bluuebunny/crossref_metadata_2025 huggingface dataset:
A national survey of demographics composition of Kenyan journalists
Authors: Ireri Kioko
Published: August 2015

This national survey conducted in 2012–2013 (N = 504) examines demographic characteristics of the Kenyan journalists. Findings indicate that the typical Kenyan journalist is male (66%), married (57%), and in his mid-30s (M = 34 years). He tends to have a Bachelor’s degree (46%) and has received college-level training in journalism or communication (91%). However, when it comes to majoring in journalism or communication, most of the journalists were trained at the level of associate degree (45%), followed by Bachelor’s degree (38.5%) and Master’s degree (13.6%). Thirty-three percent of the Kenyan journalists work in daily newspapers, with 73 percent of them employed on full-time basis. In ethnic grouping, about a quarter (24.9%) of Kenyan news people belong to the Kikuyu tribe, followed by Luhya tribe (20%). The results also indicate that the majority of the journalists are from the Rift Valley province (21.4%) – Kenya’s largest administrative unit – followed by Western (19.5%) and Central (15.5%). By religion affiliation, 62.3 percent of the journalists are Protestants and 22.5 percent Roman Catholic. While the majority of the Kenyan journalists (22%) fall in the monthly salary bracket of $375–$625, a significant number of them (17%) earn less than $375 a month.
Planning for social justice: Strategies, dilemmas, tradeoffs
Authors: Uitermark Justus , Nicholls Walter
Published: August 2015

This article charts predicaments and conundrums associated with the ambition to plan for social justice. Drawing from classical theory on the roles of intellectuals, we identify what we call the “power of representation dilemma.” This dilemma arises because the credentials, knowledge, and skills of intellectuals (like urban planners) make them into powerful agents of social justice but at the same time can put them in a position of power in relation to the very communities they represent and serve. We develop a typology of various strategies for contending with this dilemma and conclude there are no clean ways to resolve the dilemma as each strategy has significant tradeoffs. We encourage a “ realpolitik of social justice,” whereby planners become cognizant that there are only imperfect strategies to engage in the politics of social justice. Recognition of their fallibility in the pursuit of noble ideals will make them more reflexive and capable of responding to the inevitability of new injustices and silencings that arise when planning for social justice.
Social workers in multi-cultural societies: Using a phenomenological lens to develop an integrative approach
Authors: Freund Anat , Band-Winterstein Tova
Published: August 2015

Multi-culturalism is a common reality, and is expected to become even more significant in the future. One of its challenges is the need for professionals, especially social workers, to accommodate their practice to clients of various cultures. Their role demands cultural sensitivity, acceptance, a non-judgmental containing attitude and professional skills. This article will show how phenomenology can shed new light on the concept of cultural sensitivity and its implications on future interventions. We demonstrate this approach by looking at social workers’ various encounters with social problems in the ultra-Orthodox Jewish community in Israel. Several phenomenological categories will be discussed: The life-world; intentionality; the self with others; language; stock of knowledge at hand. Through the phenomenological lens, we will expose the inherent duality in the work of social workers in a multi-cultural society: awareness to cultural codes and professional ethics.
A dialectic of dreams and dispossession: the school-to-sweatshop pipeline
Authors: Cahill Caitlin , Alvarez Gutiérrez Leticia , Quijada Cerecer David Alberto
Published: August 2015

Engaging the contradictions of global restructuring that produce the school-to-sweatshop pipeline for undocumented students, our analysis makes visible the relationship between racialized cultural practices of exclusion in educational spaces and the production of ‘illegality’. Our theorizing draws upon participatory action research with intergenerational community partnerships based in Salt Lake City, Utah, that share commitments to the collective participation and action of those most affected by the ‘intimate dispossessions’ of capital accumulation. In our inquiry, we attend to the places and practices of social reproduction – the school, family and home – mining the loopholes of policy and the contours of subjectivity to uncover the critical potential of everyday struggles.
Effect of shRNA-Mediated Gene Silencing of Bmi-1 Expression on Chemosensitivity of CD44+ Nasopharyngeal Carcinoma Cancer Stem-Like Cells
Authors: Xu Xin-Hua , Liu Yang , Li Dao-Jun , Hu Juan , Su Jin , Huang Qiao , Lu Ming-Qian , Yi Fang , Bao Dan , Fu Yan-Zhi
Published: August 2015

In this study, we investigate the effect of short hairpin RNA-mediated gene silencing of Bmi-1 expression on chemosensitivity of CD44+ nasopharyngeal carcinoma cancer stem-like cells. The sequence-specific short hairpin RNA lentivirus targeting at human Bmi-1 was synthesized and used to infect CD44+ nasopharyngeal cells that were sorted by flow cytometry. We also employed flow cytometry to detect transfection efficiency. Real-time polymerase chain reaction was used to detect Bmi-1 and its downstream repressor genes p16INK4a and p14ARF messenger RNA, while each protein expression level of Bmi-1, p16INK4a, p14ARF, and p53 was confirmed by Western blotting protocol. Tumor spheroid assay was used to evaluate the self-renewal capacity. 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and colony formation assay were applied to detect proliferation capacity and colony-forming capacity under different concentrations of chemotherapeutic drugs 5-fluorouracil or cisplatin. Transwell cell migration and invasion assay were employed to observe migration and invasion capacity after cells were exposed to cisplatin for 24 hours. The constructed short hairpin RNA lentivirus targeting Bmi-1 gene successfully infected into the CD44+ nasopharyngeal carcinoma cells and effectively inhibited the Bmi-1 messenger RNA and protein expression level, while the expression level of Bim-1 target genes, p16INK4a, p14ARF, and p53 was significantly increased ( P < .05). Notably, the proliferation, colony formation, migration, and invasion capabilities of the sequence-specific short hairpin RNA lentivirus-infected CD44+ nasopharyngeal carcinoma cells reduced significantly under chemotherapeutic treatments ( P < .05). Our results indicated that Bmi-1 may play an important role in the chemosensitivity of CD44+ nasopharyngeal carcinoma cancer stem-like cells. Bmi-1 may be a potential new target for the treatment of nasopharyngeal carcinoma displaying chemotherapy resistance.
A Feasibility Study of Tumor Motion Estimate With Regional Deformable Registration Method for 4-Dimensional Radiation Therapy of Lung Cancer
Authors: Chao Ming , Yuan Yading , Sheu Ren-dih , Wang Kelin , Rosenzweig Kenneth E. , Lo Yeh-Chi
Published: August 2015

This study aims to employ 4-dimensional computed tomography to quantify intrafractional tumor motion for patients with lung cancer to improve target localization in radiation therapy. A multistage regional deformable registration was implemented to calculate the excursion of gross tumor volume (GTV) during a breathing cycle. GTV was initially delineated on 0% phase of 4-dimensional computed tomography manually, and a subregion with 20 mm margin supplemented to GTV was generated with Eclipse treatment planning system (Varian Medical Systems, Palo Alto, California). The structures, together with the 4-dimensional computed tomography set, were exported into an in-house software, with which a 3-stage B-spline deformable registration was carried out to map the subregion and warp GTV contour to other breathing phases. The center of mass of the GTV was computed using the contours, and the tumor motion was appraised as the excursion of the center of mass between 0% phase and other phases. Application of the algorithm to the 10 patients showed that clinically satisfactory outcomes were achievable with a spatial accuracy around 2 mm for GTV contour propagation between adjacent phases and 3 mm between opposite phases. The tumor excursion was determined in the vast range of 1 mm through 1.6 cm, depending on the tumor location and tumor size. Compared to the traditional whole image-based registration, the regional method was found computationally a factor of 5 more efficient. The proposed technique has demonstrated its capability in extracting thoracic tumor motion and should find its application in 4-dimensional radiation therapy in the future to maximally utilize the available spatial–temporal information.
TPGS/Phospholipids Mixed Micelles for Delivery of Icariside II to Multidrug-Resistant Breast Cancer
Authors: Song Jie , Huang Houcai , Xia Zhi , Wei Yingjie , Yao Nan , Zhang Li , Yan Hongmei , Jia Xiaobin , Zhang Zhenhai
Published: August 2015

The biggest challenge for the treatment of multidrug resistant cancer is to deliver a high concentration of anticancer drugs to cancer cells. Icariside II is a flavonoid from Epimedium koreanum Nakai with remarkable anticancer properties, but poor solubility and significant efflux from cancer cells limited its clinical use. In our previous study, a self-assembled mixture of micelles (TPGS–Icariside II–phospholipid complex) was successfully constructed, which could substantially increase the solubility of Icariside II and inhibit the efflux on Caco-2 cells. In this study, we evaluate the anticancer effect of the mixed micelles encapsulating Icariside II (Icar-MC) on MCF-7/ADR, a multidrug-resistant breast cancer cell line. The cellular uptake of the micelles was confirmed by fluorescent coumarin-6-loaded micelles. The IC50 of Icar-MC in MCF-7/ADR was 2-fold less than the free drug. The in vitro study showed Icar-MC induced more apoptosis and lactate dehydrogenase release. Intravenous injection of Icar-MC into nude mice bearing MCF-7/ADR xenograft resulted in a better antitumor efficacy compared with the administration of free drug, without causing significant body weight changes in mice. The antitumor effect was further verified by magnetic resonance imaging and immunohistochemical assays for Ki-67, a proliferative indicator. Moreover, Icar-MC treatment also elevated Bax/Bcl-2 ratio and the expressions of cleaved caspase-3, -8, -9 and AIFM1 in tumors. This study suggests that phospholipid/TPGS mixed micelles might be a suitable drug delivery system for Icariside II to treat multidrug resistant breast cancer.
Involving Research Stakeholders in Developing Policy on Sharing Public Health Research Data in Kenya
Authors: Jao Irene , Kombe Francis , Mwalukore Salim , Bull Susan , Parker Michael , Kamuya Dorcas , Molyneux Sassy , Marsh Vicki
Published: August 2015

Increased global sharing of public health research data has potential to advance scientific progress but may present challenges to the interests of research stakeholders, particularly in low-to-middle income countries. Policies for data sharing should be responsive to public views, but there is little evidence of the systematic study of these from low-income countries. This qualitative study explored views on fair data-sharing processes among 60 stakeholders in Kenya with varying research experience, using a deliberative approach. Stakeholders’ attitudes were informed by perceptions of benefit and concerns for research data sharing, including risks of stigmatization, loss of privacy, and undermining scientific careers and validity, reported in detail elsewhere. In this article, we discuss institutional trust-building processes seen as central to perceptions of fairness in sharing research data in this setting, including forms of community involvement, individual prior awareness and agreement to data sharing, independence and accountability of governance mechanisms, and operating under a national framework.
Developing Ethical Practices for Public Health Research Data Sharing in South Africa
Authors: Denny Spencer G. , Silaigwana Blessing , Wassenaar Douglas , Bull Susan , Parker Michael
Published: August 2015

The abundance of South African clinical and public health research data has the potential to unlock important and valuable future advances in biomedical science. Amid increasing calls for more effective sharing of individual-level data, commitment to promote access to research data is evident within South Africa’s public research sector, but national guidance and regulation are absent. This qualitative study examined the perceptions, experiences and concerns of 32 research stakeholders about data-sharing practices. There was consensus about the utility of data sharing in publicly funded health research. However, disparate views emerged about the possible harms and benefits of sharing data and how these should be weighed. The relative dearth of policies governing data-sharing practices needs to be addressed and a framework of support developed that incentivizes data-sharing practices for researchers that are both ethical and effective.
Trust, Respect, and Reciprocity
Authors: Merson Laura , Phong Tran Viet , Nhan Le Nguyen Thanh , Dung Nguyen Thanh , Ngan Ta Thi Dieu , Kinh Nguyen Van , Parker Michael , Bull Susan
Published: August 2015

International science funders and publishers are driving a growing trend in data sharing. There is mounting pressure on researchers in low- and middle-income settings to conform to new sharing policies, despite minimal empirically grounded accounts of the ethical challenges of implementing the policies in these settings. This study used in-depth interviews and focus group discussions with 48 stakeholders in Vietnam to explore the experiences, attitudes, and expectations that inform ethical and effective approaches to sharing clinical research data. Distinct views on the role of trust, respect, and reciprocity were among those that emerged to inform culturally appropriate best practices. We conclude by discussing the challenges that authors of data-sharing policies should consider in this unique context.
Perceived Benefits, Harms, and Views About How to Share Data Responsibly
Authors: Cheah Phaik Yeong , Tangseefa Decha , Somsaman Aimatcha , Chunsuttiwat Tri , Nosten François , Day Nicholas P. J. , Bull Susan , Parker Michael
Published: August 2015

The Thailand Major Overseas Programme coordinates large multi-center studies in tropical medicine and generates vast amounts of data. As the data sharing movement gains momentum, we wanted to understand attitudes and experiences of relevant stakeholders about what constitutes good data sharing practice. We conducted 15 interviews and three focus groups discussions involving 25 participants and found that they generally saw data sharing as something positive. Data sharing was viewed as a means to contribute to scientific progress and lead to better quality analysis, better use of resources, greater accountability, and more outputs. However, there were also important reservations including potential harms to research participants, their communities, and the researchers themselves. Given these concerns, several areas for discussion were identified: data standardization, appropriate consent models, and governance.
Sharing Public Health Research Data
Authors: Parker Michael , Bull Susan
Published: August 2015

It is increasingly recognized that effective and appropriate data sharing requires the development of models of good data-sharing practice capable of taking seriously both the potential benefits to be gained and the importance of ensuring that the rights and interests of participants are respected and that risk of harms is minimized. Calls for the greater sharing of individual-level data from biomedical and public health research are receiving support among researchers and research funders. Despite its potential importance, data sharing presents important ethical, social, and institutional challenges in low-income settings. In this article, we report on qualitative research conducted in five low- and middle-income countries exploring the experiences of key research stakeholders and their views about what constitutes good data-sharing practice.
Design and performance of demonstration house with active solar heating in the Qinghai–Tibet Plateau region
Authors: Wang Dengjia , Liu Yanfeng , Wang Yingying , Liu Jiaping
Published: August 2015

The project comprises 80 passive solar houses and 20 houses with combined passive and active solar heating in the Qinghai–Tibet Plateau region. The indoor thermal environment and the performance of the solar collection components are discussed through field testing during the coldest part and the transition part of the heating period. Moreover, the fractional energy savings, thermal efficiency, and fraction of the combined passive and active solar heating are analyzed. The results indicate that an auxiliary heat source should be used as a supplement. By comparing the heating of a passive solar house with a vernacular house, the energy savings of the passive solar house in the demonstration project were found to be approximately 62% during the study period. The thermal efficiency of the active solar heating system is 84.5%, and the solar energy utilization is 38.2%. The monthly average heat load index is 15.2 W m−2.
Cook and Chill
Authors: Deakin Sherine , Steele Dominic , Clarke Sarah , Gribben Cathryn , Bexley Anne-Marie , Laan Remmert , Kerr David
Published: August 2015

Background:

Exposure to extreme temperature can affect the performance of blood glucose monitoring systems. The aim was to determine the non-equilibrated performance of these systems at extreme high and low temperatures that can occur in daily life.

Methods:

The performances of 5 test systems, (1) Abbott FreeStyle Freedom Lite, (2) Roche AccuChek Aviva, (3) Bayer Contour, (4) LifeScan OneTouch Verio, and (5) Sanofi BG Star, were compared after “cooking” (50°C for 1 hour) or “chilling” (−5°C for 1 hour) with room temperature controls (23°C) using whole blood with glucose concentrations of 50, 100, and 200 mg/dl.

Results:

The equilibration period (time from the end of incubation to when the test system is operational) was between 1 and 8 minutes, and each test system took between 15 and 30 minutes after incubation to obtain stable measurements at room temperature. Incubating the strips at −5°C or 50°C had little effect on the glucose measurement, whereas incubating the meters introduced bias in performance between 0 and 15 minutes but not subsequently, compared to room temperature controls and at all 3 glucose levels.

Conclusions:

Compensating technologies embedded within blood glucose monitoring systems studied here perform well at extreme temperatures. People with diabetes need to be alerted to this feature to avoid perceptions of malperformance of their devices and the possible inability to get blood glucose readings on short notice (eg, during time of suspected rapid change or before an unplanned meal).
Mixed Influence of Electronic Health Record Implementation on Diabetes Order Patterns for Michigan Medicaid Adults
Authors: Corser William , Yuan Sha
Published: August 2015

Background:

These 2011-2013 analyses examined the authors’ hypothesis that relative diabetes care order changes would be measured after electronic health record (EHR) implementation for 291 Medicaid adults who received all of their office-based care at one midwestern federally qualified health center (FQHC) over a 24-month period (n = 2727 encounters, 2489 claims).

Method:

Beneficiary sociodemographic, clinical, and claims data were validated with clinic EHR and state Medicaid claims linked to providers’ national identifier numbers. Overall pre-post order rate comparisons, and a series of controlled within group binary logistic models were conducted under penalized maximum likelihood estimation terms.

Results:

After EHR implementation, both the overall order rates and odds ratios of per beneficiary hemoglobin A1C (HbA1C) orders increased significantly (ie, from mean of 0.65 [SD = 1.19] annual tests to 0.96 tests [SD = 1.24] [ P < .001]). Although the overall post-EHR order rates of dilated eye exams and microalbumin urine tests appeared fairly stable, the odds of eye exam orders being placed at the claims level decreased significantly (OR = 0.774, P = .0030).

Conclusions:

These mixed results provide evidence of the varied diabetes care ordering patterns likely seen from increased office use of EHR technologies. The authors attempt to explain these post-EHR differences (or lack of) that generally resemble some of the authors’ results from another funded project. Ideally, these findings provide Medicaid and health care officials with a more realistic indication of how EHRs may, or may not, influence diabetes care ordering patterns for vulnerable lower-income primary health care consumers.
An Exploratory and Comparative Evaluation on the Spatial Perception of Two Densities of Multioccupancy Hospital Rooms
Authors: Yildirim Kemal , Yalcin Meryem
Published: August 2015

Objective:

The objective of this article was to explore interior spatial qualifications on patient perception of two densities of multioccupancy hospital rooms.

Background:

The research setting of this study was the three- and six-person capacity hospital rooms used for treatment of patients at a large hospital in a major metropolitan city in Turkey.

Method:

The subjects used in the study were randomly selected from among patients treated in the surgical medical sciences’ departments of the hospital. Accordingly, a research questionnaire was applied to a total of 101 subjects.

Results:

Results have shown that the three-person rooms were assessed more positively for privacy, functional, and perceptual qualifications compared to the six-person rooms. An increase in the number of persons and interior units of rooms affects negatively the auditory privacy and privacy areas of other patients.

Conclusion:

Consequently, although these rooms with different spatial sizes were very similar for concentration of persons and commodities, six-person rooms were perceived to be more crowded than three-person rooms.
Primary Care Providers’ Knowledge and Practices of Diabetes Management During Ramadan
Authors: Ali Mujtaba , Adams Alexandra , Hossain Md Anwar , Sutin David , Han Benjamin Hyun
Published: August 2015

There are an estimated 3.5 million Muslims in North America. During the holy month of Ramadan, healthy adult Muslims are to fast from predawn to after sunset. While there are exemptions for older and sick adults, many adults with diabetes fast during Ramadan. However, there are risks associated with fasting and specific management considerations for patients with diabetes. We evaluated provider practices and knowledge regarding the management of patients with diabetes who fast during Ramadan. A 15-question quality improvement survey based on a literature review and the American Diabetes Association guidelines was developed and offered to providers at the outpatient primary care and geriatric clinics at an inner-city hospital in New York City. Forty-five providers completed the survey. Most respondents did not ask their Muslim patients with diabetes if they were fasting during the previous Ramadan. Knowledge of fasting practices during Ramadan was variable, and most felt uncomfortable managing patients with diabetes during Ramadan. There is room for improvement in educating providers about specific cultural and medical issues regarding fasting for patients with diabetes during Ramadan.
Factors Expressed in an Animal Model of Anteroinferior Glenohumeral Instability
Authors: Mulcahey Mary K. , Marshall Mindy , Gallacher Stacey E. , Kaback Lee A. , Blaine Theodore A.
Published: August 2015

Background:

There is little information on the molecular factors important in healing and changes that occur in the glenoid labrum in response to injury. Using a novel animal model of acute anterior shoulder dislocation, this study characterizes the factors expressed in the glenoid labrum in response to injury and correlates their expression to glenohumeral stability.

Purpose:

To study the response of the glenoid labrum to injury both biomechanically and with immunohistochemical testing.

Methods:

An injury to the anteroinferior labrum was surgically induced in 50 male Lewis rats. Rats were sacrificed at 3, 7, 14, 28, or 42 days. Immunolocalization experiments were performed to localize the expression of growth factors and cytokines. For biomechanical testing, dynamic stiffness for anterior and posterior laxity, load to failure, stiffness, and maximum load were recorded. Statistical differences were determined at P < .05.

Study Design:

Descriptive laboratory study.

Results:

Expression of interleukin–1 beta (IL-1β), transforming growth factor–beta 1 (TGF-β1), matrix metalloproteinase 3 (MMP3), and matrix metalloproteinase 13 (MMP13) were increased in injured compared with uninjured specimens. Collagen III expression was increased early and decreased with time. Biomechanical testing verified instability by demonstrating increased anterior displacement and decreased stiffness in injured shoulders at all time points.

Conclusion:

This novel animal model of acute anterior shoulder dislocation showed increased expression of IL-1β, TGF-β1, MMP3, MMP13, and collagen III in the injured labral tissue at early time points. Increased anterior laxity and decreased stiffness and maximum load to failure were seen after anterior labral injury, supporting the model’s ability to re-create anterior glenohumeral instability. These data provide important information on the temporal changes occurring in a rat model of anterior glenohumeral dislocation.

Clinical Relevance:

Identification of factors expressed in the anterior capsule and glenoid labrum in response to injury may lead to the development of novel agents that can be used to augment glenoid labrum healing and ultimately improve both surgical and nonsurgical treatment of this common shoulder injury.
In vivo genome editing of the albumin locus as a platform for protein replacement therapy
Authors: Sharma Rajiv , Anguela Xavier M. , Doyon Yannick , Wechsler Thomas , DeKelver Russell C. , Sproul Scott , Paschon David E. , Miller Jeffrey C. , Davidson Robert J. , Shivak David , Zhou Shangzhen , Rieders Julianne , Gregory Philip D. , Holmes Michael C. , Rebar Edward J. , High Katherine A.
Published: August 2015

Key Points

AAV- and ZFN-mediated targeting of the albumin locus corrects disease phenotype in mouse models of hemophilia A and B. Robust expression from the albumin locus provides a versatile platform for liver-directed protein replacement therapy.
B-cell precursor acute lymphoblastic leukemia cells use tunneling nanotubes to orchestrate their microenvironment
Authors: Polak Roel , de Rooij Bob , Pieters Rob , den Boer Monique L.
Published: August 2015

Key Points

Primary BCP-ALL cells use tunneling nanotubes to signal to mesenchymal stromal cells and thereby trigger cytokine secretion. Inhibiting tunneling nanotube signaling is a promising approach to induce apoptosis and sensitize BCP-ALL cells toward prednisolone.
The oldest described eurypterid: a giant Middle Ordovician (Darriwilian) megalograptid from the Winneshiek Lagerstätte of Iowa
Authors: Lamsdell James C. , Briggs Derek E. G. , Liu Huaibao P. , Witzke Brian J. , McKay Robert M.
Published: August 2015

Background

Eurypterids are a diverse group of chelicerates known from ~250 species with a sparse Ordovician record currently comprising 11 species; the oldest fully documented example is from the Sandbian of Avalonia. The Middle Ordovician (Darriwilian) fauna of the Winneshiek Lagerstätte includes a new eurypterid species represented by more than 150 specimens, including some juveniles, preserved as carbonaceous cuticular remains. This taxon represents the oldest described eurypterid, extending the documented range of the group back some 9 million years.

Results

The new eurypterid species is described asPentecopterus decorahensisgen. et sp. nov.. Phylogenetic analysis placesPentecopterusat the base of the Megalograptidae, united with the two genera previously assigned to this family by the shared possession of two or more pairs of spines per podomere on prosomal appendage IV, a reduction of all spines except the pair on the penultimate podomere of appendage V, and an ornamentation of guttalate scales, including angular scales along the posterior margin of the dorsal tergites and in longitudinal rows along the tergites. The morphology ofPentecopterusreveals that the Megalograptidae are representatives of the derived carcinosomatoid clade and not basal eurypterids as previously interpreted.

Conclusions

The relatively derived position of megalograptids within the eurypterids indicates that most eurypterid clades were present by the Middle Ordovician. Eurypterids either underwent an explosive radiation soon after their origination, or earlier representatives, perhaps Cambrian in age, remain to be discovered. The available instars ofPentecopterus decorahensissuggest that eurypterids underwent extreme appendage differentiation during development, a potentially unique condition among chelicerates. The high degree of appendage specialization in eurypterids is only matched by arachnids within chelicerates, supporting a sister taxon relationship between them.
let-7b suppresses apoptosis and autophagy of human mesenchymal stem cells transplanted into ischemia/reperfusion injured heart 7by targeting caspase-3
Authors: Ham Onju , Lee Se-Yeon , Lee Chang Youn , Park Jun-Hee , Lee Jiyun , Seo Hyang-Hee , Cha Min-Ji , Choi Eunhyun , Kim Soonhag , Hwang Ki-Chul
Published: August 2015

Introduction

Mesenchymal stem cells (MSCs) have therapeutic potential for the repair of myocardial injury. The efficacy of MSC therapy for myocardial regeneration mainly depends on the survival of cells after transplantation into the infarcted heart. In the transplanted regions, reactive oxygen species (ROS) can cause cell death, and this process depends on caspase activation and autophagosome formation.

Methods

A Software TargetScan was utilized to search for microRNAs (miRNAs) that target caspase-3 mRNA. Six candidate miRNAs including let-7b were selected and transfected into human MSCsin vitro. Expression of MEK-EKR signal pathways and autophagy-related genes were detected. Using ischemia/reperfusion model (I/R), the effect of MSCs enriched with let-7b was determined after transplantation into infarcted heart area. Miller catheter was used to evaluate cardiac function.

Results

Here, we report that let-7b targets caspase-3 to regulate apoptosis and autophagy in MSCs exposed to ROS. Let-7b-transfected MSCs (let-7b-MSCs) showed high expression of survival-related proteins, including p-MEK, p-ERK and Bcl-2, leading to a decrease in Annexin V/PI- and TUNEL-positive cells under ROS-rich conditions. Moreover, autophagy-related genes, including Atg5, Atg7, Atg12 and beclin-1, were significantly downregulated in let-7b-MSCs. Using a rat model of acute myocardial infarction, we found that intramyocardial injection of let-7b-MSCs markedly enhanced left ventricular (LV) function and microvessel density, in accordance with a reduced infarct size and the expression of caspase-3.

Conclusions

Taken together, these data indicate that let-7b may protect MSCs implanted into infarcted myocardium from apoptosis and autophagy by directly targeting caspase-3 signaling.
Comparison of adipose tissue- and bone marrow- derived mesenchymal stem cells for alleviating doxorubicin-induced cardiac dysfunction in diabetic rats
Authors: Ammar Hania Ibrahim , Sequiera Glen Lester , Nashed Mira B. , Ammar Rasha I. , Gabr Hala M. , Elsayed Hany E. , Sareen Niketa , Rub Ejlal Abu-El , Zickri Maha B. , Dhingra Sanjiv
Published: August 2015

Introduction

Doxorubicin (DOX) is a well-known anticancer drug. However its clinical use has been limited due to cardiotoxic effects. One of the major concerns with DOX therapy is its toxicity in patients who are frail, particularly diabetics. Several studies suggest that mesenchymal stem cells (MSCs) have the potential to restore cardiac function after DOX-induced injury. However, limited data are available on the effects of MSC therapy on DOX-induced cardiac dysfunction in diabetics. Our objective was to test the efficacy of bone marrow-derived (BM-MSCs) and adipose-derived MSCs (AT-MSCs) from age-matched humans in a non-immune compromised rat model.

Methods

Diabetes mellitus was induced in rats by streptozotocin injection (STZ, 65 mg/kg b.w, i.p.). Diabetic rats were treated with DOX (doxorubicin hydrochloride, 2.5 mg/kg b.w, i.p) 3 times/wk for 2 weeks (DOX group); or with DOX+ GFP labelled BM-MSCs (2x106cells, i.v.) or with DOX + GFP labelled AT-MSCs (2x106cells, i.v.). Echocardiography and Langendorff perfusion analyses were carried out to determine the heart function. Immunostaining and western blot analysis of the heart tissue was carried out for CD31 and to assess inflammation and fibrosis. Statistical analysis was carried out using SPSS and data are expressed as mean ± SD.

Results

Glucose levels in the STZ treated groups were significantly greater than control group. After 4 weeks of intravenous injection, the presence of injected MSCs in the heart was confirmed through fluorescent microscopy and real time PCR for ALU transcripts. Both BM-MSCs and AT-MSCs injection prevented DOX-induced deterioration of %FS, LVDP, dp/dt max and rate pressure product. Staining for CD31 showed a significant increase in the number of capillaries in BM-MSCs and AT-MSCs treated animals in comparison to DOX treated group. Assessment of the inflammation and fibrosis revealed a marked reduction in the DOX-induced increase in immune cell infiltration, collagen deposition and αSMA in the BM-MSCs and AT-MSCs groups.

Conclusions

In conclusion BM-MSCs and AT-MSCs were equally effective in mitigating DOX-induced cardiac damage by promoting angiogenesis, decreasing the infiltration of immune cells and collagen deposition.
Deficiency of FcϵR1 Increases Body Weight Gain but Improves Glucose Tolerance in Diet-Induced Obese Mice
Authors: Lee Yun-Jung , Liu Conglin , Liao Mengyang , Sukhova Galina K. , Shirakawa Jun , Abdennour Meriem , Iamarene Karine , Andre Sebastien , Inouye Karen , Clement Karine , Kulkarni Rohit N. , Banks Alexander S. , Libby Peter , Shi Guo-Ping
Published: August 2015

Prior studies demonstrated increased plasma IgE in diabetic patients, but the direct participation of IgE in diabetes or obesity remains unknown. This study found that plasma IgE levels correlated inversely with body weight, body mass index, and body fat mass among a population of randomly selected obese women. IgE receptor FcϵR1-deficient (Fcer1a−/−) mice and diet-induced obesity (DIO) mice demonstrated that FcϵR1 deficiency in DIO mice increased food intake, reduced energy expenditure, and increased body weight gain but improved glucose tolerance and glucose-induced insulin secretion. White adipose tissue from Fcer1a−/− mice showed an increased expression of phospho-AKT, CCAAT/enhancer binding protein-α, peroxisome proliferator-activated receptor-γ, glucose transporter-4 (Glut4), and B-cell lymphoma 2 (Bcl2) but reduced uncoupling protein 1 (UCP1) and phosphorylated c-Jun N-terminal kinase (JNK) expression, tissue macrophage accumulation, and apoptosis, suggesting that IgE reduces adipogenesis and glucose uptake but induces energy expenditure, adipocyte apoptosis, and white adipose tissue inflammation. In 3T3-L1 cells, IgE inhibited the expression of CCAAT/enhancer binding protein-α and peroxisome proliferator-activated receptor-γ, and preadipocyte adipogenesis and induced adipocyte apoptosis. IgE reduced the 3T3-L1 cell expression of Glut4, phospho-AKT, and glucose uptake, which concurred with improved glucose tolerance in Fcer1a−/− mice. This study established two novel pathways of IgE in reducing body weight gain in DIO mice by suppressing adipogenesis and inducing adipocyte apoptosis while worsening glucose tolerance by reducing Glut4 expression, glucose uptake, and insulin secretion.
Liver Perilipin 5 Expression Worsens Hepatosteatosis But Not Insulin Resistance in High Fat-Fed Mice
Authors: Trevino Michelle B. , Mazur-Hart David , Machida Yui , King Timothy , Nadler Joseph , Galkina Elena V. , Poddar Arjun , Dutta Sucharita , Imai Yumi
Published: August 2015

Perilipin 5 (PLIN5) is a lipid droplet (LD) protein highly expressed in oxidative tissues, including the fasted liver. However, its expression also increases in nonalcoholic fatty liver. To determine whether PLIN5 regulates metabolic phenotypes of hepatosteatosis under nutritional excess, liver targeted overexpression of PLIN5 was achieved using adenoviral vector (Ad-PLIN5) in male C57BL/6J mice fed high-fat diet. Mice treated with adenovirus expressing green fluorescent protein (GFP) (Ad-GFP) served as control. Ad-PLIN5 livers increased LD in the liver section, and liquid chromatography with tandem mass spectrometry revealed increases in lipid classes associated with LD, including triacylglycerol, cholesterol ester, and phospholipid classes, compared with Ad-GFP liver. Lipids commonly associated with hepatic lipotoxicity, diacylglycerol, and ceramides, were also increased in Ad-PLIN5 liver. The expression of genes in lipid metabolism regulated by peroxisome proliferator-activated receptor-α was reduced suggestive of slower mobilization of stored lipids in Ad-PLIN5 mice. However, the increase of hepatosteatosis by PLIN5 overexpression did not worsen glucose homeostasis. Rather, serum insulin levels were decreased, indicating better insulin sensitivity in Ad-PLIN5 mice. Moreover, genes associated with liver injury were unaltered in Ad-PLIN5 steatotic liver compared with Ad-GFP control. Phosphorylation of protein kinase B was increased in Ad-PLIN5-transduced AML12 hepatocyte despite of the promotion of fatty acid incorporation to triacylglycerol as well. Collectively, our data indicates that the increase in liver PLIN5 during hepatosteatosis drives further lipid accumulation but does not adversely affect hepatic health or insulin sensitivity.
Noncanonical roles for Tropomyosin during myogenesis
Authors: Williams Jessica , Boin Nathan G. , Valera Juliana M. , Johnson Aaron N.
Published: August 2015

For skeletal muscle to produce movement, individual myofibers must form stable contacts with tendon cells and then assemble sarcomeres. The myofiber precursor is the nascent myotube, and during myogenesis the myotube completes guided elongation to reach its target tendons. Unlike the well-studied events of myogenesis, such as myoblast specification and myoblast fusion, the molecules that regulate myotube elongation are largely unknown. In Drosophila, hoi polloi (hoip) encodes a highly-conserved RNA binding protein and hoip mutant embryos are largely paralytic due to defects in myotube elongation and sarcomeric protein expression. We used the hoip mutant background as a platform to identify novel regulators of myogenesis, and uncovered surprising developmental functions for the sarcomeric protein Tropomyosin 2 (Tm2). We have identified Hoip responsive sequences in the coding region of the Tm2 mRNA that are essential for Tm2 protein expression in developing myotubes. Tm2 overexpression rescued the hoip myogenic phenotype by promoting F-actin assembly at the myotube leading edge, by restoring the expression of additional sarcomeric RNAs, and by promoting myoblast fusion. Embryos that lack Tm2 also showed reduced sarcomeric protein expression, and embryos that expressed a gain-of-function Tm2 allele showed both fusion and elongation defects. Tropomyosin therefore dictates fundamental steps of myogenesis prior to regulating contraction in the sarcomere.
Arabidopsis HECATE genes function in phytohormone control during gynoecium development
Authors: Schuster Christoph , Gaillochet Christophe , Lohmann Jan U.
Published: August 2015

The fruit, which develops from the fertilized gynoecium formed in the innermost whorl of the flower, is the reproductive organ and one of the most complex structures of an angiosperm plant. Phytohormones play important roles during flower and fruit patterning, morphogenesis and growth, and there is emerging evidence for a crosstalk between different classes of plant hormones throughout these processes. Here, we show that the bHLH transcription factors HECATE1 (HEC1), HEC2 and HEC3, which have previously been identified as essential components of transmitting tract formation, affect both auxin and cytokinin responses during reproductive tissue development. We find that HEC1 interacts with SPATULA (SPT) to control carpel fusion and that both transcription factors restrict sensitivity to cytokinin in the gynoecium. Conversely, HEC1 is tightly integrated into the auxin-signalling network at the levels of biosynthesis, transport and transcriptional response. Based on this data, we propose that HEC1 acts as a local modulator of auxin and cytokinin responses to control gynoecium development in Arabidopsis.
Ttk69 acts as a master repressor of enteroendocrine cell specification inDrosophilaintestinal stem cell lineages
Authors: Wang Chenhui , Guo Xingting , Dou Kun , Chen Hongyan , Xi Rongwen
Published: August 2015

In adult Drosophila midgut, intestinal stem cells (ISCs) periodically produces progenitor cells that undergo a binary fate choice determined primarily by the levels of Notch activity they receive, before terminally differentiate into enterocytes (ECs) or enteroendocrine cells (EEs). Here we identified Ttk69, a BTB domain-containing transcriptional repressor, as a master repressor of EE cell specification in the ISC lineages. Depletion of ttk69 in progenitor cells induces ISC proliferation and rendered all committed progenitor cells to adopt EE cell specification, leading to the production of supernumerary EE cells in the intestinal epithelium. Conversely, forced expression of Ttk69 in progenitor cells was sufficient to prevent EE cell specification. The expression of Ttk69 was not regulated by Notch signaling, and forced activation of Notch, which is sufficient to induce EC specification of normal progenitor cells, failed to prevent EE cell specification of Ttk69-depleted progenitor cells. We found that loss of Ttk69 led to derepression of acheate-scute complex (AS-C) genes scute and asense, which then induced prospero expression to promote EE cell specification. These studies suggest that Ttk69 functions in parallel with Notch signaling and acts as a master repressor of EE cell specification in Drosophila ISC lineages primarily by suppressing AS-C genes.
A direct fate exclusion mechanism by Sonic hedgehog-regulated transcriptional repressors
Authors: Nishi Yuichi , Zhang Xiaoxiao , Jeong Jieun , Peterson Kevin A. , Vedenko Anastasia , Bulyk Martha L. , Hide Winston A. , McMahon Andrew P.
Published: August 2015

Sonic hedgehog (Shh) signaling patterns the vertebrate spinal cord by activating a group of transcriptional repressors in distinct neural progenitors of somatic motor neuron and interneuron subtypes. To identify the action of this network, we performed a genome-wide analysis of the regulatory actions of three key ventral determinants in mammalian neural tube patterning: Nkx2.2, Nkx6.1 and Olig2. Previous studies have demonstrated that each factor acts predominantly as a transcriptional repressor, at least in part, to inhibit alternative progenitor fate choices. Here, we reveal broad and direct repression of multiple alternative fates as a general mechanism of repressor action. Additionally, the repressor network targets multiple Shh signaling components providing negative feedback to ongoing Shh signaling. Analysis of chromatin organization around Nkx2.2, Nkx6.1 and Olig2 bound regions, together with co-analysis of engagement of the transcriptional activator Sox2, indicate that repressors bind to, and likely modulate the action of, neural enhancers. Together, the data suggest a model for neural progenitor specification downstream of Shh signaling wherein Nkx2.2 and Olig2 direct repression of alternative neural progenitor fate determinants, an action augmented by the overlapping activity of Nkx6.1 in each cell type. Integration of repressor and activator inputs, notably activator inputs mediated by Sox2, is likely a key mechanism in achieving cell type-specific transcriptional outcomes in mammalian neural progenitor fate specification.
A zebrafish larval model reveals early tissue-specific innate immune responses to Mucor circinelloides
Authors: Voelz Kerstin , Gratacap Remi L. , Wheeler Robert T.
Published: August 2015

Mucormycosis is an emerging fungal infection that is clinically difficult to manage, with increasing incidence and extremely high mortality rates. Individuals with diabetes, suppressed immunity and traumatic injury are at increased risk of developing disease. These patients often present with defects in phagocytic effector cell function. Research utilising mammalian models and phagocytic effector cell lines has attempted to decipher the importance of the innate immune system in host defence against mucormycosis. However, these model systems have not been satisfactory to directly analyse the interaction between innate immune effector cells and infectious sporangiospores in vivo.

Here, we report the first real-time in vivo analysis of the early innate immune response to mucormycete infection using a whole animal zebrafish larval model system. We identified differential host susceptibility, dependent on the site of infection (hindbrain ventricle and swimbladder), as well as differential functions of the two major phagocyte effector cell types in response to viable and non-viable spores. Larval susceptibility to mucormycete spore infection was increased upon immunosuppressant treatment. We show for the first time that macrophages and neutrophils were readily recruited in vivo to the site of infection in an intact host and spore phagocytosis can be observed in real-time in vivo. Whilst exploring innate immune effector recruitment dynamics, we discovered the formation of phagocyte clusters in response to fungal spores that potentially play a role in fungal spore dissemination. Spores failed to activate pro-inflammatory gene expression by six hours post infection in both infection models. After 24 hours, induction of a pro-inflammatory response was only observed in hindbrain ventricle infections. Only a weak pro-inflammatory response was initiated after spore injection into the swimbladder during the same time frame.

In the future, the zebrafish larva as a live whole animal model system will contribute greatly to the study of molecular mechanisms involved in the interaction of the host innate immune system with fungal spores during mucormycosis.
Mubarak's Egypt — Nexus of Criminality
Authors: Marfleet Philip
Published: August 2015

Employing a Marxist framework, this article examines how neo-liberal agendas for development pursued by successive regimes in Egypt have been associated with violence, fraud and corruption. Encouraged by international financial institutions and Western governments, the Egyptian state became a means of channelling public resources into private hands, using complex relations of privilege among officials and oligarchs. The article examines a growing conviction among Egypt's people that the presidency and the ruling party represented a criminal enterprise. Addressing notions of “crony capitalism”, and the idea that the revolution of 2011 punished an aberrant political leader, it argues that bodies such as the International Monetary Fund and the World Bank have been party to consolidation of corrupt networks and development of an authoritarian state acting with impunity vis-à-vis the mass of Egypt's people. The article raises pressing questions about global responsibilities for state crime manifested at the local level.