bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unemployment, sanctions and mental health: the relationship between benefit sanctions and antidepressant prescribing
Authors: WILLIAMS EVAN 
Published: October 2019

AbstractInternational social security systems increasingly place work-related conditions on individuals claiming out-of-work benefits, and enforce requirements through the use of benefit sanctions. The literature on the impacts of benefit sanctions considers both labour market and wider social effects, which this study contributes to through a focus on mental health. It considers the period of Coalition government (2010–15) in the UK, which imposed a comparatively high number of benefit sanctions and increased their severity through the Welfare Reform Act 2012. A longitudinal dataset is constructed using quarterly local authority-level data on Jobseeker’s Allowance (JSA) sanctions and antidepressant prescriptions in England. Results from fixed effects analyses indicate that, in the post-reform period, every 10 additional sanctions are associated with 4.57 additional antidepressant prescribing items (95% CI: 2.14 to 6.99), which translates to approximately one additional person receiving treatment. Importantly, this finding indicates that sanctions are associated with both adverse mental health impacts and wider public expenditure implications, which motivates further investigation at the individual-level. In addition, punitive sanctions form a core part of the new Universal Credit (UC) and so the results suggest the need to reassess the use of sanctions within the contemporary social security system.
Enhanced El Niño–Southern Oscillation Variability in Recent Decades
Authors: Grothe Pamela R. , Cobb Kim M. , Liguori Giovanni , Di Lorenzo Emanuele , Capotondi Antonietta , Lu Yanbin , Cheng Hai , Edwards R. Lawrence , Southon John R. , Santos Guaciara M. , Deocampo Daniel M. , Lynch‐Stieglitz Jean , Chen Tianran , Sayani Hussein R. , Thompson Diane M. , Conroy Jessica L. , Moore Andrea L. , Townsend Kayla , Hagos Melat , O'Connor Gemma , Toth Lauren T. 
Published: October 2019

AbstractThe El Niño–Southern Oscillation (ENSO) represents the largest source of year‐to‐year global climate variability. While Earth system models suggest a range of possible shifts in ENSO properties under continued greenhouse gas forcing, many centuries of preindustrial climate data are required to detect a potential shift in the properties of recent ENSO extremes. Here we reconstruct the strength of ENSO variations over the last 7,000 years with a new ensemble of fossil coral oxygen isotope records from the Line Islands, located in the central equatorial Pacific. The corals document a significant decrease in ENSO variance of ~20% from 3,000 to 5,000 years ago, coinciding with changes in spring/fall precessional insolation. We find that ENSO variability over the last five decades is ~25% stronger than during the preindustrial. Our results provide empirical support for recent climate model projections showing an intensification of ENSO extremes under greenhouse forcing.
Automated Detection of Dynamic Earthquake Triggering by the High‐Frequency Power Integral Ratio
Authors: Yun Naidan , Zhou Shiyong , Yang Hongfeng , Yue Han , Zhao Li 
Published: October 2019

AbstractDynamic earthquake triggering can be used to investigate the responses of faults to stress disturbances. We develop a new method to detect dynamic triggering by estimating high‐frequency energy change before and during teleseismic waves using the HIgh‐Frequency power Integral ratio (HiFi). Our method is able to identify local events independent of earthquake catalog or subjective judgements. The significance in energy change is evaluated by a statistical analysis of the background ratio in a large number of days, which can suppress the influence of noise and variations in the background seismicity and yield a confidence level of dynamic triggering (0–1). We apply the HiFi method to the Geysers Geothermal Field in California, and the results are largely consistent with previous reports from the β statistic. By comparing the results of HiFi and β statistic, we select a confidence level range of 0.918–0.947 as the optimum threshold to identify dynamic triggering in the region.
Characteristics and Generation of Low‐Frequency Magnetosonic Waves Below the Proton Gyrofrequency
Authors: Teng Shangchun , Li Wen , Tao Xin , Ma Qianli , Shen Xiaochen 
Published: October 2019

AbstractWe report a Van Allen Probes observation of large‐amplitude magnetosonic waves with the peak intensity below the proton gyrofrequency (fcp), which may potentially be misinterpreted as electromagnetic ion cyclotron waves. The frequency spacing of the wave harmonic structure suggests that these magnetosonic waves are excited at a distant source region and propagate radially inward. We also conduct a statistical analysis of low‐frequency magnetosonic waves below fcp based on the Van Allen Probes data from October 2012 to December 2018. The spatial distribution shows that these low‐frequency magnetosonic emissions are dominantly observed inside the plasmasphere from the prenoon to the midnight sector within 5° of the geomagnetic equator and typically have modest‐to‐strong wave amplitudes ranging from tens of pT to hundreds of pT. Our study provides insight into understanding the generation and propagation of these low‐frequency magnetosonic waves in the Earth's inner magnetosphere.
Interleukin-6 signaling regulates hematopoietic stem cell emergence
Authors: Tie Ruxiu , Li Honghu , Cai Shuyang , Liang Zuyu , Shan Wei , Wang Binsheng , Tan Yamin , Zheng Weiyan , Huang He 
Published: October 2019

AbstractHematopoietic stem cells (HSCs) produce all lineages of mature blood cells for the lifetime of an organism. In vertebrates, HSCs derive from the transition of the hemogenic endothelium (HE) in the floor of the embryonic dorsal aorta. Most recently, a series of proinflammatory factors, such as tumor necrosis factor-α, interferon-γ, and Toll-like receptor 4, have been confirmed to play a key role in HSC specification. However, the full complement of necessary signaling inputs remains unknown to date. Here, we show that interleukin-6R (IL6R) via IL6 is required and sufficient for HSC generation. We found that Notch activates IL6R by regulating its expression in the HE and in HSCs. The secretion of IL6 mainly originates from HSC-independent myeloid cells, but not from HSCs and their adjacent vascular endothelial cells. In addition, blocking IL6 signaling does not affect vascular development or the production of primitive erythrocytes. Taken together, our results uncover a previously obscure relationship between IL6 signaling and HSC production and provide new insights into HSC regeneration using proinflammatory factors in vitro.
Educational attainment impacts drinking behaviors and risk for alcohol dependence: results from a two-sample Mendelian randomization study with ~780,000 participants
Authors: Rosoff Daniel B. , Clarke Toni-Kim , Adams Mark J. , McIntosh Andrew M. , Davey Smith George , Jung Jeesun , Lohoff Falk W. 
Published: October 2019

AbstractObservational studies suggest that lower educational attainment (EA) may be associated with risky alcohol use behaviors; however, these findings may be biased by confounding and reverse causality. We performed two-sample Mendelian randomization (MR) using summary statistics from recent genome-wide association studies (GWAS) with >780,000 participants to assess the causal effects of EA on alcohol use behaviors and alcohol dependence (AD). Fifty-three independent genome-wide significant SNPs previously associated with EA were tested for association with alcohol use behaviors. We show that while genetic instruments associated with increased EA are not associated with total amount of weekly drinks, they are associated with reduced frequency of binge drinking ≥6 drinks (ßIVW = −0.198, 95% CI, −0.297 to –0.099, PIVW = 9.14 × 10−5), reduced total drinks consumed per drinking day (ßIVW = −0.207, 95% CI, −0.293 to –0.120, PIVW = 2.87 × 10−6), as well as lower weekly distilled spirits intake (ßIVW = −0.148, 95% CI, −0.188 to –0.107, PIVW = 6.24 × 10−13). Conversely, genetic instruments for increased EA were associated with increased alcohol intake frequency (ßIVW = 0.331, 95% CI, 0.267–0.396, PIVW = 4.62 × 10−24), and increased weekly white wine (ßIVW = 0.199, 95% CI, 0.159–0.238, PIVW = 7.96 × 10−23) and red wine intake (ßIVW = 0.204, 95% CI, 0.161–0.248, PIVW = 6.67 × 10−20). Genetic instruments associated with increased EA reduced AD risk: an additional 3.61 years schooling reduced the risk by ~50% (ORIVW = 0.508, 95% CI, 0.315–0.819, PIVW = 5.52 × 10−3). Consistency of results across complementary MR methods accommodating different assumptions about genetic pleiotropy strengthened causal inference. Our findings suggest EA may have important effects on alcohol consumption patterns and may provide potential mechanisms explaining reported associations between EA and adverse health outcomes.
Exploring lithium’s transcriptional mechanisms of action in bipolar disorder: a multi-step study
Authors: Akkouh Ibrahim A. , Skrede Silje , Holmgren Asbjørn , Ersland Kari M. , Hansson Lars , Bahrami Shahram , Andreassen Ole A. , Steen Vidar M. , Djurovic Srdjan , Hughes Timothy 
Published: October 2019

Abstract
Lithium has been the first-line treatment for bipolar disorder (BD) for more than six decades. Although the molecular effects of lithium have been studied extensively and gene expression changes are generally believed to be involved, the specific mechanisms of action that mediate mood regulation are still not known. In this study, a multi-step approach was used to explore the transcriptional changes that may underlie lithium’s therapeutic efficacy. First, we identified genes that are associated both with lithium exposure and with BD, and second, we performed differential expression analysis of these genes in brain tissue samples from BD patients (n = 42) and healthy controls (n = 42). To identify genes that are regulated by lithium exposure, we used high-sensitivity RNA-sequencing of corpus callosum (CC) tissue samples from lithium-treated (n = 8) and non-treated (n = 9) rats. We found that lithium exposure significantly affected 1108 genes (FDR < 0.05), 702 up-regulated and 406 down-regulated. These genes were mostly enriched for molecular functions related to signal transduction, including well-established lithium-related pathways such as mTOR and Wnt signaling. To identify genes with differential expression in BD, we performed expression quantitative trait loci (eQTL) analysis on BD-associated genetic variants from the most recent genome-wide association study (GWAS) using three different gene expression databases. We found 307 unique eQTL genes regulated by BD-associated variants, of which 12 were also significantly modulated by lithium treatment in rats. Two of these showed differential expression in the CC of BD cases: RPS23 was significantly down-regulated (p = 0.0036, fc = 0.80), while GRIN2A showed suggestive evidence of down-regulation in BD (p = 0.056, fc = 0.65). Crucially, GRIN2A was also significantly up-regulated by lithium in the rat brains (p = 2.2e-5, fc = 1.6), which suggests that modulation of GRIN2A expression may be a part of the therapeutic effect of the drug. These results indicate that the recent upsurge in research on this central component of the glutamatergic system, as a target of novel therapeutic agents for affective disorders, is warranted and should be intensified.
Disruption of gap junctions attenuates acute myeloid leukemia chemoresistance induced by bone marrow mesenchymal stromal cells
Authors: Kouzi Farah , Zibara Kazem , Bourgeais Jerome , Picou Frederic , Gallay Nathalie , Brossaud Julie , Dakik Hassan , Roux Benjamin , Hamard Sophie , Le Nail Louis-Romee , Hleihel Rita , Foucault Amelie , Ravalet Noemie , Rouleux-Bonnin Florence , Gouilleux Fabrice , Mazurier Frederic , Bene Marie C. , Akl Haidar , Gyan Emmanuel , Domenech Jorge , El-Sabban Marwan , Herault Olivier 
Published: October 2019

AbstractThe bone marrow (BM) niche impacts the progression of acute myeloid leukemia (AML) by favoring the chemoresistance of AML cells. Intimate interactions between leukemic cells and BM mesenchymal stromal cells (BM-MSCs) play key roles in this process. Direct intercellular communications between hematopoietic cells and BM-MSCs involve connexins, components of gap junctions. We postulated that blocking gap junction assembly could modify cell–cell interactions in the leukemic niche and consequently the chemoresistance. The comparison of BM-MSCs from AML patients and healthy donors revealed a specific profile of connexins in BM-MSCs of the leukemic niche and the effects of carbenoxolone (CBX), a gap junction disruptor, were evaluated on AML cells. CBX presents an antileukemic effect without affecting normal BM-CD34+ progenitor cells. The proapoptotic effect of CBX on AML cells is in line with the extinction of energy metabolism. CBX acts synergistically with cytarabine (Ara-C) in vitro and in vivo. Coculture experiments of AML cells with BM-MSCs revealed that CBX neutralizes the protective effect of the niche against the Ara-C-induced apoptosis of leukemic cells. Altogether, these results suggest that CBX could be of therapeutic interest to reduce the chemoresistance favored by the leukemic niche, by targeting gap junctions, without affecting normal hematopoiesis.
Human iPSC-derived iMSCs improve bone regeneration in mini-pigs
Authors: Jungbluth Pascal , Spitzhorn Lucas-Sebastian , Grassmann Jan , Tanner Stephan , Latz David , Rahman Md Shaifur , Bohndorf Martina , Wruck Wasco , Sager Martin , Grotheer Vera , Kröpil Patric , Hakimi Mohssen , Windolf Joachim , Schneppendahl Johannes , Adjaye James 
Published: October 2019

AbstractAutologous bone marrow concentrate (BMC) and mesenchymal stem cells (MSCs) have beneficial effects on the healing of bone defects. To address the shortcomings associated with the use of primary MSCs, induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) have been proposed as an alternative. The aim of this study was to investigate the bone regeneration potential of human iMSCs combined with calcium phosphate granules (CPG) in critical-size defects in the proximal tibias of mini-pigs in the early phase of bone healing compared to that of a previously reported autograft treatment and treatment with a composite made of either a combination of autologous BMC and CPG or CPG alone. iMSCs were derived from iPSCs originating from human fetal foreskin fibroblasts (HFFs). They were able to differentiate into osteoblasts in vitro, express a plethora of bone morphogenic proteins (BMPs) and secrete paracrine signaling-associated cytokines such as PDGF-AA and osteopontin. Radiologically and histomorphometrically, HFF-iMSC + CPG transplantation resulted in significantly better osseous consolidation than the transplantation of CPG alone and produced no significantly different outcomes compared to the transplantation of autologous BMC + CPG after 6 weeks. The results of this translational study imply that iMSCs represent a valuable future treatment option for load-bearing bone defects in humans.
EWS-FLI1-mediated tenascin-C expression promotes tumour progression by targeting MALAT1 through integrin α5β1-mediated YAP activation in Ewing sarcoma
Authors: He Shaohui , Huang Quan , Hu Jinbo , Li Lei , Xiao Yanbin , Yu Hongyu , Han Zhitao , Wang Ting , Zhou Wang , Wei Haifeng , Xiao Jianru 
Published: October 2019

AbstractBackgroundThe extracellular matrix has been critically associated with the tumorigenesis and progression of Ewing sarcoma (ES). However, the regulatory and prognostic roles of tenascin-C (TNC) in ES remain unclear.MethodsTNC expression was examined in specimens by immunohistochemistry, and the association of TNC expression with ES patient survival was also analysed. TNC-knockout cell lines were constructed using CRISPR/Cas9 methods. In vitro experiments and in vivo bioluminescent imaging using BALB/c nude mice were conducted to evaluate the effect of TNC on ES tumour progression. RNA sequencing was performed, and the underlying mechanism of TNC was further explored.ResultsTNC was overexpressed in ES tissue and cell lines, and TNC overexpression was associated with poor survival in ES patients. TNC enhanced cell proliferation, migration and angiogenesis in vitro and promoted ES metastasis in vivo. The oncoprotein EWS-FLI1 profoundly increased TNC expression by directly binding to the TNC promoter region. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) upregulation induced by Yes-associated protein (YAP) activation was responsible for TNC-regulated ES tumour progression. Activated integrin α5β1 signalling might be correlated with YAP dephosphorylation and nuclear translocation.ConclusionsTNC may promote ES tumour progression by targeting MALAT1 through integrin α5β1-mediated YAP activation.
ROS-mediated inactivation of the PI3K/AKT pathway is involved in the antigastric cancer effects of thioredoxin reductase-1 inhibitor chaetocin
Authors: Wen Chuangyu , Wang Huihui , Wu Xiaobin , He Lu , Zhou Qian , Wang Fang , Chen Siyu , Huang Lanlan , Chen Junxiong , Wang Huashe , Ye Weibiao , Li Wende , Yang Xiangling , Liu Huanliang , Peng Junsheng 
Published: October 2019

AbstractNovel drugs are urgently needed for gastric cancer (GC) treatment. The thioredoxin-thioredoxin reductase (TRX-TRXR) system has been found to play a critical role in GC tumorigenesis and progression. Thus, agents that target the TRX-TRXR system may be highly efficacious as GC treatments. In this study, we showed that chaetocin, a natural product isolated from the Chaetomium species of fungi, inhibited proliferation, induced G2/M phase arrest and caspase-dependent apoptosis in both in vitro and in vivo models (cell xenografts and patient-derived xenografts) of GC. Chaetocin inactivated TRXR-1, resulting in the accumulation of reactive oxygen species (ROS) in GC cells; overexpression of TRX-1 as well as cotreatment of GC cells with the ROS scavenger N-acetyl-L-cysteine attenuated chaetocin-induced apoptosis; chaetocin-induced apoptosis was significantly increased when GC cells were cotreated with auranofin. Moreover, chaetocin was shown to inactivate the PI3K/AKT pathway by inducing ROS generation; AKT-1 overexpression also attenuated chaetocin-induced apoptosis. Taken together, these results reveal that chaetocin induces the excessive accumulation of ROS via inhibition of TRXR-1. This is followed by PI3K/AKT pathway inactivation, which ultimately inhibits proliferation and induces caspase-dependent apoptosis in GC cells. Chaetocin therefore may be a potential agent for GC treatment.
DDX17 promotes hepatocellular carcinoma progression via inhibiting Klf4 transcriptional activity
Authors: Xue Ying , Jia Xuebing , Li Changcan , Zhang Ke , Li Lei , Wu Jinhuan , Yuan Jian , Li Qi 
Published: October 2019

AbstractDEAD box RNA helicase 17 (DDX17) is a transcriptional regulator of several transcription factors, which is more appreciated than its role in RNA metabolism. However, prognostic value and biofunction of DDX17 in HCC remain unclear. Illuminating the mechanism underlying the regulating HCC progression by DDX17 may contribute to therapeutic strategies. In our study, we report for the first time that DDX17 was overexpressed in HCC specimens by using The Cancer Genome Atlas (TCGA) and immunohistochemistry (IHC) and correlated to clinical pathological characteristics and patients’ survival. In vitro, DDX17 was ascertained to alter HCC migratory and invasive capacities after overexpression and knockdown in HCC cell lines. Moreover, by performing co-immunoprecipitation (Co-IP) and GST-pull down assay, the physical association between DDX17 and Klf4 was discovered and validated. Additionally, DDX17 could modulate expressions of Klf4 target genes including E-cadherin, MMP2 by inhibiting the promoter activity. The potent correlation between DDX17 and Klf4 target gene expressions was further appraised by a same set of 30 HCC tissues. Besides, we discovered that DDX17 could not deploy its function in regulating Klf4 target gene expressions and HCC progression in Klf4-depletion condition. Intriguingly, DDX17 failed to interact with Klf4 once the zinc-finger domain was deleted and inhibited the binding of Klf4 on MMP-2 promoter. Collectively, our study enucleates novel mechanism of DDX17-mediated oncogenesis by suppressing the transcriptional activity of Klf4 thus is likely to be a therapeutic target in HCC.
Enhancing dynamic actuation performance of dielectric elastomer actuators by tuning viscoelastic effects with polar crosslinking
Authors: Tan Matthew Wei Ming , Thangavel Gurunathan , Lee Pooi See 
Published: October 2019

AbstractDielectric elastomer actuators (DEAs) have shown great potential in the field of robotics, energy harvesting, or haptics for wearables. However, existing DEA materials typically require prestretching and exhibit time-dependent deformations due to their inherent viscoelastic properties. In this work, we address these issues by designing and synthesizing a polyurethane acrylate (PUA) DEA copolymerized with a polar crosslinker, polyethylene glycol diacrylate (PEGDA), to reduce viscoelastic effects through chemical crosslinking. We realized a buckling-mode actuator that displays out-of-plane deformations triggered by an electric field without the need for prestretching. Copolymerization with PEGDA showed improved dynamic response actuation performances compared to pristine PUA, wherein the former reached 90% of its maximum actuation in <1 s. In addition, precise and stable actuation was achieved, reducing viscoelastic drifts to a negligible amount. Despite the higher elastic modulus of the DEA incurred by the chemical crosslinks, the polar groups present in the PEGDA comonomer effectively increased the dielectric constant. As such, a higher area strain was achieved in comparison to that exhibited by low viscoelastic elastomers such as silicone. By eliminating the need for prestretching, rigid components can be avoided, thereby enabling greater prospects for the integration of fast response and stable DEAs into soft bodies.
Occurrence and repair of alkylating stress in the intracellular pathogen Brucella abortus
Authors: Poncin Katy , Roba Agnès , Jimmidi Ravikumar , Potemberg Georges , Fioravanti Antonella , Francis Nayla , Willemart Kévin , Zeippen Nicolas , Machelart Arnaud , Biondi Emanuele G. , Muraille Eric , Vincent Stéphane P. , De Bolle Xavier 
Published: October 2019

AbstractIt is assumed that intracellular pathogenic bacteria have to cope with DNA alkylating stress within host cells. Here we use single-cell reporter systems to show that the pathogen Brucella abortus does encounter alkylating stress during the first hours of macrophage infection. Genes encoding direct repair and base-excision repair pathways are required by B. abortus to face this stress in vitro and in a mouse infection model. Among these genes, ogt is found to be under the control of the conserved cell-cycle transcription factor GcrA. Our results highlight that the control of DNA repair in B. abortus displays distinct features that are not present in model organisms such as Escherichia coli.