bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contractile cell apoptosis regulates airway smooth muscle remodeling in asthma
Authors: Fraga-Iriso Rebeca , Amor-Carro Óscar , Brienza Nadia S. , Núñez-Naveira Laura , Lema-Costa Beatriz , González-Barcala Francisco Javier , Bazús-González Teresa , Montero-Martínez Carmen , López-Viña Antolín , Torrego Alfons , Plaza Vicente , Martínez-Rivera Carlos , Hamid Qutayba , Martin James G. , Berger Patrick , Ramos-Barbón David 
Published: February 2021

AbstractRationaleInvestigations on the mechanisms of airway smooth muscle remodeling, a prominent asthma feature contributing to its clinical manifestations and severity, have largely focused on its hyperplastic growth. Conversely, limited data and virtually no translational research have been produced on a plausible role of apoptosis in the homeostasis and remodeling of airway smooth muscle.ObjectivesWe aimed at demonstrating an involvement of apoptosis, an essential regulator of organ structure and cell turnover, in the pathophysiology of airway smooth muscle remodeling in asthma.MethodsMurine experimental asthma was modeled to analyze airway hyperresponsiveness, contractile tissue remodeling and apoptosis detection outcomes at early and late cutoffs, and under pharmacological inhibition of apoptosis by employing a caspase blocker. Clinical investigation followed through analyses on human bronchial biopsies.ResultsAirway hyperresponsiveness and contractile tissue remodeling were already established in early experimental asthma, and a subsequent upregulation of apoptosis limited the airway contractile tissue growth. Caspase inhibition elicited chaotic pulmonary mechanics and an unusual growth of airway smooth muscle that was structurally disorganized. In bronchial biopsies, airway smooth muscle increased from controls through subjects with intermittent and persistent moderate and severe asthma. Cleaved poly-ADP ribose polymerase (c-PARP, a byproduct of caspase activity) was increased in severe asthma.ConclusionsApoptosis is involved in airway contractile cell turnover and in shaping the size, structure and proper function of the airway smooth muscle layer. Apoptosis inhibitors may complicate concomitant asthma, whereas agents favouring airway contractile cell apoptosis may provide a novel pipeline of therapeutic development.Key messagesHow normal airway smooth muscle structure is preserved, and whether counteracting responses to remodeling are elicited in asthma, are outstanding questions not probed in vivo nor in the clinical setting.In this work, combined investigations on murine experimental asthma and human bronchial biopsies show that airway contractile cell apoptosis is involved in the homeostasis of airway smooth muscle, and apoptotic activity is upregulated as part of the remodeling process of this tissue in asthma.Apoptosis arises as a key regulator of the size and structure of the airway smooth muscle layer. This concept draws implications for clinical practice and drug development.
Novel SARS-CoV-2 spike variant identified through viral genome sequencing of the pediatric Washington D.C. COVID-19 outbreak
Authors: LoTempio Jonathan , Billings Erik , Draper Kyah , Ralph Christal , Moshgriz Mahdi , Duong Nhat , Bard Jennifer Dien , Gai Xiaowu , Wessel David , DeBiasi Roberta L. , Campos Joseph M. , Vilain Eric , Delaney Meghan , Michael Drew G. 
Published: February 2021

ABSTRACTThe SARS-CoV-2 virus has emerged as a global pandemic, severely impacting everyday life. Significant resources have been dedicated towards profiling the viral genome in the adult population. We present an analysis of viral genomes acquired from pediatric patients presenting to Children’s National Hospital in Washington D.C, including 24 with primary SARS CoV2 infection and 3 with Multisystem Inflammatory Syndrome in Children (MIS-C) undergoing treatment at our facility. Viral genome analysis using next generation sequencing indicated that approximately 81% of the analyzed strains were of the GH clade, 7% of the cases belonged to the GR clade, and 12% of the cases belonged to S, V, or G clades. One sample, acquired from a neonatal patient, presented with the highest viral RNA load of all patients evaluated at our center. Viral sequencing of this sample identified a SARS-CoV-2 spike variant, S:N679S. Analysis of data deposited in the GISAID global database of viral sequences shows the S:N679S variant is present in eight other sequenced samples within the US mid-Atlantic region. The similarity of the regional sequences suggests transmission and persistence of the SARS-CoV-2 variant within the Capitol region, raising the importance of increasing the frequency of SARS-CoV-2 genomic surveillance.IMPORTANCEA variant in the SARS-CoV-2 spike protein was identified in a febrile neonate who was hospitalized with COVID-19. This patient exhibited the highest viral RNA load of any COVID-19 patient tested at our center. Viral sequencing identified a spike protein variant, S:N679S, which is proximal to the cleavage site at residue 681. The SARS-CoV-2 surface spike is a protein trimer (three subunits) which serves as the key target for antibody therapies and vaccine development. Study of viral sequences from the GISAID database revealed eight related sequences from the US mid-Atlantic region. The identification of this variant in a very young patient, its critical location in the spike polyprotein, and the evidence that it has been detected in other patients in our region underscores the need for increased viral sequencing to monitor variant prevalence and emergence, which may have a direct impact on recommended public health measures and vaccination strategies.
Methylation scores for smoking, alcohol consumption, and body mass index and risk of seven types of cancer
Authors: Dugué Pierre-Antoine , Yu Chenglong , Hodge Allison M , Wong Ee Ming , Joo JiHoon E , Jung Chol-Hee , Schmidt Daniel , Makalic Enes , Buchanan Daniel D , Severi Gianluca , English Dallas R , Hopper John L , Milne Roger L , Giles Graham G , Southey Melissa C 
Published: February 2021

ABSTRACTMethylation marks of exposure to health risk factors may be useful markers of cancer risk as they might better capture current and past exposures than questionnaires, and reflect different individual responses to exposure. We used data from seven case-control studies nested within the Melbourne Collaborative Cohort Study of blood DNA methylation and risk of colorectal, gastric, kidney, lung, prostate and urothelial cancer, and B-cell lymphoma (N cases=3,123). Methylation scores (MS) for smoking, body mass index (BMI), and alcohol consumption were calculated based on published data as weighted averages of methylation values. Rate ratios (RR) and 95% confidence intervals for association with cancer risk were estimated using conditional logistic regression and expressed per standard deviation increase of the MS, with and without adjustment for health-related confounders. The contribution of MS to discriminate cases from controls was evaluated using the area under the curve (AUC). After confounder adjustment, we observed: large associations (RR∼1.5-1.7) with lung cancer risk for smoking MS; moderate associations (RR∼1.2-1.3) with urothelial cancer risk for smoking MS and with mature B-cell neoplasm risk for BMI and alcohol MS; moderate to small associations (RR∼1.1-1.2) for BMI and alcohol MS with several cancer types and cancer overall. Generally small AUC increases were observed after inclusion of several MS in the same model (colorectal, gastric, kidney, urothelial cancers: +3%; lung cancer: +7%; B-cell neoplasms: +8%). Methylation scores for smoking, BMI, and alcohol consumption show independent associations with cancer risk, and may provide some improvements in risk prediction.
Disruption of nuclear architecture as a cause of COVID-19 induced anosmia
Authors: Zazhytska Marianna , Kodra Albana , Hoagland Daisy A. , Fullard John F. , Shayya Hani , Omer Arina , Firestein Stuart , Gong Qizhi , Canoll Peter D. , Goldman James E. , Roussos Panos , tenOever Benjamin R. , Overdevest Jonathan B. , Lomvardas Stavros 
Published: February 2021

AbstractOlfaction relies on a coordinated partnership between odorant flow and neuronal communication. Disruption in our ability to detect odors, or anosmia, has emerged as a hallmark symptom of infection with SARS-CoV-2, yet the mechanism behind this abrupt sensory deficit remains elusive. Here, using molecular evaluation of human olfactory epithelium (OE) from subjects succumbing to COVID-19 and a hamster model of SARS-CoV-2 infection, we discovered widespread downregulation of olfactory receptors (ORs) as well as key components of their signaling pathway. OR downregulation likely represents a non-cell autonomous effect, since SARS-CoV-2 detection in OSNs is extremely rare both in human and hamster OEs. A likely explanation for the reduction of OR transcription is the striking reorganization of nuclear architecture observed in the OSN lineage, which disrupts multi-chromosomal compartments regulating OR expression in humans and hamsters. Our experiments uncover a novel molecular mechanism by which a virus with a very selective tropism can elicit persistent transcriptional changes in cells that evade it, contributing to the severity of COVID-19.
Improving germline transmission efficiency in chimeric chickens using a multi-stage injection approach
Authors: Naseri Danial , Dormiani Kianoush , Hajian Mehdi , Jafarpour Farnoosh , Forouzanfar Mahboobeh , Karimi Naeimeh , Nasr-Esfahani Mohammad Hossein 
Published: February 2021

AbstractAlthough different strategies have been developed to generate transgenic poultry, low efficiency of germline transgene transmission has remained a challenge in poultry transgenesis. Herein, we developed an efficient germline transgenesis method using a lentiviral vector system in chickens through multiple injections of transgenes into embryos at different stages of development. The embryo chorioallantoic membrane (CAM) vasculature was successfully used as a novel route of gene transfer into germline tissues. We established a new method of eggshell windowing for embryo manipulation at different developmental stages. Compared to the other routes of viral vector administration, the embryo’s bloodstream at Hamburger-Hamilton (HH) stages 14-15 achieved the highest rate of germline transmission (GT), 7.7%. Single injection of viral vectors into the CAM vasculature resulted in a GT efficiency of 2.7%, which was significantly higher than the 0.4% obtained by injection into embryos at the blastoderm stage. Double injection of viral vectors into the bloodstream at HH stages 14-15 and through CAM was the most efficient method for producing germline chimeras, giving a GT rate of 13.6%. The authors suggest that the new method described in this study could be efficiently used to produce transgenic poultry in virus-mediated gene transfer systems.
Archaeal extracellular vesicles are produced in an ESCRT-dependent manner and promote gene transfer and nutrient cycling in extreme environments
Authors: Liu Junfeng , Cvirkaite-Krupovic Virginija , Commere Pierre-Henri , Yang Yunfeng , Zhou Fan , Forterre Patrick , Shen Yulong , Krupovic Mart 
Published: February 2021

ABSTRACTMembrane-bound extracellular vesicles (EVs), secreted by cells from all three domains of life, transport various molecules and act as agents of intercellular communication in diverse environments. Here we demonstrate that EVs produced by a hyperthermophilic and acidophilic archaeonSulfolobus islandicuscarry not only diverse proteins but also chromosomal and plasmid DNA, and can transfer this DNA to recipient cells. Furthermore, we show that EVs can support the heterotrophic growth ofSulfolobusin minimal medium, implicating EVs in carbon and nitrogen fluxes in extreme environments. Finally, our results suggest that, similar to eukaryotes, production of EVs inS. islandicusdepends on the archaeal ESCRT machinery. Using synchronizedS. islandicuscultures, we show that EV production is linked to cell division and appears to be triggered by increased expression of ESCRT proteins during this cell cycle phase. Using a CRISPR-based knockdown system, we show that archaeal ESCRT-III and AAA+ ATPase Vps4 are required for EV production, whereas archaea-specific component CdvA appears to be dispensable. Collectively, our results suggest that ESCRT-mediated EV biogenesis has deep evolutionary roots, likely predating the divergence of eukaryotes and archaea, and that EVs play an important role in horizontal gene transfer and nutrient cycling in extreme environments.
Wing structure and neural encoding jointly determine sensing strategies in insect flight
Authors: Weber Alison I. , Daniel Thomas L. , Brunton Bingni W. 
Published: February 2021

AbstractAnimals rely on sensory feedback to generate accurate, reliable movements. In many flying insects, strain-sensitive neurons on the wings provide rapid feedback that enables stable flight control. While the impacts of wing structure on aerodynamic performance have been widely studied, the impacts of wing structure on sensing remain unexplored. In this paper, we show how the structural properties of the wing and encoding by mechanosensory neurons interact to jointly determine optimal sensing strategies and performance. Specifically, we examine how neural sensors can be placed effectively over a flapping wing to detect body rotation about different axes, using a computational wing model with varying flexural stiffness inspired by the hawkmothManduca sexta. A small set of mechanosensors, conveying strain information at key locations with a single action potential per wingbeat, permit accurate detection of body rotation. Optimal sensor locations are concentrated at either the wing base or the wing tip, and they transition sharply as a function of both wing stiffness and neural threshold. Moreover, the sensing strategy and performance is robust to both external disturbances and sensor loss. Typically, only five sensors are needed to achieve near-peak accuracy, with a single sensor often providing accuracy well above chance. Our results show that small-amplitude, dynamic signals can be extracted efficiently with spatially and temporally sparse sensors in the context of flight. The demonstrated interaction of wing structure and neural encoding properties points to the importance of their joint evolution.
Prisoner of War dynamics explains the time-dependent pattern of substitution rates in viruses
Authors: Ghafari Mahan , Simmonds Peter , Pybus Oliver G , Katzourakis Aris 
Published: February 2021

AbstractMolecular clock dating is widely used to estimate timescales of phylogenetic histories and to infer rates at which species evolve. One of the major challenges with inferring rates of molecular evolution is the observation of a strong correlation between estimated rates and the timeframe of their measurements. Recent empirical analysis of virus evolutionary rates suggest that a power-law rate decay best explains the time-dependent pattern of substitution rates and that the same pattern is observed regardless of virus type (e.g.groups I-VII in the Baltimore classification). However there exists no explanation for this trend based on molecular evolutionary mechanisms. We provide a simple predictive mechanistic model of the time-dependent rate phenomenon, incorporating saturation and host constraints on the evolution of some sites. Our model recapitulates the ubiquitous power-law rate decay with a slope of −0.65 (95% HPD: −0.72, −0.52) and can satisfactorily account for the variation in inferred molecular evolutionary rates over a wide range of timeframes. We show that once the saturation of sites starts - typically after hundreds of years in RNA viruses and thousands of years in DNA viruses - standard substitution models fail to correctly estimate divergence times among species, while our model successfully re-creates the observed pattern of rate decay. We apply our model to re-date the diversification of genotypes of hepatitis C virus (HCV) to 396,000 (95% HPD: 326,000 - 425,000) years before present, a time preceding the dispersal of modern humans out of Africa, and also showed that the most recent common ancestor of sarbecoviruses dates back to 23,500 (95% HPD: 21,100 - 25,300) years ago, nearly thirty times older than previous estimates. This not only creates a radical new perspective for our understanding the origins of HCV but also suggests a substantial revision of evolutionary timescales of other viruses can be similarly achieved.
Employee development and retention of Generation-Z employees in the post-COVID-19 workplace: a conceptual framework
Authors: Jayathilake Hasaranga Dilshan , Daud Dazmin , Eaw Hooi Cheng , Annuar Nursyamilah 
Published: February 2021

PurposeThe purpose of this article is to demonstrate a conceptual framework on employee development, organizational performances and retention of Generation-Z employees in the new normal environment beyond the COVID-19 pandemic.Design/methodology/approachWith referring to the present literature and utilizing social-exchange and human needs approach, from this study, the authors illustrate a conceptual framework with democratize learning, reverse mentoring and intrepreneurship as key modifications for employee development perspective to retain Generation-Z employees and enhance organizational performance to secure the competitiveness.FindingsDemocratize learning, reverse mentoring and intrapreneurship have a significant potential impact on enhancing Generation-Z employees' development which may effect on attaining better organizational performance and employee retention. In addition, organizational performance may have a moderating effect on employee intention to stay longer.Research limitations/implicationsThe proposed conceptual framework would be empirically validated in future research.Practical implicationsBased on the framework, the authors suggest approaches for Generation-Z specific retention strategies on upgrading the employee development subcategory under human resource function in terms of minimizing the disadvantages that are associated with the work from home concept in a post-COVID-19 pandemic era.Originality/valueOne of the very first studies to propose a holistic framework on employee development that subsequently impact on retaining Generation-Z employees in a pandemic situation. This article enriches the human resource management literature by explaining the novel moderating relationship that articulated from organizational performance to employee retention and focussing on Generation-Z employees (younger generation employees).
The effects of bank competition on firm R&D investment: an inverted-U relationship
Authors: Xia Yufeng , Liu Peisen 
Published: February 2021

Purpose
Bank financing is an important external financing source for firm research and development (R&D) investment. This study aims to use an exponential quadratic specification to investigate the effect of bank competition on firm R&D investment and its underlying mechanisms. Moreover, this study checks bank competition’s heterogeneous effects on firm R&D investment.

Design/methodology/approach
Based on data of Chinese manufacturing firms and bank branches, this study uses the Tobit estimator, instrumental variable method and Heckman two-step approach to test the relationship between bank competition and firm R&D investment.

Findings
The results show robustness evidence of an inverted-U relationship between bank competition and firm R&D investment. Specifically, increases in bank competition promote firm R&D investment until bank competition reaches the turning point and reduce firm R&D investment after crossing the turning point. Financing costs and financial constraints can explain the inverted-U relationship between bank competition and firm R&D investment. Heterogeneity examinations reveal that R&D investment is more sensitive to bank competition in non-state-owned enterprises, small firms and high-tech firms.

Originality/value
This study contributes to the literature on the relationship between bank competition and firm innovation. The authors investigate the heterogeneity of R&D investment influenced by bank competition and depict the economic effects brought by bank competition. This study sheds light on the real effects of bank competition and the determinants of firm R&D investment in transition economies. The conclusions provide empirical evidence for reducing credit discrimination and improving capital allocation efficiency in developing countries.
Digital communication, value co-creation and customer engagement in business networks: a conceptual matrix and propositions
Authors: Sashi C.M. 
Published: February 2021

Purpose
Technological innovations that resulted in the emergence and widespread adoption of digital communication in recent years have led to a surge of academic and practitioner interest in its implications for the co-creation of value and customer engagement. However, in comparison to the attention given to the study of customer engagement in consumer markets, few studies have examined its key role in business markets. This paper aims to examine the impact of digital communication on value co-creation and customer engagement in inter-organizational relationships in business networks.

Design/methodology/approach
Co-creation of value and customer engagement in business networks occurs among interconnected organizations that are partners in intermediate transactions. The paper develops a matrix of inter-organizational engagement among partners in business networks and propositions linking digital communication to value co-creation and inter-organizational engagement.

Findings
The relationships among network organizations may be characterized by the extent of relational exchange and inter-organizational bonds among them. Four types of inter-organizational engagement emerge: transactional partners, loyal partners, trusted partners and engaged partners. The partners co-create value to better satisfy customers.

Research limitations/implications
The paper is an initial attempt to develop a conceptual understanding of customer engagement in business markets and formulate propositions that can be further investigated. Networks of partner organizations co-create value, altering their input and output markets, value addition and products, permitting greater flexibility and customization in satisfying the needs of customers.

Practical implications
The ability afforded by digital communication for real-time interactive communication enables individuals from multiple departments and hierarchical positions within multiple organizations dispersed across geographic locations and industries to maintain contact, quickly and easily communicate task information, build trust and commitment in long-term relationships with network partners and provide superior customer value.

Originality/value
The paper represents a unique attempt to understand the nature of customer engagement in business markets. It discusses how digital communication alters market transactions among partner organizations in a network by facilitating changes in their make/buy decisions. It develops a matrix of inter-organizational engagement in business networks and propositions that improve understanding of the customer engagement concept and provide the foundation for strategies to better satisfy customers.