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https://www.readbyqxmd.com/read/28213379/slowed-decay-of-mrnas-enhances-platelet-specific-translation
#1
Eric W Mills, Rachel Green, Nicholas T Ingolia
Platelets are anucleate cytoplasmic fragments that lack genomic DNA, but continue to synthesize protein using a pool of mRNAs, ribosomes, and regulatory small RNAs inherited from the precursor megakaryocyte (MK). The regulatory processes that shape the platelet transcriptome and the full scope of platelet translation have remained elusive. Using RNA-Seq and ribosome profiling of primary human platelets, we show the platelet transcriptome encompasses a subset of transcripts detected by RNA-Seq analysis of in vitro derived MK cells and these platelet-enriched transcripts are broadly occupied by ribosomes...
February 17, 2017: Blood
https://www.readbyqxmd.com/read/28208333/stochastic-liouville-equation-for-particles-driven-by-dichotomous-environmental-noise
#2
Paul C Bressloff
We analyze the stochastic dynamics of a large population of noninteracting particles driven by a global environmental input in the form of a dichotomous Markov noise process (DMNP). The population density of particle states evolves according to a stochastic Liouville equation with respect to different realizations of the DMNP. We then exploit the connection with previous work on diffusion in randomly switching environments, in order to derive moment equations for the distribution of solutions to the stochastic Liouville equation...
January 2017: Physical Review. E
https://www.readbyqxmd.com/read/28177948/silicosis-and-autoimmunity
#3
Suni Lee, Hiroaki Hayashi, Hidenori Mastuzaki, Naoko Kumagai-Takei, Takemi Otsuki
PURPOSE OF REVIEW: Of the various environmental, occupational, and medical substances that cause dysregulation of autoimmunity, the effects and causative mechanisms of silica particles and asbestos fibers are discussed in this review. RECENT FINDINGS: With respect to silica, many epidemiological studies have shown a significant association between silica exposure and the occurrence of autoimmune diseases. Although the importance of the NACHT, LRR and PYD domains-containing protein 3 (NALP3) inflammasome as the initial immune reaction against silica particles has been identified, the mechanisms involved that lead to various autoimmune diseases in patients exposed to silica remain largely unknown...
February 7, 2017: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28163227/comparison-of-the-physical-characteristics-of-monodisperse-non-ionic-surfactant-vesicles-nisv-prepared-using-different-manufacturing-methods
#4
Mohammad A Obeid, Ayman M Gebril, Rothwelle J Tate, Alexander B Mullen, Valerie A Ferro
Non-ionic surfactant vesicles (NISV) are synthetic membrane vesicles formed by self-assembly of a non-ionic surfactant, often in a mixture with cholesterol and a charged chemical species. Different methods can be used to manufacture NISV, with the majority of these requiring bulk mixing of two phases. This mixing process is time-consuming and leads to the preparation of large and highly dispersed vesicles, which affects the consistency of the final product and could hinder subsequent regulatory approval. In this study, we have compared the physical characteristics of NISV prepared using two conventional methods (thin-film hydration method and heating method) with a recently introduced microfluidic method...
February 3, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28161413/relaxed-and-active-thin-filament-structures-a-new-structural-basis-for-the-regulatory-mechanism
#5
Danielle M Paul, John M Squire, Edward P Morris
The structures of muscle thin filaments reconstituted using skeletal actin and cardiac troponin and tropomyosin have been determined with and without bound Ca(2+) using electron microscopy and reference-free single particle analysis. The resulting density maps have been fitted with atomic models of actin, tropomyosin and troponin showing that: (i) the polarity of the troponin complex is consistent with our 2009 findings, with large shape changes in troponin between the two states; (ii) without Ca(2+) the tropomyosin pseudo-repeats all lie at almost equivalent positions in the 'blocked' position on actin (over subdomains 1 and 2); (iii) in the active state the tropomyosin pseudo-repeats are all displaced towards subdomains 3 and 4 of actin, but the extent of displacement varies within the regulatory unit depending upon the axial location of the pseudo-repeats with respect to troponin...
February 1, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/28159641/micro-flow-imaging-analyses-reflect-mechanisms-of-aggregate-formation-comparing-protein-particle-data-sets-using-the-kullback-leibler-divergence
#6
Nathaniel R Maddux, Austin L Daniels, Theodore W Randolph
Sub-visible particles in therapeutic protein formulations are an increasing manufacturing and regulatory concern due to their potential to cause adverse immune responses. Flow imaging microscopy is used extensively to detect sub-visible particles and investigate product deviations, typically by comparing imaging data using histograms of particle descriptors. Such an approach discards much information, and requires effort to interpret differences, which is problematic when comparing many data sets. We propose to compare imaging data by using the Kullback-Leibler divergence, an information theoretic measure of the difference of distributions...
January 31, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28157115/radiation-shielding-analysis-of-a-special-linear-accelerator-for-electron-beam-and%C3%A2-x-ray
#7
W G Kang, S H Pyo, T S Alkhuraiji, B S Han, C M Kang
The King AbdulAziz City for Science & Technology in the Kingdom of Saudi Arabia plans to build a 10 MeV, 15 kW linear accelerator (LINAC) for electron beam and X-ray. The accelerator will be supplied by EB Tech, Republic of Korea, and the design and construction of the accelerator building will be conducted in the cooperation with EB Tech. This report presents the shielding analysis of the accelerator building using the Monte Carlo N-Particle Transport Code (MCNP). In order to improve the accuracy in estimating deep radiation penetration and to reduce computation time, various variance reduction techniques, including the weight window (WW) method, the deterministic transport (DXTRAN) spheres were considered...
January 31, 2017: Journal of X-ray Science and Technology
https://www.readbyqxmd.com/read/28143946/cellular-proteomes-drive-tissue-specific-regulation-of-the-heat-shock-response
#8
Jian Ma, Christopher E Grant, Rosemary N Plagens, Lindsey N Barrett, Karen S Kim Guisbert, Eric Guisbert
The heat shock response (HSR) is a cellular stress response that senses protein misfolding and restores protein folding homeostasis, or proteostasis. We previously identified an HSR regulatory network in Caenorhabditis elegans consisting of highly conserved genes that have important cellular roles in maintaining proteostasis. Unexpectedly, the effects of these genes on the heat shock response are distinctly tissue-specific. Here, we explore this apparent discrepancy and find that muscle-specific regulation of the HSR by the TRiC/CCT chaperonin is not driven by an enrichment of TRiC/CCT in muscle, but rather by the levels of one of its most abundant substrates, actin...
January 30, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28116870/multicomponent-injectable-hydrogels-for-antigen-specific-tolerogenic-immune-modulation
#9
Catia S Verbeke, Susana Gordo, David A Schubert, Sarah A Lewin, Rajiv M Desai, Jessica Dobbins, Kai W Wucherpfennig, David J Mooney
Biomaterial scaffolds that enrich and modulate immune cells in situ can form the basis for potent immunotherapies to elicit immunity or reëstablish tolerance. Here, the authors explore the potential of an injectable, porous hydrogel to induce a regulatory T cell (Treg) response by delivering a peptide antigen to dendritic cells in a noninflammatory context. Two methods are described for delivering the BDC peptide from pore-forming alginate gels in the nonobese diabetic mouse model of type 1 diabetes: encapsulation in poly(lactide-co-glycolide) (PLG) microparticles, or direct conjugation to the alginate polymer...
January 24, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28115689/structural-insights-into-the-functional-cycle-of-the-atpase-module-of-the-26s-proteasome
#10
Marc Wehmer, Till Rudack, Florian Beck, Antje Aufderheide, Günter Pfeifer, Jürgen M Plitzko, Friedrich Förster, Klaus Schulten, Wolfgang Baumeister, Eri Sakata
In eukaryotic cells, the ubiquitin-proteasome system (UPS) is responsible for the regulated degradation of intracellular proteins. The 26S holocomplex comprises the core particle (CP), where proteolysis takes place, and one or two regulatory particles (RPs). The base of the RP is formed by a heterohexameric AAA(+) ATPase module, which unfolds and translocates substrates into the CP. Applying single-particle cryo-electron microscopy (cryo-EM) and image classification to samples in the presence of different nucleotides and nucleotide analogs, we were able to observe four distinct conformational states (s1 to s4)...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28114192/fda-benchmark-medical-device-flow-models-for-cfd-validation
#11
Richard A Malinauskas, Prasanna Hariharan, Steven W Day, Luke H Herbertson, Martin Buesen, Ulrich Steinseifer, Kenneth I Aycock, Bryan C Good, Steven Deutsch, Keefe B Manning, Brent A Craven
Computational fluid dynamics (CFD) is increasingly being used to develop blood-contacting medical devices. However, the lack of standardized methods for validating CFD simulations and blood damage predictions limits its use in the safety evaluation of devices. Through a U.S. Food and Drug Administration (FDA) initiative, two benchmark models of typical device flow geometries (nozzle and centrifugal blood pump) were tested in multiple laboratories to provide experimental velocities, pressures, and hemolysis data to support CFD validation...
March 2017: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
https://www.readbyqxmd.com/read/28109126/a-step-wise-approach-to-define-binding-mechanisms-of-surrogate-viral-particles-to-multi-modal-anion-exchange-resin-in-a-single-solute-system
#12
Matthew Brown, Sarah Johnson, Kurt Brorson, Scott Lute, David Roush
Multi-modal anion exchange resins combine properties of both anion exchange and hydrophobic interaction chromatography for commercial protein polishing and may provide some viral clearance as well. From a regulatory viral clearance claim standpoint, it is unclear if multi-modal resins are truly orthogonal to either single-mode anion exchange or hydrophobic interaction columns. To answer this, a strategy of solute surface assays and High Throughput Screening of resin in concert with a scale-down model of large scale chromatography purification was employed to determine the predominant binding mechanisms of a panel of bacteriophage (i...
January 21, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28106109/center-of-mass-in-complex-networks
#13
Chuanji Fu, Yachun Gao, Shimin Cai, Hongchun Yang, Chun Yang
Network dynamics is always a big challenge in nonlinear dynamics. Although great advancements have been made in various types of complex systems, an universal theoretical framework is required. In this paper, we introduce the concept of center of 'mass' of complex networks, where 'mass' stands for node importance or centrality in contrast to that of particle systems, and further prove that the phase transition and evolutionary state of the system can be characterized by the activity of center of 'mass'. The steady states of several complex networks (gene regulatory networks and epidemic spreading systems) are then studied by analytically calculating the decoupled equation of the dynamic activity of center of 'mass', which is derived from the dynamic equation of the complex networks...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28106049/food-grade-tio2-impairs-intestinal-and-systemic-immune-homeostasis-initiates-preneoplastic-lesions-and-promotes-aberrant-crypt-development-in-the-rat-colon
#14
Sarah Bettini, Elisa Boutet-Robinet, Christel Cartier, Christine Coméra, Eric Gaultier, Jacques Dupuy, Nathalie Naud, Sylviane Taché, Patrick Grysan, Solenn Reguer, Nathalie Thieriet, Matthieu Réfrégiers, Dominique Thiaudière, Jean-Pierre Cravedi, Marie Carrière, Jean-Nicolas Audinot, Fabrice H Pierre, Laurence Guzylack-Piriou, Eric Houdeau
Food-grade titanium dioxide (TiO2) containing a nanoscale particle fraction (TiO2-NPs) is approved as a white pigment (E171 in Europe) in common foodstuffs, including confectionary. There are growing concerns that daily oral TiO2-NP intake is associated with an increased risk of chronic intestinal inflammation and carcinogenesis. In rats orally exposed for one week to E171 at human relevant levels, titanium was detected in the immune cells of Peyer's patches (PP) as observed with the TiO2-NP model NM-105. Dendritic cell frequency increased in PP regardless of the TiO2 treatment, while regulatory T cells involved in dampening inflammatory responses decreased with E171 only, an effect still observed after 100 days of treatment...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28104452/cystoviral-rna-directed-rna-polymerases-regulation-of-rna-synthesis-on-multiple-time-and-length-scales
#15
REVIEW
Sébastien Alphonse, Ranajeet Ghose
P2, an RNA-directed RNA polymerase (RdRP), is encoded on the largest of the three segments of the double-stranded RNA genome of cystoviruses. P2 performs the dual tasks of replication and transcription de novo on single-stranded RNA templates, and plays a critical role in the viral life-cycle. Work over the last few decades has yielded a wealth of biochemical and structural information on the functional regulation of P2, on its role in the spatiotemporal regulation of RNA synthesis and its variability across the Cystoviridae family...
January 16, 2017: Virus Research
https://www.readbyqxmd.com/read/28098491/particle-sizing-methods-for-the-detection-of-protein-aggregates-in-biopharmaceuticals
#16
REVIEW
Akram Khodabandehloo, David Da Yong Chen
Protein aggregation is a common biological phenomenon which is responsible for degenerative diseases and is problematic in the pharmaceutical industry. According to the rules provided by regulatory agencies, industry is supposed to assess the product quality regarding the presence of subvisible particles. Also, they should evaluate the technologies that are used to measure these particles. Therefore, US FDA and industry have been looking for methods capable of accurately characterizing the protein products...
February 2017: Bioanalysis
https://www.readbyqxmd.com/read/28076890/suppression-of-osteogenic-activity-by-regulation-of-wnt-and-bmp-signaling-during-titanium-particle-induced-osteolysis
#17
Ju-Suk Nam, Ashish Ranjan Sharma, Supriya Jagga, Dong-Hyun Lee, Garima Sharma, Lich Thi Nguyen, Yeon Hee Lee, Jun-Dong Chang, Chiranjib Chakraborty, Sang-Soo Lee
Periprosthetic osteolysis remains the leading obstacle for total joint replacements. Primarily, it was thought that aseptic loosening is mainly caused by macrophage mediated inflammatory process arising from production of wear debris. The role of osteoclasts and its sequential bone resorption ability has been extensively studied, but little is known about impaired osteogenesis during osteolysis. In the current study, we have tried to delineate the regulatory mechanism of osteogenic signals by Ti particles in osteoprogenitor cells as well its participatory role in wear debris induced osteolysis...
March 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28073444/modelling-the-hydrodynamic-conditions-associated-with-dinophysis-blooms-in-galicia-nw-spain
#18
Manuel Ruiz-Villarreal, Luz M García-García, Marcos Cobas, Patricio A Díaz, Beatriz Reguera
The northwestern Iberian coast (Galician Rías and shelf) is frequently affected by toxic harmful algal blooms (HABs) (mainly Dinophysis spp.), leading to lengthy harvesting closures in a region where aquaculture has a strong socioeconomic impact. The project ASIMUTH (http://www.asimuth.eu) aimed to develop forecasting capabilities to warn of impending HABs along the European Atlantic coast. Simulations with the ROMS model (hydrodynamical and ecological simulations complemented with Lagrangian particle tracking simulations) of the Galician coastal circulation have been performed in the framework of the ASIMUTH project to characterize and forecast oceanographic conditions before and during HAB periods...
March 2016: Harmful Algae
https://www.readbyqxmd.com/read/28059715/control-of-meiotic-pairing-and-recombination-by-chromosomally-tethered-26s-proteasome
#19
Jasvinder S Ahuja, Rima Sandhu, Rana Mainpal, Crystal Lawson, Hanna Henley, Patricia A Hunt, Judith L Yanowitz, G Valentin Börner
During meiosis, paired homologous chromosomes (homologs) become linked via the synaptonemal complex (SC) and crossovers. Crossovers mediate homolog segregation and arise from self-inflicted double-strand breaks (DSBs). Here, we identified a role for the proteasome, the multisubunit protease that degrades proteins in the nucleus and cytoplasm, in homolog juxtaposition and crossing over. Without proteasome function, homologs failed to pair and instead remained associated with nonhomologous chromosomes. Although dispensable for noncrossover formation, a functional proteasome was required for a coordinated transition that entails SC assembly between longitudinally organized chromosome axes and stable strand exchange of crossover-designated DSBs...
January 27, 2017: Science
https://www.readbyqxmd.com/read/28053097/subcellular-localization-of-hiv-1-gag-pol-mrnas-regulates-sites-of-virion-assembly
#20
Jordan T Becker, Nathan M Sherer
: HIV-1 full-length, unspliced RNAs serve dual roles in the cytoplasm as mRNAs encoding the Gag and Gag-Pol capsid proteins as well as genomic RNAs (gRNAs) packaged by Gag into virions undergoing assembly at the plasma membrane (PM). Because Gag is sufficient to drive assembly of virus-like particles even in the absence of gRNA binding, whether viral RNA trafficking plays an active role in the native assembly pathway is unknown. In this study we tested the effects of modulating the cytoplasmic abundance or distribution of full-length viral RNAs on Gag trafficking and assembly in the context of single cells...
January 4, 2017: Journal of Virology
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