Genome-wide data from the Bubi of Bioko Island clarifies the Atlantic fringe of the Bantu dispersal.

BACKGROUND: Bioko is one of the few islands that exist around Africa, the most genetically diverse continent on the planet. The native Bantu-speaking inhabitants of Bioko, the Bubi, are believed to have colonized the island about 2000 years ago. Here, we sequenced the genome of thirteen Bubi individuals at high coverage and analysed their sequences in comparison to mainland populations from the Gulf of Guinea. RESULTS: We found that, genetically, the closest mainland population to the Bubi are Bantu-speaking groups from Angola instead the geographically closer groups from Cameroon. The Bubi possess a lower proportion of rainforest hunter-gatherer (RHG) ancestry than most other Bantu-speaking groups. However, their RHG component most likely came from the same source and could have reached them by gene flow from the mainland after island settlement. By studying identity by descent (IBD) genomic blocks and runs of homozygosity (ROHs), we found evidence for a significant level of genetic isolation among the Bubi, isolation that can be attributed to the island effect. Additionally, as this population is known to have one of the highest malaria incidence rates in the world we analysed their genome for malaria-resistant alleles. However, we were unable to detect any specific selective sweeps related to this disease. CONCLUSIONS: By describing their dispersal to the Atlantic islands, the genomic characterization of the Bubi contributes to the understanding of the margins of the massive Bantu migration that shaped all Sub-Saharan African populations.

A functional ABCA1 gene variant is associated with low HDL-cholesterol levels and shows evidence of positive selection in Native Americans.

It has been suggested that the higher susceptibility of Hispanics to metabolic disease is related to their Native American heritage. A frequent cholesterol transporter ABCA1 (ATP-binding cassette transporter A1) gene variant (R230C, rs9282541) apparently exclusive to Native American individuals was associated with low high-density lipoprotein cholesterol (HDL-C) levels, obesity and type 2 diabetes in Mexican Mestizos. We performed a more extensive analysis of this variant in 4405 Native Americans and 863 individuals from other ethnic groups to investigate genetic evidence of positive selection, to assess its functional effect in vitro and to explore associations with HDL-C levels and other metabolic traits. The C230 allele was found in 29 of 36 Native American groups, but not in European, Asian or African individuals. C230 was observed on a single haplotype, and C230-bearing chromosomes showed longer relative haplotype extension compared with other haplotypes in the Americas. Additionally, single-nucleotide polymorphism data from the Human Genome Diversity Panel Native American populations were enriched in significant integrated haplotype score values in the region upstream of the ABCA1 gene. Cells expressing the C230 allele showed a 27% cholesterol efflux reduction (P< 0.001), confirming this variant has a functional effect in vitro. Moreover, the C230 allele was associated with lower HDL-C levels (P = 1.77 x 10(-11)) and with higher body mass index (P = 0.0001) in the combined analysis of Native American populations. This is the first report of a common functional variant exclusive to Native American and descent populations, which is a major determinant of HDL-C levels and may have contributed to the adaptive evolution of Native American populations.

The Early Peopling of the Philippines based on mtDNA.

Despite the efforts made to reconstruct the history of modern humans, there are still poorly explored regions that are key for understanding the phylogeography of our species. One of them is the Philippines, which is crucial to unravel the colonization of Southeast Asia and Oceania but where little is known about when and how the first humans arrived. In order to shed light into this settlement, we collected samples from 157 individuals of the Philippines with the four grandparents belonging to the same region and mitochondrial variants older than 20,000 years. Next, we analyzed the hypervariable I mtDNA region by approximate Bayesian computation based on extensive spatially explicit computer simulations to select among several migration routes towards the Philippines and to estimate population genetic parameters of this colonization. We found that the colonization of the Philippines occurred more than 60,000 years ago, with long-distance dispersal and from both north and south migration routes. Our results also suggest an environmental scenario especially optimal for humans, with large carrying capacity and population growth, in comparison to other regions of Asia. In all, our study suggests a rapid expansion of modern humans towards the Philippines that could be associated with the establisment of maritime technologies and favorable environmental conditions.

Analyzing the genetic structure of the Tepehua in relation to other neighbouring Mesoamerican populations. A study based on allele frequencies of STR markers.

We report data on the genetic variation of the Tepehua population based on 15 autosomal microsatellites. The Tepehua, whose language belongs to the Totonac family, are settled throughout the Sierra Madre Oriental in Mexico and constitute a group in demographic decline. The results suggest that the Tepehua population remained isolated throughout a large part of its history. Phylogenetic analyses performed with other indigenous and admixed populations of Mesoamerica allow us to address their biological history. The results suggest a genetic affinity between the Tepehua and the Huastecos due to their previous shared history, and a certain degree of differentiation from the Otomões groups and the Choles (who are of Mayan origin). A clear genetic differentiation is also apparent between native and admixed populations within the greater region of Mesoamerica. It is currently accepted that the genetic composition of the American populations fits a trihybrid model of admixture. The genetic structure based on comparison of 34 populations throughout the continent (9 indigenous and 23 admixed) using hierarchical cluster analysis with an explained variance of 61.17% suggests the existence of four large groups distinguished according to the degree of admixture between Amerindians, Europeans, and Africans.

Demographic History of Indigenous Populations in Mesoamerica Based on mtDNA Sequence Data.

The genetic characterization of Native American groups provides insights into their history and demographic events. We sequenced the mitochondrial D-loop region (control region) of 520 samples from eight Mexican indigenous groups. In addition to an analysis of the genetic diversity, structure and genetic relationship between 28 Native American populations, we applied Bayesian skyline methodology for a deeper insight into the history of Mesoamerica. AMOVA tests applying cultural, linguistic and geographic criteria were performed. MDS plots showed a central cluster of Oaxaca and Maya populations, whereas those from the North and West were located on the periphery. Demographic reconstruction indicates higher values of the effective number of breeding females (Nef) in Central Mesoamerica during the Preclassic period, whereas this pattern moves toward the Classic period for groups in the North and West. Conversely, Nef minimum values are distributed either in the Lithic period (i.e. founder effects) or in recent periods (i.e. population declines). The Mesomerican regions showed differences in population fluctuation as indicated by the maximum Inter-Generational Rate (IGRmax): i) Center-South from the lithic period until the Preclassic; ii) West from the beginning of the Preclassic period until early Classic; iii) North characterized by a wide range of temporal variation from the Lithic to the Preclassic. Our findings are consistent with the genetic variations observed between central, South and Southeast Mesoamerica and the North-West region that are related to differences in genetic drift, structure, and temporal survival strategies (agriculture versus hunter-gathering, respectively). Interestingly, although the European contact had a major negative demographic impact, we detect a previous decline in Mesoamerica that had begun a few hundred years before.

[Improvement in quality of life and exercise capacity without muscular biology changes after general training in patients with severe chronic obstructive pulmonary disease]. / Mejoría de la calidad de vida y capacidad de ejercicio sin cambios en la biología muscular tras entrenamiento general en pacientes con enfermedad pulmonar obstructiva crónica grave.

BACKGROUND AND OBJECTIVE: Despite the beneficial effects of exercise training in chronic obstructive pulmonary disease (COPD) patients, several studies have revealed functional and biological abnormalities in their peripheral muscles. The objective was to determine whether exercise training of high intensity and long duration modifies oxidative stress levels and structure of respiratory and peripheral muscles of severe COPD patients, while also improving their exercise capacity and quality of life. METHODS: Multicenter study (Warsaw and Barakaldo) in which 25 severe COPD out-patients were recruited from the COPD clinics. In all patients, lung and muscle functions, exercise capacity (walking test and cycloergometer) and quality of life (QoL) were assessed, and open muscle biopsies from the vastus lateralis and external intercostals (n=14) were obtained before and after an exercise training program of high intensity (respiratory rehabilitation area, 70% maximal tolerated load in a cycloergometer) and long duration (10 weeks). Oxidative stress and muscle structural modifications were evaluated in all muscle biopsies using immunoblotting and immunohistochemistry. RESULTS: In all patients, after the training program, without any drop-outs, exercise capacity and QoL improved significantly, whereas oxidative stress, muscle damage and structure were not modified in their respiratory or limb muscles compared to baseline. CONCLUSIONS: In patients with severe COPD, exercise training of high intensity and long duration significantly improves their exercise capacity and QoL, without inducing significant modifications on oxidative stress levels or muscle structure in their respiratory or peripheral muscles. These results may have future clinical therapeutic implications.

Reconstructing the history of Mesoamerican populations through the study of the mitochondrial DNA control region.

The study of genetic information can reveal a reconstruction of human population's history. We sequenced the entire mtDNA control region (positions 16.024 to 576 following Cambridge Reference Sequence, CRS) of 605 individuals from seven Mesoamerican indigenous groups and one Aridoamerican from the Greater Southwest previously defined, all of them in present Mexico. Samples were collected directly from the indigenous populations, the application of an individual survey made it possible to remove related or with other origins samples. Diversity indices and demographic estimates were calculated. Also AMOVAs were calculated according to different criteria. An MDS plot, based on FST distances, was also built. We carried out the construction of individual networks for the four Amerindian haplogroups detected. Finally, barrier software was applied to detect genetic boundaries among populations. The results suggest: a common origin of the indigenous groups; a small degree of European admixture; and inter-ethnic gene flow. The process of Mesoamerica's human settlement took place quickly influenced by the region's orography, which development of genetic and cultural differences facilitated. We find the existence of genetic structure is related to the region's geography, rather than to cultural parameters, such as language. The human population gradually became fragmented, though they remained relatively isolated, and differentiated due to small population sizes and different survival strategies. Genetic differences were detected between Aridoamerica and Mesoamerica, which can be subdivided into "East", "Center", "West" and "Southeast". The fragmentation process occurred mainly during the Mesoamerican Pre-Classic period, with the Otomí being one of the oldest groups. With an increased number of populations studied adding previously published data, there is no change in the conclusions, although significant genetic heterogeneity can be detected in Pima and Huichol groups. This result may be explained because populations historically assigned as belonging to the same group were, in fact, different indigenous populations.

Mejoría de la calidad de vida y capacidad de ejercicio sin cambios en la biología muscular tras entrenamiento general en pacientes con enfermedad pulmonar obstructiva crónica grave / Improvement in quality of life and exercise capacity without muscular biology changes after general training in patients with severe chronic obstructive pulmonary disease

Fundamento y objetivo: A pesar de los efectos beneficiosos del entrenamiento general en la enfermedad pulmonar obstructiva crónica (EPOC), algunos estudios han demostrado anomalías funcionales y biológicas en sus músculos periféricos. El objetivo de este trabajo fue determinar si un programa de entrenamiento general de elevada intensidad y larga duración modifica los niveles de estrés oxidativo y la estructura de los músculos respiratorios y periféricos de pacientes con EPOC grave, a la vez que mejora su tolerancia al ejercicio y su calidad de vida. Pacientes y métodos: Estudio multicéntrico (Barakaldo y Varsovia) en el que se reclutaron 25 pacientes con EPOC grave desde dispensarios de Servicios de Neumología. En todos ellos se evaluó la función pulmonar y muscular, la capacidad de ejercicio y la calidad de vida, y se obtuvieron biopsias musculares del vasto lateral e intercostal externo (n = 14) antes y después de un entrenamiento general de elevada intensidad (área rehabilitación respiratoria, 70% carga máxima tolerada en cicloergómetro) y larga duración (10 semanas). En las biopsias se determinaron proteínas oxidadas, antioxidantes y alteraciones estructurales. Resultados: Tras finalizado el entrenamiento general, sin abandonos, la capacidad de ejercicio y la calidad de vida mejoro´ en todos los pacientes, mientras que los niveles de estrés oxidativo y la estructura muscular no se modificaron en sus músculos respiratorios y periféricos respecto de la situación basal. Conclusiones: En pacientes con EPOC grave, el entrenamiento general de elevada intensidad y larga duración mejora su tolerancia al ejercicio y calidad de vida, sin inducir modificaciones en los niveles de estrés oxidativo ni en la estructura de sus músculos respiratorios y periféricos (AU)

Background and objective: Despite the beneficial effects of exercise training in chronic obstructive pulmonary disease (COPD) patients, several studies have revealed functional and biological abnormalities in their peripheral muscles. The objective was to determine whether exercise training of high intensity and long duration modifies oxidative stress levels and structure of respiratory and peripheral muscles of severe COPD patients, while also improving their exercise capacity and quality of life. Methods: Multicenter study (Warsaw and Barakaldo) in which 25 severe COPD out-patients were recruited from the COPD clinics. In all patients, lung and muscle functions, exercise capacity (walking test and cycloergometer) and quality of life (QoL) were assessed, and open muscle biopsies from the vastus lateralis and external intercostals (n = 14) were obtained before and after an exercise training program of high intensity (respiratory rehabilitation area, 70% maximal tolerated load in a cycloergometer) and long duration (10 weeks). Oxidative stress and muscle structural modifications were evaluated in all muscle biopsies using immunoblotting and immunohistochemistry. Results: In all patients, after the training program, without any drop-outs, exercise capacity and QoL improved significantly, whereas oxidative stress, muscle damage and structure were not modified in their respiratory or limb muscles compared to baseline. Conclusions: In patients with severe COPD, exercise training of high intensity and long duration significantly improves their exercise capacity and QoL, without inducing significant modifications on oxidative stress levels or muscle structure in their respiratory or peripheral muscles. These results may have future clinical therapeutic implications (AU)