RTS,S/AS02A malaria vaccine does not induce parasite CSP T cell epitope selection and reduces multiplicity of infection

Objective: The candidate malaria vaccine RTS,S/AS02A is a recombinant protein containing part of the circumsporozoite protein (CSP) sequence of Plasmodium falciparum, linked to the hepatitis B surface antigen and formulated in the proprietary adjuvant system AS02A. In a recent trial conducted in children younger than age five in southern Mozambique, the vaccinedemonstrated significant and sustained efficacy against both infection and clinical disease. In a follow-up study to the main trial, breakthrough infections identified in the trial were examined to determine whether the distribution of csp sequences was affected by the vaccine and to measure the multiplicity of infecting parasite genotypes. Design: P. falciparum DNA from isolates collected during the trial was used for genotype studies. Setting: The main trial was carried out in the Manhiça district, Maputo province, Mozambique, between April 2003 and May 2004. Participants: Children from the two cohorts of the main trial provided parasite isolates as follows: children from Cohort 1 who were admitted to hospital with clinical malaria; children from Cohort 1 who were parasite-positive in a cross-sectional survey at study month 8.5; children from Cohort 2 identified as parasite-positive during follow-up by active detection of infection. Outcome: Divergence of DNA sequence encoding the CSP T cell-epitope region sequence from that of the vaccine sequence was measured in 521 isolates. The number of distinct P. falciparum genotypes was also determined. Results: We found no evidence that parasite genotypes from children in the RTS,S/AS02A arm were more divergent than those receiving control vaccines. For Cohort 1 (survey at studymonth 8.5) and Cohort 2, infections in the vaccine group contained significantly fewer genotypes than those in the control group, (p 1/4 0.035, p 1/4 0.006), respectively, for the two cohorts. This was not the case for children in Cohort 1 who were admitted to hospital (p 1/4 0.478). Conclusions: RTS,S/AS02A did not select for genotypes encoding divergent T cell epitopes in the C-terminal region of CSP in this trial. In both cohorts, there was a modest reduction in the mean number of parasite genotypes harboured by vaccinated children compared with controls, but only among those with asymptomatic infections.

Enhanced polyhydroxyalkanoates accumulation by Halomonas spp. in artificial biofilms of alginate beads.

Microbial mats are complex but stable, multi-layered and multi-functional biofilms, which are the most frequent bacterial formations in nature. The functional strategies and physiological versatility of the bacterial populations growing in microbial mats allow bacteria to resist changing conditions within their environment. One of these strategies is the accumulation of carbon- and energy-rich polymers that permit the recovery of metabolic activities when favorable conditions are restored. In the present study, we systematically screened microbial mats for bacteria able to accumulate large amounts of the ester carbon polymers polyhydroxyalkanoates (PHA). Several of these strains were isolated from Ebro Delta microbial mats and their ability to accumulate PHA up to 40-60 % of their dry weight was confirmed. According to two identification approaches (16S rRNA and ropD genes), these strains were identified as Halomonas alkaliphila (MAT-7, -13, -16), H. neptunia (MAT-17), and H. venusta (MAT-28). To determine the mode of growth yielding maximum PHA accumulation, these three different species were cultured in an artificial biofilm in which the cells were immobilized on alginate beads. PHA accumulation by cells that had detached from the biofilm was compared with that of their planktonic counterparts. Experiments in different culture media showed that PHA accumulation, measured as the relative fluorescence intensity after 48 h of incubation at 30 °C, was higher in immobilized than in planktonic cells, with the exception of cells growing in 5 % NaCl, in which PHA accumulation was drastically lower in both. Therefore, for obtaining high PHA concentrations, the use of immobilized cells may be a good alternative to the PHA accumulation by bacteria growing in the classical, planktonic mode. From the ecological point of view, increased PHA accumulation in detached cells from biofilms would be a natural strategy to improve bacterial dispersion capacity and, consequently, to increase survival in stressed environments.

Mecánica de la succión: comparación entre la lactancia artificial y la lactancia materna

Introducción: Hay poco conocimiento sobre la similitud de la mecánica entre la lactancia materna y la artificial. Evaluamos la mecánica de la succión en neonatos con lactancia materna exclusiva, lactancia artificial exclusiva y lactancia mixta. Nuestra hipótesis fue que el patrón fisiológico de los movimientos de succión varía según el tipo de alimentación. Según esta hipótesis, los niños con lactancia materna exclusiva realizan unos movimientos al mamar distintos a los de la succión de una tetina, realizados por niños con lactancia artificial. Los niños con lactancia mixta mezclan ambos tipos de movimientos de succión. Métodos: Estudio transversal de neonatos de 21-28 días de edad con lactancia materna o artificial exclusiva (124 parejas madre-hijo), y ensayo de campo, abierto, cruzado y aleatorizado, realizado en neonatos de 21-28 días (110 parejas madre-hijo) y en lactantes de 3-5 meses de edad (125 parejas madre-hijo) con lactancia mixta. Las variables principales fueron los movimientos de succión y las pausas. Resultados: Los neonatos de 21-28 días de edad alimentados con lactancia artificial exclusiva mostraron un menor número de movimientos de succión y el mismo número de pausas, pero de mayor duración, que los neonatos con lactancia materna exclusiva. Entre los niños que recibieron lactancia mixta, el número de movimientos de succión al recibir alimentación con biberón fue similar y las pausas menos numerosas y de menor duración respecto a lo observado al amamantar, tanto a los 21-28 días como a los 3-5 meses de edad. En este grupo de lactancia mixta, la cifra media de tomas de lactancia materna fue de 5,83 ± 1,93 a los 21-28 días de vida y de 4,42 ± 1,67 a los 3-5 meses de edad. En el análisis de equivalencia, realizado sobre los niños que recibieron lactancia mixta, el intervalo de confianza del 95% de la razón de movimientos con lactancia artificial y con lactancia materna se situó fuera del rango de equivalencia, indicó un número de movimientos de succión menor en un 5,9-8,7% al tomar el biberón, así como un menor número de pausas y una duración más breve de ellas en este mismo grupo. Conclusiones: En la lactancia mixta, la comparación entre las tomas de biberón y las de pecho se situó fuera del rango de equivalencia, aunque las diferencias fueron pequeñas. Los niños con lactancia mixta mezclan ambos tipos de movimientos (lactancia materna y lactancia artificial) durante la fase de aprendizaje y adoptan su propio patrón.

Mecánica de la succión: comparación entre la lactancia artificial y la lactancia materna

Introducción: Hay poco conocimiento sobre la similitud de la mecánica entre la lactancia materna y la artificial. Evaluamos la mecánica de la succión en neonatos con lactancia materna exclusiva, lactancia artificial exclusiva y lactancia mixta. Nuestra hipótesis fue que el patrón fisiológico de los movimientos de succión varía según el tipo de alimentación. Según esta hipótesis, los niños con lactancia materna exclusiva realizan unos movimientos al mamar distintos a los de la succión de una tetina, realizados por niños con lactancia artificial. Los niños con lactancia mixta mezclan ambos tipos de movimientos de succión. Métodos: Estudio transversal de neonatos de 21-28 días de edad con lactancia materna o artificial exclusiva (124 parejas madre-hijo), y ensayo de campo, abierto, cruzado y aleatorizado, realizado en neonatos de 21-28 días (110 parejas madre-hijo) y en lactantes de 3-5 meses de edad (125 parejas madre-hijo) con lactancia mixta. Las variables principales fueron los movimientos de succión y las pausas. Resultados: Los neonatos de 21-28 días de edad alimentados con lactancia artificial exclusiva mostraron un menor número de movimientos de succión y el mismo número de pausas, pero de mayor duración, que los neonatos con lactancia materna exclusiva. Entre los niños que recibieron lactancia mixta, el número de movimientos de succión al recibir alimentación con biberón fue similar y las pausas menos numerosas y de menor duración respecto a lo observado al amamantar, tanto a los 21-28 días como a los 3-5 meses de edad. En este grupo de lactancia mixta, la cifra media de tomas de lactancia materna fue de 5,83 ± 1,93 a los 21-28 días de vida y de 4,42 ± 1,67 a los 3-5 meses de edad. En el análisis de equivalencia, realizado sobre los niños que recibieron lactancia mixta, el intervalo de confianza del 95% de la razón de movimientos con lactancia artificial y con lactancia materna se situó fuera del rango de equivalencia, indicó un número de movimientos de succión menor en un 5,9-8,7% al tomar el biberón, así como un menor número de pausas y una duración más breve de ellas en este mismo grupo. Conclusiones: En la lactancia mixta, la comparación entre las tomas de biberón y las de pecho se situó fuera del rango de equivalencia, aunque las diferencias fueron pequeñas. Los niños con lactancia mixta mezclan ambos tipos de movimientos (lactancia materna y lactancia artificial) durante la fase de aprendizaje y adoptan su propio patrón.

Heterogeneity, selection and labor market disparities

We study the incentives to acquire skill in a model where heterogeneous firmsand workers interact in a labor market characterized by matching frictions and costlyscreening. When effort in acquiring skill raises both the mean and the variance of theresulting ability distribution, multiple equilibria may arise. In the high-effort equilibrium, heterogeneity in ability is sufficiently large to induce firms to select the bestworkers, thereby confirming the belief that effort is important for finding good jobs.In the low-effort equilibrium, ability is not sufficiently dispersed to justify screening,thereby confirming the belief that effort is not so important. The model has implications for wage inequality, the distribution of firm characteristics, sorting patternsbetween firms and workers, and unemployment rates that can help explaining observedcross-country variation in socio-economic and labor market outcomes.

Meta-structure correlation in protein space unveils different selection rules for folded and intrinsically disordered proteins

The number of existing protein sequences spans a very small fraction of sequence space. Natural proteins have overcome a strong negative selective pressure to avoid the formation of insoluble aggregates. Stably folded globular proteins and intrinsically disordered proteins (IDP) use alternative solutions to the aggregation problem. While in globular proteins folding minimizes the access to aggregation prone regions IDPs on average display large exposed contact areas. Here, we introduce the concept of average meta-structure correlation map to analyze sequence space. Using this novel conceptual view we show that representative ensembles of folded and ID proteins show distinct characteristics and responds differently to sequence randomization. By studying the way evolutionary constraints act on IDPs to disable a negative function (aggregation) we might gain insight into the mechanisms by which function - enabling information is encoded in IDPs.

Growth, selection and appropriate contracts

We study a dynamic model where growth requires both long-term investmentand the selection of talented managers. When ability is not ex-ante observable and contracts are incomplete, managerial selection imposes a cost, as managers facing the risk ofbeing replaced choose a sub-optimally low level of long-term investment. This generates atrade-off between selection and investment that has implications for the choice of contractualrelationships and institutions. Our analysis shows that rigid long-term contracts sacrificingmanagerial selection may prevail at early stages of economic development and when heterogeneity in ability is low. As the economy grows, however, knowledge accumulation increasesthe return to talent and makes it optimal to adopt flexible contractual relationships, wheremanagerial selection is implemented even at the cost of lower investment. Measures of investor protection aimed at limiting the bargaining power of managers improve selection undershort-term contract. Given that knowledge accumulation raises the value of selection, theoptimal level of investor protection increases with development.

Intersecciones entre visión artificial y mirada artística. Semantic Intersections between Artificial and Artistic Vision.

En el presente artículo se ha desarrollado un sistema capaz de categorizar de forma automática la base de datos de imágenes que sirven de punto de partida para la ideación y diseño en la producción artística del escultor M. Planas. La metodología utilizada está basada en características locales. Para la construcción de un vocabulario visual se sigue un procedimiento análogo al que se utiliza en el análisis automático de textos (modelo 'Bag-of-Words'-BOW) y en el ámbito de las imágenes nos referiremos a representaciones 'Bag-of-Visual Terms' (BOV). En este enfoque se analizan las imágenes como un conjunto de regiones, describiendo solamente su apariencia e ignorando su estructura espacial. Para superar los inconvenientes de polisemia y sinonimia que lleva asociados esta metodología, se utiliza el análisis probabilístico de aspectos latentes (PLSA) que detecta aspectos subyacentes en las imágenes, patrones formales. Los resultados obtenidos son prometedores y, además de la utilidad intrínseca de la categorización automática de imágenes, este método puede proporcionar al artista un punto de vista auxiliar muy interesante.

Interrogating eleven fast-evolving genes for signatures of recent positive selection in worldwide human populations

Different signatures of natural selection persist over varying time scales in our genome, revealing possible episodes of adaptative evolution during human history. Here, we identify genes showing signatures of ancestral positive selection in the human lineage and investigate whether some of those genes have been evolving adaptatively in extant human populations. Specifically, we compared more than 11,000 human genes with their orthologs inchimpanzee, mouse, rat and dog and applied a branch-site likelihood method to test for positive selection on the human lineage. Among the significant cases, a robust set of 11 genes were then further explored for signatures of recent positive selection using SNP data. We genotyped 223 SNPs in 39 worldwide populations from the HGDP Diversity panel and supplemented this information with available genotypes for up to 4,814 SNPs distributed along 2 Mb centered on each gene. After exploring the allele frequency spectrum, population differentiation and the maintainance of long unbroken haplotypes, we found signals of recent adaptative phenomena in only one of the 11 candidate gene regions. However, the signal ofrecent selection in this region may come from a different, neighbouring gene (CD5) ratherthan from the candidate gene itself (VPS37C). For this set of positively-selected genes in thehuman lineage, we find no indication that these genes maintained their rapid evolutionarypace among human populations. Based on these data, it therefore appears that adaptation forhuman-specific and for population-specific traits may have involved different genes.

Distribution of events of positive selection and population differentiation in a metabolic pathway: the case of asparagine N-glycosylation

Asparagine N-Glycosylation is one of the most important forms of protein post-translational modification in eukaryotes. This metabolic pathway can be subdivided into two parts: an upstream sub-pathway required for achieving proper folding for most of the proteins synthesized in the secretory pathway, and a downstream sub-pathway required to give variability to trans-membrane proteins, and involved in adaptation to the environment and innate immunity. Here we analyze the nucleotide variability of the genes of this pathway in human populations, identifying which genes show greater population differentiation and which genes show signatures of recent positive selection. We also compare how these signals are distributed between the upstream and the downstream parts of the pathway, with the aim of exploring how forces of population differentiation and positive selection vary among genes involved in the same metabolic pathway but subject to different functional constraints. Our results show that genes in the downstream part of the pathway are more likely to show a signature of population differentiation, while events of positive selection are equally distributed among the two parts of the pathway. Moreover, events of positive selection are frequent on genes that are known to be at bifurcation points, and that are identified as being in key position by a network-level analysis such as MGAT3 and GCS1. These findings indicate that the upstream part of the Asparagine N-Glycosylation pathway has lower diversity among populations, while the downstream part is freer to tolerate diversity among populations. Moreover, the distribution of signatures of population differentiation and positive selection can change between parts of a pathway, especially between parts that are exposed to different functional constraints. Our results support the hypothesis that genes involved in constitutive processes can be expected to show lower population differentiation, while genes involved in traits related to the environment should show higher variability. Taken together, this work broadens our knowledge on how events of population differentiation and of positive selection are distributed among different parts of a metabolic pathway.

FOSS License Selection and Code Management

With nearly 2,000 free and open source software (FLOSS) licenses, software license proliferation¿ can be a major headache for software development organizations trying to speed development through software component reuse, as well as companies redistributing software packages as components of their products. Scope is one problem: from the Free Beer license to the GPL family of licenses to platform-specific licenses such as Apache and Eclipse, the number and variety of licenses make it difficult for companies to ¿do the right thing¿ with respect to the software components in their products and applications. In addition to the sheer number of licenses, each license carries within it the author¿s specific definition of how the software can be used and re-used. Permissive licenses like BSD and MIT make it easy; software can be redistributed and developers can modify code without the requirement of making changes publicly available. Reciprocal licenses, on the other hand, place varying restrictions on re-use and redistribution. Woe to the developer who snags a bit of code after a simple web search without understanding the ramifications of license restrictions.

Selection response of growth rate in rabbits for meat production

Genetic and environmental trends in 2 lines of rabbit (B and R) selected on individual weight gain (WG) from weaning (4 wk) to slaughter (11 wk) were estimated using mixed model methodology. Line B was derived from the California breed and line R was a synthetic of stock of different origin. The data were collected from a single herd and comprised 7 718 individuals in line B and 9 391 in line R, the lines having 12 and 9 generations of selection respectively. Realized responses in the 2 lines were 2.7% and 2.2% of the initial mean per year respectively and showed that selection on WG was effective but was less than expected. Selection on slaughter weight (SW) and effects of selection on other economic traits are discussed. It is concluded that selection on either WG or SW is a simple method for improving growth rate in rabbit sire line stocks.