Ulcerative colitis (UC) is characterized by the interplay between immune responses and dysbiosis in disease development. Aiming to provide additional insights into disease development and potential treatment strategies, the present study investigates the local effect of oral treatment with polysaccharides obtained from 's submerged culture in an experimental model of DSS-induced colitis and its impact on lesion resolution. : The structure and monosaccharide composition of polysaccharides were characterized through Nuclear Magnetic Resonance (NMR).
View Article and Find Full Text PDFNeuronal communication relies on precisely maintained synaptic vesicle (SV) clusters, which assemble via liquid-liquid phase separation. This process requires synapsins, the major synaptic phosphoproteins, which are known to bind actin. Reorganization of SVs, synapsins, and actin is a hallmark of synaptic activity, but the molecular details of the interactions between these components remain unclear.
View Article and Find Full Text PDFTransl Lung Cancer Res
June 2025
Background: Consolidation therapy with the anti-programmed death-ligand 1 (PD-L1) antibody durvalumab, or other immune checkpoint inhibitors, has been associated with improved progression-free and overall survival in patients with stage III non-small cell lung cancer (NSCLC) as demonstrated in randomized clinical trials. The purpose of the present study is to evaluate the dose-response relationship for partial lung infiltrate volumes per dose bin after definitive radiochemotherapy as a sensitive end point to detect a durvalumab effect on the lung parenchyma in patients with subclinical or grade ≤2 pneumonitis.
Methods: Consecutive patients from a prospective registry with inoperable NSCLC stage III who developed no or pneumonitis grade ≤2 after definitive radiochemotherapy with or without durvalumab consolidation were included.
Following synaptic vesicle fusion, vacated release sites are replenished immediately by new vesicles for subsequent neurotransmission. These replacement vesicles are assumed to be located near release sites and used by chance. Here we find in mouse hippocampal excitatory synapses that replacement vesicles are clustered near the active zone where release sites reside by intersectin-1.
View Article and Find Full Text PDFMicrobial ecosystems are fundamental to planetary and human health, yet human activities are accelerating their loss. Disruptions to microbial communities undermine environmental stability, biodiversity, and health. Urgent action is required to preserve microbial diversity.
View Article and Find Full Text PDFProtein aggregation is a normal response to age-related exposures. According to the thermodynamic hypothesis of protein folding, soluble proteins precipitate into amyloids (pathology) under supersaturated conditions through a process similar to crystallization. This soluble-to-insoluble phase transition occurs via nucleation and may be catalyzed by ectopic surfaces such as lipid nanoparticles, microbes, or chemical pollutants.
View Article and Find Full Text PDFParkinsonism Relat Disord
July 2025
Microglia are parenchymal brain macrophages that are established during embryogenesis and form a self-containing cellular compartment that resists seeding with cells derived from adult definitive hematopoiesis. We report that monocyte-derived macrophages (MoMΦs) accumulate in the brain of aging mice with distinct topologies, including the nigrostriatum and medulla but not the frontal cortex. Parenchymal MoMΦs adopt bona fide microglia morphology and expression profiles.
View Article and Find Full Text PDFSynapsin and α-synuclein represent a growing list of condensate-forming proteins where the material states of condensates are directly linked to cellular functions (e.g., neurotransmission) and pathology (e.
View Article and Find Full Text PDFBackground: More than 115 000 cases of mpox have been confirmed since the onset of a global outbreak in 2022. In addition to global transmission of clade II monkeypox virus (MPXV), the recent spread of clade I has caused a Public Health Emergency of International Concern. The third-generation smallpox vaccine modified vaccinia Ankara-Bavarian Nordic (MVA-BN) was recommended for at-risk populations in 2022, despite a scarcity of data on safety and effectiveness against mpox.
View Article and Find Full Text PDFBiomolecular condensates play a central role in cellular processes by interacting with membranes driving wetting transitions and inducing mutual remodeling. While condensates are known to locally alter membrane properties such as lipid packing and hydration, it remains unclear how membrane composition and phase state in turn affect condensate affinity. Here, we show that it is not only the membrane phase itself, but rather the degree of lipid packing that determines the condensate affinity for membranes.
View Article and Find Full Text PDFCastleman disease (CD) describes a group of rare lymphoproliferative disorders that exhibit a wide range of symptomatology and degree of lymphadenopathy, particularly across the 2 forms of CD with unknown etiology, unicentric CD (UCD), and human herpesvirus-8-negative/idiopathic multicentric CD (iMCD). Whereas UCD cases typically present with localized lymphadenopathy and mild symptoms, iMCD involves multicentric lymphadenopathy and cytokine storm-driven symptoms with 3 recognized clinical phenotypes. Increasingly, there are anecdotal reports of cases that do not fit into this framework, but these cases have not been systematically described.
View Article and Find Full Text PDFMultiple biomolecular condensates coexist at the pre- and post- synapse to enable vesicle dynamics and controlled neurotransmitter release in the brain. In pre-synapses, intrinsically disordered regions (IDRs) of synaptic proteins are drivers of condensation that enable clustering of synaptic vesicles (SVs). Using computational analysis, we show that the IDRs of SV proteins feature evolutionarily conserved non-random compositional biases and sequence patterns.
View Article and Find Full Text PDFBackground: Dose-response relationships for optic neuropathy and optic nerve atrophy after brachytherapy for posterior uveal melanoma were poorly defined from previous studies. Here, the outcome differences were analyzed in dependence on dosimetric factors, the applicator type, and tumor dependent variables.
Purpose: Primary objective was to evaluate the association of applied dose and on-set of optic nerve atrophy after brachytherapy for posterior uveal melanoma in order to allow risk estimation for new patients.
Magnesium (Mg) is essential for life, and low levels impair immune function, promote chronic inflammation, and influence the intestinal microbiome, with the peritoneal cavity serving as a site for direct interaction between the cavity and intestinal contents, including the microbiota. This study investigates the effects of a Mg-restricted diet on peritoneal immune cells and its interplay with the intestinal microbiome. Male C57BL/6NTaq mice were divided into three groups: control, restricted, and restored.
View Article and Find Full Text PDFObjectives: To evaluate the associations between the quality of the diet and its components and microbial diversity and composition in peritoneal dialysis (PD) patients.
Design And Methods: This cross-sectional study included PD patients for at least 3 months, aged 18-75 years and clinically stable. The Diet Quality Index (DQI), validated for the Brazilian population, is based on the energy density of 11 components ("sugar and sweets;" "beef, pork, and processed meat;" "refined grains and breads;" "animal fat;" "poultry, fish, and eggs;" "whole cereals, tubers, and roots;" "fruits"; "nonstarch vegetables;" "legumes and nuts;" "milk and dairy products;" and "vegetable oil").
Parkinsonism Relat Disord
February 2025
The α-synuclein seed amplification assay (αSyn-SAA) sensitively detects Lewy pathology, the amyloid state of α-synuclein, in the cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD). The αSyn-SAA harnesses the physics of seeding, whereby a superconcentrated solution of recombinant α-synuclein lowers the thermodynamic threshold (nucleation barrier) for aggregated α-synuclein to act as a nucleation catalyst ("seed") to trigger the precipitation (nucleation) of monomeric α-synuclein into pathology. This laboratory setup increases the signal for identifying a catalyst if one is present in the tissue examined.
View Article and Find Full Text PDFSynaptic vesicle clusters or pools are functionally important constituents of chemical synapses. In the so-called reserve and the active pools, neurotransmitter-loaded synaptic vesicles (SVs) are stored and conditioned for fusion with the synaptic membrane and subsequent neurotransmitter release during synaptic activity. Vesicle clusters can be considered as so-called membraneless compartments, which form by liquid-liquid phase separation.
View Article and Find Full Text PDFThe aim of this study was to investigate the vertical transfer of microbiota from dams to the offspring. We studied a pair of 20 dams and its offspring. Maternal sources (colostrum, feces and vaginal secretion) and newborn fecal samples were analyzed using 16S rDNA amplicon sequencing on days 1, 3, 7, 14 and 28.
View Article and Find Full Text PDFSynapsin and α-synuclein represent a growing list of condensate-forming proteins where the material states of condensates are directly linked to cellular functions (e.g., neurotransmission) and pathology (e.
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