bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large-scale analysis of redox-sensitive conditionally disordered protein regions reveal their widespread nature and key roles in high-level eukaryotic processes
Authors: Erdős Gábor , Mészáros Bálint , Reichmann Dana , Dosztányi Zsuzsanna 
Published: September 2018

AbstractRecently developed quantitative redox proteomic studies enable the direct identification of redox-sensing cysteine residues that regulate the functional behavior of target proteins in response to changing levels of reactive oxygen species (ROS). At the molecular level, redox regulation can directly modify the active sites of enzymes, although a growing number of examples indicate the importance of an additional underlying mechanism that involves conditionally disordered proteins. These proteins alter their functional behavior by undergoing a disorder-to-order transition in response to changing redox conditions. However, the extent to which this mechanism is used in various proteomes is currently unknown. Here, we use a recently developed sequence-based prediction tool incorporated into the IUPred2A web server to estimate redox-sensitive conditionally disordered regions on a large scale. We show that redox-sensitive conditional disorder is fairly widespread in various proteomes and that its presence strongly correlates with the expansion of specific domains in multicellular organisms that largely rely on extra stability provided by disulfide bonds or zinc ion binding. The analyses of yeast redox proteomes and human disease data further underlie the significance of this phenomenon in the regulation of a wide range of biological processes, as well as its biomedical importance.
A tensile ring drives tissue flows to shape the gastrulating amniote embryo
Authors: Saadaoui Mehdi , Corson Francis , Rocancourt Didier , Roussel Julian , Gros Jerome 
Published: September 2018

AbstractTissue morphogenesis is driven by local cellular deformations, themselves powered by contractile actomyosin networks. While it is well demonstrated that cell-generated forces at the microscopic scale underlie a variety of local morphogenetic processes (e.g. lengthening/ narrowing1–4, bending5–8, or folding9,10), how such local forces are transmitted across tissues to shape them at a mesoscopic scale remains largely unknown. Here, by performing a quantitative analysis of gastrulation in entire avian embryos, we show that the formation of the primitive streak and the associated large-scale rotational tissue flows (i.e. ‘polonaise’ movements11,12) are integral parts of a global process that is captured by the laws of fluid mechanics. We identify a large-scale supracellular actomyosin ring (2 mm in diameter and 250 μm thick) that shapes the embryo by exerting a graded tension along the margin between the embryonic and extra-embryonic territories. Tissue-wide flows arise from the transmission of these localized forces across the embryonic disk and are quantitatively recapitulated by a fluid-mechanical model based on the Stokes equations for viscous flow. We further show that cell division, the main driver of cell rearrangements at this stage13, is required for fluid-like behavior and for the progress of gastrulation movements. Our results demonstrate the power of a hydrodynamic approach to tissue-wide morphogenetic processes14–16 and provide a simple, unified mechanical picture of amniote gastrulation. A tensile embryo margin, in addition to directing tissue motion, could act as an interface between mechanical and molecular cues, and play a central role in embryonic self-organization.
Identifying functional targets from transcription factor binding data using SNP perturbation
Authors: Xiang Jing , Kim Seyoung 
Published: September 2018

AbstractTranscription factors (TFs) play a key role in transcriptional regulation by binding to DNA to initiate the transcription of target genes. Techniques such as ChIP-seq and DNase-seq provide a genome-wide map of TF binding sites but do not offer direct evidence that those bindings affect gene expression. Thus, these assays are often followed by TF perturbation experiments to determine functional binding that leads to changes in target gene expression. However, such perturbation experiments are costly and time-consuming, and have a well-known limitation that they cannot distinguish between direct and indirect targets. In this study, we propose to use the naturally occurring perturbation of gene expression by genetic variation captured in population SNP and expression data to determine functional targets from TF binding data. We introduce a computational methodology based on probabilistic graphical models for isolating the perturbation effect of each individual SNP, given a large number of SNPs across genomes perturbing the expression of all genes simultaneously. Our computational approach constructs a gene regulatory network over TFs, their functional targets, and further downstream genes, while at the same time identifying the SNPs perturbing this network. Compared to experimental perturbation, our approach has advantages of identifying direct and indirect targets, and leveraging existing data collected for expression quantitative trait locus mapping, a popular approach for studying the genetic architecture of expression. We apply our approach to determine functional targets from the TF binding data for a lymphoblastoid cell line from the ENCODE Project, using SNP and expression data from the HapMap 3 and 1000 Genomes Project samples. Our results show that from TF binding data, functional target genes can be determined by SNP perturbation of various aspects that impact transcriptional regulation, such as TF concentration and TF-DNA binding affinity.
Invadopodia degrade ECM in the G1 phase of the cell cycle
Authors: Bayarmagnai Battuya , Perrin Louisiane , Esmaeili Pourfarhangi Kamyar , Gligorijevic Bojana 
Published: September 2018

AbstractInvadopodia are cancer cell protrusions rich in structural proteins (e.g. Tks5, cortactin) and proteases (e.g. MT1-MMP) and are responsible for degradation of the extracellular matrix (ECM). Tumor cell invasion and metastasis require cancer cells to be both proliferative and invasive, i.e. migrate through the tissue and assemble invadopodia. While several studies addressed how cell motility parameters change throughout the cell cycle, the relationship between invadopodia and cell cycle progression has not been elucidated. In this study, using invadopodia- and cell cycle- fluorescent markers, we show in 2D and 3D cell cultures, as well as in vivo, that breast carcinoma cells assemble invadopodia and invade into the surrounding ECM preferentially during the G1 phase of the cell cycle. Cells synchronized in the G0/G1 phase of the cell cycle degrade at significantly higher levels during the first 20 hours post-synchronization release. Consistent with this, mRNA and protein levels of the invadopodia key components, cortactin and MT1-MMP, peak at 14 hours post-release. Cell cycle progression is faster in cells in which invadopodia are abolished (by Tks5 knockdown), evidenced by earlier induction of cyclins A and B. A close look at the regulators of G1 revealed that the overexpression of p27kip1, but not p21cip1, causes faster turnover of invadopodia and increased ECM degradation. Furthermore, both endogenous and over-expressed p27kip1 localizes to the sites of invadopodia assembly. Taken together, these findings suggest that invadopodia function is tightly linked to cell cycle progression and is controlled by specific cell cycle regulators. Our results caution that this coordination between invasion and cell cycle must be considered when designing effective chemotherapies.
Onecut factors and Pou2f2 regulate the distribution of V2 interneurons in the mouse developing spinal cord
Authors: Harris Audrey , Masgutova Gauhar , Collin Amandine , Toch Mathilde , Hidalgo-Figueroa Maria , Jacob Benvenuto , Corcoran Lynn M. , Francius Cédric , Clotman Frédéric 
Published: September 2018

AbstractAcquisition of proper neuronal identity and position is critical for the formation of neural circuits. In the embryonic spinal cord, cardinal populations of interneurons diversify into specialized subsets and migrate to defined locations within the spinal parenchyma. However, the factors that control interneuron diversification and migration remain poorly characterized. Here, we show that the Onecut transcription factors are necessary for proper diversification and distribution of the V2 interneurons in the developing spinal cord. Furthermore, we uncover that these proteins restrict and moderate the expression of spinal isoforms ofPou2f2, a transcription factor known to regulate B-cell differentiation. By gain- or loss-of-function experiments, we show that Pou2f2 contribute to regulate the position of V2 populations in the developing spinal cord. Thus, we uncovered a genetic pathway that regulates the diversification and the distribution of V2 interneurons during embryonic development.Significance statementIn this study, we identify the Onecut and Pou2f2 transcription factors as regulators of spinal interneuron diversification and migration, two events that are critical for proper CNS development.
Quantitative comparison of camera technologies for cost-effective Super-resolution Optical Fluctuation Imaging (SOFI)
Authors: Van den Eynde Robin , Sandmeyer Alice , Vandenberg Wim , Duwé Sam , Hübner Wolfgang , Huser Thomas , Dedecker Peter , Müller Marcel 
Published: September 2018

AbstractSuper-Resolution (SR) fluorescence microscopy is typically carried out on high-end research microscopes. Super-resolution Optical Fluctuation Imaging (SOFI) is a fast SR technique capable of live-cell imaging, that is compatible with many wide-field microscope systems. However, especially when employing fluorescent proteins, a key part of the imaging system is a very sensitive and well calibrated camera sensor. The substantial costs of such systems preclude many research groups from employing super-resolution imaging techniques.Here, we examine to what extent SOFI can be performed using a range of imaging hardware comprising different technologies and costs. In particular, we quantitatively compare the performance of an industry-grade CMOS camera to both state-of-the-art emCCD and sCMOS detectors, with SOFI-specific metrics. We show that SOFI data can be obtained using a cost-efficient industry-grade sensor, both on commercial and home-built microscope systems, though our analysis also readily exposes the merits of the per-pixel corrections performed in scientific cameras.
The Integration of Pharmacophore-based 3D QSAR Modeling and Virtual Screening in Safety Profiling: a Case Study to Identify Antagonistic Activities against Adenosine Receptor, A2aR, using 1,897 Known Drugs
Authors: Fan Fan , Warshaviak Dora Toledo , Hamadeh Hisham K. , Dunn Robert T. 
Published: September 2018

ABSTRACT:Safety pharmacology screening against a wide range of unintended vital targets usingin vitroassays is crucial to understand off-target interactions with drug candidates. With the increasing demand forin vitroassays, ligand-and structure-based virtual screening approaches have been evaluated for potential utilization in safety profiling. Although ligand based approaches have been actively applied in retrospective analysis or prospectively within well-defined chemical space during the early discovery stage (i.e., HTS screening and lead optimization), virtual screening is rarely implemented in later stage of drug discovery (i.e., safety). Here we present a case study to evaluate ligand-based 3D QSAR models built based onin vitroantagonistic activity data against adenosine receptor 2A (A2aR). The resulting models, obtained from 268 chemically diverse compounds, were used to test a set of 1,897 chemically distinct drugs, simulating the real-world challenge of safety screening when presented with novel chemistry and a limited training set. Due to the unique requirements of safety screening versus discovery screening, the limitations of 3D QSAR methods (i.e., chemotypes, dependence on large training set, and prone to false positives) are less critical than early discovery screen. We demonstrated that 3D QSAR modelling can be effectively applied in safety assessment prior toin vitroassays, even with chemotypes that are drastically different from training compounds. It is also worth noting that our model is able to adequately make the mechanistic distinction between agonists and antagonists, which is important to inform subsequent in vivo studies. Overall, we present an in-depth analysis of the appropriate utilization and interpretation of pharmacophore-based 3D QSAR models for safety screening.
COMPASS Family Histone Methyltransferase ASH2L Mediates Corticogenesis via Transcriptional Regulation of Wnt Signalling
Authors: Li Liang , Ruan Xiangbin , Wen Chang , Chen Pan , Liu Wei , Zhu Liyuan , Xiang Pan , Zhang Xiaoling , Wei Qunfang , Hou Lin , Yin Bin , Yuan Jiangang , Qiang Boqin , Shu Pengcheng , Peng Xiaozhong 
Published: September 2018

AbstractCell fate specification in neural progenitor cells (NPCs) is orchestrated via extrinsic and intrinsic molecular programs, and histone methylation in these decisions has been ascribed to a crucial function regulating gene expression. Here, we show that the COMPASS family histone methyltransferase co-factor ASH2L is required in NPCs proliferation and upper layer cortical projection neurons production and position. Deletion of Ash2l impairs trimethylation of H3K4 and transcriptional machinery specifically for subsets of Wnt-β-catenin signalling, disrupting their transcription and consequently inhibiting the proliferation ability of NPCs in late stages of neurogenesis. Consistently, Ash2l conditional mutants exhibit thinning neocortex with reduced upper layer neurons and altered neuronal position. Moreover, overexpressing β-catenin after Ash2l elimination or knockdown can rescue the proliferation deficiency of NPCs both in vivo and in vitro. These results demonstrate an essential and highly specific role for Ash2l in controlling NPCs proliferation and late-born neurons lamination in corticogenesis via transcriptionally regulating Wnt-β-catenin signalling, and provide clues to how the COMPASS family epigenetic factors coordinate cell fate determination during cortex development.
The model of relationships between pay for individual performance and work engagement
Authors: Kulikowski Konrad 
Published: September 2018

Purpose
Research on the relationship between pay for individual performance (PFIP) and work engagement (WE) is limited. The purpose of this paper is to present a model outlining a threefold association between PFIP and WE: a direct association, an indirect association via pay satisfaction and a joint indirect association via pay level and pay satisfaction.

Design/methodology/approach
Structural equation modeling and bootstrapping procedures were used to test hypotheses with regard to these associations based on data obtained from two independent studies: the author’s own research project, and the European Work Conditions Survey 2015.

Findings
In both studies, the author found the hypothesized direct association between PFIP and WE; indirect association between PFIP and WE via pay satisfaction; and a joint indirect association between PFIP and WE via pay level and pay satisfaction.

Research limitations/implications
Given its limited cross-sectional design, future longitudinal research in this area is needed to test the model of relations presented in this paper.

Practical implications
The association between PFIP and WE is weak, and partially mediated by pay satisfaction; thus, it seems that to promote WE, it is not solely sufficient to introduce PFIP into remuneration systems, but that, in addition, PFIP should be aligned with employee pay expectations.

Originality/value
This study contributes to the career development literature by proposing and initially testing a model describing the three ways PFIP may be related to WE, one of the most crucial factors in achieving career success.
A controllable-accuracy stochastic time-domain technique for randomly varying microwave applications
Authors: Papadimopoulos Athanasios N. , Kantartzis Nikolaos V. 
Published: September 2018

Purpose
This paper aims to introduce an efficient time-domain formulation of adjustable accuracy for a consistent and trustworthy computation of electromagnetic field characteristics in randomly varying configurations. The developed methodology is carefully certified via comprehensive comparisons with the corresponding outcomes obtained by the Monte Carlo approach.

Design/methodology/approach
The presented methodology uses higher-order approximations of Taylor series expansions of stochastic multivariable functions for the rapid estimation of the electromagnetic field component mean value and confidence intervals of their variance. Toward this objective, new time-update equations for the mean value and the variance of the involved electromagnetic field are elaborately derived.

Findings
The featured technique presents an efficient alternative to the excessively resource-consuming Monte Carlo finite-difference time-domain (MC–FDTD) implementation, which requires an unduly number of realizations to achieve a satisfying convergence. The higher-order stochastic algorithm retrieves accurately the statistical properties of all electromagnetic field in a single simulation, presenting promising accuracy, stability and convergence.

Originality/value
The adjustable-accuracy higher-order scheme introduces a new framework for the derivation of the stochastic explicit time-update equations and precisely computes the required confidence intervals for the electromagnetic field variance instead of the variance itself, which can be deemed a key advantage over existing schemes. This fully controllable formulation results in significantly more accurate calculations of the electromagnetic field variance, especially for larger fluctuations of the involved electromagnetic media parameters.
Organisational ambidexterity in UK high-tech SMEs
Authors: Senaratne Chaminda , Wang Catherine L. 
Published: September 2018

PurposeThe purpose of this paper is to explore the nature of organisational ambidexterity, and identify drivers of and barriers to ambidexterity in the high-tech small- and medium-sized enterprises (SMEs) in the UK, using fine-grained qualitative evidence. This is much needed to generate insights on how organisational ambidexterity actually takes place in SMEs.Design/methodology/approachThis study is exploratory in nature, based on qualitative in-depth interview data collected from 20 UK high-tech SMEs in five industries.FindingsThe results reveal that SMEs leverage resources through intra-firm and inter-firm collaborations to pursue ambidexterity sequentially or simultaneously, using a range of drivers and overcoming a range of barriers.Research limitations/implicationsThe data were gathered from a single informant from each firm. Therefore, more in-depth, longitudinal, qualitative research using multiple sources of data may be required to develop deeper insights into ambidexterity.Practical implicationsManagers of high-tech SMEs need to focus on specific barriers to ambidexterity and devise effective mechanisms to promote the drivers of ambidexterity. The mechanisms to achieve ambidexterity as identified in this study will benefit high-tech SMEs in particular, and firms in general.Originality/valueThe study contributes to the understanding of organisational ambidexterity in high-tech SMEs by exploring the mechanisms through which SMEs implement organisational ambidexterity despite their resource constraints. This counteracts the conventional view that it is difficult for SMEs to pursue ambidexterity.
Etalement urbain, comportement de mobilité et fonctionnement de l'offre de transport à Yaoundé
Authors: Mfoulou Olugu Jean Patrick 
Published: September 2018

RésuméCe papier évalue le lien entre l'étalement urbain, les comportements de mobilité et le fonctionnement de l'offre de transport à Yaoundé. Il s'agit spécifiquement d'évaluer l'influence des indicateurs urbains, de mobilité, et socio‐économiques d'une zone d'origine sur les choix de mobilités d'une part et les coûts d'autre part. Utilisant les données collectées par la communauté urbaine de Yaoundé (2010), et les modèles logit multinomial et régressions continues, ce papier montre que les indicateurs urbains telles que les densités, l'accessibilité, et les distances origine‐centre centre‐destination influencent les choix de mobilité et ont un impact sur le coût. L'étalement urbain, dû à la forte croissance urbaine non contrôlée par les collectivités territoriales, joue un rôle négatif dans le fonctionnement de l'offre de transport urbain parce qu'il favorise l'offre artisanal de petite capacité et réduit l'efficacité et la compétitivité du transport collectif de masse moins coûteux. Les résultats recommandent de réguler l'étalement urbain, de faciliter l'accessibilité aux transports de masse et de développer un transport collectif efficace et compétitif.
The role of foreign and domestic venture capital in innovation: evidence from China
Authors: Que Jiangjing , Zhang Xueyong 
Published: September 2018

AbstractThis paper analyses the different effects of foreign venture capital (FVC) and domestic venture capital (DVC) on innovation for IPOs. Using patent counts to measure innovation, the results indicate that FVC‐backed firms are less innovative than DVC‐backed firms. Our findings are robust after controlling for the sample selection bias using a propensity score matching approach. One possible underlying mechanism through which FVCs nurture less innovation is their inferior geographic proximity to investment targets.
Vaginal cuff dehiscence is observed in a higher rate after total laparoscopic hysterectomy compared with other types of hysterectomy
Authors: Ala‐Nissilä Seija , Laurikainen Eija , Mäkinen Juha , Jokimaa Varpu 
Published: September 2018

AbstractIntroductionRecently, it has been suggested that the occurrence of posthysterectomy vaginal cuff dehiscence has increased. Consequently, we evaluated the incidence of vaginal cuff dehiscence after different types of hysterectomies. Our hypothesis is that vaginal cuff dehiscence is more often associated with total laparoscopic hysterectomy (TLH) than other types of uterine removal.Material and methodsA total of 13 645 hysterectomies from 1992 to 2015 were evaluated in the Turku University Hospital district, Finland. The primary outcome was occurrence of vaginal dehiscence after different types of hysterectomy. The hysterectomy and postoperative vaginal dehiscence trends were analyzed as the secondary outcome. In a subanalysis of dehiscence cases, women’s characteristics and perioperative vaginal cuff opening and closure techniques were compared between conventional hysterectomies (vaginal, abdominal, and laparoscopic with vaginal closure) and TLH.ResultsAltogether, 22 cases of vaginal cuff dehiscence were included. Most cases (n = 15) occurred after TLH (n = 1104), resulting in an incidence of 1.27%. After conventional laparoscopic hysterectomy with vaginal closure (n = 2853), vaginal (n = 4150), and abdominal (n = 5538) hysterectomies, the incidence rates were 0.11%, 0.05%, and 0.02%, respectively. Compared to abdominal hysterectomy, which was associated with the lowest incidence rate, vaginal dehiscence after TLH had an odds ratio (OR) 71.1 (9.34‐541.38, P < 0.001). In the subanalysis of possible underlying factors, the technique of opening of the vaginal cuff with or without electrocoagulation, duration of operation, and occurrence of postoperative infection or hematoma prior to VCD were observed differences between TLH and conventional hysterectomies.ConclusionsCompared with other types of hysterectomies, vaginal dehiscence was observed at the highest rate after TLH. Studies are needed to define if vaginal opening technique contributes to the risk of dehiscence.