Effects of individual Orsay virus proteins on the Intracellular Pathogen Response of C. elegans

In order to cause infection, pathogens must avoid destruction by the host immune system. However, how pathogens evolved to evade host immunity is not fully understood. Mammals have two systems of immunity, innate and adaptive, which are regulated by complex interactions between the two systems. In order to study innate immunity exclusively, the roundworm C. elegans is a useful invertebrate model because it lacks adaptive immunity and the complexities that arise from interactions between the two types of immunity. The goal of this project is to investigate whether the individual expression of the Orsay virus capsid and delta-fusion proteins can suppress the Intracellular Pathogen Response (IPR) in C. elegans. The IPR is an innate immune response activated by the Orsay virus. To investigate the effects of the viral proteins on the IPR, molecular cloning will be used to construct plasmids that will be microinjected into C. elegans, creating transgenic animals that overexpress each of the two Orsay proteins. We will then test the animals to observe the individual effects of the capsid protein and delta-fusion protein on IPR suppression. From this we will better understand how viruses evolved to evade the host immune system

Identifying Novel Triggers of the Intracellular Pathogen Response (IPR) in C. elegans

The intracellular pathogen response (IPR) is a cell signaling pathway found in C. elegans that is triggered when pathogenic microorganisms invade, and immune responses attempt to eliminate the threat. Due to the relative simplicity of C. elegans, they are an excellent model organism to analyze the cell signaling pathways triggered by various pathogens. They lack the complex immune systems of larger organisms, making it easier to study the involved cell signaling pathways. Past studies have shown that the IPR can also be triggered via intestinal wounding. Heat stress, viral infection, and proteasome stress are all known triggers of the IPR. The long-term goal of this project is to generate potential new triggers, the response of which will be compared to the response generated by known triggers. The IPR will be quantified by measuring nanoluciferase expression, which is driven by an IPR gene. The immediate goal of this project is to develop this nanoluciferase assay system to generate IPR activity data in a high-throughput fashion. We hope to eventually be able to relate our findings to similar pathways in humans and other vertebrates. While humans do not have the IPR that is found in C. elegans, they have similar pathways that perform equivalent functions. In particular, we are interested in how intestinal damage could be related to activation of innate immunity. This information could be used to gain a better understanding of gastrointestinal diseases, specifically inflammatory bowel diseases

Evaluation of the impact of distributed synchronous generation on the stochastic estimation of financial costs of voltage sags

Abstract: Power system faults can cause voltage sags that, if they are less than voltage sensitivity threshold of equipment, can lead to interruption of supply and lead to incurring of financial losses. The impact of distributed generation (DG) on these financial losses is investigated in this work. Using the method of fault positions, a stochastic approach to determine voltage sag performance, profiles of magnitudes of remaining voltages at a monitoring point for faults occurring along lines in the network is developed. It follows that an expected number of critical voltage sags at a monitoring point is calculated and the expected cost of these sags is derived for various voltage sensitivity threshold limits. An illustrative study is carried out comparing the expected costs of voltage sags for a network without DG with a DG case, for various mixes of customers. It is shown that in the presence of DG, the expected costs of voltage sags are lesser for all voltage sensitivity criteria assumed and for all customer mixes. The study demonstrates that the impact of incorporating DG sources results in a reduction in the expected cost of voltage sags

The impact of a sugar-sweetened beverages tax on oral health and costs of dental care in Australia

Despite a clear causal link between frequent consumption of sugar-sweetened beverages (SSBs) and dental disease, little is known about the implications of a tax on SSBs in the context of oral health. The aim of our study was to estimate the impacts of a SSB tax on the Australian population in the context of oral health outcomes, dental care utilisation and associated costs. We designed a cohort model that accounted for the consequences of the tax through the mechanisms of consumer response to price increase, the effect on oral health due to change in sugar intake, and the implications for dental care use. Our results indicate that in the adult population an ad valorem tax of 20% would lead to a reduction in decayed, missing and filled teeth (DMFT) by 3.9 million units over 10 years, resulting in cost savings of A$666 million. Scenario analyses show that the outcomes are sensitive to the choice of the time horizon, tax rate, price elasticity of demand for SSBs, and the definition of target population. We found that the total and per-person consequences of SSB tax were considerable, both in terms of dental caries (tooth decay) averted and dental care avoided. These results have to be compounded with the implications of SSB tax for other aspects of health and health care, especially in the context of chronic diseases. On the other hand, the improved outcomes have to be weighted against a welfare loss associated with introducing a tax

Predictors of depression recovery in HIV-infected individuals managed through measurement-based care in infectious disease clinics

Treatment of comorbid chronic disease, such as depression, in people living with HIV/AIDS (PLWHA) increasingly falls to HIV treatment providers. Guidance in who will best respond to depression treatment and which patient-centered symptoms are best to target is limited

How to Alleviate Cardiac Injury From Electric Shocks at the Cellular Level

Electric shocks, the only effective therapy for ventricular fibrillation, also electroporate cardiac cells and contribute to the high-mortality post-cardiac arrest syndrome. Copolymers such as Poloxamer 188 (P188) are known to preserve the membrane integrity and viability of electroporated cells, but their utility against cardiac injury from cardiopulmonary resuscitation (CPR) remains to be established. We studied the time course of cell killing, mechanisms of cell death, and protection with P188 in AC16 human cardiomyocytes exposed to micro- or nanosecond pulsed electric field (μsPEF and nsPEF) shocks. A 3D printer was customized with an electrode holder to precisely position electrodes orthogonal to a cell monolayer in a nanofiber multiwell plate. Trains of nsPEF shocks (200, 300-ns pulses at 1.74 kV) or μsPEF shocks (20, 100-μs pulses at 300 V) produced a non-uniform electric field enabling efficient measurements of the lethal effect in a wide range of the electric field strength. Cell viability and caspase 3/7 expression were measured by fluorescent microscopy 2–24 h after the treatment. nsPEF shocks caused little or no caspase 3/7 activation; most of the lethally injured cells were permeable to propidium dye already at 2 h after the exposure. In contrast, μsPEF shocks caused strong activation of caspase 3/7 at 2 h and the number of dead cells grew up to 24 h, indicating the prevalence of the apoptotic death pathway. P188 at 0.2–1% reduced cell death, suggesting its potential utility in vivo to alleviate electric injury from defibrillation