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https://www.readbyqxmd.com/read/27899666/structures-of-human-srp72-complexes-provide-insights-into-srp-rna-remodeling-and-ribosome-interaction
#1
Matthias M M Becker, Karine Lapouge, Bernd Segnitz, Klemens Wild, Irmgard Sinning
Co-translational protein targeting and membrane protein insertion is a fundamental process and depends on the signal recognition particle (SRP). In mammals, SRP is composed of the SRP RNA crucial for SRP assembly and function and six proteins. The two largest proteins SRP68 and SRP72 form a heterodimer and bind to a regulatory site of the SRP RNA. Despite their essential roles in the SRP pathway, structural information has been available only for the SRP68 RNA-binding domain (RBD). Here we present the crystal structures of the SRP68 protein-binding domain (PBD) in complex with SRP72-PBD and of the SRP72-RBD bound to the SRP S domain (SRP RNA, SRP19 and SRP68) detailing all interactions of SRP72 within SRP...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27886001/strategy-for-the-hemocompatibility-testing-of-microparticles
#2
S Braune, S Basu, K Kratz, J Bäckemo Johansson, M Reinthaler, A Lendlein, F Jung
Polymer-based microparticles are applied as non-thrombogenic or thrombogenic materials in a wide variety of intra- or extra-corporeal medical devices. As demanded by the regulatory agencies, the hemocompatibility of these blood contacting biomaterials has to be evaluated in vitro to ensure that the particle systems appropriately fulfill the envisioned function without causing undesired events such as thrombosis or inflammation. Currently described in vitro assays for hemocompatibility testing of particles comprise tests with different single cell types (e...
November 23, 2016: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/27883891/analysis-of-cell-lineage-trees-by-exact-bayesian-inference-identifies-negative-autoregulation-of-nanog-in-mouse-embryonic-stem-cells
#3
Justin Feigelman, Stefan Ganscha, Simon Hastreiter, Michael Schwarzfischer, Adam Filipczyk, Timm Schroeder, Fabian J Theis, Carsten Marr, Manfred Claassen
Many cellular effectors of pluripotency are dynamically regulated. In principle, regulatory mechanisms can be inferred from single-cell observations of effector activity across time. However, rigorous inference techniques suitable for noisy, incomplete, and heterogeneous data are lacking. Here, we introduce stochastic inference on lineage trees (STILT), an algorithm capable of identifying stochastic models that accurately describe the quantitative behavior of cell fate markers observed using time-lapse microscopy data collected from proliferating cell populations...
November 23, 2016: Cell Systems
https://www.readbyqxmd.com/read/27881804/upgrading-of-automobile-shredder-residue-via-innovative-granulation-process-regran
#4
Philip Holthaus, Moritz Kappes, Wolfgang Krumm
Stricter regulatory requirements concerning end-of-life vehicles and rising disposal costs necessitate new ways for automobile shredder residue utilisation. The shredder granulate and fibres, produced by the VW-SICON-Process, have a high energy content of more than 20 MJ kg(-1), which makes energy recovery an interesting possibility. Shredder fibres have a low bulk density of 60 kg m(-3), which prevents efficient storing and utilisation as a refuse-derived fuel. By mixing fibres with plastic-rich shredder granulate and heating the mixture, defined granules can be produced...
November 23, 2016: Waste Management & Research
https://www.readbyqxmd.com/read/27871833/oral-hesperidin-amorphization-and-improved-dissolution-properties-by-controlled-loading-onto-porous-silica
#5
Qionghua Wei, Cornelia M Keck, Rainer H Müller
The oral bioavailability of poorly soluble drugs can be improved by amorphization generated by loading into the pores of mesoporous particles (pore size 2-50nm). The main mechanisms are increased kinetic saturation solubility and dissolution velocity due to the amorphous drug state and the nano-size of the drug (=increased dissolution pressure). In this study, the maximum achievable drug loading compared to the theoretical drug loading, and the effect of drug loading degree on the dissolution properties (solubility, dissolution velocity) were investigated...
November 18, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27852850/dual-function-of-the-pul7-pul51-tegument-protein-complex-in-hsv-1-infection
#6
Anna Albecka, Danielle J Owen, Lyudmila Ivanova, Juliane Brun, Rukayya Liman, Laura Davies, M Firoz Ahmed, Susanna Colaco, Michael Hollinshead, Stephen C Graham, Colin M Crump
: The tegument of herpesviruses is a highly complex structural layer between the nucleocapsid and the envelope of virions. Tegument proteins play both structural and regulatory functions during replication and spread, but the interactions and functions of many of these proteins are poorly understood. Here we focus on two tegument proteins from herpes simplex virus-1 (HSV-1), pUL7 and pUL51, which have homologues in all other herpesviruses. We have now identified that HSV-1 pUL7 and pUL51 form a stable and direct protein-protein interaction, their expression levels rely on the presence of each other and that they function as a complex in infected cells...
November 16, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27844439/simultaneous-manipulation-and-super-resolution-fluorescence-imaging-of-individual-kinetochores-coupled-to-microtubule-tips
#7
Yi Deng, Charles L Asbury
Kinetochores are large multiprotein complexes that drive mitotic chromosome movements by mechanically coupling them to the growing and shortening tips of spindle microtubules. Kinetochores are also regulatory hubs, somehow sensing when they are erroneously attached and, in response, releasing their incorrect attachments and generating diffusible wait signals to delay anaphase until proper attachments can form. The remarkable ability of a kinetochore to sense and respond to its attachment status might stem from attachment- or tension-dependent changes in the structural arrangement of its core subcomplexes...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27842971/application-of-ich-q9-quality-risk-management-tools-for-advanced-development-of-hot-melt-coated-multiparticulate-systems
#8
Elena Stocker, Karin Becker, Siddhi Hate, Roland Hohl, Wolfgang Schiemenz, Stephan Sacher, Andreas Zimmer, Sharareh Salar-Behzadi
This study aimed to apply quality risk management based on the The International Conference on Harmonisation guideline Q9 for the early development stage of hot melt coated multiparticulate systems for oral administration. N-acetylcysteine crystals were coated with a formulation composing tripalmitin and polysorbate 65. The critical quality attributes (CQAs) were initially prioritized using failure mode and effects analysis. The CQAs of the coated material were defined as particle size, taste-masking efficiency, and immediate release profile...
November 11, 2016: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27827897/comparative-analysis-of-toxic-responses-of-organic-extracts-from-diesel-and-selected-alternative-fuels-engine-emissions-in-human-lung-beas-2b-cells
#9
Helena Libalova, Pavel Rossner, Kristyna Vrbova, Tana Brzicova, Jitka Sikorova, Michal Vojtisek-Lom, Vit Beranek, Jiri Klema, Miroslav Ciganek, Jiri Neca, Katerina Pencikova, Miroslav Machala, Jan Topinka
This study used toxicogenomics to identify the complex biological response of human lung BEAS-2B cells treated with organic components of particulate matter in the exhaust of a diesel engine. First, we characterized particles from standard diesel (B0), biodiesel (methylesters of rapeseed oil) in its neat form (B100) and 30% by volume blend with diesel fuel (B30), and neat hydrotreated vegetable oil (NEXBTL100). The concentration of polycyclic aromatic hydrocarbons (PAHs) and their derivatives in organic extracts was the lowest for NEXBTL100 and higher for biodiesel...
November 3, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27820806/large-scale-atp-independent-nucleosome-unfolding-by-a-histone-chaperone
#10
Maria E Valieva, Grigoriy A Armeev, Kseniya S Kudryashova, Nadezhda S Gerasimova, Alexey K Shaytan, Olga I Kulaeva, Laura L McCullough, Tim Formosa, Pavel G Georgiev, Mikhail P Kirpichnikov, Vasily M Studitsky, Alexey V Feofanov
DNA accessibility to regulatory proteins is substantially influenced by nucleosome structure and dynamics. The facilitates chromatin transcription (FACT) complex increases the accessibility of nucleosomal DNA, but the mechanism and extent of its nucleosome reorganization activity are unknown. Here we determined the effects of FACT from the yeast Saccharomyces cerevisiae on single nucleosomes by using single-particle Förster resonance energy transfer (spFRET) microscopy. FACT binding results in dramatic ATP-independent, symmetrical and reversible DNA uncoiling that affects at least 70% of the DNA within a nucleosome, occurs without apparent loss of histones and proceeds via an 'all-or-none' mechanism...
November 7, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27814492/the-aaa-atpase-mdn1-acts-as-a-sumo-targeted-regulator-in-mammalian-pre-ribosome-remodeling
#11
Nithya Raman, Elisabeth Weir, Stefan Müller
Biogenesis of translation-competent 80S ribosomes is a multi-step process requiring the sequential action of non-ribosomal trans-acting factors. We previously identified the human PELP1-TEX10-WDR18 complex and the associated SUMO isopeptidase SENP3 as regulators of 60S maturation. We provided evidence that deconjugating SUMO from PELP1 by SENP3 is instrumental for proper ribosome biogenesis. Here we show that SUMO conjugation/deconjugation of PELP1 controls its dynamic association with the AAA ATPase MDN1, a key factor of pre-60S remodeling...
November 3, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27791164/structural-basis-for-dynamic-regulation-of-the-human-26s-proteasome
#12
Shuobing Chen, Jiayi Wu, Ying Lu, Yong-Bei Ma, Byung-Hoon Lee, Zhou Yu, Qi Ouyang, Daniel J Finley, Marc W Kirschner, Youdong Mao
The proteasome is the major engine of protein degradation in all eukaryotic cells. At the heart of this machine is a heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitylated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides. Using cryoelectron microscopy, we determined a near-atomic-resolution structure of the 2.5-MDa human proteasome in its ground state, as well as subnanometer-resolution structures of the holoenzyme in three alternative conformational states...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27784991/development-of-a-microparticle-based-dry-powder-inhalation-formulation-of-ciprofloxacin-hydrochloride-applying-the-quality-by-design-approach
#13
Keyhaneh Karimi, Edina Pallagi, Piroska Szabó-Révész, Ildikó Csóka, Rita Ambrus
Pulmonary drug delivery of ciprofloxacin hydrochloride offers effective local antibacterial activity and convenience of easy application. Spray drying is a trustworthy technique for the production of ciprofloxacin hydrochloride microparticles. Quality by design (QbD), an up-to-date regulatory-based quality management method, was used to predict the final quality of the product. According to the QbD-based theoretical preliminary parameter ranking and priority classification, dry powder inhalation formulation tests were successfully performed in practice...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27782208/differential-expression-of-lncrnas-during-the-hiv-replication-cycle-an-underestimated-layer-in-the-hiv-host-interplay
#14
Wim Trypsteen, Pejman Mohammadi, Clarissa Van Hecke, Pieter Mestdagh, Steve Lefever, Yvan Saeys, Pieter De Bleser, Jo Vandesompele, Angela Ciuffi, Linos Vandekerckhove, Ward De Spiegelaere
Studying the effects of HIV infection on the host transcriptome has typically focused on protein-coding genes. However, recent advances in the field of RNA sequencing revealed that long non-coding RNAs (lncRNAs) add an extensive additional layer to the cell's molecular network. Here, we performed transcriptome profiling throughout a primary HIV infection in vitro to investigate lncRNA expression at the different HIV replication cycle processes (reverse transcription, integration and particle production). Subsequently, guilt-by-association, transcription factor and co-expression analysis were performed to infer biological roles for the lncRNAs identified in the HIV-host interplay...
October 26, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27773535/n6-methyladenosine-in-flaviviridae-viral-rna-genomes-regulates-infection
#15
Nandan S Gokhale, Alexa B R McIntyre, Michael J McFadden, Allison E Roder, Edward M Kennedy, Jorge A Gandara, Sharon E Hopcraft, Kendra M Quicke, Christine Vazquez, Jason Willer, Olga R Ilkayeva, Brittany A Law, Christopher L Holley, Mariano A Garcia-Blanco, Matthew J Evans, Mehul S Suthar, Shelton S Bradrick, Christopher E Mason, Stacy M Horner
The RNA modification N6-methyladenosine (m(6)A) post-transcriptionally regulates RNA function. The cellular machinery that controls m(6)A includes methyltransferases and demethylases that add or remove this modification, as well as m(6)A-binding YTHDF proteins that promote the translation or degradation of m(6)A-modified mRNA. We demonstrate that m(6)A modulates infection by hepatitis C virus (HCV). Depletion of m(6)A methyltransferases or an m(6)A demethylase, respectively, increases or decreases infectious HCV particle production...
November 9, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/27773482/regulatory-t-cell-specificity-directs-tolerance-versus-allergy-against-aeroantigens-in-humans
#16
Petra Bacher, Frederik Heinrich, Ulrik Stervbo, Mikalai Nienen, Marco Vahldieck, Christina Iwert, Katrin Vogt, Jutta Kollet, Nina Babel, Birgit Sawitzki, Carsten Schwarz, Stefan Bereswill, Markus M Heimesaat, Guido Heine, Gabriele Gadermaier, Claudia Asam, Mario Assenmacher, Olaf Kniemeyer, Axel A Brakhage, Fátima Ferreira, Michael Wallner, Margitta Worm, Alexander Scheffold
FOXP3+ regulatory T cells (Tregs) maintain tolerance against self-antigens and innocuous environmental antigens. However, it is still unknown whether Treg-mediated tolerance is antigen specific and how Treg specificity contributes to the selective loss of tolerance, as observed in human immunopathologies such as allergies. Here, we used antigen-reactive T cell enrichment to identify antigen-specific human Tregs. We demonstrate dominant Treg-mediated tolerance against particulate aeroallergens, such as pollen, house dust mites, and fungal spores...
October 18, 2016: Cell
https://www.readbyqxmd.com/read/27753031/vesicular-and-extra-vesicular-rnas-of-human-blood-plasma
#17
Anna V Savelyeva, Dmitriy N Baryakin, Elena D Chikova, Elena V Kuligina, Vladimir A Richter, Dmitriy V Semenov
Human blood contains a great variety of membrane-covered RNA carrying vesicles which are spherical or tubular particles enclosed by a phospholipid bilayer. Circulating vesicles are thought to mediate cell-to-cell communication and their RNA cargo can act as regulatory molecules. In this work, we separated blood plasma of healthy donors by centrifugation and determined that vesicles precipitated at 16,000 g were enriched with CD41a, marker of platelets. At 160,000 g, the pellets were enriched with CD3 marker of T cells...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27733337/progress-on-the-autophagic-regulators-and-receptors-in-plants
#18
Zeng Xiaowei, Liu Cuicui, Han Ning, Bian Hongwu, Zhu Muyuan
Autophagy is an evolutionarily highly conserved catabolic pathway among eukaryotic cells that protects the organisms against environmental stress. Normally, autophagy is mainly involved with autophagy-related proteins(ATGs) and autophagic regulators including a series of cytoplasmic proteins and small molecules. Besides, the selective autophagy, which targets damaged organalles or protein aggregates, is mediated by the additional receptors to help the ATGs recognize different substrates. In this review, we summarize recent advances in autophagic regulators like ROS(Reactive oxygen species), TOR(Target of rapamycin) and receptors like NBR1(Neighbor of BRCA1 gene protein), RPN10(Regulatory particle non-ATPase 10) as well as their functional mechanisms mainly in Arabidopsis thaliana...
July 20, 2016: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/27730650/the-integrative-role-of-cryo-electron-microscopy-in-molecular-and-cellular-structural-biology
#19
Igor Orlov, Alexander G Myasnikov, Leonid Andronov, S Kundhavai Natchiar, Heena Khatter, Brice Beinsteiner, Jean-François Ménétret, Isabelle Hazemann, Kareem Mohideen, Karima Tazibt, Rachel Tabaroni, Hanna Kratzat, Nadia Djabeur, Tatiana Bruxelles, Finaritra Raivoniaina, Lorenza di Pompeo, Morgan Torchy, Isabelle Billas, Alexandre Urzhumtsev, Bruno P Klaholz
After gradually moving away from preparation methods prone to artefacts such as plastic embedding and negative staining for cell sections and single particles, the field of cryo electron microscopy is now heading off at unprecedented speed towards high-resolution analysis of biological objects of various sizes. This "revolution in resolution" is happening largely thanks to new developments of new-generation cameras used for recording the images in the cryo electron microscope which have much increased sensitivity being based on CMOS devices...
October 12, 2016: Biology of the Cell
https://www.readbyqxmd.com/read/27717530/effect-of-silver-nano-particles-on-soil-microbial-growth-activity-and-community-diversity-in-a-sandy-loam-soil
#20
A D Samarajeewa, J R Velicogna, J I Princz, R M Subasinghe, R P Scroggins, L A Beaudette
Silver nano-particles (AgNPs) are widely used in a range of consumer products as a result of their antimicrobial properties. Given the broad spectrum of uses, AgNPs have the potential for being released to the environment. As a result, environmental risks associated with AgNPs need to be assessed to aid in the development of regulatory guidelines. Research was performed to assess the effects of AgNPs on soil microbial activity and diversity in a sandy loam soil with an emphasis on using a battery of microbial tests involving multiple endpoints...
January 2017: Environmental Pollution
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