bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medium-chain acyl-CoA dehydrogenase, a gatekeeper of mitochondrial function in glioblastoma multiforme
Authors: Puca Francesca , Yu Fei , Bertolacci Caterina , Pettazzoni Piergiorgio , Carugo Alessandro , Huang-Hobbs Emmet , Liu Jintan , Zanca Ciro , Carbone Federica , Del Poggetto Edoardo , Gumin Joy , Dasgupta Pushan , Seth Sahil , Lang Frederick F. , Sulman Erik , Lorenzi Philip L. , Tan Lin , Shan Mengrou , Tolstyka Zachary P. , Kachman Maureen , Zhang Li , Deem Angela K. , Genovese Giannicola , Scaglioni Pier Paolo , Lyssiotis Costas A. , Viale Andrea , Draetta Giulio F. 
Published: September 2020

SUMMARYGlioblastoma (GBM) is among the deadliest of human cancers. Despite extensive efforts, it has proven to be highly resistant to chemo- and immune-based therapeutic strategies, and little headway has been made with targeted inhibitors. Like many cancers, metabolism is dysregulated in GBM. Thus, to identify new vulnerabilities and drug targets in GBM, we conducted genetic screens using pooled RNAi libraries targeting metabolic enzymes. We screened multiple glioma stem cell-derived (GSC) xenograft models, which revealed that several enzymes involved in the mitochondrial metabolism of fatty acids were required for tumor cell proliferation. From among these, we focused on medium-chain acyl-CoA dehydrogenase (MCAD), which oxidizes medium-chain fatty acids, due to its consistently high score across all of our screens, as well as its high expression level in multiple GSC models and its upregulation in GBM compared to normal brain.In this manuscript, we describe the dependence of GBM on sustained fatty acid metabolism to actively catabolize lipid species that would otherwise damage the mitochondrial structure. The uptake of mediumchain fatty acids lacks negative feedback regulation; therefore, in the absence of MCAD, medium-chain fatty acids accumulate to toxic levels, inducing reactive oxygen species (ROS), mitochondrial damage and failure, and apoptosis. Taken together, our findings uncover a previously unappreciated protective role exerted by MCAD in GBM cells, making it a unique and therapeutically exploitable vulnerability.
Host transcriptomic profiling of COVID-19 patients with mild, moderate, and severe clinical outcomes
Authors: Jain Ruchi , Ramaswamy Sathishkumar , Harilal Divinlal , Uddin Mohammed , Loney Tom , Nowotny Norbert , Alsuwaidi Hanan , Varghese Rupa , Deesi Zulfa , Alkhajeh Abdulmajeed , Khansaheb Hamda , Alsheikh-Ali Alawi , Tayoun Ahmad Abou 
Published: September 2020

AbstractCharacterizing key molecular and cellular pathways involved in COVID-19 is essential for disease prognosis and management. We perform shotgun transcriptome sequencing of human RNA obtained from nasopharyngeal swabs of patients with COVID-19, and identify a molecular signature associated with disease severity. Specifically, we identify globally dysregulated immune related pathways, such as cytokine-cytokine receptor signaling, complement and coagulation cascades, JAK-STAT, and TGF-β signaling pathways in all, though to a higher extent in patients with severe symptoms. The excessive release of cytokines and chemokines such asCCL2, CCL22, CXCL9andCXCL12and certain interferons and interleukins related genes likeIFIH1, IFI44, IFIT1andIL10were significantly higher in patients with severe clinical presentation compared to mild and moderate presentations. Moreover, early induction of the TGF-β signaling pathway might be the primary cause of pulmonary fibrosis in patients with severe disease. Differential gene expression analysis identified a small set of regulatory genes that might act as strong predictors of patient outcome. Our data suggest that rapid transcriptome analysis of nasopharyngeal swabs can be a powerful approach to quantify host molecular response and may provide valuable insights into COVID-19 pathophysiology.
Potential Rhodopsin and Bacteriochlorophyll-Based Dual Phototrophy in a High Arctic Glacier
Authors: Zeng Yonghui , Chen Xihan , Madsen Anne Mette , Zervas Athanasios , Nielsen Tue Kjærgaard , Andrei Adrian-Stefan , Lund-Hansen Lars Chresten , Liu Yongqin , Hansen Lars Hestbjerg 
Published: September 2020

AbstractConserving additional energy from sunlight through bacteriochlorophyll (BChl)‐based reaction center or proton‐pumping rhodopsin is a highly successful life strategy in environmental bacteria. Rhodopsin and BChl based systems display contrasting characteristics in the size of coding operon, cost of biosynthesis, ease of expression control, and efficiency of energy production. This raises an intriguing question of whether a single bacterium has evolved the ability to perform these two types of phototrophy complementarily according to energy needs and environmental conditions. Here we report fourTardiphagasp. strains (Alphaproteobacteria) of monophyletic origin isolated from a high Arctic glacier in northeast Greenland (81.566° N, 16.363° W) that are at different evolutionary stages concerning phototrophy. Their >99.8% identical genomes contain footprints of horizontal operon transfers (HOT) of the complete gene clusters encoding BChl and xanthorhodopsin (XR)‐based dual phototrophy. Two strains only possess a complete xanthorhodopsin (XR) operon, while the other two strains have both a photosynthesis gene cluster (PGC) and an XR operon in their genomes. All XR operons are heavily surrounded by mobile genetic elements and located close to a tRNA gene, strongly signaling that a HOT event of XR operon has occurred recently. Mining public genome databases and our High Arctic glacial and soil metagenomes revealed that phylogenetically diverse bacteria have the metabolic potential of performing BChl and rhodopsin‐based dual phototrophy. Our data provide new insights on how bacteria cope with the harsh and energy‐deficient environments in surface glaciers, possibly by maximizing the capability of exploiting solar energy.ImportanceOver billions of years of evolution, bacteria capable of light‐driven energy production have occupied every corner of surface Earth where solar irradiation can reach. Only two general biological systems have evolved in bacteria to be capable of net energy conservation via light‐harvesting: one is based on the pigment of (bacterio‐)chlorophyll and the other based on light‐sensing retinal molecules. There is emerging genomic evidence that these two rather different systems can co‐exist in a single bacterium to take advantage of their contrasting characteristics in the number of genes involved, biosynthesis cost, ease of expression control and efficiency of energy production, and thus enhance the capability of exploiting solar energy. Our data provide the first clear‐cut evidence that such dual phototrophy potentially exist in glacial bacteria. Further public genome mining suggests this understudied dual phototrophic mechanism is possibly more common than our data alone suggested.Sequence data availabilityGenomes, metagenomes and raw reads were deposited into GenBank under Bioprojects PRJNA548505 and PRJNA552582.
Molecular characterization of RIGI, TLR7 and TLR3 as immune response gene of indigenous ducks in response to Avian influenza
Authors: Pal Aruna , Pal Abantika , Baviskar Pradyumna 
Published: September 2020

AbstractAvian influenza is an alarming disease, which has every possibility to evolve as human to human pandemic situation due to frequent mutation and genetic reassortment or recombination of Avian influenza(AI) virus. The greatest concern is that till date no satisfactory medicine or vaccines are available, leading to massive culling of poultry birds causing huge economic loss, and ban on export of chicken products, which emphasise the need develop alternative strategy for control of AI. In the current study we attempt to explore the molecular mechanism of innate immune potential of ducks against common viral diseases including Avian influenza. In the present study, we have characterized immune response molecules as duck TLR3, TLR7, and RIGI and predicted to have potent antiviral activities against different identified strains of Avian influenza through in silico studies (molecular docking). Future exploitation involve immunomodulation with the recombinant protein, transgenic or gene-edited chicken resistant to bird flu.
Understanding the origins of loss of protein function by analyzing the effects of thousands of variants on activity and abundance
Authors: Cagiada Matteo , Johansson Kristoffer E. , Valanciute Audrone , Nielsen Sofie V. , Hartmann-Petersen Rasmus , Yang Jun J. , Fowler Douglas M. , Stein Amelie , Lindorff-Larsen Kresten 
Published: September 2020

AbstractUnderstanding and predicting how amino acid substitutions affect proteins is key to our basic understanding of protein function and evolution. Amino acid changes may affect protein function in a number of ways including direct perturbations of activity or indirect effects on protein folding and stability. We have analysed 6749 experimentally determined variant effects from multiplexed assays on abundance and activity in two proteins (NUDT15 and PTEN) to quantify these effects, and find that a third of the variants cause loss of function, and about half of loss-of-function variants also have low cellular abundance. We analyse the structural and mechanistic origins of loss of function, and use the experimental data to find residues important for enzymatic activity. We performed computational analyses of protein stability and evolutionary conservation and show how we may predict positions where variants cause loss of activity or abundance. In this way, our results link thermodynamic stability and evolutionary conservation to experimental studies of different properties of protein fitness landscapes.
Evolution of Modularity, Interactome and Functions of GIV/Girdin (CCDC88A) from Invertebrates to Vertebrates
Authors: Ear Jason , Ali Abd El-Hafeez Amer , Roy Suchismita , Ngo Tony , Rajapakse Navin , Choi Julie , Khandelwal Soni , Ghassemian Majid , McCaffrey Luke , Kufareva Irina , Sahoo Debashis , Ghosh Pradipta 
Published: September 2020

AbstractPDZ domains are one of the most abundant protein domains in eukaryotes and frequently found on junction-localized scaffold proteins. Various signaling molecules bind to PDZ proteinsviaPDZ-binding motifs (PBM) and finetune cellular signaling. Here we describe the presence of a PBM on GIV/Girdin (CCDC88A) that is conserved throughout evolution, from invertebrates to vertebrates, and is generated as alongisoform-variant in humans, which we namedGIV-L. Unlike GIV, which lacks PBM and is cytosolic, GIV-L localizes to the cell junctions, and has a unique PDZ-interactome, which impactsGIV-L’s ability to bind and activate trimeric G-protein, Gi through itsguanine-nucleotideexchangemodulator (GEM) module; the GEM module is found exclusively in vertebrates. Thus, the two functional modules in GIV evolved sequentially: the ability to bind PDZ proteins via the PBM evolved earlier in invertebrates, whereas G-protein binding and activation may have evolved later only among vertebrates. Phenotypic studies in Caco-2 cells revealed that GIV and GIV-L may have antagonistic effects on cell growth, proliferation (cell cycle), and survival. Immunohistochemical analyses in human colon tissues showed that GIV expression increases with a concomitant decrease in GIV-L during cancer initiation. Taken together, these findings reveal how GIV/CCDC88A in humans displays evolutionary flexibility in modularity, which allows the resultant isoforms to play opposing roles either as a tumor suppressor (GIV-L) or as an oncogene (GIV).
FHL-1 interacts with human RPE cells through the α5β1 integrin and confers protection against oxidative stress
Authors: Choudhury Rawshan , Bayatti Nadhim , Scharff Richard , Szula Ewa , Tilakaratna Viranga , Udsen Maja Søberg , McHarg Selina , Askari Janet A , Humphries Martin J , Bishop Paul N , Clark Simon J 
Published: September 2020

AbstractRetinal pigment epithelial (RPE) cells that underlie the neurosensory retina are essential for the maintenance of photoreceptor cells and hence vision. Interactions between the RPE and their basement membrane,i.e. the inner layer of Bruch’s membrane, are essential for RPE cell health and function, but the signals induced by Bruch’s membrane engagement, and their contributions to RPE cell fate determination remain poorly defined. Here, we studied the functional role of the soluble complement regulator and component of Bruch’s membrane, Factor H-like protein 1 (FHL-1). Human primary RPE cells adhered to FHL-1 in a manner that was eliminated by either mutagenesis of the integrin-binding RGD motif in FHL-1 or by using competing antibodies directed against the α5 and β1 integrin subunits. The results obtained from primary RPE cells were replicated using the hTERT-RPE cell line. RNAseq expression analysis of hTERT-RPE cells bound to FHL-1 showed an increased expression of the heat-shock protein genesHSPA6, CRYAB, HSPA1AandHSPA1Bwhen compared to cells bound to fibronectin (FN) or laminin (LA). Pathway analysis implicated changes in EIF2 signalling, the unfolded protein response, and mineralocorticoid receptor signalling as putative pathways. Subsequent cell survival assays using H2O2to induce oxidative stress-induced cell death showed hTERT-RPE cells had significantly greater protection when bound to FHL-1 or LA compared to plastic or FN. These data show a non-canonical role of FHL-1 in protecting RPE cells against oxidative stress and identifies a novel interaction that has implications for ocular diseases such as age-related macular degeneration.
A cloud-based platform for the analysis of single cell RNA sequencing data
Authors: Joshy Nithin , Yun Kyuson 
Published: September 2020

AbstractMotivationSingle-cell RNA sequencing (scRNA-seq) is a recent technology that has provided many valuable biological insights. Notable uses include identifying novel cell-types, measuring the cellular response to treatment, and tracking trajectories of distinct cell lineages in time. The raw data generated in this process typically amounts to hundreds of millions of sequencing reads and requires substantial computational infrastructure for downstream analysis, a major hurdle for a biological research lab. Fortunately, the preprocessing step that converts this huge sequence data into manageable cell-specific expression profiles is standardized and can be performed in the cloud. We demonstrate how a cloud-based computational framework can be used to transform the raw data into biologically interpretable cell-type-specific information, using either 3’ or 5’ transcriptome libraries from 10x Genomics. The processed data which is an order of magnitude smaller in size can be easily downloaded to a laptop for customized analysis to gain deeper biological insights.ResultsWe produced an automated and easily extensible pipeline in the cloud for the analysis of single-cell RNA-seq data which provides a convenient method to handle post-processing of scRNA sequencing using next generation sequencing platforms. The basic step provides the transformation of the scRNA-seq data to cell-type-specific expression profiles and computes the quality control metrics for the dataset. The extensibility of the platform is demonstrated by adding a doublet-removal algorithm and recomputing the clustering of the cells. Any additional computational steps that take a cell-type expression counts matrix as input can be easily added to this framework with minimal effort.AvailabilityThe framework and its documentation for installation is available at the Github repositoryhttp://github.com/nj3252/CB-Source/Contactkyun@houstonmethodist.orgSupplementary informationSupplementary data available atBioinformaticsonline.
Entrepreneurship education and undergraduate students' self-employment intentions: do paid employment intentions matter?
Authors: Otache Innocent , Oluwade Dorcas Omanyo , Idoko Ele-Ojo Jeremiah 
Published: September 2020

PurposeUndergraduate students have two opposing employment intentions, viz. self-employment intentions and paid-employment intentions (SEIs and PEIs). While a plethora of studies have explored the links between entrepreneurship education (EE) and SEIs, it has been noted that previous studies have ignored the effects of PEIs on the relationship between EE and SEIs. The purpose of this study, therefore, is to empirically explore the effects of PEIs on the relationship between EE and SEIs.Design/methodology/approachThis study adopted a descriptive research design and a self-reported questionnaire was administered to collect data from a randomly selected sample of 95 accounting students from two polytechnics in Nigeria. To test the hypotheses formulated, partial least squares structural equation modelling (PLS-SEM) was performed using SmartPLS.FindingsThe results of Model 1 showed that EE had a significantly positive link with SEIs. On the other hand, the analysis of Model 2 revealed an inverse relationship between PEIs and SEIs. Furthermore, it was observed that the impact of EE on SEIs did not only reduce significantly when PEIs was added to Model 1 but also the relationship between EE and SEIs that was erstwhile statistically significant became nonsignificant.Practical implicationsThe findings have implications for EE curriculum developers, governments and career guidance counsellors.Originality/valueTo the best of the authors' knowledge, this study is the first to provide empirical evidence of the effects of PEIs on the relationship between EE and SEIs. The findings provide important insights into the fundamental issue, which underlies the problem of graduate unemployment.
Nitrogen deposition regulates the clonal growth of Leymus chinensis, a typical clonal plant in arid and semi-arid regions
Authors: Liu Li , Zhou ChengYang , Pei Xiao , Guo LiZhu , Li JiaHuan , Wu RuiXin , Huang Ding 
Published: September 2020

Purpose
The purpose of this study is to examine the effects of nitrogen (N) deposition on clonal growth in a rhizome clonal plant, Leymus chinensis (Trin.) Tzvel.

Design/methodology/approach
The study established seven N concentration gradients (0, 2, 4, 8, 16, 32 and 64 g N m−2) to simulate the continuous increase in N deposition for the cultivation of L. chinensis seedlings and assess the response mechanism of the cloned L. chinensis plant at different N levels by analyzing the aboveground and belowground plant appearance traits, parent ramets and daughter ramets of resource allocation and biomass allocation.

Findings
The results of this study showed that the different N treatment levels could promote clonal growth and had certain regularity under the seven treatments. The addition of N could significantly increase the ramet number, rhizome length, rhizome spacer length, biomass of mother ramets, daughter ramets and belowground L. chinensis population when the N addition was greater than 4 g m−2; however, the clonal growth ability of L. chinensis decreased and the rhizome length, ramet number, stem and leaf biomass of daughter ramets and stem biomass of mother ramets significantly decreased when the N addition was greater than 32 g N m−2.

Originality/value
With global warming, atmospheric N deposition is increasing and it is of great significance to explore the response mechanism of different N levels for the growth of clone plants. This study provides basic data and a theoretical basis for the survival prediction of cloned plants under the background of a global climate change strategy and has important theoretical and practical significance for the scientific management of grasslands in the future.
Ecosystems 4.0: redesigning global value chains
Authors: Schmidt Marie-Christin , Veile Johannes W. , Müller Julian M. , Voigt Kai-Ingo 
Published: September 2020

PurposeThe study analyses how Industry 4.0 and underlying digital technologies influence the design of ecosystems in global value chains (GVCs).Design/methodology/approachA qualitative-exploratory research design is used. It deploys a multiple case study based on semi-structured interviews with 73 German managers of multinational enterprises. Applying a qualitative content analysis, the expert interviews are inductively analyzed and triangulated with secondary data to develop a synthesized data structure.FindingsThe analysis reveals a general tendency towards decentralization of value chain activities. Depending on the nature of each activity and several contextual factors, however, hybrids between centralization and decentralization of processes can be observed in Industry 4.0 environments. Consequences for global ecosystems are altered cooperation with business partners, new organizational forms and novel market environments.Research limitations/implicationsGiven inherent limitations in scope and methodology, the study calls for cross-industry and cross-country analyses. Further studies should research implications of Industry 4.0 changes in ecosystems and GVCs, and the role digital platforms can play in this context.Practical implicationsThe results help companies to analyze and adapt their role in ecosystems and associated GVC activities to Industry 4.0 environments, thus staying competitive in changing market conditions.Originality/valueThis study is among the first to empirically investigate the influence of Industry 4.0 on ecosystems embedded in GVCs. Reflecting existing company environments, it adds an international and company-external perspective to Industry 4.0 research.
An IT governance framework for IS portfolio management
Authors: Erasmus Wikus , Marnewick Carl 
Published: September 2020

PurposeSuccess in the information systems (IS) project domain is elusive despite extensive research on the topic. Governance is seen as the greatest contributor to project success. The purpose of this paper is to investigate and report on the current perceptions and implementation of information technology (IT) governance within IS portfolio management to develop a sub-framework to guide practitioners. This sub-framework forms part of a grand IS project, programme and portfolio governance framework of which this study forms a contributing part.Design/methodology/approachThe researchers followed a mixed-methods approach through utilising Q-methodology and inverted factor analysis.FindingsThe results provided a sub-framework recommending specific IT governance practices to be applied to IS portfolios. The recommendations are categorised as activities to be maintained, enhanced and/or implemented.Research limitations/implicationsThe research only had participants from South African organisations and as such cannot be reliably extrapolated to other regions.Originality/valueThe resultant sub-framework provides stakeholders and practitioners involved in IS portfolios an opportunity to examine their own approaches and be confronted with possibilities in their portfolio management activities. Further research to be conducted includes creating a grand framework to address the linkages between portfolio, programme and project management as it relates to IT governance on various strategic levels.