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https://www.readbyqxmd.com/read/28537755/a-pilot-study-of-noninvasive-prenatal-diagnosis-of-alpha-and-beta-thalassemia-with-target-capture-sequencing-of-cell-free-fetal-dna-in-maternal-blood
#1
Wenjuan Wang, Yuan Yuan, Haiqing Zheng, Yaoshen Wang, Dan Zeng, Yihua Yang, Xin Yi, Yang Xia, Chunjiang Zhu
AIMS: Thalassemia is a dangerous hematolytic genetic disease. In south China, ∼24% Chinese carry alpha-thalassemia or beta-thalassemia gene mutations. Given the fact that the invasive sampling procedures can only be performed by professionals in experienced centers, it may increase the risk of miscarriage or infection. Thus, most people are worried about the invasive operation. As such, a noninvasive and accurate prenatal diagnosis is needed for appropriate genetic counseling for families with high risks...
May 24, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28535425/prenatal-ambient-air-pollution-exposure-infant-growth-and-placental-mitochondrial-dna-content-in-the-inma-birth-cohort
#2
Diana B P Clemente, Maribel Casas, Bram G Janssen, Aitana Lertxundi, Loreto Santa-Marina, Carmen Iñiguez, Sabrina Llop, Jordi Sunyer, Mònica Guxens, Tim S Nawrot, Martine Vrijheid
BACKGROUND: The association between prenatal air pollution exposure and postnatal growth has hardly been explored. Mitochondrial DNA (mtDNA), as a marker of oxidative stress, and growth at birth can play an intermediate role in this association. OBJECTIVE: In a subset of the Spanish birth cohort INMA we assessed first whether prenatal nitrogen dioxide (NO2) exposure is associated with infant growth. Secondly, we evaluated whether growth at birth (length and weight) could play a mediating role in this association...
May 20, 2017: Environmental Research
https://www.readbyqxmd.com/read/28535307/intergenerational-impact-of-paternal-lifetime-exposures-to-both-folic-acid-deficiency-and-supplementation-on-reproductive-outcomes-and-imprinted-gene-methylation
#3
Lundi Ly, Donovan Chan, Mahmoud Aarabi, Mylène Landry, Nathalie A Behan, Amanda J MacFarlane, Jacquetta Trasler
STUDY QUESTION: Do paternal exposures to folic acid deficient (FD), and/or folic acid supplemented (FS) diets, throughout germ cell development adversely affect male germ cells and consequently offspring health outcomes? SUMMARY ANSWER: Male mice exposed over their lifetimes to both FD and FS diets showed decreased sperm counts and altered imprinted gene methylation with evidence of transmission of adverse effects to the offspring, including increased postnatal-preweaning mortality and variability in imprinted gene methylation...
May 23, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28528868/pleiotropic-effects-of-trait-associated-genetic-variation-on-dna-methylation-utility-for-refining-gwas-loci
#4
Eilis Hannon, Mike Weedon, Nicholas Bray, Michael O'Donovan, Jonathan Mill
Most genetic variants identified in genome-wide association studies (GWASs) of complex traits are thought to act by affecting gene regulation rather than directly altering the protein product. As a consequence, the actual genes involved in disease are not necessarily the most proximal to the associated variants. By integrating data from GWAS analyses with those from genetic studies of regulatory variation, it is possible to identify variants pleiotropically associated with both a complex trait and measures of gene regulation...
May 13, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28524376/fluorinated-peg-polypeptide-polyplex-micelles-have-good-serum-resistance-and-low-cytotoxicity-for-gene-delivery
#5
Ting Wu, Longhai Wang, Shenggang Ding, Yezi You
A novel PEGylation polypeptide, poly(ethylene glycol)-b-poly(l-lysine)-b-poly(l-cysteine) (PEG-PLL-PCys) triblock copolymer is synthesized via the sequential ring-opening polymerization of amino acid N-carboxyanhydrides initiated by methoxypolyethylene glycol amine (mPEG-NH2 , Mw is 2 kDa). Subsequently, the obtained polypeptide is partially conjugated with fluorocarbon chains via disulfide exchange reaction. PLL segment can condense plasmid DNA through an electrostatic force to form a complex core, PEG segment surrounding the complex like a corona can prevent the complex from precipitation and reduce the adsorption of serum, while PCys segment with fluorocarbon can enhance the cellular uptake and the stability of the formed polyplex micelles in physiological conditions...
May 19, 2017: Macromolecular Bioscience
https://www.readbyqxmd.com/read/28522317/the-association-between-cytochrome-p450-3a-progesterone-receptor-polymorphisms-plasma-17-ohpc-concentrations-and-spontaneous-preterm-birth
#6
Martha L Bustos, Steve N Caritis, Kathleen A Jablonski, Uma M Reddy, Yoram Sorokin, John M Thorp, Michael W Varner, Ronald J Wapner, Jay D Iams, Marshall W Carpenter, Alan M Peaceman, Brian M Mercer, Anthony Sciscione, Dwight J Rouse, Susan M Ramin
BACKGROUND: Infants born before 37 weeks' gestation are of public health concern since complications associated with preterm birth are the leading cause of mortality in children under 5 years of age and a major cause of morbidity and lifelong disability. The administration of 17-hydroxyprogesterone caproate (17-OHPC) reduces preterm birth by 33% in women with history spontaneous preterm birth (SPTB). We demonstrated previously that plasma concentrations of 17-OHPC vary widely among pregnant women and that women with 17-OHPC plasma concentrations in the lowest quartile had SPTB rates of 40% vs rates of 25% in those women with higher concentrations...
May 15, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28514925/factors-affecting-cell-free-dna-fetal-fraction-and-the-consequences-for-test-accuracy
#7
Fergus Perry Scott, Melody Menezes, Ricardo Palma-Dias, Debbie Nisbet, Philip Schluter, Fabricio da Silva Costa, Andrew Cameron McLennan
INTRODUCTION: Biological factors are known to influence the fetal fraction (FF) of cell-free DNA and may also influence the accuracy of non-invasive prenatal testing. MATERIAL AND METHODS: NIPT from 5,267 mixed risk women across three specialist clinics in Australia were analysed. Multivariable regression analysis was used to determine whether maternal characteristics, ultrasound and placental biomarkers affect FF and test accuracy. RESULTS: FF ranged from 4% - 37% (mean 11...
May 17, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28512147/nrf2-inactivation-enhances-placental-angiogenesis-in-a-preeclampsia-mouse-model-and-improves-maternal-and-fetal-outcomes
#8
Masahiro Nezu, Tomokazu Souma, Lei Yu, Hiroki Sekine, Nobuyuki Takahashi, Andrew Zu-Sern Wei, Sadayoshi Ito, Akiyoshi Fukamizu, Zsuzsanna K Zsengeller, Tomohiro Nakamura, Atsushi Hozawa, S Ananth Karumanchi, Norio Suzuki, Masayuki Yamamoto
Placental activation of the renin-angiotensin system (RAS) plays a key role in the pathogenesis of preeclampsia. Reactive oxygen species (ROS) are thought to affect placental angiogenesis, which is critical for preventing preeclampsia pathology. We examined the role of ROS in preeclampsia by genetically modifying the Keap1-Nrf2 pathway, a cellular antioxidant defense system, in a mouse model of RAS-induced preeclampsia. Nrf2 deficiency would be expected to impair cellular antioxidant responses; however, Nrf2 deficiency in preeclamptic mice improved maternal and fetal survival, ameliorated intra-uterine growth retardation, and augmented oxidative DNA damage...
May 16, 2017: Science Signaling
https://www.readbyqxmd.com/read/28507174/elevated-adenosine-induces-placental-dna-hypomethylation-independent-of-a2b-receptor-signaling-in-preeclampsia
#9
Aji Huang, Hongyu Wu, Takayuki Iriyama, Yujin Zhang, Kaiqi Sun, Anren Song, Hong Liu, Zhangzhe Peng, Lili Tang, Minjung Lee, Yun Huang, Xin Ni, Rodney E Kellems, Yang Xia
Preeclampsia is a prevalent pregnancy hypertensive disease with both maternal and fetal morbidity and mortality. Emerging evidence indicates that global placental DNA hypomethylation is observed in patients with preeclampsia and is linked to altered gene expression and disease development. However, the molecular basis underlying placental epigenetic changes in preeclampsia remains unclear. Using 2 independent experimental models of preeclampsia, adenosine deaminase-deficient mice and a pathogenic autoantibody-induced mouse model of preeclampsia, we demonstrate that elevated placental adenosine not only induces hallmark features of preeclampsia but also causes placental DNA hypomethylation...
May 15, 2017: Hypertension
https://www.readbyqxmd.com/read/28504706/the-mitochondrial-respiratory-chain-is-essential-for-haematopoietic-stem-cell-function
#10
Elena Ansó, Samuel E Weinberg, Lauren P Diebold, Benjamin J Thompson, Sébastien Malinge, Paul T Schumacker, Xin Liu, Yuannyu Zhang, Zhen Shao, Mya Steadman, Kelly M Marsh, Jian Xu, John D Crispino, Navdeep S Chandel
Adult and fetal haematopoietic stem cells (HSCs) display a glycolytic phenotype, which is required for maintenance of stemness; however, whether mitochondrial respiration is required to maintain HSC function is not known. Here we report that loss of the mitochondrial complex III subunit Rieske iron-sulfur protein (RISP) in fetal mouse HSCs allows them to proliferate but impairs their differentiation, resulting in anaemia and prenatal death. RISP-null fetal HSCs displayed impaired respiration resulting in a decreased NAD(+)/NADH ratio...
May 15, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28503212/associations-between-maternal-risk-factors-of-adverse-pregnancy-and-birth-outcomes-and-the-offspring-epigenetic-clock-of-gestational-age-at-birth
#11
Polina Girchenko, Jari Lahti, Darina Czamara, Anna K Knight, Meaghan J Jones, Anna Suarez, Esa Hämäläinen, Eero Kajantie, Hannele Laivuori, Pia M Villa, Rebecca M Reynolds, Michael S Kobor, Alicia K Smith, Elisabeth B Binder, Katri Räikkönen
BACKGROUND: A recent study has shown that it is possible to accurately estimate gestational age (GA) at birth from the DNA methylation (DNAm) of fetal umbilical cord blood/newborn blood spots. This DNAm GA predictor may provide additional information relevant to developmental stage. In 814 mother-neonate pairs, we evaluated the associations between DNAm GA and a number of maternal and offspring characteristics. These characteristics reflect prenatal environmental adversity and are expected to influence newborn developmental stage...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28502862/11-beta-hydroxysteroid-dehydrogenase-2-promoter-methylation-is-associated-with-placental-protein-expression-in-small-for-gestational-age-newborns
#12
Maria-Luisa Lazo-de-la-Vega-Monroy, Martha-Olivia Solís-Martínez, Gustavo Romero-Gutiérrez, Victor E Aguirre-Arzola, Katarzyna Wrobel, Kazimierz Wrobel, Silvio Zaina, Gloria Barbosa-Sabanero
Small for gestational age infants have greater risk of developing metabolic diseases in adult life. It has been suggested that low birth weight may result from glucocorticoid excess in utero, a key mechanism in fetal programming. The placental enzyme 11-beta hydroxysteroid dehydrogenase type 2 (11β-HSD2, HSD11B2 gene) acts as a barrier protecting the fetus from maternal corticosteroid deleterious effects. Low placental 11β-HSD2 transcription and activity have been associated with low birth weight, yet the mechanism regulating its protein expression is not fully understood...
May 11, 2017: Steroids
https://www.readbyqxmd.com/read/28502747/chicken-egg-fetal-liver-dna-and-histopathologic-effects-of-structurally-diverse-carcinogens-and-non-carcinogens
#13
M J Iatropoulos, T Kobets, J-D Duan, K D Brunnemann, E Vock, U Deschl, G M Williams
Chicken egg fetal livers were evaluated for histopathological changes produced by four genotoxic hepatocarcinogens: 2-acetylaminofluorene (AAF), aflatoxin B1 (AFB1), benzo[a]pyrene (BaP), diethylnitrosamine (DEN); four structurally related non- or weakly- carcinogenic comparators: fluorene (FLU), aflatoxin B2 (AFB2), benzo[e]pyrene (BeP), N-nitrosodiethanolamine (NDELA); two epigenetic hepatocarcinogens: clofibric acid (CFA), phenobarbital (PB); and the non-carcinogen, D-mannitol (MAN). CFA, PB and MAN were also assessed for formation of DNA adducts using the (32)P nucleotide postlabeling (NPL) assay and for DNA breaks using the comet assay...
May 11, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28501220/7-8-hydroxy-2-deoxyguanosine-2-deoxiguanosine-ratio-determined-in-hydrolysates-of-brain-dna-by-ultrachromatrography-coupled-to-tandem-mass-spectrometry
#14
Isabel Torres-Cuevas, Miguel Aupi, Miguel Angel Asensi, Máximo Vento, Ángel Ortega, Javier Escobar
7,8-hydroxy-2'-deoxyguanosine (8-OHdG) is an abundant DNA lesion formed by oxidation of the nucleoside 2'-deoxyguanosine (2-dG) and one of the most studied and accepted oxidative stress biomarkers. 8-OHdG has a strong carcinogenic potential, and prolonged oxidative stress heightens pathological conditions and especially cancer risk. Our aim was to develop, validate and apply a reliable method to assess DNA oxidation in genomic cellular DNA of sensible target organs such as brain. A procedure to isolate and digest the DNA of brain tissue properly for further detection of 8-OHdG and 2-dG by Ultra Performance Liquid Chromatography-tandem Mass Spectrometry (UPLC-MS/MS) was optimized...
August 1, 2017: Talanta
https://www.readbyqxmd.com/read/28500962/the-methylation-levels-of-the-h19-differentially-methylated-region-in-human-umbilical-cords-reflect-newborn-parameters-and-changes-by-maternal-environmental-factors-during-early-pregnancy
#15
Hidenobu Miyaso, Kenichi Sakurai, Shunya Takase, Akifumi Eguchi, Masahiro Watanabe, Hideoki Fukuoka, Chisato Mori
H19 is a tumor-suppressor gene, and changes in the methylation of the H19-differential methylation region (H19-DMR) are related to human health. However, little is known about the factors that regulate the methylation levels of H19-DMR. Several recent studies have shown that maternal environmental factors during pregnancy, such as smoking, drinking, chemical exposure, and nutrient intake, can alter the methylation levels of several genes in fetal tissues. In this study, we examined the effects of maternal factors on changes in the methylation levels of H19-DMR in the human umbilical cord (UC), an extra-embryonic tissue...
May 10, 2017: Environmental Research
https://www.readbyqxmd.com/read/28500333/novel-algorithms-for-improved-sensitivity-in-non-invasive-prenatal-testing
#16
L F Johansson, E N de Boer, H A de Weerd, F van Dijk, M G Elferink, G H Schuring-Blom, R F Suijkerbuijk, R J Sinke, G J Te Meerman, R H Sijmons, M A Swertz, B Sikkema-Raddatz
Non-invasive prenatal testing (NIPT) of cell-free DNA in maternal plasma, which is a mixture of maternal DNA and a low percentage of fetal DNA, can detect fetal aneuploidies using massively parallel sequencing. Because of the low percentage of fetal DNA, methods with high sensitivity and precision are required. However, sequencing variation lowers sensitivity and hampers detection of trisomy samples. Therefore, we have developed three algorithms to improve sensitivity and specificity: the chi-squared-based variation reduction (χ(2)VR), the regression-based Z-score (RBZ) and the Match QC score...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28497391/effect-of-lang-chuang-ding-decoction-on-dna-methylation-of-cd70-gene-promoter-in-peripheral-blood-mononuclear-cells-of-female-patients-with-systemic-lupus-erythematosus
#17
Jing Sun, Tie-Juan Shao, Dong-Yu Zhang, Xue-Qin Huang, Zhi-Jun Xie, Cheng-Ping Wen
OBJECTIVES: To investigate the effect of Lang-chuang-ding Decoction (, LCD) on the expression of DNA methylation of CD70 gene promoter in peripheral blood mononuclear cells (PBMCs) of females with systemic lupus erythematosus (SLE). METHODS: PBMCs isolated from female patients with SLE or healthy donors were cultured and treated with LCD medicated serum or normal serum for 24 or 48 h. The mRNA expressions of CD70 gene in PBMCs were detected by reverse transcription polymerase chain reaction (PCR); the DNA methylation of the CD70 gene promoter region was detected by methylation-specific PCR...
May 11, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28495194/neospora-caninum-abortion-in-a-malayan-tapir-tapirus-indicus
#18
M Peters, C Osmann, P Wohlsein, G Schares
A captive 17-year old female Malayan tapir (Tapirus indicus) aborted a fetus with a crown rump length of 19cm in early pregnancy. The fetus showed an early state of mummification. Histologically, a multifocal mononuclear encephalitis, myocarditis and periportal hepatitis was present indicating a possible protozoal cause of abortion. Although immunohistologically, Neospora (N.) caninum antigen could not be demonstrated, N. caninum DNA was detected by Polymerase Chain Reaction (PCR) in brain, heart, liver and lung of the fetus...
May 30, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/28492482/chromatin-switches-during-neural-cell-differentiation-and-their-dysregulation-by-prenatal-alcohol-exposure
#19
REVIEW
David P Gavin, Dennis R Grayson, Sajoy P Varghese, Marina Guizzetti
Prenatal alcohol exposure causes persistent neuropsychiatric deficits included under the term fetal alcohol spectrum disorders (FASD). Cellular identity emerges from a cascade of intrinsic and extrinsic (involving cell-cell interactions and signaling) processes that are partially initiated and maintained through changes in chromatin structure. Prenatal alcohol exposure influences neuronal and astrocyte development, permanently altering brain connectivity. Prenatal alcohol exposure also alters chromatin structure through histone and DNA modifications...
May 11, 2017: Genes
https://www.readbyqxmd.com/read/28490568/noninvasive-detection-of-f8-int22h-related-inversions-and-sequence-variants-in-maternal-plasma-of-hemophilia-carriers
#20
Irena Hudecova, Peiyong Jiang, Joanna Davies, Y M Dennis Lo, Rezan A Kadir, Rossa W K Chiu
Direct detection of F8 and F9 sequence variants in maternal plasma of hemophilia carriers has been demonstrated by microfluidics digital PCR. Noninvasive prenatal assessment of the most clinically relevant group of sequence variants among hemophilia patients, namely those involving int22h-related inversions disrupting the F8 gene, poses additional challenges due to its molecular complexity. We investigated the use of droplet digital PCR (ddPCR) and targeted massively parallel sequencing (MPS) for maternal plasma DNA analysis to noninvasively determine fetal mutational status in pregnancies at risk for hemophilia...
May 10, 2017: Blood
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