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https://www.readbyqxmd.com/read/28637296/omixcore-a-web-server-for-prediction-of-protein-interactions-with-large-rna
#1
Alexandros Armaos, Davide Cirillo, Gian Gaetano Tartaglia
Summary: Here we introduce omiXcore, a server for calculations of protein binding to large RNAs (> 500 nucleotides). Our webserver allows (i) use of both protein and RNA sequences without size restriction; (ii) pre-compiled library for exploration of human long intergenic RNAs (lincRNAs) interactions; (iii) prediction of binding sites. Results: omiXcore was trained and tested on enhanced UV Cross-Linking and ImmunoPrecipitation (eCLIP) data. The method discriminates interacting and non-interacting protein-RNA pairs and identifies RNA binding sites with Areas under the ROC curve > 0...
June 15, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28637186/cpg-and-methylation-dependent-dna-binding-and-dynamics-of-the-methylcytosine-binding-domain-2-protein-at-the-single-molecule-level
#2
Hai Pan, Stephanie M Bilinovich, Parminder Kaur, Robert Riehn, Hong Wang, David C Williams
The methylcytosine-binding domain 2 (MBD2) protein recruits the nucleosome remodeling and deacetylase complex (NuRD) to methylated DNA to modify chromatin and regulate transcription. Importantly, MBD2 functions within CpG islands that contain 100s to 1000s of potential binding sites. Since NuRD physically rearranges nucleosomes, the dynamic mobility of this complex is directly related to function. In these studies, we use NMR and single-molecule atomic force microscopy and fluorescence imaging to study DNA binding dynamics of MBD2...
June 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28637003/structural-recognition-of-tubulysin-b-derivatives-by-multidrug-resistance-efflux-transporters-in-human-cancer-cells
#3
Michal Stark, Yehuda G Assaraf
Multidrug resistance (MDR) is a major hindrance to curative chemotherapy of various human malignancies. Hence, novel chemotherapeutics must be evaluated for their recognition by MDR efflux transporters. Herein we explored the cytotoxic activity of synthetic tubulysin B (Tub-B, EC1009) derivatives (Tub-B-hydrazide/EC0347 and Tub-B bis-ether/EC1820), and their recognition by the MDR efflux transporters P-glycoprotein 1 (P-gp), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP)...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636969/human-virus-derived-small-rnas-can-confer-antiviral-immunity-in-mammals
#4
Yang Qiu, Yanpeng Xu, Yao Zhang, Hui Zhou, Yong-Qiang Deng, Xiao-Feng Li, Meng Miao, Qiang Zhang, Bo Zhong, Yuanyang Hu, Fu-Chun Zhang, Ligang Wu, Cheng-Feng Qin, Xi Zhou
RNA interference (RNAi) functions as a potent antiviral immunity in plants and invertebrates; however, whether RNAi plays antiviral roles in mammals remains unclear. Here, using human enterovirus 71 (HEV71) as a model, we showed HEV71 3A protein as an authentic viral suppressor of RNAi during viral infection. When the 3A-mediated RNAi suppression was impaired, the mutant HEV71 readily triggered the production of abundant HEV71-derived small RNAs with canonical siRNA properties in cells and mice. These virus-derived siRNAs were produced from viral dsRNA replicative intermediates in a Dicer-dependent manner and loaded into AGO, and they were fully active in degrading cognate viral RNAs...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636938/the-ldb1-complex-co-opts-ctcf-for-erythroid-lineage-specific-long-range-enhancer-interactions
#5
Jongjoo Lee, Ivan Krivega, Ryan K Dale, Ann Dean
Lineage-specific transcription factors are critical for long-range enhancer interactions, but direct or indirect contributions of architectural proteins such as CCCTC-binding factor (CTCF) to enhancer function remain less clear. The LDB1 complex mediates enhancer-gene interactions at the β-globin locus through LDB1 self-interaction. We find that an LDB1-bound enhancer upstream of carbonic anhydrase 2 (Car2) activates its expression by interacting directly with CTCF at the gene promoter. Both LDB1 and CTCF are required for enhancer-Car2 looping, and the domain of LDB1 contacted by CTCF is necessary to rescue Car2 transcription in LDB1-deficient cells...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636595/nlrp9b-inflammasome-restricts-rotavirus-infection-in-intestinal-epithelial-cells
#6
Shu Zhu, Siyuan Ding, Penghua Wang, Zheng Wei, Wen Pan, Noah W Palm, Yi Yang, Hua Yu, Hua-Bing Li, Geng Wang, Xuqiu Lei, Marcel R de Zoete, Jun Zhao, Yunjiang Zheng, Haiwei Chen, Yujiao Zhao, Kellie A Jurado, Ningguo Feng, Liang Shan, Yuval Kluger, Jun Lu, Clara Abraham, Erol Fikrig, Harry B Greenberg, Richard A Flavell
Rotavirus, a leading cause of severe gastroenteritis and diarrhoea in young children, accounts for around 215,000 deaths annually worldwide. Rotavirus specifically infects the intestinal epithelial cells in the host small intestine and has evolved strategies to antagonize interferon and NF-κB signalling, raising the question as to whether other host factors participate in antiviral responses in intestinal mucosa. The mechanism by which enteric viruses are sensed and restricted in vivo, especially by NOD-like receptor (NLR) inflammasomes, is largely unknown...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28636213/distribution-and-hypoxia-regulation-of-haemocyanin-in-springtails-collembola
#7
S Flachsbarth, M Kruse, T Burmester
Haemocyanin is the copper-containing respiratory protein present in many arthropods. In the hexapods, respiratory proteins had long been considered unnecessary as sufficient O2 was thought to be obtained via the trachea. Nevertheless, many ametabolous and hemimetabolous hexapod species actually possess haemocyanin. Here we investigated the occurrence of haemocyanin in Collembola (springtails). Haemocyanin was found in 22 collembolan species of the suborders Symphypleona, Tomoceroidea and Entomobryomorpha, demonstrating its widespread occurrence...
June 21, 2017: Insect Molecular Biology
https://www.readbyqxmd.com/read/28635953/rare-rnf213-variants-in-the-c-terminal-region-encompassing-the-ring-finger-domain-are-associated-with-moyamoya-angiopathy-in-caucasians
#8
Stéphanie Guey, Markus Kraemer, Dominique Hervé, Thomas Ludwig, Manoëlle Kossorotoff, Françoise Bergametti, Jan Claudius Schwitalla, Simone Choi, Lucile Broseus, Isabelle Callebaut, Emmanuelle Genin, Elisabeth Tournier-Lasserve
Moyamoya angiopathy (MMA) is a cerebral angiopathy affecting the terminal part of internal carotid arteries. Its prevalence is 10 times higher in Japan and Korea than in Europe. In East Asian countries, moyamoya is strongly associated to the R4810K variant in the RNF213 gene that encodes for a protein containing a RING-finger and two AAA+ domains. This variant has never been detected in Caucasian MMA patients, but several rare RNF213 variants have been reported in Caucasian cases. Using a collapsing test based on exome data from 68 European MMA probands and 573 ethnically matched controls, we showed a significant association between rare missense RNF213 variants and MMA in European patients (odds ratio (OR)=2...
June 21, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28635671/rab33b-controls-hepatitis-b-virus-assembly-by-regulating-core-membrane-association-and-nucleocapsid-processing
#9
Christina Bartusch, Tatjana Döring, Reinhild Prange
Many viruses take advantage of cellular trafficking machineries to assemble and release new infectious particles. Using RNA interference (RNAi), we demonstrate that the Golgi/autophagosome-associated Rab33B is required for hepatitis B virus (HBV) propagation in hepatoma cell lines. While Rab33B is dispensable for the secretion of HBV subviral envelope particles, its knockdown reduced the virus yield to 20% and inhibited nucleocapsid (NC) formation and/or NC trafficking. The overexpression of a GDP-restricted Rab33B mutant phenocopied the effect of deficit Rab33B, indicating that Rab33B-specific effector proteins may be involved...
June 21, 2017: Viruses
https://www.readbyqxmd.com/read/28635591/camoptimus-a-tool-for-exploiting-complex-adaptive-evolution-to-optimize-experiments-and-processes-in-biotechnology
#10
Ayca Cankorur-Cetinkaya, Joao M L Dias, Jana Kludas, Nigel K H Slater, Juho Rousu, Stephen G Oliver, Duygu Dikicioglu
Multiple interacting factors affect the performance of engineered biological systems in synthetic biology projects. The complexity of these biological systems means that experimental design should often be treated as a multiparametric optimization problem. However, the available methodologies are either impractical, due to a combinatorial explosion in the number of experiments to be performed, or are inaccessible to most experimentalists due to the lack of publicly available, user-friendly software. Although evolutionary algorithms may be employed as alternative approaches to optimize experimental design, the lack of simple-to-use software again restricts their use to specialist practitioners...
June 21, 2017: Microbiology
https://www.readbyqxmd.com/read/28634443/the-narrow-abdomen-ion-channel-complex-is-highly-stable-and-persists-from-development-into-adult-stages-to-promote-behavioral-rhythmicity
#11
Devon L Moose, Stephanie J Haase, Benjamin T Aldrich, Bridget C Lear
The sodium leak channel NARROW ABDOMEN (NA)/ NALCN is an important component of circadian pacemaker neuronal output. In Drosophila, rhythmic expression of the NA channel regulator Nlf-1 in a subset of adult pacemaker neurons has been proposed to contribute to circadian regulation of channel localization or activity. Here we have restricted expression of Drosophila NA channel subunits or the Nlf-1 regulator to either development or adulthood using the temperature-inducible tubulin-GAL80(ts) system. Surprisingly, we find that developmental expression of endogenous channel subunits and Nlf-1 is sufficient to promote robust rhythmic behavior in adults...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28634382/expression-of-p301l-htau-in-mouse-mec-induces-hippocampus-dependent-memory-deficit
#12
Xinghua Liu, Kuan Zeng, Mengzhu Li, Qun Wang, Rong Liu, Bin Zhang, Jian-Zhi Wang, Xiji Shu, Xiaochuan Wang
Intracellular accumulation of abnormally phosphorylated tau in different types of neurons is a pathological characteristic of Alzheimer's disease (AD). While tau modification and associated neuronal loss and hypometabolism start in the entorhinal cortex (EC) in early AD patients, the mechanism by which mutant P301L hTau leads to dementia is not fully elucidated. Here, we studied the effects of P301L hTau transduction in the medial EC (MEC) of mice on tau phosphorylation and accumulation, and cognitive deficit...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634240/leucine-biosynthesis-is-involved-in-regulating-high-lipid-accumulation-in-yarrowia-lipolytica
#13
Eduard J Kerkhoven, Young-Mo Kim, Siwei Wei, Carrie D Nicora, Thomas L Fillmore, Samuel O Purvine, Bobbie-Jo Webb-Robertson, Richard D Smith, Scott E Baker, Thomas O Metz, Jens Nielsen
The yeast Yarrowia lipolytica is a potent accumulator of lipids, and lipogenesis in this organism can be influenced by a variety of factors, such as genetics and environmental conditions. Using a multifactorial study, we elucidated the effects of both genetic and environmental factors on regulation of lipogenesis in Y. lipolytica and identified how two opposite regulatory states both result in lipid accumulation. This study involved comparison of a strain overexpressing diacylglycerol acyltransferase (DGA1) with a control strain grown under either nitrogen or carbon limitation conditions...
June 20, 2017: MBio
https://www.readbyqxmd.com/read/28634210/the-glycosylation-pathway-is-required-for-the-secretion-of-slit-and-for-the-maintenance-of-the-slit-receptor-robo-on-axons
#14
Mary Ann Manavalan, Vatsala Ruvini Jayasinghe, Rickinder Grewal, Krishna Moorthi Bhat
Slit proteins act as repulsive axon guidance cues by activating receptors of the Roundabout (Robo) family. During early neurogenesis in Drosophila melanogaster, Slit prevents the growth cones of longitudinal tract neurons from inappropriately crossing the midline, thus restricting these cells to trajectories parallel to the midline. Slit is expressed in midline glial cells, and Robo is present in longitudinal axon tracts and growth cones. We showed that the enzyme Mummy (Mmy) controlled Slit-Robo signaling through mechanisms that affected both the ligand and the receptor...
June 20, 2017: Science Signaling
https://www.readbyqxmd.com/read/28634106/biology-evolution-and-medical-importance-of-polyomaviruses-an-update
#15
REVIEW
Ugo Moens, Andi Krumbholz, Bernhard Ehlers, Roland Zell, Reimar Johne, Sébastien Calvignac-Spencer, Chris Lauber
The family Polyomaviridae encompasses non-enveloped viruses with a circular dsDNA genome that is typically approximately 5000bp in length. Originally isolated from mammals, polyomavirus sequences have now been detected in invertebrates, fish, amphibians, reptiles and birds, although it remains to be determined whether all these animals are genuine hosts. The genomes of all polyomaviruses encode at least two regulatory proteins (large and small tumour antigen) and two structural proteins (capsid proteins VP1 and VP2) whose functions have been defined...
June 17, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28634035/psoriasis-associated-late-cornified-envelope-lce-proteins-have-antibacterial-activity
#16
Hanna Niehues, Lam C Tsoi, Danique A van der Krieken, Patrick A M Jansen, Merel A W Oortveld, Diana Rodijk-Olthuis, Ivonne M J J van Vlijmen, Wiljan J A J Hendriks, Richard W Helder, Joke A Bouwstra, Ellen H van den Bogaard, Philip E Stuart, Rajan P Nair, James T Elder, Patrick L J M Zeeuwen, Joost Schalkwijk
Terminally differentiating epidermal keratinocytes express a large number of structural and antimicrobial proteins that are involved in the physical barrier function of the stratum corneum and provide innate cutaneous host defense. Late cornified envelope (LCE) genes, located in the epidermal differentiation complex on chromosome 1, encode a family of 18 proteins of unknown function, whose expression is largely restricted to epidermis. Deletion of two members, LCE3B and LCE3C (LCE3B/C-del), is a widely replicated psoriasis risk factor that interacts with the major psoriasis-psoriasis risk gene HLA-C*06...
June 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28633193/trictide-a-tricellulin-derived-peptide-to-overcome-cellular-barriers
#17
Jimmi Cording, Basak Arslan, Christian Staat, Sophie Dithmer, Susanne M Krug, Anneliese Krüger, Philipp Berndt, Ramona Günther, Lars Winkler, Ingolf E Blasig, Reiner F Haseloff
The majority of tight junction (TJ) proteins restrict the paracellular permeation of solutes via their extracellular loops (ECLs). Tricellulin tightens tricellular TJs (tTJs) and regulates bicellular TJ (bTJ) proteins. We demonstrate that the addition of recombinantly produced extracellular loop 2 (ECL2) of tricellulin opens cellular barriers. The peptidomimetic trictide, a synthetic peptide derived from tricellulin ECL2, increases the passage of ions, as well as of small and larger molecules up to 10 kDa, between 16 and 30 h after application to human epithelial colorectal adenocarcinoma cell line 2...
June 20, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28633045/mrna-transport-local-translation-in-neurons
#18
REVIEW
Caspar Glock, Maximilian Heumüller, Erin M Schuman
Neurons are amongst the most structurally complex cells and exhibit a high degree of spatial compartmentalization. Also, neurons exhibit rapid and dynamic signaling by processing information in a precise and, sometimes, spatially-restricted manner. The signaling that occurs in axons and dendrites necessitates the maintenance and modification of their local proteomes. Local translation of mRNAs into protein is one solution that neurons use to meet synaptic demand and activity. Here we review some of the key findings and recent discoveries that have shaped our understanding of local translation in neuronal function and highlight important new techniques that might pave the way for new insights...
June 17, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28632878/identification-of-novel-g-protein-coupled-receptor-143-ligands-as-pharmacologic-tools-for-investigating-x-linked-ocular-albinism
#19
Elisabetta De Filippo, Prashiela Manga, Anke C Schiedel
Purpose: GPR143 regulates melanosome biogenesis and organelle size in pigment cells. The mechanisms underlying receptor function remain unclear. G protein-coupled receptors (GPCRs) are excellent pharmacologic targets; thus, we developed and applied a screening approach to identify potential GPR143 ligands and chemical modulators. Methods: GPR143 interacts with β-arrestin; we therefore established a β-arrestin recruitment assay to screen for compounds that modulate activity...
June 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28632750/renal-sodium-handling-and-blood-pressure-changes-in-gestational-protein-restricted-offspring-role-of-renal-nerves-and-ganglia-neurokinin-expression
#20
Augusto H Custódio, Marcelo C de Lima, Bárbara Vaccari, Patrícia A Boer, José A R Gontijo
BACKGROUND: Considering long-term changes in renal sodium handling and blood pressure in maternal protein-restricted (LP) offspring, we assumed that the development of LP hypertension results from abnormal dorsal root ganglia (DRG) neurokinin expression associated with impaired responsiveness of renal sensory receptors, promoting a reduced urinary excretion of sodium. The present study investigates whether increased blood pressure in protein-restricted offspring would be associated with changes in the DRG cells and in renal pelvic wall expression of NK1R, SP and CGRP when compared to NP offspring...
2017: PloS One
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