MicroRNA-466 inhibits tumor growth and bone metastasis in prostate cancer by direct regulation of osteogenic transcription factor RUNX2.

MicroRNAs (miRNAs) have emerged as key players in cancer progression and metastatic initiation yet their importance in regulating prostate cancer (PCa) metastasis to bone has begun to be appreciated. We employed multimodal strategy based on in-house PCa clinical samples, publicly available TCGA cohorts, a panel of cell lines, in silico analyses, and a series of in vitro and in vivo assays to investigate the role of miR-466 in PCa. Expression analyses revealed that miR-466 is under-expressed in PCa compared to normal tissues. Reconstitution of miR-466 in metastatic PCa cell lines impaired their oncogenic functions such as cell proliferation, migration/invasion and induced cell cycle arrest, and apoptosis compared to control miRNA. Conversely, attenuation of miR-466 in normal prostate cells induced tumorigenic characteristics. miR-466 suppressed PCa growth and metastasis through direct targeting of bone-related transcription factor RUNX2. Overexpression of miR-466 caused a marked downregulation of integrated network of RUNX2 target genes such as osteopontin, osteocalcin, ANGPTs, MMP11 including Fyn, pAkt, FAK and vimentin that are known to be involved in migration, invasion, angiogenesis, EMT and metastasis. Xenograft models indicate that miR-466 inhibits primary orthotopic tumor growth and spontaneous metastasis to bone. Receiver operating curve and Kaplan-Meier analyses show that miR-466 expression can discriminate between malignant and normal prostate tissues; and can predict biochemical relapse. In conclusion, our data strongly suggests miR-466-mediated attenuation of RUNX2 as a novel therapeutic approach to regulate PCa growth, particularly metastasis to bone. This study is the first report documenting the anti-bone metastatic role and clinical significance of miR-466 in prostate cancer

Oncogenic microRNA-4534 regulates PTEN pathway in prostate cancer.

Prostate carcinogenesis involves alterations in several signaling pathways, the most prominent being the PI3K/AKT pathway. This pathway is constitutively active and drives prostate cancer (PCa) progression to advanced metastatic disease. PTEN, a critical tumor and metastasis suppressor gene negatively regulates cell survival, proliferation, migration and angiogenesis via the PI3K/Akt pathway. PTEN is mutated, downregulated/dysfunctional in many cancers and its dysregulation correlates with poor prognosis in PCa. Here, we demonstrate that microRNA-4534 (miR-4534) is overexpressed in PCa and show that miR-4534 is hypermethylated in normal tissues and cell lines compared to PCa tissues/cells. miR-4534 exerts its oncogenic effects partly by downregulating the tumor suppressor PTEN gene. Knockdown of miR-4534 impaired cell proliferation, migration/invasion and induced G0/G1 cell cycle arrest and apoptosis in PCa. Suppression of miR-4534 and its effects on tumor growth was confirmed in a xenograft mouse model. We performed parallel experiments in non-cancer RWPE1 cells by overexpessing miR-4534 followed by functional assays. Overexpression of miR-4534 induced pro-cancerous characteristics in this non-cancer cell line. Statistical analyses revealed that miR-4534 has potential to independently distinguish malignant from normal tissues and positively correlated with poor overall and PSA recurrence free survival. Taken together, our results show that depletion of miR-4534 in PCa induces a tumor suppressor phenotype partly through induction of PTEN. These results have important implications for identifying and defining the role of new PTEN regulators such as microRNAs in prostate tumorigenesis. Understanding aberrantly overexpressed miR-4534 and its downregulation of PTEN will provide mechanistic insight and therapeutic targets for PCa therapy

A social psychological model of citizen satisfaction with local services

This research examines citizen attitudes toward local public services. Further, it investigates the antecedents of these service attitudes, as measured by service evaluations, so as to explore the way in which citizen attitudes about public services are shaped. Nine public service areas are indicators of the major dependent variable, citizen service attitudes. In examining citizen attitudes toward local services, this research develops, applies, and tests a model of the citizen evaluation process. The model seeks to explain how differences in service attitudes arise and prevail across the mass public. The model postulates that background and social psychological factors affect an individual\u27s attitudes. Social psychological factors are hypothesized to intervene between the background factors and the dependent variable, citizen service attitudes toward local services. Stronger relationships are expected to exist among the social psychological factors and citizen service attitudes. The ultimate test of the model\u27s contribution lies in the degree of contribution the social psychological factors make in explaining citizen attitudes tov^ard local services. The model is tested by Multiple Regression Analysis. The data for this research are from a national opinion poll conducted in 1977 by Louis Harris and Associates for the U.S. Department of Housing and Urban Development. Multiple regression results indicate the model is weak in predicting social psychological factors, but more powerful in explaining service satisfaction. Based on these results certain adjustments are recommended for future research

Cadwallader Colden Jr. to Peter Van Bruch Livingston, August 28, 1760

Cadwallader Colden Jr., addressed from Coldenham, an Estate along the Hudson, wrote to Peter Van Brugh Livingston, addressed to Merchant at New York. He explained that his brother, David Colden paid Mr. Alexander. He was afraid to go to town because of smallpox.https://digitalcommons.kean.edu/lhc_1760s/1000/thumbnail.jp

H.M. Colden to John Kean, April 17, 1792

H.M. Colden in New York wrote to John Kean, addressed to Philadelphia, PA. This letter concerns financial issues related to the Bank of North America and the Bank of the United States. People included: Mr. Fitzsimons, the treasurer, Col. Lawrance [sic], Mr. Platt, Mr. Cromline [Verplanck], Mr. Martin Hoffman, Mr. McEvers, Bleeker. Places included: New York, Bank of North America, Bank of the United States.https://digitalcommons.kean.edu/lhc_1790s/1324/thumbnail.jp

Indicadores de Maduracion Sexual y Su Relacion Con Indices de Masa Corporal (IMC) y Habitos de Alimentacion en Escolares Femeninas de Arica, Chile

The basis of this investigation came from recent evidence that the age of puberty, specifically with respect to young girls, has fallen notably in the past decade. This trend exists in Chile, as well as other countries such as the United States, and has presented itself alongside a portentous epidemic of obesity and malnutrition. Knowing the risks of both disorders, and how their affects have already been manifested in the adolescent population in Chile and the city of Arica, this study sought to develop a relationship between body mass index (BMI) and pubertal development, including the appearance of secondary sexual characteristics and physical development as well as other indications of growing sexuality, such as interest in dating and sexual behaviors. Surveys containing pertinent questions were distributed in two public schools in Arica, Chile to a total of 97 girls, ages 9 to 18. During the time of the completion of these surveys, heights and weights were also measured in order to calculate BMI. The results were analyzed and several correlations were encountered, which were then able to be demonstrated graphically. A positive correlation between reported stages of Tanner as well as age of first menstruation and BMI at time of survey was developed. The findings also demonstrated a group of adolescents sexually active, the majority beginning to have sexual relations before the age of 14, and with a notable interest in dating, even at 10 and 11 years of age. The results also supported the trend of a decreasing age of puberty, given that 4 participants were found to have started their menstruation at age 9, without the presence of thyroid or related disorders, and the average age for the beginning of menstruation was measured at 12,5 and 12,4 for the 16 and 15 year-olds. The findings suggest that BMI is related to and may influence sexual development, although more research is needed to develop a causal relationship between the two, and the many factors that influence one’s pubertal development shouldn’t be ignored. However, promotion of not only sexual education, but also proper nutrition and physical activity, should be an unquestioned public health response to the worsening problems and heightened vulnerability in the adolescent population

Nutrient additions to mitigate for loss of Pacific salmon: consequences for stream biofilm and nutrient dynamics

Mitigation activities designed to supplement nutrient and organic matter inputs to streams experiencing decline or loss of Pacific salmon typically presuppose that an important pathway by which salmon nutrients are moved to fish (anadromous and/or resident) is via nutrient incorporation by biofilms and subsequent bottom-up stimulation of biofilm production, which is nutrient-limited in many ecosystems where salmon returns have declined. Our objective was to quantify the magnitude of nutrient incorporation and biofilm dynamics that underpin this indirect pathway in response to experimental additions of salmon carcasses and pelletized fish meal (a.k.a., salmon carcass analogs) to 500-m reaches of central Idaho streams over three years. Biofilm standing crops increased 2–8-fold and incorporated marine-derived nutrients (measured using 15N and 13C) in the month following treatment, but these responses did not persist year-to-year. Biofilms were nitrogen (N) limited before treatments, and remained N limited in analog, but not carcass-treated reaches. Despite these biofilm responses, in the month following treatment total N load was equal to 33–47% of the N added to the treated reaches, and N spiraling measurements suggested that as much as 20%, but more likely 2–3% of added N was taken up by microbes. Design of biologically and cost-effective strategies for nutrient addition will require understanding the rates at which stream microbes take up nutrients and the downstream distance traveled by exported nutrients

Reef height drives threshold dynamics of restored oyster reefs

Nonlinear threshold responses to biotic or abiotic forcing may produce multiple population trajectories dependent upon initial conditions, which can reinforce population recovery or drive local ex - tinction, yet experimental tests of this phenomenon are lacking in marine ecosystems. In field experiments at 4 sites in 2 tributaries of lower Chesapeake Bay, we examined demographic responses (density and survival) of eastern oyster Crassostrea virginica populations to reef height and associated gradients in sediment deposition and habitat complexity. After 2 yr, oyster reefs exhibited diverging trajectories to ward either degradation or persistence, dependent upon initial reef height. Reefs higher than 0.3 m supported greater oyster density, survival, and reef complexity, whereas sediment deposition was reduced. Reefs lower than 0.3 m experienced heavy sediment deposition and were eventually buried. These observations (1) provide experimental evidence for threshold dynamics in marine species, (2) suggest that the collapse of oyster populations was largely due to anthropo - genic habitat degradation that eliminated positive feed - backs and which may have created an alternative reef trajectory towards local extinction, and (3) indicate an avenue by which oyster restoration is achievable