Chromatin State Maps of Blood Pressure-Relevant Renal Segments Reveal Potential Regulatory Role for SNPs.

Background: Hypertension or elevated blood pressure (BP) is a worldwide clinical challenge and the leading primary risk factor for kidney dysfunctions, heart failure, and cerebrovascular disease. The kidney is a central regulator of BP by maintaining sodium-water balance. Multiple genome-wide association studies revealed that BP is a heritable quantitative trait, modulated by several genetic, epigenetic, and environmental factors.

Effects of computer-generated patterns with different temporal and spatial frequencies on choroidal thickness, retinal dopamine and candidate genes in chickens wearing lenses.

Purpose: Changes in choroidal thickness (ChT) are proposed to predict myopia development but evidence is mixed. We investigated time courses of choroidal responses, following different types of dynamic artificial stimulation in chicks with and without spectacle lenses, as well as changes in retinal dopamine metabolism and expression of candidate genes.

Methods: Chicks were kept in an arena surrounded by computer monitors presenting dynamic checkerboard fields of small, medium and large size.

Multiple Sclerosis: Glial Cell Diversity in Time and Space.

Multiple sclerosis (MS) is the most prevalent human inflammatory disease of the central nervous system with demyelination and glial scar formation as pathological hallmarks. Glial cells are key drivers of lesion progression in MS with roles in both tissue damage and repair depending on the surrounding microenvironment and the functional state of the individual glial subtype. In this review, we describe recent developments in the context of glial cell diversity in MS summarizing key findings with respect to pathological and maladaptive functions related to disease-associated glial subtypes.

Doublecortin regulates the mitochondrial-dependent apoptosis in glioma via Rho-A/Net-1/p38-MAPK signaling.

Doublecortin (DCX) is a microtubule-associated protein known to be a key regulator of neuronal migration and differentiation during brain development. However, the role of DCX, particularly in regulating the survival and growth of glioma cells, remains unclear. In this study, we utilized CRISPR/Cas9 technology to knock down DCX in the human glioma cell line (U251).

Exploiting O-GlcNAc dyshomeostasis to screen O-GlcNAc transferase intellectual disability variants.

O-GlcNAcylation is an essential protein modification catalyzed by O-GlcNAc transferase (OGT). Missense variants in OGT are linked to a novel intellectual disability syndrome known as OGT congenital disorder of glycosylation (OGT-CDG). The mechanisms by which OGT missense variants lead to this heterogeneous syndrome are not understood, and no unified method exists for dissecting pathogenic from non-pathogenic variants.

WDR49-Positive Astrocytes Mark Severity of Neurodegeneration in Frontotemporal Lobar Degeneration and Alzheimer's Disease.

A subpopulation of astrocytes expressing WD Repeat Domain 49 (WDR49) was recently identified in frontotemporal lobar degeneration (FTLD) with GRN pathogenic variants. This is the first study to investigate their expression and relation to pathology in other FTLD subtypes and Alzheimer's disease (AD). In a postmortem cohort of TDP-43 proteinopathies (12 GRN, 11 C9orf72, 9 sporadic TDP-43), tauopathies (13 MAPT, 8 sporadic tau), 10 AD, and four controls, immunohistochemistry and immunofluorescence were performed for WDR49 and pathological inclusions on frontal, temporal, and occipital cortical sections.

Intron retention of an adhesion GPCR generates 1TM isoforms required for 7TM-GPCR function.

Adhesion G protein-coupled receptors (aGPCRs) are expressed in all organs and are involved in various mechanobiological processes. They are heavily alternatively spliced, forecasting an extraordinary molecular structural diversity. Here, we uncovered the existence of unconventional single-transmembrane (1TM)-containing ADGRL/Cirl proteins devoid of the conventional GPCR layout (i.

Reliability of high-quantity human brain organoids for modeling microcephaly, glioma invasion and drug screening.

Brain organoids offer unprecedented insights into brain development and disease modeling and hold promise for drug screening. Significant hindrances, however, are morphological and cellular heterogeneity, inter-organoid size differences, cellular stress, and poor reproducibility. Here, we describe a method that reproducibly generates thousands of organoids across multiple hiPSC lines.

Exploring PDE5A upregulation in bipolar disorder: insights from single-nucleus RNA sequencing of human basal ganglia.

Basal ganglia is proposed to mediate symptoms underlying bipolar disorder (BD). To understand the cell type-specific gene expression and network changes of BD basal ganglia, we performed single-nucleus RNA sequencing of 30,752 nuclei from caudate, putamen, globus pallidus, and substantia nigra of control human postmortem brain and 24,672 nuclei from BD brain. Differential expression analysis revealed major difference lying in caudate, with BD medium spiny neurons (MSNs) expressing significantly higher PDE5A, a cGMP-specific phosphodiesterase.

Artificial intelligence in surgical pathology - Where do we stand, where do we go?

Surgical and neuropathologists continuously search for new and disease-specific features, such as independent predictors of tumor prognosis or determinants of tumor entities and sub-entities. This is a task where artificial intelligence (AI)/machine learning (ML) systems could significantly contribute to help with tumor outcome prediction and the search for new diagnostic or treatment stratification biomarkers. AI systems are increasingly integrated into routine pathology workflows to improve accuracy, reproducibility, productivity and to reveal difficult-to-see features in complicated histological slides, including the quantification of important markers for tumor grading and staging.

Insights into the neurobiology of weight loss after bariatric surgery and GLP-1R agonists.

Obesity and its related complications are growing in prevalence worldwide, with increasing impact to individuals and healthcare systems alike. Currently, the leading treatment approaches for effective and sustained weight loss are bariatric surgery and gut peptide therapeutics. At a high level, both treatment strategies work by hijacking gut-brain axis signaling to reduce food intake.

Current challenges and development strategies of bacteriocins produced by lactic acid bacteria applied in the food industry.

Given the great importance of natural biopreservatives in the modern food industry, lactic acid bacteria (LAB)-producing bacteriocins have gained considerable attention due to their antimicrobial activity against foodborne pathogens and spoilage bacteria. Although numerous LAB-producing bacteriocins have demonstrated efficiency in preserving food quality in various applications, only a limited number of these compounds have been commercially approved to date. The currently unclear gastrointestinal metabolism of bacteriocins may pose safety risks, as well as cytotoxicity and immunogenicity, which need to be seriously considered before their application.

[Transfer of knowledge in psychiatry through the 4 editions from 1980 to 2016 of the Quebec psychiatry manual].

Objectives To examine the transfer of knowledge in psychiatry, longitudinally, over more than 35 years, through the 4 editions of the manual "Psychiatrie clinique" published in Quebec, thanks to the initiative of the publication directors affiliated with the Institut universitaire en santé mentale de Montréal (formerly the Louis-H. Lafontaine Hospital). Our hypothesis is that the evolution of the content and form of such a manual reflects an evolution of knowledge in psychiatry with a naturally educational vocation which of what must be known and applicable in the discipline.

Associations between plasma osteopontin, sex, and 2-year global and cardiorenal outcomes in older outpatients screened for CKD: a secondary analysis of the SCOPE study.

Background: Plasma osteopontin (pOPN) is a promising aging-related biomarker among individuals with and without kidney disease. The interaction between sex, pOPN levels, and global and cardiorenal outcomes among older individuals was not previously evaluated.

Methods: In this study we investigated the association of pOPN with 24-month global mortality, major cardiovascular events (MACEs), MACEs + cardiovascular (CV) mortality, and renal decline among older individuals; we also evaluated whether sex modified observed associations.

Role of Anterior Cingulate Cortex in the exacerbated facial response to mechanical stimuli as a sign of early orofacial neuropathic pain.

The study of orofacial neuropathic pain necessitates the use of innovative assessment techniques, such as the facial expression of pain, which mirrors the internal state of the animals and could be utilized to identify the neural correlations involved. The Anterior Cingulate Cortex (ACC) is a crucial center in the processing of sensory and affective components of acute and neuropathic pain. However, its role in the facial response to pain remains a mystery.

Quality Controls: The Role of Self-Corrective Science in Explorations of Primate Memory Systems.

In 1978, Mort Mishkin published a landmark paper describing a monkey model of H.M.'s dense, global amnesia.

Microglial lipid phosphatase SHIP1 limits complement-mediated synaptic pruning in the healthy developing hippocampus.

The gene inositol polyphosphate-5-phosphatase D (INPP5D), which encodes the lipid phosphatase SH2-containing inositol polyphosphate 5-phosphatase 1 (SHIP1), is associated with the risk of Alzheimer's disease (AD). How it influences microglial function and brain physiology is unclear. Here, we showed that SHIP1 was enriched in early stages of healthy brain development.

Dissociable control of motivation and reinforcement by distinct ventral striatal dopamine receptors.

Dopamine (DA) release in striatal circuits, including the nucleus accumbens medial shell (mNAcSh), tracks separable features of reward like motivation and reinforcement. However, the cellular and circuit mechanisms by which DA receptors transform DA release into distinct constructs of reward remain unclear. Here we show that DA D3 receptor (D3R) signaling in the mNAcSh drives motivated behavior in mice by regulating local microcircuits.

Tbx1 haploinsufficiency leads to local skull deformity, paraflocculus and flocculus dysplasia, and motor-learning deficit in 22q11.2 deletion syndrome.

Neurodevelopmental disorders are thought to arise from intrinsic brain abnormalities. Alternatively, they may arise from disrupted crosstalk among tissues. Here we show the local reduction of two vestibulo-cerebellar lobules, the paraflocculus and flocculus, in mouse models and humans with 22q11.