Context. High contrast imaging and spectroscopy provide unique constraints for exoplanet formation models as well as for planetary atmosphere models. But this can be challenging because of the ...planet-to-star small angular separation (<1 arcsec) and high flux ratio (>105). Recently, optimized instruments like VLT/SPHERE and Gemini/GPI were installed on 8m-class telescopes. These will probe young gazeous exoplanets at large separations (≳1 au) but, because of uncalibrated phase and amplitude aberrations that induce speckles in the coronagraphic images, they are not able to detect older and fainter planets. Aims. There are always aberrations that are slowly evolving in time. They create quasi-static speckles that cannot be calibrated a posteriori with sufficient accuracy. An active correction of these speckles is thus needed to reach very high contrast levels (>106−107). This requires a focal plane wavefront sensor. Our team proposed a self coherent camera, the performance of which was demonstrated in the laboratory. As for all focal plane wavefront sensors, these are sensitive to chromatism and we propose an upgrade that mitigates the chromatism effects. Methods. First, we recall the principle of the self-coherent camera and we explain its limitations in polychromatic light. Then, we present and numerically study two upgrades to mitigate chromatism effects: the optical path difference method and the multireference self-coherent camera. Finally, we present laboratory tests of the latter solution. Results. We demonstrate in the laboratory that the multireference self-coherent camera can be used as a focal plane wavefront sensor in polychromatic light using an 80 nm bandwidth at 640 nm (bandwidth of 12.5%). We reach a performance that is close to the chromatic limitations of our bench: 1σ contrast of 4.5 × 10-8 between 5 and 17 λ0/D. Conclusions. The performance of the MRSCC is promising for future high-contrast imaging instruments that aim to actively minimize the speckle intensity so as to detect and spectrally characterize faint old or light gaseous planets.
Obesity has become a major worldwide challenge to public health, owing to an interaction between the Western 'obesogenic' environment and a strong genetic contribution. Recent extensive genome-wide ...association studies (GWASs) have identified numerous single nucleotide polymorphisms associated with obesity, but these loci together account for only a small fraction of the known heritable component. Thus, the 'common disease, common variant' hypothesis is increasingly coming under challenge. Here we report a highly penetrant form of obesity, initially observed in 31 subjects who were heterozygous for deletions of at least 593 kilobases at 16p11.2 and whose ascertainment included cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16,053 individuals from eight European cohorts. These deletions were absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (body mass index (BMI) ≥ 40 kg m-2 or BMI standard deviation score ≥ 4; P = 6.4 × 10-8, odds ratio 43.0), demonstrating the potential importance in common disease of rare variants with strong effects. This highlights a promising strategy for identifying missing heritability in obesity and other complex traits: cohorts with extreme phenotypes are likely to be enriched for rare variants, thereby improving power for their discovery. Subsequent analysis of the loci so identified may well reveal additional rare variants that further contribute to the missing heritability, as recently reported for SIM1 (ref. 3). The most productive approach may therefore be to combine the 'power of the extreme' in small, well-phenotyped cohorts, with targeted follow-up in case-control and population cohorts.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Context. Specific high-contrast imaging instruments are mandatory to characterize circumstellar disks and exoplanets around nearby stars. Coronagraphs are commonly used in these facilities to reject ...the diffracted light of an observed star and enable direct imaging and spectroscopy of its circumstellar environment. One important property of the coronagraph is to be able to work in broadband light. Aims. Among several proposed coronagraphs, the dual-zone phase mask coronagraph is a promising solution for starlight rejection in broadband light. In this paper, we perform the first validation of this concept in laboratory. Methods. First, we consider the principle of the dual-zone phase mask coronagraph. Then, we describe the high-contrast imaging THD testbed, the manufacturing of the components, and the quality control procedures. Finally, we study the sensitivity of our coronagraph to low-order aberrations (inner working angle and defocus) and estimate its contrast performance. Our experimental broadband light results are compared with numerical simulations to check agreement with the performance predictions. Results. With the manufactured prototype and using a dark hole technique based on the self-coherent camera, we obtain contrast levels down to 2 × 10-8 between 5 and 17λ0/D in monochromatic light (640 nm). We also reach contrast levels of 4 × 10-8 between 7 and 17λ0/D in broadband (λ0 = 675 nm, Δλ = 250 and Δλ/λ0 = 40%), which demonstrates the excellent chromatic performance of the dual-zone phase mask coronagraph. Conclusions. The performance reached by the dual-zone phase mask coronagraph is promising for future high-contrast imaging instruments that aim to detect and spectrally characterize old or light gaseous planets.
Glycogen synthase kinase 3 β (GSK-3β) is an essential negative regulator or “brake” on many anabolic-signaling pathways including Wnt and insulin. Global deletion of GSK-3β results in perinatal ...lethality and various skeletal defects. The goal of our research was to determine GSK-3β cell-autonomous effects and postnatal roles in the skeleton. We used the 3.6-kb Col1a1 promoter to inactivate the Gsk3b gene (Col1a1-Gsk3b knockout) in skeletal cells. Mutant mice exhibit decreased body fat and postnatal bone growth, as well as delayed development of several skeletal elements. Surprisingly, the mutant mice display decreased circulating glucose and insulin levels despite normal expression of GSK-3β in metabolic tissues. We showed that these effects are due to an increase in global insulin sensitivity. Most of the male mutant mice died after weaning. Prior to death, blood glucose changed from low to high, suggesting a possible switch from insulin sensitivity to resistance. These male mice die with extremely large bladders that are preceded by damage to the urogenital tract, defects that are also seen type 2 diabetes. Our data suggest that skeletal-specific deletion of GSK-3β affects global metabolism and sensitizes male mice to developing type 2 diabetes.
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•Genotyping-by-sequencing has resolved relationships in the spruce budworm complex.•Multiple analyses agreed on an unexpectedly basal placement forChoristoneura pinus.•Relationships ...remain ambiguous for a clade of western species.•Speciation has likely been driven by a combination of ecological factors.
High throughput sequencing technologies have revolutionized the potential to reconcile incongruence between gene and species trees, and numerous approaches have been developed to take advantage of these advances. Genotyping-by-sequencing is becoming a regular tool for gathering phylogenetic data, yet comprehensive evaluations of phylogenetic methods using these data are sparse. Here we use multiple phylogenetic and population genetic methods for genotyping-by-sequencing data to assess species relationships in a group of forest insect pests, the spruce budworm (Choristoneura fumiferana) species complex. With few exceptions, all methods agree on the same relationships, most notably placing C. pinus as basal to the remainder of the group, rather than C. fumiferana as previously suggested. We found strong support for the monophyly of C. pinus, C. fumiferana, and C. retiniana, but more ambiguous relationships and signatures of introgression in a clade of western lineages, including C. carnana, C. lambertiana, C. occidentalis occidentalis, C. occidentalis biennis, and C. orae. This represents the most taxonomically comprehensive genomic treatment of the spruce budworm species group, which is further supported by the broad agreement among multiple methodologies.
Upstream open reading frames (uORFs) are tissue-specific cis-regulators of protein translation. Isolated reports have shown that variants that create or disrupt uORFs can cause disease. Here, in a ...systematic genome-wide study using 15,708 whole genome sequences, we show that variants that create new upstream start codons, and variants disrupting stop sites of existing uORFs, are under strong negative selection. This selection signal is significantly stronger for variants arising upstream of genes intolerant to loss-of-function variants. Furthermore, variants creating uORFs that overlap the coding sequence show signals of selection equivalent to coding missense variants. Finally, we identify specific genes where modification of uORFs likely represents an important disease mechanism, and report a novel uORF frameshift variant upstream of NF2 in neurofibromatosis. Our results highlight uORF-perturbing variants as an under-recognised functional class that contribute to penetrant human disease, and demonstrate the power of large-scale population sequencing data in studying non-coding variant classes.
NWChem: Past, present, and future
Journal of chemical physics online/The Journal of chemical physics/Journal of chemical physics,
05/2020
Journal Article
Hybrid zones provide unique natural laboratories for studying mechanisms of evolution. But identification and classification of hybrid individuals (F1, F2, backcross, etc.) can be complicated by real ...population changes over time as well as by use of different marker types, both of which challenge documentation of hybrid dynamics. Here, we use multiple genetic markers (mitochondrial DNA, microsatellites and genomewide single nucleotide polymorphisms) to re‐examine population structure in a hybrid zone between two species of swallowtail butterflies in western Canada, Papilio machaon and P. zelicaon. Our aim was to test whether their hybrid dynamics remain the same as found 30 years ago using morphology and allozymes, and we compared different genetic data sets as well as alternative hybrid identification and classification methods. Overall, we found high differentiation between the two parental species, corroborating previous research from the 1980s. We identified fewer hybrid individuals in the main zone of hybridization in recent years, but this finding depended on the genetic markers considered. Comparison of methods with simulated data sets generated from our data showed that single nucleotide polymorphisms were more powerful than microsatellites for both hybrid identification and classification. Moreover, substantial variation among comparisons underlined the value of multiple markers and methods for documenting evolutionarily dynamic systems.
Numerous clinical conditions can lead to organ fibrosis and functional failure. There is a great need for therapies that could effectively target pathophysiological pathways involved in fibrosis. ...GPR40 and GPR84 are G protein-coupled receptors with free fatty acid ligands and are associated with metabolic and inflammatory disorders. Although GPR40 and GPR84 are involved in diverse physiological processes, no evidence has demonstrated the relevance of GPR40 and GPR84 in fibrosis pathways. Using PBI-4050 (3-pentylbenzeneacetic acid sodium salt), a synthetic analog of a medium-chain fatty acid that displays agonist and antagonist ligand affinity toward GPR40 and GPR84, respectively, we uncovered an antifibrotic pathway involving these receptors. In experiments using Gpr40- and Gpr84-knockout mice in models of kidney fibrosis (unilateral ureteral obstruction, long-term post-acute ischemic injury, and adenine-induced chronic kidney disease), we found that GPR40 is protective and GPR84 is deleterious in these diseases. Moreover, through binding to GPR40 and GPR84, PBI-4050 significantly attenuated fibrosis in many injury contexts, as evidenced by the antifibrotic activity observed in kidney, liver, heart, lung, pancreas, and skin fibrosis models. Therefore, GPR40 and GPR84 may represent promising molecular targets in fibrosis pathways. We conclude that PBI-4050 is a first-in-class compound that may be effective for managing inflammatory and fibrosis-related diseases.
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