French Meteor Network for High Precision Orbits of Meteoroids

There is a lack of precise meteoroids orbit from video observations as most of the meteor stations use off-the-shelf CCD cameras. Few meteoroids orbit with precise semi-major axis are available using film photographic method. Precise orbits are necessary to compute the dust flux in the Earth s vicinity, and to estimate the ejection time of the meteoroids accurately by comparing them with the theoretical evolution model. We investigate the use of large CCD sensors to observe multi-station meteors and to compute precise orbit of these meteoroids. An ideal spatial and temporal resolution to get an accuracy to those similar of photographic plates are discussed. Various problems faced due to the use of large CCD, such as increasing the spatial and the temporal resolution at the same time and computational problems in finding the meteor position are illustrated

Differential, Phosphorylation Dependent Trafficking of AQP2 in LLC-PK1 Cells

The kidney maintains water homeostasis by modulating aquaporin 2 (AQP2) on the plasma membrane of collecting duct principal cells in response to vasopressin (VP). VP mediated phosphorylation of AQP2 at serine 256 is critical for this effect. However, the role of phosphorylation of other serine residues in the AQP2 C-terminus is less well understood. Here, we examined the effect of phosphorylation of S256, S261 and S269 on AQP2 trafficking and association with recycling pathway markers. We used LLC-PK1 cells expressing AQP2(S-D) or (S-A) phospho mutants and a 20°C cold block, which allows endocytosis to continue, but prevents protein exit from the trans Golgi network (TGN), inducing formation of a perinuclear AQP2 patch. AQP2-S256D persists on the plasma membrane during cold block, while wild type AQP2, AQP2-S256A, S261A, S269A and S269D are internalized and accumulate in the patch. Development of this patch, a measure of AQP2 internalization, was most rapid with AQP2-S256A, and slowest with S261A and S269D. AQP2-S269D exhibited a biphasic internalization profile with a significant amount not internalized until 150 minutes of cold block. After rewarming to 37°C, wt AQP2, AQP2-S261A and AQP2-S269D rapidly redistributed throughout the cytoplasm within 20 minutes, whereas AQP2-S256A dissipated more slowly. Colocalization of AQP2 mutants with several key vesicular markers including clathrin, HSP70/HSC70, EEA, GM130 and Rab11 revealed no major differences. Overall, our data provide evidence supporting the role of S256 and S269 in the maintenance of AQP2 at the cell surface and reveal the dynamics of internalization and recycling of differentially phosphorylated AQP2 in cell culture

Discovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3 H)-one

© 2015 American Chemical Society. In the face of the clinical challenge posed by resistant bacteria, the present needs for novel classes of antibiotics are genuine. In silico docking and screening, followed by chemical synthesis of a library of quinazolinones, led to the discovery of (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one (compound 2) as an antibiotic effective in vivo against methicillin-resistant Staphylococcus aureus (MRSA). This antibiotic impairs cell-wall biosynthesis as documented by functional assays, showing binding of 2 to penicillin-binding protein (PBP) 2a. We document that the antibiotic also inhibits PBP1 of S. aureus, indicating a broad targeting of structurally similar PBPs by this antibiotic. This class of antibiotics holds promise in fighting MRSA infections.Peer Reviewe

Early crustal processes revealed by the ejection site of the oldest martian meteorite

The formation and differentiation of the crust of Mars in the first tens of millions of years after its accretion can only be deciphered from incredibly limited records. The martian breccia NWA 7034 and its paired stones is one of them. This meteorite contains the oldest martian igneous material ever dated: ~4.5 Ga old. However, its source and geological context have so far remained unknown. Here, we show that the meteorite was ejected 5–10 Ma ago from the north-east of the Terra Cimmeria—Sirenum province, in the southern hemisphere of Mars. More specifically, the breccia belongs to the ejecta deposits of the Khujirt crater formed 1.5 Ga ago, and it was ejected as a result of the formation of the Karratha crater 5–10 Ma ago. Our findings demonstrate that the Terra Cimmeria—Sirenum province is a relic of the differentiated primordial martian crust, formed shortly after the accretion of the planet, and that it constitutes a unique record of early crustal processes. This province is an ideal landing site for future missions aiming to unravel the first tens of millions of years of the history of Mars and, by extension, of all terrestrial planets, including the Earth

Integrative structural biology of the penicillin-binding protein-1 from Staphylococcus aureus, an essential component of the divisome machinery

14 pags., 6 figs., 2 tabs.The penicillin-binding proteins are the enzyme catalysts of the critical transpeptidation crosslinking polymerization reaction of bacterial peptidoglycan synthesis and the molecular targets of the penicillin antibiotics. Here, we report a combined crystallographic, small-angle X-ray scattering (SAXS) in-solution structure, computational and biophysical analysis of PBP1 of Staphylococcus aureus (saPBP1), providing mechanistic clues about its function and regulation during cell division. The structure reveals the pedestal domain, the transpeptidase domain, and most of the linker connecting to the “penicillin-binding protein and serine/threonine kinase associated” (PASTA) domains, but not its two PASTA domains, despite their presence in the construct. To address this absence, the structure of the PASTA domains was determined at 1.5 Å resolution. Extensive molecular-dynamics simulations interpret the PASTA domains of saPBP1 as conformationally mobile and separated from the transpeptidase domain. This conclusion was confirmed by SAXS experiments on the full-length protein in solution. A series of crystallographic complexes with β-lactam antibiotics (as inhibitors) and penta-Gly (as a substrate mimetic) allowed the molecular characterization of both inhibition by antibiotics and binding for the donor and acceptor peptidoglycan strands. Mass-spectrometry experiments with synthetic peptidoglycan fragments revealed binding by PASTA domains in coordination with the remaining domains. The observed mobility of the PASTA domain in saPBP1 could play a crucial role for in vivo interaction with its glycosyltransferase partner in the membrane or with other components of the divisome machinery, as well as for coordination of transpeptidation and polymerization processes in the bacterial divisome.The work in the USA was supported by grants AI104987 (to SM)and AI116548 (to MC) from the NIH. The work in Spain was fundedby a grant from the Spanish Ministry of Science, Innovation and Competitiveness (BFU2017-90030-P and PID2020-115331GB-100 to JAH). We thank the staff from ALBA and Diamond Light Sourcesynchrotrons for help during X-ray and SAXS data collection,respectivel

Rochechouart 2017-Drilling Campaign: First Results

No abstract available

Vasopressin V2R-Targeting Peptide Carrier Mediates siRNA Delivery into Collecting Duct Cells

Internalization of receptor proteins after interacting with specific ligands has been proposed to facilitate siRNA delivery into the target cells via receptor-mediated siRNA transduction. In this study, we demonstrated a novel method of vasopressin V2 receptor (V2R)-mediated siRNA delivery against AQP2 in primary cultured inner medullary collecting duct (IMCD) cells of rat kidney. We synthesized the dDAVP conjugated with nine D-arginines (dDAVP-9r) as a peptide carrier for siRNA delivery. The structure of synthetic peptide carrier showed two regions (i.e., ligand domain to V2R (dDAVP) and siRNA carrying domain (nine D-arginine)) bisected with a spacer of four glycines. The results revealed that 1) synthesized dDAVP-9r peptides formed a stable polyplex with siRNA; 2) siRNA/dDAVP-9r polyplex could bind to the V2R of IMCD cells and induced AQP2 phosphorylation (Ser 256); 3) siRNA/dDAVP-9r polyplex was stable in response to the wide range of different osmolalities, pH levels, or to the RNases; 4) fluorescein-labeled siRNA was delivered into V2R-expressing MDCK and LLC-PK1 cells by siRNA/dDAVP-9r polyplex, but not into the V2R-negative Cos-7 cells; and 5) AQP2-siRNA/dDAVP-9r polyplex effectively delivered siRNA into the IMCD cells, resulting in the significant decrease of protein abundance of AQP2, but not AQP4. Therefore, for the first time to our knowledge, we demonstrated that V2R-mediated siRNA delivery could be exploited to deliver specific siRNA to regulate abnormal expression of target proteins in V2R-expressing kidney cells. The methods could be potentially used in vivo to regulate abnormal expression of proteins associated with disease conditions in the V2R-expressing kidney cells

Next-Generation NAMPT Inhibitors Identified by Sequential High-Throughput Phenotypic Chemical and Functional Genomic Screens

Phenotypic high-throughput chemical screens allow for discovery of small molecules that modulate complex phenotypes and provide lead compounds for novel therapies; however, identification of the mechanistically relevant targets remains a major experimental challenge. We report the application of sequential unbiased high-throughput chemical and ultracomplex small hairpin RNA (shRNA) screens to identify a distinctive class of inhibitors that target nicotinamide phosphoribosyl transferase (NAMPT), a rate-limiting enzyme in the biosynthesis of nicotinamide adenine dinucleotide, a crucial cofactor in many biochemical processes. The lead compound STF-118804 is a highly specific NAMPT inhibitor, improves survival in an orthotopic xenotransplant model of high-risk acute lymphoblastic leukemia, and targets leukemia stem cells. Tandem high-throughput screening using chemical and ultracomplex shRNA libraries, therefore, provides a rapid chemical genetics approach for seamless progression from small-molecule lead identification to target discovery and validation

Perception of epidemic's related anxiety in the General French Population: a cross-sectional study in the Rhône-Alpes region

International audienceBackgroundTo efficiently plan appropriate public health interventions during possible epidemics, governments must take into consideration the following factors about the general population: their knowledge of epidemics, their fears of and psychological responses to them, their level of compliance with government measures and their communities' trusted sources of information. However, such surveys among the French general population are rare.MethodsA cross-sectional study was conducted in 2006 in a representative sample of 600 subjects living in the Rhône-Alpes region (south-east France) to investigate self-reported knowledge about infectious diseases and anxiety generated by epidemic risk with particular reference to avian influenza. Data on reactions to potentially new epidemics and the confidence level in various sources of information were also collected.ResultsRespondents were most knowledgeable about AIDS, followed by avian influenza. Overall, 75% of respondents had adequate knowledge of avian influenza. The percentage was even higher (88%) among inhabitants of the Ain district, where an avian influenza epidemic had previously been reported. However, 39% expressed anxiety about this disease. In total, 20% of respondents with knowledge about avian influenza stated that they had changed their behaviours during the epizooty. Epidemics were perceived as a real threat by 27% of respondents. In the event of a highly contagious outbreak, the majority of respondents said they would follow the advice given by authorities. The study population expressed a high level of confidence in physicians and scientists, but had strong reservations about politicians, deputies and the media.ConclusionsAlthough the survey was conducted only four months after the avian influenza outbreak, epidemics were not perceived as a major threat by the study population. The results showed that in the event of a highly infectious disease, the population would comply with advice given by public authorities