Substrate-dependent activation of the Vibrio cholerae vexAB RND efflux system requires vexR

Vibrio cholerae encodes six resistance-nodulation-division (RND) efflux systems which function in antimicrobial resistance, virulence factor production, and intestinal colonization. Among the six RND efflux systems, VexAB exhibited broad substrate specificity and played a predominant role in intrinsic antimicrobial resistance. The VexAB system was encoded in an apparent three gene operon that included vexR; which encodes an uncharacterized TetR family regulator. In this work we examined the role of vexR in vexRAB expression. We found that VexR bound to the vexRAB promoter and vexR deletion resulted in decreased vexRAB expression and increased susceptibility to VexAB antimicrobial substrates. Sub-strate-dependent induction of vexRAB was dependent on vexR and episomal vexR expression provided a growth advantage in the presence of the VexAB substrate deoxycholate. The expression of vexRAB increased, in a vexR-dependent manner, in response to the loss of RND efflux activity. This suggested that VexAB may function to export intracellular metabolites. Support for this hypothesis was provided by data showing that vexRAB was upregulated in several metabolic mutants including tryptophan biosynthetic mutants that were predicted to accumulate indole. In addition, vexRAB was found to be upregulated in response to exogenous indole and to contribute to indole resistance. The collective results indicate that vexR is required for vexRAB expression in response to VexAB substrates and that the VexAB RND efflux system modulates the intracellular levels of metabolites that could otherwise accumulate to toxic levels

Strontium mineralization of shark vertebrae

Determining the age of sharks using vertebral banding is a vital component of management, but the causes of banding are not fully understood. Traditional shark ageing is based on fish otolith ageing methods where growth bands are assumed to result from varied seasonal calcification rates. Here we investigate these assumptions by mapping elemental distribution within the growth bands of vertebrae from six species of sharks representing four different taxonomic orders using scanning x-ray fluorescence microscopy. Traditional visual growth bands, determined with light microscopy, were more closely correlated to strontium than calcium in all species tested. Elemental distributions suggest that vertebral strontium bands may be related to environmental variations in salinity. These results highlight the requirement for a better understanding of shark movements, and their influence on vertebral development, if confidence in age estimates is to be improved. Analysis of shark vertebrae using similar strontium-focused elemental techniques, once validated for a given species, may allow more successful estimations of age on individuals with few or no visible vertebral bands. © 2016 Macmillan Publishers Limite

The Economic Impact of Early Life Environmental Tobacco Smoke Exposure: Early Intervention for Developmental Delay

BACKGROUND AND OBJECTIVES: Early-life exposure to environmental tobacco smoke (ETS) can result in developmental delay as well as childhood asthma and increased risk of cancer. The high cost of childhood asthma related to ETS exposure has been widely recognized; however, the economic impact of ETS-related developmental delay has been less well understood. METHODS AND RESULTS:The Columbia Center for Children\u27s Environmental Health (CCCEH) has reported adverse effects of prenatal ETS exposure on child development in a cohort of minority women and children in New York City (odds ratio of developmental delay = 2.36; 95% confidence interval 1.22-4.58). Using the environmentally attributable fraction (EAF) approach, we estimated the annual cost of one aspect of ETS-related developmental delay: Early Intervention Services. The estimated cost of these services per year due to ETS exposure is \u3e Dollars 50 million per year for New York City Medicaid births and Dollars 99 million per year for all New York City births. CONCLUSION:The high annual cost of just one aspect of developmental delay due to prenatal exposure to ETS provides further impetus for increased prevention efforts such as educational programs to promote smoke-free homes, additional cigarette taxes, and subsidizing of smoking cessation programs

Movement variability in stroke patients and controls performing two upper limb functional tasks: a new assessment methodology

Background: In the evaluation of upper limb impairment post stroke there remains a gap between detailed kinematic analyses with expensive motion capturing systems and common clinical assessment tests. In particular, although many clinical tests evaluate the performance of functional tasks, metrics to characterise upper limb kinematics are generally not applicable to such tasks and very limited in scope. This paper reports on a novel, user-friendly methodology that allows for the assessment of both signal magnitude and timing variability in upper limb movement trajectories during functional task performance. In order to demonstrate the technique, we report on a study in which the variability in timing and signal magnitude of data collected during the performance of two functional tasks is compared between a group of subjects with stroke and a group of individually matched control subjects. Methods: We employ dynamic time warping for curve registration to quantify two aspects of movement variability: 1) variability of the timing of the accelerometer signals' characteristics and 2) variability of the signals' magnitude. Six stroke patients and six matched controls performed several trials of a unilateral ('drinking') and a bilateral ('moving a plate') functional task on two different days, approximately 1 month apart. Group differences for the two variability metrics were investigated on both days. Results: For 'drinking from a glass' significant group differences were obtained on both days for the timing variability of the acceleration signals' characteristics (p = 0.002 and p = 0.008 for test and retest, respectively); all stroke patients showed increased signal timing variability as compared to their corresponding control subject. 'Moving a plate' provided less distinct group differences. Conclusion: This initial application establishes that movement variability metrics, as determined by our methodology, appear different in stroke patients as compared to matched controls during unilateral task performance ('drinking'). Use of a user-friendly, inexpensive accelerometer makes this methodology feasible for routine clinical evaluations. We are encouraged to perform larger studies to further investigate the metrics' usefulness when quantifying levels of impairment

Testing the gaugino AMSB model at the Tevatron via slepton pair production

Gaugino AMSB models-- wherein scalar and trilinear soft SUSY breaking terms are suppressed at the GUT scale while gaugino masses adopt the AMSB form-- yield a characteristic SUSY particle mass spectrum with light sleptons along with a nearly degenerate wino-like lightest neutralino and quasi-stable chargino. The left- sleptons and sneutrinos can be pair produced at sufficiently high rates to yield observable signals at the Fermilab Tevatron. We calculate the rate for isolated single and dilepton plus missing energy signals, along with the presence of one or two highly ionizing chargino tracks. We find that Tevatron experiments should be able to probe gravitino masses into the ~55 TeV range for inoAMSB models, which corresponds to a reach in gluino mass of over 1100 GeV.Comment: 14 pages including 6 .eps figure

Expression Levels of a Kinesin-13 Microtubule Depolymerase Modulates the Effectiveness of Anti-Microtubule Agents

Chemotherapeutic drugs often target the microtubule cytoskeleton as a means to disrupt cancer cell mitosis and proliferation. Anti-microtubule drugs inhibit microtubule dynamics, thereby triggering apoptosis when dividing cells activate the mitotic checkpoint. Microtubule dynamics are regulated by microtubule-associated proteins (MAPs); however, we lack a comprehensive understanding about how anti-microtubule agents functionally interact with MAPs. In this report, we test the hypothesis that the cellular levels of microtubule depolymerases, in this case kinesin-13 s, modulate the effectiveness of the microtubule disrupting drug colchicine.We used a combination of RNA interference (RNAi), high-throughput microscopy, and time-lapse video microscopy in Drosophila S2 cells to identify a specific MAP, kinesin-like protein 10A (KLP10A), that contributes to the efficacy of the anti-microtubule drug colchicine. KLP10A is an essential microtubule depolymerase throughout the cell cycle. We find that depletion of KLP10A in S2 cells confers resistance to colchicine-induced microtubule depolymerization to a much greater extent than depletion of several other destabilizing MAPs. Using image-based assays, we determined that control cells retained 58% (+/-2%SEM) of microtubule polymer when after treatment with 2 microM colchicine for 1 hour, while cells depleted of KLP10A by RNAi retained 74% (+/-1%SEM). Likewise, overexpression of KLP10A-GFP results in increased susceptibility to microtubule depolymerization by colchicine.Our results demonstrate that the efficacy of microtubule destabilization by a pharmacological agent is dependent upon the cellular expression of a microtubule depolymerase. These findings suggest that expression levels of Kif2A, the human kinesin-13 family member, may be an attractive biomarker to assess the effectiveness of anti-microtubule chemotherapies. Knowledge of how MAP expression levels affect the action of anti-microtubule drugs may prove useful for evaluating possible modes of cancer treatment

Supersymmetric Monojets at the Large Hadron Collider

Supersymmetric monojets may be produced at the Large Hadron Collider by the process qg -> squark neutralino_1 -> q neutralino_1 neutralino_1, leading to a jet recoiling against missing transverse momentum. We discuss the feasibility and utility of the supersymmetric monojet signal. In particular, we examine the possible precision with which one can ascertain the neutralino_1-squark-quark coupling via the rate for monojet events. Such a coupling contains information on the composition of the neutralino_1 and helps bound dark matter direct detection cross-sections and the dark matter relic density of the neutralino_1. It also provides a check of the supersymmetric relation between gauge couplings and gaugino-quark-squark couplings.Comment: 46 pages, 10 figures. The appendix has been rewritten to correct an error that appears in all previous versions of the appendix. This error has no effect on the results in the main body of the pape

The association between alcohol exposure and self-reported health status: The effect of separating former and current drinkers

Aims: To investigate the direction and degree of potential bias introduced to analyses of drinking and health status which exclude former drinkers from exposure groups. Design: Pooled analysis of 14 waves (1997–2010) of the U.S. National Health Interview Survey (NHIS). Setting: General population-based study. Participants: 404,462 participants, from 14 waves of the NHIS, who had known self-reported health status and alcohol consumption status. Measurements: Self-reported health status was used as the indicator of health. Two approaches were used to classify alcohol consumption: (i) separation of former drinkers and current drinkers, and (ii) combined former and current drinkers. The prevalence of fair/ poor health by alcohol use, gender and age with 95% confidence intervals was estimated. The difference in prevalence of fair/ poor health status for lifetime abstainers, former drinkers, current drinkers and drinkers (former drinkers and current drinkers combined) were compared using Poisson regression with robust estimations of variance. Findings: Excluding former drinkers from drinker groups exaggerates the difference in health status between abstainers and drinkers, especially for males. Conclusions: In cohort study analyses, former drinkers should be assigned to a drinking category based on their previous alcohol consumption patterns and not treated as a discrete exposure group

First Neutrino Observations from the Sudbury Neutrino Observatory

The first neutrino observations from the Sudbury Neutrino Observatory are presented from preliminary analyses. Based on energy, direction and location, the data in the region of interest appear to be dominated by 8B solar neutrinos, detected by the charged current reaction on deuterium and elastic scattering from electrons, with very little background. Measurements of radioactive backgrounds indicate that the measurement of all active neutrino types via the neutral current reaction on deuterium will be possible with small systematic uncertainties. Quantitative results for the fluxes observed with these reactions will be provided when further calibrations have been completed.Comment: Latex, 7 pages, 10 figures, Invited paper at Neutrino 2000 Conference, Sudbury, Canada, June 16-21, 2000 to be published in the Proceeding

Simultaneously Hermaphroditic Shrimp Use Lipophilic Cuticular Hydrocarbons as Contact Sex Pheromones

Successful mating is essentially a consequence of making the right choices at the correct time. Animals use specific strategies to gain information about a potential mate, which is then applied to decision-making processes. Amongst the many informative signals, odor cues such as sex pheromones play important ecological roles in coordinating mating behavior, enabling mate and kin recognition, qualifying mate choice, and preventing gene exchange among individuals from different populations and species. Despite overwhelming behavioral evidence, the chemical identity of most cues used in aquatic organisms remains unknown and their impact and omnipresence have not been fully recognized. In many crustaceans, including lobsters and shrimps, reproduction happens through a cascade of events ranging from initial attraction to formation of a mating pair eventually leading to mating. We examined the hypothesis that contact pheromones on the female body surface of the hermaphroditic shrimp Lysmata boggessi are of lipophilic nature, and resemble insect cuticular hydrocarbon contact cues. Via chemical analyses and behavioural assays, we show that newly molted euhermaphrodite-phase shrimp contain a bouquet of odor compounds. Of these, (Z)-9-octadecenamide is the key odor with hexadecanamide and methyl linoleate enhancing the bioactivity of the pheromone blend. Our results show that in aquatic systems lipophilic, cuticular hydrocarbon contact sex pheromones exist; this raises questions on how hydrocarbon contact signals evolved and how widespread these are in the marine environment