A new mechanism for the aerobic catabolism of dimethyl sulfide.

Aerobic degradation of dimethyl sulfide (DMS), previously described for thiobacilli and hyphomicrobia, involves catabolism to sulfide via methanethiol (CH3SH). Methyl groups are sequentially eliminated as HCHO by incorporation of O2 catalyzed by DMS monooxygenase and methanethiol oxidase. H2O2 formed during CH3SH oxidation is destroyed by catalase. We recently isolated Thiobacillus strain ASN-1, which grows either aerobically or anaerobically with denitrification on DMS. Comparative experiments with Thiobacillus thioparus T5, which grows only aerobically on DMS, indicate a novel mechanism for aerobic DMS catabolism by Thiobacillus strain ASN-1. Evidence that both organisms initially attacked the methyl group, rather than the sulfur atom, in DMS was their conversion of ethyl methyl sulfide to ethanethiol. HCHO transiently accumulated during the aerobic use of DMS by T. thioparus but not with Thiobacillus strain ASN-1. Catalase levels in cells grown aerobically on DMS were about 100-fold lower in Thiobacillus strain ASN-1 than in T. thioparus T5, suggesting the absence of H2O2 formation during DMS catabolism. Also, aerobic growth of T. thioparus T5 on DMS was blocked by the catalase inhibitor 3-amino-1,2,4-triazole whereas that of Thiobacillus strain ASN-1 was not. Methyl butyl ether, but not CHCl3, blocked DMS catabolism by T. thioparus T5, presumably by inhibiting DMS monooxygenase and perhaps methanethiol oxidase. In contrast, DMS metabolism by Thiobacillus strain ASN-1 was unaffected by methyl butyl ether but inhibited by CHCl3. DMS catabolism by Thiobacillus strain ASN-1 probably involves methyl transfer to a cobalamin carrier and subsequent oxidation as folate-bound intermediates.     

Marker-assisted introgression using non-unique marker alleles I: selection on the presence of linked marker alleles

This paper investigates marker-assisted introgression of a major gene into an outbred line, where identification of the introgressed gene is incomplete because marker alleles are not unique to the base populations (the same marker allele can occur in both donor and recipient population). Those markers are used to identify the introgressed allele as well as the background genotype. The effect of using those markers, as if they were completely informative on the retention of the introgressed allele, was examined over five generations of backcrossing by using a single marker or a marker bracket for different starting frequencies of the marker alleles. Results were calculated by using both a deterministic approach, where selection is only for the desired allele, and by a stochastic approach, where selection is also on background genotype. When marker allele frequencies in donor and recipient population diverged from 1 and 0 (using a diallelic marker), the ability to retain the desired allele rapidly declined. Marker brackets performed notably better than single markers. If selection on background marker genotype was applied, the desired allele could be lost even more quickly than expected at random because the chance that the allele, which is common in the donor line, is present on the locus identifying the introgressed allele and is surrounded by alleles common in the recipient line on the background marker loci, will descend from the donor line (double recombination has taken place), is a lot smaller than the chance that this allele will stem from the recipient line (in which the allele occurs in low frequency). Marker brackets again performed better. Preselection against marker homozygotes (producing uninformative gametes) gave a slightly better retention of the introgressed allele.     

Memory keeps you at home: a mechanistic model for home range emergence

Despite its central place in animal ecology no general mechanistic movement model with an emergent home-range pattern has yet been proposed. Random walk models, which are commonly used to model animal movement, show diffusion instead of a bounded home range and therefore require special modifications. Current approaches for mechanistic modeling of home ranges apply only to a limited set of taxa, namely territorial animals and/or central place foragers. In this paper we present a more general mechanistic movement model based on a biased correlated random walk, which shows the potential for home-range behavior. The model is based on an animal tracking a dynamic resource landscape, using a biologically plausible two-part memory system, i.e. a reference- and a working-memory. Our results show that by adding these memory processes the random walker produces home-range behavior as it gains experience, which also leads to more efficient resource use. Interestingly, home-range patterns, which we assessed based on home-range overlap and increase in area covered with time, require the combined action of both memory components to emerge. Our model has the potential to predict home-range size and can be used for comparative analysis of the mechanisms shaping home-range patterns.     

Heritability in the genomics era--concepts and misconceptions

Heritability allows a comparison of the relative importance of genes and environment to the variation of traits within and across populations. The concept of heritability and its definition as an estimable, dimensionless population parameter was introduced by Sewall Wright and Ronald Fisher nearly a century ago. Despite continuous misunderstandings and controversies over its use and application, heritability remains key to the response to selection in evolutionary biology and agriculture, and to the prediction of disease risk in medicine. Recent reports of substantial heritability for gene expression and new estimation methods using marker data highlight the relevance of heritability in the genomics era.     

Interaction of the HIV-1 frameshift signal with the ribosome

Ribosomal frameshifting on viral RNAs relies on the mechanical properties of structural elements, often pseudoknots and more rarely stem-loops, that are unfolded by the ribosome during translation. In human immunodeficiency virus (HIV)-1 type B a long hairpin containing a three-nucleotide bulge is responsible for efficient frameshifting. This three-nucleotide bulge separates the hairpin in two domains: an unstable lower stem followed by a GC-rich upper stem. Toeprinting and chemical probing assays suggest that a hairpin-like structure is retained when ribosomes, initially bound at the slippery sequence, were allowed multiple EF-G catalyzed translocation cycles. However, while the upper stem remains intact the lower stem readily melts. After the first, and single step of translocation of deacylated tRNA to the 30 S P site, movement of the mRNA stem-loop in the 5′ direction is halted, which is consistent with the notion that the downstream secondary structure resists unfolding. Mechanical stretching of the hairpin using optical tweezers only allows clear identification of unfolding of the upper stem at a force of 12.8 ± 1.0 pN. This suggests that the lower stem is unstable and may indeed readily unfold in the presence of a translocating ribosome.     

Replication study of candidate genes for cognitive abilities: the Lothian Birth Cohort 1936

As the proportion of older people in societies has increased, research into the determinants of cognitive ageing has risen in importance. Genetic influences account for over 50% of the variance in adult cognitive abilities. Previous studies on cognition and illnesses with cognitive impairments have identified single nucleotide polymorphisms ( SNPs) within candidate genes that might influence cognition or age-related cognitive change. This study investigated 10 candidate genes in over 1000 Scots: the Lothian Birth Cohort 1936 (LBC1936). These participants were tested on general cognitive ability (Scottish Mental Survey 1947) at age 11. At mean age 70, they completed the same general cognitive ability test and a battery of diverse cognitive tests. Nineteen SNPs in 10 genes previously associated with cognition, Alzheimer's disease or autism were genotyped in 1063 individuals. The genes include BDNF, COMT, DISC1, KL, NCSTN, PPP1R1B, PRNP, SHANK3, SORL1 and WRN . Linear regression analysis investigated the additive effect of each SNP on the cognitive variables, covarying for gender and age. Childhood cognitive ability was also included as a covariate to identify associations specifically with cognitive ageing. Certain SNPs reached the conventional significance threshold for association with cognitive traits or cognitive ageing in LBC1936 ( P   <   0.05). No SNPs reached the Bonferroni-level of significance (all P   >   0.0015). Of the 10 genes, we discuss that COMT , KL , PRNP, PPP1R1B, SORL1 and WRN especially merit further attention for association with cognitive ability and/or age-related cognitive change. All results are also presented so that they are valuable for future meta-analyses of candidate genes for cognition.     

A genome scan for quantitative trait loci in a wild population of red deer (Cervus elaphus)

Recent empirical evidence indicates that although fitness and fitness components tend to have low heritability in natural populations, they may nonetheless have relatively large components of additive genetic variance. The molecular basis of additive genetic variation has been investigated in model organisms but never in the wild. In this article we describe an attempt to map quantitative trait loci (QTL) for birth weight (a trait positively associated with overall fitness) in an unmanipulated, wild population of red deer (Cervus elaphus). Two approaches were used: interval mapping by linear regression within half-sib families and a variance components analysis of a six-generation pedigree of >350 animals. Evidence for segregating QTL was found on three linkage groups, one of which was significant at the genome-wide suggestive linkage threshold. To our knowledge this is the first time that a QTL for any trait has been mapped in a wild mammal population. It is hoped that this study will stimulate further investigations of the genetic architecture of fitness traits in the wild.     

Inhalation Therapy

Joint Accord on the Role of Respiratory (Inhalation) Therapy Personnel in Airway Management and Endotracheal Intubation endorsed by the California Medical Association, the California Hospital Association, the California Society for Respiratory Therapy, the California Society of Anesthesiologists and the California Thoracic Society.