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https://www.readbyqxmd.com/read/28531192/overexpression-of-the-essential-sis1-chaperone-reduces-tdp-43-effects-on-toxicity-and-proteolysis
#1
Sei-Kyoung Park, Joo Y Hong, Fatih Arslan, Vydehi Kanneganti, Basant Patel, Alex Tietsort, Elizabeth M H Tank, Xingli Li, Sami J Barmada, Susan W Liebman
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by selective loss of motor neurons with inclusions frequently containing the RNA/DNA binding protein TDP-43. Using a yeast model of ALS exhibiting TDP-43 dependent toxicity, we now show that TDP-43 overexpression dramatically alters cell shape and reduces ubiquitin dependent proteolysis of a reporter construct. Furthermore, we show that an excess of the Hsp40 chaperone, Sis1, reduced TDP-43's effect on toxicity, cell shape and proteolysis...
May 22, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28531096/the-lys-asp-tyr-triad-within-the-mite-allergen-der-p-1-propeptide-is-a-critical-structural-element-for-the-ph-dependent-initiation-of-the-protease-maturation
#2
Andy Chevigné, Vincenzo Campizi, Martyna Szpakowska, David Bourry, Marie-Eve Dumez, José C Martins, André Matagne, Moreno Galleni, Alain Jacquet
The major house dust mite allergen, Der p 1, is a papain-like cysteine protease expressed as an inactive precursor, proDer p 1, carrying an N-terminal propeptide with a unique structure. The maturation of the zymogen into an enzymatically-active form of Der p 1 is a multistep autocatalytic process initiated under acidic conditions through conformational changes of the propeptide, leading to the loss of its inhibitory ability and its subsequent gradual cleavage. The aims of this study were to characterize the residues present in the Der p 1 propeptide involved in the initiation of the zymogen maturation process, but also to assess the impact of acidic pH on the propeptide structure, the activity of Der p 1 and the fate of the propeptide...
May 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28528102/cheese-milk-low-homogenization-enhanced-early-lipolysis-and-volatiles-compounds-production-in-hard-cooked-cheeses
#3
María A Vélez, Erica R Hynes, Carlos A Meinardi, Verónica I Wolf, María C Perotti
Homogenization applied to cheese milk has shown to increase lipolysis but its use is not spread as it can induce detrimental effects. The aim of this work was to assess the effect of low-pressure homogenization of the cream followed by pre-incubation of cheese milk on the composition, ripening index, lipolysis and volatile profiles of hard cooked cheeses. For that, control and experimental miniature Reggianito cheeses were made and analyzed during ripening (3, 45 and 90days). Homogenization had no impact on composition and proteolysis...
June 2017: Food Research International
https://www.readbyqxmd.com/read/28526746/region-specific-proteolysis-differentially-regulates-type-1-inositol-1-4-5-trisphosphate-receptor-activity
#4
Liwei Wang, Larry E Wagner, Kamil J Alzayady, David I Yule
The inositol 1,4,5 trisphosphate receptor (IP3R) is an intracellular Ca2+ release channel expressed predominately on the membranes of the endoplasmic reticulum. IP3R1 can be cleaved by caspase or calpain into at least two receptor fragments. However, the functional consequences of receptor fragmentation are poorly understood. Our previous work has demonstrated that IP3R1 channels, formed following either enzymatic fragmentation or expression of the corresponding complementary polypeptide chains, retain tetrameric architecture and are still activated by IP3 binding, despite the loss of peptide continuity...
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28525752/the-logic-of-the-26s-proteasome
#5
REVIEW
Galen Andrew Collins, Alfred L Goldberg
The ubiquitin proteasome pathway is responsible for most of the protein degradation in mammalian cells. Rates of degradation by this pathway have generally been assumed to be determined by rates of ubiquitylation. However, recent studies indicate that proteasome function is also tightly regulated and determines whether a ubiquitylated protein is destroyed or deubiquitylated and survives longer. This article reviews recent advances in our understanding of the proteasome's multistep ATP-dependent mechanism, its biochemical and structural features that ensure efficient proteolysis and ubiquitin recycling while preventing nonselective proteolysis, and the regulation of proteasome activity by interacting proteins and subunit modifications, especially phosphorylation...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28524858/caspase-dependent-non-apoptotic-processes-in-development
#6
REVIEW
Yu-Ichiro Nakajima, Erina Kuranaga
Caspases are at the core of executing apoptosis by orchestrating cellular destruction with proteolytic cascades. Caspase-mediated proteolysis also controls diverse nonlethal cellular activities such as proliferation, differentiation, cell fate decision, and cytoskeletal reorganization. During the last decade or so, genetic studies of Drosophila have contributed to our understanding of the in vivo mechanism of the non-apoptotic cellular responses in developmental contexts. Furthermore, recent studies using C...
May 19, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28524014/composition-and-enzymatic-activity-in-bulk-milk-from-dairy-farms-with-conventional-or-robotic-milking-systems
#7
Monika Johansson, Åse Lundh, Ruben de Vries, Kerstin Svennersten Sjaunja
The objective of the studies reported in this research communication was to investigate differences in composition and enzymatic activities in bulk milk samples provided from Swedish dairy farms with different management systems, i.e. automated (AMS) and conventional milking systems (CMS). A bulk milk sample was collected from each of 104 dairy farms, 51 using AMS and 53 using CMS, located in the same geographical region. Sampling took place within two consecutive days during the indoor period (October). Milk samples were analysed for contents of total fat and protein, free fatty acids (FFA), caseins and whey proteins, somatic cell count (SCC), pH, plasmin and plasminogen derived activities, and total proteolysis...
May 2017: Journal of Dairy Research
https://www.readbyqxmd.com/read/28523501/peptide-imaging-maximizing-peptide-yield-optimization-of-the-peptide-mass-fingerprint
#8
Ekta Patel
In Matrix Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI), identification of observed proteins remains a challenge primarily due to the drop in sensitivity of time-of-flight (TOF) mass spectrometers beyond the mass range of 25-35 kDa (Francese et al. High Throughput Screen 12: 156-174, 2009) and inadequate mass resolving power at those molecular weights. To counteract this, a bottom-up proteomic approach is often employed. Proteolysis digests proteins into smaller peptide fragments, typically between 500 and 3000 Da which are easier to detect with a higher mass accuracy...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28522867/movement-protein-of-apple-chlorotic-leaf-spot-virus-is-genetically-unstable-and-negatively-regulated-by-ribonuclease-e-in-e-coli
#9
Rahul Mohan Singh, Dharam Singh, Vipin Hallan
Movement protein (MP) of Apple chlorotic leaf spot virus (ACLSV) belongs to "30 K" superfamily of proteins and members of this family are known to show a wide array of functions. In the present study this gene was found to be genetically unstable in E. coli when transformed DH5α cells were grown at 28 °C and 37 °C. However, genetic instability was not encountered at 20 °C. Heterologous over expression failed despite the use of different transcriptional promoters and translational fusion constructs...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28522736/myelin-associated-glycoprotein-mag-inhibits-schwann-cell-migration-and-induces-their-death
#10
Nagarathnamma Chaudhry, Corinne Bachelin, Violetta Zujovic, Melissa Hilaire, Katherine T Baldwin, Rose M Follis, Roman Giger, Bruce D Carter, Anne Baron-Van Evercooren, Marie T Filbin
Remyelination of central nervous system (CNS) axons by Schwann cells (SC) is not efficient, in part due to their poor migration into the adult CNS. Although it is known that migrating SC avoid white matter tracts, the molecular mechanisms underlying this exclusion has never been elucidated. We now demonstrate that myelin-associated glycoprotein (MAG), a well-known inhibitor of neurite outgrowth, inhibits rat SC migration and induces their death via γ secretase-dependent regulated intramembrane proteolysis (RIP) of the p75 neurotrophin receptor (also known as p75 cleavage)...
May 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28522588/a-potential-mechanism-for-adc-induced-neutropenia-role-of-neutrophils-in-their-own-demise
#11
Hui Zhao, Sara Gulesserian, Maria Christina Malinao, Sathish Kumar-Ganesan, James Song, Mi Sook Chang, Melissa M Williams, Zhilan Zeng, Michael Mattie, Brian A Mendelsohn, David R Stover, Fernando Doñate
Neutropenia is a common adverse event in cancer patients treated with antibody-drug conjugates (ADCs) and we aimed to elucidate the potential mechanism of this toxicity. To investigate if ADCs affect neutrophil production from bone marrow, an in vitro assay was developed in which hematopoietic stem cells (HSCs) were differentiated to neutrophils. Several antibodies against targets absent in HSCs and neutrophils were conjugated to MMAE via a cleavable valine-citrulline linker (vcMMAE-ADCs) or MMAF via a non-cleavable maleimidocaproyl linker (mcMMAF-ADCs), and their cytotoxicity was tested in the neutrophil differentiation assay...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28521881/acute-fasting-inhibits-central-caspase-1-activity-reducing-anxiety-like-behavior-and-increasing-novel-object-and-object-location-recognition
#12
Albert E Towers, Maci L Oelschlager, Jay Patel, Stephen J Gainey, Robert H McCusker, Gregory G Freund
BACKGROUND: Inflammation within the central nervous system (CNS) is frequently comorbid with anxiety. Importantly, the pro-inflammatory cytokine most commonly associated with anxiety is IL-1β. The bioavailability and activity of IL-1β are regulated by caspase-1-dependent proteolysis vis-a-vis the inflammasome. Thus, interventions regulating the activation or activity of caspase-1 should reduce anxiety especially in states that foster IL-1β maturation. METHODS: Male C57BL/6j, C57BL/6j mice treated with the capase-1 inhibitor biotin-YVAD-cmk, caspase-1 knockout (KO) mice and IL-1R1 KO mice were fasted for 24h or allowed ad libitum access to food...
June 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28521486/fibronectin-induces-epithelial-mesenchymal-transition-in-human-breast-cancer-mcf-7-cells-via-activation-of-calpain
#13
Cheng-Lin Li, Dan Yang, Xin Cao, Fan Wang, Duan-Yang Hong, Jing Wang, Xiang-Chun Shen, Yan Chen
Fibronectin (FN) is a primary component of the mammary mesenchymal compartment and undergoes dramatic changes during breast cancer development. Increased FN expression is associated with an invasive and metastatic breast cancer phenotype. The present study demonstrated that FN causes an epithelial-mesenchymal transition (EMT)-like morphological change in MCF-7 breast cancer cells. FN stimulation caused the downregulation of epithelial markers E-cadherin and tight junction protein ZO-1, and the upregulation of mesenchymal markers N-cadherin and vimentin...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28517363/cleave-but-not-leave-astrotactin-proteins-in-development-and-disease
#14
REVIEW
Hao Chang
Over the years, animal studies have identified astrotactins as important membrane proteins for glial-guided neuronal migration during central nervous system development and hair follicle polarity control during skin development. Biochemical studies have revealed intramembrane proteolysis as an important feature of astrotactins. The two fragments of astrotactins remain linked together by a disulfide bond after the proteolytic cleavage. In humans, mutations in astrotactin genes have also been linked to a wide range of diseases, including several developmental brain disorders, neurodegenerative diseases and cancer...
May 18, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28516297/subcritical-water-hydrolysis-of-peptides-amino-acid-side-chain-modifications
#15
Thomas Powell, Steve Bowra, Helen J Cooper
Previously we have shown that subcritical water may be used as an alternative to enzymatic digestion in the proteolysis of proteins for bottom-up proteomics. Subcritical water hydrolysis of proteins was shown to result in protein sequence coverages greater than or equal to that obtained following digestion with trypsin; however, the percentage of peptide spectral matches for the samples treated with trypsin were consistently greater than for those treated with subcritical water. This observation suggests that in addition to cleavage of the peptide bond, subcritical water treatment results in other hydrolysis products, possibly due to modifications of amino acid side chains...
May 17, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28515901/experimental-identification-and-computational-characterization-of-a-novel-extracellular-metalloproteinase-produced-by-clostridium-sordellii
#16
Michael J Aldape, Aoxiang Tao, Dustin D Heeney, Eric R McIndoo, John M French, Dong Xu
Clostridium sordellii is a lethal pathogen for both animals and humans. Severe capillary leakage, toxic shock syndrome, and an extreme leukemoid reaction (LR), are hallmark features of C. sordellii infections and contribute to its high mortality rate. Here we report the discovery of a previously unknown and uncharacterized metalloproteinase of C. sordellii (referred as Mcs1) that cleaves human vascular cell adhesion molecule (VCAM)-1 in vitro, an adhesion molecule critical to hematopoietic precursor retention and leukocyte diapedesis...
March 2, 2017: RSC Advances
https://www.readbyqxmd.com/read/28515678/soluble-ectodomain-of-neuroligin-1-decreases-synaptic-activity-by-activating-metabotropic-glutamate-receptor-2
#17
Michelle D Gjørlund, Eva M M Carlsen, Andreas B Kønig, Oksana Dmytrieva, Anders V Petersen, Jacob Jacobsen, Vladimir Berezin, Jean-François Perrier, Sylwia Owczarek
Synaptic cell adhesion molecules represent important targets for neuronal activity-dependent proteolysis. Postsynaptic neuroligins (NLs) form trans-synaptic complexes with presynaptic neurexins (NXs). Both NXs and NLs are cleaved from the cell surface by metalloproteases in an activity-dependent manner, releasing a soluble extracellular fragment and membrane-tethered C-terminal fragment. The cleavage of NL1 depresses synaptic transmission, but the mechanism by which this occurs is unknown. Metabotropic glutamate receptor 2 (mGluR2) are located primarily at the periphery of presynaptic terminals, where they inhibit the formation of cyclic adenosine monophosphate (cAMP) and consequently suppress the release of glutamate and decrease synaptic transmission...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28513755/re-assembled-casein-micelles-improve-in-vitro-bioavailability-of-vitamin-d-in-a-caco-2-cell-model
#18
Yifat Cohen, Moran Levi, Uri Lesmes, Marielle Margier, Emmanuelle Reboul, Yoav D Livney
The pandemic of vitamin D (VD) deficiency, and the global rise in obesity stimulate a need for staple low-fat foods and beverages enriched with VD. In light of consumer demand for a clean label, the use of natural endogenous food ingredients as delivery vehicles is of great interest. To this end, re-assembled casein micelles (rCM) have been shown to help retain VD during processing and shelf life and provide high bioavailability in low-fat milk and non-fat yoghurt. This follow-up study focused on the performance of VD-loaded rCM after drying and reconstitution, considering VD retention during simulated digestion, and the subsequent in vitro bioavailability of the vitamin...
May 17, 2017: Food & Function
https://www.readbyqxmd.com/read/28512454/new-insights-into-the-regulation-of-cell-surface-signaling-activity-acquired-from-a-mutagenesis-screen-of-the-pseudomonas-putida-iuty-sigma-anti-sigma-factor
#19
Karlijn C Bastiaansen, Cristina Civantos, Wilbert Bitter, María A Llamas
Cell-surface signaling (CSS) is a signal transfer system that allows Gram-negative bacteria to detect environmental signals and generate a cytosolic response. These systems are composed of an outer membrane receptor that senses the inducing signal, an extracytoplasmic function sigma factor (σ(ECF)) that targets the cytosolic response by modifying gene expression and a cytoplasmic membrane anti-sigma factor that keeps the σ(ECF) in an inactive state in the absence of the signal and transduces its presence from the outer membrane to the cytosol...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28511966/identification-of-potential-target-genes-and-related-regulatory-transcription-factors-in-spontaneous-hairline-fracture-induced-by-hypervitaminosis-a
#20
Chuangang Peng, Qi Yang, Bo Wei, Yong Liu, Yuxiang Li, Dawei Gu, Guochao Yin, Bo Wang, Dehui Xu, Xuebing Zhang, Daliang Kong
BACKGROUND: The aim was to research the molecular changes of bone cells induced by excessive dose of vitamin A, and analyze molecular mechanism underlying spontaneous fracture. METHODS: The gene expression profile of GSE29859, including 4 cortical bone marrow samples with excessive doses of Vitamin A and 4 control cortical bone marrow samples, was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DGEs) between cortical bone marrow samples and control samples were screened out and pathway enrichment analysis was undertaken...
May 2, 2017: Injury
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