Ancestry of the Brazilian TP53 c.1010G>A (p.Arg337His, R337H) founder mutation : clues from haplotyping of short tandem repeats on Chromosome 17p

Rare germline mutations in TP53 (17p13.1) cause a highly penetrant predisposition to a specific spectrum of early cancers, defining the Li-Fraumeni Syndrome (LFS). A germline mutation at codon 337 (p.Arg337His, c1010G>A) is found in about 0.3% of the population of Southern Brazil. This mutation is associated with partially penetrant LFS traits and is found in the germline of patients with early cancers of the LFS spectrum unselected for familial his- tory. To characterize the extended haplotypes carrying the mutation, we have genotyped 9 short tandem repeats on chromosome 17p in 12 trios of Brazilian p.Arg337His carriers. Results confirm that all share a common ancestor haplotype of Caucasian/Portuguese-Ibe- ric origin, distant in about 72–84 generations (2000 years assuming a 25 years intergenera- tional distance) and thus pre-dating European migration to Brazil. So far, the founder p. Arg337His haplotype has not been detected outside Brazil, with the exception of two resi- dents of Portugal, one of them of Brazilian origin. On the other hand, increased meiotic recombination in p.Arg337His carriers may account for higher than expected haplotype diversity. Further studies comparing haplotypes in populations of Brazil and of other areas of Portuguese migration are needed to understand the historical context of this mutation in Brazil.This study was funded by grant # 478430/2012-4 from CNPq (RFA MCT/CNPq - No 14/2012; Universal), Brazil.We would like to thank UFRGS, UFPA, AC Camargo, HC Barretos and University of Minho for their support during this work

Genome Sequence Analysis of Dengue Virus 1 Isolated in Key West, Florida

Dengue virus (DENV) is transmitted to humans through the bite of mosquitoes. In November 2010, a dengue outbreak was reported in Monroe County in southern Florida (FL), including greater than 20 confirmed human cases. The virus collected from the human cases was verified as DENV serotype 1 (DENV-1) and one isolate was provided for sequence analysis. RNA was extracted from the DENV-1 isolate and was used in reverse transcription polymerase chain reaction (RT-PCR) to amplify PCR fragments to sequence. Nucleic acid primers were designed to generate overlapping PCR fragments that covered the entire genome. The DENV-1 isolate found in Key West (KW), FL was sequenced for whole genome characterization. Sequence assembly, Genbank searches, and recombination analyses were performed to verify the identity of the genome sequences and to determine percent similarity to known DENV-1 sequences. We show that the KW DENV-1 strain is 99% identical to Nicaraguan and Mexican DENV-1 strains. Phylogenetic and recombination analyses suggest that the DENV-1 isolated in KW originated from Nicaragua (NI) and the KW strain may circulate in KW. Also, recombination analysis results detected recombination events in the KW strain compared to DENV-1 strains from Puerto Rico. We evaluate the relative growth of KW strain of DENV-1 compared to other dengue viruses to determine whether the underlying genetics of the strain is associated with a replicative advantage, an important consideration since local transmission of DENV may result because domestic tourism can spread DENVs

My Hand or Yours? Markedly Different Sensitivity to Egocentric and Allocentric Views in the Hand Laterality Task

In the hand laterality task participants judge the handedness of visually presented stimuli – images of hands shown in a variety of postures and views - and indicate whether they perceive a right or left hand. The task engages kinaesthetic and sensorimotor processes and is considered a standard example of motor imagery. However, in this study we find that while motor imagery holds across egocentric views of the stimuli (where the hands are likely to be one's own), it does not appear to hold across allocentric views (where the hands are likely to be another person's). First, we find that psychophysical sensitivity, d', is clearly demarcated between egocentric and allocentric views, being high for the former and low for the latter. Secondly, using mixed effects methods to analyse the chronometric data, we find high positive correlation between response times across egocentric views, suggesting a common use of motor imagery across these views. Correlations are, however, considerably lower between egocentric and allocentric views, suggesting a switch from motor imagery across these perspectives. We relate these findings to research showing that the extrastriate body area discriminates egocentric (‘self’) and allocentric (‘other’) views of the human body and of body parts, including hands

Association of Sleep Duration with Chronic Diseases in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study

Background: In view of the reduced number of hours devoted to sleep in modern western societies the question arises what effects might result from sleep duration on occurrence of chronic diseases. Methods: Data from 23 620 middle-aged participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study, that were recruited between 1994–1998, were analyzed by using Cox proportional hazard regression to examine the association between self-reported sleep duration at baseline and incidence of chronic diseases, such as diabetes, myocardial infarction, stroke, and cancer. Results: During a mean follow-up period of 7.8 years 841 incident cases of type 2 diabetes, 197 cases of myocardial infarction, 169 incident strokes, and 846 tumor cases were observed. Compared to persons sleeping 7-,8 h/day, participants with sleep duration of,6 h had a significantly increased risk of stroke (Hazard Ratio (HR) = 2.06, 95

A human PrM antibody that recognizes a novel cryptic epitope on dengue E glycoprotein

10.1371/journal.pone.0033451PLoS ONE74

Coalition-structured governance improves cooperation to provide public goods

While the benefits of common and public goods are shared, they tend to be scarce when contributions are provided voluntarily. Failure to cooperate in the provision or preservation of these goods is fundamental to sustainability challenges, ranging from local fisheries to global climate change. In the real world, such cooperative dilemmas occur in multiple interactions with complex strategic interests and frequently without full information. We argue that voluntary cooperation enabled across overlapping coalitions (akin to polycentricity) not only facilitates a higher generation of non-excludable public goods, but it may also allow evolution toward a more cooperative, stable, and inclusive approach to governance. Contrary to any previous study, we show that these merits of multi-coalition governance are far more general than the singular examples occurring in the literature, and they are robust under diverse conditions of excludability, congestion of the non-excludable public good, and arbitrary shapes of the return-to-contribution function. We first confirm the intuition that a single coalition without enforcement and with players pursuing their self-interest without knowledge of returns to contribution is prone to cooperative failure. Next, we demonstrate that the same pessimistic model but with a multi-coalition structure of governance experiences relatively higher cooperation by enabling recognition of marginal gains of cooperation in the game at stake. In the absence of enforcement, public-goods regimes that evolve through a proliferation of voluntary cooperative forums can maintain and increase cooperation more successfully than singular, inclusive regimes.Supported by US Defense Advanced Research Projects Agency (D17AC00005), National Science Foundation grant GEO-1211972, and Fundacao para a Ciencia e Tecnologia (FCT) through grants PTDC/MAT/STA/3358/2014, PTDC/EEI-SII/5081/2014, and UID/BIA/04050/2013. P.M.H. was supported by the Walbridge Fund at the Princeton Environmental Institute

Spatial point analysis based on dengue surveys at household level in central Brazil

<p>Abstract</p> <p>Background</p> <p>Dengue virus (DENV) affects nonimunne human populations in tropical and subtropical regions. In the Americas, dengue has drastically increased in the last two decades and Brazil is considered one of the most affected countries. The high frequency of asymptomatic infection makes difficult to estimate prevalence of infection using registered cases and to locate high risk intra-urban area at population level. The goal of this spatial point analysis was to identify potential high-risk intra-urban areas of dengue, using data collected at household level from surveys.</p> <p>Methods</p> <p>Two household surveys took place in the city of Goiania (~1.1 million population), Central Brazil in the year 2001 and 2002. First survey screened 1,586 asymptomatic individuals older than 5 years of age. Second survey 2,906 asymptomatic volunteers, same age-groups, were selected by multistage sampling (census tracts; blocks; households) using available digital maps. Sera from participants were tested by dengue virus-specific IgM/IgG by EIA. A Generalized Additive Model (GAM) was used to detect the spatial varying risk over the region. Initially without any fixed covariates, to depict the overall risk map, followed by a model including the main covariates and the year, where the resulting maps show the risk associated with living place, controlled for the individual risk factors. This method has the advantage to generate smoothed risk factors maps, adjusted by socio-demographic covariates.</p> <p>Results</p> <p>The prevalence of antibody against dengue infection was 37.3% (95%CI [35.5–39.1]) in the year 2002; 7.8% increase in one-year interval. The spatial variation in risk of dengue infection significantly changed when comparing 2001 with 2002, (ORadjusted = 1.35; p < 0.001), while controlling for potential confounders using GAM model. Also increasing age and low education levels were associated with dengue infection.</p> <p>Conclusion</p> <p>This study showed spatial heterogeneity in the risk areas of dengue when using a spatial multivariate approach in a short time interval. Data from household surveys pointed out that low prevalence areas in 2001 surveys shifted to high-risk area in consecutive year. This mapping of dengue risks should give insights for control interventions in urban areas.</p