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Robert A Seaborne, Juliette Strauss, Matthew Cocks, Sam Shepherd, Thomas D O'Brien, Ken A van Someren, Phillip G Bell, Christopher Murgatroyd, James P Morton, Claire E Stewart, Adam P Sharples
It is unknown if adult human skeletal muscle has an epigenetic memory of earlier encounters with growth. We report, for the first time in humans, genome-wide DNA methylation (850,000 CpGs) and gene expression analysis after muscle hypertrophy (loading), return of muscle mass to baseline (unloading), followed by later hypertrophy (reloading). We discovered increased frequency of hypomethylation across the genome after reloading (18,816 CpGs) versus earlier loading (9,153 CpG sites). We also identified AXIN1, GRIK2, CAMK4, TRAF1 as hypomethylated genes with enhanced expression after loading that maintained their hypomethylated status even during unloading where muscle mass returned to control levels, indicating a memory of these genes methylation signatures following earlier hypertrophy...
January 30, 2018: Scientific Reports
Jie Liu, Ranran Liu, Jie Wang, Yonghong Zhang, Siyuan Xing, Maiqing Zheng, Huanxian Cui, Qinghe Li, Peng Li, Xiaoyan Cui, Wei Li, Guiping Zhao, Jie Wen
Improving feed efficiency is a major goal in poultry production to reduce production costs and increase profitability. The genomic variants and possible molecular mechanisms responsible for residual feed intake (RFI) in chickens, however, remain poorly understood. In this study, using both local and commercial breeds, genome re-sequencing of low RFI and high RFI chickens was performed to elucidate the genomic variants underlying RFI. Results showed that 8,505,214 and 8,479,041 single nucleotide polymorphisms (SNPs) were detected in low and high RFI Beijing-You chickens, respectively; 8,352,008 and 8,372,769 SNPs were detected in low- and high-RFI Cobb chickens, respectively...
January 24, 2018: Genes
Emily A Voigt, Diane E Grill, Michael T Zimmermann, Whitney L Simon, Inna G Ovsyannikova, Richard B Kennedy, Gregory A Poland
PBMC transcriptomes after influenza vaccination contain valuable information about factors affecting vaccine responses. However, distilling meaningful knowledge out of these complex datasets is often difficult and requires advanced data mining algorithms. We investigated the use of the data-driven Weighted Gene Correlation Network Analysis (WGCNA) gene clustering method to identify vaccine response-related genes in PBMC transcriptomic datasets collected from 138 healthy older adults (ages 50-74) before and after 2010-2011 seasonal trivalent influenza vaccination...
January 15, 2018: Scientific Reports
Cristina T Vicente, Joana A Revez, Manuel A R Ferreira
Twenty-five genome-wide association studies (GWAS) of asthma were published between 2007 and 2016, the largest with a sample size of 157242 individuals. Across these studies, 39 genetic variants in low linkage disequilibrium (LD) with each other were reported to associate with disease risk at a significance threshold of P <5 × 10-8 , including 31 in populations of European ancestry. Results from analyses of the UK Biobank data ( n =380 503) indicate that at least 28 of the 31 associations reported in Europeans represent true-positive findings, collectively explaining 2...
December 2017: Clinical & Translational Immunology
Hui Zhang, Jia-Qiang Yu, Li-Li Yang, Luke M Kramer, Xin-Yang Zhang, Wei Na, James M Reecy, Hui Li
BACKGROUND: In addition to additive genetic effects, epistatic interactions can play key roles in the control of phenotypic variation of traits of interest. In the current study, 475 male birds from lean and fat chicken lines were utilized as a resource population to detect significant epistatic effects associated with growth and carcass traits. RESULTS: A total of 421 significant epistatic effects were associated with testis weight (TeW), from which 11 sub-networks (Sub-network1 to Sub-network11) were constructed...
November 21, 2017: BMC Genomics
Shu Ye, Ting-Ting Wang, Biao Cai, Yan Wang, Jing Li, Ji-Xian Zhan, Guo-Ming Shen
Genistein has a neuroprotective effect in Alzheimer's disease, but its mechanism of action needs further clarification. Accumulating evidence suggests that excessive phosphorylation of tau protein causes production of neurofibrillary tangles, which is one of the main pathological characteristics of Alzheimer's disease, and tau protein can be phosphorylated by calcium/calmodulin dependent protein kinase IV (CAMK4). After 7 days of pre-administration of genistein (90 mg/kg), an Alzheimer's disease rat model was established using an intraperitoneal injection of D-galactose combined with an intracerebral injection of amyloid-β peptide (25-35)...
September 2017: Neural Regeneration Research
Deepa Srikanta, Camaron R Hole, Matthew Williams, Shabaana A Khader, Tamara L Doering
Cryptococcus neoformans , the causative agent of cryptococcosis, is an opportunistic fungal pathogen that kills over 200,000 individuals annually. This yeast may grow freely in body fluids, but it also flourishes within host cells. Despite extensive research on cryptococcal pathogenesis, host genes involved in the initial engulfment of fungi and subsequent stages of infection are woefully understudied. To address this issue, we combined short interfering RNA silencing and a high-throughput imaging assay to identify host regulators that specifically influence cryptococcal uptake...
December 2017: Infection and Immunity
Majid Motaghinejad, Manijeh Motevalian, Mohammad Abdollahi, Mansour Heidari, Zahra Madjd
Methylphenidate (MPH) abuse can cause serious neurological damages. The neuroprotective effects of topiramate (TPM) have been reported already, but its mechanism of action still remains unclear. The current study evaluates in vivo role of CREB/BDNF in TPM protection of the rat hippocampal cells from methylphenidate-induced apoptosis, oxidative stress, and inflammation. A total of 60 adult male rats were divided into six groups. Groups 1 and 2 received normal saline (0.7 ml/rat) and MPH (10 mg/kg) respectively for 14 days...
April 2017: Neurotoxicity Research
Hung-Sheng Shang, Jia-You Liu, Hsu-Feng Lu, Han-Sun Chiang, Chia-Hain Lin, Ann Chen, Yuh-Feng Lin, Jing-Gung Chung
Casticin, a polymethoxyflavone, derived from natural plant Fructus Viticis exhibits biological activities including anti-cancer characteristics. The anti-cancer and alter gene expression of casticin on human colon cancer cells and the underlying mechanisms were investigated. Flow cytometric assay was used to measure viable cell, cell cycle and sub-G1 phase, reactive oxygen species (ROS) and Ca(2+) productions, level of mitochondria membrane potential (ΔΨm ) and caspase activity. Western blotting assay was used to detect expression of protein level associated with cell death...
August 2017: Environmental Toxicology
Majid Motaghinejad, Manijeh Motevalian, Reza Falak, Mansour Heidari, Mahshid Sharzad, Elham Kalantari
Methylphenidate (MPH) abuse damages brain cells. The neuroprotective effects of topiramate (TPM) have been reported previously, but its exact mechanism of action still remains unclear. This study investigated the in vivo role of various doses of TPM in the protection of rat amygdala cells against methylphenidate-induced oxidative stress and inflammation. Seventy adult male rats were divided into seven groups. Groups 1 and 2 received normal saline (0.7 ml/rat) and MPH (10 mg/kg), respectively, for 21 days...
December 2016: Journal of Neural Transmission
Rong Lin, Yunxia Zhang, Dongjing Yan, Xiaoping Liao, Yunxin Fu, Wangwei Cai
No abstract text is available yet for this article.
September 2016: Journal of Genetics
Guangwei Zhong, Yusi Chen, Lihua Liu, Yingzhe Liu, Liu Yang, Yanli Luo, Jiamei Yao
OBJECTIVE: To evaluate the association between single nucleotide polymorphisms of calcium/calmodulin-dependent kinase 4 (CAMK4) and the therapeutic effect of amlodipine in essential hypertensive patients in Chinese Han nationality.
 METHODS: A total of 108 mild-to-moderate essential hypertension patients in Chinese Han nationality were treated with amlodipine for 8 weeks at a dosage of 5 mg/d. Polymerase chain reaction-restriction fragment length polymorphism was performed to detect the genotypes (rs10491334)...
August 2016: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
B K Binukumar, Steven L Pelech, Catherine Sutter, Varsha Shukla, Niranjana D Amin, Philip Grant, Manju Bhaskar, Suzanne Skuntz, Joseph Steiner, Harish C Pant
Cyclin-dependent kinase 5 (CDK5) is a multifunctional serine/threonine kinase that regulates a large number of neuronal processes essential for nervous system development and function with its activator p35 CDK5R1. Upon neuronal insults, p35 is proteolyzed and cleaved to p25 producing deregulation and hyperactivation of CDK5 (CDK5/p25), implicated in tau hyperphosphorylation, a pathology in some neurodegenerative diseases. A truncated, 24 amino acid peptide, p5, derived from p35 inhibits the deregulated CDK5 phosphotransferase activity and ameliorates Alzheimer's disease (AD) phenotypes in AD model mice...
September 6, 2016: Journal of Alzheimer's Disease: JAD
Nor Aijratul Asikin Mohamad Shalan, Noordin M Mustapha, Suhaila Mohamed
Morinda citrifolia fruit, (noni), enhanced performances in athletes and post-menopausal women in clinical studies. This report shows the edible noni leaves water extract enhances performance in a weight-loaded swimming animal model better than the fruit or standardized green tea extract. The 4weeks study showed the extract (containing scopoletin and epicatechin) progressively prolonged the time to exhaustion by threefold longer than the control, fruit or tea extract. The extract improved (i) the mammalian antioxidant responses (MDA, GSH and SOD2 levels), (ii) tissue nutrient (glucose) and metabolite (lactate) management, (iii) stress hormone (cortisol) regulation; (iv) neurotransmitter (dopamine, noradrenaline, serotonin) expressions, transporter or receptor levels, (v) anti-inflammatory (IL4 & IL10) responses; (v) skeletal muscle angiogenesis (VEGFA) and (v) energy and mitochondrial biogenesis (via PGC, UCP3, NRF2, AMPK, MAPK1, and CAMK4)...
December 1, 2016: Food Chemistry
Fei Yang, Huabin Cao, Qingyang Xiao, Xiaoquan Guo, Yu Zhuang, Caiying Zhang, Tiancheng Wang, Huayuan Lin, Yalu Song, Guoliang Hu, Ping Liu
BACKGROUND: Pulmonary arterial hypertension, also known as Ascites syndrome (AS), remains a clinically challenging disease with a large impact on both humans and broiler chickens. Pulmonary arterial remodeling presents a key step in the development of AS. The precise molecular mechanism of pulmonary artery remodeling regulating AS progression remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: We obtained pulmonary arteries from two positive AS and two normal broilers for RNA sequencing (RNA-seq) analysis and pathological observation...
2016: PloS One
Kristofer K Rau, Caitlin E Hill, Benjamin J Harrison, Gayathri Venkat, Heidi M Koenig, Sarah B Cook, Alexander G Rabchevsky, Bradley K Taylor, Tsonwin Hai, Jeffrey C Petruska
Tissue damage is one of the major etiological factors in the emergence of chronic/persistent pain, although mechanisms remain enigmatic. Using incision of the back skin of adult rats as a model for tissue damage, we observed sensitization in a nociceptive reflex enduring to 28days post-incision (DPI). To determine if the enduring behavioral changes corresponded with a long-term impact of tissue damage on sensory neurons, we examined the temporal expression profile of injury-regulated genes and the electrophysiological properties of traced dorsal root ganglion (DRG) sensory neurons...
September 2016: Experimental Neurology
Shijie Xu, Ung Gu Kang
The 5' adenosine monophosphate-activated protein kinase (AMPK) functions as an intracellular energy sensor that regulates and maintains energy balance. The psychostimulant drug cocaine has profound effects on behavior that are accentuated with repeated use, which is a process termed sensitization. Thus, the present study examined whether the sensitizing effects of cocaine could be observed in the AMPK system and aimed to determine whether these effects were mediated by dopamine (DA) D1 or D2 receptors. In the first set of experiments, rats were injected daily for 5days with either cocaine (15mg/kg, intraperitoneal [IP]) or saline...
July 2016: Pharmacology, Biochemistry, and Behavior
Tomohiro Koga, Kotaro Otomo, Masayuki Mizui, Nobuya Yoshida, Masataka Umeda, Kunihiro Ichinose, Atsushi Kawakami, George C Tsokos
OBJECTIVE: The recruitment of interleukin-17 (IL-17)-producing T helper (Th17) cells to inflammatory sites has been implicated in the development of organ damage in inflammatory and autoimmune diseases including systemic lupus erythematosus (SLE). To define the mechanism of calcium/calmodulin-dependent kinase IV (CaMKIV) activation of Th17 cell recruitment to target tissues, we performed anti-glomerular basement membrane antibody-induced glomerulonephritis (AIGN) experiments in mice and studied samples from patients with SLE...
August 2016: Arthritis & Rheumatology
S Z Chen, Z Wang, L N Zhang, G L Lu, C M Zhou, D W Wang, Z M Tang, L Wang, L Qin, Z H Zhai
Considering that calcium/calmodulin-dependent kinase 4 (CAMK4) plays a pivotal role in blood pressure regulation, we investigated the association between a CAMK4 polymorphism (rs10491334) and hypertension in the Han, Kazak, and Uygur ethnic groups. We studied 1224 patients with hypertension and 967 normotensive controls classified into three ethnic groups (Han, Kazak, and Uygur). The rs10491334 polymorphism was genotyped using a TaqMan® 5'-nuclease assay. In the Uygur group, the T-allele frequency in patients with hypertension was twice that of the controls (12...
January 22, 2016: Genetics and Molecular Research: GMR
Jian-Da Wang, Yu-Lan Cao, Qian Li, Ya-Ping Yang, Mengmeng Jin, Dong Chen, Fen Wang, Guang-Hui Wang, Zheng-Hong Qin, Li-Fang Hu, Chun-Feng Liu
Autophagy dysfunction is implicated in the pathogenesis of Parkinson disease (PD). BECN1/Beclin 1 acts as a critical regulator of autophagy and other cellular processes; yet, little is known about the function and regulation of BECN1 in PD. In this study, we report that dopamine D2 and D3 receptor (DRD2 and DRD3) activation by pramipexole and quinpirole could enhance BECN1 transcription and promote autophagy activation in several cell lines, including PC12, MES23.5 and differentiated SH-SY5Y cells, and also in tyrosine hydroxylase positive primary midbrain neurons...
November 2, 2015: Autophagy
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