Purification and Preliminary Crystallographic Analysis of a New Lys49-PLA2 from B. Jararacussu

BjVIII is a new myotoxic Lys49-PLA2 isolated from Bothrops jararacussu venom that exhibits atypical effects on human platelet aggregation. To better understand the mode of action of BjVIII, crystallographic studies were initiated. Two crystal forms were obtained, both containing two molecules in the asymmetric unit (ASU). Synchrotron radiation diffraction data were collected to 2.0 Å resolution and 1.9 Å resolution for crystals belonging to the space group P212121 (a = 48.4 Å, b = 65.3 Å, c = 84.3 Å) and space group P3121 (a = b = 55.7 Å, c = 127.9 Å), respectively. Refinement is currently in progress and the refined structures are expected to shed light on the unusual platelet aggregation activity observed for BjVIII

Evaluation of two methods for computational HLA haplotypes inference using a real dataset

<p>Abstract</p> <p>Background</p> <p>HLA haplotype analysis has been used in population genetics and in the investigation of disease-susceptibility locus, due to its high polymorphism. Several methods for inferring haplotype genotypic data have been proposed, but it is unclear how accurate each of the methods is or which method is superior. The accuracy of two of the leading methods of computational haplotype inference – Expectation-Maximization algorithm based (implemented in Arlequin V3.0) and Bayesian algorithm based (implemented in PHASE V2.1.1) – was compared using a set of 122 HLA haplotypes (A-B-Cw-DQB1-DRB1) determined through direct counting. The accuracy was measured with the Mean Squared Error (<it>MSE</it>), Similarity Index (<it>I</it>_<it>F</it>) and Haplotype Identification Index (<it>I</it>_<it>H</it>).</p> <p>Results</p> <p>None of the methods inferred all of the known haplotypes and some differences were observed in the accuracy of the two methods in terms of both haplotype determination and haplotype frequencies estimation. Working with haplotypes composed by low polymorphic sites, present in more than one individual, increased the confidence in the assignment of haplotypes and in the estimation of the haplotype frequencies generated by both programs.</p> <p>Conclusion</p> <p>The PHASE v2.1.1 implemented method had the best overall performance both in haplotype construction and frequency calculation, although the differences between the two methods were insubstantial. To our knowledge this was the first work aiming to test statistical methods using real haplotypic data from the HLA region.</p

Cymoxanil inhibits respiration through inhibition of mitochondrial complex IV

Cymoxanil is a synthetic acetamide fungicide, used against oomycetes. It was first introduced in 1977 and can be used against downy mildew diseases induced by Plasmopara viticola in grapevine cultures and late blight diseases caused by Phytophthora infestans, in tomatoes and potatoes cultures. This fungicide is used in mixed formulations and its higher solubility enables a relatively widespread occurrence in toxic concentrations in aquatic environments. Although it has been used over the years, its biochemical mode of action is not yet known. Some studies reported that cymoxanil affects growth, respiration, DNA, RNA and protein synthesis and RNA polymerase activity of Phytophthora infestans, and it was reported to inhibit cell growth and biomass production and decrease the respiration rate of S. cerevisiae. Using yeast S. cerevisiae as model, we further characterized its effect on mitochondria. We found that whole cells treated with cymoxanil present a higher inhibition of oxygen consumption after 3 h of treatment that remains over time. Using isolated mitochondria, we observe that cymoxanil inhibits respiratory rate of yeast cells by inhibiting oxidative phosphorylation, through inhibition of complex IV activity. Although other targets cannot be excluded, our data provide new information about mode of action of cymoxanil that can be instrumental to drive informed management regarding the use of this fungicide.info:eu-repo/semantics/publishedVersio

Magnetic response dependence of ZnO based thin films on Ag doping and processing architecture

Multifunctional and multiresponsive thin films are playing an increasing role in modern technology. This work reports a study on the magnetic properties of ZnO and Ag-doped ZnO semiconducting films prepared with a zigzag-like columnar architecture and their correlation with the processing conditions. The films were grown through Glancing Angle Deposition (GLAD) co-sputtering technique to improve the induced ferromagnetism at room temperature. Structural and morphological characterizations have been performed and correlated with the paramagnetic resonance measurements, which demonstrate the existence of vacancies in both as-cast and annealed films. The magnetic measurements reveal changes in the magnetic order of both ZnO and Ag-doped ZnO films with increasing temperature, showing an evolution from a paramagnetic (at low temperature) to a diamagnetic behavior (at room temperature). Further, the room temperature magnetic properties indicate a ferromagnetic order even for the un-doped ZnO film. The results open new perspectives for the development of multifunctional ZnO semiconductors, the GLAD co-sputtering technique enables the control of the magnetic response, even in the un-doped semiconductor materials.The Brazilian agencies CNPq, CAPES partially supports the research. From Portugal side, this work was supported by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding UID/FIS/04650/2020 and the junior research contract (A.F.). Financial support from the Basque Government Industry Department under the ELKARTEK. HAZITEK and PIBA programs is also acknowledged

SOPHIE velocimetry of Kepler transit candidates XVII. The physical properties of giant exoplanets within 400 days of period

While giant extrasolar planets have been studied for more than two decades now, there are still some open questions such as their dominant formation and migration process, as well as their atmospheric evolution in different stellar environments. In this paper, we study a sample of giant transiting exoplanets detected by the Kepler telescope with orbital periods up to 400 days. We first defined a sample of 129 giant-planet candidates that we followed up with the SOPHIE spectrograph (OHP, France) in a 6-year radial velocity campaign. This allow us to unveil the nature of these candidates and to measure a false-positive rate of 54.6 +/- 6.5 % for giant-planet candidates orbiting within 400 days of period. Based on a sample of confirmed or likely planets, we then derive the occurrence rates of giant planets in different ranges of orbital periods. The overall occurrence rate of giant planets within 400 days is 4.6 +/- 0.6 %. We recover, for the first time in the Kepler data, the different populations of giant planets reported by radial velocity surveys. Comparing these rates with other yields, we find that the occurrence rate of giant planets is lower only for hot jupiters but not for the longer period planets. We also derive a first measurement on the occurrence rate of brown dwarfs in the brown-dwarf desert with a value of 0.29 +/- 0.17 %. Finally, we discuss the physical properties of the giant planets in our sample. We confirm that giant planets receiving a moderate irradiation are not inflated but we find that they are in average smaller than predicted by formation and evolution models. In this regime of low-irradiated giant planets, we find a possible correlation between their bulk density and the Iron abundance of the host star, which needs more detections to be confirmed.Comment: To appear in Astronomy and Astrophysic

SOPHIE velocimetry of Kepler transit candidates XII. KOI-1257 b: a highly eccentric three-month period transiting exoplanet

In this paper we report a new transiting warm giant planet: KOI-1257 b. It was first detected in photometry as a planet-candidate by the ${\it Kepler}$ space telescope and then validated thanks to a radial velocity follow-up with the SOPHIE spectrograph. It orbits its host star with a period of 86.647661 d $\pm$ 3 s and a high eccentricity of 0.772 $\pm$ 0.045. The planet transits the main star of a metal-rich, relatively old binary system with stars of mass of 0.99 $\pm$ 0.05 Msun and 0.70 $\pm$ 0.07 Msun for the primary and secondary, respectively. This binary system is constrained thanks to a self-consistent modelling of the ${\it Kepler}$ transit light curve, the SOPHIE radial velocities, line bisector and full-width half maximum (FWHM) variations, and the spectral energy distribution. However, future observations are needed to confirm it. The PASTIS fully-Bayesian software was used to validate the nature of the planet and to determine which star of the binary system is the transit host. By accounting for the dilution from the binary both in photometry and in radial velocity, we find that the planet has a mass of 1.45 $\pm$ 0.35 Mjup, and a radius of 0.94 $\pm$ 0.12 Rjup, and thus a bulk density of 2.1 $\pm$ 1.2 g.cm$^{-3}$. The planet has an equilibrium temperature of 511 $\pm$ 50 K, making it one of the few known members of the warm-jupiter population. The HARPS-N spectrograph was also used to observe a transit of KOI-1257 b, simultaneously with a joint amateur and professional photometric follow-up, with the aim of constraining the orbital obliquity of the planet. However, the Rossiter-McLaughlin effect was not clearly detected, resulting in poor constraints on the orbital obliquity of the planet.Comment: 39 pages, 17 figures, accepted for publication in Astronomy & Astrophysic

Neurodevelopmental regression, severe generalized dystonia, and metabolic acidosis caused by POLR3A mutations.

OBJECTIVE: To expand the clinical phenotype of POLR3A mutations by assessing the functional consequences of a missense and a splicing acceptor mutation. METHODS: We performed whole-exome sequencing for identification of likely pathogenic mutations in a 9-year-old female patient with severe generalized dystonia, metabolic acidosis, leukocytosis, hypotonia, and dysphagia. Brain MRI showed basal ganglia atrophy and presence of lactate and lipid peaks by [1H]-magnetic resonance spectroscopy. Expression levels of Pol III target genes were measured by quantitative real-time (qRT)-PCR to study the pathogenicity of the biallelic mutations in patient fibroblasts. RESULTS: The patient is a compound heterozygous for a novel missense c.3721G>A (p.Val1241Met) and the splicing region c.1771-6C>G mutation in POLR3A, the gene coding for the catalytic subunit of RNA polymerase III (Pol III). Aberrant splicing was observed for the c.1771-6C>G mutation. Decreased RNA expression levels of Pol III targets (HNRNPH2, ubiquitin B, lactotransferrin, and HSP90AA1) were observed in patient fibroblasts with rescue to normal levels by overexpression of the wild-type protein but not by the p.Val1241Met variant. CONCLUSIONS: Mutations in the POLR3A gene cause POLR3A-related hypomyelinating leukodystrophy with or without oligodontia or hypogonadotropic hypogonadism (HLD7, OMIM: 607694) and neonatal progeroid syndrome (OMIM: 264090), both with high phenotypic variability. We demonstrated the pathogenicity of c.1771-6C>G and c.3721G>A mutations causing an early-onset disorder. The phenotype of our patient expands the clinical presentation of POLR3A-related mutations and suggests a new classification that we propose designating as Neurodevelopmental Disorder with Regression, Abnormal Movements, and Increased Lactate

Dark Matter Results from 100 Live Days of XENON100 Data

We present results from the direct search for dark matter with the XENON100 detector, installed underground at the Laboratori Nazionali del Gran Sasso of INFN, Italy. XENON100 is a two-phase time projection chamber with a 62 kg liquid xenon target. Interaction vertex reconstruction in three dimensions with millimeter precision allows to select only the innermost 48 kg as ultra-low background fiducial target. In 100.9 live days of data, acquired between January and June 2010, no evidence for dark matter is found. Three candidate events were observed in a pre-defined signal region with an expected background of 1.8 +/- 0.6 events. This leads to the most stringent limit on dark matter interactions today, excluding spin-independent elastic WIMP-nucleon scattering cross-sections above 7.0x10^-45 cm^2 for a WIMP mass of 50 GeV/c^2 at 90% confidence level.Comment: 5 pages, 5 figures; matches accepted versio

Implications on Inelastic Dark Matter from 100 Live Days of XENON100 Data

The XENON100 experiment has recently completed a dark matter run with 100.9 live-days of data, taken from January to June 2010. Events in a 48kg fiducial volume in the energy range between 8.4 and 44.6 keVnr have been analyzed. A total of three events have been found in the predefined signal region, compatible with the background prediction of (1.8 \pm 0.6) events. Based on this analysis we present limits on the WIMP-nucleon cross section for inelastic dark matter. With the present data we are able to rule out the explanation for the observed DAMA/LIBRA modulation as being due to inelastic dark matter scattering off iodine at a 90% confidence level.Comment: 3 pages, 3 figure