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https://www.readbyqxmd.com/read/28446664/analysis-of-competing-hiv-1-splice-donor-sites-uncovers-a-tight-cluster-of-splicing-regulatory-elements-within-exon-2-2b
#1
Anna-Lena Brillen, Lara Walotka, Frank Hillebrand, Lisa Müller, Marek Widera, Stephan Theiss, Heiner Schaal
The HIV-1 accessory protein Vif is essential for viral replication by counteracting the host restriction factor APOBEC3G (A3G), and balanced levels of both proteins are required for efficient viral replication. Non-coding exons 2/2b contain the Vif start codon between their alternatively used splice donors 2 and 2b (D2 and D2b). For the vif mRNA, intron 1 must be removed, while intron 2 must be retained. Thus, splice acceptor 1 (A1) must be activated by U1 snRNP binding to either D2 or D2b, while splicing at D2 or D2b must be prevented...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28442575/structure-and-energetics-of-pairwise-interactions-between-proteasome-subunits-rpn2-rpn13-and-ubiquitin-clarify-a-substrate-recruitment-mechanism
#2
Ryan T VanderLinden, Casey W Hemmis, Tingting Yao, Howard Robinson, Christopher P Hill
The 26S proteasome is a large cellular assembly that mediates the selective degradation of proteins in the nucleus and cytosol and is an established target for anti-cancer therapeutics. Protein substrates are typically targeted to the proteasome through modification with a polyubiquitin chain, which can be recognized by several proteasome-associated ubiquitin receptors. One of these receptors, RPN13/ADRM1, is recruited to the proteasome through direct interaction with the large scaffolding protein RPN2 within the 19S regulatory particle...
April 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28439515/endogenous-retroviruses-with-us-and-against-us
#3
REVIEW
Thomas J Meyer, Jimi L Rosenkrantz, Lucia Carbone, Shawn L Chavez
Mammalian genomes are scattered with thousands of copies of endogenous retroviruses (ERVs), mobile genetic elements that are relics of ancient retroviral infections. After inserting copies into the germ line of a host, most ERVs accumulate mutations that prevent the normal assembly of infectious viral particles, becoming trapped in host genomes and unable to leave to infect other cells. While most copies of ERVs are inactive, some are transcribed and encode the proteins needed to generate new insertions at novel loci...
2017: Frontiers in Chemistry
https://www.readbyqxmd.com/read/28433707/genetic-susceptibility-to-toxicologic-lung-responses-among-inbred-mouse-strains-following-exposure-to-carbon-nanotubes-and-profiling-of-underlying-gene-networks
#4
Evan A Frank, Vinicius S Carreira, Kumar Shanmukhappa, Mario Medvedovic, Daniel R Prows, Jagjit S Yadav
The risk of human exposure to fiber nanoparticles has risen in recent years due to increases in the manufacture and utilization of carbon nanotubes (CNTs). CNTs are present as airborne particulates in occupational settings and their hazard potential has been demonstrated in experimental lung exposure studies using inbred mouse strains. However, it is not known whether different inbred strains differ in lung responses to CNTs by virtue of their genetics. In this work, common inbred strains (BALB/c, C57Bl/6, DBA/2, and C3H/He) were exposed to CNTs via oropharyngeal aspiration and lung histology and bronchoalveolar lavage (BAL) samples were evaluated over 28days with the objective of evaluating sensitivity/resistance among strains...
April 19, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28427840/aav-id-a-rapid-and-robust-assay-for-batch-to-batch-consistency-evaluation-of-aav-preparations
#5
Simon Pacouret, Mohammed Bouzelha, Rajani Shelke, Eva Andres-Mateos, Ru Xiao, Anna Maurer, Mathieu Mevel, Heikki Turunen, Trisha Barungi, Magalie Penaud-Budloo, Frédéric Broucque, Véronique Blouin, Philippe Moullier, Eduard Ayuso, Luk H Vandenberghe
Adeno-associated virus (AAV) vectors are promising clinical candidates for therapeutic gene transfer, and a number of AAV-based drugs may emerge on the market over the coming years. To insure the consistency in efficacy and safety of any drug vial that reaches the patient, regulatory agencies require extensive characterization of the final product. Identity is a key characteristic of a therapeutic product, as it ensures its proper labeling and batch-to-batch consistency. Currently, there is no facile, fast, and robust characterization assay enabling to probe the identity of AAV products at the protein level...
April 17, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28423226/rvx-208-a-novel-bet-protein-inhibitor-role-as-an-inducer-of-apo-a-i-hdl-and-beyond
#6
Gopal C Ghosh, Rajarshi Bhadra, Raktim K Ghosh, Kinjal Banerjee, Anjan Gupta
Low density cholesterol (LDL) has been the prime target of currently available lipid-lowering therapies although current research is expanding the focus beyond LDL lowering and has included high density cholesterol (HDL) also as the target. Bromo and extra-terminal (BET) proteins are implicated in the regulation of transcription of several regulatory genes and regulation of pro-inflammatory pathways. As atherosclerosis is an inflammatory pathway and studies showed that BET inhibition has a role in inhibiting inflammation, the concept of BET inhibition came in the field of atherosclerosis...
April 19, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28420668/hypercholesterolemia-induces-differentiation-of-regulatory-t-cells-in-the-liver
#7
Reiner K Mailer, Anton Gisterå, Konstantinos A Polyzos, Daniel F Ketelhuth, Göran K Hansson
Rationale: The liver is the central organ that responds to dietary cholesterol intake and facilitates the release and clearance of lipoprotein particles. Persistent hypercholesterolemia leads to immune responses against lipoprotein particles that drive atherosclerosis. However, the effect of hypercholesterolemia on hepatic T cell differentiation remains unknown. Objective: To investigate hepatic T cell subsets upon hypercholesterolemia. Methods and Results: We observed that hypercholesterolemia elevated the intrahepatic regulatory T (Treg) cell population and increased the expression of transforming growth factor beta 1 in the liver...
April 18, 2017: Circulation Research
https://www.readbyqxmd.com/read/28416611/the-deubiquitinating-enzyme-usp14-allosterically-inhibits-multiple-proteasomal-activities-and-ubiquitin-independent-proteolysis
#8
Hyoung Tae Kim, Alfred L Goldberg
The proteasome-associated deubiquitinating enzyme Usp14/Ubp6 inhibits protein degradation by catalyzing substrate deubiquitination and by poorly understood allosteric actions. However, upon binding a ubiquitin chain, Usp14 enhances proteasomal degradation by stimulating ATP and peptide degradation. These studies were undertaken to clarify these seemingly opposite regulatory roles of Usp14 and their importance. To learn how the presence of Usp14 on 26S proteasomes influences its different activities, we compared enzymatic and regulatory properties of 26S proteasomes purified from wild type MEF cells and ones lacking Usp14...
April 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28396413/ubiquitinated-proteins-promote-the-association-of-proteasomes-with-the-deubiquitinating-enzyme-usp14-and-the-ubiquitin-ligase-ube3c
#9
Chueh-Ling Kuo, Alfred Lewis Goldberg
In mammalian cells, the 26S proteasomes vary in composition. In addition to the standard 28 subunits in the 20S core particle and 19 subunits in each 19S regulatory particle, a small fraction (about 10-20% in our preparations) also contains the deubiquitinating enzyme Usp14/Ubp6, which regulates proteasome activity, and the ubiquitin ligase, Ube3c/Hul5, which enhances proteasomal processivity. When degradation of ubiquitinated proteins in cells was inhibited, levels of Usp14 and Ube3c on proteasomes increased within minutes...
April 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28395311/exploring-manganese-fractionation-using-a-sequential-extraction-method-to-evaluate-welders-gas-metal-arc-welding-exposures-during-heavy-equipment-manufacturing
#10
Kevin W Hanley, Ronnee Andrews, Steven Bertke, Kevin Ashley
The National Institute for Occupational Safety and Health (NIOSH) has conducted an occupational exposure assessment study of manganese (Mn) in welding fume at three factories where heavy equipment was manufactured. The objective of this study was to evaluate exposures to different Mn fractions using a sequential extraction procedure. One hundred nine worker-days were monitored for either total or respirable Mn during gas metal arc welding. The samples were analyzed using an experimental method to separate different Mn fractions based on selective chemical solubility...
January 1, 2017: Annals of Work Exposures and Health
https://www.readbyqxmd.com/read/28391931/characterization-of-particulate-matter-from-diesel-passenger-cars-tested-on-chassis-dynamometers
#11
Sungwoon Jung, Jaehyun Lim, Sangil Kwon, Sangwoo Jeon, Jeongsoo Kim, Jongtae Lee, Sunmoon Kim
Emission characterization of particle number as well as particle mass from three diesel passenger cars equipped with diesel particulate filter (DPF), diesel oxidation catalyst (DOC) and exhaust gas recirculation (EGR) under the vehicle driving cycles and regulatory cycle. Total particle number emissions (PNEs) decreased gradually during speed-up of vehicle from 17.3 to 97.3km/hr. As the average vehicle speed increases, the size-segregated peak of particle number concentration shifts to smaller size ranges of particles...
April 2017: Journal of Environmental Sciences (China)
https://www.readbyqxmd.com/read/28391123/aminomethylphosphonic-acid-ampa-in-natural-waters-its-sources-behavior-and-environmental-fate
#12
REVIEW
Alexis Grandcoin, Stéphanie Piel, Estelle Baurès
The widely occurring degradation product aminomethylphosphonic acid (AMPA) is a result of glyphosate and amino-polyphosphonate degradation. Massive use of the parent compounds leads to the ubiquity of AMPA in the environment, and particularly in water. The purpose of this review is to summarize and discuss current insights into AMPA formation, transport, persistence and toxicity. In agricultural soils, AMPA is concentrated in the topsoil, and degrades slowly in most soils. It can reach shallow groundwater, but rarely managed to enter deep groundwater...
March 27, 2017: Water Research
https://www.readbyqxmd.com/read/28360865/bosutinib-therapy-ameliorates-lung-inflammation-and-fibrosis-in-experimental-silicosis
#13
Priscila J Carneiro, Amanda L Clevelario, Gisele A Padilha, Johnatas D Silva, Jamil Z Kitoko, Priscilla C Olsen, Vera L Capelozzi, Patricia R M Rocco, Fernanda F Cruz
Silicosis is an occupational lung disease for which no effective therapy exists. We hypothesized that bosutinib, a tyrosine kinase inhibitor, might ameliorate inflammatory responses, attenuate pulmonary fibrosis, and thus improve lung function in experimental silicosis. For this purpose, we investigated the potential efficacy of bosutinib in the treatment of experimental silicosis induced in C57BL/6 mice by intratracheal administration of silica particles. After 15 days, once disease was established, animals were randomly assigned to receive DMSO or bosutinib (1 mg/kg/dose in 0...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28349962/preparation-and-characterization-of-epigallocatechin-3-gallate-egcg-loaded-nanoparticles-and-their-inhibitory-effects-on-human-breast-cancer-mcf-7-cells
#14
Liang Zeng, Jingna Yan, Liyong Luo, Mengjun Ma, Huiqun Zhu
We were employing nanotechnology to improve the targeting ability of (-)-Epigallocatechin-3-gallate (EGCG) towards MCF-7 cells, and two kinds of EGCG nanoparticles (FA-NPS-PEG and FA-PEG-NPS) were obtained, besides, their characteristics and effects on MCF-7 cells were studied. The results indicated that (i) both FA-NPS-PEG and FA-PEG-NPS have high stabilities; (ii) their particles sizes were 185.0 ± 13.5 nm and 142.7 ± 7.2 nm, respectively; (iii) their encapsulation efficiencies of EGCG were 90...
March 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331097/loss-of-the-human-cytomegalovirus-us16-protein-abrogates-virus-entry-into-endothelial-and-epithelial-cells-by-reducing-the-virion-content-of-the-pentamer
#15
Anna Luganini, Noemi Cavaletto, Stefania Raimondo, Stefano Geuna, Giorgio Gribaudo
The Human Cytomegalovirus (HCMV) US12 gene family encodes a group of predicted seven-transmembrane proteins whose functions have yet to be established. While inactivation of individual US12 members in laboratory strains of HCMV does not affect viral replication in fibroblasts, disruption of the US16 gene in the low-passage TR strain prevents viral growth in endothelial and epithelial cells. In these cells, the US16-null viruses fail to express IE, E, and L viral proteins due to a defect which occurs prior to IE gene expression...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28322792/molecular-chaperones-of-the-hsp70-family-assist-in-the-assembly-of-20s-proteasomes
#16
Lindsay J Hammack, Kyle Firestone, William Chang, Andrew R Kusmierczyk
The eukaryotic 26S proteasome is a large protease comprised of two major sub assemblies, the 20S proteasome, or core particle (CP), and the 19S regulatory particle (RP). Assembly of the CP and RP is assisted by an expanding list of dedicated assembly factors. For the CP, this includes Ump1 and the heterodimeric Pba1-Pba2 and Pba3-Pba4 proteins. It is not known how many additional proteins that assist in proteasome biogenesis remain to be discovered. Here, we demonstrate that two members of the Hsp70 family in yeast, Ssa1 and Ssa2, play a direct role in CP assembly...
March 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28294971/exploring-the-functions-of-9-lipoxygenase-dklox3-in-ultrastructural-changes-and-hormonal-stress-response-during-persimmon-fruit-storage
#17
Kun Meng, Yali Hou, Ye Han, Qiuyan Ban, Yiheng He, Jiangtao Suo, Jingping Rao
Lipoxygenase (LOX) initiates the hydroperoxidation of polyunsaturated fatty acids and is involved in multiple physiological processes. In this study, investigation of various microscopic techniques showed that the fruit peel cellular microstructure of the two persimmon cultivars differed after 12 days of storage, resulting in fruit weight loss and an increased number and depth of microcracks. Analysis of subcellular localization revealed that greater amounts of DkLOX3-immunolabelled gold particles accumulated in "Fupingjianshi" than in "Ganmaokui" during storage...
March 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28274239/occupational-exposure-to-particles-and-mitochondrial-dna-relevance-for-blood-pressure
#18
Yiyi Xu, Huiqi Li, Maria Hedmer, Mohammad Bakhtiar Hossain, Håkan Tinnerberg, Karin Broberg, Maria Albin
BACKGROUND: Particle exposure is a risk factor for cardiovascular diseases. Mitochondrial DNA (mtDNA) is a primary target for oxidative stress generated by particle exposure. We aimed to elucidate the effects of occupational exposure to particle-containing welding fumes on different biomarkers of mtDNA function, and in turn, explore if they modify the association between particle exposure and cardiovascular response, measured as blood pressure. METHODS: We investigated 101 welders and 127 controls (all non-smoking males) from southern Sweden...
March 9, 2017: Environmental Health: a Global Access Science Source
https://www.readbyqxmd.com/read/28255608/solubility-of-tin-in-aqueous-media-implications-for-regulatory-ecotoxicity-testing
#19
Iain Wilson, Adam Peters, Graham Merrington, Jeremy Pearce, Jonathan Rickwood, Paul Cusack, Kay Nimmo
Effects caused in ecotoxicity tests by physical factors due to precipitated particles cannot be used for classification in Europe under the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH). For tin (Sn), results from ecotoxicity tests have been observed to be difficult to interpret in regard to exposures of dissolved Sn. Experiments were undertaken with Sn(IV) chloride at 2-2000 µg L(-1) in aquatic test media of differing pHs and hardness. A predictive Sn precipitation model was derived using these data and speciation modelling...
March 2, 2017: Bulletin of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/28254518/effect-of-modeled-microgravity-on-radiation-induced-adaptive-response-of-root-growth-in-arabidopsis-thaliana
#20
Chenguang Deng, Ting Wang, Jingjing Wu, Wei Xu, Huasheng Li, Min Liu, Lijun Wu, Jinying Lu, Po Bian
Space particles have an inevitable impact on organisms during space missions; radio-adaptive response (RAR) is a critical radiation effect due to both low-dose background and sudden high-dose radiation exposure during solar storms. Although it is relevant to consider RAR within the context of microgravity, another major space environmental factor, there is no existing evidence as to its effects on RAR. In the present study, we established an experimental method for detecting the effects of gamma-irradiation on the primary root growth of Arabidopsis thaliana, in which RAR of root growth was significantly induced by several dose combinations...
February 2017: Mutation Research
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