Microarray analysis of Shigella flexneri-infected epithelial cells identifies host factors important for apoptosis inhibition

<p>Abstract</p> <p>Background</p> <p><it>Shigella flexneri </it>inhibits apoptosis in infected epithelial cells. In order to understand the pro-survival effects induced by the bacteria, we utilized apoptosis-specific microarrays to analyze the changes in eukaryotic gene expression in both infected and uninfected cells in the presence and absence of staurosporine, a chemical inducer of the intrinsic pathway of apoptosis. The goal of this research was to identify host factors that contribute to apoptosis inhibition in infected cells.</p> <p>Results</p> <p>The microarray analysis revealed distinct expression profiles in uninfected and infected cells, and these changes were altered in the presence of staurosporine. These profiles allowed us to make comparisons between the treatment groups. Compared to uninfected cells, <it>Shigella-</it>infected epithelial cells, both in the presence and absence of staurosporine, showed significant induced expression of <it>JUN</it>, several members of the inhibitor of apoptosis gene family, nuclear factor κB and related genes, genes involving tumor protein 53 and the retinoblastoma protein, and surprisingly, genes important for the inhibition of the extrinsic pathway of apoptosis. We confirmed the microarray results for a selection of genes using <it>in situ </it>hybridization analysis.</p> <p>Conclusion</p> <p>Infection of epithelial cells with <it>S. flexneri </it>induces a pro-survival state in the cell that results in apoptosis inhibition in the presence and absence of staurosporine. The bacteria may target these host factors directly while some induced genes may represent downstream effects due to the presence of the bacteria. Our results indicate that the bacteria block apoptosis at multiple checkpoints along both pathways so that even if a cell fails to prevent apoptosis at an early step, <it>Shigella </it>will block apoptosis at the level of caspase-3. Apoptosis inhibition is most likely vital to the survival of the bacteria <it>in vivo</it>. Future characterization of these host factors is required to fully understand how <it>S. flexneri </it>inhibits apoptosis in epithelial cells.</p

Fluorescence Measurements Of Phototrophic Sulfur Bacteria For Applications In Water Column Profiling

poster abstractUnlike plants that produce oxygen during photosynthesis, phototrophic sulfur bacteria use sulfide and sunlight to produce carbohydrates and elemental sulfur. These bacteria require a unique aquatic environment to thrive: one that is anoxic (depleted of oxygen) and rich in hydrogen sulfide. Such conditions are found in a number of stratified lakes around the world including several in Northern Indiana. Studying the ecology and geochemical conditions that promote habitable conditions for phototrophic bacteria in lakes provides insight into the Early Earth (thought to be anoxic), ocean anoxic events of the Mesozoic (70-250 million years ago) and modern low oxygen conditions of coastal environments such as the Dead Zone of the Gulf of Mexico. However, locating and directly sampling these bacterial populations in vast bodies of water is not an easy task. In this project, we investigate fluorescent properties of purple sulfur bacteria in order to develop a dependable sensor that can be deployed in the water column. We report a number of measurements of purple sulfur bacterium fluorescence in the near infrared region when excited at discrete wavelengths in the UV range. We use these bench-top measurements to design a water-proof apparatus equipped with an absorption and luminescent detector for localization of bacteria in lake water. This device will be deployed in anoxic lakes of Northern Indiana to find the in situ water column position of phototrophic bacteria

The Semi-Chiral Quotient, Hyperkahler Manifolds and T-duality

We study the construction of generalized Kahler manifolds, described purely in terms of N=(2,2) semichiral superfields, by a quotient using the semichiral vector multiplet. Despite the presence of a b-field in these models, we show that the quotient of a hyperkahler manifold is hyperkahler, as in the usual hyperkahler quotient. Thus, quotient manifolds with torsion cannot be constructed by this method. Nonetheless, this method does give a new description of hyperkahler manifolds in terms of two-dimensional N=(2,2) gauged non-linear sigma models involving semichiral superfields and the semichiral vector multiplet. We give two examples: Eguchi-Hanson and Taub-NUT. By T-duality, this gives new gauged linear sigma models describing the T-dual of Eguchi-Hanson and NS5-branes. We also clarify some aspects of T-duality relating these models to N=(4,4) models for chiral/twisted-chiral fields and comment briefly on more general quotients that can give rise to torsion and give an example.Comment: 31 page

A demographic model for sex ratio evolution and the effects of sex-biased offspring costs

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Ecology and Evolution 6 (2016): 1470–1492, doi:10.1002/ece3.1902.The evolution of the primary sex ratio, the proportion of male births in an individual's offspring production strategy, is a frequency-dependent process that selects against the more common sex. Because reproduction is shaped by the entire life cycle, sex ratio theory would benefit from explicitly two-sex models that include some form of life cycle structure. We present a demographic approach to sex ratio evolution that combines adaptive dynamics with nonlinear matrix population models. We also determine the evolutionary and convergence stability of singular strategies using matrix calculus. These methods allow the incorporation of any population structure, including multiple sexes and stages, into evolutionary projections. Using this framework, we compare how four different interpretations of sex-biased offspring costs affect sex ratio evolution. We find that demographic differences affect evolutionary outcomes and that, contrary to prior belief, sex-biased mortality after parental investment can bias the primary sex ratio (but not the corresponding reproductive value ratio). These results differ qualitatively from the widely held conclusions of previous models that neglect demographic structure.National Science Foundation Graduate Research Grant Number: 1122374; NSF Grant Numbers: DEB1145017, DEB1257545; European Research Council Grant Number: 322989; Woods Hole Oceanographic Institution Academic Programs Offic

Superconducting Effects in Optimization of Magnetic Penetration Thermometers for X-ray Microcalorimeters

Like MMCs, MPTs enable high energy microcalorimeters with zero bias power dissipation and potential resolution < 1 eV. MPTs can provide d(phi)/dT as large as 1000 (Phi)(sub 0)/K, with no excess noise, thereby reducing the importance of SQUID noise. Long coherence length in a Type-I superconducting MoAu film offers multiple advantages for efficient flux expulsion in MPT. Region of steepest d(phi)/dT is the Meissner effect in the small device; flux is expelled/penetrates to minimize free energy. Steepness of transition can be engineered with choice of film thickness and coil pitch relative to lambda(sub eff)(0), ratio of T/T(sub c), and bias circuit inductance

Evaluating the Psychometric Quality of Social Skills Measures: A Systematic Review

Introduction - Impairments in social functioning are associated with an array of adverse outcomes. Social skills measures are commonly used by health professionals to assess and plan the treatment of social skills difficulties. There is a need to comprehensively evaluate the quality of psychometric properties reported across these measures to guide assessment and treatment planning. Objective - To conduct a systematic review of the literature on the psychometric properties of social skills and behaviours measures for both children and adults. Methods - A systematic search was performed using four electronic databases: CINAHL, PsycINFO, Embase and Pubmed; the Health and Psychosocial Instruments database; and grey literature using PsycExtra and Google Scholar. The psychometric properties of the social skills measures were evaluated against the COSMIN taxonomy of measurement properties using pre-set psychometric criteria. Results - Thirty-Six studies and nine manuals were included to assess the psychometric properties of thirteen social skills measures that met the inclusion criteria. Most measures obtained excellent overall methodological quality scores for internal consistency and reliability. However, eight measures did not report measurement error, nine measures did not report cross-cultural validity and eleven measures did not report criterion validity. Conclusions - The overall quality of the psychometric properties of most measures was satisfactory. The SSBS-2, HCSBS and PKBS-2 were the three measures with the most robust evidence of sound psychometric quality in at least seven of the eight psychometric properties that were appraised. A universal working definition of social functioning as an overarching construct is recommended. There is a need for ongoing research in the area of the psychometric properties of social skills and behaviours instruments

Direct and Inverse Variational Problems on Time Scales: A Survey

We deal with direct and inverse problems of the calculus of variations on arbitrary time scales. Firstly, using the Euler-Lagrange equation and the strengthened Legendre condition, we give a general form for a variational functional to attain a local minimum at a given point of the vector space. Furthermore, we provide a necessary condition for a dynamic integro-differential equation to be an Euler-Lagrange equation (Helmholtz's problem of the calculus of variations on time scales). New and interesting results for the discrete and quantum settings are obtained as particular cases. Finally, we consider very general problems of the calculus of variations given by the composition of a certain scalar function with delta and nabla integrals of a vector valued field.Comment: This is a preprint of a paper whose final and definite form will be published in the Springer Volume 'Modeling, Dynamics, Optimization and Bioeconomics II', Edited by A. A. Pinto and D. Zilberman (Eds.), Springer Proceedings in Mathematics & Statistics. Submitted 03/Sept/2014; Accepted, after a revision, 19/Jan/201

The Complete Genome Sequence of Helicobacter pylori Strain G27

Helicobacter pylori is a gram-negative pathogen that colonizes the stomachs of over half the world's population and causes a spectrum of gastric diseases including gastritis, ulcers, and gastric carcinoma. The H. pylori species exhibits unusually high levels of genetic variation between strains. Here we announce the complete genome sequence of H. pylori strain G27, which has been used extensively in H. pylori research

The Total Syntheses of JBIR-94 and Two Synthetic Analogs and Their Cytotoxicities Against A549 (CCL-185) Human Small Lung Cancer Cells

We here disclose the total syntheses of the natural polyphenol JBIR-94 and two nonnatural analogs, whose structures are of interest for their bioactivity potential as radical scavengers. Although we initially attempted this by dually acylating both of putrecine’s amine nitrogens in a single pot, our endeavors with this method (which has been successfully reported by other groups) proved ineffectual. We accordingly opted for the lengthier approach of acylating each amine individually, which gratuitously prevailed and also aligns with separate literature precedent. Moreover, we here share our analysis of these target compounds’ cytotoxicities and IC50 values against A549 (CCL-185) human small lung cancer cells