ARID3B: A novel regulator of the Kaposi's sarcoma-associated herpesvirus lytic cycle

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of commonly fatal malignancies of immunocompromised individuals, including primary effusion lymphoma (PEL) and Kaposi's sarcoma (KS). A hallmark of all herpesviruses is their biphasic life cycle—viral latency and the productive lytic cycle—and it is well established that reactivation of the KSHV lytic cycle is associated with KS pathogenesis. Therefore, a thorough appreciation of the mechanisms that govern reactivation is required to better understand disease progression. The viral protein replication and transcription activator (RTA) is the KSHV lytic switch protein due to its ability to drive the expression of various lytic genes, leading to reactivation of the entire lytic cycle. While the mechanisms for activating lytic gene expression have received much attention, how RTA impacts cellular function is less well understood. To address this, we developed a cell line with doxycycline-inducible RTA expression and applied stable isotope labeling of amino acids in cell culture (SILAC)-based quantitative proteomics. Using this methodology, we have identified a novel cellular protein (AT-rich interacting domain containing 3B [ARID3B]) whose expression was enhanced by RTA and that relocalized to replication compartments upon lytic reactivation. We also show that small interfering RNA (siRNA) knockdown or overexpression of ARID3B led to an enhancement or inhibition of lytic reactivation, respectively. Furthermore, DNA affinity and chromatin immunoprecipitation assays demonstrated that ARID3B specifically interacts with A/T-rich elements in the KSHV origin of lytic replication (oriLyt), and this was dependent on lytic cycle reactivation. Therefore, we have identified a novel cellular protein whose expression is enhanced by KSHV RTA with the ability to inhibit KSHV reactivation

Systematic Review and Meta-analysis of Long-term survival After Elective Infrarenal Abdominal Aortic Aneurysm Repair 1969-2011: 5 Year Survival Remains Poor Despite Advances in Medical Care and Treatment Strategies.

BACKGROUND: Improved critical care, pre-operative optimization, and the advent of endovascular surgery (EVAR) have improved 30 day mortality for elective abdominal aortic aneurysm (AAA) repair. It remains unknown whether this has translated into improvements in long-term survival, particularly because these factors have also encouraged the treatment of older patients with greater comorbidity. The aim of this study was to quantify how 5 year survival after elective AAA repair has changed over time. METHODS: A systematic review was performed identifying studies reporting 5 year survival after elective infrarenal AAA repair. An electronic search of the Embase and Medline databases was conducted to January 2014. Thirty-six studies, 60 study arms, and 107,814 patients were identified. Meta-analyses were conducted to determine 5 year survival and to report whether 5 year survival changed over time. RESULTS: Five-year survival was 69% (95% CI 67 to 71%, I(2) = 87%). Meta-regression on study midpoint showed no improvement in 5 year survival over the period 1969-2011 (log OR -0.001, 95% CI -0.014-0.012). Larger average aneurysm diameter was associated with poorer 5 year survival (adjusted log OR -0.058, 95% CI -0.095 to -0.021, I(2) = 85%). Older average patient age at surgery was associated with poorer 5 year survival (adjusted log OR -0.118, 95% CI -0.142 to -0.094, I(2) = 70%). After adjusting for average patient age, an improvement in 5 year survival over the period that these data spanned was obtained (adjusted log OR 0.027, 95% CI 0.012 to 0.042). CONCLUSION: Five-year survival remains poor after elective AAA repair despite advances in short-term outcomes and is associated with AAA diameter and patient age at the time of surgery. Age-adjusted survival appears to have improved; however, this cohort as a whole continues to have poor long-term survival. Research in this field should attempt to improve the life expectancy of patients with repaired AAA and to optimise patient selection

Multi-modal hydrogel-based platform to deliver and monitor cardiac progenitor/stem cell engraftment

Retention and survival of transplanted cells are major limitations to the efficacy of regenerative medicine, with short-term paracrine signals being the principal mechanism underlying current cell therapies for heart repair. Consequently, even improvements in short-term durability may have a potential impact on cardiac cell grafting. We have developed a multimodal hydrogel-based platform comprised of a poly(ethylene glycol) network cross-linked with bioactive peptides functionalized with Gd(III) in order to monitor the localization and retention of the hydrogel in vivo by magnetic resonance imaging. In this study, we have tailored the material for cardiac applications through the inclusion of a heparin-binding peptide (HBP) sequence in the cross-linker design and formulated the gel to display mechanical properties resembling those of cardiac tissue. Luciferase-expressing cardiac stem cells (CSC-Luc2) encapsulated within these gels maintained their metabolic activity for up to 14 days in vitro. Encapsulation in the HBP hydrogels improved CSC-Luc2 retention in the mouse myocardium and hind limbs at 3 days by 6.5- and 12- fold, respectively. Thus, this novel heparin-binding based, Gd(III)-tagged hydrogel and CSC-Luc2 platform system demonstrates a tailored, in vivo detectable theranostic cell delivery system that can be implemented to monitor and assess the transplanted material and cell retention

Re-presenting the Paralympics: (contested) philosophies, production practices and the hypervisibility of disability

Studies that have engaged para-sport broadcasting, particularly through a narrative lens, have almost exclusively relied on textual and/or content analysis of the Paralympic Games as the source of cultural critique. We know far less about the decisions taken inside Paralympic broadcasters that have led to such representations. In this study – based on interviews with senior production and promotion staff at the UK’s Paralympic broadcaster, Channel 4 – we provide the first detailed examination of mediated para-sport from this vantage point. We explore the use of promotional devices such as athletes’ backstories – the “Hollywood treatment” – to both hook audiences and serve as a vehicle for achieving its social enterprise mandate to change public attitudes toward disability. In so doing, we reveal myriad tensions that coalesce around representing the Paralympics; with respect to the efforts made to balance the competing goals of key stakeholders and a stated desire to make the Paralympics both a commercial and socially progressive success

Understanding the impact of legislation on 'reduction of disease risk' claims on food and drinks: The REDICLAIM project

The Nutrition and Health Claims Regulation (EC No. 1924/2006) has established a common framework for the regulation of nutrition and health claims used on foods across the European Union. This regulation aims to provide the European food industry opportunities for product innovation whilst protecting consumer interests with respect to controlling misleading advertising and promoting public health. However, in order to satisfy the approval of new health claims procedure particularly for new 'reduction of disease risk' claims [Article 14(1)(a) claims], significant research activity is required by industry to scientifically substantiate the claims they wish to make. There is a need to establish whether the implementation of this legislation is in fact driving product innovation and the development of healthy foods or whether it forms a barrier to such developments. The EU-funded REDICLAIM project is currently considering these issues. This article describes the project's preliminary results and outlines the further programme of work

Neural correlates of enhanced visual short-term memory for angry faces: An fMRI study

Copyright: © 2008 Jackson et al.Background: Fluid and effective social communication requires that both face identity and emotional expression information are encoded and maintained in visual short-term memory (VSTM) to enable a coherent, ongoing picture of the world and its players. This appears to be of particular evolutionary importance when confronted with potentially threatening displays of emotion - previous research has shown better VSTM for angry versus happy or neutral face identities.Methodology/Principal Findings: Using functional magnetic resonance imaging, here we investigated the neural correlates of this angry face benefit in VSTM. Participants were shown between one and four to-be-remembered angry, happy, or neutral faces, and after a short retention delay they stated whether a single probe face had been present or not in the previous display. All faces in any one display expressed the same emotion, and the task required memory for face identity. We find enhanced VSTM for angry face identities and describe the right hemisphere brain network underpinning this effect, which involves the globus pallidus, superior temporal sulcus, and frontal lobe. Increased activity in the globus pallidus was significantly correlated with the angry benefit in VSTM. Areas modulated by emotion were distinct from those modulated by memory load.Conclusions/Significance: Our results provide evidence for a key role of the basal ganglia as an interface between emotion and cognition, supported by a frontal, temporal, and occipital network.The authors were supported by a Wellcome Trust grant (grant number 077185/Z/05/Z) and by BBSRC (UK) grant BBS/B/16178

Schistosomiasis and Urinary Bladder Cancer in North Western Tanzania: A Retrospective Review of 185 Patients.

Worldwide, cancers of the urinary bladder are well known to be associated with environmental chemical carcinogens such as smoking and occupational exposure to polycyclic aromatic hydrocarbons. These cancers are typically transitional cell carcinoma (urothelial carcinoma). In areas where schistosomiasis is endemic there is a high incidence of squamous cell carcinoma of the urinary bladder. Schistosomiasis causes chronic granulomatous cystitis leading to squamous metaplasia of transitional epithelium, and subsequently development of squamous cell carcinoma. The western part of Tanzania on the shores of Lake Victoria is such an endemic area. This study was done to document the burden of urinary bladder cancer associated with schistosomiasis in this region. This was a descriptive retrospective study of histologically confirmed cases of urinary bladder cancer seen at the Department of Pathology Bugando Medical Centre (BMC) over a period of 10 years. Data were retrieved from the records of the Departments of Pathology, Medical Records and Surgery. Data were analyzed by the use of contingency tables. A total of 185 patients were diagnosed with cancer of the urinary bladder during the study period, where as 90 (48.6%) were males and 95 (51.4) were females. The mean age at diagnosis was 54.3 years. Squamous cell carcinoma was the most frequent histological type (55.1%), followed by conventional transitional cell carcinoma (40.5%). Eighty three of all cancer cases (44.9%) were found to have schistosomal eggs. Schistosomiasis was commonly associated with squamous cancers compared to non squamous cancers. Most of the cancers associated with schistosomiasis had invaded the muscularis propria of the urinary bladder at the time of diagnosis (p<0.001) and such cancers were frequent below 50 years of age with a significant statistical difference (p<0.001). Poorly differentiated tumors were more frequent in females than males with a significant statistical difference (p=0.006). The majority of urinary bladder cancers seen in the Lake Region were squamous cell carcinoma associated with schistosomiasis. These cancers showed an aggressive behavior and were commonly seen in the younger age groups. Effective control of schistosomiasis in this region should significantly reduce the burden of urinary bladder cancer

Belowground DNA-based techniques: untangling the network of plant root interactions

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