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Thomas W Winkler, Caroline Brandl, Felix Grassmann, Mathias Gorski, Klaus Stark, Julika Loss, Bernhard H F Weber, Iris M Heid
Late-stage age-related macular degeneration (AMD) is the leading cause of visual impairment in the elderly with a complex etiology. The most important non-modifiable risk factors for onset and progression of late AMD are age and genetic risk factors, however, little is known about the interplay between genetics and age or sex. Here, we conducted a large-scale age- and sex-stratified genome-wide association study (GWAS) using 1000 Genomes imputed genome-wide and ExomeChip data (>12 million variants). The data were established by the International Age-related Macular Degeneration Genomics Consortium (IAMDGC) from 16,144 late AMD cases and 17,832 controls...
2018: PloS One
F Chen, W Yuan, X Mo, J Zhuang, Y Wang, J Chen, Z Jiang, X Zhu, Q Zeng, Y Wan, F Li, Y Shi, L Cao, X Fan, S Luo, X Ye, Y Chen, G Dai, J Gao, X Wang, H Xie, P Zhu, Y Li, X Wu
Four-and-a-half LIM domains protein 1 (FHL1) mutations are associated with human myopathies. However, the function of this protein in skeletal development remains unclear. Zebrafish Fhl1A is the homologue of human FHL1. In the present study, we showed that fhl1A knockdown causes defective skeletal muscle development, while injection with fhl1A mRNA largely recovered the muscle development in these fhl1A morphants. We also demonstrated that fhl1A knockdown decreases the number of satellite cells. This decrease in satellite cells and the emergence of skeletal muscle abnormalities were associated with alterations in the gene expression of myoD, pax7, mef2ca and skMLCK...
March 7, 2018: Current Molecular Medicine
Jing Tian, Jiapan Liu, Jieqiong Li, Jingxin Zheng, Lifang Chen, Yujuan Wang, Qiong Liu, Jiazuan Ni
Background: Selenoprotein F (SELENOF, was named as 15-kDa selenoprotein) has been reported to play important roles in oxidative stress, endoplasmic reticulum (ER) stress and carcinogenesis. However, the biological function of SELENOF is still unclear. Methods: A yeast two-hybrid system was used to screen the interactive protein of SELENOF in a human fetal brain cDNA library. The interaction between SELENOF and interactive protein was validated by fluorescence resonance energy transfer (FRET), co-immunoprecipitation (co-IP) and pull-down assays...
2018: Nutrition & Metabolism
Saishu Yoshida, Ken Fujiwara, Hiroto Nishihara, Takako Kato, Takashi Yashiro, Yukio Kato
Development of the anterior pituitary proceeds via spatiotemporal patterning of transcription factors and signalling molecules. Among them, retinoic acid (RA) functions as an important signalling molecule for vertebrate organogenesis in many tissues. However, little is known regarding target genes in the developing pituitary. The present study aimed to clarify the relationship between endogenous RA signalling and mRNA expression of the pituitary-specific transcription factor Prop1 in the pituitary primordium of Rathke's pouch...
January 22, 2018: Journal of Neuroendocrinology
Yehuda Shabtai, Liat Bendelac, Halim Jubran, Joseph Hirschberg, Abraham Fainsod
Alcohol consumption during pregnancy induces Fetal Alcohol Spectrum Disorder (FASD), which has been proposed to arise from competitive inhibition of retinoic acid (RA) biosynthesis. We provide biochemical and developmental evidence identifying acetaldehyde as responsible for this inhibition. In the embryo, RA production by RALDH2 (ALDH1A2), the main retinaldehyde dehydrogenase expressed at that stage, is inhibited by ethanol exposure. Pharmacological inhibition of the embryonic alcohol dehydrogenase activity, prevents the oxidation of ethanol to acetaldehyde that in turn functions as a RALDH2 inhibitor...
January 10, 2018: Scientific Reports
Timothy S Owen, David Salom, Wenyu Sun, Krzysztof Palczewski
Three types of cone cells exist in the human retina, each containing a different pigment responsible for the initial step of photo-transduction. These pigments are distinguished by their specific absorbance maxima, 425 nm (blue), 530 nm (green) and 560 nm (red). Each pigment contains a common chromophore, 11-cis-retinal covalently bound to an opsin protein via a Schiff base. The 11-cis-retinal protonated Schiff base has an absorbance maxima at 440 nm in methanol. Unfortunately, the chemistry allowing the same chromophore interacting with different opsin proteins to tune the absorbance of the resulting pigments to distinct λmax values is poorly understood...
January 10, 2018: Biochemistry
Jin Won Park, Kyung-Ho Jung, Jin Hee Lee, Seung Hwan Moon, Young Seok Cho, Kyung-Han Lee
We hypothesized that aldehyde dehydrogenase1 (ALDH1) protects cancer cells from retinaldehyde-induced cytotoxicity, and that targeting this enzyme would enhance the therapeutic effect of retinaldehyde. ALDEFLUOR™ assays showed high ALDH activity in A549 and H522 cancer cells and low activity in H1666 and T47D cancer cells. Immunoblots showed that expression of ALDH1A1 and ALDH1A3 was high in A549 and H522 cells, but low in H1666 cells. HPLC confirmed that N, N-diethylaminobenzaldehyde (DEAB) inhibits ALDH-mediated disposal of retinaldehyde in A549 cells and lysates...
November 21, 2017: Oncotarget
Krysta Mila Coyle, Selena Maxwell, Margaret Lois Thomas, Paola Marcato
Retinoids, derivatives of vitamin A, are key physiological molecules with regulatory effects on cell differentiation, proliferation and apoptosis. As a result, they are of interest for cancer therapy. Specifically, models of breast cancer have varied responses to manipulations of retinoid signaling. This study characterizes the transcriptional response of MDA-MB-231 and MDA-MB-468 breast cancer cells to retinaldehyde dehydrogenase 1A3 (ALDH1A3) and all-trans retinoic acid (atRA). We demonstrate limited overlap between ALDH1A3-induced gene expression and atRA-induced gene expression in both cell lines, suggesting that the function of ALDH1A3 in breast cancer progression extends beyond its role as a retinaldehyde dehydrogenase...
November 30, 2017: Scientific Reports
Maria M M Kaisar, Leonard R Pelgrom, Alwin J van der Ham, Maria Yazdanbakhsh, Bart Everts
Recently, it has become clear that short-chain fatty acids (SCFAs), and in particular butyrate, have anti-inflammatory properties. Murine studies have shown that butyrate can promote regulatory T cells via the induction of tolerogenic dendritic cells (DCs). However, the effects of SCFAs on human DCs and how they affect their capacity to prime and polarize T-cell responses have not been addressed. Here, we report that butyrate suppresses LPS-induced maturation and metabolic reprogramming of human monocyte-derived DCs (moDCs) and conditions them to polarize naive CD4+ T cells toward IL-10-producing type 1 regulatory T cells (Tr1)...
2017: Frontiers in Immunology
Made Airanthi K Widjaja-Adhi, Grzegorz Palczewski, Kali Dale, Elizabeth A Knauss, Mary E Kelly, Marcin Golczak, Alan D Levine, Johannes von Lintig
The intestinal epithelium is a major site for the conversion of dietary β-carotene to retinaldehyde by the enzyme BCO1. The majority of retinaldehyde is further metabolized to retinol (vitamin A), esterified and packaged into triacylglycerol-rich chylomicrons for bodily distribution. Some serve on-site for the synthesis of retinoic acid, a hormone-like compound, which exerts pleiotropic and dominant effects on gastrointestinal immunity. We report here that the intestine-specific homeobox protein ISX is critical to control the metabolic flow of β-carotene through this important branching point of vitamin A metabolism...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
Nicolás Cuenca, Isabel Ortuño-Lizarán, Isabel Pinilla
PURPOSE: Optical coherence tomography has been a technological breakthrough in the diagnosis, treatment, and follow-up of many ocular diseases, especially retinal and neuro-ophthalmologic pathologic conditions. Until now, several controversies have arisen over the specific cell types that the bands observed in the OCT represent, especially over the 4 outer retinal bands. DESIGN: To correlate the 4 outer hyperreflective bands observed in the OCT with the histologic structures using human retinal sections and immunocytochemistry at the fovea level...
October 13, 2017: Ophthalmology
Yehuda Shabtai, Abraham Fainsod
Several models have been proposed to explain the neurodevelopmental syndrome induced by alcohol exposure of human embryos, known as Fetal Alcohol Spectrum Disorder (FASD). One of the proposed models suggests a competition for the enzymes required for retinoic acid biosynthesis. The outcome of such competition is the development under conditions of reduced retinoic acid signaling. Retinoic acid is one of the biologically-active metabolites of vitamin A (retinol) and regulates numerous embryonic and differentiation processes...
October 5, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
Takahiro Tagami, Daichi Miyahara, Yoshiaki Nakamura
Germ cells transmit genetic information to the next generation through gametogenesis. Primordial germ cells (PGCs) are the first germ-cell population established during development, and are the common origins of both oocytes and spermatogonia. Unlike in other species, PGCs in birds undergo blood circulation to migrate toward the genital ridge, and are one of the major biological properties of avian PGCs. Germ cells enter meiosis and arrest at prophase I during embryogenesis in females, whereas in males they enter mitotic arrest during embryogenesis and enter meiosis only after birth...
2017: Advances in Experimental Medicine and Biology
Kritika Nayak, Sameer S Katiyar, Varun Kushwah, Sanyog Jain
The present study depicts coenzyme Q10 (CoQ10) and retinaldehyde (RAL) co-loaded Nanostructured Lipid Carriers (NLCs); having activity on different targets of photoageing, which can overcome deficits of conventional topical dosage forms. The developed NLCs were characterized for particle size, polydispersity index, and % Entrapment efficiency, followed by their incorporation into Carbopol® 934P-NF gel. In vitro cellular uptake and cytotoxicity assay was performed to evaluate NLCs and in vivo study on UV induced wrinkle model to determine efficacy of NLCs...
September 12, 2017: Journal of Drug Targeting
Saghar Bagheri, Madhulatha Pantrangi, Simrat K Sodhi, Sayeh Bagheri, Patrick Oellers, Hendrik P N Scholl
PURPOSE: To report the phenotypic and genotypic data of a patient with retinitis punctata albescens carrying a novel deletion in the RLBP1 gene. RESULTS: A woman of Iranian descent in her forties with a history of progressive visual deterioration since early childhood exhibited phenotypic features of retinitis punctata albescens with multiple white dots in the posterior pole and macular atrophy in both eyes. The microarray analysis identified a ∼2.160 kb homozygous deletion corresponding to a minimum deletion boundary of chr15q26...
August 18, 2017: Retinal Cases & Brief Reports
Carole Haushalter, Laure Asselin, Valérie Fraulob, Pascal Dollé, Muriel Rhinn
A tight regulation of neuron production is required to generate a functional cerebral cortex and is achieved by a proper balance between proliferation and differentiation of progenitor cells. Though the vitamin A (retinol) active derivative retinoic acid (RA) has been implicated as one of the signals acting during mammalian forebrain neurogenesis, its function at the onset of neurogenesis as well as during establishment of cortical layers and neuronal subtypes remains elusive. One limitation is that murine mutants for genes encoding key enzymes involved in RA synthesis die during early embryonic development...
October 1, 2017: Developmental Biology
Concetta Scimone, Luigi Donato, Teresa Esposito, Carmela Rinaldi, Rosalia D'Angelo, Antonina Sidoti
BACKGROUND: Autosomal recessive forms of retinitis punctata albescens (RPA) have been described. RPA is characterized by progressive retinal degeneration due to alteration in visual cycle and consequent deposit of photopigments in retinal pigment epithelium. Five loci have been linked to RPA onset. Among these, the retinaldehyde-binding protein 1 gene, RLBP1, is the most frequently involved and several founder mutations were reported. We report results of a genetic molecular investigation performed on a large Sicilian family in which appears a young woman with RPA...
August 1, 2017: Human Genomics
Barbora Hermankova, Jan Kossl, Eliska Javorkova, Pavla Bohacova, Michaela Hajkova, Alena Zajicova, Magdalena Krulova, Vladimir Holan
Retinal disorders represent the main cause of decreased quality of vision and even blindness worldwide. The loss of retinal cells causes irreversible damage of the retina, and there are currently no effective treatment protocols for most retinal degenerative diseases. A promising approach for the treatment of retinal disorders is represented by stem cell-based therapy. The perspective candidates are mesenchymal stem cells (MSCs), which can differentiate into multiple cell types and produce a number of trophic and growth factors...
October 1, 2017: Stem Cells and Development
Yehuda Shabtai, Natalie Shukrun, Abraham Fainsod
Retinoic acid (RA) signaling is a central pathway regulating anterior-posterior patterning of the embryo through its targets, the Hox genes. RA is produced by two sequential oxidations from vitamin A (retinol) and this biosynthesis has to be regulated temporally, spatially and quantitatively. Mining Xenopus embryonic expression databases identified a novel component of the RA metabolic network, ADHFe1. Using Xenopus laevis embryos as our experimental system we determined the temporal and spatial pattern of AdhFe1 expression...
2017: International Journal of Developmental Biology
Monique Boily, Philippe Aras, Catherine Jumarie
In Quebec, Canada, the cultivation of maize dominates the agricultural territory. This crop requires a sustained supply of fertilizers from different sources: chemical, natural or from residual materials (sludge). These amendments contain metallic trace elements, which may lead to metal-contaminated maize pollen, a possible source of prooxidants for the foraging bees. Our objective was to determine whether maize fields environment influences the oxidation processes and the accumulation of metals in bees. A few days prior to pollen shedding, beehives were installed in maize fields: one organically grown (site A) and three conventionally grown (sites B, C and D)...
December 1, 2017: Science of the Total Environment
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