bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homozygosity for the WRN Helicase-Inactivating Variant, R834C, does not confer a Werner syndrome clinical phenotype
Authors: Kamath-Loeb Ashwini S. , Zavala-van Rankin Diego G. , Flores-Morales Jeny , Emond Mary J. , Sidorova Julia M. , Carnevale Alessandra , Cárdenas-Cortés Maria del Carmen , Norwood Thomas H. , Monnat Raymond J. , Loeb Lawrence A. , Mercado-Celis Gabriela E. 
Published: March 2017

AbstractLoss-of-function mutations in theWRNhelicase gene cause Werner syndrome- a progeroid syndrome with an elevated risk of cancer and other age-associated diseases. Large numbers of single nucleotide polymorphisms have been identified inWRN. We report here the organismal, cellular, and molecular phenotypes of variant rs3087425 (c. 2500C > T) that results in an arginine to cysteine substitution at residue 834 (R834C) and up to 90% reduction of WRN helicase activity. This variant is present at a high (5%) frequency in Mexico, where we identified 153 heterozygous and three homozygous individuals among 3,130 genotyped subjects. Family studies of probands identified ten additional TT homozygotes. Biochemical analysis of WRN protein purified from TT lymphoblast cell lines confirmed that the R834C substitution strongly and selectively reduces WRN helicase, but not exonuclease activity. Replication track analyses showed reduced replication fork progression in some homozygous cells following DNA replication stress. Among the thirteen TT homozygotes, we identified a previously unreported and statistically significant gender bias in favor of males (p = 0.0016), but none of the clinical findings associated with Werner syndrome. Our results indicate that WRN helicase activity alone is not rate-limiting for the development of clinical WS.
Behavioral responses to noxious stimuli shape the perception of pain
Authors: May Elisabeth S. , Tiemann Laura , Schmidt Paul , Nickel Moritz M. , Wiedemann Nina , Dresel Christian , Sorg Christian , Ploner Markus 
Published: March 2017

AbstractPain serves vital protective functions. To fulfill these functions, a noxious stimulus might induce a percept which, in turn, induces a behavioral response. Here, we investigated an alternative view in which behavioral responses do not exclusively depend on but themselves shape perception. We tested this hypothesis in an experiment in which healthy human subjects performed a reaction time task and provided perceptual ratings of noxious and tactile stimuli. A multi-level moderated mediation analysis revealed that behavioral responses are significantly involved in the translation of a stimulus into perception. This involvement was significantly stronger for noxious than for tactile stimuli. These findings show that the influence of behavioral responses on perception is particularly strong for pain which likely reflects the utmost relevance of behavioral responses to protect the body. These observations parallel recent concepts of emotions and entail implications for the understanding and treatment of pain.
B-Myb Induces APOBEC3B Expression Leading to Somatic Mutation in Multiple Cancers
Authors: Chou Wen-Cheng , Chen Wei-Ting , Hsiung Chia-Ni , Hu Ling-Yueh , Yu Jyh-Cherng , Hsu Huan-Ming , Shen Chen-Yang 
Published: March 2017

AbstractThe key signature of cancer genomes is the accumulation of DNA mutations, the most abundant of which is the cytosine-to-thymine (C-to-T) transition that results from cytosine deamination. Analysis of The Cancer Genome Atlas (TCGA) database has demonstrated that this transition is caused mainly by upregulation of the cytosine deaminase APOBEC3B (A3B), but the mechanism has not been completely characterized. We found that B-Myb (encoded by MYBL2) binds the A3B promoter, causing transactivation, and this is responsible for the C-to-T transitions and DNA hypermutation in breast cancer cells. Analysis of TCGA database yielded similar results, supporting that MYBL2 and A3B are upregulated and putatively promote C-to-T transitions in multiple cancer types. Moreover, blockade of EGF receptor with afatinib attenuated B-Myb–A3B signaling, suggesting a clinically relevant means of suppressing mutagenesis. Our results suggest that B-Myb–A3B contributes to DNA damage and could be targeted by inhibiting EGF receptor.
Vascular transcriptome profiling identifies Sphingosine kinase 1 as a modulator of angiotensin II-induced vascular dysfunction
Authors: Siedlinski Mateusz , Nosalski Ryszard , Szczepaniak Piotr , Ludwig-Gałęzowska Agnieszka H. , Mikołajczyk Tomasz , Filip Magdalena , Osmenda Grzegorz , Wilk Grzegorz , Nowak Michał , Wołkow Paweł , Guzik Tomasz J. 
Published: March 2017

AbstractVascular dysfunction is an important phenomenon in hypertension. We hypothesized that angiotensin II (AngII) affects transcriptome in the vasculature in a region-specific manner, which may help to identify genes related to vascular dysfunction in AngII-induced hypertension. Mesenteric artery and aortic transcriptome was profiled using Illumina WG-6v2.0 chip in control and AngII infused (490 ng/kg/min) hypertensive mice. Gene set enrichment and leading edge analyses identified Sphingosine kinase 1 (Sphk1) in the highest number of pathways affected by AngII. Sphk1 mRNA, protein and activity were up-regulated in the hypertensive vasculature. Chronic sphingosine-1-phosphate (S1P) infusion resulted in a development of significantly increased vasoconstriction and endothelial dysfunction. AngII-induced hypertension was blunted in Sphk1−/− mice (systolic BP 167 ± 4.2 vs. 180 ± 3.3 mmHg, p < 0.05), which was associated with decreased aortic and mesenteric vasoconstriction in hypertensive Sphk1−/− mice. Pharmacological inhibition of S1P synthesis reduced vasoconstriction of mesenteric arteries. While Sphk1 is important in mediating vasoconstriction in hypertension, Sphk1−/− mice were characterized by enhanced endothelial dysfunction, suggesting a local protective role of Sphk1 in the endothelium. S1P serum level in humans was correlated with endothelial function (arterial tonometry). Thus, vascular transcriptome analysis shows that S1P pathway is critical in the regulation of vascular function in AngII-induced hypertension, although Sphk1 may have opposing roles in the regulation of vasoconstriction and endothelium-dependent vasorelaxation.
miR-193a-3p interaction with HMGB1 downregulates human endothelial cell proliferation and migration
Authors: Khoo Cheen P. , Roubelakis Maria G. , Schrader Jack B. , Tsaknakis Grigorios , Konietzny Rebecca , Kessler Benedikt , Harris Adrian L. , Watt Suzanne M. 
Published: March 2017

AbstractCirculating endothelial colony forming cells (ECFCs) contribute to vascular repair where they are a target for therapy. Since ECFC proliferative potential is increased in cord versus peripheral blood and to define regulatory factors controlling this proliferation, we compared the miRNA profiles of cord blood and peripheral blood ECFC-derived cells. Of the top 25 differentially regulated miRNAs selected, 22 were more highly expressed in peripheral blood ECFC-derived cells. After validating candidate miRNAs by q-RT-PCR, we selected miR-193a-3p for further investigation. The miR-193a-3p mimic reduced cord blood ECFC-derived cell proliferation, migration and vascular tubule formation, while the miR-193a-3p inhibitor significantly enhanced these parameters in peripheral blood ECFC-derived cells. Using in silico miRNA target database analyses combined with proteome arrays and luciferase reporter assays of miR-193a-3p mimic treated cord blood ECFC-derived cells, we identified 2 novel miR-193a-3p targets, the high mobility group box-1 (HMGB1) and the hypoxia upregulated-1 (HYOU1) gene products. HMGB1 silencing in cord blood ECFC-derived cells confirmed its role in regulating vascular function. Thus, we show, for the first time, that miR-193a-3p negatively regulates human ECFC vasculo/angiogenesis and propose that antagonising miR-193a-3p in less proliferative and less angiogenic ECFC-derived cells will enhance their vasculo/angiogenic function.
Accumulation of high OPDA level correlates with reduced ROS and elevated GSH benefiting white cell survival in variegated leaves
Authors: Sun Ying-Hsuan , Hung Chiu-Yueh , Qiu Jie , Chen Jianjun , Kittur Farooqahmed S. , Oldham Carla E. , Henny Richard J. , Burkey Kent O. , Fan Longjiang , Xie Jiahua 
Published: March 2017

AbstractVariegated ‘Marble Queen’ (Epipremnum aureum) plant has white (VMW) and green (VMG) sectors within the same leaf. The white sector cells containing undifferentiated chloroplasts are viable, but the underlying mechanism for their survival and whether these white cells would use any metabolites as signal molecules to communicate with the nucleus for maintaining their viability remain unclear. We analyzed and compared phytohormone levels with their precursors produced in chloroplasts between VMW and VMG, and further compared their transcriptomes to understand the consequences related to the observed elevated 12-oxo phytodienoic acid (OPDA), which was 9-fold higher in VMW than VMG. Transcriptomic study showed that a large group of OPDA-responsive genes (ORGs) were differentially expressed in VMW, including stress-related transcription factors and genes for reactive oxygen species (ROS) scavengers, DNA replication and repair, and protein chaperones. Induced expression of these ORGs could be verified in OPDA-treated green plants. Reduced level of ROS and higher levels of glutathione in VMW were further confirmed. Our results suggest that elevated OPDA or its related compounds are recruited by white cells as a signaling molecule(s) to up-regulate stress and scavenging activity related genes that leads to reduced ROS levels and provides survival advantages to the white cells.
Separation of Oligosaccharides from Lotus Seeds via Medium-pressure Liquid Chromatography Coupled with ELSD and DAD
Authors: Lu Xu , Zheng Zhichang , Miao Song , Li Huang , Guo Zebin , Zhang Yi , Zheng Yafeng , Zheng Baodong , Xiao Jianbo 
Published: March 2017

AbstractLotus seeds were identified by the Ministry of Public Health of China as both food and medicine. One general function of lotus seeds is to improve intestinal health. However, to date, studies evaluating the relationship between bioactive compounds in lotus seeds and the physiological activity of the intestine are limited. In the present study, by using medium pressure liquid chromatography coupled with evaporative light-scattering detector and diode-array detector, five oligosaccharides were isolated and their structures were further characterized by electrospray ionization-mass spectrometry and gas chromatography-mass spectrometry.In vitrotesting determined that LOS3-1 and LOS4 elicited relatively good proliferative effects onLactobacillus delbrueckiisubsp.bulgaricus.These results indicated a structure-function relationship between the physiological activity of oligosaccharides in lotus seeds and the number of probiotics applied, thus providing room for improvement of this particular feature. Intestinal probiotics may potentially become a new effective drug target for the regulation of immunity.
Image deformation as a cue to material category judgment
Authors: Kawabe Takahiro , Kogovšek Rok 
Published: March 2017

AbstractHuman observers easily recognize complex natural phenomena, such as flowing water, which often generate highly chaotic dynamic arrays of light on the retina. It has not been clarified how the visual system discerns the source of a fluid flow. Here we show that the magnitude of image deformation caused by light refraction is a critical factor for the visual system to determine the perceptual category of fluid flows. Employing a physics engine, we created computer-rendered scenes of water and hot air flows. For each flow, we manipulated the rendering parameters (distortion factors and the index of refraction) that strongly influence the magnitude of image deformation. The observers rated how strongly they felt impressions of water and hot air in the video clips of the flows. The ratings showed that the water and hot air impressions were positively and negatively related to the magnitude of image deformation. Based on the results, we discuss how the visual system heuristically utilizes image deformation to discern non-rigid materials such as water and hot air flows.
Antimicrobial peptide cWFW kills by combining lipid phase separation with autolysis
Authors: Scheinpflug Kathi , Wenzel Michaela , Krylova Oxana , Bandow Julia E. , Dathe Margitta , Strahl Henrik 
Published: March 2017

AbstractThe synthetic cyclic hexapeptide cWFW (cyclo(RRRWFW)) has a rapid bactericidal activity against both Gram-positive and Gram-negative bacteria. Its detailed mode of action has, however, remained elusive. In contrast to most antimicrobial peptides, cWFW neither permeabilizes the membrane nor translocates to the cytoplasm. Using a combination of proteome analysis, fluorescence microscopy, and membrane analysis we show that cWFW instead triggers a rapid reduction of membrane fluidity both in live Bacillus subtilis cells and in model membranes. This immediate activity is accompanied by formation of distinct membrane domains which differ in local membrane fluidity, and which severely disrupts membrane protein organisation by segregating peripheral and integral proteins into domains of different rigidity. These major membrane disturbances cause specific inhibition of cell wall synthesis, and trigger autolysis. This novel antibacterial mode of action holds a low risk to induce bacterial resistance, and provides valuable information for the design of new synthetic antimicrobial peptides.
Loss of forebrain MTCH2 decreases mitochondria motility and calcium handling and impairs hippocampal-dependent cognitive functions
Authors: Ruggiero Antonella , Aloni Etay , Korkotian Eduard , Zaltsman Yehudit , Oni-Biton Efrat , Kuperman Yael , Tsoory Michael , Shachnai Liat , Levin-Zaidman Smadar , Brenner Ori , Segal Menahem , Gross Atan 
Published: March 2017

AbstractMitochondrial Carrier Homolog 2 (MTCH2) is a novel regulator of mitochondria metabolism, which was recently associated with Alzheimer’s disease. Here we demonstrate that deletion of forebrain MTCH2 increases mitochondria and whole-body energy metabolism, increases locomotor activity, but impairs motor coordination and balance. Importantly, mice deficient in forebrain MTCH2 display a deficit in hippocampus-dependent cognitive functions, including spatial memory, long term potentiation (LTP) and rates of spontaneous excitatory synaptic currents. Moreover, MTCH2-deficient hippocampal neurons display a deficit in mitochondria motility and calcium handling. Thus, MTCH2 is a critical player in neuronal cell biology, controlling mitochondria metabolism, motility and calcium buffering to regulate hippocampal-dependent cognitive functions.
Safety and efficacy of minimal biliary sphincterotomy with papillary balloon dilation (m-EBS+EPBD) in patients using clopidogrel or anticoagulation
Authors: Mok Shaffer , Arif Murtaza , Diehl David , Khara Harshit , Ho Henry , Elfant Adam 
Published: March 2017

Abstract
Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic biliary sphincterotomy (EBS) or endoscopic papillary balloon dilation (EPBD) are common techniques of biliary decompression. Potential risks include gastrointestinal hemorrhage, which can be increased by antiplatelet agents, anticoagulants (AC) and/or novel oral anticoagulants (NOACs) (ie. apixaban, dabigatran and rivaroxaban). The study aim is to evaluate the safety/efficacy of an alternative technique, minimal-EBS plus EPBD (m-EBS + EPBD), in individuals for whom clopidogrel, AC, and/or NOACs cannot be interrupted due to high cardiovascular or thromboembolic risk.
Patients and methods Patients undergoing m-EBS + EPBD while taking clopidogrel and/or AC were retrospectively evaluated at two United States tertiary care centers for efficacy, GIB and procedure-related, cardiovascular and thromboembolic adverse events (AE).
Results Ninety-five patients were identified [55 = clopidogrel and 45 = AC (31.1 % NOACs)]. The main indication for ERCP was choledocholithiasis (34 %). 100 % clinical improvement and 97.9 % endoscopic success were found. The incidence of AE was 5.3 %. There was a 4.2 % incidence of gastrointestinal hemorrhage (2 cases requiring endoscopic intervention). Both severe gastrointestinal hemorrhages also experienced the cases of post-ERCP pancreatitis, and 2 /3 of cholangitis (all aspirin + AC). There was 1cardiovascular event (non-ST elevation myocardial infarction), and no thromboembolic events.
Conclusions Minimal-EBS + EPBD is an effective and safe therapy with an incidence of gastrointestinal hemorrhage of 4.2 %, (2.1 % requiring endoscopic intervention), for patients on clopidogrel and/or AC, with a high risk for cardiovascular/thromboembolic events.
Bioactivity studies of Huh-7 cells derived human epidermal growth factor expressed in Pichia pastoris
Authors: Khan Mohsin Ahmad , Ahmed Nadeem , Khan Muhammad Islam , Zafar Ahmad Usman , Tahir Saad , Anjum Muhammad Sohail , Ali Muhammad , Khan Faidad , Husnain Tayyab 
Published: March 2017

Abstract
Previously, we have reported cloning of human epidermal growth factor gene from Huh-7 cells and its extracellular expression in Pichia pastoris. The presented work is a detailed report regarding molecular characterization of Huh-7 cells-derived hEGF expressed in Pichia pastoris with special reference to its glycosylation profiling and bioactivity studies. Densitometric scanning of SDS-PAGE separated extracellular proteins from hEGF recombinant Pichia pastoris strain indicated that about 84% of the extracellular proteins were glycosylated. Size exclusion chromatography using Superdex 75 prep grade column was successfully utilized to separate fractions containing glycosylated and non-glycosylated extracellular proteins. In dot blot assay, hEGF was detected in both glycosylated and non-glycosylated fractions. Bioactivity assays revealed that both glycosylated and non-glycosylated fractions were bioactive as determined by cell viability assay. It was also observed that hEGF present in non-glycosylated fraction was relatively more bioactive than hEGF present in glycosylated fraction.
A Zoom-Focus algorithm (ZFA) to locate the optimal testing region for rare variant association tests
Authors: Wang Maggie Haitian , Weng Haoyi , Sun Rui , Lee Jack , Wu William Ka Kei , Chong Ka Chun , Zee Benny Chung-Ying 
Published: March 2017

Abstract

Motivation
Increasing amounts of whole exome or genome sequencing data present the challenge of analysing rare variants with extremely small minor allele frequencies. Various statistical tests have been proposed, which are specifically configured to increase power for rare variants by conducting the test within a certain bin, such as a gene or a pathway. However, a gene may contain from several to thousands of markers, and not all of them are related to the phenotype. Combining functional and non-functional variants in an arbitrary genomic region could impair the testing power.

Results
We propose a Zoom-Focus algorithm (ZFA) to locate the optimal testing region within a given genomic region. It can be applied as a wrapper function in existing rare variant association tests to increase testing power. The algorithm consists of two steps. In the first step, Zooming, a given genomic region is partitioned by an order of two, and the best partition is located. In the second step, Focusing, the boundaries of the zoomed region are refined. Simulation studies showed that ZFA substantially increased the statistical power of rare variants’ tests, including the SKAT, SKAT-O, burden test and the W-test. The algorithm was applied on real exome sequencing data of hypertensive disorder, and identified biologically relevant genetic markers to metabolic disorders that were undetectable by a gene-based method. The proposed algorithm is an efficient and powerful tool to enhance the power of association study for whole exome or genome sequencing data.

Availability and Implementation
The ZFA software is available at: http://www2.ccrb.cuhk.edu.hk/statgene/software.html

Supplementary information
Supplementary data are available at Bioinformatics online.
DNA Compass: a secure, client-side site for navigating personal genetic information
Authors: Curnin Charles , Gordon Assaf , Erlich Yaniv 
Published: March 2017

Abstract

Motivation
Millions of individuals have access to raw genomic data using direct-to-consumer companies. The advent of large-scale sequencing projects, such as the Precision Medicine Initiative, will further increase the number of individuals with access to their own genomic information. However, querying genomic data requires a computer terminal and computational skill to analyze the data—an impediment for the general public.

Results
DNA Compass is a website designed to empower the public by enabling simple navigation of personal genomic data. Users can query the status of their genomic variants for over 1658 markers or tens of millions of documented single nucleotide polymorphisms (SNPs). DNA Compass presents the relevant genotypes of the user side-by-side with explanatory scientific resources. The genotype data never leaves the user’s computer, a feature that provides improved security and performance. More than 12 000 unique users, mainly from the general genetic genealogy community, have already used DNA Compass, demonstrating its utility.

Availability and Implementation
DNA Compass is freely available on https://compass.dna.land.
Estimating gene regulatory networks with pandaR
Authors: Schlauch Daniel , Paulson Joseph N , Young Albert , Glass Kimberly , Quackenbush John 
Published: March 2017

Abstract
PANDA (Passing Attributes between Networks for Data Assimilation) is a gene regulatory network inference method that begins with a model of transcription factor–target gene interactions and uses message passing to update the network model given available transcriptomic and protein–protein interaction data. PANDA is used to estimate networks for each experimental group and the network models are then compared between groups to explore transcriptional processes that distinguish the groups. We present pandaR (bioconductor.org/packages/pandaR), a Bioconductor package that implements PANDA and provides a framework for exploratory data analysis on gene regulatory networks.
Availability and Implementation: PandaR is provided as a Bioconductor R Package and is available at bioconductor.org/packages/pandaR.
Underestimated Health Inequalities Among Older People—A Consequence of Excluding the Most Disabled and Disadvantaged
Authors: Kelfve Susanne 
Published: March 2017

Abstract

Objectives
The present study analyzed whether estimates of health inequalities in old age are sensitive to the exclusion of people living in institutions and nonuse of proxy interviews.

Method
Pooled data from the 2004 wave (n = 1,180, aged 69–100, primarily interviewed over the phone) and the 2011 wave (n = 931, aged 76–101, primarily interviewed face-to-face) of the Swedish Panel Study of Living Conditions of the Oldest Old were used to compare absolute and relative differences in disability and mortality between people with compulsory education and people with more than compulsory education.

Results
Both absolute and relative health inequalities would have been underestimated in a survey that excluded institutionalized people and proxy-interviewed community dwellers. The same patterns were found in men and women and regardless of the mode of data collection (telephone or face-to-face interview). The degree of underestimation was lower in those 85 years and older than in those 69 to 84 years.

Discussion
A survey that only includes people who live in the community and can participate without the help of a proxy might give the impression that those with low levels of education have less extensive health disadvantages than they actually have.