Skin sensitization in silico protocol

The assessment of skin sensitization has evolved over the past few years to include in vitro assessments of key events along the adverse outcome pathway and opportunistically capitalize on the strengths of in silico methods to support a weight of evidence assessment without conducting a test in animals. While in silico methods vary greatly in their purpose and format; there is a need to standardize the underlying principles on which such models are developed and to make transparent the implications for the uncertainty in the overall assessment. In this contribution, the relationship of skin sensitization relevant effects, mechanisms, and endpoints are built into a hazard assessment framework. Based on the relevance of the mechanisms and effects as well as the strengths and limitations of the experimental systems used to identify them, rules and principles are defined for deriving skin sensitization in silico assessments. Further, the assignments of reliability and confidence scores that reflect the overall strength of the assessment are discussed. This skin sensitization protocol supports the implementation and acceptance of in silico approaches for the prediction of skin sensitization

Two super-Earths at the edge of the habitable zone of the nearby M dwarf TOI-2095

The main scientific goal of TESS is to find planets smaller than Neptune around stars bright enough to allow further characterization studies. Given our current instrumentation and detection biases, M dwarfs are prime targets to search for small planets that are in (or nearby) the habitable zone of their host star. Here we use photometric observations and CARMENES radial velocity measurements to validate a pair of transiting planet candidates found by TESS. The data was fitted simultaneously using a Bayesian MCMC procedure taking into account the stellar variability present in the photometric and spectroscopic time series. We confirm the planetary origin of the two transiting candidates orbiting around TOI-2095 (TIC 235678745). The star is a nearby M dwarf ($d = 41.90 \pm 0.03$ pc, $T_{\rm eff} = 3759 \pm 87$ K, $V = 12.6$ mag) with a stellar mass and radius of $M_\star = 0.44 \pm 0.02 \; M_\odot$ and $R_\star = 0.44 \pm 0.02 \; R_\odot$, respectively. The planetary system is composed of two transiting planets: TOI-2095b with an orbital period of $P_b = 17.66484 \pm (7\times 10^{-5})$ days and TOI-2095c with $P_c = 28.17232 \pm (14\times 10^{-5})$ days. Both planets have similar sizes with $R_b = 1.25 \pm 0.07 \; R_\oplus$ and $R_c = 1.33 \pm 0.08 \; R_\oplus$ for planet b and c, respectively. We put upper limits on the masses of these objects with $M_b < 4.1 \; M_\oplus$ for the inner and $M_c < 7.4 \; M_\oplus$ for the outer planet (95\% confidence level). These two planets present equilibrium temperatures in the range of 300 - 350 K and are close to the inner edge of the habitable zone of their star.Comment: Submitted to Astronomy & Astrophysic

Mitochondrial Redox Metabolism in Trypanosomatids Is Independent of Tryparedoxin Activity

Tryparedoxins (TXNs) are oxidoreductases unique to trypanosomatids (including Leishmania and Trypanosoma parasites) that transfer reducing equivalents from trypanothione, the major thiol in these organisms, to sulfur-dependent peroxidases and other dithiol proteins. The existence of a TXN within the mitochondrion of trypanosomatids, capable of driving crucial redox pathways, is considered a requisite for normal parasite metabolism. Here this concept is shown not to apply to Leishmania. First, removal of the Leishmania infantum mitochondrial TXN (LiTXN2) by gene-targeting, had no significant effect on parasite survival, even in the context of an animal infection. Second, evidence is presented that no other TXN is capable of replacing LiTXN2. In fact, although a candidate substitute for LiTXN2 (LiTXN3) was found in the genome of L. infantum, this was shown in biochemical assays to be poorly reduced by trypanothione and to be unable to reduce sulfur-containing peroxidases. Definitive conclusion that LiTXN3 cannot directly reduce proteins located within inner mitochondrial compartments was provided by analysis of its subcellular localization and membrane topology, which revealed that LiTXN3 is a tail-anchored (TA) mitochondrial outer membrane protein presenting, as characteristic of TA proteins, its N-terminal end (containing the redox-active domain) exposed to the cytosol. This manuscript further proposes the separation of trypanosomatid TXN sequences into two classes and this is supported by phylogenetic analysis: i) class I, encoding active TXNs, and ii) class II, coding for TA proteins unlikely to function as TXNs. Trypanosoma possess only two TXNs, one belonging to class I (which is cytosolic) and the other to class II. Thus, as demonstrated for Leishmania, the mitochondrial redox metabolism in Trypanosoma may also be independent of TXN activity. The major implication of these findings is that mitochondrial functions previously thought to depend on the provision of electrons by a TXN enzyme must proceed differently

TOI-150b And TOI-163b: Two Transiting Hot Jupiters, One Eccentric And One Inflated, Revealed By TESS Near And At The Edge Of The JWST CVZ

We present the discovery of TYC9191-519-1b (TOI-150b, TIC 271893367) and HD271181b (TOI-163b, TIC 179317684), two hot Jupiters initially detected using 30-min cadence Transiting Exoplanet Survey Satellite (TESS) photometry from Sector 1 and thoroughly characterized through follow-up photometry (CHAT, Hazelwood, LCO/CTIO, El Sauce, TRAPPIST-S), high-resolution spectroscopy (FEROS, CORALIE), and speckle imaging (Gemini/DSSI), confirming the planetary nature of the two signals. A simultaneous joint fit of photometry and radial velocity using a new fitting package juliet reveals that TOI-150b is a 1.254±0.016 RJ⁠, massive (⁠2.61+0.19−0.12 MJ⁠) hot Jupiter in a 5.857-d orbit, while TOI-163b is an inflated (⁠RP = 1.478+0.022−0.029RJ⁠, MP = 1.219±0.11MJ⁠) hot Jupiter on a P = 4.231-d orbit; both planets orbit F-type stars. A particularly interesting result is that TOI-150b shows an eccentric orbit (⁠e=0.262+0.045−0.037⁠), which is quite uncommon among hot Jupiters. We estimate that this is consistent, however, with the circularization time-scale, which is slightly larger than the age of the system. These two hot Jupiters are both prime candidates for further characterization – in particular, both are excellent candidates for determining spin-orbit alignments via the Rossiter–McLaughlin (RM) effect and for characterizing atmospheric thermal structures using secondary eclipse observations considering they are both located closely to the James Webb Space Telescope (JWST) Continuous Viewing Zone (CVZ)

Leishmania Mitochondrial Peroxiredoxin Plays a Crucial Peroxidase-Unrelated Role during Infection: Insight into Its Novel Chaperone Activity

Two-cysteine peroxiredoxins are ubiquitous peroxidases that play various functions in cells. In Leishmania and related trypanosomatids, which lack catalase and selenium-glutathione peroxidases, the discovery of this family of enzymes provided the molecular basis for peroxide removal in these organisms. In this report the functional relevance of one of such enzymes, the mitochondrial 2-Cys peroxiredoxin (mTXNPx), was investigated along the Leishmania infantum life cycle. mTXNPx null mutants (mtxnpx−) produced by a gene replacement strategy, while indistinguishable from wild type promastigotes, were found unable to thrive in a murine model of infection. Unexpectedly, however, the avirulent phenotype of mtxnpx− was not due to lack of the peroxidase activity of mTXNPx as these behaved like controls when exposed to oxidants added exogenously or generated by macrophages during phagocytosis ex vivo. In line with this, mtxnpx− were also avirulent when inoculated into murine hosts unable to mount an effective oxidative phagocyte response (B6.p47phox−/− and B6.RAG2−/− IFN-γ−/− mice). Definitive conclusion that the peroxidase activity of mTXNPx is not required for parasite survival in mice was obtained by showing that a peroxidase-inactive version of this protein was competent in rescuing the non-infective phenotype of mtxnpx−. A novel function is thus proposed for mTXNPx, that of a molecular chaperone, which may explain the impaired infectivity of the null mutants. This premise is based on the observation that the enzyme is able to suppress the thermal aggregation of citrate synthase in vitro. Also, mtxnpx− were more sensitive than controls to a temperature shift from 25°C to 37°C, a phenotype reminiscent of organisms lacking specific chaperone genes. Collectively, the findings reported here change the paradigm which regards all trypanosomatid 2-Cys peroxiredoxins as peroxide-eliminating devices. Moreover, they demonstrate, for the first time, that these 2-Cys peroxiredoxins can be determinant for pathogenicity independently of their peroxidase activity

Two long-period transiting exoplanets on eccentric orbits: NGTS-20 b (TOI-5152 b) and TOI-5153 b

Long-period transiting planets provide the opportunity to better understand the formation and evolution of planetary systems. Their atmospheric properties remain largely unaltered by tidal or radiative effects of the host star, and their orbital arrangement reflects a different, and less extreme, migrational history compared to close-in objects. The sample of long-period exoplanets with well determined masses and radii is still limited, but a growing number of long-period objects reveal themselves in the TESS data. Our goal is to vet and confirm single transit planet candidates detected in the TESS space-based photometric data through spectroscopic and photometric follow up observations with ground-based instruments. We use the Next Generation Transit Survey (NGTS) to photometrically monitor the candidates in order to observe additional transits. We report the discovery of two massive, warm Jupiter-size planets, one orbiting the F8-type star TOI-5153 and the other orbiting the G1-type star NGTS-20 (=TOI-5152). From our spectroscopic analysis, both stars are metal-rich with a metallicity of 0.12 and 0.15, respectively. Follow-up radial velocity observations were carried out with CORALIE, CHIRON, FEROS, and HARPS. TOI-5153 hosts a 20.33 day period planet with a planetary mass of 3.26 (+-0.18) Mj, a radius of 1.06 (+-0.04) Rj , and an orbital eccentricity of 0.091 (+-0.026). NGTS-20 b is a 2.98 (+-0.16) Mj planet with a radius of 1.07 (+-0.04) Rj on an eccentric (0.432 +- 0.023) orbit with an orbital period of 54.19 days. Both planets are metal-enriched and their heavy element content is in line with the previously reported mass-metallicity relation for gas giants. Both warm Jupiters orbit moderately bright host stars making these objects valuable targets for follow-up studies of the planetary atmosphere and measurement of the spin-orbit angle of the system.Comment: 17 pages, 13 figures, accepted to A&

A long-period transiting substellar companion in the super-Jupiters to brown dwarfs mass regime and a prototypical warm-Jupiter detected by TESS

We report on the confirmation and follow-up characterization of two long-period transiting substellar companions on low-eccentricity orbits around TIC 4672985 and TOI-2529, whose transit events were detected by the TESS space mission. Ground-based photometric and spectroscopic follow up from different facilities, confirmed the substellar nature of TIC 4672985 b, a massive gas giant, in the transition between the super-Jupiters and brown-dwarfs mass regime. From the joint analysis we derived the following orbital parameters: P = 69.0480+0.0004−0.0005 d, Mp = 12.74+1.01−1.01 MJ, Rp =1.026+0.065−0.067 RJ and e = 0.018+0.004−0.004 . In addition, the RV time series revealed a significant trend at the ∼ 350 m s−1 yr−1level, which is indicative of the presence of a massive outer companion in the system. TIC 4672985 b is a unique example of a transiting substellar companion with a mass above the deuterium-burning limit, located beyond 0.1 AU and in a nearly circular orbit. These planetary properties are difficult to reproduce from canonical planet formation and evolution models. For TOI-2529 b, we obtained the following orbital parameters: P = 64.5949+0.0003−0.0003 d, Mp =2.340+0.197−0.195 MJ, Rp = 1.030+0.050−0.050 RJ and e = 0.021+0.024−0.015 , making this object a new example of a growing population of transiting warm giant planets

A long-period transiting substellar companion in the super-Jupiters to brown dwarfs mass regime and a prototypical warm-Jupiter detected by TESS

We report on the confirmation and follow-up characterization of two long-period transiting substellar companions on low-eccentricity orbits around TIC 4672985 and TOI-2529, whose transit events were detected by the TESS space mission. Ground-based photometric and spectroscopic follow-up from different facilities, confirmed the substellar nature of TIC 4672985 b, a massive gas giant, in the transition between the super Jupiters and brown dwarfs mass regime. From the joint analysis we derived the following orbital parameters: P = 69.0480 d, Mp = 12.74 Mjup, Rp = 1.026 Rjup and e = 0.018. In addition, the RV time series revealed a significant trend at the 350 m/s/yr level, which is indicative of the presence of a massive outer companion in the system. TIC 4672985 b is a unique example of a transiting substellar companion with a mass above the deuterium-burning limit, located beyond 0.1 AU and in a nearly circular orbit. These planetary properties are difficult to reproduce from canonical planet formation and evolution models. For TOI-2529 b, we obtained the following orbital parameters: P = 64.5949 d, Mp = 2.340 Mjup, Rp = 1.030 Rjup and e = 0.021, making this object a new example of a growing population of transiting warm giant planets.Comment: Accepted in A&

HD 213885b: A Transiting 1-D-Period Super-Earth With An Earth-Like Composition Around A Bright (V = 7.9) Star Unveiled By TESS

We report the discovery of the 1.008-d, ultrashort period (USP) super-Earth HD 213885b (TOI-141b) orbiting the bright (V = 7.9) star HD 213885 (TOI-141, TIC 403224672), detected using photometry from the recently launched TESS mission. Using FEROS, HARPS, and CORALIE radial velocities, we measure a precise mass of 8.8 ± 0.6 M⊕ for this 1.74 ± 0.05 R⊕ exoplanet, which provides enough information to constrain its bulk composition – similar to Earth’s but enriched in iron. The radius, mass, and stellar irradiation of HD 213885b are, given our data, very similar to 55 Cancri e, making this exoplanet a good target to perform comparative exoplanetology of short period, highly irradiated super-Earths. Our precise radial velocities reveal an additional 4.78-d signal which we interpret as arising from a second, non-transiting planet in the system, HD 213885c, whose minimum mass of 19.9 ± 1.4 M⊕ makes it consistent with being a Neptune-mass exoplanet. The HD 213885 system is very interesting from the perspective of future atmospheric characterization, being the second brightest star to host an USP transiting super-Earth (with the brightest star being, in fact, 55 Cancri). Prospects for characterization with present and future observatories are discussed

The CARMENES search for exoplanets around M dwarfs

Context. The CARMENES instrument, installed at the 3.5 m telescope of the Calar Alto Observatory in Almería, Spain, was conceived to deliver high-accuracy radial velocity (RV) measurements with long-term stability to search for temperate rocky planets around a sample of nearby cool stars. Moreover, the broad wavelength coverage was designed to provide a range of stellar activity indicators to assess the nature of potential RV signals and to provide valuable spectral information to help characterise the stellar targets. Aims: We describe the CARMENES guaranteed time observations (GTO), spanning from 2016 to 2020, during which 19 633 spectra for a sample of 362 targets were collected. We present the CARMENES Data Release 1 (DR1), which makes public all observations obtained during the GTO of the CARMENES survey. Methods: The CARMENES survey target selection was aimed at minimising biases, and about 70% of all known M dwarfs within 10 pc and accessible from Calar Alto were included. The data were pipeline-processed, and high-level data products, including 18 642 precise RVs for 345 targets, were derived. Time series data of spectroscopic activity indicators were also obtained. Results: We discuss the characteristics of the CARMENES data, the statistical properties of the stellar sample, and the spectroscopic measurements. We show examples of the use of CARMENES data and provide a contextual view of the exoplanet population revealed by the survey, including 33 new planets, 17 re-analysed planets, and 26 confirmed planets from transiting candidate follow-up. A subsample of 238 targets was used to derive updated planet occurrence rates, yielding an overall average of 1.44 ± 0.20 planets with 1 M⊕ &lt; Mpl sin i &lt; 1000 M⊕ and 1 day &lt; Porb &lt; 1000 days per star, and indicating that nearly every M dwarf hosts at least one planet. All the DR1 raw data, pipeline-processed data, and high-level data products are publicly available online. Conclusions: CARMENES data have proven very useful for identifying and measuring planetary companions. They are also suitable for a variety of additional applications, such as the determination of stellar fundamental and atmospheric properties, the characterisation of stellar activity, and the study of exoplanet atmospheres