bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of different human NFAT isoforms by neuronal activity
Authors: Vihma Hanna , Luhakooder Mirjam , Pruunsild Priit , Timmusk Tõnis
Published: February 2016

Nuclear factor of activated T‐cells (NFAT) is a family of transcription factors comprising four calcium‐regulated members: NFATc1, NFATc2, NFATc3, and NFATc4. Upon activation by the calcium‐dependent phosphatase calcineurin (CaN), NFATs translocate from cytosol to the nucleus and regulate their target genes, which in the nervous system are involved in axon growth, synaptic plasticity, and neuronal survival. We have shown previously that there are a number of different splice variants of NFAT genes expressed in the brain. Here, we studied the subcellular localizations and transactivation capacities of alternative human NFAT isoforms in rat primary cortical or hippocampal neurons in response to membrane depolarization and compared the induced transactivation levels in neurons to those obtained from HEK293 cells in response to calcium signaling. We confirm that in neurons the translocation to the nucleus of all NFAT isoforms is reliant on the activity of CaN. However, our results suggest that both the regulation of subcellular localization and transcriptional activity of NFAT proteins in neurons is isoform specific. We show that in primary hippocampal neurons NFATc2 isoforms have very fast translocation kinetics, whereas NFATc4 isoforms translocate relatively slowly to the nucleus. Moreover, we demonstrate that the strongest transcriptional activators in HEK293 cells are NFATc1 and NFATc3, but in neurons NFATc3 and NFATc4 lead to the highest induction, and NFATc2 and NFATc1 display isoform‐specific transcription activation capacities. Altogether, our results indicate that the effects of calcium signaling on the action of NFAT proteins are isoform‐specific and can differ between cell types.

image

We show that the effects of calcium signaling on the action of NFAT proteins are isoform‐specific and differ between cell types. Although nuclear localization of all NFAT isoforms in neurons requires calcineurin, the subcellular distributions, neuronal activity‐induced nuclear translocation extent and kinetics, and transcription activation capacities of alternative NFAT proteins vary.
The contribution of alpha synuclein to neuronal survival and function – Implications for Parkinson's disease
Authors: Benskey Matthew J. , Perez Ruth G. , Manfredsson Fredric P.
Published: February 2016

The aggregation of alpha synuclein (α‐syn) is a neuropathological feature that defines a spectrum of disorders collectively termed synucleinopathies, and of these, Parkinson's disease (PD) is arguably the best characterized. Aggregated α‐syn is the primary component of Lewy bodies, the defining pathological feature ofPD, while mutations or multiplications in the α‐syn gene result in familialPD. The high correlation between α‐syn burden andPDhas led to the hypothesis that α‐syn aggregation produces toxicity through a gain‐of‐function mechanism. However, α‐syn has been implicated to function in a diverse range of essential cellular processes such as the regulation of neurotransmission and response to cellular stress. As such, an alternative hypothesis with equal explanatory power is that the aggregation of α‐syn results in toxicity because of a toxic loss of necessary α‐syn function, following sequestration of functional forms α‐syn into insoluble protein aggregates. Within this review, we will provide an overview of the literature linking α‐syn toPDand the knowledge gained from current α‐syn‐based animal models ofPD. We will then interpret these data from the viewpoint of the α‐syn loss‐of‐function hypothesis and provide a potential mechanistic model by which loss of α‐syn function could result in at least some of the neurodegeneration observed inPD. By providing an alternative perspective on the etiopathogenesis ofPDand synucleinopathies, this may reveal alternative avenues of research in order to identify potential novel therapeutic targets for disease modifying strategies.

image

The correlation between α‐synuclein burden and Parkinson's disease pathology has led to the hypothesis that α‐synuclein aggregation produces toxicity through a gain‐of‐function mechanism. However, in this review, we discuss data supporting the alternative hypothesis that the aggregation of α‐synuclein results in toxicity because of loss of necessary α‐synuclein function at the presynaptic terminal, following sequestration of functional forms of α‐synuclein into aggregates.
A Comparison of Intravascular Imaging Modalities for Detection of Stent Struts in Acute Coronary Syndrome
Authors: Hyeon Seong Hyeop , Lee Wang Soo , Kim Doo Il , Shin Eun Seok , Kim Ki Seok , Hong Young Joon , Lee Sung Yun , Won Hoyoun , Kim Tae Ho , Kim Sang‐Wook
Published: February 2016

Background

We used optical coherence tomography (OCT) and intravascular ultrasound (IVUS) to assess the struts of implanted stents in patients with acute coronary syndrome (ACS).

Methods

A totle of 10,756 stent struts were analyzed with OCT in 42 patients of ACS. Of them, both of IVUS and OCT imaging were performed in 33 patients. Appearance of stent struts was classified as well apposed, buried, malapposed, and nondetectable, and the number of stent struts were counted by OCT and IVUS was compared.

Results

Most of stent struts were well apposed (78.1%, 8,407/10,756). However, malapposed struts were 5.6% (607/10,756), and 14.1% (1,514/10,756) of stent struts were buried by thrombus. The nondetectable struts were 2.11% (228/10,756) in ACS. 94.7% (216/228) of nondetectable stent struts were associated with red thrombus, and plaque prolapse was in 5.3% (12/228). The number of stent struts counted by OCT were larger than that of IVUS. The mean number of stent struts at the proximal and distal stent edges were 24 ± 6.57 in OCT, the stent struts IVUS counted were 20 ± 4.18 (P < 0.0001). Although the frequency of malapposed struts were similar 4.6% (376/8,248) in OCT versus 4.8% (369/7,674) in IVUS (P = 0.788). Stent struts were often buried by thrombus in ACS 15.2% (1,252/8,248) in OCT versus 9.7% (747/7,674) in IVUS; P = 0.006. The nondetectable struts were fewer in IVUS than OCT 0.2% (16/7,674) in IVUS versus 2.2% (187/8,248) in OCT; P < 0.0001.

Conclusion

Stent struts are frequently buried and nondetectable due to thrombi burden in ACS patients. Adequate thrombus removal and proper selection of the imaging device is warranted in ACS. (J Interven Cardiol 2016;29:99–107)
Endovascular Interventional Cardiology: 2015 in Review
Authors: White Derek C. , Elder Mahir , Mohamad Tamam , Kaki Amir , Schreiber Theodore L.
Published: February 2016

Minimally invasive interventional procedures have become an appealing option for patients with endovascular disease historically referred to surgery. This article reviews the major advancements and trials published in 2015. (J Interven Cardiol 2016;29:5–10)
A contemporary justice perspective on dual ladders for R&D professionals
Authors: Hoffmann Patrick , Hoegl Martin , Muethel Miriam , Weiss Matthias
Published: February 2016

Research and development (R&D) professionals play a key role in companies' innovation performance. Whereas prior research has indicated the potential benefits of dual ladder career systems to retain and motivate R&D professionals, there is a lack of knowledge regarding the design properties of dual ladders that facilitate such positive effects. The purpose of this study is to address this research gap by exploring how organizations can design dual ladders to enhance R&D professionals' organizational commitment and career satisfaction. Drawing on contemporary justice theory, we point to two factors integral for the successful application of dual ladders: the perceived equality of the technical ladder and the transparency of the dual ladder. These factors are related to R&D professionals' organizational commitment and career satisfaction. Furthermore, this study investigates whether these relationships are moderated by R&D professionals' age and self‐directedness in career management as well as firm size. The hypotheses are tested in a cross‐level study with 9 heads of R&D departments, 32 human resource managers, and 382 R&D professionals from 32 organizations. Based on the analyses, this study finds positive relationships between the perceived equality and the transparency of the dual ladder with R&D professionals' organizational commitment and career satisfaction. In addition, the findings show that the effects of the perceived equality of the technical ladder on R&D professionals' career satisfaction are weaker at high levels of self‐directed career management. The study contributes by developing theory on the consequences of dual ladders' design properties and moderating influences thereon. Thus, this research has implications for the literature on innovation management by expanding the knowledge on the interplay between career management and the human side of innovation.
Objective but not subjective sleep predicts memory in community‐dwelling older adults
Authors: Cavuoto Marina G. , Ong Ben , Pike Kerryn E. , Nicholas Christian L. , Bei Bei , Kinsella Glynda J.
Published: February 2016

Research on the relationship between habitual sleep patterns and memory performance in older adults is limited. No previous study has used objective and subjective memory measures in a large, older‐aged sample to examine the association between sleep and various domains of memory. The aim of this study was to examine the association between objective and subjective measures of sleep with memory performance in older adults, controlling for the effects of potential confounds. One‐hundred and seventy‐three community‐dwelling older adults aged 65–89 years in Victoria, Australia completed the study. Objective sleep quality and length were ascertained using the Actiwatch 2 Mini‐Mitter, while subjective sleep was measured using the Pittsburgh Sleep Quality Index. Memory was indexed by tests of retrospective memory (Hopkins Verbal Learning Test – Revised), working memory (n‐back, 2‐back accuracy) and prospective memory (a habitual button pressing task). Compared with normative data, overall performance on retrospective memory function was within the average range. Hierarchical regression was used to determine whether objective or subjective measures of sleep predicted memory performances after controlling for demographics, health and mood. After controlling for confounds, actigraphic sleep indices (greater wake after sleep onset, longer sleep‐onset latency and longer total sleep time) predicted poorer retrospective (∆R2 = 0.05, P = 0.016) and working memory (∆R2 = 0.05, P = 0.047). In contrast, subjective sleep indices did not significantly predict memory performances. In community‐based older adults, objectively‐measured, habitual sleep indices predict poorer memory performances. It will be important to follow the sample longitudinally to determine trajectories of change over time.
Interleukin‐6 trans‐signalling induces vascular endothelial growth factor synthesis partly via Janus kinases‐STAT3 pathway in human mesothelial cells
Authors: Yang Xiaoxiao , Lin Aiwu , Jiang Na , Yan Hao , Ni Zhaohui , Qian Jiaqi , Fang Wei
Published: February 2016

Aims

Interleukin‐6 (IL‐6) is a vital inflammatory factor in the peritoneal cavity of peritoneal dialysis (PD) patients. Because intraperitoneal inflammation is closely associated with angiogenesis, we sought to explore the effect of IL‐6 on vascular endothelial growth factor (VEGF) synthesis and its transduction pathway in mesothelial cells.

Methods

Human mesothelial cells (Met‐5A) were incubated with different concentrations of glucose and mannitol, and the effect of glucose and mannitol on the expression of IL‐6 was determined. Then, the cells were stimulated by IL‐6 with or without two soluble receptors of IL‐6 (sIL‐6R or sgp130), and VEGF synthesis was detected. Finally, the cells were incubated with IL‐6/sIL‐6R combined with or without the inhibitor of Janus kinases (JAK) AG490. The phosphorylation of the signal transducer and activator of transcription 3 (STAT3) and its intracellular translocation were examined.

Results

1. High glucose and mannitol could upregulate IL‐6 mRNA expression and IL‐6 secretion in mesothelial cells significantly, and there was no difference of its effect between high glucose and mannitol. 2. Met‐5A was a cell line with a single IL‐6 receptor. The IL‐6/sIL‐6R complex induced VEGF synthesis of mesothelial cells, which was alleviated by sgp130 or AG490. IL‐6 trans‐signalling could induce the phosphorylation of STAT3, which is recruited to the cellular nucleus of Met‐5A cells.

Conclusion

The present study might provide evidence that high glucose upregulates IL‐6 synthesis in Met‐5A cells, to some extent, depending on its osmolality and that IL‐6 trans‐signalling could induce VEGF synthesis partly dependent on the JAK/STAT3 pathway.
Bloating is associated with worse quality of life, treatment satisfaction, and treatment responsiveness among patients with constipation‐predominant irritable bowel syndrome and functional constipation
Authors: Neri L. , Iovino P. ,   the Laxative Inadequate Relief Survey (LIRS) Group
Published: February 2016

Background

The management of bloating is unclear and its relationship with patients' well‐being and treatment satisfaction independent of other abdominal symptoms is uncharacterized. We evaluated the association of bloating with patient‐reported outcomes.

Methods

Thirty‐nine centers for functional gastrointestinal disorders joined the laxative inadequate relief survey. We enrolled 2203 consecutive outpatients with functional constipation (FC) or constipation‐predominant irritable bowel syndrome (IBS‐C) in two cross‐sectional waves. Both wave 1 and 2 included the SF‐12, the patient assessment of constipation‐symptoms (PAC‐SYM), and the treatment satisfaction questionnaire for medication (TSQM‐2). Wave 2 only included a global rating of change (GRC) scale to assess patients' assessment of efficacy concerning treatment switches occurred in the 3 months prior to the interview. Bloating in the abdomen was defined on the basis of PAC‐SYM item 3.

Key Results

The average age was 50.1 years (SD, 16.7) and 82.1% of patients were women. The prevalence of bloating was 91.6% (n = 1970). Bloating was associated with SF‐12 Physical Composite Score (p < 0.01), SF‐12 Mental Composite Score (p < 0.01), GRC (p < 0.01), Satisfaction with treatment effectiveness (p < 0.01), convenience of administration (p < 0.01), and side effects (p < 0.01) after adjustment for possible confounders.

Conclusions & Inferences

Our data suggest that patients regard bloating as a key element in assessing clinical changes and treatments' efficacy as this symptom exerts a strong influence on patient‐reported outcomes independent of possible confounders and other symptoms of constipation. Our data provide the rationale to investigate the efficacy and tolerability of new treatments specifically addressing this important, yet disregarded, patients' complain.
Proteomic alteration of a thermo‐sensitive male sterility SP2S in rapeseed (Brassica napus) in response to mild temperature stress
Authors: Zhang Jingwen , Liu Zhiquan , Liu Xiqiong , Dong Jungang , Pang Honghxi , Yu Chengyu
Published: February 2016

We conducted a proteomic comparison between thermo‐sensitive genic male sterility (TGMS) SP2S and its near‐isogenic line SP2F grown at 22°C. The proteomes at microsporocyte meiosis and uninucleate microspore stages were profiled using 2‐dimensional gel electrophoresis. Twenty‐five well‐reproducible spots (10 spots at microsporocyte meiosis stage and 15 spots at uninucleate microspore stage) containing 28 proteins were successfully identified by MALDI‐TOF/TOF mass spectrometry. An elongation factor EF‐2 at microsporocyte stage and 4 proteins (aconitate hydratase, triosephosphate isomerase, serine/arginine‐rich mRNA splicing factor and glutathione S‐transferase) at uninucleate microspore stage accumulated in SP2S, but more proteins were lost or reduced, including those associated with amino acid metabolism, photosynthesis, synthesis and degradation of protein, lipid metabolism, cytoskeleton, RNA modification, oxidoreductase and defence response. The dramatic decrease of tubulin, actin and Translationally controlled tumour protein (TCTP) crucial for microtubule and cell division and three enzymes for amino acid metabolite at early stage indicated a serious defect on the cytokinesis. They were important clues for us to search the TGMS genes and its interacting genes.
Treatment of Moderate to Severe Pediatric Psoriasis: A Retrospective Case Series
Authors: Klufas Daniel M. , Wald Jenna M. , Strober Bruce E.
Published: February 2016

Background

Psoriasis has an estimated prevalence of 0.5% to 2.0% in children. There is a paucity of data regarding the management and safety of treatments currently available for children with moderate to severe psoriasis. The aim of this study was to evaluate the treatment response and safety of systemic therapies used to manage moderate to severe pediatric psoriasis in a single referral center. Despite a small sample size, it was hypothesized that multiple therapeutics used for adult psoriasis would have a similar side‐effect profile and positive disease response when used in a pediatric population.

Methods

A retrospective case series evaluated 51 children with moderate to severe psoriasis treated with systemic therapies for adverse event occurrence and for disease response using a 5‐point Physician Global Assessment scale.

Results

Fifty‐one patients, some of whom used multiple treatment options, produced 80 treatment data points. Adverse events were reported in 29 of these 80 treatments, with most being minor, subjective side effects. Overall, the most commonly reported side effect was fatigue, which was reported in 7.5% of treatments. Because of the small sample size, the data collected are limited and may not represent a comprehensive safety profile, nor do they allow comparison of efficacy between therapies. This case series found that biologic and immunomodulating therapies provide well‐tolerated treatments with positive disease response for moderate to severe pediatric psoriasis.

Conclusion

Although sample size and study design limit the data from this study, the study provides some guidance where little exists and helps to support the use of these treatments in this setting.
Decentralization, District Chief Executives, and District Assemblies in Ghana's Fourth Republic
Authors: Debrah Emmanuel
Published: February 2016

The article shows how District Chief Executives (DCEs) exert extraordinary influence on Ghana's decentralization. Analyzing data from Afrobarometer surveys and 100 interviews, the article establishes that DCEs’ position is very complex, involving the exercise of political and administrative functions aimed to influence grassroots support for the president. While politicization allowed the DCEs to perform their assigned functions, it polarized the district assemblies with assembly members divided in support of or against their policies/activities. It further led to conflict and tension between the DCEs, administrators, and Members of Parliament, which proved counterproductive to rural development. Subnational leaders who owe their position to political appointment lack autonomy to pursue grassroots preference. Yet with constitutional reforms that ensure direct election of DCEs, and the creation of a local supervisory body with review and veto powers over DCE policy and administration, responsiveness, and accountability to the people can be encouraged. This, in turn, can foster cooperation/positive interaction among the varying actors and perspectives for effective decentralization.

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Authors: Sahakyan Davit
Published: February 2016

The fivefold increase of the number of preferential trade agreements (PTAs) during the last quarter century has been largely explained by the discriminative nature of such agreements, which has triggered “competitive liberalization” and PTA formation among nonmembers through a domino effect. Based on the author's interviews with European Union (EU) trade officials and policy makers at the European Commission, this article evaluates EU trade policy developments during the last quarter century and lays out EU policy responses to the proliferation of PTAs in Latin America and East and Southeast Asia. The article concludes that the EU has adopted “defensive” and “proactive” trade policy responses in Latin America and East and Southeast Asia, thus augmenting the discriminative pressures and reinforcing the discrimination‐fueled proliferation of PTAs.

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Determinants of Growth in Fast‐Developing Countries: Evidence from Bundling and Unbundling Institutions
Authors: Asongu Simplice A.
Published: February 2016

This study assesses growth determinants in the Brazil, Russia, India, China, and South Africa and Mexico, Indonesia, Nigeria, and Turkey nations the period 2001‐11. Particular emphasis is laid on the bundling and unbundling of ten governance dynamics. Contemporary and noncontemporary fixed‐ and random‐effects regressions are employed. The following are some findings. First, governance is more positively significant in noncontemporary specifications as opposed to contemporary regressions. Second, there is some interesting evidence on the heterogeneity of political governance as a driver. Political governance and its constituents (political stability and voice and accountability) are significantly positive in gross domestic product (GDP) growth but insignificant in real GDP output regressions. Third, the other governance dynamics are more significant determinants of real GDP output, as opposed to GDP growth. Accordingly, they are insignificant in contemporary regressions and negatively significant in noncontemporary regressions for GDP growth. Fourth, the constituents of economic governance have the highest magnitude in the positive effects of governance dynamics on real GDP output.

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Dennis C. Mueller. 2013. “.” Kyklos 65 (): 371‐407. http://onlinelibrary.wiley.com/doi/10.1111/j.1467-6435.2012.00543.x/abstract
Empirically Derived Subgroups of Self‐Injurious Thoughts and Behavior: Application of Latent Class Analysis
Authors: Dhingra Katie , Boduszek Daniel , Klonsky E. David
Published: February 2016

Latent class analysis was applied to the sample data to identify homogenous subtypes or classes of self‐injurious thoughts and behavior (SITB) based on indicators indexing suicide ideation, suicide gesture, suicide attempt, thoughts of nonsuicidal self‐injury (NSSI), and NSSI behavior. Analyses were based on a sample of 1,809 healthy adults. Associations between the emergent latent classes and demographic, psychological, and clinical characteristics were assessed. Two clinically relevant subtypes were identified, in addition to a class who reported few SITBs, and were labeled as follows: low SITBs (25.8%), NSSI and ideation (25%), and suicidal behavior (29.2%). Several unique differences between the latent classes and external measures emerged. For instance, those belonging to the NSSI and ideation class compared with the suicidal behavior class reported lower levels of entrapment, burdensomeness, fearlessness about death, exposure to the attempted suicide or self‐injury of family members and close friends, and higher levels of goal disengagement and acute agitation. SITBs are best explained by three homogenous subgroups that display quantitative and qualitative differences. Profiling the behavioral and cognitive components of suicidal and nonsuicidal self‐injury is potentially useful as a first step in developing tailored intervention and treatment programs.
Canine and feline retinal lymphoma: a retrospective review of 12 cases
Authors: Malmberg Jennifer L. , Garcia Teresa , Dubielzig Richard R. , Ehrhart E. J.
Published: February 2016

This retrospective study identified 12 cases (6 canine and 6 feline) of ocular lymphoma with extensive retinal involvement and relative sparing of other ocular tissues. Our objectives were to describe the morphologic and immunohistochemical features of retinal lymphoma, assess the degree of correlation to the human counterpart, assign subtypes based on the veterinary‐adapted WHO classification system, and promote accurate reporting of retinal involvement in cases of intraocular lymphoma. Our findings suggest that a distinct retinal tropism is quite rare, representing approximately 1% of all cases of canine and feline ocular lymphoma. No breed or sex predispositions were identified. The mean age of the affected animal was 7 years (range 4–10) and 11 years (range 6–19) for dogs and cats, respectively. Nine cases (5 canine and 4 feline) were classified as diffuse large B‐cell lymphoma (DLBCL) subtype. The remaining cases were classified as peripheral T‐cell lymphoma (PTCL).
Application of Dynamic ϕ–T Map: Analysis on a Natural Gas/Diesel Fueled RCCI Engine
Authors: Li Jing , Yang Wenming , An Hui , Zhou Dezhi , Kraft Markus
Published: February 2016

In this study, dynamic ϕ–T map analysis was applied to a reactivity controlled compression ignition (RCCI) engine fueled with natural gas (NG) and diesel. The combustion process of the engine was simulated by coupled kiva4-chemkin with a diesel oil surrogate (DOS) chemical mechanism. The ϕ–T maps were constructed by the mole fractions of soot and NO obtained from senkin and ϕ–T conditions from engine simulations. Five parameters, namely, NG fraction, first start of injection (SOI) timing, second SOI timing, second injection duration, and exhaust gas recirculation (EGR) rate, were varied in certain ranges individually, and the ϕ–T maps were compared and analyzed under various conditions. The results revealed how the five parameters would shift the ϕ–T conditions and influence the soot–NO contour. Among the factors, EGR rate could limit the highest temperature due to its dilute effect, hence maintaining RCCI combustion within low-temperature combustion (LTC) region. The second significant parameter is the premixed NG fraction. It could set the lowest temperature; moreover, the tendency of soot formation can be mitigated due to the lessened fuel impingement and the absence of C–C bond. Finally, the region of RCCI combustion was added to the commonly known ϕ–T map diagram.
Cochlear implant speech intelligibility outcomes with structured and unstructured binary mask errors
Authors: Kressner Abigail A. , Westermann Adam , Buchholz Jörg M. , Rozell Christopher J.
Published: February 2016

It has been shown that intelligibility can be improved for cochlear implant (CI) recipients with the ideal binary mask (IBM). In realistic scenarios where prior information is unavailable, however, the IBM must be estimated, and these estimations will inevitably contain errors. Although the effects of both unstructured and structured binary mask errors have been investigated with normal-hearing (NH) listeners, they have not been investigated with CI recipients. This study assesses these effects with CI recipients using masks that have been generated systematically with a statistical model. The results demonstrate that clustering of mask errors substantially decreases the tolerance of errors, that incorrectly removing target-dominated regions can be as detrimental to intelligibility as incorrectly adding interferer-dominated regions, and that the individual tolerances of the different types of errors can change when both are present. These trends follow those of NH listeners. However, analysis with a mixed effects model suggests that CI recipients tend to be less tolerant than NH listeners to mask errors in most conditions, at least with respect to the testing methods in each of the studies. This study clearly demonstrates that structure influences the tolerance of errors and therefore should be considered when analyzing binary-masking algorithms.
Transtheoretical Principles and Processes for Adopting Physical Activity: A Longitudinal 24-Month Comparison of Maintainers, Relapsers, and Nonchangers
Authors: Lipschitz Jessica M. , Yusufov Miryam , Paiva Andrea , Redding Colleen A. , Rossi Joseph S. , Johnson Sara , Blissmer Bryan , Gokbayrak N. Simay , Velicer Wayne F. , Prochaska James O.
Published: February 2016

This study examined longitudinal differences in use of transtheoretical model (TTM) behavior change constructs in maintainers (who reached and maintained exercise guidelines), relapsers (who reached guidelines, then regressed), and nonchangers (who did not reach guidelines). Data from two population-based TTM-tailored randomized trial intervention groups targeting exercise behavior (N = 1050) were pooled, and analyses assessed differences in TTM constructs between the three groups at baseline, 12 months, and 24 months. Findings indicated that relapsers tended to use TTM variables similarly to maintainers with the exception of self-efficacy, consciousness raising, and most behavioral processes of change, at 24 months. Nonchangers, however, used all TTM variables less than maintainers at nearly every time point. Findings suggest that relapsers remain more active than nonchangers in terms of use of change processes. Poor response to interventions (nonchangers) may be predicted by low baseline engagement in change processes. Although relapsers reverted to physical inactivity, their overall greater use of TTM constructs suggests that their efforts to change remain better than those of the stable nonchanger group. Future research can focus on treatment engagement strategies to help the stable nonchangers initiate change and to help relapsers to maintain treatment gains.
Record ozone hole may open over Arctic in the spring
Authors: Hand Eric
Published: February 2016

Unusual polar cold produces clouds that could help push ozone losses beyond 2011 mark, releasing extra UV radiation.
A crystal ball for chemical safety
Authors: Rabesandratana Tania
Published: February 2016

By comparing new chemicals to known compounds, toxicologists seek early hazard warnings.
Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5
Authors: Mavrakis Konstantinos J. , McDonald E. Robert , Schlabach Michael R. , Billy Eric , Hoffman Gregory R. , deWeck Antoine , Ruddy David A. , Venkatesan Kavitha , Yu Jianjun , McAllister Gregg , Stump Mark , deBeaumont Rosalie , Ho Samuel , Yue Yingzi , Liu Yue , Yan-Neale Yan , Yang Guizhi , Lin Fallon , Yin Hong , Gao Hui , Kipp D. Randal , Zhao Songping , McNamara Joshua T. , Sprague Elizabeth R. , Zheng Bing , Lin Ying , Cho Young Shin , Gu Justin , Crawford Kenneth , Ciccone David , Vitari Alberto C. , Lai Albert , Capka Vladimir , Hurov Kristen , Porter Jeffery A. , Tallarico John , Mickanin Craig , Lees Emma , Pagliarini Raymond , Keen Nicholas , Schmelzle Tobias , Hofmann Francesco , Stegmeier Frank , Sellers William R.
Published: February 2016

Tumors put in a vulnerable position

Cancer cells often display alterations in metabolism that help fuel their growth. Such metabolic “rewiring” may also work against the cancer cells, however, by creating new vulnerabilities that can be exploited therapeutically. A variety of human tumors show changes in methionine metabolism caused by loss of the gene coding for 5-methylthioadenosine phosphorylase (MTAP). Mavrakis
et al.
and Kryukov
et al.
found that the loss of MTAP renders cancer cell lines sensitive to growth inhibition by compounds that suppress the activity of a specific arginine methyltransferase called PRMT5. Conceivably, drugs that inhibit PRMT5 activity could be developed into a tailored therapy for MTAP-deficient tumors.

Science
, this issue pp.
1208
and
1214
Draft Genome Sequence of the Radioresistant Bacterium Deinococcus grandis, Isolated from Freshwater Fish in Japan
Authors: Satoh Katsuya , Onodera Takefumi , Omoso Kota , Takeda-Yano Kiyoko , Katayama Takeshi , Oono Yutaka , Narumi Issay
Published: February 2016

Deinococcus grandis
is a radioresistant bacterium isolated from freshwater fish in Japan. Here we reported the draft genome sequence of
D. grandis
(4.1 Mb), which will be useful for elucidating the common principles of radioresistance in
Deinococcus
species through the comparative analysis of genomic sequences.
Draft Genome Sequence of
Hymenobacter
sp. Strain AT01-02, Isolated from a Surface Soil Sample in the Atacama Desert, Chile
Authors: Holm Hansen Anders Cai , Paulino-Lima Ivan Glaucio , Fujishima Kosuke , Rothschild Lynn Justine , Jensen Peter Ruhdal
Published: February 2016

Here, we report the 5.09-Mb draft genome sequence of
Hymenobacter
sp. strain AT01-02, which was isolated from a surface soil sample in the Atacama Desert, Chile. The isolate is extremely resistant to UV-C radiation and is able to accumulate high intracellular levels of Mn/Fe.
Complete Genome Sequences of Two Interactive Moderate Thermophiles,
Paenibacillus napthalenovorans
32O-Y and
Paenibacillus
sp. 32O-W
Authors: Butler Robert R. , Wang Jia , Stark Benjamin C. , Pombert Jean-François
Published: February 2016

Microorganisms with the capability to desulfurize petroleum are in high demand with escalating restrictions currently placed on fuel purity. Thermophilic desulfurizers are particularly valuable in high-temperature industrial applications. We report the whole-genome sequences of
Paenibacillus napthalenovorans
32O-Y and
Paenibacillus
sp. 32O-W, which can and cannot, respectively, metabolize dibenzothiophene.
Draft Genome Sequence of
Vibrio
sp. Strain Evh12, a Bacterium Retrieved from the Gorgonian Coral
Eunicella verrucosa
Authors: Franco Telma , Califano Gianmaria , Gonçalves Ana C. S. , Cúcio Catarina , Costa Rodrigo
Published: February 2016

To shed light on the associations established between
Vibrio
species and soft corals in coastal ecosystems, we report here the draft genome sequence of
Vibrio
sp. strain Evh12, a bacterium that has been isolated from the gorgonian coral
Eunicella verrucosa
and that shows antagonistic activity against
Escherichia coli
.
Donor blood screening and moral responsibility: how safe should blood be?
Authors: Verweij Marcel , Kramer Koen
Published: February 2016

Some screening tests for donor blood that are used by blood services to prevent transfusion-transmission of infectious diseases offer relatively few health benefits for the resources spent on them. Can good ethical arguments be provided for employing these tests nonetheless? This paper discusses—and ultimately rejects—three such arguments. According to the ‘rule of rescue’ argument, general standards for cost-effectiveness in healthcare may be ignored when rescuing identifiable individuals. The argument fails in this context, however, because we cannot identify beforehand who will benefit from additional blood screening tests. On the ‘imposed risk’ argument, general cost-effectiveness standards do not apply when healthcare interventionsimposerisks on patients. This argument ignores the fact that imposing risks on patients is inevitable in healthcare and that these risks can be countered only within reasonable limits. Finally, the ‘manufacturing standard’ argument premises that general cost-effectiveness standards do not apply to procedures preventing the contamination of manufactured medical products. We contend that while this argument seems reasonable insofar as commercially manufactured medical products are concerned, publicly funded blood screening tests should respect the standards for general healthcare. We conclude that these particular arguments are unpersuasive, and we offer directions to advance the debate.
The impact of clinical maturity on competency in evidence-based medicine: a mixed-methods study
Authors: Ilic Dragan , Diug Basia
Published: February 2016

Objective

To identify whether the clinical maturity of medical trainees impacts upon the level of trainee competency in evidence-based medicine (EBM).

Materials and methods

Undergraduate and graduate-entry medical trainees entering their first year of training in the clinical environment were recruited for this study. Competency in EBM was measured using a psychometrically validated instrument. EBM competency scores were analysed using Student's t tests, in order to differentiate between undergraduate and graduate-entry trainee performance. Ten focus group discussions were conducted with undergraduate and graduate-entry trainees. Audio transcripts were thematically analysed.

Results

Data on a total of 885 medical trainees were collected over a 5-year period. Undergraduate trainees had significantly higher EBM competency scores during years in which the programme was presented in a didactic format (mean difference (MD)=1.24 (95% CI)CI 0.21 to 2.26; 1.78 (0.39 to 3.17); 2.13 (1.16 to 3.09)). Graduate trainee EBM competency scores increased when a blended learning approach to EBM was adopted, demonstrating no significant difference in EBM competency scores between undergraduate and graduate cohorts (−0.27 (−1.38 to 0.85); −0.39 (−1.57 to 0.79). Qualitative findings indicated that differences in learning and teaching preference among undergraduate and graduate-entry trainees influenced the level of competency obtained in EBM.

Conclusions

Clinical maturity is the only one factor that may influence medical trainees' competency in EBM. Other predictors of EBM competency may include previous training and exposure to epidemiology, biostatistics and information literacy. While graduate-entry medical students may have more ‘life’ experience, or maturity, it does not necessarily translate into clinical maturity and integration into the clinical environment.
Working together to safeguard animal health
Authors: Gibbens Nigel
Published: February 2016

Nigel Gibbens, the UK's Chief Veterinary Officer, gives an update on some of the areas of animal health and welfare of particular interest to government and considers how farmers, vets and government can work together to control and respond to animal disease
Nerve growth factor enhances the CRE-dependent transcriptional activity activated by nobiletin in PC12 cells
Authors: Takito Jiro , Kimura Junko , Kajima Koji , Uozumi Nobuyuki , Watanabe Makoto , Yokosuka Akihito , Mimaki Yoshihiro , Nakamura Masanori , Ohizumi Yasushi
Published: February 2016

Prevention and treatment of Alzheimer disease are urgent problems for elderly people in developed countries. We previously reported that nobiletin, a poly-methoxylated flavone from the citrus peel, improved the symptoms in various types of animal models of memory loss and activated the cAMP responsive element (CRE)-dependent transcription in PC12 cells. Nobiletin activated the cAMP/PKA/MEK/Erk/MAPK signaling pathway without using the TrkA signaling activated by nerve growth factor (NGF). Here, we examined the effect of combination of nobiletin and NGF on the CRE-dependent transcription in PC12 cells. Although NGF alone had little effect on the CRE-dependent transcription, NGF markedly enhanced the CRE-dependent transcription induced by nobiletin. The NGF-induced enhancement was neutralized by a TrkA antagonist, K252a. This effect of NGF was effective on the early signaling event elicited by nobiletin. These results suggested that there was crosstalk between NGF and nobiletin signaling in activating the CRE-dependent transcription in PC12 cells.
Modulation of the neurological and vascular complications by grape seed extract in a rat model of spinal cord ischemia–reperfusion injury by downregulation of both osteopontin and cyclooxygenase-2
Authors: Sakr Hussein F. , Abbas Amr M. , Bin-Jaliah Ismaeel
Published: February 2016

In this study, we investigated the effects of grape seed extract (GSE) on the expression of osteopontin (OPN) and cyclooxygenase-2 (COX-2) in a rat model of spinal cord ischemia–reperfusion injury (SC-IRI). Fifty male rats were divided into 5 groups: control (CON); control + GSE (CON + GSE) (received GSE for 28 days); sham operated (Sham); IRI; and IRI + GSE. SC-IRI was induced by clamping the aorta just above the bifurcation for 45 min, and then the clamp was released for 48 h for reperfusion. IRI + GSE group received GSE for 28 days before SC-IRI. Sensory, motor, and placing/stepping reflex assessment was performed. Prostaglandin E2 (PGE2), thiobarbituric acid reactive substances (TBARs), and total antioxidant capacity (TAC) were measured in spinal cord homogenate. Immunohistochemical examination of the spinal cord for OPN and COX-2 were carried out. SC-IRI resulted in significant increase in plasma nitrite/nitrate level and spinal cord homogenate levels of TBARs and PGE2, and OPN and COX-2 expression with significant decrease in TAC. GSE improves the sensory and motor functions through decreasing OPN and COX-2 expression with reduction of oxidative stress parameters. We conclude a neuroprotective effect of GSE in SC-IRI through downregulating COX-2 and OPN expression plus its antioxidants effects.
Hindlimb unloading: rodent analog for microgravity
Authors: Globus Ruth K. , Morey-Holton Emily
Published: February 2016

The rodent hindlimb unloading (HU) model was developed in the 1980s to make it possible to study mechanisms, responses, and treatments for the adverse consequences of spaceflight. Decades before development of the HU model, weightlessness was predicted to yield deficits in the principal tissues responsible for structure and movement on Earth, primarily muscle and bone. Indeed, results from early spaceflight and HU experiments confirmed the expected sensitivity of the musculoskeletal system to gravity loading. Results from human and animal spaceflight and HU experiments show that nearly all organ systems and tissues studied display some measurable changes, albeit sometimes minor and of uncertain relevance to astronaut health. The focus of this review is to examine key HU results for various organ systems including those related to stress; the immune, cardiovascular, and nervous systems; vision changes; and wound healing. Analysis of the validity of the HU model is important given its potential value for both hypothesis testing and countermeasure development.
Gold Nanorods-Based Theranostics for Simultaneous Fluorescence/Two-Photon Luminescence Imaging and Synergistic Phototherapies
Authors: Fang Shan , Li Chunxiao , Lin Jing , Zhu Haigang , Cui Daxiang , Xu Yunsheng , Li Zhiming
Published: February 2016

Gold nanorods (GNRs) have shown great potential applications in cancer theranostics due to the unique phenomenon of surface plasmon resonance, which leads to strong electric fields on the surface and consequently enhances the absorption and scattering in the near-infrared (NIR) region. Indocyanine green (ICG), an amphipathic dye, is not only an excellent NIR imaging agent but also an ideal light absorber for laser-mediated photodynamic and photothermal therapy. In this study, in order to integrate the merits of GNRs and ICG in biomedical applications, we developed ICG conjugated silica-coated GNRs (GNR@SiO2-ICG) for cancer imaging and phototherapy. The covalent coupling strategy reduces the probability of leakage/desorption during the delivery. The as-prepared GNR@SiO2-ICG could serve as efficient probes to simultaneously enhance fluorescence (FL) imaging and two-photon luminescence (TPL) imaging.In vitroexperiments indicated that A375 cells could be killed through synergistic phototherapies effect of GNRs and ICG using single wavelength continuous-wave laser irradiation. Our results indicated that the synthesized GNR@SiO2-ICG are effective for simultaneously enhancing FL/TPL imaging and synergistic phototherapies.
Contribution of Cell Surface Hydrophobicity in the Resistance ofStaphylococcus aureusagainst Antimicrobial Agents
Authors: Lather Puja , Mohanty A. K. , Jha Pankaj , Garsa Anita Kumari
Published: February 2016

Staphylococcus aureusis found in a wide variety of habitats, including human skin, where many strains are commensals that may be clinically significant or contaminants of food. To determine the physiological characteristics of resistant strain ofStaphylococcus aureusagainst pediocin, a class IIa bacteriocin, a resistant strain was compared with wild type in order to investigate the contribution of hydrophobicity to this resistance. Additional clumping of resistant strain relative to wild type in light microscopy was considered as an elementary evidence of resistance attainment. A delay in log phase attainment was observed in resistant strain compared to the wild type strain. A significant increase in cell surface hydrophobicity was detected for resistant strain in both hexadecane and xylene indicating the contribution of cell surface hydrophobicity as adaptive reaction against antimicrobial agents.
Innervation of Cochlear Hair Cells by Human Induced Pluripotent Stem Cell‐Derived Neurons In Vitro
Authors: Gunewardene Niliksha , Crombie Duncan , Dottori Mirella , Nayagam Bryony A.
Published: February 2016

Induced pluripotent stem cells (iPSCs) may serve as an autologous source of replacement neurons in the injured cochlea, if they can be successfully differentiated and reconnected with residual elements in the damaged auditory system. Here, we explored the potential of hiPSC‐derived neurons to innervate early postnatal hair cells, using established in vitro assays. We compared two hiPSC lines against a well‐characterized hESC line. After ten days’ coculture in vitro, hiPSC‐derived neural processes contacted inner and outer hair cells in whole cochlear explant cultures. Neural processes from hiPSC‐derived neurons also made contact with hair cells in denervated sensory epithelia explants and expressed synapsin at these points of contact. Interestingly, hiPSC‐derived neurons cocultured with hair cells at an early stage of differentiation formed synapses with a higher number of hair cells, compared to hiPSC‐derived neurons cocultured at a later stage of differentiation. Notable differences in the innervation potentials of the hiPSC‐derived neurons were also observed and variations existed between the hiPSC lines in their innervation efficiencies. Collectively, these data illustrate the promise of hiPSCs for auditory neuron replacement and highlight the need to develop methods to mitigate variabilities observed amongst hiPSC lines, in order to achieve reliable clinical improvements for patients.