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Minjeong Kim, Jun-Won Yun, Kyeho Shin, Yejin Cho, Mijeong Yang, Ki Taek Nam, Kyung-Min Lim
Drug-induced liver injury (DILI) is the serious and fatal drug-associated adverse effect, but its incidence is very low and individual variation in severity is substantial. Acetaminophen (APAP)-induced liver injury accounts for >50% of reported DILI cases but little is known for the cause of individual variations in the severity. Intrinsic genetic variation is considered a key element but the identity of the genes was not well-established. Here, pre-biopsy method and microarray technique was applied to uncover the key genes for APAP-induced liver injury in mice, and a cause and effect experiment employing quantitative real-time PCR was conducted to confirm the correlation between the uncovered genes and APAP-induced hepatotoxicity...
August 19, 2016: Biomolecules & Therapeutics
Adam H Freedman, Rena M Schweizer, Diego Ortega-Del Vecchyo, Eunjung Han, Brian W Davis, Ilan Gronau, Pedro M Silva, Marco Galaverni, Zhenxin Fan, Peter Marx, Belen Lorente-Galdos, Oscar Ramirez, Farhad Hormozdiari, Can Alkan, Carles Vilà, Kevin Squire, Eli Geffen, Josip Kusak, Adam R Boyko, Heidi G Parker, Clarence Lee, Vasisht Tadigotla, Adam Siepel, Carlos D Bustamante, Timothy T Harkins, Stanley F Nelson, Tomas Marques-Bonet, Elaine A Ostrander, Robert K Wayne, John Novembre
Controlling for background demographic effects is important for accurately identifying loci that have recently undergone positive selection. To date, the effects of demography have not yet been explicitly considered when identifying loci under selection during dog domestication. To investigate positive selection on the dog lineage early in the domestication, we examined patterns of polymorphism in six canid genomes that were previously used to infer a demographic model of dog domestication. Using an inferred demographic model, we computed false discovery rates (FDR) and identified 349 outlier regions consistent with positive selection at a low FDR...
March 2016: PLoS Genetics
M Wang, Z Zhou, M J Khan, J Gao, J J Loor
The transition from late gestation to early lactation is the most critical phase of the lactation cycle for mammals. Research in rodents has revealed changes in the clock circadian regulator (CLOCK) gene network expression around parturition. However, their expression profiles and putative functions during the periparturient period in ruminants remain to be determined. The present study aimed to investigate the expression pattern of the CLOCK network and selected metabolic genes simultaneously in mammary gland (MG), liver (LIV), and subcutaneous adipose tissue (AT)...
July 2015: Journal of Dairy Science
Fanny Charbonnier-Beaupel, Marion Malerbi, Cristina Alcacer, Khadija Tahiri, Wassila Carpentier, Chuansong Wang, Matthew During, Desheng Xu, Paul F Worley, Jean-Antoine Girault, Denis Hervé, Jean-Christophe Corvol
In Parkinson's disease, long-term dopamine replacement therapy is complicated by the appearance of L-DOPA-induced dyskinesia (LID). One major hypothesis is that LID results from an aberrant transcriptional program in striatal neurons induced by L-DOPA and triggered by the activation of ERK. To identify these genes, we performed transcriptome analyses in the striatum in 6-hydroxydopamine-lesioned mice. A time course analysis (0-6 h after treatment with L-DOPA) identified an acute signature of 709 genes, among which genes involved in protein phosphatase activity were overrepresented, suggesting a negative feedback on ERK activation by l-DOPA...
January 7, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Xingbin Wang, Oscar L Lopez, Robert A Sweet, James T Becker, Steven T DeKosky, Mahmud M Barmada, F Yesim Demirci, M Ilyas Kamboh
There is a strong genetic basis for late-onset Alzheimer's disease (LOAD); thus far 22 genes/loci have been identified that affect the risk of LOAD. However, the relationships among the genetic variations at these loci and clinical progression of the disease have not been fully explored. In the present study, we examined the relationships of 22 known LOAD genes to the progression of AD in 680 AD patients recruited from the University of Pittsburgh Alzheimer's Disease Research Center. Patients were classified as "rapid progressors" if the Mini-Mental State Examination (MMSE) changed ≥3 points in 12 months and "slow progressors" if the MMSE changed ≤2 points...
2015: Journal of Alzheimer's Disease: JAD
Patricia Couto, Debora Miranda, Renalice Vieira, Alyne Vilhena, Luiz De Marco, Luciana Bastos-Rodrigues
Circadian rhythms comprise of daily oscillations in a variety of biological processes and are regulated by an endogenous clock. Disruption of these rhythms has been associated with cancer progression, and understanding natural oscillations in cellular growth control, tumor suppression and cancer treatment, may reveal how clock and clock‑controlled genes are regulated in normal physiological functioning. To investigate the association between clock genes and non‑small cell lung cancer (NSCLC), we genotyped three tag SNPs (rs938836, rs17050680, rs3805213) in the Nocturnin gene (CCRN4L), five SNPs (rs228727, rs228644, rs228729, rs707467, rs104620202) in the period 3 (PER3) gene and one SNP (rs6855837) in the CLOCK gene, in 78 Brazilian patients with NSCLC...
July 2014: Molecular Medicine Reports
T Sadkowski, A Ciecierska, A Majewska, J Oprządek, K Dasiewicz, M Ollik, Z Wicik, T Motyl
The purpose of this study was to identify novel marbling-related genes by comparison of the global gene expression in semitendinosus muscle of 15-month-old Limousin (LIM), Holstein-Friesian (HF) and Hereford (HER) bulls. Muscle of LIM was lean with low intramuscular fat (IMF) content (0.53%) unlike the marbled muscles of HER and HF characterized by higher amounts of IMF (1.10 and 0.81%, respectively). The comparison of muscle transcriptional profile between marbled and lean beef revealed significant differences in expression of 144 genes, presumably involved in consecutive stages of adipose tissue development, such as preadipocyte proliferation and differentiation, adipocyte maturation, lipid filling and lipid metabolism leading to increased IMF deposition and marbling development...
May 2014: Meat Science
Yi-Cheng Chang, Yen-Feng Chiu, Pi-Hua Liu, Siow Wei Hee, Tien-Jyun Chang, Yi-Der Jiang, Wei-Jei Lee, Po-Chu Lee, Hui-Yi Kao, Juey-Jen Hwang, Lee-Ming Chuang
UNLABELLED: Circadian clock genes are critical regulators of energy homeostasis and metabolism. However, whether variation in the circadian genes is associated with metabolic phenotypes in humans remains to be explored. In this study, we systemically genotyped 20 tag single nucleotide polymorphisms (SNPs) in 8 candidate genes involved in circadian clock, including CLOCK, BMAL1(ARNTL), PER1, PER2, CRY1, CRY2, CSNK1E,, and NOC(CCRN4L) in 1,510 non-diabetic Chinese subjects in Taipei and Yunlin populations in Taiwan...
2013: PloS One
Siow-Wey Hee, Shu-Huei Tsai, Yi-Cheng Chang, Ching-Jin Chang, I-Shing Yu, Po-Chu Lee, Wei-Jei Lee, Emily Yun-Chia Chang, Lee-Ming Chuang
The deadenylase nocturnin (Noc, Ccrn4l) has been recently found to regulate lipid metabolism and to control preadipocyte differentiation. Here, we showed that among the five deadenylases tested, Noc and Pan2 exhibited a biphasic expression which is out of phase to each other during adipocyte differentiation of 3T3-L1 cells. The expression levels of other deadenylases, including Parn, Ccr4, and Caf1, were relatively unchanged or reduced. The immediate early expressed Noc during 3T3-L1 adipogenesis was involved in regulating mitotic clonal expansion (MCE) and cyclin D1 expression, as demonstrated in Noc-silenced 3T3-L1 cells and Noc(-/-) primary mouse embryonic fibroblasts (MEFs)...
August 2012: Obesity
Anyonya R Guntur, Masanobu Kawai, Phuong Le, Mary L Bouxsein, Sheila Bornstein, Carla B Green, Clifford J Rosen
The role of circadian proteins in regulating whole-body metabolism and bone turnover has been studied in detail and has led to the discovery of an elemental system for timekeeping involving the core genes Clock, Bmal1, Per, and Cry. Nocturnin (Noc; Ccrn4l), a peripheral circadian-regulated gene has been shown to play a very important role in regulating adipogenesis by deadenylation of key mRNAs and intracytoplasmic transport of PPARγ. The role that it plays in osteogenesis has previously not been studied in detail...
November 2011: Annals of the New York Academy of Sciences
Gwonhwa Song, Hee Won Seo, Jin Won Choi, Deivendran Rengaraj, Tae Min Kim, Bo Ram Lee, Young Min Kim, Tae Won Yun, Jae-Wook Jeong, Jae Yong Han
Estrogen is a key regulator in the development of the female reproductive system. It also stimulates oviduct development in immature chicks. We identified candidate genes and pathways associated with the development of chicken oviducts. A pellet containing the synthetic estrogen analog diethylstilbestrol (DES) was implanted subcutaneously in 1-wk-old female chicks for 10 days. The pellet was removed from half the group for 10 days, and an additional dose was given for a further 10 days. Total RNA was extracted from the oviducts of DES-treated and untreated chicks and subjected to an Affymetrix chicken GeneChip analysis...
August 2011: Biology of Reproduction
Pierre-Yves Bourillot, Irène Aksoy, Valerie Schreiber, Florence Wianny, Herbert Schulz, Oliver Hummel, Norbert Hubner, Pierre Savatier
Leukemia inhibitory factor (LIF) activates the transcription factor signal transducer and activator of transcription 3 (STAT3), which results in the maintenance of mouse embryonic stem cells in the pluripotent state by inhibiting both mesodermal and endodermal differentiation. How the LIF/STAT3 pathway inhibits commitment to both mesoderm and endoderm lineages is presently unknown. Using a hormone-dependent STAT3 and with microarray analysis, we identified 58 targets of STAT3 including 20 unknown genes. Functional analysis showed that 22 among the 23 STAT3 target genes analyzed contribute to the maintenance of the undifferentiated state, as evidenced by an increase in the frequency of differentiated colonies in a self-renewal assay and a concomitant elevation of early differentiation markers upon knockdown...
August 2009: Stem Cells
Carla B Green, Nicholas Douris, Shihoko Kojima, Carl A Strayer, Joseph Fogerty, David Lourim, Susanna R Keller, Joseph C Besharse
The mammalian circadian system consists of a central oscillator in the suprachiasmatic nucleus of the hypothalamus, which coordinates peripheral clocks in organs throughout the body. Although circadian clocks control the rhythmic expression of a large number of genes involved in metabolism and other aspects of circadian physiology, the consequences of genetic disruption of circadian-controlled pathways remain poorly defined. Here we report that the targeted disruption of Nocturnin (Ccrn4l) in mice, a gene that encodes a circadian deadenylase, confers resistance to diet-induced obesity...
June 5, 2007: Proceedings of the National Academy of Sciences of the United States of America
Eduardo Garbarino-Pico, Shuang Niu, Mark D Rollag, Carl A Strayer, Joseph C Besharse, Carla B Green
Nocturnin (Noc, also called Ccrn4l [carbon catabolite repression 4-like]) is a circadian deadenylase that is rhythmically expressed in multiple tissues in mice with peak mRNA levels in early night. Since several other circadian genes are induced by extracellular stimuli, we tested the hypothesis that Noc is acutely regulated in NIH3T3 cells. A serum shock and the phorbol ester TPA induced Noc transcript levels in quiescent NIH3T3 cultures while dexamethasone and forskolin, which are known to induce other clock genes in culture, were without effect...
May 2007: RNA
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