Genotoxicity of diphenyl diselenide in bacteria and yeast

Diphenyl diselenide (DPDS) is an electrophilic reagent used in the synthesis of a variety of pharmacologically active organic selenium compounds. This may increase the risk of human exposure to the chemical at the workplace. We have determined its mutagenic potential in the Salmonella/microsome assay and used the yeast Saccharomyces cerevisiae to assay for putative genotoxicity, recombinogenicity and to determine whether DNA damage produced by DPDS is repairable. Only in exponentially growing cultures was DPDS able to induce frameshift mutations in S. typhimurium and haploid yeast and to increase crossing over and gene conversion frequencies in diploid strains of S. cerevisiae. Thus, DPDS presents a behavior similar to that of an intercalating agent. Mutants defective in excision-resynthesis repair (rad3, rad1), in error-prone repair (rad6) and in recombinational repair (rad52) showed higher than WT-sensitivity to DPDS. It appears that this compound is capable of inducing single and/or double strand breaks in DNA. An epistatic interaction was shown between rad3-e5 and rad52-1 mutant alleles, indicating that excision-resynthesis and strand-break repair may possess common steps in the repair of DNA damage induced by DPDS. DPDS was able to enhance the mutagenesis induced by oxidative mutagens in bacteria. N-acetylcysteine, a glutathione biosynthesis precursor, prevented mutagenesis induced by DPDS in yeast. We have shown that DPDS is a weak mutagen which probably generates DNA strand breaks through both its intercalating action and pro-oxidant effect.     

Effect of mouse genotype on interferon production

Upon induction with Newcastle disease virus, peritoneal macrophages derived from C57BL/6 mice produced ten times as much interferon as macrophages derived from BALB/c mice. This suggested that the alleles of theIf-1 locus are expressed in vitro by these cells. Further evidence for this was obtained by studying interferon production by peritoneal macrophages derived from seven recombinant inbred and one congenic line: in each case there was complete correlation between in vivo and in vitro phenotype: macrophages fromIf-1^l mice were low producers in vitro, and macrophages fromIf-1 ^h mice were high producers in vitro.     

SRComp: Short Read Sequence Compression Using Burstsort and Elias Omega Coding

Next-generation sequencing (NGS) technologies permit the rapid production of vast amounts of data at low cost. Economical data storage and transmission hence becomes an increasingly important challenge for NGS experiments. In this paper, we introduce a new non-reference based read sequence compression tool called SRComp. It works by first employing a fast string-sorting algorithm called burstsort to sort read sequences in lexicographical order and then Elias omega-based integer coding to encode the sorted read sequences. SRComp has been benchmarked on four large NGS datasets, where experimental results show that it can run 5–35 times faster than current state-of-the-art read sequence compression tools such as BEETL and SCALCE, while retaining comparable compression efficiency for large collections of short read sequences. SRComp is a read sequence compression tool that is particularly valuable in certain applications where compression time is of major concern.     

A differential proteomics study of cerebrospinal fluid from individuals with Niemann-Pick disease,Type C1

Niemann-Pick, type C1 (NPC1) is a fatal, neurodegenerative disease, which belongs to the family of lysosomal diseases. In NPC1, endo/lysosomal accumulation of unesterified cholesterol and sphingolipids arise from improper intracellular trafficking resulting in multi-organ dysfunction. With the proximity between the brain and cerebrospinal fluid (CSF), performing differential proteomics provides a means to shed light to changes occurring in the brain. In this study, CSF samples obtained from NPC1 individuals and unaffected controls were used for protein biomarker identification. A subset of these individuals with NPC1 are being treated with miglustat, a glycosphingolipid synthesis inhibitor. Of the 300 identified proteins, 71 proteins were altered in individuals with NPC1 compared to controls including cathepsin D, and members of the complement family. Included are a report of 10 potential markers for monitoring therapeutic treatment. We observed that pro-neuropeptide Y (NPY) was significantly increased in NPC1 individuals relative to healthy controls; however, individuals treated with miglustat displayed levels comparable to healthy controls. In further investigation, NPY levels in a NPC1 mouse model corroborated our findings. We posit that NPY could be a potential therapeutic target for NPC1 due to its multiple roles in the central nervous system such as attenuating neuroinflammation and reducing excitotoxicity.     

Scale-sensitive landscape complementation determines habitat suitability for a territorial generalist

Evaluating habitat suitability is often complex, as habitat effects may be scale‐dependent, critical resources may be spatially segregated, and resource availability may also depend on intra‐ and inter‐specific interactions. Using analyses that spanned multiple years and spatial scales, we investigated habitat requirements of a territorial generalist, the common raven Corvus corax, in a relatively pristine woodland, Bia?owie?a Forest (E Poland). We compiled data from multiple raven surveys conducted between 1985 and 2001. Ravens were regularly distributed over the entire study area but declined in density over 50% within the 16 yr interval. In the same period game and forest management significantly reduced ungulate densities and likely diminished the habitat quality with regard to food supply, especially carrion. To better understand habitat requirements of ravens we studied breeding performance in relation to three different habitat types across multiple scales: open areas, coniferous‐dominated forest, and deciduous‐dominated forest. We found a prominent dissimilarity between raven nesting and foraging habitats highlighting the importance of resource complementation for ravens. On a fine scale, large old pines were exclusively selected as nesting trees and nesting areas were generally coniferous‐dominated. However, at increasingly broader scales, coniferous habitats were negatively associated with raven reproductive success as those habitats likely provide a lower food supply. Only where the coniferous nesting areas at smaller scales were complemented with high percentages of deciduous forests and open areas at broader scales did the breeding performance increase. In addition to habitat composition, intra‐specific interactions were important determinants of reproductive performance and very successful neighbors decreased reproductive performance of a focal pair. Most of previous studies have investigated resource complementation in terms of habitat edges or proximity of complementing resource patches. Our study demonstrates that the concept of landscape complementation also applies to gradients in landscape composition and emphasizes the importance of scales and intraspecific interactions in habitat analyses.     

Presence of qacEΔ1 gene and susceptibility to a hospital biocide in clinical isolates of Pseudomonas aeruginosa resistant to antibiotics

Biocides play an important role in healthcare-associated infection control by either minimizing or preventing microorganism dissemination. This study evaluated the susceptibility of Pseudomonas aeruginosa clinical isolates to a quaternary ammonium (QAC) disinfectant and antibiotics, and verified the presence of qacEΔ1, a determinant of resistance to QAC. The disinfectant test was the Association of Official Analytical Chemists Use-Dilution Test, and polymerase chain reaction was used to examine for qacEΔ1. The qacEΔ1 gene was detected in 48% of the isolates. Eighty-eight percent of the multiresistant isolates carried qacEΔ1 gene, while 35% of the non-multiresistant isolates was positive to this gene, and multiresistance well correlated with its presence. Among isolates tested for the disinfectant, 46% showed a reduced susceptibility to the disinfectant. qacEΔ1 gene was present in 70% of the susceptible isolates to the biocide, whereas 90% of the less susceptible strains harbored this gene. Reduced susceptibility to the disinfectant was independent of presence of qacEΔ1 suggesting that it does not play an important role in biocide resistance in P. aeruginosa. As far as we know, it is the first report confirming this fact and testing with disinfectant at its in-use concentration. The evidence of less susceptible strains than the reference bacterium used in disinfectant testing, and the high percentage of qacEΔ1 gene detected are of special concern and suggests continued investigation in laboratory and in situ, not only in healthcare settings, but also in all areas of biocide usage, including different micro-organisms and biocides.     

Determination of the lysosomal hydrolase activity in blood collected on filter paper,an alternative to screen high risk populations

This study aimed to determine the enzymatic activity in dried blood samples collected on filter paper (DBS) for the diagnosis of the following diseases: Fabry, Pompe, Mucopolysaccharidosis type I (MPS I) and Mucopolysaccharosis type VI (MPS VI). DBS was used for high risk patientscreening, according to clinical suspicion. Plasma, leukocytes and cultured fibroblasts were used to confirm the diagnosis when necessary. Among the 529 DBS samples sent to the laboratory, 164 had abnormal results. Confirmatory materials of 73 individuals were rerouted. The frequency of diagnosis for lysosomal storage disorders was 5.9%. DBS is an alternative screening technique used in high risk populations, which should lead to earlier diagnosis for lysosomal storage disorders (LSDs), help patients get treatment sooner and improve the outcome of the disease.