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https://www.readbyqxmd.com/read/28821611/the-proteasome-interacting-ecm29-protein-disassembles-the-26s-proteasome-in-response-to-oxidative-stress
#1
Xiaorong Wang, Ilan E Chemmama, Clinton Yu, Alexander Huszagh, Yue Xu, Rosa Viner, Sarah Ashley Block, Peter Cimermancic, Scott D Rychnovsky, Yihong Ye, Andrej Sali, Lan Huang
Oxidative stress has been implicated in multiple human neurological and other disorders. Proteasomes are multi-subunit proteases critical for the removal of oxidatively damaged proteins. To understand stress-associated human pathologies, it is important to uncover the molecular events underlying the regulation of proteasomes upon oxidative stress. To this end, we investigated H2O2 stress-induced molecular changes of the human 26S proteasome and determined that stress-induced 26S proteasome disassembly is conserved from yeast to human...
August 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28816053/in-vitro-exposure-systems-and-dosimetry-assessment-tools-for-inhaled-tobacco-products-workshop-proceedings-conclusions-and-paths-forward-for-in-vitro-model-use
#2
Holger Behrsing, Erin Hill, Hans Raabe, Raymond Tice, Suzanne Fitzpatrick, Robert Devlin, Kent Pinkerton, Günter Oberdörster, Chris Wright, Roman Wieczorek, Michaela Aufderheide, Sandro Steiner, Tobias Krebs, Bahman Asgharian, Richard Corley, Michael Oldham, Jason Adamson, Xiang Li, Irfan Rahman, Sonia Grego, Pei-Hsuan Chu, Shaun McCullough, Rodger Curren
In 2009, the passing of the Family Smoking Prevention and Tobacco Control Act facilitated the establishment of the FDA Center for Tobacco Products (CTP), and gave it regulatory authority over the marketing, manufacture and distribution of tobacco products, including those termed 'modified risk'. On 4-6 April 2016, the Institute for In Vitro Sciences, Inc. (IIVS) convened a workshop conference entitled, In Vitro Exposure Systems and Dosimetry Assessment Tools for Inhaled Tobacco Products, to bring together stakeholders representing regulatory agencies, academia and industry to address the research priorities articulated by the FDA CTP...
July 2017: Alternatives to Laboratory Animals: ATLA
https://www.readbyqxmd.com/read/28808191/shunts-channels-and-lipoprotein-endosomal-traffic-a-new-model-of-cholesterol-homeostasis-in-the-hepatocyte
#3
Robert Scott Kiss, Allan Sniderman
The liver directs cholesterol metabolism in the organism. All the major fluxes of cholesterol within the body involve the liver: dietary cholesterol is directed to the liver; cholesterol from peripheral cells goes to the liver; the liver is a major site of cholesterol synthesis for the organism; cholesterol is secreted from the liver within the bile, within apoB lipoproteins and translocated to nascent HDL. The conventional model of cholesterol homeostasis posits that cholesterol from any source enters a common, rapidly exchangeable pool within the cell, which is in equilibrium with a regulatory pool...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28802881/recent-topics-of-research-in-the-characterization-and-quality-control-of-biopharmaceuticals-in-japan
#4
Akiko Ishii-Watabe, Hiroko Shibata, Akira Harazono, Masashi Hyuga, Masato Kiyoshi, Satoshi Saitoh, Takafumi Iwura, Tetsuo Torisu, Yukihiro Goda, Susumu Uchiyama
The research and development of next-generation innovative medicines is a prominent interest of both the government and industries in Japan. On June 29, 2017, a kickoff meeting of a new research group focused on the quality issues of biopharmaceuticals was held in Tokyo with Prof. John Carpenter as an invited guest. The group's research focuses mainly on the evaluation and control of protein aggregates/subvisible particles in drug products, but the research topics also include glycan analysis, host-cell protein evaluation, bioassay validation, and analytical quality-by-design...
August 9, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28800690/community-airborne-particulate-matter-from-mining-for-sand-used-as-hydraulic-fracturing-proppant
#5
Thomas M Peters, Patrick T O'Shaughnessy, Ryan Grant, Ralph Altmaier, Elizabeth Swanton, Jeffrey Falk, David Osterberg, Edith Parker, Nancy G Wyland, Sinan Sousan, Aimee Liz Stark, Peter S Thorne
Field and laboratory studies were conducted to evaluate the impact of proppant sand mining and processing activities on community particulate matter (PM) concentrations. In field studies outside 17 homes within 800m of sand mining activities (mining, processing, and transport), respirable (PM4) crystalline silica concentrations were low (<0.4μg/m(3)) with crystalline silica detected on 7 samples (2% to 4% of mass). In long-term monitoring at 6 homes within 800m of sand mining activities, the highest daily mean PM concentrations observed were 14...
August 7, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28779897/study-on-emission-of-hazardous-trace-elements-in-a-350%C3%A2-mw-coal-fired-power-plant-part-1-mercury
#6
Shilin Zhao, Yufeng Duan, Lei Chen, Yaning Li, Ting Yao, Shuai Liu, Meng Liu, Jianhong Lu
Hazardous trace elements (HTEs), especially mercury, emitted from coal-fired power plants had caused widespread concern worldwide. Field test on mercury emissions at three different loads (100%, 85%, 68% output) using different types of coal was conducted in a 350 MW pulverized coal combustion power plant equipped with selective catalytic reduction (SCR), electrostatic precipitator and fabric filter (ESP + FF), and wet flue gas desulfurization (WFGD). The Ontario Hydro Method was used for simultaneous flue gas mercury sampling for mercury at the inlet and outlet of each of the air pollutant control device (APCD)...
August 2, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28777969/method-validation-and-nanoparticle-characterization-assays-for-an-innovative-amphothericin-b-formulation-to-reach-increased-stability-and-safety-in-infectious-diseases
#7
Maraine Catarina Tadini, Ana Maria de Freitas Pinheiro, Daniel Blascke Carrão, Ana Luiza Scarano Aguillera Forte, Sofia Nikolaou, Anderson R M de Oliveira, Andresa Aparecida Berretta, Franciane Marquele-Oliveira
Drug Delivery Systems (DDS) of known drugs are prominent candidates towards new and more-effective treatments of various infectious diseases as they may increase drug bioavailability, control drug delivery and target the site of action. In this sense, the encapsulation of Amphotericin B (AmB) in Nanostructured Lipid Carriers (NLCs) designed with pH-sensible phospholipids to target infectious tissues was proposed and suitable analytical methods were validated, as well as, proper nanoparticle characterization were conducted...
July 8, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28767417/a-novel-deubiquitinase-inhibitor-b-ap15-triggers-apoptosis-in-both-androgen-receptor-dependent-and-independent-prostate-cancers
#8
Jianyu Cai, Xiaohong Xia, Yuning Liao, Ningning Liu, Zhiqiang Guo, Jinghong Chen, Li Yang, Huidan Long, Qianqian Yang, Xiaolan Zhang, Lu Xiao, Xuejun Wang, Hongbiao Huang, Jinbao Liu
Prostate cancer (PCa) remains a leading cause of cancer-related death in men. Especially, a subset of patients will eventually progress to the metastatic castrate-resistant prostate cancer (CRPC) which is currently incurable. Deubiquitinases (DUBs) associated with the 19S proteasome regulatory particle are increasingly emerging as significant therapeutic targets in numerous cancers. Recently, a novel small molecule b-AP15 is identified as an inhibitor of the USP14/UCHL5 (DUBs) of the 19S proteasome, resulting in cell growth inhibition and apoptosis in several human cancer cell lines...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28763652/nox-nh3-n2o-and-pn-real-driving-emissions-from-a-euro-vi-heavy-duty-vehicle-impact-of-regulatory-on-road-test-conditions-on-emissions
#9
Pablo Mendoza-Villafuerte, Ricardo Suarez-Bertoa, Barouch Giechaskiel, Francesco Riccobono, Claudia Bulgheroni, Covadonga Astorga, Adolfo Perujo
Euro VI emission standards for heavy-duty vehicles (HDVs) introduced for the first time limits for solid particle number (PN) and NH3 emissions. EU regulation also includes a Portable Emissions Measurement System (PEMS) based test at type approval, followed by in-service conformity (ISC) testing. A comprehensive study on the real-time on-road emissions of NOx, NH3, N2O and PN from a Euro VI HDV equipped with a Diesel Oxidation Catalyst (DOC), a Diesel Particle Filter (DPF), a Selective Catalytic Reduction (SCR) system and an Ammonia Oxidation Catalyst (AMOX) is presented...
July 27, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28760985/distinct-functions-of-diaphanous-related-formins-regulate-hiv-1-uncoating-and-transport
#10
Michael Keegan Delaney, Viacheslav Malikov, Qingqing Chai, Guangyuan Zhao, Mojgan H Naghavi
Diaphanous (Dia)-related formins (DRFs) coordinate cytoskeletal remodeling by controlling actin nucleation and microtubule (MT) stabilization to facilitate processes such as cell polarization and migration; yet the full extent of their activities remains unknown. Here, we uncover two discrete roles and functions of DRFs during early human immunodeficiency virus type 1 (HIV-1) infection. Independent of their actin regulatory activities, Dia1 and Dia2 facilitated HIV-1-induced MT stabilization and the intracellular motility of virus particles...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28758619/sus-scrofa-papillomavirus-2-genetic-characterization-of-a-novel-suid-papillomavirus-from-wild-boar-in-germany
#11
Ellen Kathrin Link, Marc Hoferer, Birte Strobel, Kerstin Rigbers, Martin Christoph Langenmayer, Gerd Sutter, Robert Fux
We identified a novel papillomavirus, Sus scrofa papillomavirus 2 (SsPV2), which is the first papillomavirus associated with papillomas in pigs. In skin alterations of a German wild boar, showing typical gross and histological appearance of papillomas, papillomavirus-like particles were demonstrated by electron microscopy. Degenerate papillomavirus-specific primers were used to amplify and sequence parts of the viral DNA. Subsequently, the complete genomic DNA was cloned and sequenced. The SsPV2 genome had a length of 8218 bp, encoded the early proteins E6, E7, E1 and E2, the late proteins L1 and L2 and contained an upstream regulatory region...
July 31, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28751218/brain-lipoprotein-lipase-as-a-regulator-of-energy-balance
#12
Céline Cruciani-Guglielmacci, Christophe Magnan
The central nervous system is an essential actor in the control of the energy balance. Indeed, many signals of nervous (vagal afferent for example) or circulating (hormone, nutrients) origin converge towards the brain to inform it permanently of the energetic status of the organism. In turn, the brain sends information to the periphery (sympathetic vagal balance, thyroid or corticotropic axis) which allows a fine regulation of the energy fluxes by acting on the hepatic glucose production, the secretion of the pancreatic hormones (glucagon, insulin) or food behavior...
July 24, 2017: Biochimie
https://www.readbyqxmd.com/read/28748400/reconstructing-genetic-regulatory-networks-using-two-step-algorithms-with-the-differential-equation-models-of-neural-networks
#13
Chi-Kan Chen
BACKGROUND: The identification of genetic regulatory networks (GRNs) provides insights into complex cellular processes. A class of recurrent neural networks (RNNs) captures the dynamics of GRN. Algorithms combining the RNN and machine learning schemes were proposed to reconstruct small-scale GRNs using gene expression time series. RESULTS: We present new GRN reconstruction methods with neural networks. The RNN is extended to a class of recurrent multilayer perceptrons (RMLPs) with latent nodes...
July 26, 2017: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/28738173/simulating-the-meteorology-and-pm10-concentrations-in-arizona-dust-storms-with-the-weather-research-and-forecasting-model-with-chemistry-wrf-chem
#14
Peter Hyde, Alex Mahalov, Jialun Li
Nine dust storms in south-central Arizona, USA were simulated with the Weather Research and Forecasting with Chemistry model (WRF-Chem) at 2-km resolution. The windblown dust emission algorithm was the Air Force Weather Agency model. In comparison with ground-based PM10 observations, the model unevenly reproduces the dust storm events. The model adequately estimates the location and timing of the events, but it is unable to precisely replicate the magnitude and timing of the elevated hourly concentrations of particles 10 microns and smaller ([PM10])...
July 24, 2017: Journal of the Air & Waste Management Association
https://www.readbyqxmd.com/read/28713164/human-immunodeficiency-virus-type-1-induces-a-regulatory-b-cell-like-phenotype-in-vitro
#15
Jacobo Lopez-Abente, Adrián Prieto-Sanchez, Maria-Ángeles Muñoz-Fernandez, Rafael Correa-Rocha, Marjorie Pion
Individuals infected with human immunodeficiency virus type-1 (HIV-1) usually show a general dysregulation and hyper-activation of the immune system. A direct influence of HIV-1 particles on B-cell phenotypes and functions has been previously described. However, the consequences of B-cell dysregulation are still poorly understood. We evaluated the phenotypic changes in primary B cells after direct contact with HIV-1 particles in comparison with different types of stimuli. The functionality of treated B cells was challenged in co-culture experiments with autologous CD4+ and CD8+ T cells...
July 17, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28699320/a-three-plus-three-parameters-mechanistic-model-for-viral-filtration
#16
Prakhar Misra, Abhishek Sinha, Fasil Q Mir, Anurag S Rathore, Anupam Shukla
Viral filtration is an expensive regulatory requirement in downstream processing of monoclonal antibodies (mAbs). This process step is typically operated with an overdesigned filter in order to account for any batch to batch variability in the filter, as well as the feed characteristics. Here, we propose a simple, six-parameter mechanistic model for viral filtration where three parameters are membrane-specific while the other three depend on feed characteristics and membrane-feed interactions. Viruses are considered as passive particles which are retained by the membrane on the basis of size exclusion...
July 11, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28689658/conformational-landscape-of-the-p28-bound-human-proteasome-regulatory-particle
#17
Ying Lu, Jiayi Wu, Yuanchen Dong, Shuobing Chen, Shuangwu Sun, Yong-Bei Ma, Qi Ouyang, Daniel Finley, Marc W Kirschner, Youdong Mao
The proteasome holoenzyme is activated by its regulatory particle (RP) consisting of two subcomplexes, the lid and the base. A key event in base assembly is the formation of a heterohexameric ring of AAA-ATPases, which is guided by at least four RP assembly chaperones in mammals: PAAF1, p28/gankyrin, p27/PSMD9, and S5b. Using cryogenic electron microscopy, we analyzed the non-AAA structure of the p28-bound human RP at 4.5 Å resolution and determined seven distinct conformations of the Rpn1-p28-AAA subcomplex within the p28-bound RP at subnanometer resolutions...
July 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28678347/trap1-controls-cell-cycle-g2-m-transition-through-the-regulation-of-cdk1-and-mad2-expression-ubiquitination
#18
Lorenza Sisinni, Francesca Maddalena, Valentina Condelli, Giuseppe Pannone, Vittorio Simeon, Valeria Li Bergolis, Elvira Lopes, Annamaria Piscazzi, Danilo Swann Matassa, Carmela Mazzoccoli, Filomena Nozza, Giacomo Lettini, Maria Rosaria Amoroso, Pantaleo Bufo, Franca Esposito, Matteo Landriscina
Regulation of tumor cell proliferation by molecular chaperones is still a complex issue. Here, the role of the HSP90 molecular chaperone TRAP1 in cell cycle regulation was investigated in a wide range of human breast, colorectal and lung carcinoma cell lines and tumor specimens. TRAP1 modulates the expression and/or the ubiquitination of key cell cycle regulators through a dual mechanism: i) a transcriptional regulation of CDK1, CYCLIN B1 and MAD2, as suggested by a gene expression profiling of TRAP1-silenced breast carcinoma cells, and ii) a post-transcriptional quality control of CDK1 and MAD2, being the ubiquitination of these two proteins enhanced upon TRAP1 downregulation...
July 5, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28676422/kinetics-of-transport-through-the-nuclear-pore-complex
#19
REVIEW
Ulrich Kubitscheck, Jan-Peter Siebrasse
Single molecule microscopy techniques allow to visualize the translocation of single transport receptors and cargo molecules or particles through nuclear pore complexes. These data indicate that cargo molecule import into the nucleus takes less than 10 milliseconds and nuclear export of messenger RNA (mRNA) particles takes 50 to 350 milliseconds, up to several seconds for extremely bulky particles. This review summarizes and discusses experimental results on transport of nuclear transport factor 2 (NTF2), importin β and mRNA particles...
July 1, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28666554/characterization-of-pharmaceutically-relevant-materials-at-the-solid-state-employing-chemometrics-methods
#20
REVIEW
Natalia L Calvo, Rubén M Maggio, Teodoro S Kaufman
The understanding of materials and processes is a requirement when it comes to build quality into pharmaceutical products. This can be achieved through the development of rapid, efficient and versatile analytical methods able to perform qualification or quantification tasks along the manufacturing and control process. Process monitoring, capable of providing reliable real-time insights into the processes performance during the manufacturing of solid dosage forms, are the key to improve such understanding. In response to these demands, in recent times multivariate chemometrics algorithms have been increasingly associated to different analytical techniques, mainly vibrational spectroscopies [Raman, mid-infrared (MIR), near-infrared (NIR)], but also ultraviolet-visible (UV-vis) spectroscopy, X-ray powder diffraction and other methodologies...
June 15, 2017: Journal of Pharmaceutical and Biomedical Analysis
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