Trace amine-associated receptor 1 agonist reduces aggression in brain serotonin-deficient tryptophan hydroxylase 2 knockout rats.

Introduction: Aggression and self-harm disproportionately occur in youths preoccupied with social status tracking. These pathological conditions are linked to a serotonin (5-HT) deficit in the brain. Ablation of 5-HT biosynthesis by tryptophan hydroxylase 2 knockout (TPH2-KO) increases aggression in rodents.

Gene-editing in patient and humanized-mice primary muscle stem cells rescues dysferlin expression in dysferlin-deficient muscular dystrophy.

Dystrophy-associated fer-1-like protein (dysferlin) conducts plasma membrane repair. Mutations in the DYSF gene cause a panoply of genetic muscular dystrophies. We targeted a frequent loss-of-function, DYSF exon 44, founder frameshift mutation with mRNA-mediated delivery of SpCas9 in combination with a mutation-specific sgRNA to primary muscle stem cells from two homozygous patients.

Paracrine role of endothelial IGF-1 receptor in depot-specific adipose tissue adaptation in male mice.

During recent decades, changes in lifestyle have led to widespread nutritional obesity and its related complications. Remodelling adipose tissue as a therapeutic goal for obesity and its complications has attracted much attention and continues to be actively explored. The endothelium lines all blood vessels and is close to all cells, including adipocytes.

Loss of structural specificity in 3D genome organization upon viral infection is predicted by polymer physics.

In the last years, it has been proved that some viruses are able to re-structure chromatin organization and alter the epigenomic landscape of the host genome. In addition, they are able to affect the physical mechanisms shaping chromatin 3D structure, with a consequent impact on gene activity. Here, we investigate with polymer physics genome re-organization of the host genome upon SARS-CoV-2 viral infection and how it can impact structural variability within the population of single-cell chromatin configurations.

Microscopy image reconstruction with physics-informed denoising diffusion probabilistic model.

Light microscopy is a practical tool for advancing biomedical research and diagnostics, offering invaluable insights into the cellular and subcellular structures of living organisms. However, diffraction and optical imperfections actively hinder the attainment of high-quality images. In recent years, there has been a growing interest in applying deep learning techniques to overcome these challenges in light microscopy imaging.

Real-world multicentre cohort study on choices and effectiveness of immunotherapies in NMOSD and MOGAD.

Background: Recurrent attacks in neuromyelitis optica spectrum disorders (NMOSDs) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can lead to severe disability. We aimed to analyse the real-world use of immunotherapies in patients with NMOSD and MOGAD, focusing on changes in treatment strategies, effects on attack rates (ARR) and risk factors for attacks.

Methods: This longitudinal registry-based cohort study included 493 patients (320 with aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive NMOSD (65%), 44 with AQP4-IgG seronegative NMOSD (9%) and 129 MOGAD (26%)) with 1247 treatments from 19 German and one Austrian centre from the registry of the neuromyelitis optica study group (NEMOS).

High-resolution DNA methylation changes reveal biomarkers of heart failure with preserved ejection fraction versus reduced ejection fraction.

Novel biomarkers are needed to better identify-and distinguish-heart failure with preserved ejection fraction (HFpEF) from other clinical phenotypes. The goal of our study was to identify epigenetic-sensitive biomarkers useful to a more accurate diagnosis of HFpEF. We performed a network-oriented genome-wide DNA methylation study of circulating CD4 T lymphocytes isolated from peripheral blood using reduced representation bisulfite sequencing (RRBS) in two cohorts (i.

Impact of genetic test interpretation on a missense variant in Cohen syndrome.

Introduction: Cohen syndrome (CS) is an early-onset pediatric neurodevelopmental disorder characterized by postnatal microcephaly and intellectual disability. An accurate diagnosis for individuals with CS is crucial, particularly for their caretakers and future prospects. CS is predominantly caused by rare homozygous or compound heterozygous pathogenic variants in the vacuolar protein sorting-associated 13B () gene, which disrupt protein translation and lead to a loss of function (LoF) of the encoded VPS13B protein.

Distinguishing Transient From Persistent Brain Structural Changes in Pediatric Patients With Acute Disseminated Encephalomyelitis.

Background And Objectives: Pediatric patients with acute disseminated encephalomyelitis (ADEM) are at risk of impaired brain growth, with long-term neuropsychiatric consequences. We previously reported transient expansions of cerebral ventricle volume (VV) in experimental autoimmune encephalomyelitis, which subsequently normalized. In this study, we investigated changes in VV in ADEM in relation to other brain structures and clinical outcomes.

Blood-Based Biomarkers for Identifying Disease Activity in AQP4-IgG-Positive Neuromyelitis Optica Spectrum Disorder.

Importance: The temporal dynamics of serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) as biomarkers of disease activity for neuromyelitis optica spectrum disorder (NMOSD) remain underexplored.

Objective: To determine optimal timing for assessing sGFAP and sNfL, establish cutoff values differentiating between attacks and remissions in NMOSD, and evaluate these findings across independent cohorts.

Design, Setting, And Participants: This retrospective, longitudinal, multicenter cohort study was conducted among patients with aquaporin-4 antibody (AQP4-IgG)-positive NMOSD.

Protocol for high-resolution 3D spatial transcriptomics using Open-ST.

Spatial transcriptomics (ST) is fundamental for understanding molecular mechanisms in health and disease. Here, we present a protocol for efficient and high-resolution ST in 2D/3D with Open-ST. We describe all steps for repurposing Illumina flow cells into spatially barcoded capture areas and preparing ST libraries from stained cryosections.

Hyperphenylalaninemia and serotonin deficiency in Dnajc12-deficient mice.

Serotonin exerts numerous neurological and physiological actions in the brain and in the periphery. It is generated by two different tryptophan hydroxylase enzymes, TPH1 and TPH2, in the periphery and in the brain, respectively, which are members of the aromatic amino acid hydroxylase (AAAH) family together with phenylalanine hydroxylase (PAH), degrading phenylalanine, and tyrosine hydroxylase (TH), generating dopamine. In this study, we show that the co-chaperone DNAJC12 is downregulated in serotonergic neurons in the brain of mice lacking TPH2 and thereby central serotonin.

A biomathematical model of SARS-CoV-2 in Syrian hamsters.

When infected with SARS-CoV-2, Syrian hamsters (Mesocricetus auratus) develop moderate disease severity presenting key features of human COVID-19. We here develop a biomathematical model of the disease course by translating known biological mechanisms of virus-host interactions and immune responses into ordinary differential equations. We explicitly describe the dynamics of virus population, affected alveolar epithelial cells, and involved relevant immune cells comprising for example CD4+ T cells, CD8+ T cells, macrophages, natural killer cells and B cells.

Stem Cell Markers LGR5, LGR4 and Their Immediate Signalling Partners are Dysregulated in Preeclampsia.

Leucine-rich repeat-containing G protein-coupled receptors 5/4 (LGR5/LGR4) are critical stem cell markers in epithelial tissues including intestine. They agonise wingless-related integration site (WNT) signalling. Until now, LGR5/LGR4 were uncharacterised in placenta, where analogous functions may exist.

Alzheimer's Disease Risk Gene SORL1 Promotes Receptiveness of Human Microglia to Pro-Inflammatory Stimuli.

Sorting protein-related receptor containing class A repeats (SORLA) is an intracellular trafficking receptor encoded by the Alzheimer's disease (AD) gene SORL1 (sortilin-related receptor 1). Recent findings argue that altered expression in microglia may underlie the genome-wide risk of AD seen with some SORL1 gene variants, however, the functional significance of the receptor in microglia remains poorly explained. Using unbiased omics and targeted functional analyses in iPSC-based human microglia, we identified a crucial role for SORLA in sensitizing microglia to pro-inflammatory stimuli.

Low income, being without employment, and living alone: how they are associated with cognitive functioning-Results from the German national cohort (NAKO).

Aim was to investigate to what extent cognitive functioning differs by three socioeconomic conditions: low income, being without employment, and living alone. A total of N = 158,144 participants of the population-based German National Cohort (NAKO) provided data on socioeconomic conditions and completed cognitive tests. Multivariable confounder-adjusted regression analyses indicated that cognitive functioning was lower in those with low income (b = -0.

The big chill: Growth of structural biology with cryo-electron tomography.

structural biology with cryo-electron tomography (cryo-ET) and subtomogram averaging (StA) is evolving as a major method to understand the structure, function, and interactions of biological molecules in cells in a single experiment. Since its inception, the method has matured with some stellar highlights and with further opportunities to broaden its applications. In this short review, I want to provide a personal perspective on the developments in cryo-ET as I have seen it for the last ~20 years and outline the major steps that led to its success.

A quantitative multi-parameter mapping protocol standardized for clinical research in multiple sclerosis.

Quantitative magnetic resonance imaging (qMRI) involves mapping microstructure in standardized units sensitive to histological properties and supplements conventional MRI, which relies on contrast weighted images where intensities have no biophysical meaning. While measuring tissue properties such as myelin, iron or water content is desired in a disease context, qMRI changes may typically reflect mixed influences from aging or pre-clinical degeneration. We used a fast multi-parameter mapping (MPM) protocol for clinical routine at 3T to reconstruct whole-brain quantitative maps of magnetization transfer saturation (MT), proton density (PD), longitudinal (R1), and transverse relaxation rate (R2*) with 1.

TransferGWAS of T1-weighted brain MRI data from UK Biobank.

Genome-wide association studies (GWAS) traditionally analyze single traits, e.g., disease diagnoses or biomarkers.

PDGFRA is a conserved HAND2 effector during early cardiac development.

The basic helix-loop-helix transcription factor HAND2 has multiple roles during vertebrate organogenesis, including cardiogenesis. However, much remains to be uncovered about its mechanism of action. Here, we show the generation of several hand2 mutant alleles in zebrafish and demonstrate that dimerization-deficient mutants display the null phenotype but DNA-binding-deficient mutants do not.