bluuebunny/crossref_metadata_2025_split huggingface dataset:
The midpoint of cortical thinning between late childhood and early adulthood differs between individuals and brain regions: Evidence from longitudinal modelling in a 12-wave neuroimaging sample
Authors: Fuhrmann Delia , Madsen Kathrine Skak , Baruël Johansen Louise , Baaré William FC , Kievit Rogier A 
Published: February 2022

AbstractCharting human brain maturation between childhood and adulthood is a fundamental prerequisite for understanding the rapid biological and psychological changes during human development. Two barriers have precluded the quantification of maturational trajectories: demands on data and demands on estimation. Using high-temporal resolution neuroimaging data of up to 12-waves in the HUBU cohort (N = 90, aged 7-21 years) we investigate changes in apparent cortical thickness across childhood and adolescence. Fitting a four-parameter logistic nonlinear random effects mixed model, we quantified the characteristic, s-shaped, trajectory of cortical thinning in adolescence. This approach yields biologically meaningful parameters, including the midpoint of cortical thinning (MCT), which corresponds to the age at which the cortex shows most rapid thinning - in our sample occurring, on average, at 14 years of age. These results show that, given suitable data and models, cortical maturation can be quantified with precision for each individual and brain region.
A mechanical transition from tension to buckling underlies the jigsaw puzzle shape morphogenesis of histoblasts in the Drosophila epidermis
Authors: Rigato Annafrancesca , Meng Huicheng , Chardes Claire , Runions Adam , Abouakil Faris , Smith Richard S , LeGoff Loïc 
Published: February 2022

ABSTRACTThe polygonal shape of cells in proliferating epithelia is a result of the tensile forces of the cytoskeletal cortex and packing geometry set by the cell cycle1, 2. In the larval Drosophila epidermis, two cell populations, histoblasts and larval epithelial cells, compete for space as they grow on a limited body surface. They do so in the absence of cell divisions.We report a striking morphological transition of histoblasts during larval development, where they change from a tensed network configuration with straight cell outlines at the level of adherens junctions to a highly folded morphology. The apical surface of histoblasts shrinks while their growing adherens junctions fold, forming deep lobules. Volume increase of growing histoblasts is accommodated basally, compensating for the shrinking apical area. The folded geometry of apical junctions resembles elastic buckling, and we show that the imbalance between the shrinkage of the apical domain of histoblasts and the continuous growth of junctions triggers buckling. Our model is supported by laser dissections and optical tweezer experiments together with computer simulations. Our analysis pinpoints the ability of histoblasts to store mechanical energy to a much greater extent than most other epithelial cell types investigated so far, while retaining the ability to dissipate stress on the hours time scale. Finally, we propose a possible mechanism for size regulation of histoblast apical size through the lateral pressure of the epidermis, driven by the growth of cells on a limited surface.Buckling effectively compacts histoblasts at their apical plane and may serve to avoid physical harm to these adult epidermis precursors during larval life. Our work indicates that in growing non-dividing cells, compressive forces, instead of tension, may drive cell morphology.
Histone H4K20 Trimethylation is Decreased in Murine Models of Heart Disease
Authors: Hickenlooper Samuel M. , Davis Kathryn , Sheikh Hanin , Miller Mickey , Bia Ryan , Valdez Steven , Szulik Marta W. , Franklin Sarah 
Published: February 2022

ABSTRACTHeart disease is the leading cause of death in the developed world, and its comorbidities such as hypertension, diabetes, and heart failure are accompanied by major transcriptomic changes in the heart. During cardiac dysfunction, which leads to heart failure, there are global epigenetic alterations to chromatin that occur concomitantly with morphological changes in the heart in response to acute and chronic stress. These epigenetic alterations include the reversible methylation of lysine residues on histone proteins. Lysine methylation on histone H3K4 and H3K9 were among the first methylated lysine residues identified and have been linked to gene activation and silencing, respectively. However, much less is known regarding other methylated histone residues, including histone H4K20. Trimethylation of histone H4K20 has been shown to repressive gene expression, however this mark has never been examined in the heart. Here we utilized immunoblotting and mass spectrometry to quantify histone H4K20 trimethylation in three models of cardiac dysfunction. Our results show that lysine methylation at this site is regulated in a biphasic manner leading to increased H4K20 trimethylation during acute hypertrophic stress and decreased H4K20 trimethylation during sustained ischemic injury and cardiac dysfunction. In addition, we examined publicly available datasets to analyze enzymes that regulate H4K20 methylation and identified one demethylase (KDM7C) and two methyltransferases (KMT5A and SMYD5) which were all upregulated in heart failure patients. This is the first study to examine histone H4K20 trimethylation in the heart and to determine how this post-translational modification is differentially regulated in multiple models of cardiac disease.Abstract Figure
Comparison of Proton Transfer Paths to the QAand QBSites of theRb. sphaeroidesPhotosynthetic Reaction Centers
Authors: Wei Rongmei Judy , Zhang Yingying , Mao Junjun , Kaur Divya , Khaniya Umesh , Gunner M.R. 
Published: February 2022

AbstractThe photosynthetic bacterial reaction centers from purple non-sulfur bacteria use light energy to drive the transfer of electrons from cytochrome c to ubiquinone. Ubiquinone bound in the QAsite cycles between quinone, QA, and anionic semiquinone, QA•-, being reduced once and never binding protons. In the QBsite, ubiquinone is reduced twice by QA•-, binds two protons and is released into the membrane as the quinol, QH2. The network of hydrogen bonds formed in a molecular dynamics trajectory was drawn to investigate proton transfer pathways from the cytoplasm to each quinone binding site. QAis isolated with no path for protons to enter from the surface. In contrast, there is a complex and tangled network requiring residues and waters that can bring protons to QB. There are three entries from clusters of surface residues centered around HisH126, GluH224, and HisH68. The network is in good agreement with earlier studies, Mutation of key nodes in the network, such as SerL223, were previously shown to slow proton delivery. Mutational studies had also shown that double mutations of residues such as Asp M17 and AspL210 along multiple paths in the network presented here slow the reaction, while single mutations do not. Likewise, mutation of both HisH126 and HisH128, which are at the entry to two paths reduce the rate of proton uptake.
The RNA-binding protein landscapes differ between mammalian organs and cultured cells
Authors: Perez-Perri Joel I. , Ferring-Appel Dunja , Huppertz Ina , Schwarzl Thomas , Stein Frank , Rettel Mandy , Galy Bruno , Hentze Matthias W. 
Published: February 2022

SummarySystem-wide approaches have unveiled an unexpected breadth of the RNA-bound proteomes of cultured cells. Corresponding information regarding RNA-binding proteins (RBPs) of mammalian organs is still missing, largely due to technical challenges. Here, we describe ex vivo eRIC (enhanced RNA interactome capture) to characterize the poly(A)RNA-bound proteomes of three different mouse organs. The resulting organ atlases encompass more than 1300 RBPs active in brain, kidney or liver. Nearly a quarter (291) of these had formerly not been identified in cultured cells, with more than 100 being metabolic enzymes. Remarkably, RBP activity differs between organs independent of RBP abundance, suggesting organ-specific levels of control. Similarly, we identify systematic differences in RNA binding between animal organs and cultured cells. The pervasive RNA binding of enzymes of intermediary metabolism in organs points to tightly knit connections between gene expression and metabolism, and displays a particular enrichment for enzymes that use nucleotide cofactors. We describe a generically applicable refinement of the eRIC technology and provide an instructive resource of RBPs active in intact mammalian organs, including the brain.
Architecture of the human erythrocyte ankyrin-1 complex
Authors: Vallese F. , Kim K. , Yen L.Y. , Johnston J.D. , Noble A.J. , Calì T. , Clarke O.B. 
Published: February 2022

AbstractThe stability and shape of the erythrocyte membrane is provided by the ankyrin-1 complex, but how it tethers the spectrin-actin cytoskeleton to the lipid bilayer and the nature of its association with the band 3 anion exchanger and the Rhesus glycoproteins remains unknown. Here we present structures of ankyrin-1 complexes purified from human erythrocytes. We reveal the architecture of a core complex of ankyrin-1, the Rhesus proteins RhAG and RhCE, the band 3 anion exchanger, protein 4.2 and glycophorin A. The distinct T-shaped conformation of membrane-bound ankyrin-1 facilitates recognition of RhCE and unexpectedly, the water channel aquaporin-1. Together, our results uncover the molecular details of ankyrin-1 association with the erythrocyte membrane, and illustrate the mechanism of ankyrin-mediated membrane protein clustering.
The Voices of Medical Education Science: Describing the Published Landscape
Authors: Maggio Lauren A. , Costello Joseph A. , Ninkov Anton , Frank Jason R. , Artino Anthony R. 
Published: February 2022

AbstractIntroductionMedical education has been described as a dynamic and growing field, driven in part by its unique body of scholarship. The voices of authors who publish medical education literature have a powerful impact on the discourses of the community. While there have been numerous studies looking at aspects of this literature, there has been no comprehensive view of recent publications.MethodThe authors conducted a bibliometric analysis of all articles published in 24 medical education journals published between 2000-2020 to identify article characteristics, with an emphasis on author gender, geographic location, and institutional affiliation. This study replicates and greatly expands on two previous investigations by examining all articles published in these core medical education journals.ResultsThe journals published 37,263 articles with the majority of articles published in 2020 (n=3,957, 10.7%) and the least in 2000 (n=711, 1.9%) representing a 456.5% increase. The articles were authored by 139,325 authors of which 62,708 were unique. Males were more prevalent across all authorship positions (n=62,828; 55.7%) than females (n=49,975; 44.3%). Authors listed 154 country affiliations with the United States (n=42,236, 40.4%), United Kingdom (n=12,967, 12.4%), and Canada (n=10,481, 10.0%) most represented. Ninety-three countries (60.4%) were low- or middle-income countries accounting for 9,684 (9.3%) author positions. Few articles were written by multinational teams (n=3,765; 16.2%). Authors listed affiliations with 4,372 unique institutions. Across all author positions, 48,189 authors (46.1%) were affiliated with a top 200 institution, as ranked by the Times Higher Education ranking.DiscussionThere is a relative imbalance of author voices in medical education. If the field values a diversity of perspectives, there is considerable opportunity for improvement.
Evolution of inflammation and immunity in a dengue virus 1 human infection model
Authors: Waickman Adam T. , Lu Joseph Q. , Fang HengSheng , Waldran Mitchell , Gebo Chad , Currier Jeffrey R. , Van Wesenbeeck Liesbeth , Verpoorten Nathalie , Lenz Oliver , Tambuyzer Lotke , Herrera-Taracena Guillermo , Van Loock Marnix , Endy Timothy P. , Thomas Stephen J. 
Published: February 2022

ABSTRACTDengue virus (DENV) infections are significant sources of morbidity and mortality throughout the tropics and subtropics. Over 400 million infections are estimated to occur every year, resulting in nearly 100 million symptomatic infections and over 20,000 deaths. Early immune response kinetics to infection remain unclear, in large part due to the variable incubation period exhibited by the DENVs after introduction into a susceptible host. To fill this knowledge gap, we performed a comprehensive virologic and immunologic analysis of individuals experimentally infected with the under-attenuated DENV-1 strain 45AZ5. This analysis captured both the kinetics and composition of the innate, humoral, and cellular immune responses elicited by experimental DENV-1 infection, as well as virologic and clinical features. Revealed in this analysis was a robust DENV-specific IgA antibody response that manifested between the appearance of DENV-specific IgM and IgG in all challenged individuals, as well as the presence of a non-neutralizing/NS1-specific antibody response that was delayed relative to the appearance of DENV-virion specific humoral immunity. RNAseq analysis also revealed several distinct and temporally-restricted gene modules that allowed for the identification and differentiation of the innate and adaptive immune response to DENV-infection. Our analysis provides a detailed description, in time and space, of the evolving matrix of DENV-elicited human inflammation and immunity and reveals several previously unappreciated immunological aspects of primary DENV-1 infection that can inform countermeasure development and evaluation.
Machine learning-assisted discovery of growth decision elements by relating bacterial population dynamics to environmental diversity
Authors: Aida Honoka , Hashizume Takamasa , Ashino Kazuha , Ying Bei-Wen 
Published: February 2022

AbstractMicroorganisms growing in their habitat constitute a complex system. How the individual constituents of the environment contribute to microbial growth remains largely unknown. The present study focused on the contribution of environmental constituents to population dynamics via a high-throughput assay and data-driven analysis of a wild-type Escherichia coli strain. A large dataset constituting a total of 12,828 bacterial growth curves with 966 medium combinations, which were composed of 44 pure chemical compounds, was acquired. Machine learning analysis of the big data relating the growth parameters to the medium combinations revealed that the decision-making components for bacterial growth were distinct among various growth phases, e.g., glucose, sulfate and serine for maximum growth, growth rate and growth delay, respectively. Further analyses and simulations indicated that branched-chain amino acids functioned as global coordinators for population dynamics, as well as, a survival strategy of risk diversification to prevent the bacterial population from undergoing extinction.
Goitered Gazelle’s (Gazella Subgutturosa) Habitat Desirability Modeling by Using Maximum Entropy (Maxent) Method
Authors: Naqibzadeh Abbas , Sarhangzadeh Jalil , Sotoudeh Ahad , Mashkour Marjan , Thomalsky Judith 
Published: February 2022

AbstractThe models predicting the spatial distribution of species can simulate the suitability of species habitats on different spatial scales, based on species records and site characteristics to gain insight into ecological or evolutionary drivers or to help predict habitat suitability across large scales. Species distribution models (SDMs) based on presence-absence or presence-only data use widely in biogeography to characterize the ecological niche of species and to predict the geographical distribution of their habitat. Although presence-absence data is generally of higher quality, it is also less common than presence-only data because it requires more rigorous planning to visit a set of pre-determined sites. Among the algorithms available, one of the most widely used methods of developing SDMs is the Maximum Entropy (MaxEnt) method. The MaxEnt uses entropy to generalize specific observations of presence-only data and does not require or even incorporate points where the species is absent within the theoretical framework. The purpose of this study is to predict the suitable habitat for Goitered gazelle (Gazella subgutturosa) in the Samelghan plain in northeastern Iran. The results showed that the variables of the Mediterranean climate classes, slope 0-5% class and semi-dense pastures with type Acantholimon-Astragalus are more important than other environmental variables used in modeling. The area under curve (AUC), Receiver Operating Characteristic (ROC), and the classification threshold shows model performance. Based on the ROC (AUC=0.99) results in this study, it was found that Maxent’s performance was very good. Desirability habitat was classified based on the threshold value (0.0277) and the ROC, which approx 11% of the area, predicted suitable habitat for Goitered gazelle.
Active tactile discrimination is coupled with and modulated by the cardiac cycle
Authors: Galvez-Pol Alejandro , Virdee Pavandeep , Villacampa Javier , Kilner James M 
Published: February 2022

AbstractPerception and cognition are modulated by the phase of the cardiac signal in which the stimuli are presented. This has been shown by locking the presentation of stimuli to distinct cardiac phases. However, in everyday life sensory information is not presented in this phase-locked and passive manner, instead we actively sample the world. Whether active sensing is coupled and modulated with the cardiac cycle remains largely unknown. Here we recorded the ECGs of human participants while they actively performed a tactile grating orientation task. Here we show that the duration of subjects’ touch varied as a function of the cardiac phase in which they initiated it. Touches initiated in the systolic phase of the cardiac cycle were held for longer periods of time than touches initiated in the diastolic phase. This effect was driven by the elongation of their holds to sample the most difficult gratings. Conversely, while touches in the control condition were coupled to the cardiac cycle, their length was not modulated as a function of when in the cycle these were initiated. In line with interoceptive inference accounts, these results are consistent with the hypotheses that we actively adjust our sensory sampling so that we spend more time in the diastole period of the cardiac cycle in which perceptual sensory sensitivity is greatest.
The Ndc80 complex is essential for the initial kinetochore-microtubule capture during early mitosis
Authors: Amin Mohammed Abdullahel , Wallace Destiny Ariel , Varma Dileep 
Published: February 2022

ABSTRACTMitotic kinetochores are initially captured by dynamic microtubules via a ‘search-and-capture’ mechanism. The microtubule motor, dynein, is critical for kinetochore capture as it has been shown to transport microtubule-attached chromosomes towards the spindle pole during early mitosis. In metaphase, the kinetochore localized, microtubule-binding complex, Ndc80, plays a central role in stabilizing kinetochore-microtubule (kMT) attachments. It is not yet clear, however, if Ndc80, which is recruited to kinetochores very early during mitosis contributes to initial kMT capture. Here, by combining CRISPR/Cas9-mediated knockout and RNAi technology with assays specifically targeted to study kMT capture, we show that mitotic cells lacking Ndc80 exhibit severe defects in this function during prometaphase. Rescue experiments show that Ndc80 mutants deficient in microtubule-binding are unable to execute proper kMT capture. While cells inhibited of dynein alone are predominantly able to make initial kMT attachments, cells co-depleted of Ndc80 and dynein show severe defects in kMT capture. Further, we demonstrate a novel physical interaction between Ndc80 and dynein during prometaphase. Thus, our studies, for the first time, identify a distinct event in the formation of initial kMT attachments, which is directly mediated by Ndc80 followed by a coordinated function with dynein, both of which are required for efficient kMT capture and proper chromosome alignment.
Identification of CD317-Positive Pro-inflammatory Immune Stromal Cells in Human Mesenchymal Stromal Cell Preparations
Authors: Kay Alasdair G , Fox James M , Hewitson James , Stone Andrew , Robertson Sophie , James Sally , Wang Xiao-nong , Kapasa Elizabeth , Yang Xuebin , Genever Paul G 
Published: February 2022

AbstractMesenchymal stromal cell (MSC) heterogeneity clouds biological understanding and hampers their clinical development. In MSC cultures most commonly used in research and therapy, we have identified an MSC subtype characterised by CD317 expression (CD317pos(29.77±3.00% of the total MSC population), comprising CD317dim(28.10±4.60%) and CD317bright(1.67±0.58%) MSCs) and a constitutive interferon signature linked to human disease. We demonstrate that CD317posMSCs induced cutaneous tissue damage when applied a skin explant model of inflammation, whereas CD317negMSCs had no effect. Only CD317negMSCs were able to suppress proliferative cycles of activated human T cellsin vitro, whilst CD317posMSCs increased polarisation towards pro-inflammatory Th1 cells and CD317negcell lines did not. Using anin vivoperitonitis model, we found that CD317negand CD317posMSCs suppressed leukocyte recruitment but only CD317negMSCs suppressed macrophage numbers. Using MSC-loaded scaffolds implanted subcutaneously in immunocompromised mice we were able to observe tissue generation and blood vessel formation with CD317negMSC lines, but not CD317posMSC lines. Our evidence is consistent with the identification of an immune stromal cell, which is likely to contribute to specific physiological and pathological functions and influence clinical outcome of therapeutic MSCs.
Relation of incident Type 1 diabetes to recent COVID-19 infection: cohort study using e-health record linkage in Scotland
Authors: McKeigue Paul M , McGurnaghan Stuart , Blackbourn Luke , Bath Louise E , McAllister David A , Caparrotta Thomas M , Wild Sarah H , Wood Simon N , Stockton Diane , Colhoun Helen M 
Published: February 2022

AbstractBackgroundStudies using claims databases have reported that SARS-CoV-2 infection >30 days earlier increased the incidence of type 1 diabetes (T1DM). Using exact dates of type 1 diabetes diagnosis from the national register in Scotland linked to virology laboratory data we sought to replicate this finding.MethodsA cohort of 1849411 individuals aged <35 years without diabetes, including all those in Scotland who subsequently tested positive for SARS-CoV-2, was followed from 1 March 2020 to 22 November 2021. Incident T1DM was identified by linkage to the national registry. Cox regression was used to test the association of time-updated infection with incident T1DM. Trends in incidence of T1DM in the total population from 2015-2021 were estimated in a generalized additive model.FindingsThere were 365080 in the cohort with at least one detected SARS-CoV-2 infection during follow-up and 1074 who developed T1DM. The rate ratio for incident T1DM associated with first positive test for SARS-CoV-2 (with no previous infection as reference category) was 0.88 (95% CI 0.63 to 1.23) for infection more than 30 days earlier and 2.62 (95% CI 1.81 to 3.79) for infection in the previous 30 days. However negative and positive SARS-CoV-2 tests were more frequent in the days surrounding T1DM presentation. In those aged 0-14 years incidence of T1DM during 2020-2021 was 20% higher than the 7-year average.InterpretationT1DM incidence in children increased during the pandemic. However the cohort analysis does not support a causal effect of SARS-CoV-2 infection itself on T1DM incidence.FundingNone