Rapid ascent of rhyolitic magma at Chaitén volcano, Chile

International audienceAlthough rhyolite magma has fuelled some of the Earth's largest explosive volcanic eruptions, our understanding of these events is incomplete due to the previous lack of direct observation of these eruptions. On 1 May 2008, Chaitén volcano in Chile erupted rhyolite magma unexpectedly and explosively. Here, petrological and experimental data are presented that indicate that the hydrous rhyolite magma at Chaitén ascended very rapidly from storage depth to near-surface, with velocities of the order of one metre per second

Risk reduction through community-based monitoring:the vigías of Tungurahua, Ecuador

Since 2000, a network of volunteers known as vigías has been engaged in community-based volcano monitoring, which involves local citizens in the collection of scientific data, around volcán Tungurahua, Ecuador. This paper provides the first detailed description and analysis of this well-established initiative, drawing implications for volcanic risk reduction elsewhere. Based on 32 semi-structured interviews and other qualitative data collected in June and July 2013 with institutional actors and with vigías themselves, the paper documents the origins and development of the network, identifies factors that have sustained it, and analyses the ways in which it contributes to disaster risk reduction. Importantly, the case highlights how this community-based network performs multiple functions in reducing volcanic risk. The vigías network functions simultaneously as a source of observational data for scientists; as a communication channel for increasing community awareness, understanding of hazard processes and for enhancing preparedness; and as an early warning system for civil protection. Less tangible benefits with nonetheless material consequences include enhanced social capital – through the relationships and capabilities that are fostered – and improved trust between partners. Establishing trust-based relationships between citizens, the vigías, scientists and civil protection authorities is one important factor in the effectiveness and resilience of the network. Other factors discussed in the paper that have contributed to the longevity of the network include the motivations of the vigías, a clear and regular communication protocol, persistent volcanic activity, the efforts of key individuals, and examples of successful risk reduction attributable to the activities of the network. Lessons that can be learned about the potential of community-based monitoring for disaster risk reduction in other contexts are identified, including what the case tells us about the conditions that can affect the effectiveness of such initiatives and their resilience to changing circumstances

Correction of Population Stratification in Large Multi-Ethnic Association Studies

The vast majority of genetic risk factors for complex diseases have, taken individually, a small effect on the end phenotype. Population-based association studies therefore need very large sample sizes to detect significant differences between affected and non-affected individuals. Including thousands of affected individuals in a study requires recruitment in numerous centers, possibly from different geographic regions. Unfortunately such a recruitment strategy is likely to complicate the study design and to generate concerns regarding population stratification.We analyzed 9,751 individuals representing three main ethnic groups - Europeans, Arabs and South Asians - that had been enrolled from 154 centers involving 52 countries for a global case/control study of acute myocardial infarction. All individuals were genotyped at 103 candidate genes using 1,536 SNPs selected with a tagging strategy that captures most of the genetic diversity in different populations. We show that relying solely on self-reported ethnicity is not sufficient to exclude population stratification and we present additional methods to identify and correct for stratification.Our results highlight the importance of carefully addressing population stratification and of carefully “cleaning” the sample prior to analyses to obtain stronger signals of association and to avoid spurious results

A Functional Variant of the Dimethylarginine Dimethylaminohydrolase-2 Gene Is Associated with Insulin Sensitivity

Background: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide synthase, which was associated with insulin resistance. Dimethylarginine dimethylaminohydrolase (DDAH) is the major determinant of plasma ADMA. Examining data from the DIAGRAM+ (Diabetes Genetics Replication And Meta-analysis), we identified a variant (rs9267551) in the DDAH2 gene nominally associated with type 2 diabetes (P =3610 25). Methodology/Principal Findings: initially, we assessed the functional impact of rs9267551 in human endothelial cells (HUVECs), observing that the G allele had a lower transcriptional activity resulting in reduced expression of DDAH2 and decreased NO production in primary HUVECs naturally carrying it. We then proceeded to investigate whether this variant is associated with insulin sensitivity in vivo. To this end, two cohorts of nondiabetic subjects of European ancestry were studied. In sample 1 (n = 958) insulin sensitivity was determined by the insulin sensitivity index (ISI), while in sample 2 (n = 527) it was measured with a euglycemic-hyperinsulinemic clamp. In sample 1, carriers of the GG genotype had lower ISI than carriers of the C allele (67633 vs.79644; P = 0.003 after adjusting for age, gender, and BMI). ADMA levels were higher in subjects carrying the GG genotype than in carriers of the C allele (0.6860.14 vs. 0.5760.14 mmol/l; P = 0.04). In sample 2, glucose disposal was lower in GG carriers as compared with C carriers (9.364.1 vs. 11.064.2 mg6Kg 21 free fat mass6min 21; P = 0.009)

Informed Conditioning on Clinical Covariates Increases Power in Case-Control Association Studies

Genetic case-control association studies often include data on clinical covariates, such as body mass index (BMI), smoking status, or age, that may modify the underlying genetic risk of case or control samples. For example, in type 2 diabetes, odds ratios for established variants estimated from low–BMI cases are larger than those estimated from high–BMI cases. An unanswered question is how to use this information to maximize statistical power in case-control studies that ascertain individuals on the basis of phenotype (case-control ascertainment) or phenotype and clinical covariates (case-control-covariate ascertainment). While current approaches improve power in studies with random ascertainment, they often lose power under case-control ascertainment and fail to capture available power increases under case-control-covariate ascertainment. We show that an informed conditioning approach, based on the liability threshold model with parameters informed by external epidemiological information, fully accounts for disease prevalence and non-random ascertainment of phenotype as well as covariates and provides a substantial increase in power while maintaining a properly controlled false-positive rate. Our method outperforms standard case-control association tests with or without covariates, tests of gene x covariate interaction, and previously proposed tests for dealing with covariates in ascertained data, with especially large improvements in the case of case-control-covariate ascertainment. We investigate empirical case-control studies of type 2 diabetes, prostate cancer, lung cancer, breast cancer, rheumatoid arthritis, age-related macular degeneration, and end-stage kidney disease over a total of 89,726 samples. In these datasets, informed conditioning outperforms logistic regression for 115 of the 157 known associated variants investigated (P-value = 1×10−9). The improvement varied across diseases with a 16% median increase in χ2 test statistics and a commensurate increase in power. This suggests that applying our method to existing and future association studies of these diseases may identify novel disease loci

Hydrothermal alteration of andesitic lava domes can lead to explosive volcanic behaviour

Dome-forming volcanoes are among the most hazardous volcanoes on Earth. Magmatic outgassing can be hindered if the permeability of a lava dome is reduced, promoting pore pressure augmentation and explosive behaviour. Laboratory data show that acid-sulphate alteration, common to volcanoes worldwide, can reduce the permeability on the sample lengthscale by up to four orders of magnitude and is the result of pore- and microfracture-filling mineral precipitation. Calculations using these data demonstrate that intense alteration can reduce the equivalent permeability of a dome by two orders of magnitude, which we show using numerical modelling to be sufficient to increase pore pressure. The fragmentation criterion shows that the predicted pore pressure increase is capable of fragmenting the majority of dome-forming materials, thus promoting explosive volcanism. It is crucial that hydrothermal alteration, which develops over months to years, is monitored at dome-forming volcanoes and is incorporated into real-time hazard assessments

ENPP1 Affects Insulin Action and Secretion: Evidences from In Vitro Studies

The aim of this study was to deeper investigate the mechanisms through which ENPP1, a negative modulator of insulin receptor (IR) activation, plays a role on insulin signaling, insulin secretion and eventually glucose metabolism. ENPP1 cDNA (carrying either K121 or Q121 variant) was transfected in HepG2 liver-, L6 skeletal muscle- and INS1E beta-cells. Insulin-induced IR-autophosphorylation (HepG2, L6, INS1E), Akt-Ser473, ERK1/2-Thr202/Tyr204 and GSK3-beta Ser9 phosphorylation (HepG2, L6), PEPCK mRNA levels (HepG2) and 2-deoxy-D-glucose uptake (L6) was studied. GLUT 4 mRNA (L6), insulin secretion and caspase-3 activation (INS1E) were also investigated. Insulin-induced IR-autophosphorylation was decreased in HepG2-K, L6-K, INS1E-K (20%, 52% and 11% reduction vs. untransfected cells) and twice as much in HepG2-Q, L6-Q, INS1E-Q (44%, 92% and 30%). Similar data were obtained with Akt-Ser473, ERK1/2-Thr202/Tyr204 and GSK3-beta Ser9 in HepG2 and L6. Insulin-induced reduction of PEPCK mRNA was progressively lower in untransfected, HepG2-K and HepG2-Q cells (65%, 54%, 23%). Insulin-induced glucose uptake in untransfected L6 (60% increase over basal), was totally abolished in L6-K and L6-Q cells. GLUT 4 mRNA was slightly reduced in L6-K and twice as much in L6-Q (13% and 25% reduction vs. untransfected cells). Glucose-induced insulin secretion was 60% reduced in INS1E-K and almost abolished in INS1E-Q. Serum deficiency activated caspase-3 by two, three and four folds in untransfected INS1E, INS1E-K and INS1E-Q. Glyburide-induced insulin secretion was reduced by 50% in isolated human islets from homozygous QQ donors as compared to those from KK and KQ individuals. Our data clearly indicate that ENPP1, especially when the Q121 variant is operating, affects insulin signaling and glucose metabolism in skeletal muscle- and liver-cells and both function and survival of insulin secreting beta-cells, thus representing a strong pathogenic factor predisposing to insulin resistance, defective insulin secretion and glucose metabolism abnormalities

Genetic Associations of Type 2 Diabetes with Islet Amyloid Polypeptide Processing and Degrading Pathways in Asian Populations

10.1371/journal.pone.0062378PLoS ONE86

Functional impact and evolution of a novel human polymorphic inversion that disrupts a gene and creates a fusion transcript

Since the discovery of chromosomal inversions almost 100 years ago, how they are maintained in natural populations has been a highly debated issue. One of the hypotheses is that inversion breakpoints could affect genes and modify gene expression levels, although evidence of this came only from laboratory mutants. In humans, a few inversions have been shown to associate with expression differences, but in all cases the molecular causes have remained elusive. Here, we have carried out a complete characterization of a new human polymorphic inversion and determined that it is specific to East Asian populations. In addition, we demonstrate that it disrupts the ZNF257 gene and, through the translocation of the first exon and regulatory sequences, creates a previously nonexistent fusion transcript, which together are associated to expression changes in several other genes. Finally, we investigate the potential evolutionary and phenotypic consequences of the inversion, and suggest that it is probably deleterious. This is therefore the first example of a natural polymorphic inversion that has position effects and creates a new chimeric gene, contributing to answer an old question in evolutionary biology