Of mice and men...and viruses!

Beyond the main factors of infectious disease emergence, it is crucial to understand mechanisms of the host-parasite relationships through several significant models. We studied here the bank vole- Puumala hantavirus system, which constitutes a model for emerging zoonoses as Puumala is the agent of a human nephropathy. Studies used mathematical modeling based on field data. We present a hierarchical questioning and the associated scenarios are explored. They deal with host and virus ecology and dynamics. Human cases appear in a limited range of the host geographic distribution. Indirect transmission through the contaminated litter and the viral shedding dynamics appeared crucial for the virus spread and persistence. The human contamination may also depend on a synergy in bank vole and virus dynamics. The endemic area of the nephropathy is likely to extend geographically under the effect of the environmental modificationsAu delà des grands facteurs d’émergence des infections, il faut comprendre les mécanismes de la relation hôte-parasite qui mènent à l’épidémie. L’association campagnol roussâtre-Hantavirus Puumala est un modèle de nombreuses zoonoses émergentes car ce virus cause une néphropathie humaine. Il est étudié ici par la modélisation mathématique basée sur des suivis de terrain. Les questions sont hiérarchisées et abordées progressivement à travers les scénarios associés ayant trait à l'écologie des acteurs et aux dynamiques résultantes. Les cas humains n’ont lieu que dans certaines parties de l'aire de répartition du réservoir. La transmission par le sol apparaît décisive dans la propagation du virus tout comme la dynamique d'excrétion qui, en synergie avec la dynamique du réservoir, pourrait conduire à une concentration élevé de virus dans le milieu. Les observations révèlent que la maladie est susceptible de s’étendre géographiquement sous l’effet des modifications environnementales, des dynamiques du réservoir et du viru

The Spitzer Survey of the Small Magellanic Cloud: S3MC Imaging and Photometry in the Mid- and Far-Infrared Wavebands

We present the initial results from the Spitzer Survey of the Small Magellanic Cloud (S3MC), which imaged the star-forming body of the Small Magellanic Cloud (SMC) in all seven MIPS and IRAC wavebands. We find that the F_8/F_24 ratio (an estimate of PAH abundance) has large spatial variations and takes a wide range of values that are unrelated to metallicity but anticorrelated with 24 um brightness and F_24/F_70 ratio. This suggests that photodestruction is primarily responsible for the low abundance of PAHs observed in star-forming low-metallicity galaxies. We use the S3MC images to compile a photometric catalog of ~400,000 mid- and far-infrared point sources in the SMC. The sources detected at the longest wavelengths fall into four main categories: 1) bright 5.8 um sources with very faint optical counterparts and very red mid-infrared colors ([5.8]-[8.0]>1.2), which we identify as YSOs. 2) Bright mid-infrared sources with mildly red colors (0.16<[5.8]-[8.0]<0.6), identified as carbon stars. 3) Bright mid-infrared sources with neutral colors and bright optical counterparts, corresponding to oxygen-rich evolved stars. And, 4) unreddened early B stars (B3 to O9) with a large 24 um excess. This excess is reminiscent of debris disks, and is detected in only a small fraction of these stars (<5%). The majority of the brightest infrared point sources in the SMC fall into groups one to three. We use this photometric information to produce a catalog of 282 bright YSOs in the SMC with a very low level of contamination (~7%).Comment: Accepted for publication in The Astrophysical Journal. Given the draconian figure file-size limits implemented in astro-ph, readers are encouraged to download the manuscript with full quality images from http://celestial.berkeley.edu/spitzer/publications/s3mcsurvey.pd

Targeting Superficial or Nodular Basal Cell Carcinoma with Topically Formulated Small Molecule Inhibitor of Smoothened

Purpose: Inappropriate activation of the Hedgehog (Hh) signaling pathway in skin is critical for the development of basal cell carcinomas (BCC). We have investigated the anti-BCC efficacy of topically-applied CUR61414, an inhibitor of the Hh signal transduction molecule Smoothened. Experimental Design: In preclinical studies, we used a depilatory model to evaluate the ability of topical formulations of CUR61414 to repress Hh responsive cells found at the base of hair follicles in normal skin. We also tested the in vivo effects of topical CUR61414 on murine BCCs developed in $Ptch1^{ +/−}$ K14-CreER2 p53 fl/fl mice. In a phase I clinical study, we evaluated the safety, tolerability, and efficacy of a multidose regimen of CUR61414 (0.09%, 0.35%, 1.1%, and 3.1%) applied topically to human superficial or nodular BCCs for up to 28 days. Results: In mice, topical CUR61414 significantly inhibited skin Hh signaling, blocked the induction of hair follicle anagen, and shrank existing BCCs. However, we observed no clinical activity of this formulation in human superficial or nodular BCCs in a phase I clinical study. Conclusions: Our data highlight some of the challenges of translating preclinical experience into successful human results for a topical anticancer agent.Stem Cell and Regenerative Biolog

Complete Genome and Phylogeny of Puumala Hantavirus Isolates Circulating in France

Puumala virus (PUUV) is the agent of nephropathia epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS) in Europe. NE incidence presents a high spatial variation throughout France, while the geographical distribution of the wild reservoir of PUUV, the bank vole, is rather continuous. A missing piece of the puzzle is the current distribution and the genetic variation of PUUV in France, which has been overlooked until now and remains poorly understood. During a population survey, from 2008 to 2011, bank voles were trapped in eight different forests of France located in areas known to be endemic for NE or in area from where no NE case has been reported until now. Bank voles were tested for immunoglobulin (Ig)G ELISA serology and two seropositive animals for each of three different areas (Ardennes, Jura and Orleans) were then subjected to laboratory analyses in order to sequence the whole S, M and L segments of PUUV. Phylogenetic analyses revealed that French PUUV isolates globally belong to the central European (CE) lineage although isolates from Ardennes are clearly distinct from those in Jura and Orleans, suggesting a different evolutionary history and origin of PUUV introduction in France. Sequence analyses revealed specific amino acid signatures along the N protein, including in PUUV from the Orleans region from where NE in humans has never been reported. The relevance of these mutations in term of pathophysiology is discussed.Peer reviewe

Validity and limitations of simple reaction kinetics to calculate concentrations of organic compounds from ion counts in PTR-MS

In September 2017, we conducted a proton-transfer-reaction mass-spectrometry (PTR-MS) intercomparison campaign at the CESAR observatory, a rural site in the central Netherlands near the village of Cabauw. Nine research groups deployed a total of 11 instruments covering a wide range of instrument types and performance. We applied a new calibration method based on fast injection of a gas standard through a sample loop. This approach allows calibrations on timescales of seconds, and within a few minutes an automated sequence can be run allowing one to retrieve diagnostic parameters that indicate the performance status. We developed a method to retrieve the mass-dependent transmission from the fast calibrations, which is an essential characteristic of PTR-MS instruments, limiting the potential to calculate concentrations based on counting statistics and simple reaction kinetics in the reactor/drift tube. Our measurements show that PTR-MS instruments follow the simple reaction kinetics if operated in the standard range for pressures and temperature of the reaction chamber (i.e. 1-4 mbar, 30-120 degrees, respectively), as well as a reduced field strength E/N in the range of 100-160 Td. If artefacts can be ruled out, it becomes possible to quantify the signals of uncalibrated organics with accuracies better than +/- 30 %. The simple reaction kinetics approach produces less accurate results at E/N levels below 100 Td, because significant fractions of primary ions form water hydronium clusters. Deprotonation through reactive collisions of protonated organics with water molecules needs to be considered when the collision energy is a substantial fraction of the exoergicity of the proton transfer reaction and/or if protonated organics undergo many collisions with water molecules.Peer reviewe

Integrating hydrological features and genetically validated occurrence data in occupancy modeling of an endemic and endangered semi-aquatic mammal species, Galemys pyrenaicus, in a Pyrenean catchment

As freshwater habitats are among the most endangered, there is an urgent need to identify critical areas for conservation, especially those that are home to endangered species. The Pyrenean desman (Galemys pyrenaicus) is a semi-aquatic mammal whose basic ecological requirements are largely unknown, hindering adequate conservation planning even though it is considered as a threatened species. Species distribution modelling is challenging for freshwater species. Indeed, the complexity of aquatic ecosystems (e.g., linear and hierarchical ordering) must be taken into account as well as imperfect sampling. High-quality and relevant hydrological descriptors should also be used. To understand the influence of environmental covariates on the occupancy and detection of the Pyrenean desman, we combine both a robust sign-survey data set (i.e. with genetic validation ensuring true presence information) and a hydrological model to simulate the flow regime across a whole catchment. Markovian site-occupancy analysis, taking into account sign detection and based on spatially adjacent replicates, indicated a positive influence of heterogeneity of substrate and shelters, and a negative influence of flow variability on Pyrenean desman detection. This valuable information should help to improve monitoring programs for this endangered species. Our results also highlighted a spatially clustered distribution and a positive influence of stream flow and number of tributaries on occupancy. Hence, modifications of flow regime (e.g. hydropower production, irrigation, climate change) and habitat fragmentation appear to be major threats for this species, altering the connectivity between tributaries and the mainstream river as well as between adjacent sub-catchments