bluuebunny/crossref_metadata_2025_split huggingface dataset:
wnt16regulates spine and muscle morphogenesis through parallel signals from notochord and dermomyotome
Authors: Watson Claire J. , Tang W. Joyce , Rojas Maria F. , Fiedler Imke A.K. , de Oca Ernesto Morfin Montes , Cronrath Andrea R. , Callies Lulu K. , Swearer Avery Angell , Ahmed Ali R. , Sethuraman Visali , Addish Sumaya , Farr Gist H. , Gomez Arianna E. , Rai Jyoti , Monstad-Rios Adrian T. , Gardiner Edith M. , Karasik David , Maves Lisa , Busse Bjorn , Hsu Yi-Hsiang , Kwon Ronald Young 
Published: August 2021

ABSTRACTBone and muscle interact through developmental, mechanical, paracrine, and autocrine signals. Genetic variants at theCPED1-WNT16locus are dually associated with bone- and muscle-related traits. WhileWnt16is necessary for bone mass and strength, this fails to explain pleiotropy at this locus. Here, we showwnt16is required for spine and muscle morphogenesis in zebrafish. In embryos,wnt16is expressed in dermomyotome and developing notochord, and contributes to larval myotome morphology and notochord elongation. Later,wnt16is expressed at the ventral midline of the notochord sheath, and contributes to spine mineralization and osteoblast recruitment. Morphological changes inwnt16mutant larvae are mirrored in adults, indicating thatwnt16impacts bone and muscle morphology throughout the lifespan. Finally, we show thatwnt16is a gene of major effect on lean mass at theCPED1-WNT16locus. Our findings indicate that Wnt16 is secreted in structures adjacent to developing bone (notochord) and muscle (dermomyotome) where it affects the morphogenesis of each tissue, thereby renderingwnt16expression into dual effects on bone and muscle morphology. This work expands our understanding ofwnt16in musculoskeletal development and supports the potential for variants to act throughWNT16to influence bone and muscle via parallel morphogenetic processes.AUTHOR SUMMARYIn humans, genetic variants (DNA sequences that vary amongst individuals) have been identified that appear to influence bone and skeletal muscle mass. However, how single genes and genetic variants exert dual influence on both tissues is not well understood. In this study, we found a gene calledwnt16is necessary for specifying the size and shape of muscle and bone during development in zebrafish. Moreover, we disentangled howwnt16affects both tissues: distinct cellular populations adjacent to muscle and bone secrete Wnt16, where it acts as a signal this guides the size and shape of each tissue. This is important because in humans, genetic variants near theWNT16gene have effects on both bone- and muscle-related traits. This study expands our understanding of the role ofWNT16in bone and muscle development, and helps to explain how genetic variants nearWNT16affect traits for both tissues. Moreover, WNT16 is actively being explored as a target for osteoporosis therapies; our study could have implications with regard to the potential to target WNT16 to treat bone and muscle simultaneously.
Phylogenetic reconciliation reveals extensive ancestral recombination in Sarbecoviruses and the SARS-CoV-2 lineage
Authors: Zaman Sumaira , Sledzieski Samuel , Berger Bonnie , Wu Yi-Chieh , Bansal Mukul S. 
Published: August 2021

AbstractAn accurate understanding of the evolutionary history of rapidly-evolving viruses like SARS-CoV-2, responsible for the COVID-19 pandemic, is crucial to tracking and preventing the spread of emerging pathogens. However, viruses undergo frequent recombination, which makes it difficult to trace their evolutionary history using traditional phylogenetic methods. Here, we present a phylogenetic workflow, virDTL, for analyzing viral evolution in the presence of recombination. Our approach leverages reconciliation methods developed for inferring horizontal gene transfer in prokaryotes, and, compared to existing tools, is uniquely able to identify ancestral recombinations while accounting for several sources of inference uncertainty, including in the construction of a strain tree, estimation and rooting of gene family trees, and reconciliation itself. We apply this workflow to theSarbecovirussubgenus and demonstrate how a principled analysis of predicted recombination gives insight into the evolution of SARS-CoV-2. In addition to providing confirming evidence for the horseshoe bat as its zoonotic origin, we identify several ancestral recombination events that merit further study.
Lipid Tails Modulate Antimicrobial Peptide Membrane Incorporation and Activity
Authors: Walker Lawrence R. , Marty Michael T. 
Published: August 2021

AbstractAntimicrobial peptides (AMPs) are cationic, amphipathic peptides that interact directly with lipid bilayers. AMPs generally interact with anionic lipid head groups, but it is less clear how the lipid tail length and saturation modulates interactions with membranes. Here we used native mass spectrometry to measure the stoichiometry of three different AMPs—LL-37, indolicidin, and magainin-2—in lipid nanodiscs. We also measured the activity of these AMPs in large unilamellar vesicle leakage assays. We found that LL-37 formed specific hexamer complexes but with different assembly pathways and affinities that depended on the bilayer thickness. LL-37 was also most active in lipid bilayers containing longer, unsaturated lipids. In contrast, indolicidin incorporated to a higher degree into more fluid lipid bilayers but was more active with thinner, less fluid bilayers. Finally, magainin-2 incorporated to a higher degree into longer, unsaturated bilayers and showed more activity in these same conditions. Together, these data show that higher amounts of peptide incorporation generally led to higher activity and that AMPs tend to incorporate more into longer unsaturated lipid bilayers. However, the activity of AMPs was not always directly related to amount of peptide incorporated.Graphical Abstract
Temporal properties of painful contrast enhancement using repetitive stimulation
Authors: Szikszay Tibor M. , Adamczyk Waclaw M. , Lévénez Juliette L. M. , Gouverneur Philip , Luedtke Kerstin 
Published: August 2021

AbstractOffset analgesia is characterized by a disproportionately large reduction in pain following a small decrease in a heat stimulus and is based on the phenomenon of temporal pain contrast enhancement (TPCE). The aim of this study is to investigate whether this phenomenon can also be induced by repetitive stimulation, i.e., by stimuli that are clearly separated in time. With this aim, the repetitive TPCE paradigm was induced in healthy, pain-free subjects (n=33) at the volar non-dominant forearm using heat stimuli. This paradigm was performed applying three different interstimulus intervals (ISIs): 5, 15, and 25 seconds. All paradigms were contrasted with a control paradigm without temperature change. Participants continuously rated the perceived pain intensity. In addition, electrodermal activity was recorded as a surrogate measure of autonomic arousal. Temporal pain contrast enhancement was confirmed for both ISI 5 seconds (p < 0.001) and ISI 15 seconds (p = 0.005), but not for ISI 25 seconds (p = 0.07), however the magnitude of TPCE did not differ between ISIs (p = 0.11). Electrodermal activity was consistent previous pain ratings, but showing significantly higher autonomic activity being measured. Thus, the phenomenon of temporal contrast enhancement of pain can also be induced by repetitive stimulation. Both the involvement of the autonomic nervous system and the involvement of habituation processes are conceivable, which consequently points to both central and peripheral mechanisms of TPCE.SummaryThe temporal contrast enhancement of pain and electrodermal activity can be provoked by stimuli that are clearly separated in time.
Identification of a MarR subfamily that regulates arsenic resistance genes
Authors: Yu Yanshuang , Feng Renwei , Chen Jichen , Li Yuanping , Liang Jinxuan , Xie Zhenchen , Alwathnani Hend A. , Rosen Barry P. , Grove Anne , Chen Jian , Rensing Christopher 
Published: August 2021

ABSTRACTMembers of the family of Multiple Antibiotic Resistance Regulators (MarR) often regulate genes that encode antibiotic resistance in bacteria. In this study, comprehensive analyses were performed to determine the function of an atypical MarR homolog in Achromobacter sp. As-55. Genomic analyses showed that this marR is located in an arsenic gene island in Achromobacter sp. As-55 adjacent to an arsV gene. ArsV is a flavin-dependent monooxygenase that confers resistance to the antibiotic methylarsenite (MAs(III)), the organoarsenic compound roxarsone(III) (Rox(III)), and the inorganic antimonite (Sb(III)). Similar marR genes are widely distributed in arsenic-resistant bacteria. Phylogenetic analyses showed that these MarRs are found in operons predicted to be involved in resistance to inorganic and organic arsenic species, so the subfamily was named MarRars. MarRars orthologs have three conserved cysteine residues, which are Cys36, Cys37 and Cys157 in Achromobacter sp. As-55, mutation of which compromises the response to MAs(III)/Sb(III). GFP-fluorescent biosensor assays show that AdMarRars (MarR protein of Achromobacter deleyi As-55) responds to trivalent As(III) and Sb(III) but not to pentavalent As(V) or Sb(V). The results of RT-qPCR assays show that arsV is expressed constitutively in a marR deletion mutant, indicating that marR represses transcription of arsV. Moreover, electrophoretic mobility shift assays (EMSA) demonstrate that AdMarRars binds to the promoters of both marR and arsV in the absence of ligands and that DNA binding is relieved upon binding of As(III) and Sb(III). Our results demonstrate that AdMarRars is a novel As(III)/Sb(III)-responsive transcriptional repressor that controls expression of arsV, which confers resistance to MAs(III), Roxarsone(III) and Sb(III). AdMarRars and its orthologs form a subfamily of MarR proteins that regulate genes conferring resistance to arsenic-containing antibiotics.IMPORTANCEIn this study, a MarR family member, AdMarRars was shown to regulate the arsV gene, which confers resistance to arsenic-containing antibiotics. It is a founding member of a distinct subfamily that we refer to as MarRars, regulating genes conferring resistance to arsenic and antimony antibiotic compounds. AdMarRars was shown to be a repressor containing conserved cysteine residues that are required to bind As(III) and Sb(III), leading to a conformational change and subsequent derepression. Here we show that members of the MarR family are involved in regulating arsenic-containing compounds.
A mathematical framework for analyzing wild tomato root architecture
Authors: Chandrasekhar Arjun , Julkowska Magdalena M 
Published: August 2021

AbstractThe root architecture of wild tomato, Solanum pimpinellifolium, can be viewed as a network connecting the main root to various lateral roots. Several constraints have been proposed on the structure of such biological networks, including minimizing the total amount of wire necessary for constructing the root architecture (wiring cost), and minimizing the distances (and by extension, resource transport time) between the base of the main root and the lateral roots (conduction delay). For a given set of lateral root tip locations, these two objectives compete with each other — optimizing one results in poorer performance on the other — raising the question how well S. pimpinellifolium root architectures balance this network design trade-off in a distributed manner. Here, we describe how well S. pimpinellifolium roots resolve this trade-off using the theory of Pareto optimality. We describe a mathematical model for characterizing the network structure and design trade-offs governing the structure of S. pimpinellifolium root architecture. We demonstrate that S. pimpinellifolium arbors construct architectures that are more optimal than would be expected by chance. Finally, we use this framework to quantify structural differences between arbors grown in the presence of salt stress, classify arbors into four distinct architectural ideotypes, and test for heritability of variation in root architecture structure.
Healthcare presentations with self-harm and the association with COVID-19: an e-cohort whole-population-based study using individual-level linked routine electronic health records in Wales, UK, 2016 - March 2021
Authors: DelPozo-Banos Marcos , Lee Sze Chim , Friedmann Yasmin , Akbari Ashley , Torabi Fatemeh , Lloyd Keith , Lyons Ronan A , John Ann 
Published: August 2021

AbstractBackgroundMulti-setting population-based studies on healthcare service presentations with self-harm covering the first 12 months of the COVID-19 pandemic are yet to be published.AimsAscertain changes across settings in healthcare service presentations with self-harm during Waves 1 and 2 of the COVID-19 pandemic.MethodE-cohort study using individual-level linked routine healthcare data from Wales, UK, 2016-March 2021. We measured weekly proportion of self-harm contacts and people who self-harmed in contact with general practice (GP), emergency department (ED) and hospital admissions. We modelled weekly trends using linear regression and generalised estimated equations, quantifying time differences using difference-in-difference (DiD).ResultsWe included 3,552,210 Welsh residents aged ≥10 years. Counts of self-harm presentations across settings was at a minimum at the start of stay-at-home restrictions during both waves and recovered compared to previous years in 3-5 months. Those who self-harmed in April 2020 were more likely to be seen in GP compared to other settings and previous years – mean rate of OR=1.2, although actual numbers fell. The proportion of self-harm ED contacts admitted to hospital dropped from June 2020 (1.9 [1.5-2.3] pp/month). Self-harm and COVID-19 infection had a bidirectional effect – self-harm history had OR=1.4 [1.2-1.6] and incidence had DiD=1.1 [0.8-1.4].ConclusionsThose that self-harmed and sought help during the COVID-19 pandemic potentially encountered stringent criteria for hospitalisation, particularly in Wave 2, while in Wave 1 they preferentially presented to GP. Reductions in contacts likely resulted in unmet healthcare needs which may later emerge placing further burden on individuals and healthcare services.Relevance statementThis study provides novel findings on how the COVID-19 pandemic and the measures taken to curb its spread affected self-harm healthcare service presentations. To our knowledge no other population-based studies in the UK have linked routinely collected general practice (GP), emergency department (ED) and hospital admission data covering Waves 1 and 2 of the pandemic.Reductions in presentations with self-harm during the pandemic may be the result of those not requiring ED care or hospitalisation avoiding seeking help during the pandemic as often as before. Those that did seek help potentially encountered more stringent criteria for hospitalisation, particularly during Wave 2. This likely resulted in unmet healthcare needs which may later emerge placing further burden on individuals and healthcare services. Measures should be put in place to ensure that those who self-harm receive appropriate assessment and intervention.
Altered increase in STAT1 expression and phosphorylation in severe COVID-19
Authors: Rincon-Arevalo Hector , Aue Arman , Ritter Jacob , Szelinski Franziska , Khadzhynov Dmytro , Zickler Daniel , Stefanski Luisa , Lino Andreia C. , Körper Sixten , Eckardt Kai-Uwe , Schrezenmeier Hubert , Dörner Thomas , Schrezenmeier Eva V. 
Published: August 2021

AbstractThe interferon pathway represents a key antiviral defense mechanism and is being considered as a therapeutic target in COVID-19. Both, substitution of interferon and blocking interferon signaling through JAK STAT inhibition to limit cytokine storms have been proposed. However, little is known so far about possible abnormalities in STAT signaling in immune cells during SARS-CoV-2 infection. In the current study, we investigated downstream targets of interferon signaling, including STAT1, pSTAT1 and 2 and IRF1, 7 and 9 by flow cytometry in 30 patients with COVID-19, 17 with mild and 13 with severe infection. We report an upregulation of STAT1 and IRF9 in mild and severe COVID-19 cases, which correlated with the IFN-signature assessed by Siglec-1 (CD169) expression on peripheral monocytes. Most interestingly, Siglec-1 and STAT1 in CD14+ monocytes and plasmablasts showed lower expression among severe COVID-19 cases compared to mild cases. Contrary to the baseline whole protein STAT1 expression, the phosphorylation of STAT1 was enhanced in severe COVID-19 cases, indicating a dysbalanced JAK STAT signaling that fails to induce transcription of interferon stimulated response elements (ISRE). This abnormality persisted after IFN-α and IFN-γ stimulation of PBMCs from patients with severe COVID-19. The data suggest impaired STAT1 transcriptional upregulation among severely infected patients which may represent a potential predictive biomarker and may allow stratification of patients for certain interferon-pathway targeted treatments.
Topological changes in telechelic micelles: flowers versus stars
Authors: Baulin Vladimir A. 
Published: August 2021

AbstractMicellization and morphology of spherical telechelic micelles formed by tri-block copolymers with short solvophobic end blocks at low concentrations is discussed within scaling argumentsand Single Chain Mean Field Theory (SCMFT). In ultra-dilute regime, individual telechelic polymer chains can exist in solution in two distinct states: open linear chain conformation with two free ends and closed loop conformation, when two ends are connected by the effective attraction between two solvophobic ends. At concentrations below gelation point, closed loops tend to form micelles comprised mostly of loops in flower-like micelles, while linear polymers in open conformations tend to form star-shaped aggregates with one hydrophobic dangling end. Resulting two kinds of micelles have remarkably different topology and dimensions, while the transition between them can be driven by the entropy, namely conformation changes between domination of the looped and linear conformations. The transition between two types of micelles lies in a narrow interaction parameters range. Thus, these topological micelles are very sensitive to the changes in external environment and they can serve as a very sensitive stimuli-responsive smart materials.Graphical TOC Entry
O-GlcNAcylation is essential for rapid Pomc expression and cell proliferation in corticotropic tumor cells
Authors: Massman Logan J , Pereckas Michael , Zwagerman Nathan T , Olivier-Van Stichelen Stephanie 
Published: August 2021

ABSTRACTPituitary adenomas have a staggering 16.7% lifetime prevalence and can be devastating in many patients due to profound endocrine and neurologic dysfunction. To date, no clear genomic or epigenomic markers correlates with their onset or severity. Herein, we investigate the impact of the O-GlcNAc post-translational modification in their etiology. Found in over 5000 human proteins to date, O-GlcNAcylation dynamically regulates proteins in critical signaling pathways, and its deregulation is involved in cancers progression and endocrine diseases such as diabetes.In this study, we demonstrate that O-GlcNAcylation enzymes were upregulated, particularly in aggressive ACTH-secreting tumors, suggesting a role for O-GlcNAcylation in pituitary adenoma etiology. In addition to the demonstration that O-GlcNAcylation was essential for their proliferation, we show that the endocrine function of pituitary adenoma is also dependent on O-GlcNAcylation. In corticotropic tumors, hyper-secretion of the proopiomelanocortin (POMC)-derived hormone ACTH leads to Cushing’s disease, materialized by severe endocrine disruption and increased mortality. We demonstrate that Pomc mRNA is stabilized in an O-GlcNAc-dependent manner in response to corticotropic-stimulating hormone (CRH). By impacting Pomc mRNA splicing and stability, O-GlcNAcylation contributes to this new mechanism of fast hormonal response in corticotropes. Thus, this study stresses the essential role of O-GlcNAcylation in ACTH-secreting adenomas’ pathophysiology, including cellular proliferation and hypersecretion.
Humanoid robots are perceived as an evolutionary threat
Authors: Wei Zhengde , Chen Ying , Ren Jiecheng , Yi Piao , Zhang Pengyu , Zha Rujing , Qiu Bensheng , Zhang Daren , Bi Yanchao , Han Shihui , Zhang Xiaochu 
Published: August 2021

AbstractStudying how we perceive humanoid robots will provide insights for a deeper understanding of human-robot interaction. Our ideas about humanoid robots are mainly informed by science fiction, and humanoid robots are generally described as an evolutionary threat in science fiction that has not been tested. The preparedness model has emphasized that the fear module is automatically activated by evolutionary threats, and its underlying neural circuit is centered on the amygdala. We hypothesized that if humanoid robots are perceived as an evolutionary threat even though humanoid robots are manmade, modern objects, we would expect to observe a monocular advantage for humanoid robots and an amygdala response to unconsciously presented humanoid robots that were previously only evident in evolutionary threats. Here, we observed a monocular advantage for the perception of humanoid robots the same as an evolutionary threat (i.e., snakes). Our neuroimaging analysis indicated that unconscious presentation of humanoid robot vs. human images led to significant amygdala activation. Despite a positive humanoid robot-related association had been established by associative learning (as evidenced by results of successfully weakening the negative implicit attitude to humanoid robots and enhancing functional connectivity between the amygdala and hippocampus), the amygdala could still automatically and quickly detect humanoid robots. Our results reveal that processing of information about humanoid robots displays automaticity with regard to recruitment of visual pathway and amygdala activation. Our findings that humans apparently perceive humanoid robots as an evolutionary threat may help inform redefinition of human-robot interaction and robot ethics.
How leader contingent reward behavior impacts employee work engagement and turnover intention: the moderating role of age
Authors: Laulié Lyonel , Pavez Ignacio , Martínez Echeverría Javier , Cea Pablo , Briceño Jiménez Gabriel 
Published: August 2021

PurposeThe purpose of this article is to explore employee age as a moderating factor in the relationship between leader contingent reward behavior (CRB) and work engagement. In doing so, the authors seek to provide a more nuanced understanding of the mediating role of work engagement in the negative effect of leader CRB on turnover intention.Design/methodology/approachThe authors used online surveys among a sample of employees of a retail company in Chile to capture individual perceptions about supervisor CRB, work engagement and turnover intention. To test the authors’ hypotheses, they modeled a first-stage moderated mediation effect using Hayes’ Process macro.FindingsThe authors’ results confirm the hypothesis that the negative effect of leader CRB on employee turnover intention is partially mediated by employee work engagement. Interestingly, age was a significant moderator of the mediation effect only for individuals working at headquarters, but not for employees working in stores.Originality/valueThis study expands current knowledge about how the leadership–engagement relationship can predict organizational outcomes, including age as a boundary condition. Following the job demands-resources theory, the authors also prove that conceptualizing leader CRB as a job resource can benefit the integration of leadership and work engagement research. The authors’ findings may help organizational researchers and practitioners acknowledge contextual differences in understanding the combined effects of leadership styles and work engagement.