64 research outputs found
Reactivity of OH and CH3OH between 22 and 64 K: Modelling the gas phase production of CH3O in Barnard 1b
In the last years, ultra-low temperature chemical kinetic experiments have
demonstrated that some gas-phase reactions are much faster than previously
thought. One example is the reaction between OH and CH3OH, which has been
recently found to be accelerated at low temperatures yielding CH3O as main
product. This finding opened the question of whether the CH3O observed in the
dense core Barnard 1b could be formed by the gas-phase reaction of CH3OH and
OH. Several chemical models including this reaction and grain-surface processes
have been developed to explain the observed abundance of CHO with little
success. Here we report for the first time rate coefficients for the gas-phase
reaction of OH and CH3OH down to a temperature of 22 K, very close to those in
cold interstellar clouds. Two independent experimental set-ups based on the
supersonic gas expansion technique coupled to the pulsed laser photolysis-laser
induced fluorescence technique were used to determine rate coefficients in the
temperature range 22-64 K. The temperature dependence obtained in this work can
be expressed as k(22-64 K) = (3.6+/-0.1)e-12 (T/ 300)^(-1.0+/-0.2) cm3
molecule-1 s-1. Implementing this expression in a chemical model of a cold
dense cloud results in CH3O/CH3OH abundance ratios similar or slightly lower
than the value of 3e-3 observed in Barnard 1b. This finding confirms that the
gas-phase reaction between OH and CH3OH is an important contributor to the
formation of interstellar CH3O. The role of grain-surface processes in the
formation of CH3O, although it cannot be fully neglected, remains
controversial.Comment: Accepted for publication in The Astrophysical Journa
(Acetylacetonato-κ2 O,O′)chloridotrimethanolatoniobium(V)
In the title compound, [Nb(CH3O)3(C5H7O2)Cl], the NbV atom is coordinated by two O atoms from the chelating acetylacetonate ligand, three O atoms from the methanolate groups and one chloride ligand. The octahedral environment around niobium is slightly distorted with Nb—O distances in the range 1.8603 (15)–2.1083 (15) Å and an Nb—Cl distance of 2.4693 (9) Å. The O—Nb—O angles vary between 80.74 (6) and 100.82 (7)°, while the trans Cl—Nb—O angle is 167.60 (5)°. There are no hydrogen bonds observed, only an intermolecular C—H⋯O interaction
Contribution of RET, NTRK3 and EDN3 to the expression of Hirschsprung disease in a multiplex family
Exome sequencing reveals a high genetic heterogeneity on familial Hirschsprung disease
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Hirschsprung disease, associated syndromes and genetics: A review
Hirschsprung disease (HSCR, aganglionic megacolon) represents the main genetic cause of functional intestinal obstruction with an incidence of 1/5000 live births. This developmental disorder is a neurocristopathy and is characterised by the absence of the enteric ganglia along a variable length of the intestine. In the last decades, the development of surgical approaches has importantly decreased mortality and morbidity which allowed the emergence of familial cases. Isolated HSCR appears to be a non-Mendelian malformation with low, sex-dependent penetrance, and variable expression according to the length of the aganglionic segment. While all Mendelian modes of inheritance have been described in syndromic HSCR, isolated HSCR stands as a model for genetic disorders with complex patterns of inheritance. The tyrosine kinase receptor RET is the major gene with both rare coding sequence mutations and/or a frequent variant located in an enhancer element predisposing to the disease. Hitherto, 10 genes and five loci have been found to be involved in HSCR development.published_or_final_versio
Whole exome sequencing coupled with unbiased functional analysis reveals new Hirschsprung disease genes
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Whole exome sequencing coupled with unbiased functional analysis reveals new Hirschsprung disease genes
Background: Hirschsprung disease (HSCR), which is congenital obstruction of the bowel, results from a failure of enteric nervous system (ENS) progenitors to migrate, proliferate, differentiate, or survive within the distal intestine. Previous studies that have searched for genes underlying HSCR have focused on ENS-related pathways and genes not fitting the current knowledge have thus often been ignored. We identify and validate novel HSCR genes using whole exome sequencing (WES), burden tests, in silico prediction, unbiased in vivo analyses of the mutated genes in zebrafish, and expression analyses in zebrafish, mouse, and human. Results: We performed de novo mutation (DNM) screening on 24 HSCR trios. We identify 28 DNMs in 21 different genes. Eight of the DNMs we identified occur in RET, the main HSCR gene, and the remaining 20 DNMs reside in genes not reported in the ENS. Knockdown of all 12 genes with missense or loss-of-function DNMs showed that the orthologs of four genes (DENND3, NCLN, NUP98, and TBATA) are indispensable for ENS development in zebrafish, and these results were confirmed by CRISPR knockout. These genes are also expressed in human and mouse gut and/or ENS progenitors. Importantly, the encoded proteins are linked to neuronal processes shared by the central nervous system and the ENS. Conclusions: Our data open new fields of investigation into HSCR pathology and provide novel insights into the development of the ENS. Moreover, the study demonstrates that functional analyses of genes carrying DNMs are warranted to delineate the full genetic architecture of rare complex diseases
X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients
Rett syndrome (RTT) is a severe neurological disorder usually caused by mutations in the MECP2 gene. Since the MECP2 gene is located on the X chromosome, X chromosome inactivation (XCI) could play a role in the wide range of phenotypic variation of RTT patients; however, classical methylation-based protocols to evaluate XCI could not determine whether the preferentially inactivated X chromosome carried the mutant or the wild-type allele. Therefore, we developed an allele-specific methylation-based assay to evaluate methylation at the loci of several recurrent MECP2 mutations. We analyzed the XCI patterns in the blood of 174 RTT patients, but we did not find a clear correlation between XCI and the clinical presentation. We also compared XCI in blood and brain cortex samples of two patients and found differences between XCI patterns in these tissues. However, RTT mainly being a neurological disease complicates the establishment of a correlation between the XCI in blood and the clinical presentation of the patients. Furthermore, we analyzed MECP2 transcript levels and found differences from the expected levels according to XCI. Many factors other than XCI could affect the RTT phenotype, which in combination could influence the clinical presentation of RTT patients to a greater extent than slight variations in the XCI pattern
MMMM syndrome (macrocephaly, megalocornea, motor and mental retardation) and refractory epilepsy
Evaluation of the ELOVL4 gene in families with retinitis pigmentosa linked to the RP25 locus
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