Support for a possible schizophrenia vulnerability locus in region 5q22-31 in Irish families

In our genome scan for schizophrenia genes in 265 Irish pedigrees, marker D5S818 in 5q22 produced the second best result of the first 223 markers tested (P = 0.002). We then tested an additional 13 markers and the evidence suggests the presence of a vulnerability locus for schizophrenia in region 5q22-31. This region appears to be distinct from those chromosome 5 regions studied in two prior reports, but the same as that producing positive results in the report by Wildenauer and colleagues found elsewhere in this issue. The largest pairwise heterogeneity LOD (H-LOD) score was found with marker D5S393 (max 3.04, P = 0.0005), assuming a narrow phenotypic category, and a genetic model with intermediate heterozygotic liability. In marked contrast to the H-LOD scores from our sample with markers from the regions of interest on chromosomes 6p and 8p, expanding the disease definition to include schizophrenia spectrum or nonspectrum disorders produced substantially smaller scores, with a number of markers failing to yield positive values at any recombination fraction. Using multipoint H-LODS, the strongest evidence for linkage occurs under the narrow phenotypic definition and recessive genetic model, with a peak at marker D5S804 (max 3.35, P = 0.0002). Multipoint nonparametric linkage analysis produced a peak in the same location (max z = 2.84, P = 0.002) with the narrow phenotypic definition. This putative vulnerability locus appears to be segregating in 10-25% of the families studied, but this estimate is tentative. Comparison of individual family multipoint H-LOD scores at the regions of interest on chromosomes 6p, 8p and 5q showed that only a minority of families yield high lod scores in two or three regions.

miR-31 Dysregulation in Cystic Fibrosis Airways Contributes to Increased Pulmonary Cathepsin S Production

Rationale:
Cathepsin S (CTSS) activity is increased in bronchoalveolar lavage (BAL) fluid from patients with cystic fibrosis (CF). This activity contributes to lung inflammation via degradation of antimicrobial proteins, such as lactoferrin and members of the β-defensin family.

Objectives:
In this study, we investigated the hypothesis that airway epithelial cells are a source of CTSS, and mechanisms underlying CTSS expression in the CF lung.

Methods:
Protease activity was determined using fluorogenic activity assays. Protein and mRNA expression were analyzed by ELISA, Western blotting, and reverse-transcriptase polymerase chain reaction.Measurements and Main Results: In contrast to neutrophil elastase, CTSS activity was detectable in 100% of CF BAL fluid samples from patients without Pseudomonas aeruginosa infection. In this study, we identified epithelial cells as a source of pulmonary CTSS activity with the demonstration that CF airway epithelial cells express and secrete significantly more CTSS than non-CF control cells in the absence of proinflammatory stimulation. Furthermore, levels of the transcription factor IRF-1 correlated with increased levels of its target gene CTSS. We discovered that miR-31, which is decreased in the CF airways, regulates IRF-1 in CF epithelial cells. Treating CF bronchial epithelial cells with a miR-31 mimic decreased IRF-1 protein levels with concomitant knockdown of CTSS expression and secretion.

Conclusions:
The miR-31/IRF-1/CTSS pathway may play a functional role in the pathogenesis of CF lung disease and may open up new avenues for exploration in the search for an effective therapeutic target.

Genomic Resources Notes Accepted 1 June 2015 - 31 July 2015

This article documents the public availability of (i) microbiomes in diet and gut of larvae from the dipteran Dilophus febrilis using massive parallel sequencing, (ii) SNP and SSR discovery and characterization in the transcriptome of the Atlantic mackerel (Scomber scombrus, L) and (iii) assembled transcriptome for an endangered, endemic Iberian cyprinid fish (Squalius pyrenaicus).

Photoionization cross sections for the trans-iron element Se + from 18 to 31 eV

Absolute photoionization cross-section calculations are presented for Se + using large-scale close-coupling calculations within the Breit--Pauli and Dirac--Coulomb R -matrix approximations. The results from our theoretical work are compared with recent measurements (Esteves 2010 PhD Thesis publication number AAI3404727, University of Reno, NV, USA; Sterling et al 2011 J. Phys. B: At. Mol. Opt. Phys. 44 025701; Esteves et al 2011 Phys. Rev. A 84 013406) made at the advanced light source (ALS) radiation facility in Berkeley, CA, USA. We report on results for the photon energy range 18.0--31.0 eV, which spans the ionization thresholds of the 4 S o 3/2 ground state and the low-lying 2 D o 5/2,3/2 and 2 P o 3/2,1/2 metastable states. Metastable fractions are inferred from our present work. Resonance energies and quantum defects of the prominent Rydberg resonances series identified in the spectra are compared for the 4p → n d transitions with the recent ALS experimental measurements made on this complex trans-iron element.

Experimental and theoretical photoionization cross sections for Se + from 18 eV to 31 eV

Absolute Se photoionization cross-section measurements and Dirac-Coulomb R -matrix calculations are reported for the photon energy range 18.0 eV – 31.0 eV, which spans the ionization thresholds of the 4 S 0 3/2 ground state and the low-lying 2 D 0 3/2,5/2 and 2 P 0 1/2,3/2 metastable states. The determination of the photoionization and recombination properties of n -capture element ions is motivated by their astrophysical detection and the importance of their elemental abundances in testing theories of nucleosynthesis and stellar structure.