Competitive Regulation of E-Cadherin JuxtaMembrane Domain Degradation by p120-Catenin Binding and Hakai-Mediated Ubiquitination

p120-Catenin binding to, and Hakai-mediated ubiquitination of the E-cadherin juxtamembrane domain (JMD) are thought to be involved in regulating E-cadherin internalization and degradation. However, the relationship between these two pathways is not understood. We targeted the E-cadherin JMD to mitochondria (WT-JMD) to isolate this domain from the plasma membrane and internalization, and to examine protein modifications and degradation. WT-JMD localized to mitochondria, but did not accumulate there except when proteasome activity was inhibited. We found WT-JMD was ubiquitinated, and arginine substitution of lysines at position 5 (K5R) and 83 (K83R) resulted in the stable accumulation of mutant JMD at mitochondria. p120-Catenin did not localize, or bind to WT-JMD even upon proteasome inhibition, whereas the K5,83R-JMD mutant bound and localized p120-catenin to mitochondria. Mutation of the p120-catenin binding site in combination with these lysine mutations inhibited p120-catenin binding, but did not decrease JMD stability or its accumulation at mitochondria. Thus, increased stability of JMD lysine mutants was due to inhibition of ubiquitination and not to p120-catenin binding. Finally, mutation of these critical lysines in full length E-cadherin had similar effects on protein stability as WT-JMD. Our results indicate that ubiquitination of the JMD inhibits p120-catenin binding, and targets E-cadherin for degradation

Absorption Enhancement in Peridinin–Chlorophyll–Protein Light-Harvesting Complexes Coupled to Semicontinuous Silver Film

We report on experimental and theoretical studies of plasmon-induced effects in a hybrid nanostructure composed of light-harvesting complexes and metallic nanoparticles in the form of semicontinuous silver film. The results of continuous-wave and time-resolved spectroscopy indicate that absorption of the light-harvesting complexes is strongly enhanced upon coupling with the metallic film spaced by 25 nm of a dielectric silica layer. This conclusion is corroborated by modeling, which confirms the morphology of the silver island film

Histories of forced sex and health outcomes among Southern African lesbian and bisexual women: a cross-sectional study

BACKGROUND: Experiences of forced sex have been shown to be prevalent in Southern Africa. Negative outcomes of forced sex have been documented in general populations of women and men and include alcohol abuse, drug use, mental health problems, mental distress, sexual health problems and poor overall health. This study is the first to examine experiences of forced sex and associated health problems among lesbian and bisexual women in Southern Africa. METHODS: This study is based on data collected as part of a collaborative endeavor involving various Southern African community-based organizations. Lesbian and bisexual women in four Southern African countries participated in a cross-sectional survey, for a total study sample of 591. RESULTS: Nearly one-third of participants had been forced to have sex at some time in their lives. Thirty-one percent of all women reported to have experienced forced sex at least once in their life: 14.9% reported forced sex by men only; 6.6% reported forced sex by women only; 9.6% had had forced sexual experiences with both men and women. Participants experienced forced sex by men as more serious than forced sex by women; forced sex by women was more likely to involve intimate partners compared to forced sex by men. Participants who experienced forced sex by men were more likely to report drug problems, mental distress and lower sense of belonging. Forced sex by women was associated with drinking problems and mental distress. Having experienced forced sex by both men and women was associated with lower sense of belonging to the LGBT community, drug use problem and mental distress. CONCLUSIONS: The findings indicate that forced sex among Southern African women is a serious issue that needs further exploration. Clinicians should be made aware of the prevalence and possible consequences of forced sex among lesbian and bisexual women. Policies and community interventions should be designed to address this problem

P-cadherin expression in breast cancer: a review

P-cadherin is frequently over-expressed in high-grade invasive breast carcinomas and has been reported to be an enhancer of migration and invasion of breast cancer cells, being correlated with tumour aggressiveness. In addition, expression of P-cadherin is well established as an indicator of poor prognosis in human breast cancer, which has stimulated our interest in studying its role in this setting. This review describes the most important findings on P-cadherin expression and function in normal mammary tissue and breast cancer cells, emphasizing that further research is required to elucidate the role played by this protein in human mammary tumours

Luteinising hormone-releasing hormone analogue reverses the cell adhesion profile of EGFR overexpressing DU-145 human prostate carcinoma subline

Cetrorelix, a luteinising hormone-releasing hormone (LHRH) analogue, has been shown to limit growth of the human androgen-independent prostate cell line DU-145, although other inhibitory actions may also be affected. Both growth and invasion of DU-145 cells are linked to autocrine epidermal growth factor receptor (EGFR) signalling. Invasiveness requires not only cells to migrate to conduits, but also reduced adhesiveness between tumour cells to enable separation from the tumour mass. Thus, we investigated whether Cetrorelix alters the DU-145 cell–cell adhesion and if this occurs via altered EGFR signalling. Pharmacologic levels of Cetrorelix limited the invasiveness of a highly invasive DU-145 subline overexpressing full-length EGFR (DU-145 WT). Extended exposure of the cells to Cetrorelix resulted in increased levels of the cell–cell adhesion complex molecules E-cadherin, α- and β-catenin, and p120. Puromycin blocked the increases in E-cadherin and β-catenin levels, suggesting that de novo protein synthesis is required. The Cetrorelix effect appears to occur via transmodulation of EGFR by a protein kinase C (PKC)-dependent mechanism, as there were no changes in DU-145 cells expressing EGFR engineered to negate the PKC transattenuation site (DU-145 A654); downregulation of EGFR signalling produced a similar upregulation in adhesion complex proteins, further suggesting a role for autocrine signalling. Cetrorelix increased the cell–cell adhesiveness of DU-145 WT cells to an extent similar to that seen when autocrine EGFR signalling is blocked; as expected, DU-145 A654 cell–cell adhesion also was unaffected by Cetrorelix. The increased adhesiveness is expected as the adhesion complex molecules moved to the cells' periphery. These data offer direct insight into the possible crosstalk pathways between the LHRH and EGFR receptor signalling. The ability of Cetrorelix to downregulate EGFR signalling and subsequently reverse the antiadhesiveness found in metastatic prostate cancer highlights a novel potential target for therapeutic strategies

Understanding the retinal basis of vision across species

The vertebrate retina first evolved some 500 million years ago in ancestral marine chordates. Since then, the eyes of different species have been tuned to best support their unique visuoecological lifestyles. Visual specializations in eye designs, large-scale inhomogeneities across the retinal surface and local circuit motifs mean that all species' retinas are unique. Computational theories, such as the efficient coding hypothesis, have come a long way towards an explanation of the basic features of retinal organization and function; however, they cannot explain the full extent of retinal diversity within and across species. To build a truly general understanding of vertebrate vision and the retina's computational purpose, it is therefore important to more quantitatively relate different species' retinal functions to their specific natural environments and behavioural requirements. Ultimately, the goal of such efforts should be to build up to a more general theory of vision

Risk factors involved in treatment delays and differences in treatment type for patients with prostate cancer by risk category in an academic safety net hospital

Objectives: Understanding the drivers of delays from diagnosis to treatment can elucidate how to reduce the time to treatment (TTT) in patients with prostate cancer. In addition, the available treatments depending on the stage of cancer can vary widely for many reasons. This study investigated the relationship of TTT and treatment choice with sociodemographic factors in patients with prostate cancer who underwent external beam radiation therapy (RT), radical prostatectomy (RP), androgen deprivation therapy (ADT), or active surveillance (AS) at a safety-net academic medical center. Methods and materials: A retrospective review was performed on 1088 patients who were diagnosed with nonmetastatic prostate cancer between January 2005 and December 2013. Demographic data as well as data on TTT, initial treatment choice, American Joint Committee on Cancer stage, and National Comprehensive Cancer Network risk categories were collected. Analyses of variance and multivariable logistic regression models were performed to analyze the relationship of these factors with treatment choice and TTT. Results: Age, race, and marital status were significantly related to treatment choice. Patients who were nonwhite and older than 60 years were less likely to undergo RP. Black patients were 3.8 times more likely to undergo RT compared with white patients. The median TTT was 75 days. Longer time delays were significant in patients of older age, nonwhite race/ethnicity, non-English speakers, those with noncommercial insurance, and those with non-married status. The average TTT of high-risk patients was 25 days longer than that of low-risk patients. Patients who underwent RT had an average TTT that was 34 days longer than that of RP patients. Conclusions: The treatment choice and TTT of patients with prostate cancer are affected by demographic factors such as age, race, marital status, and insurance, as well as clinical factors including stage and risk category of disease