3-(Adamantan-1-yl)-4-ethyl-1-{[4-(2-methoxyphenyl)piperazin-1-yl]methyl}-1H-1,2,4-triazole-5(4H)-thione

In the title compound, C26H37N5OS, the piperazine ring adopts a chair conformation. The triazole ring forms dihedral angles of 67.85 (9) and 59.41 (9)� with the piperazine and benzene rings, respectively, resulting in an approximate Vshaped conformation for the molecule. An intramolecular C— H...O hydrogen bond generates an S(6) ring motif. The crystal structure features C—H...n interactions, producing a two-dimensional supramolecular architecture

Relationship Between Sonic Hedgehog Protein, Brain-Derived Neurotrophic Factor and Oxidative Stress in Autism Spectrum Disorders

The etiology of autism spectrum disorders (ASD) is not well known but oxidative stress has been suggested to play a pathological role. We report here that the serum levels of Sonic hedgehog (SHH) protein and brain-derived neurotrophic factor (BDNF) might be linked to oxidative stress in ASD. By using the whole blood or polymorphonuclear leukocytes, we demonstrated that autistic children produced a significantly higher level of oxygen free radicals (OFR). In addition, we found significantly higher levels of serum SHH protein in children with mild as well as severe form of autism. We also found that the serum level of BDNF was significantly reduced in autistic children with mild form of the disorder but not with severe form of the disorder. Our findings are the first to report a correlation between SHH, BDNF and OFR in autistic children, suggesting a pathological role of oxidative stress and SHH in autism spectrum disorders

Interaction between genetic and epigenetic variation defines gene expression patterns at the asthma-associated locus 17q12-q21 in lymphoblastoid cell lines

Phenotypic variation results from variation in gene expression, which is modulated by genetic and/or epigenetic factors. To understand the molecular basis of human disease, interaction between genetic and epigenetic factors needs to be taken into account. The asthma-associated region 17q12-q21 harbors three genes, the zona pellucida binding protein 2 (ZPBP2), gasdermin B (GSDMB) and ORM1-like 3 (ORMDL3), that show allele-specific differences in expression levels in lymphoblastoid cell lines (LCLs) and CD4+ T cells. Here, we report a molecular dissection of allele-specific transcriptional regulation of the genes within the chromosomal region 17q12-q21 combining in vitro transfection, formaldehyde-assisted isolation of regulatory elements, chromatin immunoprecipitation and DNA methylation assays in LCLs. We found that a single nucleotide polymorphism rs4795397 influences the activity of ZPBP2 promoter in vitro in an allele-dependent fashion, and also leads to nucleosome repositioning on the asthma-associated allele. However, variable methylation of exon 1 of ZPBP2 masks the strong genetic effect on ZPBP2 promoter activity in LCLs. In contrast, the ORMDL3 promoter is fully unmethylated, which allows detection of genetic effects on its transcription. We conclude that the cis-regulatory effects on 17q12-q21 gene expression result from interaction between several regulatory polymorphisms and epigenetic factors within the cis-regulatory haplotype region

Noncompliance with Non-Accounting Securities Regulations and GAAP Violations

Using enforcement actions by the Securities and Exchange Commission (SEC) as a proxy for noncompliance with securities regulations, we examine whether a firm’s compliance with non-accounting laws and regulations is associated with GAAP violations. We find that firms that violate securities regulations related to non-accounting issues are more likely to report accounting restatements than control firms that comply with securities regulations. We also find that the difference between the two groups is significant only for the periods subsequent to the start of the noncompliance period but not for periods prior to this date. Our results highlight the interrelation between the accounting and compliance systems, and suggest that managers who are non-compliant with non-accounting regulations are also more likely to be non-compliant with accounting rules

Environmental and Social Disclosures and Firm Risk

ArticleWe examine the link between a firm’s environmental (E) and social (S) disclosures and measures of its risk including total, systematic, and idiosyncratic risk. While we do not find any link between a firm’s E and S disclosures and its systematic risk, we find a negative and significant association between these disclosures and a firm’s total and idiosyncratic risk. These are novel findings and are consistent with the predictions of the stakeholder theory and the resource based view of the firm suggesting that firms which make extensive and objective E and S disclosures promote corporate transparency that can help them build a positive reputation and trust with its stakeholders, which in turn can help mitigate the firm’s idiosyncratic/operational risk. These findings are important for all corporate stakeholders including managers, employees, and suppliers who have a significant economic interest in the survival and success of the firm

Ten / ninety (10 / 90) report on health research, 2003 - 2004

This comprehensive report was prepared by the Secretariat of the Global Forum for Health Research. Less than 10% of global funding for research is spent on diseases that afflict more than 90% of the world's population. The overall objective of the Global Forum is to help correct the 10/90 gap in health research and focus research efforts on the diseases and risk factors which account for the highest disease burden worldwide, yet which receive relatively little funding for research. This report urges priority-setting in health research and reviews priority-setting methodologies along with progress in measuring and closing the 10/90 gap

N-(Adamantan-1-yl)-1,2,3,4-tetrahydroisoquinoline-2-carbothioamide

In the title compound, C20H26N2S, the N-containing six-membered ring adopts a boat conformation and the dihedral angle between the thiocarbamide group and the benzene ring is 49.67 (9)°. An intramolecular C—H...S hydrogen bond generates an S(6) ring motif. The N—H group is sterically hindered and there are no significant intermolecular interactions beyond van der Waals contacts