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Translational genomics

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https://www.readbyqxmd.com/read/28340510/the-diverse-family-of-mmpl-transporters-in-mycobacteria-from-regulation-to-antimicrobial-developments
#1
REVIEW
Albertus Viljoen, Violaine Dubois, Fabienne Girard-Misguich, Mickael Blaise, Jean-Louis Herrmann, Laurent Kremer
Mycobacterial genomes contain large sets of loci encoding membrane proteins that belong to a family of multidrug resistance pumps designated Resistance-Nodulation-Cell Division (RND) permeases. Mycobacterial membrane protein Large (MmpL) transporters represent a subclass of RND transporters known to participate in the export of lipid components across the cell envelope. These surface-exposed lipids with unusual structures play key roles in the physiology of mycobacteria and/or can act as virulence factors and immunomodulators...
March 24, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28340407/transmission-of-persistent-ionizing-radiation-induced-foci-through-cell-division-in-human-primary-cells
#2
Aurelie Vaurijoux, Pascale Voisin, Amelie Freneau, Joan Francesc Barquinero, Gaetan Gruel
Unrepaired DNA double-strand breaks (DSBs) induced by ionizing radiation are associated with lethal effects and genomic instability. After the initial breaks and chromatin destabilization, a set of post-translational modifications of histones occurs, including phosphorylation of serine 139 of histone H2AX (γH2AX), which leads to the formation of ionizing radiation-induced foci (IRIF). DSB repair results in the disappearance of most IRIF within hours after exposure, although some remain 24h after irradiation...
March 10, 2017: Mutation Research
https://www.readbyqxmd.com/read/28338950/non-replicative-rna-recombination-of-an-animal-plus-strand-rna-virus-in-the-absence-of-efficient-translation-of-viral-proteins
#3
Maximiliane Kleine Büning, Denise Meyer, Sophia Austermann-Busch, Gleyder Roman-Sosa, Tillmann Rümenapf, Paul Becher
RNA recombination is a major driving force for the evolution of RNA viruses and is significantly implicated in the adaptation of viruses to new hosts, changes of virulence, as well as in the emergence of new viruses including drug-resistant and escape mutants. However, the molecular details of recombination in animal RNA viruses are only poorly understood. In order to determine whether viral RNA recombination depends on translation of viral proteins, a non-replicative recombination system was established which is based on cotransfection of cells with synthetic bovine viral diarrhea virus (family Flaviviridae) RNA genome fragments either lacking the internal ribosome entry site required for cap-independent translation or lacking almost the complete polyprotein coding region...
March 11, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28338832/evidence-of-translation-efficiency-adaptation-of-the-coding-regions-of-the-bacteriophage-lambda
#4
Eli Goz, Oriah Mioduser, Alon Diament, Tamir Tuller
Deciphering the way gene expression regulatory aspects are encoded in viral genomes is a challenging mission with ramifications related to all biomedical disciplines. Here, we aimed to understand how the evolution shapes the bacteriophage lambda genes by performing a high resolution analysis of ribosomal profiling data and gene expression related synonymous/silent information encoded in bacteriophage coding regions.We demonstrated evidence of selection for distinct compositions of synonymous codons in early and late viral genes related to the adaptation of translation efficiency to different bacteriophage developmental stages...
February 28, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/28338761/influence-of-polynucleosome-preparation-methods-on-sedimentation-velocity-analysis-of-chromatin
#5
Tomoya Kujirai, Shinichi Machida, Akihisa Osakabe, Hitoshi Kurumizaka
Chromatin dynamics and higher order structures play essential roles in genomic DNA functions. Histone variants and histone post-translational modifications are involved in the regulation of chromatin structure and dynamics, cooperatively with DNA methylation and chromatin binding proteins. Therefore, studies of higher-order chromatin conformations have become important to reveal how genomic DNA is regulated during DNA transcription, replication, recombination and repair. The sedimentation velocity analysis by analytical ultracentrifugation has been commonly used to evaluate the higher-order conformation of in vitro reconstituted polynucleosomes, as model chromatin...
December 22, 2016: Journal of Biochemistry
https://www.readbyqxmd.com/read/28336253/mitochondrial-matters-mitochondrial-bottlenecks-self-assembling-structures-and-entrapment-in-the-female-germline
#6
Florence L Marlow
Mitochondrial replacement therapy, a procedure to generate embryos with the nuclear genome of a donor mother and the healthy mitochondria of a recipient egg, has recently emerged as a promising strategy to prevent transmission of devastating mitochondrial DNA diseases and infertility. The procedure may produce an embryo that is free of diseased mitochondria. A recent study addresses important fundamental questions about the mechanisms underlying maternal inheritance and translational questions regarding the transgenerational effectiveness of this promising therapeutic strategy...
March 15, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28335732/lung-function-associated-gene-integrator-complex-subunit-12-regulates-protein-synthesis-pathways
#7
Alexander K Kheirallah, Cornelia H de Moor, Alen Faiz, Ian Sayers, Ian P Hall
BACKGROUND: Genetic studies of human lung function and Chronic Obstructive Pulmonary Disease have identified a highly significant and reproducible signal on 4q24. It remains unclear which of the two candidate genes within this locus may regulate lung function: GSTCD, a gene with unknown function, and/or INTS12, a member of the Integrator Complex which is currently thought to mediate 3'end processing of small nuclear RNAs. RESULTS: We found that, in lung tissue, 4q24 polymorphisms associated with lung function correlate with INTS12 but not neighbouring GSTCD expression...
March 23, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28334743/comparative-genomic-analysis-of-translation-initiation-mechanisms-for-genes-lacking-the-shine-dalgarno-sequence-in-prokaryotes
#8
So Nakagawa, Yoshihito Niimura, Takashi Gojobori
In prokaryotes, translation initiation is believed to occur through an interaction between the 3΄ tail of a 16S rRNA and a corresponding Shine-Dalgarno (SD) sequence in the 5΄ untranslated region (UTR) of an mRNA. However, some genes lack SD sequences (non-SD genes), and the fraction of non-SD genes in a genome varies depending on the prokaryotic species. To elucidate non-SD translation initiation mechanisms in prokaryotes from an evolutionary perspective, we statistically examined the nucleotide frequencies around the initiation codons in non-SD genes from 260 prokaryotes (235 bacteria and 25 archaea)...
February 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334050/improving-transcriptome-de-novo-assembly-by-using-a-reference-genome-of-a-related-species-translational-genomics-from-oil-palm-to-coconut
#9
Alix Armero, Luc Baudouin, Stéphanie Bocs, Dominique This
The palms are a family of tropical origin and one of the main constituents of the ecosystems of these regions around the world. The two main species of palm represent different challenges: coconut (Cocos nucifera L.) is a source of multiple goods and services in tropical communities, while oil palm (Elaeis guineensis Jacq) is the main protagonist of the oil market. In this study, we present a workflow that exploits the comparative genomics between a target species (coconut) and a reference species (oil palm) to improve the transcriptomic data, providing a proteome useful to answer functional or evolutionary questions...
2017: PloS One
https://www.readbyqxmd.com/read/28332826/packaged-and-free-stmv-rna-genomes-adopt-distinct-conformational-states
#10
Bridget C Larman, Elizabeth A Dethoff, Kevin M Weeks
The RNA genomes of viruses likely undergo multiple functionally important conformational changes during their replication cycles, changes that are poorly understood at present. We used two complementary in-solution RNA structure probing strategies (SHAPE-MaP and RING-MaP) to examine the structure of the RNA genome of satellite tobacco mosaic virus inside authentic virions and in a capsid-free state. Both RNA states feature similar three-domain architectures in which each major replicative function - translation, capsid coding, and genome synthesis - fall into distinct domains...
March 23, 2017: Biochemistry
https://www.readbyqxmd.com/read/28331970/disease-modeling-in-genetic-kidney-diseases-zebrafish
#11
REVIEW
Heiko Schenk, Janina Müller-Deile, Mark Kinast, Mario Schiffer
Growing numbers of translational genomics studies are based on the highly efficient and versatile zebrafish (Danio rerio) vertebrate model. The increasing types of zebrafish models have improved our understanding of inherited kidney diseases, since they not only display pathophysiological changes but also give us the opportunity to develop and test novel treatment options in a high-throughput manner. New paradigms in inherited kidney diseases have been developed on the basis of the distinct genome conservation of approximately 70 % between zebrafish and humans in terms of existing gene orthologs...
March 22, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28331418/optimization-of-pcr-condition-the-first-study-of-high-resolution-melting-technique-for-screening-of-apoa1-variance
#12
Hesty Wahyuningsih, Ferdy K Cayami, Udin Bahrudin, Mochamad A Sobirin, Farmaditya Ep Mundhofir, Sultana Mh Faradz, Ichiro Hisatome
BACKGROUND: High resolution melting (HRM) is a post-PCR technique for variant screening and genotyping based on the different melting points of DNA fragments. The advantages of this technique are that it is fast, simple, and efficient and has a high output, particularly for screening of a large number of samples. APOA1 encodes apolipoprotein A1 (apoA1) which is a major component of high density lipoprotein cholesterol (HDL-C). This study aimed to obtain an optimal quantitative polymerase chain reaction (qPCR)-HRM condition for screening of APOA1 variance...
March 2017: Yonago Acta Medica
https://www.readbyqxmd.com/read/28330383/progress-in-nonviral-gene-therapy-for-breast-cancer-and-what-comes-next
#13
Giulia Bottai, Marta Truffi, Fabio Corsi, Libero Santarpia
The possibility of correcting defective genes and modulating gene expression through gene therapy has emerged as a promising treatment strategy for breast cancer. Furthermore, the relevance of tumor immune microenvironment in supporting the oncogenic process has paved the way for novel immunomodulatory applications of gene therapy. Areas covered: In this review, the authors describe the most relevant delivery systems, focusing on nonviral vectors, along with the description of the major approaches used to modify target cells, including gene transfer, RNA interference (RNAi), and epigenetic regulation...
March 22, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28328998/combinatorial-selection-for-replicable-rna-by-q%C3%AE-replicase-while-maintaining-encoded-gene-function
#14
Mio Yumura, Natsuko Yamamoto, Katsushi Yokoyama, Hirotada Mori, Tetsuya Yomo, Norikazu Ichihashi
Construction of a complex artificial self-replication system is challenging in the field of in vitro synthetic biology. Recently, we developed a translation-coupled RNA replication system, wherein an artificial genomic RNA replicates with the Qβ RNA replicase gene encoded on itself. The challenge is to introduce additional genes into the RNA to develop a complex system that mimics natural living systems. However, most RNA sequence encoding genes are not replicable by the Qβ replicase owing to its requirement for strong secondary structures throughout the RNA sequence that are absent in most genes...
2017: PloS One
https://www.readbyqxmd.com/read/28328372/psychiatric-genomics-and-mental-health-treatment-setting-the-ethical-agenda
#15
Camillia Kong, Michael Dunn, Michael Parker
Realizing the benefits of translating psychiatric genomics research into mental health care is not straightforward. The translation process gives rise to ethical challenges that are distinctive from challenges posed within psychiatric genomics research itself, or that form part of the delivery of clinical psychiatric genetics services. This article outlines and considers three distinct ethical concerns posed by the process of translating genomic research into frontline psychiatric practice and policy making...
April 2017: American Journal of Bioethics: AJOB
https://www.readbyqxmd.com/read/28327901/data-resources-for-the-identification-and-interpretation-of-actionable-mutations-by-clinicians
#16
A Prawira, T J Pugh, T L Stockley, L L Siu
Following initial characterization of the reference human genome, initiatives have evolved worldwide to identify genomic aberrations in cancer with the aim of deriving diagnostic, prognostic and predictive information. However, the functional and clinical relevance of many somatic variants in cancer are presently unknown and there is no consensus definition of "actionability" for genomic aberrancies. Therefore, while robust detection of a variety of genetic aberrations in clinical specimens remains a technical hurdle, the greater challenge lies in the interpretation of these alterations...
January 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327571/insights-from-early-experience-of-a-rare-disease-genomic-medicine-multidisciplinary-team-a-qualitative-study
#17
Elizabeth Ormondroyd, Michael P Mackley, Edward Blair, Jude Craft, Julian C Knight, John Taylor, Jenny C Taylor, Andrew Om Wilkie, Hugh Watkins
Whole-exome/whole-genome sequencing (WES/WGS) has the potential to enhance genetic diagnosis of rare disease, and is increasingly becoming part of routine clinical care in mainstream medicine. Effective translation will require ongoing efforts in a number of areas including: selection of appropriate patients, provision of effective consent, pre- and post-test genetic counselling, improving variant interpretation algorithms and practices, and management of secondary findings including those found incidentally and those actively sought...
March 22, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28327113/low-cell-number-single-tube-amplification-sta-of-total-rna-revealed-transcriptome-changes-from-pluripotency-to-endothelium
#18
Yi-Hsuan Lee, Ya-Wen Hsueh, Yao-Hung Peng, Kung-Chao Chang, Kuen-Jer Tsai, H Sunny Sun, Ih-Jen Su, Po-Min Chiang
BACKGROUND: In addition to messenger RNA (mRNA), noncoding RNAs (ncRNAs) are essential components in cellular machineries for translation and splicing. Besides their housekeeping functions, ncRNAs are involved in cell type-specific regulation of translation, mRNA stability, genome structure, and accessibility. To have a comprehensive understanding of the identities and functions of different cell types, a method to comprehensively quantify both mRNA and ncRNA in a sensitive manner is highly desirable...
March 21, 2017: BMC Biology
https://www.readbyqxmd.com/read/28326191/global-histone-modification-fingerprinting-in-human-cells-using-epigenetic-reverse-phase-protein-array
#19
Marina Partolina, Hazel C Thoms, Kenneth G MacLeod, Giovanny Rodriguez-Blanco, Matthew N Clarke, Anuroop V Venkatasubramani, Rima Beesoo, Vladimir Larionov, Vidushi S Neergheen-Bhujun, Bryan Serrels, Hiroshi Kimura, Neil O Carragher, Alexander Kagansky
The balance between acetylation and deacetylation of histone proteins plays a critical role in the regulation of genomic functions. Aberrations in global levels of histone modifications are linked to carcinogenesis and are currently the focus of intense scrutiny and translational research investments to develop new therapies, which can modify complex disease pathophysiology through epigenetic control. However, despite significant progress in our understanding of the molecular mechanisms of epigenetic machinery in various genomic contexts and cell types, the links between epigenetic modifications and cellular phenotypes are far from being clear...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28324015/paternally-inherited-dlk1-deletion-associated-with-familial-central-precocious-puberty
#20
Andrew Dauber, Marina Cunha-Silva, Delanie B Macedo, Vinicius N Brito, Ana Paula Abreu, Stephanie A Roberts, Luciana R Montenegro, Melissa Andrew, Andrew Kirby, Matthew T Weirauch, Guillaume Labilloy, Danielle S Bessa, Rona S Carroll, Dakota C Jacobs, Patrick E Chappell, Berenice B Mendonca, David Haig, Ursula B Kaiser, Ana Claudia Latronico
Context: Central precocious puberty (CPP) results from premature activation of the hypothalamic-pituitary-gonadal axis. Few genetic causes of CPP have been identified with the most common being mutations in the paternally expressed imprinted gene MKRN3. Objective: To identify the genetic etiology of CPP in a large multigenerational family. Design: Linkage analysis followed by whole genome sequencing was performed in a family with 5 female members with nonsyndromic CPP...
January 27, 2017: Journal of Clinical Endocrinology and Metabolism
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