Evolutionary Dynamics of the Short-Nosed Fruit Bat, \u3ci\u3eCynopterus sphinx \u3c/i\u3e (Pteropodidae): Inferences from the Spatial Scale of Genetic and Phenotypic Differentiation

We report the results of a population-genetic study of the short-nosed fruit bat, Cynopterus sphinx (Pteropodidae). The purpose of our study was to assess the relative importance of drift, gene flow, and spatially varying selection in shaping patterns of genetic and phenotypic variation across a latitudinal climatic gradient in peninsular India. At a microgeographic scale, polygynous mating resulted in a substantial reduction of effective population size. However, at a macrogeographic scale, rates of migration were sufficiently high to prevent a pronounced degree of stochastic differentiation via drift. Spatial analysis of genetic and phenotypic differentiation revealed that clinal variation in body size of C. sphinx cannot be explained by a neutral model of isolation by distance. The geographic patterning of morphometric variation is most likely attributable to spatially varying selection and/or the direct influence of latitudinally ordered environmental effects. The combined analysis of genetic and phenotypic variation indicates that recognized subspecies of C. sphinx in peninsular India represent arbitrary subdivisions of a continuous spectrum of clinal size variation

Partial Inhibition of Estrogen-Induced Mammary Carcinogenesis in Rats by Tamoxifen: Balance between Oxidant Stress and Estrogen Responsiveness

Epidemiological and experimental evidences strongly support the role of estrogens in breast tumor development. Both estrogen receptor (ER)-dependent and ER-independent mechanisms are implicated in estrogen-induced breast carcinogenesis. Tamoxifen, a selective estrogen receptor modulator is widely used as chemoprotectant in human breast cancer. It binds to ERs and interferes with normal binding of estrogen to ERs. In the present study, we examined the effect of long-term tamoxifen treatment in the prevention of estrogen-induced breast cancer. Female ACI rats were treated with 17β-estradiol (E2), tamoxifen or with a combination of E2 and tamoxifen for eight months. Tissue levels of oxidative stress markers 8-iso-Prostane F2α (8-isoPGF2α), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, and oxidative DNA damage marker 8-hydroxydeoxyguanosine (8-OHdG) were quantified in the mammary tissues of all the treatment groups and compared with age-matched controls. Levels of tamoxifen metabolizing enzymes cytochrome P450s as well as estrogen responsive genes were also quantified. At necropsy, breast tumors were detected in 44% of rats co-treated with tamoxifen+E2. No tumors were detected in the sham or tamoxifen only treatment groups whereas in the E2 only treatment group, the tumor incidence was 82%. Co-treatment with tamoxifen decreased GPx and catalase levels; did not completely inhibit E2-mediated oxidative DNA damage and estrogen-responsive genes monoamine oxygenase B1 (MaoB1) and cell death inducing DFF45 like effector C (Cidec) but differentially affected the levels of tamoxifen metabolizing enzymes. In summary, our studies suggest that although tamoxifen treatment inhibits estrogen-induced breast tumor development and increases the latency of tumor development, it does not completely abrogate breast tumor development in a rat model of estrogen-induced breast cancer. The inability of tamoxifen to completely inhibit E2-induced breast carcinogenesis may be because of increased estrogen-mediated oxidant burden

S100A7-Downregulation Inhibits Epidermal Growth Factor-Induced Signaling in Breast Cancer Cells and Blocks Osteoclast Formation

S100A7 is a small calcium binding protein, which has been shown to be differentially expressed in psoriatic skin lesions, as well as in squamous cell tumors of the skin, lung and breast. Although its expression has been correlated to HER+ high-grade tumors and to a high risk of progression, the molecular mechanisms of these S100A7-mediated tumorigenic effects are not well known. Here, we showed for the first time that epidermal growth factor (EGF) induces S100A7 expression in both MCF-7 and MDA-MB-468 cell lines. We also observed a decrease in EGF-directed migration in shRNA-downregulated MDA-MB-468 cell lines. Furthermore, our signaling studies revealed that EGF induced simultaneous EGF receptor phosphorylation at Tyr1173 and HER2 phosphorylation at Tyr1248 in S100A7-downregulated cell lines as compared to the vector-transfected controls. In addition, reduced phosphorylation of Src at tyrosine 416 and p-SHP2 at tyrosine 542 was observed in these downregulated cell lines. Further studies revealed that S100A7-downregulated cells had reduced angiogenesis in vivo based on matrigel plug assays. Our results also showed decreased tumor-induced osteoclastic resorption in an intra-tibial bone injection model involving SCID mice. S100A7-downregulated cells had decreased osteoclast number and size as compared to the vector controls, and this decrease was associated with variations in IL-8 expression in in vitro cell cultures. This is a novel report on the role of S100A7 in EGF-induced signaling in breast cancer cells and in osteoclast formation

A novel pictorial smile chart:Reliability and validity

INTRODUCTION: Smile analysis provides data on the positive and negative elements of a patient's smile. We aimed to develop a simple pictorial chart to record relevant parameters of the smile analysis in a single diagram and to investigate the reliability and validity of this chart.METHODS: A panel of 5 orthodontists developed a graphical chart, which was reviewed by 12 orthodontists and 10 orthodontic residents. The chart comprises facial, perioral, and dentogingival zones analyzing 8 continuous and 4 discrete variables. The chart was tested on frontal smiling photographs of 40 young (aged 15-18 years) and 40 old (aged 50-55 years) patients. All measurements were performed twice with an interval of 2 weeks by 2 observers.RESULTS: Pearson's correlation coefficients for observers and age groups varied from 0.860 to 1.000 and between observers from 0.753 to 0.999. Minor significant mean differences were found between the first and second observations, which were not clinically relevant. The kappa scores for the dichotomous variables were in perfect agreement. To test the sensitivity of the smile chart, differences between the two age groups were assessed as differences because aging is expected. In the older age group, philtrum height and visibility of mandibular incisors were significantly larger, whereas the upper lip fullness and buccal corridor visibility were significantly lesser (P &lt;0.001).CONCLUSIONS: The newly developed smile chart can record essential smile parameters to aid diagnosis, treatment planning, and research. The chart is simple and easy to use, has face and content validity and good reliability.</p

A novel pictorial smile chart: Reliability and validity.

INTRODUCTION Smile analysis provides data on the positive and negative elements of a patient's smile. We aimed to develop a simple pictorial chart to record relevant parameters of the smile analysis in a single diagram and to investigate the reliability and validity of this chart. METHODS A panel of 5 orthodontists developed a graphical chart, which was reviewed by 12 orthodontists and 10 orthodontic residents. The chart comprises facial, perioral, and dentogingival zones analyzing 8 continuous and 4 discrete variables. The chart was tested on frontal smiling photographs of 40 young (aged 15-18 years) and 40 old (aged 50-55 years) patients. All measurements were performed twice with an interval of 2 weeks by 2 observers. RESULTS Pearson's correlation coefficients for observers and age groups varied from 0.860 to 1.000 and between observers from 0.753 to 0.999. Minor significant mean differences were found between the first and second observations, which were not clinically relevant. The kappa scores for the dichotomous variables were in perfect agreement. To test the sensitivity of the smile chart, differences between the two age groups were assessed as differences because aging is expected. In the older age group, philtrum height and visibility of mandibular incisors were significantly larger, whereas the upper lip fullness and buccal corridor visibility were significantly lesser (P <0.001). CONCLUSIONS The newly developed smile chart can record essential smile parameters to aid diagnosis, treatment planning, and research. The chart is simple and easy to use, has face and content validity and good reliability