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Integrative genomics

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https://www.readbyqxmd.com/read/28737715/latency-integration-and-reactivation-of-human-herpesvirus-6
#1
REVIEW
Shara N Pantry, Peter G Medveczky
Human herpesvirus-6A (HHV-6A) and human herpesvirus-6B (HHV-6B) are two closely related viruses that infect T-cells. Both HHV-6A and HHV-6B possess telomere-like repeats at the terminal regions of their genomes that facilitate latency by integration into the host telomeres, rather than by episome formation. In about 1% of the human population, human herpes virus-6 (HHV-6) integration into germline cells allows the viral genome to be passed down from one generation to the other; this condition is called inherited chromosomally integrated HHV-6 (iciHHV-6)...
July 24, 2017: Viruses
https://www.readbyqxmd.com/read/28737169/actomyosin-drives-cancer-cell-nuclear-dysmorphia-and-threatens-genome-stability
#2
Tohru Takaki, Marco Montagner, Murielle P Serres, Maël Le Berre, Matt Russell, Lucy Collinson, Karoly Szuhai, Michael Howell, Simon J Boulton, Erik Sahai, Mark Petronczki
Altered nuclear shape is a defining feature of cancer cells. The mechanisms underlying nuclear dysmorphia in cancer remain poorly understood. Here we identify PPP1R12A and PPP1CB, two subunits of the myosin phosphatase complex that antagonizes actomyosin contractility, as proteins safeguarding nuclear integrity. Loss of PPP1R12A or PPP1CB causes nuclear fragmentation, nuclear envelope rupture, nuclear compartment breakdown and genome instability. Pharmacological or genetic inhibition of actomyosin contractility restores nuclear architecture and genome integrity in cells lacking PPP1R12A or PPP1CB...
July 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28736627/personalized-and-precision-medicine-integrating-genomics-into-treatment-decisions-in-gastrointestinal-malignancies
#3
REVIEW
Trang H Au, Kai Wang, David Stenehjem, Ignacio Garrido-Laguna
The advent of next generation sequencing (NGS) technologies has advanced our understanding of the intrinsic biology of different gastrointestinal (GI) tumor types. The use of novel, more efficient sequencing platforms has improved turnaround times of sequencing results. This is providing real time opportunities to put precision medicine to the test. A number of early phase clinical trials are testing targeted therapies in unique molecularly characterized subsets of patients (baskets). While basket studies are gaining momentum, treatment failures serve to remind us that shifting from a histology-driven to a histology-agnostic approach is unlikely to be a failure-free strategy for a number of tumor types as recently learnt from vemurafenib failure in BRAF mutated metastatic colorectal cancer (mCRC)...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28736510/a-genomic-perspective-on-the-generation-and-maintenance-of-genetic-diversity-in-herbivorous-insects
#4
Andrew D Gloss, Simon C Groen, Noah K Whiteman
Understanding the processes that generate and maintain genetic variation within populations is a central goal in evolutionary biology. Theory predicts that some of this variation is maintained as a consequence of adapting to variable habitats. Studies in herbivorous insects have played a key role in confirming this prediction. Here, we highlight theoretical and conceptual models for the maintenance of genetic diversity in herbivorous insects, empirical genomic studies testing these models, and pressing questions within the realm of evolutionary and functional genomic studies...
November 2016: Annual Review of Ecology, Evolution, and Systematics
https://www.readbyqxmd.com/read/28736156/improving-the-economics-of-nash-nafld-treatment-through-the-use-of-systems-biology
#5
REVIEW
Jim Bosley, Christofer Boren, Sunjae Lee, Morten Grøtli, Jens Nielsen, Mathias Uhlen, Jan Boren, Adil Mardinoglu
Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD). We surveyed NASH therapies currently in development, and found a significant variety of targets and approaches. Evaluation and clinical testing of these targets is an expensive and time-consuming process. Systems biology approaches could enable the quantitative evaluation of the likely efficacy and safety of different targets. This motivated our review of recent systems biology studies that focus on the identification of targets and development of effective treatments for NASH...
July 20, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28735853/a-comparative-study-of-genome-organization-and-epigenetic-mechanisms-in-model-ciliates-with-an-emphasis-on-tetrahymena-paramecium-and-oxytricha
#6
REVIEW
Yurui Wang, Yuanyuan Wang, Yalan Sheng, Jie Huang, Xiao Chen, Khaled A S Al-Rasheid, Shan Gao
As a group of unicellular eukaryotes, ciliates offer a unique system to explore epigenetic regulation, mostly due to their nuclear dualism. Ciliates launched a successful radiation after their early evolutionary branching, therefore harboring an unexpectedly rich pool of diverse biological functions and mechanisms. In this review, we compare distinct features of different ciliates in mating type determination, genome organization, DNA methylation, and removal of internal eliminated sequences (IES), with emphasis on Tetrahymena, Paramecium and Oxytricha...
July 1, 2017: European Journal of Protistology
https://www.readbyqxmd.com/read/28735781/the-future-of-fracture-risk-assessment-in-the-management-of-osteoporosis
#7
Sanford Baim
There have been many advances in the field of osteoporosis that add to a greater understanding of skeletal integrity and the adverse effects menopause and aging have on bone. The World Health Organization, the International Osteoporosis Foundation, and numerous additional governmental and privately sponsored organizations, societies, and their respective task forces have provided guidance for the use of appropriate fracture assessment methodologies and fracture risk assessment tools, and for the prevention and management of osteoporosis...
July 20, 2017: Journal of Clinical Densitometry
https://www.readbyqxmd.com/read/28735414/bone-mechanobiology-in-mice-toward-single-cell-in-vivo-mechanomics
#8
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
#9
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/28735012/fgwas-functional-genome-wide-association-analysis
#10
Chao Huang, Paul Thompson, Yalin Wang, Yang Yu, Jingwen Zhang, Dehan Kong, Rivka R Colen, Rebecca C Knickmeyer, Hongtu Zhu
Functional phenotypes (e.g., subcortical surface representation), which commonly arise in imaging genetic studies, have been used to detect putative genes for complexly inherited neuropsychiatric and neurodegenerative disorders. However, existing statistical methods largely ignore the functional features (e.g., functional smoothness and correlation). The aim of this paper is to develop a functional genome-wide association analysis (FGWAS) framework to efficiently carry out whole-genome analyses of functional phenotypes...
July 19, 2017: NeuroImage
https://www.readbyqxmd.com/read/28734077/integrative-studies-implicate-matrix-metalloproteinase-12-as-a-culprit-gene-for-large-artery-atherosclerotic-stroke
#11
Hovsep Mahdessian, Ljubica Perisic Matic, Mariette Lengquist, Karl Gertow, Bengt Sennblad, Damiano Baldassarre, Fabrizio Veglia, Steve E Humphries, Rainer Rauramaa, Ulf de Faire, Andries J Smit, Philippe Giral, Sudhir Kurl, Elmo Mannarino, Elena Tremoli, Anders Hamsten, Per Eriksson, Ulf Hedin, Anders Mälarstig
BACKGROUND: Ischemic stroke and coronary heart disease are important contributors to the global disease burden and share atherosclerosis as the main underlying cause. Recent evidence from a genome-wide association study (GWAS) suggested that single nucleotide polymorphisms (SNP) near the MMP12 gene at chromosome 11q22.3 were associated with large-vessel ischemic stroke. Here we evaluated and extended these results by examining the relationship between MMP12 and atherosclerosis in clinical and experimental studies...
July 22, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28734047/preselection-of-recombinant-gene-integration-sites-enabling-high-transcription-rates-in-cho-cells-using-alternate-start-codons-and-recombinase-mediated-cassette-exchange
#12
Martina Baumann, Elisabeth Gludovacz, Natalie Sealover, Scott Bahr, Henry George, Nan Lin, Kevin Kayser, Nicole Borth
Site-specific Recombinase Mediated Cassette Exchange (RMCE) enables the transfer of the gene of interest (GOI) into pre-selected genomic locations with defined expression properties. For the generation of recombinant production cell lines this has the advantage that screening for high transcription rates at the genome integration site would be required only once, with the possibility to reuse the selected site for new products. Here we describe a strategy that aims at the selection of transcriptionally active genome integration sites in Chinese Hamster Ovary (CHO) cells by using alternate start codons in the surface reporter protein CD4, in combination with FACS sorting for high expressers...
July 22, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28733909/genetics-molecular-and-proteomics-advances-in-filamentous-fungi
#13
REVIEW
Prakriti Sharma Ghimire, Cheng Jin
Filamentous fungi play a dynamic role in health and the environment. In addition, their unique and complex hyphal structures are involved in their morphogenesis, integrity, synthesis, and degradation, according to environmental and physiological conditions and resource availability. However, in biotechnology, it has a great value in the production of enzymes, pharmaceuticals, and food ingredients. The beginning of nomenclature of overall fungi started in early 1990 after which the categorization, interior and exterior mechanism, function, molecular and genetics study took pace...
July 22, 2017: Current Microbiology
https://www.readbyqxmd.com/read/28733552/new-insights-in-the-clinical-and-translational-relevance-of-mir483-5p-in-adrenocortical-cancer
#14
Francesca Salvianti, Letizia Canu, Giada Poli, Roberta Armignacco, Cristian Scatena, Giulia Cantini, Alessandra Di Franco, Stefania Gelmini, Tonino Ercolino, Mario Pazzagli, Gabriella Nesi, Massimo Mannelli, Pamela Pinzani, Michaela Luconi
Adrenocortical cancer (ACC) is a rare aggressive malignancy. Recent ACC integrated genomics analysis contributed to redefine the risk groups on molecular basis, including tumor microRNAs (miRs), detectable also in the bloodstream. We developed a quantitative real-time (RT) assay for the measurement of miR483 and miR483-5p absolute levels in plasma samples. miR483/miR483-5p levels were evaluated in plasma samples of 27 patients with ACC before surgery and at follow-up.Statistically significant differences in miR483-5p and miR483 levels were found between stage 1/2 and stage 3/4 ACCs in pre-surgery and post-surgery samples...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733402/analysis-of-dna-metabolism-in-fission-yeast
#15
Francisco Antequera, Timothy C Humphrey
The fission yeast Schizosaccharomyces pombe is an excellent model organism to study DNA metabolism, in which the DNA replication and repair mechanisms are evolutionarily conserved. In this introduction we describe a range of methods commonly used to study aspects of DNA metabolism in fission yeast, focusing on approaches used for the analysis of genome stability, DNA replication, and DNA repair. We describe the use of a minichromosome, Ch(16), for monitoring different aspects of genome stability. We introduce two-dimensional gel electrophoresis and immunofluorescent visualization of combed DNA molecules for the analysis of DNA replication...
July 21, 2017: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/28733400/visualization-of-a-specific-genome-locus-by-the-laco-laci-gfp-system
#16
Da-Qiao Ding, Yasushi Hiraoka
Observing the dynamics of a specific chromosome locus in living cells can provide important information as to the molecular mechanisms underlying events such as chromosome segregation, homologous chromosome pairing, chromosome arrangement, and gene expression. The lacO/LacI-GFP system provides a simple and useful method in which a chromosome locus is visualized by inserting lacO repeat arrays and then expressing an LacI-GFP fusion that specifically binds to the lacO sequence. This system has been adapted for use in Schizosaccharomyces pombe by expressing the LacI-GFP under a promoter of the dis1(+) gene...
July 21, 2017: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/28733194/breast-cancer-molecular-stratification-from-intrinsic-subtypes-to-integrative-clusters
#17
REVIEW
Hege G Russnes, Ole Christian Lingjærde, Anne-Lise Børresen-Dale, Carlos Caldas
Breast carcinomas can be stratified into different entities based on clinical behavior, histological features and/or by biological properties. A classification of breast cancer should be based on underlying biology, which we know must be determined by the somatic genomic landscape of mutations. Moreover, as the latest generations of anti-cancer agents are founded on biological mechanisms, a detailed molecular stratification is a requirement for appropriate clinical management. Such stratification, based on genomic drivers, will be important for selecting patients for clinical trials...
July 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28732548/genome-wide-mapping-of-transcriptional-enhancer-candidates-using-dna-and-chromatin-features-in-maize
#18
Rurika Oka, Johan Zicola, Blaise Weber, Sarah N Anderson, Charlie Hodgman, Jonathan I Gent, Jan-Jaap Wesselink, Nathan M Springer, Huub C J Hoefsloot, Franziska Turck, Maike Stam
BACKGROUND: While most cells in multicellular organisms carry the same genetic information, in each cell type only a subset of genes is being transcribed. Such differentiation in gene expression depends, for a large part, on the activation and repression of regulatory sequences, including transcriptional enhancers. Transcriptional enhancers can be located tens of kilobases from their target genes, but display characteristic chromatin and DNA features, allowing their identification by genome-wide profiling...
July 21, 2017: Genome Biology
https://www.readbyqxmd.com/read/28732532/gate-an-efficient-procedure-in-study-of-pleiotropic-genetic-associations
#19
Wei Zhang, Liu Yang, Larry L Tang, Aiyi Liu, James L Mills, Yuanchang Sun, Qizhai Li
BACKGROUND: The association studies on human complex traits are admittedly propitious to identify deleterious genetic markers. Compared to single-trait analyses, multiple-trait analyses can arguably make better use of the information on both traits and markers, and thus improve statistical power of association tests prominently. Principal component analysis (PCA) is a well-known useful tool in multivariate analysis and can be applied to this task. Generally, PCA is first performed on all traits and then a certain number of top principal components (PCs) that explain most of the trait variations are selected to construct the test statistics...
July 21, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28732479/an-integrated-computational-experimental-approach-reveals-yersinia-pestis-genes-essential-across-a-narrow-or-a-broad-range-of-environmental-conditions
#20
Nicola J Senior, Kalesh Sasidharan, Richard J Saint, Andrew E Scott, Mitali Sarkar-Tyson, Philip M Ireland, Helen L Bullifent, Z Rong Yang, Karen Moore, Petra C F Oyston, Timothy P Atkins, Helen S Atkins, Orkun S Soyer, Richard W Titball
BACKGROUND: The World Health Organization has categorized plague as a re-emerging disease and the potential for Yersinia pestis to also be used as a bioweapon makes the identification of new drug targets against this pathogen a priority. Environmental temperature is a key signal which regulates virulence of the bacterium. The bacterium normally grows outside the human host at 28 °C. Therefore, understanding the mechanisms that the bacterium used to adapt to a mammalian host at 37 °C is central to the development of vaccines or drugs for the prevention or treatment of human disease...
July 21, 2017: BMC Microbiology
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