Sbf/MTMR13 coordinates PI(3)P and Rab21 regulation in endocytic control of cellular remodeling.

Cells rely on the coordinated regulation of lipid phosphoinositides and Rab GTPases to define membrane compartment fates along distinct trafficking routes. The family of disease-related myotubularin (MTM) phosphoinositide phosphatases includes catalytically inactive members, or pseudophosphatases, with poorly understood functions. We found that Drosophila MTM pseudophosphatase Sbf coordinates both phosphatidylinositol 3-phosphate (PI(3)P) turnover and Rab21 GTPase activation in an endosomal pathway that controls macrophage remodeling. Sbf dynamically interacts with class II phosphatidylinositol 3-kinase and stably recruits Mtm to promote turnover of a PI(3)P subpool essential for endosomal trafficking. Sbf also functions as a guanine nucleotide exchange factor that promotes Rab21 GTPase activation associated with PI(3)P endosomes. Of importance, Sbf, Mtm, and Rab21 function together, along with Rab11-mediated endosomal trafficking, to control macrophage protrusion formation. This identifies Sbf as a critical coordinator of PI(3)P and Rab21 regulation, which specifies an endosomal pathway and cortical control

San Jacinto Battleground and State Historical Park: A Historical Synthesis and Archaeological Management Plan

The San Jacinto Battleground State Historical Park is located in Harris County, about 20 miles (32 kilometers) east of downtown Houston. The park is situated adjacent the San Jacinto River and about five miles (eight kilometers) northwest of where the river empties into Galveston Bay. The park is comprised of a little over 1,100 acres (hectares) that have been accumulated over the years, beginning in 1883. Management of the park has been in the hands of the Texas Parks and Wildlife Department since 1965. The adoption of a new master plan and anticipated park development underscored the need to better understand the park’s history and cultural resources. In early-2001, Texas Parks and Wildlife contracted The University of Texas at San Antonio, Center for Archaeological Research, to undertake a review and synthesis of the park’s history. The work involved an archaeological resource evaluation of the park. In addition to developing a historical synthesis, this project was also designed to utilize the available historical documents, as well as interviews, to assess the probability that buried cultural resources are present throughout the park and to make recommendations as to the need for additional archaeological work, particularly prior to ground-disturbing activities

Human platelet activation by Escherichia coli: roles for FcγRIIA and integrin αIIbβ3

Gram-negative Escherichia coli cause diseases such as sepsis and hemolytic uremic syndrome in which thrombotic disorders can be found. Direct platelet–bacterium interactions might contribute to some of these conditions; however, mechanisms of human platelet activation by E. coli leading to thrombus formation are poorly understood. While the IgG receptor FcγRIIA has a key role in platelet response to various Gram-positive species, its role in activation to Gram-negative bacteria is poorly defined. This study aimed to investigate the molecular mechanisms of human platelet activation by E. coli, including the potential role of FcγRIIA. Using light-transmission aggregometry, measurements of ATP release and tyrosine-phosphorylation, we investigated the ability of two E. coli clinical isolates to activate platelets in plasma, in the presence or absence of specific receptors and signaling inhibitors. Aggregation assays with washed platelets supplemented with IgGs were performed to evaluate the requirement of this plasma component in activation. We found a critical role for the immune receptor FcγRIIA, αIIbβ3, and Src and Syk tyrosine kinases in platelet activation in response to E. coli. IgG and αIIbβ3 engagement was required for FcγRIIA activation. Moreover, feedback mediators adenosine 5’-diphosphate (ADP) and thromboxane A₂ (TxA₂) were essential for platelet aggregation. These findings suggest that human platelet responses to E. coli isolates are similar to those induced by Gram-positive organisms. Our observations support the existence of a central FcγRIIA-mediated pathway by which human platelets respond to both Gram-negative and Gram-positive bacteria

Persistent Offenders in the North West of England, 1880-1940: Some Critical Research Questions

This article examines the concept of the persistent offender as a group within society, and the presumed impact of that discrete group upon society via a case study of offending in Crewe between 1880 and 1940. The findings of persistent offending in Crewe challenge the assumptions and prejudices of the period, about the links between unemployment and crime and the extent to which crime was an enduring ‘career’. There were no ‘hardened’ persistent offenders in the sample of the type envisaged by contemporary comment, though the role of drink in offending was sustained; and there was no clear ‘type’ of offender either. Examination of the life histories of a selection of offenders is shown to raise a number of interdisciplinary questions, challenging the assumptions of criminologists and legal scholars in relation to the role of legislation in the management of criminality, including the concept (of interest also to historians) that reformation of the criminal was more achievable in the past than it is in the overregulated present