bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shifting levels of ecological network's analysis reveals different system properties
Authors: Niquil Nathalie , Haraldsson Matilda , Sime-Ngando Télesphore , Huneman Philippe , Borrett Stuart R. 
Published: February 2020

Network analyses applied to models of complex systems generally contain at least three levels of analyses. Whole-network metrics summarize general organizational features (properties or relationships) of the entire network, while node-level metrics summarize similar organization features but consider individual nodes. The network- and node-level metrics build upon the primary pairwise relationships in the model. As with many analyses, sometimes there are interesting differences at one level that disappear in the summary at another level of analysis. We illustrate this phenomenon with ecosystem network models, where nodes are trophic compartments and pairwise relationships are flows of organic carbon, such as when a predator eats a prey. For this demonstration, we analysed a time-series of 16 models of a lake planktonic food web that describes carbon exchanges within an autumn cyanobacteria bloom and compared the ecological conclusions drawn from the three levels of analysis based on inter-time-step comparisons. A general pattern in our analyses was that the closer the levels are in hierarchy (node versus network, or flow versus node level), the more they tend to align in their conclusions. Our analyses suggest that selecting the appropriate level of analysis, and above all regularly using multiple levels, may be a critical analytical decision.
This article is part of the theme issue ‘Unifying the essential concepts of biological networks: biological insights and philosophical foundations'.
Analysing brain networks in population neuroscience: a case for the Bayesian philosophy
Authors: Bzdok Danilo , Floris Dorothea L. , Marquand Andre F. 
Published: February 2020

Network connectivity fingerprints are among today's best choices to obtain a faithful sampling of an individual's brain and cognition. Widely available MRI scanners can provide rich information tapping into network recruitment and reconfiguration that now scales to hundreds and thousands of humans. Here, we contemplate the advantages of analysing such connectome profiles using Bayesian strategies. These analysis techniques afford full probability estimates of the studied network coupling phenomena, provide analytical machinery to separate epistemological uncertainty and biological variability in a coherent manner, usher us towards avenues to go beyond binary statements on existence versus non-existence of an effect, and afford credibility estimates around all model parameters at play which thus enable single-subject predictions with rigorous uncertainty intervals. We illustrate the brittle boundary between healthy and diseased brain circuits by autism spectrum disorder as a recurring theme where, we argue, network-based approaches in neuroscience will require careful probabilistic answers.
This article is part of the theme issue ‘Unifying the essential concepts of biological networks: biological insights and philosophical foundations’.
What drives the assembly of plant-associated protist microbiomes?
Authors: Dumack Kenneth , Feng Kai , Flues Sebastian , Sapp Melanie , Schreiter Susanne , Grosch Rita , Rose Laura , Deng Ye , Smalla Kornelia , Bonkowski Michael 
Published: February 2020

AbstractIn a field experiment we investigated the influence of the environmental filters soil type and plant species identity on rhizosphere community assembly of Cercozoa, a dominant group of (mostly bacterivorous) soil protists. The experiment was set up with two plant species, lettuce and potato, grown in an experimental plot system with three contrasting soils. Plant species (14%) and rhizosphere origin (vs. bulk soil) with 13%, together explained four times more variation in cercozoan beta diversity than the three soil types (7% explained variation in beta diversity). Our results clearly confirm the existence of plant species-specific protist communities. Network analyses of bacteria-Cercozoa rhizosphere communities identified scale-free small world topologies, indicating mechanisms of self-organization. While the assembly of rhizosphere bacterial communities is bottom-up controlled through the resource supply from root (secondary) metabolites, our results support the hypothesis that the net effect may depend on the strength of top-down control by protist grazers. Since grazing of protists has a strong impact on the composition and functioning of bacteria communities, protists expand the repertoire of plant genes by functional traits, and should be considered as ‘protist microbiomes’ in analogy to ‘bacterial microbiomes’.HighlightMicrobiomes of rhizosphere protists are plant species-specific and tightly co-evolving with their bacterial prey, thereby extending and modifying the functional repertoire of the bacterial-plant symbiosis.
Potential T-cell and B-cell Epitopes of 2019-nCoV
Authors: Fast Ethan , Altman Russ B. , Chen Binbin 
Published: February 2020

As of early March, 2019-nCoV has infected more than one hundred thousand people and claimed thousands of lives. 2019-nCoV is a novel form of coronavirus that causes COVID-19 and has high similarity with SARS-CoV. No approved vaccine yet exists for any form of coronavirus. Here we use computational tools from structural biology and machine learning to identify 2019-nCoV T-cell and B-cell epitopes based on viral protein antigen presentation and antibody binding properties. These epitopes can be used to develop more effective vaccines and identify neutralizing antibodies. We identified 405 viral peptides with good antigen presentation scores for both human MHC-I and MHC-II alleles, and two potential neutralizing B-cell epitopes near the 2019-nCoV spike protein receptor binding domain (440-460 and 494-506). Analyzing mutation profiles of 68 viral genomes from four continents, we identified 96 coding-change mutations. These mutations are more likely to occur in regions with good MHC-I presentation scores (p=0.02). No mutations are present near the spike protein receptor binding domain. Based on these findings, the spike protein is likely immunogenic and a potential vaccine candidate. We validated our computational pipeline with SARS-CoV experimental data.Significance StatementThe novel coronavirus 2019-nCoV has affected more than 100 countries and continues to spread. There is an immediate need for effective vaccines that contain antigens which trigger responses from human T-cells and B-cells (known as epitopes). Here we identify potential T-cell epitopes through an analysis of human antigen presentation, as well as B-cell epitopes through an analysis of protein structure. We identify a list of top candidates, including an epitope located on 2019-nCoV spike protein that potentially triggers both T-cell and B-cell responses. Analyzing 68 samples, we observe that viral mutations are more likely to happen in regions with strong antigen presentation, a potential form of immune evasion. Our computational pipeline is validated with experimental data from SARS-CoV.
Effects of substituents on anticancer activity of thiosemicarbazone against MCF-7 human breast cancer cell line
Authors: Sibuh Belay Zeleke , Taneja Pankaj , Khanna Sonia 
Published: February 2020

AbstractBackground/AimBreast cancer is one of the world’s leading cause of deaths in women. This study evaluated the in-vitro anticancer activity of different thiosemicarbazones (HacTSc, HSTsc, 3-MBTSc, 4-NBTSc and 4-HBTSc) against MCF-7 human breast cancer cell line and MCF-10 normal cell.Materials and MethodsThe ligands were prepared and characterized by UV vis, IR,1H NMR. MTT assay was used to determine cell viability. Then data were analyzed using two-way ANOVA with Tukey post-hoc test. Result: The ligands have IC50value ranging from 2.271µg/ml to 7.081µg/ml. Acetone thiosemicarbazone and 3-Methoxybenzaldehyde thiosemicarbazone, were identified as the most potent against MCF-7 breast cancer cells with IC50value of 2.271µg/ml and 2.743µg/ml respectively. Whereas 4-Nitrobenzaldehyde thiosemicarbazone was the least potent. Also, the IC50of the normal MCF-10 cell indicated their activity were selective. Conclusion: The activity of the ligands were dose, position and substituents dependent. Acetone thiosemicarbazone and 3-Methoxybenzaldehyde thiosemicarbazone are promising anticancer agents for further study.
Genomic risk scores for juvenile idiopathic arthritis and its subtypes
Authors: Cánovas Rodrigo , Cobb Joanna , Brozynska Marta , Bowes John , Li Yun R. , Smith Samantha L , Hakonarson Hakon , Thomson Wendy , Ellis Justine , Abraham Gad , Munro Jane , Inouye Michael 
Published: February 2020

AbstractAimsJuvenile idiopathic arthritis (JIA) is an autoimmune disease and a common cause of chronic disability in children. Diagnosis of JIA is based purely on clinical symptoms, leading to treatment delays. Despite JIA having substantial heritability, the construction of genomic risk scores (GRSs) to aid or expedite diagnosis has not been assessed. Here, we generate GRSs for JIA and its subtypes and evaluate their performance.MethodsWe examined three case/control cohorts (UK, US, and Australia) with genome-wide single nucleotide polymorphism (SNP) genotypes. We trained GRSs for JIA and its subtypes using lasso-penalised linear models in cross-validation on the UK cohort, and externally tested in the Australian and US cohorts.ResultsThe JIA GRS alone achieved cross-validated AUC=0.670 in the UK cohort and externally validated AUCs of 0.657 and 0.671 in US-based and Australian cohorts, respectively. In logistic regression of case/control status, the corresponding odds ratios per standard deviation (s.d.) of GRS were 1.831 [1.685-1.991] and 2.008 [1.731-2.345], and were unattenuated by adjustment for sex or the top 10 genetic principal components. Extending our analysis to JIA subtypes revealed that enthesitis-related JIA had both the longest time-to-referral and the subtype GRS with the strongest predictive capacity overall across datasets: AUCs 0.80 in UK; 0.83 Australian; 0.69 US-based. The particularly common oligoarthritis JIA subtype also had a subtype GRS outperformed those for JIA overall, with AUCs of 0.71, 0.75 and 0.77, respectively.ConclusionsA genomic risk score for JIA has potential to augment purely clinical JIA diagnosis protocols, prioritising higher-risk individuals for follow-up and treatment. Consistent with JIA heterogeneity, subtype-specific GRSs showed particularly high performance for enthesitis-related and oligoarthritis JIA.
Differential Disease Severity and Whole Genome Sequence Analysis for Human Influenza A/H1N1pdm Virus in 2015-2016 Influenza Season
Authors: Liu Hsuan , Gong Yu-Nong , Shaw-Saliba Kathryn , Mehoke Thomas , Evans Jared , Liu Zhen-Ying , Lewis Mitra , Sauer Lauren , Thielen Peter , Rothman Richard , Chen Kuan-Fu , Pekosz Andrew 
Published: February 2020

AbstractDuring the 2015-16 winter, the US experienced a relatively mild influenza season compared to Taiwan which had a higher number of total and severe cases. While H1N1pdm viruses dominated global surveillance efforts that season, the global distribution of genetic variants and their contributions to disease severity have not been investigated. Samples collected from influenza A positive patients by the Johns Hopkins Center of Excellence for Influenza Research and Surveillance (JH-CEIRS) active surveillance in the emergency rooms in Baltimore, Maryland, USA and northern Taiwan between November 2015 and April 2016, were processed for influenza A virus whole genome sequencing. In Baltimore, the majority of the viruses were the H1N1pdm clade 6B.1 and no H1N1pdm clade 6B.2 viruses were detected. In northern Taiwan, more than half of the H1N1pdm viruses were clade 6B.1 and 38% were clade 6B.2, consistent with the global observation that most 6B.2 viruses circulated in Asia and not North America. Whole virus genome sequence analysis identified two genetic subgroups present in each of the 6B.1 and 6B.2 clades and one 6B.1 intraclade reassortant virus. Clinical data showed 6B.2 patients had more disease symptoms including higher crude and inverse probability weighted odds of pneumonia than 6B.1 patients, suggesting 6B.2 circulation may contribute to the severe flu season in Taiwan. Local surveillance efforts linking H1N1pdm virus sequences to patient clinical and demographic data improve our understanding of influenza circulation and disease potential.
Human complex exploration strategies are extended via noradrenaline-modulated heuristics
Authors: Dubois M , Habicht J , Michely J , Moran R , Dolan RJ , Hauser TU 
Published: February 2020

AbstractAn exploration-exploitation trade-off, the arbitration between sampling a lesser-known against a known rich option, is thought to be solved using computationally demanding exploration algorithms. Given known limitations in human cognitive resources, we hypothesised the presence of additional cheaper strategies. We examined for such heuristics in choice behaviour where we show this involves a value-free random exploration, that ignores all prior knowledge, and a novelty exploration that targets novel options alone. In a double-blind, placebo-controlled drug study, assessing contributions of dopamine (400mg amisulpride) and noradrenaline (40mg propranolol), we show that value-free random exploration is attenuated under the influence of propranolol, but not under amisulpride. Our findings demonstrate that humans deploy distinct computationally cheap exploration strategies and where value-free random exploration is under noradrenergic control.Data and materials availabilityData and code will be provided upon acceptance.
Loss-of-function myeloperoxidase mutations are associated with increased neutrophil counts and pustular skin disease
Authors: Vergnano Marta , Grys Katarzyna , Benzian-Olsson Natashia , Mahil Satveer K , Chaloner Charlotte , Barbosa Ines A , August Suzannah , Burden A David , Choon Siew-Eng , Cooper Hywel , Reynolds Nick , Wahie Shyamal , Warren Richard B , Wright Andrew ,   The APRICOT and PLUM study team, Huffmeier Ulrike , Baum Patrick , Visvanathan Sudha , Barker Jonathan , Smith Catherine , Capon Francesca 
Published: February 2020

AbstractThe identification of disease alleles underlying human autoinflammatory diseases can provide important insights into the mechanisms that maintain neutrophil homeostasis. Here, we focused on generalized pustular psoriasis (GPP), a potentially life-threatening disorder presenting with cutaneous and systemic neutrophilia. Following the whole exome sequencing of 19 unrelated cases, we identified one affected individual harbouring a homozygous splice-site mutation (c.2031-2A>C) inMPO. The same homozygous change was subsequently identified in a further subject suffering from acral pustular psoriasis, a disease phenotypically related to GPP.MPOencodes myeloperoxidase, an essential component of neutrophil azurophil granules. Of interest, the c.2031-2A>C allele was previously described as a genetic determinant of myeloperoxidase deficiency (MPOD), a condition which can causes recurrent infections. Here, a systematic literature review identified four individuals suffering from MPOD and pustular skin disease, further strengthening the link betweenMPOand pustular inflammation.A subsequent analysis of the UK Biobank cohort demonstrated that the c.2031-2A>C allele was associated with increased neutrophil abundance in the general population (P=5.1×10−6). The same applied to three further MPOD mutations for which genotype data was available, with two alleles generating p-values <10−10. Finally, treatment of healthy neutrophils with an MPO inhibitor reduced cell apoptosis, highlighting a mechanism wherebyMPOmutations affect granulocyte numbers.These findings identifyMPOmutations as genetic determinants of pustular skin disease and neutrophil abundance. Given the recent interest in the development of MPO antagonists for the treatment of neurodegenerative disease, our results also suggest that the pro-inflammatory effects of these agents should be closely monitored.
Efficient Retroelement-Mediated DNA Writing in Bacteria
Authors: Farzadfard Fahim , Gharaei Nava , Citorik Robert J. , Lu Timothy K. 
Published: February 2020

AbstractThe ability to efficiently and dynamically change information stored in genomes would enable powerful strategies for studying cell biology and controlling cellular phenotypes. Current recombineering-mediated DNA writing platforms in bacteria are limited to specific laboratory conditions, often suffer from suboptimal editing efficiencies, and are not suitable forin situapplications. To overcome these limitations, we engineered a retroelement-mediated DNA writing system that enables efficient and precise editing of bacterial genomes without the requirement for target-specific elements or selection. We demonstrate that this DNA writing platform enables a broad range of applications, including efficient, scarless, andcis-element-independent editing of targeted microbial genomes within complex communities, the high-throughput mapping of spatial information and cellular interactions into DNA memory, and the continuous evolution of cellular traits.One Sentence SummaryHighly-efficient, dynamic, and conditional genome writers are engineered for DNA memory, genome engineering, editing microbial communities, high-resolution mapping of cellular connectomes, and modulating cellular evolution.
Telomerase inhibition causes premature senescence of fetal guinea pig muscle cells
Authors: Hallows Stephanie E. , Regnault Timothy R.H. , Betts Dean H. 
Published: February 2020

AbstractPremature senescence in low birth weight rodents is associated with later life metabolic disease, including the development of insulin resistance. Telomerase, a reverse transcriptase enzyme with telomeric and non-telomeric functions, is present at high levels during development to maintain and repair long telomere lengths and to protect cells from oxidative stress-induced growth arrest. AdverseIn uteroenvironments are often associated with increased reactive oxygen species (ROS), and ROS have been documented to impair/alter telomerase function. We postulate that telomerase protects cells against oxidative stress-induced damage, and its inhibition could lead to premature senescence. A primary cell line of fetal guinea pig muscle cells was differentiated under high (20%) and low (1-2%) oxygen concentrations and telomerase activity was pharmacologically inhibited using a synthetic tea catechin. Following 48 hours, ROS detection was conducted with MitoSOX, Mitotracker and 6-carboxy-2’,7’-dichlorodihydrofluorescein diacetate staining. Cells cultured at 20% O2and treated with a telomerase activity inhibitor displayed reduced cell growth rates and increased levels of senescence markers, including p21 and p53. Telomeric DNA damage, measured by phosphorylated-γH2A.X staining at telomeres, was significantly increased in cells cultured at all oxygen concentrations with telomerase inhibition. Telomerase inhibition altered metabolic signaling (e.g. mTOR, p66Shc) and increased mitochondrial ROS levels. Telomerase may protect cells during development from adversein uteroenvironments that cause premature senescence.
Derivation of Airway Basal Stem Cells from Human Pluripotent Stem Cells
Authors: Hawkins Finn J. , Suzuki Shingo , Beermann Mary Lou , Barillà Cristina , Wang Ruobing , Villacorta-Martin Carlos , Berical Andrew , Jean J.C. , Suer Jake Le , Simone-Roach Chantelle , Tang Yang , Schlaeger Thorsten M. , Crane Ana M. , Huang Sarah X. L. , Randell Scott H. , Rab Andras , Sorscher Eric J. , Horani Amjad , Brody Steven L. , Davis Brian R. , Kotton Darrell N. 
Published: February 2020

SummaryThe derivation of self-renewing tissue-specific stem cells from human induced pluripotent stem cells (iPSCs) would shorten the time needed to engineer mature cell typesin vitroand would have broad reaching implications for the field of regenerative medicine. Here we report the directed differentiation of human iPSCs into putative airway basal cells (“iBCs”), a population resembling the epithelial stem cell of lung airways. Using a dual fluorescent reporter system (NKX2-1GFP;TP63tdTomato) we track and purify these cells over time, as they first emerge from iPSC-derived foregut endoderm as developmentally immature NKX2-1GFP+lung progenitors which then augment a TP63 program during subsequent proximal airway epithelial patterning. These cells clonally proliferate, initially as NKX2-1GFP+/TP63tdTomato+immature airway progenitors that lack expression of the adult basal cell surface marker NGFR. However, in response to primary basal cell medium, NKX2-1GFP+/ TP63tdTomato+cells upregulate NGFR and display the molecular and functional phenotype of airway basal stem cells, including the capacity to clonally self-renew or undergo multilineage ciliated and secretory epithelial differentiation in air-liquid interface cultures. iBCs and their differentiated progeny recapitulate several fundamental physiologic features of normal primary airway epithelial cells and model perturbations that characterize acquired and genetic airway diseases. In an asthma model of mucus metaplasia, the inflammatory cytokine IL-13 induced an increase in MUC5AC+ cells similar to primary cells. CFTR-dependent chloride flux in airway epithelium generated from cystic fibrosis iBCs or their syngeneic CFTR-corrected controls exhibited a pattern consistent with the flux measured in primary diseased and normal human airway epithelium, respectively. Finally, multiciliated cells generated from an individual with primary ciliary dyskinesia recapitulated the ciliary beat and ultrastructural defects observed in the donor. Thus, we demonstrate the successfulde novogeneration of a tissue-resident stem cell-like populationin vitrofrom iPSCs, an approach which should facilitate disease modeling and future regenerative therapies for a variety of diseases affecting the lung airways.
Smartphone-based m-shopping behavior and innovative entrepreneurial tendency among women in emerging Asia
Authors: Hossain Syed Far Abid , Nurunnabi Mohammad , Hussain Khalid , Shan Xu 
Published: February 2020

Purpose
This paper aims to explore the ubiquitous role of the smartphone in expanding entrepreneurial opportunity among women in emerging Asia. This study attempted to explore the hidden issues behind increased innovative entrepreneurial tendency.

Design/methodology/approach
This study used a mixed research methodology. First, prior research based on different aspects of entrepreneurial tendency was reviewed in a systematic way. Second, a person-administered survey was conducted based on 265 women who are involved in entrepreneurial activities in different regions in Asia. Structural equation modeling (Amos) is used to analyze the person-administered survey.

Findings
Results show a significant relationship among the independent and dependent variables of the study which indicates a significant entrepreneurship opportunity for women in emerging Asia.

Research limitations/implications
This study was conducted with a limited number of entrepreneurs from a few Asian countries which may affect the generalizability of the result.

Originality/value
This study fulfills the gap in the current literature by analyzing innovativeness in entrepreneurship with the usage of smartphones and increased tendency among women to conduct business.