Increased human pathogenic potential of Escherichia coli from polymicrobial urinary tract infections in comparison to isolates from monomicrobial culture samples

The current diagnostic standard procedure outlined by the Health Protection Agency for urinary tract infections (UTIs) in clinical laboratories does not report bacteria isolated from samples containing three or more different bacterial species. As a result many UTIs go unreported and untreated, particularly in elderly patients, where polymicrobial UTI samples are especially prevalent. This study reports the presence of the major uropathogenic species in mixed culture urine samples from elderly patients, and of resistance to front-line antibiotics, with potentially increased levels of resistance to ciprofloxacin and trimethoprim. Most importantly, the study highlights that Escherichia coli present in polymicrobial UTI samples are statistically more invasive (P<0.001) in in vitro epithelial cell infection assays than those isolated from monomicrobial culture samples. In summary, the results of this study suggest that the current diagnostic standard procedure for polymicrobial UTI samples needs to be reassessed, and that E. coli present in polymicrobial UTI samples may pose an increased risk to human health

Roles of Candida albicans Mig1 and Mig2 in glucose repression, pathogenicity traits, and SNF1 essentiality.

Metabolic adaptation is linked to the ability of the opportunistic pathogen Candida albicans to colonize and cause infection in diverse host tissues. One way that C. albicans controls its metabolism is through the glucose repression pathway, where expression of alternative carbon source utilization genes is repressed in the presence of its preferred carbon source, glucose. Here we carry out genetic and gene expression studies that identify transcription factors Mig1 and Mig2 as mediators of glucose repression in C. albicans. The well-studied Mig1/2 orthologs ScMig1/2 mediate glucose repression in the yeast Saccharomyces cerevisiae; our data argue that C. albicans Mig1/2 function similarly as repressors of alternative carbon source utilization genes. However, Mig1/2 functions have several distinctive features in C. albicans. First, Mig1 and Mig2 have more co-equal roles in gene regulation than their S. cerevisiae orthologs. Second, Mig1 is regulated at the level of protein accumulation, more akin to ScMig2 than ScMig1. Third, Mig1 and Mig2 are together required for a unique aspect of C. albicans biology, the expression of several pathogenicity traits. Such Mig1/2-dependent traits include the abilities to form hyphae and biofilm, tolerance of cell wall inhibitors, and ability to damage macrophage-like cells and human endothelial cells. Finally, Mig1 is required for a puzzling feature of C. albicans biology that is not shared with S. cerevisiae: the essentiality of the Snf1 protein kinase, a central eukaryotic carbon metabolism regulator. Our results integrate Mig1 and Mig2 into the C. albicans glucose repression pathway and illuminate connections among carbon control, pathogenicity, and Snf1 essentiality

The Search for Intergalactic Hydrogen Clouds in Voids

I present the results of a search for intergalactic hydrogen clouds in voids. Clouds are detected by their HI LyA absorption lines in the HST spectra of low-redshift AGN. The parameter with which the environments of clouds are characterized is the tidal field, which places a lower limit on the cloud mass-density which is dynamically stable against disruption. Galaxy redshift catalogs are used to sum the tidal fields along the lines of sight, sorting clouds according to tidal field upper, or lower limits. The analytical methodology employed is designed to detect gas clouds whose expansion following reionization is restrained by dark matter perturbations. End-products are the cloud equivalent width distribution functions (EWDF) of catalogs formed by sorting clouds according to various tidal field upper, or lower limits. Cumulative EWDFs are steep in voids (S ~ -1.5 \pm 0.2), but flatter in high tidal field zones (S ~ -0.5 \pm 0.1). Most probable cloud Doppler parameters are ~30 km/s in voids and ~60 km/s in proximity to galaxies. In voids, the cumulative line density at low EW (~ 15 mA) is ~ 500 per unit redshift. The void filling factor is found to be 0.87 <= f_v <= 0.94. The void EWDF is remarkably uniform over this volume, with a possible tendency for more massive clouds to be in void centers. The size and nature of the void cloud population suggested by this study is completely unanticipated by the results of published 3-D simulations, which predict that most clouds are in filamentary structures around galaxy concentrations, and that very few observable absorbers would lie in voids. Strategies for modeling this population are briefly discussed.Comment: 21 pages, 19 figures, apjemulate style, to appear in ApJ vol. 57

On stochastic sea of the standard map

Consider a generic one-parameter unfolding of a homoclinic tangency of an area preserving surface diffeomorphism. We show that for many parameters (residual subset in an open set approaching the critical value) the corresponding diffeomorphism has a transitive invariant set $\Omega$ of full Hausdorff dimension. The set $\Omega$ is a topological limit of hyperbolic sets and is accumulated by elliptic islands. As an application we prove that stochastic sea of the standard map has full Hausdorff dimension for sufficiently large topologically generic parameters.Comment: 36 pages, 5 figure

Polyelectrolyte Persistence Length: Attractive Effect of Counterion Correlations and Fluctuations

The persistence length of a single, strongly charged, stiff polyelectrolyte chain is investigated theoretically. Path integral formulation is used to obtain the effective electrostatic interaction between the monomers. We find significant deviations from the classical Odijk, Skolnick and Fixman (OSF) result. An induced attraction between monomers is due to thermal fluctuations and correlations between bound counterions. The electrostatic persistence length is found to be smaller than the OSF value and indicates a possible mechanical instability (collapse) for highly charged polyelectrolytes with multivalent counterions. In addition, we calculate the amount of condensed counterions on a slightly bent polyelectrolyte. More counterions are found to be adsorbed as compared to the Manning condensation on a cylinder.Comment: 5 pages, 1 ps figur

Charge Fluctuation Forces Between Stiff Polyelectrolytes in Salt Solution: Pairwise Summability Re-examined

We formulate low-frequency charge-fluctuation forces between charged cylinders - parallel or skewed - in salt solution: forces from dipolar van der Waals fluctuations and those from the correlated monopolar fluctuations of mobile ions. At high salt concentrations forces are exponentially screened. In low-salt solutions dipolar energies go as $R^{-5}$ or $R^{-4}$; monopolar energies vary as $R^{-1}$ or $\ln{R}$, where $R$ is the minimal separation between cylinders. However, pairwise summability of rod-rod forces is easily violated in low-salt conditions. Perhaps the most important result is not the derivation of pair potentials but rather the demonstration that some of these expressions may not be used for the very problems that originally motivated their derivation.Comment: 8 pages and 1 fig in ps forma

On Hilberg's Law and Its Links with Guiraud's Law

Hilberg (1990) supposed that finite-order excess entropy of a random human text is proportional to the square root of the text length. Assuming that Hilberg's hypothesis is true, we derive Guiraud's law, which states that the number of word types in a text is greater than proportional to the square root of the text length. Our derivation is based on some mathematical conjecture in coding theory and on several experiments suggesting that words can be defined approximately as the nonterminals of the shortest context-free grammar for the text. Such operational definition of words can be applied even to texts deprived of spaces, which do not allow for Mandelbrot's ``intermittent silence'' explanation of Zipf's and Guiraud's laws. In contrast to Mandelbrot's, our model assumes some probabilistic long-memory effects in human narration and might be capable of explaining Menzerath's law.Comment: To appear in Journal of Quantitative Linguistic

Fv antibodies to aflatoxin B1 derived from a pre-immunized antibody phage display library system

The production and characterization of recombinant antibodies to aflatoxin B[SUB1] (AFB[SUB1]), a potent mycotoxin and carcinogen is described. The antibody fragments produced were then applied for use in a surface plasmon resonance-based biosensor (BIAcore), which measures biomolecular interactions in 'real-time'. Single chain Fv (scFv) antibodies were generated to aflatoxin B1 from an established phage display system, which incorporated a range of different plasmids for efficient scFv expression. The scFv's were used in the development of a competitive ELISA, and also for the development of surface plasmon resonance (SPR)-based inhibition immunoassays. They were found to be suitable for the detection of AFB[SUB1], in this format, with the assays being sensitive and reproducible

Collapse of Stiff Polyelectrolytes due to Counterion Fluctuations

The effective elasticity of highly charged stiff polyelectrolytes is studied in the presence of counterions, with and without added salt. The rigid polymer conformations may become unstable due to an effective attraction induced by counterion density fluctuations. Instabilities at the longest, or intermediate length scales may signal collapse to globule, or necklace states, respectively. In the presence of added-salt, a generalized electrostatic persistence length is obtained, which has a nontrivial dependence on the Debye screening length.Comment: 4 pages RevTex, 3 ps figures included using epsf, final version as appeared in PR

Evidence of oxidative stress in young and aged DJ-1-deficient mice

AbstractLoss of DJ-1 function contributes to pathogenesis in Parkinson’s disease. Here, we investigate the impact of aging and DJ-1 deficiency in transgenic mice. Ventral midbrain from young DJ-1-deficient mice revealed no change in 4-hydroxy-2-nonenal (4-HNE), but HSP60, HSP40 and striatal dopamine turnover were significantly elevated compared to wildtype. In aged mice, the chaperone response observed in wildtype animals was absent from DJ-1-deficient transgenics, and nigral 4-HNE immunoreactivity was enhanced. These changes were concomitant with increased striatal dopamine levels and uptake. Thus, increased oxidants and diminished protein quality control may contribute to nigral oxidative damage with aging in the model