Analysis of autophagy and inflammasome regulation in neuronal cells and monocytes infected with Chlamydia Pneumoniae: Implications for Alzheimer’s disease

Objectives: Our laboratory has been studying the role of infection with the obligate intracellular bacterium Chlamydia pneumoniae in sporadic late-onset Alzheimer disease (LOAD). This infection may be a trigger for the pathology observed in LOAD as a function of initiating changes in gene regulation following entry of the organism into the brain. As such, we are analyzing how this infection can promote changes in autophagy and inflammasome gene regulation as both have been shown to be altered in LOAD. Methods: Human SKNMC neuronal cells and THP1 monocytes were infected in vitro for 24-72 hrs with a laboratory strain of Chlamydia pneumoniae followed by RNA extraction, cDNA synthesis and analysis using Real-Time PCR microarrays for autophagy and inflammasome genes. Results: Gene expression for autophagy and inflammasome pathways was altered dramatically following infection. Genes encoding for co-regulation of autophagy, apoptosis, and the cell cycle that were significantly changed included: BCL2L1, FAS, PIK3CG, APP, and TP53. In addition, ATG3, and GABARAP, genes encoding for protein transport & ubiquitination and autophagic vacuole formation were significantly deregulated. Of the inflammasome genes, 4 NOD-like receptor genes were significantly up-regulated. IL-1beta, AIM2, CCL2, and CCL7 genes were all dramatically up-regulated in monocytes during the 72 hrs of infection. Conclusions: Our data suggest that Chlamydia pneumoniae-infected human SKNMC neuronal cells and THP1 monocytes exhibit specific changes in gene regulation for both autophagy and inflammasome pathways. These gene changes appear to correlate with pathologic changes previously reported in AD and further support the contention that infection with Chlamydia pneumoniae plays a role in LOAD pathogenesis

Diamonds on the Hat: Globular Clusters in The Sombrero Galaxy (M104)

Images from the HST ACS are used to carry out a new photometric study of the globular clusters (GCs) in M104, the Sombrero galaxy. The primary focus of our study is the characteristic distribution function of linear sizes (SDF) of the GCs. We measure the effective radii for 652 clusters with PSF-convolved King and Wilson dynamical model fits. The SDF is remarkably similar to those measured for other large galaxies of all types, adding strong support to the view that it is a "universal" feature of globular cluster systems. We develop a more general interpretation of the size distribution function for globular clusters, proposing that the shape of the SDF that we see today for GCs is strongly influenced by the early rapid mass loss during their star forming stage, coupled with stochastic differences from cluster to cluster in the star formation efficiency (SFE) and their initial sizes. We find that the observed SDF shape can be accurately predicted by a simple model in which the protocluster clouds had characteristic sizes of $0.9 \pm 0.1$ pc and SFEs of $0.3 \pm 0.07$. The colors and luminosities of the M104 clusters show the clearly defined classic bimodal form. The blue sequence exhibits a mass/metallicity relation (MMR), following a scaling of heavy-element abundance with luminosity of $Z \sim L^{0.3}$ very similar to what has been found in most giant elliptical galaxies. A quantitative self-enrichment model provides a good first-order match to the data for the same initial SFE and protocluster size that were required to explain the SDF. We also discuss various forms of the globular cluster Fundamental Plane (FP) of structural parameters, and show that useful tests of it can be extended to galaxies beyond the Local Group.Comment: In press for MNRA

Inclination-Independent Galaxy Classification

We present a new method to classify galaxies from large surveys like the Sloan Digital Sky Survey using inclination-corrected concentration, inclination-corrected location on the color-magnitude diagram, and apparent axis ratio. Explicitly accounting for inclination tightens the distribution of each of these parameters and enables simple boundaries to be drawn that delineate three different galaxy populations: Early-type galaxies, which are red, highly concentrated, and round; Late-type galaxies, which are blue, have low concentrations, and are disk dominated; and Intermediate-type galaxies, which are red, have intermediate concentrations, and have disks. We have validated our method by comparing to visual classifications of high-quality imaging data from the Millennium Galaxy Catalogue. The inclination correction is crucial to unveiling the previously unrecognized Intermediate class. Intermediate-type galaxies, roughly corresponding to lenticulars and early spirals, lie on the red sequence. The red sequence is therefore composed of two distinct morphological types, suggesting that there are two distinct mechanisms for transiting to the red sequence. We propose that Intermediate-type galaxies are those that have lost their cold gas via strangulation, while Early-type galaxies are those that have experienced a major merger that either consumed their cold gas, or whose merger progenitors were already devoid of cold gas (the ``dry merger'' scenario).Comment: Accepted for publication in ApJ. 7 pages in emulateap

CP violation and modular symmetries

We reconsider the origin of CP violation in fundamental theory. Existing string models of spontaneous CP violation make ambiguous predictions, due to the arbitrariness of CP transformation and the apparent non-invariance of the results under duality. We find an unambiguous modular CP invariance condition, applicable to predictive models of spontaneous CP violation, which circumvents these problems; it strongly constrains CP violation by heterotic string moduli. The dilaton is also evaluated as a source of CP violation, but is likely experimentally excluded. We consider the prospects for explaining CP violation in strongly-coupled strings and brane worlds.Comment: 6 pages, REVTeX 4b5+amssymb. 2 references added, substantially the same as published versio

The history of stellar metallicity in a simulated disc galaxy

We explore the chemical distribution of stars in a simulated galaxy. Using simulations of the same initial conditions but with two different feedback schemes (McMaster Unbiased Galaxy Simulations – MUGS – and Making Galaxies in a Cosmological Context – MaGICC), we examine the features of the age–metallicity relation (AMR), and the three-dimensional age– [Fe/H]–[O/Fe] distribution, both for the galaxy as a whole and decomposed into disc, bulge, halo and satellites. The MUGS simulation, which uses traditional supernova feedback, is replete with chemical substructure. This substructure is absent from the MaGICC simulation, which includes early feedback from stellar winds, a modified initial mass function and more efficient feedback. The reduced amount of substructure is due to the almost complete lack of satellites in MaGICC. We identify a significant separation between the bulge and disc AMRs, where the bulge is considerably more metal-rich with a smaller spread in metallicity at any given time than the disc. Our results suggest, however, that identifying the substructure in observations will require exquisite age resolution, of the order of 0.25 Gyr. Certain satellites show exotic features in the AMR, even forming a ‘sawtooth’ shape of increasing metallicity followed by sharp declines which correspond to pericentric passages. This fact, along with the large spread in stellar age at a given metallicity, compromises the use of metallicity as an age indicator, although alpha abundance provides a more robust clock at early times. This may also impact algorithms that are used to reconstruct star formation histories from resolved stellar populations, which frequently assume a monotonically increasing AMR

Neutrino scattering off pair-breaking and collective excitations in superfluid neutron matter and in color-flavor locked quark matter

We calculate the correlation functions needed to describe the linear response of superfluid matter, and go on to calculate the differential cross section for neutral-current neutrino scattering in superfluid neutron matter and in color-flavor locked quark matter (CFL). We report the first calculation of scattering rates that includes neutrino interactions with both pair-breaking excitations and low-lying collective excitations (Goldstone modes). Our results apply both above and below the critical temperature, allowing use in simulations of neutrino transport in supernovae and neutron stars.Comment: 22 pages, 9 figure

Globular Cluster Systems in Brightest Cluster Galaxies. III: Beyond Bimodality

We present new deep photometry of the rich globular cluster (GC) systems around the Brightest Cluster Galaxies UGC 9799 (Abell 2052) and UGC 10143 (Abell 2147), obtained with the HST ACS and WFC3 cameras. For comparison, we also present new reductions of similar HST/ACS data for the Coma supergiants NGC 4874 and 4889. All four of these galaxies have huge cluster populations (to the radial limits of our data, comprising from 12000 to 23000 clusters per galaxy). The metallicity distribution functions (MDFs) of the GCs can still be matched by a bimodal-Gaussian form where the metal-rich and metal-poor modes are separated by ~0.8 dex, but the internal dispersions of each mode are so large that the total MDF becomes very broad and nearly continuous from [Fe/H] = -2.4 to Solar. There are, however, significant differences between galaxies in the relative numbers of \emph{metal-rich} clusters, suggesting that they underwent significantly different histories of mergers with massive, gas-rich halos. Lastly, the proportion of metal-poor GCs rises especially rapidly outside projected radii R > 4 R_eff, suggesting the importance of accreted dwarf satellites in the outer halo. Comprehensive models for the formation of GCs as part of the hierarchical formation of their parent galaxies will be needed to trace the systematic change in structure of the MDF with galaxy mass, from the distinctly bimodal form in smaller galaxies up to the broad continuum that we see in the very largest systems.Comment: In press for Astrophysical Journa