Cell type-specific expression and localization of cytochrome P450 isoforms in tridimensional aggregating rat brain cell cultures.

Within the Predict-IV FP7 project a strategy for measurement of in vitro biokinetics was developed, requiring the characterization of the cellular model used, especially regarding biotransformation, which frequently depends on cytochrome P450 (CYP) activity. The extrahepatic in situ CYP-mediated metabolism is especially relevant in target organ toxicity. In this study, the constitutive mRNA levels and protein localization of different CYP isoforms were investigated in 3D aggregating brain cell cultures. CYP1A1, CYP2B1/B2, CYP2D2/4, CYP2E1 and CYP3A were expressed; CYP1A1 and 2B1 represented almost 80% of the total mRNA content. Double-immunolabeling revealed their presence in astrocytes, in neurons, and to a minor extent in oligodendrocytes, confirming the cell-specific localization of CYPs in the brain. These results together with the recently reported formation of an amiodarone metabolite following repeated exposure suggest that this cell culture system possesses some metabolic potential, most likely contributing to its high performance in neurotoxicological studies and support the use of this model in studying brain neurotoxicity involving mechanisms of toxication/detoxication

The 2017 reversal of the Beaufort Gyre: Can dynamic thickening of a seasonal ice cover during a reversal limit summer ice melt in the Beaufort Sea?

During winter 2017 the semi‐permanent Beaufort High collapsed and the anticyclonic Beaufort Gyre reversed. The reversal drove eastward ice motion through the Western Arctic, causing sea ice to converge against Banks Island, and halted the circulation of multiyear sea ice via the gyre, preventing its replenishment in the Beaufort Sea. Prior to the reversal, an anomalously thin seasonal ice cover had formed in the Beaufort following ice‐free conditions during September 2016. With the onset of the reversal in January 2017, convergence drove uncharacteristic dynamic thickening during winter. By the end of March, despite seasonal ice comprising 97% of the ice cover, the reversal created the thickest, roughest and most voluminous regional ice cover of the CryoSat‐2 record. Within the Beaufort Sea, previous work has shown that winter ice export can precondition the region for increased summer ice melt, but that a short reversal during April 2013 contributed to a reduction in summer ice loss. Hence the deformed ice cover at the end of winter 2017 could be expected to limit summer melt. In spite of this, the Beaufort ice cover fell to its fourth lowest September area as the gyre re‐established during April and divergent ice drift broke up the pack, negating the reversal's earlier preconditioning. Our work highlights that dynamic winter thickening of a regional sea ice cover, for instance during a gyre reversal, offers the potential to limit summer ice loss, but that dynamic forcing during spring dictates whether this conditioning carries through to the melt season

Workgroup Report: Incorporating In Vitro Alternative Methods for Developmental Neurotoxicity into International Hazard and Risk Assessment Strategies

This is the report of the first workshop on Incorporating In Vitro Alternative Methods for Developmental Neurotoxicity (DNT) Testing into International Hazard and Risk Assessment Strategies, held in Ispra, Italy, on 19–21 April 2005. The workshop was hosted by the European Centre for the Validation of Alternative Methods (ECVAM) and jointly organized by ECVAM, the European Chemical Industry Council, and the Johns Hopkins University Center for Alternatives to Animal Testing. The primary aim of the workshop was to identify and catalog potential methods that could be used to assess how data from in vitro alternative methods could help to predict and identify DNT hazards. Working groups focused on two different aspects: a) details on the science available in the field of DNT, including discussions on the models available to capture the critical DNT mechanisms and processes, and b) policy and strategy aspects to assess the integration of alternative methods in a regulatory framework. This report summarizes these discussions and details the recommendations and priorities for future work

ESPRESSO: The next European exoplanet hunter

The acronym ESPRESSO stems for Echelle SPectrograph for Rocky Exoplanets and Stable Spectroscopic Observations; this instrument will be the next VLT high resolution spectrograph. The spectrograph will be installed at the Combined-Coud\'e Laboratory of the VLT and linked to the four 8.2 m Unit Telescopes (UT) through four optical Coud\'e trains. ESPRESSO will combine efficiency and extreme spectroscopic precision. ESPRESSO is foreseen to achieve a gain of two magnitudes with respect to its predecessor HARPS, and to improve the instrumental radial-velocity precision to reach the 10 cm/s level. It can be operated either with a single UT or with up to four UTs, enabling an additional gain in the latter mode. The incoherent combination of four telescopes and the extreme precision requirements called for many innovative design solutions while ensuring the technical heritage of the successful HARPS experience. ESPRESSO will allow to explore new frontiers in most domains of astrophysics that require precision and sensitivity. The main scientific drivers are the search and characterization of rocky exoplanets in the habitable zone of quiet, nearby G to M-dwarfs and the analysis of the variability of fundamental physical constants. The project passed the final design review in May 2013 and entered the manufacturing phase. ESPRESSO will be installed at the Paranal Observatory in 2016 and its operation is planned to start by the end of the same year.Comment: 12 pages, figures included, accepted for publication in Astron. Nach

A major genetic locus in <i>Trypanosoma brucei</i> is a determinant of host pathology

The progression and variation of pathology during infections can be due to components from both host or pathogen, and/or the interaction between them. The influence of host genetic variation on disease pathology during infections with trypanosomes has been well studied in recent years, but the role of parasite genetic variation has not been extensively studied. We have shown that there is parasite strain-specific variation in the level of splenomegaly and hepatomegaly in infected mice and used a forward genetic approach to identify the parasite loci that determine this variation. This approach allowed us to dissect and identify the parasite loci that determine the complex phenotypes induced by infection. Using the available trypanosome genetic map, a major quantitative trait locus (QTL) was identified on T. brucei chromosome 3 (LOD = 7.2) that accounted for approximately two thirds of the variance observed in each of two correlated phenotypes, splenomegaly and hepatomegaly, in the infected mice (named &lt;i&gt;TbOrg1&lt;/i&gt;). In addition, a second locus was identified that contributed to splenomegaly, hepatomegaly and reticulocytosis (&lt;i&gt;TbOrg2&lt;/i&gt;). This is the first use of quantitative trait locus mapping in a diploid protozoan and shows that there are trypanosome genes that directly contribute to the progression of pathology during infections and, therefore, that parasite genetic variation can be a critical factor in disease outcome. The identification of parasite loci is a first step towards identifying the genes that are responsible for these important traits and shows the power of genetic analysis as a tool for dissecting complex quantitative phenotypic traits

Characterization of the K2-38 planetary system: Unraveling one of the densest planets known to date

.-- Toledo-Padrón, B. et al.Context. An accurate characterization of the known exoplanet population is key to understanding the origin and evolution of planetary systems. Determining true planetary masses through the radial velocity (RV) method is expected to experience a great improvement thanks to the availability of ultra-stable echelle spectrographs. Aims. We took advantage of the extreme precision of the new-generation echelle spectrograph ESPRESSO to characterize the transiting planetary system orbiting the G2V star K2-38 located at 194 pc from the Sun with V 11.4. This system is particularly interesting because it could contain the densest planet detected to date. Methods. We carried out a photometric analysis of the available K2 photometric light curve of this star to measure the radius of its two known planets, K2-38b and K2-38c, with Pb = 4.01593 ± 0.00050 d and Pc = 10.56103 ± 0.00090 d, respectively. Using 43 ESPRESSO high-precision RV measurements taken over the course of 8 months along with the 14 previously published HIRES RV measurements, we modeled the orbits of the two planets through a Markov chain Monte Carlo analysis, significantly improving their mass measurements. Results. Using ESPRESSO spectra, we derived the stellar parameters, Teff = 5731 ± 66, log g = 4.38 ± 0.11 dex, and [Fe/H] = 0.26 ± 0.05 dex, and thus the mass and radius of K2-38, Ma = 1.03-0.02+0.04 MaS and Ra = 1.06-0.06+0.09 RaS. We determine new values for the planetary properties of both planets. We characterize K2-38b as a super-Earth with RP = 1.54 ± 0.14 RaS and Mp = 7.3-1.0+1.1 MaS, and K2-38c as a sub-Neptune with RP = 2.29 ± 0.26 RaS and Mp = 8.3-1.3+1.3 MaS. Combining the radius and mass measurements, we derived a mean density of ρp = 11.0-2.8+4.1 g cm-3 for K2-38b and ρp = 3.8-1.1+1.8 g cm-3 for K2-38c, confirming K2-38b as one of the densest planets known to date. Conclusions. The best description for the composition of K2-38b comes from an iron-rich Mercury-like model, while K2-38c is better described by a rocky-model with H2 envelope. The maximum collision stripping boundary shows how giant impacts could be the cause for the high density of K2-38b. The irradiation received by each planet places them on opposite sides of the radius valley. We find evidence of a long-period signal in the RV time-series whose origin could be linked to a 0.25-3 MJ planet or stellar activity.With funding from the Spanish government through the "María de Maeztu Unit of Excellence" accreditation (MDM-2017-0737

HD 142527: quantitative disk polarimetry with SPHERE

We present high-precision photometry and polarimetry for the protoplanetary disk around HD142527, with a focus on determining the light scattering parameters of the dust. We re-reduced polarimetric differential imaging data of HD142527 in the VBB (735 nm) and H-band (1625 nm) from the ZIMPOL and IRDIS subinstruments of SPHERE/VLT. With polarimetry and photometry based on reference star differential imaging, we were able to measure the linearly polarized intensity and the total intensity of the light scattered by the circumstellar disk with high precision. We used simple Monte Carlo simulations of multiple light scattering by the disk surface to derive constraints for three scattering parameters of the dust: the maximum polarization of $P_{\rm max}$, the asymmetry parameter $g$, and the single-scattering albedo $\omega$. We measure a reflected total intensity of $51.4\pm1.5$ mJy and $206\pm12$ mJy and a polarized intensity of $11.3\pm0.3$ mJy and $55.1\pm3.3$ mJy in the VBB and H-band, respectively. We also find in the visual range a degree of polarization that varies between $28\%$ on the far side of the disk and $17\%$ on the near side. The disk shows a red color for the scattered light intensity and the polarized intensity, which are about twice as high in the near-infrared when compared to the visual. We determine with model calculations the scattering properties of the dust particles and find evidence for strong forward scattering ($g\approx 0.5-0.75$), relatively low single-scattering albedo ($\omega \approx 0.2-0.5$), and high maximum polarization ($P_{\rm max} \approx 0.5-0.75$) at the surface on the far side of the disk for both observed wavelengths. The optical parameters indicate the presence of large aggregate dust particles, which are necessary to explain the high maximum polarization, the strong forward-scattering nature of the dust, and the observed red disk color.Comment: 20 pages, 14 figure

Search for scalar leptoquarks and T-odd quarks in the acoplanar jet topology using 2.5 fb-1 of ppbar collision data at sqrt(s)=1.96 TeV

A search for new physics in the acoplanar jet topology has been performed in 2.5 fb-1 of data from ppbar collisions at sqrt(s)=1.96 TeV, recorded by the D0 detector at the Fermilab Tevatron Collider. The numbers of events with exactly two acoplanar jets and missing transverse energy are in good agreement with the standard model expectations. The result of this search has been used to set a lower mass limit of 205 GeV at the 95% C.L. on the mass of a scalar leptoquark when this particle decays exclusively into a quark and a neutrino. In the framework of the Little Higgs model with T-parity, limits have also been obtained on the T-odd quark mass as a function of the T-odd photon mass

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE