bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vps34 PI 3-kinase inactivation enhances insulin sensitivity through reprogramming of mitochondrial metabolism
Authors: Bilanges Benoit , Alliouachene Samira , Pearce Wayne , Morelli Daniele , Szabadkai Gyorgy , Chung Yuen-Li , Chicanne Gaëtan , Valet Colin , Hill Julia M. , Voshol Peter J. , Collinson Lucy , Peddie Christopher , Ali Khaled , Ghazaly Essam , Rajeeve Vinothini , Trichas Georgios , Srinivas Shankar , Chaussade Claire , Salamon Rachel S. , Backer Jonathan M. , Scudamore Cheryl L. , Whitehead Maria A. , Keaney Erin P. , Murphy Leon O. , Semple Robert K. , Payrastre Bernard , Tooze Sharon A. , Vanhaesebroeck Bart 
Published: November 2017

AbstractVps34 PI3K is thought to be the main producer of phosphatidylinositol-3-monophosphate, a lipid that controls intracellular vesicular trafficking. The organismal impact of systemic inhibition of Vps34 kinase activity is not completely understood. Here we show that heterozygous Vps34 kinase-dead mice are healthy and display a robustly enhanced insulin sensitivity and glucose tolerance, phenotypes mimicked by a selective Vps34 inhibitor in wild-type mice. The underlying mechanism of insulin sensitization is multifactorial and not through the canonical insulin/Akt pathway. Vps34 inhibition alters cellular energy metabolism, activating the AMPK pathway in liver and muscle. In liver, Vps34 inactivation mildly dampens autophagy, limiting substrate availability for mitochondrial respiration and reducing gluconeogenesis. In muscle, Vps34 inactivation triggers a metabolic switch from oxidative phosphorylation towards glycolysis and enhanced glucose uptake. Our study identifies Vps34 as a new drug target for insulin resistance in Type-2 diabetes, in which the unmet therapeutic need remains substantial.
A very large-scale microelectrode array for cellular-resolution electrophysiology
Authors: Tsai David , Sawyer Daniel , Bradd Adrian , Yuste Rafael , Shepard Kenneth L. 
Published: November 2017

AbstractIn traditional electrophysiology, spatially inefficient electronics and the need for tissue-to-electrode proximity defy non-invasive interfaces at scales of more than a thousand low noise, simultaneously recording channels. Using compressed sensing concepts and silicon complementary metal-oxide-semiconductors (CMOS), we demonstrate a platform with 65,536 simultaneously recording and stimulating electrodes in which the per-electrode electronics consume an area of 25.5 μm by 25.5 μm. Application of this platform to mouse retinal studies is achieved with a high-performance processing pipeline with a 1 GB/s data rate. The platform records from 65,536 electrodes concurrently with a ~10 µV r.m.s. noise; senses spikes from more than 34,000 electrodes when recording across the entire retina; automatically sorts and classifies greater than 1700 neurons following visual stimulation; and stimulates individual neurons using any number of the 65,536 electrodes while observing spikes over the entire retina. The approaches developed here are applicable to other electrophysiological systems and electrode configurations.
Quantitative measurement of post-concussion syndrome Using Electrovestibulography
Authors: Suleiman Abdelbaset , Lithgow Brian , Dastgheib Zeinab , Mansouri Behzad , Moussavi Zahra 
Published: November 2017

AbstractIn this study, a noninvasive quantitative measure was used to identify short and long term post-concussion syndrome (PCS) both from each other and from healthy control populations. We used Electrovestibulography (EVestG) for detecting neurophysiological PCS consequent to a mild traumatic brain injury (mTBI) in both short-term (N = 8) and long-term (N = 30) (beyond the normal recovery period) symptomatic individuals. Peripheral, spontaneously evoked vestibuloacoustic signals incorporating - and modulated by - brainstem responses were recorded using EVestG, while individuals were stationary (no movement stimulus). Tested were 38 individuals with PCS in comparison to those of 33 age-and-gender-matched healthy controls. The extracted features were based on the shape of the averaged extracted field potentials (FPs) and their detected firing pattern. Linear discriminant analysis classification, incorporating a leave-one-out routine, resulted in (A) an unbiased 84% classification accuracy for separating healthy controls from a mix of long and short-term symptomatology PCS sufferers and (B) a 79% classification accuracy for separating between long and short-term symptomatology PCS sufferers. Comparatively, short-term symptomatology PCS was generally detected as more distal from controls. Based on the results, the EVestG recording shows promise as an assistive objective tool for detecting and monitoring individuals with PCS after normal recovery periods.
Hydrogen gas mediates ascorbic acid accumulation and antioxidant system enhancement in soybean sprouts under UV-A irradiation
Authors: Jia Li , Tian Jiyuan , Wei Shengjun , Zhang Xiaoyan , Xu Xuan , Shen Zhenguo , Shen Wenbiao , Cui Jin 
Published: November 2017

AbstractThe soybean sprout is a nutritious and delicious vegetable that is rich in ascorbic acid (AsA). Hydrogen gas (H2) may have potential applications in the vegetable processing industry. To investigate whether H2 is involved in the regulation of soybean sprouts AsA biosynthesis under UV irradiation, we set 4 different treatments: white light(W), W+HRW, UV-A and UV-A+HRW. The results showed that H2 significantly blocked the UV-A-induced accumulation of ROS, decreased TBARS content and enhanced SOD and APX activity in soybean sprouts. We also observed that the UV-A induced accumulation of AsA was enhanced more intensely when co-treated with HRW. Molecular analyses showed that UV-A+HRW significantly up-regulated AsA biosynthesis and recycling genes compared to UV-A in soybean sprouts. These data demonstrate that the H2 positively regulates soybean sprouts AsA accumulation under UV-A and that this effect is mediated via the up-regulation of AsA biosynthesis and recycling genes.
Estimation of the molecular vibration of gases using electron microscopy
Authors: Katsukura Hirotaka , Miyata Tomohiro , Shirai Manabu , Matsumoto Hiroaki , Mizoguchi Teruyasu 
Published: November 2017

AbstractReactions in gaseous phases and at gas/solid interfaces are widely used in industry. Understanding of the reaction mechanism, namely where, when, and how these gaseous reactions proceed, is crucial for the development of further efficient reaction systems. To achieve such an understanding, it is indispensable to grasp the dynamic behavior of the gaseous molecules at the active site of the chemical reaction. However, estimation of the dynamic behavior of gaseous molecules in specific nanometer-scale regions is always accompanied by great difficulties. Here, we propose a method for the identification of the dynamic behavior of gaseous molecules using an electron spectroscopy observed with a transmission electron microscope in combination with theoretical calculations. We found that our method can successfully identify the dynamic behavior of some gaseous molecules, such as O2 and CH4, and the sensitivity of the method is affected by the rigidity of the molecule. The method has potential to measure the local temperature of gaseous molecules as well. The knowledge obtained from this technique is fundamental for further high resolution studies of gaseous reactions using electron microscopy.
FAD104, a regulator of adipogenesis, is a novel suppressor of TGF-β–mediated EMT in cervical cancer cells
Authors: Goto Motoharu , Osada Shigehiro , Imagawa Masayoshi , Nishizuka Makoto 
Published: November 2017

AbstractEpithelial-to-mesenchymal transition (EMT) is a biological process in which epithelial cells translate into a mesenchymal phenotype with invasive capacities, contributing to tumour progression, metastasis, and the acquisition of chemotherapy resistance. To identify new therapeutic targets for cancers, it is important to clarify the molecular mechanism of induction of EMT. We have previously reported that fad104, a positive regulator of adipocyte differentiation, suppressed the invasion and metastasis of melanoma and breast cancer cells. In this study, we showed that FAD104 functions as a novel suppressor of transforming growth factor-β (TGF-β)–mediated EMT in cervical cancer cells. Expression of FAD104 is upregulated during TGF-β–mediated EMT in human cervical cancer HeLa cells. Reduction of fad104 expression enhanced TGF-β–mediated EMT and migration in HeLa cells. Conversely, overexpression of FAD104 suppressed TGF-β–induced EMT. In addition, we showed that FAD104 negatively regulated phosphorylation of Smad2 and Smad3 but positively regulated phosphorylation of Smad1/5/8 via treatment with TGF-β. These findings demonstrate that FAD104 is a novel suppressor of TGF-β signalling and represses TGF-β–mediated EMT in cervical cancer cells.
In silico-based screen synergistic drug combinations from herb medicines: a case using Cistanche tubulosa
Authors: Liu Jianling , Zhu Jinglin , Xue Jun , Qin Zonghui , Shen Fengxia , Liu Jingjing , Chen Xuetong , Li Xiaogang , Wu Ziyin , Xiao Wei , Zheng Chunli , Wang Yonghua 
Published: November 2017

AbstractNeuroinflammation is characterized by the elaborated inflammatory response repertoire of central nervous system tissue. The limitations of the current treatments for neuroinflammation are well-known side effects in the clinical trials of monotherapy. Drug combination therapies are promising strategies to overcome the compensatory mechanisms and off-target effects. However, discovery of synergistic drug combinations from herb medicines is rare. Encouraged by the successfully applied cases we move on to investigate the effective drug combinations based on system pharmacology among compounds from Cistanche tubulosa (SCHENK) R. WIGHT. Firstly, 63 potential bioactive compounds, the related 133 direct and indirect targets are screened out by Drug-likeness evaluation combined with drug targeting process. Secondly, Compound-Target network is built to acquire the data set for predicting drug combinations. We list the top 10 drug combinations which are employed by the algorithm Probability Ensemble Approach (PEA), and Compound-Target-Pathway network is then constructed by the 12 compounds of the combinations, targets, and pathways to unearth the corresponding pharmacological actions. Finally, an integrating pathway approach is developed to elucidate the therapeutic effects of the herb in different pathological features-relevant biological processes. Overall, the method may provide a productive avenue for developing drug combination therapeutics.
Functional interplay between the transcription factors USF1 and PDX-1 and protein kinase CK2 in pancreatic β-cells
Authors: Spohrer Sarah , Groß Rebecca , Nalbach Lisa , Schwind Lisa , Stumpf Heike , Menger Michael D. , Ampofo Emmanuel , Montenarh Mathias , Götz Claudia 
Published: November 2017

AbstractGlucose homeostasis is regulated by insulin, which is produced in the β-cells of the pancreas. The synthesis of insulin is controlled by several transcription factors including PDX-1, USF1 and USF2. Both, PDX-1 and USF1 were identified as substrates for protein kinase CK2. Here, we have analysed the interplay of PDX-1, USF1 and CK2 in the regulation of PDX-1 gene transcription. We found that the PDX-1 promoter is dose-dependently transactivated by PDX-1 and transrepressed by USF1. With increasing glucose concentrations the transrepression of the PDX-1 promoter by USF1 is successively abrogated. PDX-1 binding to its own promoter was not influenced by glucose, whereas USF1 binding to the PDX-1 promoter was reduced. The same effect was observed after inhibition of the protein kinase activity by three different inhibitors or by using a phospho-mutant of USF1. Moreover, phosphorylation of USF1 by CK2 seems to strengthen the interaction between USF1 and PDX-1. Thus, CK2 is a negative regulator of the USF1-dependent PDX-1 transcription. Moreover, upon inhibition of CK2 in primary islets, insulin expression as well as insulin secretion were enhanced without affecting the viability of the cells. Therefore, inhibition of CK2 activity may be a promising approach to stimulate insulin production in pancreatic β-cells.
Systemic clearance and brain distribution of carbazole-based cyanine compounds as Alzheimer’s disease drug candidates
Authors: Zhou Wei , Hu Xiaohui , Tam Kin Yip 
Published: November 2017

AbstractSLM and SLOH, two analogues of carbazole-based cyanine compounds, have been shown to inhibit β-amyloid peptide aggregation in vitro and in Alzheimer’s disease model mice, which could be potentially developed into drugs for disease treatment. To pave the way for further pharmacokinetics-pharmacodynamics study, we set to investigate these compounds’ systemic clearance pathways and their brain exposure. We found that they generally exhibited relatively low plasma clearance which comprised of hepatic clearance and biliary clearance. Phase I oxidative metabolites for SLM and for SLOH upon microsomes incubation were identified, and the metabolism by CYP3A4 were found to be the major (>70%) hepatic clearance pathway, while the efflux by P-gp and BCRP located in the canalicular membrane of hepatocytes led to high biliary clearance. The permeation of SLM and SLOH through the brain endothelium was affected by the efflux transporters (P-gp and BCRP) and influx transporter (OATP2B1). The unbound interstitial fluid to plasma ratio (Kpuu,brain) was 8.10 for SLOH and 11.0 for SLM, which favored brain entry and were several folds higher than that in wild-type mice. Taken together, these carbazole compounds displayed low plasma clearance and high brain permeability, which entitle further development.
The Relationship between Secondary Forest and Environmental Factors in the Southern Taihang Mountains
Authors: Zhao Hui , Wang Qi-Rui , Fan Wei , Song Guo-Hua 
Published: November 2017

AbstractIt is important to understand the effects of environmental factors on secondary forest assembly for effective afforestation and vegetation restoration. We studied 24 20 m × 20 m quadrats of natural secondary forest in the southern Taihang Mountains. Canonical correspondence analysis (CCA) and two-way indicator hydrocarbon analysis were used to analyse the relationship between community vegetation and environmental factors. The CCA showed that 13 terrain and soil variables shared 68.17% of the total variance. The principal environmental variables, based on the most parsimonious CCA model, were (in order) elevation, soil total N, soil gravel content, slope, soil electrical conductivity, and pH. Samples were clustered into four forest types, with forest diversity affected by elevation, nutrients, and water gradients. Topographical variables affected forest assembly more than soil variables. Species diversity was evaluated using the Shannon–Wiener, Simpson’s diversity, and Pielou’s evenness indexes. The environmental factors that affected species distribution had different effects on species diversity. The vegetation-environment relationship in the southern region was different than the central region of the Taihang Mountains, and vegetation restoration was at an early stage. The terrain of the southern region, especially elevation and slope, should be considered for vegetation restoration and conservation.
Novel Common Variants Associated with Obesity and Type 2 Diabetes Detected Using a cFDR Method
Authors: Zhang Qiang , Wu Ke-Hao , He Jing-Yang , Zeng Yong , Greenbaum Jonathan , Xia Xin , Liu Hui-Min , Lv Wan-Qiang , Lin Xu , Zhang Wei-Dong , Xi Yuan-Lin , Shi Xue-Zhong , Sun Chang-Qing , Deng Hong-Wen 
Published: November 2017

AbstractGenome-wide association studies (GWASs) have been performed extensively in diverse populations to identify single nucleotide polymorphisms (SNPs) associated with complex diseases or traits. However, to date, the SNPs identified fail to explain a large proportion of the variance of the traits/diseases. GWASs on type 2 diabetes (T2D) and obesity are generally focused on individual traits independently, and genetic intercommunity (common genetic contributions or the product of over correlated phenotypic world) between them are largely unknown, despite extensive data showing that these two phenotypes share both genetic and environmental risk factors. Here, we applied a recently developed genetic pleiotropic conditional false discovery rate (cFDR) approach to discover novel loci associated with BMI and T2D by incorporating the summary statistics from existing GWASs of these two traits. Conditional Q-Q and fold enrichment plots were used to visually demonstrate the strength of pleiotropic enrichment. Adopting a cFDR nominal significance level of 0.05, 287 loci were identified for BMI and 75 loci for T2D, 23 of which for both traits. By incorporating related traits into a conditional analysis framework, we observed significant pleiotropic enrichment between obesity and T2D. These findings may provide novel insights into the etiology of obesity and T2D, individually and jointly.
CSA13 inhibits colitis-associated intestinal fibrosis via a formyl peptide receptor like-1 mediated HMG-CoA reductase pathway
Authors: Xu Chunlan , Ghali Sally , Wang Jiani , Shih David Q. , Ortiz Christina , Mussatto Caroline C. , Lee Elaine C. , Tran Diana H. , Jacobs Jonathan P. , Lagishetty Venu , Fleshner Phillip , Robbins Lori , Vu Michelle , Hing Tressia C. , McGovern Dermot P. B , Koon Hon Wai 
Published: November 2017

AbstractMany Crohn’s disease (CD) patients develop intestinal strictures, which are difficult to prevent and treat. Cationic steroid antimicrobial 13 (CSA13) shares cationic nature and antimicrobial function with antimicrobial peptide cathelicidin. As many functions of cathelicidin are mediated through formyl peptide receptor-like 1 (FPRL1), we hypothesize that CSA13 mediates anti-fibrogenic effects via FPRL1. Human intestinal biopsies were used in clinical data analysis. Chronic trinitrobenzene sulfonic acid (TNBS) colitis-associated intestinal fibrosis mouse model with the administration of CSA13 was used. Colonic FPRL1 mRNA expression was positively correlated with the histology scores of inflammatory bowel disease patients. In CD patients, colonic FPRL1 mRNA was positively correlated with intestinal stricture. CSA13 administration ameliorated intestinal fibrosis without influencing intestinal microbiota. Inhibition of FPRL1, but not suppression of intestinal microbiota, reversed these protective effects of CSA13. Metabolomic analysis indicated increased fecal mevalonate levels in the TNBS-treated mice, which were reduced by the CSA13 administration. CSA13 inhibited colonic HMG-CoA reductase activity in an FPRL1-dependent manner. Mevalonate reversed the anti-fibrogenic effect of CSA13. The increased colonic FPRL1 expression is associated with severe mucosal disease activity and intestinal stricture. CSA13 inhibits intestinal fibrosis via FPRL1-dependent modulation of HMG-CoA reductase pathway.
Comparison of graphical optimization or IPSA for improving brachytheraphy plans associated with inadequate target coverage for cervical cancer
Authors: Liu ZhiJie , Liang HuanQing , Wang Xiao , Yang HaiMing , Deng Ye , Luo TingJun , Yang ChaoFeng , Lu Min , Fu QingGuo , Zhu XiaoDong 
Published: November 2017

AbstractMany studies have reported that inverse planning by simulated annealing (IPSA) can improve the quality of brachytherapy plans, and we wanted to examine whether IPSA could improve cervical cancer brachytherapy plans giving D90 < 6 Gy (with 7 Gy per fraction) at our institution. Various IPSA plans involving the tandem and ovoid applicators were developed for 30 consecutive cervical cancer patients on the basis of computed tomography: IPSA1, with a constraint on the maximum dose in the target volume; IPSA1-0, identical to IPSA1 but without a dwell-time deviation constraint; IPSA2, without a constraint on the maximum dose; and IPSA2-0, identical to IPSA2 but without a dwell-time deviation constraint. IPSA2 achieved similar results as graphical optimization, and none of the other IPSA plans was significantly better than graphical optimization. Therefore, other approaches, such as combining interstitial and intracavitary brachytherapy, may be more appropriate for improving the quality of brachytherapy plans associated with inadequate target coverage.
Regulation of human and mouse telomerase genes by genomic contexts and transcription factors during embryonic stem cell differentiation
Authors: Cheng De , Wang Shuwen , Jia Wenwen , Zhao Yuanjun , Zhang Fan , Kang Jiuhong , Zhu Jiyue 
Published: November 2017

AbstractDifferential regulation of telomerase reverse transcriptase (TERT) genes contribute to distinct aging and tumorigenic processes in humans and mice. To study TERT regulation, we generated mouse embryonic stem cell (ESC) lines containing single-copy bacterial artificial chromosome (BAC) reporters, covering hTERT and mTERT genes and their neighboring loci, via recombinase-mediated BAC targeting. ESC lines with chimeric BACs, in which two TERT promoters were swapped, were also generated. Using these chromatinized BACs, we showed that hTERT silencing during differentiation to embryoid bodies (EBs) and to fibroblast-like cells was driven by the human-specific genomic context and accompanied by increases of repressive epigenetic marks, H3K9me3 and H3K27me3, near its promoter. Conversely, the mouse genomic context did not repress TERT transcription until late during differentiation. The hTERT promoter was more active than its mouse counterpart when compared in the same genomic contexts. Mutations of E-box and E2F consensus sites at the promoter had little effect on hTERT transcription in ESCs. However, the mutant promoters were rapidly silenced upon EB differentiation, indicating that transcription factors (TFs) bound to these sites were critical in maintaining hTERT transcription during differentiation. Together, our study revealed a dynamic hTERT regulation by chromatin environment and promoter-bound TFs during ESC differentiation.
The influence of convective blueshift on radial velocities of F, G, and K stars
Authors: Bauer F. F. , Reiners A. , Beeck B. , Jeffers S. V. 
Published: November 2017

Context.Apparent radial velocity (RV) signals induced by stellar surface features such as spots and plages can result in a false planet detection or hide the presence of an orbiting planet. Our ability to detect rocky exoplanets is currently limited by our understanding of such stellar signals.Aims.We model RV variations caused by active regions on the stellar surface of typical exoplanet-hosting stars of spectral type F, G, and K. We aim to understand how the stellar magnetic field strength, convective blueshift, and spot temperatures can influence RV signals caused by active regions.Methods.We use magneto-hydrodynamic (MHD) simulations for stars with spectral types F3V, a G2V, and a K5V. We quantify the impact of the magnetic field strength inside active regions on the RV measurement using the magnetic and non-magnetic FeI lines at 6165 Å and 6173 Å. We also quantify the impact of spot temperature and convective blueshift on the measured RV values.Results.Increasing the magnetic field strength increases the efficiency to suppress convection in active regions which results in an asymmetry between red- and blueshifted parts of the RV curves. A stronger suppression of convection also leads to an observed increase in RV amplitude for stronger magnetic fields. The MHD simulations predict convective motions to be faster in hotter stars. The suppression of faster convection leads to a stronger RV amplitude increase in hotter stars when the magnetic field is increased. While suppression of convection increases the asymmetry in RV curves,c a decreasing spot temperature counteracts this effect. When using observed temperatures for dark spots in our simulations we find that convective blueshift effects are negligible.