bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased DNA methylation variability in type 1 diabetes across three immune effector cell types
Authors: Paul Dirk S. , Teschendorff Andrew E. , Dang Mary A.N. , Lowe Robert , Hawa Mohammed I. , Ecker Simone , Beyan Huriya , Cunningham Stephanie , Fouts Alexandra R. , Ramelius Anita , Burden Frances , Farrow Samantha , Rowlston Sophia , Rehnstrom Karola , Frontini Mattia , Downes Kate , Busche Stephan , Cheung Warren A. , Ge Bing , Simon Marie-Michelle , Bujold David , Kwan Tony , Bourque Guillaume , Datta Avik , Lowy Ernesto , Clarke Laura , Flicek Paul , Libertini Emanuele , Heath Simon , Gut Marta , Gut Ivo G , Ouwehand Willem H. , Pastinen Tomi , Soranzo Nicole , Hofer Sabine E. , Karges Beate , Meissner Thomas , Boehm Bernhard O. , Cilio Corrado , Elding Larsson Helena , Lernmark Åke , Steck Andrea K. , Rakyan Vardhman K. , Beck Stephan , Leslie R. David 
Published: November 2016

AbstractThe incidence of type 1 diabetes (T1D) has substantially increased over the past decade, suggesting a role for non-genetic factors such as epigenetic mechanisms in disease development. Here we present an epigenome-wide association study across 406,365 CpGs in 52 monozygotic twin pairs discordant for T1D in three immune effector cell types. We observe a substantial enrichment of differentially variable CpG positions (DVPs) in T1D twins when compared with their healthy co-twins and when compared with healthy, unrelated individuals. These T1D-associated DVPs are found to be temporally stable and enriched at gene regulatory elements. Integration with cell type-specific gene regulatory circuits highlight pathways involved in immune cell metabolism and the cell cycle, including mTOR signalling. Evidence from cord blood of newborns who progress to overt T1D suggests that the DVPs likely emerge after birth. Our findings, based on 772 methylomes, implicate epigenetic changes that could contribute to disease pathogenesis in T1D.
A design principle of polymers processable into 2D homeotropic order
Authors: Chen Zhen , Chan Yi-Tsu , Miyajima Daigo , Kajitani Takashi , Kosaka Atsuko , Fukushima Takanori , Lobez Jose M. , Aida Takuzo 
Published: November 2016

AbstractHow to orient polymers homeotropically in thin films has been a long-standing issue in polymer science because polymers intrinsically prefer to lie down. Here we provide a design principle for polymers that are processable into a 2D homeotropic order. The key to this achievement was a recognition that cylindrical polymers can be designed to possess oppositely directed local dipoles in their cross-section, which possibly force polymers to tightly connect bilaterally, affording a 2D rectangular assembly. With a physical assistance of the surface grooves on Teflon sheets that sandwich polymer samples, homeotropic ordering is likely nucleated and gradually propagates upon hot-pressing towards the interior of the film. Consequently, the 2D rectangular lattice is constructed such that its b axis (side chains) aligns along the surface grooves, while its c axis (polymer backbone) aligns homeotropically on a Teflon sheet. This finding paves the way to molecularly engineered 2D polymers with anomalous functions.
Parvalbumin- and vasoactive intestinal polypeptide-expressing neocortical interneurons impose differential inhibition on Martinotti cells
Authors: Walker F. , Möck M. , Feyerabend M. , Guy J. , Wagener R. J. , Schubert D. , Staiger J. F. , Witte M. 
Published: November 2016

AbstractDisinhibition of cortical excitatory cell gate information flow through and between cortical columns. The major contribution of Martinotti cells (MC) is providing dendritic inhibition to excitatory neurons and therefore they are a main component of disinhibitory connections. Here we show by means of optogenetics that MC in layers II/III of the mouse primary somatosensory cortex are inhibited by both parvalbumin (PV)- and vasoactive intestinal polypeptide (VIP)-expressing cells. Paired recordings revealed stronger synaptic input onto MC from PV cells than from VIP cells. Moreover, PV cell input showed frequency-independent depression, whereas VIP cell input facilitated at high frequencies. These differences in the properties of the two unitary connections enable disinhibition with distinct temporal features.
EZH1 and EZH2 promote skeletal growth by repressing inhibitors of chondrocyte proliferation and hypertrophy
Authors: Lui Julian C. , Garrison Presley , Nguyen Quang , Ad Michal , Keembiyehetty Chithra , Chen Weiping , Jee Youn Hee , Landman Ellie , Nilsson Ola , Barnes Kevin M. , Baron Jeffrey 
Published: November 2016

AbstractHistone methyltransferases EZH1 and EZH2 catalyse the trimethylation of histone H3 at lysine 27 (H3K27), which serves as an epigenetic signal for chromatin condensation and transcriptional repression. Genome-wide associated studies have implicated EZH2 in the control of height and mutations in EZH2 cause Weaver syndrome, which includes skeletal overgrowth. Here we show that the combined loss of Ezh1 and Ezh2 in chondrocytes severely impairs skeletal growth in mice. Both of the principal processes underlying growth plate chondrogenesis, chondrocyte proliferation and hypertrophy, are compromised. The decrease in chondrocyte proliferation is due in part to derepression of cyclin-dependent kinase inhibitors Ink4a/b, while ineffective chondrocyte hypertrophy is due to the suppression of IGF signalling by the increased expression of IGF-binding proteins. Collectively, our findings reveal a critical role for H3K27 methylation in the regulation of chondrocyte proliferation and hypertrophy in the growth plate, which are the central determinants of skeletal growth.
A statistical algorithm showing coenzyme Q10 and citrate synthase as biomarkers for mitochondrial respiratory chain enzyme activities
Authors: Yubero D. , Adin A. , Montero R. , Jou C. , Jiménez-Mallebrera C. , García-Cazorla A. , Nascimento A. , O’Callaghan M. M. , Montoya J. , Gort L. , Navas P. , Ribes A. , Ugarte M. D. , Artuch R. 
Published: November 2016

AbstractLaboratory data interpretation for the assessment of complex biological systems remains a great challenge, as occurs in mitochondrial function research studies. The classical biochemical data interpretation of patients versus reference values may be insufficient, and in fact the current classifications of mitochondrial patients are still done on basis of probability criteria. We have developed and applied a mathematic agglomerative algorithm to search for correlations among the different biochemical variables of the mitochondrial respiratory chain in order to identify populations displaying correlation coefficients >0.95. We demonstrated that coenzyme Q10 may be a better biomarker of mitochondrial respiratory chain enzyme activities than the citrate synthase activity. Furthermore, the application of this algorithm may be useful to re-classify mitochondrial patients or to explore associations among other biochemical variables from different biological systems.
Evolution of the intrinsic electronic phase separation in La0.6Er0.1Sr0.3MnO3 perovskite
Authors: Chen Lili , Fan Jiyu , Tong Wei , Hu Dazhi , Ji Yanda , Liu Jindong , Zhang Lei , Pi Li , Zhang Yuheng , Yang Hao 
Published: November 2016

AbstractMagnetic and electronic transport properties of perovskite manganite La0.6Er0.1Sr0.3MnO3 have been thoroughly examined through the measurements of magnetization, electron paramagnetic resonance(EPR), and resistivity. It was found that the substitution of Er3+ for La3+ ions introduced the chemical disorder and additional strain in this sample. An extra resonance signal occurred in EPR spectra at high temperatures well above T
C
gives a strong evidence of electronic phase separation(EPS). The analysis of resistivity enable us to identify the polaronic transport mechanism in the paramagnetic region. At low temperature, a new ferromagnetic interaction generates in the microdomains of Er3+-disorder causing the second increase of magnetization. However, the new ferromagnetic interaction does not improve but decreases electronic transport due to the enhancement of interface resistance among neighboring domains. In view of a really wide temperature region for the EPS existence, this sample provides an ideal platform to uncover the evolution law of different magnetic structures in perovskite manganites.
Discovery of an enzyme and substrate selective inhibitor of ADAM10 using an exosite-binding glycosylated substrate
Authors: Madoux Franck , Dreymuller Daniela , Pettiloud Jean-Phillipe , Santos Radleigh , Becker-Pauly Christoph , Ludwig Andreas , Fields Gregg B. , Bannister Thomas , Spicer Timothy P. , Cudic Mare , Scampavia Louis D. , Minond Dmitriy 
Published: November 2016

AbstractADAM10 and ADAM17 have been shown to contribute to the acquired drug resistance of HER2-positive breast cancer in response to trastuzumab. The majority of ADAM10 and ADAM17 inhibitor development has been focused on the discovery of compounds that bind the active site zinc, however, in recent years, there has been a shift from active site to secondary substrate binding site (exosite) inhibitor discovery in order to identify non-zinc-binding molecules. In the present work a glycosylated, exosite-binding substrate of ADAM10 and ADAM17 was utilized to screen 370,276 compounds from the MLPCN collection. As a result of this uHTS effort, a selective, time-dependent, non-zinc-binding inhibitor of ADAM10 with Ki = 883 nM was discovered. This compound exhibited low cell toxicity and was able to selectively inhibit shedding of known ADAM10 substrates in several cell-based models. We hypothesize that differential glycosylation of these cognate substrates is the source of selectivity of our novel inhibitor. The data indicate that this novel inhibitor can be used as an in vitro and, potentially, in vivo, probe of ADAM10 activity. Additionally, results of the present and prior studies strongly suggest that glycosylated substrate are applicable as screening agents for discovery of selective ADAM probes and therapeutics.
Stepwise onset of the Icehouse world and its impact on Oligo-Miocene Central Asian mammals
Authors: Harzhauser Mathias , Daxner-Höck Gudrun , López-Guerrero Paloma , Maridet Olivier , Oliver Adriana , Piller Werner E. , Richoz Sylvain , Erbajeva Margarita A. , Neubauer Thomas A. , Göhlich Ursula B. 
Published: November 2016

AbstractCentral Asia is a key area to study the impact of Cenozoic climate cooling on continental ecosystems. One of the best places to search for rather continuous paleontological records is the Valley of Lakes in Mongolia with its outstandingly fossil-rich Oligocene and Miocene terrestrial sediments. Here, we investigate the response by mammal communities during the early stage of Earth’s icehouse climate in Central Asia. Based on statistical analyses of occurrence and abundance data of 18608 specimens representing 175 mammal species and geochemical (carbon isotopes) and geophysical (magnetic susceptibility) data we link shifts in diversities with major climatic variations. Our data document for the first time that the post-Eocene aridification of Central Asia happened in several steps, was interrupted by short episodes of increased precipitation, and was not a gradual process. We show that the timing of the major turnovers in Oligocene mammal communities is tightly linked with global climate events rather than slow tectonics processes. The most severe decline of up 48% of total diversity is related to aridification during the maximum of the Late Oligocene Warming at 25 Ma. Its magnitude was distinctly larger than the community turnover linked to the mid-Oligocene Glacial Maximum.
Coupled multiple-mode theory for s± pairing mechanism in iron based superconductors
Authors: Kiselev M. N. , Efremov D. V. , Drechsler S. L. , van den Brink Jeroen , Kikoin K. 
Published: November 2016

AbstractWe investigate the interplay between the magnetic and the superconducting degrees of freedom in unconventional multi-band superconductors such as iron pnictides. For this purpose a dynamical mode-mode coupling theory is developed based on the coupled Bethe-Salpeter equations. In order to investigate the region of the phase diagram not too far from the tetracritical point where the magnetic spin density wave, (SDW) and superconducting (SC) transition temperatures coincide, we also construct a Ginzburg-Landau functional including both SC and SDW fluctuations in a critical region above the transition temperatures. The fluctuation corrections tend to suppress the magnetic transition, but in the superconducting channel the intraband and interband contribution of the fluctuations nearly compensate each other.
On-site Rapid Diagnosis of Intracranial Hematoma using Portable Multi-slice Microwave Imaging System
Authors: Mobashsher Ahmed Toaha , Abbosh A. M. 
Published: November 2016

AbstractRapid, on-the-spot diagnostic and monitoring systems are vital for the survival of patients with intracranial hematoma, as their conditions drastically deteriorate with time. To address the limited accessibility, high costs and static structure of currently used MRI and CT scanners, a portable non-invasive multi-slice microwave imaging system is presented for accurate 3D localization of hematoma inside human head. This diagnostic system provides fast data acquisition and imaging compared to the existing systems by means of a compact array of low-profile, unidirectional antennas with wideband operation. The 3D printed low-cost and portable system can be installed in an ambulance for rapid on-site diagnosis by paramedics. In this paper, the multi-slice head imaging system’s operating principle is numerically analysed and experimentally validated on realistic head phantoms. Quantitative analyses demonstrate that the multi-slice head imaging system is able to generate better quality reconstructed images providing 70% higher average signal to clutter ratio, 25% enhanced maximum signal to clutter ratio and with around 60% hematoma target localization compared to the previous head imaging systems. Nevertheless, numerical and experimental results demonstrate that previous reported 2D imaging systems are vulnerable to localization error, which is overcome in the presented multi-slice 3D imaging system. The non-ionizing system, which uses safe levels of very low microwave power, is also tested on human subjects. Results of realistic phantom and subjects demonstrate the feasibility of the system in future preclinical trials.
Chemical induction of hairpin RNAi molecules to silence vital genes in plant roots
Authors: Liu Siming , Yoder John I. 
Published: November 2016

AbstractUnderstanding the functions encoded by plant genes can be facilitated by reducing transcript levels by hairpin RNA (hpRNA) mediated silencing. A bottleneck to this technology occurs when a gene encodes a phenotype that is necessary for cell viability and silencing the gene inhibits transformation. Here we compared the use of two chemically inducible plant promoter systems to drive hpRNA mediated gene silencing in transgenic, hairy roots. We cloned the gene encoding the Yellow Fluorescence Protein (YFP) into the dexamethasone inducible vector pOpOff2 and into the estradiol induced vector pER8. We then cloned a hpRNA targeting YFP under the regulation of the inducible promoters, transformed Medicago truncatula roots, and quantified YFP fluorescence and mRNA levels. YFP fluorescence was normal in pOpOff2 transformed roots without dexamethasone but was reduced with dexamethasone treatment. Interestingly, dexamethasone removal did not reverse YFP inhibition. YFP expression in roots transformed with pER8 was low even in the absence of inducer. We used the dexamethasone system to silence acetyl-CoA carboxylase gene and observed prolific root growth when this construct was transformed into Medicago until dexamethasone was applied. Our study shows that dexamethasone inducibility can be useful to silence vital genes in transgenic roots.
Thickness Effects for Thermoelectric Property of Antimony Telluride Nanoplatelets via Solvothermal Method
Authors: Yan Xinxin , Zheng Wenwen , Liu Fengming , Yang Shuhua , Wang Ziyu 
Published: November 2016

AbstractNanostructures have the potential to exhibit good thermoelectric properties by tuning and controlling their size and thickness, and the competing electrical and thermal properties can be decoupled by engineering the interface and grain boundary. In the present study, Sb2Te3 nanoplatelets with different sizes were fabricated using a practical solvothermal method. The thickness of the platelets were regulated between sizes of 10 nm and 100 nm, and the opposite edge length was varied between 1 and 10 μm by altering chemical conditions. Consequently, manipulating the grain size made it suitable to benefit the carrier transport and also block phonons for the thin platelets, resulting in a significant decrease in thermal conductivity and simultaneous increase in electrical conductivity. The results showed that the optimized figure of merit ZT, increased from 0.2 to 1.0 for thin samples, providing a comprehensive understanding of size-dependent thermoelectric performance.
Monotreme glucagon-like peptide-1 in venom and gut: one gene – two very different functions
Authors: Tsend-Ayush Enkhjargal , He Chuan , Myers Mark A. , Andrikopoulos Sof , Wong Nicole , Sexton Patrick M. , Wootten Denise , Forbes Briony E. , Grutzner Frank 
Published: November 2016

AbstractThe importance of Glucagon like peptide 1 (GLP-1) for metabolic control and insulin release sparked the evolution of genes mimicking GLP-1 action in venomous species (e.g. Exendin-4 in Heloderma suspectum (gila monster)). We discovered that platypus and echidna express a single GLP-1 peptide in both intestine and venom. Specific changes in GLP-1 of monotreme mammals result in resistance to DPP-4 cleavage which is also observed in the GLP-1 like Exendin-4 expressed in Heloderma venom. Remarkably we discovered that monotremes evolved an alternative mechanism to degrade GLP-1. We also show that monotreme GLP-1 stimulates insulin release in cultured rodent islets, but surprisingly shows low receptor affinity and bias toward Erk signaling. We propose that these changes in monotreme GLP-1 are the result of conflicting function of this peptide in metabolic control and venom. This evolutionary path is fundamentally different from the generally accepted idea that conflicting functions in a single gene favour duplication and diversification, as is the case for Exendin-4 in gila monster. This provides novel insight into the remarkably different metabolic control mechanism and venom function in monotremes and an unique example of how different selective pressures act upon a single gene in the absence of gene duplication.
Fabrication of WS2/GaN p-n Junction by Wafer-Scale WS2 Thin Film Transfer
Authors: Yu Yang , Fong Patrick W. K. , Wang Shifeng , Surya Charles 
Published: November 2016

AbstractHigh quality wafer-scale free-standing WS2 grown by van der Waals rheotaxy (vdWR) using Ni as a texture promoting layer is reported. The microstructure of vdWR grown WS2 was significantly modified from mixture of crystallites with their c-axes both parallel to (type I) and perpendicular to (type II) the substrate to large type II crystallites. Wafer-scale transfer of vdWR grown WS2 onto different substrates by an etching-free technique was demonstrated for the first time that utilized the hydrophobic property of WS2 and hydrophilic property of sapphire. Our results show that vdWR is a reliable technique to obtain type-II textured crystallites in WS2, which is the key factor for the wafer-scale etching-free transfer. The transferred films were found to be free of observable wrinkles, cracks, or polymer residues. High quality p-n junctions fabricated by room-temperature transfer of the p-type WS2 onto an n-type GaN was demonstrated with a small leakage current density of 29.6 μA/cm2 at −1 V which shows superior performances compared to the directly grown WS2/GaN heterojunctions.
Soil respiration and its environmental response varies by day/night and by growing/dormant season in a subalpine forest
Authors: Hu Zongda , Liu Shirong , Liu Xingliang , Fu Liyong , Wang Jingxin , Liu Kuan , Huang Xueman , Zhang Yuandong , He Fei 
Published: November 2016

AbstractComparisons of soil respiration (RS) and its components of heterotrophic (RH) and rhizospheric (RR) respiration during daytime and nighttime, growing (GS) and dormant season (DS), have not being well studied and documented. In this study, we compared RS, RH, RR, and their responses to soil temperature (T5) and moisture (θ5) in daytime vs. nighttime and GS vs. DS in a subalpine forest in 2011. In GS, nighttime RS and RH rates were 30.5 ± 4.4% (mean ± SE) and 30.2 ± 6.5% lower than in daytime, while in DS, they were 35.5 ± 5.5% and 37.3 ± 8.5% lower, respectively. DS RS and RH accounted for 27.3 ± 2.5% and 27.6 ± 2.6% of GS RS and RH, respectively. The temperature sensitivities (Q10) of RS and RH were higher in nighttime than daytime, and in DS than GS, while they all decreased with increase of T5. Soil C fluxes were more responsive to θ5 in nighttime than daytime, and in DS than GS. Our results suggest that the DS and nighttime RS play an important role in regulating carbon cycle and its response to climate change in alpine forests, and therefore, they should be taken into consideration in order to make accurate predictions of RS and ecosystem carbon cycle under climate change scenarios.
The incidence and drug resistance of Clostridium difficile infection in Mainland China: a systematic review and meta-analysis
Authors: Tang Chenjie , Cui Lunbiao , Xu Yuqiao , Xie Le , Sun Pengfei , Liu Chengcheng , Xia Wenying , Liu Genyan 
Published: November 2016

AbstractIt has been widely reported that the incidence and severity ofClostridium difficileinfection (CDI) have increased dramatically in North America and Europe. However, little is known about CDI in Mainland China. In this study, we aimed to investigate the incidence of CDI and the main epidemic and drug-resistant strains ofC. difficilein Mainland China through meta-analysis of related studies published after the year 2010. A total of 51 eligible studies were included. The pooled incidence of toxigenicC. difficileamong patients with diarrhoea was 14% (95% CI = 12–16%). In Mainland China, ST-37 and ST-3 were the most prevalent strains; fortunately, hypervirulent strains, such as ST-1 (BI/NAP1/027) and ST-11 (RT 078), have only occurred sporadically to date. The rates ofC. difficileresistance to ciprofloxacin (98.3%; 95% CI = 96.9–99.7%), clindamycin (81.7%; 95% CI = 76.1–87.3%) and erythromycin (80.2%; 95% CI = 73.5–86.9%) are higher than in other counties; however, none of theC. difficileisolates reported in Mainland China were resistant to metronidazole (n/N = 0/960), vancomycin (n/N = 0/960), tigecycline (n/N = 0/41) or piperacillin/tazobactam(n/N = 0/288).