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https://www.readbyqxmd.com/read/29915147/proteomics-reveals-scope-of-mycolactone-mediated-sec61-blockade-and-distinctive-stress-signature
#1
Jean-David Morel, Anja O Paatero, Jiajie Wei, Jonathan W Yewdell, Laure Guenin-Macé, Delphi Van Haver, Francis Impens, Natalia Pietrosemoli, Ville O Paavilainen, Caroline Demangel
Mycolactone is a bacteria-derived macrolide that blocks the biogenesis of a large array of secretory and integral transmembrane proteins (TMP) through potent inhibition of the Sec61 translocon. Here, we used quantitative proteomics to delineate the direct and indirect effects of mycolactone-mediated Sec61 blockade in living cells. In T lymphocytes, dendritic cells and sensory neurons, Sec61 substrates downregulated by mycolactone were in order of incidence: secretory proteins (with a signal peptide but no transmembrane domain), TMPs with a signal peptide (Type I) and TMPs without signal peptide and a cytosolic N-terminus (Type II)...
June 18, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29912442/eqtls-weighted-genetic-correlation-analysis-detected-brain-region-differences-in-genetic-correlations-for-complex-psychiatric-disorders
#2
Yan Wen, Feng Zhang, Xiancang Ma, Qianrui Fan, Wenyu Wang, Jiawen Xu, Feng Zhu, Jingcan Hao, Awen He, Li Liu, Xiao Liang, Yanan Du, Ping Li, Cuiyan Wu, Sen Wang, Xi Wang, Yujie Ning, Xiong Guo
Background: Psychiatric disorders are usually caused by the dysfunction of various brain regions. Incorporating the genetic information of brain regions into correlation analysis can provide novel clues for pathogenetic and therapeutic studies of psychiatric disorders. Methods: The latest genome-wide association study (GWAS) summary data of schizophrenia (SCZ), bipolar disorder (BIP), autism spectrum disorder (AUT), major depression disorder (MDD), and attention-deficit/hyperactivity disorder (ADHD) were obtained from the Psychiatric GWAS Consortium (PGC)...
June 15, 2018: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/29897997/the-exposure-to-uteroplacental-insufficiency-is-associated-with-activation-of-unfolded-protein-response-in-postnatal-life
#3
Annalisa Deodati, Josepmaría Argemí, Daniela Germani, Antonella Puglianiello, Anna Alisi, Cristiano De Stefanis, Roberto Ferrero, Valerio Nobili, Tomás Aragón, Stefano Cianfarani
Early life events are associated with the susceptibility to chronic diseases in adult life. Perturbations of endoplasmic reticulum (ER) homeostasis activate the unfolded protein response (UPR), which contributes to the development of metabolic alterations. Our aim was to evaluate liver UPR in an animal model of intrauterine growth restriction (IUGR). A significantly increased expression of X-box binding protein-1 spliced (XBP1s) mRNA (p<0.01), Endoplasmic Reticulum-localized DnaJ homologue (Erdj4) mRNA (p<0...
2018: PloS One
https://www.readbyqxmd.com/read/29897001/the-challenges-of-working-with-men-who-perpetrate-partner-violence-perspectives-and-observations-of-experts-who-work-with-batterer-intervention-programs
#4
Penelope K Morrison, Lynn Hawker, Patricia A Cluss, Elizabeth Miller, Rhonda Fleming, Terry Bicehouse, Donna George, Jessica Burke, Kalem Wright, Judy C Chang
Batterer intervention programs (BIPs) constitute the primary treatment for perpetrators of intimate partner violence (IPV). Systematic evaluations of BIPs, however, have yielded modest results in terms of these programs' ability to reduce perpetration. Descriptive studies, which can provide information on the contexts and process associated with BIPs, can provide insights into the underlying mechanisms that might promote change among BIP clients, and as such are important to improving efficacy measures for BIPs...
June 1, 2018: Journal of Interpersonal Violence
https://www.readbyqxmd.com/read/29890204/emerging-fields-in-chaperone-proteins-a-french-workshop
#5
Elisabetta Mileo, Marianne Ilbert, Alessandro Barducci, Patricia Bordes, Marie-Pierre Castanié-Cornet, Cyrille Garnier, Pierre Genevaux, Reynald Gillet, Pierre Goloubinoff, Françoise Ochsenbein, Gilbert Richarme, Chantal Iobbi-Nivol, Marie-Thérèse Giudici-Orticoni, Brigitte Gontero, Olivier Genest
The "Bioénergétique et Ingénierie des Protéines (BIP)" laboratory, CNRS (France), organized its first French workshop on molecular chaperone proteins and protein folding in November 2017. The goal of this workshop was to gather scientists working in France on chaperone proteins and protein folding. This initiative was a great success with excellent talks and fruitful discussions. The highlights were on the description of unexpected functions and posttranslational regulation of known molecular chaperones (such as Hsp90, Hsp33, SecB, GroEL) and on state-of-the-art methods to tackle questions related to this theme, including Cryo-electron microscopy, Nuclear Magnetic Resonance (NMR), Electron Paramagnetic Resonance (EPR), simulation and modeling...
June 8, 2018: Biochimie
https://www.readbyqxmd.com/read/29864738/physical-frailty-and-cognitive-function-among-men-with-cardiovascular-disease
#6
Galit Weinstein, Miri Lutski, Uri Goldbourt, David Tanne
AIMS: To assess the relationship between physical frailty and cognitive function among elderly men with a history of cardiovascular disease (CVD). METHODS: Three-hundred-twenty-four community-dwelling men with chronic CVD (mean age 77.2 ± 6.4 years) who previously participated in the Bezafibrate Infarction Prevention (BIP) trial (1990-1998) underwent assessment of frailty and cognitive function between 2011 and 2013. Physical frailty was assessed using the Fried phenotypic model, and cognitive performance overall and in memory, executive function, visuospatial and attention domains was evaluated using a validated set of computerized cognitive tests...
May 29, 2018: Archives of Gerontology and Geriatrics
https://www.readbyqxmd.com/read/29851562/dynamic-changes-in-complexes-of-ire1%C3%AE-perk-and-atf6%C3%AE-during-endoplasmic-reticulum-stress
#7
Arunkumar Sundaram, Suhila Appathurai, Rachel Plumb, Malaiyalam Mariappan
The endoplasmic reticulum (ER) localized unfolded protein response (UPR) sensors, IRE1α, PERK, and ATF6α, are activated by the accumulation of misfolded proteins in the ER. It is unclear how the endogenous UPR sensors are regulated by both ER stress and the ER luminal chaperone BiP, which is a negative regulator of UPR sensors. Here we simultaneously examined the changes in the endogenous complexes of UPR sensors by blue native PAGE immunoblotting in unstressed and stressed cells. We found that all three UPR sensors exist as preformed complexes even in unstressed cells...
June 1, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29848262/the-effect-of-culture-temperature-on-the-aggregation-of-recombinant-tnfr-fc-is-regulated-by-the-perk-eif2a-pathway-in-cho-cells
#8
Kai Wang, Tu Zhang, Jing Chen, Chen Xuexuan Liu, Jie Tang, Qiuling Xie
Recombinant human tumor necrosis factor receptor II-Fc (TNFR-Fc) is a therapeutic protein expressed in Chinese hamster ovary (CHO) cells. The desired TNFR-Fc is a dimer; however, aggregates are often formed during culture and need to be removed to minimize the risk of immunogenicity to patients. Lower temperatures improve recombinant protein production in CHO cells. Here, we investigated the effect of different culture temperatures (37°C and 31°C, or a shift from 37°C to 31°C on the 3rd day) on the aggregation of recombinant TNFR-Fc...
May 30, 2018: Protein and Peptide Letters
https://www.readbyqxmd.com/read/29845288/fgf21-attenuates-hypoxia%C3%A2-induced-dysfunction-and-apoptosis-in-hpaecs-through-alleviating-endoplasmic-reticulum-stress
#9
Ali Chen, Jingjing Liu, Jianfeng Zhu, Xuetao Wang, Zhaona Xu, Zhimin Cui, Dan Yao, Zhifeng Huang, Min Xu, Mayun Chen, Peiliang Wu, Manxiang Li, Liangxing Wang, Xiaoying Huang
Vascular endothelial apoptosis and dysfunction have a crucial role in triggering pathological vascular remodeling of hypoxia‑induced pulmonary arterial hypertension (PAH). Fibroblast growth factor (FGF)21, an endocrine regulator, has recently been reported to protect cardiac endothelial cells from damage and suppress inflammatory responses. In addition, FGF21 is reported to be involved in endoplasmic reticulum stress (ERS). Previous studies have suggested that ERS participates in the development of PAH, and attenuation of ERS could be an effective therapeutic strategy for the protection of pulmonary arteries...
May 24, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29843048/reduction-of-the-molecular-chaperone-binding-immunoglobulin-protein-bip-accentuates-the-effect-of-aging-on-sleep-wake-behavior
#10
Nirinjini Naidoo, Jingxu Zhu, Raymond J Galante, Jie Lian, Ewa Strus, Amy Lee, Brendan T Keenan, Allan I Pack
Sleep and wake quality, quantity, and architecture become modified with aging. Sleep and wake quality decline coinciding with increased fragmentation of both states across aging. We have previously shown that this age-related decline in sleep-wake quality is associated with increased endoplasmic reticular (ER) stress and decreased expression of the major ER chaperone binding immunoglobulin protein (BiP). BiP, also known as glucose-regulated protein 78, plays a key role in controlling the cellular response to ER stress, acting as a regulator of a protein homeostatic signaling pathway known as the unfolded protein response...
April 30, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29843019/endoplasmic-reticulum-stress-in-bipolar-disorder-bip-and-chop-gene-expression-and-xbp1-splicing-analysis-in-peripheral-blood
#11
Susanne A Bengesser, Eva Z Reininghaus, Nina Dalkner, Armin Birner, Helena Hohenberger, Robert Queissner, Frederike Fellendorf, Martina Platzer, Rene Pilz, Carlo Hamm, Alexandra Rieger, Hans-Peter Kapfhammer, Harald Mangge, Bernd Reininghaus, Nathalie Meier-Allard, Anika Stracke, Robert Fuchs, Sandra Holasek
BACKGROUND: Endoplasmic Reticulum stress activates the Unfolded Protein Response, which is partially impaired in Bipolar Disorder (BD) according to previous in-vitro studies. Thus, BiP and CHOP gene expression and XBP1 splicing were analyzed in peripheral blood of study participants with BD and controls. METHODS: RNA was isolated from fasting blood of study participants with BD (n = 81) and controls (n = 54) and reverse transcribed into cDNA. BiP and CHOP gene expression was analyzed with quantitative RT-PCR...
May 21, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29806786/a-chimeric-mutant-analysis-in-yeast-cells-suggests-bip-independent-regulation-of-the-mammalian-endoplasmic-reticulum-stress-sensor-ire1%C3%AE
#12
Thanh Chi Mai, Takeo Munakata, Duc Minh Tran, Hiroshi Takagi, Yukio Kimata
An endoplasmic reticulum (ER)-located transmembrane protein, Ire1, triggers cytoprotective events upon ER stress. Chimeric yeast Ire1 carrying the luminal domain of the mammalian major Ire1 paralogue IRE1α is upregulated in ER-stressed yeast cells, but is poorly associated with the ER-located chaperone BiP even under non-stressed conditions. This observation contradicts the theory that BiP is the master regulator of IRE1α.
May 28, 2018: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/29795763/structure-activity-relationships-of-radioiodinated-benzoimidazopyridine-derivatives-for-detection-of-tau-pathology
#13
Sho Kaide, Masahiro Ono, Hiroyuki Watanabe, Ayane Kitada, Masashi Yoshimura, Yoichi Shimizu, Masafumi Ihara, Hideo Saji
It is generally accepted that neurofibrillary tangles consisting of tau proteins are involved in the pathogenesis of Alzheimer's disease (AD). For selective detection of tau pathology, we synthesized and evaluated radioiodinated benzoimidazopyridine (BIP) derivatives with an alkylamino group as tau imaging probes. In vitro selectivity to tau aggregates and in vivo pharmacokinetics of BIP derivatives varied markedly, being strongly dependent on the alkylamino group. In in vitro autoradiography with AD brain sections, the BIP derivative with a dimethylamino group (BIP-NMe2 ) showed the highest selectivity to tau aggregates...
May 10, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29795639/propofol-elicits-autophagy-via-endoplasmic-reticulum-stress-and-calcium-exchange-in-c2c12-myoblast-cell-line
#14
Xi Chen, Long-Yun Li, Jin-Lan Jiang, Kai Li, Zhen-Bo Su, Fu-Qiang Zhang, Wen-Jing Zhang, Guo-Qing Zhao
In this study, we investigated the relationship between propofol and autophagy and examined whether this relationship depends on ER stress, production of ROS (reactive oxygen species), and disruption of calcium (Ca2+) homeostasis. To this end, we measured C2C12 cell apoptosis in vitro, along with Ca2+ levels; ROS production; and expression of proteins and genes associated with autophagy, Ca2+ homeostasis, and ER stress, including LC3 (microtubule-associate protein 1 light chain 3), p62, AMPK (adenosine 5'-monophosphate (AMP)-activated protein kinase), phosphorylated AMPK, mTOR (the mammalian target of rapamycin), phosphorylated mTOR, CHOP (C/BEP homologous protein), and Grp78/Bip (78 kDa glucose-regulated protein)...
2018: PloS One
https://www.readbyqxmd.com/read/29788004/juvenile-traumatic-brain-injury-results-in-cognitive-deficits-associated-with-impaired-endoplasmic-reticulum-stress-and-early-tauopathy
#15
Michael J Hylin, Ryan C Holden, Aidan C Smith, Aric F Logsdon, Rabia Qaiser, Brandon P Lucke-Wold
The leading cause of death in the juvenile population is trauma, and in particular neurotrauma. The juvenile brain response to neurotrauma is not completely understood. Endoplasmic reticulum (ER) stress has been shown to contribute to injury expansion and behavioral deficits in adult rodents and furthermore has been seen in adult postmortem human brains diagnosed with chronic traumatic encephalopathy. Whether endoplasmic reticulum stress is increased in juveniles with traumatic brain injury (TBI) is poorly delineated...
May 22, 2018: Developmental Neuroscience
https://www.readbyqxmd.com/read/29784843/high-dose-and-delayed-treatment-with-bile-acids-ineffective-in-rml-prion-infected-mice
#16
Grant Norman, Jody Campeau, Valerie L Sim
Prion diseases are a group of neurodegenerative diseases associated with the misfolding of the cellular prion protein (PrPC ) into the infectious form (PrPSc ). There are currently no treatments for prion disease. Bile acids have the ability to protect hepatocytes from apoptosis and are neuroprotective in animal models of other protein folding neurodegenerative diseases including Huntington's, Parkinson's, and Alzheimer's disease. Importantly, bile acids are approved for clinical use in patients with cirrhosis, and have recently been shown to be safe and possibly effective in pilot trials of patients with amyotrophic lateral sclerosis (ALS)...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29779173/long-lasting-high-lysine-diet-aggravates-white-matter-injury-in-glutaryl-coa-dehydrogenase-deficient-gcdh-mice
#17
Silvia Olivera-Bravo, Bianca Seminotti, Eugenia Isasi, César A Ribeiro, Guilhian Leipnitz, Michael Woontner, Stephen I Goodman, Diogo Souza, Luis Barbeito, Moacir Wajner
Glutaric acidemia type I (GA-I) is a neurometabolic disease caused by deficient activity of glutaryl-CoA dehydrogenase (GCDH) that results in accumulation of metabolites derived from lysine (Lys), hydroxylysine, and tryptophan catabolism. GA-I patients typically develop encephalopatic crises with striatal degeneration and progressive white matter defects. However, late onset patients as well as Gcdh-/- mice only suffer diffuse myelinopathy, suggesting that neuronal death and white matter defects are different pathophysiological events...
May 19, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29768020/chemical-diversity-of-the-essential-oils-of-twenty-populations-of-tanacetum-polycephalum-sch-bip-from-iran
#18
Mehran Mojarrad, Siavash Hosseini Sarghein, Ali Sonboli
Chemical diversity of the essential oils of twenty wild populations of Tanacetum polycephalum Sch. Bip., was investigated. The aerial parts of T. polycephalum were collected at full flowering stage from West Azerbaijan Province of Iran, air-dried; hydrodistilled to produce essential oils. The essential oils were analyzed by GC-FID and GC-MS. A total of forty compounds were identified accounting for 96.4-99.9% of the total oils. The most principal compounds were cis-thujone (0-82.3%), trans-thujone (0-79.8%), camphor (1...
May 16, 2018: Natural Product Research
https://www.readbyqxmd.com/read/29761871/autophagy-may-protect-against-parenteral-nutrition-associated-liver-disease-by-suppressing-endoplasmic-reticulum-stress
#19
Tian Zhang, Junkai Yan, Nan Wang, Lina Dai, Ying Wang, Wei Cai
BACKGROUND: The objectives of this study were to address the role of autophagy in the pathogenesis of parenteral nutrition (PN)-associated liver disease (PNALD) and its possible mechanism in vivo. METHODS: Five-week-old male Sprague Dawley rats were fed Shoobree chow (Xietong Organism, Jiangsu, China) and administered intravenous 0.9% saline (sham group), PN (PN group), PN plus rapamycin (1 mg/kg; PN + Rapa group), or rapamycin (Rapa group) for 7 days. Before and after study, body weight, biochemical indicators, hepatic histology, level of autophagy, hepatocyte apoptosis, reactive oxygen species (ROS), and endoplasmic reticulum (ER) stress indicators including binding immunoglobulin protein (BIP), spliced X-box-binding protein-1 (sXBP1), and CCAAT-enhancer-binding protein homologous protein (CHOP) were measured...
May 15, 2018: JPEN. Journal of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/29757357/the-revival-of-the-gini-importance
#20
Stefano Nembrini, Inke R König, Marvin N Wright
Motivation: Random forests are fast, flexible and represent a robust approach to analyze high dimensional data. A key advantage over alternative machine learning algorithms are variable importance measures, which can be used to identify relevant features or perform variable selection. Measures based on the impurity reduction of splits, such as the Gini importance, are popular because they are simple and fast to compute. However, they are biased in favor of variables with many possible split points and high minor allele frequency...
May 10, 2018: Bioinformatics
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