Mitochondrial echoes of first settlement and genetic continuity in El Salvador

Background: From Paleo-Indian times to recent historical episodes, the Mesoamerican isthmus played an important role in the distribution and patterns of variability all around the double American continent. However, the amount of genetic information currently available on Central American continental populations is very scarce. In order to shed light on the role of Mesoamerica in the peopling of the New World, the present study focuses on the analysis of the mtDNA variation in a population sample from El Salvador. Methodology/Principal Findings: We have carried out DNA sequencing of the entire control region of the mitochondrial DNA (mtDNA) genome in 90 individuals from El Salvador. We have also compiled more than 3,985 control region profiles from the public domain and the literature in order to carry out inter-population comparisons. The results reveal a predominant Native American component in this region: by far, the most prevalent mtDNA haplogroup in this country (at ~90%) is A2, in contrast with other North, Meso- and South American populations. Haplogroup A2 shows a star-like phylogeny and is very diverse with a substantial proportion of mtDNAs (45%; sequence range 16090–16365) still unobserved in other American populations. Two different Bayesian approaches used to estimate admixture proportions in El Salvador shows that the majority of the mtDNAs observed come from North America. A preliminary founder analysis indicates that the settlement of El Salvador occurred about 13,400±5,200 Y.B.P.. The founder age of A2 in El Salvador is close to the overall age of A2 in America, which suggests that the colonization of this region occurred within a few thousand years of the initial expansion into the Americas. Conclusions/Significance: As a whole, the results are compatible with the hypothesis that today's A2 variability in El Salvador represents to a large extent the indigenous component of the region. Concordant with this hypothesis is also the observation of a very limited contribution from European and African women (~5%). This implies that the Atlantic slave trade had a very small demographic impact in El Salvador in contrast to its transformation of the gene pool in neighbouring populations from the Caribbean facade

Rudimentary G-Quadruplex-Based Telomere Capping In Saccharomyces Cerevisiae

Telomere capping conceals chromosome ends from exonucleases and checkpoints, but the full range of capping mechanisms is not well defined. Telomeres have the potential to form G-quadruplex (G4) DNA, although evidence for telomere G4 DNA function in vivo is limited. In budding yeast, capping requires the Cdc13 protein and is lost at nonpermissive temperatures in cdc13-1 mutants. Here, we use several independent G4 DNA-stabilizing treatments to suppress cdc13-1 capping defects. These include overexpression of three different G4 DNA binding proteins, loss of the G4 DNA unwinding helicase Sgs1, or treatment with small molecule G4 DNA ligands. In vitro, we show that protein-bound G4 DNA at a 3\u27 overhang inhibits 5\u27-\u3e 3\u27 resection of a paired strand by exonuclease I. These findings demonstrate that, at least in the absence of full natural capping, G4 DNA can play a positive role at telomeres in vivo

Estudio de la influencia de la automatización en el proyecto arquitectónico

Estudio de la influencia de la automatización en el proyecto arquitectónic

Molecular Mechanisms Associated with Nicotine Pharmacology and Dependence.

Tobacco dependence is a leading cause of preventable disease and death worldwide. Nicotine, the main psychoactive component in tobacco cigarettes, has also been garnering increased popularity in its vaporized form, as derived from e-cigarette devices. Thus, an understanding of the molecular mechanisms underlying nicotine pharmacology and dependence is required to ascertain novel approaches to treat drug dependence. In this chapter, we review the field's current understanding of nicotine's actions in the brain, the neurocircuitry underlying drug dependence, factors that modulate the function of nicotinic acetylcholine receptors, and the role of specific genes in mitigating the vulnerability to develop nicotine dependence. In addition to nicotine's direct actions in the brain, other constituents in nicotine and tobacco products have also been found to alter drug use, and thus, evidence is provided to highlight this issue. Finally, currently available pharmacotherapeutic strategies are discussed, along with an outlook for future therapeutic directions to achieve to the goal of long-term nicotine cessation

Multiplexed SNP typing of ancient DNA clarifies the origin of Andaman mtDNA haplogroups amongst South Asian tribal populations

© 2006 Endicott et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The issue of errors in genetic data sets is of growing concern, particularly in population genetics where whole genome mtDNA sequence data is coming under increased scrutiny. Multiplexed PCR reactions, combined with SNP typing, are currently under-exploited in this context, but have the potential to genotype whole populations rapidly and accurately, significantly reducing the amount of errors appearing in published data sets. To show the sensitivity of this technique for screening mtDNA genomic sequence data, 20 historic samples of the enigmatic Andaman Islanders and 12 modern samples from three Indian tribal populations (Chenchu, Lambadi and Lodha) were genotyped for 20 coding region sites after provisional haplogroup assignment with control region sequences. The genotype data from the historic samples significantly revise the topologies for the Andaman M31 and M32 mtDNA lineages by rectifying conflicts in published data sets. The new Indian data extend the distribution of the M31a lineage to South Asia, challenging previous interpretations of mtDNA phylogeography. This genetic connection between the ancestors of the Andamanese and South Asian tribal groups ~30 kya has important implications for the debate concerning migration routes and settlement patterns of humans leaving Africa during the late Pleistocene, and indicates the need for more detailed genotyping strategies. The methodology serves as a low-cost, high-throughput model for the production and authentication of data from modern or ancient DNA, and demonstrates the value of museum collections as important records of human genetic diversity.Phillip Endicott, Mait Metspalu, Chris Stringer, Vincent Macaulay, Alan Cooper, Juan J. Sanche

Studies on Calf Diarrhoea in Mozambique: Prevalence of Bacterial Pathogens

The prevalence of diarrhoea in calves was investigated in 8 dairy farms in Mozambique at 4 occasions during 2 consecutive years. A total of 1241 calves up to 6 months of age were reared in the farms, and 63 (5%) of them had signs of diarrhoea. Two farms had an overall higher prevalence (13% and 21%) of diarrhoea. Faecal samples were collected from all diarrhoeal calves (n = 63) and from 330 healthy calves and analysed for Salmonella species, Campylobacter jejuni and enterotoxigenic Escherichia coli (ETEC). Salmonella spp. was isolated in only 2% of all calves. Campylobacter was isolated in 11% of all calves, irrespective of health condition, and was more frequent (25%) in one of the 2 diarrhoeal farms (p = 0.001). 80% of the isolates were identified as C. jejuni. No ETEC strains were detected among the 55 tested strains from diarrhoeal calves, but 22/55 (40%) strains from diarrhoeal calves and 14/88 (16%) strains from healthy calves carried the K99 adhesin (p = 0.001). 6,757 E. coli isolates were typed with a biochemical fingerprinting method (the PhenePlate™) giving the same E. coli diversity in healthy and diarrhoeal calves. Thus it was concluded: i) the overall prevalence of diarrhoea was low, but 2 farms had a higher prevalence that could be due to an outbreak situation, ii) Salmonella did not seem to be associated with diarrhoea, iii) Campylobacter jejuni was common at one of the 2 diarrhoeal farms and iv) ETEC strains were not found, but K99 antigen was more prevalent in E. coli strains from diarrhoeal calves than from healthy, as well as more prevalent in one diarrhoeal farm

Circulating microRNAs as novel biomarkers for diabetes mellitus.

Diabetes mellitus is characterized by insulin secretion from pancreatic β cells that is insufficient to maintain blood glucose homeostasis. Autoimmune destruction of β cells results in type 1 diabetes mellitus, whereas conditions that reduce insulin sensitivity and negatively affect β-cell activities result in type 2 diabetes mellitus. Without proper management, patients with diabetes mellitus develop serious complications that reduce their quality of life and life expectancy. Biomarkers for early detection of the disease and identification of individuals at risk of developing complications would greatly improve the care of these patients. Small non-coding RNAs called microRNAs (miRNAs) control gene expression and participate in many physiopathological processes. Hundreds of miRNAs are actively or passively released in the circulation and can be used to evaluate health status and disease progression. Both type 1 diabetes mellitus and type 2 diabetes mellitus are associated with distinct modifications in the profile of miRNAs in the blood, which are sometimes detectable several years before the disease manifests. Moreover, circulating levels of certain miRNAs seem to be predictive of long-term complications. Technical and scientific obstacles still exist that need to be overcome, but circulating miRNAs might soon become part of the diagnostic arsenal to identify individuals at risk of developing diabetes mellitus and its devastating complications

Dipteran parasitoids as biocontrol agents

Numerous studies conducted on a variety of temporal and spatial scales around the world show that dipteran parasitoids can exert effective control over some insect pests. This paper provides an overview of major examples of successful classical and augmentative biological control initiatives, organized by major dipteran families which include parasitoid species (i.e., Tachinidae, Phoridae, Sarcophagidae, Cryptochetidae, Bombyliidae, Syrphidae) and according to different global regions. In addition, examples of unsuccessful attempts at biological control using dipteran parasitoids are discussed, along with potential reasons for these failures. A notable drawback found during our literature review is that many parasitoids and host species are not correctly identified, and information on laboratory and field studies is rather scarce. Reproductive strategies of dipteran parasitoids and host-parasitoid associations need to be better investigated. Expanding the knowledge of these parasitoids is crucial for improving biocontrol strategies, especially against pests for which dipterans are key natural enemies

Multiple Local and Recent Founder Effects of TGM1 in Spanish Families

<div><h3>Background</h3><p>Mutations in the <em>TGM1</em> gene encoding transglutaminase 1 are a major cause of autosomal recessive congenital ichthyosis. In the Galician (NW Spain) population, three mutations, c.2278C>T, c.1223_1227delACAC and c.984+1G>A, were observed at high frequency, representing ∼46%, ∼21% and ∼13% of all <em>TGM1</em> gene mutations, respectively. Moreover, these mutations were reported only once outside of Galicia, pointing to the existence of historical episodes of local severe genetic drift in this region.</p> <h3>Methodology/Principal Findings</h3><p>In order to determine whether these mutations were inherited from a common ancestor in the Galician population, and to estimate the number of generations since their initial appearance, we carried out a haplotype-based analysis by way of genotyping 21 SNPs within and flanking the <em>TGM1</em> gene and 10 flanking polymorphic microsatellite markers spanning a region of 12 Mb. Two linkage disequilibrium based methods were used to estimate the time to the most recent common ancestor (TMRCA), while a Bayesian-based procedure was used to estimate the age of the two mutations. Haplotype reconstruction from unphased genotypes of all members of the affected pedigrees indicated that all carriers for each of the two mutations harbored the same haplotypes, indicating common ancestry.</p> <h3>Conclusions/Significance</h3><p>In good agreement with the documentation record and the census, both mutations arose between 2,800–2,900 years ago (y.a.), but their TMRCA was in the range 600–1,290 y.a., pointing to the existence of historical bottlenecks in the region followed by population growth. This demographic scenario finds further support on a Bayesian Coalescent Analysis based on <em>TGM1</em> haplotypes that allowed estimating the occurrence of a dramatic reduction of effective population size around 900–4,500 y.a. (95% highest posterior density) followed by exponential growth.</p> </div

Dissecting the Within-Africa Ancestry of Populations of African Descent in the Americas

The ancestry of African-descended Americans is known to be drawn from three distinct populations: African, European, and Native American. While many studies consider this continental admixture, few account for the genetically distinct sources of ancestry within Africa--the continent with the highest genetic variation. Here, we dissect the within-Africa genetic ancestry of various populations of the Americas self-identified as having primarily African ancestry using uniparentally inherited mitochondrial DNA.We first confirmed that our results obtained using uniparentally-derived group admixture estimates are correlated with the average autosomal-derived individual admixture estimates (hence are relevant to genomic ancestry) by assessing continental admixture using both types of markers (mtDNA and Y-chromosome vs. ancestry informative markers). We then focused on the within-Africa maternal ancestry, mining our comprehensive database of published mtDNA variation (∼5800 individuals from 143 African populations) that helped us thoroughly dissect the African mtDNA pool. Using this well-defined African mtDNA variation, we quantified the relative contributions of maternal genetic ancestry from multiple W/WC/SW/SE (West to South East) African populations to the different pools of today's African-descended Americans of North and South America and the Caribbean.Our analysis revealed that both continental admixture and within-Africa admixture may be critical to achieving an adequate understanding of the ancestry of African-descended Americans. While continental ancestry reflects gender-specific admixture processes influenced by different socio-historical practices in the Americas, the within-Africa maternal ancestry reflects the diverse colonial histories of the slave trade. We have confirmed that there is a genetic thread connecting Africa and the Americas, where each colonial system supplied their colonies in the Americas with slaves from African colonies they controlled or that were available for them at the time. This historical connection is reflected in different relative contributions from populations of W/WC/SW/SE Africa to geographically distinct Africa-derived populations of the Americas, adding to the complexity of genomic ancestry in groups ostensibly united by the same demographic label