2,159 research outputs found

    Current advances of nitric oxide in cancer and anticancer therapeutics

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    Nitric oxide (NO) is a short-lived, ubiquitous signaling molecule that affects numerous critical functions in the body. There are markedly conflicting findings in the literature regarding the bimodal effects of NO in carcinogenesis and tumor progression, which has important consequences for treatment. Several preclinical and clinical studies have suggested that both pro- and antitumorigenic effects of NO depend on multiple aspects, including, but not limited to, tissue of generation, the level of production, the oxidative/reductive (redox) environment in which this radical is generated, the presence or absence of NO transduction elements, and the tumor microenvironment. Generally, there are four major categories of NO-based anticancer therapies: NO donors, phosphodiesterase inhibitors (PDE-i), soluble guanylyl cyclase (sGC) activators, and immunomodulators. Of these, NO donors are well studied, well characterized, and also the most promising. In this study, we review the current knowledge in this area, with an emphasis placed on the role of NO as an anticancer therapy and dysregulated molecular interactions during the evolution of cancer, highlighting the strategies that may aid in the targeting of cancer

    Competition-induced stress does not explain deceptive alarm calling in tufted capuchin monkeys

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    Tactical deception has long attracted interest because it is often assumed to entail complex cognitive mechanisms. However, systematic evidence of tactical deception is rare and no study has attempted to determine whether such behaviours may be underpinned by relatively simple mechanisms. This study examined whether deceptive alarm calling among wild tufted capuchin monkeys, Cebus apella nigritus, feeding on contestable food resources can be potentially explained by a physiological mechanism, namely increased activation in the adrenocortex and the resulting production of glucocorticoids (GCs; ‘stress hormones’). This was tested experimentally in Iguazu? National Park, Argentina, by manipulating the potential for contest competition over food and noninvasively monitoring GC production through analysis of faecal hormone metabolites. If deceptive false alarms are indeed associated with adreno- cortical activity, it was predicted that the patterns of production of these calls would match the patterns of GC output, generally being higher in callers than noncallers in cases in which food is most contestable, and specifically being higher in callers on those occasions when a deceptive false alarm was produced. This hypothesis was not supported, as (1) GC output was significantly lower in association with the experimental introduction of contestable resources than in natural contexts wherein the potential for contest is lower, (2) within experimental contexts, there was a nonsignificant tendency for noncallers to show higher GC output than callers when food was most contestable, and (3) individuals did not show higher GC levels in cases in which they produced deceptive alarms relative to cases in which they did not. A learned association between the production of alarms and increased access to food may be the most likely cognitive explanation for this case of tactical deception, although unexplored physiological mechanisms also remain possible

    Behind the confession: Relating false confession, interrogative compliance, personality traits, and psychopathy

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    The present study further supports the established notion that personality traits contribute to the phenomenon of false confessions and compliance in an interrogative setting. Furthermore, the study provides an investigation into the more recent interest in the potential effect of psychopathic traits in this context. A sample of university students (N = 607) completed questionnaires measuring psychopathic traits, interrogative compliance, and the big five personality factors. Of these, only 4.9% (n=30) claimed to have falsely confessed to an academic or criminal offense, with no participant taking the blame for both types of offense. Across measures the big five personality traits were the strongest predictors of compliance. The five personality traits accounted for 17.9 % of the total variance in compliance, with neuroticism being the strongest predictor, followed by openness and agreeableness. Psychopathy accounted for 3.3% of variance, with the lifestyle facet being the only significant predictor. After controlling for the big five personality factors, psychopathy only accounted for a small percentage of interrogative compliance, indicating that interrogators should take into account a person’s personality traits during the interrogation.N/

    Alcohol Binge Drinking:Negative and Positive Valence System Abnormalities

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    This work was supported by an award from Dundee University Medical School (ref. AT27) to ST and JDS. Spectroscopy was supported by an unrestricted ‘Work in Progress’ agreement with Siemens.Background: Three million deaths occur each year due to alcohol misuse. Translational studies are crucial to translate preclinical findings to patients. Preclinical studies have highlighted abnormalities in specific brain systems with these forming the basis of allostasis theory. However, few studies have tested predictions in humans using neuroimaging. Methods: Here we used a Research Domain Criteria (RDoC) approach to testallostasis theory predictions of blunted positive valence system (PVS) and abnormally increased negative valence system (NVS) responses in fifty-seven binge alcohol drinking subjects and healthy controls who completed an instrumental task during fMRI. Results: As hypothesised, binge alcohol drinkers showed abnormally increased activity in NVS-linked regions such as the hippocampus and dorsal cingulate, and abnormally blunted activity in PVS-linked regions such as the striatum, compared to controls. Higher measures of problematic alcohol use were associated with more abnormal brain activity, only for binge drinkers who had been most recently drinking. Conclusions: These results support allostasis theory predictions of abnormally increased NVS and blunted PVS responses in binge alcohol drinkers. Further similar translational neuroimaging studies are indicated, particularly focusing on the NVSPostprintPeer reviewe

    Modeling spatiotemporal variability of the bioclimate envelope of Homarus americanus in the coastal waters of Maine and New Hampshire

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    A bioclimate envelope model was developed to evaluate the potential impacts of climate variability on American lobster (Homarus americanus). Bioclimate envelopes were defined by season-, sex-, and stage- specific Habitat Suitability Indices (HSI) based on (1) bottom temperature, (2) bottom salinity, and (3) depth. The species’ association to each of these three environmental attributes was expressed using Suitability Indices (SIs) calibrated by standardized lobster abundance derived from 14 years of fishery independent survey. A regional ocean model (Finite-Volume Community Ocean Model) was integrated with the HSI to hindcast spatiotemporal variability of bioclimate envelopes for American lobster in coastal waters of Maine and New Hampshire from 1978 to 2013. The model predictions indicated higher habitat suitability in inshore waters for both adult and juvenile lobsters. A statistically significant increasing trend in habitat suitability was observed for both sexes and stages (juvenile and adult) during the spring (April–June), while no significant trend in habitat suitability was observed in the fall (September–November). This study provides a modeling framework to reconstruct climatically suitable lobster ranges that can be used to formulate climate-based hypotheses for future studies of this species

    Risky Business: Rhesus Monkeys Exhibit Persistent Preferences for Risky Options

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    Rhesus monkeys have been shown to prefer risky over safe options in experiential decision-making tasks. These findings might be due, however, to specific contextual factors, such as small amounts of fluid reward and minimal costs for risk-taking. To better understand the factors affecting decision-making under risk in rhesus monkeys, we tested multiple factors designed to increase the stakes including larger reward amounts, distinct food items rather than fluid reward, a smaller number of trials per session, and risky options with greater variation that also included non-rewarded outcomes. We found a consistent preference for risky options, except when the expected value of the safe option was greater than the risky option. Thus, with equivalent mean utilities between the safe and risky options, rhesus monkeys appear to have a robust preference for the risky options in a broad range of circumstances, akin to the preferences found in human children and some adults in similar tasks. One account for this result is that monkeys make their choices based on the salience of the largest payoff, without integrating likelihood and value across trials. A related idea is that they fail to override an impulsive tendency to select the option with the potential to obtain the highest possible outcome. Our results rule out strict versions of both accounts and contribute to an understanding of the diversity of risky decision-making among primates

    Victim awareness : re-examining a probation fundamental

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    ‘Ensuring offenders' awareness of the effects of crime on the victims of crime and the public’ is one of five stated aims of the National Probation Service of England and Wales and specifically undertaking victim awareness work is an expectation of the service’s work. The nature and putative value of such work appears to be rarely questioned however. It is argued that ‘victim awareness’ is a confused concept in terms of its rationale, definition, and empirical basis as a criminogenic need. These issues are evaluated and the practice implications discussed. A possible model of victim awareness work is described

    Limits on Anomalous Triple Gauge Couplings in ppbar Collisions at sqrt{s}=1.96 TeV

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    We present a search for anomalous triple gauge couplings (ATGC) in WW and WZ boson production. The boson pairs are produced in ppbar collisions at sqrt{s}=1.96 TeV, and the data sample corresponds to 350 pb-1 of integrated luminosity collected with the CDF II detector at the Fermilab Tevatron. In this search one W decays to leptons, and the other boson (W or Z) decays hadronically. Combining with a previously published CDF measurement of Wgamma boson production yields ATGC limits of -0.18 < lambda < 0.17 and -0.46 < Delta kappa < 0.39 at the 95% confidence level, using a cut-off scale Lambda=1.5 TeV.Comment: 7 pages, 3 figures. Submitted to Phys. Rev.

    Search for Third Generation Vector Leptoquarks in p anti-p Collisions at sqrt(s) = 1.96 TeV

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    We describe a search for a third generation vector leptoquark (VLQ3) that decays to a b quark and tau lepton using the CDF II detector and 322 pb^(-1) of integrated luminosity from the Fermilab Tevatron. Vector leptoquarks have been proposed in many extensions of the standard model (SM). Observing a number of events in agreement with SM expectations, assuming Yang-Mills (minimal) couplings, we obtain the most stringent upper limit on the VLQ3 pair production cross section of 344 fb (493 fb) and lower limit on the VLQ3 mass of 317 GeV/c^2 (251 GeV/c^2) at 95% C.L.Comment: 7 pages, 2 figures, submitted to PR
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