University of Virginia

About: University of Virginia is a education organization based out in Charlottesville, Virginia, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 52543 authors who have published 113268 publications receiving 5220506 citations. The organization is also known as: U of V & UVa.

Constitutive activation of Stat3 by the Src and JAK tyrosine kinases participates in growth regulation of human breast carcinoma cells.

Abstract: Constitutive activation of signal transducer and activator of transcription (STAT) proteins has been detected in a wide variety of human primary tumor specimens and tumor cell lines including blood malignancies, head and neck cancer, and breast cancer. We have previously demonstrated a high frequency of Stat3 DNA-binding activity that is constitutively-induced by an unknown mechanism in human breast cancer cell lines possessing elevated EGF receptor (EGF-R) and c-Src kinase activities. Using tyrosine kinase selective inhibitors, we show here that Src and JAK family tyrosine kinases cooperate to mediate constitutive Stat3 activation in the absence of EGF stimulation in model human breast cancer cell lines. Inhibition of Src or JAKs results in dose-dependent suppression of Stat3 DNA-binding activity, which is accompanied by growth inhibition and induction of programmed cell death. In addition, transfection of a dominant-negative form of Stat3 leads to growth inhibition involving apoptosis of breast cancer cells. These results indicate that the biological effects of the Src and JAK tyrosine kinase inhibitors are at least partially mediated by blocking Stat3 signaling. While EGF-R kinase activity is not required for constitutive Stat3 activation in breast cancer cells, EGF stimulation further increases STAT DNA-binding activity, consistent with an important role for EGF-R in STAT signaling and malignant progression. Analysis of primary breast tumor specimens from patients with advanced disease revealed that the majority exhibit elevated STAT DNA-binding activity compared to adjacent non-tumor tissues. Our findings, taken together, suggest that tyrosine kinases transduce signals through Stat3 protein that contribute to the growth and survival of human breast cancer cells in culture and potentially in vivo.

Methylation of histone H4 at arginine 3 facilitating transcriptional activation by nuclear hormone receptor

Abstract: Acetylation of core histone tails plays a fundamental role in transcription regulation. In addition to acetylation, other posttranslational modifications, such as phosphorylation and methylation, occur in core histone tails. Here, we report the purification, molecular identification, and functional characterization of a histone H4–specific methyltransferase PRMT1, a protein arginine methyltransferase. PRMT1 specifically methylates arginine 3(Arg 3) of H4 in vitro and in vivo. Methylation of Arg 3 by PRMT1 facilitates subsequent acetylation of H4 tails by p300. However, acetylation of H4 inhibits its methylation by PRMT1. Most important, a mutation in theS-adenosyl-l-methionine–binding site of PRMT1 substantially crippled its nuclear receptor coactivator activity. Our finding reveals Arg 3 of H4 as a novel methylation site by PRMT1 and indicates that Arg 3 methylation plays an important role in transcriptional regulation.

Spitzer Survey of the Large Magellanic Cloud: Surveying the Agents of a Galaxy's Evolution (SAGE). I. Overview and Initial Results

Abstract: We are performing a uniform and unbiased imaging survey of the Large Magellanic Cloud (LMC; ~7° × 7°) using the IRAC (3.6, 4.5, 5.8, and 8 μm) and MIPS (24, 70, and 160 μm) instruments on board the Spitzer Space Telescope in the Surveying the Agents of a Galaxy's Evolution (SAGE) survey, these agents being the interstellar medium (ISM) and stars in the LMC. This paper provides an overview of the SAGE Legacy project, including observing strategy, data processing, and initial results. Three key science goals determined the coverage and depth of the survey. The detection of diffuse ISM with column densities >1.2 × 10^(21) H cm^(-2) permits detailed studies of dust processes in the ISM. SAGE's point-source sensitivity enables a complete census of newly formed stars with masses >3 M_☉ that will determine the current star formation rate in the LMC. SAGE's detection of evolved stars with mass-loss rates >1 × 10^(-8) M_☉ yr^(-1) will quantify the rate at which evolved stars inject mass into the ISM of the LMC. The observing strategy includes two epochs in 2005, separated by 3 months, that both mitigate instrumental artifacts and constrain source variability. The SAGE data are nonproprietary. The data processing includes IRAC and MIPS pipelines and a database for mining the point-source catalogs, which will be released to the community in support of Spitzer proposal cycles 4 and 5. We present initial results on the epoch 1 data for a region near N79 and N83. The MIPS 70 and 160 μm images of the diffuse dust emission of the N79/N83 region reveal a similar distribution to the gas emissions, especially the H I 21 cm emission. The measured point-source sensitivity for the epoch 1 data is consistent with expectations for the survey. The point-source counts are highest for the IRAC 3.6 μm band and decrease dramatically toward longer wavelengths, consistent with the fact that stars dominate the point-source catalogs and the dusty objects detected at the longer wavelengths are rare in comparison. The SAGE epoch 1 point-source catalog has ~4 × 10^6 sources, and more are anticipated when the epoch 1 and 2 data are combined. Using Milky Way (MW) templates as a guide, we adopt a simplified point-source classification to identify three candidate groups—stars without dust, dusty evolved stars, and young stellar objects—that offer a starting point for this work. We outline a strategy for identifying foreground MW stars, which may comprise as much as 18% of the source list, and background galaxies, which may comprise ~12% of the source list.

Public Health Ethics: Mapping the Terrain

Abstract: , 30 (2002): 170 –178.© 2002 by the American Society of Law, Medicine & Ethics.ublic health ethics, like the field of public health itaddresses, traditionally has focused more on practiceand particular cases than on theory, with the resultthat some concepts, methods, and boundaries remain largelyundefined. This paper attempts to provide a rough concep-tual map of the terrain of public health ethics. We begin bybriefly defining public health and identifying general fea-tures of the field that are particularly relevant for a discussionof public health ethics.Public health is primarily concerned with the health ofthe entire population, rather than the health of individuals.Its features include an emphasis on the promotion of healthand the prevention of disease and disability; the collectionand use of epidemiological data, population surveillance,and other forms of empirical quantitative assessment; a rec-ognition of the multidimensional nature of the determinantsof health; and a focus on the complex interactions of manyfactors — biological, behavioral, social, and environmental— in developing effective interventions.How can we distinguish public health from medicine?While medicine focuses on the treatment and cure of indi-vidual patients, public health aims to understand andameliorate the causes of disease and disability in a popula-tion. In addition, whereas the physician-patient relationshipis at the center of medicine, public health involves interac-tions and relationships among many professionals andmembers of the community as well as agencies of govern-ment in the development, implementation, and assessmentof interventions. From this starting point, we can suggestthat public health systems consist of all the people and ac-tions, including laws, policies, practices, and activities, thathave the primary purpose of protecting and improving thehealth of the public.

Pipeline persistence: Examining the association of educational experiences with earned degrees in STEM among U.S. students

Abstract: As the global economic crisis continues, sustaining the United States' position as a leader in research and development is a top concern of policy makers. Looking to increase the number of students pursuing degrees in STEM (science, technology, engineering, and mathematics), calls for improved mathematics and science education abound. We completed a two-part analysis to assess the school-based factors related to students choosing to complete a major in STEM. The results indicate that the majority of students who concentrate in STEM make that choice during high school, and that choice is related to a growing interest in mathematics and science rather than enrollment or achievement. These results indicate that the current policy focus on advanced-level course taking and achievement as measures to increase the flow of students into STEM may be misguided. © 2011 Wiley Periodicals, Inc. Sci Ed95:877–907, 2011