Infrared studies of dust grains in infrared reflection nebulae

IR reflection nebulae, regions of dust which are illuminated by nearby embedded sources, were observed in several regions of ongoing star formation. Near IR observation and theoretical modelling of the scattered light form IR reflection nebulae can provide information about the dust grain properties in star forming regions. IR reflection nebulae were modelled as plane parallel slabs assuming isotropically scattering grains. For the grain scattering properties, graphite and silicate grains were used with a power law grain size distribution. Among the free parameters of the model are the stellar luminosity and effective temperature, the optical depth of the nebula, and the extinction by foreground material. The typical results from this model are presented and discussed

Endothelial Progenitor Cells: New Targets for Therapeutics for Inflammatory Conditions With High Cardiovascular Risk

Over the past decade, we have witnessed an exponential growth of interest into the role of endothelial progenitor cells (EPCs) in cardiovascular disease. While the major thinking revolves around EPC angiogenic repair properties, we have used a hypothesis-driven approach to discover disease-related defects in their characteristics and based on these findings, have identified opportunities for functional enhancement, which offer an exciting avenue for translation into clinical intervention. In this review, we focus on two groups; circulating myeloid angiogenic cells (MACs) and late outgrowth endothelial colony forming cells (ECFCs), and will discuss the unique properties and defects of each population, as new insights have been gained into the potential function of each sub-type using current techniques and multiomic technology. We will discuss their role in inflammatory disorders and alterations in mitochondrial function. In addition, we share key insights into the glycocalyx, and propose this network of membrane-bound proteoglycans and glycoproteins, covering the endothelium warrants further investigation in order to clarify its significance in ECFC regulation of vascularization and angiogenesis and ultimately for potential translational therapeutic aspects

The Interstellar Medium toward the Galactic Center Source 2MASS J17470898-2829561

We describe and discuss remarkable infrared spectra, covering key portions of the $2-5$ $\mu$m wavelength interval, of the probable OH/IR supergiant 2MASS J17470898$-$2829561 (2M1747), located in direction of the Sgr B molecular cloud complex within the Central Molecular Zone (CMZ) of the Galaxy. This star was originally singled out for examination based on its suitability for spectroscopy of lines of H$_3^+$ in the CMZ. Analysis of the spectra shows that 2M1747 is deeply embedded within Sgr B1, with A$_V$ $\gtrsim$ 100 mag, making it the only star within Sgr B for which infrared spectra have been obtained at present, and thereby a unique infrared probe of the dense interstellar medium within the CMZ. Despite the high extinction, spectra of 2M1747 reveal a veiled photosphere in the $K$ band and circumstellar gas in the $M$ band, giving clues as to its nature. Its $3.5-4.0$ $\mu$m spectrum contains the strongest absorption lines of H$_3^+$ observed toward any object to date. The $4.5-4.8$ $\mu$m spectrum has impressively deep and wide absorption lines of interstellar CO, most of which arise in dense gas within Sgr B1. The $3-5$ $\mu$m spectrum also contains several solid state absorption features, which are characteristic of both dense and diffuse clouds, and which raise questions about the identifications of some of these features. We discuss the nature of the star, the extinction to it, the extinction law for dust in the CMZ, and the identifications of the various solid-state features and where they are produced along this complex line of sight.Comment: 17 pages, 10 figures; accepted by ApJ 2021 March 1

Endothelial progenitor cells: a new player in lupus?

Patients with systemic lupus erythematosus (SLE) have a greatly increased risk of cardiovascular disease. There is growing interest in the link between vascular damage and lupus-specific inflammatory factors. Impaired endothelial repair could account for the endothelial dysfunction in this patient group. This review describes the contribution that endothelial progenitor cells could play in the pathogenesis of premature vascular damage in this disease. The methods of isolation, detection, and characterization of endothelial progenitor cells, together with their potential role in repair of the endothelium and as a therapeutic target in SLE, are discussed

Tree species richness differentially affects the chemical composition of leaves, roots and root exudates in four subtropical tree species

Plants produce thousands of compounds, collectively called the metabolome, which mediate interactions with other organisms. The metabolome of an individual plant may change according to the number and nature of these interactions. We tested the hypothesis that tree diversity level affects the metabolome of four subtropical tree species in a biodiversity–ecosystem functioning experiment, BEF‐China. We postulated that the chemical diversity of leaves, roots and root exudates increases with tree diversity. We expected that the strength of this diversity effect differs among leaf, root and root exudates samples. Considering their role in plant competition, we expected to find the strongest effects in root exudates. Roots, root exudates and leaves of four tree species ( Cinnamomum camphora , Cyclobalanopsis glauca , Daphniphyllum oldhamii and Schima superba ) were sampled from selected plots in BEF‐China. The exudate metabolomes were normalized over their non‐purgeable organic carbon level. Multivariate analyses were applied to identify the effect of both neighbouring (local) trees and plot diversity on tree metabolomes. The species‐ and sample‐specific metabolites were assigned to major compound classes using the ClassyFire tool, whereas potential metabolites related to diversity effects were annotated manually. Individual tree species showed distinct leaf, root and root exudate metabolomes. The main compound class in leaves was the flavonoids, whereas carboxylic acids, prenol lipids and specific alkaloids were most prominent in root exudates and roots. Overall, plot diversity had a stronger effect on metabolome profiles than the local diversity. Leaf metabolomes responded more often to tree diversity level than exudates, whereas root metabolomes varied the least. We found no uniform or general pattern of alterations in metabolite richness or diversity in response to variation in tree diversity. The response differed among species and tissues. Synthesis . Classification of metabolites supported initial ecological interpretation of differences among species and organs. Particularly, the metabolomes of leaves and root exudates respond to differences in tree diversity. These responses were neither linear nor uniform and individual metabolites showed different dynamics. More controlled interaction experiments are needed to dissect the causes and consequences of the observed shifts in plant metabolomes

Can 1D radiative equilibrium models of faculae be used for calculating contamination of transmission spectra?

The reliable characterization of planetary atmospheres with transmission spectroscopy requires realistic modeling of stellar magnetic features, since features that are attributable to an exoplanet atmosphere could instead stem from the host star's magnetic activity. Current retrieval algorithms for analysing transmission spectra rely on intensity contrasts of magnetic features from 1D radiative-convective models. However, magnetic features, especially faculae, are not fully captured by such simplified models. Here we investigate how well such 1D models can reproduce 3D facular contrasts, taking a G2V star as an example. We employ the well established radiative magnetohydrodynamic code MURaM to obtain three-dimensional simulations of the magneto-convection and photosphere harboring a local small-scale-dynamo. Simulations without additional vertical magnetic fields are taken to describe the quiet solar regions, while simulations with initially 100 G, 200 G and 300 G vertical magnetic fields are used to represent different magnetic activity levels. Subsequently, the spectra emergent from the MURaM cubes are calculated with the MPS-ATLAS radiative transfer code. We find that the wavelength dependence of facular contrast from 1D radiative-convective models cannot reproduce facular contrasts obtained from 3D modeling. This has far reaching consequences for exoplanet characterization using transmission spectroscopy, where accurate knowledge of the host star is essential for unbiased inferences of the planetary atmospheric properties.Comment: 7 pages, 2 figures, submitted to APJ

The modulatory role of sulfated and non-sulfated small molecule heparan sulfate-glycomimetics in endothelial dysfunction:absolute structural clarification, molecular docking and simulated dynamics, SAR analyses and ADME studies

The conceptual technology of small molecule glycomimetics, exemplified by compounds C1–4, has shown promising protective effects against lipid-induced endothelial dysfunction, restorative effects on diabetic endothelial colony forming cells, and preventative effects on downstream vascular calcification amongst other important in vitro and ex vivo studies. We report the optimised synthesis of an array of 17 small molecule glycomimetics, including the regio-, enantio- and diastereo-meric sulfated scaffolds of a hit structure along with novel desulfated examples. For the first time, the absolute stereochemical configurations of C1–4 have been clarified based on an identified and consistent anomaly with the Sharpless asymmetric dihydroxylation reaction. We have investigated the role and importance of sulfation pattern, location, regioisomers, and spatial orientation of distal sulfate groups on the modulation of endothelial dysfunction through their interaction with hepatocyte growth factor (HGF). In silico studies demonstrated the key interactions the persulfated glycomimetics make with HGF and revealed the importance of both sulfate density and positioning (both point chirality and vector) to biological activity. In vitro biological data of the most efficient binding motifs, along with desulfated comparators, support the modulatory effects of sulfated small molecule glycomimetics in the downstream signaling cascade of endothelial dysfunction. In vitro absorption, distribution, metabolism, elimination and toxicity (ADMET) data demonstrate the glycomimetic approach to be a promising approach for hit-to-lead studies

Health-related quality of life in patients with autoimmune hepatitis

Background Autoimmune hepatitis (AIH) is a rare chronic liver disease. Impaired health-related quality of life (HRQL) contributes to the overall disease burden. At current, only limited data related to the impact of treatment response on HRQL are available. Objective The aim of the study was to determine the impact of biochemical remission on HRQL. Methods Patients with AIH were prospectively enrolled between July 2018 and June 2019. A liver disease-specific tool, the chronic liver disease questionnaire (CLDQ) and the generic EQ-5D-5L were used to quantify HRQL. Treatment response was assessed biochemically by measurement of immunoglobulin G, ALT and AST. The cohort was divided into two groups according to their biochemical remission status in either complete vs. incomplete remission. Clinical as well as laboratory parameters and comorbidities were analysed using univariable and multivariable analysis to identify predictors of poor HRQL. Results A total of 116 AIH patients were included (median age: 55; 77.6% female), of which 9.5% had liver cirrhosis. In this cohort, 38 (38.4%) showed a complete and 61 (61.6%) an incomplete biochemical remission at study entry. The HRQL was significantly higher in patients with a complete as compared to an incomplete biochemical remission (CLDQ overall score: 5.66 ± 1.15 vs. 5.10 ± 1.35; p = 0.03). In contrast, the generic EQ-5D-5L UI-value was not different between the groups. Multivariable analysis identified AST (p = 0.02) and an incomplete biochemical remission (p = 0.04) as independent predictors of reduced HRQL (CLDQ total value). Conclusion Patients with a complete biochemical remission had a significantly higher HRQL. Liver-related quality of life in patients living with AIH is dependent on the response to immunosuppressive treatment

Novel Glycomimetics Protect Against Glycated Low-Density Lipoprotein-Induced Vascular Calcification In Vitro by Attenuation of the RAGE/ERK/CREB Pathway

Heparan sulphate (HS) can act as a co-receptor on the cell surface and alterations in this process underpin many pathological conditions. We have previously described the usefulness of mimics of HS (glycomimetics) in protection against β-glycerophosphate-induced vascular calcification and in the restoration of the functional capacity of diabetic endothelial colony-forming cells in vitro. This study aims to investigate whether our novel glycomimetic compounds can attenuate glycated low-density lipoprotein (g-LDL)-induced calcification by inhibiting RAGE signalling within the context of critical limb ischemia (CLI). We used an established osteogenic in vitro vascular smooth muscle cell (VSMC) model. Osteoprotegerin (OPG), sclerostin and glycation levels were all significantly increased in CLI serum compared to healthy controls, while the vascular calcification marker osteocalcin (OCN) was down-regulated in CLI patients vs. controls. Incubation with both CLI serum and g-LDL (10 µg/mL) significantly increased VSMC calcification vs. controls after 21 days, with CLI serum-induced calcification apparent after only 10 days. Glycomimetics (C2 and C3) significantly inhibited g-LDL and CLI serum-induced mineralisation, as shown by a reduction in alizarin red (AR) staining and alkaline phosphatase (ALP) activity. Furthermore, secretion of the osteogenic marker OCN was significantly reduced in VSMCs incubated with CLI serum in the presence of glycomimetics. Phosphorylation of cyclic AMP response element-binding protein (CREB) was significantly increased in g-LDL-treated cells vs. untreated controls, which was attenuated with glycomimetics. Blocking CREB activation with a pharmacological inhibitor 666-15 replicated the protective effects of glycomimetics, evidenced by elevated AR staining. In silico molecular docking simulations revealed the binding affinity of the glycomimetics C2 and C3 with the V domain of RAGE. In conclusion, these findings demonstrate that novel glycomimetics, C2 and C3 have potent anti-calcification properties in vitro, inhibiting both g-LDL and CLI serum-induced VSMC mineralisation via the inhibition of LDLR, RAGE, CREB and subsequent expression of the downstream osteogenic markers, ALP and OCN