Involvement of chromatin and histone deacetylation in SV40 T antigen transcription regulation

Simian Virus 40 (SV40) large T antigen (T Ag) is a multifunctional viral oncoprotein that regulates viral and cellular transcriptional activity. However, the mechanisms by which such regulation occurs remain unclear. Here we show that T antigen represses CBP-mediated transcriptional activity. This repression is concomitant with histone H3 deacetylation and is TSA sensitive. Moreover, our results demonstrate that T antigen interacts with HDAC1 in vitro in an Rb-independent manner. In addition, the overexpression of HDAC1 cooperates with T antigen to antagonize CBP transactivation function and correlates with chromatin deacetylation of the TK promoter. Finally, decreasing HDAC1 levels with small interfering RNA (siRNA) partially abolishes T antigen-induced repression. These findings highlight the importance of the histone acetylation/deacetylation balance in the cellular transformation mediated by oncoviral proteins

Dementia and guardianship: challenges in social work practice in a health care setting

This thesis critically examines social work practice in complex and disputed situations where an alternative legal decision-maker is perceived as necessary for a person with dementia. Australia has unique adult guardianship legislation and social workers are actively engaged in the process in a variety of ways, such as weighing the benefits against the possible harm and lodging applications. Yet within the profession this is an area where there is very little research. The purpose of this study is therefore to enable social workers to better understand the dynamics involved in adult guardianship proceedings for a person with dementia and provide knowledge that can be used for more effective practice. The theoretical approach is to use perspectives from social constructionism, with the links which can be made to modernism and postmodernism being taken into account. Five research case studies were investigated drawing from the caseload of social workers in an aged care service at a large metropolitan hospital in Australia. A thematic network analysis of the findings showed that the research case studies are constantly evolving, where different players participate by bringing their own perspectives, and in this process alliances are formed which reflect underlying dynamics of power. There are many diverse and contested issues, such as varied understandings of dementia and capacity and differing constructions of the notions of risk, protection and responsibility. The implications for social work practice are that in a contemporary health and welfare context social work is well placed to make an important contribution through its traditional roles of negotiation, interpretation and mediation between those who have discursive rights and those who do not

Biochemical markers of bone turnover and clinical outcome in patients with renal cell and bladder carcinoma with bone metastases following treatment with zoledronic acid: The TUGAMO study

Background: Levels of bone turnover markers (BTM) might be correlated with outcome in terms of skeletal-related events (SRE), disease progression, and death in patients with bladder cancer (BC) and renal cell carcinoma (RCC) with bone metastases (BM). We try to evaluate this possible correlation in patients who receive treatment with zoledronic acid (ZOL). Methods: This observational, prospective, and multicenter study analysed BTM and clinical outcome in these patients. Serum levels of bone alkaline phosphatase (BALP), procollagen type I amino-terminal propeptide (PINP), and beta-isomer of carboxyterminal telopeptide of type I collagen (b-CTX) were analysed. Results: Patients with RCC who died or progressed had higher baseline b-CTX levels and those who experienced SRE during follow-up showed high baseline BALP levels. In BC, a poor rate of survival was related with high baseline b-CTX and BALP levels, and new SRE with increased PINP levels. Cox univariate analysis showed that b-CTX levels were associated with higher mortality and disease progression in RCC and higher mortality in BC. Bone alkaline phosphatase was associated with increased risk of premature SRE appearance in RCC and death in BC. Conclusion: Beta-isomer of carboxy-terminal telopeptide of type I collagen and BALP can be considered a complementary tool for prediction of clinical outcomes in patients with BC and RCC with BM treated with ZOLNovartis Oncology Spain for supporting this stud

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum