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Translational genomics

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https://www.readbyqxmd.com/read/28938540/microrna-128-3p-regulates-mitomycin-c-induced-dna-damage-response-in-lung-cancer-cells-through-repressing-sptan1
#1
Rui Zhang, Chang Liu, Yahan Niu, Ying Jing, Haiyang Zhang, Jin Wang, Jie Yang, Ke Zen, Junfeng Zhang, Chen-Yu Zhang, Donghai Li
The DNA damage response is critical for maintaining genome integrity and preventing damage to DNA due to endogenous and exogenous insults. Mitomycin C (MMC), a potent DNA cross-linker, is used as a chemotherapeutic agent because it causes DNA inter-strand cross-links (DNA ICLs) in cancer cells. While many microRNAs, which may serve as oncogenes or tumor suppressors, are grossly dysregulated in human cancers, little is known about their roles in MMC-treated lung cancer. Here, we report that miR-128-3p can attenuate repair of DNA ICLs by targeting SPTAN1 (αII Sp), resulting in cell cycle arrest and promoting chromosomal aberrations in lung cancer cells treated with MMC...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938163/tumor-cell-targeted-delivery-of-crispr-cas9-by-aptamer-functionalized-lipopolymer-for-therapeutic-genome-editing-of-vegfa-in-osteosarcoma
#2
Chao Liang, Fangfei Li, Luyao Wang, Zong-Kang Zhang, Chao Wang, Bing He, Jie Li, Zhihao Chen, Atik Badshah Shaikh, Jin Liu, Xiaohao Wu, Songlin Peng, Lei Dang, Baosheng Guo, Xiaojuan He, D W T Au, Cheng Lu, Hailong Zhu, Bao-Ting Zhang, Aiping Lu, Ge Zhang
Osteosarcoma (OS) is a highly aggressive pediatric cancer, characterized by frequent lung metastasis and pathologic bone destruction. Vascular endothelial growth factor A (VEGFA), highly expressed in OS, not only contributes to angiogenesis within the tumor microenvironment via paracrine stimulation of vascular endothelial cells, but also acts as an autocrine survival factor for tumor cell themselves, thus making it a promising therapeutic target for OS. CRISPR/Cas9 is a versatile genome editing technology and holds tremendous promise for cancer treatment...
September 13, 2017: Biomaterials
https://www.readbyqxmd.com/read/28937686/serine-392-phosphorylation-modulates-p53-mitochondrial-translocation-and-transcription-independent-apoptosis
#3
Cédric Castrogiovanni, Béranger Waterschoot, Olivier De Backer, Patrick Dumont
The tumor suppressor p53 is a key regulator of apoptosis induced by various cellular stresses. p53 can induce apoptosis by two mechanisms. First, p53 acts as a transcription factor inducing and repressing pro-apoptotic and anti-apoptotic targets genes, respectively. Second, p53 is able to translocate to the mitochondria, where it interacts with BCL-2 family members to induce membrane permeabilization and cytochrome c release. p53 transcriptional activity is regulated by a set of post-translational modifications that have been well documented...
September 22, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28935841/light-and-plastid-signals-regulate-different-sets-of-genes-in-the-albino-mutant-pap7-1
#4
Björn Grübler, Livia Merendino, Sven O Twardziok, Morgane Mininno, Guillaume Allorent, Fabien Chevalier, Monique Liebers, Robert Blanvillain, Klaus Mayer, Silva Lerbs-Mache, Stephane Ravanel, Thomas Pfannschmidt
Plants possessing dysfunctional plastids due to defects in pigment biosynthesis or translation are known to repress photosynthesis-associated nuclear genes (PhANGs) via retrograde signals from the disturbed organelles towards the nucleus. These signals are thought to be essential for proper biogenesis and function of the plastid. Mutants lacking plastid-encoded RNA polymerase-associated proteins (PAPs) display a genetic arrest in eoplast-chloroplast transition leading to an albino phenotype in the light. Retrograde signaling in these mutants, thus, could be expected to be similar as under conditions inducing plastid dysfunction...
September 21, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28935584/vih-from-the-mud-crab-is-specifically-expressed-in-the-eyestalk-and-potentially-regulated-by-transactivator-of-sox9-oct4-oct1
#5
Chunyun Liu, Xiwei Jia, Zhihua Zou, Xiaowei Wang, Yilei Wang, Ziping Zhang
Vitellogenesis-inhibiting hormone (VIH) is known to regulate ovarian maturation by suppressing the synthesis of vitellogenin (Vtg) in crustaceans, which belongs to a member of crustacean hyperglycemic hormone (CHH) family synthesized and secreted from the X-organ/sinus gland complex of eyestalks. In this study, the cDNA, genomic DNA (gDNA) and the 5'-upstream regulatory (promoter region) sequences of VIH gene were obtained by conventional PCR, genome walker and tail-PCR techniques according to our transcriptomic database of Scylla paramamosain...
September 18, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28935272/genome-wide-association-study-evaluating-single-nucleotide-polymorphisms-and-outcomes-in-patients-with-advanced-stage-serous-ovarian-or-primary-peritoneal-cancer-an-nrg-oncology-gynecologic-oncology-group-study
#6
Kathleen N Moore, David Tritchler, Kenneth M Kaufman, Heather Lankes, Michael C J Quinn, Linda Van Le, Andrew Berchuck, Floor J Backes, Krishnansu S Tewari, Roger B Lee, Joshua P Kesterson, Robert M Wenham, Deborah K Armstrong, Thomas C Krivak, Michael A Bookman, Michael J Birrer
OBJECTIVE: This study evaluated single nucleotide polymorphisms (SNPs) associated with progression free (PFS) and overall survival (OS) in patients with advanced stage serous EOC. METHODS: Patients enrolled in GOG-172 and 182 who provided specimens for translational research and consent were included. Germline DNA was evaluated with the Illumina's HumanOMNI1-Quad beadchips and scanned using Illumina's iScan optical imaging system. SNPs with allele frequency>0...
September 18, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28934492/concerted-action-of-two-3-cap-independent-translation-enhancers-increases-the-competitive-strength-of-translated-viral-genomes
#7
Zhiyou Du, Olga M Alekhina, Konstantin S Vassilenko, Anne E Simon
Several families of plant viruses evolved cap-independent translation enhancers (3'CITE) in the 3' untranslated regions of their genomic (g)RNAs to compete with ongoing cap-dependent translation of cellular mRNAs. Umbravirus Pea enation mosaic virus (PEMV)2 is the only example where three 3'CITEs enhance translation: the eIF4E-binding Panicum mosaic virus-like translational enhancer (PTE) and ribosome-binding 3' T-shaped structure (TSS) have been found in viruses of different genera, while the ribosome-binding kl-TSS that provides a long-distance interaction with the 5' end is unique...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28932757/a-five-repeat-micro-dystrophin-gene-ameliorated-dystrophic-phenotype-in-the-severe-dba-2j-mdx-model-of-duchenne-muscular-dystrophy
#8
Chady H Hakim, Nalinda B Wasala, Xiufang Pan, Kasun Kodippili, Yongping Yue, Keqing Zhang, Gang Yao, Brittney Haffner, Sean X Duan, Julian Ramos, Joel S Schneider, N Nora Yang, Jeffrey S Chamberlain, Dongsheng Duan
Micro-dystrophins are highly promising candidates for treating Duchenne muscular dystrophy, a lethal muscle disease caused by dystrophin deficiency. Here, we report robust disease rescue in the severe DBA/2J-mdx model with a neuronal nitric oxide synthase (nNOS)-binding micro-dystrophin vector. 2 × 10(13) vector genome particles/mouse of the vector were delivered intravenously to 10-week-old mice and were evaluated at 6 months of age. Saturated micro-dystrophin expression was detected in all skeletal muscles and the heart and restored the dystrophin-associated glycoprotein complex and nNOS...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28931413/topological-organization-and-dynamic-regulation-of-human-trna-genes-during-macrophage-differentiation
#9
Kevin Van Bortle, Douglas H Phanstiel, Michael P Snyder
BACKGROUND: The human genome is hierarchically organized into local and long-range structures that help shape cell-type-specific transcription patterns. Transfer RNA (tRNA) genes (tDNAs), which are transcribed by RNA polymerase III (RNAPIII) and encode RNA molecules responsible for translation, are dispersed throughout the genome and, in many cases, linearly organized into genomic clusters with other tDNAs. Whether the location and three-dimensional organization of tDNAs contribute to the activity of these genes has remained difficult to address, due in part to unique challenges related to tRNA sequencing...
September 20, 2017: Genome Biology
https://www.readbyqxmd.com/read/28930517/mirna-as-viral-transcription-tuners-in-hpv-mediated-cervical-carcinogenesis
#10
Gauri Shishodia, Gaurav Verma, Bhudev Chandra Das, Alok Chandra Bharti
High-risk human papillomaviruses (HPVs) are oncogenic DNA viruses that promote carcinogenic signaling by their oncoproteins mainly E6 and E7. A well-defined promoter regulates expression and enhancer region on HPV genome containing number of cis elements that essentially require a set of cognate host transcription factors to regulate viral promoter gene activity. Expression of these host factors is tightly regulated at multiple levels such as transcriptional, post-transcriptional and post-translational level...
January 1, 2018: Frontiers in Bioscience (Scholar Edition)
https://www.readbyqxmd.com/read/28929852/the-ethics-of-genome-editing-in-the-clinic-a-dose-of-realism-for-healthcare-leaders
#11
Tania Bubela, Yael Mansour, Dianne Nicol
Genome editing technologies promise therapeutic advances for genetic diseases. We discuss the ethical and societal issues raised by these technologies, including their use in preclinical research, their potential to address mutations in somatic cells, and their potential to make germ line alterations that may be passed to subsequent generations. We call for a proportionate response from health leaders based on a realistic assessment of benefits, risks, and timelines for clinical translation.
May 2017: Healthcare Management Forum
https://www.readbyqxmd.com/read/28929627/strategies-and-challenges-in-identifying-function-for-thousands-of-sorf-encoded-peptides-in-meiosis
#12
Ina Hollerer, Andrea Higdon, Gloria A Brar
Recent genomic analyses have revealed pervasive translation from formerly unrecognized short Open Reading Frames (sORFs) during yeast meiosis. Despite their short length, which has caused these regions to be systematically overlooked by traditional gene annotation approaches, meiotic sORFs share many features with classical genes, implying the potential for similar types of cellular functions. We found that sORF expression accounts for ∼10-20% of the cellular translation capacity in yeast during meiotic differentiation and occurs within well-defined time windows, suggesting the production of relatively abundant peptides with stage-specific meiotic roles from these regions...
September 20, 2017: Proteomics
https://www.readbyqxmd.com/read/28929311/tbi-rehabilomics-research-an-exemplar-of-a-biomarker-based-approach-to-precision-care-for-populations-with-disability
#13
REVIEW
Amy K Wagner
PURPOSE OF REVIEW: The purpose of this review is to summarize how "-omics" technologies can inform rehabilitation-relevant outcomes for a range of populations with neurologically related disability by including outcome metrics linked to the World Health Organization's International Classification of Functioning, Disability, and Health (WHO-ICF) domains of impairments in body function, activity limitations, and participation restrictions. RECENT FINDINGS: To date, nearly every area of medicine uses biomarkers in some capacity to aid in understanding how personal biology informs clinical care...
September 19, 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28928394/rna-localization-is-a-key-determinant-of-neurite-enriched-proteome
#14
Alessandra Zappulo, David van den Bruck, Camilla Ciolli Mattioli, Vedran Franke, Koshi Imami, Erik McShane, Mireia Moreno-Estelles, Lorenzo Calviello, Andrei Filipchyk, Esteban Peguero-Sanchez, Thomas Müller, Andrew Woehler, Carmen Birchmeier, Enrique Merino, Nikolaus Rajewsky, Uwe Ohler, Esteban O Mazzoni, Matthias Selbach, Altuna Akalin, Marina Chekulaeva
Protein subcellular localization is fundamental to the establishment of the body axis, cell migration, synaptic plasticity, and a vast range of other biological processes. Protein localization occurs through three mechanisms: protein transport, mRNA localization, and local translation. However, the relative contribution of each process to neuronal polarity remains unknown. Using neurons differentiated from mouse embryonic stem cells, we analyze protein and RNA expression and translation rates in isolated cell bodies and neurites genome-wide...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28928387/bi-directional-effects-of-vitamin-b12-and-methotrexate-on-daphnia-magna-fitness-and-genomic-methylation
#15
Fitore Kusari, Alan M O'Doherty, Nikolas J Hodges, Marcin W Wojewodzic
Here we interrogated, using three separate but complementary experimental approaches, the impact of vitamin B12 availability and methotrexate exposure on Daphnia magna, which we hypothesised should have an opposite effect on One carbon metabolism (OCM). OCM is a vital biological process supporting a variety of physiological processes, including DNA methylation. Contrary to mammalian models, this process remains largely unexplored in invertebrates. The purpose of this study was to elucidate the impact of OCM short-term alteration on the fitness and epigenome of the keystone species, Daphnia...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28928286/hpv-integration-in-hnscc-correlates-with-survival-outcomes-immune-response-signatures-and-candidate-drivers
#16
Lada A Koneva, Yanxiao Zhang, Shama Virani, Pelle B Hall, Jonathan B McHugh, Douglas B Chepeha, Gregory Wolf, Thomas E Carey, Laura S Rozek, Maureen A Sartor
The incidence of human papillomavirus (HPV)-related oropharynx cancer has steadily increased over the past two decades, and now represents a majority of oropharyngeal cancer cases. Integration of the HPV genome into the host genome is a common event during carcinogenesis that has clinically-relevant effects if the viral early genes are transcribed. Understanding the impact of HPV integration on clinical outcomes of head and neck squamous cell carcinoma (HNSCC) is critical for implementing de-escalated treatment approaches for HPV-positive HNSCC patients...
September 19, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28927457/p53-key-conductor-of-all-anti-acne-therapies
#17
REVIEW
Bodo C Melnik
This review based on translational research predicts that the transcription factor p53 is the key effector of all anti-acne therapies. All-trans retinoic acid (ATRA) and isotretinoin (13-cis retinoic acid) enhance p53 expression. Tetracyclines and macrolides via inhibiting p450 enzymes attenuate ATRA degradation, thereby increase p53. Benzoyl peroxide and hydrogen peroxide elicit oxidative stress, which upregulates p53. Azelaic acid leads to mitochondrial damage associated with increased release of reactive oxygen species inducing p53...
September 19, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28926624/molecular-characterization-expression-analysis-and-heterologous-expression-of-two-translationally-controlled-tumor-protein-genes-from-cucumis-sativus
#18
Xiang Nan Meng, Qiu Min Chen, Hai Yan Fan, Tie Feng Song, Na Cui, Ju Yong Zhao, Shu Min Jia, Ke Xin Meng
The translationally controlled tumor protein (TCTP) is a family of abundant and ubiquitous proteins involved in several important primary functions. Cucumbers harbor two TCTP genes, CsTCTP1 and CsTCTP2; however, their functional roles remain unclear. In this study, we isolated CsTCTP1 and CsTCTP2 (XP-004134215 and XP-004135602, respectively) promoters, full-length cDNA and genomic sequences from Cucumis sativus. Bioinformatics analysis, containing cis-acting elements, structural domains, phylogenetic tree and conserved motifs, suggested the conservation and divergence of CsTCTP1 and CsTCTP2, thus providing knowledge regarding their functions...
2017: PloS One
https://www.readbyqxmd.com/read/28926565/a-snp-panel-and-online-tool-for-checking-genotype-concordance-through-comparing-qr-codes
#19
Yonghong Du, Joshua S Martin, John McGee, Yuchen Yang, Eric Yi Liu, Yingrui Sun, Matthias Geihs, Xuejun Kong, Eric Lingfeng Zhou, Yun Li, Jie Huang
In the current precision medicine era, more and more samples get genotyped and sequenced. Both researchers and commercial companies expend significant time and resources to reduce the error rate. However, it has been reported that there is a sample mix-up rate of between 0.1% and 1%, not to mention the possibly higher mix-up rate during the down-stream genetic reporting processes. Even on the low end of this estimate, this translates to a significant number of mislabeled samples, especially over the projected one billion people that will be sequenced within the next decade...
2017: PloS One
https://www.readbyqxmd.com/read/28925795/application-of-replication-defective-west-nile-virus-vector-to-non-flavivirus-vaccine-targets
#20
Maryann Giel-Moloney, Michael Vaine, Linong Zhang, Mark Parrington, Beata Gajewska, Thorsten U Vogel, Svetlana O Pougatcheva, Xiaochu Duan, Timothy Farrell, Irina Ustyugova, Sanjay Phogat, Harry Kleanthous, Konstantin V Pugachev
The RepliVaxvaccine platform(RV) is based on flavivirus genomes that are rationally attenuated by deletion. The self-limiting infection provided by RV has been demonstrated to be safe, highly immunogenic and efficacious for several vaccine candidates against flaviviruses. Here respiratory syncytial virus (RSV) F, influenza virus HA, and Simian Immunodeficiency virus (SIV) Env proteins were expressed in place of either prM-E or C-prM-E gene deletions of the West Nile (WN) genome. The resulting RV-RSV, -influenza and -SIV vaccine prototypes replicated efficiently in complementing helper cells expressing the WN structural proteins in trans...
September 19, 2017: Human Vaccines & Immunotherapeutics
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