Arf GAPs as Regulators of the Actin Cytoskeleton—An Update

Arf GTPase-activating proteins (Arf GAPs) control the activity of ADP-ribosylation factors (Arfs) by inducing GTP hydrolysis and participate in a diverse array of cellular functions both through mechanisms that are dependent on and independent of their Arf GAP activity. A number of these functions hinge on the remodeling of actin filaments. Accordingly, some of the effects exerted by Arf GAPs involve proteins known to engage in regulation of the actin dynamics and architecture, such as Rho family proteins and nonmuscle myosin 2. Circular dorsal ruffles (CDRs), podosomes, invadopodia, lamellipodia, stress fibers and focal adhesions are among the actin-based structures regulated by Arf GAPs. Arf GAPs are thus important actors in broad functions like adhesion and motility, as well as the specialized functions of bone resorption, neurite outgrowth, and pathogen internalization by immune cells. Arf GAPs, with their multiple protein-protein interactions, membrane-binding domains and sites for post-translational modification, are good candidates for linking the changes in actin to the membrane. The findings discussed depict a family of proteins with a critical role in regulating actin dynamics to enable proper cell function

Significant Reductions in Mortality in Hospitalized Patients with Systemic Lupus Erythematosus in Washington State from 2003 to 2011

<div><p>Background</p><p>Systemic lupus erythematosus (SLE or lupus) is an autoimmune multisystem disease. While a complete understanding of lupus’ origins, mechanisms, and progression is not yet available, a number of studies have demonstrated correlations between disease prevalence and severity, gender, and race. There have been few population based studies in the United States</p><p>Objectives</p><p>To assess temporal changes in demographics and hospital mortality of patients with lupus in Washington State from 2003 to 2011</p><p>Study Design</p><p>This study used data from the Healthcare Cost and Utilization Project (HCUP), a patient information database, and data from the Washington State census to study a group of patients in the state. Lupus hospitalizations were defined as any hospitalization with an ICD-9-CM diagnosis code for systemic lupus erythematosus. Regression analysis was used to assess the effect of calendar time on demographics and hospital outcomes.</p><p>Results</p><p>There were a total of 18,905 patients in this study with a diagnostic code for lupus. The mean age of the group was 51.5 years (95% CI: 50.6-52.3) in 2003 and 51.3 years (95% CI: 50.6-52.0) in 2011. The population was 88.6% female. Blacks were 2.8 times more likely to have a lupus hospitalization than whites when compared to the Washington population. While hospital mortality decreased during this eight year period (3.12% in 2003 to 1.28% in 2011, p=0.001) hospital length of stay remained statistically unchanged at an average of 4.9 days during that eight year period. We found a significant decrease in annual hospital mortality over the study period [odds ratio(OR): 0.92 per year, 95% CI 0.88-0.96, P<0.001]. Hospital mortality was higher in males (2.6% male death to 1.8% female death)</p><p>Conclusions</p><p>In this large group of hospitalized lupus patients in Washington, hospital length of stay remained relatively stable over time but hospital mortality decreased by over 50% over the eight year study period.</p></div

Prevalence of lupus hospitalizations in Hispanics and non-Hispanics based on Washington State population estimates, 2008 through 2011.

<p>Prevalence of lupus hospitalizations in Hispanics and non-Hispanics based on Washington State population estimates, 2008 through 2011.</p

The percentage of lupus patients hospitalized every year by gender, age category, and hospital mortality and mean length of stay in Washington State from years 2003 through 2011.

<p>The percentage of lupus patients hospitalized every year by gender, age category, and hospital mortality and mean length of stay in Washington State from years 2003 through 2011.</p

Prevalence of lupus hospitalizations by race based on Washington State population estimates, 2008 through 2011.

<p>Prevalence of lupus hospitalizations by race based on Washington State population estimates, 2008 through 2011.</p