Development of a panel of genome-wide ancestry informative markers to study admixture throughout the Americas

Most individuals throughout the Americas are admixed descendants of Native American, European, and African ancestors. Complex historical factors have resulted in varying proportions of ancestral contributions between individuals within and among ethnic groups. We developed a panel of 446 ancestry informative markers (AIMs) optimized to estimate ancestral proportions in individuals and populations throughout Latin America. We used genome-wide data from 953 individuals from diverse African, European, and Native American populations to select AIMs optimized for each of the three main continental populations that form the basis of modern Latin American populations. We selected markers on the basis of locus-specific branch length to be informative, well distributed throughout the genome, capable of being genotyped on widely available commercial platforms, and applicable throughout the Americas by minimizing within-continent heterogeneity. We then validated the panel in samples from four admixed populations by comparing ancestry estimates based on the AIMs panel to estimates based on genome-wide association study (GWAS) data. The panel provided balanced discriminatory power among the three ancestral populations and accurate estimates of individual ancestry proportions (R2 > 0.9 for ancestral components with significant between-subject variance). Finally, we genotyped samples from 18 populations from Latin America using the AIMs panel and estimated variability in ancestry within and between these populations. This panel and its reference genotype information will be useful resources to explore population history of admixture in Latin America and to correct for the potential effects of population stratification in admixed samples in the region.     

Successful colon cancer eradication after chemoimmunotherapy is associated with profound phenotypic change of intratumoral myeloid cells

IL-12 is a potent immunostimulatory cytokine, but its impact as an antitumor drug in clinical practice is limited. Upsurge of regulatory T cells (Treg) in the tumor milieu has been proposed to limit the efficacy of the treatment. In this paper, two drugs (cyclophosphamide [CPA] and anti-CD25 mAb) widely used to eliminate Treg were used in an attempt to enhance the antitumor effect of IL-12 gene therapy. Both anti-CD25 and CPA combined with IL-12 were able to deplete intratumoral Treg and myeloid-derived suppressor cells (MDSC), but only IL-12 plus CPA achieved significant antitumor activity in mice with large established s.c. colon carcinoma. This therapeutic effect was associated with the emergence of a heterogeneous population of myeloid cells within the tumor, termed inflammatory myeloid cells (IMC), composed of Ly6C(high)Ly6G(low) inflammatory monocytes and Ly6G(high)Ly6C(+) neutrophils. IMC showed a distinctive pattern of cytokine/chemokine production, and in contrast to MDSC, they did not induce conversion of naive CD4(+) T cells into Treg. The appearance of IMC coincided with intense tumor infiltration by effector T cells, which was abrogated by elimination of IMC by anti-Gr1 mAb, a maneuver that abolished the antitumor effect of the therapy. Therefore, the combination of IL-12 and CPA eliminates intratumoral Treg and MDSC, while it induces the appearance of IMC within the tumor microenvironment. The latter effect is essential to facilitate effector T cell infiltration and subsequent tumor elimination.     

Gas exchange and water balance of a mistletoe species and its mangrove hosts

Summary The gas exchange and water relations of the hemiparasite Pthirusa maritima and two its mangrove host species, Conocarpus erectus and Coccoloba uvifera, were studied in an intertidal zone of the Venezuelan coast. Carbon uptake and transpiration, leaf osmotic and total water potential, as well as nutrient content in the xylem sap and leaves of mistletoes and hosts were followed through the dry and wet season. In addition, carbon isotope ratios of leaf tissue were measured to further evaluate water use efficiency. Under similar light and humidity conditions, mistletoes had higher transpiration rates, lower leaf water potentials, and lower water use efficiencies than their hosts. Potassium content was much higher in mistletoes than in host leaves, but mineral nutrient content in the xylem sap of mistletoes was relatively low. The resistance of the liquid pathway from the soil to the leaf surface of mistletoes was larger than the total liquid flow resistance of host plants. Differences in the daily cycles of osmotic potential of the xylem sap also indicate the existence of a high resistance pathway along the vascular connection between the parasite pathway along the vascular connection between the parasite and its host. P. maritima mistletoes adjust to the different physiological characteristics of the host species which it parasitizes, thus ensuring an adequate water and carbon balance.     

1H, 13C, and 15N resonance assignments of the N-terminal domain of human Tubulin Binding Cofactor C

Human Tubulin Binding Cofactor C (hTBCC) is a 346 amino acid protein composed of two domains, which is involved in the folding pathway of newly synthesized α and β-tubulins. The 3D structure of the 111-residue hTBCC N-terminal domain of the protein has not yet been determined. As a previous step to that end, here we report the NMR ¹H, ¹⁵N, and ¹³C chemical shift assignments at pH 6.0 and 25°C, based on a uniformly doubly labelled ¹³C/¹⁵N sample of the domain.     

Detection of a Salmonella enterica Serovar California Strain Spreading in Spanish Feed Mills and Genetic Characterization with DNA Microarrays

We performed an epidemiological study on Salmonella isolated from raw plant-based feed in Spanish mills. Overall, 32 different Salmonella serovars were detected. Despite its rare occurrence in humans and animals, Salmonella enterica serovar California was found to be the predominant serovar in Spanish feed mills. Different typing techniques showed that isolates of this serovar were genetically closely related, and comparative genomic hybridization using microarray technology revealed 23 S. enterica serovar Typhimurium LT2 gene clusters that are absent from serovar California.     

Effect of human activities on Egyptian vulture breeding success

Habitat loss, electrocution on power poles and persecution by humans are the main threats to birds of prey. Nevertheless, the effects of human disturbance on endangered species are becoming notorious due to the increasing recreational use of the natural environment. We evaluated the effects of human disturbances on Egyptian vulture Neophron percnopterus breeding success and developed conservation measures based on minimum distance of effect and buffer areas in a high human density area of northern Spain. A total of 100 breeding attempts of 15 breeding pairs were monitored over 8 years. Human disturbances affected 42 of the breeding attempts. Those disturbances related to and originating in forestry work had the most severe effect on breeding success, being associated with the loss of 100% of 13 breeding attempts, while human disturbances related to free-time activities caused 44% failures in 25 breeding attempts by four pairs, two of them within Natural Parks. The breeding success was significantly less in territories affected by disturbances than in those free of disturbances. Some pairs affected by disturbances changed their nest site, increasing breeding success. Adults were prevented from entering the nest to feed chicks when anyone was detected at an average distance of 307 m, while an average distance of 837.5 m allowed them access. The maximum alert distance was estimated at 605 m and the buffer area was 57 ha. We discuss the application of our results for management schemes and conservation of this species.     

Effects of a mass mortality event on gorgonian reproduction

The impact of a disturbance is normally measured in terms of its effects on adult mortality, whilst the less obvious impact on reproductive biology is generally ignored. Although previous studies have contributed to understanding the effects of a mass mortality of gorgonians in 1999 at NW Mediterranean Sea, none of them have considered its impact on reproduction. The goal of this study was to determine the impact of mass mortality events on the reproduction of the gorgonian Paramuricea clavata, and examine the effect of the damage 1 year (June 2000) and 2 years (June 2001) after the event. The reproductive parameters of female colonies were more affected than those of males. In female colonies that were moderately or severely damaged, the proportion of fertile polyps decreased by about 22–35%, whilst in the worst affected males there was only a 12% decrease. Female colonies showed a progressive decrease in gonadal biomass with increasing damage to a maximum reduction of 73–75% of oocyte production observed in colonies with >33% injury. In contrast, in males, the gonadal biomass decreased rapidly for colonies with 5% of injured surface, with a reduction in spermary production of 49–64%. The same pattern of decrease in gonadal output compared to the extent of the injury was observed in 2001, two years after the mass mortality event. This indicated that the observed pattern was a response to the extent of the injury rather than a direct effect of the event. These severe effects on the reproduction of the red gorgonian species have implications for the recovery of affected populations in the long-term. This study demonstrated that an evaluation of the impact over different demographic parameters is needed to understand all the consequences of these disturbances.