Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

Studies in group IV organometallic chemistry XXXI. Organotin hydride adducts with tin atoms in α,β- or β,β-positions

The structure of several organotin hydride adducts which previously were assumed to contain tin atoms in β,α-positions (β-addition followed by α-addition) has been reinvestigated. As appeared from NMR spectroscopy the greater part of these linear molecules, polymers and heterocycles are in fact β,β-adducts. Mechanistic aspects of the formation of these compounds have been discussed

Studies in group IV organometallic chemistry XXIV. Structure of products obtained in the hydrostannation of ethynes

Organotin monohydrides were brought into reaction with a variety of mono- and disubstituted ethynes. The identity of the resulting products was established by means of elementary analysis, infrared absorption spectroscopy and proton magnetic resonance spectroscopy. In the hydrostannation of monosubstituted ethynes both α- and β- adducts are formed. Electron-withdrawing sustituents favour the formation of α-adducts. In the formation of the β-adducts, as well as in the hydrostannation of disubstituted ethynes, trans-addition seems to be the rule

Studies in group VI organometallic chemistry XXV. Necleophilic trans-addtition of organotin hydrides to carbon — carbon triple bonds

Mechanistic aspects of the hydrostannation of electrophilic ethynes have been studied. As appears from stereochemical data, kinetics, and substituent, solvent and isotope effects, the addition reaction proceeds by a trans-mechanism in which nucleophilic attack of the hydride hydrogen on carbon is the first and rate-determining step. In the hydrostannation of diethyl ethynedicarboxylate most probably a five-membered cyclic transition state is involved

Studies in group IV organometallic chemistry XXVII. Isomerization of the primary trans-addition products formed in the hydrostannation of ethynes

The isomerization of the primary trans-addition products formed in the hydrostannation of ethynes has been shown to proceed under the influence of organotin radicals. Attack of such radicals on the carbon-carbon double bond produces an ethyl radical containing two organotin groups. Elimination of one of the organotin moieties as a radical may result in the formation of the isomerized product. The course of the latter step is determined by several factors. One of these seems to be a preference for those conformers of the free radical intermediate in which both tin atoms at the β-carbon atom are in gauche-position with respect to the polar substituent at the α-carbon atom. At the same time these studies reveal that in hydrostannations of certain carbon-carbon double bonds the hydrogen transfer, following the reversible attack of an organotin radical, is the rate-determining step in the propagation reaction

Stable arylsilver compounds containing dimethylamino, (dimethylamino)methyl or methoxy groups at the aryl nucleus

The following organosilver compounds have been prepared from the corresponding lithium compounds and silver bromide : {2-[(dimethylamino)methyl]phenyl}silver, {2-[(dimethylamino)methyl]phenyl}silver.silver bromide, bis{[2-(dimethylamino)phenyl]silver} . silver bromide, (2, 6-dimethoxyphenyl)silver and (2,4,6-trimethoxyphenyl)silver. These substituted phenylsilvers, which have been characterized by elemental analysis, mol. wt. determinations, IR and PMR spectroscopy and by degradation reactions, show greater thermal, oxidative and hydrolytic stability than phenylsilver. In general the compounds decompose between 100}o{ and 200}o{ and react slowly with oxygen and water