues that hindering to acquire the global savvy inthe current system. This survey result indicated that the causes of these issues are likely due tothe discrepancies between the current educational system (traditional) and the ideal conditions(future-oriented). It also proposed the importance of 1. Introduce the liberal arts education, 2.
Transfer course units after returning from studying at the overseas, and 3. Reform the contentsof college entrance examination to meet the global perspectives. Objectives of this study isto propose a new framework for developing next generation of the global leaders based on the
SPDL (Search-Plan-Do-Learn) model combined with the research results of the meta-cognitive
approach of learning global leadership competency (2013). This revised model will provide
a new horizon of developing problem solving skills, a key global leadership competency.
Implications from this study will include a new training and development program as well as
pedagogy to educate next generation of the global leaders.

132

NOTE

133

NOTE

134

Student Presentations– The 9th Tsukuba Medical Science
Research Meeting –Faculty of Medicine, University of Tsukuba
Ph.D. Program in Human Biology, University of Tsukuba
Tsukuba Society for Molecular Medicine/TSMM

135

136

Sep 29 (Mon)International Conference RoomStudent Presentations -The 9th Tsukuba Medical Science Research Meeting-9:00-9:05

Introduction

9:05-9:18

Haojun Xu

University of Tsukuba

Assessment of drug therapy efficacy for pregnancy-induced
hypertension using genetically modified mouse model

9:18-9:31

Takato Honda

University of Tsukuba

Induction of associative olfactory memory by targeted activation of thememory circuits in Drosophila larvae

9:31-9:44

Daiki Nakatsuka

University of Tsukuba

The pontomedullary tegmentum GABAergic neurons regulate thestates of sleep and wakefulness

9:44-9:57

Imke Jenniches

University of Bonn

Cannabinoid signaling in stress and depression: the role of DAGLα

9:57-10:10

Tomotsune Ameku

University of Tsukuba

Mating controls female germline stem cell proliferation via steroid
hormone biosynthesis in Drosophila melanogaster10:10-10:23

Yuri Ushijima

University of Tsukuba

Ferroxidase activity of staphylococcal MrgA is essential for oxidative
stress resistance

10:23-10:40

Coffee Break

10:40-10:53

Girish Mali

University of Edinburgh

Multisystem functional characterisation of motile ciliopathy genes
HEATR2 and ZMYND10

10:53-11:06

Jaehyun Kim

University of Tsukuba

USP15 regulates neuromuscular functions mediated by the control of
RNA splicing

11:06-11:19

Daniel Quang

Unviersity of California, Irvine Motif signatures in stretch enhancers

11:19-11:32

Yen-Yun Chen

Unviersity of California, Irvine The role of NIPBL in Cornelia de Lange Syndrome

11:32-11:45

Keisuke Yoshida

University of Tsukuba

Marine-derived antiviral compound eudistomin C is a proteintranslation inhibitor

11:45-11:58

Nathana Barbosa Lopes

University of Sao Paulo

Floral fluorescent dyes and derivatives for cell staining

11:58-12:11

Eszter Németh

University of Szeged

Redesign of the colicin E7 nuclease domain into a controlled andspecific artificial enzyme

137

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12:11-13:40

Break

13:40-14:15

2-min presentation

14:15-14:25

Coffee Break

14:25-14:38

Tomokazu Kimura

University of Tsukuba

GPNMB impacts to invasive properties of bladder cancer

14:38-14:51

Thanh Thao Vo Nguyen

University of Tsukuba

Cooperative expression of transmembrane prostate androgen induced
protein –TMEPAI by TGF-β and EGF signaling

14:51-15:04

Yihao Li

Leiden University

Genetic depletion and pharmacological targeting of αv integrin in
breast cancer cells impairs metastasis in zebrafish and mouse
xenograft models

15:04-15:17

Antoniana Batsivari

University of Edinburgh

Analysis of proliferation in hematopoietic stem cell development

15:17-15:30

Pei-Han Tai

National Taiwan University

SIK2 controls dynamics of insulin production in pancreatic β cells

15:30-15:43

Tran Thi Nhu Mai

University of Tsukuba

MafB deficiency impairs the apoptotic cell clearance of macrophages

15:43-15:55

Coffee Break

15:55-16:30

2-min presentation

16:30-17:20

Poster Session (Exchange Hall)

17:20-17:33

Mizuho Fukushige

University of Edinburgh

A meta-analysis of experimental studies of radiation attenuatedschistosome vaccines in the animal model

17:33-17:46

Xerxes Seposo

University of Tsukuba

The effect of temperature on all-cause mortality in the three
metropolitan cities in the Philippines, 2006-2010

17:46-17:59

Md. Harunor Rashid

University of Tsukuba

The early marriage and maternal health care utilization in rural
Bangladesh: Analysis of Bangladesh Demographic Health Survey

17:59-18:12

Keiko Yamaguchi

University of Tsukuba

Relationships of family function, QOL and family empowerment of thefamily rearing a child with severe motor and intellectual disabilities athome

18:12-18:25

Hiromi Tobe

University of Tsukuba

How a group-based anger-management parenting program changed
mothers’ cognition, attitude and behavior

138

P-1 to P-14

P-15 to P-27

Sep 28 (Sun), 29 (Mon)

Exchange Hall
Poster Display (Student Presentations, Global Aging Center Tsukuba)

P-1

Min Li

The effect of different soil utilizition on the RIP of 137Cs contaminated soil from northern Japan

P-2

Anna Ignatochkina

Function characterization of a second and novel mRNA capping apparatus in Trypanosoma brucei

P-3

Yoshimi Harada

The genetic compatibility among influenza virus polymerase subunits for the generation of reassortantvirusesP-4

Tomomi Fukuda

A Cullin-related protein regulates posttranslational modification of PML

P-5

Tatsuya Komura-Kawa

A novel transcriptional regulation of steroid hormone biosynthesis in Drosophila melanogasterP-6

Yuto Masuda

The budding yeast AMPK ortholog Snf1 negatively regulates endoplasmic reticulum stress response
Challenges for sustainable tomato production: Isolation of a novel tomato mutant with enhanced fruit
set efficiency and candidate gene approaches by Next Generation Sequencing
Construction of genetic analysis available multidrug sensitive yeast strain by both the disruption of
drug efflux system and the conditional repression of membrane barrier system

P-7

Hitomi Takei

P-8

Takumi Chinen

P-9

Taito Miyachi

Involvement of the small GTPase Arf6 in PDGF-induced dorsal ruffling

P-10

Ngo Thai Bich Van

Tumor-infiltrating CD8 T lymphocytes are decreased in Phospholipase D2 knockout mice

P-11

Ling Zheng

Role of THG-1 in tumor angiogenesis through stabilization of HIF-1α in normoxic condition

P-12

Kazuya Ito

Dormant cancer cells have high reserved antioxidant capacity that may promote their radioresistanceP-13

Shota Sakaguchi

Non-invasive in vivo near-infrared fluorescent imaging of tumors with iRFP

P-14

Miki Shimbo

Chondrodysplasia in mice lacking both chondroitin sulfate N -acetylgalactosaminyltransferase-1 and -2

P-15

Zeinab Kosibaty

MafB regulates macrophage-osteoclast progenitor cell function

P-16

Ahmed Abdellatif

MafK overexpression impairs pancreatic β-cells development in vivo

P-17

Yunshin Jung

The role of large maf transcription factors in the β-like cell conversion from mouse liver

P-18

Jian-Huang Lin

NPM1 functions as a subunit of enhanceosome for NF-κB-mediated transcription

P-19

Yu Ishikawa

Involvement of oviductal peristalsis in fertilization of the mouse

P-20

Kouta Niizuma

Identification and characterization of human CD300H, the eighth member of the CD300-family
receptors

P-21

Eri Takenaka

DNAM-1 (CD226) plays an important role in antigen presentation by small peritoneal macrophages

P-22

Haruka Miki

The role of CD300a (MAIR-I) in allergic airway inflammation

P-23

Tran B. Nguyen

Somatic mosaic mutations in TET2 and DNMT3A in a case of peripheral T-cell lymphoma

P-24

Yuki Hachiya

P-25

Misaki Hidaka

P-26

Miki Kagami

Temperature during pregnancy influences birth size

P-27

Tomoko Suga

The intervention research on Domestic Violence prevention program for high school students

Association of leukocyte immunoglobulin-like receptor A3 (LILRA3 ) deletion polymorphism withsystemic sclerosis
Association of TRIM21 (RO52 ) polymorphisms with systemic lupus erythematosus in a Japanese
population139

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Oral Presentation

O-1

Assessment of drug therapy efficacy for pregnancy-induced
hypertension using genetically modified mouse model
Haojun Xu1,2, Junji Ishida2, Tomohiro Ishimaru2, Altansarnai Baasanjav2,
Misuzu Hashimoto1,2, Kazuyuki Noguchi2,3, and Akiyoshi Fukamizu1,2
Ph. D. Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba
2Life Science Center, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba
3
Department of Nephrology, Faculty of Medicine, University of Tsukuba

1

Pregnancy-induced hypertension (PIH) is characterized by elevated blood pressureaccompanied with the significant amount of protein in the urine in the second or third trimesterof pregnancy. This syndrome brings high risk to both maternal and fetal health, while themolecular mechanism of the pathogenesis remains unclear. It is reported that L-type calcium
channel (LCC) on smooth muscle cell plays a dominant role in regulation of vasoconstriction.
Hence, dihydropyridine, a basic structure of LCC specific blocker (LCCBs), is widely usedin chronic hypertension therapy but not to PIH patients because of the ethical difficulties for
examining the drug effect including unknown risk on mothers and fetuses.
In this research, we aim to evaluate the pharmaceutical effect of LCCB on the above
pathology using pregnancy-associated hypertensive (PAH) mice, an animal model for PIH.
By treating amlodipine, one kind of dihydropyridine LCCB, to PAH mice, blood pressure wassuppressed in a dose-dependent manner. Urinary protein level was also reduced to the levelof normal pregnancy. In addition, cardiac abnormality and placental structure were partiallyameliorated, while fetal intrauterine growth retardation is not affected by amlodipine. These
results suggested a variety of ameliorative effects of LCCB on the progressive pathologies
during pregnancy-associated hypertension in mice.

140

Oral Presentation

O-2

Induction of associative olfactory memory by targeted
activation of the memory circuits in Drosophila larvae
Takato Honda1,2, Chi-Yu Lee2, Maki Yoshida-Kashikawa2, Ken Honjo2,3, andKatsuo Furukubo-Tokunaga2
Ph.D. Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba
2Graduate School of Life and Environmental Sciences, University of Tsukuba
3
National Institiute of Genetics

1

The fruit fly Drosophila melanogaster has been used as a model animal for the study ofthe genetic and molecular mechanisms of learning and memory. Appetitive olfactory memory
is formed in Drosophila by at least two sets of external stimuli, conditioned odor stimuli (CS)mediated by the olfactory receptor neurons (ORNs) and unconditioned reward stimuli (US)mediated by the octopaminergic (OA) neurons. Previous works showed that synaptic output
from OA neurons is necessary for appetitive memory formation. Signals of OA neurons areintegrated with the olfactory information pathway at antennal lobes and mushroom bodies,to establish appetitive associative memory trace. However, whether associative memory canbe induced by the activation of only the olfactory CS and a biogenic amine-mediated US
pathways remains to be elucidated.
With its simple neuroanatomical design, the larval brain of Drosophila can be utilized as an
excellent model system for the elucidation of the neurocircuitry mechanism of memory. In thisstudy, we took the advantages of optogenetic and thermogenetic techniques. We substituted
sugar reward stimuli by thermogenetic activation of OA neurons with the dTrpA1 channel,
and odor stimuli by optical activation of a specific class of ORNs with Channelrhodopsin-2(ChR2). We showed that targeted activation of the converging memory circuitry with blue
light and heat produces associative memory in the transgenic larvae. We also showed thatmemory thus produced is specific to the odorant determined by the type of the activated
ORNs. Furthermore, we demonstrated that this artificial memory persists for medium term,
and as stable as natural memory produced by using a real odorant. Our results thus provide
direct evidence that targeted stimulation of only a single type of olfactory receptor neurons issufficient to induce olfactory memory that is indistinguishable from natural memory induced by
the activation of multiple ORNs (Honda T et al., Scientific Reports, 2014). Given its simplicity
and robustness, this method could be utilized to further our knowledge on the neurocuircuitry
mechanisms of memory.

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O-3

The pontomedullary tegmentum GABAergic neurons regulate
the states of sleep and wakefulness
Daiki Nakatsuka1, Takeshi Kanda1, Tatsuya Kurokawa1, and Masashi Yanagisawa1,2International Institute for Integrative Sleep Medicine (IIIS), University of Tsukuba
2
University of Texas Southwestern Medical Center

1

The states of sleep and wakefulness are regulated by several subcortical regions including
the brainstem. The medulla oblongata is thought to contain the neural circuits responsible forsleep. However, the detailed cellular and systems level mechanisms are poorly understood.
Here, we focused on GABAergic neurons in the pontomedullary tegmentum. To determine
whether and how they contribute to the regulation of sleep states, we specifically manipulated their firing patterns and traced their projection patterns. Cell-type and location specificgene delivery was achieved by local injection of Cre-inducible adeno-associated virus vectors(AAV) into the pontomedullary tegmentum of GAD1-Cre mice in which Cre recombinase isexpressed specifically in GABAergic neurons. To silence their firing, inhibitory DREADD
hM4Di was targeted to them. In patch-clamp experiments, bath application of the hM4Di
agonist CNO suppressed their discharge in brain slices. Total time of NREM sleep after
intraperitoneal administration of CNO was markedly increased in the mice in which hM4Di was expressed in the dorsal area of pontomedullary tegmentum, whereas comparatively
little effect on sleep pattern was observed in the mice expressing hM4Di in the medial area.
Spectral analysis of EEG activity showed that EEG power, especially delta power (1-4 Hz),during NREM sleep was markedly decreased in the mice expressing hM4Di in the dorsal area,
but not in the medial area. To elucidate the anatomical basis for the control of sleep states by
the dorsal pontomedullary tegmentum GABAergic neurons, we traced their axonal fibers with
GFP appended to a palmitoylation sequence of GAP43. Their axons were found not only inthe medulla, pons and midbrain, but also in the thalamic reticular nucleus which is thought tobe a sleep spindle pacemaker. These results suggest that GABAergic neurons in the dorsal
pontomedullary tegmentum connect with the thalamocortical networks and contribute to theregulation of sleep states.

142

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O-4

Cannabinoid signaling in stress and depression:
the role of DAGLαImke Jenniches, Svenja Ternes, Andras Bilkei-Gorzo, and Andreas Zimmer
Institute of Molecular Psychiatry, University of Bonn, Germany

Depression is a highly prevalent psychiatric disorder and is associated with high levels ofmorbidity and mortality. Even though the knowledge of the pathophysiology of depression
has evolved significantly in the last decades, vast gaps still remain in the comprehension ofdepression and its treatment. The endogenous cannabinoid system plays a modulatory role inmany cognitive and emotional processes and is therefore strongly involved in neuropsychiatricdisorders. For instance, long-term treatment with rimonabant, the first clinically usedcannabinoid receptor 1 (CB1) antagonist, showed adverse psychiatric side effects in patients
including anxiety and depression. In rodents the genetic or pharmacologic blockade of CB1,
the major neuronal cannabinoid receptor, increases depression- and anxiety-like behavior.
The two main endogenous cannabinoids, anandamide and 2-arachidonoylglycerol (2AG), bind to presynaptic CB1 receptor and thereby inhibit the secretion of both excitatory andinhibitory neurotransmitters. The key enzyme for the formation of 2-AG, the most abundantendocannabinoid in the brain, is diacylglycerol lipase α (DAGLα). We assume that the absenceof DAGLα, and thus the lack of 2-AG, leads to a depressive-like phenotype that is similar tothat observed in CB1 knockout mice. To investigate the role of DAGLα in different cell types,
we recently generated constitutive, as well as microglia- and neuron-specific knockout miceand tested these animals in various anxiety- and depression-related behavior tests. Our first
results indicate that DAGLα knockout mice are more prone to stress than wildtype controls andtherefore very likely more susceptible to develop a depression-like phenotype after exposure
to chronic stress.

143

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O-5

Mating controls female germline stem cell proliferation via
steroid hormone biosynthesis in Drosophila melanogaster
Tomotsune Ameku1, Yuko Shimada-Niwa1, and Ryusuke Niwa1,2
Graduate School of Life and Environmental Sciences, University of Tsukuba
2
PRESTO, JST

1

In animals, mating is a pivotal behavior to produce offspring in the next generation andto achieve prosperity of species. In many insect species, mating elicits a number of criticalchanges in female reproductive behavior, such as an increase of egg-laying (Heifetz Y et al.,Curr Biol 10:99-102, 2000). Whereas behavioral changes in mated females are well studied, it
is still unclear how physiological changes are controlled by mating. To address this question,
we used the fruit fly Drosophila melanogaster as a model organism.
Here we show a relationship between post-mating oogenesis and the major insect steroid
hormone ecdysteroid. We found that mating induce an increase in the number of female germline stem cells (GSCs). We also found that ecdysteroid level in the adult ovary is significantly
elevated after mating. To examine whether post-mating ecdysteroid biosynthesis in the ovaryis crucial for controlling female GSC numbers, we created adult ovary-specific RNAi animals
for neverland (nvd), which encodes the ecdysteroidogenic enzyme responsible for converting
dietary cholesterol into 7-dehydrocholesterol (7dC). nvd RNAi animals did not exhibit postmating increase of not only ovarian ecdysteroid titer but also female GSC numbers. Importantly, the GSC phenotype was rescued by oral administration of 7dC. These results suggestthat post-mating ecdysteroid biosynthesis in the ovary plays a pivotal role in controlling GSC
proliferation in adult Drosophila female. Our study illustrates a role of ecdysteroids in theadaptive maintenance of female GSC numbers, which might contribute to positively activating
oogenesis after mating.

144

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O-6

Ferroxidase activity of staphylococcal MrgA is essential foroxidative stress resistanceYuri Ushijima1, Ryosuke L. Ohniwa1, Shinji Saito1, Yoshikazu Tanaka2, and Kazuya Morikawa1
Microbiology, Faculty of Medicine, University of Tsukuba
Creative Research Institution Sousei, Hokkaido University

1
2

Staphylococcus aureus MrgA (encoded by mrgA) belongs to Dps family proteins that play
important roles to cope with a broad range of stresses. The staphylococcal mrgA gene is specifically expressed under oxidative stress conditions and is one of the most highly induced ones
during phagocytic killing by macrophages. We previously reported that mrgA is essential foroxidative stress resistance, and can cause nucleoid compaction. However, whether nucleoidcompaction by itself would contribute to oxidative stress resistance was elusive, because Dps
family proteins generally have ferroxidase activity to prevent the hydroxyl radical formation
via Fenton reaction. In the present study, we solved the crystal structure of MrgA and conducted mutation analysis of Asp56 and Glu60 that locate at the expected ferroxidase center. In the
mrgA* strain that expresses Asp56Ala/Glu60Ala MrgA (MrgA*), MrgA* retained dodecamer
formation and nucleoid compaction ability. On the other hand, the ferroxidase activity of
MrgA* decreased about half. Viability of the mrgA* strain was as low as the mrgA null mutant
in oxidative stress, and phagocytic killing assays. These results suggest that nucleoid compaction by itself is not sufficient for oxidative stress resistance, and Asp56 and Glu60 constituteessential molecular site in MrgA for oxidative stress resistance and survival against phagocytic
killing.

145

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O-7

Multisystem functional characterisation of motile ciliopathy
genes HEATR2 and ZMYND10Girish Mali1,2, Ian Jackson1, Andrew Jarman2, and Pleasantine Mill1
MRC Human Genetics Unit, MRC IGMM, University of Edinburgh, UK
Centre for Integrative Physiology, Hugh Robson Building, University of Edinburgh, UK
1

2

Cilia are polarized extensions of the cells microtubule-based cytoskeleton dedicated tosensory, signaling and motility-related functions. They are essential for development and adulthomeostasis and loss of cilia formation or function leads to a spectrum of human disorders
called ciliopathies. In mammals, there are two main types of cilia, immotile and motile, where
motile cilia generate fluid flow at the embryonic node, in the airways, cerebral ventricles andthe oviduct in addition to sperm propulsion via the flagellum. Ciliary specialization correlateswith an ancient transcriptional code, which has been fine-tuned over evolution. Core ciliary
genes are transcriptionally activated by members of the winged-helix transcription factor RFX
family. The forkhead transcription factor FOXJ1 additionally activates motility genes such as
the ones encoding dynein motors which generate the ciliary beat in an ATP-dependent manner.
Thus, RFX3 and FOXJ1 co-operatively switch on a genetic programme required to make motile
cilia. Mutations affecting this genetic programme lead to a congenital motile ciliopathy called
Primary Ciliary Dyskinesia (PCD). Using the highly conserved RFX-FOX transcriptionalcode, we identified two putative PCD candidates CG31320/HEATR2 and CG11253/ZMYND10
through expression analysis in Drosophila. Conserved roles in ciliary motility were confirmedwith fly mutant analysis in parallel to identification and characterization of human PCD
mutations in these genes. Proteomic studies are underway to define the interaction networks
for each of these distinct assembly factors required to deliver functional dynein motor protein
complexes to the cilia. Preliminary results for CRISPR mutant mice, generated in collaboration
with Prof. Takahashi and Dr. Mizuno (University of Tsukuba) will be presented.

146

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O-8

USP15 regulates neuromusucular functions mediated by thecontrol of RNA splicing
Jaehyun Kim, Fuminori Tsuruta, and Tomoki Chiba
Graduate School of Life and Environmental Sciences, University of Tsukuba

Alternative pre-mRNA splicing plays an important role in protein diversity and complexity.
It enables eukaryotic cells to produce a huge number of proteins from restricted genes throughthe selective elimination of introns and exon rejoining, and thereby contributes to tissue-specificgene functions. In brain, alternative splicing constitutes the basis for neuronal functions
regulated by gene expression. Given the importance of alternative mRNA splicing in regulatingneuronal functions, it is hardly surprising that disruption of RNA splicing leads to neuronal
dysfunction. Indeed, recent studies have revealed that disruption and misregulation of RNA
splicing result in neuromuscular disorders such as amyotrophic lateral sclerosis and spinal
muscular atrophy. However, the molecular mechanism of how the failure in RNA splicing leads
to neuromuscular disorder is yet to be elucidated. In this study, we found that deubiquitinating
enzyme, ubiquitin specific peptidase 15 (USP15), is associated with neuromuscular functions
via the control of RNA splicing. USP15 deficient mice exhibit ataxia-like behaviors resulting
from the morphological defect of cerebellum and skeletal muscle. We also found that USP15
is involved in a deubiquitinization of particular target, which plays a key role in RNA splicing.
Furthermore, loss of USP15 widely affects splicing patterns of substantial genes potentiallyassociated with neuromuscular disorders. Taken together, these data suggest that loss of
USP15 may bring about aberrant gene expression mediated by misregulation of RNA splicing,
and thereby impairs neuromuscular functions. Therefore, this study is expected to be a novel
clue for clarifying the relationship between mRNA splicing and neuromuscular diseases.

147

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O-9

Motif signatures in stretch enhancers
Daniel Quang1,2, Stephen Parker3,4, Peter Chines3, Narisu Narisu3, Brooke Wolford3,
Leland Taylor3, Michael Stitzel5, Michael Erdos3, and Francis Collins3
Department of Computer Science, University of California, Irvine
Center for Complex Biological Systems, University of California, Irvine
3
National Human Genome Research Institute, National Institutes of Health4
Department of Computational Medicine & Bioinformatics, University of Michigan(starting September 1, 2014)5
The Jackson Laboratory for Genomic Medicine, Farmington, CT
12

Enhancers are regions of DNA where transcription factor proteins bind and modulatetranscription of a gene or genes. A cell’s gene expression signature can uniquely identify its
cell type. Stretch enhancers are chromatin-defined enhancer regions that are much larger(≥3000 DNA base pairs) than typical enhancers (median size = 800 base pairs). They tend tobe cell-type specific, regulate cell-type specific gene expression, and are enriched to co-occur
with disease-associated genetic variants, highlighting the importance of stretch enhancers forcellular function. These observations motivated us to investigate molecular signatures thatdifferentiate stretch enhancers from typical enhancers, with a focus on identifying biologicalinsights for why stretch enhancers are so long. To answer these questions, we performed
transcription factor motif analyses. Motifs describe the sequence binding preference oftranscription factors and can be used to identify the identities and locations of the transcription
factors that are binding to these sequences. We developed an experimental and computational
approach that can systematically identify stretch and typical enhancers in a cell type at a
genome-wide level and applied motif signature analyses to these enhancer sequences. Our
analyses across 32 diverse cell types led to the identification of motifs associated with known
factors and novel motifs with no known associated factors. Some of these associated factors
are well-known “master” transcription factors that are important for establishing cell identity.
Many of the genes encoding these master transcription factors also have a nearby, associatedcell-type specific stretch enhancer that are enriched for potential binding sites for other mastertranscription factors as well as the transcription factors that the gene encodes. These motifs cantherefore be used to generate tight auto-regulatory networks, which we believe is an importantmechanism for different cells to maintain their identities. In the future, understanding stretchenhancer motif signatures may lead to targeted engineering of cell-specific states.

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O-10

The role of NIPBL in Cornelia de Lange Syndrome
Yen-Yun Chen1, Daniel A. Newkirk1, Ebony Flowers1,5,6, Xiangduo Kong1, Chengguo Yao2,
Alex Ball, Jr.1, Richard Chien1, Shimako Kawauchi3, Rosaysela Santos3, Anne L. Calof 3,
Arthur D. Lander4, Yongsheng Shi2, and Kyoko Yokomori1
1

Department of Biological Chemistry, School of Medicine, 2Department of Microbiology & Molecular Genetics,
3
Department of Anatomy & Neurobiology, School of Medicine,
4
Department of Developmental & Cell Biology, School of Biological Sciences, University of California, Irvine
5
California State University Long Beach
6
Current address: UT Southwestern Medical Center

Cornelia de Lange Syndrome (CdLS) is an autosomal dominant multisystem developmental
disorder characterized by facial dysmorphism, hirsutism, upper limb abnormalities, cognitive
retardation, and growth abnormalities. Over 60% of cases are associated with mutations in
the NIPBL gene, and NIPBL haploinsufficiency is linked to severe cases of CdLS. NIPBL(Nipbl in mice) is required for loading of the essential multiprotein complex “cohesin” onto
chromatin. Cohesin mediates sister chromatid cohesion important for mitosis, but is also
increasingly being recognized as a regulator of gene expression. In CdLS patient cells andanimal models, the presence of multiple gene expression changes with little or no cohesion
defect suggests that disruption of gene regulation underlies this disorder. However, the effect of
NIPBL haploinsufficiency on cohesin binding, and how this relates to the clinical presentationof CdLS, has not been fully investigated. We examined genome-wide cohesin binding and its
relationship to gene expression using mouse embryonic fibroblasts (MEFs) from Nipbl +/- micethat recapitulate the CdLS phenotype. We found a global decrease in cohesin binding, including
those at CTCF sites and repeat regions. Cohesin-bound genes are enriched for H3K4me3 at thepromoters and are mostly downregulated in Nipbl mutant MEFs with evidence for reduced
promoter-enhancer interaction, suggesting that gene activation is the primary cohesin function
sensitive to Nipbl reduction. Over 50% of genes affected in mutant MEFs are cohesin target
genes, including those involved in adipogenesis, indicating that dysregulation of cohesintarget genes directly contributes to the Nipbl haploinsufficiency-induced CdLS phenotype.
Interestingly, we also found that a subpopulation of Nipbl localizes to the nucleolus and affects
ribosomal RNA (rRNA) biosynthesis. Abnormalities in nucleolar function and ribosome
biogenesis are known to cause phenotypically similar “ribosomopathies” with growth andmental retardation. Our results raise the possibility that the CdLS phenotype is the result of
the combinatorial effects of dysregulation of cohesin target genes and nucleolar function of
NIPBL.
This work was supported in part by NIH grants HD052860, HD062951, and HD078849.
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O-11

Marine-derived antiviral compound eudistomin C is a proteintranslation inhibitor
Keisuke Yoshida1, Yu Ota1, Takumi Chinen1, Ryosuke Yamada2, Hiroshi Masumoto3,
Yoko Nagumo1, Satoshi Yokoshima2, Toru Fukuyama2, and Takeo Usui1
Faculty of Life and Environmental Sciences, University of Tsukuba
2Graduate School of Pharmaceutical Sciences, Nagoya University
3
School of Medicine, Graduate School of Biomedical Sciences, Nagasaki University
1

Eudistomin C (EudiC), a natural product isolated from Caribbean tunicate Eudistoma
olivaseum, is an antitumor and antiviral compound. The unique structure and the broad
spectrum antiviral activity, for example against Herpes simplex virus type 1, Polio vaccine type1 virus and so on (Van Maarseveen JH et al. J Med Chem, 35: 3223-3230, 1992), has attracted
pharmaceutical companies as a lead compound, but several trial for clinical development of
EudiC has failed by its strong cytotoxicity on mammalian cells. Previously we found that the
point mutation in rps14A, a component of small subunit of eukaryotic ribosome, conferred the
EudiC resistance in budding yeast, and that EudiC inhibited a protein translation in yeast and
HeLa cells. These genetical and biochemical results strongly suggest that EudiC is a proteintranslation inhibitor which binds on ribosome in yeast and mammalian cells. However, thedirect interaction of EudiC and ribosome remained to be revealed. In this study, we investigate
the EudiC-binding proteins and the direct interaction between EudiC and Rps14 in mammaliancells and yeast.
For detection of the EudiC-binding protein, biotinylated photoaffinity probe of EudiC(EudiC-probe) was synthesized. IC50 values of synthesized EudiC-probe to HeLa cells were
almost the same with that of nat ural EudiC. Pull down assay using EudiC-probe from HeLa
cell and yeast lysate revealed that there were several binding proteins. Some of the proteins
were identified by western blotting and mass spectrometory as ribosomal proteins including
Rps14 and Rps5. Furthermore, melting point shifts were observed in the protein denature
assay using purified yeast ribosome in the presence of EudiC. These results indicate that
EudiC binds to ribosome directly and inhibit protein synthesis in yeast and mammalian cells.

150Oral Presentation

O-12

Floral fluorescent dyes and derivatives for cell staining
Nathana Barbosa Lopes1, Renata Rosito Tonelli2, and Erick Leite Bastos1
Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo
2
Departamento de Ciências Biológicas, Universidade Federal de São Paulo1

Betalains are water-soluble vacuolar alkaloids that replace anthocyanins in the pigmentationof some families of plants. According to their chemical structure, these pigments can be
subdivided into red-violet betacyanins or yellow betaxanthins. Interestingly, flowers whose
petals are pigmented with betaxanthins are fluorescent (Gandia-Herrero F et al., Nature
437: 334-334, 2005). Betanin (CI Natural Red 33, E-code E162, hº = 336, betanidin 5-O-βglucoside) is obtained almost entirely from red beet crops and is the only betalain approved by
the FDA for use in food. This betalain has been used in several different applications such asdyes in solar cells (Calogero G et al., Sol Energy 86: 1563-1575, 2012), as a starting material in
the semisynthesis of fluorescent probes for the live imaging of Plasmodium-infected red blood
cells (Gonçalves LCP et al., Plos One 8: e53874, 2013), and for the colorimetric quantificationof Bacillus anthracis spores (Gonçalves LCP et al., Plos One 8: e73701, 2013). Herewith we
describe the design of non-cytotoxic semisynthetic fluorescent betalains for the staining oftumor cells and parasites. The dyes were semisynthesized by aldiminic coupling between
betalamic acid, obtained from the alkaline hydrolysis of betanin, and adequate amines. The
resulting betaxanthins are fluorescent in aqueous media and relatively stable to hydrolysis innear-neutral pH. Submicromolar concentration of the derivatives bearing electron-withdrawing
groups conjugated to the betalainic 1,7-diazaheptamethinic were suitable for the fluorescent
staining of U87 human glioblastoma cells, but not the KATO III human gastric carcinoma
cell line. The results suggest that calcium transport may play a role in the internalization andaccumulation of the dye in subcellular compartments. Some derivatives were also effective tostain Tripanosoma cruzi, the causative agent of the neglected Chagas disease as well as Giardia
lamblia, the flagellated protozoan parasite that colonizes the duodenum causing giardiasis.

151

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O-13

Redesign of the colicin E7 nuclease domain into a controlled andspecific artificial enzyme
Eszter Németh1, Masamitsu Asaka2, Kyosuke Nagata2, Chris Oostenbrink3, andBéla Gyurcsik1,4
Department of Inorganic and Analytical Chemistry, University of Szeged, Hungary
2
Nagata Special Laboratory, Faculty of Medicine, University of Tsukuba, Japan
3
Institute of Molecular Modeling and Simulation, University of Natural Resources and Life Sciences, Austria
4
MTA-SZTE Bioinorganic Chemistry Research Group, Hungary
1Zinc-finger nucleases (ZFN) became useful tools for targeted cleavage of genomic DNA.
The majority of these chimeric enzymes use the FokI nuclease domain as their hydrolytic unit,
fused to the specific DNA-binding zinc-fingers. Since the DNA binding properties can beredesigned, ZFN-s provide a promising tool as therapeutic agents for monogenetic diseases.
However, the cytotoxic side-effect of the presently available ZFN-s prevents such applications.
Our research is focused on the design of a safely controlled ZFN being inactive in theabsence of the specific sequence substrate, while binding to the target DNA induces its active
conformation. Instead of the commonly used FokI domain, we fused NColE7 to zinc fingers.
The first part of the project included the study of the NColE7 protein, which is a bacterial
nonspecific metallonuclease. Its special structural feature is that its Zn2+-binding C-terminal
catalytic domain (HNH-motif) cooperates with the N-terminus of the protein during the
enzymatic reaction. We would like to use this feature in the redesign procedure (Czene A
et al. J Biol Inorg Chem. 2013,18(3):309-21, Németh E et al. Protein Sci 2014 DOI: 10.1002/
pro.2497).
In the following step computational modelling was applied to design the insertion of thezinc-fingers in between the N- and C-terminal parts of NColE7 (Németh E et al., J Comput
Aided Mol Des 2014 DOI 10.1007/s10822-014-9765-8). Finally, the genes encoding the four
designed proteins have been constructed and the proteins were expressed in E.coli cells. The
DNA-binding affinity, specificity and nuclease activity of the proteins were studied. The mostpromising model was shown to perform specific single strand cuts on the recognition sequence
containing plasmid DNA.

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O-14

GPNMB impacts to invasive properties of bladder cancer
Tomokazu Kimura1,2, Yukari Okita2, Yukihide Watanabe2, Hiroyuki Suzuki2,
Hiroyuki Nishiyama1, and Mitsuyasu Kato2
Department of Urology, Faculty of Medicine, University of Tsukuba
Department of Experimental Pathology, Faculty of Medicine, University of Tsukuba
1

2

Glycoprotein non-metastatic melanoma protein B (GPNMB) is a type 1 transmembrane
glycoprotein. It is expressed in normal tissue and also in cancer cell. Recent evidence describes that GPNMB expression correlates with metastasis and poor prognosis of the patientswith several cancer. We evaluated how GPNMB impact on invasion of bladder cancer cells.
We examined mRNA and protein expression of GPNMB in nine cell lines using realtimePCR and western blotting. To investigate how GPNMB contributes to the aggressive phenotype, we knocked it down by short hairpin RNA or over expressed human GPNMB in invasive
bladder cancer cell lines. Cell invasion was examined by the transwell assay with matrigel
coating.
Every cell line expressed GPNMB mRNA and protein in each manner. There was any
relation between GPNMB expression and invasiveness. However, the short hairpin RNA targeting GPNMB significantly suppressed invasive ability in bladder cancer cells. Conversely,
overexpressing wild type GPNMB greatly promoted invasiveness in these cells.
GPNMB is correlated to invasive properties of bladder cancer.

153

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O-15

Cooperative expression of transmembrane prostate androgen
induced protein –TMEPAI by TGF-β and EGF signaling
Thanh Thao Vo Nguyen, Shun Azami, Yukihide Watanabe, and Mitsuyasu Kato
Department of Experimental Pathology, Graduate School of Comprehensive Human Sciences andFaculty of Medicine, University of Tsukuba, JapanTMEPAI is a transmembrane protein that was identified as a direct target gene of transforming growth factor-β (TGF-β)/Smad signaling. TMEPAI participates in negative feedback regulation of the duration and intensity of TGF-β/Smad signaling. Moreover, it has beenreported that the expression of TMEPAI is also enhanced by EGF signaling; however, themechanism in which TMEPAI is regulated by EGF signaling remained unclear. Here, wereport that TGF-β and EGF signaling cooperatively regulate the transcription of TMEPAI. In
addition, expression of TMEPAI in cancer cells was significantly suppressed by MEK kinase
inhibitor U016, suggesting that the EGFR/Ras/MAPK pathway involved in the regulation of
TMEPAI. There are three ELK-1 binding sites in the first intron of the TMEPAI gene. EGFinduced activation of ELK-1, but not the mutant ELK-1S383A potentiated the TGF-β-induced
transcriptional activation of the TMEPAI gene. Mutations in the ELK-1 binding sites abrogated the transcriptional activation of a TMEPAI reporter. Furthermore, the Chromatin
immunoprecipitation (ChIP) assay reveals that ELK-1 binds to its binding sites in the first intronof the TMEPAI gene in response to EGF signaling. Taken together, these results indicatedthat the EGF/Ras/ELK-1 pathway, together with TGF-β signaling regulates the expression of
TMEPAI.

154

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O-16

Genetic depletion and pharmacological targeting of αv integrin
in breast cancer cells impairs metastasis in zebrafish and mouse
xenograft models
Yihao Li1, Yvette Drabsch1, Philippe Pujuguet2, Theo van Laar1, Long Zhang1,4,
Hans van Dam1, Philippe Clément-Lacroix2, and Peter ten Dijke1,3
Department of Molecular Cell Biology, Cancer Genomics Centre Netherlands andCentre for Biomedical Genetics, Leiden University Medical Center
2
Galapagos SASU, Romainville3
Ludwig Institute for Cancer Research, Science for Life Laboratory, Uppsala University
4Life Sciences Institute, Zhejiang University
1

Increased expression of αv integrins is frequently associated with tumor cell adhesion,
migration, invasion and metastasis, and correlates with poor prognosis in breast cancer.
However, the mechanism by which αv integrins can enhance breast cancer progression is stilllargely unclear. The effects of therapeutic targeting of αv integrins in breast cancer also have
yet to be investigated. In these study, we found that Genetic interference and pharmacologicaltargeting of αv integrin with GLPG0187 in different breast cancer cell lines inhibited theirinvasion and metastasis in the zebrafish xenograft model. Depletion of αv integrin in MDAMB-231 cells inhibited the expression of the mesenchymal markers and TGF-β pathway.
TGF-β induce αv expression and cell migration in MDA-MB-231 cells. In a preclinical mousemodel of breast cancer, GLPG0187 inhibited the progression of bone metastasis. Maximum
efficacy of inhibition of bone metastasis was achieved when GLPG0187 was combined withthe standard-of-care metastatic breast cancer treatments. These findings show that αv integrin
is required for breast cancer metastasis by maintaining the invasive mesenchymal phenotypeof the tumor cells. Our results also provide evidence that targeting αv integrin could be aneffective therapeutic approach for treatment of breast cancer tumors and/or metastases thatoverexpress αv integrin.

155

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O-17

Analysis of proliferation in hematopoietic stem cell development
Antoniana Batsivari, Stanislav Rybtsov, David Hills, Suling Zhao, and Alexander Medvinsky
MRC Centre for Regenerative Medicine, University of Edinburgh, UK

The origin and biology of hematopoietic stem cells (HSCs) during embryogenesis has
been an intensely studied topic. Definitive HSCs are generated intra-embryonically in theaorta-gonad-mesonephros (AGM) region of the mid-gestation embryo (A. Medvinsky and E.
Dzierzak, Cell, 1996). Recent in vitro research revealed that HSCs emerge through a multistep
maturation process and are slowly cycling in comparison with the progenitor’s population (S.
Taoudi et al., Cell Stem Cell, 2008, S. Rybtsov et al., JEM, 2011; S. Rybtsov et al., 2014).
However, the exact role of proliferation during early HSC development remains unclear.
Here we used Fucci transgenic mouse lines that enable visualisation of the cell cycle. Thissystem is based on two fluorescent reporters of cell cycle proteins (Geminin and Cdt1) whose
protein levels inversely oscillate during cell cycle (A. Sakaue-Sawano et al., Cell, 2008). Ourfunctional and phenotypic analysis showed that pre-HSC type I cells mainly reside in G0-G1
phases and thus likely cycle slowly. Meanwhile, pre-HSC type II population appears to be in
both S-G2-M and G0-G1 phases and divides in a synchronised manner. Wholemount staining
showed that cells within intra-arterial hematopoietic clusters are predominantly found in
S-G2-M phases, whereas some cells at the base of clusters, which are in close contact with thevascular endothelium reside in G0-G1 phases. Fetal hematopoietic cells from E14.5 fetal livers
were also characterised with regard to their cell cycle status with phenotypic and functional
experiments. Notably, the multipotency of hematopoietic cells could be correlated with G0-G1
cell cycle phases. HSCs in the fetal liver mainly reside in G0-G1 phases, whereas committedprogenitors are found mainly in S-G2-M phases. As expected, HSCs in bone marrow are
mainly quiescent. Overall, our data indicate that transition from pre-HSC type I to pre-HSC
type II is accompanied by increase in proliferation and that HSCs become progressively
quiescent during development.

156

Oral Presentation

O-18

SIK2 controls dynamics of insulin production inpancreatic β cells
Pei-Han Tai1,2, Hisashi Oishi2, Satoru Takahashi2, and Han-Yi Chou1
Graduate Institute of Oral Biology, National Taiwan University, Taiwan
Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Japan
1

2

Salt-inducible Kinase 2 (SIK2), is a member of AMPK family, has been reported to play
an important role in metabolism and it also regulates cell survival by driving IRS-2 (insulin
receptor substrate 2) gene expression upon glucose stimulation. In our group, the SIK2
expression was found in insulin vesicles in cytosol; however, the specific function of SIK2
in pancreatic β cells remains unclear. Here we present evidence that the SIK2 participates inregulating insulin secretion. SIK2 is localized to insulin containing large dense-core vesicles
and is phosphorylated at residue S587 upon glucose stimulation. This phosphorylation isaccompanied by mobilization of the reserved pool insulin vesicles towards the cell peripheryfor exocytosis. Furthermore, inactivation of SIK2 kinase activity results in unconstrained
reserved pool insulin vesicle mobilization and concomitant increase in insulin secretion.
Our data suggest that SIK2 participates in regulating insulin secretion through its kinase
activity, which imposes constrain for insulin release. For further examine the physiologicalrelevance of SIK2 in pancreatic β cells, the β cell-specific sik2 transgenic mice were generated.
Glucose-stimulated insulin secretion test from transgenic mice fed with regular diet showed
higher fasting blood glucose and lower insulin secretion compared to control. Consistently,
transgenic mice under metabolic stress by feeding high fat diet showed significant decreased
in glucose clearance rate. This phenotype revealed that over-expressed SIK2 protein would
lead to defect of insulin secretion. In addition, both down-regulation of Ins1 mRNA level andslightly increased α cells, an event in early stage of diabetes, were observed. These collecting
phenotypes indicated that the sik2 over-expression might have the tendency for development
abnormal glucose homeostasis. Taken together, our results uncovered a novel function of
SIK2 in the regulation of insulin secretion in β-cells via insulin vesicle transportation. Thesefindings suggested that SIK2 is an attractive target for developing new strategies for diabetes.

157

Oral Presentation

O-19

MafB deficiency impairs the apoptotic cell clearance ofmacrophages
Tran Thi Nhu Mai1,2, Michito Hamada1,2, Risako Shiraishi1, Keigo Asano1,2, andSatoru Takahashi1,2Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba
12Macrophage is one of the main phagocytes recognize and engulf apoptotic cells to maintain peripheral immune tolerance. The failure of apoptotic cell clearance by macrophages
induces autoimmunity. Although most of apoptotic cell recognition factors have been identified, the mechanism of transcriptional regulation of these factors remains unknown. MafB
is a transcription factor that affects proliferation and differentiation of macrophage. Here weshow that MafB involves in apoptotic cells clearance. The depletion of MafB in macrophagedecreases the expression of apoptotic cell recognition genes, especially C1qa, C1qb, C1qc,
leads to the impairment of phagocytosis both in vitro and in vivo. While wild-type serum isable to recover phagocytosis in Mafb-/- macrophages, C1q-depleted serum could not rescue thisphenotype. In addition, promoter analysis of C1q genes showed that MafB directly regulates
expression of C1qa, C1qb and C1qc. In Mafb-/- mice, production of autoantibody is increased.
Our results indicate that MafB might has a pivotal role in phagocytosis of apoptotic cells via
C1q regulation.

158

Oral Presentation

O-20

A meta-analysis of experimental studies of radiation attenuatedschistosome vaccines in the animal model
Mizuho Fukushige1, Kate M. Mitchell2, Claire D. Bourke3, Mark E.J. Woolhouse1, andFrancisca Mutapi4
Centre for Immunity, Infection and Evolution, College of Medicine and Veterinary Medicine,
University of Edinburgh, Edinburgh, UK
2
Department of Global Health and Development, London School of Hygiene and Tropical Medicine,
London, UK
3
Centre for Immunology and Infection, University of York, York, UK
4
Institute for Immunology and Infection Research, Centre for Immunity, Infection and Evolution,
School of Biological Sciences, University of Edinburgh, Edinburgh, UK
1

BACKGROUND: Schistosomiasis is a water-borne parasitic disease of great public healthimportance. There has been considerable effort for several decades towards the developmentof a vaccine against schistosomiasis. Numerous animal experimental studies using attenuatedschistosome parasites for vaccination have been published since the 1960s. However, thesehave never been systematically analysed. The aim of this study is to identify measurable
experiment conditions that affect the level of protection against re-infection in vaccinatedanimals.
METHODS: Following a systematic review, a total of 957 observations were extracted from
130 articles meeting the search criteria (published 1963-2007). Of these, 755 observations from
106 articles quantified the protective effect of irradiated S. mansoni cercariae vaccination in
the mouse model. The analysis was initially conducted using data for S. mansoni in mice, andthen expanded to other animal host species (rat and baboon) and other schistosome species (S.
haematobium, S. japonicum, and S. bovis). Random effects meta-regression models, weighted
by the study size (number of control animals) were used to identify the influential predictors.
RESULTS: Three predictors were found to have statistically significant effects (P<0.05) on
the level of protection: number of immunizing parasites; irradiation dose; and time between thelast immunization and challenge. Increasing numbers of immunizing parasites had a positiveeffect on fraction protected whereas increasing radiation dose and time to challenge infection
had negative effects. Comparable results were obtained using data on S. japonicum in miceand S. mansoni in rats.
CONCLUSIONS: The models showed that the irradiated cercariae vaccine has a potentialof achieving as high as 85% protection with a single vaccination. Protection declines slowly
over time but persists for at least 8 months after the last immunization. These findings provide
insights into the mechanisms of immunity to schistosome infection and the optimal delivery
of attenuated parasite vaccination.
159

Oral Presentation

O-21

The effect of temperature on all-cause mortality in the three
metropolitan cities in the Philippines, 2006-2010
Xerxes Seposo1 and Yasushi Honda2
Graduate School of Comprehensive Human Sciences, University of Tsukuba
2Faculty of Health and Sports Sciences, University of Tsukuba

1

Effects of temperature on all-cause mortality have been extensively studied in temperate
countries such that in US, UK, Japan, Korea and China, but only few studies were carriedout in tropical countries in the Southeast Asian region. In the previous study we found outthat mortality becomes higher when daily average temperature exceeds 30 degrees Celsius
in the National Capital Region. This time-series study explores the effect of temperature
on mortality across the three metropolitan cities. Average daily temperature, daily allcause mortality data, and other daily meteorological parameters were collected from 20062010 from relevant government agencies. We used Poisson regression model accounting foroverdispersion in fitting the city-specific effects of daily temperature on daily mortality. Metaanalysis was carried out using mvmeta package of R stastistical programming in analyzing therelationship of temperature on mortality across the cities. Results showed that at Lag 0, thecities are heterogenous from each other compared to the other lags. Meta-regression showedthat latitude does not modify the hot effects in the different lags which is in contrast to existingstudies. SES (Socioeconomic Status) and education were not included in the study due to data
unavailability. Further research is warranted in quantifying the effects of SES and education.

160

Oral Presentation

O-22

The early marriage and maternal health care utilization in rural
Bangladesh: Analysis of Bangladesh Demographic Health Survey
Md. Harunor Rashid, Enbo Ma, and Yukiko Wagatsuma
Clinical Trial and Clinical Epidemiology, Graduate School of Comprehensive Human Sciences,
University of Tsukuba

Introduction: The marriage before 18 years of age is a major public health problem in bothdeveloped and developing countries. The situation of pregnancy and childbirth related
morbidity and mortality is worse in Bangladesh because of low utilization of maternal healthservices. Currently the World Health Organization is emphasized in reviewing and revising
policies inproviding access to contraception and reproductive health care services.
Objective: This study aimed to explore the relationship between early marriage and utilizationof maternal health services inrural Bangladesh.
Methods: This study used the Bangladesh Demographic Health Survey (BDHS) databasefrom 1994 to 2011 and extracted out 32,565 maternal cases. The early married categorized as
married less than18 years of age. The BDHS had a large sample and internationally accepted
method.
Results: The early marriage was 89.9% in non-educated women and 25.6% in higher educatedwomen. Compared with adult marriage women, the early marriage women was lower in thecontraception utilization (54.4% vs 57.5%, P<0.0001), Antenatal Natal Care (ANC) rate (46.2%
vs 69.4%, P<0.0001), and the facility delivery (13.7% vs 39.9%, P<0.0001). Adjusted odd ratio(95% Confidence Interval) of maternal health service utilization by early marriage womencompared with adult marriage women was 0.85 (0.76-0.94) for contraceptive utilization, 1.38
(1.23-1.56) for ANC and 1.4 (1.27-1.71) for facility delivery.
Conclusion: The utilization of contraception, ANC and facility deliveries are poorer among
the early marriage women than adult marriage women. This information would be useful inreviewing the policies of early marriage.

161

Oral Presentation

O-23

Relationships of family function, QOL and family empowermentof the family rearing a child with severe motor and intellectual
disabilities at home
Keiko Yamaguchi1 and Rie Wakimizu2
Clinical nursing section, Faculty of Nursing Sciences, University of Tsukuba
Department of Child Health Care Nursing, Division of Health Innovation and Nursing,
Faculty of Medicine, University of Tsukuba
1

2

There are approximately 36,650 children with severe motor and intellectual disabilities
in Japan, on national average about 70% of those lives local life (Ozawa et al., Brain &Development 39;279-282, 2007.). In the family with seriously disabled child, especiallyprimary caregiver, often mother has physical and mental burden immeasurably. We conducteda study on primary caregiver and other family members, focused on their family function,
each QOL, and family empowerment by questionnaire. Thirty-three family units participatedin our study. The questionnaire included Family Assessment Device (FAD), WHOQOL and
KINDLRQOL, and Family Empowerment Scale (FES). Age of seriously disabled child is
4-22 years old. Mean age of primary caregiver is 40.8 years old (range 30-53), 82% of themhas become out of condition physically or mentally. All primary caregivers have a role inrearing are mothers. All domains of FAD had a strong correlation with psychological healthand social relationships of WHOQOL (each, p˂0.01). And domains of social relationships
and environment of WHOQOL had a correlation with family empowerment function of FES(p˂0.01, p˂0.05). About brothers and sisters’ affective intervention of FAD correlated with
self-esteem of KINDL (p˂0.05). Our results suggested each of these outcomes was intimately
linked cyclically. And we discussed it is necessary to enhance family function, QOL, family
empowerment totally. Therefore, it is required to build or improve the comprehensive care
support system / empowerment system in community life, for the family rearing child withsevere motor and intellectual disabilities at home, in Japan.
Reference
Ozawa H et al, The Present Situation of Children with Psycho-Motor Disabilities and Their
Parents. Brain & Development 39(4);279-282, 2007.

162

Oral Presentation

O-24

How a group-based anger-management parenting programchanged mothers’ cognition, attitude and behavior
Hiromi Tobe and Yoko Emori
Maternity Nursing and Midwifery, Faculty of Medicine, University of Tsukuba

Background: Parenting can be very challenging since it requires much time, energy and patience; while at the same time, parents get almost no training to fulfill this difficult duty. Manymothers rearing children claim that they get too angry with their children too often and express
their anger in negative ways, and they feel guilty about it.
Objective: This study aimed to examine how participating in a group-based anger-management parenting program changed mothers’ cognition of their anger, their attitude and their
behavior toward their children.
Methods: A group-based parenting program, applying both anger-management skills and parenting skills, was conducted for 50 mothers. Each group consisted of 5-8 mothers who had atleast one child aged 4-12 years and wanted to cope with their anger toward their children inbetter ways. Each group received three two-hour long programs. The trained anger-management facilitator with parenting experience led the program by giving lectures and supporting
the participants by frankly discussing their problems, negative feelings and desires. At the second and the third program, the participants reported the changes they had experienced using
the skills and knowledge they had obtained in the programs. Also an original questionnaire
was used to examine how the mothers changed.
Results: The following are the statements with which most mothers either agreed or strongly
agreed: I have increased my knowledge and understanding of anger. I feel less guilty when I
feel or express my anger. I can see my anger more objectively. I get angry with my child lessoften. I express my anger with harsh words less often. I have more realistic expectations toward my child. I try to focus on the things my child can do rather than the things he/she can’t
do. I try not to worry too much about my child’s future.
Conclusion: By participating in the group-based anger-management parenting program,
mothers increased their knowledge and understanding of anger, eased their guilt, changed
their perspective of the child, decreased the frequency of their anger and expressed their anger
in more appropriate ways.

163

Poster Presentation

P-1

The effect of different soil utilizition on the RIP of 137Cs
contaminated soil from northern Japan
Min Li1, Kenji Tamura2, Junko Takahashi2, and Yuichi Onda2
1

Graduate School of Life and Environmental Sciences, University of Tsukuba
2Faculty of Life and Environmental Sciences, University of Tsukuba

In the earthquake of Mar. 11st 2011, the explosion of Fukushima Dai-ichi NPP madethe rounding environment contaminanted, Caesium-137 is the most important long-term
contributor to environmental contamination because of the high release rate, and longer halflife. The extent of radiocaesium retention in soil is important to quantify the risk of further
foodchain contamination. Modelling how the caesium transfer from soil to plants and hence
into the food chain is also a complicated work. Therefore, in the research the immobilizationof Cs and the Radiocaesium Interception Potential have been focused on.Radiocaesium
interception potential (RIP), which is introduced by Cremers et al. has proven to be a usefulparameter to characterise the sorption of radiocaesium by soils, is an intrinsic soil parameter
which can be used to categorize soils or minerals in terms of their capacity to selectively
adsorb radiocaesium. In the research, the simpllified experiment by J.Wauters was used. The
RIP is defined as
RIP = [FES] KcFES( Cs + )K+
where [FES] is the sorption capacity for radiocaesium by the frayed edge sites (FES) of
micaceous clay minerals and K FES (Cs+/K+) is the selectivity coefficient of the ion exchange
Cs+/K+ .
The objective of the research is analyze the effect of content of C, N and the soil type on the
RIP, and the movement and migration of Cs in soil. For result: RIP of samples from Fukushima
are 289.820~2150.915mmol/ kg; RIP of samples from Miyagi are 705.529~1104.083 mmol/ kg;
RIP of samples from Ibaraki are 256.971~914.704 mmol/ kg the RIP in forest soil is higher
than in farmland.

164

Poster Presentation

P-2

Function characterization of a second and novel mRNA capping
apparatus in Trypanosoma brucei
Anna Ignatochkina and Kiong Ho
Infection Biology Section, Faculty of Medicine, University of Tsukuba

The 5’ end of kinetoplastid mRNA possesses a hypermethylated cap 4 structure, which
is derived from standard m7GpppN with additional methylations at seven sites within
the first four nucleosides on the spliced leader RNA by trans splicing. Earlier studies
indicated that Trypanosoma brucei encodes two separate capping apparatus, exemplified byguanylyltransferases TbCgm1 and TbCe1. The TbCgm1 was shown to be expressed in the
nucleus and was responsible for capping of the spliced leader RNA. In contrast TbCe1 waspredominantly expressed in the cytoplasm, but the biological function and it`s RNA target is
not known. The aim of this project is to understand the function of TbCe1 in Trypanosoma
RNA metabolism. Our results demonstrate that TbCe1 is a bifunctional capping enzyme with
an N-terminal phosphotransferase and C-terminal guanylyltransferase activities, and may
function to regulate the abundance of translatable mRNA in the cytoplasm. This study may
lead to a new paradigms in cellular mRNA regulation.

165

Poster Presentation

P-3

The genetic compatibility among influenza virus polymerase
subunits for the generation of reassortant viruses
Yoshimi Harada1,3, Kyosuke Nagata2, and Atsushi Kawaguchi1,2,3
Department of Infection Biology,
2
Faculty of Medicine and3
Graduate School of Comprehensive Human Sciences, University of Tsukuba
1

The genome of influenza virus consists of eight-segmented and different viral protein-coded
RNAs of negative polarity. When different influenza strains coincidentally infect a single cell,
new type of viruses will appear by reassortment of segmented genomes. Theoretically, 256
reassorted genotypes can be generated from two distinct strains, but the infectious reassortants
hardly emerge in nature, suggesting that the compatibility between viral genomes or/and
encoded viral proteins regulates the product efficiency of infectious reassortants. However,
the molecular mechanism responsible for this compatibility is largely unknown.
Here we found that genetic interaction between viral polymerase subunits is important forthe production of reassortant viruses. We generated single gene reassortants between A/Puerto
Rico/8/34 (H1N1) (PR8) and A/Hong Kong/483/97 (H5N1) (HK483) by reverse genetics system.
Among them, reassortant viruses possessing genes encoding PB2 and PA viral polymerase
subunits from HK483 (designated HK483-PB2 and HK483-PA, respectively) with other PR8
genes were hardly recovered. The viral polymerase consisting of PB1, PB2, and PA subunits isrequired for the viral genome replication and transcription, and the replicated viral genomes areassembled into viral ribonucleoprotein (vRNP) by interacting with viral polymerase complexes
and nucleoprotein. Since HK483-PB2 with PR8 other subunits did not have the RNA synthesis
activity, it is likely that the genetic compatibility among viral polymerase subunits is important
for the viral polymerase activity. In contrast, the RNA synthesis activity of HK483-PA with
PR8 other subunits was unaffected, suggesting that the genetic compatibility among viral
polymerase subunits is also responsible for a post replicational process(es). To address this,we examined the intracellular localization of vRNP. After the nuclear export, vRNP with
HK483-PA and PR8 other subunits was found in unknown cytoplasmic granules at juxtanuclear regions. Taken altogether, it is possible that the viral polymerase complex is involvedin the intracellular transport of vRNP to the assembly site of viral particles beneath the plasma
membrane.

166

Poster Presentation

P-4

A Cullin-related protein regulates posttranslational modificationof PML
Tomomi Fukuda, Yu Kigoshi, and Tomoki Chiba
Graduate School of Life and Environmental Sciences, University of Tsukuba

Posttranslational modification of proteins is involved in diverse phenomena. SUMOylation
is a posttranslational modification that regulates various cellular processes, includingtranscription, cell-cycle progression and DNA damage repair. PML is known to be
SUMOylated and also has a SUMO interacting motif, both important for PML Nuclear Bodies(PML-NBs) formation. PML-NBs are (de)SUMOylation platforms where SUMO is coupled
to or detached from its target protein leading to regulation of nuclear activities. Furthermore,
SUMO2 modification of PML leads to its ubiquitination by ubiquitin E3 ligase RNF4 in the
PML-NBs and degradation by the proteasome.
Recently, we revealed that a Cullin-related protein iCul inhibits the ubiquitination activityof Cullin3-based E3 ligases. In addition, recent proteomics analysis revealed SUMO2 as iCul
interaction partner. Therefore, we hypothesised that iCul may be associated with protein
SUMOylation. Here, we demonstrate that iCul interacts with PML and SUMO E2 enzyme
Ubc9, and that iCul inhibits SUMOylation and ubiquitination of PML. Immunocytochemical
analysis showed that both iCul and Ubc9 accumulate to PML-NBs by PML overexpression.
These results suggest that iCul negatively regulates posttranslational modification of PML at
PML-NBs.

167

Poster Presentation

P-5

A novel transcriptional regulation of steroid hormone
biosynthesis in Drosophila melanogaster
Tatsuya Komura-Kawa1, Sora Enya1, Tetsuro Shinoda1, Michael B. O’Connor3, andRyusuke Niwa1,4
Graduate School of Life and Environmental Sciences, University of Tsukuba, Japan
2
Division of Insect Science, National Institute of Agrobiological Sciences, Japan3
Department of Genetics, Cell Biology and Development, University of Minnesota, USA
4
PRESTO, JST, Japan1

In insects, molting and metamorphosis are regulated by the steroid hormones calledecdysteroids, such as ecdysone and its derivative 20-hydroxyecdysone (20E). During postembryonic development, ecdysteroids are synthesized from dietary cholesterol via a series ofhydroxylation and oxidation steps in the prothoracic gland (PG). The steroidogenic function of
the PG is defined by the restricted expression of ecdysteroidogenic enzyme genes. The precise
dynamics of ecdysteroid titers and the cell-type specific pattern imply a tight transcriptional
regulation of these enzymes in the PG. However, the PG specific transcriptional regulatory
networks have not yet been fully elucidated. In this presentation, we report a gene tentatively
called ouib, encoding a C2H2-type Zn-finger transcription factor, plays an essential rolein controlling expression of the ecdysteroidogenic enzyme gene in the fruit fly Drosophilamelanogaster. ouib is predominantly expressed in the PG. A PG-specific RNAi knock-down
for ouib resulted in larval developmental arrest, which was rescued by administering 20E.
Interestingly, ouib RNAi animals exhibited a drastic reduction of expression level of one but
not any other ecdysteroidogenic enzyme genes examined so far. Moreover, we establishedouib mutant lines by CRISPR/Cas9 system, which showed similar phenotypes to ouib RNAianimals. A luciferase-reporter assay revealed that Ouib protein indeed had transcriptional
activity for the specific ecdysteroidogenic enzyme gene. Using this assay system, we identified
a specific enhancer element necessary for the transcriptional regulatory activity of Ouib. Our
study illustrates that a certain transcription factor is required for the very small subset ofsteroidogenic gene(s) essential for specific catalytic step(s), providing a novel insight into theregulatory mechanism of steroid hormone biosynthesis.

168

Poster Presentation

P-6

The budding yeast AMPK ortholog Snf1 negatively regulates
endoplasmic reticulum stress response
Yuto Masuda, Mizuno Tomoaki, and Kenji Irie
Department of Molecular Cell Biology, Graduate School of Comprehensive Human Sciences,
University of Tsukuba

AMP-activated protein kinase (AMPK) is highly conserved in eukaryotes and importantfor cellular energy homeostasis. The budding yeast ortholog of AMPK, Snf1, is required
primarily for the adaptation of yeast cells to glucose limitation and for growth on carbon
sources that are less preferred than glucose. Snf1 is also involved in responses to otherenvironmental stresses, including heat shock, alkaline pH and oxidative stress. However, itremains unknown whether Snf1 functions in endoplasmic reticulum (ER) stress response. In
this study, we found that Snf1 is involved in ER stress response. The snf1Δ mutation exhibits
resistance to ER stress. This snf1Δ mutant phenotype is rescued by expression of wild-type
Snf1, but not by expression of a kinase dead form of Snf1, suggesting that Snf1 negatively
regulates ER stress response in a manner dependent on its kinase activity. Previous studies
demonstrated that Snf1 activity is regulated by its phosphorylation: the phosphorylated form isactive; the dephosphorylated form is inactive. Therefore, we examined the effect of ER stresson Snf1 phosphorylation and found that the phosphorylated form of Snf1 is upregulated by
ER stress. Taken together, these results suggest that ER stress activates Snf1, which, in turn,negatively regulates ER stress response.

169

Poster Presentation

P-7

Challenges for sustainable tomato production:
Isolation of a novel tomato mutant with enhanced fruit set
efficiency and candidate gene approaches
by Next Generation Sequencing
Hitomi Takei, Yoshihito Shinozaki, Hiroshi Ezura, and Tohru Ariizumi
College of Agrobiological Resource Sciences, University of Tsukuba

Tomato (Solanum lycopersicum) belongs to the flowering plant family Solanaceae that
includes many important vegetable crops. Although tomato is cultivated worldwide, its
production strongly depends on the successful fruit set, which is the developmental transition
from ovary to fruit after pollination and fertilization. However, fruit set is easily hindered byenvironmental conditions such as high/low temperatures. To improve the efficiency of fruit
set under the severe conditions, farmers must artificially induce pollination by application ofplant hormones or with insect vectors, although such artificial pollination systems require formany costs and working time. Meanwhile, parthenocarpy, a fruit formation in the absence ofpollination and fertilization, is an attractive trait to relieve farmers from artificial pollination.
To date, several genetic loci inducing parthenocarpy, known as pat, have been identified, butthey often carry undesirable fruit traits (e.g. over-softening, malformation of leaf and fruit etc.)
simultaneously. Therefore development of new parthenocarpy tomato varieties without these
undesirable traits is an important subject for agriculture.
The aim of this research is to identify the responsible gene for parthenocarpy by using
map-based cloning and next generation sequencing (NGS). To isolate novel gene associatewith parthenocarpy, we have been developing mutagenized populations of tomato in variety‘Micro-Tom’ and successfully isolated a mutant that exhibits efficient parthenocarpy. By the
map-based cloning, the genetic locus responsible for mutant phenotype was refined to ~2.0 Mbp
in physical length which spans 205 open reading frames (ORFs). Furthermore NGS analysis
revealed DNA substitutions or deletions within several ORFs. Here we present the evidence
that one mutation is tightly associated with mutant phenotype. Future work will determine
whether this mutation is responsible for the mutant phenotype by genetic complementation
experiments. Our research would provide a great potential for agriculture to produce fruits
easily and efficiently, result in improved yield of tomato.

170

Poster Presentation

P-8

Construction of genetic analysis available multidrug sensitive
yeast strain by both the disruption of drug efflux system and theconditional repression of membrane barrier system
Takumi Chinen1, Yoko Nagumo2, and Takeo Usui2
Graduate School of Life and Environmental Science, University of Tsukuba
2Faculty of Life and Environmental Sciences, University of Tsukuba

1

The budding yeast Saccharomyces cerevisiae, is a useful tool for chemical biology studies,including drug screening, target identification, and speculation, and the verification of bioactive
compounds. However, the high-level drug resistance of S. cerevisiae makes analyses ofcompounds difficult. There are two systems conferring multidrug resistance in S. cerevisiae,
one is the drug efflux system, and the other is the permeability barrier system. The drug efflux
system is composed of ABC transporters that export xenotoxic compounds to outside of thecells or inside of vacuole. The major factor of the permeability barrier system is ergosterolin the yeast plasma membrane. These mechanisms confer drug resistance against different
group of drugs, thus to make yeast sensitive to several compounds, the disruption of ABC
transporters and ergosterol biosynthetic genes (ERG genes, e.g., ERG6) are required. However,
the gene disruption involved in ergosterol biosynthesis, especially erg6 gene, decreases thetransformation, mating and sporulation efficiencies, which are required for genetic analyses.
In this study, we constructed 12geneΔ0HSR-iERG6 by introduce the ERG6 conditional
expression system based on GAL1 promoter into 12geneΔ0HSR, a strain lacks drug efflux
system by disruption of ABC transporters on the plasma membrane (T. Chinen et al., Biosci.
Biotechnol. Biochem., 75, 1588-1593 (2011)). 12geneΔ0HSR-iERG6 showed improved drug
sensitivity to several compounds under glucose condition, and its drug sensitivity spectrum
was resembled with that of erg6 disruptant of 12geneΔ0HSR. These results suggest that
12geneΔ0HSR-iERG6 lacks both the drug efflux system and the membrane barrier system
required for multidrug resistance. Moreover, 12geneΔ0HSR-iERG6 showed sufficientefficiencies of transformation, mating, and sporulation for genetic analysis under the galactose
condition. Therefore, 12geneΔ0HSR-iERG6 is a useful tool for chemical biology studies
including the drug screening, target identification (T. Chinen et al., J. Gen. Appl. Microbiol.,in press).

171

Poster Presentation

P-9

Involvement of the small GTPase Arf6 in PDGF-induced
dorsal ruffling
Taito Miyachi, Tsunaki Hongu, Yuji Funakoshi, and Yasunori Kanaho
Department of Physiological Chemistry, Faculty of Medicine and Graduate School ofComprehensive Human Sciences, University of Tsukuba

Activation of receptor tyrosine kinases induces the dynamic rearrangement of plasma
membrane structure, such as ruffle formation, which is mediated by the reorganization ofactin cytoskeleton at plasma membrane. The ruffling membranes are subdivided into two
independent types. One is the peripheral ruffle, which is upward-bending structures of the cell
membrane at the leading edge of cells and plays crucial roles in cell adhesion and directed cell
motility. Another is the dorsal ruffle, which is characterized by their unique appearance on thedorsal surface of cells as a ring-shaped structures and is essential for receptor internalizationand cell migration. Although formation of both types of ruffles require the reorganization ofactin cytoskeleton, precise regulatory mechanism has not yet been clarified.
The small GTPase ADP-ribosylation factor 6 (Arf6) exclusively localizes to the plasma
membrane and endosomal compartments, and plays important roles in actin cytoskeleton
reorganization. We have previously found that Arf6 regulates the growth factor-induced
peripheral ruffle formation. However, the involvement of Arf6 in dorsal ruffle formation has
not yet been clarified. Here, we show that Arf6 also regulates dorsal ruffle formation. In
response to the platelet-derived growth factor (PDGF) stimulation, Arf6 was activated andlocalized at dorsal ruffle membrane in mouse embryonic fibroblasts. In addition, genetic
ablation of Arf6 suppressed PDGF-induced dorsal ruffle formation. These results demonstrate
the critical role of Arf6 in tyrosine kinase receptor-mediated membrane ruffle formation.

172

Poster Presentation

P-10

Tumor-infiltrating CD8 T lymphocytes are decreased in
Phospholipase D2 knockout mice
Ngo Thai Bich Van, Takanobu Sato, Tsunaki Hongu, Yuji Funakoshi, and Yasunori Kanaho
Department of Physiological Chemistry, Faculty of Medicine and Graduate School ofComprehensive Human Sciences, University of Tsukuba

Phospholipase D (PLD) hydrolyzes a membrane phospholipid phosphatidylcholine (PC)to produce choline and the lipid messenger phosphatidic acid (PA). Two isozymes, PLD1 and
PLD2 have been identified in mammalian cells. Through the production of PA, both PLD1 and
PLD2 are involved in various cellular functions such as vesicular trafficking, intracellular secretory response, cell motility, and cell proliferation. Recently, it has been reported in a mousemodel that PLD1 is involved in tumor growth through the promotion of tumor angiogenesis.
PLD2 is also implicated in tumor growth and metastasis, however, the mechanism how PLD2
is involved in cancer progression remains to be elucidated. Here, by using PLD2-knock out(KO) mice, we demonstrate that PLD2 suppresses tumor growth through the regulation of Tcell functions.
To investigate the function of PLD2 in tumor growth, we subcutaneously transplanted
B16 melanoma cells into WT and PLD2-KO mice. Unlike the previous report on PLD1-KO
mice, the tumor growth of B16 melanoma cells was significantly enhanced in PLD2-KO mice,indicating that PLD2 has a suppressive function in tumorigenesis. When we analyzed sectionsof the tumors, the number of apoptotic cells in the tumor was decreased in PLD2-KO mice,
whereas tumor angiogenesis was not affected. These results indicate that enhancement oftumor growth in PLD2-KO mice is attributable to inhibition of cell apoptosis. Since the immune system is known to affect survival of cancer cells, we next examined infiltration of immune cells into the tumor. The number of CD8-positive cytotoxic T lymphocytes in the tumor
was significantly decreased in PLD2-KO mice, whereas the number of CD4-positive helper T
lymphocytes was not changed. In addition, CD8-positive but not CD4-positive T lymphocytes
were reduced in spleen of PLD2-KO mice. Furthermore, the directional migration of activatedCD8-positive T cells towards chemokine CXCL12 (50 ng/ml) in vitro was inhibited in the cells
lacking PLD2. Taken together, these results indicate that PLD2 plays a key role in the regulation of CD8-positive T lymphocyte that might suppress tumorigenesis.

173

Poster Presentation

P-11

Role of THG-1 in tumor angiogenesis through stabilization of
HIF-1α in normoxic condition
Ling Zheng, Hiroyuki Suzuki, and Mitsuyasu Kato
Department of Experimental Pathology, Graduate School of Comprehensive Human Sciences andFaculty of Medicine, University of Tsukuba

THG-1/Tsc22D4 is one of Tsc22 family member. We found that THG-1 is localized in thebasal layer of normal squamous epithelium, and is ubiquitously expressed in squamous cell
carcinoma cells. THG-1 is phosphorylated by EGF signaling and promotes cell proliferation,
invasion and tumorigenesis. Our previous data showed that THG-1 knockdown reduced not
only tumor sizes but also blood vessel densities compared with THG-1 expressing control
tumors. It suggested that THG-1 may be involved in tumor angiogenesis. Interactome analysis
suggested that THG-1 binds to prolyl hydroxylase domain-containing protein 2 (PHD2), which
regulates the stability of a transcription factor hypoxia inducible factor-1α (HIF-1α). Hypoxia
is a condition that is known to drive angiogenesis in tumors. HIF-1α is a transcription factor
that induces vascular endothelial cell growth factor. Our data showed that phosphorylated
THG-1 interact with PHD2 and stabilize HIF-1α. These results indicated that THG-1 promotes
angiogenesis by binding to PHD2 and regulating HIF-1α stability even in the normoxic
condition.

174

Poster Presentation

P-12

Dormant cancer cells have high reserved antioxidant capacitythat may promote their radioresistanceKazuya Ito1, Takashi Moritake2, Lue Sun1, Kenshi Suzuki1,
Ariungerel Gerelchuluun1, and Koji Tsuboi1
Radiation biology section, University of Tsukuba
Medical science for occupational and environmental health, University of Occupational andEnvironmental Health12[Background] It is known that dormant cancer cells are radioresisitant, however, the precise
mechanisms of their radioresistance have not been elucidated yet. As reactive oxygen
species (ROS) play an important role in cellular response to ionizing radiation, we compared“antioxidant capacity” of dormant and growing cells in this study. [Materials & Methods]
Human medulloblastoma cell lines ONS-76 were harvested at 48, 72 and 96 hours after seeding(1.0 × 106 cells in each 75 cm2 Flask). The cells at 48 hours were at the exponentially growing
phase and those at 72 and 96 hours were in dormancy. In each sample, levels of intracellular
ROS were measured by flowcytometry using 2’, 7’-Dichlorodihydrofluorescin diacetate(DCFH-DA). Also, antioxidant capacity was evaluated by the electron spin resonance (ESR)
method using 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (Tempol). The ESR signals were
measured every 15 minutes for 2 hours to calculate the reaction rate constant (k [min-1]).
[Results] DCF assay showed that the amounts of ROS in dormant cells (72 and 96 hours)
were lower than those in growing cells (48 hour) and they were not increase even after 8 Gyof X-ray irradiation. Although antioxidant capacity of dormant cells (k = 1.4 × 10-2 and 1.3 ×
10-2 for 72 h and 96 h, respectively) was smaller than that in growing cells (k = 1.7 × 10-2 for 48h), they became almost the same level (k ~− 1.9 × 10-2) 4 hours after irradiation. [Conclusions]
As the difference of k-values between pre- and post-irradiation indicates potentially reserved
antioxidant capacity of cells, larger difference of k-values in dormant cells as compared to
growing cells may explain the property of radioresistance of dormant cells. (prepared forsubmission to Free radic. Boil. Med.)175

Poster Presentation

P-13

Non-invasive in vivo near-infrared fluorescent imaging oftumors with iRFP
Shota Sakaguchi1,2, Junko Tanaka1,3, Yuka Sugiyama1, Tomoki Sakasai1,2,
Takanobu Kuroyama1,2, and Yoshihiro Miwa1,3
Department of Molecular Pharmacology, University of Tsukuba
Graduate School of Comprehensive Human Sciences, University of Tsukuba
3
Faculty of Medicine, University of Tsukuba
1

2

An optimal fluorescent protein for in vivo imaging should have excitation and emission
maxima within a NIR region from 650 nm to 900 nm because mammalian tissue has the lowest
absorbance in this region. For 1~2 cm-thick mouse body, non-invasive whole-body fluorescentimaging is possible within the NIR region (Jobsis, F.F., Science 198, 1264-1267, 1977). Recently,
Phytochrome-based near-infrared fluorescent protein (iRFP) was engineered (G.S. Filonov, etal., Nat Biotech.29, 757-761, 2011). In this study, we have demonstrated fluorescence imaging
of mice tumor with iRFP. First, we established iRFP-expressing Lewis Lung Carcinoma(LLC) cell line derived from C57BL/6. iRFP-expressing LLC cells were injected via the tailvein of BALB/c-nu/nu. Then, we monitored metastases into lungs non-invasively by using
an In Vivo Imaging System (IVIS Spectrum) and an X-ray CT. NIR fluorescence signal fromlungs were detected with both two-dimensional and three-dimensional imaging. Next, iRFPexpressing LLC cells and wild-type (WT) LLC cells were injected s.c. to three kinds of mice :C57BL/6 albino, C57BL/6 iRFP Tg mice expressing iRFP in whole-body, and BALB/c-nu/nu.
Then, we monitored the growth of the tumors and NIR fluorescence. In C57BL/6 albino mice,
WT-LLC cells formed tumors rapidly after injection. However, iRFP-expressing LLC cells
formed tumors slowly and NIR fluorescence signal was disappeared in most of tumors. On theother hand, in iRFP Tg and BALB/c-nu/nu mice, iRFP-expressing LLC cells rapidly formed
tumors like WT-LLC cells and kept high intensity of NIR fluorescence. In conclusion, NIR
fluorescence from iRFP-expressing tumors was detected non-invasively in internal organs ofliving mice. However, iRFP-expressing cells could be immunologically rejected in allogeneic
C57BL/6 mice. Now, we are investigating the mechanism of this rejection and searching ways
to overcome this rejection to establish further applications of in vivo imaging.

176

Poster Presentation

P-14

Chondrodysplasia in mice lacking both chondroitin sulfate
N-acetylgalactosaminyltransferase-1 and -2
Miki Shimbo1, Takashi Sato2, Kozue Hagiwara2, Hisashi Narimatsu2, Satoru Takahashi1, andTakashi Kudo1
Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba
2
Glycomedicine Technology Research Center, AIST

1

Chondroitin sulfate (CS), a sulfated glycosaminoglycan chain that consists of repeating
disaccharide units, is a main component of extracellular matrix (ECM) in cartilage. Although
CS is widely known to play an important structural role in cartilage function, its role inchondral development is less known. To assess the role of CS in chondral development, wepreviously generated mice lacking chondroitin sulfate N-acetylgalactosaminyltransferase-1(Csgalnact-1), one of the CS synthases predicted to initiate CS chain synthesis. Our results
revealed that Csgalnact-1 null mice exhibit slight dwarfism. However, the amounts of CS in
Csgalnact-1 null cartilage still remained about 50% that of wild-type mice, indicating that
other CS synthases also contribute to CS chain initiation. Based on the previous studies
showing the initiation activity of Csgalnact-2 in vitro, here, we generated Csgalnact-1 and-2 double null mice. The double null mice died shortly after birth due to respiratory failure
and they showed slightly shorter length of long bones than that of wild-type. To examine
the role of CS in postnatal chondral development, we then generated a cartilage-specificCsgalnact-1 and -2 deleted mouse (Col2-t1::t2). Most Col2-t1::t2 mice died shortly after birth
due to respiratory failure, but a few newborn mice were survived. Interestingly, although theCol2-t1::t2 mice had no difference in body weights at the day of birth, they developed a severedwarfism showing almost 50% reduction in body weight compared with that of wild-type.
Histological analysis of growth plate in Col2-t1::t2 proximal tibial epiphysial cartilage at P7
and P14 revealed a chondrodysplasia characterized by reduction of the glycosaminoglycan
content in ECM, an abnormal shape of chondrocytes, and disorganization of the growth plate.
These results indicate that the CS synthesized by both Csgalnact-1 and -2 plays a critical rolein postnatal endochondral bone formation.

177

Poster Presentation

P-15

MafB regulates macrophage-osteoclast progenitor cell function
Zeinab Kosibaty1,2, Michito Hamada1,2, Kyoko Sawaguchi1, and Satoru Takahashi1
Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba
2International Institute for Integrative Sleep Medicine (WPI-IIIS)

1

Osteoclasts are multinucleated cells of hematopoietic origin, which are unique in their ability
to resorb bone. Receptor activator of nuclear factor kappaB (RANK) and its ligand RANKL
is essential for osteoclast differentiation and survival. Osteoclasts are derived from myeloid
lineage cells that also required macrophage colony-stimulating factor (M-CSF). Previous
studies showed that osteoclasts and macrophages share a common hematopoietic progenitor
defined by CD11b- CD3- B220- CD115+ cells in bone marrow (BM) or spleen. However, it islargely unknown which mechanisms decide their fate differentiation to osteoclast.
MafB is a member of the large Maf family of transcription factors. MafB is highly
expressed in monocytes and macrophages. It has been reported that MafB inhibits osteoclastdifferentiation. In human, mutations in the amino-terminal transcriptional activation domainof MAFB have been identified in Multicentric Carpotarsal Osteolysis (MCTO) patients.
However, the molecular mechanism of MafB in osteoclastgenesis is still unclear.
Here, we analyzed the function of MafB in myeloid linage, including macrophage andosteoclast. Numbers of macrophage colonies from Mafb-/- fetal liver cells were significantly
increased. Moreover, in Mafb-/- BM cells, number of colonies induced by M-CSF from sorted
fraction lin-c-kit-sca-1- were dramatically increased. GFP was expressed in lin-c-kit- sca-1CD115+ in Mafb-/- (GFP knock in) mice. We suggest that abnormal fraction that sensitive
to M-CSF is caused to increase osteoclast. Whereas we conducted osteoclast formation by
M-CSF and RANKL using Mafb deficient bone marrow and fetal liver cells. The result was
showed abnormal osteoclast differentiation in Mafb-/- mice in both BM and fetal liver cells.
These results indicate that MafB regulates osteoclast differentiation in specific myeloid cells
lin-c-kit- sca-1- CD115+.
Our results revealed that MafB has a critical role in osteoclast differentiation throughspecific myeloid cells lin-c-kit-sca-1- CD115+. This study will help to clarify the molecularmechanism of bone diseases.

178

Poster Presentation

P-16

MafK overexpression impairs pancreatic β-cells development
in vivo
Ahmed Abdellatif, Hisashi Oishi, Takahiro Itagaki, and Satoru Takahashi
Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Japan

The pancreatic β-cells are the only cells that can produce insulin to maintain normal
glycaemia. Deficiency of insulin can cause a chronic metabolic disorder, diabetes mellitus(DM). The MAF family of transcription factor, which is a member of the bZip transcription
factors, is homologs of v-Maf, the oncogenic component of the avian retrovirus AS42. It
is subdivided into two groups, small and large MAF proteins. MAFA is a member of thelarge MAF family, which has been shown to be involved in insulin gene transcription,and Mafa knockout (KO) mice developed DM around 8 weeks of age. In addition, β-cells
specific overexpression of Mafk, which is a member of small MAF group, in a Mafa knockout
background has developed more severe DM compared to the Mafa KO mice. The aim of thecurrent work is to study the effect of specific Mafk overexpression in pancreatic β-cells ofmouse embryos. The developing islets of the transgenic embryos appeared disorganized witha reduction in the total insulin+ cell numbers at both E15.5 and E18.5 compared to control
embryos. Moreover, the total insulin content significantly decreased in transgenic embryos(WT; 5.6±0.59 ng vs. Tg; 1.1±0.09 ng (E15.5), WT; 13.4±0.48 ng vs. Tg; 10.02±0.48 ng (E18.5)).
The examination of gene expression profiles by quantitative real time PCR revealed that both
Ins1 and Ins2 genes were significantly decreased. As well several genes related to β-cellfunction including Slc30A8, Npy, and G6pc2 showed reduced expression levels. On the other
hand, both beta and alpha cells transcription factors like Pax4, Nkx2.2, Arx, and Mafb were
found increased; indicating that compensatory mechanisms of these cells might be mediatedby Mafk overexpression. Lastly, immunohistochemical staining using Ki67 antibody showed
lower ratio of proliferating β-cells in the transgenic embryos (4.2% vs. 1% and 14.3% vs. 3%
at E15.5 and E18.5 respectively). Our results suggest that Mafk overexpression impair β-celldevelopment in embryos. Understanding factors that govern normal β-cell development isfundamental for revealing the mechanisms of their failure in disease conditions.

179

Poster Presentation

P-17

The role of large maf transcription factors in the β-like cellconversion from mouse liver
Yunshin Jung, Hisashi Oishi, Tokio Katsumata, Pei-Han Tai, Ryusuke Koshida, andSatoru Takahashi
Anatomy and Embryology Laboratory Animal Resource Center, Department of Anatomy andEmbryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

Recent studies have shown that MAFB and MAFA have their distinctive roles on β-celldevelopment and maturation, respectively. However, what causes the discrepancy in β-cell is
not clearly explained yet. Their different gene expression timing could be one reason; Mafb
expressed before birth and Mafa after birth. Our aim is to examine the functional difference
between these closely related genes in β-cells using an in vivo mouse model that are designed
for β-like cell production, MIP-luc reporter mouse. We monitored the insulin transcriptional
activity using bioluminescence emitted from the liver of insulin promoter-luciferase transgenic
mice upon gene transfers. Adenoviral gene transfers of Pdx1/Neurod/Mafa (PDA) and Pdx1/
Neurod/Mafb (PDB) combinations generated intense luminescence from the liver with thepeak emission 3 days after transduction and lasted more than a week. The signal intensities of
PDA and PDB were comparable. However, PDA not PDB gene transfer resulted in significant
luminescence on day 10, suggesting that Mafa has a more sustainable role on insulin geneactivation than Mafb. PDA gene transfer induced several gene expressions necessary for
glucose sensing and insulin secretion in the liver on day 9. However, glucose tolerance test andliver perfusion experiment showed that induced β-like cells did not respond to high glucose
concentration. These results suggest that Mafa has markedly intense and sustainable role on
β-like cell production in comparison with Mafb.

180

Poster Presentation

P-18

NPM1 functions as a subunit of enhanceosome for
NF-κB-mediated transcription
Jian-Huang Lin1,2, Mitsuyasu Kato1,3,4, Kyosuke Nagata4, and Mitsuru Okuwaki1,2,4
School of Integrative and Global Majors, University of Tsukuba
2
Department of Infection Biology, University of Tsukuba
3
Department of Experimental Pathology, University of Tsukuba
4
Faculty of Medicine, University of Tsukuba

1

Nucleophosmin/NPM1, a nucleolar protein that shuttles continuously between the nucleus
and the cytoplasm functions as a histone chaperone and plays important roles in cell growthand proliferation. Being over-expressed in cancer cells compared with normal cells, NPM1 has
been thought to be involved in oncogenesis, but it is still not clear how it exerts its oncogenicrole. In this study, we found that in the nucleus NPM1 interacts with NF-κB, a transcription
factor that plays important roles in cancer development and progression. Activation of NF-κB
by treatment of TNF-α enhanced the interaction with NPM1 in the nucleus. Interaction domain
analyses revealed that NPM1 interacts with the N-terminal Rel homology domain of NF-κB
p65 which contains its DNA binding domain and its inhibitory protein IκBα binding domain,indicating that NPM1 might affect the DNA binding activity of NF-κB. Knockdown of NPM1
impaired the NF-κB transactivation activity and NF-κB-mediated target gene expression. In
addition, preliminary data indicated that TNF-α stimulation caused the recruitment of not
only NF-κB but also NPM1 to the NF-κB target gene promoters. This suggests that NPM1
is a critical positive regulator of NF-κB-dependent gene expressions. Furthermore, there isa strong correlation found between the expression of NPM1 and the activated NF-κB p65 incolon tumor tissue, suggesting that NPM1 regulates NF-κB in vivo. This study provides anovel clue into the molecular mechanism by which NPM1 exerts its oncogenic role through thecrosstalk with the NF-κB pathway.

181

Poster Presentation

P-19

Involvement of oviductal peristalsis in fertilization of the mouse
Yu Ishikawa1,2, Tomoyuki Usui2, Misuzu Yamashita2, and Tadashi Baba2
Ph.D. Program in Human Biology, School of Integrative and Global Majors,
University of Tsukuba, Japan
2
Graduate School of Life and Environmental Science, University of Tsukuba, Japan
1

Fusion between two gametes, sperm and oocyte, is one of the most important events infertilization. Ejaculated sperm migrate from the uterus to oviduct in the female reproductive
tract, and fertilize the oocytes at the oviductal ampulla. Recently, sperm have been reported
to recognize a high-viscosity fluid flow in the oviduct, suggesting that sperm are guided byrheotaxis to reach the oocytes. Indeed, sperm exhibit the ability to swim against the fluid
flow. Since peristaltic and antiperistaltic waves in the oviduct walls is thought to generate
the fluid flow directed to the isthmus in the oviduct, it is reasonable to consider that oviductal
peristalsis plays a key role in pumping sperm up to the ampulla. In this study, we have focusedon migration of sperm through the female reproductive tract under the control of oviductal
peristalsis. When prifinium bromide (padrin), a well-known inhibitor of intestinal peristalsis,
was administrated to mice, oviductal peristalsis was also prevented. The rate of fertilizationby artificial insemination was gradually decreased by administration of padrin in a dosedependent manner. As compared with the control group, the number of sperm reached theampulla was significantly decreased by padrin administration. Moreover, sperm were barely
capable of gaining access to the oocytes in the padrin-administrated mice. These results
suggest that the fluid flow generated by ovidutal peristalsis is crucial for fertilization in vivo.

182

Poster Presentation

P-20

Identification and characterization of human CD300H,
the eighth member of the CD300-family receptors
Kouta Niizuma1,3, Satoko Tahara-Hanaoka1,4,5, Emiko Noguchi2,5, and Akira Shibuya1,4,5
Department of Immunology andDepartment of Medical Genetics, Faculty of Medicine,3
Ph.D. Program in Human Biology,
4
Center for TARA, University of Tsukuba, Japan
5
CREST, Japan Science and Technology Agency
1

2

CD300 family molecules, which are encoded by a multigene family consisting of sevengenes on a segment of chromosome 17 in human, are expressed on myeloid lineage cells andmediate either activating or inhibitory signals. Here, we have identified a previously unannotated gene located in the CD300 gene cluster and termed it as CD300H. CD300H hasa short cytoplasmic tail and associates with an ITAM-containing adaptor, DAP12. A newly
generated monoclonal antibody (mAb) against CD300H (TX93) detected CD300H expression
on CD16+ monocytes and myeloid dendritic cells. To clarify the function of CD300H, wepurified CD16+ monocytes and stimulated them with TX93 mAb, resulting in production ofproinflammatory cytokines and chemokines for neutrophils attraction.
Interestingly, CD300H expression was variable among individuals; it can be classified
as “high-,” “moderate-,” and “no-” expression group as defined by flow cytometry analyses.
Genomic sequence analysis revealed the existence of a single-nucleotide mutation, rs905709(G→A), at splice donor site in exon 1, which is a leading cause of these individual differencesin CD300H expression. The international HapMap project database demonstrated that 16.7%
of Japanese carry A/A genotype (no-expression). Together, these results suggest CD300H may
play an important role in regulation of inflammatory responses in certain population who carry
G/G or G/A genotype of CD300H.

183

Poster Presentation

P-21

DNAM-1 (CD226) plays an important role in antigen
presentation by small peritoneal macrophages
Eri Takenaka1,3, Akira Shibuya1,2,4, and Kazuko Shibuya1
Department of Immunology, Faculty of Medicine,
Life Science Center of Tsukuba Advanced Research Alliance, University of Tsukuba
3Japan Society for the Promotion of Science
4Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency
1

2

Recent reports have revealed two distinct subsets of mouse peritoneal macrophages(CD11bhi F4/80hi large peritoneal macrophages (LPMs) and CD11b+ F4/80lo small peritoneal
macrophages (SPMs)) (Ghosn EE et al., PNAS. 2010). Although LPM is a classical macrophage
subset, the functional characteristics of SPMs remain unclear. We found that SPM expressed
cd226 gene, which encodes an activating receptor DNAM-1 expressed on T cells and NK cells,
58-fold higher than did LPMs, based on the microarray data of Immunological genome project(Heng TS et al., Nat Immunol. 2008). In fact, DNAM-1 protein was strongly expressed on
SPMs, but not on LPMs, suggesting that DNAM-1 may contribute to the function of SPMs.
When we compared the percentages and cell number of SPMs between wild-type (WT)and DNAM-1-deficient mice, these were not significantly different in both mice, suggestingthat DNAM-1 is not involved in the generation and maintenance of SPMs. Because SPMs
express a higher level of MHC class II compared with LPMs, we investigated whether SPMs
had antigen presenting ability and, if any, the role of DNAM-1 in the function by SPMs. We
show that coculture of SPMs, but not LPMs, with naïve CD4+ T cells derived from OT-II
mice in the presence of OVA peptide effectively induced CD4+ T cell priming, indicating that
SPMs are antigen presenting cells. Furthermore, SPMs derived from DNAM-1-deficient mice
showed significantly lower effect on induction of CD4+ T cell priming than those from WT
mice, suggesting that DNAM-1 on SPMs is involved in antigen presentation. Taken together,
we propose that SPMs are functionally distinct from LPMs, and DNAM-1 plays an importantrole in the antigen presentation by SPMs.

184

Poster Presentation

P-22

The role of CD300a (MAIR-I) in allergic airway inflammation
Haruka Miki1,2, Chigusa Nakahashi-Oda1, Takayuki Sumida2, and Akira Shibuya1,3,4
Department of Immunology, Faculty of Medicine, University of Tsukuba
Department of Internal Medicine, Faculty of Medicine, University of Tsukuba
3Life Science Center of Tsukuba Advanced Research Alliance (TARA)
4Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency
1

2

CD300 family molecules are members of Ig super family bearing one Ig-like domain
in the extracellular portion. One of the CD300 molecules, CD300a (MAIR-I), has a longcytoplasmic region containing the consensus immunoreceptor tyrosine-based inhibitory motif(ITIM) sequence and transmits an inhibitory signal. Recently we have reported that CD300a
specifically binds to phosphatidylserine exposed on the outer leaflet of apoptotic cell plasma
membrane. By crosslinking with monoclonal antibodies, CD300a inhibits mast cell or basophil
degranulation in mice and human in vitro. However the physiological role of CD300a and its
ligand has not been fully revealed.
To explore the role of CD300a in allergic responses in vivo, we generated CD300a-deficient
mice and investigated ovalbumin (OVA)-induced widely used experimental asthma model.
Eosinophil infiltration in bronchoalveolar lavage (BAL) fluid, serum IgE levels, and airway
hyperreactivity index were significantly decreased in CD300a-deficient mice compared to WT
mice. CD300a is highly expressed on monocyte-derived inflammatory dendritic cells in theperitoneal cavity after injection of OVA antigen plus alum. In vitro experiments demonstrated
that CD300a on inflammatory dendritic cells induce robust Th2 responses. Blockade ofCD300a interaction with phosphatidylserine by anti-CD300a neutralizing antibody resulted
in inhibition of the development of allergic airway inflammation. These results suggest thatinteraction of CD300a on inflammatory dendritic cells with apoptotic cells play an importantrole in the development and pathogenesis of allergic airway inflammation.

185

Poster Presentation

P-23

Somatic mosaic mutations in TET2 and DNMT3A in a case of
peripheral T-cell lymphoma
Tran B. Nguyen1, Mamiko Sakata-Yanagimoto1,2,3, Rie Nakamoto-Matsubara1, andShigeru Chiba1,2,3
Department of Hematology, Comprehensive Human Biosciences, University of Tsukuba
2
Department of Hematology, Faculty of Medicine, University of Tsukuba
3
Department of Hematology, University of Tsukuba Hospital

1[Backgrounds] Somatic mutations in DNMT3A and TET2 are frequently found in peripheral
T-cell lymphomas (PTCLs). These mutations are found not only in tumor cell, but also inapparently normal blood cells. This has led to an idea that the cell origin of the DNMT3A andTET2 mutations may be hematopoietic stem cells (HSCs). However, origins of these mutations
have not been elucidated.
[Objective] We analyzed distribution of TET2/DNMT3A mutations in various tissues of a
PTCL patient to estimate the origins of these mutations.
[Method] Genomic DNA was collected from various tissues/cells of a 74 year-old PTCL
patient and subjected to amplicon-based deep sequencing.
[Results] CD4+PD1+ tumor cells purified from peripheral blood (PB) showed mutations in
DNMT3A and TET2 at allele frequencies of 50% and 47%, indicating that all circulating tumor
cells had both mutations. The identical DNMT3A and TET2 mutations were detected in CD19+
B, CD4+PD1- T, and CD8+ T cells, and CD14+ monocytes in PB, as well as in PB derived
colonies. Furthermore, these mutations were also identified in genomic DNA collected fromnail, indicating somatic mosaic mutations (SMMs), although the allele frequencies were lessthan 1%.
[Discussion] This is the first report describing SMMs in two tumor driver genes inlymphogenesis. Discordance between mutation allele frequencies between nail and blood cell
DNA indicates growth advantage of mosaic cells after bone marrow establishment. In somecases, the origin of PTCL could be traced back to mosaic cells acquiring two major driver
mutations, during early embryogenesis.

186

Poster Presentation

P-24

Association of leukocyte immunoglobulin-like receptor A3(LILRA3) deletion polymorphism with systemic sclerosis
Yuki Hachiya1, Aya Kawasaki1, Takashi Matsushita2, Hiroshi Furukawa3, Shouhei Nagaoka4,
Kota Shimada5, Shoji Sugii5, Takayuki Sumida6, Shigeto Tohma3, Minoru Hasegawa7,
Manabu Fujimoto8, Shinichi Sato9, Kazuhiko Takehara2, and Naoyuki Tsuchiya1
Molecular and Genetic Epidemiology, University of Tsukuba
2
Department of Dermatology, Kanazawa University
3
Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, National Hospital Organization
4
Department of Rheumatology, Yokohama Minami Kyosai Hospital
5
Department of Rheumatology, Tokyo Metropolitan Tama Medical Center
6
Department of Internal Medicine, University of Tsukuba
7
Department of Dermatology, University of Fukui
8
Department of Dermatology, University of Tsukuba
9
Department of Dermatology, University of Tokyo
1

Background: The leukocyte immunoglobulin-like receptors (LILRs) are a gene family locatedat 19q13.4. LILRs are expressed mainly in immune cells as transmembrane receptors, andsome of LILRs have been shown to regulate immune cell activation. LILRA3 is the only
secreted protein among LILRs, whose function remains unclear. Furthermore, LILRA3 hasa 6.7-kb deletion polymorphism which lacks most of the coding region, and its frequency isespecially high in the East Asian population (71.0% in the Japanese) (Hirayasu et al., 2006).
Previous studies in European populations reported association of the deletion allele withmultiple sclerosis (MS) (Koch et al., 2005) and Sjögren’s syndrome (SS) (Kabalak et al., 2009),
while recent studies from China reported association of homozygous non-deletion genotype
with rheumatoid arthritis (Du et al., 2014a), systemic lupus erythematosus (SLE) and SS (Du etal., 2014b). In this study, we examined whether LILRA3 deletion polymorphism is associatedwith systemic sclerosis (SSc) in a Japanese population.
Methods: 377 Japanese patients with SSc and 867 healthy Japanese controls were examined.
The LILRA3 deletion was genotyped by PCR-sequence specific primers.
Results: We observed higher frequency of LILRA3 deletion in anti-topoisomerase 1 antibody
positive (ATA+) SSc patients compared with healthy controls (P=0.012, OR=1.68). This
association was not observed in anti-centromere antibody positive (ACA+) SSc. In the caseonly analysis, the deletion allele frequency of ATA+ACA- SSc was significantly increased
when compared with ATA-ACA+ SSc (P=0.020, OR=1.77).
Conclusion: Our study demonstrated the first evidence for the association between the LILRA3
deletion and ATA+ SSc. The risk allele was in agreement with that of MS and SS in the German
population, but was the opposite to that of RA and SLE in the Chinese population. This
study supported the association of LILRA3 with genetic susceptibility to multiple autoimmune
diseases, and its role requires further study.
187

Poster Presentation

P-25

Association of TRIM21 (RO52) polymorphisms with systemic
lupus erythematosus in a Japanese population
Misaki Hidaka1, Aya Kawasaki1, Hiroshi Furukawa2, Yuya Kondo1, Satoshi Ito3,
Isao Matsumoto1, Makio Kusaoi4, Hirofumi Amano4, Akiko Suda5, Keigo Setoguchi6,
Tatsuo Nagai7, Kota Shimada8, Shoji Sugii8, Akira Okamoto9, Noriyuki Chiba10,
Eiichi Suematsu11, Masao Katayama12, Akiko Okamoto13, Hajime Kono13, Shigeru Ohno14,
Shunsei Hirohata7, Shouhei Nagaoka5, Yoshinari Takasaki4, Hiroshi Hashimoto15,
Shigeto Tohma2, Takayuki Sumida1, and Naoyuki Tsuchiya1
Faculty of Medicine, University of Tsukuba, 2Sagamihara Hospital, National Hospital Organization,
3
Niigata Rheumatic Center, 4Department of Internal Medicine and Rheumatology, Juntendo University,
5
Yokohama Minami Kyosai Hospital, 6Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital,
7
Department of Rheumatology and Infectious Diseases, Kitasato University, 8Tokyo Metropolitan Tama Medical Center,
9
Himeji Medical Center, National Hospital Organization, 10Morioka Hospital, National Hospital Organization,
11
Kyushu Medical Center, National Hospital Organization, 12Nagoya Medical Center, National Hospital Organization,
13
Department of Medicine, Teikyo University, 14 Yokohama City University Medical Center,
15
Juntendo University School of Medicine
1

Background: TRIM21, also referred to as Ro52 or SS-A1, belongs to the tripartite motifcontaining (TRIM) family. TRIM21 is an autoantigen recognized by autoantibodies in seraof patients with systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SS). TRIM21
is induced by type I interferon, ubiquitylates proteins of the interferon-regulatory factor
family, and regulates type I interferon and proinflammatory cytokines. It is not clear how
these different aspects of TRIM21 can be reasonably explained. Until now, several small
scale studies suggested the association of SNPs in TRIM21 with susceptibility to SLE and SS.
However, to our knowledge, systematic association study which covered all the tagSNPs has
not been reported. In this study, we conducted a systematic association study between SLE
and TRIM21 in a Japanese case-control set with more than 1,000 individuals.
Methods: Nine tagSNPs in TRIM21 region were selected based on JPT HapMap data with thecriteria of minor allele frequency > 0.05 and r2 threshold of 0.80. 530 Japanese SLE and 518
healthy Japanese controls were genotyped for the tagSNPs using TaqMan SNP genotyping
assay, and case-control association study was performed.
Results: Among the 9 tagSNPs, marginal association was detected in 3 SNPs. At rs7947461
in intron 1, the frequency of the T/T genotype (P=0.04, odds ratio [OR] 0.72, 95% confidence
interval [CI] 0.53-0.99) was decreased. At rs9261010 in exon 2 coding for a synonymous
substitution, T allele frequency (P=0.04, OR 0.81, 95%CI 0.67-0.99) and T/T genotype
frequency (P=0.05, OR 0.62, 95% CI 0.39-1.00) were marginally decreased. Furthermore,
at rs4144331 in the 3’ untranslated region, decrease in T allele frequency (P=0.04, OR 0.76,
95%CI 0.58-0.98) and in T/T genotype frequency (P=0.04, OR 0.75, 95% CI 0.56-0.99) wereobserved.
Conclusion: TRIM21 polymorphisms may be associated with susceptibility to SLE.
188

Poster Presentation

P-26

Temperature during pregnancy influences birth size
Miki Kagami1, Enbo Ma2, and Yukiko Wagatsuma2
Graduate School of Comprehensive Human Sciences, University of Tsukuba
Department of Clinical Trial and Clinical Epidemiology, Faculty of Medicine,
University of Tsukuba, Tsukuba, Japan
1

2

Background: Birth weight and length are known to fluctuate with season of birth. However,
it is uncertain which meteorological element has an effect upon birth weight and length, andwhich timing of pregnancy would explain such effect. Objectives: The purpose of this study
is to examine whether temperature during pregnancy and which timing effects on size at birth.
Methods: A large, randomized, controlled trial of food and micronutrient supplementation for
pregnant women was conducted in Matlab, Bangladesh (MINIMat Study). The fetal growthdata which included the size at birth and information of their mothers were obtained (n=3267,
respectively). Meteorological data such as temperature, precipitation and daily sunshine hours
were observed at the nearest observatory site of Bangladesh Meteorological Department. Results: A seasonal pattern of birth weight and length was seen. Infants who were born in hot
and dry season (March – May) tended to be heavier (not significant). Infants born in winter(October – February) were shorter than those born in other seasons (Hot and dry season,
P<0.01, Monsoon season; June – September, P<0.001). From the results of multivariate analyses, when the temperature at 8 weeks of gestation increased, birth length became shorter. On
the other hand, temperature at the last month of pregnancy affected birth length in a reversed
direction. For birth weight, as temperature increased at 17 and 19 weeks of gestation, birthweight was increased 4.2 to 4.7 mm, respectively. Conclusion: These findings suggest thattemperature affects both birth weight and length. More temperature increased at the lastmonth of pregnancy, longer birth length became. For birth weight, the temperature at mid
pregnancy affected positive way.

189

Poster Presentation

P-27

The intervention research on Domestic Violence prevention
program for high school students
Tomoko Suga1,2 and Nobuaki Morita1
Social Psychiatry and Mental Health, Human Care Science, University of Tsukuba
2
Ibaraki National College of Technology

1This study examined the effects of the Domestic Violence prevention program that we had
made as an original program for high school students in Japan.
We named the program “Educational program to respect each other to have a good
relationship. How do we prevent Domestic Violence?” The program contents are 1)meet
people, 2)What is ‘respect’?, 3)story telling about DV, 4)relationship, 5)violence, 6)What is
DV?, 7)make communication for respect.
The intervention students were 78 persons, and control students 73 persons. The intervention
group answered the questionnaire through an experimental repeated design, before program,
after program and 1 month later. The control group was measured the scores of questionnaire‘recognition of controlled relationship’ and ‘coercive action’.
The effect of ‘recognition of controlled relationship’ and ‘coercive action’ were kept after
the program, but decreased 1 month later almost to the same values seen before program.
However, when the students were asked about the program, both boy’s students and thegirl’s students found it useful even after one month has passed. It was suggested that highschool students will assimilate the knowledge, but find it hard to change their way of thinking
toward violence.

190

NOTE

191

NOTE

192

Risk, Agent x, Science & Technology
Cultural Anthropology,
Doctoral Program in History and Anthropology,
University of Tsukuba

193

194

Sep 29 (Mon)

Meeting Room 5
Risk, Agent x, Science & Technology

Chair

Yasushi Uchiyamada

University of Tsukuba

9:00-9:10

Yasushi Uchiyamada

University of Tsukuba

Introduction

9:10-9:40

Paul Hansen

University of Tsukuba

Indexing Risk: Hearing More-than-human Publics in Japan

9:40-10:10

Robin O'Day

University of Tsukuba

Anti-Nuclear Activism and the Rise of Japan’s “Invisible” Civil Society

10:10-10:25

Daniel White

University of Hosei

Discussant

10:25-10:40

Akironi Kubo

Hitotsubashi University

Discussant

10:40-10:55

Discussion

11:00-12:00

Poster Session: Risk, Technology and Anthropology (Multimedia Room)

12:30-13:30
Session 2

Lunch

13:30-14:00

Hiroki Fukagawa

Kyoto University

Curse of Uncertainty: Healing Ritual and Multiple Causes of Misfortune

14:00-14:30

Sophie Chave-Dartoen

Unversity of Bordeaux

Uncertainty, Risks, Catastrophes and Agency

14:30-14:45

Keiji Maegawa

University of Tsukuba

Discussant

14:45-15:00

Toru Yamada

University of Tsukuba

Discussant

15:00-15:15

Discussion

15:15-15:30
Session 3

Coffee Break

15:30-16:00

Sébastien Guigner

Sciences Po BordeauxStar Wars, International comparisons of public policies as tools of
power: the case of health policies

16:00-16:30

Shuhei Kimura

University of Tsukuba

Technologies to make future

16:30-17:00

Yasushi Uchiyamada

University of Tsukuba

Agent x in the perceived world: a case of invisible uncanny inFukushima

17:00-17:20

David Sprague

National Institute for AgroEnvironmental Sciences

Discussant

17:20-17:40

Junko Teruyama

University of Tsukuba

Discussant

17:40-18:00

Discussion

Session 1

195

10 / 26 ページ

Indexing Risk: Hearing More-than-human Publics in Japan
Paul Hansen
University of Tsukuba

In 2003 companion animals began to outnumber children under the age of sixteen in Japanand this divide has increased yearly. Noting the ever-expanding range of goods and services
geared towards particular and significant furry others (cf. Haraway 2008, Derrida 2008), it isclear that domesticated dogs and cats play an ever-expanding role in urban Japan’s social andcultural milieu. Post-2011, popular depictions of rural suffering did not feature human inhabitants alone; domestic animals captured much media attention. Distraught livestock farmers
brought to the fore a sense that these non-humans represented more to them than a means toan end – their value was expressed as more than ‘livestock’ or a living commodity. This paperquestions if these more-than-human conditions can be read as an index of growing precarity inJapan; perhaps even an indication of the precariousness of being Japanese. Utilizing the concept of “flexible personhood” (Shir-Vertesh 2012) alongside ideas drawn from cosmopolitan
studies and posthuman theory this paper suggests that risks and precarity in Japan can be readin registers that move beyond the human.

196

Anti-Nuclear Activism and the Rise of Japan’s “Invisible” Civil
Society
Robin O’Day
University of Tsukuba

In the weeks and months after the Tohoku disaster on March 11, 2011, tens of thousands ofpeople took to the streets in Japan to protest and voice their concerns about the government’s
role in exacerbating the crisis. Of particular focus within these protests were the perceived
mishandling of the Fukushima Daiichi nuclear accident, and the broader dangers associated withrelying on nuclear energy. These protests were significant since they were some of the largest
street protest to occur in Japan since the 1960s and 1970s when hundreds of thousands took to
the streets of Tokyo to oppose the revisions of the US-Japan Security Treaty (AMPO). How
should scholars, therefore, interpret and explain the recent anti-nuclear street protests within
a broader perspective on popular forms of political dissent in Japan? What do these protests
suggest about the Japanese public’s willingness to accept the risks associated with nuclear
energy? Furthermore, what can these protests tell us about civil society’s ability to challenge,
oppose, and re-frame the official narratives of safety and risk promoted by state, corporate,and scientific experts? In an effort to help answer these questions, this paper approaches thesequestions ethnographically from the perspectives of different social movements that wereorganizing public protests around precarious employment and growing economic inequalities
before the disaster. What role did these groups play in the post-3.11 protests? How did they
shape the street politics of the 3.11 crisis? Conversely, how did the crisis shape their politics?

197

Curse of Uncertainty: Healing Ritual and Multiple Causes ofMisfortune
Hiroki Fukagawa
Kyoto University

In this presentation, I consider how people deal with the cause of illness and misfortune,
in terms of technology and risk management, taking the case of healing rituals in the New
Guinea Highlands. In Enga Province, when a person is angry with others by the conflicts, thefeeling itself becomes a curse. It is assumed that the cursed person is injured in a sickness
and an unexpected accident, and dies. Moreover, angry person also becomes sick and dies.
Therefore social discord appears as bodily disorder. The method to remove a curse is to restore
a disturbed social relation. It takes the form of the healing ritual.
However, the curse is not the only cause of illness and misfortune. There are multiplecauses. Therefore they perform the healing ritual in order to solve the problem of unknown
causes (agent x). Technology is used to solve the problem. In this presentation, I analyze thecase that healing rituals fails and examine technology to treat the uncertainties of life such as
illness and misfortune.

198

Uncertainty, Risks, Catastrophes and Agency
Sophie Chave-Dartoen
Université de Bordeaux

In the western/modern societies, to raise the question of uncertainty in terms of risks
implies a focus on the choices (technical, commercial, political…) that individual or collective
social agents operate. To raise this question in terms of disaster reaches another issue: itemphasizes disorders within the distinct domains that nature and culture constitute.
This communication tries to keep at distance this double dichotomy to analyse it,considering the presuppositions on which it is based. The cultural construction associatedwith the concept of risks will be presented via a fast review of its debt to the first Anglo-Saxon
economic liberalism and to the French Lumières. It will then be pointed out through thecontrast offered by the study of a totally different case. The way relationships to the world andhuman agency are conceived in a Polynesian society will be used for comparison. I will thenexamine how the question of catastrophes is handled, risks are perceived and experienced, inthe contemporary Wallisian society which is open to the rest of the world and connected to
globalized networks and flows.
These developments will open a reflection on the translatability of the concept of risk and on
its operational character, in particular in the context of national and international managementof risks and of the flows it can suppose.

199

Stat wars
International comparisons of public policies as tools of power:
the case of health policies
Sébastien Guigner
Associate professor, Institute of Political Studies, University of BordeauxInternational comparisons have become unavoidable for anyone who wants to govern
modern democracies. The belief in the virtue of international comparisons is part of a wider
dynamic where public policy and governance are more and more expected to be rationallyconducted to face society challenges. Since it is believed that comparing is the better way
to produce “evidence-based social science”, comparing internationally would be the betterway to produce “evidence-based policies”. But the many and recurrent flaws of thesecomparisons cast doubt on their actual role and effects. Among the most common deficiencies
are the comparability of data, the lack of clear definitions of terms and the state-centrism ofcomparisons.
Why thus such a success of international comparisons among policy-makers? The studyof the health field shows that under the guise of rationalizing and depoliticizing decisions,international comparisons are less a tool of learning than a tool of power. Actually, behind
their technical substrate and their apparent neutrality, international comparisons carry values,
interests and power relations.
Basically, international comparisons can be associated with social statistics, which can“have two purposes, one public, the other often hidden. Their public purpose is to give an
accurate, true description of society. But people also use statistics to support particular views
about social problems. Numbers are created and repeated because they supply ammunition
for political struggles, and this purpose is often hidden behind assertions that numbers, simply
because they are numbers, must be correct” (Best, 2012: 13).
That is probably the fundamental reason for success, rather than fostering learning. First,
comparisons hide that policies are always value-laden; they deliver “the truth”. Comparisonsseems to be in themselves “scientific” and thus “true”. Moreover, the language throughwhich comparisons are presented create effects of truth which rule out any debate. Second,
international comparisons create political pressure, notably because this language is easily
understandable and particularly well-suited for the mass media.

200

Technologies to make future
Shuhei Kimura
University of Tsukuba

This paper examines so-called “reconstruction” of a coastal village in Iwate Prefecture,
Japan. The consequences of the East Japan Great Earthquake still poses a challenge to bothsociety and anthropology, especially in Japan. By providing ethnographic sketches of theways the affected people and people coming there from outside embrace the future, this paper
observes how the low and high technologies such as tsunami risk assessment, project proposals
and reconstruction plan, and phatic labor (Elyachar 2010) frame the temporality of the village.
The process of reconstruction is on the one hand iteration of past (and future) event, but
simultaneously, on the other hand, it is an entanglement of infinite beginnings and ends, inwhich people struggle to reconcile their past and future in their own rhythm. Then this paper
explores how future is being made in between linear and cyclic time.

201

Agent x in the perceived world: a case of invisible uncannyin Fukushima
Yasushi Uchiyamada
University of Tsukuba

In a ramen shop in Hisanohama, a small fishing port, which was seriously affected by thetsunami, the fire, and the Fukushima Daiichi nuclear disaster, two local women and a municipal employee were talking right next to me. The tone was somewhat intent. “I wonder if themunicipality does the radiological test of well water,” says the first woman. “Is there a counterin the City Hall where I could ask for a water analysis? You know, our granny [her mother]has been using the well water for every thing for the past three years… and she says “I amstill alive so I think I am alright”… but it’s worrying.” “That’s not our responsibility,” says
the municipal employee, “that’s the jurisdiction of the public health center.” “Do they checkradioactive materials?” “Well… that’s… unlikely.” The woman goes silent. “The more frequently you use well water,” the second woman intervenes, “the cleaner it becomes, isn’t it?”
The first woman and the municipal employee do not respond to her assurance. She then casts
a glace at me. I nod vaguely. The sense experience of the lived body in the world seemed tohave become a misplaced phenomenology in this particular instance. There are imperceptible
agents at work in the environment. We are anxious about their efficacies. In this paper I shalldescribe the awkward milieus of living things in the post-3/11 Fukushama, and then I shallrevisit the life-world of Husserl and Merleau-Ponty to discuss the problematic notion of givenness of the lifte-world from the interactionist perspective. In what ways is the surrounding
world given?

202

NOTE

203

NOTE

204

Life and Medical Sciences inSouth East Asia
Faculty of Medicine,
University of Tsukuba

205

206

Sep 29 (Mon)

Meeting Room 6
Life and Medical Sciences in South East Asia

Chair

Koji Hisatake

University of Tsukuba

13:30-13:55

Hoang Nghia Son

Institute of Tropical
Biology, Viet Nam
Academy of Science andTechnology

The genetic relationship of Vietnamese pigs in Central Highlands
assessed by cytochrome b

13:55-14:20

Binh Nguyen Quoc

Biotechnology Center of
Ho Chi Minh City, Vietnam

Influence of Wzz gene on the pathogenicity of knock out gene
Edwardsiella ictaluri and Aeromonas hydrophila strains in catfish

14:20-14:45

Septelia Inawati Wanandi

Universitas Indonesia

Biomedical Sciences in Indonesia: A cutting-edge knowledge in theera of globalization

14:45 -15:00
Chair

Tea Break
Hoang Nghia Son

Institute of Tropical Biology

15:00-15:25

Amarila Malik

Universitas Indonesia

15:25-15:50

Dang Thi Phuong Thao

University of Science,
Vietnam National University
Ho Chi Minh City

15:50-16:15

Koji Hisatake

University of Tsukuba

16:15-16:30
Chair

Tea Break
Septelia Inawati Wanandi

Universitas Indonesia

16:30-16:50

Rina Mutiara Willy

Universitas Indonesia

Multidrug Resistance MDR1 Gene Polymorphism (C3435T) in PediatricAcute Lymphoblastic Leukemia patients in Indonesia National Referral
Hospital, Jakarta

16:50-17:10

Resda Akhra Syahrani

Universitas Indonesia

The sensitivity of breast cancer stem cells to doxorubicin modulatedby oxidative stress

17:10-17:25

Nguyen Thi Thanh Nhan

University of Science,
Vietnam National University
Ho Chi Minh City

Establishment of herbal collection and Evaluation of herbal bioactivity
in wound healing

17:25-17:40

Vuong Cat Khanh

University of Tsukuba

Analysis of adipose tissue-derived mesenchymal stem cells fromchronic kidney disease patients

17:40-17:55

Rudy

University of Tsukuba

Molecular Mechanism of Gpnmb-inducible Tumorigenesis

17:55

Koji Hisatake

University of Tsukuba

Closing statement

Exploiting the microorganism diversity from Indonesia’s biospherefor potential applications in health, pharmaceutical and nutrition:a mini review
Age-Accelerated Locomotion Deficit and Dopaminergic Neuron
Degeneration in Drosophila Ubiquitin Carboxyl-Terminal Hydrolase
Knockdown Model
Manipulation of Klf4 expression generates partially reprogrammed
iPS cells paused at successive stages of reprogramming

207

21 / 26 ページ

The genetic relationship of Vietnamese pigs in Central
Highlands assessed by cytochrome b
Hoang Nghia Son
Animal Biotechnology Department, Institute of Tropical Biology,
Viet Nam Academy of Science and Technology

To estimate the genetic relationship of Vietnamese pigs in Central Highlands, we compared cytochrome b sequences of Vietnamese wild boars and Vietnamese domestic pigs withother Asian and European wild boars. The results showed that there were two wild boar populations locating in Vietnam Central Highlands including wild boars of group I and wild boars
of group II. The Vietnamese wild boars of group II and domestic pigs were genetically close
to Asian A1 and Asian A2 wild boar groups, whereas the Vietnamese wild boars of group I
were genetically distinct from Asian A1, Asian A2 wild boar groups. The phylogenetic tree
demonstrated that the Vietnamese wild boars of group I were clustered in one clade which was
distinct from Asian wild boars and Europe wild boars. In addition, the Vietnamese wild boars
of group I were estimated to have diverged from European wild boars at 421500 YBP, indicating that Vietnamese wild boar of group I could be isolated from other Asian wild boars. The
single nucleotide polymorphism analysis showed that three Asian haplotypes were contributedin Vietnamese wild boars including A3 (TATG) haplotype in Vietnamese wild boar of group
I and A1 (CATA) haplotype and A2 (CATG) haplotype in Vietnamese wild boars of group II.
The A1 haplotype and A2 haplotype were also distributed in Vietnamese domestic pigs. Thus,
there is a high possibility that Vietnam Central Highlands is a principal source for research on
genetic diversity in Asian wild boar and domestic pig populations.

208

Influence of Wzz gene on the pathogenicity of knock out gene
Edwardsiella ictaluri and Aeromonas hydrophila strains
in catfish
Binh Nguyen Quoc
Biotechnology Center of Hochiminh City, Vietnam

Wzz gene is known as the regulator for the length of the O-antigen in the lypopolysacharide of bacterial cell wall. The length of the O-antigen chain can be determined the immunity
respond of the host against pathogen bacteria. In the goad to create attenuated pathogen bacterial strains using as live vaccine for catfish, the Wzz gene of E. ictaluri and A. hydrophila wasdeleted in different length. All mutants knock-out Wzz gene of both E. Ictaluri and A. Hydrophila shown a great lower pathogenicity than that of wild-type. Interestingly, the complete
gene deletion of the Wzz gen in both cases showing a remarkably low pathogenicity comparedto the partial deletion. The attenuated knock out gene Wzz gene of E. ictaluri can be use asa live attenuated vaccine for the catfish. Those results clearly show that the pathogenicity of
E.ictaluri and A. hydrophila on the catfish determined by Wzz gene activity.

209

Biomedical Sciences in Indonesia: A cutting-edge knowledge inthe era of globalization
Septelia Inawati Wanandi**Department of Biochemistry and Molecular Biology, Faculty of Medicine,Universitas Indonesia
septelia.inawati@ui.ac.id

For many years, Indonesia - an archipelago country with unique diversity - has experienced
the impact of globalization in almost every field of life aspects. The increasing globalization ofhealth sector such as the mobilization of health professionals and the use of new technologies
has encouraged the improvement of medical sciences. A significant rise of biomedical
sciences as a cutting-edge knowledge of medical sciences has been observed during the last
decade in Indonesia, which involved the advancement of technology based on applied theory
and triggering the approach of translational medicine. The enhancement of the utilization of
biomedical skills can be seen in numerous activities in medicine, such as the development of
diagnostic tools, preventive and therapeutic agents, including targeted therapy, and therefore
has led to an increased necessity of biomedical analysis in the clinical practice of physicians.
An example of ‘Millennium Development Goals’ implementation in Indonesia influenced by
the advancement of biomedical sciences is the development of vaccine originated from Indonesian virus strain in order to reduce child mortality. Globalization has also improved thestandard qualification of biomedical education in Indonesia through international networking and collaboration. It should be realized, however, that these improvements could not be
separated from the supports of Indonesian government and private companies through healthpolicies and research funding. Nowadays, scientists all over the world believe that the futureof biomedical sciences is promising due to its important role in the medical field. Biomedical
sciences are not just basic theories, but would also play a major role in numerous health industries in Indonesia in the era of globalization.

210

Exploiting the microorganism diversity from Indonesia’s
biosphere for potential applications in health, pharmaceuticaland nutrition: a mini review
Amarila Malik1, Shu Ishikawa2, Nick C. K. Heng3, Slavko Krlaj4, Iwao Ohtsu2,
Naotake Ogasawara2, Hiroshi Takagi2, Lubbert Dijkhuizen4
1

Division of Pharmaceutical Biotechnology, Faculty of Pharmacy, Universitas Indonesia, Indonesia
2
Graduate School of Biological Sciences, Nara Institute of Science and Technology, Japan3
Sir John Walsh Research Institute, University of Otago, New Zealand
4
Groningen Biomolecular and Biotechnology Institute, Rijksuniversiteit Groningen, The Netherlands
E-mail:amarila.malik@ui.ac.id

Indonesia is known for its mega-biodiversity. Bacteria that have shown an importanteconomic value is lactic acid bacteria (LAB) due to their application in food, and have potential
uses in health and pharmaceutical. Exopolysaccharide (EPS) produced by LAB has been
widely used as prebiotic (e.g. GOS and FOS), and as protein/peptide stabilizer in formulationof biotech drugs (e.g. inulin). Enzyme involved in homo-EPS synthesis are the sucrases,
i.e. glucansucrases (GTF, GS), and fructansucrases (FTF, FS). Our study aimed to exploit
potential LAB strain obtained from various local sources which carries potential gene/genes tobe developed for the production of useful substances to be applied in health, pharmaceutical,
and nutrition. Strain Weissella confusa MBF8-2 showed single gtf and ftf, while W. confusa
MBF8-1 carries two putative gtf genes; Weissella is a genus which has not been reported
much for sucrase encoding gene. Strain W. confusa MBFCNC2-1 carries inulosucrase typeof ftf gene but possessed a unique feature of fructansucrase gene sequence. A recombinantsucrosephosphorylase (SPase), an enzyme able to transfer glucosyl moiety to various sugars andsugar alcohols, and phenolic or alcoholic –OH groups of various substances, was successfullycloned and expressed in E. coli from Leu. mesenteroides MBFWRS-3(1) strain; it showed
98.40% activity as of the SPase reference protein. Some LAB also produce bacteriocins like
inhibitory substance (BLIS). The resistance of microbe to the existing antibiotic is of highly
concern; therefore developing an antibiotic complement for bacterial chemotherapy strategy
has been the center of attention. In an attempt to obtain recombinant antimicrobial peptide,
sequencing of whole genome sequence of strain MBF8-1 has been carried-out, while of thestrongest BLIS producer strain, Streptococcus macedonicus MBF10-2, will be next. Bacteria
evolved defense mechanisms against stress that allow them to withstand harsh conditions andsudden environmental changes. We studied how LAB response to growth condition by using
advances genomic technique RNA-seq.
Keywords: sucrase, sucrosephosphorylase, bacteriocin, Weissella, Streptococcus macedonicus

211

Multidrug Resistance MDR1 Gene Polymorphism (C3435T) in
Pediatric Acute Lymphoblastic Leukemia patients in Indonesia
National Referral Hospital, Jakarta
Rina Mutiaraˡ, Bernadius Agustinus², Christian Badia Sitompul²,
Djajadiman Gatot³, Amarila Malik²
Graduate School of Biomedicine, Faculty of Medicine, Universitas Indonesia,
UI Campus Salemba, Jalan Salemba Raya no. 4, Jakarta 10430, Indonesia
2
Pharmaceutical Biotechnology Division, Faculty of Pharmacy, Universitas Indonesia,
UI Campus Depok, Depok 16424, Indonesia
3
Cipto Mangunkusumo Hospital, Jalan Diponegoro no. 71, Jakarta 10320, Indonesia
1

Acute lymphoblastic leukemia (ALL) is the most frequently occurring cancer in children.
The main problem is 25–30% of the patients will experience a relapsing that leads to die of
teenagers. There were estimated 4100 new cases pediatric ALL every year in Indonesia. Basedon data in pediatric oncology Child Health Department Cipto Mangunkusumo Hospital period
2005-2011 was found 40% patients relapse of 126 pediatric ALL. The Multi Drug Resistance
1 (MDR1) gene codes for P-glycoprotein (P-gp) is an ATP-dependent efflux pump which has
great importance in elimination of several important drugs and xenobiotic. It has been shown to
be polymorphic. One of the multiple variants of the MDR1 gene is namely C3435T. It has beenshown to modulate the metabolism and thus the response to the drug or xenobiotic substrates for
P-gp such as steroid, anthracycline and Vinca alkaloid which associated with drug resistancemechanism. In many studies this polymorphism also can be used to evaluate the contributionof candidate gene to the understanding genetic susceptibility to pediatric acute lymphoblastic
leukemia (ALL). Our study was first, to analyze the MDR1 gene polymorphism profile. We
screened for the C3435T polymorphism 44 children with ALL, using PCR-RFLP assay with
MboI as the restriction enzyme. We found 6 (13,6%) ALL samples were digestible (C allele)and 38 (86,4%) were indigestible. C allele indicates high expression of p-gp which eliminates
ant leukemic drug, resulting in high risk diagnosis. On the other hand, the T allele which was
found abundant in our patients might be associated with the incidence of ALL. Further studies
on SNP are in progress to confirm these results, as well as expression of multidrug resistance
related protein (MRP) gene.

Key words:
Acute lymphoblastic leukemia, relapse, MDR1, P-glycoprotein, polymorphism, PCRRFLP

212

The sensitivity of breast cancer stem cells to doxorubicin
modulated by oxidative stressResda Akhra Syahrani1, Melva Louisa2 and Septelia Inawati Wanandi3
Master Programme in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia
2
Departement of Pharmacology, Faculty of Medicine, Universitas Indonesia
3
Departement of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia
1

Breast cancer is serious global health problem being the second most common of allcancers and by far has been the highest incidence among other cancers in Indonesian women.
Doxorubicin is an anthracycline antibiotic which induces cancer cell death by many mechanism,
most importantly by generation of radical oxygen species (ROS). Although breast cancer isconsidered one of the most chemosensitive solid tumors, most initially tumors relapse anddevelop resistance to drugs, even to doxorubicin which is considered as the most active drug
available for the treatments of breast cancer. It has been found that solid tumors contain asmall number of population that are highly resistant to drug treatment, known as cancer stem
cells (CSCs). The aim of this study is to analyze the sensitivity of breast cancer stem cells todoxorubicin. In our previous study, human breast CSCs (CD24-/CD44+) were sorted frombreast cancer tissue of patient. Breast CSCs were treated with doxorubicin for 14 days. The
effect of doxorubicin was examined by analyzing intracellular ROS level using superoxide
probe dihydro-ethidium (DHE) and hydrogen peroxide probe 2’-7’-Dichlorodihydrofluoresceindiacetate (DCFH-DA). The antioxidant defense system was analyzed using Real Time RTPCR to determine the level of MnSOD mRNA expression. The result showed that the viabilityof breast CSCs treated with doxorubicin was first decreased on the second day and started
to increase on the eight day of treatment, indicating reduced sensitivity of breast CSCs todoxorubicin after eight days of treatment. Interestingly, the level of ROS, both superoxides
and hydrogen peroxides, as well as the level of MnSOD mRNA expression were increased on
the second day and decreased on the eight day, revealing that the viability of breast CSCs was
associated with their redox status. In conclusion, this study could suggest that the sensitivity ofbreast CSCs to doxorubicin was modulated by oxidative stress.

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Global Aging: Emerging Challenges
and Opportunities
Division of Health Innovation and Nursing,
Faculty of Medicine,
University of Tsukuba
Center for Global Aging Tsukuba (CGAT),
University of Tsukuba

215

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Sep 29 (Mon)Special Conference RoomGlobal Aging: Emerging Challenges and Opportunities -CGAT Oral Session-

Chair

Nanako Tamiya

University of Tsukuba

9:00-12:30

Peter Lloyd-Sherlock

University of East Anglia

Gerhard Igl

University of KielLong term care for older people in Latin America: a growing challenge

Public Oral Presentation

Sep 30 (Tue)Special Conference RoomGlobal Aging: Emerging Challenges and Opportunities

Chair

Masao Ichikawa

University of Tsukuba

9:10-9:30

Chang-Chuan ChanNational Taiwan University

Political and social determinants of life expectancy in less developed
countries: a longitudinal study

9:30-9:50

Marlene J. Egger

University of Utah

Continuous quality improvement of primary care in an aging world: theUniversity of Utah Family Medicine Resident CQI Program

9:50-10:10

Yue Leon Guo

National Taiwan University

Effects of climate and air pollutants on human health: Multinational
studies

10:10-10:30

Yasushi Honda

University of Tsukuba

Population aging and climate change impact on heat-related mortality

10:30-11:00

Coffee Break

11:00-11:20

Holli A. DeVon

University of Illinois at Chicago Effects of Aging on Coronary Heart Disease in the United States

11:20-11:40

Tomoko Sankai

University of Tsukuba

Characteristics of Circulatory Diseases in Japan: Based on the
Circulatory Risk in Communitiesy Study (CIRCS)

11:40-12:00

Judith SC Shiao

National Taiwan University

The Nurse Occupational Stressor Scale (NOSS) Development and
Mental Health Investigation

12:00-12:20

Tomoyo Sasahara

University of Tsukuba

Development and dissemination of End-of-Life Care Nursing Education
Consortium-Japan (ELNEC-J)

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Long term care for older people in Latin America:a growing challengePeter Lloyd-Sherlock
University of East Anglia

This paper will demonstrate the growing demand for long term care services in Latin
America and the increasing pressures on the supply of informal care in the region. It will
discuss current patterns of provision in the region, including state services, private sector provision and family arrangements. It will identify a number of related policy challenges anddiscuss the scope for more comprehensive and coherent policies. Drawing on results of studies
in Argentina, Mexico and Peru, particular attention is paid to the rapid growth in unregulated,semi-legal care homes and the use of paid domestic workers and young children as informal
carers.

218

Political and social determinants of life expectancy in lessdeveloped countries: a longitudinal study
Ro-Ting Lin1, Ya-Mei Chen1, Lung-Chang Chien2 and Chang-Chuan Chan1,3
Institute of Occupational Medicine and Industrial Hygiene, college of Public Health,National Taiwan University
2
Department of Internal Medicine, Division of Health Behavior Research,
School of Medicine, Washington University
3
Global Health Center, College of Public Health, National Taiwan University

1

This study aimed to examine the longitudinal contributions of four political andsocioeconomic factors to the increase in life expectancy in less developed countries (LDCs)
between 1970 and 2004. We collected 35 years of annual data for 119 LDCs on life expectancy
at birth and on four key socioeconomic indicators: economy, measured by log10 gross domestic
product per capita at purchasing power parity; educational environment, measured by theliteracy rate of the adult population aged 15 years and over; nutritional status, measured by
the proportion of undernourished people in the population; and political regime, measured by
the regime score from the Polity IV database. Using linear mixed models, we analyzed thelongitudinal effects of these multiple factors on life expectancy at birth with a lag of 0-10 years,
adjusting for both time and regional correlations. The LDCs’ increases in life expectancy
over time were associated with all four factors. Political regime had the least influence on
increased life expectancy to begin with, but became significant starting in the 3rd year andcontinued to increase, while the impact of the other socioeconomic factors began strong but
continually decreased over time. The combined effects of these four socioeconomic andpolitical determinants contributed 54.74% - 98.16% of the life expectancy gains throughout
the lag periods of 0-10 years. Though the effect of democratic politics on increasing life
expectancy was relatively small in the short term when compared to the effects of the othersocioeconomic factors, the long-term impact of democracy should not be underestimated.

219

Continuous quality improvement of primary care in an aging
world: the University of Utah Family Medicine Resident CQIProgramMarlene J1. Egger, Susan Pohl2
Division of Public Health, Department of Family and Preventive Medicine, University of Utah
Division of Family Medicine, Department of Family and Preventive Medicine, University of Utah
1

2

Continuous quality improvement (QI) has been adopted extensively by industry to keep
pace with a quickly-changing world. Its uptake is increasing in clinical care and public health.
In the face of resource pressures driven by global aging, QI provides rapid-cycle tools to analyze
and improve health care processes. American medical schools now build training in clinicalquality improvement (CQI) into medical undergraduate and residency curricula. Family
medicine board certification now requires CQI activities in one’s own practice. Elements ofa successful CQI training program include policy mandates; a physician-led program witha limited, focused curriculum; hands-on experience with a project important to the clinic;
designated time and resources to work on it; being held accountable by the clinic; populationbased thinking; interprofessional respect; and teamwork skills. This case study shows how
the University of Utah Family Medicine Resident CQI Program uses the Batalden FOCUSPDSA paradigm for rapid-cycle CQI, together with a limited toolset of resources available atthe Institute for Healthcare Improvement, to equip family medicine physicians with skills they
will use to improve care of an increasingly aging society.

220Effects of climate and air pollutants on human health:Multinational studies
Yue Leon Guo1,2, Yasushi Honda3, Ho Kim4
Environmental and Occupational Medicine, National Taiwan University (NTU) College of Medicine
and NTU Hospital, Taipei, TAIWAN
2
Institute of Occupational Medicine and Industrial Hygiene, NTU College of Public Health,Taipei, TAIWAN
3
Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba, Japan
4
Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea

1

Climate change and air pollution have been important health issues in many countries.
International collaborations provide opportunities for examining in depth hypotheses andphenomena that have never been possible in the past. Pooled environmental data like climate
factors and air pollutants can be combined with outcome data like mortality and morbidity.
Comparisons of climate effects on mortality have been made to reveal consistent findingsthat cold and warm temperature are associated with increased deaths, especially due tocardiovascular and respiratory diseases. On the other hand, optimal temperature in regard to
mortality varies among different countries. Health effects have been related to air pollutants,
such as carbon monoxide, nitrogen oxides, ozone, particulates, and sulfur dioxide, amongcollaborative countries. Mortality and emergency room visits due to cardiovascular andrespiratory diseases appear to be sensitive outcomes caused by air pollutants. Susceptible
sub-populations can be identified by meta-analyses. For example, adverse birth outcomes havebeen related to air pollutants. Elderly people are especially vulnerable to temperature extremes
and air pollutants. In conclusion, international collaborations with pooled environmental dataand population outcome data result in large numbers of subjects and allow for cross-ethnicalcomparisons, as well as higher statistical power to examine hypotheses related to human healtheffects.

221

Population aging and climate change impact on heat-related
mortality
Yasushi Honda
Faculty of Health and Sport Sciences

Heat-related mortality is statistically defined as follows: At a certain temperature, a mortality
level of a population becomes lowest. This temperature is called “optimum temperature”(= OT). When the temperature is higher than the OT, the mortality level would be higher
than that at the OT. The difference between these mortality levels is considered to be excess
mortality due to heat, and thus defined as heat-related mortality. This heat-related mortality
is one of the biggest mortality effect of the climate change in developed countries, and this
impact has been included in the Climate Change Risk Assessment conducted by World HealthOrganization (the report of which will be published soon). This heat-related mortality, alongwith other general mortality, is higher for older people. In addition, for prevention of heatrelated deaths, although frequent water supply and adequate use of air-conditioner are very
important, elderly people’s sensitivity to heat is lower than younger people. This lack ofsensitivity and mental deterioration of elderly people makes the prevention difficult. For thesereasons, in developed countries including Japan, climate change impact on the heat-related
mortality will be more serious because of the population aging.
In the presentation, I will first demonstrate the heat-mortality relation in various countries
and our finding that can be used for future projection of climate change impact on heat-related
mortality. Then, showing the age-group specific heat-mortality relations, I will discuss about
the impact of population aging on heat-related mortality.

222

Effects of Aging on Coronary Heart Disease in the United States
Holli A. DeVon
University of Illinois at Chicago; College of Nursing, Department of Biobehavioral Health Science

Background/Significance: Cardiovascular disease (CVD) is the leading cause of death anddisability worldwide and older adults carry a higher burden of CVD. The purpose of thisstudy was to determine if there were differences in clinical presentation, comorbidities, andhealthcare utilization in Medicare eligible (≥65 years) and non-Medicare eligible (<65 years)
adults with acute coronary syndrome (ACS).
Methods: Patients admitted to five high volume emergency departments (ED) wereenrolled. The 13-item validated ACS Symptom Checklist was used to measure symptoms onpresentation to the ED. The Charlson Comorbidity Index (CCI) was used to assess comorbid
conditions. Analysis of variance or Chi-square tests were used to evaluate group differences
across age in clinical presentation, comorbidities, and healthcare utilization.
Results: The convenience sample of 421 patients were predominantly male (73.4%),
Caucasian (70.1%), and with a mean age of 61.7 years. There were more women (p=.032) andCaucasians (.003) in the older group. Older patients were more likely to be diagnosed with
non-ST elevation myocardial infarction (p=.003); arrive to the ED by ambulance (p=.016), andbe overweight (p<.0001) and were less likely to be a current smoker (p<.0001). As expected,
older patients had a higher CCI mean score (p=.019) with a significantly higher incidence ofcancer (p<.0001). Older patients were less likely to report chest pressure (p<.0001), chest
discomfort (p=.010), and shortness of breath (p=.022), and experienced fewer symptoms(p=.038). Following discharge, younger patients made more calls to clinicians and had moreclinic visits.
Conclusions: There were more similarities than differences between older and younger
groups in clinical presentation and health utilization in the six months following discharge.
However, lack of chest pressure, chest discomfort, and shortness of breath, key symptoms
triggering a decision to seek emergent care, may put elders at risk for delayed treatment.

223

Characteristics of Circulatory Diseases in Japan: Based on the
Circulatory Risk in Communities Study (CIRCS)
Tomoko Sankai1,2, Kazumasa Yamagishi1,2, for the CIRCS Investigators
Department of Public Health Medicine, Faculty of Medicine, University of Tsukuba
2Osaka Center for Cancer and Cardiovascular Diseases Prevention

1

The Circulatory Risk in Communities Study (CIRCS), which is a community-based dynamic
prospective study on circulatory diseases, i.e. stroke and Coronary Heart Disease (CHD), hasconsisted of the four rural and one suburban communities in Akita and Osaka started from1963, in Kochi started from 1969, and in Ibaraki prefectures started from 1981. The long-term
follow-up investigations of the CIRCS have shown many characteristics on stroke and CHD
among Japanese. The mortality and incidence rates of CHD in Japan have been observed
to be lower than that in Western countries, and those of stroke in Japan have been observed
higher. Further in stroke, the proportion of cerebral hemorrhage and lacunar infarction causedby arteriolosclerotic change in small penetrating arteries is higher and that of cortical artery
infarction caused by atherosclerotic change is lower in Japan than in Western countries.
Hypertension and its complications were the most significant risk factors of stroke and CHD.
On the other hand, serum total cholesterol is inversely associated with cerebral hemorrhage
among Japanese. The recent studies shows that the dietary changes, such as lowered sodium
intake and increased animal food intake, which may lead to decrease stroke incidence throughdeclining blood pressure level. However, not yet to increase CHD incidence through risingserum total cholesterol level except male residents in urban area. In order to achieve the aimof a reduction by half of the incidence of stroke in Kyowa town in Ibaraki, a community-based
population approach to prevent hypertension, nutritional education campaigns to reduce salt
intake has been conducted since 1981. After that, the systolic and diastolic blood pressure levelin the participants of annual medical examinations in Kyowa town had begun to decline. In
thirty years follow-up, elderly people’s stroke incidence rate was reduced almost by half, andalso they have led to control of national insurance medical expenses and a premium for careinsurance compared with neighbor communities.

224

The Nurse Occupational Stressor Scale (NOSS) Development
and Mental Health Investigation
Dr. Judith SC Shiao
Associate Professor, Department of Nursing
College of Medicine, National Taiwan University

Nurses are the frontline providers of healthcare and are exposed to stressful work
environment, and their job characteristics are important predictors of occupational stresshealth outcome. The adverse outcomes of occupational stress on nurse’s physical health andemotional well-being have been well documented. In the last few years, there have been
increasing concerns over the adverse health impacts of job stress and building positive healthpractice environment, to promote nurses’ retention rate. The Occupational Safety and Health
Act were passed in Taiwan in 2013, aimed to reduce occupational chemicals, physical andbiological hazards for all workers. Under this new act, the employers are also responsible toprovide a friendly work environment in terms of mentor health. Most of nurse work stressstudies are reporting self-perceived health status of nurses using developed measurement
tools. However, the magnitude of the adverse effects on nurses’ general health, i.e. prevalence
and types of health outcomes of occupational stress in nurses, commonly seen nurses’ job
stressors, should be identified. In 2013, the Institute of Occupational Safety and Health andNational Taiwan University Nursing Department had conducted a join study entitled: “Riskassessment and factor analysis for occupational stress in nurses”, and developed a draft “TheNursing Characteristics related Job Stress Scale”. In 2014, the scale will be amended, tested andfinalized as: {The Nurse Occupational Stressor Scale (NOSS) Development and Mental HealthInvestigation}. A nationwide survey is intended using the new scale, to early detect nurses withhigh score of occupational stress. A psychiatric physician will be consulted for those caseswith significant high scores, and to confirm the diagnosis if there are psychiatric conditions
detected by the NOSS. A user guide for the NOSS will also be prepared. Recommendations
related to reduce/avoid nurses’ occupational stressors are to be discussed and formulated.

225

Development and dissemination of End-of-Life Care
Nursing Education Consortium-Japan (ELNEC-J)
Tomoyo Sasahara1 and Tomoko Arahata2
Health Innovation and Nursing, Faculty of Medicine, University of Tsukuba
Nursing Sciences, Comprehensive Human Sciences, University of Tsukuba

1

2

The rapidly increasing percentage of elderly people is a growing issue in Japan. In fact,people aged 65 or older will account for about 40 percent of the total population by 2060. Thismeans that our society will face unprecedented demand for the provision of end-of-life care.
The End-of-Life Care Nursing Education Consortium (ELNEC) project is a national
education initiative that began in 2000 in the United States to improve end-of-life care. The
project provides nurses with a higher level of training in end-of-life care so they can pass onthese essential skills to staff nurses. ELNEC has 7 curricula including in ELNEC-Core. They
are systematic and comprehensive programs and expanding internationally.
From 2007, our research group began to develop the Japanese version of ELNEC-Core.
After translating the original guide into Japanese, we modified it to apply to Japanese culture
and health care system. The Japanese version called “ELNEC-J core curriculum trainer’s
guide” was prepared by adding a module named “End-of-Life Care for Geriatric” to original 9
modules: “Palliative Nursing Care,” “Pain Management,” “Symptom Management,” “EthicalIssues in Palliative Care Nursing,” “Cultural and Spiritual Considerations in End-of-Life
Care,” “Communication,” “Loss, Grief & Bereavement,” “Preparation for and Care at the Timeof Death,” and “Achieving Quality Palliative Care.”
In 2009 the ELNEC-J “Train the Trainer” program was first conducted by the JapaneseSociety for Palliative Medicine and now there are 997 ELNEC-J trainers. ELNEC-J trainers
have conducted an end-user program in their institution or region using the ELNEC-J corecurriculum trainer’s guide and the number of end-user programs held has reached 221,
providing education to 6,787 staff nurses.
The ELNEC-J project has been successful and more staff nurses are expected to participate
in the end-user program to provide more quality end-of-life care for elderly people.

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228

Broadening your horizonsinternational collaboration in the life
sciences
Human Frontier Science Program

229

230

Sep 29 (Mon)International Conference RoomBroadening your horizons international collaboration in the life sciences

12:30-12:40

12:40-13:30

Hideki Mizuma

Goeff Richards

Human Frontier Science
Program
Human Frontier Science
ProgramBroadening your horizons – international collaboration in the life
sciences

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Broadening your horizons – international collaboration in thelife sciences
Goeff Richards and Hideki Mizuma
Human Frontier Science Program

HFSP (the Human Science Frontier Program) was established to encourage innovativeinternational collaboration in the life sciences. Working abroad for postdoctoral studies
enables young scientists to obtain a wider understanding on the way science is conducted
outside of their home institute. It is challenging but will lay the basis of a modern international
scientific career. Similarly young scientists setting up their own laboratories should be awareof the possibilities of collaborative research to bring new approaches into their field. In thistalk we will discuss the HFSP programs (fellowships and grants) that can help in making theseimportant career steps.
http://www.hfsp.org http://jhfsp.jsf.or.jp (Japanese sister site)
Geoff Richards’ scientific career started with an entrance scholarship in chemistry at
Queens’ College, Cambridge in 1969. During his studies he switched fields and completed
a Ph.D in 1975 in Drosophila developmental cytogenetics with Michael Ashburner (Genetics
Dept, Cambridge) and was immediately appointed to a junior faculty position in the department
which he held for 5 years.
Dr. Richards moved to Strasbourg in 1980 to join Pierre Chambon’s laboratory to learn
molecular biology techniques and apply them to his studies of the hormonal regulation of
Drosophila development. He used P element transformation extensively for in vivo studies ofgene regulation and later developed micro RT-PCR techniques to study multiple transcripts
in individual staged/treated Drosophila tissues. He was appointed as a junior group leader
in 1982 and has been a senior Research Director of the French CNRS (full Professor) for
more than 20 years. He worked in the IGBMC in Strasbourg, an internationally recognizedbiomedical research institute with 600 members.
Dr. Richards joined HFSP in 2004 as Director of Research Grants. Prior to that he spentsome 10 years in a dual role as both a scientific group leader at the IGBMC and its Executive
Secretary with the overall responsibility for national and international, academic and industrial
research contracts including intellectual property issues. In his current role at HFSP he has
followed the progress of some 7000 applications to the HFSP international collaborative grant
program.

232

Hideki Mizuma received his Master’s degree in Engineering from the Graduate School ofEngineering at Hokkaido University in 1983.
He joined the Science and Technology Agency (STA) of Prime Minister’s Office in 1983.
He has served as Director of Fuel Cycle Research and Development Division of Ministryof Education, Culture, Sports, Science and Technology (MEXT), Director of Regulatory
Guides and Review Division, Director of General Affairs Division of Secretariat of Nuclear
Safety Commission (NSC) of the Cabinet Office and as a cost free expert to the International
Atomic Energy Agency (IAEA) in the Vienna Headquarters. At the IAEA, he acted as aSpecial Projects Coordinator in the Division of Public Information and SSAC (State Systemof Accounting for and Control of Nuclear Materials) Training Expert in the Department of
Safeguards).
Recently, he also served as Director for Science and Technology Research Partnership for
Sustainable Development (SATREPS) of Japan Science and Technology (JST). SATREPS
is a joint project with the JST and the Japan International Cooperation Agency (JICA),
targeting global issues and involving partnerships between principal investigators in Japanand colleagues in developing countries.
In April 2014, Hideki Mizuma joined the International Human Frontier Science Program
Organization (HFSPO) as Deputy Secretary General.

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234

Universe Evolution and Matter Origin
Division of Physics,
Faculty of Pure and Applied Sciences,
University of Tsukuba

235

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Sep 29 (Mon)Special Conference Room
Universe Evolution and Matter Origin

Chair

Tatsuya Chujo

University of Tsukuba

13:00-13:30

William Trischuk

University of Toronto

The Discovery of the Higgs Boson with the ATLAS Experiment at CERN

13:30-14:00

Yves Schutz

CERN

ALICE at LHC: the thermodynamics of strongly interacting matter

14:00-14:30

Marco van Leeuwen

Utrecht University

Jet Physics in Heavy Ion Collisions: Hard probes of the Quark Gluon
Plasma14:30-14:50

Hideki Okawa

Univesity of Tsukuba

Search for invisible decays of a Higgs boson produced in association
with a Z boson in ATLAS

14:50-15:00

Daisuke Watanabe

Univesity of Tsukuba

Jet azimuthal distributions with high pT neutral pion triggers in pp
collisions √s = 7 TeV from LHC-ALICE

15:00-15:10

Sanshiro Mizuno

Univesity of Tsukuba

Measurement of direct photon collective flow in √sNN =200GeV AuAu
collisions at RHIC-PHENIX experiment

15:10-15:20
Chair

Break
Fumihiko Ukegawa

University of Tsukuba

15:20-16:00

Soo-Bong Kim

Seoul National Univesity

Current Results and Future Perspectives of Reactor Neutrino
Experiments

16:00-16:40

Ricardo Finger

University of Chile

Chile, the capital of Observational Astronomy

16:40-17:00

Yuji Takeuchi

Univesity of Tsukuba

Experimental search for the cosmic background neutrino decay in thecosmic far-infrared background17:00-17:20

Dragan Salak

Univesity of Tsukuba

Bursts of star formation and gas outflows in galaxies

17:20-17:30

Kenji Kiuchi

Univesity of Tsukuba

Search for the Standard Model Higgs boson decaying to a bottomquark pair with the ATLAS detector

17:30-17:40

Takuya Okudaira

Univesity of Tsukuba

Development of Superconducting Tunnel Junction Photon Detector
with SOI Preamplifier Board to Search for Radiative decays of Cosmic
Background Neutrino

17:40

Shinhong Kim

Univesity of Tsukuba

Closing statement237

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The Discovery of the Higgs Boson with the ATLAS Experimentat CERN
William Trischuk
Depoartment of Physics, University of Toronto

CERN built the Large Hadron Collider with the express goal of clarifying the source ofmass in the Standard Model of particle physics. In the 1960s Brout, Englert, Higgs, and others
postulated the addition of a scalar field to the SU(2)xU(1) theory of weak and electromagnetic
interactions that would generate the masses of the fundamental bosons and fermions. Theirmasses would be proportional to their couplings to the “Higgs” field. While elegant, this theory
has been around for almost 50 years without any evidence to support the existence of a Higgs
boson. Searches at the CERN LEP collider and the Fermilab Tevatron produced only indirect
evidence for the Higgs mechanism. It was not until the Large Hadron Collider produced
first 7 TeV and later 8 TeV proton-proton collisions that we produced un-equivocal evidence
for the existence of a Higgs-like boson. I will describe the Higgs results from the ATLAS
experiment from the first period LHC run that took place between 2009 and 2012. After a brief
review of the discovery evidence presented in 2012 I will focus on the work that has gone on
since to determine whether this new boson is the simplest version, envisaged by Higgs et al.,or something more exotic, that might be a harbinger of physics beyond the Standard Model.
Preparations are now underway to increase the LHC beam energy to its design, potentially
producing 13 TeV proton-proton collisions in early 2015. I will briefly outline some of thethings we hope to learn about the Higgs from this new data.

238

ALICE at LHC: the thermodynamics of strongly interacting matter
Yves Schutz
CERN Genève, Switzerland and SUBATECH, Nantes, France

ALICE (A Large Ion Collider Experiment) is among the four large experiments operated
at the CERN LHC (Large Hadron Collider) particle-accelerator complex the one dedicated tothe heavy-ion scientific program. The scientific objectives of this program are to establish how
the strong interaction structures elementary particles to form matter or in other words how themacroscopic properties of QCD (Quantum Chromodynamics, the theory of strong interaction)
matter emerge from the first principles that constitute the cornerstones of the Standard Model of particle physics. To tackle this fundamental problem, one explores the phase diagramof nuclear matter in particular in the high temperature sector where matter is predicted toundergo a phase transition from today’s ordinary matter to the phase called QGP (Quark Gluon
Plasma), the primordial phase of matter during the early tens of microseconds in the historyof the universe.
At LHC, ALICE exploits the collisions of heavy ions (presently nuclei of lead accelerated
at quasi the speed of light) to heat up matter to extremely high temperatures, well above thecritical temperature of the QGP phase transition, and create droplets of primordial matter
during a fleetingly short time. Through the detection and identification of the swarm ofparticles created in every of such collisions and through the detailed study of these collisiondebris, ALICE attempts to establish the nature and the fundamental properties of the QGP.
Following a brief contextual introduction to heavy-ion physics, the empirical approach is
discussed illustrated by a few results obtained so far at LHC on the fundamental properties of
the QGP.

239

Jet Physics in Heavy Ion Collisions: Hard probes of the Quark
Gluon Plasma
Marco van Leeuwen
Nikhef, National Institute for Subatomic Physics and Institute for Subatomic Phsyics,
Utrecht University, Netherlands

High-energy nuclear collisions are used to create and study strongly interacting matter atvery high energy density in systems that are much larger than the size of the proton (about 1fm), which is the typical range of the strong force. In the early stages of these collisions, quarks
and gluons are expected to be the relevant degrees of freedom, forming a Quark Gluon Plasma.
High-energy quarks and gluons (partons) that are produced early in the collision, interact with
the Quark Gluon Plasma while propagating outwards and thus provide information about theearly stages of the collsion. Experimentally, this process is studied by measuring particle
production at large transverse momentum (pT) and by reconstructing jets, which are collimatedsprays of particles that originate from high-momentum partons. I will review recent results ofsuch measurements in Pb+Pb collisions with a center-of-mass energy of 2.76 TeV per nucleon
pair at the Large Hadron Collider and discuss how they contribute to our understanding of theinteractions between a highly energetic parton and the Quark Gluon Plasma and the propertiesof the Quark Gluon Plasma produced at the LHC.

240

Search for invisible decays of a Higgs boson produced inassociation with a Z boson in ATLAS
Hideki Okawa on behalf of the ATLAS Collaboration
Division of Physics, Faculty of Pure and Applied Sciences, University of Tsukuba

A Higgs boson has been discovered at the ATLAS and CMS experiments with the Run
1 data collected at the Large Hadron Collider (LHC) at CERN (ATLAS Collaboration, Phys.
Lett. B 716: 1, 2012; CMS Collaboration, Phys. Lett. B 716: 30, 2012). As the best upper limiton the total decay width of the Higgs boson is still several times larger than the standard model
expectation (CMS Collaboration, Phys. Lett. B 736: 64, 2014; ATLAS Collaboration, ATLAS
Note, ATLAS-CONF-2014-042, 2014), the presence of beyond-the- standard-model decays ofthe Higgs boson cannot be excluded. Invisible decays of the Higgs boson to weakly interacting
particles such as dark matter are among promising scenarios. A search is performed forevidence of such invisible decays of a Higgs boson produced in association with a Z boson. No
deviation from the standard model expectation is observed in 4.5 fb-1 (20.3 fb-1) of 7 (8) TeV
pp collision data collected with the ATLAS experiment. Assuming the standard model crosssection rate for ZH production, an upper limit of 75%, at the 95% confidence level is set on the
branching ratio to invisible-particle decay modes of the Higgs boson at a mass of 125.5 GeV(ATLAS Collaboration, Phys. Rev. Lett. 112: 201802, 2014). The limit on the branching ratio isalso interpreted in terms of an upper limit on the allowed dark matter-nucleon scattering crosssection within Higgs-portal dark matter scenarios. Limits are also set on an additional neutral
Higgs boson, in the mass range 110<m H<400 GeV, produced in association with a Z boson anddecaying to invisible particles. Finally, prospects of invisibly decaying Higgs boson searchwith the future LHC data are presented (ATLAS Collaboration, ATLAS Note, ATL-PHYSPUB-2013-014, 2013).

241

Jet azimuthal distributions with high pT neutral pion triggers
in pp collisions s = 7 TeV from LHC-ALICE
Daisuke Watanabe
grad. student, University of Tsukuba

242

Measurement of direct photon collective flow in s NN =200GeV
AuAu collisions at RHIC-PHENIX experiment
Sanshiro Mizuno
grad. student, University of Tsukuba

243

Current Results and Future Perspectives of Reactor Neutrino
Experiments
Soo-Bong Kim
Department of Physics and Astronomy, Seoul National University

Neutrino physics has gone through remarkable progress during the last two decades.
A new generation of reactor neutrino experiments measured the last unknown, weakest
neutrino mixing angle, so-called theta 13, based on a clear observation of reactor antineutrino
disappearance. The exciting result of solving the longstanding puzzle provides a comprehensive
picture of neutrino transformation among three kinds of neutrinos. A surprisingly large valueof theta 13 has opened up a new window to find the leptonic CP phase angle and the neutrinomass hierarchy, and thus has promoted the next round of neutrino experiments. The reactor
experiments have continued data-collection since 2011, to obtain precise measurements of themixing angle as well as the reactor neutrino flux and spectrum. In this talk, I will present
recent results from the three reactor experiments of Daya Bay, Double-Chooz and RENO, andintroduce future reactor experiments of JUNO and RENO-50 to determine the neutrino massordering.

244

Chile, the capital of Observational Astronomy
Ricardo Finger
Assistant Professor, University of Chile

245

Experimental search for the cosmic background neutrino decay
in the cosmic far-infrared backgroundYuji Takeuchi1, Shin Hong Kim1, Kenichi Takemasa1, Kenji Kiuchi1,
Kazuki Nagata1, Kota Kasahara1, Takuya Okudaira1, Tatsuya Ichimura1, Masahiro
Kanamaru1, Kouya Moriuchi1, Ren Senzaki1, Hirokazu Ikeda2, Shuji Matsuura2,
Takehiko Wada2, Hirokazu Ishino3, Atsuko Kibayashi3, Satoru Mima4, Takuo Yoshida5,
Shota Komura5, Keishuke Orikasa5, Ryuta Hirose5, Yukihiro Kato6, Masashi Hazumi7,
Yasuo Arai7, Erik ramberg8, Jonghee Yoo8, Mark Kozlovsky8, Paul Rubinov8,
Dmitri Sergatskov8, Soo-Bong Kim9
Institute of Physics, University of Tsukuba
Institute of Space and Astronautical Science, JAXA
3
Okayama University
4
RIKEN
5
University of Fukui
6
Kinki University
7
High Energy Accelerator Research Organization, KEK
8
Fermi National Accelerator Laboratory
9
Seoul National University
1

2

We present a proposal for an experiment to search for the cosmic background neutrino
decay in the cosmic far-infrared background, and discuss the feasibility of the applicationof Superconducting Tunnel Junction (STJ) detectors to the experiment as far-infrared single
photon detector. Due to the mixing between the different mass generations of the neutrino,a heavier neutrino is expected to decay to a lighter neutrino with a photon, and the cosmic
background neutrino (CνB) is predicted as a relic of the big bang, while neither of the neutrino
decay nor the CνB is confirmed experimentally yet. The photon energy spectrum from theneutrino radiative decays in the CνB is expected to have a sharp edge at high energy end ina far-infrared region ranging from 14meV to 25meV (from 50um to 90um in wavelength).
We explore the cosmic infrared background photon energy spectrum in this region for feeble
contribution from neutrino decays. Thus, the detector is required to measure photon-by-photon
energies with high resolution enough to identify the edge structure, as well as to be designed
for a rocket or satellite experiment. One of promising choices for the detector is STJ using
hafnium (Hf-STJ) which is expected to have 2% energy resolution for single photon of 25meV
due to very small superconducting gap energy of hafnium. Another choice for the detector
is a combination of a diffraction grating and an array of niobium-aluminum STJ (Nb/Al-STJ)
pixels, where each the Nb/Al-STJ pixel is capable of single photon detection for a far-infrared
photon delivered to each pixel according to its wavelength by the grating. By a 200-second
measurement with these detectors if successfully implemented, we expect the detection ofneutrino decays in the CνB for the neutrino lifetime up to the order of 1014 years.
246

Bursts of star formation and gas outflows in galaxies
Dragan Salak
Division of Physics, Faculty of Pure and Applied Sciences, University of TsukubaStars in galaxies are formed in molecular clouds. Massive stars blow stellar winds andexplode as supernovae thereby returning most of the baryons back to the interstellar
medium (ISM). The material then becomes fuel for further star formation and the cycle
can be sustained over ~109 years. By contrast, in starburst galaxies, stars are formed at afurious rate, which leads to rapid consumption of molecular gas. Newly formed massive stars
provide strong feedback on the ambient ISM: radiation pressure and supernova explosions.
The energy of the feedback is high enough for a superwind to form: large-scale outflow ofgas and dust from the starburst region that restricts further star formation. In this talk, I
present recent observations of M82, an archetypal superwind galaxy. Due to proximity (3.5
Mpc) and peculiar starburst nucleus, M82 is one of the best-studied galaxies. Our observationsof molecular gas traced with CO (J=1-0) revealed that molecular gas clouds are ejected
up to >3 kpc above the galactic plane. At the base of the outflow is a 300-pc molecular-gas
ring. Molecular gas is ejected from the nuclear ring in two prominent expanding shells andfilaments. The mass outflow rate is comparable to the star formation rate (10-20 M sun /yr).
We show that the kinetic energy of the outflow can be provided from radiation pressure andsupernova explosions. With current starburst activity in the nuclear ring, molecular gas may
be consumed within ~107 years hence suppress further star formation.

247

Search for the Standard Model Higgs boson decaying
to a bottom-quark pair with the ATLAS detector
Kenji Kiuchi
grad. student, Univesity of Tsukuba

248

Development of Superconducting Tunnel Junction Photon
Detector with SOI Preamplifier Board to Search for Radiative
decaysof Cosmic Background Neutrino
Takuya Okudairagrad. student, Univesity of Tsukuba

249

NOTE

250

Symposium for Food Security andSustainable Agriculture
Food Security Research Unit, University of Tsukuba
Graduate School of Life and Environmental Sciences,
University of Tsukuba

251

252

Sep 29 (Mon)

5C216
Symposium for Food Security and Sustainable Agriculture

13:30-13:40

Miyako Kusano

University of Tsukuba

Brief Introdution

Chair

Miyako Kusano

University of Tsukuba

13:40-14:10

Nicolas Schauer

Metabolomic DiscoveriesGmbHComprehensive Metabolomics to Study Flavour in Natural Food

14:10-14:40

Yee-yung Charng

Agricultural Biotechnology
Research Center, Academia
SinicaExploring thermotolerance diversity in plants in the context of global
warming

14:40-15:10

Satoko Yoshida

RIKEN Center for Sustainable
Resource Science

Molecular and genomic analyses of the witchweed Striga

15:10-16:00

Alain Blanchard

University of Bordeaux

Building minimal cellular chassis using synthetic biology

16:00-16:20
Chair

Coffee BreakYasuhiro Ishiga

University of Tsukuba

16:20-16:35

Kimiyo Matsukura

University of Tsukuba

Distribution of Rhytismataceous fungi on Camellia japonica leaves inJapan

16:35-16:50

Syariful Mubarok

University of Tsukuba

Characterization and evaluation of F1 hybrid lines with SlETR1 mutant
alleles

16:50-17:05

Yuho Ando

University of Tsukuba

Molecular phylogenetic and morphological approach for species leveltaxonomy of the Grosmannia piceiperda complex

17:05-17:20

Takuya Uehara

University of Tsukuba

Identification of novel sex pheromone component in Lepidoptera

17:20-17:30

Yuichi Yamaoka

University of Tsukuba

Closing Statement253

18 / 26 ページ

Comprehensive Metabolomics to Study Flavour in Natural Food
Nicolas Schauer
Metabolomic Discoveries GmbH, Potsdam, Germany

Flavour analysis has been thus far principally a matter of sensory profiling by experts or
consumers. Products are being assessed on taste, aroma and texture based on the frame ofreference of the taste panel. Although sensory profiling provides very valuable information for
product development or the monitoring of product quality, it does not provide an objective andcomplete picture of the whole complexity of compounds that determine flavour. A relatively
new way of analyzing flavour is through metabolomics. This technology gives an unbiased
and most comprehensive analysis of the biochemical or metabolic state of a sample. Here, wehave developed a platform, the Flavor Profiler™, which combines a multi-parallel analytical
approach with high-performance computing pattern identification and modelling of flavour.
This allows to identify flavour relevant compounds and model optimal flavour compositions.
It further allows to control and ensure flavour quality in an objective way.

254

Exploring thermotolerance diversity in plants
in the context of global warming
Yee-yung Charng, Hsiang-chin Liu, Wei-di Wang, Kuo-hsing Chai and Yu-ting Juan
Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan

Temperature fluctuates dynamically in the natural environment. Elevations in temperatureof different intensity and duration result in different types of heat stress in plants. For example,
the effect induced in plants by acute heat stress associated with brief exposure to extremely hightemperature is different from that induced by chronic heat stress caused by prolonged exposure
to moderately high temperature; not withstanding, both these types of stress could lead to death
if the tolerance threshold is exceeded. Being mostly sessile during their life cycle, plants haveapparently evolved mechanisms to adapt to different types of heat stress; however, the detailsof these adapative mechanisms are not clear. In this presentation, I will cover recent progressin functional genomic studies that indicate that plants have evolved diverse thermotolerance
responses for different heat stress regimes. These responses include basal thermotolerance,
short-term and long-term acquired thermotolerance, and thermotolerance to moderately hightemperatures. Distinguishing between these different types of thermotolerance is important
to increase understanding of how plants respond to heat stress in the natural environment.
Phenotyping of genetic mutants with thermotolerance assays that address the distinct responses
is one strategy through which the genes required for tolerance to specific heat stress regimes
can be identified. Genes encoding proteins involved in various biological functions includingtranscription, translation, molecular chaperoning, protein degradation, RNA stability, lipid
metabolism, chromatin modulation, and posttranslational modification have been shown toform a complex thermotolerance network. In the context of global warming, it is critical toknow how plants adapt to climate change by coarse- or fine-tuning of the components in thisnetwork. Understanding of diversity in thermotolerance and its underlying mechanisms may
facilitate the breeding of heat tolerant crops that can better adapt to a changing climate.

255

Molecular and genomic analyses of the witchweed Striga
Satoko Yoshida and Ken Shirasu
RIKEN Center for Sustainable Resource Science, Japan

The parasitic plant Striga spp (common name, witchweed) is a major constrain in African
agriculture. Striga parasitize economically important crops such as maize, sorghum and riceand suck their nutrients and water up. The host plants are severely affected in their growth andyields and the losses caused by Striga are estimated as much as 1 billion USD. However, themolecular mechanisms of Striga parasitism are not well understood and effective management
methods have not been established.
Striga is an obligate parasite and therefore has a unique life cycle. The germination requires
host-derived strigolactones, which have also been characterized as host symbiotic signals forarbuscular mycorrhizal fungi in addition to their role as endogenous plant hormones that
regulate various developmental processes. The germinated Striga seedlings form an invasive
organ called a haustorium. The haustorium penetrates into a host root and eventually establishes
vascular connections with its host. Aiming to understand the molecular mechanisms of Striga
parasitism, we have performed genome and transcriptome analyses. Complete genome of S.
asiatica was sequenced and predicted genes were annotated. The genome features, such as GC
contents and frequency of repeat elements, are similar to autotrophic plants. Striga genome
contains evidences of horizontal gene transfers from host plants. Transcriptome analysis
revealed that genes harboring hydrolase activities are up-regulated during host invasion,suggesting active degradation of cellular components. For further characterization of genes
involved in parasitism, we have developed a model system using a Japanese native facultative
parasite, Phtheirospermum japonicum, which facilitate in vivo functional analyses of parasite
genes.

256

Building minimal cellular chassis using synthetic biology
Alain Blanchard, Pascal Sirand-Pugnet, Carole Lartigue
University of Bordeaux, France
UMR1332 Fruit Biology and Pathology, INRA, France

Synthetic biology (SB) is a key enabling technology with the potential to fundamentallychange the approach, tools and techniques of modern biological research and innovation, tothe benefit of the bioeconomy and society as a whole1. SB is the engineering and/or the designof biological systems that do not already exist in the natural world. It includes a number ofcomplementary approaches such as the building of minimal cells, the metabolic engineeringof existing cells for biotechnological purposes, the assembly of bio-components into protocells and the use of modified biochemicals to create artificial genetic systems. The concept ofminimal cell has attracted much attention in past years as it offers the possibility to understandthe functioning of all DNA-encoded elements that are necessary to support life, at least in thelaboratory. To reach this goal, it is logical to start with a living organism, which through thecourse of streamlining evolution, came to resemble a minimal cell. Arguably bacteria belonging
to the genus Mycoplasma are among the best candidates for this purpose and have been used as
starting material to develop SB technologies in order to manipulate their cell components ona large scale. In our laboratory, using mycoplasma cells we are pursuing the development oftechnologies with the aim of obtaining different cellular chassis that fulfill various applications.
A prerequisite to the building of a cellular minimal chassis is the identification of the genome
components that are able to support life. By using comparative genomics, we have shown that
there are different minimal sets of genes to support complex and essential functions such as thesynthesis of proteins. This chassis once obtained will be modified by plugging-in heterologous
sets of genes to deliver products in different environments.
: ERASynBio strategic vision;
https://www.erasynbio.eu/lw_resource/datapool/_items/item_59/erasynbiostrategicvision.pdf

1257

Distribution of Rhytismataceous fungi on Camellia japonica
leaves in Japan
Kimiyo Matsukura1, Yuichi Yamaoka1, Maiko Kagami2, Takashi Osono3 and Yasuhiro Ishiga1
Faculty of Life and Environmental Sciences, University of Tsukuba, Japan
2
Faculty of Science, Toho University, Japan
3
Center for Ecological Research, Kyoto University, Japan1

Pathogen outbreaks in important crop plants could give a significant impact on human
life. For example, the outbreak of soybean rust and wheat stem rust impacted the economy allover the world in recent years. Therefore, it is important to understand the fungal distribution
and factors affecting it for sustainability of agriculture and ecosystem. Rhytismataceae is
a common family known as endophytic, parasitic and saprotrophic fungi associated withvarious plants. Rhytismataceous fungi on Camellia japonica are known as primary selective
decomposers for lignin after colonizing, and also isolated from living leaves as endophytes.
However, the distribution of these fungi in Japan and possible factors affecting the distribution
are still unknown. In this study, we investigated the distribution of Rhytismataceous fungi on
C. japonica leaf litter across Japan. The distribution analysis revealed that there were three
Rhytismataceous fungi (Coccomyces sp., Lophodermium jiangnanense and Rhytismataceaesp.) on C. japonica leaves in Japan. Coccomyces sp. distributed all sites investigated broadly,
whereas L. jiangnanense was restricted in southwestern region that was characterized by much
precipitation and high temperature in early summer. Rhytismataceae sp. localized around
Kanto district in warm-temperate zone. Coccomyces sp. was most abundant among three
species in most of sites, excluding where L. jiangnanense colonized abundantly. On the other
hand, L. jiangnanense and Rhytismataceae sp. were detected from living leaves at sites where
they have not formed fruiting body on litter by PCR methods using species-specific primers.
These results suggest that Rhytismataceous fungi might show different distribution patterns
on living leaves. Further analyses for distribution patterns of Rhytismataceous fungi on leaf
litter and living leaves, are needed to estimate the possible factors affecting their distribution.

258

Characterization and evaluation of F1 hybrid lines with SlETR1
mutant alleles
Mubarok S, Y. Okabe, T. Ariizumi, N. Fukuda and H. Ezura
Graduate School of Life and Environmental Sciences,
University of Tsukuba, Japan

Fruit shelf life is one of the most important characters for breeding program that isregulated by ethylene. Control ethylene perception by modifying the ethylene receptor would
be a possible method for improving shelf life of tomato fruits. Two Sletr1 tomato mutant
alleles, Sletr1-1 and Sletr1-2, with a mutation in the ethylene receptor gene (SlETR1) havebeen isolated in our previous study. Those mutants showed reduced ethylene sensitivity andextended fruit shelf life that is expecting the potential as a breeding material. This study aimed
to characterize and evaluate fruit quality of F1 hybrid lines from two Sletr1 mutant alleles.
Those mutants and the wild type, Micro-Tom as control were crossed with four commercial
pure line cultivars (‘Aichi First’, ‘Ailsa Craig’, ‘Money Maker’ and ‘M82’) to obtain F1 hybridlines that would be evaluated. Sletr1-1 was not appropriate for breeding material because its
F1 hybrid lines showed strong ethylene insensitivity and high sensitivity to biotic and abiotic
stress, whereas Sletr1-2 would be potential for breeding material. Fruit of Sletr1-2 F1 hybridlines delayed in the ripening process and the shelf life was improved 4 – 5 days longer dependon genetic background of its pure line cultivars. In other characters, there are no significant
effect of Sletr1-2 mutation on vegetative and generative plant characters, fruit size, ethylene
production and respiration rate of harvested fruits. However it shows significant effect on
fruit color, fruit firmness, carotenoid content, and organic acid content at the harvesting time.
These results indicate the potential Sletr1-2 mutant as a breeding material to develop new
cultivar with improved fruit shelf life.

259

Molecular phylogenetic and morphological approach for species
level taxonomy of the Grosmannia piceiperda complex
Yuho Ando1, Hayato Masuya2, Riikka Linnakoski3, Z. Wilhelm de Beer4,
Michael J. Wingfield4, and Yuichi Yamaoka1
Faculty of Life and Environmental Sciences, University of Tsukuba, Japan
Tohoku Research Center, Forestry and Forest Products Research Institute (FFPRI), Japan3
Department of Forest Sciences, University of Helsinkii, Finland4
Department of Microbiology, Forestry and Agricultural Biotechnology Institute (FABI),
University of Pretoria, South Africa
1

2

The control of plant diseases has risen to become one of the most important issues for
global food security and sustainable agriculture. The taxonomy of plant pathogenic organisms
with correct identification is critical aspect of disease control. The genus Leptographium sensu
lato (Ophiostomatales, Ascomycota) is characterized by black ascomata, sheathed ascospores,
and dark erect conidiophores giving rise to series of branches bearing conidiophores withconidia produced in slimy masses. Most species in this genus cause sap stain of conifer
timber and are vectored by bark beetles. Phylogenetic studies have revealed nine species
complexes in Leptographium s. l. One of these, the Grosmannia piceiperda complex, currently
accommodates four species, but a recent multigene study has revealed seven lineages in thecomplex. The aim of this study was to resolve species boundaries in the complex usingreference isolates of the known species from the USA and Eurasia, and including Japaneseisolates. The results of phylogenetic analyses based on the ITS-LSU regions, as well as partsof the β-tubulin, EF-1α, and actin genes, showed eleven well supported lineages in the G.
piceiperda complex. No authentic isolates are available for G. piceiperda and G. europhioides,
both originally described from Canada. However, one lineage including only USA isolates
most likely represents one of these two species. The second lineage included only European
isolates and clearly represents an undescribed species. The Japanese isolates separated into
eight lineages, including G. aenigmatica, G. laricis, and apparently six new lineages, one ofwhich included isolates from Russia. In this way, the lineages of G. piceiperda complex were
showed tendency that these lineages were separated by association of intercontinental andconifer genus.

260

Identification of novel sex pheromone component in Lepidoptera
Takuya Uehara1,2, Hideshi Naka3, Shigeru Matsuyama4, Tetsu Ando5 and Hiroshi Honda4
Graduate School of Life and Environmental Sciences, University of Tsukuba, Japan
2
Research Fellow of the Japan Society for the Promotion of Science
3
Faculty of Agriculture, Tottori University, Japan
4
Faculty of Life and Environmental Sciences, University of Tsukuba, Japan
5
Graduate School of Bio-Applications and Systems Engineering,Tokyo University of Agriculture and Technology, Japan

1

In order to clarify how species specificity of sex pheromones develops in the processof speciation, we have determined the sex pheromones from 17 species of hawk moths.
Most of these sex pheromones consist of C16 unsaturated aldehydes, 11-hexadecenals and10,12-hexadecadienals (Uehara et al. 2012). Interestingly, one species, Dolbina tancrei uses
C15 dienyl aldehyde, (9E,11Z)- and (9Z,11Z)-9,11-pentadecadienals (Uehara et al. 2013).
D. tancrei commonly occurs in Japan and is a sporadic pest of Oleaceae ornamental
plants including sweet osmanthus, sweet scented olive, and privet. Larvae of the mothwere collected from privet, Ligustrum obtusifolium (Lamiales, Oleaceae) and reared in alaboratory condition until their pupation. After emergence, female pheromone glands wereextracted with distilled hexane, and then the extracts were subjected to Gas Chromatography–
Electroantennograhic Detection (GC-EAD), Gas Chromatography–Mass Spectrometry(GC-MS), and gas chromatography (GC) analyses. GC-EAD analyses showed that the maleantenna responded to two components in the crude pheromone extracts. GC-MS analysis
determined these two components to be pentadecadienals. GC-MS of their MTAD derivatives
showed conjugated double bonds at the 9- and 11-positions, indicating 9,11-pentadecadienals.
Geometrical isomers of these candidates were determined based on comparison of their Kováts
retention indices with those of synthetic compounds. Field bioassays with four isomers of
9,11-pentadecadienal and their mixtures confirmed that the two sex pheromone componentsof D. tancrei are (9E,11Z)-9,11-pentadecadienal and (9Z,11Z)-9,11-pentadecadienal with thehighest male catches observed for a 90:10 ratio. This is the first report of 9,11-pentadecadienals
as sex pheromone components in lepidopteran species.

261

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262

Initiatives of Research, Preservation andManagement for Granting UNESCO World Heritage
Status at the Pyu and Bagan Monument
World Heritage Studies,
Graduate School of Comprehensive Human Sciences,
University of Tsukuba

263

264

Sep 30 (Tue)Meeting Room 5

Initiatives of Research, Preservation and Management for Granting UNESCO World Heritage Status at the Pyu and Bagan Monument
Moderator

Junko Okahashi

University of Tsukuba

9:00-9:05

Junko Okahashi

University of Tsukuba

Brief Introduction

9:05-10:05

U Win Kyaing

Field School of Archaeology(Pyay)

Challenges for the future at the World Heritage inscribe site, Pyu
Ancient Cities

10:05-11:05

Kai Weise

UNESCO

Issues on the safeguarding of Bagan monuments

11:05-11:35

Ichita Shimoda

University of Tsukuba

Conservation of the architectural heritages in the Southeast Asia

11:35-12:05

Discussion U Win Kyaing,
Kai Weise, Nobuko Inaba,
Ichita Shimoda

12:00-12:20

Questions from the floor

12:20-12:25

Nobuko Inaba

University of Tsukuba

Summary265

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Initiatives of Research, Preservation and Management for
Granting UNESCO World Heritage Status at the Pyu and Bagan
Monument
Kai Weise, UNESCO (Keynote Speech/Discussion)
U Win Kyaing, Field school of Archaeology (Pyay) (Keynote Speech/Discussion)
Inaba Nobuko (Discussion)
Shimoda Ichita (Report, Discussion)
Okahashi Junko (Moderator)

Many countries including the neighboring ASEAN region are strongly interested
in the international cooperation to Republic of the Union of Myanmar which is seeing
the prospect of democracy and accelerated the economic development in recent years. In
June this year, one of the significant archaeological site, Pyu Ancient Cities was inscribedto the UNESCO World Heritage site that is the Myanmar’s first inscribed site to the List.
Three archaeological sites, Halin, Beikthano and Sri Ksetra are located along the Ayeyarwady
river and flourished from 2nd to 9th century as the capital city of the Pyu Empire. There are
numerous archaeological remains include excavated palace citadels, burial grounds and earlyindustrial production sites, as well as monumental brick Buddhist stupas, partly standing walls
and water management features that underpinned the organized intensive agriculture.
Subsequently, the Myanmar government is expected to begin in earnest to prepare forthe next World Heritage application of Bagan Monuments. Bagan monument is sometime
referred as one of the three greatest Buddhism sites in the world, with Angkor monuments in
Cambodia and Borobudur temple in Indonesia. Several thousands of brick structures wereconstructed mainly from 11th to 13th century, and still maintain the highest historical valuable
sites in Myanmar from architectural, artistic and landscape points of view. In addition, thissite is inheriting the practice of this unique region. This site was attempted to be inscribed
as a UNESCO World Heritage in 1990s, but they were interrupted this first challenges.
While a rapid increase of tourists in the past few years, pressure and expectations of tourism
development increases, it is assumed to ensure the value of the ruins, and comprehensive
approach towards the maintenance has been required.
In this session, two of the significant person who involved in the preservation andcultural development work in these sites will lecture the direction of the international cultural
cooperation including government and UNESCO projects on the research, restoration, andsustainable development. Then, we discussed the issues on the current state of the preservation
management including some case studies of archaeological sites in Southeast and South Asia,and clarify the needs of the further research, conservation, sustainable development, andinternational cooperation for the future.

266

NOTE

267

NOTE

268

Symposium on Health andSport Sciences
Faculty of Health and Sport Sciences,
University of Tsukuba

269

270

Sep 30 (Tue)

5C216
Symposium on Health and Sport Sciences

9:00-9:05

Michiyoshi Ae(1) Biomechanics / Sports Technology
Chair
Michiyoshi Ae

University of Tsukuba

Opening statement

University of Tsukuba

9:05-9:40

Jill L. Mcnitt-Gray

University of Southern
California

Improving the Biomechanics of Aerial Skills performed by Olympic
Athletes

9:40-10:15

Takeshi Asai

University of Tsukuba

Research and Development of Sport Equipments at the University ofTsukuba

10:15-10:50

Andy Harland

Loughborough University

Sports technology and performance; how athletes of all standards canbenefit

10:50-11:10
Coffee Break(2) Health Science
Chair
Seiji Maeda

University of Tsukuba

11:10-11:45

Tomohiro Okura

University of Tsukuba

A novel fall- and dementia-exercise program for successful aging ofolder adults

11:45-12:20

Hyon Park

Kyung Hee University

Application of Korean Red Ginseng or Some Specific Ginsenosides
as a Nutritional Ergogenic

12:20-12:25

Akira Nakagawa

University of Tsukuba

Closing statement271

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Improving the Biomechanics of Aerial Skills performed by
Olympic Athletes
Jill L. McNitt-Gray, PhD, FASB
Departments of Biological Sciences and Biomedical Engineering
University of Southern California, Los Angeles, CA

Satisfying mechanical objectives of sports-specific tasks requires effective interaction between the neuromuscular system, the musculoskeletal system and the environment. Analysis
of complex aerial skills, such as those requiring the generation of linear and angular momentum, indicates that the nervous system organizes the human body into a number of operational
subsystems that are coordinated according to priorities specific to the individual performer.
By determining multi-joint control strategies used by elite athletes across different tasks, we
can advance our understanding of the biomechanics and facilitate learning and improvementsin performance. The acquisition of evidence for modifications in movement technique requires
systematic experimentation conducted in realistic contexts, including the Olympic Games.
The combination of laboratory-based experimentation and dynamic modeling with evidence
from field-based studies allows us to determine how athletes are generating the forces causing
the observed movements and ascertain why certain factors affect performance. These quantitative results acquired under realistic conditions can then be used as a basis for designingskill progressions used to improve performance for athletes at all skill levels. As part of thistalk, we will discuss how knowledge of flight and contact phase biomechanics can be used to
improve the performance of Olympic level divers and gymnasts during competition.

272

Research and Development of Sport Equipments at the
University of Tsukuba
Takeshi Asai, Norihisa Fujii, Sekiya Koike, Michiyoshi Ae
Faculty of Health and Sport Sciences, University of Tsukuba, Japan

Research projects related to sport fluid engineering are being conducted at the Universityof Tsukuba, as a part of the ‘Multi-support Project’, sponsored by Ministry of Education, Culture, Sports, Science and Technology, Japan.
For example, research and development related to bicycle competitions, including the areasof competitive bicycle frames, wheels, helmets, and wear, have been conducted jointly withmany affiliated companies. The sport wind tunnel at the University of Tsukuba has been used
to examine the aerodynamic characteristics of sport products, in order to improve the performance of competitive bicycles. In the case of competition wear, examinations include ways todelay the boundary layer separation on the back surface of an athlete, the turbulence effects
on the lower body caused by pedalling, and the rectification of the air flow from the stomach
region to the back, and findings have been implemented.
In addition, in the research and development for ski jump suits, the fabric resistance of ski
jump wear was measured using an airfoil tool, and a full scale mannequin was used to analyze
the aerodynamic characteristics of ski jump suits, while taking into consideration the forms
and sewing portions of the latest ski jump suits. Furthermore, computational fluid dynamics
was employed to analyze the flow velocity distribution and pressure distribution of an athlete
during flight phase of ski jump, for the purpose of improving ski jump suits. The developed
ski jump suits were worn by all the Japanese athletes who participated in the 2014 Winter Olympics at Sochi in Russia, where the ski jump team won a silver medal (men’s individual largehill) and bronze medal (men’s team large hill), and the Nordic combined team won a bronze
medal.

273

Sports technology and performance; how athletes of all
standards can benefit
Andy Harland
Director, Sports Technology Institute, Loughborough University, UK

Technology plays an ever increasing role in sport, from training and conditioning aids,
through enhanced equipment used in competition to performance analysis and feedback
systems. In his talk Dr Harland will reflect on recent technological developments in sport anddiscuss how these have affected sports performance. He will consider the role that technology
might play in future and explore the boundaries between technological advantage and unfair
advantage. Drawing on case studies from his own group’s research, Dr Harland will discuss
how partnership based, athlete centered approaches to research have led to successful outcomesin a range of individual and team sports. He will also discuss how the public appetite fortechnology is important in driving advances in sports technology and how the needs of elite
athlete compare to those of recreational athletes and why it is important to consider both.

274

A novel fall- and dementia-exercise program for successful agingof older adults
Tomohiro OKURA, PhD
Faculty of Health and Sport Sciences, University of Tsukuba

To prevent physical frailty and a decline in cognitive function in older adults, regularphysical activity and exercise training are considered indispensable. We have developed anovel exercise program for preventing falls and dementia called “Square-Stepping Exercise”(SSE), which can induce functional activation of the brain.
The purpose of this study was to investigate the longitudinal effect on the physical andcognitive functions of community-dwelling, older, Japanese adults who regularly performed
the SSE over 3 years.
Our study had 2 groups: the SSE Group (n=40; mean age 70.2±3.6 years) in which participants voluntarily continued the SSE program once or twice per week for 3 years, and theControl (C) Group (n=40; mean age 70.1±3.6 years) who were randomly selected from the basic
resident register. We evaluated physical performance with 7 performance tests and assessed
cognitive function using the 5-cog test.
In the SSE Group, results of the 5-repetition sit-to-stand (SIS) and timed up-and-go (TUG)
tests improved significantly over 3 years (SIS: 7.0 to 6.4 sec; TUG: 5.7 to 5.4 sec, trend P<0.05).
On the other hand, no changes were observed in the C Group. There were also significant
differences between the two groups when we look at the change in SIS and TUG results fromyear 2 to year 3: SIS (2nd year: 5.8 vs. 7.2 sec; 3rd year: 6.4 vs. 7.2 sec, P < 0.05) and TUG (2ndyear: 5.1 vs. 5.7 sec; 3rd year: 5.4 vs. 5.9 sec, P<0.05) (SSE Group vs. C group, respectively).
Furthermore, 5-cog test scores in the SSE Group increased significantly over 3 years while nochange was observed in the C Group (SSE 69.7 to 84.1, P<0.05; C 69.3 to 76.3, not significant).
The scores of the 5-cog test indicated a significant difference in the third year between the SSE
and C groups (84.1 vs. 76.3 points, P<0.05).
These results suggest that regular and voluntary participation in SSE by older adults overthree years could help them maintain or improve their physical and cognitive functions.

275

Application of Korean Red Ginseng or Some Specific Ginsenosides
as a Nutritional Ergogenic
Hyon Park, Ph.D.
Professor at the Department of Sports Medicine, Kyung Hee University, Korea

Ginseng, which is often called the root of life, is a deciduous perennial plant which has avery long history of use for the promotion of health, especially in far eastern countries and inEurope. From 11 ginseng species, Korean ginseng is known to be the highest-quality one that
contains the largest variety of ginsenosides, efficacy components of ginseng, as around 32 outof 37 known ginsenosides so far. A processed form as of red ginseng is the popular productin the market, and its Korean FDA certified efficacies are as follows; 1) enhances the immune
system, 2) aids in recovery from fatigue, 3) promotes blood circulation, and 4) promotes
memory functions. Other studies on Korean ginseng have proposed additional efficacies:
control over blood sugar level and vast improvement on male sexual function.
Korean red ginseng or other purified ginsenosides as Rg1, Rg3, Rb1, and Rh1, have beentested as an ergogenic for athletic performance for decades. Effects on the attenuation ofnegatives caused by lipid-peroxidation, the increase of immune function, and the ability offaster recovery from severe physical activity are agreed in most of studies on animals andhuman subjects. On the other hand, supporting evidences of performance improvement havenot produced enough result to be accepted yet, but some results of possible beneficial effects ofspecific purified ginsenosides on physical performance have been shown in several recent welldesigned(randomized, double-blind, placebo-controlled, and crossover) studies. Proposedmechanism of effects involves several biochemical processes of oxidative stress buffering andanti-inflammatory works of applied ginsenosides.
We still need to look deeper on ginseng and its efficacy components, ginsenosides, on
optimum dose, types, and timing to use them as safe and recommendable nutritional ergogenic
supplements. This presentation will cover from the general information of ginseng to theapplication of ginseng as an ergogenic with various scientific evidences.
Key words ; Korean red ginseng, ginsenosides, health, physical performance, ergogenics

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Symposium for expanding application of
new power semiconductor devices
Power Electronics Laboratory,
Graduate School of Pure and Applied Sciences,
University of Tsukuba

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Sep 30 (Tue)Meeting Room 6
Symposium for expanding application of new power semiconductor devices

Chair

Noriyuki Iwamuro

University of Tsukuba

13:00-14:30

Marta Molinas

Norwegian University of
Science and Technology

Power Electronics in the Modern Power System

Jon Are Suul

Norwegian University of
Science and Technology

Challenges for Operation and Control of Grid Connected Power
Converters

University of Tsukuba

Closing statement

14:30-15:00

Discussion

Hiroshi Tadano281

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Power Electronics in the Modern Power System
Marta Molinas
Department of Engineering Cybernetics, Norwegian University of Science and Technology,
7495 Trondheim, Norway

The use of power electronics in power systems has for long time been increasing due tothe widespread application of electric drives and switch mode power supplies. More recently,
this trend has been accentuated with the grid integration of renewable energy sources which
due to their basic incompatibility with the grid requirements has introduced new challenges.
In this context, power electronics enables a very effective, flexible and active coupling withthe grid system offering high controllability and buffering capabilities (e.g. energy storage).
Simultaneously, the range of applications of power electronics has been moving beyond thedomains of generation and traditional loads, migrating into compensation devices (FACTS),
actively controlled loads, harmonic filters, DC circuit breakers, electronic transformer, HVDC,
energy storage and transportation in the form of moving loads in the system. When thispervading presence of power electronics combines with other features such as nonlinear timevarying loads and equipment in modern power system, the new properties introduced by thecybernetic nature of power electronics are defining the overall behavior of the system, making
it an increasingly complex issue. The presentation will cover aspects of the new dimensionthat the pervasive use of power electronics is introducing in modern power systems, highlightresearch findings in some of the above areas, and conclude with the identification of new
avenues for research triggered by the many challenges of the new scenario.

282

Challenges for Operation and Control of Grid Connected Power
Converters
Jon Are Suul1,2
1

Department of Electric Power Engineering, Norwegian University of Science and Technology, Norway
2
SINTEF Energy Research, Norway

The utilization of actively controlled Power Electronic Converters for grid connected
applications is continuously increasing, expanding into a wide range of power and voltage
levels. In addition to distributed generation units like wind turbines and photovoltaic
generation systems where power electronic converters are necessary for grid integration,loads, transmission schemes and energy storage units are also increasingly utilizing actively
controlled converters as their grid interface. As the penetration of power electronic converters
in the power system is increasing, it is expected that they will meet stricter and more demanding
operation and control requirements, for utilizing their controllability and multi-function
capability to the advantage of the power system. Examples of requirements for Low Voltage
Ride Through (LVRT) capability and reactive power support are already well established inmany countries as specified in the Grid Codes for connection of wind farms to the powersystem. It is also well known that other auxiliary functions like active filtering capability andresonance damping can be incorporated in the control of grid connected converters. Abilityof temporarily operating limited parts of the power system as islanded Micro-Grid is also
appearing as an advantageous option in the emerging SmartGrid context. Implementationof such additional functionalities can influence the design requirements of the converters andwill lead to additional challenges for the control system. This is especially the case for highpower converters designed with conventional high voltage Si-based semiconductors requiring
low switching frequencies for achieving acceptable power conversion efficiency. By startingfrom conventional and emerging applications of grid connected power electronic converters,
this presentation will identify and discuss the most critical challenges for design and control
of converter units with multi-function capability. On this basis, it will be discussed how new
semiconductor devices with lower losses and/or capability for higher switching frequencies canbe utilized to improve the performance and alleviate the control challenges of grid connected
power electronic converters.

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Information Schools in Asia-Pacific andtheir Collaboration
Faculty of Library, Information and Media Science,
University of Tsukuba
Research Center for Knowledge Communities,
University of Tsukuba

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Sep 30 (Tue)Meeting Room 5
Information Schools in Asia-Pacific and their Collaboration

Chair

Shigeo Sugimoto

University of Tsukuba

13:30-13:35

Shigeo Sugimoto

University of Tsukuba

Introduction

13:35-14:00

Li Guangjian

Peking University

Development of Library and Information Science Major in China: Status
and Trends

14:00-14:25

Kulthida Tuamsuk

Khon Kaen University

Information Schools in Thailand and Southeast Asia

14:25-14:50

Andrew B. Wertheimer

University of Hawaii

Studying Information as a Way to Promote Peace and Sustainability

14:50-15:15

Emi Ishita

Kyushu University

Educating Information Professionals in the Department of Library
Science at Kyushu University, Japan

15:15-15:25

Discussion

15:25-15:30

Shigeo Sugimoto

University of Tsukuba

Closing statement287

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Development of Library and Information Science Major in
China: Status and Trends
Dr. Li Guangjian
Department of Information Management, Peking University
E-mail: ligj@pku.edu.cn

The history of library and information science education in China will be described. Special attention will be paid to the development of LIS major since late 1990s. Connection between the major and society, especially the collaboration with other social institutions will also
be discussed.

288

Information Schools in Thailand and Southeast Asia
Dr. Kulthida Tuamsuk
Faculty of Humanities and Social Sciences, Khon Kaen University
E-mail: kultua@kku.ac.th

The report on situation of information education in Thailand and Southeast Asia at bothundergraduate and post-graduate levels which covers: the policies at national and regional
levels, the higher institutions which provide information education, the curricula and courses,
the learning and teaching approaches, the international collaborations among them and withinformation schools in other regions, the information professions and its future.

289

Studying Information as a Way to Promote Peace andSustainability
Dr. Andrew B. Wertheimer
Library & Information Science Program, Information & Computer Sciences Department,
University of Hawaii
E-mail: wertheim@hawaii.edu

For several decades people have said that we are in the “Information Age,” but few
disciplines have critically examined what this means, including the field of Library andInformation Science (LIS). This presentation will build on Christine Pawley’s claim that LIS
has been “Hegemony’s Handmaiden” ever since Melvil Dewey (1851-1931) established thefield with help from Andrew Carnegie. After briefly critically reviewing these origins, thepresentation will suggest we reconsider the vision of Belgian Paul Otlet (1868-1944) and his
pre-internet Repertoire bibliographique universel (Universal Bibliographic Repertory), which
also received Carnegie Funding. Otlet believed that organizing and providing global accessto information worldwide would promote world peace. The presentation will also look at“Critical LIS” as a way of seeing how information can encourage peace and sustainability,
by using counter-examples of those in power have grossly manipulated information given tovoters, such as the disinformation which led to America’s Iraq War (2003-11). The presentation
will conclude with a set of research agendas that could demonstrate the relevance of a Critical
LIS in today’s complex information economy.

290

Educating Information Professionals in the Department ofLibrary Science at Kyushu University, Japan
Dr. Emi Ishita
Department of Library Science, Graduate School of Integrated Frontier Sciences, Kyushu University
E-mail: ishita.emi.982@m.kyushu-u.ac.jp

The Department of Library Science, Graduate School of Integrated Frontier Sciences,
Kyushu University started the Master and Doctoral program in 2011 and 2013, respectively. Our
department offers an integrated program base on Library and Information Science, Archival
and Records Management Studies conducted by scholars with many different disciplines Social Sciences, Humanities, and Computer and Information Sciences. Our department has
strong relationship with the Kyushu University Library for education and training of students
and for collaboration in the scholarly information community. This talk will overview the
Department of Library Science at Kyushu University and briefly discuss its collaborative
activities in the information schools’ community.

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Innovative Approaches to Natural
Resources for Development of North
African and Mediterranean Regions
Alliance for Research on North Africa (ARENA),
University of Tsukuba
Tunis Office, University of Tsukuba

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Sep 30 (Tue)Special Conference Room

Innovative Approaches to Natural Resources for Development of North African and Mediterranean Regions
Chair

Kennichi Kashiwagi

University of Tsukuba

Hiroko Isoda

ARENA, University of Tsukuba Introduction

13:40-14:20

Ismaili Alaoui Mustapha

IAV Hassan II

Application of Biotransformation as Lever of Development of Vegetable
Biomasses

14:20-15:00

Brahim Bessaïs

Research and Technology
Centre of Energy BP. Tunisia

Energetic transition in Tunisia:
Impacts on research activities and capacity buildings

15:00-15:20

Coffee Break

15:20-16:00

Majed Abu-Zreig

German-Jordanian University

Control of Agricultural Land Erosion in Jordan with Polyacrylamide

16:00-16:40

Mohammed Abdulla AlSadiq

University of Bahrain, Bahrain. Oil and Gulf Economies within a Changing Regional Environment

16:40

Mitsutoshi Nakajima

ARENA, University of Tsukuba Closing statement295

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Application of Biotransformation as Lever of Development of
Vegetable Biomasses
Ismaili Alaoui Mustapha
IAV Hassan II, BP 6202, Rabat Institute, Morocco

ungi I. Metabolism of R (+) pulègone. Tetrahedron Letters, Vol. 33, N°17, pp. 2349-2352.
Morocco is a North African country that has a rich tradition in food technology. Many traditional foods of animal or plant origin are still widely consumed and highly appreciated.
Moroccan government is trying to promote the agriculture sector, in particular food industry
using several programs and plans (Green Moroccan plan, Emergence plan, Human development programs, etc.). These programs aim to enhance productivity and quality through optimization of culture, technology and biotechnology. The major Food biotechnology program
can be grouped around three main axis:
1-	Control of traditional fermentations: A large part of process are still mainly located at thehousehold level in poor sanitary conditions and marketed through informal channels. They
remain beyond official control for compliance with national regulations and international
standards. A large part of 120,000 tons of Moroccan table olives are exported after industrial
fermentation process using selected endogenous strains from traditional fermentations.
The objective is to valorize vegetables and animals products using microorganisms, spices,aromatic herbs and natural dehydration process.
2-	Value-added products of sub-agro-industrial products by fermentation: Moroccan foodindustry produces more than 1 million tons of by-products (300 tons of olives cake, 300
tons of bagasse sugar, 200.000 tons of flour fish.etc.). A large part of these raw materials are
scarcely exploited, and their elimination in nature is a threat to the environment. Proteins
content of Olive cake were increased from 6 to 20 % using solid state fermentation withhigh digestibility. Some of selecting fungus was used to ferment olive cake to produce
a large quantity of enzymes (lipases, esterase’s, phytase). Natural aromas, compounds
used for cosmetic, food, and pharmaceutical industries were produced. The objective is totransform wastes into feeds or producing enzymes or aromas using solids state fermentation
by fungus.
3-	Valorization of natural materials by bioconversion using selecting strains of Fungus: The
products of biological oxidation of some terpenoïds abundantly present in aromatic herbs(Eucalyptus, Mentha pulegium, Artemisia herba alba.etc) will be described with focus on
the diverse region and stereoselectivities obtained from these terpenic compounds.

296

Energetic transition in Tunisia:
Impacts on research activities and capacity buildings
Brahim Bessaïs and Amen-Allah Guizani
Research and Technology Centre of Energy BP. Tunisia

The energy balance of Tunisia reached a deficit beyond 2000. To overcome this deficit,
Tunisia developed a strategy based on integrating renewable energy (RE) in the balance, aiming
to constitute 30% of the total national energy production around 2030. Industrial integration
development of RE and then creation of employment and value need capacities strengthening
while focusing on research and development (R&D), innovation and technology Transfer. The
ambitious energetic strategy of Tunisia needs the development of skills in RE technologies.
RE may efficiently contribute to sustainable development (creation of jobs and development ofinland regions) targeting to reduce the regional instability and the impact of fossil fuels.
In this context, as a government institution the Research and Technology Centre of Energy(CRTEn) has among other responsibilities capacity building, and technology survey andtransfer mainly in Solar thermal and Solar PV.
Solar thermal activities address low and mid temperature starting with interest to thematerial, the component and the complete systems, aiming to master technologies that support
local industries. The main solar applications targeted are production of Domestic Hot Water,
agricultural greenhouses, cooling, drying and desalination. Efforts are focused the last three
years on CSP (Concentrated Solar Power), which could have an important impact as somepower plants are planned using this concept in the near future, in an effort to enhance theRenewable Energy share in the energy mix.
Tunisia (CRTEn) was the first Arab and African country who produces silicon solar cells
at a pilot level in 1990 with a yield of about 11%. Technological progress led in 1993 to an
average efficiency of 12-13%.
Thanks to nanosciences, the CRTEn succeeded to introduce silicon nanostructures as:• Antireflective and passivation coatings in Si solar cells.
• Precursors for achieving cheap grooves using inexpensive chemical techniques.
•	Precursors to purify the base material, and improve the electrical and optoelectronic
properties of Si solar cells.

297

Control of Agricultural Land Erosion in Jordan with
Polyacrylamide
Majed Abu-Zreig
Department of Water and Environmental Engineering, German-Jordanian University, Jordan

Land erosion is considered one of the most detrimental processes to the productivity anddegradation of agricultural lands. The damaging effect is even more profound in arid andsemi arid climates where lands are subjected to sever droughts and scarce rainfall conditions
such as in Jordan. The use of polyacryamide for soil conservation is being considered by theauthors under filed and natural rainfall conditions. Two types of polyacrylamide were used totest their influence on soil erosion and runoff of sloping land in Jordan under natural rainfall
conditions. The two PAM used in this study, commercially named as A836 and A870, havedifferent molecular weight ranging qualitatively from high to low and surface charge from
20% to 70%, respectively. Fourteen field plots with 2 m wide by 10 m long having a slope of
11% were constructed in the field. A runoff collection barrels were installed at the end of plots
to monitor the amount of runoff and sediment loss after each storm. The PAMs were applied
at 2 application rates of 10 and 30 kg/ha plus a control. Experimental results showed that
Both types of PAM caused large reduction in soil loss with an average value of 22% compared
to control and 70% compared to compacted plots. Application of A836 reduced runoff andsediment loss by 23% and 35%, respectively compared to control. The corresponding average
decreases in runoff and soil loss for A870 were lower at 16% and 8%, respectively. Differencesin runoff among PAM treated plots at 10 and 30 kg/ha were negligible but soil loss was slightly
lower in the 30 kg/ha PAM treated plots.
Key Words: PAM, Field plots, Soil loss, Moisture conservation

298

Oil and Gulf Economies within a Changing Regional
Environment
Mohammed Abdulla Al-Sadiq
Dept. of Finance and Business Studies Unit,
Deanship of Scientific Research - University of Bahrain, Bahrain

For more than 50 years, the oil sector has had an important impact on the overall economies
of Gulf Cooperation Council (GCC) countries. It is worth mentioning that Bahrain was thefirst country in the Arabian Gulf region in which oil was discovered in 1932. But it was not
until the quadrupling of oil prices during the period October 1973 to January 1974, as a resultof the coordinated action by OPEC members to raise the price of oil, that substantial amounts offinancial capital became available and provided the potential for rapid economic development.
Since the mid-seventies, the role of the GCC countries in the international oil market (IOM)
has been increasingly important. It has played an important role, through OPEC, in directing
the oil sector in the world.
Oil revenues have transformed most of the aspects of socio-economic life in the GCC
countries. They have contributed to the establishment of the infrastructure, support in founding
industrial companies, and for the financing of education, culture, defense and security.
The banking offshore industry expanded rapidly, and since 1980, Bahrain has become an
important financial centre in the region.
The acceleration of investment spending and the continuous growth of various economic
sectors led to a rapid inflow of foreign labour which recently accounts for more than half of thetotal labour force in GCC economies.
The 2003-2008 oil price boom spurred economic activity in the area and strengthened
the performance of all economic sectors. Since 2004 at the latest, many GCC countries havejoined the ranks of the fastest growing economies in the world. Tremendous prosperity has
been witnessed in the cities like Riyadh, Kuwait, Manama, Doha, Abu-Dhabi, Dubai, andMuscatThis paper attempts to look at the impact of oil on the GCC economies with special emphasis on its development, security and future prospects.

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G30 Joint Seminar
Borderless Challenge Towards Global
Aging by Young Power:
Comparative Analysis of Long Term
Care in the World
Faculty of Humanities and Social Sciences
Faculty of Medicine
University of Tsukuba

301

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Sep 30 (Tue)Annex Hall

G30 Joint Seminar Borderless Challenge Towards Global Aging by Young Power: Comparative Analysis of Long Term Care in the World
Chair
Chair

Miyoko Motozawa
Nanako Tamiya

University of Tsukuba
University of Tsukuba

Gerhard Igl

University of Kiel

13：00-13：40

Introduction
Nanako Tamiya

University of Tsukuba

13:40-13:55

Jason Thompson

University of Tsukuba

Aging and long term care in U.S.A

13:55-14:10

Issei Watanabe

University of Tsukuba

Aging and long term care in Japan

14:10-14:25

DaEun Ariana Han

University of Tsukuba

Aging and long term care in South Korea

14:25-14:40

Eric Adjepong Kwarteng

University of Tsukuba

Aging and long term care in Ghana

14:40-14:55

Drauna Adi Miriama

University of Tsukuba

Aging and long term care in Fiji

14:55-15:10

Josephine Laker

University of Tsukuba

Aging and long term care in South Africa

15:10-15:25

Comments

Gerhard Igl

University of Kiel

15:25-15:45

Closing statement
Nanako Tamiya

University of Tsukuba

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G30 Joint Seminar
Borderless Challenge Towards Global Aging by Young Power:
Comparative Analysis of Long Term Care in the World
Prof. Miyoko Motozawa and Prof. Nanako Tamiya

The world is aging rapidly and will continue to age at a great speed. A report by UFPA
predicts that by 2050, senior person aged 60 years and over will make up more than 80 percentof the population in developing countries. Developed countries have been experiencing thisageing phenomenon from an earlier point in time and have been pushed to adapt their systems
accordingly at a great expense of resources. This unprecedented phenomenon in human history
will also force emerging economies to adapt themselves to face the upcoming challenges.
However, social and economic disparities among developing and emerging economies pose aneven harder and complex scenario. These countries are eagerly looking at what more advanced
aged countries are doing to tackle the problems arisen from an increasing greyer population.
Many countries around the world, developed and developing ones have a great interest inwhat the fruits of long term care system in Japan and Germany. However, it might be very
important to discuss whether these countries need to adapt the system or not. It is under thesecircumstances that we, at the university of Tsukuba, G30 joint seminar (Faculty of Humanities
and Social Sciences and Faculty of Medicine), to create a meeting point of discussion wherestudents and faculty from all over the world have been invited to participate and share theirexperiences around the aging of our societies, and by doing this being able to acquire a global
perspective of a problems that affects us all. Our section aims at understanding and comparing
the situation of the ageing process in each participant country from a varied set of viewpoints,
and building a road to a long-term care policy adapted to each particular setting base on joint
seminar held on September 24 and 25, 2014.

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Symposium for International Collaboration of
Science & Technology, and Innovative Development
in Central and East Asia
Center for Innovative Development of Science and
New Technologies of Academy of Sciences of the
Republic of Tajikistan
Department of International Exchange & Cooperation,
Dalian Nationalities University, China
Faculty of Life and Environmental Sciences,
University of Tsukuba

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Sep 30 (Tue)Meeting Room 3

Symposium for International Collaboration of Science & Technology, and Innovative Development in Central and East Asia
(1) International Collaboration of Science & Technology, and Innovative Development in Central and East Asia: PART1
Chair
Kenji Tamura
University of Tsukuba
13:30-14:30

Mamadsho Ilolov

Science Academy of the
Republic of Tajikistan

14:30-15:10

Ubaidulloev Zubaidullo

University of Tsukuba

15:10-15:30

Discussion<Keynote Speech>
Innovative development of the Republic of Tajikistan<Contribution Speech>

15:30-15:50
Coffee Break(2) International Collaboration of Science & Technology, and Innovative Development in Central and East Asia: PART2
Chair
Kenji Tamura
University of Tsukuba<Keynote Speech>
15:50-16:20
Xiaohui Wang
Dalian Nationalities University International Exchange and Cooperation of Science & Technology,
Sports, & Arts- between China and Japan
16:20-16:50

Wuyunna<Keynote Speech>
International Collaboration for Conservation of Asian Steppe Grassland<Contribution Speech>

16:50-17:20

17:20-17:50

Dalian Nationalities University

Discussion

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