Identification and characterization of downstream effector protein(s) regulated by p53 and pRb

A commonality among cancer types is the high frequency of mutations that inhibit or alter signaling of the p53 and pRb (Retinoblastoma) tumor suppressors. These genes regulate processes vital for cancer suppression such as apoptosis, senescence, and cell cycle arrest among others. Loss of both p53 and pRb promotes processes that support cancer progression and is associated with decreased patient survival and increased rates of tumor reoccurrence. Although data points to the ability of p53 and pRb to collaborate and to inhibit tumorigenesis, it remains unclear how p53 and pRb cooperate toward this task. Using RNA expression profiling, 179 p53 and pRb cross-talk candidates were identified in normal lung fibroblasts (WI38) cells exogenously coexpressing p53 and pRb. Regulator of G protein signaling 16 (RGS16) was among the p53 and pRb cross-talk candidates and reports suggest it inhibits the activation of several oncogenic pathways associated with proliferation, migration, and invasion of cancer cells. RGS16 is downregulated in pancreatic cancer patients with metastases compared to patients without metastasized pancreatic cancer. The role of RGS16 in cancer cell metastasis is unknown; therefore I tested the hypothesis that RGS16 inhibits pancreatic cancer cell migration and invasion in vitro. Expression of RGS16 was decreased in the pancreatic cancer cell lines tested compared to control. Expression of RGS16 inhibited fetal bovine serum (FBS) and epidermal growth factor (EGF) induced migration of the BxPC-3 and AsPC-1 but not PANC-1 pancreatic cancer cells. It also inhibited EGF induced invasion of BxPC-3 and AsPC-1 cells with no impact on cell viability. Although RGS16 inhibited cell migration and invasion of BxPC-3 and AsPC-1 cells, there was no change in F-actin polymerization or the amounts of p-AKT, pERK and the epithelial mesenchymal transition (EMT) marker vimentin proteins, but there was a slight increase in E-cadherin protein expression in BxPC-3 cells. Our data suggests the inhibitory effect of RGS16 on EGF induced pancreatic cancer cell migration is independent of the PI3K and MAPK pathways. To our knowledge, for the first time, we performed analyses to identify p53 and pRb cross-talk candidates and demonstrated a role for RGS16 in suppressing EGF and FBS induced pancreatic cancer migration and invasion

What influences our decision to vaccinate? The social amplification of risk framework and vaccination

The current study applies the social amplification risk framework to the anti-vaccination movement, specifically to the social factors that influence the likelihood to vaccinate. A total of 264 participants were recruited using Amazon’s Mechanical Turk engine and students from a large southern university. Participants responded to questions about their personal, friend, and family experiences with vaccines, their discussion about vaccines, and trust in vaccine literature (CDC, Facebook, family, etc.). Lastly, participants responded to a modified Duke’s social support scale. Results indicated that the likelihood to vaccinate is impacted by several social factors and that those factors can be amplified based on the experiences of others. The results support using the social amplification of risk on individual perceptions of risk

Barriers to enrollment in a randomized controlled trial of hydrocortisone for cardiovascular insufficiency in term and late preterm newborn infants.

ObjectiveTo analyze reasons for low enrollment in a randomized controlled trial (RCT) of the effect of hydrocortisone for cardiovascular insufficiency on survival without neurodevelopmental impairment (NDI) in term/late preterm newborns.Study designThe original study was a multicenter RCT. Eligibility: ⩾34 weeks' gestation, <72 h old, mechanically ventilated, receiving inotrope. Primary outcome was NDI at 2 years; infants with diagnoses at high risk for NDI were excluded. This paper presents an analysis of reasons for low patient enrollment.ResultsTwo hundred and fifty-seven of the 932 otherwise eligible infants received inotropes; however, 207 (81%) had exclusionary diagnoses. Only 12 infants were randomized over 10 months; therefore, the study was terminated. Contributing factors included few eligible infants after exclusions, open-label steroid therapy and a narrow enrollment window.ConclusionDespite an observational study to estimate the population, very few infants were enrolled. Successful RCTs of emergent therapy may require fewer exclusions, a short-term primary outcome, waiver of consent and/or other alternatives

Holding Companies, The New Deal, and the Development of the Aircraft Industry: A Historical Retrospective

William B. Carper is an Associate Professor of Management and Head, Department of Management in the School of Business at Georgia Southern College. Carl Swickley is Director of the Experimental Aircraft Association Museum, Wittman Air Field at Oshkosh. Wisconsin

Outsourcing a High Speed Internet Access Project: An Information Technology Class Case Study in Three Parts

In early 2004, the Hilton Hotels Corporation (HHC) required that all of its hotels (both owned and franchised) install highspeed Internet access (HSIA) in all of their rooms by June 2004. This case focuses on how one of its franchise properties located on the northern gulf coast of Florida (the Hilton Sandestin Beach Golf Resort & Spa—hereinafter referred to as the HSB) responded to this mandate. The (A) part of the HSB case includes the industry situation for the HSB in 2004 plus the details surrounding the initial phase of the HSIA project. Also presented in this part are descriptions of how and why the HSB management made the decision to use a wireless (versus wired) solution as well as to outsource both the installation of the HSIA wireless hardware and the customer support aspects of the HSIA project to what turned out to be a less than experienced vendor. The (B) part of this case describes the situation at HSB after the high speed internet system was installed and made operational, as well as the various problems that the system and its lack of customer support created for the hotel. Part (C) details the actions of the new HSB General Manager who arrived in late 2004 after the initial HSIA implementation and how he resolved the issues that had been created by his predecessor

Role of early second-trimester uterine artery Doppler screening to predict small-for-gestational-age babies in nulliparous women

Background Trophoblastic invasion of the uterine spiral arteries substantially increases compliance to accommodate increased blood flow to the placenta. Failure of this process impedes uterine artery blood flow, and this may be detected by uterine artery Doppler flow studies. However, the clinical utility of uterine artery Doppler flow studies in the prediction of adverse pregnancy outcomes in a general population remains largely unknown. Objective We sought to determine the utility of early second-trimester uterine artery Doppler studies as a predictor of small-for-gestational-age neonates. Study Design Nulliparous women with a viable singleton pregnancy were recruited during their first trimester into an observational prospective cohort study at 8 institutions across the United States. Participants were seen at 3 study visits during pregnancy and again at delivery. Three indices of uterine artery Doppler flow (resistance index, pulsatility index, and diastolic notching) were measured in the right and left uterine arteries between 16 weeks 0 days’ and 22 weeks 6 days’ gestation. Test characteristics for varying thresholds in the prediction of small for gestational age (defined as birthweight <5th percentile for gestational age [Alexander growth curve]) were evaluated. Results Uterine artery Doppler indices, birthweight, and gestational age at birth were available for 8024 women. Birthweight <5th percentile for gestational age occurred in 358 (4.5%) births. Typical thresholds for the uterine artery Doppler indices were all associated with birthweight <5th percentile for gestational age (P < .0001 for each), but the positive predictive values for these cutoffs were all <15% and areas under receiver operating characteristic curves ranged from 0.50-0.60. Across the continuous scales for these measures, the areas under receiver operating characteristic curves ranged from 0.56-0.62. Incorporating maternal age, early pregnancy body mass index, race/ethnicity, smoking status prior to pregnancy, chronic hypertension, and pregestational diabetes in the prediction model resulted in only modest improvements in the areas under receiver operating characteristic curves ranging from 0.63-0.66. Conclusion In this large prospective cohort, early second-trimester uterine artery Doppler studies were not a clinically useful test for predicting small-for-gestational-age babies

RGS16, a novel p53 and pRb cross-talk candidate inhibits migration and invasion of pancreatic cancer cells

Data collected since the discovery of p53 and pRb/RB1 suggests these tumor suppressors cooperate to inhibit tumor progression. Patients who have mutations in both p53 and RB1 genes have increased tumor reoccurrence and decreased survival compared to patients with only one tumor suppressor gene inactivated. It remains unclear how p53 and pRb cooperate toward inhibiting tumorigenesis. Using RNA expression profiling we identified 179 p53 and pRb cross-talk candidates in normal lung fibroblasts (WI38) cells exogenously coexpressing p53 and pRb. Regulator of G protein signaling 16 (RGS16) was among the p53 and pRb cross-talk candidates and has been implicated in inhibiting activation of several oncogenic pathways associated with proliferation, migration, and invasion of cancer cells. RGS16 has been found to be downregulated in pancreatic cancer patients with metastases compared to patients without metastasis. Expression of RGS16 mRNA was decreased in the pancreatic cancer cell lines tested compared to control. Expression of RGS16 inhibited migration of the BxPC-3 and AsPC-1 but not PANC-1 cells and inhibited invasion of BxPC-3 and AsPC-1 cells with no impact on cell viability. We have identified for the first time p53 and pRb cross-talk candidates and a role for RGS16 to inhibit pancreatic cancer migration and invasion

Mapping Philanthropic Foundations’ Characteristics: towards an international integrative framework of foundation types

As philanthropic foundations take on increasingly prominent sociopolitical roles, the need for stronger conceptualizations of foundations as an organizational form is articulated widely across academic, policy, and practice contexts. Building on institutional research’s tradition of categorizing, classifying and typologizing organizational forms, our article critically explores the different ways in which foundations have been cast and differentiated in international academic and practice literatures. Examining and integrating these, we propose an integrative framework of foundation types. Incorporating 13 categories—three contextual, five organizational, and five strategic ones—the framework allows for clarifying distinctions and identifying commonalities between different foundation forms, offering a basis for developing more reflective and differentiated research and practice knowledge

Neurobiology of social behavior abnormalities in autism and Williams syndrome

Social behavior is a basic behavior mediated by multiple brain regions and neural circuits, and is crucial for the survival and development of animals and humans. Two neuropsychiatric disorders that have prominent social behavior abnormalities are autism spectrum disorders (ASD), which is characterized mainly by hyposociability, and Williams syndrome (WS), whose subjects exhibit hypersociability. Here we review the unique properties of social behavior in ASD and WS, and discuss the major theories in social behavior in the context of these disorders. We conclude with a discussion of the research questions needing further exploration to enhance our understanding of social behavior abnormalities