Proc Natl Acad Sci U S A
December 2024
Plasma membrane protein degradation and recycling are regulated by the endolysosomal system, wherein endocytic vesicles bud from the plasma membrane into the cytoplasm and mature into endosomes and then degradative lysosomes. As such, the endolysosomal system plays a critical role in determining the abundance of proteins on the cell surface and influencing cellular identity and function. Highly polarized cells, like neurons, rely on the endolysosomal system for axonal and dendritic specialization and synaptic compartmentalization.
View Article and Find Full Text PDFOne method to reduce the spread of pathogens is to use clean surfaces. These have long-acting components, and their use would reduce the massive consumption of disinfectants and cleaning products. In order to ensure the safety of these surfaces in water-based systems and prevent mishandling and potential health and environmental risks, this study analyzed the stability of clean surfaces made of polyethylene with three silver compounds with different water solubility.
View Article and Find Full Text PDFPlasma membrane protein degradation and recycling is regulated by the endolysosomal system, wherein endosomes bud from the plasma membrane into the cytosol and mature into degradative lysosomes. As such, the endolysosomal system plays a critical role in determining the abundance of proteins on the cell surface, influencing cellular identity and function. Highly polarized cells, like neurons, rely on the endolysosomal system for axonal and dendritic specialization and synaptic compartmentalization.
View Article and Find Full Text PDFThe endoplasmic reticulum (ER) employs a diverse proteome landscape to orchestrate many cellular functions, ranging from protein and lipid synthesis to calcium ion flux and inter-organelle communication. A case in point concerns the process of neurogenesis, where a refined tubular ER network is assembled via ER shaping proteins into the newly formed neuronal projections to create highly polarized dendrites and axons. Previous studies have suggested a role for autophagy in ER remodelling, as autophagy-deficient neurons in vivo display axonal ER accumulation within synaptic boutons, and the membrane-embedded ER-phagy receptor FAM134B has been genetically linked with human sensory and autonomic neuropathy.
View Article and Find Full Text PDFThe ecotoxic effect of Zn species arising from the weathering of the marmatite-like sphalerite ((Fe, Zn)S) in Allium cepa systems was herein evaluated in calcareous soils and connected with its sulfide oxidation mechanism to determine the chemical speciation responsible of this outcome. Mineralogical analyses (X-ray diffraction patterns, Raman spectroscopy, scanning electron microscopy and atomic force microscopy), chemical study of leachates (total Fe, Zn, Cd, oxidation-reduction potential, pH, sulfates and total alkalinity) and electrochemical assessments (chronoamperometry, chronopotentiometry, cyclic voltammetry, and electrochemical impedance spectroscopy) were carried out using (Fe, Zn)S samples to elucidate interfacial mechanisms simulating calcareous soil conditions. Results indicate the formation of polysulfides (S), elemental sulfur (S), siderite (FeCO)-like, hematite (FeO)-like with sorbed CO species, gunningite (ZnSO·HO)-like phase and smithsonite (ZnCO)-like compounds in altered surface under calcareous conditions.
View Article and Find Full Text PDFGABA receptors are the major inhibitory receptors in the brain. They are hetero-pentamers with a composition of predominantly two α, two β, and one γ or δ subunit. Of the six α subunit genes, the α5 subunit displays a limited spatial expression pattern and is known to mediate both phasic and tonic inhibition.
View Article and Find Full Text PDFThe endoplasmic reticulum (ER) employs a diverse proteome landscape to orchestrate many cellular functions ranging from protein and lipid synthesis to calcium ion flux and inter-organelle communication. A case in point concerns the process of neurogenesis: a refined tubular ER network is assembled via ER shaping proteins into the newly formed neuronal projections to create highly polarized dendrites and axons. Previous studies have suggested a role for autophagy in ER remodeling, as autophagy-deficient neurons display axonal ER accumulation within synaptic boutons, and the membrane-embedded ER-phagy receptor FAM134B has been genetically linked with human sensory and autonomic neuropathy.
View Article and Find Full Text PDFAutism spectrum disorders (ASDs) have been linked to genes with enriched expression in the brain, but it is unclear how these genes converge into cell-type-specific networks. We built a protein-protein interaction network for 13 ASD-associated genes in human excitatory neurons derived from induced pluripotent stem cells (iPSCs). The network contains newly reported interactions and is enriched for genetic and transcriptional perturbations observed in individuals with ASDs.
View Article and Find Full Text PDFIn fragile X syndrome (FX), the leading monogenic cause of autism, excessive neuronal protein synthesis is a core pathophysiology; however, an overall increase in protein expression is not observed. Here, we tested whether excessive protein synthesis drives a compensatory rise in protein degradation that is protective for FX mouse model (Fmr1) neurons. Surprisingly, although we find a significant increase in protein degradation through ubiquitin proteasome system (UPS), this contributes to pathological changes.
View Article and Find Full Text PDFAbsence of presynaptic protein MUNC18-1 (gene: ) leads to neuronal cell death at an immature stage before synapse formation. Here, we performed transcriptomic and proteomic profiling of immature knockout (KO) cells to discover which cellular processes depend on MUNC18-1. Hippocampi of KO mice showed cell-type specific dysregulation of 2123 transcripts primarily related to synaptic transmission and immune response.
View Article and Find Full Text PDFThe aim of this study was to determine the potential fertilizing of spermatozoa from the epididymal tail in different periods of time post-orchiectomy (P-OQ). Therefore, the study was approached in two stages. In the first stage, the orchiectomy was performed in 30 adult pigs.
View Article and Find Full Text PDFAlzheimer's disease (AD) is the most common neurodegenerative disorder in the human population, for which there is currently no cure. The cause of AD is unknown; however, the toxic effects of amyloid-β (Aβ) are believed to play a role in its onset. To investigate this, we examined changes in global protein levels in a hippocampal synaptosome fraction of the Amyloid Precursor Protein swe/Presenelin 1 dE9 (APP/PS1) mouse model of AD at 6 and 12 months of age (moa).
View Article and Find Full Text PDFMutations in SHANK genes play an undisputed role in neuropsychiatric disorders. Until now, research has focused on the postsynaptic function of SHANKs, and prominent postsynaptic alterations in glutamatergic signal transmission have been reported in Shank KO mouse models. Recent studies have also suggested a possible presynaptic function of SHANK proteins, but these remain poorly defined.
View Article and Find Full Text PDFA balanced t(1;11) translocation that directly disrupts DISC1 is linked to schizophrenia and affective disorders. We previously showed that a mutant mouse, named Der1, recapitulates the effect of the translocation upon DISC1 expression. Here, RNAseq analysis of Der1 mouse brain tissue found enrichment for dysregulation of the same genes and molecular pathways as in neuron cultures generated previously from human t(1;11) translocation carriers via the induced pluripotent stem cell route.
View Article and Find Full Text PDFMass spectrometry is the driving force behind current brain proteome analysis. In a typical proteomics approach, a protein isolate is digested into tryptic peptides and then analyzed by liquid chromatography-mass spectrometry. The recent advancements in data independent acquisition (DIA) mass spectrometry provide higher sensitivity and protein coverage than the classic data dependent acquisition.
View Article and Find Full Text PDFSorting nexin 4 (SNX4) is an evolutionary conserved protein that mediates recycling from endosomes back to the plasma membrane in yeast and mammalian cells. SNX4 is expressed in the brain. Altered protein levels are associated with Alzheimer's disease, but the neuronal localization and function of SNX4 have not been addressed.
View Article and Find Full Text PDFSynaptic transmission is the predominant form of communication in the brain. It requires functionally specialized molecular machineries constituted by thousands of interacting synaptic proteins. Here, we made use of recent advances in cross-linking mass spectrometry (XL-MS) in combination with biochemical and computational approaches to reveal the architecture and assembly of synaptic protein complexes from mouse brain hippocampus and cerebellum.
View Article and Find Full Text PDFPotassium hexatitanate (PHT) with chemical formula KTiO has a tunnel structure formed by TiO octahedra sharing edges or corners and with the potassium atoms located in the tunnels. This material has attracted great interest in the areas of photocatalysis, reinforcement of materials, biomaterials, etc. This work summarizes a large number of studies about methods to prepare PHT since particle size can be modified from millimeter to nanometric scale according to the applied method.
View Article and Find Full Text PDFIntra-partum asphyxia is the most common non-infectious etiology limiting the performance of neonate piglets. Previous studies indicate caffeine (orally and subcutaneously) reverses the effects of intra-partum asphyxia in neonate piglets. In this study, there was investigation of whether use of a novel therapeutic protocol for administering caffeine subcutaneously to pregnant sows would improve the newborn piglets' vitality, physio-metabolic profiles and body weight gain.
View Article and Find Full Text PDFA simple and fast immunoprecipitation (IP) protocol is designed with the sample preparation incorporated, applicable to both low and high throughput. This new protocol combines two procedures based on magnetic beads in 96-well plate format. Protein complexes are captured by antibodies and magnetic beads conjugated with protein A.
View Article and Find Full Text PDFThe objective of this study was to determine the effect of local anesthesia and the number of incisions performed on the physiological blood profile of piglets after surgical castration. A total of 60 male piglets were divided into five groups of 12 each, based on the surgical method employed and the use, or not, of local anesthesia, as follows: surgical castration using one horizontal incision in both testicles with (C1+L) and without (C1) local anesthesia; surgical castration using two vertical scrotal incisions with and without local anesthesia (C2+L and C2); and control piglets which were removed from their pens and held head-down by their hind limbs for approximately 90 s to simulate castration (SIM). Reference blood samples were drawn 24 h before castration (RV), immediately after surgery or simulated castration (PC), and at 24 and 48 h post-castration, to determine physiological profiles including; pH, hematocrit, glucose, electrolytes, lactate, pCO (mmHg), SO (mmHg), and bicarbonate.
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