1H, 13C, and 15N resonance assignments for the tandem PHD finger motifs of human CHD4

The plant homeodomain (PHD) zinc finger is a structural motif of about 40–60 amino acid residues found in many eukaryotic proteins that are involved in chromatin-mediated gene regulation. The human chromodomain helicase DNA binding protein 4 (CHD4) is a multi-domain protein that harbours, at its N-terminal end, a pair of PHD finger motifs (dPHD) connected by a ~30 amino acid linker. This tandem PHD motif is thought to be involved in targeting CHD4 to chromatin via its interaction with histone tails. Here we report the 1H, 13C and 15N backbone and side-chain resonance assignment of the entire dPHD by heteronuclear multidimensional NMR spectroscopy. These assignments provide the starting point for the determination of the structure, dynamics and histone-binding properties of this tandem domain pair

Identification of genes expressed by immune cells of the colon that are regulated by colorectal cancer-associated variants.

A locus on human chromosome 11q23 tagged by marker rs3802842 was associated with colorectal cancer (CRC) in a genome-wide association study; this finding has been replicated in case-control studies worldwide. In order to identify biologic factors at this locus that are related to the etiopathology of CRC, we used microarray-based target selection methods, coupled to next-generation sequencing, to study 103 kb at the 11q23 locus. We genotyped 369 putative variants from 1,030 patients with CRC (cases) and 1,061 individuals without CRC (controls) from the Ontario Familial Colorectal Cancer Registry. Two previously uncharacterized genes, COLCA1 and COLCA2, were found to be co-regulated genes that are transcribed from opposite strands. Expression levels of COLCA1 and COLCA2 transcripts correlate with rs3802842 genotypes. In colon tissues, COLCA1 co-localizes with crystalloid granules of eosinophils and granular organelles of mast cells, neutrophils, macrophages, dendritic cells and differentiated myeloid-derived cell lines. COLCA2 is present in the cytoplasm of normal epithelial, immune and other cell lineages, as well as tumor cells. Tissue microarray analysis demonstrates the association of rs3802842 with lymphocyte density in the lamina propria (p = 0.014) and levels of COLCA1 in the lamina propria (p = 0.00016) and COLCA2 (tumor cells, p = 0.0041 and lamina propria, p = 6 × 10(-5)). In conclusion, genetic, expression and immunohistochemical data implicate COLCA1 and COLCA2 in the pathogenesis of colon cancer. Histologic analyses indicate the involvement of immune pathways

Effects of Air Pollutants on Childhood Asthma

Epidemiologic studies have suggested the association between environmental exposure to volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) and the increased risk of incurring asthma. Yet there is little data regarding the relationship between personal exposure to air pollution and the incidence of asthma in children. This study was designed to evaluate the effect of exposure to air pollution on children with asthma by using exposure biomarkers. We assessed the exposure level to VOCs by measuring urinary concentrations of hippuric acid and muconic acid, and PAHs by 1-OH pyrene and 2-naphthol in 30 children with asthma and 30 children without asthma (control). The mean level of hippuric acid was 0.158 ± 0.169 µmol/mol creatinine in the asthma group and 0.148 ± 0.249 µmol/mol creatinine in the control group, with no statistical significance noted (p=0.30). The mean concentration of muconic acid was higher in the asthma group than in the control group (7.630 ± 8.915 µmol/mol creatinine vs. 3.390 ± 4.526 µmol/mol creatinine p=0.01). The mean level of urinary 1-OHP was higher in the asthma group (0.430 ± 0.343 µmol/mol creatinine) than the control group (0.239 ± 0.175 µmol/mol creatinine), which was statistically significant (p=0.03). There was no difference in the mean concentration of 2-NAP between the two groups (9.864 ± 10.037 µmol/mol in the asthma group vs. 9.157 ± 9.640 µmol/mol in the control group, p=0.96). In conclusion, this study suggests that VOCs and PAHs have some role in asthma

Recommendations for the treatment of epilepsy in adult patients in general practice in Belgium: an update

In 2008, a group of Belgian epilepsy experts published recommendations for antiepileptic drug (AED) treatment of epilepsies in adults and children. Selection of compounds was based on the registration and reimbursement status in Belgium, the level of evidence for efficacy, common daily practice and the personal views and experiences of the authors. In November 2011 the validity of these recommendations was reviewed by the same group of Belgian epilepsy experts who contributed to the preparation of the original paper. The recommendations made in 2008 for initial monotherapy in paediatric patients were still considered to be valid, except for the first choice treatment for childhood absence epilepsy. This update therefore focuses on the treatment recommendations for initial monotherapy and add-on treatment in adult patients. Several other relevant aspects of treatment with AEDs are addressed, including considerations for optimal combination of AEDs (rational polytherapy), pharmacokinetic properties, pharmacodynamic and pharmacokinetic interaction profile, adverse effects, comorbidity, treatment of elderly patients, AED treatment during pregnancy, and generic substitution of AEDs

Sources of pro-cyclicality in east Asian financial systems

Procyclicality is a normal feature of economic systems, but financial sector weaknesses can exacerbate it sufficiently to pose a threat to macroeconomic and financial stability. These include shortcomings in bank risk management and governance, in supervision and in terms of dependence on volatile sources of funds. The paper tests econometrically for the importance of such features leading to pro-cyclicality in the financial systems of 11 East Asian countries. This analysis makes it possible to identify specific policy measures for East Asian countries that could limit the extent to which financial systems exacerbate pro-cyclicality

International Veterinary Epilepsy Task Force Consensus Proposal: Outcome of therapeutic interventions in canine and feline epilepsy

Common criteria for the diagnosis of drug resistance and the assessment of outcome are needed urgently as a prerequisite for standardized evaluation and reporting of individual therapeutic responses in canine epilepsy. Thus, we provide a proposal for the definition of drug resistance and partial therapeutic success in canine patients with epilepsy. This consensus statement also suggests a list of factors and aspects of outcome, which should be considered in addition to the impact on seizures. Moreover, these expert recommendations discuss criteria which determine the validity and informative value of a therapeutic trial in an individual patient and also suggest the application of individual outcome criteria. Agreement on common guidelines does not only render a basis for future optimization of individual patient management, but is also a presupposition for the design and implementation of clinical studies with highly standardized inclusion and exclusion criteria. Respective standardization will improve the comparability of findings from different studies and renders an improved basis for multicenter studies. Therefore, this proposal provides an in-depth discussion of the implications of outcome criteria for clinical studies. In particular ethical aspects and the different options for study design and application of individual patient-centered outcome criteria are considered