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https://www.readbyqxmd.com/read/28821723/structural-and-developmental-expression-of-ss-riok-2-an-rio-protein-kinase-encoding-gene-of-strongyloides-stercoralis
#1
Wei-Qiang Lei, James B Lok, Wang Yuan, Yue-Zhou Zhang, Jonathan D Stoltzfus, Robin B Gasser, Si-Yuan He, Huan Zhou, Rui Zhou, Jun-Long Zhao, Min Hu
RIO kinases are essential atypical protein kinases in diverse prokaryotic and eukaryotic organisms, playing significant roles in yeast and humans. However, little is known about their functions in parasitic nematodes. In the present study, we have isolated and characterized the full-length cDNA, gDNA and a putative promoter of a RIOK-2 protein kinase (Ss-RIOK-2) encoding gene (Ss-riok-2) from Strongyloides stercoralis, a medically important parasitic nematode (Order Rhabditida). A three-dimensional structure (3D) model of Ss-RIOK-2 was generated using the Chaetomium thermophilum RIOK-2 protein kinase (Ct-RIOK-2) crystal structure 4GYG as a template...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808136/eplant-visualizing-and-exploring-multiple-levels-of-data-for-hypothesis-generation-in-plant-biology
#2
Jamie Waese, Jim Fan, Asher Pasha, Hans Yu, Geoffrey Fucile, Ruian Shi, Matthew Cumming, Lawrence Kelley, Michael Sternberg, Vivek Krishnakumar, Erik Ferlanti, Jason Miller, Chris Town, Wolfgang Stuerzlinger, Nicholas J Provart
A big challenge in current systems biology research arises when different types of data must be accessed from separate sources and visualized using separate tools. The high cognitive load required to navigate such a workflow is detrimental to hypothesis generation. Accordingly, there is a need for a robust research platform that incorporates all data, and provides integrated search, analysis, and visualization features through a single portal. Here, we present ePlant (http://bar.utoronto.ca/eplant), a visual analytic tool for exploring multiple levels of Arabidopsis data through a zoomable user interface...
August 14, 2017: Plant Cell
https://www.readbyqxmd.com/read/28802252/exploiting-radiation-induced-signaling-to-increase-the-susceptibility-of-resistant-cancer-cells-to-targeted-drugs-akt-and-mtor-inhibitors-as-an-example
#3
Iris Eke, Adeola Y Makinde, Molykutty J Aryankalayil, Veit Sandfort, Sanjeewani T Palayoor, Barbara H Rath, Lance Liotta, Mariaelena Pierobon, Emanuel F Petricoin, Matthew F Brown, Jayne M Stommel, Mansoor M Ahmed, C Norman Coleman
Implementing targeted drug therapy in radio-oncologic treatment regimens has greatly improved the outcome of cancer patients. However, the efficacy of molecular targeted drugs such as inhibitory antibodies or small molecule inhibitors essentially depends on target expression and activity, which both can change during the course of treatment. Radiotherapy has previously been shown to activate pro-survival pathways which can help tumor cells to adapt and thereby survive treatment. Therefore, we aimed to identify changes in signaling induced by radiation and evaluate the potential of targeting these changes with small molecules to increase the therapeutic efficacy on cancer cell survival...
August 11, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28792605/single-cell-hi-c-bridges-microscopy-and-genome-wide-sequencing-approaches-to-study-3d-chromatin-organization
#4
REVIEW
Sergey V Ulianov, Kikue Tachibana-Konwalski, Sergey V Razin
Recent years have witnessed an explosion of the single-cell biochemical toolbox including chromosome conformation capture (3C)-based methods that provide novel insights into chromatin spatial organization in individual cells. The observations made with these techniques revealed that topologically associating domains emerge from cell population averages and do not exist as static structures in individual cells. Stochastic nature of the genome folding is likely to be biologically relevant and may reflect the ability of chromatin fibers to adopt a number of alternative configurations, some of which could be transiently stabilized and serve regulatory purposes...
August 9, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28792224/supramolecular-protein-assemblies-based-on-dna-templates
#5
Chunxi Hou, Shuwen Guan, Ruidi Wang, Wei Zhang, Fanchao Meng, Linlu Zhao, Jiayun Xu, Junqiu Liu
DNA plays an important role in the process of protein assembly. DNA viruses such as M13 virus are typical examples in which single DNA genome behaves as template to induce multiple major coat protein (PⅧ) monomers assembling. Thus, design of protein assemblies based on DNA templatesattracts much interest in construction of supramolecular structructures and materials. With the development of DNA nanotechnology, precise 1D and 3D protein nanostructures have been designed and constructed by using DNA templates through DNA-protein interactions, protein-ligand interactions and protein-adapter interactions...
August 9, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28774341/modeling-tumor-cell-adaptations-to-hypoxia-in-multicellular-tumor-spheroids
#6
REVIEW
Stephen Riffle, Rashmi S Hegde
Under hypoxic conditions, tumor cells undergo a series of adaptations that promote evolution of a more aggressive tumor phenotype including the activation of DNA damage repair proteins, altered metabolism, and decreased proliferation. Together these changes mitigate the negative impact of oxygen deprivation and allow preservation of genomic integrity and proliferative capacity, thus contributing to tumor growth and metastasis. As a result the presence of a hypoxic microenvironment is considered a negative clinical feature of many solid tumors...
August 3, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28771695/challenges-for-visualizing-three-dimensional-data-in-genomic-browsers
#7
REVIEW
Mike Goodstadt, Marc A Marti-Renom
Genomic interactions reveal the spatial organization of genomes and genomic domains, which is known to play key roles in cell function. Physical proximity can be represented as two-dimensional heat maps or matrices. From these, three-dimensional (3D) conformations of chromatin can be computed revealing coherent structures that highlight the importance of non-sequential relationships across genomic features. Mainstream genomic browsers have been classically developed to display compact, stacked tracks based on a linear, sequential, per-chromosome coordinate system...
August 3, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28770387/data-to-decisions-creating-a-culture-of-model-driven-drug-discovery
#8
Frank K Brown, Farida Kopti, Charlie Zhenyu Chang, Scott A Johnson, Meir Glick, Chris L Waller
Merck & Co., Inc., Kenilworth, NJ, USA, is undergoing a transformation in the way that it prosecutes R&D programs. Through the adoption of a "model-driven" culture, enhanced R&D productivity is anticipated, both in the form of decreased attrition at each stage of the process and by providing a rational framework for understanding and learning from the data generated along the way. This new approach focuses on the concept of a "Design Cycle" that makes use of all the data possible, internally and externally, to drive decision-making...
August 2, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28766343/isothermal-point-mutation-detection-toward-a-first-pass-screening-strategy-for-multidrug-resistant-tuberculosis
#9
Benjamin Y C Ng, Eugene J H Wee, Kyra Woods, Will Anderson, Fiach Antaw, Hennes Z H Tsang, Nicholas P West, Matt Trau
Point mutations in DNA are useful biomarkers that can provide critical classification of disease for accurate diagnosis and to inform clinical decisions. Conventional approaches to detect point mutations are usually based on technologies such as real-time polymerase chain reaction (PCR) or DNA sequencing, which are typically slow and require expensive lab-based equipment. While rapid isothermal strategies such as recombinase polymerase amplification (RPA) have been proposed, they tend to suffer from poor specificity in discriminating point mutations...
August 15, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28762410/accurate-nanoscale-flexibility-measurement-of-dna-and-dna-protein-complexes-by-atomic-force-microscopy-in-liquid
#10
Divakaran Murugesapillai, Serge Bouaziz, L James Maher, Nathan E Israeloff, Craig E Cameron, Mark C Williams
The elasticity of double-stranded DNA (dsDNA), as described by its persistence length, is critical for many biological processes, including genomic regulation. A persistence length value can be obtained using atomic force microscopy (AFM) imaging. However, most AFM studies have been done by depositing the sample on a surface using adhesive ligands and fitting the contour to a two-dimensional (2D) wormlike chain (WLC) model. This often results in a persistence length measurement that is different from the value determined using bulk and single molecule methods...
August 1, 2017: Nanoscale
https://www.readbyqxmd.com/read/28757610/the-il-1r-tlr-signaling-pathway-is-essential-for-efficient-cd8-t-cell-responses-against-hepatitis-b-virus-in-the-hydrodynamic-injection-mouse-model
#11
Zhiyong Ma, Jia Liu, Weimin Wu, Ejuan Zhang, Xiaoyong Zhang, Qian Li, Gennadiy Zelinskyy, Jan Buer, Ulf Dittmer, Carsten J Kirschning, Mengji Lu
The outcome of hepatitis B viral (HBV) infection is determined by the complex interactions between replicating HBV and the immune system. While the role of the adaptive immune system in the resolution of HBV infection has been studied extensively, the contribution of innate immune mechanisms remains to be defined. Here we examined the role of the interleukin-1 receptor/Toll-like receptor (IL-1R/TLR) signaling pathway in adaptive immune responses and viral clearance by exploring the HBV mouse model. Hydrodynamic injection with a replication-competent HBV genome was performed in wild-type mice (WT) and a panel of mouse strains lacking specific innate immunity component expression...
July 31, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28755265/an-in-silico-strategy-for-identification-of-novel-drug-targets-against-plasmodium-falciparum
#12
Subhashree Rout, Namrata Priyadarshini Patra, Rajani Kanta Mahapatra
The apicomplexan parasite Plasmodium falciparum is responsible for global malaria burden. With the reported resistance to artemisinin chemotherapy, there is an urgent need to maintain early phase drug discovery and identify novel drug targets for successful eradication of the pathogen from the host. In our previous work on comparative genomics study for identification of putative essential genes and therapeutic candidates in P. falciparum, we predicted 11 proteins as anti-malarial drug targets from PlasmoDB database...
July 28, 2017: Parasitology Research
https://www.readbyqxmd.com/read/28751906/observation-of-extensive-chromosome-axis-remodeling-during-the-diffuse-phase-of-meiosis-in-large-genome-cereals
#13
Isabelle Colas, Benoit Darrier, Mikel Arrieta, Sybille U Mittmann, Luke Ramsay, Pierre Sourdille, Robbie Waugh
The production of balanced fertile haploid gametes requires the faithful separation of paired (synapsed) chromosomes toward the end of meiotic prophase I (desynapsis). This involves the timely dissolution of the synaptonemal complex during the pachytene-diplotene transition, a stage traditionally referred to as the "diffuse stage." In species with large genomes such as, barley (Hordeum vulgare L.) and wheat (Triticum aestivum L.) we know most about the early stages of meiotic prophase I. There, synapsis initiates at the telomeric ends of chromosomes and progresses toward the centromeric regions through the ordered assembly of the synaptonemal complex (SC)...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28751582/chromemt-visualizing-3d-chromatin-structure-and-compaction-in-interphase-and-mitotic-cells
#14
Horng D Ou, Sébastien Phan, Thomas J Deerinck, Andrea Thor, Mark H Ellisman, Clodagh C O'Shea
The chromatin structure of DNA determines genome compaction and activity in the nucleus. On the basis of in vitro structures and electron microscopy (EM) studies, the hierarchical model is that 11-nanometer DNA-nucleosome polymers fold into 30- and subsequently into 120- and 300- to 700-nanometer fibers and mitotic chromosomes. To visualize chromatin in situ, we identified a fluorescent dye that stains DNA with an osmiophilic polymer and selectively enhances its contrast in EM. Using ChromEMT (ChromEM tomography), we reveal the ultrastructure and three-dimensional (3D) organization of individual chromatin polymers, megabase domains, and mitotic chromosomes...
July 28, 2017: Science
https://www.readbyqxmd.com/read/28741488/extraordinary-cancer-epigenomics-thinking-outside-the-classical-coding-and-promoter-box
#15
REVIEW
Matthew Murtha, Manel Esteller
The advent of functional genomics powered by high-throughput sequencing has given us a new appreciation of the genomic sequences that lie outside the canonical promoter-coding sequence box. These regions harbor distant regulatory elements, enhancers, super-enhancers, insulators, alternative promoters, and sequences that transcribe as noncoding RNAs (ncRNAs) such as miRNAs and long ncRNAs. These functional genomics studies have also enabled a clearer understanding of the role of the 3D structure of the genome in epigenetic regulation...
October 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28735414/bone-mechanobiology-in-mice-toward-single-cell-in-vivo-mechanomics
#16
Ariane Scheuren, Esther Wehrle, Felicitas Flohr, Ralph Müller
Mechanically driven bone (re)modeling is a multiscale process mediated through complex interactions between multiple cell types and their microenvironments. However, the underlying mechanisms of how cells respond to mechanical signals are still unclear and are at the focus of the field of bone mechanobiology. Traditionally, this complex process has been addressed by reducing the system to single scales and cell types. It is only recently that more integrative approaches have been established to study bone mechanobiology across multiple scales in which mechanical load at the organ level is related to molecular responses at the cellular level...
July 22, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28735107/integrative-modelling-of-cellular-assemblies
#17
REVIEW
Agnel Praveen Joseph, Guido Polles, Frank Alber, Maya Topf
A wide variety of experimental techniques can be used for understanding the precise molecular mechanisms underlying the activities of cellular assemblies. The inherent limitations of a single experimental technique often requires integration of data from complementary approaches to gain sufficient insights into the assembly structure and function. Here, we review popular computational approaches for integrative modelling of cellular assemblies, including protein complexes and genomic assemblies. We provide recent examples of integrative models generated for such assemblies by different experimental techniques, especially including data from 3D electron microscopy (3D-EM) and chromosome conformation capture experiments, respectively...
July 20, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28728879/identification-of-universal-diagnostic-peptide-candidates-for-neglected-tropical-diseases-caused-by-cestodes-through-the-integration-of-multi-genome-wide-analyses-and-immunoinformatic-predictions
#18
Sebastián Miles, Marco Navatta, Sylvia Dematteis, Gustavo Mourglia-Ettlin
Neglected tropical diseases caused by helminth infections currently affect millions of people worldwide. Among them, there are three tapeworm species of outstanding importance: Echinococcus granulosus, E. multilocularis, and Taenia solium, which are responsible for cystic echinococcosis, alveolar echinococcosis, and cysticercosis, respectively. Despite several attempts, there is still a need for an effective and low-cost serological diagnostic test that can be used in endemic countries. In the present work, we described an innovative bioinformatic workflow for a rational prediction of putative peptide candidates for one-step serological diagnosis of any of these infections...
July 17, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28724077/physical-map-of-the-short-arm-of-bread-wheat-chromosome-3d
#19
Kateřina Holušová, Jan Vrána, Jan Šafář, Hana Šimková, Barbora Balcárková, Zeev Frenkel, Benoit Darrier, Etienne Paux, Federica Cattonaro, Helene Berges, Thomas Letellier, Michael Alaux, Jaroslav Doležel, Jan Bartoš
Bread wheat ( L.) is one of the most important crops worldwide. Although a reference genome sequence would represent a valuable resource for wheat improvement through genomics-assisted breeding and gene cloning, its generation has long been hampered by its allohexaploidy, high repeat content, and large size. As a part of a project coordinated by the International Wheat Genome Sequencing Consortium (IWGSC), a physical map of the short arm of wheat chromosome 3D (3DS) was prepared to facilitate reference genome assembly and positional gene cloning...
July 2017: Plant Genome
https://www.readbyqxmd.com/read/28723903/automatic-analysis-and-3d-modelling-of-hi-c-data-using-tadbit-reveals-structural-features-of-the-fly-chromatin-colors
#20
François Serra, Davide Baù, Mike Goodstadt, David Castillo, Guillaume J Filion, Marc A Marti-Renom
The sequence of a genome is insufficient to understand all genomic processes carried out in the cell nucleus. To achieve this, the knowledge of its three-dimensional architecture is necessary. Advances in genomic technologies and the development of new analytical methods, such as Chromosome Conformation Capture (3C) and its derivatives, provide unprecedented insights in the spatial organization of genomes. Here we present TADbit, a computational framework to analyze and model the chromatin fiber in three dimensions...
July 2017: PLoS Computational Biology
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