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https://www.readbyqxmd.com/read/27899641/3d-genome-structure-modeling-by-lorentzian-objective-function
#1
Tuan Trieu, Jianlin Cheng
The 3D structure of the genome plays a vital role in biological processes such as gene interaction, gene regulation, DNA replication and genome methylation. Advanced chromosomal conformation capture techniques, such as Hi-C and tethered conformation capture, can generate chromosomal contact data that can be used to computationally reconstruct 3D structures of the genome. We developed a novel restraint-based method that is capable of reconstructing 3D genome structures utilizing both intra-and inter-chromosomal contact data...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899590/different%C3%A2-enhancer-classes-in-drosophila-bind-distinct-architectural-proteins-and-mediate-unique-chromatin-interactions-and-3d-architecture
#2
Caelin Cubeñas-Potts, M Jordan Rowley, Xiaowen Lyu, Ge Li, Elissa P Lei, Victor G Corces
Eukaryotic gene expression is regulated by enhancer-promoter interactions but the molecular mechanisms that govern specificity have remained elusive. Genome-wide studies utilizing STARR-seq identified two enhancer classes in Drosophila that interact with different core promoters: housekeeping enhancers (hkCP) and developmental enhancers (dCP). We hypothesized that the two enhancer classes are occupied by distinct architectural proteins, affecting their enhancer-promoter contacts. By evaluating ChIP-seq occupancy of architectural proteins, typical enhancer-associated proteins, and histone modifications, we determine that both enhancer classes are enriched for RNA Polymerase II, CBP, and architectural proteins but there are also distinctions...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27890013/in-silico-characterization-of-a-hypothetical-protein-rv1288-of-mycobacterium-tuberculosis-containing-an-esterase-signature-and-an-uncommon-lyte-domain
#3
Arbind Kumar, Pratibha Maan, Gurpreet Singh, Jagdeep Kaur
BACKGROUND: Death toll due to tuberculosis is still rising day by day. Whole genome sequence of Mycobacterium tuberculosis has provided a platform to conduct research in order to identify the probable drug target. OBJECTIVES: Out of 4000 gene products of M. tuberculosis, approximately 40% of proteins are annotated as hypothetical. Identifying and characterizing these proteins could provide a new prescriptive for developing new TB drugs. Rv1288, a protein of M. tuberculosis H37Rv has been annotated as a hypothetical protein in database...
November 24, 2016: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/27889058/mutations-in-reep6-cause-autosomal-recessive-retinitis-pigmentosa
#4
Gavin Arno, Smriti A Agrawal, Aiden Eblimit, James Bellingham, Mingchu Xu, Feng Wang, Christina Chakarova, David A Parfitt, Amelia Lane, Thomas Burgoyne, Sarah Hull, Keren J Carss, Alessia Fiorentino, Matthew J Hayes, Peter M Munro, Ralph Nicols, Nikolas Pontikos, Graham E Holder, Chinwe Asomugha, F Lucy Raymond, Anthony T Moore, Vincent Plagnol, Michel Michaelides, Alison J Hardcastle, Yumei Li, Catherine Cukras, Andrew R Webster, Michael E Cheetham, Rui Chen
Retinitis pigmentosa (RP) is the most frequent form of inherited retinal dystrophy. RP is genetically heterogeneous and the genes identified to date encode proteins involved in a wide range of functional pathways, including photoreceptor development, phototransduction, the retinoid cycle, cilia, and outer segment development. Here we report the identification of biallelic mutations in Receptor Expression Enhancer Protein 6 (REEP6) in seven individuals with autosomal-recessive RP from five unrelated families...
December 1, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27882067/bioinformatic-identification-of-rare-codon-clusters-rccs-in-hbv-genome-and-evaluation-of-rccs-in-proteins-structure-of-hepatitis-b-virus
#5
Mojtaba Mortazavi, Mohammad Zarenezhad, Saeid Gholamzadeh, Seyed Moayed Alavian, Mohammad Ghorbani, Reza Dehghani, Abdorrasoul Malekpour, Mohammadhasan Meshkibaf, Ali Fakhrzad
BACKGROUND: Hepatitis B virus (HBV) as an infectious disease that has nine genotypes (A - I) and a 'putative' genotype J. OBJECTIVES: The aim of this study was to identify the rare codon clusters (RCC) in the HBV genome and to evaluate these RCCs in the HBV proteins structure. METHODS: For detection of protein family accession numbers (Pfam) in HBV proteins, the UniProt database and Pfam search tool were used. Protein family accession numbers is a comprehensive and accurate collection of protein domains and families...
October 2016: Hepatitis Monthly
https://www.readbyqxmd.com/read/27879651/prediction-of-protein-protein-interactions-by-evidence-combining-methods
#6
REVIEW
Ji-Wei Chang, Yan-Qing Zhou, Muhammad Tahir Ul Qamar, Ling-Ling Chen, Yu-Duan Ding
Most cellular functions involve proteins' features based on their physical interactions with other partner proteins. Sketching a map of protein-protein interactions (PPIs) is therefore an important inception step towards understanding the basics of cell functions. Several experimental techniques operating in vivo or in vitro have made significant contributions to screening a large number of protein interaction partners, especially high-throughput experimental methods. However, computational approaches for PPI predication supported by rapid accumulation of data generated from experimental techniques, 3D structure definitions, and genome sequencing have boosted the map sketching of PPIs...
November 22, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27877188/identification-of-genomic-associations-for-adult-plant-resistance-in-the-background-of-popular-south-asian-wheat-cultivar-pbw343
#7
Huihui Li, Sukhwinder Singh, Sridhar Bhavani, Ravi P Singh, Deepmala Sehgal, Bhoja R Basnet, Prashant Vikram, Juan Burgueno-Ferreira, Julio Huerta-Espino
Rusts, a fungal disease as old as its host plant wheat, has caused havoc for over 8000 years. As the rust pathogens can evolve into new virulent races which quickly defeat the resistance that primarily rely on race specificity, adult plant resistance (APR) has often been found to be race non-specific and hence is considered to be a more reliable and durable strategy to combat this malady. Over decades sets of donor lines have been identified at International Maize and Wheat Improvement Center (CIMMYT) representing a wide range of APR sources in wheat...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27875274/sirt1-inhibits-ev71-genome-replication-and-rna-translation-by-interfering-viral-polymerase-and-5-utr-rna
#8
Yang Han, Lvyin Wang, Jin Cui, Yu Song, Zhen Luo, Junbo Chen, Ying Xiong, Qi Zhang, Fang Liu, Wenzhe Ho, Yingle Liu, Kailang Wu, Jianguo Wu
Enterovirus 71 (EV71) possesses a single-stranded positive RNA genome that contains a single open reading frame (ORF) flanked by a 5'untranslated region (5'UTR) and a polyadenylated 3'UTR. Here, we demonstrated that EV71 activates the production of silent mating type information regulation 2 homolog 1 (SIRT1), a histone deacetylase (HDAC). EV71 further stimulates SIRT1 sumoylation and deacetylase activity, and enhances SIRT1 translocation from nuclear to cytoplasm. More interestingly, activated SIRT1 subsequently binds with EV71 3D protein (a viral RNA-dependent RNA polymerase, RdRp) to repress the acetylation and RdRp activity of 3D, resulting in the attenuation of viral genome replication...
November 14, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27874016/mitochondrial-growth-during-the-cell-cycle-of-trypanosoma-brucei-bloodstream-forms
#9
Martin Jakob, Anneliese Hoffmann, Simona Amodeo, Camille Peitsch, Benoît Zuber, Torsten Ochsenreiter
Mitochondrial organelles need to be replicated during cell division. Many aspects of this process have been studied in great detail, however the actual size increase and the position of organelle growth are less well understood. We use the protozoan parasite Trypanosoma brucei that contains a single mitochondrion to study organelle biogenesis by fluorescence microscopy. From the analysis of more than 1000 T. brucei bloodstream form cells of a nonsynchronous population we conclude that the mitochondrial network mostly grows from two areas along the main organelle axis, posterior and anterior of the nucleus...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27871886/tetrahalogenated-benzimidazole-d-ribonucleosides-are-active-against-rat-cytomegalovirus
#10
Alexandra Dittmer, Ina Woskobojnik, Rebekka Adfeldt, John C Drach, Leroy B Townsend, Sebastian Voigt, Elke Bogner
BACKGROUND: Benzimidazole D-ribonucleosides are potent and selective inhibitors of CMV infection that have been shown to target the viral terminase, the enzyme complex responsible for viral DNA cleavage into single unit-length genomes and subsequent DNA packaging into procapsids. Here, we evaluated the viral inhibition by benzimidazole D-ribonucleosides against rat cytomegalovirus (RCMV). METHODS: Antiviral activity of compounds Cl4RB and BTCRB against RCMV was quantified by measurement of plaque formation...
November 18, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27869826/pan-cancer-analysis-of-somatic-copy-number-alterations-implicates-irs4-and-igf2-in-enhancer-hijacking
#11
Joachim Weischenfeldt, Taronish Dubash, Alexandros P Drainas, Balca R Mardin, Yuanyuan Chen, Adrian M Stütz, Sebastian M Waszak, Graziella Bosco, Ann Rita Halvorsen, Benjamin Raeder, Theocharis Efthymiopoulos, Serap Erkek, Christine Siegl, Hermann Brenner, Odd Terje Brustugun, Sebastian M Dieter, Paul A Northcott, Iver Petersen, Stefan M Pfister, Martin Schneider, Steinar K Solberg, Erik Thunissen, Wilko Weichert, Thomas Zichner, Roman Thomas, Martin Peifer, Aslaug Helland, Claudia R Ball, Martin Jechlinger, Rocio Sotillo, Hanno Glimm, Jan O Korbel
Extensive prior research focused on somatic copy-number alterations (SCNAs) affecting cancer genes, yet the extent to which recurrent SCNAs exert their influence through rearrangement of cis-regulatory elements (CREs) remains unclear. Here we present a framework for inferring cancer-related gene overexpression resulting from CRE reorganization (e.g., enhancer hijacking) by integrating SCNAs, gene expression data and information on topologically associating domains (TADs). Analysis of 7,416 cancer genomes uncovered several pan-cancer candidate genes, including IRS4, SMARCA1 and TERT...
November 21, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27869745/many-activities-one-structure-functional-plasticity-of-ribozyme-folds
#12
REVIEW
Matthew W L Lau, Adrian R Ferré-D'Amaré
Catalytic RNAs, or ribozymes, are involved in a number of essential biological processes, such as replication of RNA genomes and mobile genetic elements, RNA splicing, translation, and RNA degradation. The function of ribozymes requires the formation of active sites decorated with RNA functional groups within defined three-dimensional (3D) structures. The genotype (sequence) of RNAs ultimately determines what 3D structures they adopt (as a function of their environmental conditions). These 3D structures, in turn, give rise to biochemical activity, which can further elaborate them by catalytic rearrangements or association with other molecules...
November 18, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27869158/mapping-the-3d-genome-aiming-for-consilience
#13
Job Dekker
The spatial organization of genomes is studied using microscopy- and chromosome conformation capture (3C)-based methods. The two types of methods produce data that are often consistent, but there are cases where they appear discordant. These cases provide opportunities to derive better models of chromatin folding, which can reconcile the datasets.
November 21, 2016: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/27866227/genome-wide-association-mapping-of-resistance-to-eyespot-disease-pseudocercosporella-herpotrichoides-in-european-winter-wheat-triticum-aestivum-l-and-fine-mapping-of-pch1
#14
Christine D Zanke, Bernd Rodemann, Jie Ling, Quddoos H Muqaddasi, Jörg Plieske, Andreas Polley, Sonja Kollers, Erhard Ebmeyer, Viktor Korzun, Odile Argillier, Gunther Stiewe, Thomas Zschäckel, Martin W Ganal, Marion S Röder
Genotypes with recombination events in the Triticum ventricosum introgression on chromosome 7D allowed to fine-map resistance gene Pch1, the main source of eyespot resistance in European winter wheat cultivars. Eyespot (also called Strawbreaker) is a common and serious fungal disease of winter wheat caused by the necrotrophic fungi Oculimacula yallundae and Oculimacula acuformis (former name Pseudocercosporella herpotrichoides). A genome-wide association study (GWAS) for eyespot was performed with 732 microsatellite markers (SSR) and 7761 mapped SNP markers derived from the 90 K iSELECT wheat array using a panel of 168 European winter wheat varieties as well as three spring wheat varieties and phenotypic evaluation of eyespot in field tests in three environments...
November 19, 2016: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
https://www.readbyqxmd.com/read/27859262/functional-and-prognostic-significance-of-the-genomic-amplification-of-frizzled-receptor-6-fzd6-in-breast-cancer
#15
Gabriele Corda, Gianluca Sala, Rossano Lattanzio, Manuela Iezzi, Michele Sallese, Giorgia Fragassi, Alessia Lamolinara, Hasan Mirza, Daniela Barcaroli, Sibylle Ermler, Elisabete Silva, Hemad Yasaei, Robert F Newbold, Paola Vagnarelli, Marcella Mottolese, Pier Giorgio Natali, Letizia Perracchio, Jelmar Quist, Anita Grigoriadis, Pierfrancesco Marra, Andrew N Tutt, Mauro Piantelli, Stefano Iacobelli, Vincenzo De Laurenzi, Arturo Sala
Frizzled receptors mediate Wnt ligands' signalling, which is crucially involved in regulating tissue development, differentiation and is often deregulated in cancer. In this study we found that the Wnt receptor frizzled 6 (FZD6) is frequently amplified in breast cancer, with an increased incidence in the triple negative breast cancer (TNBC) subtype. Ablation of FZD6 gene expression in mammary cancer cell lines: a) inhibited motility and invasion b) induced a more symmetric shape of organoid 3D cultures c) inhibited bone and liver metastasis in vivo...
November 9, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27856763/normal-chromosome-conformation-depends-on-subtelomeric-facultative-heterochromatin-in-neurospora-crassa
#16
Andrew D Klocko, Tereza Ormsby, Jonathan M Galazka, Neena A Leggett, Miki Uesaka, Shinji Honda, Michael Freitag, Eric U Selker
High-throughput chromosome conformation capture (Hi-C) analyses revealed that the 3D structure of the Neurospora crassa genome is dominated by intra- and interchromosomal links between regions of heterochromatin, especially constitutive heterochromatin. Elimination of trimethylation of lysine 9 on histone H3 (H3K9me3) or its binding partner Heterochromatin Protein 1 (HP1)-both prominent features of constitutive heterochromatin-have little effect on the Hi-C pattern. It remained possible that di- or trimethylation of lysine 27 on histone H3 (H3K27me2/3), which becomes localized in regions of constitutive heterochromatin when H3K9me3 or HP1 are lost, plays a critical role in the 3D structure of the genome...
November 16, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27856720/non-destructive-cryo-micro-ct-imaging-enables-structural-and-molecular-analysis-of-human-lung-tissue
#17
Dragos Mihai Vasilescu, André B Phillion, Naoya Tanabe, Daisuke Kinose, David F Paige, Jacob J Kantrowitz, Gang Liu, Hanqiao Liu, Nick Fishbane, Stijn E Verleden, Bart M Vanaudenaerde, Marc E Lenburg, Christopher S Stevenson, Avrum Spira, Joel D Cooper, Tillie-Louise Hackett, James C Hogg
Micro Computed Tomography (CT) enables 3-dimensional (3D) imaging of complex soft tissue structures, but current protocols used to achieve this goal preclude cellular and molecular phenotyping of the tissue. Here we describe a radiolucent cryo stage that permits micro CT imaging of unfixed frozen human lung samples at a spatial resolution of 11 µm under conditions where the sample is maintained frozen at -30°C during imaging. The cryo stage was tested for thermal stability to maintain samples frozen up to 8 hours...
November 17, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27846345/systems-biology-for-organotypic-cell-cultures
#18
Sonia Grego, Edward R Dougherty, Francis J Alexander, Scott S Auerbach, Brian R Berridge, Michael L Bittner, Warren Casey, Philip C Cooley, Ajit Dash, Stephen S Ferguson, Timothy R Fennell, Brian T Hawkins, Anthony J Hickey, Andre Kleensang, Michael N J Liebman, Florian Martin, Elizabeth A Maull, Jason Paragas, Guilin Gary Qiao, Sreenivasa Ramaiahgari, Susan J Sumner, Miyoung Yoon
Translating in vitro biological data into actionable information related to human health holds the potential to improve disease treatment and risk assessment of chemical exposures. While genomics has identified regulatory pathways at the cellular level, translation to the organism level requires a multiscale approach accounting for intra-cellular regulation, inter-cellular interaction, and tissue/organ-level effects. Tissue-level effects can now be probed in vitro thanks to recently developed systems of three-dimensional (3D), multicellular, "organotypic" cell cultures, which mimic functional responses of living tissue...
November 14, 2016: ALTEX
https://www.readbyqxmd.com/read/27844287/modeling-of-autism-using-organoid-technology
#19
REVIEW
Hwan Choi, Juhyun Song, Guiyeon Park, Jongpil Kim
Autism is a neurodevelopmental disease caused by multiple mutations during development. However, a suitable disease model to study the molecular pathway of disease onset and progression is not available. Although many studies have used human stem cells such as induced pluripotent stem cells and embryonic stem cells to investigate the disease pathogenesis, these stem cell techniques are limited in their abilities to study the pathology and mechanism of pathogenesis of neurodevelopmental diseases such as autism...
November 14, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27836759/the-effect-of-single-nucleotide-polymorphisms-in-g-rich-regions-of-high-risk-human-papillomaviruses-on-structural-diversity-of-dna
#20
Maja Marušič, Lea Hošnjak, Petra Krafčikova, Mario Poljak, Viktor Viglasky, Janez Plavec
BACKGROUND: Infection with high-risk human papillomaviruses (HPVs) can lead to development of cancer of the head and neck and anogenital regions. G-rich sequences found in genomes of high-risk HPVs can fold into non-canonical secondary structures that could serve as 3D motifs distinct from double-stranded DNA and present recognition sites for ligands and opportunity for gene expression modulation. METHODS: Combination of UV, CD and NMR spectroscopy and PAGE electrophoresis were used as they offer complementary insights into structural changes of G-rich oligonucleotides...
November 9, 2016: Biochimica et Biophysica Acta
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