Pincher, a pinocytic chaperone for nerve growth factor/TrkA signaling endosomes

Acentral tenet of nerve growth factor (NGF) action that is poorly understood is its ability to mediate cytoplasmic signaling, through its receptor TrkA, that is initiated at the nerve terminal and conveyed to the soma. We identified an NGF-induced protein that we termed Pincher (pinocytic chaperone) that mediates endocytosis and trafficking of NGF and its receptor TrkA. In PC12 cells, overexpression of Pincher dramatically stimulated NGF-induced endocytosis of TrkA, unexpectedly at sites of clathrin-independent macropinocytosis within cell surface ruffles. Subsequently, a system of Pincher-containing tubules mediated the delivery of NGF/TrkA-containing vesicles to cytoplasmic accumulations. These vesicles selectively and persistently mediated TrkA-erk5 mitogen-activated protein kinase signaling. A dominant inhibitory mutant form of Pincher inhibited the NGF-induced endocytosis of TrkA, and selectively blocked TrkA-mediated cytoplasmic signaling of erk5, but not erk1/2, kinases. Our results indicate that Pincher mediates pinocytic endocytosis of functionally specialized NGF/TrkA endosomes with persistent signaling potential

EXPRES I. HD~3651 an Ideal RV Benchmark

The next generation of exoplanet-hunting spectrographs should deliver up to an order of magnitude improvement in radial velocity precision over the standard 1 m/s state of the art. This advance is critical for enabling the detection of Earth-mass planets around Sun-like stars. New calibration techniques such as laser frequency combs and stabilized etalons ensure that the instrumental stability is well characterized. However, additional sources of error include stellar noise, undetected short-period planets, and telluric contamination. To understand and ultimately mitigate error sources, the contributing terms in the error budget must be isolated to the greatest extent possible. Here, we introduce a new high cadence radial velocity program, the EXPRES 100 Earths program, which aims to identify rocky planets around bright, nearby G and K dwarfs. We also present a benchmark case: the 62-d orbit of a Saturn-mass planet orbiting the chromospherically quiet star, HD 3651. The combination of high eccentricity (0.6) and a moderately long orbital period, ensures significant dynamical clearing of any inner planets. Our Keplerian model for this planetary orbit has a residual RMS of 58 cm/s over a $\sim 6$ month time baseline. By eliminating significant contributors to the radial velocity error budget, HD 3651 serves as a standard for evaluating the long term precision of extreme precision radial velocity (EPRV) programs.Comment: 11 pages, 6 figures, accepted for publication in Astronomical Journa

The need for illness

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45466/1/11089_2005_Article_BF01845887.pd

The EXPRES Stellar Signals Project II. State of the Field in Disentangling Photospheric Velocities

Measured spectral shifts due to intrinsic stellar variability (e.g., pulsations, granulation) and activity (e.g., spots, plages) are the largest source of error for extreme-precision radial-velocity (EPRV) exoplanet detection. Several methods are designed to disentangle stellar signals from true center-of-mass shifts due to planets. The Extreme-precision Spectrograph (EXPRES) Stellar Signals Project (ESSP) presents a self-consistent comparison of 22 different methods tested on the same extreme-precision spectroscopic data from EXPRES. Methods derived new activity indicators, constructed models for mapping an indicator to the needed radial-velocity (RV) correction, or separated out shape- and shift-driven RV components. Since no ground truth is known when using real data, relative method performance is assessed using the total and nightly scatter of returned RVs and agreement between the results of different methods. Nearly all submitted methods return a lower RV rms than classic linear decorrelation, but no method is yet consistently reducing the RV rms to sub-meter-per-second levels. There is a concerning lack of agreement between the RVs returned by different methods. These results suggest that continued progress in this field necessitates increased interpretability of methods, high-cadence data to capture stellar signals at all timescales, and continued tests like the ESSP using consistent data sets with more advanced metrics for method performance. Future comparisons should make use of various well-characterized data sets—such as solar data or data with known injected planetary and/or stellar signals—to better understand method performance and whether planetary signals are preserved

An Extreme Precision Radial Velocity Pipeline: First Radial Velocities from EXPRES

The EXtreme PREcision Spectrograph (EXPRES) is an environmentally stabilized, fiber-fed, $R=137,500$, optical spectrograph. It was recently commissioned at the 4.3-m Lowell Discovery Telescope (LDT) near Flagstaff, Arizona. The spectrograph was designed with a target radial-velocity (RV) precision of 30$\mathrm{~cm~s^{-1}}$. In addition to instrumental innovations, the EXPRES pipeline, presented here, is the first for an on-sky, optical, fiber-fed spectrograph to employ many novel techniques---including an "extended flat" fiber used for wavelength-dependent quantum efficiency characterization of the CCD, a flat-relative optimal extraction algorithm, chromatic barycentric corrections, chromatic calibration offsets, and an ultra-precise laser frequency comb for wavelength calibration. We describe the reduction, calibration, and radial-velocity analysis pipeline used for EXPRES and present an example of our current sub-meter-per-second RV measurement precision, which reaches a formal, single-measurement error of 0.3$\mathrm{~m~s^{-1}}$ for an observation with a per-pixel signal-to-noise ratio of 250. These velocities yield an orbital solution on the known exoplanet host 51 Peg that matches literature values with a residual RMS of 0.895$\mathrm{~m~s^{-1}}$

Identification of the top TESS objects of interest for atmospheric characterization of transiting exoplanets with JWST

Funding: Funding for the TESS mission is provided by NASA's Science Mission Directorate. 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 paper is based on observations made with the MuSCAT3 instrument, developed by the Astrobiology Center and under financial support by JSPS KAKENHI (grant No. JP18H05439) and JST PRESTO (grant No. JPMJPR1775), at Faulkes Telescope North on Maui, HI, operated by the Las Cumbres Observatory. This paper makes use of data from the MEarth Project, which is a collaboration between Harvard University and the Smithsonian Astrophysical Observatory. The MEarth Project acknowledges funding from the David and Lucile Packard Fellowship for Science and Engineering, the National Science Foundation under grant Nos. AST-0807690, AST-1109468, AST-1616624 and AST-1004488 (Alan T. Waterman Award), the National Aeronautics and Space Administration under grant No. 80NSSC18K0476 issued through the XRP Program, and the John Templeton Foundation. C.M. would like to gratefully acknowledge the entire Dragonfly Telephoto Array team, and Bob Abraham in particular, for allowing their telescope bright time to be put to use observing exoplanets. B.J.H. acknowledges support from the Future Investigators in NASA Earth and Space Science and Technology (FINESST) program (grant No. 80NSSC20K1551) and support by NASA under grant No. 80GSFC21M0002. K.A.C. and C.N.W. acknowledge support from the TESS mission via subaward s3449 from MIT. D.R.C. and C.A.C. acknowledge support from NASA through the XRP grant No. 18-2XRP18_2-0007. C.A.C. acknowledges that this research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration (80NM0018D0004). S.Z. and A.B. acknowledge support from the Israel Ministry of Science and Technology (grant No. 3-18143). 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 No. PDR T.0120.21. The postdoctoral fellowship of K.B. is funded by F.R.S.-FNRS grant No. T.0109.20 and by the Francqui Foundation. H.P.O.'s contribution has been carried out within the framework of the NCCR PlanetS supported by the Swiss National Science Foundation under grant Nos. 51NF40_182901 and 51NF40_205606. F.J.P. acknowledges financial support from the grant No. CEX2021-001131-S funded by MCIN/AEI/ 10.13039/501100011033. A.J. acknowledges support from ANID—Millennium Science Initiative—ICN12_009 and from FONDECYT project 1210718. Z.L.D. acknowledges the MIT Presidential Fellowship and that this material is based upon work supported by the National Science Foundation Graduate Research Fellowship under grant No. 1745302. P.R. acknowledges support from the National Science Foundation grant No. 1952545. This work is partly supported by JSPS KAKENHI grant Nos. JP17H04574, JP18H05439, JP21K20376; JST CREST grant No. JPMJCR1761; and Astrobiology Center SATELLITE Research project AB022006. This publication benefits from the support of the French Community of Belgium in the context of the FRIA Doctoral Grant awarded to M.T. D.D. acknowledges support from TESS Guest Investigator Program grant Nos. 80NSSC22K1353, 80NSSC22K0185, and 80NSSC23K0769. A.B. acknowledges the support of M.V. Lomonosov Moscow State University Program of Development. T.D. was supported in part by the McDonnell Center for the Space Sciences. V.K. acknowledges support from the youth scientific laboratory project, topic FEUZ-2020-0038.JWST has ushered in an era of unprecedented ability to characterize exoplanetary atmospheres. While there are over 5000 confirmed planets, more than 4000 Transiting Exoplanet Survey Satellite (TESS) planet candidates are still unconfirmed and many of the best planets for atmospheric characterization may remain to be identified. We present a sample of TESS planets and planet candidates that we identify as “best-in-class” for transmission and emission spectroscopy with JWST. These targets are sorted into bins across equilibrium temperature Teq and planetary radius Rp and are ranked by a transmission and an emission spectroscopy metric (TSM and ESM, respectively) within each bin. We perform cuts for expected signal size and stellar brightness to remove suboptimal targets for JWST. Of the 194 targets in the resulting sample, 103 are unconfirmed TESS planet candidates, also known as TESS Objects of Interest (TOIs). We perform vetting and statistical validation analyses on these 103 targets to determine which are likely planets and which are likely false positives, incorporating ground-based follow-up from the TESS Follow-up Observation Program to aid the vetting and validation process. We statistically validate 18 TOIs, marginally validate 31 TOIs to varying levels of confidence, deem 29 TOIs likely false positives, and leave the dispositions for four TOIs as inconclusive. Twenty-one of the 103 TOIs were confirmed independently over the course of our analysis. We intend for this work to serve as a community resource and motivate formal confirmation and mass measurements of each validated planet. We encourage more detailed analysis of individual targets by the community.Peer reviewe

Phosphorylcholine Allows for Evasion of Bactericidal Antibody by Haemophilus influenzae

The human pathogen Haemophilus influenzae has the ability to quickly adapt to different host environments through phase variation of multiple structures on its lipooligosaccharide (LPS), including phosphorylcholine (ChoP). During colonization with H. influenzae, there is a selection for ChoP+ phase variants. In a murine model of nasopharyngeal colonization, this selection is lost in the absence of adaptive immunity. Based on previous data highlighting the importance of natural antibody in limiting H. influenzae colonization, the effect of ChoP expression on antibody binding and its bactericidal activity was investigated. Flow cytometric analysis revealed that ChoP+ phase variants had decreased binding of antibody to LPS epitopes compared to ChoP− phase variants. This difference in antibody binding correlated with increased survival of ChoP+ phase variants in the presence of antibody-dependent, complement-mediated killing. ChoP+ phase variants were also more resistant to trypsin digestion, suggesting a general effect on the physical properties of the outer membrane. Moreover, ChoP-mediated protection against antibody binding correlated with increased resilience of outer membrane integrity. Collectively, these data suggest that ChoP expression provides a selective advantage during colonization through ChoP-mediated effects on the accessibility of bactericidal antibody to the cell surface