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Xinxin Tian, Hui Zhang, Yali Zhao, Khalid Mehmood, Xiaoxing Wu, Zhenyu Chang, Min Luo, Xueting Liu, Muhammad Ijaz, Muhammad Tariq Javed, Donghai Zhou
Chromium (Cr) is one of the most important environmental pollutants which are released into the environment due to their wide usage in numerous industries. The excess of Cr (VI) can induce hepatotoxicity, while the molecular mechanism that is involved in Cr (VI)-induced hepatotoxicity is unclear. We demonstrated the induction of chromium poisoning model in chickens to identify the differentially expressed genes (DEGs), and their functions were analyzed under different physiological and pathological conditions...
March 21, 2018: Environmental Science and Pollution Research International
Alexandra G Evstafieva, Irina E Kovaleva, Maria S Shoshinova, Andrei V Budanov, Peter M Chumakov
The ATF4 transcription factor is a key regulator of the adaptive integrated stress response (ISR) induced by various stresses and pathologies. Identification of novel transcription targets of ATF4 during ISR would contribute to the understanding of adaptive networks and help to identify novel therapeutic targets. We were previously searching for genes that display an inverse regulation mode by the transcription factors ATF4 and p53 in response to mitochondrial respiration chain complex III inhibition. Among the selected candidates the human genes for cytokeratine 16 (KRT16), anti-apoptotic protein Niban (FAM129A) and hexokinase HKDC1 have been found highly responsive to ATF4 overexpression...
2018: PloS One
Md Wasim Khan, Xianzhong Ding, Scott J Cotler, Michael Clarke, Brian T Layden
Hexokinase domain component 1 (HKDC1) is a recently discovered novel protein, which is being promoted as a putative fifth hexokinase. Although the exact role HKDC1 plays in physiology is still unclear, it has been shown to be important during pregnancy in the regulation of glucose homeostasis. In this study, we have comprehensively studied the expression pattern of HKDC1 in the human body. Using human tissue sample, immunohistochemistry imaging was performed. Our studies indicate that the tissues with highest HKDC1 expression were the brush border epithelium of the intestines, parts of the pancreas, and lung alveolar macrophages...
May 2018: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
Ivyna Pau Ni Bong, Ching Ching Ng, Puteri Baharuddin, Zubaidah Zakaria
Epigenetic changes have emerged as key causes in the development and progression of multiple myeloma (MM). In this study, global microRNA (miRNA) expression profiling were performed for 27 MM (19 specimens and 8 cell lines) and 3 normal controls by microarray. miRNA-targets were identified by integrating the miRNA expression profiles with mRNA expression profiles of the matched samples (unpublished data). Two miRNAs were selected for verification by RT-qPCR (miR-150-5p and miR-4430). A total of 1791 and 8 miRNAs were over-expressed and under-expressed, respectively in MM compared to the controls (fold change ≥2...
2017: Genes & Genomics
Jun Li, Jing Wang, Yanbin Chen, Lijie Yang, Sheng Chen
Squamous cell lung carcinoma (SQCLC), a common and fatal subtype of lung cancer, caused lots of mortalities and showed different outcomes in prognosis. This study was to screen key genes and to figure a prognostic signature to cluster the patients with SQCLC. RNA-Seq data from 550 patients with SQCLC were downloaded from The Cancer Genome Atlas (TCGA). Genetically changed genes were identified and analyzed in univariate survival analysis. Genes significantly influencing prognosis were selected with frequency higher than 100 in lasso regression...
December 2017: Journal of Cellular Physiology
Justyna A Karolak, Tomasz Gambin, Jose A Pitarque, Andrea Molinari, Shalini Jhangiani, Pawel Stankiewicz, James R Lupski, Marzena Gajecka
Keratoconus (KTCN) is a protrusion and thinning of the cornea, resulting in impairment of visual function. The extreme genetic heterogeneity makes it difficult to discover factors unambiguously influencing the KTCN phenotype. In this study, we used whole-exome sequencing (WES) and Sanger sequencing to reduce the number of candidate genes at the 5q31.1-q35.3 locus and to prioritize other potentially relevant variants in an Ecuadorian family with KTCN. We applied WES in two affected KTCN individuals from the Ecuadorian family that showed a suggestive linkage between the KTCN phenotype and the 5q31...
January 2016: European Journal of Human Genetics: EJHG
Anton E Ludvik, Carolina M Pusec, Medha Priyadarshini, Anthony R Angueira, Cong Guo, Amy Lo, Korri S Hershenhouse, Guang-Yu Yang, Xianzhong Ding, Timothy E Reddy, William L Lowe, Brian T Layden
In a recent genome-wide association study, hexokinase domain-containing protein 1, or HKDC1, was found to be associated with gestational glucose levels during 2-hour glucose tolerance tests at 28 weeks of pregnancy. Because our understanding of the mediators of gestational glucose homeostasis is incomplete, we have generated the first transgenic mouse model to begin to understand the role of HKDC1 in whole-body glucose homeostasis. Interestingly, deletion of both HKDC1 alleles results in in utero embryonic lethality...
September 2016: Endocrinology
Sekar Kanthimathi, Samuel Liju, Dhandapani Laasya, Ranjit Mohan Anjana, Viswanathan Mohan, Venkatesan Radha
Hexokinase domain containing 1 (HKDC1), a novel human hexokinase gene, is known to affect glucose metabolism and was shown to have a strong association with 2-h plasma glucose in pregnant women in a recent genome wide association study. This study aimed to evaluate the association of these regulatory variants of HKDC1 (rs1076224, rs4746822, rs2394529 and rs9645501) with gestational diabetes mellitus (GDM) in a South Indian population. The regulatory variants of HKDC1 were genotyped in unrelated 500 women with GDM and 510 non-GDM individuals by using the MassARRAY system and by direct DNA sequencing...
July 2016: Annals of Human Genetics
Zijian Zhang, Shanzhou Huang, Huanyu Wang, Jian Wu, Dong Chen, Baogang Peng, Qi Zhou
Rapid progress and metastasis remain the major treatment failure modes of hepatocarcinoma (HCC). Unfortunately, the underlying molecular mechanisms of hepatoma cell proliferation and migration are poorly understood. Metabolic abnormalities play critical roles in tumorigenesis and progression. Hexokinase domain containing 1 (HKDC1) catalyzes the phosphorylation of glucose. However, the functions and mechanisms of HKDC1 in cancer remain unknown. In this study, real-time RT-PCR and Western blotting assays were used to detect the HKDC1 expression levels in HCC tissues and cell lines...
June 10, 2016: Biochemical and Biophysical Research Communications
William L Lowe, Denise M Scholtens, Victoria Sandler, M Geoffrey Hayes
Gestational diabetes mellitus (GDM) is defined as abnormal glucose tolerance with onset or first recognition during pregnancy. Women with a history of GDM are at long-term risk for developing type 2 diabetes (T2DM), raising the question to what extent GDM and T2DM share a common genetic architecture. Meta-analysis of candidate gene studies and genome-wide association analysis (GWAS) have identified a number of genes which are reproducibly associated with GDM, including TCF7L2, GCK, KCNJ11, KCNQ1, CDKAL1, IGF2BP2, MTNR1B, and IRS1...
February 2016: Current Diabetes Reports
Cong Guo, Anton E Ludvik, Michelle E Arlotto, M Geoffrey Hayes, Loren L Armstrong, Denise M Scholtens, Christopher D Brown, Christopher B Newgard, Thomas C Becker, Brian T Layden, William L Lowe, Timothy E Reddy
Maternal glucose levels during pregnancy impact the developing fetus, affecting metabolic health both early and later on in life. Both genetic and environmental factors influence maternal metabolism, but little is known about the genetic mechanisms that alter glucose metabolism during pregnancy. Here, we report that haplotypes previously associated with gestational hyperglycaemia in the third trimester disrupt regulatory element activity and reduce expression of the nearby HKDC1 gene. We further find that experimentally reducing or increasing HKDC1 expression reduces or increases hexokinase activity, respectively, in multiple cellular models; in addition, purified HKDC1 protein has hexokinase activity in vitro...
2015: Nature Communications
Hirwa Claire D Andre, Wallace Paul, Xu Shen, Xinzheng Jia, Rong Zhang, Liang Sun, Zhang Xiquan
BACKGROUND: Fat deposits in chickens contribute significantly to meat quality attributes such as juiciness, flavor, taste and other organoleptic properties. The quantity of fat deposited increases faster and earlier in the fast-growing chickens than in slow-growing chickens. In this study, Affymetrix Genechip(R) Chicken Genome Arrays 32773 transcripts were used to compare gene expression profiles in liver and hypothalamus tissues of fast-growing and slow-growing chicken at 8 wk of age...
November 9, 2013: Journal of Animal Science and Biotechnology
Gong-Hua Li, Jing-Fei Huang
MOTIVATION: The discovery of therapeutic targets is important for cancer treatment. Although dozens of targets have been used in cancer therapies, cancer remains a serious disease with a high mortality rate. Owing to the expansion of cancer-related data, we now have the opportunity to infer therapeutic targets using computational biology methods. RESULTS: Here, we describe a method, termed anticancer activity enrichment analysis, used to determine genes that could be used as therapeutic targets...
March 15, 2014: Bioinformatics
M Geoffrey Hayes, Margrit Urbanek, Marie-France Hivert, Loren L Armstrong, Jean Morrison, Cong Guo, Lynn P Lowe, Douglas A Scheftner, Anna Pluzhnikov, David M Levine, Caitlin P McHugh, Christine M Ackerman, Luigi Bouchard, Diane Brisson, Brian T Layden, Daniel Mirel, Kimberly F Doheny, Marysa V Leya, Rachel N Lown-Hecht, Alan R Dyer, Boyd E Metzger, Timothy E Reddy, Nancy J Cox, William L Lowe
Maternal metabolism during pregnancy impacts the developing fetus, affecting offspring birth weight and adiposity. This has important implications for metabolic health later in life (e.g., offspring of mothers with pre-existing or gestational diabetes mellitus have an increased risk of metabolic disorders in childhood). To identify genetic loci associated with measures of maternal metabolism obtained during an oral glucose tolerance test at ∼28 weeks' gestation, we performed a genome-wide association study of 4,437 pregnant mothers of European (n = 1,367), Thai (n = 1,178), Afro-Caribbean (n = 1,075), and Hispanic (n = 817) ancestry, along with replication of top signals in three additional European ancestry cohorts...
September 2013: Diabetes
Benjamin M Neale, Sarah Medland, Stephan Ripke, Richard J L Anney, Philip Asherson, Jan Buitelaar, Barbara Franke, Michael Gill, Lindsey Kent, Peter Holmans, Frank Middleton, Anita Thapar, Klaus-Peter Lesch, Stephen V Faraone, Mark Daly, Thuy Trang Nguyen, Helmut Schäfer, Hans-Christoph Steinhausen, Andreas Reif, Tobias J Renner, Marcel Romanos, Jasmin Romanos, Andreas Warnke, Susanne Walitza, Christine Freitag, Jobst Meyer, Haukur Palmason, Aribert Rothenberger, Ziarih Hawi, Joseph Sergeant, Herbert Roeyers, Eric Mick, Joseph Biederman
OBJECTIVE: Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. Thus additional genomewide association studies (GWAS) are needed. METHOD: We used case-control analyses of 896 cases with DSM-IV ADHD genotyped using the Affymetrix 5.0 array and 2,455 repository controls screened for psychotic and bipolar symptoms genotyped using Affymetrix 6...
September 2010: Journal of the American Academy of Child and Adolescent Psychiatry
David M Irwin, Huanran Tan
Hexokinases (HK) phosphorylate sugar immediately upon its entry into cells allowing these sugars to be metabolized. A total of four hexokinases have been characterized in a diversity of vertebrates-HKI, HKII, HKIII, and HKIV. HKIV is often called glucokinase (GCK) and has half the molecular weight of the other hexokinases, as it only has one hexokinase domain, while other vertebrate HKs have two. Differing hypothesis has been proposed to explain the diversification of the hexokinase gene family. We used a genomic approach to characterize hexokinase genes in a diverse array of vertebrate species and close relatives...
March 2008: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
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