bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stress-induced changes in inflammatory and atherosclerosis markers during official basketball games in professional coaches
Authors: Zerva Athina , Chronaki Marianna , Rojas Gil Andrea Paola , Paschalidis Nikolaos , Andriopoulos Panagiotis , Tsironi Maria 
Published: September 2021

ABSTRACTObjectiveTop-level competitive sports coaches repeatedly cope with situations of acute stress in order to succeed and manage high team performance. Occupational stress-induced biochemical and immune system markers are not well studied for this specific group of people. The purpose of this study was to evaluate stress-induced alterations of inflammatory markers and atherosclerosis risk factors during an official basketball game in top-level professional basketball coaches (head and assistant).MethodsBlood samples and vital signs were obtained from 27 healthy coaches (Greek A1 Men’s National Basketball League), 30 minutes before and 30 minutes after the games. We performed a full blood count and measured inflammatory cytokines, atherosclerosis markers and cortisol levels. Data were statistically analysed using two-tailed paired and independent samples t-tests and Pearson’s Correlations.ResultsPost-game neutrophils (NEU) and apolipoprotein B (ApoB) levels were significantly increased while lymphocytes (LYM) were significantly decreased in comparison to pre-game values. Blood pressure (systolic and diastolic) levels were considered as a pre-hypertension state at both measurements. We found significant alterations between head and assistant coaches in diastolic blood pressure and cortisol levels after the game. Cortisol was negatively correlated to inflammatory cytokine levels and positively correlated with ApoB levels.ConclusionsGame-induced acute psychological stress initiates an aseptic inflammatory response in top-level professional coaches and can be related to the atherosclerosis pathways posing as an acute as well as chronic health threat for top-level coaches who have to deal with long periods of stressful working conditions.SUMMARY BOXWhat are the new findings?Top-level basketball games induce an aseptic inflammatory response in professional basketball coaches mainly manifested by increased levels of peripheral blood neutrophilsThe response to game conditions also included elevated levels of ApoB after the game that were positively correlated with cortisol levelsStressful game conditions over a long season of games could pose as a serious health issue for professional coachesHealth monitoring for professional coaches in top-level competitive sports such as basketball should be implemented more often with particular focus on inflammatory and atherosclerosis markers
Predictors of real-world parents’ acceptance to vaccinate their children against the COVID-19
Authors: Galanis Petros , Vraka Irene , Siskou Olga , Konstantakopoulou Olympia , Katsiroumpa Aglaia , Moisoglou Ioannis , Kaitelidou Daphne 
Published: September 2021

AbstractBackgroundAs the COVID-19 pandemic continues to threaten public health, the vaccination of children against the disease appears to be a key factor to control the pandemic.ObjectiveTo investigate the prevalence of parents who have vaccinated their children against the COVID-19 and the factors influencing this decision.MethodsWe conducted a web-based cross-sectional study in Greece during the first week of September 2021. The study questionnaire was distributed through social media and a convenience sample was obtained. Only parents with children aged 12-17 years old could participate in the study. We collected socio-demographic data of parents and we measured their attitudes towards vaccination and COVID-19 pandemic.ResultsStudy population included 656 parents. Mean age of parents was 45.5 years, while most of them were mothers with a high level of education. Regarding vaccination, 27.1% of parents had their children vaccinated against the COVID-19, while almost all children had a complete vaccination history (98.9%). The most important reasons for decline of COVID-19 vaccination were doubts about the safety and effectiveness of COVID-19 vaccines (45.3%) and fear of side effects (36.6%). Regarding the information about the COVID-19 vaccines, parents showed more trust in family doctors than in scientists and the government. Multivariate regression analysis identified that increased parents’ age, increased trust in COVID-19 vaccines, and positive attitude of parents towards vaccination had a positive effect on children’s vaccination.ConclusionsUnderstanding the factors influencing parents’ decision to vaccinate their children against the COVID-19 is crucial to increase the COVID-19 vaccination coverage rate. Implementation of public health policies is necessary to spread knowledge about COVID-19 vaccines and to regain vaccine confidence.
Sex-dependent parameters of social behavior show marked variations between distinct laboratory mouse strains and their mixed offspring
Authors: Kopachev Natalia , Netser Shai , Wagner Shlomo 
Published: September 2021

AbstractBackgroundThe survival of individuals of gregarious species depends on their ability to properly form social interactions. In humans, atypical social behavior is a hallmark of several psychopathological conditions, such as depression and autism spectrum disorder, many of which have sex-specific manifestations. Various strains of laboratory mice are used to reveal the mechanisms mediating typical and atypical social behavior in mammals.MethodsHere we used three social discrimination tests (social preference, social novelty preference, and sex preference) to characterize social behavior in males and females of three widely used laboratory mouse strains (C57BL/6J, BALB/c, and ICR).ResultsWe found marked sex- and strain-specific differences in the preference exhibited by subjects in a test-dependent manner. Interestingly, we found some characteristics that were strain-dependent, while others were sex-dependent. Moreover, even in the social preference test, where both sexes of all strains prefer social over object stimuli, we revealed sex- and strain-specific differences in the behavioral dynamics. We then cross-bred C57BL/6J and BALB/c mice and demonstrated that the offspring of such cross-breeding exhibit a profile of social behavior which is different from both parental strains and depends on the specific combination of parental strains.ConclusionsWe conclude that social behavior of laboratory mice is highly sex- and strain-specific and strongly depends on genetic factors.
Myelin imaging of the basal forebrain in first-episode psychosis
Authors: Park Min Tae M. , Jeon Peter , French Leon , Dempster Kara , Chakravarty M. Mallar , MacKinley Michael , Richard Julie , Khan Ali R. , Théberge Jean , Palaniyappan Lena 
Published: September 2021

AbstractCholinergic dysfunction has been implicated in the pathophysiology of psychiatric disorders such as schizophrenia, depression, and bipolar disorder. The basal forebrain (BF) cholinergic nuclei, defined as cholinergic cell groups Ch1-3 and Ch4 (Nucleus Basalis of Meynert; NBM), provide extensive cholinergic projections to the rest of the brain. Here, we examined microstructural neuroimaging measures of the cholinergic nuclei in patients with untreated psychosis (∼ 31 weeks of psychosis, <2 defined daily dose of antipsychotics) and used Magnetic Resonance Spectroscopy (1H-MRS) and transcriptomic data to support our findings. We used a cytoarchitectonic atlas of the BF to map the nuclei and obtained measures of myelin (quantitative T1, or qT1 as myelin surrogate) and microstructure (axial diffusion; AxD). In a clinical sample (n=85; 29 healthy controls, 56 first-episode psychosis), we found significant correlations between qT1 and 1H-MRS-based dorsal anterior cingulate choline in healthy controls, while this relationship was disrupted in FEP. Case-control differences in qT1 and AxD were observed in the Ch1-3, with increased qT1 (reflecting reduced myelin content) and AxD (reflecting reduced axonal integrity). We found clinical correlates between left NBM qT1 with manic symptom severity, and AxD with negative symptom burden in FEP. Intracortical and subcortical myelin maps were derived and correlated with BF myelin. BF-cortical and BF-subcortical myelin correlations demonstrate known projection patterns from the BF. Using data from the Allen Human Brain Atlas, cholinergic nuclei showed significant enrichment for schizophrenia and depression-related genes. Cell-type specific enrichment indicated enrichment for cholinergic neuron markers as expected. Further relating the neuroimaging correlations to transcriptomics demonstrated links with cholinergic receptor genes and cell type markers of oligodendrocytes and cholinergic neurons, providing biological validity to the measures. These results provide genetic, neuroimaging, and clinical evidence for cholinergic dysfunction in schizophrenia and other psychiatric disorders such as depression.
AtRBOHC/RHD2 vesicular delivery to the apical plasma membrane domain during root hair development
Authors: Kuběnová Lenka , Tichá Michaela , Šamaj Jozef , Ovečka Miroslav 
Published: September 2021

AbstractArabidopsis root hairs develop as long tubular extensions from the rootward pole of trichoblasts and exert polarized tip growth. The establishment and maintenance of root hair polarity is a complex process involving the local apical production of reactive oxygen species (ROS) generated by NADPH oxidase RESPIRATORY BURST OXIDASE HOMOLOG PROTEIN C/ROOT HAIR DEFECTIVE 2 (AtRBOHC/RHD2). It has been shown that loss-of-function rhd2 mutants have short root hairs that are unable to elongate by tip growth, and this phenotype was fully complemented by GFP-RHD2 expressed under the RHD2 promoter. However, the spatiotemporal mechanism of AtRBOHC/RHD2 subcellular redistribution and delivery to the plasma membrane (PM) during root hair initiation and tip growth are still unclear. Here, we used advanced microscopy for detailed qualitative and quantitative analysis of vesicular compartments containing GFP-RHD2 and characterization of their movements in developing bulges and growing root hairs. These compartments, identified by an independent marker such as the trans-Golgi network (TGN), deliver GFP-RHD2 to the apical PM domain, the extent of which correlates with the stage of root hair formation. Movements of TGN/early endosomes, but not late endosomes, were affected in the bulging domains of the rhd2-1 mutant. Finally, we reveal that accumulation in the growing tip, docking, and incorporation of TGN compartments containing GFP-RHD2 to the apical PM of root hairs requires structural sterols. These results help clarify the mechanism of polarized AtRBOHC/RHD2 targeting, maintenance, and recycling at the apical PM domain, coordinated with different developmental stages of root hair initiation and growth.One-sentence summaryAdvanced microscopy and quantitative analysis of vesicular TGN compartments revealed that delivering GFP-RHD2 to the apical plasma membrane domains of developing bulges and growing root hairs requires structural sterols.
Characterizing cellular heterogeneity in chromatin state with scCUT&Tag-pro
Authors: Zhang Bingjie , Srivastava Avi , Mimitou Eleni , Stuart Tim , Raimondi Ivan , Hao Yuhan , Smibert Peter , Satija Rahul 
Published: September 2021

AbstractNew technologies that profile chromatin modifications at single-cell resolution offer enormous promise for functional genomic characterization. However, the sparsity of these measurements and the challenge of integrating multiple binding maps represent significant challenges. Here we introduce scCUT&Tag-pro, a multimodal assay for profiling protein-DNA interactions coupled with the abundance of surface proteins in single cells. In addition, we introduce scChromHMM, which integrates data from multiple experiments to infer and annotate chromatin states based on combinatorial histone modification patterns. We apply these tools to perform an integrated analysis across nine different molecular modalities in circulating human immune cells. We demonstrate how these two approaches can characterize dynamic changes in the function of individual genomic elements across both discrete cell states and continuous developmental trajectories, nominate associated motifs and regulators that establish chromatin states, and identify extensive and cell type-specific regulatory priming. Finally, we demonstrate how our integrated reference can serve as a scaffold to map and improve the interpretation of additional scCUT&Tag datasets.
Spatial and temporal diversity of astrocyte phenotypes in Spinocerebellar ataxia type 1 mice
Authors: Rosa Juao-Guilherme , Hamel Katherine , Sheeler Carrie , Borgenheimer Ella , Gilliat Stephen , Soles Alyssa , Ghannoum Fares , Sbrocco Kaelin , Handler Hillary P. , Rainwater Orion , Kang Ryan , Cvetanovic Marija 
Published: September 2021

AbstractWhile astrocyte heterogeneity is an important feature of the healthy brain, less is understood about spatiotemporal heterogeneity of astrocytes in brain disease. Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disease caused by a CAG repeat expansion mutation in the gene Ataxin1 (ATXN1). We characterized astrocytes across disease progression in the four clinically relevant brain regions, cerebellum, brainstem, hippocampus, and motor cortex of Atxn1154Q/2Q mice, a knock-in mouse model of SCA1. We found brain region specific changes in astrocyte density, GFAP expression and area, early in disease and prior to neuronal loss. Expression of astrocytic core homeostatic genes was also altered in a brain-region specific manner and correlated with neuronal activity indicating that astrocytes may compensate or exacerbate neuronal dysfunction in a brain region specific manner. Late in disease, expression of astrocytic homeostatic genes was reduced in all four brain regions indicating loss of astrocyte functions. We observed spatiotemporal changes in microglia with no obvious correlation with spatiotemporal astrocyte alterations indicating a complex orchestration of glial phenotypes in disease. These results support spatiotemporal diversity of glial phenotypes as an important feature of the brain disease that may contribute to SCA1 pathogenesis in a brain-region and disease stage-specific manner.
Random Forest Factorization Reveals Latent Structure in Single Cell RNA Sequencing Data
Authors: Brenerman Boris M. , Shapiro Benjamin D. , Schatz Michael C. , Battle Alexis 
Published: September 2021

AbstractSingle-cell RNA sequencing data contain patterns of correlation that are poorly captured by techniques that rely on linear estimation or assumptions of Gaussian behavior. We apply random forest regression to scRNAseq data from mouse brains, which identifies the co-regulation of genes within specific cellular contexts. By analyzing the estimators of the random forest, we identify several novel candidate gene regulatory networks and compare these networks in aged and young mice. We demonstrate that cell populations have cell-type specific phenotypes of aging that are not detected by other methods, including the collapse of differentiating oligodendrocytes but not precursors or mature oligodendrocytes.
Core genes can have higher recombination rates than accessory genes within global microbial populations
Authors: Steinberg Asher Preska , Lin Mingzhi , Kussell Edo 
Published: September 2021

AbstractRecombination is essential to microbial evolution1–4, and is involved in the spread of antibiotic resistance, antigenic variation, and adaptation to the host niche5–8. Yet quantifying the impact of homologous recombination on different gene classes, which is critical to understanding how selection acts on variation to shape species diversity and genome structure, remains challenging. This is largely due to the dynamic nature of bacterial genomes, whose high intraspecies genome content diversity9 and complex phylogenetic relationships10–12 present difficulties for inferring rates of recombination, particularly for rare genes. In this work, we apply a computationally efficient, non-phylogenetic approach13,14 to measure homologous recombination rates in the core and accessory genome (genes present in all strains and only a subset of strains, respectively) using >100,000 whole genome sequences from 12 microbial species. Our analysis suggests that even well-resolved sequence clusters sampled from global populations interact with overlapping gene pools, which has implications for the role of population structure in genome evolution. We show that in a majority of species, core genes have shorter coalescence times and higher recombination rates than accessory genes, and that gene frequency is often positively correlated with increased recombination. Our results provide a new line of population genomic evidence supporting the hypothesis that core genes are under strong, purifying selection15–17, and indicate that homologous recombination may play a key role in increasing the efficiency of selection in those parts of the genome most conserved within each species.
Molecular and cellular adaptations in hippocampal parvalbumin neurons mediate behavioral responses to chronic social stress
Authors: Bhatti Dionnet L. , Medrihan Lucian , Chen Michelle X. , Jin Junghee , McCabe Kathryn , Wang Wei , Azevedo Estefania P. , Ledo Jose H. , Kim Yong 
Published: September 2021

ABSTRACTParvalbumin-expressing interneurons (PV neurons) maintain inhibitory control of local circuits implicated in behavioral responses to environmental stressors. However, the roles of molecular and cellular adaptations in PV neurons in stress susceptibility or resilience have not been clearly established. Here, we show behavioral outcomes of chronic social defeat stress (CSDS) are mediated by differential neuronal activity and gene expression in hippocampal PV neurons in mice. Using in vivo electrophysiology and chemogenetics, we find increased PV neuronal activity in the ventral dentate gyrus is required and sufficient for behavioral susceptibility to CSDS. PV neuron-selective translational profiling indicates mitochondrial oxidative phosphorylation is the most significantly altered pathway in stress-susceptible versus resilient mice. Among differentially expressed genes associated with stress-susceptibility and resilience, we find Ahnak, an endogenous regulator of L-type calcium channels which are implicated in the regulation of mitochondrial function and gene expression. Notably, Ahnak deletion in PV neurons impedes behavioral susceptibility to CSDS. Altogether, these findings indicate behavioral effects of chronic stress can be controlled by selective modulation of PV neuronal activity or a regulator of L-type calcium signaling in PV neurons.
Heterodimers of functionally divergent ARF-GEF paralogues prevented by self-interacting dimerisation domain
Authors: Brumm Sabine , Singh Manoj K. , Beckmann Hauke , Richter Sandra , Huhn Kerstin , Kucera Tim , Baumann Sarah , Kriechbaum Choy , Wolters Hanno , Takada Shinobu , Jürgens Gerd 
Published: September 2021

AbstractFunctionally divergent paralogs of homomeric proteins do not form potentially deleterious heteromers, which requires distinction between self and non-self (Hochberg et al., 2018; Marchant et al, 2019; Marsh and Teichmann, 2015). In Arabidopsis, two ARF guanine-nucleotide exchange factors (ARF-GEFs) related to mammalian GBF1, named GNOM and GNL1, can mediate coatomer complex (COPI)-coated vesicle formation in retrograde Golgi-endoplasmic reticulum (ER) traffic (Geldner et al., 2003; Richter et al., 2007; Teh and Moore, 2007). Unlike GNL1, however, GNOM is also required for polar recycling of endocytosed auxin efflux regulator PIN1 from endosomes to the plasma membrane. Here we show that these paralogues form homodimers constitutively but no heterodimers. We also address why and how GNOM and GNL1 might be kept separate. These paralogues share a common domain organisation and each N-terminal dimerisation (DCB) domain can interact with the complementary fragment (ΔDCB) of its own and the other protein. However, unlike self-interacting DCBGNOM (Grebe et al., 2000; Anders et al., 2008), DCBGNL1 did not interact with itself nor DCBGNOM. DCBGNOM removal or replacement with DCBGNL1, but not disruption of cysteine bridges that stabilise DCB-DCB interaction, resulted in GNOM-GNL1 heterodimers which impaired developmental processes such as lateral root formation. We propose precocious self-interaction of the DCBGNOM domain as a mechanism to preclude formation of fitness-reducing GNOM-GNL1 heterodimers.
Enhanced Specificity Mutations Perturb Allosteric Signaling in CRISPR-Cas9
Authors: Nierzwicki Łukasz , East Kyle W. , Morzan Uriel N. , Arantes Pablo R. , Batista Victor S. , Lisi George P. , Palermo Giulia 
Published: September 2021

ABSTRACTCRISPR-Cas9 is a molecular tool with transformative genome editing capabilities. At the molecular level, an intricate allosteric signaling is critical for DNA cleavage, but its role in the specificity enhancement of the Cas9 endonuclease is poorly understood. Here, solution NMR is combined with multi-microsecond molecular dynamics and graph theory-derived models to probe the allosteric role of key enhancement specificity mutations. We show that the mutations responsible for increasing the specificity of Cas9 alter the allosteric structure of the catalytic HNH domain, impacting the signal transmission from the DNA recognition region to the catalytic sites for cleavage. Specifically, the K855A mutation strongly disrupts the HNH domain allosteric structure, exerting the highest perturbation on the signaling transfer, while K810A and K848A result in more moderate effects on the allosteric intercommunication. This differential perturbation of the allosteric signaling reflects the different capabilities of the single mutants to increase Cas9 specificity, with the mutation achieving the highest specificity also strongly perturbing the signaling transfer. These outcomes reveal that the allosteric regulation is critical for the specificity enhancement of the Cas9 enzyme, and are valuable to harness the signaling network to improve the system’s specificity.
Human mitochondrial protein complexes revealed by large-scale coevolution analysis and deep learning-based structure modeling
Authors: Pei Jimin , Zhang Jing , Cong Qian 
Published: September 2021

AbstractRecent development of deep-learning methods has led to a breakthrough in the prediction accuracy of 3-dimensional protein structures. Extending these methods to protein pairs is expected to allow large-scale detection of protein-protein interactions and modeling protein complexes at the proteome level. We applied RoseTTAFold and AlphaFold2, two of the latest deep-learning methods for structure predictions, to analyze coevolution of human proteins residing in mitochondria, an organelle of vital importance in many cellular processes including energy production, metabolism, cell death, and antiviral response. Variations in mitochondrial proteins have been linked to a plethora of human diseases and genetic conditions. RoseTTAFold, with high computational speed, was used to predict the coevolution of about 95% of mitochondrial protein pairs. Top-ranked pairs were further subject to the modeling of the complex structures by AlphaFold2, which also produced contact probability with high precision and in many cases consistent with RoseTTAFold. Most of the top ranked pairs with high contact probability were supported by known protein-protein interactions and/or similarities to experimental structural complexes. For high-scoring pairs without experimental complex structures, our coevolution analyses and structural models shed light on the details of their interfaces, including CHCHD4-AIFM1, MTERF3-TRUB2, FMC1-ATPAF2, ECSIT-NDUFAF1 and COQ7-COQ9, among others. We also identified novel PPIs (PYURF-NDUFAF5, LYRM1-MTRF1L and COA8-COX10) for several proteins without experimentally characterized interaction partners, leading to predictions of their molecular functions and the biological processes they are involved in.