Teaching politics after the practice turn

The ‘practice turn’ and its associated ontology, epistemology and methodology are now well established in political research. In this article, we identify and explore a corollary pedagogy. After outlining the principal components of practice theory, we compare case- and placement-based approaches to learning, designed to develop skills for use in practice. We introduce and describe our own rather different course, which we designed to develop an understanding of the nature of practice as such. We discuss its scope and dynamics, particularly with regard to power in the classroom, and identify broader opportunities and challenges for the development of practice-based pedagogy

Bacterial Phenotype Variants in Group B Streptococcal Toxic Shock Syndrome1

Variants with markedly different expression of virulence factors can arise in invasive infection in humans

Lipid analogs reveal features critical for hemolysis and diminish granadaene mediated Group B Streptococcus infection

Although certain microbial lipids are toxins, the structural features important for cytotoxicity remain unknown. Increased functional understanding is essential for developing therapeutics against toxic microbial lipids. Group B Streptococci (GBS) are bacteria associated with preterm births, stillbirths, and severe infections in neonates and adults. GBS produce a pigmented, cytotoxic lipid, known as granadaene. Despite its importance to all manifestations of GBS disease, studies towards understanding granadaene’s toxic activity are hindered by its instability and insolubility in purified form. Here, we report the synthesis and screening of lipid derivatives inspired by granadaene, which reveal features central to toxin function, namely the polyene chain length. Furthermore, we show that vaccination with a non-toxic synthetic analog confers the production of antibodies that inhibit granadaene-mediated hemolysis ex vivo and diminish GBS infection in vivo. This work provides unique structural and functional insight into granadaene and a strategy to mitigate GBS infection, which will be relevant to other toxic lipids encoded by human pathogens.This work was supported by funding from the National Institutes of Health Grants R01AI112619, R01AI133976, R01AI100989, and R21AI125907 and seed funds from Seattle Childrens Research Institute to L.

Remodeling of the Streptococcus agalactiae Transcriptome in Response to Growth Temperature

BACKGROUND: To act as a commensal bacterium and a pathogen in humans and animals, Streptococcus agalactiae (group B streptococcus, GBS) must be able to monitor and adapt to different environmental conditions. Temperature variation is a one of the most commonly encountered variables. METHODOLOGY/PRINCIPAL FINDINGS: To understand the extent to which GBS modify gene expression in response to temperatures encountered in the various hosts, we conducted a whole genome transcriptome analysis of organisms grown at 30 degrees C and 40 degrees C. We identified extensive transcriptome remodeling at various stages of growth, especially in the stationary phase (significant transcript changes occurred for 25% of the genes). A large proportion of genes involved in metabolism was up-regulated at 30 degrees C in stationary phase. Conversely, genes up-regulated at 40 degrees C relative to 30 degrees C include those encoding virulence factors such as hemolysins and extracellular secreted proteins with LPXTG motifs. Over-expression of hemolysins was linked to larger zones of hemolysis and enhanced hemolytic activity at 40 degrees C. A key theme identified by our study was that genes involved in purine metabolism and iron acquisition were significantly up-regulated at 40 degrees C. CONCLUSION/SIGNIFICANCE: Growth of GBS in vitro at different temperatures resulted in extensive remodeling of the transcriptome, including genes encoding proven and putative virulence genes. The data provide extensive new leads for molecular pathogenesis research

Group B Streptococcal β-Hemolysin/Cytolysin Directly Impairs Cardiomyocyte Viability and Function

BACKGROUND: Group B Streptococcus (GBS) is a leading cause of neonatal sepsis where myocardial dysfunction is an important contributor to poor outcome. Here we study the effects of the GBS pore-forming beta-hemolysin/cytolysin (Bh/c) exotoxin on cardiomyocyte viability, contractility, and calcium transients. METHODOLOGY/PRINCIPAL FINDINGS: HL-1 cardiomyocytes exposed to intact wild-type (WT) or isogenic Deltabeta h/c mutant GBS, or to cell-free extracts from either strain, were assessed for viability by trypan blue exclusion and for apoptosis by TUNEL staining. Functionality of exposed cardiomyocytes was analyzed by visual quantitation of the rate and extent of contractility. Mitochondrial membrane polarization was measured in TMRE-loaded cells exposed to GBS beta h/c. Effects of GBS beta h/c on calcium transients were studied in fura-2AM-loaded primary rat ventricular cardiomyocytes. Exposure of HL-1 cardiomyocytes to either WT GBS or beta h/c extracts significantly reduced both rate and extent of contractility and later induced necrotic and apoptotic cell death. No effects on cardiomyocyte viability or function were observed after treatment with Deltabeta h/c mutant bacteria or extracts. The beta h/c toxin was associated with complete and rapid loss of detectable calcium transients in primary neonatal rat ventricular cardiomyocytes and induced a loss of mitochondrial membrane polarization. These effects on viability and function were abrogated by the beta h/c inhibitor, dipalmitoyl phosphatidylcholine (DPPC). CONCLUSIONS/SIGNIFICANCE: Our data show a rapid loss of cardiomyocyte viability and function induced by GBS beta h/c, and these deleterious effects are inhibited by DPPC, a normal constituent of human pulmonary surfactant.. These findings have clinical implications for the cardiac dysfunction observed in neonatal GBS infections

Integrative neurobiology of metabolic diseases, neuroinflammation, and neurodegeneration

Alzheimer’s disease (AD) is a complex, multifactorial disease with a number of leading mechanisms, including neuroinflammation, processing of amyloid precursor protein (APP) to amyloid β peptide, tau protein hyperphosphorylation, relocalization and deposition. These mechanisms are propagated by obesity, the metabolic syndrome and type-2 diabetes mellitus. Stress, sedentariness, dietary overconsumption of saturated fat and refined sugars, and circadian derangements/disturbed sleep contribute to obesity and related metabolic diseases, but also accelerate age-related damage and senescence that all feed the risk of developing AD too. The complex and interacting mechanisms are not yet completely understood and will require further analysis. Instead of investigating AD as a mono- or oligocausal disease we should address the disease by understanding the multiple underlying mechanisms and how these interact. Future research therefore might concentrate on integrating these by systems biology approaches, but also to regard them from an evolutionary medicine point of view. The current review addresses several of these interacting mechanisms in animal models and compares them with clinical data giving an overview about our current knowledge and puts them into an integrated framework

Hierarchical Clustering for Paired Watershed Experiments: Case Study in Southeastern Arizona, U.S.A.

Watershed studies are often onerous due to a lack of data available to portray baseline conditions with which to compare results of monitoring environmental effects. A paired-watershed approach is often adopted to simulate baseline conditions in an adjacent watershed that can be comparable but assumes there is a quantifiable relationship between the control and treated watersheds. Finding suitably matched pairs that can most accurately depict similar responses is challenging and attributes are rarely quantified. In southeastern Arizona, United States, researchers are investigating the effectiveness of watershed restoration techniques employed by land managers. We selected Smith Canyon to develop a rigorous and quantitatively defensible paired-watershed experimental design. The Smith Canyon watershed consists of 91 structurally similar sub-basins that have a defined basin-like structure and flow channel, allowing for consideration as replicate units. We developed a statistical approach to group sub-basins based on similar structural, biophysical, and hydrologic traits. Our geospatial database consisted of 35 environmental variables, which we reduced to 12 through a correlation analysis. We identified three primary collections of paired sub-basins within the larger watershed. These clusters are being used to inform studies actively being employed in the watershed. Overall, we propose a hierarchical clustering protocol for justification of watershed pairing experiments

Factors involved in applicant interview selection and ranking for chronic pain medicine fellowship.

IntroductionApplicants to chronic pain medicine fellowship programs often express confusion regarding the importance of various selection criteria. This study sought to elucidate program directors' considerations in applicant selection for fellowship interviews and ranking and to correlate these criteria with match statistics to provide a guide for prospective candidates.MethodsAn electronic survey was sent to all Accreditation Council for Graduate Medical Education-accredited chronic pain fellowship directors. The importance of various applicant characteristics were evaluated and compared with recent match data.ResultsFifty-seven program directors completed the survey. The most important factors involved in applicant interview selection were perceived commitment to the specialty, letters of recommendation from pain faculty, scholarly activities, and leadership experiences. Although completion of a pain rotation was valued highly, experience with procedures was of relatively low importance. There was no preference if rotations were completed within the responders' department. Variability was noted when considering internal applicants or the applicant's geographic location. When citing main factors in ranking applicants, interpersonal skills, interview impression and applicant's fit within the institution were highly ranked by most responders.DiscussionAssessment of an applicant's commitment to chronic pain is challenging. Most responders prioritize the applicant's commitment to chronic pain as a specialty, scholarly activity, participation in chronic pain rotations, pain-related conferences and letters of recommendation from pain faculty. Chronic pain medicine fellowship candidates should establish a progressive pattern of genuine interest and involvement within the specialty during residency training to optimize their fellowship match potential