Density functional theory based screening of ternary alkali-transition metal borohydrides: a computational material design project.

We present a computational screening study of ternary metal borohydrides for reversible hydrogen storage based on density functional theory. We investigate the stability and decomposition of alloys containing 1 alkali metal atom, Li, Na, or K (M(1)); and 1 alkali, alkaline earth or 3d/4d transition metal atom (M(2)) plus two to five (BH(4))(-) groups, i.e., M(1)M(2)(BH(4))(2-5), using a number of model structures with trigonal, tetrahedral, octahedral, and free coordination of the metal borohydride complexes. Of the over 700 investigated structures, about 20 were predicted to form potentially stable alloys with promising decomposition energies. The M(1)(Al/Mn/Fe)(BH(4))(4), (Li/Na)Zn(BH(4))(3), and (Na/K)(Ni/Co)(BH(4))(3) alloys are found to be the most promising, followed by selected M(1)(Nb/Rh)(BH(4))(4) alloys.

Candidate gene analysis of 21q22: support for S100B as a susceptibility gene for bipolar affective disorder with psychosis.

A genome-wide scan in 60 bipolar affective disorder (BPAD) affected sib-pairs (ASPs) identified linkage on chromosome 21 at 21q22 (D21S1446, NPL = 1.42, P = 0.08), a BPAD susceptibility locus supported by multiple studies. Although this linkage only approaches significance, the peak marker is located 12 Kb upstream of S100B, a neurotrophic factor implicated in the pathology of psychiatric disorders, including BPAD and schizophrenia. We hypothesized that the linkage signal at 21q22 may result from pathogenic disease variants within S100B and performed an association analysis of this gene in a collection of 125 BPAD type I trios. S100B single nucleotide polymorphisms (SNPs) rs2839350 (P = 0.022) and rs3788266 (P = 0.031) were significantly associated with BPAD. Since variants within S100B have also been associated with schizophrenia susceptibility, we reanalyzed the data in trios with a history of psychosis, a phenotype in common between the two disorders. SNPs rs2339350 (P = 0.016) and rs3788266 (P = 0.009) were more significantly associated in the psychotic subset. Increased significance was also obtained at the haplotype level. Interestingly, SNP rs3788266 is located within a consensus-binding site for Six-family transcription factors suggesting that this variant may directly affect S100B gene expression. Fine-mapping analyses of 21q22 have previously identified transient receptor potential gene melastatin 2 (TRPM2), which is 2 Mb upstream of S100B, as a possible BPAD susceptibility gene at 21q22. We also performed a family-based association analysis of TRPM2 which did not reveal any evidence for association of this gene with BPAD. Overall, our findings suggest that variants within the S100B gene predispose to a psychotic subtype of BPAD, possibly via alteration of gene expression.

Genome-wide scan of bipolar disorder and investigation of population stratification effects on linkage: support for susceptibility loci at 4q21, 7q36, 9p21, 12q24, 14q24, and 16p13.

Bipolar disorder (BPD) is a complex genetic disorder with cycling symptoms of depression and mania. Despite the extreme complexity of this psychiatric disorder, attempts to localize genes which confer vulnerability to the disorder have had some success. Chromosomal regions including 4p16, 12q24, 18p11, 18q22, and 21q21 have been repeatedly linked to BPD in different populations. Here we present the results of a whole genome scan for linkage to BPD in an Irish population. Our most significant result was at 14q24 which yielded a non-parametric LOD (NPL) score of 3.27 at the D14S588 marker with a nominal P-value of 0.0006 under a narrow (bipolar type I only) model of affection. We previously reported linkage to 14q22-24 in a subset of the families tested in this analysis. We also obtained suggestive evidence for linkage at 4q21, 9p21, 12q24, and 16p13, chromosomal regions that have all been previously linked to BPD. Additionally, we report on a novel approach to linkage analysis, STRUCTURE-Guided Linkage Analysis (SGLA), which is designed to reduce genetic heterogeneity and increase the power to detect linkage. Application of this technique resulted in more highly significant evidence for linkage of BPD to three regions including 16p13, a locus that has been repeatedly linked to numerous psychiatric disorders.

Molecular dynamics of haloalkane corral formation and surface halogenation at Si(111)-7 x 7.

Long-chain organic molecules, 1-halododecane, RX (X = Cl,Br), adsorbed on Si(111)-7 x 7 were shown to form stable dimeric corrals; type I around corner holes and type II around corner adatoms S. Dobrin et al. [Surf. Sci. Lett. 600, L43 (2006)]. Here we examine the molecular dynamics of corral formation, in which mobile physisorbed adsorbates spontaneously convert to immobile. At high coverage the mechanism gives evidence of involving collisions between mobile vertical monomers, giving types I and II immobile horizontal dimers, vD +vD -->h2 (I, II). At low coverage mobile vertical monomers collide with immobile horizontal ones to form largely type-II corrals, vD + h-->h2 (II). Thermal reaction of corrals with X = Br brominates the surface by two distinct molecular pathways, thought to have more general applicability: "daughter-mediated" reaction of vertical v(A) with a low activation energy (here Ea approximately 5 kcal mol(-1)) and "parent-mediated" reaction of horizontal h or h2 with high activation energy (here Ea = 29 kcal mol(-1)).

No causative DLL4 mutations in periodic catatonia patients from 15q15 linked families.

Two well-supported theories of schizophrenia pathogenesis are the neurotransmitter theory and the neurodevelopmental theory, suggesting, respectively, that dysregulation of neurotransmitter signaling and abnormal brain development are causative in this disease. The strongest evidence of neurotransmitter involvement are suggestions of abnormal dopamine signaling in the prefrontal cortex and one of the strongest indications of developmental abnormalities contributing to this disease is an inverse layering of the prefrontal cortex. These two theories of schizophrenia pathogenesis can be united by their involvement of the prefrontal cortex, where structural abnormalities could lead to neurochemical abnormalities. Accordingly, any gene expressed in the prefrontal cortex of developing brains is a functional candidate for schizophrenia. We have previously reported strong linkage to 15q15 (LOD = 3. 57; P = 2.6 x 10(-5)) in a collection of German multiplex families segregating the periodic catatonia subtype of schizophrenia in a nearly Mendelian fashion. A gene within our 15q15 linkage region, DLL4, is expressed in developing forebrain and produces a NOTCH4 ligand. Variants of NOTCH4 are associated with schizophrenia, thus DLL4 is both a functional as well as a positional candidate for schizophrenia. We screened this gene for mutations in three affected individuals and two unrelated controls and found two previously unreported SNPs, one non-synonymous polymorphism that changed an arganine to a histadine in Exon 7 and one synonymous polymorphism in exons. The non-synonymous SNP is a rare variant in that it was not found in 100 control chromosomes; however, it did not cosegregate with the disease in the extended family so it is not causative in this pedigree. It is unlikely that mutations in DLL4 are causative in this collection of families with linkage to 15q15.