Contribution of the X chromosome to a marked reduction in lifespan in interspecies female hybrids of Drosophila simulans and D. mauritiana.

When two species come into contact and interbreed, the production of unfit hybrids can limit or prevent gene flow between the populations, thus maintaining each species' separate identity. The genetic basis of this hybrid dysfunction has recently begun to be elucidated, particularly for hybrid sterility and inviability. Although these dysfunctions can certainly act as a barrier to gene flow, other post-zygotic barriers may also play an important role in isolating species from one another. This study examines the genetic basis of the more subtle mechanism of species isolation via a marked reduction in lifespan of interspecies hybrid offspring. We found that females with homozygous X chromosomes in an otherwise interspecies hybrid background displayed a significant reduction in lifespan; this effect is not due to genetic background and appears to arise from complex genetic interactions. Separately, there is an additional severe reduction in lifespan for attached-X females when they have mated with males of either parental species, which is partly due to interspecific genetic interactions, but primarily due to a female's increased sensitivity to mating when bearing a Y chromosome or the attached-X chromosome construct.

E-Health intervention for subthreshold depression: Reach and two-year effects of a randomized controlled trial.

BACKGROUND: There is evidence for e-Health interventions for full-blown depression. Little is known regarding commonly untreated subthreshold depression in primary care. This randomized controlled multi-centre trial assessed reach and two-year-effects of a proactive e-Health intervention (ActiLife) for patients with subthreshold depression. METHODS: Primary care and hospital patients were screened for subthreshold depression. Over 6 months, ActiLife participants received three individualized feedback letters and weekly messages promoting self-help strategies against depression, e.g., dealing with unhelpful thoughts or behavioural activation. The primary outcome depressive symptom severity (Patient Health Questionnaire;PHQ-8) and secondary outcomes were assessed 6, 12 and 24 months. RESULTS: Of those invited, n = 618(49.2 %) agreed to participate. Of them, 456 completed the baseline interview and were randomized to ActiLife (n = 227) or assessment only (n = 226). Generalised estimation equation analyses adjusting for site, setting and baseline depression revealed that depressive symptom severity declined over time, with no significant group differences at 6 (mean difference = 0.47 points; d = 0.12) and 24 months (mean difference = -0.05 points; d = -0.01). Potential adverse effects were observed at 12 months, with higher depressive symptom severity for ActiLife than control participants (mean difference = 1.33 points; d = 0.35). No significant differences in rates of reliable deterioration or reliable improvement of depressive symptoms were observed. ActiLife increased applied self-help strategies at 6 (mean difference = 0.32; d = 0.27) and 24 months (mean difference = 0.22; d = 0.19), but not at 12 months (mean difference = 0.18; d = 0.15). LIMITATIONS: Self-report measures and lack of information on patients' mental health treatment. DISCUSSION: ActiLife yielded satisfactory reach and increased the use of self-help strategies. Data were inconclusive in terms of depressive symptom changes.

Fine-scale genetic analysis of species-specific female preference in Drosophila simulans.

Behavioural differences are thought to be the first components to contribute to species isolation, yet the precise genetic basis of behavioural isolation remains poorly understood. Here, we used a combination of behaviour assays and genetic mapping to provide the first refined map locating candidate genes for interspecific female preference isolating Drosophila simulans from D. melanogaster. First, we tested whether two genes identified as affecting D. melanogaster female intraspecific mate choice also affect interspecific mate choice; neither of these genes was found to contribute to species-specific female preference. Next, we used deficiency mapping to locate genes on the right arm of the third chromosome for species-specific female preference and identified five small significant regions that contain candidate genes contributing to behavioural isolation. All five regions were located in areas that would have low interspecific recombination, which mirrors the results of other behavioural isolation studies that used quantitative trait locus (QTL) mapping, but without the potential concern of bias towards regions of low recombination that QTL mapping may have. As this model system may be refined to the individual gene level using the same methodology, this initial map we provide may potentially serve as a ready template for the identification and characterization of the first behavioural isolation genes.

Role of poly(ADP-ribose) polymerase activity in imatinib mesylate-induced cell death.

Imatinib targets Bcr-Abl, the causative event of chronic myelogenous leukemia (CML), and addresses leukemic cells to growth arrest and cell death. The exact mechanisms responsible for imatinib-induced cell death are still unclear. We investigated the role of poly(ADP-ribose) polymerase (PARP) activity in imatinib-induced cell death in Bcr-Abl-positive cells. Imatinib leads to a rapid increase of poly(ADP-ribosyl)ation (PAR) preceding loss of integrity of mitochondrial membrane and DNA fragmentation. The effect of imatinib on PAR can be mimicked by inhibition of phosphatidylinositol 3-kinase (PI3-K) implicating a central role of the PI3-K pathway in Bcr-Abl-mediated inhibition of PAR. Importantly, inhibition of PAR in imatinib-treated cells partially prevented cell death to an extent comparable to that observed after caspase inhibition. Simultaneous blockade of both caspases and PAR revealed additive cytoprotective effects indicating that both pathways function in parallel. In conclusion, our results suggest that in addition to the well-documented caspase-dependent pathway, imatinib also induces a PARP-mediated death process.

Electrochemical surface analysis with the scanning droplet cell.

A new electrochemical device, the scanning droplet cell, is presented. Small electrolyte droplets are positioned on the sample surface and enable a spatially resolved surface analysis or modification. The droplet is simply held by its surface tension and, therefore, no surface pretreatment is necessary. According to the conventional 3-electrode arrangement all common potentiostatic and galvanostatic techniques, e.g. impedance spectroscopy, cyclic voltammetry, or current transients of potentiostatic steps, are possible.