Oscillations and traveling waves of calcium: a simplified model

We construct a heuristic model of calcium oscillations in pancreatic acinar cells. The model is based on the two-state model of Sneyd et al. (Sneyd, J., A. LeBeau and D. Yule, 2000, Traveling waves of calcium in pancreatic acinar cells: model construction and bifurcation analysis, Physica D, in press) and is similar in spirit to the FitzHugh reduction of the Hodgkin-Huxley equations. The simpli¯ed model successfully reproduces the oscillatory behavior and wave behaviour of the more complex model. In particular, the simpli¯ed model provides an example of a simple, physiologically relevant model that has a T-point and an associated spiral branch of homoclinic orbits

Preinfection Risk Perceptions of Human Immunodeficiency Virus Positive Homosexual and Bisexual Men

In 2017, there were 4,949 persons diagnosed with human immunodeficiency virus (HIV), 116,944 persons living with HIV, and 2,044 acquired immunodeficiency syndrome (AIDS) cases in Florida. Of the 4,972 new HIV diagnoses in Florida, 60% were related to male-to-male sexual contact, 4% from intravenous drug use, 2% from male-to-male sexual contact and intravenous drug use, 33% from heterosexual sexual contact, and 1% from other sources. Guided by the health belief model (HBM), this qualitative study sought to understand the lived experiences of HIV positive adult men who have sex with men (MSM) living in Florida, regarding their preinfection perceptions of risk of contracting HIV. The HBM guided this study as it examined health-related decision making and has been used in previous HIV prevention studies. A purposive sample of 11 HIV positive, adult MSM, living in Florida, who were knowledgeable and willing to discuss their HIV perceptions and lived experiences, were interviewed. Data analysis procedures included coding and categorizing the data, validation of the codes, identification of patterns and themes, interpretation of the data, and member checks. Participants had a general knowledge of HIV, and 7 out of the 11 men recognized they were at risk for HIV due to engaging in unprotected sex and substance abuse practices. Seven participants reported having access to HIV prevention tools but that they did not access these tools. All participants reported receiving ongoing health care. Developing HIV prevention programs targeting those engaging in at risk behaviors has the potential to produce positive social change by increasing HIV prevention education, testing opportunities, and treatment options

The glycine transporter 1 inhibitor SSR504734 enhances working memory performance in a continuous delayed alternation task in C57BL/6 mice

Rationale: Inhibition of the glycine transporter 1 (GlyT1) activity increases extra-cellular glycine availability in the CNS. At glutamatergic synapses, increased binding to the glycine-B site located in the N-methyl-d-aspartate receptor (NMDAR) can enhance neurotransmission via NMDARs. Systemic treatment of 2-chloro-N-[(S)-phenyl [(2S)-piperidin-2-yl] methyl]-3-trifluoromethyl benzamide, monohydrochloride (SSR504734), a selective GlyT1 inhibitor, is effective against social recognition impairment induced by neonatal phencyclidine treatment and enhances pre-pulse inhibition in a mouse strain (DBA/2) with intrinsic sensorimotor gating deficiency, suggesting that SSR504734 may be an effective cognitive enhancer. Objective: The objective of the study was to examine if SSR504734 exhibits a promnesic effect on working memory function in wild-type C57BL/6 mice using an automatic continuous alternation task. Materials and methods: Hungry mice were trained to alternate their nose pokes between two food magazines across successive discrete trials in an operant chamber in order to obtain food reward. Correct choice on a given trial thus followed a non-matching or win-shift rule in relation to the preceding trial, with manipulation of the demand on memory retention, by varying the delay between successive trials. Results: Pre-treatment with SSR504734 (30mg/kg, i.p.) improved choice accuracy when the delay from the previous trial was extended to 12-16s. Furthermore, a dose-response analysis (3, 10, 30mg/kg) revealed a clear dose-dependent efficacy of the drug: 3mg/kg was without effect, whilst 10mg/kg led to an intermediate enhancement in performance. Conclusion: The present findings represent the first demonstration of the promnesic effects of SSR504734 under normal physiological conditions, lending further support to the suggestion of its potential as a cognitive enhance

Are DBA/2 mice associated with schizophrenia-like endophenotypes? A behavioural contrast with C57BL/6 mice

Rationale: Due to its intrinsic deficiency in prepulse inhibition (PPI), the inbred DBA/2 mouse strain has been considered as an animal model for evaluating antipsychotic drugs. However, the PPI impairment observed in DBA/2 mice relative to the common C57BL/6 strain is confounded by a concomitant reduction in baseline startle reactivity. In this study, we examined the robustness of the PPI deficit when this confound is fully taken into account. Materials and methods: Male DBA/2 and C57BL/6 mice were compared in a PPI experiment using multiple pulse stimulus intensities, allowing the possible matching of startle reactivity prior to examination of PPI. The known PPI-enhancing effect of the antipsychotic, clozapine, was then evaluated in half of the animals, whilst the other half was subjected to two additional schizophrenia-relevant behavioural tests: latent inhibition (LI) and locomotor reaction to the psychostimulants—amphetamine and phencyclidine. Results: PPI deficiency in DBA/2 relative to C57BL/6 mice was essentially independent of the strain difference in baseline startle reactivity. Yet, there was no evidence that DBA/2 mice were superior in detecting the PPI-facilitating effect of clozapine when startle difference was balanced. Compared with C57BL/6 mice, DBA/2 mice also showed impaired LI and a different temporal profile in their responses to amphetamine and phencyclidine. Conclusion: Relative to the C57BL/6 strain, DBA/2 mice displayed multiple behavioural traits relevant to schizophrenia psycho- and physiopathology, indicative of both dopaminergic and glutamatergic/N-methyl-d-aspartic acid receptor dysfunctions. Further examination of their underlying neurobiological differences is therefore warranted in order to enhance the power of this specific inter-strain comparison as a model of schizophreni

The postweaning social isolation in C57BL/6 mice: preferential vulnerability in the male sex

Introduction: Social deprivation during early life can severely affect mental health later in adulthood, leading to the development of behavioural traits associated with several major psychiatric disorders including schizophrenia. This has led to the application of social isolation in laboratory animals to model the impact of environmental factors on the aetiopathology of schizophrenia. However, controversy exists over the precise behavioural profile and the robustness of some of the reported effects of social isolation rearing. Materials and methods: Here, we evaluated the efficacy of postweaning social isolation to induce schizophrenia-related behavioural deficits in C57BL/6 mice of both sexes. Results: The effects of social isolation clearly differed between sexes: isolated male but not female mice exhibited multiple habituation deficits and enhanced locomotor reaction to amphetamine. Discussion: The preferential vulnerability in the male sex corresponds well with the earlier disease onset and poorer prognosis in male relative to female schizophrenic patients. In contrast, we observed no evidence for a disruption of sensorimotor gating in the prepulse inhibition paradigm despite the efficacy of social isolation to alter startle reactivity. With both success and failure in the induction of schizophrenia-related endophenotypes, the present study thus provides important characterizations and qualifications to the application of the social isolation model in mice. Conclusions: We conclude that social isolation in mice represents a valuable tool for the examination of candidate genes within the context of the "two-hit” hypothesis of the aetiological processes in schizophreni

The Moorean argument for the full moral status of those with profound intellectual disability: a rejoinder to Roberts

In a recent paper we argued that a Moorean strategy can be employed to justify our continued belief in the following proposition, even in the presence of philosophical views that entail it is false, without any philosophical argument against those views, and without any positive philosophical argument in its favour: H>A: Humans have an equal moral status that is higher than the moral status of non-human animals. The basic idea is that our confidence in the truth of this proposition is greater than our confidence in the propositions that make up those philosophical views that entail it is false, and that this is sufficient to justify rejecting those views and continue to believe H>A. Roberts has recently responded to our suggestion by claiming: (i) Although the Moorean strategy is valid, it is not powerful. (ii) A resort to the Moorean strategy reflects too great a pessimism about the accounts available that purport to justify H>A.2. In this short rejoinder we explain why we think that Roberts's two claims are false