TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy

Significance Alzheimer’s disease (AD) is the most common cause of dementia and is a major public health problem for which there is currently no disease-modifying treatment. There is an urgent need for greater understanding of the molecular mechanisms underlying neurodegeneration in patients to create better therapeutic options. Recently, genetic studies uncovered novel AD risk variants in the microglial receptor, triggering receptor expressed on myeloid cells 2 (TREM2). Previous studies suggested that loss of TREM2 function worsens amyloid-β (Aβ) plaque-related toxicity. In contrast, we observe TREM2 deficiency mitigates neuroinflammation and protects against brain atrophy in the context of tau pathology. These findings indicate dual roles for TREM2 and microglia in the context of amyloid versus tau pathology, which are important to consider for potential treatments targeting TREM2.</jats:p

Constraints on thick disc and halo parameters from HST photometry of field stars in the Galaxy

We analyse a sample of over 1000 stars from 32 fields imaged in the V and I bands with the Wide Field and Planetary Camera, on board of the Hubble Space Telescope. The fields are located at Galactic latitudes | b | >= 15deg and in various directions on the sky. We consider models for the structure of the Galaxy with different choices for the main parameters governing the shape and luminosity function of the thick disk and stellar halo. Comparing model predictions with the observed colour-magnitude diagram we are able to rule out an increasing or flat stellar luminosity function at the low-luminosity end. We also rule out large values of the vertical scale height of the thick disc, z_0, finding it to be in the range 800 <= z_0 <= 1200 pc. As for the local density normalization, values within the range 4 % <= n_0 <= 8 % seem to better reproduce the data. Our data essentially rule out a flattened stellar halo (c/a <~ 0.5) or models with both large local normalization and effective radii.Comment: 7 pages LaTeX, 9 Postscript figure

Stellar Subsystems of the Galaxy NGC 2366

Hubble Space Telescope archive data are used to perform photometry of stars in seven fields at the center and periphery of the galaxy NGC2366. The variation of the number density of stars of various ages with galactocentric radius and along the minor axis of the galaxy are determined. The boundaries of the thin and thick disks of the galaxy are found. The inferred sizes of the subsystems of NGC2366 ($Z_{thin} = 4$ kpc and $Z_{thick} = 8$ kpc for the thin and thick disks, respectively) are more typical for spiral galaxies. Evidence for a stellar halo is found at the periphery of NGC2366 beyond the thick disk of the galaxy.Comment: 16 pages, 4 figures, Astronomy Reports, 2008,v. 52, n.1, p. 1

Stellar disks and halos of the edge-on spiral galaxies: NGC 891, NGC 4144 and NGC 4244

The results of the stellar photometry of the images ACS/WFC and WFPC2 of the HST are used to study stellar population and spatial distribution of stars in three edge-on galaxies: NGC 891, NGC 4144 and NGC 4244. The measuring of the number density of the old stars revealed two stellar substructures in these galaxies: thick disk and halo. The borders of these substructures consisting mainly of red giants, are determined by the change of number density gradient of the old stars. The revealed halos have flattened shapes and extend up to 25 kpc from the galaxy planes. The obtained results of number density distributions of different type stars perpendicular to the galaxy planes allow us to verify our stellar model of spiral galaxies. Using the determination of the tip of red giant branch (TRGB method) we have derived the following distances: D = 9.82 Mpc (NGC 891), D = 7.24 Mpc (NGC 4144), D = 4.29 Mpc (NGC 4244).Comment: 18 pages, 9 figures. accepted to Astrofizic

Exploring venlafaxine pharmacokinetic variability with a phenotyping approach, a multicentric french-swiss study (MARVEL study).

It is well known that the standard doses of a given drug may not have equivalent effects in all patients. To date, the management of depression remains mainly empirical and often poorly evaluated. The development of a personalized medicine in psychiatry may reduce treatment failure, intolerance or resistance, and hence the burden and costs of mood depressive disorders. The Geneva Cocktail Phenotypic approach presents several advantages including the "in vivo" measure of different cytochromes and transporter P-gp activities, their simultaneous determination in a single test, avoiding the influence of variability over time on phenotyping results, the administration of low dose substrates, a limited sampling strategy with an analytical method developed on DBS analysis. The goal of this project is to explore the relationship between the activity of drug-metabolizing enzymes (DME), assessed by a phenotypic approach, and the concentrations of Venlafaxine (VLX) + O-demethyl-venlafaxine (ODV), the efficacy and tolerance of VLX. This study is a multicentre prospective non-randomized open trial. Eligible patients present a major depressive episode, MADRS over or equal to 20, treatment with VLX regardless of the dose during at least 4 weeks. The Phenotype Visit includes VLX and ODV concentration measurement. Following the oral absorption of low doses of omeprazole, midazolam, dextromethorphan, and fexofenadine, drug metabolizing enzymes activity is assessed by specific metabolite/probe concentration ratios from a sample taken 2 h after cocktail administration for CYP2C19, CYP3A4, CYP2D6; and by the determination of the limited area under the curve from the capillary blood samples taken 2-3 and 6 h after cocktail administration for CYP2C19 and P-gp. Two follow-up visits will take place between 25 and 40 days and 50-70 days after inclusion. They include assessment of efficacy, tolerance and observance. Eleven french centres are involved in recruitment, expected to be completed within approximately 2 years with 205 patients. Metabolic ratios are determined in Geneva, Switzerland. By showing an association between drug metabolism and VLX concentrations, efficacy and tolerance, there is a hope that testing drug metabolism pathways with a phenotypical approach would help physicians in selecting and dosing antidepressants. The MARVEL study will provide an important contribution to increasing the knowledge of VLX variability and in optimizing the use of methods of personalized therapy in psychiatric settings. ClinicalTrials.gov NCT02590185 (10/27/2015). This study is currently recruiting participants

Nature of the wilt of carnations caused by Pseudomonas caryophylli, The

Includes bibliographical references (pages 52-54).June, 1952