Existing regulatory circuitries govern backbone and acquired host association factors in the human pathogen Vibrio parahaemolyticus

Vibrio parahaemolyticus is a poorly characterized human gastrointestinal pathogen whose virulence mechanisms are not well understood. Though closely related to Vibrio cholerae, V. parahaemolyticus infections are inflammatory and utilize virulence traits that are unique from the Cholera toxins yet remain poorly characterized. Vibrio spp. in general share an extensive core genome dedicated to environmental survival and unique, often horizontally acquired, gene content that is reserved for species specific lifestyles. This diversity has resulted in a genus of highly specialized bacteria partaking in dramatically different lifestyles ranging from symbiosis to pathogenesis. We propose that a comparative genomic and transcriptomic analysis of a conserved host association regulon (GacA) in the closely related V. fischeri (symbiont) and V. parahaemolyticus (pathogen), to exploit key lifestyle differences will expose genes that are unique to pathogenesis. In this study we identified a small, core regulon that is GacA activated comprised mostly of genes involved in central metabolism. Unique gene content in the V. parahaemolyticus GacA regulon contained both backbone and horizontally acquired elements that were activated or repressed in a highly selective fashion. Temperature was an important cue in virulence gene activation as determined through phenotypic and transcriptional assays and acted with GacA in an additive fashion. Specifically, expression of the classic virulence marker tdh was enhanced in a GacA mutant at 37°C; however the mutant was defective at initiating an infection in mice potentially discounting the relevance of TDH in disease. Though TDH is currently accepted as a clinical identifier, further work may be necessary to confirm a genuine correlation with disease causing strains. In addition, comparative genomics revealed a significant reorganization of the GacA regulon in V. parahaemolyticus suggesting that its control has been uncoupled from quorum sensing circuitry unlike in other characterized regulons. The GacA regulon of V. parahaemolyticus has undergone subtle regulatory changes resulting in GacA repression of select horizontally acquired elements and may serve as an ideal model of the evolution of regulatory networks and the emergence of novel virulence mechanisms

The relationship of individual comorbid chronic conditions to diabetes care quality.

ObjectiveMultimorbidity affects 26 million persons with diabetes, and care for comorbid chronic conditions may impact diabetes care quality. The aim of this study was to determine which chronic conditions were related to lack of achievement or achievement of diabetes care quality goals to determine potential targets for future interventions.Research design and methodsThis is an exploratory retrospective analysis of electronic health record data for 23 430 adults, aged 18-75, with diabetes who were seen at seven Midwestern US health systems. The main outcome measures were achievement of six diabetes quality metrics in the reporting year, 2011 (glycated haemoglobin (HbA1c) control and testing, low-density lipoprotein control and testing, blood pressure control, kidney testing). Explanatory variables were 62 chronic condition indicators. Analyses were adjusted for baseline patient sociodemographic and healthcare utilization factors.ResultsThe 62 chronic conditions varied in their relationships to diabetes care goal achievement for specific care goals. Congestive heart failure was related to lack of achievement of cholesterol management goals. Obesity was related to lack of HbA1c and BP control. Mental health conditions were related to both lack of achievement and achievement of different care goals. Three conditions were related to lack of cholesterol testing, including congestive heart failure and substance-use disorders. Of 17 conditions related to achieving control goals, 16 were related to achieving HbA1c control. One-half of the comorbid conditions did not predict diabetes care quality.ConclusionsFuture interventions could target patients at risk for not achieving diabetes care for specific care goals based on their individual comorbidities

Intellectual Property Management in Health and Agricultural Innovation: Executive Guide

Prepared by and for policy-makers, leaders of public sector research establishments, technology transfer professionals, licensing executives, and scientists, this online resource offers up-to-date information and strategies for utilizing the power of both intellectual property and the public domain. Emphasis is placed on advancing innovation in health and agriculture, though many of the principles outlined here are broadly applicable across technology fields. Eschewing ideological debates and general proclamations, the authors always keep their eye on the practical side of IP management. The site is based on a comprehensive Handbook and Executive Guide that provide substantive discussions and analysis of the opportunities awaiting anyone in the field who wants to put intellectual property to work. This multi-volume work contains 153 chapters on a full range of IP topics and over 50 case studies, composed by over 200 authors from North, South, East, and West. If you are a policymaker, a senior administrator, a technology transfer manager, or a scientist, we invite you to use the companion site guide available at http://www.iphandbook.org/index.html The site guide distills the key points of each IP topic covered by the Handbook into simple language and places it in the context of evolving best practices specific to your professional role within the overall picture of IP management

Intellectual Property Management in Health and Agricultural Innovation: A Handbook of Best Practices, Vol. 1

Prepared by and for policy-makers, leaders of public sector research establishments, technology transfer professionals, licensing executives, and scientists, this online resource offers up-to-date information and strategies for utilizing the power of both intellectual property and the public domain. Emphasis is placed on advancing innovation in health and agriculture, though many of the principles outlined here are broadly applicable across technology fields. Eschewing ideological debates and general proclamations, the authors always keep their eye on the practical side of IP management. The site is based on a comprehensive Handbook and Executive Guide that provide substantive discussions and analysis of the opportunities awaiting anyone in the field who wants to put intellectual property to work. This multi-volume work contains 153 chapters on a full range of IP topics and over 50 case studies, composed by over 200 authors from North, South, East, and West. If you are a policymaker, a senior administrator, a technology transfer manager, or a scientist, we invite you to use the companion site guide available at http://www.iphandbook.org/index.html The site guide distills the key points of each IP topic covered by the Handbook into simple language and places it in the context of evolving best practices specific to your professional role within the overall picture of IP management

Seeking Northlake:place, technology, and public as enabling constraints for urban transdisciplinary research

This article reviews the urban transdisciplinary research of the Northlake Collective, a multidisciplinary group of graduate students in the University of Washington's Lake Union Laboratory. Through a series of place-based investigations, we explored a small slice of Seattle ultimately seeking to engage the public through an online digital humanities portal. The broader goal of our work and this paper is to address how we, as a team of emerging scholars, understand and investigate ‘cities’ in the current century as both networked at the global scale and dynamic places for everyday interactions and processes. The paradoxes and complexity inherent to understanding the ‘city’ and how to address these concerns led us to develop a framework that might enrich grounded urban theory through the ‘enabling constraints’ of place, technology and public. The productive character of these three concepts, combined with the practical constraints and interrelationships they bring to bear, allowed us to deepen our work and produced the context for our research of Northlake. We propose this tripartite framework for exploring the contemporary city via the structure afforded by transdisciplinary, born-digital collaborations

Degradation of cognitive timing mechanisms in behavioural variant frontotemporal dementia.

The current study examined motor timing in frontotemporal dementia (FTD), which manifests as progressive deterioration in social, behavioural and cognitive functions. Twenty-patients fulfilling consensus clinical criteria for behavioural variant FTD (bvFTD), 11 patients fulfilling consensus clinical criteria for semantic-variant primary progressive aphasia (svPPA), four patients fulfilling criteria for nonfluent/agrammatic primary progressive aphasia (naPPA), eight patients fulfilling criteria for Alzheimer׳s disease (AD), and 31 controls were assessed on both an externally- and self-paced finger-tapping task requiring maintenance of a regular, 1500 ms beat over 50 taps. Grey and white matter correlates of deficits in motor timing were examined using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI). bvFTD patients exhibited significant deficits in aspects of both externally- and self-paced tapping. Increased mean inter-response interval (faster than target tap time) in the self-paced task was associated with reduced grey matter volume in the cerebellum bilaterally, right middle temporal gyrus, and with increased axial diffusivity in the right superior longitudinal fasciculus, regions and tracts which have been suggested to be involved in a subcortical-cortical network of structures underlying timing abilities. This suggests that such structures can be affected in bvFTD, and that impaired motor timing may underlie some characteristics of the bvFTD phenotype

Archaeology of the Planned Location of the Toyota Motor Manufacturing Plant, San Antonio, Bexar County, Texas

From October 2002 to January 2004, the Center for Archaeological Research (CAR) of The University of Texas at San Antonio conducted archaeological investigations for the City of San Antonio in a 2,570.25-acre project area that is the future site of the San Antonio Toyota Motor Manufacturing Plant. The work was conducted under Texas Antiquities Permit No. 2982 with Dr. Steve A. Tomka, CAR Director, serving as Principal Investigator. The project included the reconnaissance of over 500 acres of the project area, the excavation of 376 shovel tests, 250 mechanical auger borings, and 42 backhoe and Gradall trenches. The backhoe and Gradall trenches were dug for geoarchaeological investigations and in one instance to search for a presumed historic cemetery. Reassessment for National Register of Historic Places and State Archeological Landmark status was conducted for 16 previously documented archaeological sites (41BX125, 41BX349, 41BX652, 41BX653, 41BX654, 41BX655, 41BX656, 41BX657, 41BX658, 41BX659, 41BX660, 41BX661, 41BX662, 41BX676, 41BX681, and 41BX832) and five newly identified sites (41BX1571–41BX1575). Of the 21 sites examined during this project, 12 are prehistoric, seven are historic and two have both prehistoric and historic components. The prehistoric sites are lithic and burned rock scatters, possibly the remnants of campsites. Diagnostic artifacts found in previous surveys indicate Archaic and Late Prehistoric time frames. The historic sites present are farmstead-ranch complexes including residential structures and outbuildings. Also encountered were tenant farmer residences and a small brick kiln. The historic components are primarily late-nineteenth and early-twentieth-century, although original surveys noted early-nineteenth-century artifacts. All artifacts collected are curated at the Center for Archaeological Research laboratory facility