bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monitoring Protein Import into the Endoplasmic Reticulum in Living Cells with Proximity Labeling
Authors: Lyu Ziqi , Sycks Melody M. , Espinoza Mateo F. , Nguyen Khanh K. , Montoya Maureen R. , Galapate Cheska M. , Mei Liangyong , Genereux Joseph C. 
Published: December 2021

ABSTRACTThe proper trafficking of eukaryotic proteins is essential to cellular function. Genetic, environmental, and other stresses can induce protein mistargeting, and in turn threaten cellular protein homeostasis. Current methods for measuring protein mistargeting are difficult to translate to living cells, and thus the role of cellular signaling networks in stress-dependent protein mistargeting processes, such as ER pre-emptive quality control (ER pQC), are difficult to parse. Herein, we use genetically encoded peroxidases to characterize protein import into the endoplasmic reticulum (ER). We show that the ERHRP/cytAPEX pair provides good selectivity and sensitivity for identifying protein mistargeting, using the known ER pQC substrate transthyretin (TTR). Although ERHRP labeling induces formation of detergent-resistant TTR aggregates, this is minimized by using low ERHRP expression, without loss of labeling efficiency. cytAPEX labeling recovers TTR that is mistargeted as a consequence of Sec61 inhibition or ER stress-induced ER pQC. Furthermore, we demonstrate that stress-free activation of the ER stress-associated transcription factor ATF6 recapitulates the TTR import deficiency of ER pQC. Hence, proximity labeling is an effective strategy for characterizing factors that influence ER protein import in living cells.
Comparative genomics of Nocardia seriolae reveals recent importation and subsequent widespread dissemination in mariculture farms in South Central Coast, Vietnam
Authors: Le Cuong T. , Price Erin P. , Sarovich Derek S. , Nguyen Thu T.A , Powell Daniel , Vu-Khac Hung , Kurtböke Ipek , Knibb Wayne , Chen Shih-Chu , Katouli Mohammad 
Published: December 2021

AbstractBetween 2010 and 2015, nocardiosis outbreaks caused by Nocardia seriolae affected many permit farms throughout Vietnam, causing mass fish mortalities. To understand the biology, origin, and epidemiology of these outbreaks, 20 N. seriolae strains collected from farms in four provinces in the South-Central Coast of Vietnam, along with two Taiwanese strains, were analysed using genetics and genomics. Pulsed-field gel electrophoresis identified a single cluster amongst all Vietnamese strains that was distinct from the Taiwanese strains. Like the PFGE findings, phylogenomic and single-nucleotide polymorphism (SNP) genotyping analyses revealed that all Vietnamese N. seriolae strains belonged to a single, unique clade. Strains fell into two subclades that differed by 103 SNPs, with almost no diversity within clades (0-2 SNPs). There was no association between geographic origin and subclade placement, suggesting frequent N. seriolae transmission between Vietnamese mariculture facilities during the outbreaks. Vietnamese strains shared a common ancestor with strains from Japan and China, with the closest strain, UTF1 from Japan, differing by just 217 SNPs from the Vietnamese ancestral node. Draft Vietnamese genomes range from 7.55-7.96 Mbp in size, have an average G+C content of 68.2%, and encode 7,602-7,958 predicted genes. Several putative virulence factors were identified, including genes associated with host cell adhesion, invasion, intracellular survival, antibiotic and toxic compound resistance, and haemolysin biosynthesis. Our findings provide important new insights into N. seriolae epidemiology and pathogenicity and will aid future vaccine development and disease management strategies, with the ultimate goal of nocardiosis-free aquaculture.
R code and downstream analysis objects for the scRNA-seq atlas of human breast spanning normal, preneoplastic and tumorigenic states
Authors: Chen Yunshun , Pal Bhupinder , Lindeman Geoffrey J , Visvader Jane E , Smyth Gordon K 
Published: December 2021

ABSTRACTBreast cancer is a common and highly heterogeneous disease. Understanding the cellular diversity in the mammary gland and its surrounding micro-environment across different states can provide insight into the cancer development in human breast. Recently, a large-scale single-cell RNA expression atlas was constructed of the human breast spanning normal, preneoplastic and tumorigenic states. Single-cell expression profiles of nearly 430,000 cells were obtained from 69 distinct surgical tissue specimens from 55 patients. This article extends the study by providing downstream processed R data objects, complete cell annotation and R code to reproduce all the analyses. Details of all the bioinformatic analyses that produced the results described in the study are provided.
A single-cell transcriptome atlas of human early embryogenesis
Authors: Xu Yichi , Zhang Tengjiao , Zhou Qin , Hu Mengzhu , Qi Yao , Xue Yifang , Wang Lihui , Nie Yuxiao , Bao Zhirong , Shi Weiyang 
Published: December 2021

AbstractThe early window of human embryogenesis is largely a black box for developmental biologists. Here we probed the cellular diversity of 4- to 6-week human embryos when essentially all organs are just laid out. Based on over 180,000 single-cell transcriptomes, we generated a comprehensive atlas of 313 cell types in 18 developmental systems, which were annotated with a collection of ontology and markers from 157 publications. Together with spatial transcriptome on embryonic sections, we characterized the molecule and spatial architecture of previously unappreciated cell types. Combined with data from other vertebrates, the rich information shed light on spatial patterning of axes, systemic temporal regulation of developmental progression and potential human-specific regulation. Our study provides a compendium of early progenitor cells of human organs, which can serve as the root of lineage analysis in organogenesis.
ChiMera: An easy to use pipeline for Bacterial Genome Based Metabolic Network Reconstruction, Evaluation and Visualization
Authors: Tamasco Gustavo , da Silva Ricardo R. , Silva-Rocha Rafael 
Published: December 2021

AbstractSeveral genome scale metabolic reconstruction tools have been developed in the last decades. They have helped to construct many metabolic models, which have contributed to a variety of fields, e.g., genetic engineering, drug discovery, prediction of phenotypes, and other model-driven discoveries. However, the use of these programs requires a higher level of bioinformatic skills, and most of them are not scalable for multiple genomes. Moreover, the functionalities required to build models are generally scattered through multiple tools, requiring knowledge of their utilization.Here, we present ChiMera, which combines the most efficient tools in model reconstruction, prediction, and visualization. ChiMera uses CarveMe top-down approach based on genomic evidence to prune a global model with a high level of curation, generating a draft genome able to produce growth predictions using flux balance analysis for gram-positive and gram-negative bacteria. ChiMera also contains two modules of visualization implemented, predefined and universal. The first generates maps for the most important pathways, e.g., core-metabolism, fatty acid oxidation and biosynthesis, nucleotides and amino acids biosynthesis, glycolysis, and others. The second module produces a genome-wide metabolic map, which can be used to harvest KEGG pathway information for each compound in the model. A module of gene essentiality and knockout is also present. Overall, ChiMera combines model creation, gap-filling, FBA and metabolic visualization to create a simulation ready genome-scale model, helping genetic engineering projects, prediction of phenotypes, and other model-driven discoveries in a friendly manner.
MuDCoD: Multi-Subject Community Detection in Personalized Dynamic Gene Networks from Single Cell RNA Sequencing
Authors: Şapcı Ali Osman Berk , Lu Shan , Yan Shuchen , Ay Ferhat , Tastan Oznur , Keleş Sündüz 
Published: December 2021

AbstractMotivationWith the wide availability of single-cell RNA-seq (scRNA-seq) technology, population-scale scRNA-seq datasets across multiple individuals and time points are emerging. While the initial investigations of these datasets tend to focus on standard analysis of clustering and differential expression, leveraging the power of scRNA-seq data at the personalized dynamic gene co-expression network level has the potential to unlock subject and/or time-specific network-level variation, which is critical for understanding phenotypic differences. Community detection from co-expression networks of multiple time points or conditions has been well-studied; however, none of the existing settings included networks from multiple subjects and multiple time points simultaneously. To address this, we develop MuDCoD for multi-subject community detection in personalized dynamic gene networks from scRNA-seq. MuDCoD builds on the spectral clustering framework and promotes information sharing among the networks of the subjects as well as networks at different time points. It clusters genes in the personalized dynamic gene networks and reveals gene communities that are variable or shared not only across time but also among subjects.ResultsEvaluation and benchmarking of MuDCoD against existing approaches reveal that MuDCoD effectively leverages apparent shared signals among networks of the subjects at individual time points, and performs robustly when there is no or little information sharing among the networks. Applications to population-scale scRNA-seq datasets of human-induced pluripotent stem cells during dopaminergic neuron differentiation and CD4+ T cell activation indicate that MuDCoD enables robust inference for identifying time-varying personalized gene modules. Our results illustrate how personalized dynamic community detection can aid in the exploration of subject-specific biological processes that vary across time.AvailabilityMuDCoD is publicly available athttps://github.com/bo1929/MuDCoDas a Python package. Implementation includes simulation and real-data experiments together with extensive documentation.Contactkeles@stat.wisc.edu,otastan@sabanciuniv.eduSupplementary informationSupplementary data are available atBioinformaticsonline.
The three-dimensional chromatin structure of the major human pancreatic cell types reveals lineage-specific regulatory architecture of T2D risk
Authors: Su Chun , Gao Long , May Catherine L. , Pippin James A. , Boehm Keith , Lee Michelle , Liu Chengyang , Pahl Matthew C. , Golson Maria L. , Naji Ali ,   the HPAP Consortium, Grant Struan F.A. , Wells Andrew D. , Kaestner Klaus H. 
Published: December 2021

AbstractThree-dimensional (3D) chromatin organization maps help to dissect cell type-specific gene regulatory programs. Furthermore, 3D chromatin maps have contributed to elucidating the pathogenesis of complex genetic diseases by connecting distal regulatory regions and genetic risk variants to their respective target genes. To understand the cell type-specific regulatory architecture of diabetes risk, we generated transcriptomic and 3D epigenomic profiles of human pancreatic acinar, alpha, and beta cells using single-cell RNA-seq, single-cell ATAC-seq, and high-resolution Hi-C of sorted cells. Comparisons of these profiles revealed differential A/B (open/closed) chromatin compartmentalization, chromatin looping, and transcriptional factor mediated control of cell type-specific gene regulatory programs. We identified a total of 4,750 putative causal-variant-target-gene pairs at 194 type 2 diabetes GWAS signals using pancreatic 3D chromatin maps. We found that the connections between candidate causal variants and their putative target effector genes are cell-type stratified and emphasize previously underappreciated roles for alpha and acinar cells in diabetes pathogenesis.
Copper nanoparticles as modulator of active bacterial population and their physiology in ecosphere
Authors: Alboloushi Ali , Alum Absar , Abbaszadegan Morteza 
Published: December 2021

AbstractThe widespread use of nanoparticles (NPs) in industrial and consumer products has resulted in their emergence as significant environmental contaminants that can potentially modulate the role of bacteria in environment. This study examines the impact of different sizes of Copper nanoparticles (CuNPs) on the population and physiology of environmentally relevant gram positive (Bacillus) and gam negative (Alcaligenes, and Pseudomonas) bacteria. In general, exposure to CuNPs resulted in 4 to >6 log inactivation in bacterial population. More specifically, after 2hr exposure of Alcaligenes and Pseudomonas to 50 CuNPs, 5.75 and 6.64 log reduction noted, respectively; and their exposure to 100 CuNPs resulted in 5.97 and 6.58 log reduction, respectively. A similar exposure of laboratory and environmental isolates of Bacillus to 50 and 100 CuNPs resulted in 4.84, 4.16 and 4.35, 3.61 log reduction, correspondingly. The exposure induced elicitation of different toxicity pathways in the test bacteria. Bacterial exposure to 50 CuNPs resulted in elevated levels of LDH in Pseudomonas, in contrast these levels decreased in Alcaligenes and Bacillus. Our toxicity studies showed that exposure to CuNP can have various levels of metabolic and cellular modulation in bacterial species, suggesting that the presence of CuNPs in environment can potentially impact the pollutants-attenuation-role of bacteria in environments such as wastewater biological treatment processes.
Mitochondrial DNA metabolism is coupled with 20S proteasome function via regulation of deoxyribonucleotide homeostasis in Saccharomyces cerevisiae
Authors: Wang Xiaowen , Rana Arnav , Coyne Liam P. , Loh Daniel M. , La Thuy , Chen Xin Jie 
Published: December 2021

SUMMARYThe synthesis of mitochondrial DNA (mtDNA) is not coupled with cell cycle. Previous studies have shown that the size of deoxyribonucleoside triphosphate (dNTP) pools plays an important role in regulating mtDNA replication and amplification. In yeast, dNTPs are synthesized by the cytosolic ribonucleotide reductase (RNR). It is currently poorly understood as to how RNR activity is regulated in non-dividing or quiescent cells to finely tune mtDNA metabolism to cope with different metabolic states. Here, we show that defect in the 20S proteasome drastically destabilizes mtDNA. The mtDNA instability phenotype in 20S proteasome mutants is suppressed by overexpression of RNR3 or by the deletion of SML1, encoding a minor catalytic subunit and an intrinsic inhibitor of RNR respectively. We found that Sml1 is stabilized in the 20S proteasomal mutants, suggesting that 20S affects mtDNA stability by stabilizing Sml1. Interestingly, defect in the regulatory 19S proteasomal function has only subtle effect on mtDNA stability, supporting a role of the 20S proteasome in dNTP homeostasis independent of 19S. Finally, we found that when cells are transitioned from glycolytic to oxidative growth, Sml1 level is reduced in a 20S-dependent manner. In summary, our study establishes a link between cellular proteostasis and mtDNA metabolism through the regulation of dNTP homeostasis. We propose that increased degradation of Sml1 by the 20S proteasome under respiratory conditions provides a mechanism to stimulate dNTP synthesis and promote mtDNA amplification.
Homeostatic active zone remodeling consolidates memories in the Drosophila mushroom body
Authors: Turrel Oriane , Ramesh Niraja , Escher Marc J.F. , Sigrist Stephan J. 
Published: December 2021

Establishing a detailed understanding of how the distinct forms of synaptic plasticity spatio-temporally engage into the initial storage and subsequent consolidation of memories remains a fundamental challenge of neuroscience. In addition to the better understood postsynaptic plasticity, different forms of presynaptic plasticity are widely expressed in mammalian brains and apparently operate along Hebbian or homeostatic rules. Their behavioral relevance remains enigmatic, however. Lately, acute upregulation of active zone (AZ) scaffold protein BRP and release factor Unc13A via specific axonal transport factors were shown to mediate stable expression of presynaptic homeostatic plasticity (PHP) at Drosophila neuromuscular junctions (NMJs).We here demonstrate that AZ scaling processes are specifically needed for stable expression of both, NMJ PHP as well as aversive olfactory mid-term memory within intrinsic neurons of the Drosophila mushroom body (MB). We first demonstrate that AZ upscaling via BRP is specifically needed for expression but not induction of NMJ homeostatic plasticity, thus establishing a direct temporal plasticity sequence of molecularly distinct AZ remodeling steps. Notably, when we reduced BRP and associated transport factors in MB intrinsic neurons, short-term memory persisted but robust deficits in stable memory expression for a few hours after conditioning were observed. In contrast, AZ release site protein RIM-BP affecting PHP induction was additionally needed for successful formation of short-term memory.Taken together, our data establish a specific role of homeostatic presynaptic long-term plasticity for memory consolidation. Such homeostatic refinement processes might well be needed to successfully integrate and display synaptic engrams constituting intermediary term memories.
Tandem WW/PPxY motif interactions in WWOX: the multifaceted role of the second WW domain
Authors: Rotem-Bamberger Shahar , Fahoum Jamal , Keinan-Adamsky Keren , Tsaban Tomer , Avraham Orly , Shalev Deborah E. , Chill Jordan H. , Schueler-Furman Ora 
Published: December 2021

AbstractClass I WW domains mediate protein interactions by binding short linear PPxY motifs. They occur predominantly as tandem repeats, and their target proteins often contain multiple PPxY motifs, but the interplay of WW/peptide interactions is not always intuitive. WW domain-containing oxidoreductase (WWOX) protein harbors two WW domains: unstable WW1 capable of PPxY binding, and well-folded but mutated WW2 that cannot bind such motifs. WW2 is considered to act as a WW1 chaperone, but the underlying mechanism remains to be revealed. Here we combine NMR, ITC and structural modeling to elucidate the role of both WW domains in WWOX binding to single and double motif peptides derived from its substrate ErbB4. Using NMR we identified an interaction surface between the two domains that supports a WWOX conformation that is compatible with peptide substrate binding. ITC and NMR measurements reveal that while binding affinity to a single motif is marginally increased in the presence of WW2, affinity to a dual motif peptide increases tenfold, and that WW2 can directly bind double motif-peptides using its canonical binding site. Finally, differential binding of peptides in a mutagenesis study is consistent with a parallel orientation binding to the WW1-WW2 tandem domain, agreeing with structural models of the interaction. Our results reveal the complex nature of tandem WW domain organization and substrate binding, highlighting the contribution of WWOX WW2 to both stability and binding. This opens the way to assess how evolution can utilize the multivariate nature of binding to fine-tune interactions for specific biological functions.
A national framework for promoting business excellence (NFPBE)
Authors: Lobo Stanislaus , Samaranayake Premaratne , Matawie Kenan M. 
Published: December 2021

PurposeThe purpose of this paper is to propose a national framework for promoting business excellence (NFPBE) using a quality management assessment framework (QMAF) with information knowledge communication (IKC) as an enabler.Design/methodology/approachThe NFPBE using the plan–do–check–act (PDCA) cycle is developed, re-enforcing key quality management aspects/areas including national quality awards, QMAF summary and national innovation programmes using a meta-analysis.FindingsThe operationalising of the NFPBE is enabled and supported by an auditing tool to assess the degree of mentoring provided by universities/research institutions/consulting firms to participating firms whose progress will be assessed by the QMAF. It was emphasised that the success of the framework requires the buy-in of national governments to support the programme through stimulus incentives such as government assistance with the costs of research and development, and cooperative research ventures between universities and companies.Research limitations/implicationsThe framework is conceptualised into a process flowchart, which is a blueprint to advancing business excellence in organisations at a national scale. The study is limited to only the conceptualisation of the framework. Therefore, an extended study of the framework implementation/application is required for revealing implementation guidelines.Practical implicationsThe national framework has a propensity to enhancing the business excellence of organisations at a national level. Therefore, quality managers and policy makers could use the framework to understand the quality management shortfalls and consider strategies to achieving business excellence.Originality/valueThis research study proposed a blueprint to advancing quality excellence in organisations at a national level, guided by several quality frameworks.
A state-of-the-art overview of job-crafting research: current trends and future research directions
Authors: Tims Maria , Twemlow Melissa , Fong Christine Yin Man 
Published: December 2021

PurposeIn celebration of the 25th anniversary of the founding of Career Development International, a state-of-the-art overview of recent trends in job-crafting research was conducted. Since job crafting was introduced twenty years ago as a type of proactive work behavior that employees engage in to adjust their jobs to their needs, skills, and preferences, research has evolved tremendously.Design/methodology/approachTo take stock of recent developments and to unravel the latest trends in the field, this overview encompasses job-crafting research published in the years 2016–2021. The overview portrays that recent contributions have matured the theoretical and empirical advancement of job-crafting research from three perspectives (i.e. individual, team and social).FindingsWhen looking at the job-crafting literature through these three perspectives, a total of six trends were uncovered that show that job-crafting research has moved to a more in-depth theory-testing approach; broadened its scope; examined team-level job crafting and social relationships; and focused on the impact of job crafting on others in the work environment and their evaluations and reactions to it.Originality/valueThe overview of recent trends within the job-crafting literature ends with a set of recommendations for how future research on job crafting could progress and create scientific impact for the coming years.