Search results for "Surge"

ALS-Related Mutant FUS Protein Is Mislocalized to Cytoplasm and Is Recruited into Stress Granules of Fibroblasts from Asymptomatic <b><i>…

2017

<b><i>Background:</i></b> Amyotrophic lateral sclerosis (ALS) shows a strong genetic basis, with <i>SOD1</i>, <i>FUS</i>, <i>TARDBP</i>, and <i>C9ORF72 </i>being the genes most frequently involved<i>. </i>This has allowed identification of asymptomatic mutation carriers, which may be of help in understanding the molecular changes preceding disease onset. <b><i>Objectives:</i></b> We studied the cellular expression of FUS protein and the effect of heat-shock- and dithiothreitol-induced stress in fibroblasts from <i>FUS</i> P525L mutation carriers, healthy controls, and pati…

GABA and Gap Junctions in the Development of Synchronized Activity in Human Pluripotent Stem Cell-Derived Neural Networks.

2017

The electrical activity of the brain arises from single neurons communicating with each other. However, how single neurons interact during early development to give rise to neural network activity remains poorly understood. We studied the emergence of synchronous neural activity in human pluripotent stem cell (hPSC)-derived neural networks simultaneously on a single-neuron level and network level. The contribution of gamma-aminobutyric acid (GABA) and gap junctions to the development of synchronous activity in hPSC-derived neural networks was studied with GABA agonist and antagonist and by blocking gap junctional communication, respectively. We characterized the dynamics of the network-wide…

A minimal molecular toolkit for mineral deposition? Biochemistry and proteomics of the test matrix of adult specimens of the sea urchin Paracentrotus…

2016

12 pages; International audience; The sea urchin endoskeleton consists of a magnesium-rich biocalcite comprising a small amount of occluded organic macromolecules. This structure constitutes a key-model for understanding the mineral - organics interplay, and for conceiving in vitro bio-inspired materials with tailored properties. Here we employed a deep-clean technique to purify the occluded proteins from adult Paracentrotus lividus tests. We characterized them by 1- and 2D-electrophoreses, ELISA and immunoblotting, and using liquid chromatography coupled with Mass Spectrometry (nanoLC-MS/MS), we identified two metalloenzymes (carbonic anhydrase and MMP), a set of MSP130 family members, sev…

Ultrastructural characterization of human oligodendrocytes and their progenitor cells by pre-embedding immunogold.

2021

Oligodendrocytes are the myelinating cells of the central nervous system. They provide trophic, metabolic, and structural support to neurons. In several pathologies such as multiple sclerosis (MS), these cells are severely affected and fail to remyelinate, thereby leading to neuronal death. The gold standard for studying remyelination is the g-ratio, which is measured by means of transmission electron microscopy (TEM). Therefore, studying the fine structure of the oligodendrocyte population in the human brain at different stages through TEM is a key feature in this field of study. Here we study the ultrastructure of oligodendrocytes, its progenitors, and myelin in 10 samples of human white …

Human Achilles tendon glycation and function in diabetes

2016

Diabetic patients have an increased risk of foot ulcers, and glycation of collagen may increase tissue stiffness. We hypothesized that the level of glycemic control (glycation) may affect Achilles tendon stiffness, which can influence gait pattern. We therefore investigated the relationship between collagen glycation, Achilles tendon stiffness parameters, and plantar pressure in poorly ( n = 22) and well ( n = 22) controlled diabetic patients, including healthy age-matched (45–70 yr) controls ( n = 11). There were no differences in any of the outcome parameters (collagen cross-linking or tendon stiffness) between patients with well-controlled and poorly controlled diabetes. The overall effe…

Decreased consumption of branched-chain amino acids improves metabolic health

2016

Protein-restricted (PR), high-carbohydrate diets improve metabolic health in rodents, yet the precise dietary components that are responsible for these effects have not been identified. Furthermore, the applicability of these studies to humans is unclear. Here, we demonstrate in a randomized controlled trial that a moderate PR diet also improves markers of metabolic health in humans. Intriguingly, we find that feeding mice a diet specifically reduced in branched-chain amino acids (BCAAs) is sufficient to improve glucose tolerance and body composition equivalently to a PR diet via metabolically distinct pathways. Our results highlight a critical role for dietary quality at the level of amino…

CD36-fibrin interaction propagates FXI-dependent thrombin generation of human platelets.

2019

Thrombin converts fibrinogen to fibrin and activates blood and vascular cells in thrombo-inflammatory diseases. Platelets are amplifiers of thrombin formation when activated by leukocyte- and vascular cell-derived thrombin. CD36 on platelets acts as sensitizer for molecules with damage-associated molecular patterns, thereby increasing platelet reactivity. Here, we investigated the role of CD36 in thrombin-generation on human platelets, including selected patients with advanced chronic kidney disease (CKD). Platelets deficient in CD36 or blocked by anti-CD36 antibody FA6.152 showed impaired thrombin generation triggered by thrombin in calibrated automated thrombography. Using platelets with …

2016

Introduction: cognitive deterioration and reductions of bone health coincide with increasing age. We examine the relationship between bone composition and plasma markers of bone remodelling with measures of cognitive performance in healthy adults. Methods: this cross-sectional study included 225 old (52% women, mean age: 74.4 ± 3.3 years) and 134 young (52% women, mean age: 23.4 ± 2.7 years) adult participants from the MyoAge project. Whole body bone mineral density was measured by dualenergy X-ray absorptiometry. Blood analyses included a panel of bone-related peptides (dickkopf-1, osteoprotegerin, osteocalcin (OC), osteopontin, sclerostin, parathyroid hormone and fibroblast growth factor …

Refining the genetic structure and relationships of European cattle breeds through meta-analysis of worldwide genomic SNP data, focusing on Italian c…

2020

AbstractThe availability of genotyping assays has allowed the detailed evaluation of cattle genetic diversity worldwide. However, these comprehensive studies did not include some local European populations, including autochthonous Italian cattle. In this study, we assembled a large-scale, genome-wide dataset of single nucleotide polymorphisms scored in 3,283 individuals from 205 cattle populations worldwide to assess genome-wide autozygosity and understand better the genetic relationships among these populations. We prioritized European cattle, with a special focus on Italian breeds. Moderate differences in estimates of molecular inbreeding calculated from runs of homozygosity (FROH) were o…

Haploinsufficiency of the Primary Familial Brain Calcification Gene SLC20A2 Mediated by Disruption of a Regulatory Element

2020

OBJECTIVE Primary familial brain calcification (PFBC) is a rare cerebral microvascular calcifying disorder with diverse neuropsychiatric expression. Five genes were reported as PFBC causative when carrying pathogenic variants. Haploinsufficiency of SLC20A2, which encodes an inorganic phosphate importer, is a major cause of autosomal-dominant PFBC. However, PFBC remains genetically unexplained in a proportion of patients, suggesting the existence of additional genes or cryptic mutations. We analyzed exome sequencing data of 71 unrelated, genetically unexplained PFBC patients with the aim to detect copy number variations that may disrupt the expression of core PFBC-causing genes. METHODS Afte…