bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypusinated eIF5A is required for the translation of collagen
Authors: Barba-Aliaga Marina , Mena Adriana , Espinoza Vanessa , Apostolova Nadezda , Costell Mercedes , Alepuz Paula 
Published: February 2021

AbstractThe evolutionary conserved elongation factor eIF5A is required for the translation of mRNAs that encode protein sequences with consecutive prolines or combined with glycine and charged amino acids. Mammalian collagens are enriched in putative eIF5A-dependent Pro-Gly-containing tripeptides. Here, we show that eIF5A is needed for heterologous expression of collagen in yeast, and using a dual luciferase reporter system we confirmed that eIF5A depletion interrupts translation at Pro-Gly-collagenic motifs. Using mouse fibroblasts, we showed that depletion of active eIF5A reduced collagen 1α (Col1a1) content, which became concentrated around the nuclei, in contrast to a stronger and all over the cell collagen signal in untreated cells. Active eIF5A-depleted mouse fibroblast showed upregulation of endoplasmic reticulum (ER) stress markers, suggesting retention of partially synthesized Col1a1 in the ER. A dramatically lower level of Col1α1 protein was also observed in functional eIF5A-depleted human hepatic stellate cells treated with the profibrotic cytokine TGF-β1. Our results show that collagen expression requires eIF5A and imply its potential as a target for regulating collagen production in fibrotic diseases.
GPI-anchored FGF directs cytoneme-mediated bidirectional signaling to self-regulate tissue-specific dispersion
Authors: Du Lijuan , Sohr Alex , Li Yujia , Roy Sougata 
Published: February 2021

ABSTRACTHow signaling proteins generate a multitude of information to organize tissue patterns is critical to understanding morphogenesis. InDrosophila, FGF produced in wing-disc cells regulates the development of the disc-associated air-sac-primordium (ASP). Here, we show that FGF is Glycosylphosphatidylinositol-anchored to the producing cell surface and that this modification both inhibits free FGF secretion and activates target-specific bidirectional FGF-FGFR signaling through cytonemes. FGF-source and recipient ASP cells extend cytonemes that present FGF and FGFR on their surfaces and reciprocally recognize each other over distance by contacting through CAM-like FGF-FGFR binding. Contact-mediated FGF-FGFR binding induces bidirectional signaling, which, in turn, promotes ASP and source cells to polarize cytonemes toward each other and reinforce signaling contacts. Subsequent un-anchoring of FGFR-bound-FGF from the source cell membrane dissociates cytoneme contacts and delivers FGF target-specifically to ASP cytonemes for paracrine functions. Thus, GPI-anchored FGF organizes both source and recipient cells and self-regulates its cytoneme-mediated tissue-specific dispersion and signaling.
Morphological Landscapes from High Content Imaging Identify Optimal Priming Strategies that Enhance MSC Immunosuppression
Authors: Andrews Seth H. , Klinker Matthew W. , Bauer Steven R. , Marklein Ross A. 
Published: February 2021

AbstractSuccessful clinical translation of mesenchymal stromal cell (MSC) products has not been achieved in the United States and may be in large part due to MSC functional heterogeneity. Efforts have been made to identify ‘priming’ conditions that produce MSCs with consistent immunomodulatory function; however, challenges remain with predicting and understanding how priming impacts MSC behavior. The purpose of this study was to develop a high throughput, image-based approach to assess MSC morphology in response to combinatorial priming treatments and establish morphological profiling as an effective approach to screen the effect of manufacturing changes (i.e. priming) on MSC immunomodulation. We characterized the morphological response of multiple MSC lines/passages to an array of Interferon-gamma (IFN-γ) and Tumor Necrosis Factor alpha (TNF-α) priming conditions, as well as the effects of priming on MSC modulation of activated T cells and MSC secretome. Although considerable functional heterogeneity, in terms of T cell suppression, was observed between different MSC lines and at different passages, this heterogeneity was significantly reduced with combined IFN-γ/TNF-α priming. The magnitude of this change correlated strongly with multiple morphological features and was also reflected by MSC secretion of immunomodulatory factors e.g. PGE2, ICAM-1, and CXCL16. Overall, this study further demonstrates the ability of priming to enhance MSC function, as well as the ability of morphology to better understand MSC heterogeneity and predict changes in function due to manufacturing.
Combinatorial transcription factor profiles predict mature and functional human islet α and β cells
Authors: Shrestha Shristi , Saunders Diane C. , Walker John T. , Camunas-Soler Joan , Dai Xiao-Qing , Haliyur Rachana , Aramandla Radhika , Poffenberger Greg , Prasad Nripesh , Bottino Rita , Stein Roland , Cartailler Jean-Philippe , Parker Stephen C. J. , MacDonald Patrick E. , Levy Shawn E. , Powers Alvin C. , Brissova Marcela 
Published: February 2021

ABSTRACTIslet-enriched transcription factors (TFs) exert broad control over cellular processes in pancreatic α and β cells and changes in their expression are associated with developmental state and diabetes. However, the implications of heterogeneity in TF expression across islet cell populations are not well understood. To define this TF heterogeneity and its consequences for cellular function, we profiled >40,000 cells from normal human islets by scRNA-seq and stratified α and β cells based on combinatorial TF expression. Subpopulations of islet cells co-expressingARX/MAFB(α cells) andMAFA/MAFB(β cells) exhibited greater expression of key genes related to glucose sensing and hormone secretion relative to subpopulations expressing only one or neither TF. Moreover, all subpopulations were identified in native pancreatic tissue from multiple donors. By Patch-seq,MAFA/MAFBco-expressing β cells showed enhanced electrophysiological activity. Thus, these results indicate combinatorial TF expression in islet α and β cells predicts highly functional, mature subpopulations.
Multiple mechanisms of photoreceptor spectral tuning following loss of UV color vision inHeliconiusbutterflies
Authors: McCulloch Kyle J. , Macias-Muñoz Aide , Mortazavi Ali , Briscoe Adriana D. 
Published: February 2021

AbstractColor vision modifications occur in animals via a process known as spectral tuning. InHeliconiusbutterflies, a genus-specificUVRhopsin duplication led to the evolution of UV color discrimination inHeliconius eratofemales, a rare trait among butterflies. In theH. melpomeneandH. ismeniuslineages, the UV2 receptor has been lost. Here we compare how loss of the UV2 photoreceptor has altered the visual system of these butterflies. We compare visual system evolution in threeHeliconiusbutterfly species using a combination of intracellular recordings, ATAC-seq, and antibody staining. We identify several spectral tuning mechanisms including adaptive evolution of opsins, deployment of two types of filtering pigments, and co-expression of two distinct opsins in the same cell. Our data show that opsin gain and loss is driving rapid divergence inHeliconiusvisual systems via tuning of multiple spectral classes of photoreceptor in distinct lineages, potentially contributing to ongoing speciation in this genus.
PredictProtein – Predicting Protein Structure and Function for 29 Years
Authors: Bernhofer Michael , Dallago Christian , Karl Tim , Satagopam Venkata , Heinzinger Michael , Littmann Maria , Olenyi Tobias , Qiu Jiajun , Schütze Konstantin , Yachdav Guy , Ashkenazy Haim , Ben-Tal Nir , Bromberg Yana , Goldberg Tatyana , Kajan Laszlo , O’Donoghue Sean , Sander Chris , Schafferhans Andrea , Schlessinger Avner , Vriend Gerrit , Mirdita Milot , Gawron Piotr , Gu Wei , Jarosz Yohan , Trefois Christophe , Steinegger Martin , Schneider Reinhard , Rost Burkhard 
Published: February 2021

AbstractSince 1992PredictProtein(https://predictprotein.org) is a one-stop online resource for protein sequence analysis with its main site hosted at the Luxembourg Centre for Systems Biomedicine (LCSB) and queried monthly by over 3,000 users in 2020.PredictProteinwas the first Internet server for protein predictions. It pioneered combining evolutionary information and machine learning. Given a protein sequence as input, the server outputs multiple sequence alignments, predictions of protein structure in 1D and 2D (secondary structure, solvent accessibility, transmembrane segments, disordered regions, protein flexibility, and disulfide bridges) and predictions of protein function (functional effects of sequence variation or point mutations, Gene Ontology (GO) terms, subcellular localization, and protein-, RNA-, and DNA binding). PredictProtein’s infrastructure has moved to the LCSB increasing throughput; the use of MMseqs2 sequence search reduced runtime five-fold; user interface elements improved usability, and new prediction methods were added. PredictProtein recently included predictions from deep learning embeddings (GO and secondary structure) and a method for the prediction of proteins and residues binding DNA, RNA, or other proteins. PredictProtein.org aspires to provide reliable predictions to computational and experimental biologists alike. All scripts and methods are freely available for offline execution in high-throughput settings.AvailabilityFreely accessible webserverPredictProtein.org; Source and docker images:github.com/rostlab
Metagenomic diagnosis and pathogenic network profile of SARS-CoV-2 in patients co-morbidly affected by type 2 diabetes
Authors: Al-Emran Hassan M. , Rahman M. Shaminur , Hasan Md. Shazid , Rubayet Ul Alam A. S. M. , Islam Ovinu Kibria , Anwar Ajwad , Jahid Iqbal Kabir , Hossain M. Anwar 
Published: February 2021

AbstractBackgroundThe mortality of COVID-19 disease is very high among males or elderly or individuals having comorbidities with obesity, cardiovascular diseases, lung infections, hypertension, and/or diabetes. Our study characterizes SARS-CoV-2 infected patients’ metagenomic features with or without type 2 diabetes to identify the microbial interactions associated with its fatal consequences.MethodThis study compared the baseline nasopharyngeal microbiome of SARS-CoV-2 infected diabetic and non-diabetic patients with controls adjusted with age and gender. The mNGS were performed using Ion GeneStudio S5 Series and the data were analyzed by the Vegan-package in R.ResultsAll three groups possessed significant bacterial diversity and dissimilarity indexes (p<0.05). Spearman’s correlation coefficient network analysis illustrated 183 significant positive correlations and 13 negative correlations of pathogenic bacteria (r=0.6-1.0, p<0.05), and 109 positive correlations among normal-flora and probiotic bacteria (r>0.6, p<0.05). The SARS-CoV-2 diabetic group exhibited a significant increase of pathogens (p<0.05) and opportunistic pathogens (p<0.05) with a simultaneous decrease of normal-flora (p<0.05). The molecular docking analysis of Salivaricin, KLD4 (alpha), and enterocin produced by several enriched probiotic strains presented strong binding affinity with Shiga toxin, outer membrane proteins (ompA, omp33) or hemolysin.ConclusionThe dysbiosis of the bacterial community might be linked with severe consequences of COVID-19 infected diabetic patients, although few probiotic strains inhibited numerous pathogens in the same pathological niches. This study suggested that the promotion of normal-flora and probiotics through dietary changes and reduction of excessive pro-inflammatory states by preventing pathogenic environment might lead to a better outcome for those co-morbid patients.
Cerebellar connectivity maps embody individual adaptive behavior
Authors: Spaeth Ludovic , Bahuguna Jyotika , Gagneux Theo , Dorgans Kevin , Sugihara Izumi , Poulain Bernard , Battaglia Demian , Isope Philippe 
Published: February 2021

AbstractFrom planification to execution, cerebellar microcircuits encode different features of skilled movements. However, it is unknown whether cerebellar synaptic connectivity maps encode movement features in a motor context specific manner. Here we investigated the spatial organization of excitatory synaptic connectivity in mice cerebellar cortex in different locomotor contexts: during development and in normal, trained or altered locomotor conditions. We combined optical, electrophysiological and graph modelling approaches to describe synaptic connectivity between granule cells (GCs) and Purkinje cells (PCs). Synaptic map maturation during development revealed a critical period in juvenile animals before the establishment of a stereotyped functional organization in adults. However, different locomotor conditions lead to specific GC-PC connectivity maps in PCs. Ultimately, we demonstrated that the variability in connectivity maps directly accounts for individual specific behavioral features of mice locomotion, suggesting that GC-PC networks encode a general motor context as well as individual specific internal models underlying motor adaptation.
Intracellular pools of DAG-activated TRPC3 channels are essential for TLR4 activation
Authors: Casas Javier , Meana Clara , López-López José Ramón , Balsinde Jesús , Balboa María A. 
Published: February 2021

ABSTRACTToll-like receptor 4, the receptor for bacterial lipopolysaccharide (LPS), drives inflammatory responses that protect against pathogens and boost the adaptive immunity. LPS responses are known to depend on calcium fluxes, but the molecular mechanisms involved are poorly understood. Here we present evidence that the transient receptor potential canonical channel 3 (TRPC3) is activated intracellularly during macrophage exposure to LPS and is essential for Ca2+release from internal stores. In this way TRPC3 participates in cytosolic Ca2+elevations, TLR4 endocytosis, activation of inflammatory transcription factors and cytokine upregulation. We also report that TRPC3 is activated by diacylglycerol (DAG) generated by the phosphatidic acid phosphatase lipin-1. In accord with this, lipin-1-deficient cells show reduced Ca2+responses to LPS challenge. A cameleon indicator directed to the endoplasmic reticulum shows that this is the organelle from which TRPC3 mediates the Ca2+release. Finally, pharmacological inhibition of TRPC3 reduces systemic inflammation induced by LPS in mice. Collectively, our study unveils a central component of LPS-triggered Ca2+signaling that involves intracellular sensing of lipin-1-derived DAG by TRPC3.
The oncogenic transcription factor FUS-CHOP can undergo nuclear liquid-liquid phase separation
Authors: Owen Izzy , Yee Debra , Wyne Hala , Perdikari Theodora Myrto , Johnson Victoria , Smyth Jeremy , Kortum Robert , Fawzi Nicolas L. , Shewmaker Frank 
Published: February 2021

AbstractMyxoid liposarcoma is caused by a chromosomal translocation resulting in a fusion protein comprised of the N-terminus of FUS (fused in sarcoma) and the full-length transcription factor CHOP (CCAAT/Enhancer Binding Protein Homologous Protein). FUS functions in RNA metabolism and CHOP is a stress-induced transcription factor. The FUS-CHOP fusion protein causes unique gene expression and oncogenic transformation. The FUS segment is required for oncogenic transformation, but the mechanism of FUS-CHOP-induced transcriptional activation is unknown. Recently, some transcription factors and super enhancers were proposed to undergo liquid-liquid phase separation and form membraneless compartments that recruit transcription machinery to gene promoters. Since phase separation of FUS depends on its N-terminus, transcriptional activation by FUS-CHOP could result from the N-terminus driving nuclear phase transitions. Here, we characterized FUS-CHOP in cells andin vitro, and observed novel phase-separating properties relative to unmodified CHOP. Our data indicate FUS-CHOP forms phase-separated condensates at super enhancer transcriptional sites. We provide strong evidence that the FUS-CHOP phase transition is a novel oncogenic mechanism and potential therapeutic target for treatment of myxoid liposarcoma.
Assessment of visibility in industrial construction projects: a viewpoint from supply chain stakeholders
Authors: Dharmapalan Vineeth , O’Brien William J. , Morrice Douglas , Jung Minhyuk 
Published: February 2021

Purpose
Stakeholders of construction projects exhibit different perceptions regarding the visibility of materials in the supply chain, which affects the timely delivery and installation of materials. This study aims to quantitatively investigate the differences in viewpoints of owners, contractors, designers and suppliers about the visibility of materials at supply chain locations and different material types during the construction of industrial projects.

Design/methodology/approach
Survey data about visibility at nine typical supply chain locations and three common material types were collected from owner, contractor, designer and supplier groups and analyzed using frequency statistics, relative importance index and tests for equality of odds.

Findings
Offsite Tier-2 supplier, ports and kitting site shows the lowest visibility level for the owner, contractor, supplier and designer groups. Also, the supplier group tends to have adequate to extreme visibility at the Tier-2 supplier, kitting site and during transportation compared to owner, contractor and designer groups. An example finding concerning the visibility of material types is that owners and contractors perceive prefabricated material requires higher visibility than all other material types.

Research limitations/implications
The findings are limited to construction projects in the industrial sector. Further, the survey participants were based in North America at the time of participation.

Practical implications
The study’s findings indicate how visibility is spread across supply chain locations and for material types for the owners, contractors, suppliers and designers of industrial projects. As such, academia and industry’s research and investment efforts can be more focused on locations and material types that need improvement.

Social implications
Industrial projects play an essential part in improving society’s daily lives, and this study’s findings contribute to improving the efficiency of the supply chain during construction of industrial projects.

Originality/value
Although previous studies mentioned the need and importance of visibility improvement, none have sought to understand the perception of leading supply chain stakeholders about visibility at supply chain locations and of material types. This study’s findings provide specific insights and directions for advancing in these areas with regard to supply chain visibility.
User compensation as a data breach recovery action: a methodological replication and investigation of generalizability based on the Home Depot breach
Authors: Hoehle Hartmut , Wei Jia , Schuetz Sebastian , Venkatesh Viswanath 
Published: February 2021

PurposeIn the aftermath of data breaches, many firms offer compensation to affected customers to recover from damaged customer sentiments. To understand the effectiveness of such compensation offerings, Goode et al. (2017) examined the effects of compensation offered by Sony following the PlayStation Network breach in 2011. Although Goode et al. (2017) present key insights on data breach compensation, it is unclear whether their findings generalize beyond the context of subscription-based gaming platforms whose customers are young and experience substantial switching costs. To address this issue, we conducted a methodological replication in a retail context with low switching costs.Design/methodology/approachIn our replication, we examine the effects of compensation offered by Home Depot in the aftermath of its data breach in 2014. Home Depot is the largest home improvement retailer in the US and presents a substantially different context. Data were collected from 901 participants using surveys.FindingsOur results were consistent with the original study. We found that in retail breaches, effective compensation needs to meet customers' expectations because overcompensation or undercompensation leads to negative outcomes, such as decreased repurchase intention.Originality/valueOur study provides insights into the effectiveness of compensation in the retail context and confirms the findings of Goode et al. (2017).
Did the environmental jolt matter? Corporate entrepreneurship and firm financial performance in Egypt
Authors: Tantawy Ahmed Adel , Elaasi Sherif , Elshawadfy Mohamed 
Published: February 2021

PurposeEvidence suggests that corporate entrepreneurship (CE), namely, innovativeness, risk-taking and corporate venturing, enhances a firm’s performance. However, the study of CE in developing markets – particularly in Egypt – is still new and undeveloped. The literature stresses the importance of incorporating environmental factors into the study of CE. Therefore, the purpose of this study is to examine the relationship between CE, environmental jolts (unexpected abrupt environmental events such as the Arab Spring) and the firm’s financial performance. Based on the periods before and after the series of anti-government protests known as the Arab Spring, this paper argues that after an environmental jolt, CE will negatively affect financial performance.Design/methodology/approachThis study analyzes and correlates CE, environmental jolts and firm performance in Egypt for a period over 10 years (from 2007 through 2016) using a sample of 94 manufacturing firms listed on the Egyptian Stock Exchange. Data were manually collected through archival/secondary data using financial and accounting information from the annual reports released by the firms. These reports were downloaded from the firms’ webpages and the Egyptian Exchange website.FindingsThe main results of this paper indicate that environmental factors play a role in the effect of CE on firm performance. Using the 2011 Arab Spring as a quasi-natural experiment, this paper finds that CE’s effect on firm performance is higher pre-jolt and lower post-jolt.Practical implicationsThis study provides useful implications for managers and practitioners. Firms need to find new ways of allocating their resources to help provide innovative products and to have a competitive advantage. Although innovation, risk-taking and corporate venturing may have a delayed impact on a firm’s financial performance, managers should evaluate the implications and the success of CE activities in the long-term, not from a short-term perspective.Originality/valueBuilding upon the existing literature, this is the first paper to investigate the effect of CE on a firm’s financial performance in Egypt during the Arab Spring. The manufacturing firms listed on the Egyptian Exchange were analyzed in a quasi-natural experiment, taking into account the moderating role of an environmental jolt, namely, the Arab Spring.