The HIV-1 Viral Protein R Induces Apoptosis via a Direct Effect on the Mitochondrial Permeability Transition Pore

Viral protein R (Vpr) encoded by HIV-1 is a facultative inducer of apoptosis. When added to intact cells or purified mitochondria, micromolar and submicromolar doses of synthetic Vpr cause a rapid dissipation of the mitochondrial transmembrane potential (ΔΨm), as well as the mitochondrial release of apoptogenic proteins such as cytochrome c or apoptosis inducing factor. The same structural motifs relevant for cell killing are responsible for the mitochondriotoxic effects of Vpr. Both mitochondrial and cytotoxic Vpr effects are prevented by Bcl-2, an inhibitor of the permeability transition pore complex (PTPC). Coincubation of purified organelles revealed that nuclear apoptosis is only induced by Vpr when mitochondria are present yet can be abolished by PTPC inhibitors. Vpr favors the permeabilization of artificial membranes containing the purified PTPC or defined PTPC components such as the adenine nucleotide translocator (ANT) combined with Bax. Again, this effect is prevented by addition of recombinant Bcl-2. The Vpr COOH terminus binds purified ANT, as well as a molecular complex containing ANT and the voltage-dependent anion channel (VDAC), another PTPC component. Yeast strains lacking ANT or VDAC are less susceptible to Vpr-induced killing than control cells yet recover Vpr sensitivity when retransfected with yeast ANT or human VDAC. Hence, Vpr induces apoptosis via a direct effect on the mitochondrial PTPC

Prevalence of overweight and obesity among Chinese Yi nationality: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Overweight and obesity are considered a serious health problem. There are little data on the prevalence of overweight and obesity among the Yi ethnic group in China. This study aimed to investigate the epidemiologic features of overweight/obesity among Chinese Yi nationality.</p> <p>Methods</p> <p>A cross-sectional study, including 1255 subjects aged 20-75 years, was carried out in Liangshan Yi Autonomous Prefecture of Sichuan province from 2007 to 2008. Overweight/overall obesity was defined by World Health Organization (WHO) or the Working Group on Obesity in China.</p> <p>Results</p> <p>Overall, the prevalence of overweight and obesity was 19.0% and 2.9%, respectively, based on the WHO definition, while it was 21.0% and 7.4%, respectively, according to the Working Group on Obesity in China, which is similar to data reported in the 2002 Chinese National Nutrition and Health Survey. Urban residents had a significantly higher prevalence of obesity (WHO criteria: 4.3% vs 1.7% <it>p </it>= 0.008; China criteria: 11.4% vs 3.7%, <it>p </it>< 0.001) and overweight (WHO criteria: 28.9% vs 8.9% <it>p </it>< 0.001; China criteria: 31.2% vs 10.4%, <it>p </it>< 0.001) than that in rural residents. Older age, a family history of obesity, higher income, drinking and urban residence were significantly associated with an increased risk of overweight/obesity.</p> <p>Conclusions</p> <p>The prevalence of overweight/obesity in the Yi nationality is similar to that in Chinese adults 5 years ago. However, urban residents have a much higher prevalence of overweight/obesity than their rural counterparts. Lifestyle and diet patterns associated with socioeconomic status may explain the difference between urban and rural residents. The prevention of overweight/obesity among urban inhabitants deserves more attention in national health education programs.</p

Adaptive data acquisition strategies for energy-efficient, smartphone-based, continuous processing of sensor streams

Ministry of Education, Singapore under its Academic Research Funding Tier

Control and Scheduling Joint Design

International audienceControl systems and real-time computing have for a long time been associated in control systems, with the aim of controlling a process and bringing it towards a state which complies with the objectives specified by the user. The process is often a phys- ical device, for instance mechanical (rolling mills), electromechanical (DVD player, robots), thermal (internal combustion engines), chemical (reactors), hydraulic (energy production). . . These can be complex processes associating several of these technolo- gies, for instance in terrestrial, aerial or underwater vehicles. They can also be com- puting components (scheduling of tasks, network gateway, website management) or electronic (power supply of a chip, phase locked loop), or even simulated components (avatar control in a virtual world, "hardware-in-the-loop" real-time simulators). The increasing complexity of these systems requires reviewing their properties in order to better integrate the control system design and implementation constraints executed on computing systems. The first section will recall the main properties of closed loop control as well as the constraints and limitations induced by their digital implementation. Section 1.2 examines how the control task scheduling constraints can be relaxed by exploiting these properties. The design of scheduling controllers can be performed in the formalism of sampled systems (Section 1.3), but also in that of weakly strong real-time scheduling (Section 1.4). Finally, an example of designing and implementing the scheduling control of tasks in a video decoder will be detailed in Section 1.5

Computational Models of HIV-1 Resistance to Gene Therapy Elucidate Therapy Design Principles

Gene therapy is an emerging alternative to conventional anti-HIV-1 drugs, and can potentially control the virus while alleviating major limitations of current approaches. Yet, HIV-1's ability to rapidly acquire mutations and escape therapy presents a critical challenge to any novel treatment paradigm. Viral escape is thus a key consideration in the design of any gene-based technique. We develop a computational model of HIV's evolutionary dynamics in vivo in the presence of a genetic therapy to explore the impact of therapy parameters and strategies on the development of resistance. Our model is generic and captures the properties of a broad class of gene-based agents that inhibit early stages of the viral life cycle. We highlight the differences in viral resistance dynamics between gene and standard antiretroviral therapies, and identify key factors that impact long-term viral suppression. In particular, we underscore the importance of mutationally-induced viral fitness losses in cells that are not genetically modified, as these can severely constrain the replication of resistant virus. We also propose and investigate a novel treatment strategy that leverages upon gene therapy's unique capacity to deliver different genes to distinct cell populations, and we find that such a strategy can dramatically improve efficacy when used judiciously within a certain parametric regime. Finally, we revisit a previously-suggested idea of improving clinical outcomes by boosting the proliferation of the genetically-modified cells, but we find that such an approach has mixed effects on resistance dynamics. Our results provide insights into the short- and long-term effects of gene therapy and the role of its key properties in the evolution of resistance, which can serve as guidelines for the choice and optimization of effective therapeutic agents

Introduction to Control Theory And Its Application to Computing Systems

Feedback control is central to managing computing systems and dat