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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
William J Gammerdinger, Matthew A Conte, Jean-François Baroiller, Helena D'Cotta, Thomas D Kocher
BACKGROUND: Inversions and other structural polymorphisms often reduce the rate of recombination between sex chromosomes, making it impossible to fine map sex-determination loci using traditional genetic mapping techniques. Here we compare distantly related species of tilapia that each segregate an XY system of sex-determination on linkage group 1. We use whole genome sequencing to identify shared sex-patterned polymorphisms, which are candidates for the ancestral sex-determination mutation...
October 18, 2016: BMC Genomics
Daniel Pelaez, Zenith Acosta Torres, Tsz Kin Ng, Kwong Wai Choy, Chi Pui Pang, Herman S Cheung
Cellular therapies for the treatment of myocardial infarction have proven to be an invaluable tool in recent years and provide encouraging evidence for the possibility to restore normal heart function. However, questions still remain as to the optimal cell source, pre-conditioning methods and delivery techniques for such an application. This study explores the use of a population of stem cells arising from the neural crest and isolated from adult human periodontal ligament along with short-term mechanical strain as an inducer of cardiomyogenesis and possibly pre-conditioning stimulus for cellular cardiomyoplasty...
October 17, 2016: Cell and Tissue Research
Yi Li, Xiaoli Shi, Lei Tian, Hongyu Sun, Yujing Wu, Xia Li, Jianjun Li, Yujie Wei, Xinxiao Han, Jiao Zhang, Xiaowei Jia, Rui Bai, Limin Jing, Peng Ding, Huiliang Liu, Dong Han
A schematic for the mechanism of accelerating the assembly of intercalated discs (IDs) in cardiac myocytes regulated by gold nanoparticles (AuNPs) is presented. AuNPs with local nanoscale stiffness in the substrate activate β1-integrin signaling, which mediates the activation of integrin-linked kinase (ILK) and its downstream signal kinase by stimulating expression of the transcription factors GATA4 and MEF-2c.
October 10, 2016: Advanced Materials
Xiaoyue Pan, Christopher A Bradfield, M Mahmood Hussain
Circadian rhythms controlled by clock genes affect plasma lipids. Here we show that global ablation of Bmal1 in Apoe(-/-) and Ldlr(-/-) mice and its liver-specific ablation in Apoe(-/-) (L-Bmal1(-/-)Apoe(-/-)) mice increases, whereas overexpression of BMAL1 in L-Bmal1(-/-)Apoe(-/-) and Apoe(-/-)mice decreases hyperlipidaemia and atherosclerosis. Bmal1 deficiency augments hepatic lipoprotein secretion and diminishes cholesterol excretion to the bile. Further, Bmal1 deficiency reduces expression of Shp and Gata4...
October 10, 2016: Nature Communications
Na Zhang, Feiming Ye, Wei Zhu, Dexing Hu, Changchen Xiao, Jinliang Nan, Sheng'an Su, Yingchao Wang, Mingfei Liu, Kanglu Gao, Xinyang Hu, Jinghai Chen, Hong Yu, Xiaojie Xie, Jian'an Wang
Cardiac ankyrin repeat protein (CARP) is a nuclear transcriptional co-factor that has additional functions in the myoplasm as a component of the muscle sarcomere. Previous studies have demonstrated increased expression of CARP in cardiovascular diseases, however, its role in cardiomyocyte apoptosis is unclear and controversial. In the present study, we investigated possible roles of CARP in hypoxia/reoxygenation (H/R) -induced cardiomyocyte apoptosis and the underlying mechanisms. Neonatal mouse ventricular cardiomyocytes were isolated and infected with adenovirus encoding Flag-tagged CARP (Ad-CARP) and lentivirus encoding CARP targeted shRNA (sh-CARP), respectively...
October 3, 2016: Biochimica et Biophysica Acta
Liyong Zhang, David J Tester, Di Lang, Yili Chen, Jinxiang Zheng, Rui Gao, Robert F Corliss, Shuangbo Tang, John W Kyle, Chao Liu, Michael J Ackerman, Jonathan C Makielski, Jianding Cheng
OBJECTIVE: To look for previously unrecognized cardiac structural abnormalities and address the genetic cause for sudden unexplained nocturnal death syndrome (SUNDS). METHODS: Data for 148 SUNDS victims and 444 controls (matched 1:3 on sex, race, and age of death within 1 year) were collected from Sun Yat-sen University from January 1, 1998, to December 31, 2014, to search morphological changes. An additional 17 patients with Brugada syndrome (BrS) collected from January 1, 2006, to December 31, 2014, served as a comparative disease cohort...
October 1, 2016: Mayo Clinic Proceedings
Yuhee Ryu, Li Jin, Hae Jin Kee, Zhe Hao Piao, Jae Yeong Cho, Gwi Ran Kim, Sin Young Choi, Ming Quan Lin, Myung Ho Jeong
Gallic acid, a type of phenolic acid, has been shown to have beneficial effects in inflammation, vascular calcification, and metabolic diseases. The present study was aimed at determining the effect and regulatory mechanism of gallic acid in cardiac hypertrophy and fibrosis. Cardiac hypertrophy was induced by isoproterenol (ISP) in mice and primary neonatal cardiomyocytes. Gallic acid pretreatment attenuated concentric cardiac hypertrophy. It downregulated the expression of atrial natriuretic peptide, brain natriuretic peptide, and beta-myosin heavy chain in vivo and in vitro...
October 5, 2016: Scientific Reports
Pouria HosseinNia, Mehdi Hajian, Mojtaba Tahmoorespur, Sayyed Morteza Hosseini, Somayyeh Ostadhosseini, Mohammad Reza Nasiri, Mohammad Hossein Nasr-Esfahani
BACKGROUND: Little is understood about the regulation of gene expression during early goat embryo development. This study investigated the expression profile of 19 genes, known to be critical for early embryo development in mouse and human, at five different stages of goat in vitro embryo development (oocyte, 8-16 cell, morula, day-7 blastocyst, and day 14 blastocyst). MATERIALS AND METHODS: In this experimental study, stage-specific profiling using real time-quantitative polymerase chain reaction (RT-qPCR) revealed robust and dynamic patterns of stage-specific gene activity that fall into four major clusters depending on their respective mRNA profiles...
October 2016: International Journal of Fertility & Sterility
Tze-Wen Chung, Hsin-Yu Lo, Tzung-Han Chou, Jan-Hou Chen, Shoei-Shen Wang
Bone marrow-derived mesenchymal stem cell microtissues (BMSCMT) enhanced cardiomyogenesis in vitro and cardiac repairs of myocardial infarcted hearts in vivo are documented. Producing human BMSCMT onto patches in vitro for cardiac tissue engineering has not been reported. For possibly producing human bone marrow-derived mesenchymal stem cell microtissues (hBMSCMT) on an elastic silk fibroin (SF)-poly(ε-caprolactone) (PCL) based patches is hereby designed. After an elastic SF-PCL (SP) patch is fabricated, hyaluronic acid (HA)/SF-PCL(HSP) and HA-GRGD/SF-PCL(HGSP) patches are fabricated by photochemically grafting HA and HA-GRGD onto SP surfaces...
September 28, 2016: Macromolecular Bioscience
Toshiaki Takahashi, Florian Friedmacher, Julia Zimmer, Prem Puri
PURPOSE: Congenital diaphragmatic hernia (CDH) is presumed to originate from defects in the primordial diaphragmatic mesenchyme, mainly comprising of muscle connective tissue (MCT). Thus, normal diaphragmatic morphogenesis depends on the structural integrity of the underlying MCT. Developmental mutations that inhibit normal formation of diaphragmatic MCT have been shown to result in CDH. Desmin (DES) is a major filament protein in the MCT, which is essential for the tensile strength of the developing diaphragm muscle...
September 20, 2016: Pediatric Surgery International
Rita Carmona, Ana Cañete, Elena Cano, Laura Ariza, Anabel Rojas, Ramon Muñoz-Chápuli
Congenital diaphragmatic hernia (CDH) is a severe birth defect. Wt1-null mouse embryos develop CDH but the mechanisms regulated by WT1 are unknown. We have generated a murine model with conditional deletion of WT1 in the lateral plate mesoderm, using the G2 enhancer of the Gata4 gene as a driver. 80% of G2-Gata4(Cre);Wt1(fl/fl) embryos developed typical Bochdalek-type CDH. We show that the posthepatic mesenchymal plate coelomic epithelium gives rise to a mesenchyme that populates the pleuroperitoneal folds isolating the pleural cavities before the migration of the somitic myoblasts...
2016: ELife
Rodolphe Soret, Nicolas Pilon
Hirschsprung disease (HSCR), also named aganglionic megacolon, is a severe congenital malformation characterized by a lack of enteric nervous system (ENS) in the terminal regions of the bowel (Bergeron et al., 2013). As the ENS notably regulates motility in the whole gastrointestinal track, the segment without neurons remains tonically contracted, resulting in functional intestinal obstruction and accumulation of fecal material (megacolon). HSCR occurs when enteric neural progenitors of vagal neural crest origin fail to fully colonize the developing intestines...
September 5, 2016: Bio-protocol
Michele M Nava, Alessio Piuma, Marina Figliuzzi, Irene Cattaneo, Barbara Bonandrini, Tommaso Zandrini, Giulio Cerullo, Roberto Osellame, Andrea Remuzzi, Manuela T Raimondi
BACKGROUND: The use of pluripotent cells in stem cell therapy has major limitations, mainly related to the high costs and risks of exogenous conditioning and the use of feeder layers during cell expansion passages. METHODS: We developed an innovative three-dimensional culture substrate made of "nichoid" microstructures, nanoengineered via two-photon laser polymerization. The nichoids limit the dimension of the adhering embryoid bodies during expansion, by counteracting cell migration between adjacent units of the substrate by its microarchitecture...
2016: Stem Cell Research & Therapy
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
Yifan Xu, Wu Xu, Tianyu Lu, Yuxiang Dai, Weibang Liang
We aimed to explore the relationship between miR-126 and glioma. miR-126 was highly expressed in low-grade clinical glioma tissue samples but lowly expressed in high-grade ones (P < .01). A human endogenous miR-126 expression vector was constructed. The migration capacity of cells transfected with the vector significantly decreased (P < .05). Up-regulation of miR-126 suppressed GATA4 protein expression. After transfection, they slightly contracted and became ovally or spherically shaped. F-actin significantly reduced, and microfilaments shortened or disappeared...
September 6, 2016: Artificial Cells, Nanomedicine, and Biotechnology
Joanna Lazier, Deborah Fruitman, Julie Lauzon, Francois Bernier, Bob Argiropoulos, Judy Chernos, Oana Caluseriu, Rebecca Simrose, Mary Ann Thomas
OBJECTIVES: To examine the diagnostic performance of array comparative genomic hybridization (CGH) for fetal cardiac anomalies in two medium-sized Canadian prenatal genetics clinics. METHODS: We prospectively recruited 22 pregnant women with fetal structural cardiac anomalies, normal rapid aneuploidy detection, and FISH for 22q11.2 testing for array CGH analysis. RESULTS: One case had an 8p deletion that was also visible on karyotype and included the GATA4 gene, which has been associated with congenital heart disease...
July 2016: Journal of Obstetrics and Gynaecology Canada: JOGC, Journal D'obstétrique et Gynécologie du Canada: JOGC
Julia Dörner, Verena Martinez Rodriguez, Ricarda Ziegler, Theresa Röhrig, Rebecca S Cochran, Ronni M Götz, Mark D Levin, Marjut Pihlajoki, Markku Heikinheimo, David B Wilson
As certain strains of mice age, hyperplastic lesions resembling gonadal tissue accumulate beneath the adrenal capsule. Gonadectomy (GDX) accelerates this heterotopic differentiation, resulting in the formation of wedge-shaped adrenocortical neoplasms that produce sex steroids. Stem/progenitor cells that reside in the adrenal capsule and retain properties of the adrenogonadal primordium are thought to be the source of this heterotopic tissue. Here, we demonstrate that GLI1(+) progenitors in the adrenal capsule give rise to gonadal-like cells that accumulate in the subcapsular region...
August 29, 2016: Molecular and Cellular Endocrinology
Shigeo Otake, Min Kyun Park
Gonadal sex differentiation proceeds by interplay of various genes including the transcription factors and secretory factors in a complex network. The sex-differentiating genes are expressed not only during early sex differentiation but also throughout the gonadal development, and even in the adult gonads. In addition, the evidence that they actually function in the adult gonads have been accumulated from the studies using the conditional knockout mice. However, many previous studies were focused on one single gene though those genes function in a network...
August 31, 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
Shima Rastegar-Pouyani, Niusha Khazaei, Ping Wee, Moein Yaqubi, Abdulshakour Mohammadnia
Ectopic expression of a defined set of transcription factors (TFs) can directly convert fibroblasts into a cardiac myocyte cell fate. Beside inefficiency in generating induced cardiomyocytes (iCMs), the molecular mechanisms that regulate this process remained to be well defined. The main purpose of this study was to provide better insight on the transcriptome regulation and to introduce a new strategy for candidating TFs for the transdifferentiation process. Eight mouse and three human high quality microarray data sets were analyzed to find differentially expressed genes (DEGs), which we integrated with TF-binding sites and protein-protein interactions to construct gene regulatory and protein-protein interaction networks...
August 31, 2016: Journal of Cellular Physiology
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