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Translational genomics

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https://www.readbyqxmd.com/read/28535374/discovery-of-stromal-regulatory-networks-that-suppress-ras-sensitized-epithelial-cell-proliferation
#1
Huayang Liu, James A Dowdle, Safiya Khurshid, Nicholas J Sullivan, Nicholas Bertos, Komal Rambani, Markus Mair, Piotr Daniel, Esther Wheeler, Xing Tang, Kyle Toth, Michael Lause, Markus E Harrigan, Karl Eiring, Connor Sullivan, Matthew J Sullivan, Serena W Chang, Siddhant Srivastava, Joseph S Conway, Raleigh Kladney, Joseph McElroy, Sooin Bae, Yuanzhi Lu, Ali Tofigh, Sadiq M I Saleh, Soledad A Fernandez, Jeffrey D Parvin, Vincenzo Coppola, Erin R Macrae, Sarmila Majumder, Charles L Shapiro, Lisa D Yee, Bhuvaneswari Ramaswamy, Michael Hallett, Michael C Ostrowski, Morag Park, Helen M Chamberlin, Gustavo Leone
Mesodermal cells signal to neighboring epithelial cells to modulate their proliferation in both normal and disease states. We adapted a Caenorhabditis elegans organogenesis model to enable a genome-wide mesodermal-specific RNAi screen and discovered 39 factors in mesodermal cells that suppress the proliferation of adjacent Ras pathway-sensitized epithelial cells. These candidates encode components of protein complexes and signaling pathways that converge on the control of chromatin dynamics, cytoplasmic polyadenylation, and translation...
May 22, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28534634/non-coding-after-all-biases-in-proteomics-data-do-not-explain-observed-absence-of-lncrna-translation-products
#2
Kenneth Verheggen, Pieter-Jan Volders, Pieter Mestdagh, Gerben Menschaert, Petra Van Damme, Kris Gevaert, Lennart Martens, Jo Vandesompele
Over the past decade, long non-coding RNAs (lncRNAs) have emerged as novel functional entities of the eukaryotic genome. However, the scientific community remains divided over the amount of true non-coding transcripts among the large number of unannotated transcripts identified by recent large scale and deep RNAsequencing efforts. Here, we systematically exclude possible technical reasons underlying the absence of lncRNA-encoded proteins in mass spectrometry datasets, strongly suggesting that the large majority of lncRNAs is indeed not translated...
May 23, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28533414/manipulating-dna-damage-response-signaling-for-the-treatment-of-immune-mediated-diseases
#3
Jonathan P McNally, Scott H Millen, Vandana Chaturvedi, Nora Lakes, Catherine E Terrell, Eileen E Elfers, Kaitlin R Carroll, Simon P Hogan, Paul R Andreassen, Julie Kanter, Carl E Allen, Michael M Henry, Jay N Greenberg, Stephan Ladisch, Michelle L Hermiston, Michael Joyce, David A Hildeman, Jonathan D Katz, Michael B Jordan
Antigen-activated lymphocytes undergo extraordinarily rapid cell division in the course of immune responses. We hypothesized that this unique aspect of lymphocyte biology leads to unusual genomic stress in recently antigen-activated lymphocytes and that targeted manipulation of DNA damage-response (DDR) signaling pathways would allow for selective therapeutic targeting of pathological T cells in disease contexts. Consistent with these hypotheses, we found that activated mouse and human T cells display a pronounced DDR in vitro and in vivo...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28532511/challenges-and-strategies-for-implementing-genomic-services-in-diverse-settings-experiences-from-the-implementing-genomics-in-practice-ignite-network
#4
Nina R Sperber, Janet S Carpenter, Larisa H Cavallari, Laura J Damschroder, Rhonda M Cooper-DeHoff, Joshua C Denny, Geoffrey S Ginsburg, Yue Guan, Carol R Horowitz, Kenneth D Levy, Mia A Levy, Ebony B Madden, Michael E Matheny, Toni I Pollin, Victoria M Pratt, Marc Rosenman, Corrine I Voils, Kristen W Weitzel, Russell A Wilke, R Ryanne Wu, Lori A Orlando
BACKGROUND: To realize potential public health benefits from genetic and genomic innovations, understanding how best to implement the innovations into clinical care is important. The objective of this study was to synthesize data on challenges identified by six diverse projects that are part of a National Human Genome Research Institute (NHGRI)-funded network focused on implementing genomics into practice and strategies to overcome these challenges. METHODS: We used a multiple-case study approach with each project considered as a case and qualitative methods to elicit and describe themes related to implementation challenges and strategies...
May 22, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28532423/the-various-aspects-of-genetic-and-epigenetic-toxicology-testing-methods-and-clinical-applications
#5
REVIEW
Ning Ren, Manar Atyah, Wan-Yong Chen, Chen-Hao Zhou
Genotoxicity refers to the ability of harmful substances to damage genetic information in cells. Being exposed to chemical and biological agents can result in genomic instabilities and/or epigenetic alterations, which translate into a variety of diseases, cancer included. This concise review discusses, from both a genetic and epigenetic point of view, the current detection methods of different agents' genotoxicity, along with their basic and clinical relation to human cancer, chemotherapy, germ cells and stem cells...
May 22, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28531174/genome-partitioner-a-web-tool-for-multi-level-partitioning-of-large-scale-dna-constructs-for-synthetic-biology-applications
#6
Matthias Christen, Luca Del Medico, Heinz Christen, Beat Christen
Recent advances in lower-cost DNA synthesis techniques have enabled new innovations in the field of synthetic biology. Still, efficient design and higher-order assembly of genome-scale DNA constructs remains a labor-intensive process. Given the complexity, computer assisted design tools that fragment large DNA sequences into fabricable DNA blocks are needed to pave the way towards streamlined assembly of biological systems. Here, we present the Genome Partitioner software implemented as a web-based interface that permits multi-level partitioning of genome-scale DNA designs...
2017: PloS One
https://www.readbyqxmd.com/read/28531161/development-of-optimized-inhibitor-rnas-allowing-multisite-targeting-of-the-hcv-genome
#7
Cristina Romero-López, Thomas Lahlali, Beatriz Berzal-Herranz, Alfredo Berzal-Herranz
Engineered multivalent drugs are promising candidates for fighting infection by highly variable viruses, such as HCV. The combination into a single molecule of more than one inhibitory domain, each with its own target specificity and even a different mechanism of action, results in drugs with potentially enhanced therapeutic properties. In the present work, the anti-HCV chimeric inhibitor RNA HH363-10, which has a hammerhead catalytic domain and an aptamer RNA domain, was subjected to an in vitro selection strategy to isolate ten different optimised chimeric inhibitor RNAs...
May 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28528452/tumor-suppressor-protein-p53-exerts-negative-transcriptional-regulation-on-human-sodium-iodide-symporter-gene-expression-in-breast-cancer
#8
Madhura G Kelkar, Bhushan Thakur, Abhishek Derle, Sushmita Chatterjee, Pritha Ray, Abhijit De
PURPOSE: Aberrant expression of human sodium iodide symporter (NIS) in breast cancer (BC) is well documented but the transcription factors (TF) regulating its aberrant expression is poorly known. We identify the presence of three p53 binding sites on the human NIS promoter sequence by conducting genome-wide TF analysis, and further investigate their regulatory role. METHODS: The differences in transcription and translation were measured by real-time PCR, luciferase reporter assay, site-directed mutagenesis, in vivo optical imaging, and chromatin immunoprecipitation...
May 20, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28528441/herpesvirus-latency-on-the-importance-of-positioning-oneself
#9
Patrick Lomonte
The nucleus is composed of multiple compartments and domains, which directly or indirectly influence many cellular processes including gene expression, RNA splicing and maturation, protein post-translational modifications, and chromosome segregation. Nuclear-replicating viruses, especially herpesviruses, have co-evolved with the cell, adopting strategies to counteract and eventually hijack this hostile environment for their own benefit. This allows them to persist in the host for the entire life of an individual and to ensure their maintenance in the target species...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28527665/therapeutic-editing-of-hepatocyte-genome-in-vivo
#10
REVIEW
Marina Ruiz de Galarreta, Amaia Lujambio
The recent development of gene editing platforms enables making precise changes in the genome of eukaryotic cells. Programmable nucleases, such as meganucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)-associated nucleases, have revolutionized the way research is conducted as they facilitate the rapid production of mutant or knock-out cellular and animal models. These same genetic tools can potentially be applied to cure or alleviate a variety of diseases, including genetic diseases that lack an efficient therapy...
May 17, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28527373/-i-don-t-believe-it-acceptance-and-skepticism-of-genetic-health-information-among-african-american-and-white-smokers
#11
Erika A Waters, Linda Ball, Sarah Gehlert
RATIONALE: Effective translation of genomics research into practice depends on public acceptance of genomics-related health information. OBJECTIVE: To explore how smokers come to accept or reject information about the relationship between genetics and nicotine addiction. METHODS: Thirteen focus groups (N = 84) were stratified by education (seven < Bachelor's degree, six ≥ Bachelor's degree) and race (eight black, five white). Participants viewed a 1-min video describing the discovery of a genetic variant associated with increased risk of nicotine addiction and lung cancer...
May 3, 2017: Social Science & Medicine
https://www.readbyqxmd.com/read/28525563/omics-biomarkers-in-ophthalmology
#12
Susette Lauwen, Eiko K de Jong, Dirk J Lefeber, Anneke I den Hollander
"Omics" refers to high-throughput analyses of genes, proteins, or metabolites in a biological system, and is increasingly used for ophthalmic research. These system-based approaches can unravel disease-related processes and are valuable for biomarker discovery. Furthermore, potential therapeutic targets can be identified based on omics results, and targeted follow-up experiments can be designed to gain molecular understanding of the disease and to test new therapies. Here, we review the application of omics techniques in eye diseases, focusing on age-related macular degeneration (AMD), diabetic retinopathy (DR), retinal detachment (RD), myopia, glaucoma, Fuchs' corneal dystrophy (FCD), cataract, keratoconus, and dry eyes...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28523967/comparative-assessment-of-dna-methylation-patterns-between-reduced-representation-bisulfite-sequencing-and-sequenom-epityper-methylation-analysis
#13
Aniruddha Chatterjee, Erin C Macaulay, Antonio Ahn, Jackie L Ludgate, Peter A Stockwell, Rob J Weeks, Matthew F Parry, Timothy J Foster, Ingrid M Knarston, Michael R Eccles, Ian M Morison
AIM: Validation of sequencing-based DNA methylation data is an important step for meaningful translation of findings. However, there has been limited assessment of different platforms to validate methylation data from next generation sequencing. METHODS: We performed a comparative methylation analysis between the genome-wide platform of reduced representation bisulfite sequencing with a targeted, Sequenom EpiTyper platform (four genes were analyzed in 15 cell lines covering 52 CpG sites)...
May 19, 2017: Epigenomics
https://www.readbyqxmd.com/read/28523359/arginine-cga-codons-as-a-source-of-nonsense-mutations-a-possible-role-in-multivariant-gene-expression-control-of-mrna-quality-and-aging
#14
Georgy A Romanov, Victor S Sukhoverov
Methylation of cytosine residues in DNA of higher eukaryotes, including humans, creates "hot spots" of C→T transitions in the genome. The predominantly methylated sequence in mammalian DNAs is CG (CpG). Among CG-containing codons, CGA codons for arginine are unique due to their ability to create stop codons TGA (UGA in mRNA) upon epigenetic-mediated mutation. As such nonsense mutations can have a strong adverse effect on the cell and organism, we have performed a study, on the example of human genes, aimed to characterise the anticipated effects of epigenetic-mediated nonsense mutations CGA→TGA in somatic cells...
May 18, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28521338/klebsiella-pneumoniae-a-major-worldwide-source-and-shuttle-for-antibiotic-resistance
#15
Shiri Navon-Venezia, Kira Kondratyeva, Alessandra Carattoli
Klebsiella pneumoniae is an important multidrug-resistant (MDR) pathogen affecting humans and a major source for hospital infections associated with high morbidity and mortality due to limited treatment options. We summarize the wide resistome of this pathogen, which encompasses plentiful chromosomal and plasmid-encoded antibiotic resistance genes (ARGs). Under antibiotic selective pressure, K. pneumoniae continuously accumulates ARGs, by de novo mutations, and via acquisition of plasmids and transferable genetic elements, leading to extremely drug resistant (XDR) strains harboring a 'super resistome'...
May 1, 2017: FEMS Microbiology Reviews
https://www.readbyqxmd.com/read/28520982/genome-wide-mrna-processing-in-methanogenic-archaea-reveals-post-transcriptional-regulation-of-ribosomal-protein-synthesis
#16
Lei Qi, Lei Yue, Deqin Feng, Fengxia Qi, Jie Li, Xiuzhu Dong
Unlike stable RNAs that require processing for maturation, prokaryotic cellular mRNAs generally follow an 'all-or-none' pattern. Herein, we used a 5΄ monophosphate transcript sequencing (5΄P-seq) that specifically captured the 5΄-end of processed transcripts and mapped the genome-wide RNA processing sites (PSSs) in a methanogenic archaeon. Following statistical analysis and stringent filtration, we identified 1429 PSSs, among which 23.5% and 5.4% were located in 5΄ untranslated region (uPSS) and intergenic region (iPSS), respectively...
May 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28517993/your-dna-your-say
#17
Anna Middleton
Genomic and medical data sharing is pivotal if the promise of genomic medicine is to be fully realised. Social scientists working in the genomics arena ask the public 'how is the technology working for you?' Empirical studies on attitudes, values and beliefs are incredibly valuable; they offer a voice from those who are, or will be, directly affected. This is paramount if personalised medicine is to be truly personal. An International attitude study, Your DNA, Your Say, uses film to provide background information and an online survey to gather public views on donating one's own personal DNA and medical data for use by others...
April 2017: New Bioethics: a Multidisciplinary Journal of Biotechnology and the Body
https://www.readbyqxmd.com/read/28516784/in-culture-cross-linking-of-bacterial-cells-reveals-large-scale-dynamic-protein-protein-interactions-at-the-peptide-level
#18
Luitzen de Jong, Edward A de Koning, Winfried Roseboom, Hansuk Buncherd, Martin J Wanner, Irena Dapic, Petra J Jansen, Jan H van Maarseveen, Garry L Corthals, Peter J Lewis, Leendert Willem Hamoen, Chris G de Koster
Identification of dynamic protein-protein interactions at the peptide level on a proteomic scale is a challenging approach that is still in its infancy. We have developed a system to cross-link cells directly in culture with the special lysine cross-linker bis(succinimidyl)-3-azidomethyl-glutarate (BAMG). We used the Gram positive model bacterium Bacillus subtilis as an exemplar system. Within 5 min extensive intracellular cross-linking was detected, while intracellular cross-linking in a Gram-negative species, Escherichia coli, was still undetectable after 30 min, in agreement with the low permeability in this organism for lipophilic compounds like BAMG...
May 18, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28516387/a-diffusion-weighted-imaging-informed-continuum-model-of-the-rabbit-triceps-surae-complex
#19
M Alipour, K Mithraratne, J Fernandez
The NZ white rabbit is the animal of choice for much experimental work due to its muscular frame and similar response to human diseases, and is one of the few mammals that have had their genome sequenced. However, continuum-level computational models of rabbit muscle detailing fibre architecture are limited in the literature, especially the triceps surae complex (gastrocnemius, plantaris and soleus), which has similar biomechanics and translatable findings to the human. This study presents a geometrical model of the rabbit triceps surae informed with diffusion-weighted imaging (DWI)-based fibres...
May 18, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28515301/the-influenza-a-virus-ns1-protein-promotes-efficient-nuclear-export-of-unspliced-viral-m1-mrna
#20
Carina F Pereira, Eliot K C Read, Helen M Wise, Maria J Amorim, Paul Digard
Influenza A virus mRNAs are transcribed by the viral RNA-dependent RNA polymerase in the cell nucleus before being exported to the cytoplasm for translation. Segment 7 produces two major transcripts: an unspliced mRNA that encodes the M1 matrix protein and a spliced transcript that encodes the M2 ion channel. Export of both mRNAs is dependent on the cellular NXF1/TAP pathway but it is unclear how they are recruited to the export machinery or how the intron-containing but unspliced M1 mRNA bypasses the normal quality control checkpoints...
May 17, 2017: Journal of Virology
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