Quantenchemische Rechnungen an Elektronenmangelverbindungen mit Bor und anderen Elementen der 3. und 4. Hauptgruppe

Zusammenhänge zwischen elektronischer Struktur, Geometrien und Energien

Transforming Growth Factor Beta 2 and Heme Oxygenase 1 Genes Are Risk Factors for the Cerebral Malaria Syndrome in Angolan Children

BACKGROUND: Cerebral malaria (CM) represents a severe outcome of the Plasmodium falciparum infection. Recent genetic studies have correlated human genes with severe malaria susceptibility, but there is little data on genetic variants that increase the risk of developing specific malaria clinical complications. Nevertheless, susceptibility to experimental CM in the mouse has been linked to host genes including Transforming Growth Factor Beta 2 (TGFB2) and Heme oxygenase-1 (HMOX1). Here, we tested whether those genes were governing the risk of progressing to CM in patients with severe malaria syndromes. METHODOLOGY/PRINCIPAL FINDINGS: We report that the clinical outcome of P. falciparum infection in a cohort of Angolan children (n = 430) correlated with nine TGFB2 SNPs that modify the risk of progression to CM as compared to other severe forms of malaria. This genetic effect was explained by two haplotypes harboring the CM-associated SNPs (Pcorrec. = 0.035 and 0.036). In addition, one HMOX1 haplotype composed of five CM-associated SNPs increased the risk of developing the CM syndrome (Pcorrec. = 0.002) and was under-transmitted to children with uncomplicated malaria (P = 0.036). Notably, the HMOX1-associated haplotype conferred increased HMOX1 mRNA expression in peripheral blood cells of CM patients (P = 0.012). CONCLUSIONS/SIGNIFICANCE: These results represent the first report on CM genetic risk factors in Angolan children and suggest the novel hypothesis that genetic variants of the TGFB2 and HMOX1 genes may contribute to confer a specific risk of developing the CM syndrome in patients with severe P. falciparum malaria. This work may provide motivation for future studies aiming to replicate our findings in larger populations and to confirm a role for these genes in determining the clinical course of malaria

A Crossed Molecular Beam and Ab-Initio Investigation of the Reaction of Boron Monoxide (BO; X²Σ⁺) with Methylacetylene (CH₃CCH; X¹A₁): Competing Atomic Hydrogen and Methyl Loss Pathways

The gas-phase reaction of boron monoxide (¹¹BO; X²Σ⁺) with methylacetylene (CH₃CCH; X¹A₁) was investigated experimentally using crossed molecular beam technique at a collision energy of 22.7 kJ mol^–1 and theoretically <i>using state of the art electronic structure calculation</i>, for the first time. The scattering dynamics were found to be indirect (complex forming reaction) and the reaction proceeded through the barrier-less formation of a van-der-Waals complex (¹¹BOC₃H₄) followed by isomerization via the addition of ¹¹BO­(X²Σ⁺) to the C1 and/or C2 carbon atom of methylacetylene through submerged barriers. The resulting ¹¹BOC₃H₄ doublet radical intermediates underwent unimolecular decomposition involving three competing reaction mechanisms via two distinct atomic hydrogen losses and a methyl group elimination. Utilizing partially deuterated methylacetylene reactants (CD₃CCH; CH₃CCD), we revealed that the initial addition of ¹¹BO­(X²Σ⁺) to the C1 carbon atom of methylacetylene was followed by hydrogen loss from the acetylenic carbon atom (C1) and from the methyl group (C3) leading to 1-propynyl boron monoxide (CH₃CC¹¹BO) and propadienyl boron monoxide (CH₂CCH¹¹BO), respectively. Addition of ¹¹BO­(X²Σ⁺) to the C1 of methylacetylene followed by the migration of the boronyl group to the C2 carbon atom and/or an initial addition of ¹¹BO­(X²Σ⁺) to the sterically less accessible C2 carbon atom of methylacetylene was followed by loss of a methyl group leading to the ethynyl boron monoxide product (HCC¹¹BO) in an overall exoergic reaction (78 ± 23 kJ mol^–1). The branching ratios of these channels forming CH₂CCH¹¹BO, CH₃CC¹¹BO, and HCC¹¹BO were derived to be 4 ± 3%, 40 ± 5%, and 56 ± 15%, respectively; these data are in excellent agreement with the calculated branching ratios using statistical RRKM theory yielding 1%, 38%, and 61%, respectively