bluuebunny/crossref_metadata_2025 huggingface dataset:
An automated pipeline for extracting histological stain area fraction for voxelwise quantitative MRI-histology comparisons
Authors: Kor Daniel Z.L. , Jbabdi Saad , Huszar Istvan N. , Mollink Jeroen , Tendler Benjamin C. , Foxley Sean , Wang Chaoyue , Scott Connor , Smart Adele , Ansorge Olaf , Pallebage-Gamarallage Menuka , Miller Karla L. , Howard Amy F.D.
Published: February 2022

The acquisition of MRI and histology in the same post-mortem tissue sample enables direct correlation between MRI and histologically-derived parameters. However, there still lacks a standardised automated pipeline to process histology data, with most studies relying on heavy manual intervention. Here, we introduce an automated pipeline to extract a quantitative histological measure for staining density (stain area fraction) from multiple immunohistochemical (IHC) stains. The pipeline is designed to directly address key IHC artefacts related to tissue staining and slide digitisation. Here, the pipeline was applied to post-mortem human brain data from multiple subjects, relating MRI parameters (FA, MD, R2*, R1) to IHC slides stained for myelin, neurofilaments, microglia and activated microglia. Utilising high-quality MRI-histology coregistrations, we then performed whole-slide voxelwise comparisons (simple correlations, partial correlations and multiple regression analyses) between multimodal MRI- and IHC-derived parameters. The pipeline was found to be reproducible, robust to artefacts and generalisable across multiple IHC stains. Our partial correlation results suggest that some simple MRI-SAF correlations should be interpreted with caution, due to the co-localisation of certain tissue features (e.g. myelin and neurofilaments). Further, we find activated microglia to consistently be the strongest predictor of DTI FA, which may suggest sensitivity of diffusion MRI to neuroinflammation. Taken together, these results show the utility of this approach in carefully curating IHC data and performing multimodal analyses to better understand microstructural relationships with MRI.
Inferring cell motility in complex environments with incomplete tracking data
Authors: Bundgaard Nils , Harmel Christoph , Imle Andrea , Sid Ahmed Samy , Frey Benjamin , Starruß Jörn , Fackler Oliver T. , Graw Frederik
Published: February 2022

Cell motility has important influence on cell interactions and functionality for various biological aspects. Deciphering these dynamics often relies on live-cell microscopy measurements, which partly have to deal with limitations that could impair a reliable quantification of their motility. Especially given complex environments and tissue structures, limited observation periods, cells moving in and out of focus and impaired calibration of observation axes often lead to loss of cell tracks and insufficient tracking of motility within several dimensions. However, a reliable quantification of cell motility dynamics is essential when aiming at extrapolating the observed dynamics in order to understand cell population dynamics at larger temporal and spatial scales using appropriate simulation environments.

To analyze how incomplete observations affect interpretation and parameterization of cell motility, we combined experimental observations with computational models. Studying individual cell dynamics within 3D collagen environments, we found that the gradual loss of cell tracks leads to an underestimation of several motility parameters with the effect dependent on the collagen density. By extending the automated fitting strategy FitMultiCell to account for cell track loss, we show that we are able to retrieve the actual cell dynamics and, thus, to reliably parameterize cell motility from such incomplete data. Applying our approach to the analysis of CD4+ T cells within 3D collagen environments that were infected with HIV-1, we could show that despite a considerable loss of cell tracks, the data still contained sufficient information to compare individual cell motilities by inferring and simulating their dynamics. Thereby, the analysis allowed us to disentangle the effect of HIV-1 infection and collagen density on individual cell motility. Our extended FitMultiCell-approach presented here provides a solution for the elimination of artifacts from cell track data analysis to robustly infer cell motility dynamics.
Rhamnan Sulfate Reduces Atherosclerotic Plaque Formation and Vascular Inflammation
Authors: Patil Nikita P. , Gómez-Hernández Almudena , Zhang Fuming , Cancel Limary , Feng Xu , Yan Lufeng , Xia Ke , Takematsu Eri , Yang Emily Y. , Le Victoria , Fisher Megan E. , Gonzalez-Rodriguez Agueda , Garcia-Monzon Carmelo , Tunnell James , Tarbell John , Linhardt Robert J. , Baker Aaron B.
Published: February 2022

Objective

While lipid-lowering drugs have become a mainstay of clinical therapy these treatments only slow the progression of the disease and can have side effects. Thus, new treatment options are needed to supplement the effects of lipid lowering therapy for treating atherosclerosis. We examined the use of an inexpensive and widely available marine polysaccharide rhamnan sulfate as an oral therapeutic for limiting vascular inflammation and atherosclerosis.

Methods and Results

We found rhamnan sulfate enhanced the barrier function of endothelial cells, preventing the deposition of LDL and maintaining barrier function even in the presence of glycocalyx-degrading enzymes. Rhamnan sulfate was also found to bind directly to FGF-2, PDGF-BB and NF-κB subunits with high affinity. In addition, rhamnan sulfate was a potent inhibitor of NF-κB pathway activation in endothelial cells by TNF-α. We treated ApoE-/- mice with a high fat diet for 4 weeks and then an addition 9 weeks of high fat diet with or without rhamnan sulfate. Rhamnan sulfate reduced vascular inflammation and atherosclerosis in both sexes of ApoE-/- mice but had a stronger therapeutic effect in female mice. Oral consumption of rhamnan sulfate induced a significant decrease in cholesterol plasma levels in female mice but not in male mice.

Conclusions

Rhamnan sulfate has beneficial effects in reducing inflammation, binding growth factors and NF-κB, enhancing endothelial barrier function and reducing atherosclerotic plaque formation in ApoE-/- mice.
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

Charting 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

The 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

Heart 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

The 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

System-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

The 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

Introduction

Medical 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.

Method

The 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.

Results

The 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.

Discussion

There 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

Dengue 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

Microorganisms 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

The 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

Perception 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

Mitotic 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

Mesenchymal 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

Background

Studies 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.

Methods

A 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.

Findings

There 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.

Interpretation

T1DM 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.

Funding

None
MOSPD2 a new endoplasmic reticulum-lipid droplet tether functioning in LD homeostasis
Authors: Zouiouich Mehdi , Di Mattia Thomas , Martinet Arthur , Eichler Julie , Wendling Corinne , Tomishige Nario , Grandgirard Erwan , Fuggetta Nicolas , Ramain Catherine , Mizzon Giulia , Dumesnil Calvin , Carpentier Maxime , Reina-San-Martin Bernardo , Mathelin Carole , Schwab Yannick , Thiam Abdou Rachid , Kobayashi Toshihide , Drin Guillaume , Tomasetto Catherine , Alpy Fabien
Published: February 2022

Membrane contact sites between organelles are organized by protein bridges. Among the components of these contacts, the VAP family comprises endoplasmic reticulum (ER)-anchored proteins, such as MOSPD2, functioning as major ER-organelle tethers. MOSPD2 distinguishes itself from the other members of the VAP family by the presence of a CRAL-TRIO domain. In this study, we show that MOSPD2 forms ER-LD contacts thanks to its CRAL-TRIO domain. MOSPD2 ensures the attachment of the ER to LDs through a direct protein-membrane interaction involving an amphipathic helix that has an affinity for lipid packing defects present at the surface of LDs. Remarkably, the absence of MOSPD2 markedly disturbs the assembly of lipid droplets. These data show that MOSPD2, in addition to being a general ER receptor for inter-organelle contacts, possesses an additional tethering activity and is specifically implicated in the biology of LDs via its CRAL-TRIO domain.
Timely Schwann cell division during migration drives peripheral myelination in vivo via Laminin/cAMP pathway
Authors: Mikdache Aya , Boueid Marie-José , Lesport Emilie , Delespierre Brigitte , Loisel-Duwattez Julien , Degerny Cindy , Tawk Marcel
Published: February 2022

Schwann cells (SC) migrate along peripheral axons and divide intensively to generate the right number of cells prior to axonal ensheathment; however, little is known regarding the temporal and molecular control of their division, particularly during migration, and its impact on myelination. We report that Sil, a spindle pole protein associated with autosomal recessive primary microcephaly (MCPH), is required for temporal mitotic exit of SC. In sil-deficient cassiopeia (csp-/-) mutants, SC fail to radially sort and myelinate peripheral axons. Elevation of cAMP, but not Rac1 activity in csp-/- restores myelin ensheathment. Most importantly, we show a significant decrease in Laminin expression within csp-/- posterior lateral line nerve and that forcing Laminin2 expression in csp-/- fully restores SC ability to myelinate. We also discovered that SC have a restricted time window during which they have to divide, while migrating, in order to trigger myelination. Thus, we unravel a novel and essential role for timely SC division during migration in mediating Laminin expression to orchestrate radial sorting and peripheral myelination in vivo.
Crest maturation at the cardiomyocyte surface contributes to a new late postnatal development stage that controls the diastolic function of the adult heart
Authors: Karsenty Clément , Guilbeau-Frugier Céline , Genet Gaël , Seguelas Marie-Hélène , Alzieu Philippe , Cazorla Olivier , Montagner Alexandra , Blum Yuna , Dubroca Caroline , Maupoint Julie , Tramunt Blandine , Cauquil Marie , Sulpice Thierry , Richard Sylvain , Arcucci Silvia , Flores-Flores Remy , Pataluch Nicolas , Montoriol Romain , Sicard Pierre , Deney Antoine , Couffinhal Thierry , Sénard Jean-Michel , Galés Céline
Published: February 2022

RATIONALE

In addition to its typical rod-shape, the mammalian adult cardiomyocyte (CM) harbors a unique lateral membrane surface architecture with periodic crests, relying on the presence of subsarcolemmal mitochondria (SSM) the role of which is still unknown.

OBJECTIVE

To investigate the development and functional role of CM crests during the postnatal period.

METHODS AND RESULTS

Electron/confocal microscopy and western-blot of left ventricular tissues from rat hearts indicated a late CM surface crest maturation, between postnatal day 20 (P20) and P60, as shown by substantial SSM swelling and increased claudin-5 cell surface expression. The P20-P60 postnatal stage also correlates with an ultimate maturation of the T-Tubules and the intercalated disk. At the cellular level, we identified an atypical CM hypertrophy characterized by an increase in long- and short-axes without myofibril addition and with sarcomere lateral stretching, indicative of lateral stretch-based CM hypertrophy. We confirmed the P20-P60 hypertrophy at the organ level by echocardiography but also demonstrated a transcriptomic program after P20 targeting all the cardiac cell populations. At the functional level, using Doppler echocardiography, we found that the P20-P60 period is specifically dedicated to the improvement of relaxation. Mechanistically, using CM-specific knock-out mice, we identified ephrin-B1 as a determinant of CM crest maturation after P20 controlling lateral CM stretch-hypertrophy and relaxation. Interestingly, while young adultEfnb1CMspe−/−mice essentially show a relaxation impairment with exercise intolerance, they progressively switch toward heart failure with 100% KO mice dying after 13 months.

CONCLUSIONS

This study highlights a new late P20-P60 postnatal developmental stage of the heart in rodents during which the CM surface crests mature through an ephrin-B1-dependant mechanism and regulate the diastolic function. Moreover, we demonstrate for the first time that the CM crest architecture is cardioprotective.
Hebbian and homeostatic plasticity mechanisms are segregated in sub-types of layer 5 neuron in the visual cortex
Authors: Pandey Anurag , Hardingham Neil , Fox Kevin
Published: February 2022

Cortical layer 5 contains two major types of projection neuron known as IB (intrinsic bursting) cells that project sub-cortically and RS (regular spiking) cells that project between cortical areas. We studied the plasticity properties of RS and IB cells in the visual cortex during the critical period for ocular dominance plasticity in mice. RS neurons exhibited synaptic depression in response to both dark exposure (DE) and monocular deprivation (MD), and their homeostatic recovery from depression was dependent on TNFα. In contrast, IB cells demonstrated opposite responses to DE and MD, potentiating to DE and depressing to MD. IB cells’ potentiation depended on CaMKII-autophosphorylation and not TNFα. IB cells showed mature synaptic properties at the start of the critical period while RS cells matured during the critical period. Together with observations in somatosensory cortex, these results suggest that differences in RS and IB plasticity mechanisms are a general cortical property.

Significance Statement

The neocortex contains cells that project to different locations in the brain. In this study we show that neurons projecting to different target locations exhibit different synaptic plasticity mechanisms. Cortically projecting cells show synaptic depression and homeostatic up-regulation, subcortically projecting cells show classical Hebbian potentiation. This is important because it implies that the way a cortical neuron responds to experience and encodes information depends on the neuronal subcircuits in which it is embedded. We show that ignoring this distinction leads to erroneous conclusions regarding plasticity time-course and significance. These findings constitute an important step toward understanding how learning and memory is organized within subcircuits in the cerebral cortex.
Accumulation and ineffective silencing of transposable elements on an avian W Chromosome
Authors: Warmuth Vera M. , Weissensteiner Matthias H. , Wolf Jochen B.W.
Published: February 2022

One of the defining features of transposable elements (TEs) is their ability to move to new locations in the host genome. To minimize the potentially deleterious effects of de novo TE insertions, hosts have evolved several mechanisms to control TE activity, including recombination-mediated removal and epigenetic silencing; however, increasing evidence suggests that silencing of TEs is often incomplete. The crow family experienced a recent radiation of LTR retrotransposons (LTRs), offering an opportunity to gain insight into the regulatory control of young, potentially still active TEs. We quantified the abundance of TE-derived transcripts across several tissues in 15 Eurasian crows (Corvus (corone) spp.) raised under common garden conditions and find evidence for ineffective TE suppression on the female-specific W Chromosome. Using RNA-seq data, we show that ∼9.5% of all transcribed TEs had considerably greater (average, 16-fold) transcript abundance in female crows and that >85% of these female-biased TEs originated on the W Chromosome. After accounting for differences in TE density among chromosomal classes, W-linked TEs were significantly more highly expressed than TEs residing on other chromosomes, consistent with ineffective silencing on the former. Together, our results suggest that the crow W Chromosome acts as a source of transcriptionally active TEs, with possible negative fitness consequences for female birds analogous to Drosophila (an X/Y system), in which overexpression of Y-linked TEs is associated with male-specific aging and fitness loss (“toxic Y”).
Static and dynamic components of Debye–Waller coefficients in the novel cubic polymorph of low-temperature disordered Cu2ZnSnS4
Authors: Isotta Eleonora , Mukherjee Binayak , Bette Sebastian , Dinnebier Robert , Scardi Paolo
Published: February 2022

Cu2ZnSnS4(CZTS) is an attractive material for sustainable photovoltaics and thermoelectrics, and several properties originate from its marked polymorphism. High-energy mechanical alloying is found to lead to a disordered phase that possesses a sphalerite-like cubic structure. This is investigated in detail with the aid of laboratory and synchrotron radiation X-ray diffraction, Raman spectroscopy, electron microscopy andab initiomolecular dynamics. The disordered cubic polymorph is preserved below 663 K. With thermal treatments above 663 K, the tetragonal kesterite phase forms, used here as a reference for structural and microstructural features. Particular attention is paid to the stacking arrangement: a significant fraction of twin faults was found in the disordered cubic samples, which then progressively annealed with domain growth and with the transition to the ordered tetragonal phase. This study also focuses on Debye–Waller coefficients, which were found to be considerably larger for the disordered cubic than the tetragonal sample. Indeed, disorder leads to an ∼1 Å2upward shift through the temperature range 100–700 K, a feature confirmed byab initiocalculations, which points to a particularly high contribution from disordered Sn cations. This supports the general understanding that structural disorder introduces a temperature-independent static contribution to the atomic mean-square displacement. Debye–Waller coefficients are found to be a good measure of this disorder, known to have a critical effect on transport properties.
Digital Skills for Performance: a framework for assessing current and future digital skills needs in the performing arts sector
Authors: Webb Aleksandra , Layton James
Published: February 2022

Purpose

The COVID-19 pandemic has accelerated the need to embrace digital ways of producing work and reaching audiences in the hard-hit sectors such as performing arts. In the context of post-pandemic recovery, this paper explores the notion of digital performance and proposes a framework for categorisation of digital skills currently associated with the digital making and sharing of performance work. It also aims to review the current digital skills offering in the performing arts training at Scottish universities and suggests strategies to drive accelerated digital skills development in performance education.

Design/methodology/approach

Literature on digitalisations, digital skills and digital performance have been reviewed to provide the context and inform the proposed Digital Skills for Performance Framework. Subsequently, a pilot desk-based study selected 15 Scottish Higher Education Institutions in the area of performance and analysed their publicly available programme documentation for the presence of digital skills.

Findings

While all of the programme specifications mentioned the use of “digital portfolios” and “digital performance”, there was little specific detail concerning “baseline” (transferable) and “specific” (technical) digital skills such as competency in the use of specific technologies. More notably, there was a complete absence of content relating to digital aesthetic identity.

Originality/value

Upskilling future performance makers in digital competencies seems particularly important at present. This paper offers a useful categorisation of the digital skills in performing arts context, which higher education programmes can use to update their curricula, prepare the work-ready graduates and explore technological opportunities for the sector's long-term post-pandemic recovery.
Identification of markers and artificial intelligence-based classification of radical Twitter data
Authors: Fraiwan Mohammad
Published: February 2022

Purpose

Social networks (SNs) have recently evolved from a means of connecting people to becoming a tool for social engineering, radicalization, dissemination of propaganda and recruitment of terrorists. It is no secret that the majority of the Islamic State in Iraq and Syria (ISIS) members are Arabic speakers, and even the non-Arabs adopt Arabic nicknames. However, the majority of the literature researching the subject deals with non-Arabic languages. Moreover, the features involved in identifying radical Islamic content are shallow and the search or classification terms are common in daily chatter among people of the region. The authors aim at distinguishing normal conversation, influenced by the role religion plays in daily life, from terror-related content.

Design/methodology/approach

This article presents the authors' experience and the results of collecting, analyzing and classifying Twitter data from affiliated members of ISIS, as well as sympathizers. The authors used artificial intelligence (AI) and machine learning classification algorithms to categorize the tweets, as terror-related, generic religious, and unrelated.

Findings

The authors report the classification accuracy of the K-nearest neighbor (KNN), Bernoulli Naive Bayes (BNN) and support vector machine (SVM) [one-against-all (OAA) and all-against-all (AAA)] algorithms. The authors achieved a high classification F1 score of 83\%. The work in this paper will hopefully aid more accurate classification of radical content.

Originality/value

In this paper, the authors have collected and analyzed thousands of tweets advocating and promoting ISIS. The authors have identified many common markers and keywords characteristic of ISIS rhetoric. Moreover, the authors have applied text processing and AI machine learning techniques to classify the tweets into one of three categories: terror-related, non-terror political chatter and news and unrelated data-polluting tweets.
Conformable fractional order controller design and optimization for sensorless control of induction motor
Authors: Ilten Erdem
Published: February 2022

Purpose

In recent years, use of sensorless control methods for electrical motor-based variable speed drive systems has been increasing rapidly to compensate the increasing costs in industrial systems. Also, use of induction motors is popular for a long time to decrease the cost of these industrial systems. This study aims to design an effective controller to improve the sensorless speed control performance of induction motor. To achieve this, a conformable fractional order proportional integral (CFOPI) controller is designed.

Design/methodology/approach

The system is modeled based on small signal analysis by using the input–output data, experimentally. To do this, system identification toolbox of Matlab is used. The proposed controller is established on conformable fractional integral approach proposed by Khalil et al. (2014). CFOPI controller coefficients are optimized using particle swarm optimization method on the created small signal-based simulation model of the system to minimize the integral time absolute error. To prove the success of the proposed method, a traditional fractional order proportional integral (TFOPI) controller is tested under the same experimental system with the CFOPI controller.

Findings

TFOPI and CFOPI controllers are tested with the optimum parameters. Reference and actual speed trends are obtained for both methods. In induction motor start-up test, settling-times are measured as 8.73 and 8.44 s and steady-state oscillations are 2.66% and 0% (almost) for TFOPI and CFOPI controllers, respectively. In variable referenced speed tracking test, CFOPI performs well at all speed levels, while TFOPI fails to reach the reference speed at most speed levels.

Practical implications

Proposed CFOPI control method can be easily implemented in industrial systems, thanks to its simple algorithm. digital signal peripheral interface controller (dsPIC) based driver circuit with designed CFOPI controller used in this study can be applied directly to industrial systems such as elevators, conveyors, cranes and drills. Moreover, it can improve the performance of induction motor-based variable speed drive systems.

Originality/value

The proposed method provides robust performance for induction motor used in control systems. Additionally, it does this by using less complex algorithm written on the processors according to the traditional fractional order controllers.