bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation guided Network Integration (CoNI) reveals novel genetic regulators of hepatic metabolism
Authors: Klaus Valentina S. , Schriever Sonja C. , Peter Andreas , Monroy Kuhn José Manuel , Irmler Martin , Tokarz Janina , Prehn Cornelia , Kastenmüller Gabi , Beckers Johannes , Adamski Jerzy , Königsrainer Alfred , Müller Timo D. , Heni Martin , Tschöp Matthias H. , Pfluger Paul T. , Lutter Dominik 
Published: January 2020

ABSTRACTThe steadily increasing amount of newly generated omics data of various types from genomics to metabolomics is a chance and a challenge to systems biology. To fully use its potential, one key is the meaningful integration of different types of omics. We here present a fully unsupervised and versatile correlation-based method, termed Correlation guided Network Integration (CoNI), to integrate multi-omics data into a hypergraph structure that allows for identification of effective regulators. Our approach further unravels single transcripts mapped to specific densely connected metabolic sub-graphs or pathways. By applying our method on transcriptomics and metabolomics data from murine livers under standard chow or high-fat-diet, we isolated eleven genes with a regulatory effect on hepatic metabolism. Subsequentin vitroandex vivoexperiments in human liver cells and human obtained liver biopsies validated seven candidates includingINHBEandCOBLL1, to alter lipid metabolism and to correlate with diabetes related traits such as overweight, hepatic fat content and insulin resistance (HOMA-IR). Last, we successfully applied our methods to an independent data-set to confirm its versatile and transferable character.
Spatial distribution and hotspots of mammals in Canada
Authors: Cameron Victor , Hargreaves Anna L. 
Published: January 2020

AbstractHigh-latitude countries often contain the polar range edge of species that are common farther south. The more peripherally a species occurs in a country, the smaller its national range will be and the more its national range will consist of range-edge populations, which are often predicted to be relatively small, isolated, and unproductive. Together, this may focus national conservation efforts toward peripheral species whose global conservation value is controversial. However, if range-edge taxa occur where overall diversity is also high, there would be fewer trade-offs in protecting them. Using 153 of the 158 terrestrial mammal species in Canada, we tested how species’ distributions relate to their national conservation status and total mammal richness. Half of ‘Canadian’ mammals had <20% of their global range in Canada. Range area in Canada was strongly associated with national threat status; mammals considered ‘at-risk’ in Canada had 42% smaller Canadian ranges than mammals considered secure. However, after accounting for range area, being more peripheral (smaller proportion of global range in Canada) did not increase the likelihood that a taxon was considered at-risk. We overlaid the 153 maps to calculate mammal diversity across Canada, divided into 100×100 km grid cells. We found that hotspots of at-risk mammals (cells with >4 at-risk taxa) and hotspots of range-edge mammals (cells with >12 taxa with ≤20% of their range in Canada) were about twice as species rich as non-hotspot cells, containing up to 44% of Canadian mammal diversity per grid-cell. Our results suggest that protecting areas with the most at-risk or range-edge mammals would simultaneously protect habitat for many species currently deemed secure.
mSWI/SNF promotes polycomb repression both directly and through genome-wide redistribution
Authors: Weber Christopher M. , Hafner Antonina , Braun Simon M. G. , Kirkland Jacob G. , Stanton Benjamin Z. , Boettiger Alistair N. , Crabtree Gerald R. 
Published: January 2020

AbstractThe mammalian SWI/SNF, or BAF complex, has a conserved and direct role in antagonizing polycomb-mediated repression. Yet, BAF appears to also promote repression by polycomb in stem cells and cancer. How BAF both antagonizes and promotes polycomb-mediated repression remains unknown. Here, we utilize targeted protein degradation to dissect the BAF-polycomb axis in embryonic stem cells on the timescale of hours. We report that rapid BAF depletion redistributes both PRC1 and PRC2 complexes from highly occupied domains, likeHoxclusters, to weakly occupied sites that are normally opposed by BAF. Polycomb redistribution from highly repressed domains results in their decompaction, gain of active epigenomic features, and transcriptional derepression. Surprisingly, through dose-dependent degradation of PRC1 & PRC2 we identify both a conventional role for BAF in polycomb-mediated repression and a second mechanism acting by global redistribution of polycomb. These findings provide new mechanistic insight into the highly dynamic state of the Polycomb-Trithorax axis.
Early detection of biomarkers for circulating tumor cells in Bone marrow and Peripheral blood in a fast-progressing gastric cancer model
Authors: Bali Prerna , Lozano-Pope Ivonne , Pachow Collin , Obonyo Marygorret 
Published: January 2020

AbstractHelicobacter pyloriposes one of the greatest risks for development of gastric cancer. We previously established a crucial role for myeloid differentiation primary response 88 (MyD88) in the regulation ofHelicobacter-induced gastric cancer. Mice deficient inMyd88rapidly progressed to neoplasia when infected withH. felis, a close relative ofH. pylori. For this study we examined circulating tumor cells (CTCs) by measuring expression of cytokeratins, epithelial to mesenchymal transition (EMT) and cancer stem cell (CSC) markers in in the bone marrow and peripheral blood of gastric cancer models we termed fast (Myd88-/-)- and slow (WT)-“progressors”. We detected cytokeratins CK8/18 as early as 3 months post infection in the fast “progressors”. In contrast, cytokeratins were not detected in slow “progressor” gastric cancer model even after 7 months post infection. Expression of MUC1 was observed in both bone marrow and peripheral blood at different time points suggesting its role in gastric cancer metastasis. Snail, Twist and ZEB were expressed at different levels in bone marrow and peripheral blood. Expression of these EMT markers suggests manifestation of cancer metastasis in the early stages of disease development. Lgr5, CD44 and CD133 were the most prominent CSC markers detected. Detection of CSC and EMT markers along with cytokeratins does reinforce their use as biomarkers for gastric cancer metastasis. This early detection of markers suggests that CTCs leave primary site even before cancer is well established. Thus, cytokeratins, EMT, and CSCs could be used as biomarkers to detect aggressive forms of gastric cancers. This information will be important in stratifying patients for treatment before the onset of severe disease characteristics.
Family History Assessment Significantly Enhances Delivery of Precision Medicine in the Genomics Era
Authors: Bylstra Yasmin , Lim Weng Khong , Kam Sylvia , Tham Koei Wan , Wu R. Ryanne , Teo Jing Xian , Davila Sonia , Kuan Jyn Ling , Chan Sock Hoai , Bertin Nicolas , Yang ChengXi , Rozen Steve , Teh Bin Tean , Yeo Khung Keong , Cook Stuart Alexander , Orlando Lori A. , Jamuar Saumya Shekhar , Ginsburg Geoffrey S. , Tan Patrick 
Published: January 2020

AbstractBackgroundFamily history has traditionally been an essential part of clinical care to assess health risks. However, declining sequencing costs have precipitated a shift towards genomics-first approaches in population screening programs, with less emphasis on family history assessment. We evaluated the utility of family history for genomic sequencing selection.MethodsWe analysed whole genome sequences of 1750 healthy research participants, with and without preselection based on standardised family history collection, screening 95 cancer genes.ResultsThe frequency of likely pathogenic/ pathogenic (LP/P) variants in 884 participants with no family history available (FH not available group) (2%) versus 866 participants with family history available (FH available group) (3.1%) was not significant (p=0.158). However, within the FH available group, amongst 73 participants with an increased family history cancer risk (increased FH risk), 1 in 7 participants carried a LP/P variant inferring a six-fold increase compared with 1 in 47 participants assessed at average family history cancer risk (average FH risk) and a seven-fold increase compared to the FH not available group. The enrichment was further pronounced (up to 18-fold) when assessing the 25 cancer genes in the ACMG 59-gene panel. Furthermore, 63 participants had an increased family history cancer risk in absence of an apparent LP/P variant.ConclusionOur findings show that systematic family history collection remains critical for health risk assessment, providing important actionable data and augmenting the yield from genomic data. Family history also highlights the potential impact of additional hereditary, environmental and behavioural influences not reflected by genomic sequencing.
Priming is dispensable for NLRP3 inflammasome activation in human monocytes
Authors: Gritsenko Anna , Yu Shi , Martin-Sanchez Fatima , del Olmo Ines Diaz , Nichols Eva-Maria , Davis Daniel M. , Brough David , Lopez-Castejon Gloria 
Published: January 2020

ABSTRACTInterleukin (IL)-1 family of cytokines modulate immune responses during infection and inflammation. IL-18 and IL-1β are members of the IL-1 family, which contribute to inflammatory conditions such as rheumatoid arthritis and Alzheimer’s disease. IL-18 and IL-1β are produced as inactive precursors that are activated by large macromolecular complexes called inflammasomes upon sensing damage or pathogenic signals. Canonical NLRP3 inflammasome activation is regarded to require a priming step that causes NLRP3 and IL-1β gene upregulation, and also NLRP3 post-translational licencing. A subsequent activation step leads to the assembly of the inflammasome and the cleavage of pro-IL-18 and pro-IL-1β by caspase-1 into their mature forms, allowing their release. Here we show that in primary human monocytes, the initial priming step is dispensable to form an active NLRP3 inflammasome. We found that, in the absence of priming, the NLRP3 activator nigericin caused the processing and release of constitutively expressed IL-18. Another IL-1 family member, IL-37, is constitutively cleaved but the release of its mature form was mediated by inflammasome activation, also in the absence of a priming step. This NLRP3 activation was characterised by ASC oligomerisation as well as caspase-1 and GSDMD cleavage and was blocked by the NLRP3 inhibitor MCC950 and in NLRP3 deficient cells. IL-18 and IL-37 release were impaired in GSDMD deficient THP-1s, suggesting that pyroptosis is required for release of these cytokines. This work highlights the readiness of the NLRP3 inflammasome to assemble in the absence of priming and hence contribute to sterile inflammatory processes in health and disease.Significance StatementThe NLRP3 inflammasome is a driver of inflammation through the processing of Interleukins (IL)-1β and IL-18. Human monocytes coordinate the innate immune response through inflammasome activation following exposure to pathogens and damage signals. We currently think of NLRP3 activation as a 2 step process: priming (NLRP3 gene upregulation and post-translational licencing) and assembly. Here we show that the priming step is dispensable for NLRP3 inflammasome activation in human monocytes. The second signal alone is sufficient for caspase-1 activation, leading to cell death and the release of the constitutively expressed IL-18 and mIL-37. This reveals that in human monocytes, the NLRP3 inflammasome is already licenced and able to quickly assemble to mount an inflammatory response.
A Unified De Novo Approach for Predicting the Structures of Ordered and Disordered Proteins
Authors: Ferrie John J. , Petersson E. James 
Published: January 2020

AbstractAs recognition of the abundance and relevance of intrinsically disordered proteins (IDPs) continues to grow, demand increases for methods that can rapidly predict the conformational ensembles populated by these proteins. To date, IDP simulations have largely been dominated by molecular dynamics (MD) simulations, which require significant compute times and/or complex hardware. Recent developments in MD have afforded methods capable of simulating both ordered and disordered proteins, yet to date accurate fold prediction from sequence has been dominated by Monte-Carlo (MC) based methods such as Rosetta. To overcome the limitations of current approaches in IDP simulation using Rosetta while maintaining its utility for modeling folded domains, we developed PyRosetta-based algorithms that allow for the accuratede novoprediction of proteins across all degrees of foldedness along with structural ensembles of disordered proteins. Our simulations have an accuracy comparable to state-of-the-art MD with vastly reduced computational demands.
A single-cell transcriptome atlas during Cashmere goat hair follicle morphogenesis
Authors: Ge Wei , Zhang Wei-Dong , Zhang Yue-Lang , Zheng Yu-Jie , Li Fang , Wang Shan-He , Liu Jin-Wang , Tan Shao-Jing , Yan Zi-Hui , Wang Lu , Shen Wei , Qu Lei , Wang Xin 
Published: January 2020

AbstractCashmere, also known as soft gold, is produced from the secondary hair follicles in Cashmere goats and it’s therefore of significance to investigate the molecular profiles during Cashmere goat hair follicle development. However, our current understanding of the machinery underlying Cashmere goat hair follicle remains largely unexplored and researches regarding hair follicle development mainly used the mouse as a research model. To provides comprehensively understanding on the cellular heterogeneity and cell lineage cell fate decisions, we performed single-cell RNA sequencing on 19,705 single cells from induction (embryonic day 60), organogenesis (embryonic day 90) and cytodifferentiation (embryonic day 120) stages of fetus Cashmere goat dorsal skin. Unsupervised clustering analysis identified 16 cell clusters and their corresponding cell types were also unprecedentedly characterized. Based on the lineage inference, we revealed detailed molecular landscape along the dermal and epidermal cell lineage developmental pathways. Notably, by cross-species comparasion of single cell data with murine model, we revelaed conserved programs during dermal condensate fate commitment and the heterochrony development of hair follicle development between mouse and Cashmere goat were also discussed here. Our work here delineate unparalleled molecular profiles of different cell populations during Cashmere goat hair follicle morphogenesis and provide a valuable resource for identifying biomarkers during Cashmere goat hair follicle development.
Tumor control via targeting PD-L1 with chimeric antigen receptor modified NK cells
Authors: Robbins Yvette , Greene Sarah , Friedman Jay , Clavijo Paul E. , Van Waes Carter , Fabian Kellsye P. , Padget Michelle R. , Sater Houssein Abdul , Lee John H. , Soon-Shiong Patrick , Gulley James , Schlom Jeffrey , Hodge James W. , Allen Clint T. 
Published: January 2020

AbstractFailed T cell-based immunotherapies in the presence of genomic alterations in antigen presentations pathways may be overcome by NK cell-based immunotherapy. This approach may still be limited by the presence of immunosuppressive myeloid populations. Here we demonstrate that NK cells (haNKs) engineered to express a PD-L1 chimeric antigen receptor (CAR) haNKs killed a panel of human and murine head and neck cancer cells at low effector-to-target ratios in a PD-L1-dependent fashion. Treatment of syngeneic tumors resulted in CD8 and PD-L1-dependent tumor rejection or growth inhibition and a reduction in myeloid cells endogenously expressing high levels of PD-L1. Treatment of xenograft tumors resulted in PD-L1 dependent tumor growth inhibition. PD-L1 CAR haNKs reduced levels of macrophages and other myeloid cells endogenously expressing high PD-L1 in peripheral blood from patients with head and neck cancer. The clinical study of PD-L1 CAR haNKs is warranted.
Effects of scent lure on camera trap detections vary across mammalian predator and prey species
Authors: Holinda Dacyn , Burgar Joanna M. , Burton A. Cole 
Published: January 2020

AbstractCamera traps are a unique survey tool used to monitor a wide variety of mammal species. Camera trap (CT) data can be used to estimate animal distribution, density, and behaviour. Attractants, such as scent lures, are often used in an effort to increase CT detections; however, the degree which the effects of attractants vary across species is not well understood. We investigated the effects of scent lure on mammal detections by comparing detection rates between 404 lured and 440 unlured CT stations sampled in Alberta, Canada over 120 day survey periods between February and August in 2015 and 2016. We used zero-inflated negative binomial generalized linear mixed models to test the effect of lure on detection rates for a) all mammals, b) six functional groups (all predator species, all prey, large carnivores, small carnivores, small mammals, ungulates), and c) four varied species of management interest (fisher,Pekania pennanti; gray wolf,Canis lupus; moose,Alces alces; and Richardson’s ground squirrel;Urocitellus richardsonii). Mammals were detected at 800 of the 844 CTs, with nearly equal numbers of total detections at CTs with (7110) and without (7530) lure, and variable effects of lure on groups and individual species. Scent lure significantly increased detections of predators as a group, including large and small carnivore sub-groups and fisher specifically, but not of gray wolf. There was no effect of scent lure on detections of prey species, including the small mammal and ungulate sub-groups and moose and Richardson’s ground squirrel specifically. We recommend that researchers explicitly consider the variable effects of scent lure on CT detections across species when designing, interpreting, or comparing multi-species surveys. Additional research is needed to further quantify variation in species responses to scent lures and other attractants, and to elucidate the effect of attractants on community-level inferences from camera trap surveys.
The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes
Authors: Zhang Hao , Kang Zijian , Gong Haiyi , Xu Da , Wang Jing , Li Zifu , Cui Xingang , Xiao Jianru , Meng Tong , Zhou Wang , Liu Jianmin , Xu Huji 
Published: January 2020

AbstractSince December 2019, a newly identified coronavirus (2019 novel coronavirus, 2019-nCov) is causing outbreak of pneumonia in one of largest cities, Wuhan, in Hubei province of China and has draw significant public health attention. The same as severe acute respiratory syndrome coronavirus (SARS-CoV), 2019-nCov enters into host cells via cell receptor angiotensin converting enzyme II (ACE2). In order to dissect the ACE2-expressing cell composition and proportion and explore a potential route of the 2019-nCov infection in digestive system infection, 4 datasets with single-cell transcriptomes of lung, esophagus, gastric, ileum and colon were analyzed. The data showed that ACE2 was not only highly expressed in the lung AT2 cells, esophagus upper and stratified epithelial cells but also in absorptive enterocytes from ileum and colon. These results indicated along with respiratory systems, digestive system is a potential routes for 2019-nCov infection. In conclusion, this study has provided the bioinformatics evidence of the potential route for infection of 2019-nCov in digestive system along with respiratory tract and may have significant impact for our healthy policy setting regards to prevention of 2019-nCoV infection.
Study of an aluminium mixing system based on permanent magnets
Authors: Morev Andrey , Aliferov Alexander 
Published: January 2020

Purpose
The purpose of this paper is to investigate the effect of the rotating magnetic field of permanent magnets on the aluminium melt bath.

Design/methodology/approach
This model was developed in the ANSYS software package and is based on the application of the finite element method and finite volume.

Findings
The distribution of the velocity of the melt in a cylindrical vertical bath and the dependence of the maximum value of the melt displacement on the angular rotation velocity of the system of permanent magnets is obtained.

Originality/value
This work focusses on the interaction of the magnetic field of the moving magnets with the molten metal.
100 years multivibrator-history, circuits and mathematical analysis
Authors: Mathis Wolfgang 
Published: January 2020

Purpose
This work is intended to historically commemorate the one hundredth anniversary of the invention of a new type of electronic circuit, referred to in 1919 by Abraham and Bloch as a multivibrator and by Eccles and Jordan as a trigger relay (later known as a flip-flop).

Design/methodology/approach
The author also considers the circuit-technical side of this new type of circuit, considering the technological change as well as the mathematical concepts developed in the context of the analysis of the circuit.

Findings
The multivibrator resulted in a “circuit shape” which became one of the most applied nonlinear circuits in electronics. It is shown that at the beginning the multivibrator as well as the flip-flop circuits were used because their interesting properties in the frequency domain.

Originality/value
Therefore, it is a very interesting subject to consider the history of the multivibrator as electronic circuits in different technologies including tube, transistors and integrated circuits as well as the mathematical theory based on the concept from electrical circuit theory.
Analysis of national human resource development (NHRD) policies of 2016 in South Korea with implications
Authors: Roh Kyungran , Ryu Hyunok , McLean Gary N. 
Published: January 2020

PurposeThe purpose of this study is to explore ways to improve the effectiveness and efficiency of national human resource development (NHRD) policies led by South Korean central government agencies, identifying what policy decisions have been made and how they were implemented.Design/methodology/approachThe authors collected data from the 2016 NHRD policy budget plans of the ministries and used content analysis. The unit of analysis was the fourth level, a sub-task, in each ministry’s policy budget plan. All coded policy contents were analyzed in terms of the centralized NHRD model, as well as through the perspective of developmental task theory.FindingsThe study yielded the following policy and implementation problems. First, the current system of NHRD policies established and implemented by individual ministries risks hampering the validity and effectiveness of the policies. Second, the structure of NHRD policy execution may cause similarity and redundancy across policies, thereby hindering the efficiency of the policies. Third, it is problematic when NHRD policies focus on solving short-term problems to the exclusion of long-term ones.Originality/valueThis study provides public recommendations to improve the effectiveness and efficiency of NHRD policies created by South Korea’s Central Government. If such an analysis has been made internally by the government, it has not been made publicly available. It also offers practical insights that might help to improve state-led human resource development policies for other countries – especially developing countries – that are planning to introduce central government-led NHRD or to improve existing NHRD policies.