All cells rely on highly conserved protein folding and clearance pathways to detect resolve damage maintain homeostasis (proteostasis). Because age is associated with an imbalance in proteostasis, there a need understand how regulated multicellular organism that undergoes aging. We have observed the ability of Caenorhabditis elegans proteostasis declines sharply following onset oocyte biomass production, suggesting restricted capacity may be linked reproduction. To test this hypothesis, we...

Abstract The sensitivity of the protein-folding environment to chaperone disruption can be highly tissue-specific. Yet, organization system across physiological human tissues has received little attention. Through computational analyses large-scale tissue transcriptomes, we unveil that is composed core elements are uniformly expressed tissues, and variable differentially fit with tissue-specific requirements. We demonstrate via a proteomic analysis muscle-specific signature functional...

Protein phosphorylation underlies cellular response pathways across eukaryotes and is governed by the opposing actions of phosphorylating kinases de-phosphorylating phosphatases. While phosphatases have been extensively studied, their organization mechanisms which they balance each other are not well understood. To address these questions we performed quantitative analyses large-scale 'omics' datasets from yeast, fly, plant, mouse human. We uncovered an asymmetric a previously-hidden scale:...

Safeguarding the proteome is central to health of cell. In multi-cellular organisms, composition proteome, and by extension, protein-folding requirements, varies between cells. agreement, chaperone network differs tissues. Here, we ask how expression regulated in a cell type-specific manner whether cellular differentiation affects expression. Our bioinformatics analyses show that myogenic transcription factor HLH-1 (MyoD) can bind promoters genes expressed or required for folding muscle...

A longstanding puzzle in human genetics is what limits the clinical manifestation of hundreds hereditary diseases to certain tissues, while their causal genes are expressed throughout body. general conception that tissue-selective disease phenotypes emerge when masking factors operate unaffected but specifically absent or insufficient disease-manifesting tissues. Although this has critical impact on understanding manifestation, it was never challenged a systematic manner across variety and...

Protein folding and clearance networks sense respond to misfolded aggregation-prone proteins by activating cytoprotective cell stress responses that safeguard the proteome against damage, maintain health of cell, enhance lifespan. Surprisingly, cellular proteostasis undergoes a sudden widespread failure early in Caenorhabditis elegans adulthood, with marked consequences on functions later life. These changes regulation quality control systems, such as chaperones, ubiquitin proteasome system...

Protein homeostasis is remodeled early in Caenorhabditis elegans adulthood, resulting a sharp decline folding capacity and reduced ability to cope with chronic acute stress. Endocrine signals from the reproductive system can ameliorate this proteostatic collapse reshape quality control network. Given that environmental conditions, such as food availability, impact success, we asked whether conditions of dietary restriction (DR) also reverse function at transition if so, gonadal signaling...

Abstract We mimicked mild mitochondrial-distress robustly reported in bipolar-disorder (BD) by chronic exposure to uniquely low doses of inhibitors mitochondrial-respiration complexes vitro and vivo. Exposure the neuronal-originating SH-SY5Y cells very dose (10 pM) rotenone, a complex (Co)I inhibitor, for 72 or 96 h did not affect cell viability reactive oxygen species (ROS) levels. Yet, it induced dual effect on mitochondrial-respiration: overshooting statistically significant several-fold...

The folding and assembly of proteins is essential for protein function, the long-term health cell, longevity organism. Historically, function regulation was studied in vitro, isolated tissue culture cells unicellular organisms. Recent studies have uncovered links between homeostasis (proteostasis), metabolism, development, aging, temperature-sensing. These findings led to development new tools monitoring model metazoan organism Caenorhabditis elegans. In our laboratory, we combine behavioral...

Caenorhabditis elegans somatic protein homeostasis (proteostasis) is actively remodeled at the onset of reproduction. This proteostatic collapse regulated cell-nonautonomously by signals from reproductive system that transmit commitment to reproduction cells. Here, we asked whether link between and proteostasis could be uncoupled activating downstream effectors in gonadal longevity cascade. Specifically, examined overexpression lipl-4 (lipl-4(oe)), a target gene pathway, or increase...

Cell-non-autonomous signals dictate the functional state of cellular quality control systems, remodeling ability cells to cope with stress and maintain protein homeostasis (proteostasis). One highly regulated cell-non-autonomous switch controls proteostatic capacity in Caenorhabditis elegans adulthood. Signals from reproductive system down-regulate cyto-protective pathways, unless countered by reporting on germline proliferation disruption. Here, we utilized dihomo-γ-linolenic acid (DGLA)...

Background Weed control is essential in modern agriculture, though it has become more difficult with the emergence of resistance to most current herbicides and slow registration process for new compounds. Objective Identify herbicide candidates using an innovative artificial intelligence algorithm that takes into effect biological parameters goal reducing research development time herbicides. Results We describe discovery 4-chloro-2-pentenamides as novel inhibitors protoporphyrinogen oxidase...

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins) systems provide acquired heritable protection to bacteria and archaea against selfish DNA elements, such as viruses. These must be tightly regulated because they can capture fragments from foreign also occasionally self-chromosomes, resulting in autoimmunity. Most known species the halophilic archaeal genus Haloferax contain type I-B CRISPR-Cas systems, strongest hotspot for self-spacer...

The folding and assembly of proteins is essential for protein function, the long-term health cell, longevity organism. Historically, function regulation was studied in vitro, isolated tissue culture cells unicellular organisms. Recent studies have uncovered links between homeostasis (proteostasis), metabolism, development, aging, temperature-sensing. These findings led to development new tools monitoring model metazoan organism Caenorhabditis elegans. In our laboratory, we combine behavioral...

<h3>Background</h3> Quinolinic acid (QA) induced striatal lesion is a well established model for excitotoxicity, one of the key hallmarks Huntington9s disease pathophysiological processes. Stem cell based treatment promising frontier this incurable condition. One major caveats stem transplantation their fate post transplantation. <h3>Aims</h3> To follow transplanted cells9 using in vivo MRI scans followed by histological study. <h3>Methods</h3> Rat mesenchymal cells (MSC) went through two...

ABSTRACT A longstanding puzzle in human genetics is what limits the clinical manifestation of hundreds hereditary diseases to certain tissues or cell types, while their causal genes are present and expressed throughout body. Here we considered a possible role for paralogs affecting this tissue selectivity. It has been shown across organisms that can compensate loss each other. We hypothesized specifically disease imbalanced, leading insufficient compensation emergence phenotypes. While...

Abstract The sensitivity of the protein-folding environment to chaperone disruption can be highly tissue-specific. Yet, organization system across physiological human tissues has received little attention. Here, we used tissue RNA-sequencing profiles analyze expression and chaperones 29 main tissues. We found that relative protein-coding genes, were significantly more ubiquitously expressed all Nevertheless, differential analysis revealed most up- or down-regulated in certain tissues,...

Abstract Weed control is essential in modern agriculture, though it has become more difficult with the emergence of resistance to most current herbicides and a slow registration process new compounds. A approach identify possible herbicide candidates using an artificial intelligence algorithm that takes into effect biological parameters goal reducing R&amp;D time on herbicides. Herein we describe discovery 4-chloro-2-pentenamides as novel inhibitors protoporphyrinogen oxidase, known target...