Developmental Exposure of Rats to Chlorpyrifos Leads to Behavioral Alterations in Adulthood, Involving Serotonergic Mechanisms and Resembling Animal Models of Depression

Developmental exposure to chlorpyrifos (CPF) causes persistent changes in serotonergic (5HT) systems. We administered 1 mg/kg/day CPF to rats on postnatal days 1–4, a regimen below the threshold for systemic toxicity. When tested in adulthood, CPF-exposed animals showed abnormalities in behavioral tests that involve 5HT mechanisms. In the elevated plus maze, males treated with CPF spent more time in the open arms, an effect seen with 5HT deficiencies in animal models of depression. Similarly, in an anhedonia test, the CPF-exposed group showed a decreased preference for chocolate milk versus water. Developmental CPF exposure also has lasting effects on cognitive function. We replicated our earlier finding that developmental CPF exposure ablates the normal sex differences in 16-arm radial maze learning and memory: during acquisition training, control male rats typically perform more accurately than do control females, but CPF treatment eliminated this normal sex difference. Females exposed to CPF showed a reduction in working and reference memory errors down to the rate of control males. Conversely, CPF-exposed males exhibited an increase in working and reference memory errors. After radial-arm acquisition training, we assessed the role of 5HT by challenging the animals with the 5HT(2) receptor antagonist ketanserin. Ketanserin did not affect performance in controls but elicited dose-dependent increases in working and reference memory errors in the CPF group, indicating an abnormal dependence on 5HT systems. Our results indicate that neonatal CPF exposures, classically thought to be subtoxic, produce lasting changes in 5HT-related behaviors that resemble animal models of depression

Organophosphate Insecticides Target the Serotonergic System in Developing Rat Brain Regions: Disparate Effects of Diazinon and Parathion at Doses Spanning the Threshold for Cholinesterase Inhibition

BACKGROUND: In the developing brain, serotonin (5HT) systems are among the most sensitive to disruption by organophosphates. OBJECTIVES: We exposed neonatal rats to daily doses of diazinon or parathion on postnatal days (PND)1–4 and evaluated 5HT receptors and the 5HT transporter in brainstem and forebrain on PND5, focusing on doses of each agent below the maximum tolerated dose and spanning the threshold for cholinesterase inhibition: 0.5, 1, or 2 mg/kg for diazinon, and 0.02, 0.05, and 0.1 mg/kg for parathion. RESULTS: Diazinon evoked up-regulation of 5HT(1A) and 5HT(2) receptor expression even at doses devoid of effects on cholinesterase activity, a pattern similar to that seen earlier for another organophosphate, chlorpyrifos. In contrast, parathion decreased 5HT(1A) receptors, again at doses below those required for effects on cholinesterase. The two agents also differed in their effects on the 5HT transporter. Diazinon evoked a decrease in the brainstem and an increase in the forebrain, again similar to that seen for chlorpyrifos; this pattern is typical of damage of nerve terminals and reactive sprouting. Parathion had smaller, nonsignificant effects. CONCLUSIONS: Our results buttress the idea that, in the developing brain, the various organophosphates target specific neurotransmitter systems differently from each other and without the requirement for cholinesterase inhibition, their supposed common mechanism of action

Improved Heterosis Prediction by Combining Information on DNA- and Metabolic Markers

Background: Hybrids represent a cornerstone in the success story of breeding programs. The fundamental principle underlying this success is the phenomenon of hybrid vigour, or heterosis. It describes an advantage of the offspring as compared to the two parental lines with respect to parameters such as growth and resistance against abiotic or biotic stress. Dominance, overdominance or epistasis based models are commonly used explanations. Conclusion/Significance: The heterosis level is clearly a function of the combination of the parents used for offspring production. This results in a major challenge for plant breeders, as usually several thousand combinations of parents have to be tested for identifying the best combinations. Thus, any approach to reliably predict heterosis levels based on properties of the parental lines would be highly beneficial for plant breeding. Methodology/Principal Findings: Recently, genetic data have been used to predict heterosis. Here we show that a combination of parental genetic and metabolic markers, identified via feature selection and minimum-description-length based regression methods, significantly improves the prediction of biomass heterosis in resulting offspring. These findings will help furthering our understanding of the molecular basis of heterosis, revealing, for instance, the presence of nonlinear genotype-phenotype relationships. In addition, we describe a possible approach for accelerated selection in plant breeding

The Putative Liquid-Liquid Transition is a Liquid-Solid Transition in Atomistic Models of Water

We use numerical simulation to examine the possibility of a reversible liquid-liquid transition in supercooled water and related systems. In particular, for two atomistic models of water, we have computed free energies as functions of multiple order parameters, where one is density and another distinguishes crystal from liquid. For a range of temperatures and pressures, separate free energy basins for liquid and crystal are found, conditions of phase coexistence between these phases are demonstrated, and time scales for equilibration are determined. We find that at no range of temperatures and pressures is there more than a single liquid basin, even at conditions where amorphous behavior is unstable with respect to the crystal. We find a similar result for a related model of silicon. This result excludes the possibility of the proposed liquid-liquid critical point for the models we have studied. Further, we argue that behaviors others have attributed to a liquid-liquid transition in water and related systems are in fact reflections of transitions between liquid and crystal

Efficacy and acceptability of selective serotonin reuptake inhibitors for the treatment of depression in Parkinson's disease: a systematic review and meta-analysis of randomized controlled trials

<p>Abstract</p> <p>Background</p> <p>Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants for the treatment of depression in patients with Parkinson's Disease (PD) but data on their efficacy are controversial.</p> <p>Methods</p> <p>We conducted a systematic review and meta-analysis of randomized controlled trials to investigate the efficacy and acceptability of SSRIs in the treatment of depression in PD.</p> <p>Results</p> <p>Ten studies were included. In the comparison between SSRIs and Placebo (n = 6 studies), the combined risk ratio (random effects) was 1.08 (95% confidence interval: 0.77 - 1.55, p = 0.67). In the comparison between SSRIs and Tricyclic Antidepressants (TCAs) (n = 3 studies) the combined risk ratio was 0.75 (0.39 - 1.42, p = 0.37). An acceptability analysis showed that SSRIs were generally well tolerated.</p> <p>Conclusions</p> <p>These results suggest that there is insufficient evidence to reject the null hypothesis of no differences in efficacy between SSRIs and placebo in the treatment of depression in PD. Due to the limited number of studies and the small sample sizes a type II error (false negative) cannot be excluded. The comparison between SSRIs and TCAs is based on only three studies and further trials with more pragmatic design are needed.</p

Search for a Technicolor omega_T Particle in Events with a Photon and a b-quark Jet at CDF

If the Technicolor omega_T particle exists, a likely decay mode is omega_T -> gamma pi_T, followed by pi_T -> bb-bar, yielding the signature gamma bb-bar. We have searched 85 pb^-1 of data collected by the CDF experiment at the Fermilab Tevatron for events with a photon and two jets, where one of the jets must contain a secondary vertex implying the presence of a b quark. We find no excess of events above standard model expectations. We express the result of an exclusion region in the M_omega_T - M_pi_T mass plane.Comment: 14 pages, 2 figures. Available from the CDF server (PS with figs): http://www-cdf.fnal.gov/physics/pub98/cdf4674_omega_t_prl_4.ps FERMILAB-PUB-98/321-