\u3cem\u3ePseudomonas aeruginosa\u3c/em\u3e reverse diauxie is a multidimensionl, optimized, resource utilization strategy

Pseudomonas aeruginosa is a globally-distributed bacterium often found in medical infections. The opportunistic pathogen uses a different, carbon catabolite repression (CCR) strategy than many, model microorganisms. It does not utilize a classic diauxie phenotype, nor does it follow common systems biology assumptions including preferential consumption of glucose with an ‘overflow’ metabolism. Despite these contradictions, P. aeruginosa is competitive in many, disparate environments underscoring knowledge gaps in microbial ecology and systems biology. Physiological, omics, and in silico analyses were used to quantify the P. aeruginosa CCR strategy known as ‘reverse diauxie’. An ecological basis of reverse diauxie was identified using a genome-scale, metabolic model interrogated with in vitro omics data. Reverse diauxie preference for lower energy, nonfermentable carbon sources, such as acetate or succinate over glucose, was predicted using a multidimensional strategy which minimized resource investment into central metabolism while completely oxidizing substrates. Application of a common, in silico optimization criterion, which maximizes growth rate, did not predict the reverse diauxie phenotypes. This study quantifies P. aeruginosa metabolic strategies foundational to its wide distribution and virulence including its potentially, mutualistic interactions with microorganisms found commonly in the environment and in medical infections

Robustness analysis of culturing perturbations on Escherichia coli colony biofilm beta-lactam and aminoglycoside antibiotic tolerance

<p>Abstract</p> <p>Background</p> <p>Biofilms are ubiquitous. For instance, the majority of medical infections are thought to involve biofilms. However even after decades of investigation, the <it>in vivo </it>efficacy of many antimicrobial strategies is still debated suggesting there is a need for better understanding of biofilm antimicrobial tolerances. The current study's goal is to characterize the robustness of biofilm antibiotic tolerance to medically and industrially relevant culturing perturbations. By definition, robust systems will return similar, predictable responses when perturbed while non-robust systems will return very different and potentially unpredictable responses. The predictability of an antibiotic tolerance response is essential to developing, testing, and employing antimicrobial strategies.</p> <p>Results</p> <p>The antibiotic tolerance of <it>Escherichia coli </it>colony biofilms was tested against beta-lactam and aminoglycoside class antibiotics. Control scenario tolerances were compared to tolerances under culturing perturbations including 1) different nutritional environments 2) different temperatures 3) interruption of cellular quorum sensing and 4) different biofilm culture ages. Here, antibiotic tolerance was defined in terms of culturable biofilm cells recovered after a twenty four hour antibiotic treatment.</p> <p>Colony biofilm antibiotic tolerances were not robust to perturbations. Altering basic culturing parameters like nutritional environment or temperature resulted in very different, non-intuitive antibiotic tolerance responses. Some minor perturbations like increasing the glucose concentration from 0.1 to 1 g/L caused a ten million fold difference in culturable cells over a twenty four hour antibiotic treatment.</p> <p>Conclusions</p> <p>The current study presents a basis for robustness analysis of biofilm antibiotic tolerance. Biofilm antibiotic tolerance can vary in unpredictable manners based on modest changes in culturing conditions. Common antimicrobial testing methods, which only consider a single culturing condition, are not desirable since slight culturing variations can lead to very different outcomes. The presented data suggest it is essential to test antimicrobial strategies over a range of culturing perturbations relevant to the targeted application. In addition, the highly dynamic antibiotic tolerance responses observed here may explain why some current antimicrobial strategies occasionally fail.</p

Light Neutralinos in B-Decays

We consider the decays of a $B_s$-meson into a pair of lightest supersymmetric particles (LSP) in the minimal supersymmetric standard model. It is found that the parameter space for light LSP's in the range of 1 GeV can be appreciably constrained by looking for such decays.Comment: 9 pages, LaTex, 2 figures (hard copies of the figures available from the Authors on request

Differences in trauma history and psychopathology between PTSD patients with and without co-occurring dissociative disorders

Wabnitz P, Gast U, Catani C. Differences in trauma history and psychopathology between PTSD patients with and without co-occurring dissociative disorders. European Journal of Psychotraumatology. 2013;2013(4): 21452.Background: The interplay between different types of potentially traumatizing events, posttraumatic symptoms, and the pathogenesis of PTSD or major dissociative disorders (DD) has been extensively studied during the last decade. However, the phenomenology and nosological classification of posttraumatic disorders is currently under debate. The current study was conducted to investigate differences between PTSD patients with and without co-occurring major DD with regard to general psychopathology, trauma history, and trauma-specific symptoms. Methods: Twenty-four inpatients were administered the Clinician-Administered PTSD Scale for DSM-IV (CAPS) and the Mini-Structured Clinical Interview for DSM-IV Dissociative Disorders (MINI-SKID-D) to assess DD and PTSD. Additionally, participants completed questionnaires to assess general psychopathology and health status. Results: Symptom profiles and axis I comorbidity were similar in all patients. Traumatic experiences did not differ between the two groups, with both reporting high levels of childhood trauma. Only trauma-specific avoidance behavior and dissociative symptoms differed between groups. Conclusion: Results support the view that PTSD and DD are affiliated disorders that could be classified within the same diagnostic category. Our results accord with a typological model of dissociation in which profound forms of dissociation are specific to DD and are accompanied with higher levels of trauma-specific avoidance in DD patients

In silico approaches to study mass and energy flows in microbial consortia: a syntrophic case study

<p>Abstract</p> <p>Background</p> <p>Three methods were developed for the application of stoichiometry-based network analysis approaches including elementary mode analysis to the study of mass and energy flows in microbial communities. Each has distinct advantages and disadvantages suitable for analyzing systems with different degrees of complexity and <it>a priori </it>knowledge. These approaches were tested and compared using data from the thermophilic, phototrophic mat communities from Octopus and Mushroom Springs in Yellowstone National Park (USA). The models were based on three distinct microbial guilds: oxygenic phototrophs, filamentous anoxygenic phototrophs, and sulfate-reducing bacteria. Two phases, day and night, were modeled to account for differences in the sources of mass and energy and the routes available for their exchange.</p> <p>Results</p> <p>The <it>in silico </it>models were used to explore fundamental questions in ecology including the prediction of and explanation for measured relative abundances of primary producers in the mat, theoretical tradeoffs between overall productivity and the generation of toxic by-products, and the relative robustness of various guild interactions.</p> <p>Conclusion</p> <p>The three modeling approaches represent a flexible toolbox for creating cellular metabolic networks to study microbial communities on scales ranging from cells to ecosystems. A comparison of the three methods highlights considerations for selecting the one most appropriate for a given microbial system. For instance, communities represented only by metagenomic data can be modeled using the pooled method which analyzes a community's total metabolic potential without attempting to partition enzymes to different organisms. Systems with extensive <it>a priori </it>information on microbial guilds can be represented using the compartmentalized technique, employing distinct control volumes to separate guild-appropriate enzymes and metabolites. If the complexity of a compartmentalized network creates an unacceptable computational burden, the nested analysis approach permits greater scalability at the cost of more user intervention through multiple rounds of pathway analysis.</p

Yukawa correction to top-quark production at the Tevatron

We calculate the correction to \qbq\to\tbt of order \gmm. This correction, proportional to the square of the Higgs-boson Yukawa coupling to the top quark, arises from loops of Higgs bosons and the scalar component of virtual vector bosons. The Yukawa correction to the total \tbt\ production cross section at the Fermilab Tevatron in the standard Higgs model is found to be much less than the theoretical uncertainty in the cross section. However, in a two-Higgs-doublet model, Yukawa couplings are generally enhanced. The Yukawa correction can increase the total $t\bar t$ production cross section in this model by as much as $20$-$35\%$, which is potentially observable at the Tevatron.Comment: 16 pages, Fermilab-pub-93/027-T, BNL-4857

Environment Constrains Fitness Advantages of Division of Labor in Microbial Consortia Engineered for Metabolite Push or Pull Interactions

Fitness benefits from division of labor are well documented in microbial consortia, but the dependency of the benefits on environmental context is poorly understood. Two synthetic Escherichia coli consortia were built to test the relationships between exchanged organic acid, local environment, and opportunity costs of different metabolic strategies. Opportunity costs quantify benefits not realized due to selecting one phenotype over another. The consortia catabolized glucose and exchanged either acetic or lactic acid to create producer-consumer food webs. The organic acids had different inhibitory properties and different opportunity costs associated with their positions in central metabolism. The exchanged metabolites modulated different consortial dynamics. The acetic acid-exchanging (AAE) consortium had a “push” interaction motif where acetic acid was secreted faster by the producer than the consumer imported it, while the lactic acid-exchanging (LAE) consortium had a “pull” interaction motif where the consumer imported lactic acid at a comparable rate to its production. The LAE consortium outperformed wild-type (WT) batch cultures under the environmental context of weakly buffered conditions, achieving a 55% increase in biomass titer, a 51% increase in biomass per proton yield, an 86% increase in substrate conversion, and the complete elimination of by-product accumulation all relative to the WT. However, the LAE consortium had the trade-off of a 42% lower specific growth rate. The AAE consortium did not outperform the WT in any considered performance metric. Performance advantages of the LAE consortium were sensitive to environment; increasing the medium buffering capacity negated the performance advantages compared to WT

Implications of supersymmetric models with natural R-parity conservation

In the minimal supersymmetric standard model, the conservation of R-parity is phenomenologically desirable, but is ad hoc in the sense that it is not required for the internal consistency of the theory. However, if B-L is gauged at very high energies, R-parity will be conserved automatically and exactly, provided only that all order parameters carry even integer values of 3(B-L). We propose a minimal extension of the supersymmetric standard model in which R-parity conservation arises naturally in this way. This approach predicts the existence of a very weakly coupled, neutral chiral supermultiplet of particles with electroweak-scale masses and lifetimes which may be cosmologically interesting. Neutrino masses arise via an intermediate-scale seesaw mechanism, and a solution to the $\mu$ problem is naturally incorporated. The apparent unification of gauge couplings at high energies is shown to be preserved in this approach. We also discuss a next-to-minimal extension, which predicts a pair of electroweak-scale chiral supermultiplets with electric charge 2.Comment: 19 pages, plain TeX, no figure

The AMANDA Neutrino Telescope

With an effective telescope area of order $10^4$ m$^2$ for TeV neutrinos, a threshold near $\sim$50 GeV and a pointing accuracy of 2.5 degrees per muon track, the AMANDA detector represents the first of a new generation of high energy neutrino telescopes, reaching a scale envisaged over 25 years ago. We describe early results on the calibration of natural deep ice as a particle detector as well as on AMANDA's performance as a neutrino telescope.Comment: 12 pages, Latex2.09, uses espcrc2.sty and epsf.sty, 13 postscript files included. Talk presented at the 18th International Conference on Neutrino Physics and Astrophysics (Neutrino 98), Takayama, Japan, June 199