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https://www.readbyqxmd.com/read/29932955/biological-mechanisms-of-non-linear-dose-response-for-respirable-mineral-fibers
#1
Louis Anthony Tony Cox
Sufficiently high and prolonged inhalation exposures to some respirable elongated mineral particles (REMPs), notably including amphibole asbestos fibers, can increase risk of inflammation-mediated diseases including malignant mesothelioma, pleural diseases, fibrosis, and lung cancer. Chronic inflammation involves ongoing activation of the NLRP3 inflammasome, which enables immune cells to produce potent proinflammatory cytokines IL-1β and IL-18. Reactive oxygen species (ROS) (in particular, mitochondrial ROS) contribute to NRLP3 activation via a well-elucidated mechanism involving oxidation of reduced thioredoxin and association of thioredoxin-interacting protein with NLRP3...
June 19, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29925569/fitness-advantages-conferred-by-the-l20-interacting-rna-cis-regulator-of-ribosomal-protein-synthesis-in-bacillus-subtilis
#2
Arianne M Babina, Darren J Parker, Gene-Wei Li, Michelle M Meyer
In many bacteria, ribosomal proteins autogenously repress their own expression by interacting with RNA structures typically located in the 5'-UTRs of their mRNA transcripts. This regulation is necessary to maintain a balance between ribosomal proteins and rRNA to ensure proper ribosome production. Despite advances in non-coding RNA discovery and validation of RNA-protein regulatory interactions, the selective pressures that govern the formation and maintenance of such RNA cis-regulators in the context of an organism remain largely undetermined...
June 20, 2018: RNA
https://www.readbyqxmd.com/read/29908710/p-bodies-cytosolic-droplets-for-coordinated-mrna-storage
#3
REVIEW
Nancy Standart, Dominique Weil
P-bodies (PBs) are cytosolic RNP granules that are conserved among eukaryotic organisms. In the past few years, major progress has been made in understanding the biochemical and biophysical mechanisms that lead to their formation. However, whether they play a role in mRNA storage or decay remains actively debated. P-bodies were recently isolated from human cells by a novel fluorescence-activated particle sorting (FAPS) approach that enabled the characterization of their protein and RNA content, providing new insights into their function...
June 13, 2018: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/29858582/antigen-specific-regulatory-t-cell-responses-against-aeroantigens-and-their-role-in-allergy
#4
REVIEW
Petra Bacher, Alexander Scheffold
The mucosal immune system of the respiratory tract is specialized to continuously monitor the external environment and to protect against invading pathogens, while maintaining tolerance to innocuous inhaled particles. Allergies result from a loss of tolerance against harmless antigens characterized by formation of allergen-specific Th2 cells and IgE. Tolerance is often described as a balance between harmful Th2 cells and various types of protective "regulatory" T cells. However, the identity of the protective T cells in healthy vs...
June 1, 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/29849065/environmental-responsiveness-of-tubulin-glutamylation-in-sensory-cilia-is-regulated-by-the-p38-mapk-pathway
#5
Yoshishige Kimura, Koji Tsutsumi, Alu Konno, Koji Ikegami, Saira Hameed, Tomomi Kaneko, Oktay Ismail Kaplan, Takayuki Teramoto, Manabi Fujiwara, Takeshi Ishihara, Oliver E Blacque, Mitsutoshi Setou
Glutamylation is a post-translational modification found on tubulin that can alter the interaction between microtubules (MTs) and associated proteins. The molecular mechanisms regulating tubulin glutamylation in response to the environment are not well understood. Here, we show that in the sensory cilia of Caenorhabditis elegans, tubulin glutamylation is upregulated in response to various signals such as temperature, osmolality, and dietary conditions. Similarly, tubulin glutamylation is modified in mammalian photoreceptor cells following light adaptation...
May 30, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29808415/immune-stimuli-shape-the-small-non-coding-transcriptome-of-extracellular-vesicles-released-by-dendritic-cells
#6
Tom A P Driedonks, Susanne G van der Grein, Yavuz Ariyurek, Henk P J Buermans, Henrike Jekel, Franklin W N Chow, Marca H M Wauben, Amy H Buck, Peter A C 't Hoen, Esther N M Nolte-'t Hoen
The release and uptake of nano-sized extracellular vesicles (EV) is a highly conserved means of intercellular communication. The molecular composition of EV, and thereby their signaling function to target cells, is regulated by cellular activation and differentiation stimuli. EV are regarded as snapshots of cells and are, therefore, in the limelight as biomarkers for disease. Although research on EV-associated RNA has predominantly focused on microRNAs, the transcriptome of EV consists of multiple classes of small non-coding RNAs with potential gene-regulatory functions...
May 28, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29803105/ingestible-roasted-barley-for-contrast-enhanced-photoacoustic-imaging-in-animal-and-human-subjects
#7
Depeng Wang, Dong Hyeun Lee, Haoyuan Huang, Tri Vu, Rachel Su Ann Lim, Nikhila Nyayapathi, Upendra Chitgupi, Maggie Liu, Jumin Geng, Jun Xia, Jonathan F Lovell
Photoacoustic computed tomography (PACT) is an emerging imaging modality. While many contrast agents have been developed for PACT, these typically cannot immediately be used in humans due to the lengthy regulatory process. We screened two hundred types of ingestible foodstuff samples for photoacoustic contrast with 1064 nm pulse laser excitation, and identified roasted barley as a promising candidate. Twenty brands of roasted barley were further screened to identify the one with the strongest contrast, presumably based on complex chemical modifications incurred during the roasting process...
May 17, 2018: Biomaterials
https://www.readbyqxmd.com/read/29795272/extracellular-vesicles-in-cancer-implications-for-future-improvements-in-cancer-care
#8
REVIEW
Rong Xu, Alin Rai, Maoshan Chen, Wittaya Suwakulsiri, David W Greening, Richard J Simpson
The sustained growth, invasion, and metastasis of cancer cells depend upon bidirectional cell-cell communication within complex tissue environments. Such communication predominantly involves the secretion of soluble factors by cancer cells and/or stromal cells within the tumour microenvironment (TME), although these cell types have also been shown to export membrane-encapsulated particles containing regulatory molecules that contribute to cell-cell communication. These particles are known as extracellular vesicles (EVs) and include species of exosomes and shed microvesicles...
May 23, 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29790401/translational-gaps-in-animal-models-of-human-infusion-reactions-to-nanomedicines
#9
S Moein Moghimi, Dmitri Simberg
Adverse infusion reactions to regulatory approved nanomedicines in human subjects are idiosyncratic, but outwardly reproducible in pigs. A large body of evidence suggests that the porcine reactions are related to robust nanoparticle clearance by pulmonary intravascular macrophages (PIMs), and rapid release of arachidonate metabolites from these cells. Similar to pigs, other animals that have resident PIMs in their lungs also respond to intravenously injected particles, where rapid particle clearance by PIMs correlate with peak periods of cardiopulmonary distress...
May 2018: Nanomedicine
https://www.readbyqxmd.com/read/29743343/multiple-effects-of-cold-exposure-on-livers-of-male-mice
#10
Aldo Grefhorst, Johanna C van den Beukel, Wieneke Dijk, Jacobie Steenbergen, Gardi J Voortman, Selmar Leeuwenburgh, Theo J Visser, Sander Kersten, Edith Ch Friesema, Axel Pn Themmen, Jenny A Visser
Cold exposure of mice is a common method to stimulate brown adipose tissue (BAT) activity and induce browning of white adipose tissue (WAT) that has beneficial effects on whole body lipid metabolism, including reduced plasma triglyceride (TG) concentrations. The liver is a key regulatory organ in lipid metabolism as it can take up as well as oxidize fatty acids. The liver can also synthesize, store and secrete triglycerides (TGs) in very low density lipoprotein (VLDL) particles. The effects of cold exposure on murine hepatic lipid metabolism have not been addressed...
May 9, 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/29739903/identification-of-the-intragenomic-promoter-controlling-hepatitis-e-virus-subgenomic-rna-transcription
#11
Qiang Ding, Ila Nimgaonkar, Nicholas F Archer, Yaron Bram, Brigitte Heller, Robert E Schwartz, Alexander Ploss
Approximately 20 million hepatitis E virus (HEV) infections occur annually in both developing and industrialized countries. Most infections are self-limiting, but they can lead to chronic infections and cirrhosis in immunocompromised patients, and death in pregnant women. The mechanisms of HEV replication remain incompletely understood due to scarcity of adequate experimental platforms. HEV undergoes asymmetric genome replication, but it produces an additional subgenomic (SG) RNA encoding the viral capsid and a viroporin in partially overlapping open reading frames...
May 8, 2018: MBio
https://www.readbyqxmd.com/read/29732666/substrate-receptors-of-proteasomes
#12
Tian-Xia Jiang, Mei Zhao, Xiao-Bo Qiu
Proteasomes are responsible for the turnover of most cellular proteins, and thus are critical to almost all cellular activities. A substrate entering the proteasome must first bind to a substrate receptor. Substrate receptors can be classified as ubiquitin receptors and non-ubiquitin receptors. The intrinsic ubiquitin receptors, including proteasome regulatory particle base subunits 1, 10 and 13 (Rpn1, Rpn10, and Rpn13), determine the capability of the proteasome to recognize a ubiquitin chain, and thus provide selectivity for the 26S proteasome...
May 6, 2018: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/29730310/analysis-and-identification-of-elongated-mineral-particles-in-road-coated-aggregates
#13
Erell Leocat, Christophe Rielland, Aurélien Urvoy, Patrice Letessier
The issue of Elongated Mineral Particles (EMP) in building materials has been revealed during roadworks in 2013 in France. In fact, road coating aggregates are made of specific rock gravels that can contain Naturally Occurring Asbestos (NOA), which is mainly actinolite. The legislation refers to six regulatory asbestos, that consist in asbestiform habitus of the six minerals. The current technical standard is not adapted for analyzing natural material, as it cannot distinguish the asbestiform fibers and the cleavage fragments fibers...
May 3, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29728587/cryo-em-of-nucleosome-core-particle-interactions-in-trans
#14
Silvija Bilokapic, Mike Strauss, Mario Halic
Nucleosomes, the basic unit of chromatin, are repetitively spaced along DNA and regulate genome expression and maintenance. The long linear chromatin molecule is extensively condensed to fit DNA inside the nucleus. How distant nucleosomes interact to build tertiary chromatin structure remains elusive. In this study, we used cryo-EM to structurally characterize different states of long range nucleosome core particle (NCP) interactions. Our structures show that NCP pairs can adopt multiple conformations, but, commonly, two NCPs are oriented with the histone octamers facing each other...
May 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29726070/a-comparative-analysis-of-heterogeneity-in-commercially-available-recombinant-factor-viii-products
#15
D Baunsgaard, A D Nielsen, P F Nielsen, A Henriksen, A K Kristensen, H W Bagger, M Ezban
INTRODUCTION: Advances in analytical technologies enable investigation of possible correlations between molecular structure, aggregation and subvisible particle content. Regulatory agencies place increasing attention on potential risks associated with protein aggregates in the micron range in biological therapeutics. AIM: Assess the heterogeneity, high-molecular-weight protein (HMWP) species, subvisible particle content and posttranslational modifications in six commercially available recombinant FVIII (rFVIII) products...
May 3, 2018: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/29720982/the-potential-biomarkers-and-immunological-effects-of-tumor-derived-exosomes-in-lung-cancer
#16
REVIEW
Shamila D Alipoor, Esmaeil Mortaz, Mohammad Varahram, Mehrnaz Movassaghi, Aletta D Kraneveld, Johan Garssen, Ian M Adcock
Lung cancer remains the leading cause of cancer-related deaths worldwide. Despite considerable achievements in lung cancer diagnosis and treatment, the global control of the disease remains problematic. In this respect, greater understanding of the disease pathology is crucially needed for earlier diagnosis and more successful treatment to be achieved. Exosomes are nano-sized particles secreted from most cells, which allow cross talk between cells and their surrounding environment via transferring their cargo...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29717206/inferring-a-nonlinear-biochemical-network-model-from-a-heterogeneous-single-cell-time-course-data
#17
Yuki Shindo, Yohei Kondo, Yasushi Sako
Mathematical modeling and analysis of biochemical reaction networks are key routines in computational systems biology and biophysics; however, it remains difficult to choose the most valid model. Here, we propose a computational framework for data-driven and systematic inference of a nonlinear biochemical network model. The framework is based on the expectation-maximization algorithm combined with particle smoother and sparse regularization techniques. In this method, a "redundant" model consisting of an excessive number of nodes and regulatory paths is iteratively updated by eliminating unnecessary paths, resulting in an inference of the most likely model...
May 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29716915/psmd5-inactivation-promotes-26s-proteasome-assembly-during-colorectal-tumor-progression
#18
Avi Levin, Adi Minis, Gadi Lalazar, Jose Rodriguez, Hermann Steller
Protein degradation by the ubiquitin-proteasome system (UPS) is central to protein homeostasis and cell survival. The active 26S proteasome is a large protease complex consisting of a catalytic 20S subunit and 19S regulatory particles. Cancer cells are exposed to considerable protein overload due to high metabolic rates, reprogrammed energy metabolism and aneuploidy. Here we report a mechanism that facilitates the assembly of active 26S proteasomes in malignant cells. Upon tumorigenic transformation of the gut epithelium, 26S proteasome assembly was significantly enhanced, but levels of individual subunits were not changed...
May 1, 2018: Cancer Research
https://www.readbyqxmd.com/read/29712961/liquid-liquid-phase-separation-of-patchy-particles-illuminates-diverse-effects-of-regulatory-components-on-protein-droplet-formation
#19
Valery Nguemaha, Huan-Xiang Zhou
Recently many cellular functions have been associated with membraneless organelles, or protein droplets, formed by liquid-liquid phase separation (LLPS). Proteins in these droplets often contain RNA-binding domains, but the effects of RNA on LLPS have been controversial. To gain better understanding on the roles of RNA and other macromolecular regulators, here we used Gibbs-ensemble simulations to determine phase diagrams of two-component patchy particles, as models for mixtures of proteins with regulatory components...
April 30, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29701768/exon-specific-u1-snrnas-improve-elp1-exon-20-definition-and-rescue-elp1-protein-expression-in-a-familial-dysautonomia-mouse-model
#20
Irving Donadon, Mirko Pinotti, Katarzyna Rajkowska, Giulia Pianigiani, Elena Barbon, Elisabetta Morini, Helena Motaln, Boris Rogelj, Federico Mingozzi, Susan A Slaugenhaupt, Franco Pagani
Familial dysautonomia (FD) is a rare genetic disease with no treatment, caused by an intronic point mutation (c.2204 + 6T>C) that negatively affects the definition of exon 20 in the Elongator complex protein 1 gene (ELP1 also known as IKBKAP). This substitution modifies the 5' splice site and, in combination with regulatory splicing factors, induces different levels of exon 20 skipping, in various tissues. Here, we evaluated the therapeutic potential of a novel class of U1 snRNA molecules, Exon-Specific U1s (ExSpeU1s), in correcting ELP1 exon 20 recognition...
April 25, 2018: Human Molecular Genetics
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