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Fetal gene expression

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https://www.readbyqxmd.com/read/28346343/lifetime-exposure-to-a-constant-environment-amplifies-the-impact-of-a-fructose-rich-diet-on-glucose-homeostasis-during-pregnancy
#1
Aleida Song, Stuart Astbury, Abha Hoedl, Brent Nielsen, Michael E Symonds, Rhonda C Bell
The need to refine rodent models of human-related disease is now being recognized, in particular the rearing environment that can profoundly modulate metabolic regulation. Most studies on pregnancy and fetal development purchase and transport young females into the research facility, which after a short period of acclimation are investigated (Gen0). We demonstrate that female offspring (Gen1) show an exaggerated hyperinsulinemic response to pregnancy when fed a standard diet and with high fructose intake, which continues throughout pregnancy...
March 25, 2017: Nutrients
https://www.readbyqxmd.com/read/28344999/long-term-engraftment-and-fetal-globin-induction-upon-bcl11a-gene-editing-in-bone-marrow-derived-cd34-hematopoietic-stem-and-progenitor-cells
#2
Kai-Hsin Chang, Sarah E Smith, Timothy Sullivan, Kai Chen, Qianhe Zhou, Jason A West, Mei Liu, Yingchun Liu, Benjamin F Vieira, Chao Sun, Vu P Hong, Mingxuan Zhang, Xiao Yang, Andreas Reik, Fyodor D Urnov, Edward J Rebar, Michael C Holmes, Olivier Danos, Haiyan Jiang, Siyuan Tan
To develop an effective and sustainable cell therapy for sickle cell disease (SCD), we investigated the feasibility of targeted disruption of the BCL11A gene, either within exon 2 or at the GATAA motif in the intronic erythroid-specific enhancer, using zinc finger nucleases in human bone marrow (BM) CD34(+) hematopoietic stem and progenitor cells (HSPCs). Both targeting strategies upregulated fetal globin expression in erythroid cells to levels predicted to inhibit hemoglobin S polymerization. However, complete inactivation of BCL11A resulting from bi-allelic frameshift mutations in BCL11A exon 2 adversely affected erythroid enucleation...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344827/perinatal-high-methyl-donor-alters-gene-expression-in-igf-system-in-male-offspring-without-altering-dna-methylation
#3
Valérie Amarger, Fanny Giudicelli, Anthony Pagniez, Patricia Parnet
AIM: To investigate the effect of a protein restriction and a supplementation with methyl donor nutrients during fetal and early postnatal life on the expression and epigenetic state of imprinted genes from the IGF system. MATERIALS & METHODS: Pregnant female rats were fed a protein-restricted diet supplemented or not with methyl donor. RESULTS: Gene expression of the Igf2, H19, Igf1, Igf2r and Plagl1 genes in the liver of male offspring at birth and weaning was strongly influenced by maternal diet...
March 2017: Future Science OA
https://www.readbyqxmd.com/read/28344151/enhancing-oligodendrocyte-differentiation-by-transient-transcription-activation-via-dna-nanoparticle-mediated-transfection
#4
Xiaowei Li, Stephany Y Tzeng, Camila Gadens Zamboni, Vassilis E Koliatsos, Guo-Li Ming, Jordan J Green, Hai-Quan Mao
Current approaches to derive oligodendrocytes from human pluripotent stem cells (hPSCs) need extended exposure of hPSCs to growth factors and small molecules, which limits their clinical application because of the lengthy culture time required and low generation efficiency of myelinating oligodendrocytes. Compared to extrinsic growth factors and molecules, oligodendrocyte differentiation and maturation can be more effectively modulated by regulation of the cell transcription network. In the developing central nervous system (CNS), two basic helix-loop-helix transcription factors, Olig1 and Olig2, are decisive in oligodendrocyte differentiation and maturation...
March 23, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28344002/establishment-of-a-human-blood-brain-barrier-co-culture-model-mimicking-the-neurovascular-unit-using-induced-pluri-and-multipotent-stem-cells
#5
Antje Appelt-Menzel, Alevtina Cubukova, Katharina Günther, Frank Edenhofer, Jörg Piontek, Gerd Krause, Tanja Stüber, Heike Walles, Winfried Neuhaus, Marco Metzger
In vitro models of the human blood-brain barrier (BBB) are highly desirable for drug development. This study aims to analyze a set of ten different BBB culture models based on primary cells, human induced pluripotent stem cells (hiPSCs), and multipotent fetal neural stem cells (fNSCs). We systematically investigated the impact of astrocytes, pericytes, and NSCs on hiPSC-derived BBB endothelial cell function and gene expression. The quadruple culture models, based on these four cell types, achieved BBB characteristics including transendothelial electrical resistance (TEER) up to 2,500 Ω cm(2) and distinct upregulation of typical BBB genes...
March 22, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28343630/de-novo-truncating-mutations-in-the-last-and-penultimate-exons-of-ppm1d-cause-an-intellectual-disability-syndrome
#6
Sandra Jansen, Sinje Geuer, Rolph Pfundt, Rachel Brough, Priyanka Ghongane, Johanna C Herkert, Elysa J Marco, Marjolein H Willemsen, Tjitske Kleefstra, Mark Hannibal, Joseph T Shieh, Sally Ann Lynch, Frances Flinter, David R FitzPatrick, Alice Gardham, Birgitta Bernhard, Nicola Ragge, Ruth Newbury-Ecob, Raphael Bernier, Malin Kvarnung, E A Helena Magnusson, Marja W Wessels, Marjon A van Slegtenhorst, Kristin G Monaghan, Petra de Vries, Joris A Veltman, Christopher J Lord, Lisenka E L M Vissers, Bert B A de Vries
Intellectual disability (ID) is a highly heterogeneous disorder involving at least 600 genes, yet a genetic diagnosis remains elusive in ∼35%-40% of individuals with moderate to severe ID. Recent meta-analyses statistically analyzing de novo mutations in >7,000 individuals with neurodevelopmental disorders highlighted mutations in PPM1D as a possible cause of ID. PPM1D is a type 2C phosphatase that functions as a negative regulator of cellular stress-response pathways by mediating a feedback loop of p38-p53 signaling, thereby contributing to growth inhibition and suppression of stress-induced apoptosis...
March 18, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28341147/cadmium-stimulates-myofibroblast-differentiation-and-mouse-lung-fibrosis
#7
Xin Hu, Jolyn Fernandes, Dean P Jones, Young-Mi Go
Increasing evidence suggests that Cd at levels found in the human diet can cause oxidative stress and activate redox-sensitive transcription factors in inflammatory signaling. Following inflammation, tissue repair often involves activation of redox-sensitive transcription factors in fibroblasts. In lungs, epithelial barrier remodeling is required to restore gas exchange and barrier function, and aberrant myofibroblast differentiation leads to pulmonary fibrosis. Contributions of exogenous exposures, such as dietary Cd, to pulmonary fibrosis remain incompletely defined...
March 21, 2017: Toxicology
https://www.readbyqxmd.com/read/28336813/the-innate-immune-response-in-fetal-lung-mesenchymal-cells-targets-vegfr2-expression-and-activity
#8
Rachel M Medal, Amanda M Im, Yasutoshi Yamamoto, Omar Lakhdari, Timothy S Blackwell, Hal M Hoffman, Debashis Sahoo, Lawrence S Prince
In preterm infants, soluble inflammatory mediators target lung mesenchymal cells, disrupting airway and alveolar morphogenesis. However, how mesenchymal cells respond directly to microbial stimuli remains poorly characterized. Our objective was to measure the genome-wide innate immune response in fetal lung mesenchymal cells exposed to the bacterial endotoxin lipopolysaccharide (LPS). Using Affymetrix MoGene 1.0st arrays, we showed that LPS induced expression of unique innate immune transcripts heavily weighted toward CC and CXC family chemokines...
March 23, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28336320/preliminary-research-on-dna-methylation-changes-during-murine-palatogenesis-induced-by-tcdd
#9
Chen Wang, Xin-Gang Yuan, Cui-Ping Liu, Sha-Na Zhai, Ding-Wen Zhang, Yue-Xian Fu
2,3,7,8-Tetrachlrodibenzo-p-dioxin (TCDD) has been shown to induce cleft palate through growth factor and receptor expression changes during palatogenesis. DNA methylation is an important epigenetic modification that can regulate gene expressions and may be involved in TCDD-induced cleft palate. In this study, we investigated the effects of TCDD on the global and CpG DNA methylation status and the expression levels of DNA methyltransferases (Dnmts) in palate tissue of fetal mice. Pregnant C57BL/6J mice were administered with corn oil or TCDD 28 μg/kg at gestation day 10...
February 12, 2017: Journal of Cranio-maxillo-facial Surgery
https://www.readbyqxmd.com/read/28334989/impaired-fetal-muscle-development-and-jak-stat-activation-mark-disease-onset-and-progression-in-a-mouse-model-for-merosin-deficient-congenital-muscular-dystrophy
#10
Andreia M Nunes, Ryan D Wuebbles, Apurva Sarathy, Tatiana M Fontelonga, Marianne Deries, Dean J Burkin, Sólveig Thorsteinsdóttir
Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is a dramatic neuromuscular disease in which crippling muscle weakness is evident from birth. Here we use the dyW mouse model for human MDC1A to trace the onset of the disease during development in utero. We find that myotomal and primary myogenesis proceed normally in homozygous dyW-/-embryos. Fetal dyW-/-muscles display the same number of myofibers as wildtype muscles, but by E18.5 dyW-/-muscles are significantly smaller and muscle size is not recovered post-natally...
March 7, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334964/mutations-in-the-leukemia-inhibitory-factor-receptor-lifr-gene-and-lifr-deficiency-cause-urinary-tract-malformations
#11
Anne Kosfeld, Frank Brand, Anna-Carina Weiss, Martin Kreuzer, Michaela Goerk, Helge Martens, Stephanie Schubert, Anne-Kathrin Schäfer, Vera Riehmer, Imke Hennies, Jan Hinrich Bräsen, Lars Pape, Kerstin Amann, Lars Krogvold, Anna Bjerre, Christoph Daniel, Andreas Kispert, Dieter Haffner, Ruthild G Weber
Congenital anomalies of the kidneys and urinary tract (CAKUT) are the most common cause of chronic kidney disease in children. As CAKUT is a genetically heterogeneous disorder and most cases are genetically unexplained, we aimed to identify new CAKUT causing genes. Using whole-exome sequencing and trio-based de novo analysis, we identified a novel heterozygous de novo frameshift variant in the leukemia inhibitory factor receptor (LIFR) gene causing instability of the mRNA in a patient presenting with bilateral CAKUT and requiring kidney transplantation at one year of age...
March 8, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28332771/prenatal-high-fat-diet-alters-placental-morphology-nutrient-transporter-expression-and-mtorc1-signaling-in-rat
#12
Lin Song, Bo Sun, Gretha J Boersma, Zachary A Cordner, Jianqun Yan, Timothy H Moran, Kellie L K Tamashiro
OBJECTIVE: This study aimed to determine how the rat placenta and fetus respond to maternal high-fat (HF) diet during gestation and to identify the possible mechanisms. METHODS: Pregnant Sprague-Dawley rats were fed with standard chow (13.5% fat) or HF (60% fat) diet during gestation. Placentas were collected on gestation day 21. RESULTS: HF dams had greater fat mass, higher plasma leptin, lower plasma adiponectin, and impaired glucose tolerance during pregnancy...
March 23, 2017: Obesity
https://www.readbyqxmd.com/read/28332752/bovine-trophectoderm-cells-induced-from-bovine-fibroblasts-with-induced-pluripotent-stem-cell-reprogramming-factors
#13
Neil C Talbot, Wendy O Sparks, Caitlin Phillips, Alan D Ealy, Anne M Powell, Thomas J Caperna, Wesley M Garrett, David M Donovan, Le Ann Blomberg
Thirteen independent induced bovine trophectroderm (iBT) cell lines were established by reprogramming bovine fetal liver-derived fibroblasts after viral-vector transduction with either 6 or 8 factors, including POU5F1 (OCT4), KLF4, SOX2, MYC, NANOG, LIN28, SV40 large T antigen, and hTERT.. Light- and electron-microscopy analysis showed that the iBT cells had epithelial cell morphology typical of bovine trophectoderm cells. Reverse-transcription-PCR assays indicated that all of the cell lines expressed interferon-tau (IFNT) at passages 1 or 2...
March 23, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28331934/microarray-analysis-of-differential-gene-expression-profile-between-human-fetal-and-adult-heart
#14
Zhimin Geng, Jue Wang, Lulu Pan, Ming Li, Jitai Zhang, Xueli Cai, Maoping Chu
Although many changes have been discovered during heart maturation, the genetic mechanisms involved in the changes between immature and mature myocardium have only been partially elucidated. Here, gene expression profile changed between the human fetal and adult heart was characterized. A human microarray was applied to define the gene expression signatures of the fetal (13-17 weeks of gestation, n = 4) and adult hearts (30-40 years old, n = 4). Gene ontology analyses, pathway analyses, gene set enrichment analyses, and signal transduction network were performed to predict the function of the differentially expressed genes...
March 22, 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28327211/reduced-fetal-vitamin-d-status-by-maternal-undernutrition-during-discrete-gestational-windows-in-sheep
#15
J K Cleal, M R Hargreaves, K R Poore, J C Y Tang, W D Fraser, M A Hanson, L R Green
Placental transport of vitamin D and other nutrients (e.g. amino acids, fats and glucose) to the fetus is sensitive to maternal and fetal nutritional cues. We studied the effect of maternal calorific restriction on fetal vitamin D status and the placental expression of genes for nutrient transport [aromatic T-type amino acid transporter-1 (TAT-1); triglyceride hydrolase/lipoprotein uptake facilitator lipoprotein lipase (LPL)] and vitamin D homeostasis [CYP27B1; vitamin D receptor (VDR)], and their association with markers of fetal cardiovascular function and skeletal muscle growth...
March 22, 2017: Journal of Developmental Origins of Health and Disease
https://www.readbyqxmd.com/read/28325913/persistent-dna-methylation-changes-associated-with-prenatal-mercury-exposure-and-cognitive-performance-during-childhood
#16
Andres Cardenas, Sheryl L Rifas-Shiman, Golareh Agha, Marie-France Hivert, Augusto A Litonjua, Dawn L DeMeo, Xihong Lin, Chitra J Amarasiriwardena, Emily Oken, Matthew W Gillman, Andrea A Baccarelli
Prenatal exposure to mercury, a known neurotoxic metal, is associated with lower cognitive performance during childhood. Disruption of fetal epigenetic programming could explain mercury's neurodevelopmental effects. We screened for epigenome-wide methylation differences associated with maternal prenatal blood mercury levels in 321 cord blood DNA samples and examined the persistence of these alterations during early (n = 75; 2.9-4.9 years) and mid-childhood (n = 291; 6.7-10.5 years). Among males, prenatal mercury levels were associated with lower regional cord blood DNA methylation at the Paraoxonase 1 gene (PON1) that persisted in early childhood and was attenuated in mid-childhood blood...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28324053/hepatic-insulin-resistance-and-altered-gluconeogenic-pathway-in-premature-baboons
#17
Lisa McGill-Vargas, Amalia Gastaldelli, Hanyu Liang, Diana Anzueto Guerra, Teresa Johnson-Pais, Steven Seidner, Donald McCurnin, Giovanna Muscogiuri, Ralph DeFronzo, Nicolas Musi, Cynthia Blanco
Premature infants have altered glucose regulation early in life and increased risk for diabetes in adulthood. Although prematurity leads to an increased risk of diabetes and metabolic syndrome in adult life, the role of hepatic glucose regulation and adaptation to an early extra-uterine environment in preterm infants remain unknown. The purpose of this study was to investigate developmental differences in glucose metabolism, hepatic protein content and gene expression of key insulin signaling/gluconeogenic molecules...
January 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28322282/maternal-immune-activation-dysregulation-of-the-fetal-brain-transcriptome-and-relevance-to-the-pathophysiology-of-autism-spectrum-disorder
#18
M V Lombardo, H M Moon, J Su, T D Palmer, E Courchesne, T Pramparo
Maternal immune activation (MIA) via infection during pregnancy is known to increase risk for autism spectrum disorder (ASD). However, it is unclear how MIA disrupts fetal brain gene expression in ways that may explain this increased risk. Here we examine how MIA dysregulates rat fetal brain gene expression (at a time point analogous to the end of the first trimester of human gestation) in ways relevant to ASD-associated pathophysiology. MIA downregulates expression of ASD-associated genes, with the largest enrichments in genes known to harbor rare highly penetrant mutations...
March 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28322134/reproductive-microbiomes
#19
Michael L Power, Caroline Quaglieri, Jay Schulkin
Almost every part of our body has a coevolved microbial community. The expressed microbial genes comprise the various microbiomes that play important roles in normal physiology and development. The various microbiomes are separate, yet often connected, with the species composition of one affecting others. The female reproductive system microbiomes (eg, vaginal, placental, and mammary/milk) remain less well explored than the gut microbiome although they comprise a large proportion of the female microbial network...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28320521/differential-mirna-expression-analysis-during-late-stage-terminal-hindgut-development-in-fetal-rats
#20
Shuguang Jin, Junxiang Wang, Hong Chen, Bo Xiang
BACKGROUND: Terminal hindgut deformity is the leading digestive tract malformation, however, the etiology and pathogenesis remained unknown. To date, gene expression abnormalities were considered the primary cause of these diseases. miRNAs have been found to play an important role in regulating the expression of genes. METHODS: A total of 24 pregnant rats were randomly divided into two groups. The experimental group (n=12) received 1% ethylenethiourea (125mg/kg) by gavage on gestational day 11, while the control group (n=12) received the same volume of distilled water...
March 12, 2017: Journal of Pediatric Surgery
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