Developmental beta-cell death orchestrates the islet's inflammatory milieu by regulating immune system crosstalk.

While pancreatic beta-cell proliferation has been extensively studied, the role of cell death during islet development remains incompletely understood. Using a genetic model of caspase inhibition in beta cells coupled with mathematical modeling, we here discover an onset of beta-cell death in juvenile zebrafish, which regulates beta-cell mass. Histologically, this beta-cell death is underestimated due to phagocytosis by resident macrophages.

Diastolic dysfunction evaluation by cardiovascular magnetic resonance derived E, a, e': Comparison to echocardiography.

Transthoracic echocardiography (TTE) is the first-line and most useful imaging modality for evaluating diastolic dysfunction (DD). Cardiovascular magnetic resonance (CMR) has not been fully evaluated for this task. We investigated the utility of CMR for DD evaluation.

An SMS-Guided Basal Insulin Titration in People with Type 2 Diabetes New on Insulin.

Introduction: The shortage of general practitioners (GPs) and the increasing prevalence of type 2 diabetes create significant pressure on primary healthcare services. To enable that medical services are available to all that need it, innovative solutions are needed. One of those, a Short Message Service (SMS)-supported basal insulin titration service is investigated in this study.

Autoantigen-specific CD4 T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases.

Pro-inflammatory autoantigen-specific CD4 T helper (auto-Th) cells are central orchestrators of autoimmune diseases (AIDs). We aimed to characterize these cells in human AIDs with defined autoantigens by combining human leukocyte antigen (HLA)-tetramer-based and activation-based multidimensional ex vivo analyses. In aquaporin4-antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) patients, auto-Th cells expressed CD154, but proliferative capacity and pro-inflammatory cytokines were strongly reduced.

The Weight of Genetic Drift: A Pedigree-Based Evaluation of the Breton Horse Population in Brazil.

The genetic diversity of Breton horses in Brazil is a critical concern, mainly due to the small population size and low number of births per year. Given that the inbreeding was overlooked by breeders for multiple generations, we estimated the genetic diversity of this population utilizing pedigree-based measures of population diversity. A total of 1394 six-generation pedigrees representing the full population of registered Breton horses in Brazil defined a total population (TP,  = 2679), with horses born between 2000 and 2022, reproductively active and alive, as reported by the breed association, representing the reference population (RP,  = 731).

Anticoagulation Alone vs Anticoagulation Plus Aspirin or DAPT Following Left Atrial Appendage Occlusion.

Background: The prevalence of and outcomes associated with different antithrombotic strategies after left atrial appendage occlusion (LAAO) are not well described.

Objectives: This study sought to evaluate patterns of antithrombotic medication strategies at discharge following LAAO with the Watchman FLX device in real-world practice and to compare the risk of adverse events among the different antithrombotic regimens.

Methods: The authors evaluated patients in the NCDR (National Cardiovascular Data Registry) LAAO Registry who underwent LAAO with the second-generation LAA closure device between 2020 and 2022.

Panton-Valentine Leukocidin-Positive Staphylococcus aureus in Family and Pet Cat.

Continued detection of Panton-Valentine leukocidin-positive Staphylococcus aureus in samples from a family with severe repeated skin infections and their pet cat suggests transmission between the family and the cat. Decolonizing the pet led to successful elimination of the bacteria from the household. Clinicians should consider pet cats as possible reinfection sources.

Compliant DNA Origami Nanoactuators as Size-Selective Nanopores.

Biological nanopores crucially control the import and export of biomolecules across lipid membranes in cells. They have found widespread use in biophysics and biotechnology, where their typically narrow, fixed diameters enable selective transport of ions and small molecules, as well as DNA and peptides for sequencing applications. Yet, due to their small channel sizes, they preclude the passage of large macromolecules, e.

Link between supercurrent diode and anomalous Josephson effect revealed by gate-controlled interferometry.

In Josephson diodes the asymmetry between positive and negative current branch of the current-phase relation leads to a polarity-dependent critical current and Josephson inductance. The supercurrent nonreciprocity can be described as a consequence of the anomalous Josephson effect -a φ-shift of the current-phase relation- in multichannel ballistic junctions with strong spin-orbit interaction. In this work, we simultaneously investigate φ-shift and supercurrent diode efficiency on the same Josephson junction by means of a superconducting quantum interferometer.

Investigating the cause of a 2021 winter wave of COVID-19 in a border region in eastern Germany: a mixed-methods study, August to November 2021.

It is so far unclear how the COVID-19 winter waves started and what should be done to prevent possible future waves. In this study, we deciphered the dynamic course of a winter wave in 2021 in Saxony, a state in Eastern Germany neighbouring the Czech Republic and Poland. The study was carried out through the integration of multiple virus genomic epidemiology approaches to track transmission chains, identify emerging variants and investigate dynamic changes in transmission clusters.

CD19-targeted chimeric antigen receptor T cell therapy in two patients with multiple sclerosis.

Background: Progressive multiple sclerosis (MS) is characterized by compartmentalized smoldering neuroinflammation caused by the proliferation of immune cells residing in the central nervous system (CNS), including B cells. Although inflammatory activity can be prevented by immunomodulatory therapies during early disease, such therapies typically fail to halt disease progression. CD19 chimeric antigen receptor (CAR)-T cell therapies have revolutionized the field of hematologic malignancies.

Spatial proteomics in neurons at single-protein resolution.

To understand biological processes, it is necessary to reveal the molecular heterogeneity of cells by gaining access to the location and interaction of all biomolecules. Significant advances were achieved by super-resolution microscopy, but such methods are still far from reaching the multiplexing capacity of proteomics. Here, we introduce secondary label-based unlimited multiplexed DNA-PAINT (SUM-PAINT), a high-throughput imaging method that is capable of achieving virtually unlimited multiplexing at better than 15 nm resolution.

Implementing Formal Mitral Heart Team Improves Multidisciplinary Evaluation Rate and Survival of Patients With Severe Primary Mitral Regurgitation.

Background: Multidisciplinary heart team (HT) evaluation is recommended for patients with severe primary mitral regurgitation to optimize treatment decisions. However, its impact on patient outcomes remains unknown. We evaluated the impact of implementing mitral HT on patient survival.

Compartmentalization and synergy of osteoblasts drive bone formation in the regenerating fin.

Zebrafish regenerate their fins which involves a component of cell plasticity. It is currently unclear how regenerate cells divide labor to allow for appropriate growth and patterning. Here, we studied lineage relationships of fluorescence-activated cell sorting-enriched epidermal, bone-forming (osteoblast), and (non-osteoblast) blastemal fin regenerate cells by single-cell RNA sequencing, lineage tracing, targeted osteoblast ablation, and electron microscopy.

Comparing divisome organization between vegetative and sporulating at the nanoscale using DNA-PAINT.

Spore-forming bacteria have two distinct division modes: sporulation and vegetative division. The placement of the foundational division machinery component (Z-ring) within the division plane is contingent on the division mode. However, investigating if and how division is performed differently between sporulating and vegetative cells remains challenging, particularly at the nanoscale.

Benefits of aHSCT over alemtuzumab in patients with multiple sclerosis besides disability and relapses: Sustained improvement in cognition and quality of life.

Background: Autologous hematopoietic stem cell transplantation (aHSCT) exhibits promising results for multiple sclerosis (MS) in the short term. We investigated the long-term outcome differences in disease progression and cognitive impairment after aHSCT and alemtuzumab treatment.

Methods: 20 patients receiving aHSCT and 21 patients treated with alemtuzumab between 2007 and 2020 were included in this monocentric observational cohort study.

Balancing the Nanoscale Organization in Multivalent Materials for Functional Inhibition of the Programmed Death-1 Immune Checkpoint.

Dendritic cells (DCs) regulate immune priming by expressing programmed death ligand 1 (PD-L1) and PD-L2, which interact with the inhibitory receptor PD-1 on activated T cells. PD-1 signaling regulates T cell effector functions and limits autoimmunity. Tumor cells can hijack this pathway by overexpressing PD-L1 to suppress antitumor T cell responses.

IFNγ-Stat1 axis drives aging-associated loss of intestinal tissue homeostasis and regeneration.

The influence of aging on intestinal stem cells and their niche can explain underlying causes for perturbation in their function observed during aging. Molecular mechanisms for such a decrease in the functionality of intestinal stem cells during aging remain largely undetermined. Using transcriptome-wide approaches, our study demonstrates that aging intestinal stem cells strongly upregulate antigen presenting pathway genes and over-express secretory lineage marker genes resulting in lineage skewed differentiation into the secretory lineage and strong upregulation of MHC class II antigens in the aged intestinal epithelium.

Global taxonomic, functional, and phylogenetic diversity of bees in apple orchards.

An essential prerequisite to safeguard pollinator species is characterisation of the multifaceted diversity of crop pollinators and identification of the drivers of pollinator community changes across biogeographical gradients. The extent to which intensive agriculture is associated with the homogenisation of biological communities at large spatial scales remains poorly understood. In this study, we investigated diversity drivers for 644 bee species/morphospecies in 177 commercial apple orchards across 33 countries and four global biogeographical biomes.

Visual function resists early neurodegeneration in the visual system in primary progressive multiple sclerosis.

Background: Neurodegeneration in multiple sclerosis (MS) affects the visual system but dynamics and pathomechanisms over several years especially in primary progressive MS (PPMS) are not fully understood.

Methods: We assessed longitudinal changes in visual function, retinal neurodegeneration using optical coherence tomography, MRI and serum NfL (sNfL) levels in a prospective PPMS cohort and matched healthy controls. We investigated the changes over time, correlations between outcomes and with loss of visual function.