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Pâmela Ferreira Todendi, Andreia Rosane de Moura Valim, Elisa Klinger, Cézane Priscila Reuter, Susana Molina, J Alfredo Martínez, Marilu Fiegenbaum
OBJECTIVE: We investigated the association of IRX3 SNP rs3751723 with anthropometric characteristics related to adiposity and potential relationships with FTO SNP rs9939609 in a population of Brazilian children and adolescents. METHODS: A total of 871 children and adolescents between 7 and 17 years of age were recruited. Adiposity measurements and biochemical parameters were assessed. The variants were genotyped by real-time PCR. Analysis of multiple linear regression, multiple logistic regression, and generalised multifactor dimensionality reduction (GMDR) adjusted for sex, age and ethnicity were applied to test the polymorphisms association with obesity-related phenotypes and the interaction between them...
January 31, 2019: Obesity Research & Clinical Practice
Marc Schneeberger
No abstract text is available yet for this article.
December 9, 2018: EBioMedicine
Jan-Inge Bjune, Christine Haugen, Oddrun Gudbrandsen, Ole P Nordbø, Hans J Nielsen, Villy Våge, Pål R Njølstad, Jørn V Sagen, Simon N Dankel, Gunnar Mellgren
OBJECTIVE: A causal obesity risk variant in the FTO locus was recently shown to inhibit adipocyte thermogenesis via increased adipose expression of the homeobox transcription factors IRX3 and IRX5. However, causal effects of IRX5 on fat storage remain to be shown in vivo, and discovery of downstream mediators may open new therapeutic avenues. METHODS: 17 WT and 13 Irx5 knockout (KO) mice were fed low-fat control (Ctr) or high-fat (HF) diet for 10 weeks. Body weight, energy intake and fat mass were measured...
December 11, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Thiago Matos de Araujo, Daniela S Razolli, Felipe Correa-da-Silva, Jose C de Lima-Junior, Rodrigo S Gaspar, Davi Sidarta-Oliveira, Sheila C Victorio, Jose Donato, Young-Bum Kim, Licio A Velloso
BACKGROUND: The Iroquois homeobox 3 (Irx3) gene has been identified as a functional long-range target of obesity-associated variants within the fat mass and obesity-associated protein (FTO) gene. It is highly expressed in the hypothalamus, and both whole-body knockout and hypothalamic restricted abrogation of its expression results in a lean phenotype, which is mostly explained by the resulting increased energy expenditure in the brown adipose tissue. Because of its potential implication in the pathogenesis of obesity, we evaluated the hypothalamic cell distribution of Irx3 and the outcomes of inhibiting its expression in a rodent model of diet-induced obesity...
December 3, 2018: EBioMedicine
Zhuangli Zhu, Xiongfeng Chen, Yiqing Xiao, Junping Wen, Jinyan Chen, Kun Wang, Gang Chen
Gestational diabetes mellitus (GDM), which has an increasing global prevalence, contributes to the susceptibility to metabolic dysregulation and obesity in the offspring via epigenetic modifications. However, the underlying mechanism remains largely obscure. The current study established a GDM mice model to investigate the alternations in the metabolic phenotypes and genomic DNA methylation in the pancreas of the offspring. We found that in the GDM offspring, intrauterine hyperglycemia induced dyslipidemia, insulin resistance, and glucose intolerance...
November 9, 2018: Journal of Diabetes and its Complications
Simmi Saini, Gagandeep Kaur Walia, Mohinder Pal Sachdeva, Vipin Gupta
Obesity is one of the largest global health problems associated with increased morbidity and mortality mediated by its association with several other metabolic disorders. The interaction between the genes and environment plays an important role in the manifestation of obesity. Despite a high heritability (40-70%) of obesity, the search for genetic variants associated with obesity susceptibility has been a challenging task. To date, limited studies have been conducted in India, restricted to the validation of few genetic variants identified by genomewide association studies...
September 2018: Journal of Genetics
Jing-Jing Jing, Ze-Yang Wang, Hao Li, Li-Ping Sun, Yuan Yuan
Background: The molecular mechanism of Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) remains elusive. A collection of molecular regulators including transcription factor and noncoding RNA (ncRNAs) may affect the carcinogenesis of EBVaGC by regulating the expression and function of key genes. In this study, integration of multi-level expression data and bioinformatics approach was used to identify key elements and their interactions involved in mechanism of EBVaGC and their network regulation...
2018: Cancer Cell International
Linda Holmquist Mengelbier, Simon Lindell-Munther, Hiroaki Yasui, Caroline Jansson, Javanshir Esfandyari, Jenny Karlsson, Kimberly Lau, Chi-Chung Hui, Daniel Bexell, Sevan Hopyan, David Gisselsson
Wilms tumour is a paediatric malignancy with features of halted kidney development. Here, we demonstrate that the Iroquois homeobox genes IRX3 and IRX5 are essential for mammalian nephrogenesis and govern the differentiation of Wilms tumour. Knock-out Irx3- /Irx5- mice showed a strongly reduced embryonic nephron formation. In human foetal kidney and Wilms tumour, IRX5 expression was already activated in early proliferative blastema, whereas IRX3 protein levels peaked at tubular differentiation. Accordingly, an orthotopic xenograft mouse model of Wilms tumour showed that IRX3-/- cells formed bulky renal tumours dominated by immature mesenchyme and active canonical WNT/β-catenin-signalling...
September 23, 2018: Journal of Pathology
Jonathan Massey, Darren Plant, Kimme Hyrich, Ann W Morgan, Anthony G Wilson, Athina Spiliopoulou, Marco Colombo, Paul McKeigue, John Isaacs, Heather Cordell, Costantino Pitzalis, Anne Barton
Rheumatoid arthritis (RA) is characterised by chronic synovial joint inflammation. Treatment has been revolutionised by tumour necrosis factor alpha inhibitors (TNFi) but each available drug shows a significant non-response rate. We conducted a genome-wide association study of 1752 UK RA TNFi-treated patients to identify predictors of change in the Disease Activity Score 28 (DAS28) and subcomponents over 3-6 months. The rs7195994 variant at the FTO gene locus was associated with infliximab response when looking at a change in the swollen joint count (SJC28) subcomponent (p = 9...
September 2018: Pharmacogenomics Journal
Xiaolan Deng, Rui Su, Savanna Stanford, Jianjun Chen
Fat mass and obesity-associated protein (FTO) single-nucleotide polymorphisms (SNPs) have been linked to increased body mass and obesity in humans by genome-wide association studies (GWAS) since 2007. Although some recent studies suggest that the obesity-related SNPs in FTO influence obesity susceptibility likely through altering the expression of the adjacent genes such as IRX3 and RPGRIP1L , rather than FTO itself, a solid link between the SNP risk genotype and the increased FTO expression in both human blood cells and fibroblasts has been reported...
2018: Frontiers in Endocrinology
Denise Vizziano-Cantonnet, André Lasalle, Santiago Di Landro, Christophe Klopp, Clémence Genthon
The sturgeon family includes many species that are lucrative for commercial caviar production, some of which face critical conservation problems. The purpose of this study was to identify genes involved in gonadal sex differentiation in sturgeons, contributing to our understanding of the biological cycle of this valuable species. A high-quality de novo Siberian sturgeon gonadal transcriptome was built for this study using gonadal samples from undifferentiated fish at 3, 5, and 6 months of age; recently sex-differentiated fish at 9 months of age; and immature males and females at 14-17 months of age...
November 1, 2018: General and Comparative Endocrinology
Yoshiyuki Kojima, Tomoyuki Koguchi, Kentaro Mizuno, Yuichi Sato, Seiji Hoshi, Junya Hata, Hidenori Nishio, Daiki Hashimoto, Shoko Matsushita, Kentaro Suzuki, Shinichi Miyagawa, Chi Chung Hui, Chizu Tanikawa, Yoshimori Murakami, Gen Yamada, Yutaro Hayashi, Koichi Matsuda
PURPOSE: We evaluated the association of hypospadias with 17 susceptibility loci previously identified by a European genome-wide association study (GWAS) in Japanese patients. We also examined the expression of candidate genes in male mouse embryos to discuss the possible underlying mechanisms of this disease. MATERIALS AND METHODS: We enrolled 169 Japanese patients (mean age at surgery: 3.7 years) who underwent repair of hypospadias. Genotyping of 17 SNPs was performed by using a multiplex-polymerase chain reaction (PCR) invader assay...
July 28, 2018: Journal of Urology
Xiang-Jun Sun, Ming-Chun Wang, Feng-Hua Zhang, Xiao Kong
Despite progress in the treatment of hepatocellular carcinoma (HCC), 5-year survival rates remain low. Thus, a more comprehensive approach to explore the mechanism of HCC is needed to provide new leads for targeted therapy. We performed an integrated analysis to discover the relationship between DNA methylation and gene expression in hepatocellular carcinoma (HCC). DNA methylation and gene expression data for HCC were downloaded from The Cancer Genome Atlas (TCGA) database, and differential analysis was performed...
July 2018: FEBS Open Bio
Tugce Boztepe, Sukru Gulec
Background: Dietary glucose consumption has increased worldwide. Long-term high glucose intake contributes to the development of obesity and type 2 diabetes mellitus (T2DM). Obese people tend to eat glucose-containing foods, which can lead to an addiction to glucose, increased glucose levels in the blood and intestine lumen, and exposure of intestinal enterocytes to high dietary glucose. Recent studies have documented a role for enterocytes in glucose sensing. However, the molecular and genetic relationship between high glucose levels and intestinal enterocytes has not been determined...
2018: Genes & Nutrition
Andrea Shergalis, Armand Bankhead, Urarika Luesakul, Nongnuj Muangsin, Nouri Neamati
Glioblastoma multiforme (GBM), the most common and aggressive primary brain tumor, has a high mortality rate despite extensive efforts to develop new treatments. GBM exhibits both intra- and intertumor heterogeneity, lending to resistance and eventual tumor recurrence. Large-scale genomic and proteomic analysis of GBM tumors has uncovered potential drug targets. Effective and "druggable" targets must be validated to embark on a robust medicinal chemistry campaign culminating in the discovery of clinical candidates...
July 2018: Pharmacological Reviews
Abidan Ainiwaer, Adalibieke Adalibieke, Bing-Xue Huang, Y E Yekejiergeli, Ya-Lan Dou, Jie Wu, Jiang-Hong Dai
OBJECTIVE: To study the association between the prevalence of overweight/obesity and copy number variations (CNVs) among Han, Uyghur, and Kazak children in Xinjiang, China. METHODS: The kindergartens in Ili, Altay, and Karamay in Xinjiang were selected as research sites, and stratified cluster sampling was used to select the children aged 3-7 years. Body height and body weight were measured, and exfoliated buccal mucosa cells were collected. CNVplex® was used to measure the CNVs of FTO_1, IRX3_1, IRX3_2, MC4R_1, and MC4R_2...
April 2018: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
Huizhen Hu, Ran Zhang, Zhangsheng Tao, Xukai Li, Yuyang Li, Jiangfeng Huang, Xinxin Li, Xiao Han, Shengqiu Feng, Guimin Zhang, Liangcai Peng
Cellulose is the most characteristic component of plant cell walls, and plays a central role in plant mechanical strength and morphogenesis. Despite the fact that cellulose synthase (CesA) mutants exhibit a reduction in cellulose level, much remains unknown about their impacts on cell growth (elongation and division) and cell wall integrity that fundamentally determine plant growth. Here, we examined three major types of AtCesA mutants (rsw1, an AtCesA1 mutant; prc1-1 and cesa6, AtCesA6-null mutants; and IRX3, an AtCesA7 mutant) and transgenic mutants that overexpressed AtCesA genes in the background of AtCesA6-null mutants...
June 1, 2018: Plant & Cell Physiology
Kentaro Mori, Harumi Nakamura, Hisanori Kurooka, Hitoshi Miyachi, Kota Tamada, Manabu Sugai, Toru Takumi, Yoshifumi Yokota
The cellular components and function of the gastrointestinal epithelium exhibit distinct characteristics depending on the region, e.g., stomach or intestine. How these region-specific epithelial characteristics are generated during development remains poorly understood. Here, we report on the involvement of the helix-loop-helix inhibitor Id2 in establishing the specific characteristics of the intestinal epithelium. Id2 -/- mice developed tumors in the small intestine. Histological analysis indicated that the intestinal tumors were derived from gastric metaplasia formed in the small intestine during development...
February 20, 2018: Molecular and Cellular Biology
Tim D D Somerville, Fabrizio Simeoni, John A Chadwick, Emma L Williams, Gary J Spencer, Katalin Boros, Christopher Wirth, Eleni Tholouli, Richard J Byers, Tim C P Somervaille
The Iroquois homeodomain transcription factor gene IRX3 is expressed in the developing nervous system, limb buds, and heart, and transcript levels specify obesity risk in humans. We now report a functional role for IRX3 in human acute leukemia. Although transcript levels are very low in normal human bone marrow cells, high IRX3 expression is found in ∼30% of patients with acute myeloid leukemia (AML), ∼50% with T-acute lymphoblastic leukemia, and ∼20% with B-acute lymphoblastic leukemia, frequently in association with high-level HOXA gene expression...
January 16, 2018: Cell Reports
Sanjana Negi, Himanshu Tak, T R Ganapathi
Secondary-wall deposition in xylem vessel elements is regulated by vascular-related NAC transcription factors (VNDs). We show that three banana VNDs (MusaVND1, MusaVND2 and MusaVND3) directly regulate multiple secondary-wall associated genes by binding to their 5'-upstream regulatory region. Transgenic banana harboring either PMusaVND1 :GUS, PMusaVND2 :GUS or PMusaVND3 :GUS showed specific GUS staining in lignified tissues. MusaVND1, MusaVND2 and MusaVND3 encodes transcriptional-activators as its C-terminal region drive expression of reporter genes in vivo in yeast...
December 2017: Plant Science: An International Journal of Experimental Plant Biology
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