bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation and validation of an anti-human PANK3 mouse monoclonal antibody
Authors: Khadka Sunada , Vien Long , Leonard Paul , Bover Laura , Muller Florian 
Published: February 2022

AbstractCoenzyme A (CoA) is an essential co-factor at the intersection of diverse metabolic pathways. Cellular CoA biosynthesis is regulated at the first committed step— phosphorylation of pantothenic acid—catalyzed by pantothenate kinases (PANK1,2,3 in humans, PANK3 being the most highly expressed). Despite the critical importance of CoA in metabolism, the differential roles of PANK isoforms remain poorly understood. Our investigations of PANK proteins as precision oncology collateral lethality targets (PANK1 is co-deleted as part of the PTEN locus in some highly aggressive cancers) were severely hindered by a dearth of commercial antibodies that can reliably detect endogenous PANK3. While we successfully validated commercial antibodies for PANK1 and PANK2 using CRISPR knockout cell lines, we found no commercial antibody that could detect endogenous PANK3. We therefore set out to generate a mouse monoclonal antibody against human PANK3 protein. We demonstrate that clone (Clone MDA-299-62A) can reliably detect endogenous PANK3 protein in cancer cell lines, with band-specificity confirmed by CRISPR PANK3 knockout cell lines. Sub-cellular fractionation indicates that PANK3 is overwhelmingly cytosolic and expressed broadly across cancer cell lines. PANK3 monoclonal antibody MDA-299-62A should prove a valuable tool for researchers investigating this understudied family of metabolic enzymes in health and disease.
Decoding Dynamically Shifting States of Parkinson’s Disease: Tremor, Bradykinesia, and Effective Motor Control
Authors: Lauro Peter M. , Lee Shane , Amaya Daniel E. , Liu David D. , Akbar Umer , Asaad Wael F 
Published: February 2022

AbstractParkinson’s Disease (PD) is characterized by distinct motor phenomena that are expressed asynchronously. Understanding the neurophysiological correlates of these different motor states could facilitate monitoring of disease progression and allow improved assessments of therapeutic efficacy, as well as enable optimal closed-loop neuromodulation. We examined neural activity in the basal ganglia and cortex of subjects with PD during a quantitative motor task to decode tremor and bradykinesia — two cardinal motor signs of this disease — and relatively asymptomatic periods of behavior. Analysis of subcortical and cortical signals revealed that tremor and bradykinesia had distinct, nearly opposite neural signatures, while effective motor control displayed unique, differentiating features. The neurophysiological signatures of these motor states depended on the type of signal recorded as well as the location; cortical decoding accuracy generally outperformed subcortical decoding, while tremor and bradykinesia were better decoded from different portions of the subthalamic nucleus (STN). These results provide a roadmap to leverage real-time neurophysiology to understand and treat PD.One Sentence SummaryMotor signs of Parkinson’s disease such as tremor and bradykinesia can be independently decoded from subthalamic and cortical recordings.
RNA velocity unraveled
Authors: Gorin Gennady , Fang Meichen , Chari Tara , Pachter Lior 
Published: February 2022

AbstractWe perform a thorough analysis of RNA velocity methods, with a view towards understanding the suitability of the various assumptions underlying popular implementations. In addition to providing a self-contained exposition of the underlying mathematics, we undertake simulations and perform controlled experiments on biological datasets to assess workflow sensitivity to parameter choices and underlying biology. Finally, we argue for a more rigorous approach to RNA velocity, and present a framework for Markovian analysis that points to directions for improvement and mitigation of current problems.
The zinc finger transcription factor Sall1 is required for the early developmental transition of microglia in mouse embryos
Authors: Scott Earl Parker , Breyak Emma , Nishinakamura Ryuichi , Nakagawa Yasushi 
Published: February 2022

ABSTRACTMicroglia play many critical roles in neural development. Recent single-cell RNA-sequencing studies have found diversity of microglia both across different stages and within the same stage in the developing brain. However, how such diversity is controlled during development is poorly understood. In this study, we first found the expression of the macrophage mannose receptor CD206 in early-stage embryonic microglia on mouse brain sections. This expression showed a sharp decline between E12.5 and E13.5 across the central nervous system. We next tested the roles of the microglia-expressed zinc finger transcription factor SALL1 in this early transition of gene expression. By deleting Sall1 specifically in microglia, we found that many microglia continued to express CD206 when it is normally downregulated. In addition, the mutant microglia continued to show less ramified morphology in comparison with controls even into postnatal stages. Thus, SALL1 is required for early microglia to transition into a more mature status during development.
hibayes: An R Package to Fit Individual-Level, Summary-Level and Single-Step Bayesian Regression Models for Genomic Prediction and Genome-Wide Association Studies
Authors: Yin Lilin , Zhang Haohao , Li Xinyun , Zhao Shuhong , Liu Xiaolei 
Published: February 2022

AbstractWith the rapid development of sequencing technology, the costs of individual genotyping have been reduced dramatically, leading to genomic prediction and genome-wide association studies being widely promoted and used to predict the unknown phenotypes and to locate causal or candidate genes for animal and plant economic traits and, increasingly, for human diseases. Developing newly advanced statistical models to improve accuracy in predicting and locating for the traits with various genetic architectures has always been a hot topic in those two research domains. The Bayesian regression model (BRM) has played a crucial role in the past decade, and it has been used widely in relevant genetic analyses owing to its flexible model assumptions on the unknown genetic architecture of complex traits. To fully utilize the available data from either a self-designed experimental population or a public database, statistical geneticists have constantly extended the fitting capacity of BRM, and a series of new methodologies have been proposed for different application scenarios. Here we introduce hibayes, which is the only one tool that can implement three types of Bayesian regression models. With the richest methods achieved thus far, it covers almost all the functions involved in genetic analyses for genomic prediction and genome-wide association studies, potentially addressing a wide range of research problems, while retaining an easy-to-use and transparent interface. We believe that hibayes will facilitate the researches conducted by human geneticists, as well as plant and animal breeders. The hibayes package is freely available from CRAN at https://cran.r-project.org/package=hibayes.
Knockout of Sorbs2 in Cardiomyocytes Leads to Dilated Cardiomyopathy in Mice
Authors: McLendon Jared M. , Zhang Xiaoming , Matasic Daniel S. , Kumar Mohit , Koval Olha M. , Grumbach Isabella M. , Sadayappan Sakthivel , London Barry , Boudreau Ryan L. 
Published: February 2022

2.AbstractRationaleSorbs2 is a cardiomyocyte-enriched, cytoskeletal adaptor protein, and given some evidence for its dysregulated expression in failing hearts, there is growing interest in understanding its roles in cardiac biology and disease. While Sorbs2 global knockout mice display lethal cardiomyopathy with severe arrhythmias, the underlying mechanisms remain unclear, and whether this results from intrinsic loss of Sorbs2 in cardiomyocytes is unknown, as Sorbs2 is also well-expressed in the nervous system and vasculature. In addition, the potential relevance of Sorbs2 in human cardiomyopathy remains underexplored.ObjectiveTo characterize the effects and potential underlying mechanisms of cardiomyocyte- specific deletion of Sorbs2 on cardiac structure and function in mice, and to further examine Sorbs2 dysregulation in failing hearts and explore potential links between Sorbs2 genetic variations and human cardiovascular disease phenotypes.Methods and ResultsWe report that myocardial Sorbs2 expression is consistently upregulated in humans with ischemic and idiopathic cardiomyopathies, and in experimental animal models of heart failure (HF). We generated mice with cardiomyocyte-specific loss of Sorbs2 (Sorbs2-cKO) and found early atrial and ventricular conduction abnormalities, despite unaltered expression of primary action potential ion channels and gap junction proteins. At mid-life, Sorbs2-cKO mice exhibit impaired cardiac contractility with cardiomyofibers failing to maintain adequate mechanical tension. As a result, these mice develop progressive diastolic and systolic dysfunction, enlarged cardiac chambers, and die with congestive HF at approximately one year of age. Comprehensive survey of potential underlying mechanisms revealed that Sorbs2-cKO hearts exhibit defective microtubule polymerization and compensatory upregulation of structural proteins desmin, vinculin, and tubulins. Finally, consistent with our observations in mice, we identified suggestive links between Sorbs2 genetic variants and related human cardiac phenotypes, including conduction abnormalities, atrial enlargement, and dilated cardiomyopathy.ConclusionsOur studies show that Sorbs2 is essential for maintaining cytoskeletal structural integrity in cardiomyocytes likely through strengthening the interactions between microtubules and other structural proteins at crosslink sites. Overall, this study provides key insights into the critical role for Sorbs2 in cardiomyocytes and likely other cell types in maintaining normal cardiac structure and function and highlights its potential clinical relevance.
Alterations of oral microbiota and impact on the gut microbiome in type 1 diabetes mellitus revealed by multi-omic analysis
Authors: Kunath B.J. , Hickl O. , Queirós P. , Martin-Gallausiaux C. , Lebrun L.A. , Halder R. , Laczny C.C. , Schmidt T.S.B. , Hayward M.R. , Becher D. , Heintz-Buschart A. , de Beaufort C. , Bork P. , May P. , Wilmes P. 
Published: February 2022

AbstractBackgroundAlterations of the gut microbiome have been linked to multiple chronic diseases. However, the drivers of such changes remain largely unknown. The oral cavity acts as a major route of exposure to exogenous factors including pathogens, and processes therein may affect the communities in the subsequent compartments of the gastrointestinal tract. Here, we perform strain-resolved, integrated multi-omic analyses of saliva and stool samples collected from eight families with multiple cases of type 1 diabetes mellitus (T1DM).ResultsWe identified distinct oral microbiota mostly reflecting competition between streptococcal species. More specifically, we found a decreased abundance of the commensalStreptococcus salivariusin the oral cavity of T1DM individuals, which is linked to its apparent competition with the pathobiontStreptococcus mutans. The decrease inS. salivariusin the oral cavity was also associated with its decrease in the gut as well as higher abundances in facultative anaerobes includingEnterobacteria. In addition, we found evidence of gut inflammation in T1DM as reflected in the expression profiles of theEnterobacteriaas well as in the human gut proteome. Finally, we were able to follow transmitted strain-variants from the oral cavity to the gut at the metagenomic, metatranscriptomic and metaproteomic levels, highlighting not only the transfer, but also the activity of the transmitted taxa along the gastrointestinal tract.ConclusionsAlterations of the oral microbiome in the context of T1DM impact the microbial communities in the lower gut, in particular through the reduction of “oral-to-gut” transfer ofStreptococcus salivarius. Our results indicate that the observed oral-cavity-driven gut microbiome changes may contribute towards the inflammatory processes involved in T1DM. Through the integration of multi-omic analyses, we resolve strain-variant “mouth-to-gut” transfer in a disease context.
Spindle reorientation in response to mechanical stress is an emergent property of the spindle positioning mechanisms
Authors: Kelkar Manasi , Bohec Pierre , Smith Matthew , Sreenivasan Varun , Lisica Ana , Valon Leo , Ferber Emma , Baum Buzz , Salbreux Guillaume , Charras Guillaume 
Published: February 2022

AbstractProper orientation of the mitotic spindle plays a crucial role in embryos, during tissue development, and in adults, where it functions to dissipate mechanical stress to maintain tissue integrity and homeostasis. While mitotic spindles have been shown to reorient in response to external mechanical stresses, the subcellular cues that mediate spindle reorientation remain unclear. Here, we have used a combination of optogenetics and computational modelling to better understand how mitotic spindles respond to inhomogeneous tension within the actomyosin cortex. Strikingly, we find that the optogenetic activation of RhoA only influences spindle orientation when it is induced at both poles of the cell. Under these conditions, the sudden local increase in cortical tension induced by RhoA activation reduces pulling forces exerted by cortical regulators on astral microtubules. This leads to a perturbation of the torque balance exerted on the spindle, which causes it to rotate. Thus, spindle rotation in response to mechanical stress is an emergent phenomenon arising from the interaction between the spindle positioning machinery and the cell cortex.
Near-atomic Structure of the Cytoplasmic Ring of the Xenopus laevis Nuclear Pore Complex
Authors: Zhu Xuechen , Huang Gaoxingyu , Zeng Chao , Zhan Xiechao , Liang Ke , Zhao Yanyu , Wang Pan , Wang Qifan , Zhou Qiang , Tao Qinghua , Liu Minhao , Lei Jianlin , Yan Chuangye , Shi Yigong 
Published: February 2022

AbstractThe nuclear pore complex (NPC) mediates nucleocytoplasmic shuttling. Here we present single-particle cryo-EM structure of the cytoplasmic ring (CR) from the Xenopus laevis NPC at 4.1-4.7 Å resolutions. The structure of an N-terminal domain of Nup358 was resolved at 3.0 Å, facilitating identification of five Nup358 molecules in each CR subunit. Aside from unveiling the assembly details of the two Y-shaped multicomponent complexes (Y complexes) in each CR subunit, the improved resolutions reveal the C-terminal fragment of Nup160 to be an organizing center at the vertex of each Y complex. Our structures show that the scaffold of a CR subunit comprises five Nup358, two Nup205 and two Nup93 molecules in addition to the previously characterized Y complexes.One-Sentence SummaryImproved resolutions of the cytoplasmic ring (CR) of the Xenopus laevis nuclear pore complex reveal that five Nup358 molecules, together with two copies of interweaved Nup205, Nup93 and Y complexes, constitute the scaffold of each CR subunit.
How does the protean career attitude influence external employability? The roles of career resilience and proactive career behavior
Authors: Park Yoonhee , Lee Jin Gu , Jeong Hong Jeon , Lim Min Sub , Oh Mi-Rae 
Published: February 2022

PurposeThe purpose of this study is to investigate the structural relationships between protean career attitude, career resilience, proactive career behavior and external employability.Design/methodology/approachThis study sampled 212 training apprentice employees who participated in training programs using a proportional stratified sampling in South Korea. The study tested the research model using structural equation modeling.FindingsThis study revealed that protean career attitude influenced external employability through career resilience and proactive career behavior. Career resilience fully mediated the relationship between protean career attitude and external employability and partially mediated protean career attitude and proactive career behavior. Proactive career behavior also mediated the relationship between protean career attitude and external employability.Research limitations/implicationsThis study has a limitation by relying on cross-sectional data. In terms of theoretical implications, this study can add new knowledge to the protean career research by demonstrating that the protean career attitude influences perceived external employability through career resilience and proactive career behavior for the sample of young training apprentice employees.Originality/valueThis study uncovers the dynamic processes between protean career attitude and perceived external employability. Moreover, this study’s sample is significant because training apprentice employees are mostly young in their 20s and 30s with less than three years of working experience and working in small and medium-sized enterprises in South Korea.
Implementing dynamic revenue management in hotels during Covid-19: value stream and wavelet coherence perspectives
Authors: Zaki Karam 
Published: February 2022

Purpose
Practicing flexible revenue management (RM) at hotels during Covid-19 is essential. The well-performed hotels ponder how to transform the target from revenue to net profits. This paper aims, first, to develop a value stream mapping (VSM) model for a productive RM based on six key drivers: organizational culture, demand forecasting, dynamic distribution channels, competition breakdown, dynamic and customized pricing and daily reviewing, and, second, to examine the nexus between RM and hotel’s efficiency during Covid-19 using the wavelet analysis (WA) to visualize this relationship’s time and frequency-based lead–lag dynamics.

Design/methodology/approach
Using time-series data, a multiple case study of 31 luxury hotels in Egypt was applied based on semi-structured interviews and self-administered questionnaires.

Findings
The first phase results showed that consensus toward the RM framework was achieved, regardless of current challenges, indicating that RM managers and scholars could use it. In Phase 2, the WA confirmed a positive correlation and significant influence between Covid-19 and RM practices at most business cycle frequencies. Furthermore, overall high causal relationships between RM practices and hotel efficiency were discovered in the short and medium terms and through different occurrence cycles. Though, the dynamic pricing in the long term was apart from this relationship. The causal effects between Covid-19 and hotel efficiency are not observable in the long-run spectra, indicating that resilience efforts with Covid-19 perhaps mitigated the impact.

Research limitations/implications
Hotel managers could use the RM model developed from this study during the downturn to improve efficiency. The outcome may lead to the recovery of the hotel market and the whole economy. WA maps display possible directions for hotel managers to be more efficient based on the time and frequency domains.

Originality/value
This study shows opportunities for RM implementation during Covid-19 based on the VSM and the WA approaches in hotels.
How project management approach impact project success? From traditional to agile
Authors: Ciric Lalic Danijela , Lalic Bojan , Delić Milan , Gracanin Danijela , Stefanovic Darko 
Published: February 2022

PurposeThis research aimed to explore whether different project management approaches (traditional, agile or hybrid) differentiate concerning their impact on project success, taking project success as multidimensional phenomena. In addition to this, the authors wanted to explore if specific project characteristics moderate these effects.Design/methodology/approachThe authors empirically addressed these on a sample of 227 project professionals worldwide. The exploratory factor analysis (EFA) of project success dimensions was done to validate these factors' constitution concerning their manifest variables. The K-means cluster method was used to distinguish respondents' profiles among agile, hybrid and traditional project management approaches. To test the significance among research groups, the research hypotheses were tested with ANOVA tests.FindingsThe authors evidenced that the agile approach has a more significant positive impact concerning the two out of five dimensions of project success, under analysis in this research (impact on the team and preparing for the future), over the traditional approach.Practical implicationsThe research is relevant for project management practitioners to tailor the success-oriented project management approach and for academics to develop project management contingency theory.Originality/valueThe authors constructed a research framework to test the impact and effectiveness of different project management approaches (traditional, agile, hybrid) on the dimensions of project success in different contextual conditions (organization industry, project type, novelty, technology, complexity and pace). The paper's main contribution is to expand data on the impact of these approaches on project success and compare them with relevant results and findings of previous research.