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Nathan R Tucker, Saagar Mahida, Jiangchuan Ye, Elizabeth J Abraham, Julie A Mina, Victoria A Parsons, Michael A McLellan, Marisa A Shea, Alan Hanley, Emelia J Benjamin, David J Milan, Honghuang Lin, Patrick T Ellinor
BACKGROUND: The genetic basis of atrial fibrillation (AF) and congenital heart disease remains incompletely understood. OBJECTIVE: We sought to determine the causative mutation in a family with AF, atrial septal and ventricular septal defects. METHODS: We evaluated a pedigree with 16 family members, one with an atrial septal defect, one with a ventricular septal defect and three with AF; we performed whole exome sequencing in three affected family members...
October 15, 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
Benjamin Klein, Anthony Destephens, Leanne Dumeny, Qiongyao Hu, Yong He, Kerri O'Malley, Zhihua Jiang, Roger Tran-Son-Tay, Scott Berceli
Pathologic vascular adaptation following local injury is the primary driver for accelerated intimal hyperplasia and an occlusive phenotype. Smooth muscle cell (SMC) proliferation within the wall, and migration into the developing intima, is a major component of this remodeling response. The primary objective in the current study was to investigate the effect of the local biomechanical forces on early vein graft adaptation, specifically focusing on the spatial and temporal response of SMC proliferation and conversion from a contractile to synthetic architecture...
September 13, 2016: Annals of Biomedical Engineering
Daniel Veraguas, Paula F Gallegos, Alejandra E Velasquez, Fidel O Castro, Lleretny Rodriguez-Alvarez
In the domestic cat, the efficiency of in vitro embryo production systems is negatively affected during the nonbreeding season. The objective of this research was to evaluate the effect of FSH stimulation in anestrous cats, on quality of cumulus-oocyte complexes (COCs) and in vitro developmental competence after parthenogenetic activation. To accomplish this purpose, anestrous cats were grouped into: (1) FSH treated (serial doses of 5 mg of porcine FSH each, every 24 hours, for 4 days) and (2) untreated control...
August 13, 2016: Theriogenology
Kousuke Uranishi, Tadayuki Akagi, Hiroshi Koide, Takashi Yokota
Estrogen-related receptor beta (Esrrb) is expressed in embryonic stem (ES) cells and is involved in self-renewal ability and pluripotency. Previously, we found that Dax1 is associated with Esrrb and represses its transcriptional activity. Further, the disruption of the Dax1-Esrrb interaction increases the expression of the extra-embryonic endoderm marker Gata6 in ES cells. Here, we investigated the influences of Esrrb and Dax1 on Gata6 expression. Esrrb overexpression in ES cells induced endogenous Gata6 mRNA and Gata6 promoter activity...
September 30, 2016: Biochemical and Biophysical Research Communications
L G Kondratyeva, A A Sveshnikova, E V Grankina, I P Chernov, M R Kopantseva, E P Kopantzev, E D Sverdlov
We show characteristic morphological changes corresponding to epithelial-mesenchymal transition (EMT) program fulfillment in PANC1 cell line stimulated with TGFβ1. Our results support downregulation of E-cadherin protein. We show 5- and 28-fold increase in SNAI1 and SNAI2 expression levels and 25- and 15-fold decrease in CDH1 and KRT8 expression levels, respectively, which confirms the EMT-program fulfillment. We demonstrate downregulation of expression of pancreatic master genes SOX9, FOXA2, and GATA4 (2-, 5-, and 4-fold, respectively) and absence of significant changes in HES1, NR5A2, and GATA6 expression levels in the cells stimulated with TGFβ1...
July 2016: Doklady. Biochemistry and Biophysics
Cheng-Shyong Wu, Kuo-Liang Wei, Jian-Liang Chou, Chung-Kuang Lu, Ching-Chuan Hsieh, Jora M J Lin, Yi-Fang Deng, Wan-Ting Hsu, Hui-Min David Wang, Chung-Hang Leung, Dik-Lung Ma, Chin Li, Michael W Y Chan
Aberrant Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling is crucial to the development of gastric cancer. In this study, we examined the role of STAT3 in the expression and methylation of its targets in gastric cancer patients. Results from RNA sequencing identified an inverse correlation between the expression of STAT3 and GATA6 in 23 pairs of gastric cancer patient samples. We discovered that the expression of GATA6 is epigenetically silenced through promoter methylation in gastric cancer cell lines...
2016: International Journal of Molecular Sciences
Shane P Duggan, Fiona M Behan, Murat Kirca, Abdul Zaheer, Sarah A McGarrigle, John V Reynolds, Gisela M F Vaz, Mathias O Senge, Dermot Kelleher
Barrett's oesophagus (BO), an intestinal-type metaplasia (IM), typically arising in conjunction with gastro-oesophageal reflux disease, is a prominent risk factor for the development of oesophageal adenocarcinoma (OAC). The molecular similarities between IM and normal intestinal tissues are ill-defined. Consequently, the contribution of intestine-enriched factors expressed within BO to oncogenesis is unclear. Herein, using transcriptomics we define the intestine-enriched genes expressed in meta-profiles of BO and OAC...
2016: Scientific Reports
Ki-Wook Kim, Jesse W Williams, Ya-Ting Wang, Stoyan Ivanov, Susan Gilfillan, Marco Colonna, Herbert W Virgin, Emmanuel L Gautier, Gwendalyn J Randolph
Peritoneal and pleural resident macrophages in the mouse share common features and in each compartment exist as two distinct subpopulations: F4/80(+) macrophages and MHC II(+) CD11c(+) macrophages. F4/80(+) macrophages derive from embryonic precursors, and their maintenance is controlled by Gata6. However, the origin and regulatory factors that maintain MHC II(+) macrophages remain unknown. Here, we show that the MHC II(+) macrophages arise postnatally from CCR2-dependent precursors that resemble monocytes...
September 19, 2016: Journal of Experimental Medicine
Rachel E J Besser, Sarah E Flanagan, Deborah G J Mackay, I K Temple, Maggie H Shepherd, Beverley M Shields, Sian Ellard, Andrew T Hattersley
BACKGROUND: Hyperglycemia in premature infants is usually thought to reflect inadequate pancreatic development rather than monogenic neonatal diabetes. No studies, to our knowledge, have investigated the prevalence of monogenic forms of diabetes in preterm infants. METHODS: We studied 750 patients with diabetes diagnosed before 6 months of age. We compared the genetic etiology and clinical characteristics of 146 preterm patients born <37 weeks and compared them with 604 born ≥37 weeks...
September 2016: Pediatrics
Gwi Ran Kim, Soo-Na Cho, Hyung-Seok Kim, Seon Young Yu, Sin Young Choi, Yuhee Ryu, Ming Quan Lin, Li Jin, Hae Jin Kee, Myung Ho Jeong
OBJECTIVE: Histone deacetylase (HDAC) inhibitors have been reported to improve essential and secondary hypertension. However, the specific HDAC that might serve as a therapeutic target and the associated upstream and downstream molecules involved in regulating hypertension remain unknown. Our study was aimed at investigating whether a selective inhibitor of class II HDAC (MC1568) modulates hypertension, elucidating the underlying mechanism. METHODS: Hypertension was established by administering angiotensin II (Ang II) to mice before treatment with MC1568...
November 2016: Journal of Hypertension
Aidong Zhou, Kangyu Lin, Sicong Zhang, Yaohui Chen, Nu Zhang, Jianfei Xue, Zhongyong Wang, Kenneth D Aldape, Keping Xie, James R Woodgett, Suyun Huang
Emerging evidence has shown that GSK3β plays oncogenic roles in multiple tumour types; however, the underlying mechanisms remain largely unknown. Here, we show that nuclear GSK3β is responsible for the accumulation of the histone demethylase KDM1A and critically regulates histone H3K4 methylation during tumorigenesis. GSK3β phosphorylates KDM1A Ser683 upon priming phosphorylation of KDM1A Ser687 by CK1α. Phosphorylation of KDM1A induces its binding with and deubiquitylation by USP22, leading to KDM1A stabilization...
September 2016: Nature Cell Biology
Haichuan Hu, Zhengliang Sun, Yuan Li, Yiliang Zhang, Hang Li, Yang Zhang, Yunjian Pan, Lei Shen, Rui Wang, Yihua Sun, Haiquan Chen
PURPOSE: Lung adenocarcinomas are a heterogeneous set of diseases with distinct genetic and histologic characteristics. Besides the discovery of oncogenic mutations as well as the introduction of 2011 IASLC/ATS/ERS and 2015 WHO histologic classification, increasing evidence has linked this inter-tumor heterogeneity to the lung lineage-specific pathways and lineage genes. Therefore, in this study, we assessed the gene expression of identified lung lineage genes to study their role in distinguishing lung adenocarcinoma diversities...
August 2, 2016: Journal of Thoracic Oncology
Parinaz Kazemi, Mojtaba Dashtizad, Mehdi Shamsara, Forough Mahdavinezhad, Ehsan Hashemi, Samaneh Fayazi, Hadi Hajarian
Artificial collapse of the blastocoel cavity before vitrification can improve the quality of warmed embryos, yet how reduction of blastocoel fluid impacts formation of the blastocyst cell lineages is not clear. The present study assessed the effect of pre-vitrification blastocoel fluid reduction on the survival, hatching rate, and the expression of genes related to apoptosis (Tp53), pluripotency (Pou5f1, Nanog), and differentiation (Cdx2, Eomes, Gata6) in mouse blastocysts. In vivo-produced blastocysts were randomly divided into three groups: The first group was vitrified and warmed; the second group underwent artificial collapse of the blastocoel cavity prior to vitrification and warming; the third group served as the control, in which neither vitrification or artificial collapse was performed...
August 2016: Molecular Reproduction and Development
Shinichi Hayashi, Ryutaro Akiyama, Julia Wong, Naoyuki Tahara, Hiroko Kawakami, Yasuhiko Kawakami
Gli3 is a major regulator of Hedgehog signaling during limb development. In the anterior mesenchyme, GLI3 is proteolytically processed into GLI3R, a truncated repressor form that inhibits Hedgehog signaling. Although numerous studies have identified mechanisms that regulate Gli3 function in vitro, it is not completely understood how Gli3 function is regulated in vivo. In this study, we show a novel mechanism of regulation of GLI3R activities in limb buds by Gata6, a member of the GATA transcription factor family...
June 2016: PLoS Genetics
Chung-Wei Yang, Chien-Lin Chen, Wei-Chun Chou, Ho-Chen Lin, Yuh-Jyh Jong, Li-Kai Tsai, Chun-Yu Chuang
Spinal muscular atrophy (SMA) is an inherited neuromuscular disease resulting from a recessive mutation in the SMN1 gene. This disease affects multiple organ systems with varying degrees of severity. Exploration of the molecular pathological changes occurring in different cell types in SMA is crucial for developing new therapies. This study collected 39 human microarray datasets from ArrayExpress and GEO databases to build an integrative transcriptomic analysis for recognizing novel SMA targets. The transcriptomic analysis was conducted through combining weighted correlation network analysis (WGCNA) for gene module detection, gene set enrichment analysis (GSEA) for functional categorization and filtration, and Cytoscape (visual interaction gene network analysis) for target gene identification...
2016: PloS One
Paola Martinelli, Enrique Carrillo-de Santa Pau, Trevor Cox, Bruno Sainz, Nelson Dusetti, William Greenhalf, Lorenzo Rinaldi, Eithne Costello, Paula Ghaneh, Núria Malats, Markus Büchler, Marina Pajic, Andrew V Biankin, Juan Iovanna, John Neoptolemos, Francisco X Real
BACKGROUND AND AIMS: The role of GATA factors in cancer has gained increasing attention recently, but the function of GATA6 in pancreatic ductal adenocarcinoma (PDAC) is controversial. GATA6 is amplified in a subset of tumours and was proposed to be oncogenic, but high GATA6 levels are found in well-differentiated tumours and are associated with better patient outcome. By contrast, a tumour-suppressive function of GATA6 was demonstrated using genetic mouse models. We aimed at clarifying GATA6 function in PDAC...
June 20, 2016: Gut
Calum C Bain, Catherine A Hawley, Hannah Garner, Charlotte L Scott, Anika Schridde, Nicholas J Steers, Matthias Mack, Anagha Joshi, Martin Guilliams, Allan Mc I Mowat, Frederic Geissmann, Stephen J Jenkins
Peritoneal macrophages are one of the most studied macrophage populations in the body, yet the composition, developmental origin and mechanisms governing the maintenance of this compartment are controversial. Here we show resident F4/80(hi)GATA6(+) macrophages are long-lived, undergo non-stochastic self-renewal and retain cells of embryonic origin for at least 4 months in mice. However, Ly6C(+) monocytes constitutively enter the peritoneal cavity in a CCR2-dependent manner, where they mature into short-lived F4/80(lo)MHCII(+) cells that act, in part, as precursors of F4/80(hi)GATA6(+) macrophages...
2016: Nature Communications
Min Yu, Ulrica Wang, Zhengxin Wang
WDR77 (WD repeat domain 77) is expressed during earlier lung development when cells are rapidly proliferating, but is absent from adult lung. It is re-activated during lung tumorigenesis and is essential for lung cancer cell proliferation. Signalling pathways/molecules that control WDR77 gene expression are unknown. Promoter mapping, gel shift assay and ChIP revealed that the WDR77 promoter contains bona fide response elements for E2F and GATA transcriptional factors as demonstrated in prostate cancer, lung cancer and erythroid cells, as well as in mouse lung tissues...
August 1, 2016: Biochemical Journal
Zeinab Chitforoushzadeh, Zi Ye, Ziran Sheng, Silvia LaRue, Rebecca C Fry, Douglas A Lauffenburger, Kevin A Janes
Signal transduction networks coordinate transcriptional programs activated by diverse extracellular stimuli, such as growth factors and cytokines. Cells receive multiple stimuli simultaneously, and mapping how activation of the integrated signaling network affects gene expression is a challenge. We stimulated colon adenocarcinoma cells with various combinations of the cytokine tumor necrosis factor (TNF) and the growth factors insulin and epidermal growth factor (EGF) to investigate signal integration and transcriptional crosstalk...
2016: Science Signaling
Kevin A Janes, Annalisa M VanHook
This Podcast features an interview with Kevin Janes, senior author of a Research Article that appears in the 7 June 2016 issue of Science Signaling, about a statistical modeling method that can extract useful information from complex data sets. Cells exist in very complex environments. They are constantly exposed to growth factors, hormones, nutrients, and many other factors that influence cellular behavior. When cells integrate information from multiple stimuli, the resulting output does not necessarily reflect a simple additive effect of the responses to each individual stimulus...
2016: Science Signaling
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