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Divergent migratory strategies among populations can result in population‐level differences in timing of reproduction (allochrony) and local adaptation. However, the mechanisms underlying among‐population variation in timing are insufficiently understood, particularly in females. We studied differences in reproductive development and its related mechanisms along the hypothalamic–pituitary–gonadal axis (HPG) in closely related migratory and sedentary (i.e. resident) female dark‐eyed juncos (Junco hyemalis) living together in sympatry during early spring. Despite exposure to the same environmental cues in early spring, residents initiate breeding prior to the departure of migrants for their breeding grounds. We investigated whether residents would be more reproductively developed than migrants based on their behavioural differences. Alternatively, females could exhibit similar reproductive development in response to the same environmental cues despite differences in migratory behaviour. To compare their degree of reproductive development during seasonal sympatry and the underlying mechanisms of these differences, we collected ovarian and liver tissue in early spring prior to migration and compared transcript abundance of genes associated with reproduction using quantitative PCR. We also used stable hydrogen isotopes to infer relative breeding and wintering latitude of migrants. We found higher transcript abundance of luteinizing hormone receptor and aromatase in the ovary in addition to significantly heavier ovaries in residents than in migrants. Together, these results suggest greater sensitivity and response to upstream endocrine stimulation in resident females. Transcript abundance for other receptors in the ovary and liver associated with reproduction, however, did not differ between populations. When comparing ovarian development within migrants, females with lower hydrogen isotopes (indicating higher breeding latitudes) had smaller ovaries, suggesting that longer‐distance migrations may further delay reproductive development. Based on differences in ovary mass and transcript abundance, we conclude that females that differ in migratory strategy also differ in timing of reproductive development. These results support that divergent migratory behaviour drives allochrony and could enable reproductive isolation between populations; mechanistic differences at the level of gonadal stimulation can explain these differences in timing of reproductive development. A free Plain Language Summary can be found within the Supporting Information of this article.

Clinical studies show that the development of lung adenocarcinomas (LACs) is correlated with smoking habits. Nicotine, the addictive component of cigarettes, accelerates human LAC proliferation thr...

Capsaicin, spicy ingredient of chili peppers, is used to topically treat pain and inflammation associated with a variety of diseases. Data from our laboratory shows that capsaicin displays apoptoti...

Small cell lung cancer (SCLC) is characterized by aggressive clinical course and a dismal survival rate. The present study examines the apoptotic activity of capsaicin (the pungent ingredient of chili peppers) in human SCLC. We observed that capsaicin induced apoptosis in a panel of human SCLC in a concentration-dependent and time-dependent manner. Most importantly, capsaicin caused robust apoptosis in a panel of human SCLC cell lines, but did not affect normal human lung epithelial cells. The dietary administration of capsaicin decreased the growth H69 and DMS53 human SCLC tumors in nude mice and in chicken chorioallantoic membrane (CAM) models. The apoptotic activity of capsaicin was reversed with the generalized TRPV antagonist ruthenium red, indicating that TRPV receptors are involved in capsaicin induced apoptosis. However, antagonists to TRPV1, namely capsazepine and SB-366791, did not affect the apoptotic activity of capsaicin, suggesting the involvement of a TRPV1-independent mechanism. In contras...

Cigarette smoking bears a strong association with the development of lung cancer. Nicotine is the addictive component of cigarettes. Several convergent studies show that nicotine facilitates the growth and angiogenesis of human lung cancers. The biological activity of nicotine is mediated by nicotinic acetylcholine receptors (nAChRs). The endogenous ligand of nAChRs is acetylcholine (ACh). Data from our laboratory and other research groups show that lung cancers express all of the genes for synthesis, transport and degradation of ACh. These include nAChRs, choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT), choline transporter (ChT1) and acetylcholinesterase (AChE). Nicotine upregulates the ACh-signaling loop in human lung cancer cells. Therefore, we conjectured that disruption of ACh-signaling pathway should suppress the growth of human cancers. We show that alpha7-nAChR antagonists robustly suppress angiogenesis in human lung and retinal microvascular endothelial cells. The anti-angiogenic activity of alpha7-nAChR antagonists was also observed in chicken chorioallantoic membrane (CAM) and nude mouse models. Similarly, vesamicol, a small molecule antagonist of VAChT, decreases nicotine-induced tumor growth in human NSCLCs. Our studies suggest that the acetylcholine signaling pathway may be have potential applications in the therapy of human lung cancers. Our results are also relevant to lung cancer patients who are exposed to nicotine via secondhand smoke, nicotine patches, gums or electronic cigarettes. Citation Format: Piyali Dasgupta, Kathleen C. Brown, Jamie K. Lau, Aaron M. Dom, Brent A. Thornhill, Clayton M. Crabtree, Theodore R. Witte, W E. Hardman, Cody A. Stover, A B. Carpenter, Yi C. Chen. Disruption of the acetylcholine signaling pathway suppresses the growth and angiogenesis of human lung cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5229. doi:10.1158/1538-7445.AM2015-5229

The nutritional compound capsaicin has been shown to display anti-neoplastic activity in breast, prostate and colon tumors xenografted in nude mice. Based on these data from other research laboratories, we wanted to determine the bioavailability of capsaicin in nude mice in vivo. We found that capsaicin was rapidly metabolized primarily in the liver. The bioavailability of intact capsaicin was highest in the lung. Therefore, we hypothesized that capsaicin should suppress the growth of lung tumors. We found that capsaicin induced robust apoptosis in human SCLC cell lines. Capsaicin decreased the growth rates of human SCLC tumors in two in vivo models, namely the CAM model and the nude mouse model. HPLC studies showed intact capsaicin in the tumors excised from nude mice. The heat-sensation activity of capsaicin is mediated by the transient receptor potential vanilloid (TRPV) family of proteins. Capsaicin functions as an agonist of the TRPV1 receptor. The apoptotic activity of capsaicin was found to be mediated by TRPV6 and not TRPV1. Preliminary data shows that capsaicin increases the expression of the TRPV6 receptor, causing apoptosis in human SCLCs. Citation Format: John D. Hurley, William D. Rollyson, Cody A. Stover, Kathleen C. Brown, Haley E. Perry, Cathryn D. Stevenson, Clayton M. Crabtree, Aaron M. Dom, Jamie K. Lau, Theodore R. Witte, W E. Hardman, Piyali Dasgupta. Bioavailability and anti-tumor activity of capsaicin in human small cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1678. doi:10.1158/1538-7445.AM2015-1678

B2 Maternal diet may influence development of the offspring and may influence future cancer risk. Maternal consumption of diet high in n-6 (omega 6) polyunsaturated fats has been shown to increase risk for mammary gland cancer (Hilakivi-Clarke et al, 1997). We wanted to know if the substitution of corn oil with canola oil in the maternal diet might reduce the risk for breast cancer. Such a change would decrease dietary n-6 fat and increase n-3 fat. A study was devised to determine whether exposure to a diet that has less omega 6 and more omega 3 FAs during gestation and lactation would reduce the risk for mammary cancer in female offspring. Female SV 129 mice were divided into two groups and placed on diets either containing 10% w/w corn oil (corn oil is 50% omega 6 and < 0.5% omega 3) or 10% w/w canola oil (canola oil is 20% omega 6 and 10% omega 3). After two weeks the females were bred with homozygous C31 Tag transgenic male mice. The transgenic mice bear a transgene for the SV40 large T antigen with a prostatic steroid binding protein promoter. The female progeny, hemizygous for the transgene, are the experimental mice for this study. On a standard diet, females would be expected to develop mammary gland cancer by 6 months of age. At weaning, female progeny from each litter were all maintained on the basal corn oil containing diet. The female hemizygous mice were euthanized at 3weeks, 110, 130, 150 and 170 days. Results showed that the total tumor weight, number of glands with tumor and fraction of mice with tumors were higher in progeny of mother fed a corn oil diet than in progeny of mother fed a canola oil diet. No significant difference in the body weight of progeny from corn oil and canola fed mothers. At weaning the lipid composition of the inguinal fat pad, mammary gland and liver shows a higher level of omega 3 fatty acids in the offspring of mice fed the high n-3 diet. Mammary gland gene expression assay performed on three weeks and 130 days old mice reveals up as well as down regulation in several genes in canola versus corn group. The up regulated genes include CCAAT-enhancer binding protein beta (CEBPβ), a transcription factor that is involved in mammary gland differentiation (550-fold at 130days) and Early growth response 1 (Egr1), a tumor suppressor gene (13-fold at 130days). Genes down regulated include Bcl2-like 1(Bcl2l1), an antiapoptotic gene (-2.03-fold at 3weeks) and Fatty acid synthase (Fas), an enzyme involved in fatty acid synthesis and active in cancer cells (-7.09 at 130days). Western blot analysis confirmed the differential gene expression of CEBPβ and Fas. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B2.

Forty-four cases of liver fluke infestation (fascioliasis hepatica) were diagnosed near Chepstow, Monmouthshire, in 1968. Intramuscular emetine hydrochloride and oral chloroquine given to the adults and children, respectively, were well tolerated. Assessment by repeated stool examination, complement fixation and liver function tests, and full blood counts indicated that treatment had been effective in most cases. It is recommended that both the growth and the sale of watercress should be strictly controlled.

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