bluuebunny/crossref_metadata_2025_split huggingface dataset:
The obesity-induced transcriptional regulator TRIP-Br2 mediates visceral fat endoplasmic reticulum stress-induced inflammation
Authors: Qiang Guifen , Kong Hyerim Whang , Fang Difeng , McCann Maximilian , Yang Xiuying , Du Guanhua , Blüher Matthias , Zhu Jinfang , Liew Chong Wee 
Published: April 2016

AbstractThe intimate link between location of fat accumulation and metabolic disease risk and depot-specific differences is well established, but how these differences between depots are regulated at the molecular level remains largely unclear. Here we show that TRIP-Br2 mediates endoplasmic reticulum (ER) stress-induced inflammatory responses in visceral fat. Using in vitro, ex vivo and in vivo approaches, we demonstrate that obesity-induced circulating factors upregulate TRIP-Br2 specifically in visceral fat via the ER stress pathway. We find that ablation of TRIP-Br2 ameliorates both chemical and physiological ER stress-induced inflammatory and acute phase response in adipocytes, leading to lower circulating levels of inflammatory cytokines. Using promoter assays, as well as molecular and pharmacological experiments, we show that the transcription factor GATA3 is responsible for the ER stress-induced TRIP-Br2 expression in visceral fat. Taken together, our study identifies molecular regulators of inflammatory response in visceral fat that—given that these pathways are conserved in humans—might serve as potential therapeutic targets in obesity.
Retroviral intasomes search for a target DNA by 1D diffusion which rarely results in integration
Authors: Jones Nathan D. , Lopez Jr Miguel A. , Hanne Jeungphill , Peake Mitchell B. , Lee Jong-Bong , Fishel Richard , Yoder Kristine E. 
Published: April 2016

AbstractRetroviruses must integrate their linear viral cDNA into the host genome for a productive infection. Integration is catalysed by the retrovirus-encoded integrase (IN), which forms a tetramer or octamer complex with the viral cDNA long terminal repeat (LTR) ends termed an intasome. IN removes two 3′-nucleotides from both LTR ends and catalyses strand transfer of the recessed 3′-hydroxyls into the target DNA separated by 4–6 bp. Host DNA repair restores the resulting 5′-Flap and single-stranded DNA (ssDNA) gap. Here we have used multiple single molecule imaging tools to determine that the prototype foamy virus (PFV) retroviral intasome searches for an integration site by one-dimensional (1D) rotation-coupled diffusion along DNA. Once a target site is identified, the time between PFV strand transfer events is 470 ms. The majority of PFV intasome search events were non-productive. These observations identify new dynamic IN functions and suggest that target site-selection limits retroviral integration.
Single-cell RNA-seq reveals cell type-specific transcriptional signatures at the maternal–foetal interface during pregnancy
Authors: Nelson Andrew C. , Mould Arne W. , Bikoff Elizabeth K. , Robertson Elizabeth J. 
Published: April 2016

AbstractGrowth and survival of the mammalian embryo within the uterine environment depends on the placenta, a highly complex vascularized organ comprised of both maternal and foetal tissues. Recent experiments demonstrate that the zinc finger transcriptional repressor Prdm1/Blimp1 is essential for specification of spiral artery trophoblast giant cells (SpA-TGCs) that invade and remodel maternal blood vessels. To learn more about functional contributions made by Blimp1+ cell lineages here we perform the first single-cell RNA-seq analysis of the placenta. Cell types of both foetal and maternal origin are profiled. Comparisons with microarray datasets from mutant placenta and in vitro differentiated trophoblast stem cells allow us to identify Blimp1-dependent transcripts enriched in SpA-TGCs. Our experiments provide new insights into the functionally distinct cell types present at the maternal–foetal interface and advance our knowledge of dynamic gene expression patterns controlling placental morphogenesis and vascular mimicry.
Dysregulation of miRNAs-COUP-TFII-FOXM1-CENPF axis contributes to the metastasis of prostate cancer
Authors: Lin Shih-Chieh , Kao Chung-Yang , Lee Hui-Ju , Creighton Chad J. , Ittmann Michael M. , Tsai Shaw-Jenq , Tsai Sophia Y. , Tsai Ming-Jer 
Published: April 2016

AbstractAlthough early detection and treatment of prostate cancer (PCa) improves outcomes, many patients still die of metastatic PCa. Here, we report that metastatic PCa exhibits reduced levels of the microRNAsmiR-101 and miR-27a. These micro-RNAs (miRNAs) negatively regulate cell invasion and inhibit the expression of FOXM1 and CENPF, two master regulators of metastasis in PCa. Interestingly, the repression of FOXM1 and CENPF by these miRNAs occurs through COUP-TFII, a member of the orphan nuclear receptors family. Loss of miR-101 positively correlates with the increase of COUP-TFII-FOXM1-CENPF activity in clinical PCa data sets, implicating clinical relevance of such regulation. Further studies show that COUP-TFII is a critical factor controlling metastatic gene networks to promote PCa metastasis. Most importantly, this miRNA-COUP-TFII-FOXM1-CENPF regulatory axis is also involved in the development of enzalutaminde resistance. Taken together, our findings highlight the contribution of specific miRNAs through the regulation of the COUP-TFII-FOXM1-CENPF cascade in PCa metastasis and drug resistance.
Phosphotransferase-dependent accumulation of (p)ppGpp in response to glutamine deprivation in Caulobacter crescentus
Authors: Ronneau Séverin , Petit Kenny , De Bolle Xavier , Hallez Régis 
Published: April 2016

AbstractThe alarmone (p)ppGpp is commonly used by bacteria to quickly respond to nutrient starvation. Although (p)ppGpp synthetases such as SpoT have been extensively studied, little is known about the molecular mechanisms stimulating alarmone synthesis upon starvation. Here, we describe an essential role of the nitrogen-related phosphotransferase system (PTSNtr) in controlling (p)ppGpp accumulation in Caulobacter crescentus. We show that cells sense nitrogen starvation by way of detecting glutamine deprivation using the first enzyme (EINtr) of PTSNtr. Decreasing intracellular glutamine concentration triggers phosphorylation of EINtr and its downstream components HPr and EIIANtr. Once phosphorylated, both HPr∼P and EIIANtr∼P stimulate (p)ppGpp accumulation by modulating SpoT activities. This burst of second messenger primarily impacts the non-replicative phase of the cell cycle by extending the G1 phase. This work highlights a new role for bacterial PTS systems in stimulating (p)ppGpp accumulation in response to metabolic cues and in controlling cell cycle progression and cell growth.
Identifying genetically driven clinical phenotypes using linear mixed models
Authors: Mosley Jonathan D. , Witte John S. , Larkin Emma K. , Bastarache Lisa , Shaffer Christian M. , Karnes Jason H. , Stein C. Michael , Phillips Elizabeth , Hebbring Scott J. , Brilliant Murray H. , Mayer John , Ye Zhan , Roden Dan M. , Denny Joshua C. 
Published: April 2016

AbstractWe hypothesized that generalized linear mixed models (GLMMs), which estimate the additive genetic variance underlying phenotype variability, would facilitate rapid characterization of clinical phenotypes from an electronic health record. We evaluated 1,288 phenotypes in 29,349 subjects of European ancestry with single-nucleotide polymorphism (SNP) genotyping on the Illumina Exome Beadchip. We show that genetic liability estimates are primarily driven by SNPs identified by prior genome-wide association studies and SNPs within the human leukocyte antigen (HLA) region. We identify 44 (false discovery rate q<0.05) phenotypes associated with HLA SNP variation and show that hypothyroidism is genetically correlated with Type I diabetes (rG=0.31, s.e. 0.12, P=0.003). We also report novel SNP associations for hypothyroidism near HLA-DQA1/HLA-DQB1 at rs6906021 (combined odds ratio (OR)=1.2 (95% confidence interval (CI): 1.1–1.2), P=9.8 × 10−11) and for polymyalgia rheumatica near C6orf10 at rs6910071 (OR=1.5 (95% CI: 1.3–1.6), P=1.3 × 10−10). Phenome-wide application of GLMMs identifies phenotypes with important genetic drivers, and focusing on these phenotypes can identify novel genetic associations.
North Atlantic forcing of moisture delivery to Europe throughout the Holocene
Authors: Smith Andrew C. , Wynn Peter M. , Barker Philip A. , Leng Melanie J. , Noble Stephen R. , Tych Wlodek 
Published: April 2016

AbstractCentury-to-millennial scale fluctuations in precipitation and temperature are an established feature of European Holocene climates. Changes in moisture delivery are driven by complex interactions between ocean moisture sources and atmospheric circulation modes, making it difficult to resolve the drivers behind millennial scale variability in European precipitation. Here, we present two overlapping decadal resolution speleothem oxygen isotope (δ18O) records from a cave on the Atlantic coastline of northern Iberia, covering the period 12.1–0 ka. Speleothem δ18O reveals nine quasi-cyclical events of relatively wet-to-dry climatic conditions during the Holocene. Dynamic Harmonic Regression modelling indicates that changes in precipitation occurred with a ~1500 year frequency during the late Holocene and at a shorter length during the early Holocene. The timing of these cycles coincides with changes in North Atlantic Ocean conditions, indicating a connectivity between ocean conditions and Holocene moisture delivery. Early Holocene climate is potentially dominated by freshwater outburst events, whilst ~1500 year cycles in the late Holocene are more likely driven by changes internal to the ocean system. This is the first continental record of its type that clearly demonstrates millennial scale connectivity between the pulse of the ocean and precipitation over Europe through the entirety of the Holocene.
A general and highly regioselective synthesis approach to multi-functionalized organoimido derivatives of Polyoxometalates
Authors: Huang Yichao , Zhang Jiangwei , Hao Jian , Wei Yongge 
Published: April 2016

AbstractOrganoimidoylization of Polyoxometalates (POMs) can dramatically modify the electronic structures of POMs and gives rise to novel “value-adding” properties of the POMs for promising material applications including photo-electronic transformation and catalysis. To date, the preparation of multi-functionalized organoimido derivatives of POMs is generally conducted under strict condition and is time-consuming with limited yields. Herein, a series of regioselective polyorganoimido derivatives of POMs, ocatant- [Mo6O13(NAr)3(μ2-NAr)3]2− (Ar = phenyl (1), p-methoxyphenyl (2) and p-ethylphenyl (3)), were synthesized with high selectivity and in good yields via a general and highly regioselective synthesis method, called as the one-octant synthesis protocol. The reaction was monitored by ESI-MS and the as-prepared products were studied by ESI-MS, IR, UV-Vis, EA, 1HNMR, single crystal XRD analysis and DFT calculations. The one-octant synthesis protocol here may serve as an idea method to design novel nanoscale POM-based organic-inorganic multi-functional hybrids.
Accelerated nucleation of the 2014 Iquique, Chile Mw 8.2 Earthquake
Authors: Kato Aitaro , Fukuda Jun’ichi , Kumazawa Takao , Nakagawa Shigeki 
Published: April 2016

AbstractThe earthquake nucleation process has been vigorously investigated based on geophysical observations, laboratory experiments and theoretical studies; however, a general consensus has yet to be achieved. Here, we studied nucleation process for the 2014 Iquique, Chile Mw 8.2 megathrust earthquake located within the current North Chile seismic gap, by analyzing a long-term earthquake catalog constructed from a cross-correlation detector using continuous seismic data. Accelerations in seismicity, the amount of aseismic slip inferred from repeating earthquakes and the background seismicity, accompanied by an increasing frequency of earthquake migrations, started around 270 days before the mainshock at locations up-dip of the largest coseismic slip patch. These signals indicate that repetitive sequences of fast and slow slip took place on the plate interface at a transition zone between fully locked and creeping portions. We interpret that these different sliding modes interacted with each other and promoted accelerated unlocking of the plate interface during the nucleation phase.
Major histocompatibility complex harbors widespread genotypic variability of non-additive risk of rheumatoid arthritis including epistasis
Authors: Wei Wen-Hua , Bowes John , Plant Darren , Viatte Sebastien , Yarwood Annie , Massey Jonathan , Worthington Jane , Eyre Stephen 
Published: April 2016

AbstractGenotypic variability based genome-wide association studies (vGWASs) can identify potentially interacting loci without prior knowledge of the interacting factors. We report a two-stage approach to make vGWAS applicable to diseases: firstly using a mixed model approach to partition dichotomous phenotypes into additive risk and non-additive environmental residuals on the liability scale and secondly using the Levene’s (Brown-Forsythe) test to assess equality of the residual variances across genotype groups per marker. We found widespread significant (P < 2.5e-05) vGWAS signals within the major histocompatibility complex (MHC) across all three study cohorts of rheumatoid arthritis. We further identified 10 epistatic interactions between the vGWAS signals independent of the MHC additive effects, each with a weak effect but jointly explained 1.9% of phenotypic variance. PTPN22 was also identified in the discovery cohort but replicated in only one independent cohort. Combining the three cohorts boosted power of vGWAS and additionally identified TYK2 and ANKRD55. Both PTPN22 and TYK2 had evidence of interactions reported elsewhere. We conclude that vGWAS can help discover interacting loci for complex diseases but require large samples to find additional signals.
Age-related impairment of humoral response to influenza is associated with changes in antigen specific T follicular helper cell responses
Authors: Lefebvre Julie S , Masters April R , Hopkins Jacob W , Haynes Laura 
Published: April 2016

AbstractT follicular helper (TFH) cell responses are essential for generation of protective humoral immunity during influenza infection. Aging has a profound impact on CD4+ T cell function and humoral immunity, yet the impact of aging on antigen specific TFH responses remains unclear. Influenza specific TFH cells are generated in similar numbers in young and aged animals during infection, but TFH cells from aged mice exhibit significant differences, including reduced expression of ICOS and elevated production of IL-10 and IFNγ, which potentially impairs interaction with cognate B cells. Also, more influenza specific T cells in aged mice have a regulatory phenotype, which could contribute to the impaired TFH function. Adoptive transfer studies with young T cells demonstrated that TGF-β1 in the aged environment can drive increased regulatory T cell accumulation. Aging and the aged environment thus impact antigen specific TFH cell function and formation, which contribute to reduced protective humoral responses.
Impact of Gender on Outcome in Octogenarians after Coronary Artery Bypass Grafting
Authors: Panholzer Bernd , Huenges Katharina , Jussli-Melchers Jill , Schoeneich Felix , Friedrich Christine , Hoffmann Grischa , Cremer Jochen , Haneya Assad , Berndt Rouven 
Published: April 2016

Background Increasing life expectancy makes cardiac surgery in octogenarians not very uncommon. In this study, the impact of gender on outcome of octogenarians after coronary artery bypass grafting (CABG) was assessed.
Materials and Methods We retrospectively studied 485 octogenarians (176 females: mean age 82.4 ± 2.2 years vs. 306 males: mean age 82.2 ± 2.4 years) who underwent isolated CABG using extracorporeal circulation between January 2005 and December 2012.
Results No significant differences were noted between both gender groups with regard to preoperative risk factors. At baseline, the groups differed significantly with respect to mean logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) (women: 22.3 ± 17.4% vs. men: 17.5 ± 13.3%; p < 0.001). Likewise, EuroSCORE II differs significantly between women and men in our cohort (women: 16.7 ± 11.9% vs. men: 13.9 ± 10.7%; p = 0.008). Intraoperatively, the number of distal anastomoses (3.1 ± 0.9 vs. 3.2 ± 0.8), the mean extracorporeal circulation time (99 ± 31 vs. 102 ± 29 minutes), and the mean aortic cross-clamp time (63 ± 31 vs. 60 ± 19 minutes) were similar in both groups. Postoperatively, no significant differences in complications and major morbidity were observed between the groups. The 30-day mortality (women 8.0 vs. men 9.7%; p = 0.62) were without statistical significance between the groups.
Conclusion Outcome of octogenarians after CABG resulted in acceptable mortality. Female gender was not associated with increased risks for morbidity and mortality after surgery. Satisfactory outcomes encourage the offering of surgery in octogenarians.
Relationship between Serum Albumin Level and Monocyte-to-High-Density Lipoprotein Cholesterol Ratio with Saphenous Vein Graft Disease in Coronary Bypass
Authors: Yayla Cagri , Balci Kevser , Ozeke Ozcan , Maden Orhan , Kisacik Halil , Temizhan Ahmet , Aydogdu Sinan , Akboga Mehmet 
Published: April 2016

Background Previous studies proposed that inflammation, oxidative stress, and impaired endothelial dysfunction have a crucial role in occurrence of saphenous vein graft (SVG) disease (SVGD). The aim of this study was to assess the relationship between monocyte-to-high-density lipoprotein cholesterol (HDL-C) ratio (MHR) and serum albumin (SA) level as readily available inflammatory and oxidative stress markers with the presence of SVGD in patients with a coronary bypass.
Methods In this retrospective cross-sectional study, a total of 257 patients (n = 112 SVGD [+] [mean age was 65.3 ± 8.4 years, 75.0% males] and n = 145 SVGD [−] [mean age was 66.5 ± 10.1 years, 74.5% males]) were enrolled. At least one SVG with ≥ 50% stenosis was defined as SVGD. Independent predictors of SVGD were determined by logistic regression analysis.
Results White blood cell, neutrophil, monocyte, the age of SVG, and MHR were significantly higher, whereas SA level was significantly lower in patients with SVGD. In regression analysis, neutrophil, age of SVG, SA (odds ratio [OR]: 0.232 [0.156–0.370], p < 0.001), and MHR (OR: 1.122 [1.072–1.174], p < 0.001) remained as independent predictors of SVGD. Moreover, age of SVG showed a significant negative correlation with SA (r = − 0.343, p < 0.001) and a positive correlation with MHR (r = 0.238, p < 0.001). In the receiver-operating characteristic curve analysis, the cutoff value of ≤ 3.75 g/dL for SA has a 73.2% sensitivity and 64.8% specificity and the cutoff value of ≥ 12.1 for MHR has a 71.4% sensitivity and 60.0% specificity for prediction of SVGD.
Conclusion Consequently, to the best of our knowledge, this is the first study showing a significant and independent association between SA and MHR with SVGD.
Components of Mortality within a Black Bass High‐Release Recreational Fishery
Authors: Kerns Janice A. , Allen Micheal S. , Hightower Joseph E. 
Published: April 2016

AbstractMortality after release can have a substantial impact on high‐release recreational sport fishes, such as Largemouth Bass Micropterus salmoides. However, little work has explored the cumulative impact of catch‐and‐release mortality at the population level. We used a combined telemetry–tag return approach to estimate all components of total mortality, including instantaneous natural mortality (M) and instantaneous fishing mortality (F), for Florida Largemouth Bass M. salmoides floridanus (hereafter, Florida Bass) within a popular fishing lake in northern Florida. Fishing mortality was subdivided into harvest (FH), recreational catch‐and‐release (FR), and tournament catch‐and‐release (FT) components. Over 2 years, we monitored the fates of 181 Florida Bass that were tagged with high‐reward external dart tags and internal radio transmitters. An additional 345 fish were tagged with variable‐reward external tags. Annual FH values were seasonal, with an increase in FH occurring in the spring of both years; FH ranged from 0.17 (SD = 0.04) in the first year to 0.60 (SD = 0.09) in the second year. Estimated mean FT ranged from 0.04 to 0.07, and mean FR ranged from 0.03 to 0.05. Estimates of M were also seasonal, with annual M ranging from 0.29 (SD = 0.06) to 0.46 (SD = 0.09), and were within the expected range relative to other published estimates. Our results showed that although the total catch‐and‐release mortality (FR plus FT) was low in comparison with the high rates of harvest (FH) for this Florida Bass fishery, it still made up 21% of total F. Our method combining passive tagging and telemetry tagging allowed for the estimation of all mortality sources, which can be important for high‐release recreational fisheries in which harvest is not the only source of mortality.Received July 14, 2015; accepted December 7, 2015 Published online April 25, 2016
Corporate social responsibility in construction industry
Authors: Ulutaş Duman Dilek , Giritli Heyecan , McDermott Peter 
Published: April 2016

Purpose
– Corporate social responsibility (CSR) has evolved to an important agenda for many industries and its scope has been widened from the responsible business to strategic decisions. Therefore, the purpose of this paper is to investigate the concept of CSR from the perspective of construction industry by questioning CSR awareness, CSR activities and CSR integration with a comparative case study between UK and Turkey.

Design/methodology/approach
– Conducting comparative and qualitative research using a case study methodology, this study sets the context for understanding differences in these two countries as to how CSR is perceived and put into practice by selected case firms.

Findings
– The results revealed that construction companies are aware of the increasing importance of the CSR; however, company scale and the characteristics of the country have great impact on CSR preferences. Despite the differences in the approaches all firms take with regard to CSR domains and CSR types, ethical domain and the social orientation have become prominent for CSR initiatives in both the UK and Turkey.

Originality/value
– This study provides the empirical evidence for the understanding and integration of the CSR concept in the construction industry; shed light on missing knowledge about CSR integration and serves as a source for further in-depth researches on CSR.