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https://www.readbyqxmd.com/read/29781215/strap-deficiency-impairs-mouse-embryonic-stem-cells-lineage-commitment-through-cyp26a1-mediated-retinoic-acid-homeostasis
#1
Lin Jin, Chenbei Chang, Kevin M Pawlik, Arunima Datta, Larry M Johnson, Trung Vu, Joseph L Napoli, Pran K Datta
Retinoic acid (RA) signaling is essential for the differentiation of embryonic stem cells (ESCs) and vertebrate development. RA biosynthesis and metabolism are controlled by a series of enzymes, but the molecular regulators of these enzymes remain largely obscure. In this study, we investigated the functional role of the WD-domain protein STRAP (serine threonine kinase receptor-associated protein) in the pluripotency and lineage commitment of murine ESCs. We generated Strap knockout (KO) mouse ESCs and subjected them to spontaneous differentiation...
May 21, 2018: Stem Cells
https://www.readbyqxmd.com/read/29715634/fenbuconazole-exposure-impacts-the-development-of-zebrafish-embryos
#2
Yuqiong Wu, Qihong Yang, Meng Chen, Ying Zhang, Zhenghong Zuo, Chonggang Wang
Fenbuconazole (FBZ), a triazole-containing fungicide, is widely used in agriculture and horticulture. In the present study, the development and cardiac functioning were observed and determined in zebrafish embryos exposed to FBZ at 5, 50 and 500 ng/L nominal concentrations for 72 h. The results showed that 500 ng/L FBZ significantly increased pericardial edema rate, spine curvature rate, disturbed cardiac function, and led a shortened lower jaw. The transcription of genes such as tbx5, nkx2.5, tnnt2, gata4, bmp2b, myl7 was altered, which might be responsible for the cardiac developmental and functioning defects in the larvae...
April 28, 2018: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/29520716/rhythmic-diurnal-synthesis-and-signaling-of-retinoic-acid-in-the-rat-pineal-gland-and-its-action-to-rapidly-downregulate-erk-phosphorylation
#3
Anna Ashton, Patrick N Stoney, Jemma Ransom, Peter McCaffery
Vitamin A is important for the circadian timing system; deficiency disrupts daily rhythms in activity and clock gene expression, and reduces the nocturnal peak in melatonin in the pineal gland. However, it is currently unknown how these effects are mediated. Vitamin A primarily acts via the active metabolite, retinoic acid (RA), a transcriptional regulator with emerging non-genomic activities. We investigated whether RA is subject to diurnal variation in synthesis and signaling in the rat pineal gland. Its involvement in two key molecular rhythms in this gland was also examined: kinase activation and induction of Aanat, which encodes the rhythm-generating melatonin synthetic enzyme...
March 8, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29483666/uncovering-the-genetic-lesions-underlying-the-most-severe-form-of-hirschsprung-disease-by-whole-genome-sequencing
#4
Clara Sm Tang, Xuehan Zhuang, Wai-Yee Lam, Elly Sau-Wai Ngan, Jacob Shujui Hsu, Y U Michelle, S O Man-Ting, Stacey S Cherny, Ngoc Diem Ngo, Pak C Sham, Paul Kh Tam, Maria-Mercè Garcia-Barcelo
Hirschsprung disease (HSCR) is a complex birth defect characterized by the lack of ganglion cells along a variable length of the distal intestine. A large proportion of HSCR patients remain genetically unexplained. We applied whole-genome sequencing (WGS) on 9 trios where the probands are sporadically affected with the most severe form of the disorder and harbor no coding sequence variants affecting the function of known HSCR genes. We found de novo protein-altering variants in three intolerant to change genes-CCT2, VASH1, and CYP26A1-for which a plausible link with the enteric nervous system (ENS) exists...
February 26, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29476041/cyp26c1-is-a-hydroxylase-of-multiple-active-retinoids-and-interacts-with-cellular-retinoic-acid-binding-proteins
#5
Guo Zhong, David Ortiz, Alex Zelter, Abhinav Nath, Nina Isoherranen
The clearance of retinoic acid (RA) and its metabolites is believed to be regulated by the CYP26 enzymes, but the specific roles of CYP26A1, CYP26B1, and CYP26C1 in clearing active vitamin A metabolites have not been defined. The goal of this study was to establish the substrate specificity of CYP26C1, and determine whether CYP26C1 interacts with cellular retinoic acid binding proteins (CRABPs). CYP26C1 was found to effectively metabolize all- trans retinoic acid ( at RA), 9- cis -retinoic acid (9- cis -RA), 13- cis -retinoic acid, and 4-oxo- at RA with the highest intrinsic clearance toward 9- cis -RA...
May 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29465800/the-cycling-gonad-retinoic-acid-synthesis-and-degradation-patterns-during-adult-zebrafish-danio-rerio-oogenesis
#6
R Ruivo, A Capitão, L F C Castro, M M Santos
The expression pattern of genes coding for enzymes of the retinoic acid (RA) synthetic and degradation pathways was characterized in adult female zebrafish Danio rerio. Females were conditioned until maturation and post-spawn expression dynamics were determined. A striking upregulation of cyp26b1, but not cyp26a1, was observed following egg deposition, decreasing to initial levels during recovery. A similar, yet lower, fluctuation was observed for aldh1a2 and rdh10a, the enzymes participating in the two-step RA biosynthesis cascade...
April 2018: Journal of Fish Biology
https://www.readbyqxmd.com/read/29449654/analysis-combining-correlated-glaucoma-traits-identifies-five-new-risk-loci-for-open-angle-glaucoma
#7
Puya Gharahkhani, Kathryn P Burdon, Jessica N Cooke Bailey, Alex W Hewitt, Matthew H Law, Louis R Pasquale, Jae H Kang, Jonathan L Haines, Emmanuelle Souzeau, Tiger Zhou, Owen M Siggs, John Landers, Mona Awadalla, Shiwani Sharma, Richard A Mills, Bronwyn Ridge, David Lynn, Robert Casson, Stuart L Graham, Ivan Goldberg, Andrew White, Paul R Healey, John Grigg, Mitchell Lawlor, Paul Mitchell, Jonathan Ruddle, Michael Coote, Mark Walland, Stephen Best, Andrea Vincent, Jesse Gale, Graham RadfordSmith, David C Whiteman, Grant W Montgomery, Nicholas G Martin, David A Mackey, Janey L Wiggs, Stuart MacGregor, Jamie E Craig
Open-angle glaucoma (OAG) is a major cause of blindness worldwide. To identify new risk loci for OAG, we performed a genome-wide association study in 3,071 OAG cases and 6,750 unscreened controls, and meta-analysed the results with GWAS data for intraocular pressure (IOP) and optic disc parameters (the overall meta-analysis sample size varying between 32,000 to 48,000 participants), which are glaucoma-related traits. We identified and independently validated four novel genome-wide significant associations within or near MYOF and CYP26A1, LINC02052 and CRYGS, LMX1B, and LMO7 using single variant tests, one additional locus (C9) using gene-based tests, and two genetic pathways - "response to fluid shear stress" and "abnormal retina morphology" - in pathway-based tests...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29337257/a-comparison-of-the-embryonic-stem-cell-test-and-whole-embryo-culture-assay-combined-with-the-bewo-placental-passage-model-for-predicting-the-embryotoxicity-of-azoles
#8
COMPARATIVE STUDY
Myrto Dimopoulou, Aart Verhoef, Caroline A Gomes, Catharina W van Dongen, Ivonne M C M Rietjens, Aldert H Piersma, Bennard van Ravenzwaay
In the present study, we show the value of combining toxico-dynamic and -kinetic in vitro approaches for embryotoxicity testing of azoles. Both the whole embryo culture (WEC) and the embryonic stem cells test (EST) predicted the in vivo potency ranking of twelve tested azoles with moderate accuracy. Combining these results with relative placental transfer rates (Papp values) as determined in the BeWo cell culture model, increased the predictability of both WEC and EST, with R2 values increasing from 0.51 to 0...
April 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29297599/genetic-contribution-of-retinoid-related-genes-to-neural-tube-defects
#9
Huili Li, Jing Zhang, Shuyuan Chen, Fang Wang, Ting Zhang, Lee Niswander
Rare variants are considered underlying causes of complex diseases. The complex and severe group of disorders called neural tube defects (NTDs) results from failure of the neural tube to close during early embryogenesis. Neural tube closure requires the coordination of numerous signaling pathways, including the precise regulation of retinoic acid (RA) concentration, which is controlled by enzymes involved in RA synthesis and degradation. Here, we used a case-control mutation screen study to reveal rare variants in retinoid-related genes in a Han Chinese NTD population by sequencing six genes in 355 NTD cases and 225 controls...
April 2018: Human Mutation
https://www.readbyqxmd.com/read/29177441/de-novo-mutations-in-caudal-type-homeo-box-transcription-factor-2-cdx2-in-patients-with-persistent-cloaca
#10
Jacob S J Hsu, Manting So, Clara S M Tang, Anwarul Karim, Robert M Porsch, Carol Wong, Michelle Yu, Fanny Yeung, Huimin Xia, Ruizhong Zhang, Stacey S Cherny, Patrick H Y Chung, Kenneth K Y Wong, Pak C Sham, Ngoc Diem Ngo, Miaoxin Li, Paul K H Tam, Vincent C H Lui, Maria-Mercè Garcia-Barcelo
The cloaca is an embryonic cavity that is divided into the urogenital sinus and rectum upon differentiation of the cloacal epithelium triggered by tissue-specific transcription factors including CDX2. Defective differentiation leads to persistent cloaca in humans (PC), a phenotype recapitulated in Cdx2 mutant mice. PC is linked to hypo/hyper-vitaminosis A. Although no gene has ever been identified, there is a strong evidence for a genetic contribution to PC. We applied whole-exome sequencing and copy-number-variants analyses to 21 PC patients and their unaffected parents...
January 15, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29131833/mek-inhibitors-enhance-therapeutic-response-towards-atra-in-nf1-associated-malignant-peripheral-nerve-sheath-tumors-mpnst-in-vitro
#11
Susan Fischer-Huchzermeyer, Anna Dombrowski, Gordon Wilke, Verena Stahn, Anna Streubel, Victor Felix Mautner, Anja Harder
OBJECTIVE: Neurofibromatosis type 1 (NF1) is a hereditary tumor syndrome characterized by an increased risk of malignant peripheral nerve sheath tumors (MPNST). Chemotherapy of MPNST is still insufficient. In this study, we investigated whether human tumor Schwann cells derived from NF1 associated MPNST respond to all-trans retinoic acid (ATRA). We analyzed effects of ATRA and MEK inhibitor (MEKi) combination therapy. METHODS: MPNST cell lines S462, T265, NSF1 were treated with ATRA and MEKi U0126 and PD0325901...
2017: PloS One
https://www.readbyqxmd.com/read/28960386/diethylstilbestrol-impaired-oogenesis-of-yellow-catfish-juveniles-through-disrupting-hypothalamic-pituitary-gonadal-axis-and-germ-cell-development
#12
Yaqin Wang, Yingwen Li, Qiliang Chen, Zhihao Liu
Diethylstilbestrol (DES), a non-steroidal estrogen, has been found to cause altered germ cell development and disordered ovarian development in fish females. However, the mechanisms that might be involved are poorly understood. In this study, female juveniles of yellow catfish (Pelteobagrus fulvidraco) (120 days post-hatching) were exposed to two doses (10 and 100 ng l-1 ) of DES for 28 days. After the endpoint of exposure, decreased ovary weight and gonadosomatic index, as well as various ovarian impairments were observed in response to DES...
March 2018: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28865861/liver-transcriptome-analysis-reveals-important-factors-involved-in-the-metabolic-adaptation-of-the-transition-cow
#13
N-T Ha, C Drögemüller, C Reimer, F Schmitz-Hsu, R M Bruckmaier, H Simianer, J J Gross
During early lactation, dairy cows experience a severe metabolic load often resulting in the development of various diseases. The inevitable deficiency in nutrients and energy at the onset of lactation requires an optimal adaptation of the hepatic metabolism to overcome metabolic stress. We conducted a whole-liver transcriptome analysis for the transition cow to identify novel factors crucial for metabolic adaptation. Liver samples were obtained from 6 Red Holstein dairy cows (parity 2 to 7, mean ± standard deviation: 3...
November 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28811909/a-fourth-subtype-of-retinoic-acid-receptor-related-orphan-receptors-is-activated-by-oxidized-all-trans-retinoic-acid-in-medaka-oryzias-latipes
#14
Kotowa Sakai, Haruka Fukushima, Yuya Yamamoto, Toshitaka Ikeuchi
BACKGROUND: The three known subtypes of the retinoic acid receptor-related orphan receptor (ROR) have been implicated in the control of immunity, brain function, and circadian rhythm in mammals. Here, we demonstrate by phylogenetic analysis that there were originally four subtypes of RORs in vertebrates. One of the novel ror paralogs, rord1 (rorca in the Ensembl database), is conserved among teleosts, but absent in mammals. Using medaka (Oryzias latipes) as a model teleost, we evaluated the expression pattern of this gene, its transactivational properties for endogenic chemicals, and its ability to activate the promoters of putative target genes...
2017: Zoological Letters
https://www.readbyqxmd.com/read/28735443/retinoic-acid-regulates-avian-lung-branching-through-a-molecular-network
#15
Hugo Fernandes-Silva, Patrícia Vaz-Cunha, Violina Baranauskaite Barbosa, Carla Silva-Gonçalves, Jorge Correia-Pinto, Rute Silva Moura
Retinoic acid (RA) is of major importance during vertebrate embryonic development and its levels need to be strictly regulated otherwise congenital malformations will develop. Through the action of specific nuclear receptors, named RAR/RXR, RA regulates the expression of genes that eventually influence proliferation and tissue patterning. RA has been described as crucial for different stages of mammalian lung morphogenesis, and as part of a complex molecular network that contributes to precise organogenesis; nonetheless, nothing is known about its role in avian lung development...
December 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28715412/cell-fate-specification-in-the-lingual-epithelium-is-controlled-by-antagonistic-activities-of-sonic-hedgehog-and-retinoic-acid
#16
Maha El Shahawy, Claes-Göran Reibring, Cynthia L Neben, Kristina Hallberg, Pauline Marangoni, Brian D Harfe, Ophir D Klein, Anders Linde, Amel Gritli-Linde
The interaction between signaling pathways is a central question in the study of organogenesis. Using the developing murine tongue as a model, we uncovered unknown relationships between Sonic hedgehog (SHH) and retinoic acid (RA) signaling. Genetic loss of SHH signaling leads to enhanced RA activity subsequent to loss of SHH-dependent expression of Cyp26a1 and Cyp26c1. This causes a cell identity switch, prompting the epithelium of the tongue to form heterotopic minor salivary glands and to overproduce oversized taste buds...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28651018/meta-analysis-of-mirna-expression-profiles-for-prostate-cancer-recurrence-following-radical-prostatectomy
#17
Elnaz Pashaei, Elham Pashaei, Maryam Ahmady, Mustafa Ozen, Nizamettin Aydin
BACKGROUND: Prostate cancer (PCa) is a leading reason of death in men and the most diagnosed malignancies in the western countries at the present time. After radical prostatectomy (RP), nearly 30% of men develop clinical recurrence with high serum prostate-specific antigen levels. An important challenge in PCa research is to identify effective predictors of tumor recurrence. The molecular alterations in microRNAs are associated with PCa initiation and progression. Several miRNA microarray studies have been conducted in recurrence PCa, but the results vary among different studies...
2017: PloS One
https://www.readbyqxmd.com/read/28643469/atra-signaling-regulates-the-expression-of-col9a1-through-bmp2-wnt4-runx1-pathway-in-antler-chondrocytes
#18
Hong-Liang Zhang, Bin Guo, Zhan-Qing Yang, Cui-Cui Duan, Shuang Geng, Kai Wang, Hai-Fan Yu, Zhan-Peng Yue
Although all-trans retinoic acid (ATRA) is involved in the regulation of cartilage growth and development, its regulatory mechanisms remain unknown. Here, we showed that ATRA could induce the expression of COL9A1 in antler chondrocytes. Silencing of cellular retinoic acid binding protein 2 (CRABP2) could impede the ATRA-induced upregulation of COL9A1, whereas overexpression of CRABP2 presented the opposite effect. RARα agonist Am80 induced the expression of COL9A1, whereas treatment with RARα antagonist Ro 41-5253 or RXRα small-interfering RNA (siRNA) caused an obvious blockage of ATRA on COL9A1...
September 2017: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
https://www.readbyqxmd.com/read/28612832/a-novel-de-novo-mutation-in-myt1-the-unique-oavs-gene-identified-so-far
#19
Marie Berenguer, Angele Tingaud-Sequeira, Mileny Colovati, Maria I Melaragno, Silvia Bragagnolo, Ana B A Perez, Benoit Arveiler, Didier Lacombe, Caroline Rooryck
Oculo-auriculo-vertebral spectrum (OAVS) is a developmental disorder characterized by hemifacial microsomia associated with ear, eyes and vertebrae malformations showing highly variable expressivity. Recently, MYT1, encoding the myelin transcription factor 1, was reported as the first gene involved in OAVS, within the retinoic acid (RA) pathway. Fifty-seven OAVS patients originating from Brazil were screened for MYT1 variants. A novel de novo missense variant affecting function, c.323C>T (p.(Ser108Leu)), was identified in MYT1, in a patient presenting with a severe form of OAVS...
September 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28570941/diet-dependent-retinoid-effects-on-liver-gene-expression-include-stellate-and-inflammation-markers-and-parallel-effects-of-the-nuclear-repressor-shp
#20
COMPARATIVE STUDY
Meghan Maguire, Justin R Bushkofsky, Michele Campaigne Larsen, Yee Hoon Foong, Sherry A Tanumihardjo, Colin R Jefcoate
For mice, a maternal vitamin A (VA)-deficient diet initiated from midgestation (GVAD) produces serum retinol deficiency in mature offspring. We hypothesize that the effects of GVAD arise from preweaning developmental changes. We compare the effect of this GVAD protocol in combination with a postweaning high-fat diet (HFD) or high-carbohydrate diet (LF12). Each is compared to an equivalent VA-sufficient combination. GVAD extensively decreased serum retinol and liver retinol, retinyl esters, and retinoid homeostasis genes (Lrat, Cyp26b1 and Cyp26a1)...
September 2017: Journal of Nutritional Biochemistry
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