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https://www.readbyqxmd.com/read/29784899/pathway-based-analysis-of-genome-wide-association-study-of-circadian-phenotypes
#1
Di-di Zhu, Jia-Min Yuan, Rui Zhu, Yao Wang, Zhi-Yong Qian, Jian-Gang Zou
Sleepiness affects normal social life, which attracts more and more attention. Circadian phenotypes contribute to obvious individual differences in susceptibility to sleepiness. We aimed to identify candidate single nucleotide polymorphisms (SNPs) which may cause circadian phenotypes, elucidate the potential mechanisms, and generate corresponding SNP-gene-pathways. A genome-wide association studies (GWAS) dataset of circadian phenotypes was utilized in the study. Then, the Identify Candidate Causal SNPs and Pathways analysis was employed to the GWAS dataset after quality control filters...
November 1, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/29776774/association-of-disrupted-circadian-rhythmicity-with-mood-disorders-subjective-wellbeing-and-cognitive-function-a-cross-sectional-study-of-91-105-participants-from-the-uk-biobank
#2
Laura M Lyall, Cathy A Wyse, Nicholas Graham, Amy Ferguson, Donald M Lyall, Breda Cullen, Carlos A Celis Morales, Stephany M Biello, Daniel Mackay, Joey Ward, Rona J Strawbridge, Jason M R Gill, Mark E S Bailey, Jill P Pell, Daniel J Smith
BACKGROUND: Disruption of sleep and circadian rhythmicity is a core feature of mood disorders and might be associated with increased susceptibility to such disorders. Previous studies in this area have used subjective reports of activity and sleep patterns, but the availability of accelerometer-based data from UK Biobank participants permits the derivation and analysis of new, objectively ascertained circadian rhythmicity parameters. We examined associations between objectively assessed circadian rhythmicity and mental health and wellbeing phenotypes, including lifetime history of mood disorder...
May 15, 2018: Lancet Psychiatry
https://www.readbyqxmd.com/read/29775885/clinical-correlates-of-hypothalamic-pituitary-adrenal-axis-measures-in-individuals-at-risk-for-psychosis-and-with-first-episode-psychosis
#3
Javier Labad, Antonio Armario, Roser Nadal, Montse Solé, Alfonso Gutiérrez-Zotes, Itziar Montalvo, Lorena Moreno-Samaniego, Lourdes Martorell, Vanessa Sánchez-Gistau, Elisabet Vilella
Hypothalamic-pituitary-adrenal (HPA) axis alterations in at-risk mental states (ARMS) resemble those observed in established psychosis but are less consistent. We aimed to explore HPA axis abnormalities in both first-episode psychosis (FEP) and ARMS patients, while controlling for psychopathological symptoms. We studied 21 ARMS, 34 FEP patients and 34 healthy subjects. Clinical assessment included psychopathological symptoms (positive, negative, disorganized, excited and depressive symptoms) and stress measures...
May 7, 2018: Psychiatry Research
https://www.readbyqxmd.com/read/29773907/an-approach-to-monitoring-home-cage-behavior-in-mice-that-facilitates-data-sharing
#4
Edoardo Balzani, Matteo Falappa, Fuat Balcà, Valter Tucci
Genetically modified mice are used as models for a variety of human behavioral conditions. However, behavioral phenotyping can be a major bottleneck in mouse genetics because many of the classic protocols are too long and/or are vulnerable to unaccountable sources of variance, leading to inconsistent results between centers. We developed a home-cage approach using a Chora feeder that is controlled by-and sends data to-software. In this approach, mice are tested in the standard cages in which they are held for husbandry, which removes confounding variables such as the stress induced by out-of-cage testing...
June 2018: Nature Protocols
https://www.readbyqxmd.com/read/29764215/myotonic-dystrophytype-1-report-of-non-24-h-sleep-wake-disorder-with-excessive-daytime-sleepiness
#5
Lucio Huebra Pimentel Filho, Ana Carolina Dias Gomes, Bruno Gonçalves, Sergio Tufik, Fernando Morgadinho Coelho
Myotonic dystrophy (MD) is a neuromuscular disease with myotonia, progressive weakness, and involvement of CNS, heart, and gastrointestinal system. Excessive daytime sleepiness (EDS) in myotonic dystrophy type 1 (MD1) is related to sleep breathing diseases, restless leg syndrome, periodic limb movements during sleep and narcoleptic-like phenotype. However, authors highlight a central dysfunction of sleep regulation. We describe a 26-year-old, female, MD1 patient with EDS. Sleep diary/actigraphy evidenced two different circadian periods with values of 1442 and 1522 min...
May 15, 2018: Chronobiology International
https://www.readbyqxmd.com/read/29760192/circadian-rhythms-influence-the-severity-of-sepsis-in-mice-via-a-tlr2-dependent-leukocyte-intrinsic-mechanism
#6
Erica L Heipertz, Jourdan Harper, Charlie A Lopez, Erol Fikrig, Michael E Hughes, Wendy E Walker
Circadian rhythms coordinate an organism's activities and biological processes to the optimal time in the 24-h daylight cycle. We previously demonstrated that male C57BL/6 mice develop sepsis more rapidly when the disease is induced in the nighttime versus the daytime. In this report, we elucidate the mechanism of this diurnal difference. Sepsis was induced via cecal ligation and puncture (CLP) at zeitgeber time (ZT)-19 (2 am) or ZT-7 (2 pm). Like the males used in our prior study, female C57BL/6 mice had a worse outcome when CLP was induced at ZT-19 versus ZT-7, and these effects persisted when we pooled the data from both sexes...
May 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29748957/circadian-alignment-in-a-foster-mother-improves-the-offspring-s-pathological-phenotype
#7
Lucie Olejníková, Lenka Polidarová, Michal Behuliak, Martin Sládek, Alena Sumová
KEY POINTS: In mammals, the mother-offspring interaction is essential for health later in adulthood. The impact of altered timing and quality of maternal care on the offspring's circadian system was assessed using a cross-strain fostering approach. Better maternal care facilitated the development of amplitudes of Bmal1 clock gene expression in the central clock, as well as the clock-driven activity/rest rhythm, and also its entrainment to the external light/dark cycle. Worse maternal care impaired entrainment of the central clock parameters in the Wistar rat during the early developmental stages...
May 10, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29735553/optimized-dosing-schedule-based-on-circadian-dynamics-of-mouse-breast-cancer-stem-cells-improves-the-anti-tumor-effects-of-aldehyde-dehydrogenase
#8
Naoya Matsunaga, Takashi Ogino, Yukinori Hara, Takahiro Tanaka, Satoru Koyanagi, Shigehiro Ohdo
Although malignant phenotypes of triple-negative breast cancer (TNBC) are subject to circadian alterations, the role of cancer stem cells (CSC) in defining this circadian change remains unclear. CSC are often characterized by high aldehyde dehydrogenase (ALDH) activity, which is associated with the malignancy of cancer cells and used for identification and isolation of CSC. Here we show that the popultation of ALDH-positive cells in a mouse 4T1 breast tumor model exhibits pronounced circadian alterations. Alterations in the number of ALDH-positive cells was generated by time-dependent increases and decreases in the expression of Aldh3a1...
May 7, 2018: Cancer Research
https://www.readbyqxmd.com/read/29735415/interventions-targeting-glucocorticoid-kr%C3%A3-ppel-like-factor-15-branched-chain-amino-acid-signaling-improve-disease-phenotypes-in-spinal-muscular-atrophy-mice
#9
Lisa M Walter, Marc-Olivier Deguise, Katharina E Meijboom, Corinne A Betts, Nina Ahlskog, Tirsa L E van Westering, Gareth Hazell, Emily McFall, Anna Kordala, Suzan M Hammond, Frank Abendroth, Lyndsay M Murray, Hannah K Shorrock, Domenick A Prosdocimo, Saptarsi M Haldar, Mukesh K Jain, Thomas H Gillingwater, Peter Claus, Rashmi Kothary, Matthew J A Wood, Melissa Bowerman
The circadian glucocorticoid-Krüppel-like factor 15-branched-chain amino acid (GC-KLF15-BCAA) signaling pathway is a key regulatory axis in muscle, whose imbalance has wide-reaching effects on metabolic homeostasis. Spinal muscular atrophy (SMA) is a neuromuscular disorder also characterized by intrinsic muscle pathologies, metabolic abnormalities and disrupted sleep patterns, which can influence or be influenced by circadian regulatory networks that control behavioral and metabolic rhythms. We therefore set out to investigate the contribution of the GC-KLF15-BCAA pathway in SMA pathophysiology of Taiwanese Smn-/- ;SMN2 and Smn2B/- mouse models...
May 4, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29723273/distinct-roles-for-rev-erb%C3%AE-and-rev-erb%C3%AE-in-oxidative-capacity-and-mitochondrial-biogenesis-in-skeletal-muscle
#10
Ariadna Amador, Sean Campbell, Melissa Kazantzis, Gary Lan, Thomas P Burris, Laura A Solt
The nuclear receptors REV-ERBα and REV-ERBβ have been demonstrated to be core members of the circadian clock and participate in the regulation of a diverse set of metabolic functions. Due to their overlapping tissue expression patterns and gene expression profiles, REV-ERBβ is thought to be redundant to REV-ERBα. Recent work has highlighted REV-ERBα's role in the regulation of skeletal muscle oxidative capacity and mitochondrial biogenesis. Considering the similarity between the REV-ERBs and the hypothesized overlap in function, we sought to determine whether REV-ERBβ-deficiency presented with a similar skeletal muscle phenotype as REV-ERBα-deficiency...
2018: PloS One
https://www.readbyqxmd.com/read/29718372/defining-the-impact-of-melanopsin-missense-polymorphisms-using-in-vivo-functional-rescue
#11
Jessica Rodgers, Steven Hughes, Carina A Pothecary, Laurence A Brown, Doron G Hickey, Stuart N Peirson, Mark W Hankins
Melanopsin (OPN4) is an opsin photopigment expressed within intrinsically photosensitive retinal ganglion cells (ipRGCs) that mediate non-image forming (NIF) responses to light. Two single nucleotide polymorphisms (SNPs) in human melanopsin (hOPN4), Pro10Leu and Thr394Ile, have recently been associated with abnormal NIF responses to light, including Seasonal Affective Disorder. It has been suggested these behavioural changes are due to altered melanopsin signalling. However, there is currently no direct evidence to support this...
April 30, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29716523/mice-lacking-galectin-3-lgals3-function-have-decreased-home-cage-movement
#12
Tammy R Chaudoin, Stephen J Bonasera
BACKGROUND: Galectins are a large family of proteins evolved to recognize specific carbohydrate moieties. Given the importance of pattern recognition processes for multiple biological tasks, including CNS development and immune recognition, we examined the home cage behavioral phenotype of mice lacking galectin-3 (Lgals3) function. Using a sophisticated monitoring apparatus capable of examining feeding, drinking, and movement at millisecond temporal and 0.5 cm spatial resolutions, we observed daily behavioral patterns from 10 wildtype male C57BL/6J and 10 Lgals3 constitutive knockout (Lgals3-/- ; both cohorts aged 2-3 months) mice over 17 consecutive days...
May 2, 2018: BMC Neuroscience
https://www.readbyqxmd.com/read/29702186/molecular-and-functional-characterization-of-the-magnesium-transporter-gene-zmmgt12-in-maize
#13
Hongyou Li, Chan Liu, Lina Zhou, Zhao Zhuo, Li Yihong, Qu Min, Kaifeng Huang, Lu Zhang, Yanli Lu, Moju Cao, Shibin Gao, Suzhi Zhang
Magnesium (Mg) is an essential mineral element for normal plant growth and development, and the CorA/MRS2/MGT-type Mg transporters play a significant role in maintaining Mg homeostasis in plants. In total, 12 maize CorA-like Mg2+ transporters have been identified, but none of them had been functionally characterized. Accordingly, we cloned and functionally characterized ZmMGT12 from the maize CorA-like gene family. ZmMGT12 exhibited the structure typical of Mg2+ transporters, i.e., two conserved TM domains and a GMN tripeptide motif...
April 24, 2018: Gene
https://www.readbyqxmd.com/read/29700553/functional-characterisation-of-naturally-occurring-mutations-in-human-melanopsin
#14
Jessica Rodgers, Stuart N Peirson, Steven Hughes, Mark W Hankins
Melanopsin is a blue light-sensitive opsin photopigment involved in a range of non-image forming behaviours, including circadian photoentrainment and the pupil light response. Many naturally occurring genetic variants exist within the human melanopsin gene (OPN4), yet it remains unclear how these variants affect melanopsin protein function and downstream physiological responses to light. Here, we have used bioinformatic analysis and in vitro expression systems to determine the functional phenotypes of missense human OPN4 variants...
April 26, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29691382/snord116-dependent-diurnal-rhythm-of-dna-methylation-in-mouse-cortex
#15
Rochelle L Coulson, Dag H Yasui, Keith W Dunaway, Benjamin I Laufer, Annie Vogel Ciernia, Yihui Zhu, Charles E Mordaunt, Theresa S Totah, Janine M LaSalle
Rhythmic oscillations of physiological processes depend on integrating the circadian clock and diurnal environment. DNA methylation is epigenetically responsive to daily rhythms, as a subset of CpG dinucleotides in brain exhibit diurnal rhythmic methylation. Here, we show a major genetic effect on rhythmic methylation in a mouse Snord116 deletion model of the imprinted disorder Prader-Willi syndrome (PWS). More than 23,000 diurnally rhythmic CpGs are identified in wild-type cortex, with nearly all lost or phase-shifted in PWS...
April 24, 2018: Nature Communications
https://www.readbyqxmd.com/read/29674279/association-of-melatonin-mtnr1b-variants-with-type-2-diabetes-in-gujarat-population
#16
Roma Patel, Nirali Rathwa, Sayantani Pramanik Palit, A V Ramachandran, Rasheedunnisa Begum
AIM/HYPOTHESIS: Melatonin is a circadian rhythm regulator and any imbalance in its levels can be related to various metabolic disorders. Melatonin and the genetic variants of Melatonin Receptor 1B (MTNR1B) are reported to be associated with Type 2 Diabetes (T2D) susceptibility. The aim of the present study was to investigate i) plasma melatonin levels ii) Single Nucleotide Polymorphisms (SNPs) of MTNR1B and iii) Genotype-phenotype correlation analysis in T2D patients. METHODS: Plasma and PBMCs were separated from venous blood of 478 diabetes patients and 502 controls...
April 16, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29673115/the-nuclear-retinoid-related-orphan-receptor-ror%C3%AE-controls-circadian-thermogenic-programming-in-white-fat-depots
#17
Chloé Monnier, Martine Auclair, Gala Le Cam, Marie-Pauline Garcia, Bénédicte Antoine
The RORα-deficient staggerer (sg/sg) mouse is lean and resistant to diet-induced obesity. Its thermogenic activity was shown to be increased not only in brown adipose tissue (BAT), but also in subcutaneous white adipose tissue (WAT) where UCP1 content was enhanced, however, without Prdm16 coexpression. Our observation of partial multilocular lipid morphology of WAT in sg/sg mice both in the inguinal and perigonadal sites led us to focus on the phenotype of both fat depots. Because RORα is a nuclear factor acting in the clock machinery, we looked at the circadian expression profile of genes involved in thermogenesis and browning in WAT and BAT depots of sg/sg and WT mice, through real-time quantitative PCR and western blotting...
April 2018: Physiological Reports
https://www.readbyqxmd.com/read/29672861/circadian-rhythms-are-associated-with-shoot-architecture-in-natural-settings
#18
Matthew J Rubin, Marcus T Brock, Robert L Baker, Stephanie Wilcox, Kyle Anderson, Seth J Davis, Cynthia Weinig
Circadian rhythms are key regulators of diverse biological processes under controlled settings. Yet, the phenotypic and fitness consequences of quantitative variation in circadian rhythms remain largely unexplored in the field. As with other pathways, phenotypic characterization of circadian outputs in the field may reveal novel clock functions. Across consecutive growing seasons, we test for associations between clock variation and flowering phenology, plant size, shoot architecture, and fruit set in clock mutants and segregating progenies of Arabidopsis thaliana expressing quantitative variation in circadian rhythms...
April 19, 2018: New Phytologist
https://www.readbyqxmd.com/read/29671710/functionally-complete-excision-of-conditional-alleles-in-the-mouse-suprachiasmatic-nucleus-by-vgat-ires-cre
#19
David R Weaver, Vincent van der Vinne, E Lela Giannaris, Thomas J Vajtay, Kristopher L Holloway, Christelle Anaclet
Mice with targeted gene disruption have provided important information about the molecular mechanisms of circadian clock function. A full understanding of the roles of circadian-relevant genes requires manipulation of their expression in a tissue-specific manner, ideally including manipulation with high efficiency within the suprachiasmatic nuclei (SCN). To date, conditional manipulation of genes within the SCN has been difficult. In a previously developed mouse line, Cre recombinase was inserted into the vesicular GABA transporter (Vgat) locus...
April 2018: Journal of Biological Rhythms
https://www.readbyqxmd.com/read/29617359/sexual-dimorphism-of-sleep-regulated-by-juvenile-hormone-signaling-in-drosophila
#20
Binbin Wu, Lingling Ma, Enyan Zhang, Juan Du, Suning Liu, Jeffrey Price, Sheng Li, Zhangwu Zhao
Sexually dimorphic phenotypes are a universal phenomenon in animals. In the model animal fruit fly Drosophila, males and females exhibit long- and short-sleep phenotypes, respectively. However, the mechanism is still a mystery. In this study, we showed that juvenile hormone (JH) is involved in regulation of sexually dimorphic sleep in Drosophila, in which gain of JH function enlarges differences of the dimorphic sleep phenotype with higher sleep in males and lower sleep in females, while loss of JH function blurs these differences and results in feminization of male sleep and masculinization of female sleep...
April 4, 2018: PLoS Genetics
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