The Epstein-Barr Virus microRNA BART11-5p\ua0targets the early B-cell transcription factor EBF1

Epstein-Barr virus (EBV) is a ubiquitous B-cell trophic herpesvirus associated with a variety of histologically diverse B-cell lymphomas, each associated with specific viral-latency gene expression programs. Initial infection drives resting B-cells to differentiate via an atypical germinal centre reaction into memory B-cells, where the virus resides in a latent state. The mechanisms that underpin this process have yet to be fully elucidated. EBV expresses more than 40 microRNAs (miRNAs). The alternatively spliced BamHI A rightward transcripts (BARTs) are the template for two large miRNA clusters (BARTs A and B), that comprise the majority of all known EBV-miRNAs. Although BART-miRNAs are abundantly expressed in all latency programs, few BART-miRNA targets have been identified and their function is poorly understood. The early B-cell factor 1 (EBF1) was identified using bioinformaticss analysis as a novel target of EBV-miRNA BART11-5p, encoded by BART cluster B. EBF1 is an important B-cell transcription factor that regulates many B-cell specific genes including Pax5, BCR and CD40 and is critical for germinal centre formation. Using luciferase reporter assays and a series of BART-constructs, we confirmed silencing via the EBF13' untranslated region (UTR) and identified the target site as 2137-2159 bp after the stop codon. Results were confirmed following transfection of a BART11-5p mimic, which was able to silence via the predicted target site. Our findings highlight a potential role of BART-miRNAs in the regulation of B-cell differentiation

DNA bending by a phantom protein

Background: Despite its stiffness, duplex DNA is extensively bent and folded during packiging and gene expression in biological systems. Modulation of the electrostatic repulsion between phosphate in the DNA backbone may be important in the bending of DNA by proteins. Here we analyze the shape of DNA molecules that have been modified chemically to mimic the electrostatic consequences of a bund proteinResults: We have simulated salt bridges between DNA phosphates and cationic amino acid sidechains of a phantom protein by tethering ammonium cations to one face of the DNA helix. Thethered ammonium cations, but not neutral acetylated controls, induced DNA to bend toward its neutralized surface.Conclusions: The shape of DNA molecules bearing a laterally-asymmetric distribution of tethered cations agrees qualitatively with theoretical predictions and with results previously obtained using neutral phosphate analogs. These data suggest principles that might be applied to the design of artificial DNA-bending proteins

Conflicting rights: How the prohibition of human trafficking and sexual exploitation infringes the right to health of female sex workers in Phnom Penh, Cambodia

While repressive laws and policies in relation to sex work have the potential to undermine HIV prevention efforts, empirical research on their interface has been lacking. In 2008, Cambodia introduced anti-trafficking legislation ostensibly designed to suppress human trafficking and sexual exploitation. Based on empirical research with female sex workers, this article examines the impact of the new law on vulnerability to HIV and other adverse health outcomes. Following the introduction of the law, sex workers reported being displaced to streets and guesthouses, impacting their ability to negotiate safe sex and increasing exposure to violence. Disruption of peer networks and associated mobility also reduced access to outreach, condoms, and health care. Our results are consistent with a growing body of research which associates the violation of sex workers’ human rights with adverse public health outcomes. Despite the successes of the last decade, Cambodia’s AIDS epidemic remains volatile and the current legal environment has the potential to undermine prevention efforts by promoting stigma and discrimination, impeding prevention uptake and coverage, and increasing infections. Legal and policy responses which seek to protect the rights of the sexually exploited should not infringe the right to health of sex workers.NIH grants: U01AI0154241, 1R21 DA025441, and 1R01NR010995 and additional funding from a Faculty Initiative grant from the Pacific Rim Research Program of the University of California. Lisa Maher is supported by a National Health and Medical Research Council Senior Research Fellowshi

Beyond a warming fingerprint: individualistic biogeographic responses to heterogeneous climate change in California.

Understanding recent biogeographic responses to climate change is fundamental for improving our predictions of likely future responses and guiding conservation planning at both local and global scales. Studies of observed biogeographic responses to 20th century climate change have principally examined effects related to ubiquitous increases in temperature - collectively termed a warming fingerprint. Although the importance of changes in other aspects of climate - particularly precipitation and water availability - is widely acknowledged from a theoretical standpoint and supported by paleontological evidence, we lack a practical understanding of how these changes interact with temperature to drive biogeographic responses. Further complicating matters, differences in life history and ecological attributes may lead species to respond differently to the same changes in climate. Here, we examine whether recent biogeographic patterns across California are consistent with a warming fingerprint. We describe how various components of climate have changed regionally in California during the 20th century and review empirical evidence of biogeographic responses to these changes, particularly elevational range shifts. Many responses to climate change do not appear to be consistent with a warming fingerprint, with downslope shifts in elevation being as common as upslope shifts across a number of taxa and many demographic and community responses being inconsistent with upslope shifts. We identify a number of potential direct and indirect mechanisms for these responses, including the influence of aspects of climate change other than temperature (e.g., the shifting seasonal balance of energy and water availability), differences in each taxon's sensitivity to climate change, trophic interactions, and land-use change. Finally, we highlight the need to move beyond a warming fingerprint in studies of biogeographic responses by considering a more multifaceted view of climate, emphasizing local-scale effects, and including a priori knowledge of relevant natural history for the taxa and regions under study

Perturbations of a Universe Filled with Dust and Radiation

A first-order perturbation approach to $k=0$ Friedmann cosmologies filled with dust and radiation is developed. Adopting the coordinate gauge comoving with the perturbed matter, and neglecting the vorticity of the radiation, a pair of coupled equations is obtained for the trace $h$ of the metric perturbations and for the velocity potential $v$. A power series solution with upwards cutoff exists such that the leading terms for large values of the dimensionless time $\xi$ agree with the relatively growing terms of the dust solution of Sachs and Wolfe.Comment: 9 pp, typeset in late

The State of Behavior Change Techniques in Virtual Reality Rehabilitation of Neurologic Populations

Background: Neurologic rehabilitation aims to restore function, address barriers to activity, and improve quality of life in those with injury to the nervous system. Virtual reality (VR) has emerged as a useful tool to enhance neurorehabilitation interventions and outcomes. However, the manner in which VR-based neurorehabilitation has been manipulated to optimize outcomes using theory-based frameworks has not been documented. Behavior Change Techniques (BCTs) are described as the smallest active ingredient in an intervention aimed to change behavior via theoretically-proposed pathways. The purpose of this review was to investigate the ways VR is being used in neurorehabilitation to improve upright mobility, and systematically code those VR interventions for active BCTs.Methods: Keyword searches were performed using database searches of PubMed, SPORTDiscus, and psycINFO. The search yielded 32 studies for inclusion. Coding for BCTs was conducted using the Behavior Change Techniques Taxonomy v1 (BCTTv1).Results: Behavioral Practice, Graded Tasks, Biofeedback, and Explicit Feedback were the most commonly used BCTs. All studies reported improvements in motor performance outcomes. However, none of the studies investigated the efficacy of each component of their VR intervention making it difficult to point to the most effective components of VR interventions overall.Conclusions: This review suggests that investigation into the specific components of VR interventions, along with purposeful implementation and reporting of BCTs will help improve understanding of the efficacy of VR as a neurorehabilitation tool. Future research could benefit from incorporating BCTs into the design process of VR interventions to produce optimal rehabilitation potential

Transcatheter Aortic Valve Implantation in Dialysis Patients

Background/Aims: Transcatheter aortic valve implantation (TAVI) has emerged as a new therapeutic option for high-risk patients. However, dialysis patients were excluded from all previous studies. The aim of this study is to compare the outcomes of TAVI for dialysis patients with those for patients with chronic kidney disease (CKD) stages 3 and 4 and to compare TAVI with open surgery in dialysis patients. Methods: Part I: comparison of 10 patients on chronic hemodialysis with 116 patients with non-dialysis-dependent CKD undergoing TAVI. Part II: comparison of transcatheter (n = 15) with open surgical (n = 24) aortic valve replacement in dialysis patients. Results: Part I: dialysis patients were significantly younger (72.3 vs. 82.0 years; p < 0.01). Hospital stay was significantly longer in dialysis patients (21.8 vs. 12.1 days; p = 0.01). Overall 30-day mortality was 3.17%, with no deaths among dialysis patients. Six-month survival rates were similar (log-rank p = 0.935). Part II: patient age was comparable (66.5 vs. 69.5 years; p = 0.42). Patients in the surgical group tended to stay longer in hospital than TAVI patients (29.5 vs. 22.5 days; p = 0.35). Conclusion: TAVI is a safe procedure in patients on chronic hemodialysis. Until new data become available, we find no compelling reason to refuse these patients TAVI. Copyright (C) 2012 S. Karger AG, Base