bluuebunny/crossref_metadata_2025 huggingface dataset:
Epitope Addition and Ablation via Manipulation of a Dengue Virus Serotype 1 Infectious Clone
Authors: Gallichotte Emily N. , Menachery Vineet D. , Yount Boyd L. , Widman Douglas G. , Dinnon Kenneth H. , Hartman Steven , de Silva Aravinda M. , Baric Ralph S.
Published: February 2017

Dengue viruses (DENVs) are significant mosquito-transmitted pathogens that cause widespread infection and can lead to severe infection and complications. Here we further characterize a novel and robust DENV serotype 1 (DENV1) infectious clone system that can be used to support basic and applied research. We demonstrate how the system can be used to probe the antigenic relationships between strains by creating viable recombinant viruses that display or lack major antibody epitopes. The DENV1 clone system and recombinant viruses can be used to analyze existing vaccine immune responses and inform second-generation bivalent vaccine designs.
Implementing One Health as an integrated approach to health in Rwanda
Authors: Nyatanyi Thierry , Wilkes Michael , McDermott Haley , Nzietchueng Serge , Gafarasi Isidore , Mudakikwa Antoine , Kinani Jean Felix , Rukelibuga Joseph , Omolo Jared , Mupfasoni Denise , Kabeja Adeline , Nyamusore Jose , Nziza Julius , Hakizimana Jean Leonard , Kamugisha Julius , Nkunda Richard , Kibuuka Robert , Rugigana Etienne , Farmer Paul , Cotton Philip , Binagwaho Agnes
Published: February 2017

It is increasingly clear that resolution of complex global health problems requires interdisciplinary, intersectoral expertise and cooperation from governmental, non-governmental and educational agencies. ‘One Health’ refers to the collaboration of multiple disciplines and sectors working locally, nationally and globally to attain optimal health for people, animals and the environment. One Health offers the opportunity to acknowledge shared interests, set common goals, and drive toward team work to benefit the overall health of a nation. As in most countries, the health of Rwanda's people and economy are highly dependent on the health of the environment. Recently, Rwanda has developed a One Health strategic plan to meet its human, animal and environmental health challenges. This approach drives innovations that are important to solve both acute and chronic health problems and offers synergy across systems, resulting in improved communication, evidence-based solutions, development of a new generation of systems-thinkers, improved surveillance, decreased lag time in response, and improved health and economic savings. Several factors have enabled the One Health movement in Rwanda including an elaborate network of community health workers, existing rapid response teams, international academic partnerships willing to look more broadly than at a single disease or population, and relative equity between female and male health professionals. Barriers to implementing this strategy include competition over budget, poor communication, and the need for improved technology. Given the interconnectedness of our global community, it may be time for countries and their neighbours to follow Rwanda's lead and consider incorporating One Health principles into their national strategic health plans.
Gene expression profiling in persons with multiple chemical sensitivity before and after a controlled n-butanol exposure session
Authors: Dantoft Thomas M , Skovbjerg Sine , Andersson Linus , Claeson Anna-Sara , Engkilde Kaare , Lind Nina , Nordin Steven , Hellgren Lars I
Published: February 2017

Objectives

To investigate the pathophysiological pathways leading to symptoms elicitation in multiple chemical sensitivity (MCS) by comparing gene expression in MCS participants and healthy controls before and after a chemical exposure optimised to cause symptoms among MCS participants.

The first hypothesis was that unexposed and symptom-free MCS participants have similar gene expression patterns to controls and a second hypothesis that MCS participants can be separated from controls based on differential gene expression upon a controlled n-butanol exposure.

Design

Participants were exposed to 3.7 ppm n-butanol while seated in a windowed exposure chamber for 60 min. A total of 26 genes involved in biochemical pathways found in the literature have been proposed to play a role in the pathogenesis of MCS and other functional somatic syndromes were selected. Expression levels were compared between MCS and controls before, within 15 min after being exposed to and 4 hours after the exposure.

Settings

Participants suffering from MCS and healthy controls were recruited through advertisement at public places and in a local newspaper.

Participants

36 participants who considered themselves sensitive were prescreened for eligibility. 18 sensitive persons fulfilling the criteria for MCS were enrolled together with 18 healthy controls.

Outcome measures

17 genes showed sufficient transcriptional level for analysis. Group comparisons were conducted for each gene at the 3 times points and for the computed area under the curve (AUC) expression levels.

Results

MCS participants and controls displayed similar gene expression levels both at baseline and after the exposure and the computed AUC values were likewise comparable between the 2 groups. The intragroup variation in expression levels among MCS participants was noticeably greater than the controls.

Conclusions

MCS participants and controls have similar gene expression levels at baseline and it was not possible to separate MCS participants from controls based on gene expression measured after the exposure.
Internet-based cognitive–behavioural writing therapy for reducing post-traumatic stress after intensive care for sepsis in patients and their spouses (REPAIR): study protocol for a randomised-controlled trial
Authors: Gawlytta Romina , Niemeyer Helen , Böttche Maria , Scherag André , Knaevelsrud Christine , Rosendahl Jenny
Published: February 2017

Introduction

As a consequence of sepsis and intensive care, considerable proportions of patients but also of their spouses develop a post-traumatic stress disorder (PTSD). However, only a very small number receive psychotherapeutic treatment. Internet-based cognitive–behavioural writing therapy (IB-CBWT) has proven to be an effective treatment option for PTSD. It seems to fit the specific needs of this cohort and to overcome treatment barriers. Aim of the REPAIR trial is to examine the efficacy, safety and applicability of IB-CBWT for PTSD in patients and their spouses after intensive care for sepsis.

Methods and analysis

Participants will be assigned randomly either to a treatment or a wait-list (WL) control group. The treatment group receives IB-CBWT for PTSD, actively involving the partners of the participants. IB-CBWT will be guided by a therapist and comprises two written assignments per week over a 5 week period. After completing the assignments, the participants obtain individual responses from the therapist. Participants of the WL control group will receive treatment after a waiting period of 5 weeks. The primary outcome is PTSD symptom severity in self-rated PTSD Checklist for Diagnostic and Statistical Manual Fifth Edition at the end of treatment and waiting time, respectively. Secondary outcomes are remission of PTSD, depression, anxiety, and somatisation measured by the Brief Symptom Inventory-18, marital satisfaction measured by the Relationship Assessment Scale, health-related quality of life measured by the EQ-5D-5L, and the feasibility of IB-CBWT for this cohort (ie, dropout rate). Statistical analysis will be performed according to the intent-to-treat principle.

Ethics and dissemination

The study is conducted according to the principles of Good Clinical Practice and has been approved by the ethics committee of the Friedrich-Schiller University Jena, Germany. Results will be disseminated at scientific conferences, published in peer-reviewed journals, and provided to consumers of healthcare.

Trial registration number

Pre-results, DRKS00010676.
Effectiveness of a ‘Do not interrupt’ bundled intervention to reduce interruptions during medication administration: a cluster randomised controlled feasibility study
Authors: Westbrook Johanna I , Li Ling , Hooper Tamara D , Raban Magda Z , Middleton Sandy , Lehnbom Elin C
Published: February 2017

Aim

To evaluate the effectiveness of a ‘Do not interrupt’ bundled intervention to reduce non-medication-related interruptions to nurses during medication administration.

Methods

A parallel eight cluster randomised controlled study was conducted in a major teaching hospital in Adelaide, Australia. Four wards were randomised to the intervention which comprised wearing a vest when administering medications; strategies for diverting interruptions; clinician and patient education; and reminders. Control wards were blinded to the intervention. Structured direct observations of medication administration processes were conducted. The primary outcome was non-medication-related interruptions during individual medication dose administrations. The secondary outcomes were total interruption and multitasking rates. A survey of nurses' experiences was administered.

Results

Over 8 weeks and 364.7 hours, 227 nurses were observed administering 4781 medications. At baseline, nurses experienced 57 interruptions/100 administrations, 87.9% were unrelated to the medication task being observed. Intervention wards experienced a significant reduction in non-medication-related interruptions from 50/100 administrations (95% CI 45 to 55) to 34/100 (95% CI 30 to 38). Controlling for clustering, ward type and medication route showed a significant reduction of 15 non-medication-related interruptions/100 administrations compared with control wards. A total of 88 nurses (38.8%) completed the poststudy survey. Intervention ward nurses reported that vests were time consuming, cumbersome and hot. Only 48% indicated that they would support the intervention becoming hospital policy.

Discussion

Nurses experienced a high rate of interruptions. Few were related to the medication task, demonstrating considerable scope to reduce unnecessary interruptions. While the intervention was associated with a statistically significant decline in non-medication-related interruptions, the magnitude of this reduction and its likely impact on error rates should be considered, relative to the effectiveness of alternate interventions, associated costs, likely acceptability and long-term sustainability of such interventions.
Home palliative care works: but how? A meta-ethnography of the experiences of patients and family caregivers
Authors: Sarmento Vera P , Gysels Marjolein , Higginson Irene J , Gomes Barbara
Published: February 2017

Objective

To understand patients and family caregivers' experiences with home palliative care services, in order to identify, explore and integrate the key components of care that shape the experiences of service users.

Methods

We performed a meta-ethnography of qualitative evidence following PRISMA recommendations for reporting systematic reviews. The studies were retrieved in 5 electronic databases (MEDLINE, EMBASE, PsycInfo, BNI, CINAHL) using 3 terms and its equivalents (‘Palliative’, ‘Home care’, ‘Qualitative research’) combined with ‘AND’, complemented with other search strategies. We included original qualitative studies exploring experiences of adult patients and/or their family caregivers (≥18 years) facing life-limiting diseases with palliative care needs, being cared for at home by specialist or intermediate home palliative care services.

Results

28 papers reporting 19 studies were included, with 814 participants. Of these, 765 were family caregivers and 90% were affected by advanced cancer. According to participants' accounts, there are 2 overarching components of home palliative care: presence (24/7 availability and home visits) and competence (effective symptom control and skilful communication), contributing to meet the core need for security. Feeling secure is central to the benefits experienced with each component, allowing patients and family caregivers to focus on the dual process of living life and preparing death at home.

Conclusions

Home palliative care teams improve patients and caregivers experience of security when facing life-limiting illnesses at home, by providing competent care and being present. These teams should therefore be widely available and empowered with the resources to be present and provide competent care.
Impact of Sustained Virological Response to Chronic Hepatitic C Antiviral Therapy on New Onset Diabetes Mellitus Type 2 after Controlling for Metabolic Syndrome
Authors: Pandya Prashant , Pant Chaitanya , Taylor Ryan , Oni Olurinde
Published: February 2017

The high cost associated with antiviral treatment for chronic hepatitis C virus (HCV) infection mandates further investigation in the context of preventing complications such as type 2 diabetes mellitus (DM2). We determined the cumulative incidence of DM2 in subjects with chronic HCV infection who received concomitant pegylated interferon (Peg-IFN) and ribavirin. We conducted a retrospective analysis of data obtained from Veterans Administrations Informatics and Computing Infrastructure (VINCI) to identify an adult cohort of patients without diabetes with chronic HCV infection who received Peg-IFN-based therapy between October 2001 and December 2011. Patients with history of HIV, hepatitis B infection, hepatocellular cancer (HCC), non-HCC cancers, and history of transplantation were excluded. Sustained virological response (SVR) was defined as negative HCV RNA 3 months after completion of therapy. Using Cox proportional hazards regression for multivariable analysis, we determined that patients who achieved SVR were at a significantly less risk of developing DM2. Adjusted survival rates showed that the responders' group was significantly less likely to develop DM2 over time (HR 0.60, CI 0.48 to 0.74, p<0.001). Peg-IFN-based therapy in chronic HCV patients that resulted in SVR significantly decreased the risk of developing DM2 and independently predicts the development of new onset disease after controlling for correlates of metabolic syndrome.
Glycyrrhizae Radix Inhibits Osteoclast Differentiation by Inhibiting c-Fos-Dependent NFATc1 Expression
Authors: Rho Tae Won , Lee Seo Young , Han Sang-Yong , Kim Ji Hoon , Lee Kyung-Hee , Kim Dong-Seon , Kwak Han Bok , Kim Yun-Kyung
Published: February 2017

Osteoporosis results from imbalance between new bone formation and bone resorption leading to bone loss and is especially troublesome for postmenopausal women who suffer from estrogen deficiency. The ability of new therapeutic agents to treat this bone disease with minimal side effects has been extensively reported on and is continuously being sought out by researchers in this field. Thus, the purpose of this study was to investigate a natural herb that was already being used as a new treatment for osteoporosis. Here we found that water extract of Glycyrrhizae radix (GR) inhibits receptor activator of nuclear factor-[Formula: see text]B ligand (RANKL)-induced osteoclast differentiation in a dose-dependent manner without causing cytotoxicity. The mRNA expression of c-Fos, nuclear factor of activated T cells cytoplasmic 1 (NFATc1), tartrate-resistant acid phosphatase (TRAP), and osteoclast-associated receptor (OSCAR) was considerably inhibited by GR treatment. GR inhibited RANKL-mediated c-Fos and NFATc1 expression in a dose-dependent manner. GR inhibited the degradation of I-[Formula: see text]B in RANKL-stimulated BMMs. However, GR-mediated inhibition of osteoclast differentiation and osteoclast-specific gene expression, including NFATc1, was reversed by ectopic expression of c-Fos. Also, GR significantly inhibited osteoclast formation in mouse calvariae in the presence of IL-1 and prostaglandin E2 (PGE2). Taken together, these results suggest that GR inhibited osteoclast differentiation, raising the possibility that GR may serve as a useful drug for osteoporosis.
Flavonoids and Tannins from Smilax china L. Rhizome Induce Apoptosis Via Mitochondrial Pathway and MDM2-p53 Signaling in Human Lung Adenocarcinoma Cells
Authors: Fu San , Yang Yanfang , Liu Dan , Luo Yan , Ye Xiaochuan , Liu Yanwen , Chen Xin , Wang Song , Wu Hezhen , Wang Yuhang , Hu Qiwei , You Pengtao
Published: February 2017

In vitro evidence indicates that Smilax china L. rhizome (SCR) can inhibit cell proliferation. Therefore, in the present study, we analyzed the effects in vitro of SCR extracts on human lung adenocarcinoma A549 cells. Our results showed that A549 cell growth was inhibited in a dose- and time-dependent manner after treatment with SCR extracts. Total flavonoids and total tannins from SCR induced A549 apoptosis in a dose-dependent manner, as shown by our flow cytometry analysis, which was consistent with the alterations in nuclear morphology we observed. In addition, the total apoptotic rate induced by total tannins was higher than the rate induced by total flavonoids at the same dose. Cleaved-caspase-3 protein levels in A549 cells after treatment with total flavonoids or total tannins were increased in a dose-dependent manner, followed by the activation of caspase-8 and caspase-9, finally triggering to PARP cleavage. Furthermore, total flavonoids and total tannins increased the expression of Bax, decreased the expression of Bcl-2, and promoted cytochrome [Formula: see text] release. Moreover, MDM2 and p-MDM2 proteins were decreased, while p53 and p-p53 proteins were increased, both in a dose-dependent manner, after A549 treatment with total flavonoids and total tannins. Finally, cleaved-caspase-3 protein levels in the total flavonoids or total tannins-treated H1299 (p53 null) and p53-knockdown A549 cells were increased. Our results indicated that total flavonoids and total tannins from SCR exerted a remarkable effect in reducing A549 growth through their action on mitochondrial pathway and disruption of MDM2-p53 balance. Hence, our findings demonstrated a potential application of total flavonoids and total tannins from SCR in the treatment of human lung adenocarcinoma.
Carbon Emission Reduction and Pricing Strategies of Supply Chain under Various Demand Forecasting Scenarios
Authors: Qin Juanjuan , Ren Liguo , Xia Liangjie
Published: February 2017

This study incorporates consumer’s low carbon awareness (CLA) and demand forecasting into supply chains that adopt the cap-and-trade system. Three demand forecasting scenarios are discussed, namely, information sharing, full information sharing, and retailer-only forecasting. Strategies for pricing and reduction of equilibrium of carbon emission are derived. We also compare the decisions and profits in the three cases and present numerical analysis.
Supplement to a chord diagram of a ribbon surface-link
Authors: Kawauchi Akio
Published: February 2017

A revised proof is given to an assertion on chord diagrams of a ribbon surface-link.
Assessing the Impact of ICT on Research Activities in Ghana: A Case Study of Selected Council for Scientific and Industrial Research (CSIR) Institutes
Authors: Bugyei Kwabena Asiedu , Obiri-Yeboah Kwabena , Kavi Raphael Kwame
Published: February 2017

The purpose of this study was to assess the impact of Information and Communication Technology (ICT) on research activities in selected institutes of the Council for Scientific and Industrial Research (CSIR). The research methodology adopted for this study was the case study approach, specifically multiple cases. This study employed structured questionnaires and semi-structured interviews as a data collection instrument to collect data from respondents in the five selected research institutes of CSIR. The study shows that ICTs have a positive impact on research activities. ICT tools have been proven to be very helpful to researchers and other non-core staff of CSIR in finding needed information quickly and easily, expedition in the research process, improvement in job performance and have also helped in information access, management and communication. The study also identified lack of training in ICT, insufficient computer hardware and suitable software applications, lack of competent Information Technology (IT) professionals, non-existent budgetary allocations for ICT and lack of required Internet bandwidth as the major hindrances faced by the researchers and senior staff in the CSIR. The study recommended improvement in ICT infrastructure, appointment of competent IT personnel and proper training and guidance for optimum utilisation of ICT-based technologies.
Time-Dependent Changes of Albumin Water Solutions After Irradiation by Electromagnetic Waves with Extremely High Radio Frequencies
Authors: Shahinyan Mariam A. , Mikaelyan Marieta S. , Darbinyan Meri R. , Vardevanyan Poghos O.
Published: February 2017

The effect of electromagnetic irradiation with extremely high radio frequencies on several parameters of albumin water-saline solutions has been studied and the changes invoked by this irradiation after long time of its effect were observed. It was shown that the electromagnetic irradiation with 51.8[Formula: see text]GHz frequency, which is resonant for water, is preserved up to 48[Formula: see text]h after which the system returns to the initial state. It was shown as well that albumin thermostability also enhances and it is preserved during 48[Formula: see text]h, after that the system tends to return to the initial state.
Low-Temperature Selective Catalytic Reduction of NO with NH3 Over Mn-Fe Mixed Metal Oxides on the Nitric Vapor Functionalized Carbon Nanotubes Prepared by a Polyol Process
Authors: Lv Xin , Zhang Liheng , Zhan Sheng , Li Zhen , Zeng Yi
Published: February 2017

Highly dispersed Mn-Fe mixed metal oxides were supported on the nitric vapor functionalized carbon nanotubes (CNTs) by the polyol process for the low-temperature selective catalytic reduction (SCR) of NO with NH3. X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), H2 temperature-programmed reduction (H2-TPR) and Fourier transform infrared (FT-IR) spectroscopy have been used to elucidate the structure and surface properties of the obtained catalysts. It was found that the Mn-Fe/VF-CNTs catalysts synthesized by the polyol process exhibited higher activity and more extensive operating-temperature window, compared to the catalysts prepared by the impregnation method. On the basis of the catalyst characterization, the better dispersion of metal oxides on the CNTs surface, the more chemisorbed oxygen species, the higher Mn[Formula: see text]/Mn and O[Formula: see text]/O[Formula: see text]O[Formula: see text] ratios played key roles in the excellent catalytic performance of the catalyst in the low-temperature SCR of NO to N2 with NH3.
Investigation of Friction and Wear Properties of Electroless Ni–P–Cu Coating Under Dry Condition
Authors: Duari Santanu , Mukhopadhyay Arkadeb , Barman Tapan Kr. , Sahoo Prasanta
Published: February 2017

This study presents the deposition and tribological characterization of electroless Ni–P–Cu coatings deposited on AISI 1040 steel specimens. After deposition, coatings are heat treated at 500[Formula: see text]C for 1[Formula: see text]h. Surface morphology study of the coatings reveals its typical cauliflower like appearance. Composition study of the coatings using energy dispersive X-ray analysis indicates that the deposit lies in the high phosphorus range. The coatings undergo crystallization on heat treatment. A significant improvement in microhardness of the coatings is also observed on heat treatment due to the precipitation of hard crystalline phases. The heat-treated coatings are subjected to sliding wear tests on a pin-on-disc type tribo-tester under dry condition by varying the applied normal load, sliding speed and sliding duration. The coefficient of friction (COF) increases with an increase in the applied normal load while it decreases with an increase in the sliding speed. The wear depth on the other hand increases with an increase in applied normal load as well as sliding speed. The worn surface morphology mainly indicates fracture of the nodules.
Palaeomagnetic and geochronological evidence for a major middle Miocene unconformity in Söke Basin (western Anatolia) and its tectonic implications for the Aegean region
Authors: Uzel Bora , Sümer Ökmen , Özkaptan Murat , Özkaymak Çağlar , Kuiper Klaudia , Sözbilir Hasan , Kaymakci Nuretdin , İnci Uğur , Langereis Cornelis G.
Published: February 2017

Cenozoic convergence between the Eurasian and African plates and concurrent slab roll-back processes have produced a progressive extension in back-arc areas, such as the Aegean region and western Anatolia. There is still a long-standing controversy as to whether this was a continuous or stepwise process. To shed light on this controversy and on the driving mechanism of regional extension, we present palaeomagnetic and geochronological results from the Söke Basin located at the southeastern rim of the İzmir–Balıkesir Transfer Zone. Our improved geochronology shows that volcanic activity in the region occurred between 11.66 and 12.85 Ma. Middle to late Miocene palaeomagnetic data for the Söke Basin show a
c.
23° clockwise rotation, whereas early Miocene data show a
c.
28° counterclockwise rotation. The primary nature of the magnetization is indicated by a positive tilt test. The resulting
c.
51° counterclockwise rotations during the middle Miocene signify a major tectonic reorganization, during a period when an interruption of exhumation of metamorphic massifs has been reported. We suggest that the İzmir–Balıkesir Transfer Zone is the main driver of the reorganization in the region. The regional fingerprint of this tectonic reorganization coincides with the acceleration of trench retreat and illustrates the surface impact of tearing of the Hellenic slab.

Supplementary material:
Details of
40
Ar/
39
Ar analysis including heating steps and the output (.pmag) file including details of paleomagnetic analysis performed in this study are available at
https://doi.org/10.6084/m9.figshare.c.3690871
Structural and geomorphological constraints on active normal faulting and landscape evolution in Calabria, Italy
Authors: Roda-Boluda Duna C. , Whittaker Alexander C.
Published: February 2017

Calabria is one of the fastest-uplifting and most seismically active regions in the Mediterranean, yet the time-averaged (
c.
10
6
 years) rates of normal faulting remain poorly constrained. Here, we use digital elevation model analysis, geological cross-sections and a compilation of published data to quantify systematically along-strike the fault throws and time-averaged throw rates of the Serre, Cittanova, Armo, East Crati and West Crati faults. We show that regional uplift has uplifted both their hanging-wall and footwall blocks by
c.
200–400 m, and the Aspromonte massif by up to
c.
1150–1300 m. We find that these faults have throws between
c.
640 and 1430 m, and throw rates between
c.
0.6 and 1.4 mm a
−1
. Their footwall ranges have variable proportions of inherited relief, up to
c.
300–800 m. The channels draining these ranges reflect the active normal faulting and relief in their steepness indices, becoming
c.
5–8 m
0.9
steeper for each 0.1 mm a
−1
throw rate increment and each 100 m relief increase. Finally, the presence of knickpoints suggests that these channels are transiently responding to changes in relative base-level, which could be due to fault linkage or regional strain rate increases for the southern Calabrian faults, and to regional uplift acceleration in the case of the Crati faults.

Supplementary material:
Topographic profiles of the marine terraces and long profiles of rivers are available at
https://doi.org/10.6084/m9.figshare.c.3689464
High-throughput screening identifies microRNAs that target Nox2 and improve function after acute myocardial infarction
Authors: Yang Junyu , Brown Milton E. , Zhang Hanshuo , Martinez Mario , Zhao Zhihua , Bhutani Srishti , Yin Shenyi , Trac David , Xi Jianzhong Jeff , Davis Michael E.
Published: February 2017

Myocardial infarction (MI) is the most common cause of heart failure. Excessive production of ROS plays a key role in the pathogenesis of cardiac remodeling after MI. NADPH with NADPH oxidase (Nox)2 as the catalytic subunit is a major source of superoxide production, and expression is significantly increased in the infarcted myocardium, especially by infiltrating macrophages. While microRNAs (miRNAs) are potent regulators of gene expression and play an important role in heart disease, there still lacks efficient ways to identify miRNAs that target important pathological genes for treating MI. Thus, the overall objective was to establish a miRNA screening and delivery system for improving heart function after MI using Nox2 as a critical target. With the use of the miRNA-target screening system composed of a self-assembled cell microarray (SAMcell), three miRNAs, miR-106b, miR-148b, and miR-204, were identified that could regulate Nox2 expression and its downstream products in both human and mouse macrophages. Each of these miRNAs were encapsulated into polyketal (PK3) nanoparticles that could effectively deliver miRNAs into macrophages. Both in vitro and in vivo studies in mice confirmed that PK3-miRNAs particles could inhibit Nox2 expression and activity and significantly improve infarct size and acute cardiac function after MI. In conclusion, our results show that miR-106b, miR-148b, and miR-204 were able to improve heart function after myocardial infarction in mice by targeting Nox2 and possibly altering inflammatory cytokine production. This screening system and delivery method could have broader implications for miRNA-mediated therapeutics for cardiovascular and other diseases.

NEW & NOTEWORTHY NADPH oxidase (Nox)2 is a promising target for treating cardiovascular disease, but there are no specific inhibitors. Finding endogenous signals that can target Nox2 and other inflammatory molecules is of great interest. In this study, we used high-throughput screening to identify microRNAs that target Nox2 and improve cardiac function after infarction.
Age-Friendliness and Life Satisfaction of Young-Old and Old-Old in Hong Kong
Authors: Au Alma M. L. , Chan Stephen C. Y. , Yip H. M. , Kwok Jackie Y. C. , Lai K. Y. , Leung K. M. , Lee Anita L. F. , Lai Daniel W. L. , Tsien Teresa , Lai Simon M. K.
Published: February 2017

Age-friendliness, promoted by the World Health Organization (WHO), aims to enable and support individuals in different aspects of life for fostering life satisfaction and personal well-being as they age. We identified specific aspect(s) of age-friendliness associated with life satisfaction and examined similarities and differences in age-friendliness and life satisfaction in young-old and old-old adults. Six hundred and eighty-two ageing adults were asked to complete a survey questionnaire consisting of the Age-friendly City Scale, Satisfaction with Life Scale, and sociodemographic variables. Multiple linear regression analysis was used to examine the effects of various domains of age-friendliness on life satisfaction among the young-old adults (aged 65 to 74, n=351) and the old-old adults (aged 75 to 97, n=331). Common domains associated with life satisfaction in both young-old and old-old groups were transportation and social participation. Community and health services were associated with life satisfaction for the young-old group only. On the other hand, civic participation and employment was significantly associated with the old-old group only. Social participation is important for the young-old and the old-old. Ageing older adults can be a resource to the society. Implications for promoting and implementing age-friendliness were discussed in the context of successful and productive ageing and the need for a more refined taxonomy of social activities.
The Cytidine Deaminase APOBEC3 Family Is Subject to Transcriptional Regulation by p53
Authors: Menendez Daniel , Nguyen Thuy-Ai , Snipe Joyce , Resnick Michael A.
Published: February 2017

The APOBEC3 (A3) family of proteins are DNA cytidine deaminases that act as sentinels in the innate immune response against retroviral infections and are responsive to IFN. Recently, a few A3 genes were identified as potent enzymatic sources of mutations in several human cancers. Using human cancer cells and lymphocytes, we show that under stress conditions and immune challenges, all A3 genes are direct transcriptional targets of the tumor suppressor p53. Although the expression of most A3 genes (including A3C and A3H) was stimulated by the activation of p53, treatment with the DNA-damaging agent doxorubicin or the p53 stabilizer Nutlin led to repression of the A3B gene. Furthermore, p53 could enhance IFN type-I induction of A3 genes. Interestingly, overexpression of a group of tumor-associated p53 mutants in TP53-null cancer cells promoted A3B expression. These findings establish that the "guardian of the genome" role ascribed to p53 also extends to a unique component of the immune system, the A3 genes, thereby integrating human immune and chromosomal stress responses into an A3/p53 immune axis.

Implications: Activated p53 can integrate chromosomal stresses and immune responses through its influence on expression of APOBEC3 genes, which are key components of the innate immune system that also influence genomic stability. Mol Cancer Res; 15(6); 735–44. ©2017 AACR.
BCL6 Antagonizes NOTCH2 to Maintain Survival of Human Follicular Lymphoma Cells
Authors: Valls Ester , Lobry Camille , Geng Huimin , Wang Ling , Cardenas Mariano , Rivas Martín , Cerchietti Leandro , Oh Philmo , Yang Shao Ning , Oswald Erin , Graham Camille W. , Jiang Yanwen , Hatzi Katerina , Agirre Xabier , Perkey Eric , Li Zhuoning , Tam Wayne , Bhatt Kamala , Leonard John P. , Zweidler-McKay Patrick A. , Maillard Ivan , Elemento Olivier , Ci Weimin , Aifantis Iannis , Melnick Ari
Published: February 2017

Although the BCL6 transcriptional repressor is frequently expressed in human follicular lymphomas (FL), its biological role in this disease remains unknown. Herein, we comprehensively identify the set of gene promoters directly targeted by BCL6 in primary human FLs. We noted that BCL6 binds and represses NOTCH2 and NOTCH pathway genes. Moreover, BCL6 and NOTCH2 pathway gene expression is inversely correlated in FL. Notably, BCL6 upregulation is associated with repression of NOTCH2 and its target genes in primary human and murine germinal center (GC) cells. Repression of NOTCH2 is an essential function of BCL6 in FL and GC B cells because inducible expression of Notch2 abrogated GC formation in mice and killed FL cells. Indeed, BCL6-targeting compounds or gene silencing leads to the induction of NOTCH2 activity and compromises survival of FL cells, whereas NOTCH2 depletion or pathway antagonists rescue FL cells from such effects. Moreover, BCL6 inhibitors induced NOTCH2 expression and suppressed growth of human FL xenografts in vivo and primary human FL specimens ex vivo. These studies suggest that established FLs are thus dependent on BCL6 through its suppression of NOTCH2.

Significance: We show that human FLs are dependent on BCL6, and primary human FLs can be killed using specific BCL6 inhibitors. Integrative genomics and functional studies of BCL6 in primary FL cells point toward a novel mechanism whereby BCL6 repression of NOTCH2 drives the survival and growth of FL cells as well as GC B cells, which are the FL cell of origin. Cancer Discov; 7(5); 506–21. ©2017 AACR.

This article is highlighted in the In This Issue feature, p. 443
Rapamycin Enhances Repressed Autophagy and Attenuates Aggressive Progression in a Rat Model of IgA Nephropathy
Authors: Liu Di , Liu Yexin , Chen Guochun , He Liyu , Tang Chengyuan , Wang Chang , Yang Danyi , Li Huiqiong , Dong Zheng , Liu Hong
Published: February 2017

Background: IgA nephropathy (IgAN) has been considered to be the most frequent form of primary glomerulonephritis that occurs worldwide with a variety of factors involved in its occurrence and development. The impact of autophagy in IgAN, however, remains partially unclear. This study was designed to investigate the effects of rapamycin in an IgAN model. Method: After establishing an IgAN rat model, SD rats were divided into 4 groups: control, control + rapamycin, IgAN, IgAN + rapamycin. Proteinuria and the pathological changes and the level of autophagy of kidney were texted. Identify the expression of phosphorylation and total mammalian target of rapamycin (mTOR) and s6k1 as well as cyclin D1 in the kidney of rats through Western blot and immunohistochemistry. Results: With rapamycin treatment, we observed a significant reduction in the progression of proteinuria as well as alleviation of pathological lesions in IgAN rats. Besides, autophagy was inhibited, while the mTOR/S6k1 pathway was activated and expression of cyclin D1 was increased in IgAN. Rapamycin treatment increased autophagy and decreased the expression of cyclin D1. Conclusion: These results may suggest that mTOR-mediated autophagy inhibition may result in mesangial cell proliferation in IgAN.
ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumours: Surgery for Small Intestinal and Pancreatic Neuroendocrine Tumours
Authors: Partelli Stefano , Bartsch Detlef K. , Capdevila Jaume , Chen Jie , Knigge Ulrich , Niederle Bruno , Nieveen van Dijkum Els J.M. , Pape Ulrich-Frank , Pascher Andreas , Ramage John , Reed Nick , Ruszniewski Philippe , Scoazec Jean-Yves , Toumpanakis Christos , Kianmanesh Reza , Falconi Massimo ,   all other Antibes Consensus Conference participants
Published: February 2017

The small intestine and pancreas are among the most frequent abdominal sites of origin of neuroendocrine tumours. Distinctive features of these forms are represented by the relatively low incidence and the wide heterogeneity in biological behaviour. In this light, it is difficult to standardize indications for surgery and the most appropriate approach. It would be helpful for surgeons managing patients with these tumours to have guidelines for surgical treatment of small intestinal neuroendocrine tumours and pancreatic neuroendocrine tumours. The proposed guidelines represent a consensus of the working group of the European Neuroendocrine Tumor Society (ENETS).
Alk2/ACVR1 and Alk3/BMPR1A Provide Essential Function for Bone Morphogenetic Protein–Induced Retinal Angiogenesis
Authors: Lee Heon-Woo , Chong Diana C. , Ola Roxana , Dunworth William P. , Meadows Stryder , Ka Jun , Kaartinen Vesa M. , Qyang Yibing , Cleaver Ondine , Bautch Victoria L. , Eichmann Anne , Jin Suk-Won
Published: February 2017

Objective—

Increasing evidence suggests that bone morphogenetic protein (BMP) signaling regulates angiogenesis. Here, we aimed to define the function of BMP receptors in regulating early postnatal angiogenesis by analysis of inducible, endothelial-specific deletion of the BMP receptor components
Bmpr2
(BMP type 2 receptor),
Alk1
(activin receptor-like kinase 1),
Alk2
, and
Alk3
in mouse retinal vessels.

Approach and Results—

Expression analysis of several BMP ligands showed that proangiogenic BMP ligands are highly expressed in postnatal retinas. Consistently, BMP receptors are also strongly expressed in retina with a distinct pattern. To assess the function of BMP signaling in retinal angiogenesis, we first generated mice carrying an endothelial-specific inducible deletion of
Bmpr2
. Postnatal deletion of
Bmpr2
in endothelial cells substantially decreased the number of angiogenic sprouts at the vascular front and branch points behind the front, leading to attenuated radial expansion. To identify critical BMPR1s (BMP type 1 receptors) associated with BMPR2 in retinal angiogenesis, we generated endothelial-specific inducible deletion of 3 BMPR1s abundantly expressed in endothelial cells and analyzed the respective phenotypes. Among these, endothelial-specific deletion of either
Alk2
/
acvr1
or
Alk3
/
Bmpr1a
caused a delay in radial expansion, reminiscent of vascular defects associated with postnatal endothelial-specific deletion of BMPR2, suggesting that ALK2/ACVR1 and ALK3/BMPR1A are likely to be the critical BMPR1s necessary for proangiogenic BMP signaling in retinal vessels.

Conclusions—

Our data identify BMP signaling mediated by coordination of ALK2/ACVR1, ALK3/BMPR1A, and BMPR2 as an essential proangiogenic cue for retinal vessels.
Intravenously Delivered Mesenchymal Stem Cells
Authors: Luger Dror , Lipinski Michael J. , Westman Peter C. , Glover David K. , Dimastromatteo Julien , Frias Juan C. , Albelda M. Teresa , Sikora Sergey , Kharazi Alex , Vertelov Grigory , Waksman Ron , Epstein Stephen E.
Published: February 2017

Rationale:

Virtually all mesenchymal stem cell (MSC) studies assume that therapeutic effects accrue from local myocardial effects of engrafted MSCs. Because few intravenously administered MSCs engraft in the myocardium, studies have mainly utilized direct myocardial delivery. We adopted a different paradigm.

Objective:

To test whether intravenously administered MSCs reduce left ventricular (LV) dysfunction both post–acute myocardial infarction and in ischemic cardiomyopathy and that these effects are caused, at least partly, by systemic anti-inflammatory activities.

Methods and Results:

Mice underwent 45 minutes of left anterior descending artery occlusion. Human MSCs, grown chronically at 5% O
2
, were administered intravenously. LV function was assessed by serial echocardiography, 2,3,5-triphenyltetrazolium chloride staining determined infarct size, and fluorescence-activated cell sorting assessed cell composition. Fluorescent and radiolabeled MSCs (1×10
6
) were injected 24 hours post–myocardial infarction and homed to regions of myocardial injury; however, the myocardium contained only a small proportion of total MSCs. Mice received 2×10
6
MSCs or saline intravenously 24 hours post–myocardial infarction (n=16 per group). At day 21, we harvested blood and spleens for fluorescence-activated cell sorting and hearts for 2,3,5-triphenyltetrazolium chloride staining. Adverse LV remodeling and deteriorating LV ejection fraction occurred in control mice with large infarcts (≥25% LV). Intravenous MSCs eliminated the progressive deterioration in LV end-diastolic volume and LV end-systolic volume. MSCs significantly decreased natural killer cells in the heart and spleen and neutrophils in the heart. Specific natural killer cell depletion 24 hours pre–acute myocardial infarction significantly improved infarct size, LV ejection fraction, and adverse LV remodeling, changes associated with decreased neutrophils in the heart. In an ischemic cardiomyopathy model, mice 4 weeks post–myocardial infarction were randomized to tail-vein injection of 2×10
6
MSCs, with injection repeated at week 3 (n=16) versus PBS control (n=16). MSCs significantly increased LV ejection fraction and decreased LV end-systolic volume.

Conclusions:

Intravenously administered MSCs for acute myocardial infarction attenuate the progressive deterioration in LV function and adverse remodeling in mice with large infarcts, and in ischemic cardiomyopathy, they improve LV function, effects apparently modulated in part by systemic anti-inflammatory activities.
The Provincialism Problem: Then and Now
Authors: Smith Terry
Published: February 2017

Published in the September 1974 issue of Artforum, my article “The Provincialism Problem” argued that a world art system, centered on the New York artworld, condemned artists elsewhere to misleadingly perceive their situation as necessarily subservient, and their art as lesser, secondary, and dependent. In fact, this system condemned all involved, including New York based artists, to a vicious cycle of mutual inequity. The article called for artists, critics, and curators to radically reimagine these relationships. Often cited in the decades since then, in recent years it is frequently used as a foil to demonstrate how, within the international artworld, the situation has improved significantly. In this essay, I review the acute awareness of these issues in the Australian artworld during the 1960s and 1970s, and the situation in New York in the early and mid-1970s that lead me to write the article in concert with other members of the Art & Language group. I note some of the critical responses to the article since its publication, explore key aspects of center-periphery theory, and conclude by arguing that the provincialism problem has not been solved—it has, rather, been globalized then neoliberalized, and thus remains problematic.
Images Taken Not for Their Images
Authors: Witt Nathan
Published: February 2017

This project is part of my practice of resisting aspects of visual culture and deconstructing images that is partly indebted to 1960s conceptual text-based artists, letterism, and Situationists, but also correlated to orthodox attitudes towards the image. It examines restrictions that Israel places upon Palestinian telecommunications in the West Bank, such as the locations of radio masts placed within Israel, the height Palestinian networks are permitted to build their masts, and that illegal Israeli settlers living illegally inside Palestine enjoy 3/4G coverage while Palestinians receive 2G. These technological infringements inhibit the movements for everyone in the West Bank and Gaza where civilians can be more easily and cheaply monitored and arrested, which is reflected in the Israeli arrests of Palestinians for a range of alleged offences on Facebook or Twitter, particularly incitement. These restrictions affect the way we receive and disseminate information, which was felt as a tourist/gentile/interloper visiting Palestine for the first time, unsure how to respond to the paranoia of being monitored or being in the wrong place. The project was made during a period of forced abstinence of Facebook and Twitter due to the paranoia of working between Lebanon and Israel, and so is a manual version of Facebook's pin-dropped album where the geographical data and time-stamp has been pulled via a simple desktop application from each JPEG's file. The response I hope reflects an overwhelming urge not to overly rely on visual representation, and to instead state as minimally as possible what the work is and to simply provide the raw data of the image.
The Contemporary Context of Gurdjieff’s Movements
Authors: Cusack Carole M.
Published: February 2017

The “sacred dances” or “Movements” were first revealed by George Ivanovitch Gurdjieff (c. 1866–1949) in 1919 in Tiflis (Tblisi), the site of the first foundation of his Institute for the Harmonious Development of Man. The proximate cause of this new teaching technique has been hypothesized to be Jeanne de Salzmann (1889–1990), an instructor of the Eurhythmics method of music education developed by Émile Jaques-Dalcroze (1865–1950). Jeanne and her husband Alexandre met at Jaques-Dalcroze’s Institute at Hellerau in 1913, and became pupils of Gurdjieff in 1919. It was to her Dalcroze class that Gurdjieff first taught Movements. Esoteric systems of dance and musical education proliferated at the time. Gurdjieff was deeply interested in music, theater, and art. When Pyotr Demianovich Ouspensky (1878–1947) met him in 1915 he spoke of dances he had seen in Eastern temples, and was working on a never-performed ballet, The Struggle of the Magicians. This article argues that body-based disciplines introduced by esoteric teachers with Theosophically-inflected systems are a significant phenomenon in the early twentieth century and that Gurdjieff’s Movements, while distinct from other dance systems, emerged in the same esoteric melting-pot and manifest common features and themes with the esoteric dance of Rudolf Steiner, Rudolf von Laban, Peter Deunov, and others.