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Sleep genomics

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https://www.readbyqxmd.com/read/28334017/genome-wide-rnai-selection-identifies-a-regulator-of-transmission-stage-enriched-gene-families-and-cell-type-differentiation-in-trypanosoma-brucei
#1
Eva Rico, Alasdair Ivens, Lucy Glover, David Horn, Keith R Matthews
Trypanosoma brucei, causing African sleeping-sickness, exploits quorum-sensing (QS) to generate the 'stumpy forms' necessary for the parasite's transmission to tsetse-flies. These quiescent cells are generated by differentiation in the bloodstream from proliferative slender forms. Using genome-wide RNAi selection we screened for repressors of transmission stage-enriched mRNAs in slender forms, using the stumpy-elevated ESAG9 transcript as a model. This identified REG9.1, whose RNAi-silencing alleviated ESAG9 repression in slender forms and tsetse-midgut procyclic forms...
March 23, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28329071/association-of-mild-obstructive-sleep-apnea-with-cognitive-performance-excessive-daytime-sleepiness-and-quality-of-life-in-the-general-population-the-korean-genome-and-epidemiology-study-koges
#2
Hyun Kim, Robert J Thomas, Chang-Ho Yun, Rhoda Au, Seung Ku Lee, Sunghee Lee, Chol Shin
Study Objectives: Research points to impaired cognitive performance in sleep clinic patients with obstructive sleep apnea (OSA). However, inconsistent findings from various epidemiologic studies make this relationship less generalizable. The current study investigated the association between OSA functional outcome measures, such as cognition, daytime sleepiness, and quality of life, in a Korean general population sample. Methods: A total of 1,492 participants from the Korean Genome and Epidemiology Study (KoGES) were included in the analyses...
January 28, 2017: Sleep
https://www.readbyqxmd.com/read/28325297/engineering-of-pedf-expressing-primary-pigment-epithelial-cells-by-the-sb-transposon-system-delivered-by-pfar4-plasmids
#3
Gabriele Thumann, Nina Harmening, Cécile Prat-Souteyrand, Corinne Marie, Marie Pastor, Attila Sebe, Csaba Miskey, Laurence D Hurst, Sabine Diarra, Martina Kropp, Peter Walter, Daniel Scherman, Zoltán Ivics, Zsuzsanna Izsvák, Sandra Johnen
Neovascular age-related macular degeneration (nvAMD) is characterized by choroidal blood vessels growing into the subretinal space, leading to retinal pigment epithelial (RPE) cell degeneration and vision loss. Vessel growth results from an imbalance of pro-angiogenic (e.g., vascular endothelial growth factor [VEGF]) and anti-angiogenic factors (e.g., pigment epithelium-derived factor [PEDF]). Current treatment using intravitreal injections of anti-VEGF antibodies improves vision in about 30% of patients but may be accompanied by side effects and non-compliance...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28319090/a-single-copy-sleeping-beauty-transposon-mutagenesis-screen-identifies-new-pten-cooperating-tumor-suppressor-genes
#4
Jorge de la Rosa, Julia Weber, Mathias Josef Friedrich, Yilong Li, Lena Rad, Hannes Ponstingl, Qi Liang, Sandra Bernaldo de Quirós, Imran Noorani, Emmanouil Metzakopian, Alexander Strong, Meng Amy Li, Aurora Astudillo, María Teresa Fernández-García, María Soledad Fernández-García, Gary J Hoffman, Rocío Fuente, George S Vassiliou, Roland Rad, Carlos López-Otín, Allan Bradley, Juan Cadiñanos
The overwhelming number of genetic alterations identified through cancer genome sequencing requires complementary approaches to interpret their significance and interactions. Here we developed a novel whole-body insertional mutagenesis screen in mice, which was designed for the discovery of Pten-cooperating tumor suppressors. Toward this aim, we coupled mobilization of a single-copy inactivating Sleeping Beauty transposon to Pten disruption within the same genome. The analysis of 278 transposition-induced prostate, breast and skin tumors detected tissue-specific and shared data sets of known and candidate genes involved in cancer...
March 20, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28314944/the-case-for-too-little-melatonin-signalling-in-increased-diabetes-risk
#5
EDITORIAL
Amélie Bonnefond, Philippe Froguel
Genome-wide association studies have detected an association between type 2 diabetes risk and a non-coding SNP located in MTNR1B, the gene encoding melatonin receptor 2 (MT2). Melatonin regulates circadian rhythms and sleep and associates with metabolic disorders. However, the mechanisms underlying these actions are still unclear. Functional genomic, animal and clinical studies have not reached the same conclusions: while some studies have reported that decreased melatonin signalling increases type 2 diabetes risk, others have found the opposite...
March 17, 2017: Diabetologia
https://www.readbyqxmd.com/read/28252665/chromatin-states-shape-insertion-profiles-of-the-piggybac-tol2-and-sleeping-beauty-transposons-and-murine-leukemia-virus
#6
Junko Yoshida, Keiko Akagi, Ryo Misawa, Chikara Kokubu, Junji Takeda, Kyoji Horie
DNA transposons and retroviruses are versatile tools in functional genomics and gene therapy. To facilitate their application, we conducted a genome-wide insertion site profiling of the piggyBac (PB), Tol2 and Sleeping Beauty (SB) transposons and the murine leukemia virus (MLV) in mouse embryonic stem cells (ESCs). PB and MLV preferred highly expressed genes, whereas Tol2 and SB preferred weakly expressed genes. However, correlations with DNase I hypersensitive sites were different for all vectors, indicating that chromatin accessibility is not the sole determinant...
March 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28251929/transposon-insertional-mutagenesis-in-mice-identifies-human-breast-cancer-susceptibility-genes-and-signatures-for-stratification
#7
Liming Chen, Piroon Jenjaroenpun, Andrea Mun Ching Pillai, Anna V Ivshina, Ghim Siong Ow, Motakis Efthimios, Tang Zhiqun, Tuan Zea Tan, Song-Choon Lee, Keith Rogers, Jerrold M Ward, Seiichi Mori, David J Adams, Nancy A Jenkins, Neal G Copeland, Kenneth Hon-Kim Ban, Vladimir A Kuznetsov, Jean Paul Thiery
Robust prognostic gene signatures and therapeutic targets are difficult to derive from expression profiling because of the significant heterogeneity within breast cancer (BC) subtypes. Here, we performed forward genetic screening in mice using Sleeping Beauty transposon mutagenesis to identify candidate BC driver genes in an unbiased manner, using a stabilized N-terminal truncated β-catenin gene as a sensitizer. We identified 134 mouse susceptibility genes from 129 common insertion sites within 34 mammary tumors...
March 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28241858/machine-learning-identifies-a-compact-gene-set-for-monitoring-the-circadian-clock-in-human-blood
#8
Jacob J Hughey
BACKGROUND: The circadian clock and the daily rhythms it produces are crucial for human health, but are often disrupted by the modern environment. At the same time, circadian rhythms may influence the efficacy and toxicity of therapeutics and the metabolic response to food intake. Developing treatments for circadian dysfunction, as well as optimizing the daily timing of treatments for other health conditions, will require a simple and accurate method to monitor the molecular state of the circadian clock...
February 28, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28207497/concurrent-presence-of-inflammation-and-obstructive-sleep-apnea-exacerbates-the-risk-of-metabolic-syndrome-a-koges-6-year-follow-up-study
#9
Jinkwan Kim, Dae Wui Yoon, Seung Ku Lee, Seunggwan Lee, Kyung-Mee Choi, Thomas J Robert, Chol Shin
Obstructive sleep apnea (OSA) leads to multiple end-organ morbidities that are mediated by the cumulative burden of oxidative stress and inflammation. Both OSA and inflammation play key roles in increased risk of cardiovascular disease (CVD). Thus, we hypothesized that the combination of inflammation and OSA could accelerate the development of metabolic syndrome (MetS) in a large cohort study.A total of 1835 participants were randomly selected from the ongoing Korean Genome and Epidemiology Study for the years between 2007 and 2015...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28192891/sleep-duration-and-chronic-kidney-disease-the-korean-genome-and-epidemiology-study-koges-kangwha-study
#10
Hansol Choi, Hyeon Chang Kim, Joo Young Lee, Ju-Mi Lee, Dong Phil Choi, Il Suh
BACKGROUND/AIMS: Sleep duration affects health in various ways. The objective of this study was to investigate the associations of sleep duration with chronic kidney disease (CKD) in a Korean adult population. METHODS: This cross-sectional analysis was conducted for total of 1,360 participants who completed baseline health examinations for the Korean Genome and Epidemiology Study-Kangwha study in 2010 to 2011. Sleep habits were measured by an interviewer-assisted questionnaire...
March 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28155201/dad-s-snoring-may-have-left-molecular-scars-in-your-dna-the-emerging-role-of-epigenetics-in-sleep-disorders
#11
REVIEW
Daniela Morales-Lara, Clelia De-la-Peña, Eric Murillo-Rodríguez
The sleep-wake cycle is a biological phenomena under the orchestration of neurophysiological, neurochemical, neuroanatomical, and genetical mechanisms. Moreover, homeostatic and circadian processes participate in the regulation of sleep across the light-dark period. Further complexity of the understanding of the genesis of sleep engages disturbances which have been characterized and classified in a variety of sleep-wake cycle disorders. The most prominent sleep alterations include insomnia as well as excessive daytime sleepiness...
February 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28141710/the-curse-of-the-dolphins-cognitive-decline-and-psychosis
#12
Randall Phelps, Anne Tsai, Arlene Hagen, Joseph Pinter, Raegan Smith, Martin T Stein
Isela is an 11-year-old Mexican-American girl with mild intellectual disability. During a vacation with her family, she went swimming with dolphins. A few days later, Isela awoke at night with laughing spells; during the day, she was pacing, aggressive, and had a decline in self-care and communication skills. Her parents attributed the symptoms to the dolphins. She was evaluated by a pediatric neurologist. The sleep-deprived electroencephalogram, brain magnetic resonance imaging, lumbar puncture, and thyroid function tests were normal...
February 2017: Journal of Developmental and Behavioral Pediatrics: JDBP
https://www.readbyqxmd.com/read/28138343/first-draft-genome-sequence-of-the-dourine-causative-agent-trypanosoma-equiperdum-strain-ovi
#13
Laurent Hébert, Bouziane Moumen, Anthony Madeline, Sascha Steinbiss, Latifa Lakhdar, Nick Van Reet, Philippe Büscher, Claire Laugier, Julien Cauchard, Sandrine Petry
Trypanosoma equiperdum is the causative agent of dourine, a sexually-transmitted infection of horses. This parasite belongs to the subgenus Trypanozoon that also includes the agent of sleeping sickness (Trypanosoma brucei) and surra (Trypanosoma evansi). We herein report the genome sequence of a T. equiperdum strain OVI, isolated from a horse in South-Africa in 1976. This is the first genome sequence of the T. equiperdum species, and its availability will provide important insights for future studies on genetic classification of the subgenus Trypanozoon...
2017: Journal of Genomics
https://www.readbyqxmd.com/read/28135585/genome-wide-profiling-reveals-remarkable-parallels-between-insertion-site-selection-properties-of-the-mlv-retrovirus-and-the-piggybac-transposon-in-primary-human-cd4-t-cells
#14
Andreas Gogol-Döring, Ismahen Ammar, Saumyashree Gupta, Mario Bunse, Csaba Miskey, Wei Chen, Wolfgang Uckert, Thomas F Schulz, Zsuzsanna Izsvák, Zoltán Ivics
The inherent risks associated with vector insertion in gene therapy need to be carefully assessed. We analyzed the genome-wide distributions of Sleeping Beauty (SB) and piggyBac (PB) transposon insertions as well as MLV retrovirus and HIV lentivirus insertions in human CD4(+) T cells with respect to a panel of 40 chromatin states. The distribution of SB transposon insertions displayed the least deviation from random, while the PB transposon and the MLV retrovirus showed unexpected parallels across all chromatin states...
March 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28115300/research-progress-of-tc1-mariner-superfamily
#15
Shen Dan, Chen Cai, Wang Saisai, Chen Wei, Gao Bo, Song Chengyi
With the rapid improvement of sequencing techniques, more and more genome annotations reveal the transposons are the important components of most genomes and present on almost all organisms. Among them, the Tc1/Mariner superfamily represents the most widespread DNA transposons. Until now, fourteen active Tc1/Mariner transposons (Minos, Mos1, etc.) have been identified and some highly active artificial transposons have been created through molecular reconstruction, such as Sleeping Beauty (SB). The transposons such as SB and Mos1 have been widely used as gene transfer vectors in the fields of transgenosis, gene trapping and gene therapy...
January 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28111420/a-follow-up-study-of-the-association-between-mobile-phone-use-and-symptoms-of-ill-health
#16
Yong Min Cho, Hee Jin Lim, Hoon Jang, Kyunghee Kim, Jae Wook Choi, Chol Shin, Seung Ku Lee, Jong Hwa Kwon, Nam Kim
The duration and frequency of mobile phone calls, and their relationship with various health effects, have been investigated in our previous cross-sectional study. This 2-year period follow-up study aimed to assess the changes in these variables of same subjects. The study population comprised 532 non-patient adult subjects sampled from the Korean Genome Epidemiology Study. The subjects underwent a medical examination at a hospital in 2012/2013 and revisited the same hospital in 2014/2015 to have the same examination for the characteristics of mobile phone use performed...
2016: Environmental Health and Toxicology
https://www.readbyqxmd.com/read/28109725/6q12-and-11p14-variants-are-associated-with-postnatal-exhaled-nitric-oxide-levels-and-respiratory-symptoms
#17
Oliver Fuchs, Olga Gorlanova, Philipp Latzin, Anne Schmidt, Maximilian Schieck, Antoaneta A Toncheva, Sven Michel, Vincent D Gaertner, Michael Kabesch, Urs Frey
BACKGROUND: Exhaled nitric oxide (eNO) is a biomarker of airway inflammation and seems to precede respiratory symptoms, such as asthma, in childhood. Identifying genetic determinants of postnatal eNO levels might aid in unraveling the role of eNO in epithelial function or airway inflammation and disease. OBJECTIVE: We sought to identify genetic determinants of early postnatal eNO levels and subsequent respiratory symptoms during the first year of life. METHODS: Within a population-based birth cohort, eNO levels were measured in healthy term infants aged 5 weeks during quiet tidal breathing in unsedated sleep...
January 19, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28107884/the-association-between-irritable-bowel-syndrome-and-the-coexistence-of-depression-and-insomnia
#18
Seung Ku Lee, Dae Wui Yoon, Sunghee Lee, Jinkwan Kim, Kyung-Mee Choi, Chol Shin
OBJECTIVE: The individual occurrence of depression or insomnia is a risk factor for irritable bowel syndrome (IBS), but few researchers have evaluated the association between comorbid depression and insomnia and IBS. The aim of the present study is to explore the relationship between IBS and the coexistence of depression and insomnia in a Korean population-based cohort study. METHODS: A total of 3429 individuals who were enrolled in the Korean Genome and Epidemiology Study were analysed...
February 2017: Journal of Psychosomatic Research
https://www.readbyqxmd.com/read/28102151/pleiotropic-genetic-effects-influencing-sleep-and-neurological-disorders
#19
REVIEW
Olivia J Veatch, Brendan T Keenan, Philip R Gehrman, Beth A Malow, Allan I Pack
Research evidence increasingly points to the large impact of sleep disturbances on public health. Many aspects of sleep are heritable and genes influencing traits such as timing, EEG characteristics, sleep duration, and response to sleep loss have been identified. Notably, large-scale genome-wide analyses have implicated numerous genes with small effects on sleep timing. Additionally, there has been considerable progress in the identification of genes influencing risk for some neurological sleep disorders. For restless legs syndrome, implicated variants are typically in genes associated with neuronal development...
February 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28100473/delineating-the-phenotypic-spectrum-of-bainbridge-ropers-syndrome-12-new-patients-with-de-novo-heterozygous-loss-of-function-mutations-in-asxl3-and-review-of-published-literature
#20
M Balasubramanian, J Willoughby, A E Fry, A Weber, H V Firth, C Deshpande, J N Berg, K Chandler, K A Metcalfe, W Lam, D T Pilz, S Tomkins
BACKGROUND: Bainbridge-Ropers syndrome (BRPS) is a recently described developmental disorder caused by de novo truncating mutations in the additional sex combs like 3 (ASXL3) gene. To date, there have been fewer than 10 reported patients. OBJECTIVES: Here, we delineate the BRPS phenotype further by describing a series of 12 previously unreported patients identified by the Deciphering Developmental Disorders study. METHODS: Trio-based exome sequencing was performed on all 12 patients included in this study, which found a de novo truncating mutation in ASXL3...
January 18, 2017: Journal of Medical Genetics
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