Rotational excitation of methylidynium (CH+) by a helium atom at high temperature

We aim to obtain accurate rate coefficients for the collisional excitation of CH+ by He for high gas temperatures. The ab initio coupled-cluster [CCSD(T)] approximation was used to compute the interaction potential energy. Cross sections are then derived in the close coupling (CC) approach and rate coefficients inferred by averaging these cross sections over a Maxwell-Boltzmann distribution of kinetic energies. Cross sections are calculated up to 10'000 cm^-1 for J ranging from 0 to 10. Rate coefficients are obtained at high temperatures up to 2000 K.Comment: 4 pages, 3 figures, table with rate coefficients, accepted for publication by A&

Effect of c-Abl tyrosine kinase on the cellular response to paclitaxel-induced microtubule damage

DNA damage has been shown to activate c-Abl tyrosine kinase. We now report that, in addition to DNA damage, microtubule damage induced by paclitaxel results in activation of c-Abl kinase. In 3T3 cells, the presence of c-Abl kinase increased paclitaxel-induced cell death. In Abl-proficient cells, paclitaxel produced a marked and prolonged G2/M arrest which peaked at 24 h and a rapid and marked induction of p21WAF1which also peaked at 24 h. In Abl-deficient cells, the G2/M arrest induced by paclitaxel was less prominent and shorter in duration and the effect of paclitaxel on p21WAF1expression was reduced and delayed. Paclitaxel had no effect on p53 expression and MAPK phosphorylation. These findings indicate that, in 3T3 cells, c-Abl kinase facilitates cell death and regulates G2/M arrest in response to paclitaxel-induced microtubule damage in a pathway that is dependent on p21WAF1and independent of MAPK activity. © 2000 Cancer Research Campaig

Optical performance of the JWST MIRI flight model: characterization of the point spread function at high-resolution

The Mid Infra Red Instrument (MIRI) is one of the four instruments onboard the James Webb Space Telescope (JWST), providing imaging, coronagraphy and spectroscopy over the 5-28 microns band. To verify the optical performance of the instrument, extensive tests were performed at CEA on the flight model (FM) of the Mid-InfraRed IMager (MIRIM) at cryogenic temperatures and in the infrared. This paper reports on the point spread function (PSF) measurements at 5.6 microns, the shortest operating wavelength for imaging. At 5.6 microns the PSF is not Nyquist-sampled, so we use am original technique that combines a microscanning measurement strategy with a deconvolution algorithm to obtain an over-resolved MIRIM PSF. The microscanning consists in a sub-pixel scan of a point source on the focal plane. A data inversion method is used to reconstruct PSF images that are over-resolved by a factor of 7 compared to the native resolution of MIRI. We show that the FWHM of the high-resolution PSFs were 5-10% wider than that obtained with Zemax simulations. The main cause was identified as an out-of-specification tilt of the M4 mirror. After correction, two additional test campaigns were carried out, and we show that the shape of the PSF is conform to expectations. The FWHM of the PSFs are 0.18-0.20 arcsec, in agreement with simulations. 56.1-59.2% of the total encircled energy (normalized to a 5 arcsec radius) is contained within the first dark Airy ring, over the whole field of view. At longer wavelengths (7.7-25.5 microns), this percentage is 57-68%. MIRIM is thus compliant with the optical quality requirements. This characterization of the MIRIM PSF, as well as the deconvolution method presented here, are of particular importance, not only for the verification of the optical quality and the MIRI calibration, but also for scientific applications.Comment: 13 pages, submitted to SPIE Proceedings vol. 7731, Space Telescopes and Instrumentation 2010: Optical, Infrared, and Millimeter Wav

Glucocorticoids with different chemical structures but similar glucocorticoid receptor potency regulate subsets of common and unique genes in human trabecular meshwork cells

<p>Abstract</p> <p>Background</p> <p>In addition to their well-documented ocular therapeutic effects, glucocorticoids (GCs) can cause sight-threatening side-effects including ocular hypertension presumably via morphological and biochemical changes in trabecular meshwork (TM) cells. In the present study, we directly compared the glucocorticoid receptor (GR) potency for dexamethasone (DEX), fluocinolone acetonide (FA) and triamcinolone acetonide (TA), examined the expression of known GRα and GRβ isoforms, and used gene expression microarrays to compare the effects of DEX, FA, and TA on the complete transcriptome in two primary human TM cell lines.</p> <p>Methods</p> <p>GR binding affinity for DEX, FA, and TA was measured by a cell-free competitive radio-labeled GR binding assay. GR-mediated transcriptional activity was assessed using the GeneBLAzer beta-lactamase reporter gene assay. Levels of GRα and GRβ isoforms were assessed by Western blot. Total RNA was extracted from TM 86 and TM 93 cells treated with 1 μM DEX, FA, or TA for 24 hr and used for microarray gene expression analysis. The microarray experiments were repeated three times. Differentially expressed genes were identified by Rosetta Resolver Gene Expression Analysis System.</p> <p>Results</p> <p>The GR binding affinity (IC₅₀) for DEX, FA, and TA was 5.4, 2.0, and 1.5 nM, respectively. These values are similar to the GR transactivation EC₅₀of 3.0, 0.7, and 1.5 nM for DEX, FA, and TA, respectively. All four GRα translational isoforms (A-D) were expressed in TM 86 and TM 93 total cell lysates, however, the C and D isoforms were more highly expressed relative to A and B. All four GRβ isoforms (A-D) were also detected in TM cells, although GRβ-D isoform expression was lower compared to that of the A, B, or C isoforms. Microarray analysis revealed 1,968 and 1,150 genes commonly regulated by DEX, FA, and TA in TM 86 and TM 93, respectively. These genes included RGC32, OCA2, ANGPTL7, MYOC, FKBP5, SAA1 and ZBTB16. In addition, each GC specifically regulated a unique set of genes in both TM cell lines. Using Ingenuity Pathway Analysis (IPA) software, analysis of the data from TM 86 cells showed that DEX significantly regulated transcripts associated with RNA post-transcriptional modifications, whereas FA and TA modulated genes involved in lipid metabolism and cell morphology, respectively. In TM 93 cells, DEX significantly regulated genes implicated in histone methylation, whereas FA and TA altered genes associated with cell cycle and cell adhesion, respectively.</p> <p>Conclusion</p> <p>Human trabecular meshwork cells in culture express all known GRα and GRβ translational isoforms, and GCs with similar potency but subtly different chemical structure are capable of regulating common and unique gene subsets and presumably biologic responses in these cells. These GC structure-dependent effects appear to be TM cell-lineage dependent.</p

Water in the terrestrial planet-forming zone of the PDS 70 disk

Terrestrial and sub-Neptune planets are expected to form in the inner ($<10~$AU) regions of protoplanetary disks. Water plays a key role in their formation, although it is yet unclear whether water molecules are formed in-situ or transported from the outer disk. So far Spitzer Space Telescope observations have only provided water luminosity upper limits for dust-depleted inner disks, similar to PDS 70, the first system with direct confirmation of protoplanet presence. Here we report JWST observations of PDS 70, a benchmark target to search for water in a disk hosting a large ($\sim54~$AU) planet-carved gap separating an inner and outer disk. Our findings show water in the inner disk of PDS 70. This implies that potential terrestrial planets forming therein have access to a water reservoir. The column densities of water vapour suggest in-situ formation via a reaction sequence involving O, H$_2$, and/or OH, and survival through water self-shielding. This is also supported by the presence of CO$_2$ emission, another molecule sensitive to UV photodissociation. Dust shielding, and replenishment of both gas and small dust from the outer disk, may also play a role in sustaining the water reservoir. Our observations also reveal a strong variability of the mid-infrared spectral energy distribution, pointing to a change of inner disk geometry.Comment: To appear in Nature on 24 July 2023. 21 pages, 10 figures; includes extended data. Part of the JWST MINDS Guaranteed Time Observations program's science enabling products. Spectra downloadable on Zenodo at https://zenodo.org/record/799102

MINDS. Abundant water and varying C/O across the disk of Sz 98 as seen by JWST/MIRI

MIRI/MRS on board the JWST allows us to probe the inner regions of protoplanetary disks. Here we examine the disk around the classical T Tauri star Sz 98, which has an unusually large dust disk in the millimetre with a compact core. We focus on the H$_2$O emission through both its ro-vibrational and pure rotational emission. Furthermore, we compare our chemical findings with those obtained for the outer disk from Atacama Large Millimeter/submillimeter Array (ALMA) observations. In order to model the molecular features in the spectrum, the continuum was subtracted and LTE slab models were fitted. The spectrum was divided into different wavelength regions corresponding to H$_2$O lines of different excitation conditions, and the slab model fits were performed individually per region. We confidently detect CO, H$_2$O, OH, CO$_2$, and HCN in the emitting layers. The isotopologue H$^{18}_2$O is not detected. Additionally, no other organics, including C$_2$H$_2$, are detected. This indicates that the C/O ratio could be substantially below unity, in contrast with the outer disk. The H$_2$O emission traces a large radial disk surface region, as evidenced by the gradually changing excitation temperatures and emitting radii. The OH and CO$_2$ emission are relatively weak. It is likely that H$_2$O is not significantly photodissociated; either due to self-shielding against the stellar irradiation, or UV-shielding from small dust particles. The relative emitting strength of the different identified molecular features point towards UV-shielding of H$_2$O in the inner disk of Sz 98, with a thin layer of OH on top. The majority of the organic molecules are either hidden below the dust continuum, or not present. In general, the inferred composition points to a sub-solar C/O ratio (<0.5) in the inner disk, in contrast with the larger than unity C/O ratio in the gas in the outer disk found with ALMA.Comment: Submitted to A&A on May 25 2023. 18 pages, 11 figure

Excitation of H2_2 in photodissociation regions as seen by Spitzer

We present spectroscopic observations obtained with the infrared Spitzer Space Telescope, which provide insight into the H$_2$ physics and gas energetics in photodissociation Regions (PDRs) of low to moderate far-ultraviolet (FUV) fields and densities. We analyze data on six well known Galactic PDRs (L1721, California, N7023E, Horsehead, rho Oph, N2023N), sampling a poorly explored range of excitation conditions ($\chi \sim 5-10^3$), relevant to the bulk of molecular clouds in galaxies. Spitzer observations of H$_2$ rotational lines are complemented with H$_2$ data, including ro-vibrational line measurements, obtained with ground-based telescopes and ISO, to constrain the relative contributions of ultraviolet pumping and collisions to the H$_2$ excitation. The data analysis is supported by model calculations with the Meudon PDR code. The observed column densities of rotationally excited H$_2$ are observed to be much higher than PDR model predictions. In the lowest excitation PDRs, the discrepancy between the model and the data is about one order of magnitude for rotational levels $J \ge$3. We discuss whether an enhancement in the H$_2$ formation rate or a local increase in photoelectric heating, as proposed for brighter PDRs in former ISO studies, may improve the data-model comparison. We find that an enhancement in the H$_2$ formation rates reduces the discrepancy, but the models still fall short of the data. This large disagreement suggests that our understanding of the formation and excitation of H$_2$ and/or of PDRs energetics is still incomplete. We discuss several explanations, which could be further tested using the Herschel Space TelescopeComment: A&A in pres

MINDS. The detection of 13^{13}CO2_{2} with JWST-MIRI indicates abundant CO2_{2} in a protoplanetary disk

We present JWST-MIRI MRS spectra of the protoplanetary disk around the low-mass T Tauri star GW Lup from the MIRI mid-INfrared Disk Survey (MINDS) GTO program. Emission from $^{12}$CO$_{2}$, $^{13}$CO$_{2}$, H$_{2}$O, HCN, C$_{2}$H$_{2}$, and OH is identified with $^{13}$CO$_{2}$ being detected for the first time in a protoplanetary disk. We characterize the chemical and physical conditions in the inner few au of the GW Lup disk using these molecules as probes. The spectral resolution of JWST-MIRI MRS paired with high signal-to-noise data is essential to identify these species and determine their column densities and temperatures. The $Q$-branches of these molecules, including those of hot-bands, are particularly sensitive to temperature and column density. We find that the $^{12}$CO$_{2}$ emission in the GW Lup disk is coming from optically thick emission at a temperature of $\sim$400 K. $^{13}$CO$_{2}$ is optically thinner and based on a lower temperature of $\sim$325 K, may be tracing deeper into the disk and/or a larger emitting radius than $^{12}$CO$_{2}$. The derived $N_{\rm{CO_{2}}}$/$N_{\rm{H_{2}O}}$ ratio is orders of magnitude higher than previously derived for GW Lup and other targets based on \textit{Spitzer}-IRS data. This high column density ratio may be due to an inner cavity with a radius in between the H$_{2}$O and CO$_{2}$ snowlines and/or an overall lower disk temperature. This paper demonstrates the unique ability of JWST to probe inner disk structures and chemistry through weak, previously unseen molecular features.Comment: 15 pages, 10 figures. Accepted to ApJ

Gi/o-protein coupled receptors in the aging brain

Cells translate extracellular signals to regulate processes such as differentiation, metabolism and proliferation, via transmembranar receptors. G protein-coupled receptors (GPCRs) belong to the largest family of transmembrane receptors, with over 800 members in the human species. Given the variety of key physiological functions regulated by GPCRs, these are main targets of existing drugs. During normal aging, alterations in the expression and activity of GPCRs have been observed. The central nervous system (CNS) is particularly affected by these alterations, which results in decreased brain functions, impaired neuroregeneration, and increased vulnerability to neuropathologies, such as Alzheimer's and Parkinson diseases. GPCRs signal via heterotrimeric G proteins, such as Go, the most abundant heterotrimeric G protein in CNS. We here review age-induced effects of GPCR signaling via the Gi/o subfamily at the CNS. During the aging process, a reduction in protein density is observed for almost half of the Gi/o-coupled GPCRs, particularly in age-vulnerable regions such as the frontal cortex, hippocampus, substantia nigra and striatum. Gi/o levels also tend to decrease with aging, particularly in regions such as the frontal cortex. Alterations in the expression and activity of GPCRs and coupled G proteins result from altered proteostasis, peroxidation of membranar lipids and age-associated neuronal degeneration and death, and have impact on aging hallmarks and age-related neuropathologies. Further, due to oligomerization of GPCRs at the membrane and their cooperative signaling, down-regulation of a specific Gi/o-coupled GPCR may affect signaling and drug targeting of other types/subtypes of GPCRs with which it dimerizes. Gi/o-coupled GPCRs receptorsomes are thus the focus of more effective therapeutic drugs aiming to prevent or revert the decline in brain functions and increased risk of neuropathologies at advanced ages.This work was supported by Fundação para a Ciência e Tecnologia, Centro 2020 and Portugal 2020, the COMPETE program, QREN, and the European Union (FEDER program) via the GoBack project (PTDC/CVT-CVT/32261/2017), the pAGE program (Centro-01-0145-FEDER-000003), and Institute for Biomedicine iBiMED (UID/BIM/04501/2013; UID/BIM/04501/2019).publishe