Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

The Extended Clinical Phenotype of 26 Patients with Chronic Mucocutaneous Candidiasis due to Gain-of-Function Mutations in STAT1

PURPOSE: Gain-of-function (GOF) mutations in the signal transducer and activator of transcription 1 (STAT1) result in unbalanced STAT signaling and cause immune dysregulation and immunodeficiency. The latter is often characterized by the susceptibility to recurrent Candida infections, resulting in the clinical picture of chronic mucocutaneous candidiasis (CMC). This study aims to assess the frequency of GOF STAT1 mutations in a large international cohort of CMC patients. METHODS: STAT1 was sequenced in genomic DNA from 57 CMC patients and 35 healthy family members. The functional relevance of nine different STAT1 variants was shown by flow cytometric analysis of STAT1 phosphorylation in patients' peripheral blood cells (PBMC) after stimulation with interferon (IFN)-α, IFN-γ or interleukin-27 respectively. Extended clinical data sets were collected and summarized for 26 patients. RESULTS: Heterozygous mutations within STAT1 were identified in 35 of 57 CMC patients (61 %). Out of 39 familial cases from 11 families, 26 patients (67 %) from 9 families and out of 18 sporadic cases, 9 patients (50 %) were shown to have heterozygous mutations within STAT1. Thirteen distinct STAT1 mutations are reported in this paper. Eight of these mutations are known to cause CMC (p.M202V, p.A267V, p.R274W, p.R274Q, p.T385M, p.K388E, p.N397D, and p.F404Y). However, five STAT1 variants (p.F172L, p.Y287D, p.P293S, p.T385K and p.S466R) have not been reported before in CMC patients. CONCLUSION: STAT1 mutations are frequently observed in patients suffering from CMC. Thus, sequence analysis of STAT1 in CMC patients is advised. Measurement of IFN- or IL-induced STAT1 phosphorylation in PBMC provides a fast and reliable diagnostic tool and should be carried out in addition to genetic testing

Uranium amides as precursors to cationic and/or pentavalent compounds

International audienceThe uranium chloroamide complexes [U(NE$t_{2}$$)_{n}$$Cl_{4−n}$] (n=1, 2) were isolated from the comproportionation reactions of [U(NE$t_{2}$$)_{4}$] and UCl4. The protonolysis reaction of the M–N$R_{2}$ bond (M=Ti, Zr, Hf, U; R=Me, Et, Si$Me_{3}$) with the ammonium salt NH$R'_{3}$B$Ph_{4}$ (R′=Et, Me) constitutes an efficient and practical route to cationic complexes. Thus were prepared a series of organometallic uranium cations in the +3, +4 and +5 oxidation states. The reactions of these cationic compounds with nucleophiles, proton acidic substrates and unsaturated molecules have been developed. The dialkylamide ligand was useful to stabilize unique examples of neutral and cationic complexes of uranium in the +5 oxidation state

Comparative radiotracer study of cadmium uptake, storage, detoxification and depuration in the oyster Crassostrea gigas: potential adaptive mechanisms

International audienceThe bioaccumulation of cadmium in the oyster Crassostrea gigas originating from a clean (Bourgneuf Bay) and a chronically Cd-contaminated area (Gironde estuary) experimentally exposed to 109Cd-labeled bulk seawater (dissolved and particulate pathways combined) was examined over 21 d. A single-component first-order kinetic model describing the behavior of the bioaccumulation factor (BAF) throughout the experiment showed that the estimated Cd BAF at 21 d was 47% higher for oysters originating from the contaminated estuary than for oysters from the clean area, suggesting an influence of the previous chronic exposure to Cd contamination in the estuarine environment. From the experimental results, the potential adaptive mechanism suggested cannot be attributed to a reduction in Cd permeability but rather to a higher Cd turnover due to the synergy between lysosomes and metallothioneins which, through chelation, are responsible for the reduction in bioavailability and toxicity of cd in oysters. The lower BAF observed for soft parts of oysters previously exposed to chronic Cd contamination corresponded to a faster response to the experimental Cd contamination due to the presence of pre-existing metallothioneins induced by the Cd present in the estuarine environment. Furthermore, based on a 2-component exponential loss kinetic model, Cd complexation to metallothioneins and lysosomes was probably responsible for the slow turnover in the long-term compartment of loss (biological half-life, Tb1/2 = 495 and 198 d for the Bourgneuf and the Gironde oysters, respectively). Of the total Cd accumulated, 40 to 60% was in the soluble form and 30 to 40% of this fraction had been detoxified by the Gironde oysters through chelation to metallothioneins or to lysosomes, which means that approximately 12 to 24% of the total Cd accumulated was potentially bioavailable to humans through oyster consumption. However, through depuration, it was also more efficiently eliminated from oyster soft parts (the edible portion) previously exposed to Cd than from control oysters. Therefore, in the light of these results, it is suggested that the way in which regulatory thresholds of Cd in oysters are presently calculated should be reconsidered and should take into account the level of Cd already detoxified by the oysters through complexation processes

Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing.

Malaria elimination strategies require surveillance of the parasite population for genetic changes that demand a public health response, such as new forms of drug resistance. Here we describe methods for the large-scale analysis of genetic variation in Plasmodium falciparum by deep sequencing of parasite DNA obtained from the blood of patients with malaria, either directly or after short-term culture. Analysis of 86,158 exonic single nucleotide polymorphisms that passed genotyping quality control in 227 samples from Africa, Asia and Oceania provides genome-wide estimates of allele frequency distribution, population structure and linkage disequilibrium. By comparing the genetic diversity of individual infections with that of the local parasite population, we derive a metric of within-host diversity that is related to the level of inbreeding in the population. An open-access web application has been established for the exploration of regional differences in allele frequency and of highly differentiated loci in the P. falciparum genome