ABSTRACT
Hirschsprung disease (HSCR) is a complex genetic disorder characterized by the absence of enteric nervous system (ENS) in the distal region of the intestine. Down Syndrome (DS) patients have a >50-fold higher risk of developing HSCR than the general population, suggesting that overexpression of human chromosome 21 (Hsa21) genes contribute to HSCR etiology. However, identification of responsible genes remains challenging. Here, we describe a genetic screening of potential candidate genes located on Hsa21, using the zebrafish. Candidate genes were located in the DS-HSCR susceptibility region, expressed in the human intestine, were known potential biomarkers for DS prenatal diagnosis, and were present in the zebrafish genome. With this approach, four genes were selected: RCAN1, ITSN1, ATP5PO and SUMO3. However, only overexpression of ATP5PO, coding for a component of the mitochondrial ATPase, led to significant reduction of ENS cells. Paradoxically, in vitro studies showed that overexpression of ATP5PO led to a reduction of ATP5PO protein levels. Impaired neuronal differentiation and reduced mitochondrial ATP production, were also detected in vitro, after overexpression of ATP5PO in a neuroblastoma cell line. Finally, epistasis was observed between ATP5PO and ret, the most important HSCR gene. Taken together, our results identify ATP5PO as the gene responsible for the increased risk of HSCR in DS patients in particular if RET variants are also present, and show that a balanced expression of ATP5PO is required for normal ENS development.
Subject(s)
Down Syndrome , Enteric Nervous System , Hirschsprung Disease , Animals , Humans , Hirschsprung Disease/genetics , Hirschsprung Disease/metabolism , Down Syndrome/genetics , Down Syndrome/metabolism , Zebrafish/genetics , Enteric Nervous System/metabolism , Biomarkers/metabolismABSTRACT
An efficient photo-induced reduction of CO2 using magnetically separable Ru-CoPc@TiO2@SiO2@Fe3O4 as a heterogeneous catalyst in which CoPc and Ru(bpy)2phene complexes were attached to a solid support via covalent attachment under visible light is described. The as-synthesized catalyst was characterized by a series of techniques including FTIR, UV-Vis, XRD, SEM, TEM, etc. and subsequently tested for the photocatalytic reduction of carbon dioxide using triethylamine as a sacrificial donor and water as a reaction medium. The developed photocatalyst exhibited a significantly higher catalytic activity to give a methanol yield of 2570.78 µmol per g cat after 48 h.
ABSTRACT
Highly dispersed Pd-nanoparticles grafted onto amino-functionalized nanocrystalline starch were found to be excellent heterogeneous catalysts for the aerobic oxidation of a variety of alcohols to their corresponding carbonyl compounds in excellent yields. The prepared catalyst was found to be selective for the oxidation of primary alcohols to aldehydes without giving over-oxidation products and was recycled several times without any leaching of the metal into the solution.
Subject(s)
Alcohols/chemistry , Metal Nanoparticles/chemistry , Oxidants/chemistry , Palladium/chemistry , Starch/chemistry , Catalysis , Oxidation-ReductionSubject(s)
Aspergillus niger , Food Contamination , Hematopoietic System/physiology , Mycotoxicosis/blood , Animals , Blood Glucose/metabolism , Blood Proteins/metabolism , Erythrocyte Count , Erythrocytes/physiology , Female , Food Microbiology , Hemoglobins/metabolism , Mycotoxicosis/etiology , RatsABSTRACT
Weanling albino rats were fed with either a control diet or one infested with Penicillium rubrum Stoll for a period of 30 days. At the end of the experimental period, determinations of haemoglobin, total proteins and transaminases were made in blood and tissues (liver, brain and kidney). The fungus was found to render the food toxic, resulting in liver and kidney damage. The toxicity of the fungus was also evidenced by poor live weight gains and organ weights.
Subject(s)
Brain/drug effects , Kidney/drug effects , Liver/drug effects , Mycotoxins/toxicity , Penicillium , Administration, Oral , Alanine Transaminase/biosynthesis , Animals , Aspartate Aminotransferases/biosynthesis , Body Weight/drug effects , Brain/enzymology , Female , Hemoglobins , Kidney/enzymology , Liver/enzymology , Male , Organ Size/drug effects , RatsABSTRACT
Iodine cyanide has been developed as an oxidant for the determination of iodide, sulphite, thiosulphate, thiocyanate, arsenic (III), antimony(III), tin(II), mercury(I), iron(II), ascorbic acid and beta-naphthol in dilute aqueous mineral acids, glacial acetic acid and 1:1 acetic acid-acetic anhydride mixture, with visual and potentiometric methods of end-point detection.
