To understand the T cell response to prostate cancer, we created transgenic mice that express a model antigen in a prostate-restricted pattern and crossed these animals to TRAMP mice that develop spontaneous prostate cancer. Adoptive transfer of prostate-specific CD4 T cells shows that, in the absence of prostate cancer, the prostate gland is mostly ignored. Tumorigenesis allows T cell recognition of the prostate gland--but this recognition is tolerogenic, resulting in abortive proliferation and ultimately in hyporesponsiveness at the systemic level. Androgen ablation (the most common treatment for metastatic prostate cancer) was able to mitigate this tolerance--allowing prostate-specific T cells to expand and develop effector function after vaccination. These results suggest that immunotherapy for prostate cancer may be most efficacious when administered after androgen ablation.

Hybrids of two Drosophila species show transposable element derepression and piRNA pathway malfunction, revealing adaptive evolution of piRNA pathway components.

No abstract

In internally fertilizing organisms, mating involves a series of highly coordinated molecular interactions between the sexes that occur within the female reproductive tract. In species where females mate multiply, traits involved in postcopulatory interactions are expected to evolve rapidly, potentially leading to postmatingprezygotic (PMPZ) reproductive isolation between diverging populations. Here, we investigate the postmating transcriptional response of the lower reproductive tract of Drosophila mojavensis females following copulation with either conspecific or heterospecific (Drosophila arizonae) males at three time points postmating. Relatively few genes (15 total) were differentially regulated in the female lower reproductive tract in response to conspecific mating. Heterospecifically mated females exhibited significant perturbations in the expression of the majority of these genes, and also down-regulated transcription of a number of others, including several involved in mitochondrial function. These striking regulatory differences indicate failed postcopulatory molecular interactions between the sexes consistent with the strong PMPZ isolation observed for this cross. We also report the transfer of male accessory-gland protein (Acp) transcripts from males to females during copulation, a finding with potentially broad implications for understanding postcopulatory molecular interactions between the sexes.n internally fertilizing organisms, the female reproductive tract serves as the arena for a series of highly coevolved molecular interactions between the sexes that are critical for successful reproduction (1, 2). Postcopulatory interactions should further increase in complexity in species in which females mate with more than one male, as intense sexual selection propels the rapid evolution of traits mediating female choice, male competitive ability, and sexual conflict (3,4). This, in turn, may facilitate divergence of such traits between populations following different coevolutionary trajectories, leading to postmating-prezygotic (PMPZ) reproductive isolation (5). Consistent with these expectations are the rapid evolution of morphological and molecular reproductive traits associated with postcopulatory processes (6) and the recognition that PMPZ barriers can serve as potent and rapidly evolving forms of reproductive isolation (5).The availability of genomic resources for an increasing number of species provides a platform for elucidating the molecular basis of postcopulatory molecular interactions between males and females. For example, recent genomic studies on Drosophila melanogaster (7-14), Anopheles gambiae (15), and Apis mellifera (16, 17) have begun to characterize the female postmating response by identifying changes in the transcriptome and/or proteome of mated females. In D. melanogaster, sperm or other specific components of the seminal fluid are known to induce some of these changes, which ultimately trigger physiological responses in females (18). Male accessory-gland proteins (Acps), in part...

Sex‐ratio (SR) males produce predominantly female progeny because most Y chromosome sperm are rendered nonfunctional. The resulting transmission advantage of XSR chromosomes should eventually cause population extinction unless segregation distortion is masked by suppressors or balanced by selection. By screening male stalk‐eyed flies, Cyrtodiopsis dalmanni, for brood sex ratio we found unique SR alleles at three X‐linked microsatellite loci and used them to determine if SR persists as a balanced polymorphism. We found that XSR/XST females produced more offspring than other genotypes and that SR males had lower sperm precedence and exhibited lower fertility when mating eight females in 24 h. Adult survival was independent of SR genotype but positively correlated with eye span. We infer that the SR polymorphism is likely maintained by a combination of weak overdominance for female fecundity and frequency dependent selection acting on male fertility. Our discovery of two SR haplotypes in the same population in a 10‐year period further suggests that this SR polymorphism may be evolving rapidly.