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https://www.readbyqxmd.com/read/28628668/dose-dependent-effects-of-gamma-radiation-on-the-early-zebrafish-development-and-gene-expression
#1
Selma Hurem, Leonardo Martín Martín, Dag Anders Brede, Eystein Skjerve, Rasoul Nourizadeh-Lillabadi, Ole Christian Lind, Terje Christensen, Vidar Berg, Hans-Christian Teien, Brit Salbu, Deborah Helen Oughton, Peter Aleström, Jan Ludvig Lyche
Ionizing radiation from natural sources or anthropogenic activity has the potential to cause oxidative stress or genetic damage in living organisms, through the ionization and excitation of molecules and the subsequent production of free radicals and reactive oxygen species (ROS). The present work focuses on radiation-induced biological effects using the zebrafish (Danio rerio) vertebrate model. Changes in developmental traits and gene expression in zebrafish were assessed after continuous external gamma irradiation (0...
2017: PloS One
https://www.readbyqxmd.com/read/28605664/soy-compared-with-milk-protein-in-a-western-diet-changes-fecal-microbiota-and-decreases-hepatic-steatosis-in-obese-oletf-rats
#2
Matthew R Panasevich, Colin M Schuster, Kathryn E Phillips, Grace M Meers, Sree V Chintapalli, Umesh D Wankhade, Kartik Shankar, Dustie N Butteiger, Elaine S Krul, John P Thyfault, R Scott Rector
Soy protein is effective at preventing hepatic steatosis; however, the mechanisms are poorly understood. We tested the hypothesis that soy vs. dairy protein-based diet would alter microbiota and attenuate hepatic steatosis in hyperphagic Otsuka Long-Evans Tokushima fatty (OLETF) rats. Male OLETF rats were randomized to "Western" diets containing milk protein isolate (MPI), soy protein isolate (SPI) or 50:50 MPI/SPI (MS) (n=9-10/group; 21% kcal protein) for 16 weeks. SPI attenuated (P<.05) fat mass and percent fat by ~10% compared with MS, but not compared with MPI...
May 31, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28597946/comprehensive-screening-for-monogenic-diabetes-in-89-japanese-children-with-insulin-requiring-antibody-negative-type-1-diabetes
#3
Kikumi Ushijima, Maki Fukami, Tadayuki Ayabe, Satoshi Narumi, Misako Okuno, Akie Nakamura, Toshikazu Takahashi, Kenji Ihara, Kazuhiro Ohkubo, Emiko Tachikawa, Shoji Nakayama, Junichi Arai, Nobuyuki Kikuchi, Toru Kikuchi, Tomoyuki Kawamura, Tatsuhiko Urakami, Kenichiro Hata, Kazuhiko Nakabayashi, Yoichi Matsubara, Shin Amemiya, Tsutomu Ogata, Ichiro Yokota, Shigetaka Sugihara
BACKGROUND: Mutations in causative genes for neonatal diabetes or maturity-onset diabetes of the young have been identified in multiple patients with autoantibody-negative type 1 diabetes (T1D). OBJECTIVES: We aimed to clarify the prevalence and phenotypic characteristics of monogenic abnormalities among 89 children with autoantibody-negative insulin-requiring T1D. METHODS: Mutations in 30 genes were screened using next-generation sequencing, and copy-number alterations of 4 major causative genes were examined using multiplex-ligation-dependent probe amplification...
June 9, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28591938/variants-in-mody-genes-associated-with-maternal-lipids-profiles-in-second-trimester-of-pregnancy
#4
Xiaojing Wang, Wei Li, Liangkun Ma, Fan Ping, Juntao Liu, Xueyan Wu, Jiangfeng Mao, Xi Wang, Min Nie
BACKGROUND: Dyslipidemia during pregnancy increase the risk of pregnancy complications. Lipid profiles has strong genetic determinant and numerous susceptibility loci has been identified. However, very few studies focused on the association of lipid-related loci and maternal serum lipids during pregnancy. We, for the first time, investigated the association of common variants in three MODY genes (HNF1A, HNF4A and HNF1B) with serum lipid concentrations and glucose metabolism related quantitative traits in the second trimester of pregnancy...
June 7, 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/28583188/hnf4a-expression-as-a-potential-diagnostic-tool-to-discriminate-primary-gastric-cancer-from-breast-cancer-metastasis-in-a-brazilian-cohort
#5
Patrícia Chaves de Freitas Campos Jucá, Stephany Corrêa, Giselle Maria Vignal, Maria Theresa de Souza Accioly, Suzana Angélica Silva Lustosa, Eliana Abdelhay, Delcio Matos
BACKGROUND: Among the many challenges in cancer diagnosis is the early distinction between metastatic cancer and a secondary tumor. This difficulty stems from the lack of markers that offer high sensitivity and specificity and can be easily applied in routine laboratory work. An example of this challenge is distinguishing gastric metastases originating from breast cancer from a gastric primary tumor. Hepatocyte nuclear factor 4 alpha (HNF4A) has been suggested as a potential marker in these cases...
June 5, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28583088/uncovering-the-transcriptomic-and-epigenomic-landscape-of-nicotinic-receptor-genes-in-non-neuronal-tissues
#6
Bo Zhang, Pamela Madden, Junchen Gu, Xiaoyun Xing, Savita Sankar, Jennifer Flynn, Kristen Kroll, Ting Wang
BACKGROUND: Nicotinic acetylcholine receptors (nAChRs) play an important role in cellular physiology and human nicotine dependence, and are closely associated with many human diseases including cancer. For example, previous studies suggest that nAChRs can re-wire gene regulatory networks in lung cancer cell lines. However, the tissue specificity of nAChRs genes and their regulation remain unexplored. RESULT: In this study, we integrated data from multiple large genomic consortiums, including ENCODE, Roadmap Epigenomics, GTEx, and FANTOM, to define the transcriptomic and epigenomic landscape of all nicotinic receptor genes across many different human tissues and cell types...
June 5, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28580277/expression-and-functional-assessment-of-candidate-type-2-diabetes-susceptibility-genes-identify-four-new-genes-contributing-to-human-insulin-secretion
#7
Fatou K Ndiaye, Ana Ortalli, Mickaël Canouil, Marlène Huyvaert, Clara Salazar-Cardozo, Cécile Lecoeur, Marie Verbanck, Valérie Pawlowski, Raphaël Boutry, Emmanuelle Durand, Iandry Rabearivelo, Olivier Sand, Lorella Marselli, Julie Kerr-Conte, Vikash Chandra, Raphaël Scharfmann, Odile Poulain-Godefroy, Piero Marchetti, François Pattou, Amar Abderrahmani, Philippe Froguel, Amélie Bonnefond
OBJECTIVES: Genome-wide association studies (GWAS) have identified >100 loci independently contributing to type 2 diabetes (T2D) risk. However, translational implications for precision medicine and for the development of novel treatments have been disappointing, due to poor knowledge of how these loci impact T2D pathophysiology. Here, we aimed to measure the expression of genes located nearby T2D associated signals and to assess their effect on insulin secretion from pancreatic beta cells...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28556992/management-of-sulfonylurea-treated-monogenic-diabetes-in-pregnancy-implications-of-placental-glibenclamide-transfer
#8
REVIEW
M Shepherd, A J Brook, A J Chakera, A T Hattersley
The optimum treatment for HNF1A/HNF4A maturity-onset diabetes of the young and ATP-sensitive potassium (KATP ) channel neonatal diabetes is sulfonylureas outside pregnancy, but there is little evidence regarding the most appropriate treatment during pregnancy. Glibenclamide has been widely used in the treatment of gestational diabetes, but recent data have established that glibenclamide crosses the placenta and increases risk of macrosomia and neonatal hypoglycaemia. This raises questions about its use in pregnancy...
May 30, 2017: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/28498607/human-hepatocellular-carcinomas-with-a-periportal-phenotype-have-the-lowest-potential-for-early-recurrence-after-curative-resection
#9
Romain Désert, Florian Rohart, Frédéric Canal, Marie Sicard, Mireille Desille, Stéphanie Renaud, Bruno Turlin, Pascale Bellaud, Christine Perret, Bruno Clément, Kim-Anh Lê Cao, Orlando Musso
Hepatocellular carcinomas (HCCs) exhibit a diversity of molecular phenotypes, raising major challenges in clinical management. HCCs detected by surveillance programs at an early stage are candidates for potentially curative therapies (local ablation, resection or transplantation). In the long term, transplantation provides the lowest recurrence rates. Treatment allocation is based on tumor number, size, vascular invasion, performance status, functional liver reserve and on the prediction of early (< 2 years) recurrence, which reflects the intrinsic aggressiveness of the tumor...
May 12, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28470094/dna-methylation-controls-unmethylated-transcription-start-sites-in-the-genome-in-trans
#10
David Cheishvili, Steffan Christiansen, Rebecca Stochinsky, Anne-Sophie Pepin, Daniel M Sapozhnikov, Rudy Zhou, Lauren Schmeltzer, Sergey Dymov, Moshe Szyf
AIM: DNA methylation downregulates transcription. However, a large number of genes, which are unmethylated in the promoter region, are inactive. We tested the hypothesis that these genes are regulated by DNA methylation of upstream regulators. METHODS: We inhibited DNMT1 with 5-aza-2'-deoxycytidine or depleted it with shRNA to map the transcription initiation positions controlled by DNMT1 using ChIPseq with RNApolIIser5 antibody. Ingenuity pathway analysis identified potential methylated upstream regulators...
May 4, 2017: Epigenomics
https://www.readbyqxmd.com/read/28465351/an-hnf4%C3%AE-microrna-194-192-signaling-axis-maintains-hepatic-cell-function
#11
Aoi Morimoto, Mana Kannari, Yuichi Tsuchida, Shota Sasaki, Chinatsu Saito, Tsuyoshi Matsuta, Tsukasa Maeda, Megumi Akiyama, Takahiro Nakamura, Masakiyo Sakaguchi, Nobukazu Nameki, Frank J Gonzalez, Yusuke Inoue
HNF4α controls the expression of liver-specific protein-coding genes. However, some microRNAs (miRNAs) are also modulated by HNF4α, and it is not known whether they are direct targets of HNF4α, and whether they influence the hepatic function. In this study, we found that HNF4α regulates miRNAs, indicated by marked down-regulation of miR-194 and miR-192 (miR-194/192) in liver-specific Hnf4a-null (Hnf4a(ΔH)) mice. Transactivation of the shared miR-194/192 promoter was dependent on HNF4α expression, indicating that miR194/192 is a target gene of HNF4α...
May 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28458902/hyperinsulinaemic-hypoglycaemia-renal-fanconi-syndrome-and-liver-disease-due-to-a-mutation-in-the-hnf4a-gene
#12
María Clemente, Alejandro Vargas, Gema Ariceta, Rosa Martínez, Ariadna Campos, Diego Yeste
SUMMARY: HNF4A gene mutations have been reported in cases of transient and persistent hyperinsulinaemic hypoglycaemia of infancy (HHI), particularly in families with adulthood diabetes. The case of a patient with HHI, liver impairment and renal tubulopathy due to a mutation in HNF4A is reported. LEARNING POINTS: Urine specimen study in cases of HHI with diazoxide response is necessary to rule out specific metabolic conditions (l-3-hydroxyacyl-coenzyme A dehydrogenase deficiency) or tubular renal involvement...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/28458900/congenital-hyperinsulinism-and-poland-syndrome-in-association-with-10p13-14-duplication
#13
Dinesh Giri, Prashant Patil, Rachel Hart, Mohammed Didi, Senthil Senniappan
SUMMARY: Poland syndrome (PS) is a rare congenital condition, affecting 1 in 30 000 live births worldwide, characterised by a unilateral absence of the sternal head of the pectoralis major and ipsilateral symbrachydactyly occasionally associated with abnormalities of musculoskeletal structures. A baby girl, born at 40 weeks' gestation with birth weight of 3.33 kg (-0.55 SDS) had typical phenotypical features of PS. She had recurrent hypoglycaemic episodes early in life requiring high concentration of glucose and glucagon infusion...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/28453780/variation-in-maturity-onset-diabetes-of-the-young-genes-influence-response-to-interventions-for-diabetes-prevention
#14
Liana K Billings, Kathleen A Jablonski, A Sofia Warner, Yu-Chien Cheng, Jarred B McAteer, Laura Tipton, Alan R Shuldiner, David A Ehrmann, Alisa K Manning, Dana Dabelea, Paul W Franks, Steven E Kahn, Toni I Pollin, William C Knowler, David Altshuler, Jose C Florez
CONTEXT: Variation in genes that cause Maturity-Onset Diabetes of the Young (MODY) has been associated with diabetes incidence and glycemic traits. OBJECTIVES: This study aimed to determine whether genetic variation in MODY genes leads to differential responses to insulin-sensitizing interventions. DESIGN AND SETTING: This was a secondary analysis of a multicenter randomized clinical trial, the Diabetes Prevention Program (DPP), involving 27 U...
April 27, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28451462/pulmonary-adenocarcinoma-with-mucin-production-modulates-phenotype-according-to-common-genetic-traits-a-reappraisal-of-mucinous-adenocarcinoma-and-colloid-adenocarcinoma
#15
Angelica Sonzogni, Fabrizio Bianchi, Alessandra Fabbri, Mara Cossa, Giulio Rossi, Alberto Cavazza, Elena Tamborini, Federica Perrone, Adele Busico, Iolanda Capone, Benedetta Picciani, Barbara Valeri, Ugo Pastorino, Giuseppe Pelosi
Whether invasive mucinous adenocarcinoma (IMA) and colloid adenocarcinoma (ICA) of the lung represent separate tumour entities, or simply lie within a spectrum of phenotypic variability, is worth investigating. Fifteen ICA, 12 IMA, 9 ALK-rearranged adenocarcinomas (ALKA), 8 non-mucinous KRAS-mutated adenocarcinomas (KRASA) and 9 mucinous breast adenocarcinomas (MBA) were assessed by immunohistochemistry for alveolar (TTF1, cytoplasmic MUC1), intestinal (CDX-2, MUC2), gastric (membrane MUC1, MUC6), bronchial (MUC5AC), mesenchymal (vimentin), neuroendocrine (chromogranin A, synaptophysin), sex steroid hormone-related (oestrogen and progesterone receptors), pan-mucinous (HNF4A) and pan-epithelial (keratin 7) lineage biomarkers and by targeted next generation sequencing (TNGS) for 50 recurrently altered cancer genes...
April 2017: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/28445515/correlation-of-histopathologic-characteristics-to-protein-expression-and-function-in-malignant-melanoma
#16
Charlotte Welinder, Krzysztof Pawłowski, A Marcell Szasz, Maria Yakovleva, Yutaka Sugihara, Johan Malm, Göran Jönsson, Christian Ingvar, Lotta Lundgren, Bo Baldetorp, Håkan Olsson, Melinda Rezeli, Thomas Laurell, Elisabet Wieslander, György Marko-Varga
BACKGROUND: Metastatic melanoma is still one of the most prevalent skin cancers, which upon progression has neither a prognostic marker nor a specific and lasting treatment. Proteomic analysis is a versatile approach with high throughput data and results that can be used for characterizing tissue samples. However, such analysis is hampered by the complexity of the disease, heterogeneity of patients, tumors, and samples themselves. With the long term aim of quest for better diagnostics biomarkers, as well as predictive and prognostic markers, we focused on relating high resolution proteomics data to careful histopathological evaluation of the tumor samples and patient survival information...
2017: PloS One
https://www.readbyqxmd.com/read/28412976/hepatic-population-derived-from-human-pluripotent-stem-cells-is-effectively-increased-by-selective-removal-of-undifferentiated-stem-cells-using-ym155
#17
Seok-Jin Kang, Young-Il Park, So-Ryeon Hwang, Hee Yi, Nga Tham, Hyun-Ok Ku, Jae-Young Song, Hwan-Goo Kang
BACKGROUND: Pluripotent stem cells (PSCs) such as embryonic stem cells and induced pluripotent stem cells are promising target cells for cell regenerative medicine together with recently advanced technology of in-vitro differentiation. However, residual undifferentiated stem cells (USCs) during in-vitro differentiation are considered a potential risk for development of cancer cells and nonspecific lineage cell types. In this study we observed that USCs still exist during hepatic differentiation, consequently resulting in poor quality of the hepatic population and forming teratoma in vivo...
April 17, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28387599/novel-insights-into-systemic-autoimmune-rheumatic-diseases-using-shared-molecular-signatures-and-an-integrative-analysis
#18
Marie Hudson, Sasha Bernatsky, Ines Colmegna, Maximilien Lora, Tomi Pastinen, Kathleen Klein Oros, Celia M T Greenwood
We undertook this study to identify DNA methylation signatures of three systemic autoimmune rheumatic diseases (SARDs), namely rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, compared to healthy controls. Using a careful design to minimize confounding, we restricted our study to subjects with incident disease and performed our analyses on purified CD4(+) T cells, key effector cells in SARD. We identified differentially methylated (using the Illumina Infinium HumanMethylation450 BeadChip array) and expressed (using the Illumina TruSeq stranded RNA-seq protocol) sites between cases and controls, and investigated the biological significance of this SARD signature using gene annotation databases...
April 7, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28385711/microbiota-regulate-intestinal-epithelial-gene-expression-by-suppressing-the-transcription-factor-hepatocyte-nuclear-factor-4-alpha
#19
James M Davison, Colin R Lickwar, Lingyun Song, Ghislain Breton, Gregory E Crawford, John F Rawls
Microbiota influence diverse aspects of intestinal physiology and disease in part by controlling tissue-specific transcription of host genes. However, host genomic mechanisms mediating microbial control of intestinal gene expression are poorly understood. Hepatocyte nuclear factor 4 (HNF4) is the most ancient family of nuclear receptor transcription factors with important roles in human metabolic and inflammatory bowel diseases, but a role in host response to microbes is unknown. Using an unbiased screening strategy, we found that zebrafish Hnf4a specifically binds and activates a microbiota-suppressed intestinal epithelial transcriptional enhancer...
April 6, 2017: Genome Research
https://www.readbyqxmd.com/read/28364040/hypoxia-reduces-hnf4%C3%AE-mody1-protein-expression-in-pancreatic-%C3%AE-cells-by-activating-amp-activated-protein-kinase
#20
Yoshifumi Sato, Tomonori Tsuyama, Chinami Sato, Md Fazlul Karim, Tatsuya Yoshizawa, Masahiro Inoue, Kazuya Yamagata
Hypoxia plays a role in the deterioration of β-cell function. Hepatocyte nuclear factor 4α (HNF4α) has an important role in pancreatic β-cells, and mutations of the human HNF4A gene cause a type of maturity-onset diabetes of the young (MODY1). However, it remains unclear whether hypoxia affects the expression of HNF4α in β-cells. Here, we report that hypoxia reduces HNF4α protein expression in β-cells. Hypoxia-inducible factor was not involved in the down-regulation of HNF4α under hypoxic conditions...
May 26, 2017: Journal of Biological Chemistry
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