bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying the Biphasic Role of Calcineurin/NFAT Signaling Enables Replacement of Sox2 in Somatic Cell Reprogramming
Authors: Khodeer Sherif , Era Takumi 
Published: January 2017

Abstract
Induction of pluripotency with defined factors (octamer-binding transcription factor 4 [Oct4], SRY (sex determining region Y)-box 2 [Sox2], Kruppel-like factor 4 [Klf4], c-Myc) raises hopes for successful clinical trials. Despite considerable efforts, the molecular mechanism of reprogramming remains poorly understood. The aim of the present study was to identify the role of calcineurin/nuclear factor of activated T cells (NFAT) in reprogramming. Our results demonstrated a biphasic role for calcineurin/NFAT signaling during reprogramming. In the early phase of reprogramming, calcineurin activity is required to maintain proper cell cycle division and for mesenchymal–epithelial transition. In the late phase, calcineurin exerts a negative effect that is mediated by NFATc2. NFATc2 interacts with Hdac3, Ezh2, and Suv39h1 to increase H3K9me3 and H3K27me3 over the Sox2 enhancer and Klf2 promoter, respectively, resulting in the downregulation of their expression. Moreover, Gαq was identified as a positive upstream regulator for calcineurin. The Gαq/calcineurin/NFATc2 axis negatively regulates the late step of reprogramming. By inhibiting NFATc2 or calcineurin, induced pluripotent stem cells could be established without exogenous Sox2. Thus, the present study revealed another regulatory level of reprogramming, and proposes a biological axis that could be useful for cancer therapy.
Effects of Collagen Crosslink Augmentation on Mechanism of Compressive Load Sharing in Intervertebral Discs
Authors: Hedman Thomas P. , Chen Weng-Pin , Lin Leou-Chyr , Lin Hsiu-Jen , Chuang Shih-Youeng 
Published: January 2017

AbstractExogenous crosslinking has been shown to have potential for treating disc degeneration and back pain due to its ability to increase the strength and toughness of the annulus fibrosus, increase intervertebral joint stability, decrease intradiscal pressure, and increase fluid flow through the disc. Some results imply that crosslink augmentation may also lead to changes in the compressive load sharing properties of the disc. The objective of the present study was to evaluate directional stress distribution changes of the disc following genipin crosslinking treatment. Bovine lumbar motion segments were randomly divided into control and crosslinked groups. Annular strains were determined from simultaneous deformation measurements at various time points during compressive creep testing. Four stress components of the annulus were then calculated according to the previously measured modulus data. Immediately after the application of a 750-N compressive load, mean axial and radial compressive stresses in the crosslinked group were twofold higher than control means. Conversely, mean lamellae-aligned and circumferential tensile stresses of the crosslinked discs were 8- and threefold lower, respectively, compared to control means. After 1-h creep loading, the two compressive mean stresses in both the control and genipin-crosslinked specimens increased approximately threefold from their initial 750-N-loaded values. The two tensile mean stresses in the crosslinked group remained lower than the respective levels of the control means after creep loading. A greater proportion of annular compressive load support under compressive creep loading, with a commensurate decrease in both tensile stresses and strains, was seen in the discs following exogenous crosslink augmentation.
A photo voice perspective on factors contributing to the resilience of HIV positive Yoruba adolescent girls in Nigeria
Authors: Adegoke Catherine O. , Steyn Miemsie G. 
Published: January 2017

ABSTRACTThere is a growing discourse worldwide on the impact of the Human Immunodeficiency Virus (HIV) on “at risk youths”. In response, five HIV‐positive Nigerian adolescent girls were qualitatively investigated in collaboration with a non‐governmental organisation (NGO) in Ibadan, an urban settlement in Nigeria in 2013. Using a secondary data analysis from a photo voice component of the research, combined with narratives, we show that participants possess the capacity to overcome their adversities from the effects of HIV infection and remain resilient. Few studies have used photovoice − a visual participatory approach − and its impact on this group. The theories of Bourdieu, Piaget and Erikson were used as tools to interpret and document, resilience, social capital and coping among participants. Findings reveal participants frame positive goals, use social competence, coping skills, and express personal challenges. These have serious implications for policy makers, researchers and programmer in strengthening adolescents' resilience.
Delayed treatment of 6‐Bromoindirubin‐3′‐oxime stimulates neurogenesis and functional recovery after focal ischemic stroke in mice
Authors: Wang Li‐Li , Li Jimei , Gu Xiaohuan , Wei Ling , Yu Shan Ping 
Published: January 2017

AbstractGlycogen synthase kinase 3β (GSK3β) was originally identified as a regulator for glycogen metabolism and is now an important therapeutic target for a variety of brain disorders including neurodegenerative diseases due to it's pivotal role in cellular metabolism, proliferation and differentiation. In the development of stroke therapies focusing on tissue repair and functional recovery, promoting neurogenesis is a main approach in regenerative medicine. In the present investigation, we explored the effects of a GSK3β specific inhibitor, 6‐Bromoindirubin‐3′‐oxime (BIO), on regenerative activities of neuroblasts in the subventricular zone (SVZ) and functional recovery after focal cerebral ischemia. Adult C57/BL mice were subjected to occlusion of distal branches of middle cerebral artery (MCA) supplying the sensorimotor barrel cortex. Three days later, BIO (8.5 μg/kg, i.p.) was administered every 2 days until sacrificed at 14 or 21 days after stroke. The BIO treatment significantly increased generation of neuroblasts labeled with BrdU and BrdU/doublecortin (DCX) in the SVZ. Comparing to vehicle controls, increased number of neuroblasts migrated to the peri‐infarct region where they differentiate into mature neurons. Along with the elevated BDNF expression at the peri‐infarct area, the number of newly formed neurons was significantly increased. BIO treatment significantly enhanced sensorimotor functional recovery after the focal ischemia. It is suggested that the GSK3 signaling may be a potential therapeutic target for regenerative treatment after ischemic stroke.
Drag reduction of circular cylinders by porous coating on the leeward side
Authors: Klausmann Katharina , Ruck Bodo 
Published: January 2017

The present paper describes the effect of drag reduction of circular cylinders due to a porous coating on their leeward sides. To investigate the coating effect, experiments were conducted in a wind tunnel of Goettingen type. Systematic drag measurements were carried out for different cylinder configurations and flow velocities. The drag measurements were complemented by pressure and particle image velocimetry (PIV) flow field measurements around selected cylinders. The Reynolds numbers were varied in the subcritical range of$3\times 10^{4}<Re<1.4\times 10^{5}$. The results show that a thin porous layer on the leeward side, either incorporated in the cylinder shape or applied on the cylinder surface, leads to an increase of base pressure on the leeward side of the cylinder. It causes a reduction of drag and dampens oscillation amplitudes when compared to a cylinder without coating. Results obtained for different configurations with varying key parameters (coating angles, layer thicknesses and pore sizes of the porous material) clearly indicate the drag-reducing and amplitude-damping potential of leeward coating. The amount of drag reduction and amplitude damping depends on the combination of key parameters. It was demonstrated that the lowered drag coefficients$c_{d}$were almost constant in the tested range of Reynolds numbers. A maximum reduction of drag of 13.2 % was measured. In addition, the results revealed a strong reduction of the pressure fluctuations around cylinders with a leeward coating due to the shift of the vortex region further downstream.
Spatially distributed runoff at the grounding line of a large Greenlandic tidewater glacier inferred from plume modelling
Authors: SLATER DONALD , NIENOW PETER , SOLE ANDREW , COWTON TOM , MOTTRAM RUTH , LANGEN PETER , MAIR DOUGLAS 
Published: January 2017

ABSTRACTUnderstanding the drivers of recent change at Greenlandic tidewater glaciers is of great importance if we are to predict how these glaciers will respond to climatic warming. A poorly constrained component of tidewater glacier processes is the near-terminus subglacial hydrology. Here we present a novel method for constraining near-terminus subglacial hydrology with application to marine-terminating Kangiata Nunata Sermia in South-west Greenland. By simulating proglacial plume dynamics using buoyant plume theory and a general circulation model, we assess the critical subglacial discharge, if delivered through a single compact channel, required to generate a plume that reaches the fjord surface. We then compare catchment runoff to a time series of plume visibility acquired from a time-lapse camera. We identify extended periods throughout the 2009 melt season where catchment runoff significantly exceeds the discharge required for a plume to reach the fjord surface, yet we observe no plume. We attribute these observations to spatial spreading of runoff across the grounding line. Persistent distributed drainage near the terminus would lead to more spatially homogeneous submarine melting and may promote more rapid basal sliding during warmer summers, potentially providing a mechanism independent of ocean forcing for increases in atmospheric temperature to drive tidewater glacier acceleration.
The acquisition of tense morphology over time by English second language children with specific language impairment: Testing the cumulative effects hypothesis
Authors: PARADIS JOHANNE , JIA RUITING , ARPPE ANTTI 
Published: January 2017

ABSTRACTThe cumulative effects hypothesis (CEH) claims that bilingual development would be a challenge for children with specific language impairment (SLI). To date, research on second language (L2) children with SLI has been limited mainly to their early years of L2 exposure; however, examining the long-term outcomes of L2 children with SLI is essential for testing the CEH. Accordingly, the present study examined production and grammaticality judgments of English tense morphology from matched groups of L2 children with SLI and L2 children with typical development (TD) for 3 years, from ages 8 to 10 with 4–6 years of exposure to English. This study found that the longitudinal acquisition profile of the L2 children with SLI and TD was similar to the acquisition profile reported for monolinguals with SLI and TD. Furthermore, L2-SLI children's accuracy with tense morphology was similar to that of their monolingual age peers with SLI at the end of the study, and exceeded that of younger monolingual peers with SLI whose age matched the L2 children's length of exposure to English. These findings are not consistent with the CEH, but instead show that morphological acquisition parallel to monolinguals with SLI is possible for L2 children with SLI.
Political support for reforms of the pension system: two experiments
Authors: GOUVEIA ANA FONTOURA 
Published: January 2017

AbstractWe conduct two randomized control trials designed to understand the role of information and priming on the willingness to retrench the pension system. The first entails a survey to a sample of Portuguese voters, who are randomly presented with a text providing factual information about the public pension system. The second surveys a sample of Portuguese University students, randomly presented with an alternative order of questions. We show that more literacy on the pension system has a positive impact on the individual willingness to support reforms. Given that public opinion is usually seen as an important deterrent of effective action by politicians and that the level of voters’ literacy can be influenced by policy action, this analysis may provide useful insights to policy makers faced with the challenge of reforming existent pension systems. Our analysis also suggests that priming effects should not be ignored, given their impact in individuals in the extremes of the political spectrum.
A systematic review of religious beliefs about major end-of-life issues in the five major world religions
Authors: Chakraborty Rajshekhar , El-Jawahri Areej R. , Litzow Mark R. , Syrjala Karen L , Parnes Aric D. , Hashmi Shahrukh K. 
Published: January 2017

ABSTRACTObjective:The objective of this study was to examine the religious/spiritual beliefs of followers of the five major world religions about frequently encountered medical situations at the end of life (EoL).Method:This was a systematic review of observational studies on the religious aspects of commonly encountered EoL situations. The databases used for retrieving studies were: Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid PsycINFO, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus. Observational studies, including surveys from healthcare providers or the general population, and case studies were included for review. Articles written from a purely theoretical or philosophical perspective were excluded.Results:Our search strategy generated 968 references, 40 of which were included for review, while 5 studies were added from reference lists. Whenever possible, we organized the results into five categories that would be clinically meaningful for palliative care practices at the EoL: advanced directives, euthanasia and physician-assisted suicide, physical requirements (artificial nutrition, hydration, and pain management), autopsy practices, and other EoL religious considerations. A wide degree of heterogeneity was observed within religions, depending on the country of origin, level of education, and degree of intrinsic religiosity.Significance of results:Our review describes the religious practices pertaining to major EoL issues and explains the variations in EoL decision making by clinicians and patients based on their religious teachings and beliefs. Prospective studies with validated tools for religiosity should be performed in the future to assess the impact of religion on EoL care.
Efficacy of an Intervention Program to Improve Employability of University Students
Authors: Hernández-Fernaud Estefanía , Ruiz-de la Rosa Carmen Inés , Negrín Fátima , Ramos-Sapena Yeray , Hernández Bernardo 
Published: January 2017

AbstractIn the current socioeconomic situation, the need to improve employability of potential workers is especially relevant. The aim of this study was to evaluate the efficacy of an intervention program focusing on improving employability of university students. To do this, a two-group study was designed: one group undertook the intervention program and the other group were used for comparison. Two measurements were taken at different times (pre-intervention and post-intervention). The sample consisted of 271 university students. The results show that the group that underwent the intervention program improved their perceived employability F(1, 269) = 17.49, p < .001; η2 = .06, openness to learning F(1, 269) = 4.24, p < .05; η2 = .02, self-efficacy for labor market insertion F(1, 269) = 75.70, p < .001; η2 = .22 and for teamwork F(1, 269) = 39.43, p < .001; η2 = .13, and their knowledge of employment resources F(1, 269) = 512.89, p < .001; η2 = .66 compared to the group that did not. Furthermore, there was a high level of satisfaction of participants with the intervention program.
Berberine-sonodynamic therapy induces autophagy and lipid unloading in macrophage
Authors: Kou Jiayuan Y , Li Ying , Zhong Zhaoyu Y , Jiang Yueqing Q , Li Xuesong S , Han Xiaobo B , Liu Zhongni N , Tian Ye , Yang Liming M 
Published: January 2017

AbstractImpaired autophagy in macrophages accompanies the progression of atherosclerosis and contributes to lipid loading in plaques and ineffective lipid degradation. Therefore, evoking autophagy and its associated cholesterol efflux may provide a therapeutic treatment for atherosclerosis. In the present study, berberine-mediated sonodynamic therapy (BBR-SDT) was used to induce autophagy and cholesterol efflux in THP-1 macrophages and derived foam cells. Following BBR-SDT, autophagy was increased in the macrophages, autophagy resistance in the foam cells was prevented, and cholesterol efflux was induced. The first two effects were blocked by the reactive oxygen species scavenger, N-acetyl cysteine. BBR-SDT also reduced the phosphorylation of Akt and mTOR, two key molecules in the PI3K/AKT/mTOR signaling pathway, which is responsible for inducing autophagy. Correspondingly, treatment with the autophagy inhibitor, 3-methyladenine, or the PI3K inhibitor, LY294002, abolished the autophagy-induced effects of BBR-SDT. Furthermore, induction of cholesterol efflux by BBR-SDT was reversed by an inhibition of autophagy by 3-methyladenine or by a small interfering RNA targeting Atg5. Taken together, these results demonstrate that BBR-SDT effectively promotes cholesterol efflux by increasing reactive oxygen species generation, and this subsequently induces autophagy via the PI3K/AKT/mTOR signaling pathway in both ‘normal’ macrophages and lipid-loaded macrophages (foam cells). Thus, BBR-SDT may be a promising atheroprotective therapy to inhibit the progression of atherosclerosis and should be further studied.
Cellular prion protein mediates early apoptotic proteome alternation and phospho-modification in human neuroblastoma cells
Authors: Zafar Saima , Behrens Christina , Dihazi Hassan , Schmitz Matthias , Zerr Inga , Schulz-Schaeffer Walter J , Ramljak Sanja , Asif Abdul R 
Published: January 2017

AbstractAnti-apoptotic properties of physiological and elevated levels of the cellular prion protein (PrPc) under stress conditions are well documented. Yet, detrimental effects of elevated PrPc levels under stress conditions, such as exposure to staurosporine (STS) have also been described. In the present study, we focused on discerning early apoptotic STS-induced proteome and phospho-proteome changes in SH-SY5Y human neuroblastoma cells stably transfected either with an empty or PRNP-containing vector, expressing physiological or supraphysiological levels of PrPc, respectively. PrPc-overexpression per se appears to stress the cells under STS-free conditions as indicated by diminished cell viability of PrPc-overexpressing versus control cells. However, PrPc-overexpression becomes advantageous following exposure to STS. Thus, only a short exposure (2 h) to 1 μM STS results in lower survival rates and significantly higher caspase-3 activity in control versus PrPc-overexpressing cells. Hence, by exposing both experimental groups to the same apoptotic conditions we were able to induce apoptosis in control, but not in PrPc-overexpressing cells (as assessed by caspase-3 activity), which allowed for filtering out proteins possibly contributing to protection against STS-induced apoptosis in PrPc-overexpressing cells. Among other proteins regulated by different PrPc levels following exposure to STS, those involved in maintenance of cytoskeleton integrity caught our attention. In particular, the finding that elevated PrPc levels significantly reduce profilin-1 (PFN-1) expression. PFN-1 is known to facilitate STS-induced apoptosis. Silencing of PFN-1 expression by siRNA significantly increased viability of PrPc-overexpressing versus control cells, under STS treatment. In addition, PrPc-overexpressing cells depleted of PFN-1 exhibited increased viability versus PrPc-overexpressing cells with preserved PFN-1 expression, both subjected to STS. Concomitant increase in caspase-3 activity was observed in control versus PrPc-overexpressing cells after treatment with siRNA- PFN-1 and STS. We suggest that reduction of PFN-1 expression by elevated levels of PrPc may contribute to protective effects PrPc-overexpressing SH-SY5Y cells confer against STS-induced apoptosis.
Foot-and-mouth disease virus infection suppresses autophagy and NF-кB antiviral responses via degradation of ATG5-ATG12 by 3Cpro
Authors: Fan Xuxu , Han Shichong , Yan Dan , Gao Yuan , Wei Yanquan , Liu Xiangtao , Liao Ying , Guo Huichen , Sun Shiqi 
Published: January 2017

AbstractAutophagy-related protein ATG5-ATG12 is an essential complex for the autophagophore elongation in autophagy, which has been reported to be involved in foot-and-mouth disease virus (FMDV) replication. Previous reports show that ATG5-ATG12 positively or negatively regulates type I interferon (IFN-α/β) pathway during virus infection. In this study, we found that FMDV infection rapidly induced LC3 lipidation and GFP-LC3 subcellular redistribution at the early infection stage in PK-15 cells. Along with infection time course to 2–5 h.p.i., the levels of LC3II and ATG5-ATG12 were gradually reduced. Further study showed that ATG5-ATG12 was degraded by viral protein 3Cpro, demonstrating that FMDV suppresses autophagy along with viral protein production. Depletion of ATG5-ATG12 by siRNA knock down significantly increased the FMDV yields, whereas overexpression of ATG5-ATG12 had the opposite effects, suggesting that degradation of ATG5-ATG12 benefits virus growth. Further experiment showed that overexpression of ATG5-ATG12 positively regulated NF-кB pathway during FMDV infection, marked with promotion of IKKα/β phosphorylation and IκBα degradation, inhibition of p65 degradation, and facilitation of p65 nuclear translocation. Meanwhile, ATG5-ATG12 also promoted the phosphorylation of TBK1 and activation of IRF3 via preventing TRAF3 degradation. The positive regulation of NF-кB and IRF3 pathway by ATG5-ATG12 resulted in enhanced expression of IFN-β, chemokines/cytokines, and IFN stimulated genes, including anti-viral protein PKR. Altogether, above findings suggest that ATG5-ATG12 positively regulate anti-viral NF-κB and IRF3 signaling during FMDV infection, thereby limiting FMDV proliferation. FMDV has evolved mechanisms to counteract the antiviral function of ATG5-ATG12, via degradation of them by viral protein 3Cpro.