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https://www.readbyqxmd.com/read/28089652/hippocampal-prefrontal-connectivity-as-a-translational-phenotype-for-schizophrenia
#1
REVIEW
Florian Bähner, Andreas Meyer-Lindenberg
Finding novel biological targets in psychiatry has been difficult, partly because current diagnostic categories are not defined by pathophysiology and difficult to model in animals. The study of species-conserved systems-level mechanisms implicated in psychiatric disease could be a promising strategy to address some of these difficulties. Altered hippocampal-prefrontal (HC-PFC) connectivity during working memory (WM) processing is a candidate for such a translational phenotype as it has been repeatedly associated with impaired cognition in schizophrenia patients and animal models for psychiatric risk factors...
January 12, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28081459/targeted-delivery-of-in-situ-pcr-amplified-sleeping-beauty-transposon-genes-to-cancer-cells-with-lipid-based-nanoparticle-like-protocells
#2
Kun Ma, Duo Fu, Dongli Yu, Changhao Cui, Li Wang, Zhaoming Guo, Chuanbin Mao
A Sleeping Beauty (SB) transposon system is made of a transposon plasmid (containing gene encoding a desired functional or therapeutic protein) and a transposase plasmid (encoding an enzyme capable of cutting and pasting the gene into the host cell genome). It is a kind of natural, nonviral gene delivery vehicle, which can achieve efficient genomic insertion, providing long-term transgenic expression. However, before the SB transposon system could play a role in promoting gene expression, it has to be delivered efficiently first across cell membrane and then into cell nuclei...
January 2, 2017: Biomaterials
https://www.readbyqxmd.com/read/28079877/genome-wide-transposon-screening-and-quantitative-insertion-site-sequencing-for-cancer-gene-discovery-in-mice
#3
Mathias J Friedrich, Lena Rad, Iraad F Bronner, Alexander Strong, Wei Wang, Julia Weber, Matthew Mayho, Hannes Ponstingl, Thomas Engleitner, Carolyn Grove, Anja Pfaus, Dieter Saur, Juan Cadiñanos, Michael A Quail, George S Vassiliou, Pentao Liu, Allan Bradley, Roland Rad
Transposon-mediated forward genetics screening in mice has emerged as a powerful tool for cancer gene discovery. It pinpoints cancer drivers that are difficult to find with other approaches, thus complementing the sequencing-based census of human cancer genes. We describe here a large series of mouse lines for insertional mutagenesis that are compatible with two transposon systems, PiggyBac and Sleeping Beauty, and give guidance on the use of different engineered transposon variants for constitutive or tissue-specific cancer gene discovery screening...
February 2017: Nature Protocols
https://www.readbyqxmd.com/read/28076377/comparative-analysis-of-vertebrate-diurnal-circadian-transcriptomes
#4
Greg Boyle, Kerstin Richter, Henry D Priest, David Traver, Todd C Mockler, Jeffrey T Chang, Steve A Kay, Ghislain Breton
From photosynthetic bacteria to mammals, the circadian clock evolved to track diurnal rhythms and enable organisms to anticipate daily recurring changes such as temperature and light. It orchestrates a broad spectrum of physiology such as the sleep/wake and eating/fasting cycles. While we have made tremendous advances in our understanding of the molecular details of the circadian clock mechanism and how it is synchronized with the environment, we still have rudimentary knowledge regarding its connection to help regulate diurnal physiology...
2017: PloS One
https://www.readbyqxmd.com/read/28057021/treatment-of-intermittent-hypoxia-increases-phosphorylated-tau-in-the-hippocampus-via-biological-processes-common-to-aging
#5
Sosuke Yagishita, Seiya Suzuki, Keisuke Yoshikawa, Keiko Iida, Ayako Hirata, Masahiko Suzuki, Akihiko Takashima, Kei Maruyama, Akira Hirasawa, Takeo Awaji
Sleep-disordered breathing produces cognitive impairments, and is possibly associated with Alzheimer disease (AD). Intermittent hypoxia treatment (IHT), an experimental model for sleep-disordered breathing, results in cognitive impairments in animals via unknown mechanisms. Here, we exposed mice to IHT protocols, and performed biochemical analyses and microarray analyses regarding their hippocampal samples. In particular, we performed gene ontology (GO)-based microarray analysis to elucidate effects of IHT on hippocampal functioning, which were compared with the effects of various previously-reported experimental conditions on that (ref...
January 5, 2017: Molecular Brain
https://www.readbyqxmd.com/read/27992416/genome-wide-association-analyses-of-sleep-disturbance-traits-identify-new-loci-and-highlight-shared-genetics-with-neuropsychiatric-and-metabolic-traits
#6
Jacqueline M Lane, Jingjing Liang, Irma Vlasac, Simon G Anderson, David A Bechtold, Jack Bowden, Richard Emsley, Shubhroz Gill, Max A Little, Annemarie I Luik, Andrew Loudon, Frank A J L Scheer, Shaun M Purcell, Simon D Kyle, Deborah A Lawlor, Xiaofeng Zhu, Susan Redline, David W Ray, Martin K Rutter, Richa Saxena
Chronic sleep disturbances, associated with cardiometabolic diseases, psychiatric disorders and all-cause mortality, affect 25-30% of adults worldwide. Although environmental factors contribute substantially to self-reported habitual sleep duration and disruption, these traits are heritable and identification of the genes involved should improve understanding of sleep, mechanisms linking sleep to disease and development of new therapies. We report single- and multiple-trait genome-wide association analyses of self-reported sleep duration, insomnia symptoms and excessive daytime sleepiness in the UK Biobank (n = 112,586)...
December 19, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27923372/community-acquired-meningitis-caused-by-a-cg86-hypervirulent-klebsiella-pneumoniae-strain-first-case-report-in-the-caribbean
#7
Bénédicte Melot, Sylvain Brisse, Sébastien Breurec, Virginie Passet, Edith Malpote, Isabelle Lamaury, Guillaume Thiery, Bruno Hoen
BACKGROUND: Community-acquired bacterial meningitis due to Klebsiella pneumoniae has mainly been described in Southeast Asia and has a poor prognosis. Severe invasive infections caused by K. pneumoniae, including meningitis, are often due to hypervirulent strains (hvKP), which are characterized by capsular serotypes K1 and K2, a gene responsible for hypermucoviscosity, and the cluster for synthesis of the siderophore aerobactin. CASE PRESENTATION: A 55 year old man with a history of essential hypertension, benign prostate hyperplasia, hyperlipidemia, obstructive sleep apnea, and chronic alcoholism was admitted for meningitis due to Klebsiella pneumoniae with a wild-type susceptibility profile...
December 7, 2016: BMC Infectious Diseases
https://www.readbyqxmd.com/read/27916472/generation-of-neural-cells-using-ipscs-from-sleep-bruxism-patients-with-5-ht2a-polymorphism
#8
Yurie Hoashi, Satoshi Okamoto, Yuka Abe, Takashi Matsumoto, Junichi Tanaka, Yuya Yoshida, Kent Imaizumi, Kenji Mishima, Wado Akamatsu, Hideyuki Okano, Kazuyoshi Baba
PURPOSE: Sleep bruxism (SB) is classified as a sleep-related movement disorder characterized by grinding and clenching of the teeth during sleep, which is responsible for a variety of clinical problems such as abnormal tooth attrition and fracture of teeth or roots. Little is known about the etiology of SB. Our previous study identified a genomic association of the serotonin 2A receptor (5-HT2A) single nucleotide polymorphism (SNP), rs6313 C>T, with SB, where the C allele carrier is associated with a 4...
December 1, 2016: Journal of Prosthodontic Research
https://www.readbyqxmd.com/read/27913727/regulated-complex-assembly-safeguards-the-fidelity-of-sleeping-beauty-transposition
#9
Yongming Wang, Diana Pryputniewicz-Dobrinska, Enikö Éva Nagy, Christopher D Kaufman, Manvendra Singh, Steve Yant, Jichang Wang, Anna Dalda, Mark A Kay, Zoltán Ivics, Zsuzsanna Izsvák
The functional relevance of the inverted repeat structure (IR/DR) in a subgroup of the Tc1/mariner superfamily of transposons has been enigmatic. In contrast to mariner transposition, where a topological filter suppresses single-ended reactions, the IR/DR orchestrates a regulatory mechanism to enforce synapsis of the transposon ends before cleavage by the transposase occurs. This ordered assembly process shepherds primary transposase binding to the inner 12DRs (where cleavage does not occur), followed by capture of the 12DR of the other transposon end...
December 1, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27898092/transposon-mediated-generation-of-cellular-and-mouse-models-of-splicing-mutations-to-assess-the-efficacy-of-snrna-based-therapeutics
#10
Elena Barbon, Mattia Ferrarese, Laetitia van Wittenberghe, Peggy Sanatine, Giuseppe Ronzitti, Fanny Collaud, Pasqualina Colella, Mirko Pinotti, Federico Mingozzi
Disease-causing splicing mutations can be rescued by variants of the U1 small nuclear RNA (U1snRNAs). However, the evaluation of the efficacy and safety of modified U1snRNAs as therapeutic tools is limited by the availability of cellular and animal models specific for a given mutation. Hence, we exploited the hyperactive Sleeping Beauty transposon system (SB100X) to integrate human factor IX (hFIX) minigenes into genomic DNA in vitro and in vivo. We generated stable HEK293 cell lines and C57BL/6 mice harboring splicing-competent hFIX minigenes either wild type (SChFIX-wt) or mutated (SChFIXex5-2C)...
November 29, 2016: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/27855737/genetic-basis-of-chronotype-in-humans-insights-from-three-landmark-gwas
#11
David A Kalmbach, Logan D Schneider, Joseph Cheung, Sarah J Bertrand, Thiruchelvam Kariharan, Allan I Pack, Philip R Gehrman
Chronotype, or diurnal preference, refers to behavioral manifestations of the endogenous circadian system that governs preferred timing of sleep and wake. As variations in circadian timing and system perturbations are linked to disease development, the fundamental biology of chronotype has received attention for its role in the regulation and dysregulation of sleep and related medical and psychiatric illnesses. Twin and family studies have shown that chronotype is a heritable trait, thus directing attention toward its genetic basis...
October 28, 2016: Sleep
https://www.readbyqxmd.com/read/27832434/monitoring-of-venus-transgenic-cell-migration-during-pregnancy-in-non-transgenic-rabbits
#12
N Lipták, O I Hoffmann, A Kerekes, G Iski, D Ernszt, K Kvell, L Hiripi, Z Bősze
Cell transfer between mother and fetus were demonstrated previously in several species which possess haemochorial placenta (e.g. in humans, mice, rats, etc.). Here we report the assessment of fetal and maternal microchimerism in non-transgenic (non-TG) New Zealand white rabbits which were pregnant with transgenic (TG) fetuses and in non-TG newborns of TG does. The TG construct, including the Venus fluorophore cDNA driven by a ubiquitous cytomegalovirus enhancer, chicken ß-actin promoter (CAGGS), was previously integrated into the rabbit genome by Sleeping Beauty transposon system...
November 10, 2016: Transgenic Research
https://www.readbyqxmd.com/read/27815038/phenotypes-in-obstructive-sleep-apnea-a-definition-examples-and-evolution-of-approaches
#13
REVIEW
Andrey V Zinchuk, Mark J Gentry, John Concato, Henry K Yaggi
Obstructive sleep apnea (OSA) is a complex and heterogeneous disorder and the apnea hypopnea index alone can not capture the diverse spectrum of the condition. Enhanced phenotyping can improve prognostication, patient selection for clinical trials, understanding of mechanisms, and personalized treatments. In OSA, multiple condition characteristics have been termed "phenotypes." To help classify patients into relevant prognostic and therapeutic categories, an OSA phenotype can be operationally defined as: "A category of patients with OSA distinguished from others by a single or combination of disease features, in relation to clinically meaningful attributes (symptoms, response to therapy, health outcomes, quality of life)...
October 12, 2016: Sleep Medicine Reviews
https://www.readbyqxmd.com/read/27807620/genetic-background-of-enhanced-radioresistance-in-an-anhydrobiotic-insect-transcriptional-response-to-ionizing-radiations-and-desiccation
#14
Alina Ryabova, Kyosuke Mukae, Alexander Cherkasov, Richard Cornette, Elena Shagimardanova, Tetsuya Sakashita, Takashi Okuda, Takahiro Kikawada, Oleg Gusev
It is assumed that resistance to ionizing radiation, as well as cross-resistance to other abiotic stresses, is a side effect of the evolutionary-based adaptation of anhydrobiotic animals to dehydration stress. Larvae of Polypedilum vanderplanki can withstand prolonged desiccation as well as high doses of ionizing radiation exposure. For a further understanding of the mechanisms of cross-tolerance to both types of stress exposure, we profiled genome-wide mRNA expression patterns using microarray techniques on the chironomid larvae collected at different stages of desiccation and after exposure to two types of ionizing radiation-70 Gy of high-linear energy transfer (LET) ions ((4)He) and the same dose of low-LET radiation (gamma rays)...
November 2, 2016: Extremophiles: Life Under Extreme Conditions
https://www.readbyqxmd.com/read/27801667/transposon-mediated-generation-of-bcr-abl1-expressing-transgenic-cell-lines-for-unbiased-sensitivity-testing-of-tyrosine-kinase-inhibitors
#15
Konstantin Byrgazov, Chantal Blanche Lucini, Bettina Berkowitsch, Margit Koenig, Oskar A Haas, Gregor Hoermann, Peter Valent, Thomas Lion
Point mutations in the ABL1 kinase domain are an important mechanism of resistance to tyrosine kinase inhibitors (TKI) in BCR-ABL1-positive and, as recently shown, BCR-ABL1-like leukemias. The cell line Ba/F3 lentivirally transduced with mutant BCR-ABL1 constructs is widely used for in vitro sensitivity testing and response prediction to tyrosine kinase inhibitors. The transposon-based Sleeping Beauty system presented offers several advantages over lentiviral transduction including the absence of biosafety issues, faster generation of transgenic cell lines, and greater efficacy in introducing large gene constructs...
October 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27801296/removal-of-unwanted-variation-reveals-novel-patterns-of-gene-expression-linked-to-sleep-homeostasis-in-murine-cortex
#16
Jason R Gerstner, John N Koberstein, Adam J Watson, Nikolai Zapero, Davide Risso, Terence P Speed, Marcos G Frank, Lucia Peixoto
BACKGROUND: Why we sleep is still one of the most perplexing mysteries in biology. Strong evidence indicates that sleep is necessary for normal brain function and that sleep need is a tightly regulated process. Surprisingly, molecular mechanisms that determine sleep need are incompletely described. Moreover, very little is known about transcriptional changes that specifically accompany the accumulation and discharge of sleep need. Several studies have characterized differential gene expression changes following sleep deprivation...
October 25, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27799067/identification-of-a-rai1-associated-disease-network-through-integration-of-exome-sequencing-transcriptomics-and-3d-genomics
#17
Maria Nicla Loviglio, Christine R Beck, Janson J White, Marion Leleu, Tamar Harel, Nicolas Guex, Anne Niknejad, Weimin Bi, Edward S Chen, Isaac Crespo, Jiong Yan, Wu-Lin Charng, Shen Gu, Ping Fang, Zeynep Coban-Akdemir, Chad A Shaw, Shalini N Jhangiani, Donna M Muzny, Richard A Gibbs, Jacques Rougemont, Ioannis Xenarios, James R Lupski, Alexandre Reymond
BACKGROUND: Smith-Magenis syndrome (SMS) is a developmental disability/multiple congenital anomaly disorder resulting from haploinsufficiency of RAI1. It is characterized by distinctive facial features, brachydactyly, sleep disturbances, and stereotypic behaviors. METHODS: We investigated a cohort of 15 individuals with a clinical suspicion of SMS who showed neither deletion in the SMS critical region nor damaging variants in RAI1 using whole exome sequencing. A combination of network analysis (co-expression and biomedical text mining), transcriptomics, and circularized chromatin conformation capture (4C-seq) was applied to verify whether modified genes are part of the same disease network as known SMS-causing genes...
November 1, 2016: Genome Medicine
https://www.readbyqxmd.com/read/27792857/sudden-infant-death-syndrome-insights-and-future-directions-from-a-utah-population-database-analysis
#18
Erik D Christensen, Justin Berger, Mouied M Alashari, Hilary Coon, Cynthia Robison, Hsu-Tso Ho, David R Adams, Willian A Gahl, Ken R Smith, John M Opitz, Dennis R Johnson
"Sudden Infant Death syndrome" (SIDS) represents the commonest category of infant death after the first month of life. As genome scale sequencing greatly facilitates the identification of new candidate disease variants, the challenges of ascribing causation to these variants persists. In order to determine the extent to which SIDS occurs in related individuals and their pedigree structure we undertook an analysis of SIDS using the Utah Population Database, recording, for example, evidence of enrichment for genetic causation following the back-to-sleep recommendations of 1992 and 1994...
January 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/27790711/transposon-mutagenesis-identifies-candidate-genes-that-cooperate-with-loss-of-transforming-growth-factor-beta-signaling-in-mouse-intestinal-neoplasms
#19
Shelli M Morris, Jerry Davison, Kelly T Carter, Rachele M O'Leary, Patty Trobridge, Sue E Knoblaugh, Lois L Myeroff, Sanford D Markowitz, Benjamin T Brett, Todd E Scheetz, Adam J Dupuy, Timothy K Starr, William M Grady
Colorectal cancer (CRC) results from the accumulation of gene mutations and epigenetic alterations in colon epithelial cells, which promotes CRC formation through deregulating signaling pathways. One of the most commonly deregulated signaling pathways in CRC is the transforming growth factor β (TGF-β) pathway. Importantly, the effects of TGF-β signaling inactivation in CRC are modified by concurrent mutations in the tumor cell, and these concurrent mutations determine the ultimate biological effects of impaired TGF-β signaling in the tumor...
February 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27788568/a-cross-sectional-study-of-the-association-between-mobile-phone-use-and-symptoms-of-ill-health
#20
Yong Min Cho, Hee Jin Lim, Hoon Jang, Kyunghee Kim, Jae Wook Choi, Chol Shin, Seung Ku Lee, Jong Hwa Kwon, Nam Kim
OBJECTIVES: This study analyzed the associations between mobile phone call frequency and duration with non-specific symptoms. METHODS: This study was conducted with a population group including 532 non-patient adults established by the Korean Genome and Epidemiology Study. The pattern of phone call using a mobile phone was investigated through face-to-face interview. Structured methods applied to quantitatively assess health effects are Headache Impact Test-6 (HIT-6), Psychosocial Well-being Index-Short Form, Beck Depression Inventory, Korean-Instrumental Activities of Daily Living, Perceived Stress Scale (PSS), Pittsburgh Sleep Quality Index, and 12-item Short Form Health Survey where a higher score represents a higher greater health effect...
2016: Environmental Health and Toxicology
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