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https://www.readbyqxmd.com/read/29053637/progress-in-genetic-studies-of-tourette-s-syndrome
#1
REVIEW
Yanjie Qi, Yi Zheng, Zhanjiang Li, Lan Xiong
Tourette's Syndrome (TS) is a complex disorder characterized by repetitive, sudden, and involuntary movements or vocalizations, called tics. Tics usually appear in childhood, and their severity varies over time. In addition to frequent tics, people with TS are at risk for associated problems including attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety, depression, and problems with sleep. TS occurs in most populations and ethnic groups worldwide, and it is more common in males than in females...
October 20, 2017: Brain Sciences
https://www.readbyqxmd.com/read/29050555/natural-variation-in-human-clocks
#2
Malcolm von Schantz
Our own species has a diurnal activity pattern and an average circadian period of 24.2h. Exact determination of circadian period requires expensive and intrusive protocols, and investigators are therefore using chronotype questionnaires as a proxy quantitative measure. Both measures show a normal distribution suggestive of a polygenic trait. The genetic components of the 24-h feedback loop that generates circadian rhythms within our cells have been mapped in detail, identifying a number of candidate genes which have been investigated for genetic polymorphisms relating to the phenotypic variance...
2017: Advances in Genetics
https://www.readbyqxmd.com/read/29037144/trypanosoma-cruzi-specific-mrna-amplification-by-in-vitro-transcription-improves-parasite-transcriptomics-in-host-parasite-rna-mixtures
#3
Rafael Luis Kessler, Daniela Parada Pavoni, Marco Aurelio Krieger, Christian Macagnan Probst
BACKGROUND: Trypanosomatids are a group of protozoan parasites that includes the etiologic agents of important human illnesses as Chagas disease, sleeping sickness and leishmaniasis. These parasites have a significant distinction from other eukaryotes concerning mRNA structure, since all mature mRNAs have an identical species-specific sequence of 39 nucleotides at the 5' extremity, named spliced leader (SL). Considering this peculiar aspect of trypanosomatid mRNA, the aim of the present work was to develop a Trypanosoma cruzi specific in vitro transcription (IVT) linear mRNA amplification method in order to improve parasite transcriptomics analyses...
October 16, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29032150/functional-analysis-of-schizophrenia-genes-using-geneanalytics-program-and-integrated-databases
#4
Tharani Sundararajan, Ann M Manzardo, Merlin G Butler
Schizophrenia (SCZ) is a chronic debilitating neuropsychiatric disorder with multiple risk factors involving numerous complex genetic influences. We examined and updated a master list of clinically relevant and susceptibility genes associated with SCZ reported in the literature and genomic databases dedicated to gene discovery for characterization of SCZ genes. We used the commercially available GeneAnalytics computer-based gene analysis program and integrated genomic databases to create a molecular profile of the updated list of 608 SCZ genes to model their impact in select categories (tissues and cells, diseases, pathways, biological processes, molecular functions, phenotypes and compounds) using specialized GeneAnalytics algorithms...
October 12, 2017: Gene
https://www.readbyqxmd.com/read/29032008/3-iodothyroacetic-acid-ta1-a-by-product-of-thyroid-hormone-metabolism-reduces-the-hypnotic-effect-of-ethanol-without-interacting-at-gaba-a-receptors
#5
Annunziatina Laurino, Elisa Landucci, Francesco Resta, Gaetano De Siena, Rosanna Matucci, Alessio Masi, Laura Raimondi
3-iodothyroacetic acid (TA1) is among the by-products of thyroid hormone metabolism suspected to mediate the non-genomic effects of the hormone (T3). We aim to investigate whether TA1 systemically administered to mice stimulated mice wakefulness, an effect already described for T3 and for another T3 metabolite (i.e. 3-iodothryonamine; T1AM), and whether TA1 interacted at GABA-A receptors (GABA-AR). Mice were pre-treated with either saline (vehicle) or TA1 (1.32, 4 and 11 μg/kg) and, after 10 min, they received ethanol (3...
October 11, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28977444/the-genetics-of-circadian-rhythms-sleep-and-health
#6
Aarti Jagannath, Lewis Taylor, Zeinab Wakaf, Sridhar R Vasudevan, Russell G Foster
Circadian rhythms are 24-h rhythms in physiology and behaviour generated by molecular clocks, which serve to coordinate internal time with the external world. The circadian system is a master regulator of nearly all physiology and its disruption has major consequences on health. Sleep and circadian rhythm disruption (SCRD) is a ubiquitous feature in today's 24/7 society, and studies on shift-workers have shown that SCRD can lead not only to cognitive impairment, but also metabolic syndrome and psychiatric illness including depression (1,2)...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28964527/gene-therapy-with-the-sleeping-beauty-transposon-system
#7
REVIEW
Partow Kebriaei, Zsuzsanna Izsvák, Suneel A Narayanavari, Harjeet Singh, Zoltán Ivics
The widespread clinical implementation of gene therapy requires the ability to stably integrate genetic information through gene transfer vectors in a safe, effective, and economical manner. The latest generation of Sleeping Beauty (SB) transposon vectors fulfills these requirements, and may overcome limitations associated with viral gene transfer vectors and transient nonviral gene delivery approaches that are prevalent in ongoing clinical trials. The SB system enables high-level stable gene transfer and sustained transgene expression in multiple primary human somatic cell types, thereby representing a highly attractive gene transfer strategy for clinical use...
September 27, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28963732/beyond-immune-escape-a-variant-surface-glycoprotein-causes-suramin-resistance-in-trypanosoma-brucei
#8
Natalie Wiedemar, Fabrice E Graf, Michaela Zwyer, Emiliana Ndomba, Christina Kunz Renggli, Monica Cal, Remo S Schmidt, Tanja Wenzler, Pascal Mäser
Suramin is one of the first drugs developed in a medicinal chemistry program (Bayer, 1916), and it is still the treatment of choice for the hemolymphatic stage of African sleeping sickness caused by Trypanosoma brucei rhodesiense. Cellular uptake of suramin occurs by endocytosis, and reverse genetic studies with T. b. brucei have linked downregulation of the endocytic pathway to suramin resistance. Here we show that forward selection for suramin resistance in T. brucei spp. cultures is fast, highly reproducible, and linked to antigenic variation...
September 30, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28930051/addiction-and-the-role-of-circadian-genes
#9
Laura A Forde, Gursharan Kalsi
OBJECTIVE: In mammals, intimate interactions exist between the circadian system and other molecular systems, and mounting evidence is suggesting that these relationships may affect substance use disorders. Research in preclinical models supports the role of circadian genes as risk factors for addiction. Here, we explore the evidence and review human genetic studies testing the association between specific circadian genes and substance use disorders. METHOD: A literature search was conducted in PubMed for studies testing variants in eight circadian genes known to be central to the functioning of the master clock in the brain...
September 2017: Journal of Studies on Alcohol and Drugs
https://www.readbyqxmd.com/read/28920716/transposons-moving-forward-from-preclinical-studies-to-clinical-trials
#10
Jaitip Tipanee, Thierry VandenDriessche, Marinee K Chuah
Transposons have emerged as promising vectors for gene therapy that can potentially overcome some of the limitations of commonly used viral vectors. Transposons stably integrate into the target cell genome, enabling persistent expression of therapeutic genes. Transposons have evolved from being used as basic tools in biomedical research to bona fide therapeutics. Currently, the most promising transposons for gene therapy applications are derived from Sleeping Beauty (SB) or piggyBac (PB). Stable transposition requires co-delivery of the transposon DNA with the corresponding transposase gene, mRNA, or protein...
August 22, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28895585/habitual-sleep-duration-and-sleep-duration-variation-are-independently-associated-with-body-mass-index
#11
X Xu, M P Conomos, O Manor, J E Rohwer, A T Magis, J C Lovejoy
BACKGROUND: Sleep plays a vital role in maintaining homeostasis and promoting health. Previous studies show that shorter sleep duration is associated with elevated body mass index (BMI) and other cardiovascular risk factors. The goal of this study was to investigate the effects of habitual sleep duration and nightly sleep duration variation based on daily device-recorded data on BMI and obesity-related biomarkers. METHOD: 748 individuals (50.6% females, 85.4% European-Americans, average age: 49...
September 12, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28888423/transposons-as-tools-for-functional-genomics-in-vertebrate-models
#12
REVIEW
Koichi Kawakami, David A Largaespada, Zoltán Ivics
Genetic tools and mutagenesis strategies based on transposable elements are currently under development with a vision to link primary DNA sequence information to gene functions in vertebrate models. By virtue of their inherent capacity to insert into DNA, transposons can be developed into powerful tools for chromosomal manipulations. Transposon-based forward mutagenesis screens have numerous advantages including high throughput, easy identification of mutated alleles, and providing insight into genetic networks and pathways based on phenotypes...
September 6, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28873402/gene-environment-interaction-study-for-bmi-reveals-interactions-between-genetic-factors-and-physical-activity-alcohol-consumption-and-socioeconomic-status
#13
Mathias Rask-Andersen, Torgny Karlsson, Weronica E Ek, Åsa Johansson
Previous genome-wide association studies (GWAS) have identified hundreds of genetic loci to be associated with body mass index (BMI) and risk of obesity. Genetic effects can differ between individuals depending on lifestyle or environmental factors due to gene-environment interactions. In this study, we examine gene-environment interactions in 362,496 unrelated participants with Caucasian ancestry from the UK Biobank resource. A total of 94 BMI-associated SNPs, selected from a previous GWAS on BMI, were used to construct weighted genetic scores for BMI (GSBMI)...
September 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28870121/wide-awake-and-ready-to-move-20-years-of-non-viral-therapeutic-genome-engineering-with-the-sleeping-beauty-transposon-system
#14
Russ Hodge, Suneel Narayanavari, Zsuzsanna Izsvák, Zoltán Ivics
Gene therapies will only become a widespread tool in the clinical treatment of human diseases with the advent of gene transfer vectors that integrate genetic information stably, safely, effectively, and economically. Two decades after the discovery of the Sleeping Beauty (SB) transposon, it has been transformed into a vector system that is fulfilling these requirements. SB may well overcome some of the limitations associated with viral gene transfer vectors and transient non-viral gene delivery approaches that are being used in the majority of ongoing clinical trials...
September 4, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28855524/rnai-combining-sleeping-beauty-transposon-system-inhibits-ex-vivo-expression-of-foot-and-mouth-disease-virus-vp1-in-transgenic-sheep-cells
#15
Shoulong Deng, Guangdong Li, Kun Yu, Xiuzhi Tian, Feng Wang, Wenting Li, Wuqi Jiang, Pengyun Ji, Hongbing Han, Juncai Fu, Xiaosheng Zhang, Jinlong Zhang, Yixun Liu, Zhengxing Lian, Guoshi Liu
Foot and mouth disease, which is induced by the foot and mouth disease virus (FMDV), takes its toll on the cloven-hoofed domestic animals. The VP1 gene in FMDV genome encodes the viral capsid, a vital element for FMDV replication. Sleeping Beauty (SB) is an active DNA-transposon system responsible for genetic transformation and insertional mutagenesis in vertebrates. In this study, a conserved VP1-shRNA which specifically targets the ovine FMDV-VP1 gene was constructed and combined with SB transposase and transposon...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28854818/recent-advances-in-preclinical-developments-using-adenovirus-hybrid-vectors
#16
Eric Ehrke-Schulz, Wenli Zhang, Jian Gao, Anja Ehrhardt
Adenovirus (Ad) based vectors are efficient gene transfer vehicles to deliver foreign DNA into living organisms offering large cargo capacity low immunogenicity and genotoxicity. As Ad shows low integration rates of their genomes into host chromosomes, vector derived gene expression decreases due to continuous cell cycling in regenerating tissues and dividing cell populations. To overcome this hurdle adenoviral delivery can be combined with mechanisms leading to maintenance of therapeutic DNA and long-term effects of the desired treatment...
August 30, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28852150/targeted-disruption-of-supraspinal-motor-circuitry-reveals-a-distributed-network-underlying-restless-legs-syndrome-rls-like-movements-in-the-rat
#17
Chun-Ni Guo, Wen-Jia Yang, Shi-Qin Zhan, Xi-Fei Yang, Michael C Chen, Patrick M Fuller, Jun Lu
In this study we uncovered, through targeted ablation, a potential role for corticospinal, cerebello-rubro-spinal, and hypothalamic A11 dopaminergic systems in the development of restless legs syndrome (RLS)-like movements during sleep. Targeted lesions in select basal ganglia (BG) structures also revealed a major role for nigrostriatal dopamine, the striatum, and the external globus pallidus (GPe) in regulating RLS-like movements, in particular pallidocortical projections from the GPe to the motor cortex. We further showed that pramipexiole, a dopamine agonist used to treat human RLS, reduced RLS-like movements...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28852016/the-histidine-rich-peptide-lah4-l1-strongly-promotes-pamam-mediated-transfection-at-low-nitrogen-to-phosphorus-ratios-in-the-presence-of-serum
#18
Nan Liu, Burkhard Bechinger, Regine Süss
Non-viral vectors are widely used and investigated for the delivery of genetic material into cells. However, gene delivery barriers like lysosomal degradation, serum inhibition and transient gene expression so far still limit their clinical applications. Aiming to overcome these limitations, a pH-sensitive hybrid gene vector (PSL complex) was designed by self-assembly of poly(amidoamine) (PAMAM) dendrimers, the histidine-rich peptide LAH4-L1 and the sleeping beauty transposon system (SB transposon system, a plasmid system capable of efficient and precise genomic insertion)...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28843021/the-nasal-and-gut-microbiome-in-parkinson-s-disease-and-idiopathic-rapid-eye-movement-sleep-behavior-disorder
#19
Anna Heintz-Buschart, Urvashi Pandey, Tamara Wicke, Friederike Sixel-Döring, Annette Janzen, Elisabeth Sittig-Wiegand, Claudia Trenkwalder, Wolfgang H Oertel, Brit Mollenhauer, Paul Wilmes
BACKGROUND: Increasing evidence connects the gut microbiota and the onset and/or phenotype of Parkinson's disease (PD). Differences in the abundances of specific bacterial taxa have been reported in PD patients. It is, however, unknown whether these differences can be observed in individuals at high risk, for example, with idiopathic rapid eye movement sleep behavior disorder, a prodromal condition of α-synuclein aggregation disorders including PD. OBJECTIVES: To compare microbiota in carefully preserved nasal wash and stool samples of subjects with idiopathic rapid eye movement sleep behavior disorder, manifest PD, and healthy individuals...
August 26, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28822964/moderate-to-severe-obstructive-sleep-apnea-is-associated-with-telomere-lengthening
#20
Katarzyna Polonis, Virend K Somers, Christiane Becari, Naima Covassin, Phillip J Schulte, Brooke R Druliner, Ruth A Johnson, Krzysztof Narkiewicz, Lisa A Boardman, Prachi Singh
Obstructive sleep apnea (OSA) is associated with cardiometabolic diseases. Telomere shortening is linked to hypertension, diabetes mellitus, and cardiovascular diseases. Because these conditions are highly prevalent in OSA, we hypothesized that telomere length (TL) would be reduced in OSA patients. We identified 106 OSA and 104 non-OSA subjects who underwent polysomnography evaluation. Quantitative PCR was used to measure telomere length in genomic DNA isolated from peripheral blood samples. The association between OSA and TL was determined using unadjusted and adjusted linear models...
August 19, 2017: American Journal of Physiology. Heart and Circulatory Physiology
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