Tuberculosis vaccine strain _Mycobacterium bovis_ BCG Russia is a natural _recA_ mutant

The current tuberculosis vaccine is a live vaccine derived from _Mycobacterium bovis_ and attenuated by serial _in vitro_ passaging. All vaccine substrains in use stem from one source, strain Bacille Calmette-Guérin. However, they differ in regions of genomic deletions, antigen expression levels, immunogenicity, and protective efficacy. As a RecA phenotype increases genetic stability and may contribute restricting the ongoing evolution of the various BCG substrains, we aimed to inactivate _recA_ by allelic replacement in BCG vaccine strains representing different phylogenetic lineages (Pasteur, Frappier, Denmark, Russia). Homologous gene replacement was successful in three out of four strains. However, only illegitimate recombination was observed in BCG substrain Russia. Sequence analyses of _recA_ revealed that a single nucleotide insertion in the 5' part of _recA_ led to a translational frameshift with an early stop codon making BCG Russia a natural _recA_ mutant. At the protein level BCG Russia failed to express RecA. According to phylogenetic analyses BCG Russia is an ancient vaccine strain most closely related to the parental _M. bovis_. Our data suggest that _recA_ inactivation in BCG Russia occurred early and is in part responsible for its high degree of genomic stability, resulting in a substrain that has less genetic alterations than other vaccine substrains with respect to _M. bovis_ AF2122/97 wild type

Tuberculosis vaccine strain Mycobacterium bovis BCG Russia is a natural recA mutant

BACKGROUND: The current tuberculosis vaccine is a live vaccine derived from Mycobacterium bovis and attenuated by serial in vitro passaging. All vaccine substrains in use stem from one source, strain Bacille Calmette-Guérin. However, they differ in regions of genomic deletions, antigen expression levels, immunogenicity, and protective efficacy. RESULTS: As a RecA phenotype increases genetic stability and may contribute restricting the ongoing evolution of the various BCG substrains while maintaining their protective efficacy, we aimed to inactivate recA by allelic replacement in BCG vaccine strains representing different phylogenetic lineages (Pasteur, Frappier, Denmark, Russia). Homologous gene replacement was achieved successfully in three out of four strains. However, only illegitimate recombination was observed in BCG substrain Russia. Sequence analyses of recA revealed that a single nucleotide insertion in the 5' part of recA led to a translational frameshift with an early stop codon making BCG Russia a natural recA mutant. At the protein level BCG Russia failed to express RecA. CONCLUSION: According to phylogenetic analyses BCG Russia is an ancient vaccine strain most closely related to the parental M. bovis. We hypothesize that recA inactivation in BCG Russia occurred early and is in part responsible for its high degree of genomic stability, resulting in a substrain that has less genetic alterations than other vaccine substrains with respect to M. bovis AF2122/97 wild-type

Integrating invasion and disease in the risk assessment of live bird trade.

AimInternational trade in plants and animals generates significant economic benefits. It also leads to substantial unintended impacts when introduced species become invasive, causing environmental disturbance or transmitting diseases that affect people, livestock, other wildlife or the environment. Policy responses are usually only implemented after these species become established and damages are already incurred. International agreements to control trade are likewise usually based on selection of species with known impacts. We aim to further develop quantitative invasive species risk assessment for bird imports and extend the tool to explicitly address disease threats.LocationUnited States of America.MethodsWe use a two-step approach for rapid risk assessment based on the expected biological risks due to both the environmental and health impact of a potentially invasive wildlife species in trade. We assess establishment probability based on a model informed by historical observations and then construct a model of emerging infectious disease threat based on economic and ecological characteristics of the exporting country.ResultsWe illustrate how our rapid assessment tool can be used to identify high-priority species for regulation based on a combination of the threat they pose for becoming established and vectoring emerging infectious diseases.Main conclusionsOur approach can be executed for a species in a matter of days and is nested in an economic decision-making framework for determining whether the biological risk is justified by trade benefits

Opportunities for using spatial property assessment data in air pollution exposure assessments

BACKGROUND: Many epidemiological studies examining the relationships between adverse health outcomes and exposure to air pollutants use ambient air pollution measurements as a proxy for personal exposure levels. When pollution levels vary at neighbourhood levels, using ambient pollution data from sparsely located fixed monitors may inadequately capture the spatial variation in ambient pollution. A major constraint to moving toward exposure assessments and epidemiological studies of air pollution at a neighbourhood level is the lack of readily available data at appropriate spatial resolutions. Spatial property assessment data are widely available in North America and may provide an opportunity for developing neighbourhood level air pollution exposure assessments. RESULTS: This paper provides a detailed description of spatial property assessment data available in the Pacific Northwest of Canada and the United States, and provides examples of potential applications of spatial property assessment data for improving air pollution exposure assessment at the neighbourhood scale, including: (1) creating variables for use in land use regression modelling of neighbourhood levels of ambient air pollution; (2) enhancing wood smoke exposure estimates by mapping fireplace locations; and (3) using data available on individual building characteristics to produce a regional air pollution infiltration model. CONCLUSION: Spatial property assessment data are an extremely detailed data source at a fine spatial resolution, and therefore a source of information that could improve the quality and spatial resolution of current air pollution exposure assessments

Olfactory sensitivity to steroid glucuronates in Mozambique tilapia suggests two distinct and specific receptors for pheromone detection

Cichlids offer an exciting opportunity to understand vertebrate speciation; chemical communication could be one of the drivers of African cichlid radiation. Chemical signals mediate key aspects in the lives of vertebrates and often are species specific. Dominant male Mozambique tilapia [Oreochromis mossambicus (Peters 1852)] release a sex pheromone, 5 beta-pregnan-3 alpha,17 alpha,20 beta-triol 3-glucuronate and its 20 alpha-epimer, via their urine. The objective of this study was to assess the sensitivity, specificity and versatility of the olfactory system of O. mossambicus to other steroids and their conjugates using the electro-olfactogram. Oreochromis mossambicus was sensitive to several 3-glucuronidated steroids, but did not respond to prostaglandins, unconjugated steroids or 17- or 20-conjugated steroids. Stimulation of the olfactory epithelium with increasing concentrations (1 pmol l(-1) to 10 mu mol l(-1)) of 5 beta-pregnan-3 alpha, 17 alpha,20 beta-triol 3-glucuronate, 5 beta-pregnan-3 alpha, 17 alpha,20 beta-triol 3-glucuronate, 3 alpha,17 alpha-dihydroxy-5 beta-pregnan-20-one 3-glucuronate, etiocholanolone 3 alpha-glucuronate and 17 beta-estradiol 3-glucuronate produced characteristic sigmoidal concentration-response curves. However, tilapia were most sensitive to 17 beta-estradiol-3-glucuronate, which also had the lowest apparent EC50 and maximal response amplitude. Cross-adaptation and binary mixture experiments suggested that 5 beta,3 alpha-reduced pregnan-and androstan-3-glucuronates share (a) common olfactory receptor(s), whereas 17 beta-estradiol 3-glucuronate is detected via (a) distinct olfactory receptor(s). In conclusion, the Mozambique tilapia has evolved high olfactory sensitivity and specificity to 3-glucuronidated steroids through two distinct olfactory receptor types; one detecting a male sex pheromone and a second detecting 17 beta-estradiol 3-glucuronate, a putative female-derived signal. However, O. mossambicus differs markedly in its olfactory perception from the more recently derived East African cichlid Astatotilapia burtoni, suggesting that chemical communication could, indeed, be involved in speciation.Science and Technology Foundation (FCT), Portugal [POCI/BIA-BDE/55463/2004]; FCT [SFRH/BD/46192/2008]info:eu-repo/semantics/publishedVersio

Quantifying inbreeding avoidance through extra-pair reproduction

© 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.Peer reviewedPublisher PD

Learning to Create Jazz Melodies Using Deep Belief Nets

We describe an unsupervised learning technique to facilitate automated creation of jazz melodic improvisation over chord sequences. Specifically we demonstrate training an artificial improvisation algorithm based on unsupervised learning using deep belief nets, a form of probabilistic neural network based on restricted Boltzmann machines. We present a musical encoding scheme and specifics of a learning and creational method. Our approach creates novel jazz licks, albeit not yet in real-time. The present work should be regarded as a feasibility study to determine whether such networks could be used at all. We do not claim superiority of this approach for pragmatically creating jazz

Long-term maternal effect on offspring immune response in song sparrows Melospiza melodia

Knowledge of the causes of variation in host immunity to parasitic infection and the time-scales over which variation persists, is integral to predicting the evolutionary and epidemiological consequences of host–parasite interactions. It is clear that offspring immunity can be influenced by parental immune experience, for example, reflecting transfer of antibodies from mothers to young offspring. However, it is less clear whether such parental effects persist or have functional consequences over longer time-scales, linking a parent's previous immune experience to future immune responsiveness in fully grown offspring. We used free-living song sparrows (Melospiza melodia) to quantify long-term effects of parental immune experience on offspring immune response. We experimentally vaccinated parents with a novel antigen and tested whether parental vaccination influenced the humoral antibody response mounted by fully grown offspring hatched the following year. Parental vaccination did not influence offspring baseline antibody titres. However, offspring of vaccinated mothers mounted substantially stronger antibody responses than offspring of unvaccinated mothers. Antibody responses did not differ between offspring of vaccinated and unvaccinated fathers. These data demonstrate substantial long-term effects of maternal immune experience on the humoral immune response of fully grown offspring in free-living birds

Large-scale genomics unveils the genetic architecture of psychiatric disorders

Family study results are consistent with genetic effects making substantial contributions to risk of psychiatric disorders such as schizophrenia, yet robust identification of specific genetic variants that explain variation in population risk had been disappointing until the advent of technologies that assay the entire genome in large samples. We highlight recent progress that has led to a better understanding of the number of risk variants in the population and the interaction of allele frequency and effect size. The emerging genetic architecture implies a large number of contributing loci (that is, a high genome-wide mutational target) and suggests that genetic risk of psychiatric disorders involves the combined effects of many common variants of small effect, as well as rare and de novo variants of large effect. The capture of a substantial proportion of genetic risk facilitates new study designs to investigate the combined effects of genes and the environment