Prior Mating Experience Modulates the Dispersal of Drosophila in Males More Than in Females

Cues from both an animal’s internal physiological state and its local environment may influence its decision to disperse. However, identifying and quantifying the causative factors underlying the initiation of dispersal is difficult in uncontrolled natural settings. In this study, we automatically monitored the movement of fruit flies and examined the influence of food availability, sex, and reproductive status on their dispersal between laboratory environments. In general, flies with mating experience behave as if they are hungrier than virgin flies, leaving at a greater rate when food is unavailable and staying longer when it is available. Males dispersed at a higher rate and were more active than females when food was unavailable, but tended to stay longer in environments containing food than did females. We found no significant relationship between weight and activity, suggesting the behavioral differences between males and females are caused by an intrinsic factor relating to the sex of a fly and not simply its body size. Finally, we observed a significant difference between the dispersal of the natural isolate used throughout this study and the widely-used laboratory strain, Canton-S, and show that the difference cannot be explained by allelic differences in the foraging gene

Reduced Myelin Basic Protein and Actin-Related Gene Expression in Visual Cortex in Schizophrenia

Most brain gene expression studies of schizophrenia have been conducted in the frontal cortex or hippocampus. The extent to which alterations occur in other cortical regions is not well established. We investigated primary visual cortex (Brodmann area 17) from the Stanley Neuropathology Consortium collection of tissue from 60 subjects with schizophrenia, bipolar disorder, major depression, or controls. We first carried out a preliminary array screen of pooled RNA, and then used RT-PCR to quantify five mRNAs which the array identified as differentially expressed in schizophrenia (myelin basic protein [MBP], myelin-oligodendrocyte glycoprotein [MOG], β-actin [ACTB], thymosin β-10 [TB10], and superior cervical ganglion-10 [SCG10]). Reduced mRNA levels were confirmed by RT-PCR for MBP, ACTB and TB10. The MBP reduction was limited to transcripts containing exon 2. ACTB and TB10 mRNAs were also decreased in bipolar disorder. None of the transcripts were altered in subjects with major depression. Reduced MBP mRNA in schizophrenia replicates findings in other brain regions and is consistent with oligodendrocyte involvement in the disorder. The decreases in expression of ACTB, and the actin-binding protein gene TB10, suggest changes in cytoskeletal organisation. The findings confirm that the primary visual cortex shows molecular alterations in schizophrenia and extend the evidence for a widespread, rather than focal, cortical pathophysiology

Sensory Integration Regulating Male Courtship Behavior in Drosophila

The courtship behavior of Drosophila melanogaster serves as an excellent model system to study how complex innate behaviors are controlled by the nervous system. To understand how the underlying neural network controls this behavior, it is not sufficient to unravel its architecture, but also crucial to decipher its logic. By systematic analysis of how variations in sensory inputs alter the courtship behavior of a naïve male in the single-choice courtship paradigm, we derive a model describing the logic of the network that integrates the various sensory stimuli and elicits this complex innate behavior. This approach and the model derived from it distinguish (i) between initiation and maintenance of courtship, (ii) between courtship in daylight and in the dark, where the male uses a scanning strategy to retrieve the decamping female, and (iii) between courtship towards receptive virgin females and mature males. The last distinction demonstrates that sexual orientation of the courting male, in the absence of discriminatory visual cues, depends on the integration of gustatory and behavioral feedback inputs, but not on olfactory signals from the courted animal. The model will complement studies on the connectivity and intrinsic properties of the neurons forming the circuitry that regulates male courtship behavior

Concomitant use of tamoxifen with radiotherapy enhances subcutaneous breast fibrosis in hypersensitive patients

Concomitant use of adjuvant tamoxifen (TAM) and radiation therapy (RT) is not widely accepted. We aim to assess whether this treatment is associated with an increased risk of developing subcutaneous fibrosis after conservative or radical surgery in breast cancer patients. We analysed 147 women with breast cancer treated with adjuvant RT, and who were included in the KFS 00539-9-1997/SKL 00778-2-1999 prospective study aimed at evaluating the predictive value of CD4 and CD8 T-lymphocyte apoptosis for the development of radiation-induced late effects. TAM (20 mg day(-1)) with concomitant RT was prescribed in 90 hormone receptor-positive patients. There was a statistically significant difference in terms of complication-relapse-free survival (CRFS) rates at 3 years, 48% (95% CI 37.2-57.6%) vs 66% (95% CI 49.9-78.6%) and complication-free survival (CFS) rates at 2 years, 51% (95% CI 40-61%) vs 80% (95% CI 67-89%) in the TAM and no-TAM groups, respectively. In each of these groups, the CRFS rates were significantly lower for patients with low levels of CD8 radiation-induced apoptosis, 20% (95% CI 10-31.9%), 66% (95% CI 51.1-77.6%), and 79% (95% CI 55-90.9%) for CD8 </=16, 16-24, and >24%, respectively. Similar results were observed for the CFS rates. The concomitant use of TAM with RT is significantly associated with an increased incidence of grade 2 or greater subcutaneous fibrosis; therefore, caution is needed for radiosensitive patients

Strategies to Target Tumor Immunosuppression

The tumor microenvironment is currently in the spotlight of cancer immunology research as a key factor impacting tumor development and progression. While antigen-specific immune responses play a crucial role in tumor rejection, the tumor hampers these immune responses by creating an immunosuppressive microenvironment. Recently, major progress has been achieved in the field of cancer immunotherapy, and several groundbreaking clinical trials demonstrated the potency of such therapeutic interventions in patients. Yet, the responses greatly vary among individuals. This calls for the rational design of more efficacious cancer immunotherapeutic interventions that take into consideration the “immune signature” of the tumor. Multimodality treatment regimens that aim to enhance intratumoral homing and activation of antigen-specific immune effector cells, while simultaneously targeting tumor immunosuppression, are pivotal for potent antitumor immunity

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants.

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling