VE-PTP maintains the endothelial barrier via plakoglobin and becomes dissociated from VE-cadherin by leukocytes and by VEGF

We have shown recently that vascular endothelial protein tyrosine phosphatase (VE-PTP), an endothelial-specific membrane protein, associates with vascular endothelial (VE)–cadherin and enhances VE-cadherin function in transfected cells (Nawroth, R., G. Poell, A. Ranft, U. Samulowitz, G. Fachinger, M. Golding, D.T. Shima, U. Deutsch, and D. Vestweber. 2002. EMBO J. 21:4885–4895). We show that VE-PTP is indeed required for endothelial cell contact integrity, because down-regulation of its expression enhanced endothelial cell permeability, augmented leukocyte transmigration, and inhibited VE-cadherin–mediated adhesion. Binding of neutrophils as well as lymphocytes to endothelial cells triggered rapid (5 min) dissociation of VE-PTP from VE-cadherin. This dissociation was only seen with tumor necrosis factor α–activated, but not resting, endothelial cells. Besides leukocytes, vascular endothelial growth factor also rapidly dissociated VE-PTP from VE-cadherin, indicative of a more general role of VE-PTP in the regulation of endothelial cell contacts. Dissociation of VE-PTP and VE-cadherin in endothelial cells was accompanied by tyrosine phoshorylation of VE-cadherin, β-catenin, and plakoglobin. Surprisingly, only plakoglobin but not β-catenin was necessary for VE-PTP to support VE-cadherin adhesion in endothelial cells. In addition, inhibiting the expression of VE-PTP preferentially increased tyrosine phosphorylation of plakoglobin but not β-catenin. In conclusion, leukocytes interacting with endothelial cells rapidly dissociate VE-PTP from VE-cadherin, weakening endothelial cell contacts via a mechanism that requires plakoglobin but not β-catenin

ACCESS: A Visual to Near-infrared Spectrum of the Hot Jupiter WASP-43b with Evidence of H2O\rm H_2O, but no evidence of Na or K

We present a new ground-based visual transmission spectrum of the hot Jupiter WASP-43b, obtained as part of the ACCESS Survey. The spectrum was derived from four transits observed between 2015 and 2018, with combined wavelength coverage between 5,300 \r{A}-9,000 \r{A} and an average photometric precision of 708 ppm in 230 \r{A} bins. We perform an atmospheric retrieval of our transmission spectrum combined with literature HST/WFC3 observations to search for the presence of clouds/hazes as well as Na, K, H$\alpha$, and $\rm H_2O$ planetary absorption and stellar spot contamination over a combined spectral range of 5,318 \r{A}-16,420 \r{A}. We do not detect a statistically significant presence of Na I or K I alkali lines, or H$\alpha$ in the atmosphere of WASP-43b. We find that the observed transmission spectrum can be best explained by a combination of heterogeneities on the photosphere of the host star and a clear planetary atmosphere with $\rm H_2O$. This model yields a log-evidence of $8.26\pm0.42$ higher than a flat (featureless) spectrum. In particular, the observations marginally favor the presence of large, low-contrast spots over the four ACCESS transit epochs with an average covering fraction $f_\text{het} = 0.27^{+0.42}_{-0.16}$ and temperature contrast $\Delta T = 132\text{ K} \pm 132\text{ K}$. Within the planet's atmosphere, we recover a log $\rm H_2O$ volume mixing ratio of $-2.78^{+1.38}_{-1.47}$, which is consistent with previous $\rm H_2O$ abundance determinations for this planet.Comment: 27 pages, 18 figures, 7 tables. Accepted for publication in AJ. Updated affiliation

ACCESS: An optical transmission spectrum of the high-gravity, hot Jupiter HAT-P-23b

We present a new ground-based visible transmission spectrum of the high-gravity, hot Jupiter HAT-P-23b, obtained as part of the ACCESS project. We derive the spectrum from five transits observed between 2016 and 2018, with combined wavelength coverage between 5200 {\AA} - 9269 {\AA} in 200 {\AA} bins, and with a median precision of 247 ppm per bin. HAT-P-23b's relatively high surface gravity (g ~ 30 m/s^2), combined with updated stellar and planetary parameters from Gaia DR2, gives a 5-scale-height signal of 384 ppm for a hydrogen-dominated atmosphere. Bayesian models favor a clear atmosphere for the planet with the tentative presence of TiO, after simultaneously modeling stellar contamination, using spots parameter constraints from photometry. If confirmed, HAT-P-23b would be the first example of a high-gravity gas giant with a clear atmosphere observed in transmission at optical/NIR wavelengths; therefore, we recommend expanding observations to the UV and IR to confirm our results and further characterize this planet. This result demonstrates how combining transmission spectroscopy of exoplanet atmospheres with long-term photometric monitoring of the host stars can help disentangle the exoplanet and stellar activity signals.Comment: 28 pages, 18 Figures, accepted for publication in AJ. arXiv admin note: text overlap with arXiv:1911.0335

Nano-surgery at the leukocyte–endothelial docking site

The endothelium has an important role in controlling the extravasation of leukocytes from blood to tissues. Endothelial permeability for leukocytes is influenced by transmembrane proteins that control inter-endothelial adhesion, as well as steps of the leukocyte transmigration process. In a cascade consisting of leukocyte rolling, adhesion, firm adhesion, and diapedesis, a new step was recently introduced, the formation of a docking structure or “transmigratory cup.” Both terms describe a structure formed by endothelial pseudopods embracing the leukocyte. It has been found associated with both para- and transcellular diapedesis. The aim of this study was to characterize the leukocyte–endothelial contact area in terms of morphology and cell mechanics to investigate how the endothelial cytoskeleton reorganizes to engulf the leukocyte. We used atomic force microscopy (AFM) to selectively remove the leukocyte and then analyze the underlying cell at this specific spot. Firmly attached leukocytes could be removed by AFM nanomanipulation. In few cases, this exposed 8–12 μm wide and 1 μm deep footprints, representing the cup-like docking structure. Some of them were located near endothelial cell junctions. The interaction area did not exhibit significant alterations neither morphologically nor mechanically as compared to the surrounding cell surface. In conclusion, the endothelial invagination is formed without a net depolymerization of f-actin, as endothelial softening at the site of adhesion does not seem to be involved. Moreover, there were no cases of phagocytotic engulfment, but instead the formation of a transmigratory channel could be observed

ACCESS & LRG-BEASTS: a precise new optical transmission spectrum of the ultrahot Jupiter WASP-103b

We present a new ground-based optical transmission spectrum of the ultrahot Jupiter WASP-103b ($T_{eq} = 2484$K). Our transmission spectrum is the result of combining five new transits from the ACCESS survey and two new transits from the LRG-BEASTS survey with a reanalysis of three archival Gemini/GMOS transits and one VLT/FORS2 transit. Our combined 11-transit transmission spectrum covers a wavelength range of 3900--9450A with a median uncertainty in the transit depth of 148 parts-per-million, which is less than one atmospheric scale height of the planet. In our retrieval analysis of WASP-103b's combined optical and infrared transmission spectrum, we find strong evidence for unocculted bright regions ($4.3\sigma$) and weak evidence for H$_2$O ($1.9\sigma$), HCN ($1.7\sigma$), and TiO ($2.1\sigma$), which could be responsible for WASP-103b's observed temperature inversion. Our optical transmission spectrum shows significant structure that is in excellent agreement with the extensively studied ultrahot Jupiter WASP-121b, for which the presence of VO has been inferred. For WASP-103b, we find that VO can only provide a reasonable fit to the data if its abundance is implausibly high and we do not account for stellar activity. Our results highlight the precision that can be achieved by ground-based observations and the impacts that stellar activity from F-type stars can have on the interpretation of exoplanet transmission spectra.Comment: 33 pages, 17 figures, 7 tables. Accepted for publication in A

ACCESS: Confirmation of no potassium in the atmosphere of WASP-31b

We present a new optical (400-950nm) transmission spectrum of the hot Jupiter WASP-31b (M=0.48 MJ; R= 1.54 RJ; P=3.41 days), obtained by combining four transits observations. These transits were observed with IMACS on the Magellan Baade Telescope at Las Campanas Observatory as part of the ACCESS project. We investigate the presence of clouds/hazes in the upper atmosphere of this planet as well as the contribution of stellar activity on the observed features. In addition, we search for absorption features of the alkali elements Na I and K I, with particular focus on K I, for which there have been two previously published disagreeing results. Observations with HST/STIS detected K I, whereas ground-based low- and high-resolution observations did not. We use equilibrium and non-equilibrium chemistry retrievals to explore the planetary and stellar parameter space of the system with our optical data combined with existing near-IR observations. Our best-fit model is that with a scattering slope consistent with a Rayleigh slope (alpha=5.3+2.9-3.1), high-altitude clouds at a log cloud top pressure of -3.6+2.7-2.1 bars, and possible muted H2O features. We find that our observations support other ground-based claims of no K I. Clouds are likely why signals like H2O are extremely muted and Na or K cannot be detected. We then juxtapose our Magellan/IMACS transmission spectrum with existing VLT/FORS2, HST/WFC3, HST/STIS, and Spitzer observations to further constrain the optical-to-infrared atmospheric features of the planet. We find that a steeper scattering slope (alpha = 8.3+/-1.5) is anchored by STIS wavelengths blueward of 400 nm and only the original STIS observations show significant potassium signal.Comment: Accepted 14 September 2020 by A

A large sub-Neptune transiting the thick-disk M4 V TOI-2406

We thank the anonymous referee for their corrections and help in improving the paper. We warmly thank the entire technical staff of the Observatorio Astronomico Nacional at San Pedro Martir in Mexico for their unfailing support to SAINT-EX operations, namely: E. Cadena, T. Calvario, E. Colorado, B. Garcia, G. Guisa, A. Franco, L. Figueroa, B. Hernandez, J. Herrera, E. Lopez, E. Lugo, B. Martinez, J. M. Nunez, J. L. Ochoa, M. Pereyra, F. Quiroz, T. Verdugo, I. Zavala. B.V.R. thanks the Heising-Simons Foundation for support. Y.G.M.C acknowledges support from UNAM-PAPIIT IG-101321. B.-O. D. acknowledges support from the Swiss National Science Foundation (PP00P2-163967 and PP00P2-190080). R.B. acknowledges the support from the Swiss National Science Foundation under grant P2BEP2_195285. M.N.G. acknowledges support from MIT's Kavli Institute as a Juan Carlos Torres Fellow. A.H.M.J.T acknowledges funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement nffi 803193/BEBOP), from the MERAC foundation, and from the Science and Technology Facilities Council (STFC; grant nffi ST/S00193X/1). T.D. acknowledges support from MIT's Kavli Institute as a Kavli postdoctoral fellow Part of this work received support from the National Centre for Competence in Research PlanetS, supported by the Swiss National Science Foundation (SNSF). The research leading to these results has received funding from the ARC grant for Concerted Research Actions, financed by the Wallonia-Brussels Federation. TRAPPIST is funded by the Belgian Fund for Scientific Research (Fond National de la Recherche Scientifique, FNRS) under the grant FRFC 2.5.594.09.F, with the participation of the Swiss National Science Fundation (SNF). M.G. and E.J. are F.R.S.-FNRS Senior Research Associate. This publication benefits from the support of the French Community of Belgium in the context of the FRIA Doctoral Grant awarded to MT. We acknowledge the use of public TESS data from pipelines at the TESS Science Office and at the TESS Science Processing Operations Center. We acknowledge the use of public TESS Alert data from pipelines at the TESS Science Office and at the TESS Science Processing Operations Center. Resources supporting this work were provided by the NASA High-End Computing (HEC) Program through the NASA Advanced Supercomputing (NAS) Division at Ames Research Center for the production of the SPOC data products. Funding for the TESS mission is provided by NASA's Science Mission Directorate. This research has made use of the Exoplanet Follow-up Observation Program website, which is operated by the California Institute of Technology, under contract with the National Aeronautics and Space Administration under the Exoplanet Exploration Program. This paper includes data collected by the TESS mission that are publicly available from the Mikulski Archive for Space Telescopes (MAST). We thank the TESS GI program G03274 PI, Ryan Cloutier, for proposing the target of this work for 2-min-cadence observations in Sector 30. This work is based upon observations carried out at the Observatorio Astronomico Nacional on the Sierra de San Pedro Martir (OAN-SPM), Baja California, Mexico. This work makes use of observations from the LCOGT network. Part of the LCOGT telescope time was granted by NOIRLab through the Mid-Scale Innovations Program (MSIP). MSIP is funded by NSF. This work includes data collected at the Vatican Advanced Technology Telescope (VATT) on Mt. Graham. This paper includes data taken on the EDEN telescope network. We acknowledge support from the Earths in Other Solar Systems Project (EOS) and Alien Earths (grant numbers NNX15AD94G and 80NSSC21K0593), sponsored by NASA. Some of the observations in the paper made use of the High-Resolution Imaging instrument Zorro (Gemini program GS-2020B-LP-105). Zorro was funded by the NASA Exoplanet Exploration Program and built at the NASA Ames Research Center by Steve B. Howell, Nic Scott, Elliott P. Horch, and Emmett Quigley. Zorro was mounted on the Gemini South telescope of the international Gemini Observatory, a program of NSF's OIR Lab, which is managed by the Association of Universities for Research in Astronomy (AURA) under a cooperative agreement with the National Science Foundation. on behalf of the Gemini partnership: the National Science Foundation (United States), National Research Council (Canada), Agencia Nacional de Investigacion y Desarrollo (Chile), Ministerio de Ciencia, Tecnologia e Innovacion (Argentina), Ministerio da Ciencia, Tecnologia, Inovacoes e Comunicacoes (Brazil), and Korea Astronomy and Space Science Institute (Republic of Korea). This research has made use of the NASA Exoplanet Archive, which is operated by the California Institute of Technology, under contract with the National Aeronautics and Space Administration under the Exoplanet Exploration Program. This work made use of the following Python packages: astropy (Astropy Collaboration 2013, 2018), lightkurve (Lightkurve Collaboration 2018), matplotlib (Hunter 2007), pandas (Wes McKinney 2010), seaborn (Waskom & The Seaborn Development team 2021), scipy (Virtanen et al. 2020) and numpy (Harris et al. 2020).Context. Large sub-Neptunes are uncommon around the coolest stars in the Galaxy and are rarer still around those that are metal-poor. However, owing to the large planet-to-star radius ratio, these planets are highly suitable for atmospheric study via transmission spectroscopy in the infrared, such as with JWST. Aims. Here we report the discovery and validation of a sub-Neptune orbiting the thick-disk, mid-M dwarf star TOI-2406. The star's low metallicity and the relatively large size and short period of the planet make TOI-2406 b an unusual outcome of planet formation, and its characterisation provides an important observational constraint for formation models. Methods. We first infer properties of the host star by analysing the star's near-infrared spectrum, spectral energy distribution, and Gaia parallax. We use multi-band photometry to confirm that the transit event is on-target and achromatic, and we statistically validate the TESS signal as a transiting exoplanet. We then determine physical properties of the planet through global transit modelling of the TESS and ground-based time-series data. Results. We determine the host to be a metal-poor M4 V star, located at a distance of 56 pc, with properties T-eff = 3100 +/- 75 K, M-* = 0.162 +/- 0.008M(circle dot), R-* = 0.202 +/- 0.011R(circle dot), and [Fe/H] = -0.38 +/- 0.07, and a member of the thick disk. The planet is a relatively large sub-Neptune for the M-dwarf planet population, with R-p = 2.94 +/- 0.17R(circle plus) and P= 3.077 d, producing transits of 2% depth. We note the orbit has a non-zero eccentricity to 3 sigma, prompting questions about the dynamical history of the system. Conclusions. This system is an interesting outcome of planet formation and presents a benchmark for large-planet formation around metal-poor, low-mass stars. The system warrants further study, in particular radial velocity follow-up to determine the planet mass and constrain possible bound companions. Furthermore, TOI-2406 b is a good target for future atmospheric study through transmission spectroscopy. Although the planet's mass remains to be constrained, we estimate the S/N using amass-radius relationship, ranking the system fifth in the population of large sub-Neptunes, with TOI-2406 b having a much lower equilibrium temperature than other spectroscopically accessible members of this population.Heising-Simons FoundationPrograma de Apoyo a Proyectos de Investigacion e Innovacion Tecnologica (PAPIIT)Universidad Nacional Autonoma de Mexico IG-101321Swiss National Science Foundation (SNSF)European Commission PP00P2-163967 PP00P2-190080 P2BEP2_195285MIT's Kavli Institute as a Juan Carlos Torres FellowEuropean Research Council (ERC) nffi 803193/BEBOPMERAC foundationUK Research & Innovation (UKRI)Science & Technology Facilities Council (STFC)Science and Technology Development Fund (STDF) nffi ST/S00193X/1MIT's Kavli Institute as a Kavli postdoctoral fellowSwiss National Science Foundation (SNSF)Australian Research CouncilFonds de la Recherche Scientifique - FNRS FRFC 2.5.594.09.FSwiss National Science Foundation (SNSF)French Community of Belgium in the context of the FRIA Doctoral GrantNASA High-End Computing (HEC) Program through the NASA Advanced Supercomputing (NAS) Division at Ames Research CenterNASA's Science Mission DirectorateNational Aeronautics and Space Administration under the Exoplanet Exploration ProgramTESS GI program G03274National Science Foundation (NSF)Earths in Other Solar Systems Project (EOS)Alien Earths - NASA NNX15AD94G 80NSSC21K0593High-Resolution Imaging instrument Zorro (Gemini program) GS-2020B-LP-105NASA Exoplanet Exploration ProgramNational Aeronautics & Space Administration (NASA)National Science Foundation (NSF

The Myeloid Receptor PILRβ Mediates the Balance of Inflammatory Responses through Regulation of IL-27 Production

Paired immunoglobulin-like receptors beta, PILRβ, and alpha, PILRα, are related to the Siglec family of receptors and are expressed primarily on cells of the myeloid lineage. PILRβ is a DAP12 binding partner expressed on both human and mouse myeloid cells. The potential ligand, CD99, is found on many cell types, such as epithelial cells where it plays a role in migration of immune cells to sites of inflammation. Pilrb deficient mice were challenged with the parasite Toxoplasma gondii in two different models of infection induced inflammation; one involving the establishment of chronic encephalitis and a second mimicking inflammatory bowel disease in order to understand the potential role of this receptor in persistent inflammatory responses. It was found that in the absence of activating signals from PILRβ, antigen-presenting cells (APCs) produced increased amounts of IL-27, p28 and promoted IL-10 production in effector T cells. The sustained production of IL-27 led ultimately to enhanced survival after challenge due to dampened immune pathology in the gut. Similar protection was also observed in the CNS during chronic T. gondii infection after i.p. challenge again providing evidence that PILRβ is important for regulating aberrant inflammatory responses

Extravasation of leukocytes in comparison to tumor cells

The multi-step process of the emigration of cells from the blood stream through the vascular endothelium into the tissue has been termed extravasation. The extravasation of leukocytes is fairly well characterized down to the molecular level, and has been reviewed in several aspects. Comparatively little is known about the extravasation of tumor cells, which is part of the hematogenic metastasis formation. Although the steps of the process are basically the same in leukocytes and tumor cells, i.e. rolling, adhesion, transmigration (diapedesis), the molecules that are involved are different. A further important difference is that leukocyte interaction with the endothelium changes the endothelial integrity only temporarily, whereas tumor cell interaction leads to an irreversible damage of the endothelial architecture. Moreover, tumor cells utilize leukocytes for their extravasation as linkers to the endothelium. Thus, metastasis formation is indirectly susceptible to localization signals that are literally specific for the immune system. We herein compare the extravasation of leukocytes and tumor cells with regard to the involved receptors and the localization signals that direct the cells to certain organs and sites of the body