The role of dyking and fault control in the rapid onset of eruption at Chaitén volcano, Chile

Rhyolite is the most viscous of liquid magmas, so it was surprising that on 2?May 2008 at Chaitén Volcano, located in Chile's southern Andean volcanic zone, rhyolitic magma migrated from more than 5?km depth in less than 4?hours (ref.?1) and erupted explosively with only two days of detected precursory seismic activity. The last major rhyolite eruption before that at Chaitén was the largest volcanic eruption in the twentieth century, at Novarupta volcano, Alaska, in 1912. Because of the historically rare and explosive nature of rhyolite eruptions and because of the surprisingly short warning before the eruption of the Chaitén volcano, any information about the workings of the magmatic system at Chaitén, and rhyolitic systems in general, is important from both the scientific and hazard perspectives. Here we present surface deformation data related to the Chaitén eruption based on radar interferometry observations from the Japan Aerospace Exploration Agency (JAXA) DAICHI (ALOS) satellite. The data on this explosive rhyolite eruption indicate that the rapid ascent of rhyolite occurred through dyking and that melt segregation and magma storage were controlled by existing faults.     

Human metabolic individuality in biomedical and pharmaceutical research

Genome-wide association studies (GWAS) have identified many risk loci for complex diseases, but effect sizes are typically small and information on the underlying biological processes is often lacking. Associations with metabolic traits as functional intermediates can overcome these problems and potentially inform individualized therapy. Here we report a comprehensive analysis of genotype-dependent metabolic phenotypes using a GWAS with non-targeted metabolomics. We identified 37 genetic loci associated with blood metabolite concentrations, of which 25 show effect sizes that are unusually high for GWAS and account for 10-60% differences in metabolite levels per allele copy. Our associations provide new functional insights for many disease-related associations that have been reported in previous studies, including those for cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, venous thromboembolism and Crohn's disease. The study advances our knowledge of the genetic basis of metabolic individuality in humans and generates many new hypotheses for biomedical and pharmaceutical research.     

A Pluto-like radius and a high albedo for the dwarf planet Eris from an occultation

The dwarf planet Eris is a trans-Neptunian object with an orbital eccentricity of 0.44, an inclination of 44 degrees and a surface composition very similar to that of Pluto. It resides at present at 95.7 astronomical units (1?AU is the Earth-Sun distance) from Earth, near its aphelion and more than three times farther than Pluto. Owing to this great distance, measuring its size or detecting a putative atmosphere is difficult. Here we report the observation of a multi-chord stellar occultation by Eris on 6 November 2010 UT. The event is consistent with a spherical shape for Eris, with radius 1,163?±?6?kilometres, density 2.52?±?0.05 grams per cm(3) and a high visible geometric albedo, Pv = 0.96(+0.09)(-0.04). No nitrogen, argon or methane atmospheres are detected with surface pressure larger than ～1?nanobar, about 10,000 times more tenuous than Pluto's present atmosphere. As Pluto's radius is estimated to be between 1,150 and 1,200 kilometres, Eris appears as a Pluto twin, with a bright surface possibly caused by a collapsed atmosphere, owing to its cold environment. We anticipate that this atmosphere may periodically sublimate as Eris approaches its perihelion, at 37.8 astronomical units from the Sun.     

Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of α-dystroglycan

Walker-Warburg syndrome (WWS) is an autosomal recessive multisystem disorder characterized by complex eye and brain abnormalities with congenital muscular dystrophy (CMD) and aberrant a-dystroglycan glycosylation. Here we report mutations in the ISPD gene (encoding isoprenoid synthase domain containing) as the second most common cause of WWS. Bacterial IspD is a nucleotidyl transferase belonging to a large glycosyltransferase family, but the role of the orthologous protein in chordates is obscure to date, as this phylum does not have the corresponding non-mevalonate isoprenoid biosynthesis pathway. Knockdown of ispd in zebrafish recapitulates the human WWS phenotype with hydrocephalus, reduced eye size, muscle degeneration and hypoglycosylated a-dystroglycan. These results implicate ISPD in a-dystroglycan glycosylation in maintaining sarcolemma integrity in vertebrates.     

Kuhn and the genesis of the "new historiography of science"

In this paper I identify a tension between the two sets of works by Kuhn regarding the genesis of the "new historiography of science". In the first, it could be said that the change from the traditional to the new historiography is strictly endogenous (referring to internal causes or reasons). In the second, the change is predominantly exogenous. To address this question, I draw on a text that is considered to be less important among Kuhn's works, but which, as shall be argued, allows some contact between Kuhn's two approaches via Koyré. I seek to point out and differentiate the roles of Koyré and Kuhn--from Kuhn's point of view--in the development of the historiography of science and, as a complement, present some reflections regarding the justification of the new historiography.     

Identification of low-frequency variants associated with gout and serum uric acid levels

We tested 16 million SNPs, identified through whole-genome sequencing of 457 Icelanders, for association with gout and serum uric acid levels. Genotypes were imputed into 41,675 chip-genotyped Icelanders and their relatives, for effective sample sizes of 968 individuals with gout and 15,506 individuals for whom serum uric acid measurements were available. We identified a low-frequency missense variant (c.1580C>G) in ALDH16A1 associated with gout (OR = 3.12, P = 1.5 × 10(-16), at-risk allele frequency = 0.019) and serum uric acid levels (effect = 0.36 s.d., P = 4.5 × 10(-21)). We confirmed the association with gout by performing Sanger sequencing on 6,017 Icelanders. The association with gout was stronger in males relative to females. We also found a second variant on chromosome 1 associated with gout (OR = 1.92, P = 0.046, at-risk allele frequency = 0.986) and serum uric acid levels (effect = 0.48 s.d., P = 4.5 × 10(-16)). This variant is close to a common variant previously associated with serum uric acid levels. This work illustrates how whole-genome sequencing data allow the detection of associations between low-frequency variants and complex traits.     

Activation of ataxia telangiectasia muted under experimental models and human Parkinson’s disease

In the present study we demonstrated that neurotoxin MPP⁺-induced DNA damage is followed by ataxia telangiectasia muted (ATM) activation either in cerebellar granule cells (CGC) or in B65 cell line. In CGC, the selective ATM inhibitor KU-55933 showed neuroprotective effects against MPP⁺-induced neuronal cell loss and apoptosis, lending support to the key role of ATM in experimental models of Parkinson’s disease. Likewise, we showed that knockdown of ATM levels in neuroblastoma B65 cells using an ATM-specific siRNA attenuates the phosphorylation of retinoblastoma protein without affecting other cell-cycle proteins involved in the G₀/G₁ cell-cycle phase. Moreover, we demonstrated DNA damage, in human brain samples of PD patients. These findings support a model in which MPP⁺ leads to ATM activation with a subsequent DNA damage response and activation of pRb. Therefore, this study demonstrates a new link between DNA damage by MPP⁺ and cell-cycle re-entry through retinoblastoma protein phosphorylation.     

Extremely low-coverage sequencing and imputation increases power for genome-wide association studies

Genome-wide association studies (GWAS) have proven to be a powerful method to identify common genetic variants contributing to susceptibility to common diseases. Here, we show that extremely low-coverage sequencing (0.1-0.5×) captures almost as much of the common (>5%) and low-frequency (1-5%) variation across the genome as SNP arrays. As an empirical demonstration, we show that genome-wide SNP genotypes can be inferred at a mean r(2) of 0.71 using off-target data (0.24× average coverage) in a whole-exome study of 909 samples. Using both simulated and real exome-sequencing data sets, we show that association statistics obtained using extremely low-coverage sequencing data attain similar P values at known associated variants as data from genotyping arrays, without an excess of false positives. Within the context of reductions in sample preparation and sequencing costs, funds invested in extremely low-coverage sequencing can yield several times the effective sample size of GWAS based on SNP array data and a commensurate increase in statistical power.