Abstract: Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily, plays a role in adipocyte differentiation, type II diabetes, macrophage response to inflammation and is suggested to influence carcinogen-induced colon cancer. Studies done in vitro and in vivo also revealed that PPARgamma ligands might promote differentiation and/or regression of mammary tumors. To directly evaluate the role of PPARgamma in mammary carcinogenesis, PPARgamma wild-type (+/+) or heterozygous (+/-) mice were administered 1 mg 7,12-dimethylbenz[a]anthracene (DMBA) by gavage once a week for 6 weeks and followed for a total of 25 weeks. Compared with congenic PPARgamma(+/+) littermate controls, PPARgamma(+/-) mice had early evidence for increased susceptibility to DMBA-mediated carcinogenesis based on a 1.6-fold increase in the percentage of mice with skin papillomas, as well as a 1.7-fold increase in the numbers of skin papillomas per mouse (P < 0.05). Similarly, PPARgamma(+/-) mice also had a 1.5-fold decreased survival rate (P = 0.059), and a 1.7-fold increased incidence of total tumors per mouse (P < 0.01). Moreover, PPARgamma(+/-) mice had an almost 3-fold increase in mammary adenocarcinomas (P < 0.05), an over 3-fold increase in ovarian granulosa cell carcinomas (P < 0.05), an over 3-fold increase in malignant tumors (P < 0.02) and a 4.6-fold increase in metastatic incidence. These results are the first to demonstrate an increased susceptibility in vivo of PPARgamma haploinsufficiency to DMBA-mediated carcinogenesis and suggest that PPARgamma may act as a tumor modifier of skin, ovarian and breast cancers. The data also support evidence suggesting a beneficial role for PPARgamma-specific ligands in the chemoprevention of mammary, ovarian and skin carcinogenesis.

Abstract: Theoreticians propose that trained winning and losing are important processes in creating linear animal dominance hierarchies, and experiments have shown that both processes can occur in animals, but their actual roles in creating natural hierarchies are unknown. We described agonism in 18 broods of three blue-footed boobies, Sula nebouxii, a species for which trained winning and losing have been demonstrated, to infer how these processes generate and maintain a natural hierarchy. Ranks in the linear hierarchy that emerged in every brood were initially assigned by asymmetries in age, size and maturity, which led to differences between broodmates in levels of expressed and received aggression and, consequently, to differences in the training of their aggressiveness and submissiveness. Later, ranks appeared to be maintained by the chicks' acquired aggressive and submissive tendencies combined with ongoing effects of persisting differences in size and maturity. Our results suggest that trained winning and trained losing are important in the construction of booby hierarchies but that these two axes of learning are largely independent. Increase in submissiveness occurs over a period of about 10-20 days, and the level of submissiveness reached varies with the amount of aggression received. After training, submissiveness is apparently maintained by a lower level of aggression and increasing use of threats. Threats become increasingly effective as chicks age, but are never as effective as attacks.

Abstract: Two-chick broods of the blue-footed booby,Sula nebouxii, ordinarily exhibit stable dominance-subordinance, with the senior (first-hatched) chick habitually aggressive and the junior one habitually submissive (Nelson 1978,The Sulidae: Gannets and Boobies. London: Oxford University Press). But are both the subordinate and the dominant chick affected in their agonistic tendencies by early social experience? To answer this, we permanently paired subordinate and dominant chicks, 2-3 weeks old, with singletons (chicks lacking experience with a nestmate) by cross-fostering. During the first 4 h after pairing, subordinate chicks were seven times less aggressive than singletons and twice as likely to be submissive; dominant chicks were six times as aggressive as singletons. Although most subordinates consistently lost agonistic encounters during the first 10 days after pairing, the proportion of dominants that won decreased progressively until, by day 6, only about half of dominant chicks were winning. Early social experience has a strong but reversable training effect on both subordinates and dominants. Training as a subordinate showed more persistent effects than training as a dominant, possibly in part because our testing situation perpetuated subordinate training and counteracted dominant training.

Abstract: We describe a state-of-the-art tunable ultraviolet (UV) Raman spectrometer for the 193-270 nm spectral region. This instrument allows for steady-state and transient UV Raman measurements. We utilize a 5 kHz Ti-sapphire continuously tunable laser (approximately 20 ns pulse width) between 193 nm and 240 nm for steady-state measurements. For transient Raman measurements we utilize one Coherent Infinity YAG laser to generate nanosecond infrared (IR) pump laser pulses to generate a temperature jump (T-jump) and a second Coherent Infinity YAG laser that is frequency tripled and Raman shifted into the deep UV (204 nm) for transient UV Raman excitation. Numerous other UV excitation frequencies can be utilized for selective excitation of chromophoric groups for transient Raman measurements. We constructed a subtractive dispersion double monochromator to minimize stray light. We utilize a new charge-coupled device (CCD) camera that responds efficiently to UV light, as opposed to the previous CCD and photodiode detectors, which required intensifiers for detecting UV light. For the T-jump measurements we use a second camera to simultaneously acquire the Raman spectra of the water stretching bands (2500-4000 cm(-1)) whose band-shape and frequency report the sample temperature.