Modulation of intracellular ROS levels by TIGAR controls autophagy

The p53-inducible TIGAR protein functions as a fructose-2,6-bisphosphatase, promoting the pentose phosphate pathway and helping to lower intracellular reactive oxygen species (ROS). ROS functions in the regulation of many cellular responses, including autophagy—a response to stress conditions such as nutrient starvation and metabolic stress. In this study, we show that TIGAR can modulate ROS in response to nutrient starvation or metabolic stress, and functions to inhibit autophagy. The ability of TIGAR to limit autophagy correlates strongly with the suppression of ROS, with no clear effects on the mTOR pathway, and is p53 independent. The induction of autophagy in response to loss of TIGAR can function to moderate apoptotic response by restraining ROS levels. These results reveal a complex interplay in the regulation of ROS, autophagy and apoptosis in response to TIGAR expression, and shows that proteins similar to TIGAR that regulate glycolysis can have a profound effect on the autophagic response through ROS regulation

Local Spatial and Temporal Processes of Influenza in Pennsylvania, USA: 2003–2009

Background: Influenza is a contagious respiratory disease responsible for annual seasonal epidemics in temperate climates. An understanding of how influenza spreads geographically and temporally within regions could result in improved public health prevention programs. The purpose of this study was to summarize the spatial and temporal spread of influenza using data obtained from the Pennsylvania Department of Health's influenza surveillance system. Methodology and Findings: We evaluated the spatial and temporal patterns of laboratory-confirmed influenza cases in Pennsylvania, United States from six influenza seasons (2003-2009). Using a test of spatial autocorrelation, local clusters of elevated risk were identified in the South Central region of the state. Multivariable logistic regression indicated that lower monthly precipitation levels during the influenza season (OR = 0.52, 95% CI: 0.28, 0.94), fewer residents over age 64 (OR = 0.27, 95% CI: 0.10, 0.73) and fewer residents with more than a high school education (OR = 0.76, 95% CI: 0.61, 0.95) were significantly associated with membership in this cluster. In addition, time series analysis revealed a temporal lag in the peak timing of the influenza B epidemic compared to the influenza A epidemic. Conclusions: These findings illustrate a distinct spatial cluster of cases in the South Central region of Pennsylvania. Further examination of the regional transmission dynamics within these clusters may be useful in planning public health influenza prevention programs. © 2012 Stark et al

Outdoor particulate matter and childhood asthma admissions in Athens, Greece: a time-series study

<p>Abstract</p> <p>Background</p> <p>Particulate matter with diameter less than 10 micrometers (PM₁₀) that originates from anthropogenic activities and natural sources may settle in the bronchi and cause adverse effects possibly via oxidative stress in susceptible individuals, such as asthmatic children. This study aimed to investigate the effect of outdoor PM₁₀concentrations on childhood asthma admissions (CAA) in Athens, Greece.</p> <p>Methods</p> <p>Daily counts of CAA from the three Children's Hospitals within the greater Athens' area were obtained from the hospital records during a four-year period (2001-2004, n = 3602 children). Mean daily PM₁₀concentrations recorded by the air pollution-monitoring network of the greater Athens area were also collected. The relationship between CAA and PM₁₀concentrations was investigated using the Generalized Linear Models with Poisson distribution and logistic analysis.</p> <p>Results</p> <p>There was a statistically significant (95% CL) relationship between CAA and mean daily PM₁₀concentrations on the day of exposure (+3.8% for 10 μg/m³increase in PM₁₀concentrations), while a 1-day lag (+3.4% for 10 μg/m³increase in PM₁₀concentrations) and a 4-day lag (+4.3% for 10 μg/m³increase in PM₁₀concentrations) were observed for older asthmatic children (5-14 year-old). High mean daily PM₁₀concentration (the highest 10%; >65.69 μg/m³) doubled the risk of asthma exacerbations even in younger asthmatic children (0-4 year-old).</p> <p>Conclusions</p> <p>Our results provide evidence of the adverse effect of PM₁₀on the rates of paediatric asthma exacerbations and hospital admissions. A four-day lag effect between PM₁₀peak exposure and asthma admissions was also observed in the older age group.</p

p73 regulates autophagy and hepatocellular lipid metabolism through a transcriptional activation of the ATG5 gene

p73, a member of the p53 tumor suppressor family, is involved in neurogenesis, sensory pathways, immunity, inflammation, and tumorigenesis. How p73 is able to participate in such a broad spectrum of different biological processes is still largely unknown. Here, we report a novel role of p73 in regulating lipid metabolism by direct transactivation of the promoter of autophagy-related protein 5 (ATG5), a gene whose product is required for autophagosome formation. Following nutrient deprivation, the livers of p73-deficient mice demonstrate a massive accumulation of lipid droplets, together with a low level of autophagy, suggesting that triglyceride hydrolysis into fatty acids is blocked owing to deficient autophagy (macrolipophagy). Compared with wild-type mice, mice functionally deficient in all the p73 isoforms exhibit decreased ATG5 expression and lower levels of autophagy in multiple organs. We further show that the TAp73α is the critical p73 isoform responsible for inducing ATG5 expression in a p53-independent manner and demonstrate that ATG5 gene transfer can correct autophagy and macrolipophagy defects in p73-deficient hepatocytes. These data strongly suggest that the p73-ATG5 axis represents a novel, key pathway for regulating lipid metabolism through autophagy. The identification of p73 as a major regulator of autophagy suggests that it may have an important role in preventing or delaying disease and aging by maintaining a homeostatic control