Signatures of Galaxy-Cluster Interactions: Spiral Galaxy Rotation Curve Asymmetry, Shape, and Extent

The environmental dependencies of the characteristics of spiral galaxy rotation curves are studied in this work. We use our large, homogeneously collected sample of 510 cluster spiral galaxy rotation curves to test the claim that the shape of a galaxy's rotation curve strongly depends on its location within the cluster, and thus presumably on the strength of the local intracluster medium and on the frequency and strength of tidal interactions with the cluster and cluster galaxies. Our data do not corroborate such a scenario, consistent with the fact that Tully-Fisher residuals are independent of galaxy location within the cluster; while the average late-type spiral galaxy shows more rise in the outer parts of its rotation curve than does the typical early-type spiral galaxy, there is no apparent trend for either subset with cluster environment. We also investigate as a function of cluster environment rotation curve asymmetry and the radial distribution of H II region tracers within galactic disks. Mild trends with projected cluster-centric distance are observed: (i) the (normalized) radial extent of optical line emission averaged over all spiral galaxy types shows a 4%+/-2% increase per Mpc of galaxy-cluster core separation, and (ii) rotation curve asymmetry falls by a factor of two between the inner and outer cluster for early-type spirals (a negligible decrease is found for late-type spirals). Such trends are consistent with spiral disk perturbations or even the stripping of the diffuse, outermost gaseous regions within the disks as galaxies pass through the dense cluster cores.Comment: 17 pages; to appear in the April 2001 Astronomical Journa

Longitudinal analysis of the behavioral phenotype in a novel transgenic rat model of early stages of Alzheimer's disease

Intraneuronal accumulation of amyloid beta (iAbeta) has been linked to mild cognitive impairment that may precede Alzheimers disease (AD) onset. This neuropathological trait was recently mimicked in a novel animal model of AD, the hemizygous transgenic McGill-R-Thy1-APP (Tg+/-) rat. The characterization of the behavioral phenotypes in this animal model could provide a baseline of efficacy for earlier therapeutic interventions. The aim of the present study was to undertake a longitudinal study of Abeta accumulation and a comprehensive behavioral evaluation of this transgenic rat model. We assessed exploratory activity, anxiety-related behaviors, recognition memory, working memory, spatial learning and reference memory at 3, 6 and 12 months of age. In parallel, we measured Abeta by ELISA, Western blots and semiquantitative immunohistochemistry in hippocampal samples. SDS-soluble Abeta peptide accumulated at low levels (9 pg/mg) without differences among ages. However, Western blots showed SDS-resistant Abeta oligomers (30 kDa) at 6 and 12 months, but not at 3 months. When compared to wild-type (WT), male Tg+/- rats exhibited a spatial reference memory deficit in the Morris Water Maze (MWM) as early as 3 months of age, which persisted at 6 and 12 months. In addition, Tg+/- rats displayed a working memory impairment in the Y-maze and higher anxiety levels in the Open Field (OF) at 6 and 12 months of age, but not at 3 months. Exploratory activity in the OF was similar to that of WT at all time points. Spatial learning in the MWM and the recognition memory, as assessed by the Novel Object Recognition Test, were unimpaired at any time point. The data from the present study demonstrate that the hemizygous transgenic McGill-R-Thy1-APP rat has a wide array of behavioral and cognitive impairments from young adulthood to middle-age. The low Abeta burden and early emotional and cognitive deficits in this transgenic rat model supports its potential use for drug discovery purposes in early AD.Fil: Galeano, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Martino Adami, Pamela Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: Do Carmo, Sonia. Mc Gill University; CanadáFil: Blanco, Eduardo. Universitat de Leida; EspañaFil: Rotondaro, Cecilia. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; ArgentinaFil: Capani, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Castaño, Eduardo Miguel. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; ArgentinaFil: Cuello, A. Claudio. Mc Gill University; CanadáFil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentin

Perturbed mitochondria-ER contacts in live neurons that model the amyloid pathology of Alzheimer\u27s disease.

The use of fixed fibroblasts from familial and sporadic Alzheimer\u27s disease patients has previously indicated an upregulation of mitochondria-ER contacts (MERCs) as a hallmark of Alzheimer\u27s disease. Despite its potential significance, the relevance of these results is limited because they were not extended to live neurons. Here we performed a dynamic in vivo analysis of MERCs in hippocampal neurons from McGill-R-Thy1-APP transgenic rats, a model of Alzheimer\u27s disease-like amyloid pathology. Live FRET imaging of neurons from transgenic rats revealed perturbed \u27lipid-MERCs\u27 (gap width \u3c10 nm), while \u27Ca2+-MERCs\u27 (10-20 nm gap width) were unchanged. In situ TEM showed no significant differences in the lipid-MERCs:total MERCs or lipid-MERCs:mitochondria ratios; however, the average length of lipid-MERCs was significantly decreased in neurons from transgenic rats as compared to controls. In accordance with FRET results, untargeted lipidomics showed significant decreases in levels of 12 lipids and bioenergetic analysis revealed respiratory dysfunction of mitochondria from transgenic rats. Thus, our results reveal changes in MERC structures coupled with impaired mitochondrial functions in Alzheimer\u27s disease-related neurons.This article has an associated First Person interview with the first author of the paper

Liver X Receptor Activation with an Intranasal Polymer Therapeutic Prevents Cognitive Decline without Altering Lipid Levels

The progressive accumulation of amyloid-beta (Aβ) in specific areas of the brain is a common prelude to late-onset of Alzheimer's disease (AD). Although activation of liver X receptors (LXR) with agonists decreases Aβ levels and ameliorates contextual memory deficit, concomitant hypercholesterolemia/hypertriglyceridemia limits their clinical application. DMHCA (N,N-dimethyl-3β-hydroxycholenamide) is an LXR partial agonist that, despite inducing the expression of apolipoprotein E (main responsible of Aβ drainage from the brain) without increasing cholesterol/triglyceride levels, shows nil activity in vivo because of a low solubility and inability to cross the blood brain barrier. Herein, we describe a polymer therapeutic for the delivery of DMHCA. The covalent incorporation of DMHCA into a PEG-dendritic scaffold via carboxylate esters produces an amphiphilic copolymer that efficiently self-assembles into nanometric micelles that exert a biological effect in primary cultures of the central nervous system (CNS) and experimental animals using the intranasal route. After CNS biodistribution and effective doses of DMHCA micelles were determined in nontransgenic mice, a transgenic AD-like mouse model of cerebral amyloidosis was treated with the micelles for 21 days. The benefits of the treatment included prevention of memory deterioration and a significant reduction of hippocampal Aβ oligomers without affecting plasma lipid levels. These results represent a proof of principle for further clinical developments of DMHCA delivery systems.Fil: Navas Guimaraes, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; Argentina. Universidad Catolica de Cuyo. Facultad de Ciencias Medicas. Instituto de Investigacion En Ciencias Biomedicas.; ArgentinaFil: Lopez Blanco, Roi. Universidad de Santiago de Compostela; EspañaFil: Correa, Juan. Universidad de Santiago de Compostela; EspañaFil: Fernandez Villamarin, Marcos. Universidad de Santiago de Compostela; EspañaFil: Bistue Millon, Maria Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; Argentina. Universidad Catolica de Cuyo. Facultad de Ciencias Medicas. Instituto de Investigacion En Ciencias Biomedicas.; ArgentinaFil: Martino Adami, Pamela Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Kumar, Vijay. University of Colorado; Estados UnidosFil: Wempe, Michael F.. University of Colorado; Estados UnidosFil: Cuello, A. C.. McGill University; CanadáFil: Fernandez Megia, Eduardo. Universidad de Santiago de Compostela; EspañaFil: Bruno, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; Argentina. Universidad Catolica de Cuyo. Facultad de Ciencias Medicas. Instituto de Investigacion En Ciencias Biomedicas.; Argentin

A GMBCG Galaxy Cluster Catalog of 55,424 Rich Clusters from SDSS DR7

We present a large catalog of optically selected galaxy clusters from the application of a new Gaussian Mixture Brightest Cluster Galaxy (GMBCG) algorithm to SDSS Data Release 7 data. The algorithm detects clusters by identifying the red sequence plus Brightest Cluster Galaxy (BCG) feature, which is unique for galaxy clusters and does not exist among field galaxies. Red sequence clustering in color space is detected using an Error Corrected Gaussian Mixture Model. We run GMBCG on 8240 square degrees of photometric data from SDSS DR7 to assemble the largest ever optical galaxy cluster catalog, consisting of over 55,000 rich clusters across the redshift range from 0.1 < z < 0.55. We present Monte Carlo tests of completeness and purity and perform cross-matching with X-ray clusters and with the maxBCG sample at low redshift. These tests indicate high completeness and purity across the full redshift range for clusters with 15 or more members.Comment: Updated to match the published version. The catalog can be accessed from: http://home.fnal.gov/~jghao/gmbcg_sdss_catalog.htm

H7N9 influenza split vaccine with SWE oil-in-water adjuvant greatly enhances cross-reactive humoral immunity and protection against severe pneumonia in ferrets

Until universal influenza vaccines become available, pandemic preparedness should include developing classical vaccines against potential pandemic influenza subtypes. We here show that addition of SWE adjuvant, a squalene-in-water emulsion, to H7N9 split influenza vaccine clearly enhanced functional antibody responses in ferrets. These were cross-reactive against H7N9 strains from different lineages and newly emerged H7N9 variants. Both vaccine formulations protected in almost all cases against severe pneumonia induced by intratracheal infection of ferrets with H7N9 influenza; however, the SWE adjuvant enhanced protection against virus replication and disease. Correlation analysis and curve fitting showed that both VN- and NI-titers were better predictors for protection than HI-titers. Moreover, we show that novel algorithms can assist in better interpretation of large data sets generated in preclinical studies. Cluster analysis showed that the adjuvanted vaccine results in robust immunity and protection, whereas the response to the non-adjuvanted vaccine is heterogeneous, such that the protection balance may be more easily tipped toward severe disease. Finally, cluster analysis indicated that the dose-sparing capacity of the adjuvant is at least a factor six, which greatly increases vaccine availability in a pandemic situation.</p

Immediate Risk for Cardiovascular Events and Suicide Following a Prostate Cancer Diagnosis: Prospective Cohort Study

Katja Fall and Fang Fang and colleagues find that men newly diagnosed with prostate cancer are at increased risk of cardiovascular events and suicide

Nicotinamide as potential biomarker for Alzheimer’s disease: A translational study based on metabolomics

Introduction: The metabolic routes altered in Alzheimer's disease (AD) brain are poorly understood. As the metabolic pathways are evolutionarily conserved, the metabolic profiles carried out in animal models of AD could be directly translated into human studies.Methods: We performed untargeted Nuclear Magnetic Resonance metabolomics in hippocampus of McGill-R-Thy1-APP transgenic (Tg) rats, a model of AD-like cerebral amyloidosis and the translational potential of these findings was assessed by targeted Gas Chromatography-Electron Impact-Mass Spectrometry in plasma of participants in the German longitudinal cohort AgeCoDe.Results: In rat hippocampus 26 metabolites were identified. Of these 26 metabolites, nine showed differences between rat genotypes that were nominally significant. Two of them presented partial least square-discriminant analysis (PLS-DA) loadings with the larger absolute weights and the highest Variable Importance in Projection (VIP) scores and were specifically assigned to nicotinamide adenine dinucleotide (NAD) and nicotinamide (Nam). NAD levels were significantly decreased in Tg rat brains as compared to controls. In agreement with these results, plasma of AD patients showed significantly reduced levels of Nam in respect to cognitively normal participants. In addition, high plasma levels of Nam showed a 27% risk reduction of progressing to AD dementia within the following 2.5 years, this hazard ratio is lost afterwards.Discussion: To our knowledge, this is the first report showing that a decrease of Nam plasma levels is observed couple of years before conversion to AD, thereby suggesting its potential use as biomarker for AD progression