bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of chromatin remodeling on gene expression at the single cell level inArabidopsis thaliana
Authors: Farmer Andrew , Thibivilliers Sandra , Ryu Kook Hui , Schiefelbein John , Libault Marc 
Published: July 2020

AbstractSimilar to other complex organisms, plants consist of diverse and highly specialized cell types. The gain of unique biological functions of these different cell types is the consequence of the establishment of cell-type-specific transcriptional programs and their associated regulatory mechanisms. Recently, single cell transcriptomic approaches have been applied onArabidopsis thalianaroot protoplasts allowing the accurate characterization of the transcriptional profiles of the cell-types composing seedling roots. As a first step in gaining a deeper understanding of the regulatory mechanisms controlling Arabidopsis gene expression, we report the use of single nucleus RNA sequencing (sNucRNA-seq) and single nucleus Assay for Transposase Accessible Chromatin sequencing (sNucATAC-seq) technologies on Arabidopsis roots. The comparison of our single nuclei transcriptomes to previously published protoplast transcriptomes validated the use of nuclei as biological entities to establish cell-type specific transcriptomes from multicellular organs. Furthermore, our sNucRNA-seq results uncovered the transcriptome of additional cell subtypes not identified by scRNA-seq. Similar to our transcriptomic approach, the sNucATAC-seq approach led to the distribution of the Arabidopsis nuclei into distinct clusters suggesting the differential remodeling of the chromatin between groups of cells according to their identity. To reveal the impact of chromatin remodeling on gene transcription, we integrated sNucRNA-seq and sNucATAC-seq data and demonstrated that cell-type-specific marker genes also display cell-type-specific pattern of chromatin accessibility. Our data suggest that the differential remodeling of the chromatin is a critical mechanism to regulate gene activity at the cell-type level.
Systemic inflammation causes microglial dysfunction with a mixed AD-like pathology
Authors: Bathini Praveen , Dupanloup Isabel , Zenaro Elena , Terrabuio Eleonora , Fischer Amrei , Ballabani Edona , Doucey Marie-Agnes , Alberi Lavinia 
Published: July 2020

AbstractBackgroundAlzheimer’s disease (AD) is the primary cause of cognitive deficit in elderly humans. Late-onset AD (LOAD) is sporadic, multifactorial, non-Mendelian accounting at present for 95% of the cases in contrast to the genetic form. Risk factors for sporadic AD include Gene: Environment interactions. There is increasing evidence that lifestyle and environmental stress such as infection and chronic inflammation are underlying culprits of neurodegenerative dementia. Dementias that share or mimic pathological processes of AD include cerebrovascular diseases, Lewy body disease, TDP-43 proteinopathy. To date, very few mouse models reproduce the pathophysiological progression of mixed-vascular-AD, while the majority of studies have employed transgenic animals reproducing the familial form.MethodsWe have re-engineered the Polyinosinic:polycytidylic acid (PolyI:C) sterile infection model in wildtype C57Bl6 mice to obtain chronic low-grade systemic inflammation. We have conducted a cross-sectional analysis of aging PolyI:C and Saline control mice (3 months, 6 months, 9 months and 16 months), taking the hippocampus as a reference brain region, based on its vulnerability, and compared the brain aging phenotype to AD progression in humans with mild AD, severe AD and Controls (CTL), parallely in Vascular dementia (VaD) patient specimens.ResultsWe found that PolyI:C mice display both peripheral and central inflammation with a peak at 6 months, associated with memory deficits. The hippocampus is characterized by a pronounced and progressive tauopathy. In PolyI:C brains, microglia undergo aging-dependent morphological rearrangements progressively adopting a phagocytic phenotype. Transcriptomic analysis reveals a profound change in gene expression over the course of aging, with a peak in differential expression at 9 months. We confirm that the proinflammatory markerLcn2is one of the genes with the strongest upregulation in PolyI:C mice upon aging. Validation in brains from patients with increasing severity of AD and VaD shows a reproducibility of some gene targets in vascular dementia specimens rather than AD ones, in which only GFAP is strongly increased at the severe stages.ConclusionsThe PolyI:C model of sterile infection demonstrates that peripheral chronic inflammation is sufficient to cause neuropathological processes resembling a mixed-VaD-AD phenotype, with progressive tau hyperphosphorylation, changes in microglia morphology, astrogliosis and gene reprogramming reflecting increased neuroinflammation, vascular remodeling and the loss of neuronal functionality seen to some extent in humans.
BRN2 and MITF together impact AXL expression in melanoma
Authors: Simmons Jacinta L. , Neuendorf Hannah M. , Boyle Glen M. 
Published: July 2020

AbstractThe inverse relationship between transcription factor MITF and receptor tyrosine kinase AXL has received much attention recently. It is thought that melanoma tumors showing AXLhigh/MITFlowlevels are resistant to therapy. We show here that a population of cells within melanoma tumors with extremely high expression of AXL are negative/low for both MITF and the transcription factor BRN2. Depletion of both transcription factors from cultured melanoma cell lines produced an increase in AXL expression greater than depletion of MITF alone. Further, re-expression of BRN2 led to decreased AXL expression, indicating a role for BRN2 in regulation of AXL levels unrelated to effects on MITF level. As AXL has been recognized as a marker of therapy resistance these cells may represent a population of cells responsible for disease relapse and as potential targets for therapeutic treatment.
Gut Microbiota Changes in Nonalcoholic Fatty Liver Disease and Concomitant Cardiovascular Diseases
Authors: Kurinna Olena H. 
Published: July 2020

AbstractNonalcoholic fatty liver disease (NAFLD) bears serious economic consequences for the health care system worldwide and Ukraine, in particular. Cardiovascular diseases (CVD) are the main cause of mortality in NAFLD patients. Changes in the gut microbiota composition can be regarded as a potential mechanism of CVD in NAFLD patients.The purpose of this work was to investigate changes in major gut microbiota phylotypes,Bacteroidetes, FirmicutesandActinobacteriawith quantification ofFirmicutes/Bacteroidetesin NAFLD patients with concomitant CVD.The author enrolled 120 NAFLD subjects (25 with concomitant arterial hypertension (AH) and 24 with coronary artery disease (CAD)). The gut microbiota composition was assessed by qPCR.Resultsthe author found a marked tendency towards an increase in the concentration ofBacteroidetes(by 37.11% and 21.30%, respectively) with a decrease inFirmicutes(by 7.38% and 7.77%, respectively) in both groups with comorbid CAD and AH with the identified changes not reaching a statistical significance. The author quantified a statistically significant decrease in the concentration ofActinobacteriain patients with NAFLD with concomitant CAD at 41.37% (p<0.05) as compared with those with an isolated NAFLD. In patients with concomitant AH, the content ofActinobacteriadropped by 12.35%, which was statistically insignificant.Conclusionsthe author established changes in the intestinal microbiota, namely decrease inActinobacteriain patients with CAD, which requires further research.
Association between stress and depressive symptoms and the Covid-19 pandemic
Authors: Novotný Jan S. , Gonzalez-Rivas Juan P. , Kunzová Šárka , Skladaná Mária , Pospíšilová Anna , Polcrová Anna , Medina-Inojosa Jose R. , Lopez-Jimenez Francisco , Geda Yonas E. , Stokin Gorazd B. 
Published: July 2020

AbstractObjectiveTo date, cross-sectional surveys reported frequency and distribution of mental health disorders on convenience samples impacted by Covid-19. Longitudinal assessment of mental health during Covid-19 in a representative population-based sample, however, is currently largely missing. The aim of this study was to investigate changes in perceived stress levels and depressive symptoms measured before and during Covid-19 pandemic in a representative population-based sample.MethodsBaseline data on stress levels and depressive symptoms from a well-established population-based sample were compared with those obtained from self-administered e-questionnaires distributed during Covid-19 pandemic. A total of 715 participants completed e-questionnaires. Wilcoxon signed-rank test was used to test repeated-measure differences, while between-group differences were analysed using Mann-Whitney and the Kruskal-Wallis tests.ResultsPerceived stress levels and depressive symptoms increased 1.4 and 5.5 times, respectively, during the Covid-19 pandemic compared to the time prior Covid-19. Changes in stress and depressive symptoms were most significant in females and did not depend on whether one quarantined alone or with others. Feeling of loneliness during Covid-19 pandemic had the greatest impact on increased stress levels and depressive symptoms.ConclusionsThis population-based longitudinal study showed that Covid-19 related measures had significant impact on mental health in a general population with the feeling of loneliness identified as the biggest risk factor. This impact indicates the need of timely and tailored treatment of mental health disorders and integration of preventive mental health measures into global public health policies to protect mental health during future pandemics.
Evaluation of a SARS-CoV-2 surrogate virus neutralization test for detection of antibody in human, canine, cat and hamster sera
Authors: Perera Ranawaka APM , Ko Ronald , Tsang Owen TY , Brackman Christopher J , To Esther M. W. , Yen Hui-ling , Leung Kathy , Cheng Samuel MS , Chan Kin Ho , Chan Karl CK , Li Ka-Chi , Saif Linda , Barrs Vanessa R. , Wu Joseph T , Sit Thomas H. C. , Poon Leo LM , Peiris Malik 
Published: July 2020

AbstractSurrogate neutralization assays for SARS-CoV-2 that can be done without biosafety-level-3 containment and across multiple species are desirable. We evaluate a recently developed surrogate virus neutralization test (sVNT) in comparison to 90% plaque reduction neutralization tests (PRNT90) in human, canine, cat and hamster sera and found excellent concordance between the two assays. Using a panel of immune sera to other coronaviruses, we confirm the lack of cross reactivity in sVNT and PRNT90 assays.
Comparative Analysis of Human Coronaviruses Focusing on Nucleotide Variability and Synonymous Codon Usage Pattern
Authors: Das Jayanta Kumar , Roy Swarup 
Published: July 2020

AbstractPrevailing pandemic across the world due to SARSCoV-2 drawing great attention towards discovering its evolutionary origin. We perform an exploratory study to understand the variability of the whole coding region of possible proximal evolutionary neighbours of SARSCoV-2. We consider seven (07) human coronavirus strains from six different species as a candidate for our study.First, we observe a good variability of nucleotides across candidate strains. We did not find a significant variation of GC content across the strains for codon position first and second. However, we interestingly see huge variability of GC-content in codon position 3rd (GC3), and pairwise mean GC-content (SARSCoV, MERSCoV), and (SARSCoV-2, hCoV229E) are quite closer. While observing the relative abundance of dinucleotide feature, we find a shared typical genetic pattern, i.e., high usage of GC and CT nucleotide pair at the first two positions (P12) of codons and the last two positions (P23) of codons, respectively. We also observe a low abundance of CG pair that might help in their evolution bio-process. Secondly, Considering RSCU score, we find a substantial similarity for mild class coronaviruses, i.e., hCoVOC43, hCoVHKU1, and hCoVNL63 based on their codon hit with high RSCU value (≥ 1.5), and minim number of codons hit (count-9) is observed for MERSCoV. We see seven codons ATT, ACT, TCT, CCT, GTT, GCT and GGT with high RSCU value, which are common in all seven strains. These codons are mostly from Aliphatic and Hydroxyl amino acid group. A phylogenetic tree built using RSCU feature reveals proximity among hCoVOC43 and hCoV229E (mild). Thirdly, we perform linear regression analysis among GC content in different codon position and ENC value. We observe a strong correlation (significant p-value) between GC2 and GC3 for SARSCoV-2, hCoV229E and hCoVNL63, and between GC1 and GC3 for hCoV229E, hCoVNL63, SARSCoV. We believe that our findings will help in understanding the mechanism of human coronavirus.
Disentangling Conditional Effects of Multiple Regime Shifts on Atlantic Cod Productivity
Authors: Perälä Tommi , Olsen Esben M. , Hutchings Jeffrey A. 
Published: July 2020

AbstractRegime shifts are increasingly prevalent in the ecological literature. However, definitions vary, and many detection methods are subjective. Here, we employ an operationally objective means of identifying regime shifts, using a Bayesian online change-point detection algorithm able to simultaneously identify shifts in the mean and(or) variance of time series data. We detected multiple regime shifts in long-term (59-154 years) patterns of coastal Norwegian Atlantic cod (>70% decline) and putative drivers of cod productivity: North Atlantic Oscillation (NAO); sea-surface temperature; zooplankton abundance; fishing mortality (F). The consequences of an environmental or climate-related regime shift on cod productivity are accentuated when regime shifts coincide, fishing mortality is high, and populations are small. The analyses suggest that increasingFincreasingly sensitized cod in the mid 1970s and late 1990s to regime shifts in NAO, zooplankton abundance, and water temperature. Our work underscores the necessity of accounting for human-induced mortality in regime shift analyses of marine ecosystems.
The impact of different negative training data on regulatory sequence predictions
Authors: Krützfeldt Louisa-Marie , Schubach Max , Kircher Martin 
Published: July 2020

AbstractRegulatory regions, like promoters and enhancers, cover an estimated 5-15% of the human genome. Changes to these sequences are thought to underlie much of human phenotypic variation and a substantial proportion of genetic causes of disease. However, our understanding of their functional encoding in DNA is still very limited. Applying machine or deep learning methods can shed light on this encoding and gapped k-mer support vector machines (gkm-SVMs) or convolutional neural networks (CNNs) are commonly trained on putative regulatory sequences.Here, we investigate the impact of negative sequence selection on model performance. By training gkm-SVM and CNN models on open chromatin data and corresponding negative training dataset, both learners and two approaches for negative training data are compared. Negative sets use either genomic background sequences or sequence shuffles of the positive sequences. Model performance was evaluated on three different tasks: predicting elements active in a cell-type, predicting cell-type specific elements, and predicting elements’ relative activity as measured from independent experimental data.Our results indicate strong effects of the negative training data, with genomic backgrounds showing overall best results. Specifically, models trained on highly shuffled sequences perform worse on the complex tasks of tissue-specific activity and quantitative activity prediction, and seem to learn features of artificial sequences rather than regulatory activity. Further, we observe that insufficient matching of genomic background sequences results in model biases. While CNNs achieved and exceeded the performance of gkm-SVMs for larger training datasets, gkm-SVMs gave robust and best results for typical training dataset sizes without the need of hyperparameter optimization.
Crystal structure of schizorhodopsin reveals mechanism of inward proton pumping
Authors: Higuchi Akimitsu , Shihoya Wataru , Konno Masae , Ikuta Tatsuya , Kandori Hideki , Inoue Keiichi , Nureki Osamu 
Published: July 2020

AbstractSchizorhodopsins (SzRs), a new rhodopsin family identified in Asgard archaea, are phylogenetically located at an intermediate position between type-1 microbial rhodopsins and heliorhodopsins. SzRs reportedly work as light-driven inward H+pumps, as xenorhodopsin. Here we report the crystal structure of SzR AM_5_00977 at 2.1 Å resolution. The SzR structure superimposes well on that of bacteriorhodopsin rather than heliorhodopsin, suggesting that SzRs are classified with type-1 rhodopsins. The structure-based mutagenesis study demonstrated that the residues N100 and V103 are essential for color tuning in SzRs. The cytoplasmic parts of transmembrane helices 2, 6, and 7 in SzR are shorter than those in the other microbial rhodopsins. Thus, E81 is located near the cytosol, playing a critical role in the inward H+release. We suggested the H+is not metastably trapped in E81 and released through the water-mediated transport network from the retinal Schiff base to the cytosol. Moreover, most residues on the H+transport pathway are not conserved between SzRs and xenorhodopsins, suggesting that they have entirely different inward H+release mechanisms.
Leveraging phenotypic variability to identify genetic interactions in human phenotypes
Authors: Marderstein Andrew R. , Davenport Emily , Kulm Scott , Van Hout Cristopher V. , Elemento Olivier , Clark Andrew G. 
Published: July 2020

AbstractWhile thousands of loci have been associated with human phenotypes, the role of gene-environment (GxE) interactions in determining individual risk of human diseases remains unclear. This is partly due to the severe erosion of statistical power resulting from the massive number of statistical tests required to detect such interactions. Here, we focus on improving the power of GxE tests by developing a statistical framework for assessing quantitative trait loci (QTLs) associated with the trait means and/or trait variances. When applying this framework to body mass index (BMI), we find that GxE discovery and replication rates are significantly higher when prioritizing genetic variants associated with the variance of the phenotype (vQTLs) compared to assessing all genetic variants. Moreover, we find that vQTLs are enriched for associations with other non-BMI phenotypes having strong environmental influences, such as diabetes or ulcerative colitis. We show that GxE effects first identified in quantitative traits such as BMI can be used for GxE discovery in disease phenotypes such as diabetes. A clear conclusion is that strong GxE interactions mediate the genetic contribution to body weight and diabetes risk.
How are research data governed at Japanese repositories? A knowledge commons perspective
Authors: Nishikawa Kai 
Published: July 2020

PurposeThe purpose of this paper is to survey how research data are governed at repositories in Japan by deductively establishing a governance typology based on the concept of openness in the context of knowledge commons and empirically assessing the conformity of repositories to each type.Design/methodology/approachThe fuzzy-set ideal type analysis (FSITA) was adopted. For data collection, a manual assessment was conducted with all Japanese research data repositories registered on re3data.org.FindingsThe typology constructed in this paper consists of three dimensions: openness to resources (here equal to research data), openness to a community and openness to infrastructure provision. This paper found that there is no case where all dimensions are open, and there are several cases where the resources are closed despite research data repositories being positioned as a basis for open science in Japanese science and technology policy.Originality/valueThis is likely the first construction of the typology and application of FSITA to the study of research data governance based on knowledge commons. The findings of this paper provide practitioners insight into how to govern research data at repositories. The typology serves as a first step for future research on knowledge commons, for example, as a criterion of case selection in conducting in-depth case studies.
Prioritization of dimensions of visual merchandising for apparel retailers using FAHP
Authors: Jakhar Riju , Verma Deepak , Rathore Ajay Pal Singh , Kumar Divesh 
Published: July 2020

PurposeVisual merchandising has a direct impact on shopping experience, making it pertinent for the retailers to ensure that their store environment has an effective design. This study blends fuzzy numbers and Analytical Hierarchy Process to create a fuzzy evaluation model prioritizing the relative weights of visual merchandising dimensions of online fashion apparel store. This study will help the fashion retailers in creating more engaging and informative online stores leading to subsequent increase in online retail sales.Design/methodology/approachVisual merchandising dimensions and sub dimensions used by retailers for online stores were identified through review of literature and discussion with experts. Twenty experts were interviewed and their responses captured. The responses were analyzed using Fuzzy AHP technique resulting in prioritizing the dimensions according to the weight. For testing the stability of the results, sensitivity analysis was conducted.FindingsFour key dimensions and sixteen sub dimensions were extracted. Weights were calculated using FAHP. “Pictorial Presentation” has the highest weight followed closely by “Product Information” dimension. Amongst the sub-dimensions “Number of Product Images” scored highest followed by “Product Presentation mode”. “Alterable Background” scored the least weight.Originality/valuePrevious studies have identified Online Visual Merchandising dimensions and have also studied the impact of some of these dimensions on consumer buying behavior, but the relative significance has not been determined yet. This study fills the gap.
Digital transformation of regional industries through asset modification
Authors: Isaksen Arne , Trippl Michaela , Kyllingstad Nina , Rypestøl Jan Ole 
Published: July 2020

Purpose
This paper aims to develop a conceptual framework for analysing wide-ranging digital transformation processes of industries in regional contexts.

Design/methodology/approach
The paper includes theoretical work to create a conceptual framework. The paper illustrates and advances the framework by analysing examples from two clusters, one focused on the production of digital products and services and one centred on applying digital tools to make firms’ existing activities more efficient.

Findings
The paper distinguishes between three main and interlinked categories of digitalisation; development of scientific principles that form the basis for developing digital technologies; making of digital products and services; and application of these in production and work processes. Digital transformation of industries located in particular regions relate to changes of (regional) innovation systems. The authors interpret this as processes of asset modification, distinguishing between re-use of existing assets, creation of new assets and (strategic) destruction of outdated assets. Digital transformation may lead to various forms of innovation and path development activities in regional economies.

Practical implications
The paper highlights the importance of modification of assets in organisations and at the level of regional innovation systems to support digitalisation. Organisations need to build absorptive capacity for digitalisation. Regional innovation systems face the challenge to build relevant common assets.

Originality/value
The paper advocates a comprehensive framework to better understand how digital transformation unfolds. It challenges established economic geography approaches, which propagate firm-based views and centre stage skill and technological relatedness. An alternative conceptual framework for scrutinising digital transformation processes in industries in regional contexts is presented.