Consequence Management Assessment Method Synthesis for Combatant Commands

One of the most important roles that the US fulfills in the global war on terror and their integration with Partner Nations (PNs) is minimizing the threats and effects  of weapons of mass destruction (WMD) as well as Chemical, Biological, Radiological, Nuclear and Explosive (CBRNE) attacks by enemy nations, rogue elements, or terrorist groups around the world. The Defense Threat Reduction Agency (DTRA) currently implements an assessment framework for determining a PN’s state of CBRNE readiness, but it is unable to conceptualize that assessment at a regional or Combatant Command (CCMD) level. This research uses the Systems Decision Process (SDP) to create an assessment metric that is capable of synchronizing PN CBRNE readiness across a CCMD into a single assessment. This research is focused on developing an effective and flexible Microsoft Access database, which evaluates all global PNs across a wide array of metrics and then synthesizes them through multi-purpose objectives in order to develop an encompassing assessment framework at the CCMD level

Dormant bacteria within Staphylococcus epidermidis biofilms have low inflammatory properties and maintain tolerance to vancomycin and penicillin after entering planktonic growth

Staphylococcus epidermidis is the most commonly isolated etiological agent of nosocomial infections mainly due to its ability to establish biofilms on indwelling medical devices. Detachment of bacteria from S. epidermidis biofilms and subsequent growth in the planktonic form is a hallmark in the pathogenesis of these infections leading to dissemination. Here we showed that S. epidermidis cells collected from biofilms cultured in conditions that promote cell viability present marked changes in their physiological status upon initiating a planktonic mode of growth. When compared to cells growing in biofilms, they displayed an increased SYBR green I staining intensity, increased transcription of the rpiA gene, decreased transcription of icaA gene as well as higher susceptibility to vancomycin and penicillin antibiotics. When bacteria collected from biofilms with high proportions of dormant cells were subsequently cultured in the planktonic mode, a large proportion of cells maintained a low SYBR staining intensity and increased resistance to vancomycin and penicillin, a profile typical of dormant cells. This phenotype further associated with a decreased ability of these biofilm-derived cells to induce the production of pro-inflammatory cytokines by bone marrow-derived dendritic cells in vitro, as determined by pro-inflammatory cytokine quantification. These results demonstrated that cells detached from the biofilm maintain a dormant cell-like phenotype, having a low pro-inflammatory effect and decreased susceptibility to antibiotics suggesting these cells may contribute for the recalcitrant nature of biofilm infections.This work was funded by Fundacao para a Ciencia e a Tecnologia (FCT) and COMPETE grants PTDC/BIA-MIC/113450/2009 and FCOMP-01-0124-FEDER-014309. Filipe Cerca, Angela Franca and Virginia Carvalhais were funded by FCT fellowships SFRH/BD/27638/2006, SFRH/BD/62359/2009 and SFRH/BD/78235/2011, respectively. Parts of the work were also supported by National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID) grants AI46706 and AI057159, a component of award number U54 AI057159. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. The authors acknowledge the technical assistance of Encarnacao Rebelo

Phosphorylation of the actin binding protein Drebrin at S647 and is regulated by neuronal activity and PTEN

Defects in actin dynamics affect activity-dependent modulation of synaptic transmission and neuronal plasticity, and can cause cognitive impairment. A salient candidate actin-binding protein linking synaptic dysfunction to cognitive deficits is Drebrin (DBN). However, the specific mode of how DBN is regulated at the central synapse is largely unknown. In this study we identify and characterize the interaction of the PTEN tumor suppressor with DBN. Our results demonstrate that PTEN binds DBN and that this interaction results in the dephosphorylation of a site present in the DBN C-terminus - serine 647. PTEN and pS647-DBN segregate into distinct and complimentary compartments in neurons, supporting the idea that PTEN negatively regulates DBN phosphorylation at this site. We further demonstrate that neuronal activity increases phosphorylation of DBN at S647 in hippocampal neurons in vitro and in ex vivo hippocampus slices exhibiting seizure activity, potentially by inducing rapid dissociation of the PTEN:DBN complex. Our results identify a novel mechanism by which PTEN is required to maintain DBN phosphorylation at dynamic range and signifies an unusual regulation of an actin-binding protein linked to cognitive decline and degenerative conditions at the CNS synapse