bluuebunny/crossref_metadata_2025_split huggingface dataset:
4‐Hydroxynonenal‐induced GPR109A (HCA2 receptor) activation elicits bipolar responses, Gαi‐mediated anti‐inflammatory effects and Gβγ‐mediated cell death
Authors: Gautam Jaya , Banskota Suhrid , Shah Sajita , Jee Jun‐Goo , Kwon Eunju , Wang Ying , Kim Dong Young , Chang Hyun Wook , Kim Jung‐Ae 
Published: February 2018

Background and PurposeIn this study, we examined the possibility that 4‐hydroxynonenal (4‐HNE) acting as a ligand for the HCA2 receptor (GPR109A) elicits both anti‐inflammatory and cell death responses.Experimental ApproachAgonistic activity of 4‐HNE was determined by observing the inhibition of cAMP generation in CHO‐K1‐GPR109A‐Gi cell line, using surface plasmon resonance (SPR) binding and competition binding assays with [3H]‐niacin. 4‐HNE‐mediated signalling pathways and cellular responses were investigated in cells expressing GPR109A and those not expressing these receptors.Key ResultsAgonistic activity of 4‐HNE was stronger than that of niacin or 3‐OHBA at inhibiting forskolin‐induced cAMP production and SPR binding affinity. In ARPE‐19 and CCD‐841 cells, activation of GPR109A by high concentrations of the agonists 4‐HNE (≥10 μM), niacin (≥1000 μM) and 3‐OHBA (≥1000 μM) induced apoptosis accompanied by elevated Ca2+ and superoxide levels. This 4‐HNE‐induced cell death was blocked by knockdown of GPR109A or NOX4 genes, or treatment with chemical inhibitors of Gβγ (gallein), intracellular Ca2+ (BAPTA‐AM), NOX4 (VAS2870) and JNK (SP600125), but not by the cAMP analogue 8‐CPT‐cAMP. By contrast, low concentrations of 4‐HNE, niacin and 3‐OHBA down‐regulated the expression of pro‐inflammatory cytokines IL‐6 and IL‐8. These 4‐HNE‐induced inhibitory effects were blocked by a cAMP analogue but not by inhibitors of Gβγ‐downstream signalling molecules.Conclusions and ImplicationsThese results revealed that 4‐HNE is a strong agonist for GPR109A that induces Gαi‐dependent anti‐inflammatory and Gβγ‐dependent cell death responses. Moreover, the findings indicate that specific intracellular signalling molecules, but not GPR109A, can serve as therapeutic targets to block 4‐HNE‐induced cell death.
Heterogeneity in the dynamic effects of uncertainty on investment
Authors: Byun Sung Je , Jo Soojin 
Published: February 2018

AbstractWe examine how aggregate profit uncertainty influences capital investment activities, focusing on heterogeneous responses of firms. We model aggregate profit uncertainty as the conditional standard deviation of a common factor across unforecasted fluctuations in the sales growth of different industries and exploit cross‐sectional variations for its estimation. From an investment forecasting model that coherently analyzes firm‐ or group‐specific effects of uncertainty, we find that the direction and the size of investment adjustment vary considerably across firms, with a significant but small negative average impact. Our results highlight the importance of accounting for heterogeneity in the transmission of uncertainty, allowing us to reconcile different views on the effect of uncertainty in the existing literature.
Do peers affect childhood obesity outcomes? Peer‐effect analysis in public schools
Authors: Asirvatham Jebaraj , Thomsen Michael R. , Nayga Rodolfo M. , Rouse Heather L. 
Published: February 2018

AbstractThis study investigates whether obese peers are a contributing factor in childhood body‐weight outcomes. Using an instrumental variables method on exogenously assigned peers (i.e., new peers), we find that the weight of peers within the same grade and school significantly impacts body mass index (BMI) z‐score of an individual student. The size of the peer effect, however, is negligible. We find no evidence of interaction between newly assigned peer groups prior to assignment. Furthermore, the obese peers variable is significant only for those peers with whom a student interacts.
Bis‐2(5H)‐furanone derivatives as new anticancer agents: Design, synthesis, biological evaluation, and mechanism studies
Authors: Wu Yan‐Cheng , Cao Liang , Mei Wen‐Jie , Wu Han‐Qing , Luo Shi‐He , Zhan Hai‐Ying , Wang Zhao‐Yang 
Published: February 2018

New bis‐2(5H)‐furanone derivatives containing a benzidine core were synthesized via a one‐step transition‐metal‐free reaction of benzidine with 5‐substituted 3,4‐dihalo‐2(5H)‐furanones. Their antitumor activities against various tumor cells have been evaluated by MTT assay. Among them, compound 4e exhibits significant inhibitory activity against C6 glioma cells with an IC50 value of 12.1 μm and low toxicity toward HaCaT human normal cells. Studies on the antitumor mechanism reveal that cell cycle arrest at S‐phase in C6 cells is induced by compound 4e. Furthermore, investigations with electronic, fluorescence emission and circular dichroism spectra show that compound 4e can significantly interact with C6‐DNA. These data indicate that DNA may be one of the potential targets for bis‐2(5H)‐furanone derivatives as anticancer drugs.
Discovery of thiophene‐containing biaryl amide derivatives as novel glucagon receptor antagonists
Authors: Li Jia , Feng Yang , Li Huihui , Shu Shuangjie , Dai Antao , Cai Xiaoqing , Wang Jiang , Yang Dehua , Ma Dakota , Wang Ming‐Wei , Liu Hong 
Published: February 2018

A novel series of thiophene‐containing biaryl amide glucagon receptor (GCGR) antagonists were designed and synthesized. Two compounds of this series, 14f and 14h, exhibited good GCGR binding (IC50 = 6.1 and 4.4 μm, respectively) and cAMP functional activities (IC50 = 4.4 and 14.4 μm, respectively). The possible binding modes of compounds 14f and 14h with GCGR were explored by molecular simulation.
Neuroimaging genomic studies in major depressive disorder: A systematic review
Authors: Zhang Hui‐Feng , Mellor David , Peng Dai‐Hui 
Published: February 2018

SummaryGenetic‐neuroimaging studies could identify new potential endophenotypes of major depressive disorder (MDD). Morphological and functional alterations may be attributable to genetic factors that regulate neurogenesis and neurodegeneration. Given that the association between gene polymorphisms and brain morphology or function has varied across studies, this systematic review aims at evaluating and summarizing all available genetic‐neuroimaging studies. Twenty‐eight gene variants were evaluated in 64 studies by structural or functional magnetic resonance imaging. Significant genetic‐neuroimaging associations were found in monoaminergic genes, BDNF genes, glutamatergic genes, HPA axis genes, and the other common genes, which were consistent with common hypotheses of the pathogenesis of MDD.
The perpetual state of emergency that sacrifices protected areas in a changing climate
Authors: Twidwell Dirac , Wonkka Carissa L. , Bielski Christine H. , Allen Craig R. , Angeler David G. , Drozda Jacob , Garmestani Ahjond S. , Johnson Julia , Powell Larkin A. , Roberts Caleb P. 
Published: February 2018

AbstractA modern challenge for conservation biology is to assess the consequences of policies that adhere to assumptions of stationarity (e.g., historic norms) in an era of global environmental change. Such policies may result in unexpected and surprising levels of mitigation given future climate‐change trajectories, especially as agriculture looks to protected areas to buffer against production losses during periods of environmental extremes. We assessed the potential impact of climate‐change scenarios on the rates at which grasslands enrolled in the Conservation Reserve Program (CRP) are authorized for emergency harvesting (i.e., biomass removal) for agricultural use, which can occur when precipitation for the previous 4 months is below 40% of the normal or historical mean precipitation for that 4‐month period. We developed and analyzed scenarios under the condition that policy will continue to operate under assumptions of stationarity, thereby authorizing emergency biomass harvesting solely as a function of precipitation departure from historic norms. Model projections showed the historical likelihood of authorizing emergency biomass harvesting in any given year in the northern Great Plains was 33.28% based on long‐term weather records. Emergency biomass harvesting became the norm (>50% of years) in the scenario that reflected continued increases in emissions and a decrease in growing‐season precipitation, and areas in the Great Plains with higher historical mean annual rainfall were disproportionately affected and were subject to a greater increase in emergency biomass removal. Emergency biomass harvesting decreased only in the scenario with rapid reductions in emissions. Our scenario‐impact analysis indicated that biomass from lands enrolled in the CRP would be used primarily as a buffer for agriculture in an era of climatic change unless policy guidelines are adapted or climate‐change projections significantly depart from the current consensus.
Chronic pain prevalence and associated factors in adolescents with and without physical disabilities
Authors: de la Vega Rocío , Groenewald Cornelius , Bromberg Maggie H , Beals‐Erickson Sarah E , Palermo Tonya M 
Published: February 2018

AimAdolescents with physical disabilities may have co‐occurring chronic pain, but the prevalence and specific associated factors are unknown. The aims of this study were to determine (1) the prevalence of chronic pain in adolescents with physical disabilities and (2) whether known correlates of chronic pain in the general population are also present in young people both with physical disability and with chronic pain relative to peers.MethodWe conducted a secondary analysis of cross‐sectional nationally representative data from the National Longitudinal Study of Adolescent to Adult Health. Multivariate linear regression analysis was used to identify demographic and psychosocial factors associated with chronic pain.ResultsA total of 989 (4.3%) adolescents reported physical disabilities. They had a significantly higher rate of pain (27.2%) compared with able‐bodied peers (15.6%, χ2=86.3550, p<0.001). There was no significant interaction between physical disability status and chronic pain in relation to depressive symptoms, anxiety, or insomnia.InterpretationAdolescents with physical disabilities experience chronic pain at a significantly higher rate than able‐bodied peers, but the comorbidity of physical disability and chronic pain is not related to depression, anxiety, or insomnia. Evaluation of chronic pain and tailored pain interventions need to be developed for this population.What this paper adds

Chronic pain and its correlates are important problems for adolescents with physical disabilities.

These adolescents present with higher rates of chronic pain than other young people.

Chronic pain is associated with increased levels of depressive symptoms, anxiety, and insomnia regardless of disability status.
Morphological and molecular characterization of Leptomelanconium allescheri associated with necrotic lesions on Pinus mugo needles in the Polish Tatra Mountains
Authors: Kowalski T. , Boroń P. , Bartnik C. , Rossa R. 
Published: February 2018

SummaryLeptomelanconium allescheri was identified for the first time in Poland in 2016 in the Tatra Mts. on Pinus mugo needles. It produced numerous conidiomata on necrotic lesions on live needles. In our study, we provide detailed characteristics of disease symptoms and describe morphology of the structures of the fungus. The shape and size of macroconidia are proven to be more variable in vitro than in situ. The malt extract agar colonies of the fungus obtained from germinating macroconidia are described for the first time. Our observations prove also that, apart from macroconidia, L. allescheri produces in vitro unicellular, hyaline microconidia, 3.5–10 × 1.8–5.0 μm in size, the previously unknown aspect in the development cycle of this species. The BLAST search with ITS and LSU sequences of L. allescheri resulted in the closest match with Cenangium acuum accessions (94%–95% and 99%, respectively). Two gene based, LSU plus ITS, phylogenetic positioning of L. allescheri proves that it belongs to Pezizomycotina, Helotiales. Further, on family level, placement of L. allescheri, as well as its two closest species C. acuum and Piceomphale bulgarioides, remains undefined. The L. allescheri barcode sequences (accession numbers: ITS—MF573935, LSU—MF573936, IGS—MF573937) and cultures were submitted to NCBI GenBank and CBS Utrecht, The Netherlands culture collection.
How do phenology, plasticity, and evolution determine the fitness consequences of climate change for montane butterflies?
Authors: Kingsolver Joel G. , Buckley Lauren B. 
Published: February 2018

AbstractSpecies have responded to climate change via seasonal (phenological) shifts, morphological plasticity, and evolutionary adaptation, but how these responses contribute to changes and variation in population fitness are poorly understood. We assess the interactions and relative importance of these responses for fitness in a montane butterfly, Colias eriphyle, along an elevational gradient. Because environmental temperatures affect developmental rates of each life stage, populations along the gradients differ in phenological timing and the number of generations each year. Our focal phenotype, wing solar absorptivity of adult butterflies, exhibits local adaptation across elevation and responds plastically to developmental temperatures. We integrate climatic data for the past half‐century with microclimate, developmental, biophysical, demographic, and evolutionary models for this system to predict how phenology, plasticity, and evolution contribute to phenotypic and fitness variation along the gradient. We predict that phenological advancements incompletely compensate for climate warming, and also influence morphological plasticity. Climate change is predicted to increase mean population fitness in the first seasonal generation at high elevation, but decrease mean fitness in the summer generations at low elevation. Phenological shifts reduce the interannual variation in directional selection and morphology, but do not have consistent effects on variation in mean fitness. Morphological plasticity and its evolution can substantially increase population fitness and adaptation to climate change at low elevations, but environmental unpredictability limits adaptive plastic and evolutionary responses at high elevations. Phenological shifts also decrease the relative fitness advantages of morphological plasticity and evolution. Our results illustrate how the potential contributions of phenological and morphological plasticity and of evolution to climate change adaptation can vary along environmental gradients and how environmental variability will limit adaptive responses to climate change in montane regions.
Extracellular bone morphogenetic protein modulator BMPER and twisted gastrulation homolog 1 preserve arterial‐venous specification in zebrafish blood vessel development and regulate Notch signaling in endothelial cells
Authors: Esser Jennifer Susanne , Steiner Rahel Elisabeth , Deckler Meike , Schmitt Hannah , Engert Bianca , Link Sandra , Charlet Anne , Patterson Cam , Bode Christoph , Zhou Qian , Moser Martin 
Published: February 2018

The bone morphogenetic protein (BMP) signaling pathway plays a central role during vasculature development. Mutations or dysregulation of the BMP pathway members have been linked to arteriovenous malformations. In the present study, we investigated the effect of the BMP modulators bone morphogenetic protein endothelial precursor‐derived regulator (BMPER) and twisted gastrulation protein homolog 1 (TWSG1) on arteriovenous specification during zebrafish development and analyzed downstream Notch signaling pathway in human endothelial cells. Silencing of bmper and twsg1b in zebrafish embryos by morpholinos resulted in a pronounced enhancement of venous ephrinB4a marker expression and concomitant dysregulated arterial ephrinb2a marker expression detected by in situ hybridization. As arteriovenous specification was disturbed, we assessed the impact of BMPER and TWSG1 protein stimulation on the Notch signaling pathway on endothelial cells from different origin. Quantitative real‐time PCR (qRT‐PCR) and western blot analysis showed increased expression of Notch target gene hairy and enhancer of split, HEY1/2 and EPHRINB2. Consistently, silencing of BMPER in endothelial cells by siRNAs decreased Notch signaling and downstream effectors. BMP receptor antagonist DMH1 abolished BMPER and BMP4 induced Notch signaling pathway activation. In conclusion, we found that in endothelial cells, BMPER and TWSG1 are necessary for regular Notch signaling activity and in zebrafish embryos BMPER and TWSG1 preserve arteriovenous specification to prevent malformations.
MicroRNA‐134 inhibits osteosarcoma angiogenesis and proliferation by targeting the VEGFA/VEGFR1 pathway
Authors: Zhang Long , Lv Zhi , Xu Jing , Chen Chenglong , Ge Qiaofeng , Li Pengcui , Wei Dinglu , Wu Zhuangzhuang , Sun Xiaojuan 
Published: February 2018

Vascular endothelial growth factor (VEGF) A and vascular endothelial growth factor receptor 1 (VEGFR1) signaling is crucial for angiogenesis and progression of osteosarcoma (OS). However, the regulation of the VEGF/VEGFR1 expression is still unclear in OS. Here, we show lower levels of miRNA‐134 (miR‐134) in OS tissues and cells. Induction of miR‐134 overexpression significantly reduced the proliferation of Saos‐2 cells and their secretion of pro‐angiogenic factors, but increased the frequency of apoptotic Saos‐2 cells. Treatment with conditioned medium from the cells transfected with miR‐134 reduced the tube formation in human umbilical vein endothelial cells, which was abrogated by a combination of VEGF and conditioned medium. Furthermore, miR‐134 significantly inhibited the growth of implanted OS tumors in vivo and attenuated the VEGFA and VEGFR1 expression and angiogenesis in the tumors. In addition, higher levels of VEGFA and VEGFR1 were detected and miR‐134 inhibited the expression of VEGFA and VEGFR1 in Saos‐2 cells and OS tumors. Bioinformatic analysis indicated that the 3′‐UTR of VEGFA and VEGFR1 contained the motif for miR‐134 binding. Co‐transfection with the luciferase reporter containing the wild‐type, but not the mutant, of the 3′‐UTR of VEGFA or VEGFR1 together with miR‐134 decreased the luciferase activity in Saos‐2 cells. Finally, miR‐134 dramatically inhibited AKT activation and proliferating cell nuclear antigen expression in Saos‐2 cells. Collectively, these findings indicate that miR‐134 is a potential tumor suppressor by targeting VEGFA/VEGFR1 signaling to attenuate the progression and angiogenesis in OS. Therefore, miR‐134 may be a novel biomarker for the prognosis of OS and a target for the design of new therapies for OS.
Rethinking relational ideas of place in more‐than‐human cities
Authors: Robertson Sarah A. 
Published: February 2018

AbstractIn theory and practice, there remains much hope that through greater human–place connections, more ecologically sustainable cities can be achieved. Yet ideas about place remain fluid, at once appealing and ambivalent. Since the 1970s, emphasis has shifted from bounded views of place to relational and progressive conceptualisations. More recently, geographers and other scholars have emphasised that humans are engaged in complex human–nonhuman entanglements. In the context of arguments and empirical moves to make more sustainable and resilient cities, these shifts have implications for the ethics and politics of place, sense of place, and place‐based practices. Continuing empirical work by geographers (and other urban scholars) to explore how place is understood, made, and experienced in more‐than‐human worlds therefore remains important. However, we also need to consider reframing existing conceptualisations of “place.” This paper reviews shifting ideas of place and reiterates the continuing importance of rethinking place and place experience in urban theory, urban dwelling, and design. The paper draws together insights from post‐phenomenology, more‐than‐human thinking, non‐representational theory, urban political ecology, and environmental justice to form a loose theoretical framework that can inform place scholarship. In particular, this framework focuses attention on the ethics and politics of the material, temporal, and discursive particularities of the socioecological entanglements that are understood to make place experience.
Effect of pearl millet silage ammoniated with urea on lamb production and metabolic performance
Authors: Carvalho G. G. P. , Freitas P. M. D. , Santos E. M. , Araújo G. G. L. , Oliveira J. S. , Pires A. J. V. , Maranhão C. M. A. , Rodrigues T. C. G. C. , Freitas Júnior J. E. , Rufino L. M. A. , Rodrigues C. S. , Leite L. C. , Araujo M. L. G. M. L. 
Published: February 2018

AbstractThe objective of this study was to determine the effect of diets containing pearl millet silage ammoniated with urea on the intake, digestibility, production performance, and nitrogen metabolism of lambs. Thirty‐two uncastrated mixed‐breed lambs at 4 to 5 months of age, with an average initial body weight of 17.39 ± 2.16 kg, were distributed into four treatments in a randomized block experimental design with eight replicates. Experimental diets consisted of pearl millet silage ammoniated with urea during ensiling at the levels of 0, 20, 40, and 60 g/kg dry matter (DM). Increasing urea levels in the pearl millet silage led to a linear decrease (p < .05) in the intakes of DM, organic matter, and total digestible nutrients by the lambs. Total and average daily weight gains decreased linearly (p < .05) with the addition of urea to the silage. Intake and digestibility of crude protein, nitrogen intake, urine urea nitrogen, plasma urea nitrogen, microbial synthesis, and microbial efficiency had a quadratic response (p < .05) to the urea levels in the silage. Pearl millet silage ammoniated with urea reduces dry‐matter intake and daily weight gain in lambs. Urea is not recommended for use in the ensiling of pearl millet.
Entering Aladdin's cave: Developing an app for children with Down syndrome
Authors: Porter J. 
Published: February 2018

AbstractTablets have much to offer children with learning difficulties, but evidence of their effectiveness to teach academic skills is limited and cannot be easily separated from the quality of the software. This paper analyses data from 3 iterative cycles of designing an app for children with Down syndrome to support their awareness of quantity through an inclusive game. Research with neurotypical children suggests that representation of quantity (or magnitude) is an area with considerable potential in supporting the foundations for children's mathematical learning. It has received little attention as an aspect for intervention for children with Down syndrome. Data collected in this study illustrate the need to carefully align the game mechanic to the target skills, strengthen levels of access, and introduce gradations of attentional demand. They also signal the interrelationship between children's cognitive and affective responses to the game, making it essential to find the optimal level of challenge. Children's strategies in response to mistakes indicate the importance of creating an agile responsive system. The data also suggest that developers routinely extend the number of features that are optional, enabling a greater level of personalization and a more inclusive game.