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https://www.readbyqxmd.com/read/28816095/new-astroglial-injury-defined-biomarkers-for-neurotrauma-assessment
#1
Julia Halford, Sean Shen, Kyohei Itamura, Jaclynn Levine, Albert C Chong, Gregg Czerwieniec, Thomas C Glenn, David A Hovda, Paul Vespa, Ross Bullock, W Dalton Dietrich, Stefania Mondello, Joseph A Loo, Ina-Beate Wanner
Traumatic brain injury (TBI) is an expanding public health epidemic with pathophysiology that is difficult to diagnose and thus treat. TBI biomarkers should assess patients across severities and reveal pathophysiology, but currently, their kinetics and specificity are unclear. No single ideal TBI biomarker exists. We identified new candidates from a TBI CSF proteome by selecting trauma-released, astrocyte-enriched proteins including aldolase C (ALDOC), its 38kD breakdown product (BDP), brain lipid binding protein (BLBP), astrocytic phosphoprotein (PEA15), glutamine synthetase (GS) and new 18-25kD-GFAP-BDPs...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28814163/protease-activated-nanomaterials-for-targeted-cancer-theranostics
#2
Yung-Chieh Chan, Michael Hsiao
Cancer metastasis accompanies irreversible proteolysis. Malignant cells that abnormally express extracellular proteases usually lead to a poor outcome during cancer progression. The development of protease-activated drugs is an important goal. Moreover, the specific proteolytic mechanism can be used as a diagnostic strategy. Currently, nanotechnology for use in medication has been extensively developed to exploit the physical and chemical properties of nanoparticles. For example, to improve the efficacy of cancer therapy drugs, targeted delivery has been attempted by combining a targeting ligand with a nanoparticle...
August 17, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28810691/improvement-of-implantation-potential-in-mouse-blastocysts-derived-from-ivf-by-combined-treatment-with-prolactin-epidermal-growth-factor-and-4-hydroxyestradiol
#3
Miki Takeuchi, Misato Seki, Etsuko Furukawa, Akihito Takahashi, Kyosuke Saito, Mitsuru Kobayashi, Kenji Ezoe, Emiko Fukui, Midori Yoshizawa, Hiromichi Matsumoto
STUDY QUESTION: Can supplementation of medium with prolactin (PRL), epidermal growth factor (EGF) and 4-hydroxyestradiol (4-OH-E2) prior to embryo transfer improve implantation potential in mouse blastocysts derived from IVF? SUMMARY ANSWER: Combined treatment with PRL, EGF and 4-OH-E2 improves mouse blastocyst implantation rates, while alone, each factor is ineffective. WHAT IS KNOWN ALREADY: Blastocyst dormancy during delayed implantation caused by ovariectomy is maintained by continued progesterone treatment in mice, and estrogen injection rapidly activates blastocysts to implantation-induced status in vivo...
August 1, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28810250/cerebral-small-vessel-disease-is-associated-with-dysregulation-in-the-ubiquitin-proteasome-system-and-other-major-cellular-pathways-in-specific-brain-regions
#4
Marie-Françoise Ritz, Caspar Grond-Ginsbach, Felix Fluri, Manja Kloss, Markus Tolnay, Nils Peters, Stefan Engelter, Philippe Lyrer
BACKGROUND/AIMS: Cerebral small vessel disease (SVD) is characterized by periventricular white matter (WM) changes and can lead to vascular dementia, the second most common form of age-dependent dementia. The pathogenesis of the disease remains poorly understood, and studies of its molecular basis are limited. By profiling gene expression of dissected postmortem brain tissue in SVD patients and comparisons with tissue of nonneurological controls, we aimed to identify genes and processes that are involved in the pathogenesis of SVD to gain new pathogenetic insights...
August 16, 2017: Neuro-degenerative Diseases
https://www.readbyqxmd.com/read/28808944/effect-of-ha330-resin-directed-hemoadsorption-on-a-porcine-acute-respiratory-distress-syndrome-model
#5
Xuefeng Xu, Chune Jia, Sa Luo, Yanming Li, Fei Xiao, Huaping Dai, Chen Wang
BACKGROUND: Blood purification is an emerging approach to dampening the cytokine storm. This study aims to assess the efficacy of HA330 resin-directed hemoadsorption (HA) on endotoxin-induced porcine acute respiratory distress syndrome (ARDS) model. METHODS: Twenty-four Chinese domestic pigs were allocated into saline group receiving intravenous infusion of saline (N = 6) and endotoxin group receiving intravenous infusion of LPS (N = 18). When ALI model was initially diagnosed, six pigs in the LPS and saline group were killed for BALF and histopathological analysis...
August 14, 2017: Annals of Intensive Care
https://www.readbyqxmd.com/read/28806970/transcriptomic-analysis-of-the-response-of-acropora-millepora-to-hypo-osmotic-stress-provides-insights-into-dmsp-biosynthesis-by-corals
#6
Catalina Aguilar, Jean-Baptiste Raina, Cherie A Motti, Sylvain Fôret, David C Hayward, Bruno Lapeyre, David G Bourne, David J Miller
BACKGROUND: Dimethylsulfoniopropionate (DMSP) is a small sulphur compound which is produced in prodigious amounts in the oceans and plays a pivotal role in the marine sulfur cycle. Until recently, DMSP was believed to be synthesized exclusively by photosynthetic organisms; however we now know that corals and specific bacteria can also produce this compound. Corals are major sources of DMSP, but the molecular basis for its biosynthesis is unknown in these organisms. RESULTS: Here we used salinity stress, which is known to trigger DMSP production in other organisms, in conjunction with transcriptomics to identify coral genes likely to be involved in DMSP biosynthesis...
August 14, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28805948/pathogenic-role-of-adgrg2-in-cbavd-patients-replicated-in-chinese-population
#7
B Yang, J Wang, W Zhang, H Pan, T Li, B Liu, H Li, B Wang
Congenital bilateral absence of the vas deferens (CBAVD) is an important cause of obstructive azoospermia and male infertility worldwide. Cystic fibrosis transmembrane conductance regulator (CFTR) mutations are the main pathogenic cause, although a proportion of cases are still unexplained. Recently, adhesion G protein-coupled receptor G2 (ADGRG2) gene, a novel pathogenic gene for CBAVD was identified. We did a single population replication study in Chinese CBAVD patients to replicate its role in CBAVD developing...
August 14, 2017: Andrology
https://www.readbyqxmd.com/read/28805686/lengths-of-the-c-terminus-and-interconnecting-loops-impact-stability-of-spider-derived-gating-modifier-toxins
#8
Akello J Agwa, Yen-Hua Huang, David J Craik, Sónia T Henriques, Christina I Schroeder
Spider gating modifier toxins (GMTs) are potent modulators of voltage-gated ion channels and have thus attracted attention as drug leads for several pathophysiological conditions. GMTs contain three disulfide bonds organized in an inhibitory cystine knot, which putatively confers them with high stability; however, thus far, there has not been a focused study to establish the stability of GMTs in physiological conditions. We examined the resistance of five GMTs including GpTx-1, HnTx-IV, HwTx-IV, PaurTx-3 and SgTx-1, to pH, thermal and proteolytic degradation...
August 12, 2017: Toxins
https://www.readbyqxmd.com/read/28804824/laboratory-testing-for-activated-protein-c-resistance-apcr
#9
Soma Mohammed, Emmanuel J Favaloro
Activated protein C resistance (APCR) describes a hemostatic disorder characterized by a poor anticoagulant response to activated protein C (APC). This results in an increased risk of venous thrombosis, including deep vein thrombosis and pulmonary embolism. Protein C is a natural anticoagulant that is synthesized in the liver and is activated to APC via proteolysis. APC then degrades Factors Va and VIIIa. APCR describes the reduced inability of APC to cleave Factors Va and VIIIa, which therefore promotes increased thrombin generation and potentially leads to a prothrombotic state...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28804003/effect-and-proposed-mechanism-of-vitamin-c-modulating-amino-acid-regulation-of-autophagic-proteolysis
#10
Md Razaul Karim, Motoni Kadowaki
Autophagy is an intracellular bulk degradation process, induced under nutrient starvation. Failure of autophagy has been recognized as a contributor to aging and multiple age related neurodegenerative diseases. Improving autophagy is a beneficial anti-aging strategy, however very few physiological regulators have been identified. Here, we demonstrate that vitamin C is a nutritional stimulator of autophagy. Supplementation of fresh hepatocytes with vitamin C increased autophagic proteolysis significantly in the presence of amino acids in a dose- and time-dependent manner, although no effect was observed in the absence of amino acids...
August 10, 2017: Biochimie
https://www.readbyqxmd.com/read/28801264/vasoactive-properties-of-antihypertensive-lactoferrin-derived-peptides-in-resistance-vessels-effects-in-small-mesenteric-arteries-from-shr-rats
#11
Aurora García-Tejedor, Paloma Manzanares, María Castelló-Ruiz, Antonio Moscardó, José F Marcos, Juan B Salom
AIMS: Bovine lactoferrin (LF) hydrolysates and peptides identified thereof have shown antihypertensive effects in rat models, mainly but not exclusively by angiotensin-converting enzyme inhibition. In this study we aimed to assess the vasoactive effects and mechanisms of an ultrafiltered (<3kDa) pepsin LF hydrolysate (LFH) and a heptapeptide identified in a LF hydrolysate produced by yeast proteolysis (DPYKLRP) in peripheral resistance arteries from spontaneously hypertensive rats (SHRs)...
August 8, 2017: Life Sciences
https://www.readbyqxmd.com/read/28801169/a-single-high-dose-of-dexamethasone-increases-gap-43-and-synaptophysin-in-the-hippocampus-of-aged-rats
#12
Vesna Tesic, Milka Perovic, Ivan Zaletel, Mirna Jovanovic, Nela Puskas, Sabera Ruzdijic, Selma Kanazir
The administration of dexamethasone, a synthetic glucocorticoid receptor agonist, has been reported to modulate cognitive performance in both animals and humans. In the present study, we demonstrate the effects of a single high dose of dexamethasone on the expression and distribution of synaptic plasticity-related proteins, growth-associated protein-43 (GAP-43) and synaptophysin, in the hippocampus of 6-, 12-, 18- and 24-month-old rats. Acute dexamethasone treatment significantly altered the expression of GAP-43 at the posttranslational level by modulating the levels of phosphorylated GAP-43 and proteolytic GAP-43-3 fragment...
August 8, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28800600/botulinum-neurotoxin-c-mutants-reveal-different-effects-of-syntaxin-or-snap-25-proteolysis-on-neuromuscular-transmission
#13
Giulia Zanetti, Stefan Sikorra, Andreas Rummel, Nadja Krez, Elisa Duregotti, Samuele Negro, Tina Henke, Ornella Rossetto, Thomas Binz, Marco Pirazzini
Botulinum neurotoxin serotype C (BoNT/C) is a neuroparalytic toxin associated with outbreaks of animal botulism, particularly in birds, and is the only BoNT known to cleave two different SNARE proteins, SNAP-25 and syntaxin. BoNT/C was shown to be a good substitute for BoNT/A1 in human dystonia therapy because of its long lasting effects and absence of neuromuscular damage. Two triple mutants of BoNT/C, namely BoNT/C S51T/R52N/N53P (BoNT/C α-51) and BoNT/C L200W/M221W/I226W (BoNT/C α-3W), were recently reported to selectively cleave syntaxin and have been used here to evaluate the individual contribution of SNAP-25 and syntaxin cleavage to the effect of BoNT/C in vivo...
August 11, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28800153/increased-autolysis-of-%C3%AE-calpain-in-skeletal-muscles-of-chronic-alcohol-fed-rats
#14
Yulia V Gritsyna, Nikolay N Salmov, Alexander G Bobylev, Anna D Ulanova, Nikolay I Kukushkin, Zoya A Podlubnaya, Ivan M Vikhlyantsev
BACKGROUND: Proteolysis can proceed via several distinct pathways such as the lysosomal, calcium-dependent, and ubiquitin (Ub)-proteasome-dependent pathways. Calpains are the main proteases that cleave a large variety of proteins, including the giant sarcomeric proteins titin and nebulin. Chronic ethanol feeding for 6 weeks did not affect the activities of μ-calpain and m-calpain in the m. gastrocnemius. In our research, changes in μ-calpain activity were studied in the m. gastrocnemius and m...
August 11, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28799085/dimerization-leads-to-changes-in-app-amyloid-precursor-protein-trafficking-mediated-by-lrp1-and-sorla
#15
Simone Eggert, A C Gonzalez, C Thomas, S Schilling, S M Schwarz, C Tischer, V Adam, P Strecker, V Schmidt, T E Willnow, G Hermey, C U Pietrzik, E H Koo, Stefan Kins
Proteolytic cleavage of the amyloid precursor protein (APP) by α-, β- and γ-secretases is a determining factor in Alzheimer's disease (AD). Imbalances in the activity of all three enzymes can result in alterations towards pathogenic Aβ production. Proteolysis of APP is strongly linked to its subcellular localization as the secretases involved are distributed in different cellular compartments. APP has been shown to dimerize in cis-orientation, affecting Aβ production. This might be explained by different substrate properties defined by the APP oligomerization state or alternatively by altered APP monomer/dimer localization...
August 10, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28798239/interaction-of-munc18c-and-syntaxin4-facilitates-invadopodium-formation-and-extracellular-matrix-invasion-of-tumour-cells
#16
Megan I Brasher, David M Martynowicz, Olivia R Grafinger, Andrea Hucik, Emma Shanks-Skinner, James Uniacke, Marc G Coppolino
Tumor cell invasion involves targeted localization of proteins required for interactions of the extracellular matrix (ECM) and for proteolysis. The localization of many proteins during these cell-ECM interactions relies on membrane trafficking mediated in part by soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). The SNARE protein syntaxin4 (Stx4) is involved in the formation of invasive structures called invadopodia; however, it is unclear how Stx4 function is regulated during tumor cell invasion...
August 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28798148/ubiquitination-of-basal-vegfr2-regulates-signal-transduction-and-endothelial-function
#17
Gina A Smith, Gareth W Fearnley, Izma Abdul-Zani, Stephen B Wheatcroft, Darren C Tomlinson, Michael A Harrison, Sreenivasan Ponnambalam
Cell surface receptors can undergo recycling or proteolysis but the cellular decision-making events that sort between these pathways remain poorly defined. Vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) regulates signal transduction and angiogenesis but how signaling and proteolysis is regulated is not well understood. Here, we provide evidence that a pathway requiring the E1 ubiquitin-activating enzyme UBA1 controls basal VEGFR2 levels, hence metering plasma membrane receptor availability for the VEGF-A-regulated response by endothelial cells...
August 10, 2017: Biology Open
https://www.readbyqxmd.com/read/28797648/overview-of-transcriptomic-analysis-of-all-human-proteases-non-proteolytic-homologs-and-inhibitors-organ-tissue-and-ovarian-cancer-cell-line-expression-profiling-of-the-human-protease-degradome-by-the-clip-chip%C3%A2-dna-microarray
#18
REVIEW
Reinhild Kappelhoff, Xose S Puente, Claire H Wilson, Arun Seth, Carlos Lopez-Otin, Christopher M Overall
The protease degradome is defined as the complete repertoire of proteases and inhibitors, and their nonfunctional homologs present in a cell, tissues or organism at any given time. We review the tissue distribution of virtually the entire degradome in 23 different human tissues and 6 ovarian cancer cell lines. To do so, we developed the CLIP-CHIP™, a custom microarray based on a 70-mer oligonucleotide platform, to specifically profile the transcripts of the entire repertoire of 473 active human proteases, 156 protease inhibitors and 92 non-proteolytically active homologs known at the design date using one specific oligonucleotide per transcript...
August 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28797647/matrix-metalloproteinases-the-sculptors-of-chronic-cutaneous-wounds
#19
REVIEW
Venkat Raghavan Krishnaswamy, Dvir Mintz, Irit Sagi
Cutaneous wound healing is a complex mechanism with multiple processes orchestrating harmoniously for structural and functional restoration of the damaged tissue. Chronic non-healing wounds plagued with infection create a major healthcare burden and is one of the most frustrating clinical problems. Chronic wounds are manifested by prolonged inflammation, defective re-epithelialization and haphazard remodeling. Matrix metalloproteinases (MMPs) are zinc dependent enzymes that play cardinal functions in wound healing...
August 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28797563/binding-of-a-type-1-rip-and-of-its-chimeric-variant-to-phospholipid-bilayers-evidence-for-a-link-between-cytotoxicity-and-protein-membrane-interactions
#20
Elio Pizzo, Rosario Oliva, Rita Morra, Andrea Bosso, Sara Ragucci, Luigi Petraccone, Pompea Del Vecchio, Antimo Di Maro
Ribosome-inactivating proteins (RIPs) are enzymes, almost all identified in plants, able to kill cells by depurination of rRNAs. Recently, in order to improve resistance to proteolysis of a type 1 RIP (PD-L4), we produced a recombinant chimera combining it with a wheat protease inhibitor (WSCI). Resulting chimeric construct, named PD-L4UWSCI, in addition to present the functions of the two domains, shows also an enhanced cytotoxic action on murine cancer cells when compared to PD-L4. Since different ways of interaction of proteins with membranes imply different resulting effects on cells, in this study we investigate conformational stability of PD-L4 and PD-L4UWSCI and their interaction with membrane models (liposomes)...
August 7, 2017: Biochimica et Biophysica Acta
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