Clostridium perfringens BETA2 TOXIN: A POTENTIAL ACCESSORY TOXIN IN GASTROINTESTINAL DISEASES OF HUMANS AND DOMESTIC ANIMALS

Clostridium perfringens is a Gram-positive, anaerobic, spore-forming, rod-shaped bacterium that causes histotoxic infections and enterotoxaemias in humans and domestic animals. This bacterium owes its pathogenicity to the production of a large arsenal of toxins, including the C. perfringens enterotoxin (CPE) and beta2 toxin (CPB2). Type A, cpe-chromosomal isolates cause human food-poisoning (FP), whereas type A, cpe-plasmid isolates cause human antibiotic associated diarrhea (AAD). Symptoms of AAD are more severe and longer in duration than symptoms of FP. We hypothesized that AAD isolates may produce an accessory toxin, which would contribute to pathogenesis, as an explanation for these symptomatic differences. Consequently, the goal of this dissertation was to determine; 1) whether the recently discovered, plasmid-encoded, CPB2 toxin was produced by AAD isolates, 2) how this toxin functions in vitro, and 3) its role in vivo (in the context of human and animal disease). PCR analysis, pulsed-field gel electrophoresis/Southern blotting, and DNA sequencing determined that the cpb2 gene is preferentially associated with AAD isolates (but not FP isolates), in part, due to its presence on some cpe-encoding plasmids. Sequencing of cpe and cpe/cpb2 plasmids found a large region of plasmid DNA, encoding a conjugal-gene cluster, which appears conserved amongst most C. perfringens virulence plasmids. Subsequent sequencing of a number of cpb2 genes identified two CPB2 variants, both of which are produced (detected using Western blot). Neutral red cytotoxicity assays using purified CPB2 demonstrated that CPB2h1 is more cytotoxic for Caco-2 cells than CPB2h2 and this activity is heat labile. Further in vitro work (using 86Rubidium release assays and osmotic stabilizers) suggested that CPB2 acts by disrupting membrane permeability. In vivo experiments confirmed that our CPB2 preparations also were lethal using a mouse intravenous injection model. However, efforts to develop a more realistic model of pathogenesis (which initiates in the intestines) should be continued to furtheranalyze the role of CPB2 in pathogenesis. Ultimately, the production of CPB2 by most AAD isolates, as opposed to FP isolates, could provide an explanation for the more severe symptoms associated with AAD cases and suggests that CPB2 may be involved in human gastrointestinal disease

Ground zero

Thesis (M. Arch.)--Massachusetts Institute of Technology, Dept. of Architecture, 1998.Includes bibliographical references (p. 63-64).Derek S. Fisher.M.Arch

Panel 2: Art Law and Blockchain

Panel presentation on Art Law and Blockchain at 2019 AELJ Spring Symposium: Digital Art & Blockchain

Recent advances in genetic systems in obligate intracellular human-pathogenic bacteria

The ability to genetically manipulate a pathogen is fundamental to discovering factors governing host–pathogen interactions at the molecular level and is critical for devising treatment and prevention strategies. While the genetic “toolbox” for many important bacterial pathogens is extensive, approaches for modifying obligate intracellular bacterial pathogens were classically limited due in part to the uniqueness of their obligatory lifestyles. Many researchers have confronted these challenges over the past two and a half decades leading to the development of multiple approaches to construct plasmid-bearing recombinant strains and chromosomal gene inactivation and deletion mutants, along with gene-silencing methods enabling the study of essential genes. This review will highlight seminal genetic achievements and recent developments (past 5 years) for Anaplasma spp., Rickettsia spp., Chlamydia spp., and Coxiella burnetii including progress being made for the still intractable Orientia tsutsugamushi. Alongside commentary of the strengths and weaknesses of the various approaches, future research directions will be discussed to include methods for C. burnetii that should have utility in the other obligate intracellular bacteria. Collectively, the future appears bright for unraveling the molecular pathogenic mechanisms of these significant pathogens

On the possibility of a metallic phase in granular superconducting films

We investigate the possibility of finding a zero-temperature metallic phase in granular superconducting films. We are able to identify the breakdown of the conventional treatment of these systems as dissipative Bose systems. We do not find a metallic state at zero temperature. At finite temperatures, we find that the system exhibit crossover behaviour which may have implications for the analysis of experimental results. We also investigate the effect of vortex dissipation in these systems.Comment: 7 pages, ReVTeX3.0, 3 EPS figure

Tropical larval and juvenile fish critical swimming speed (U-crit) and morphology data

Fish swimming capacity is a key life history trait critical to many aspects of their ecology. U-crit (critical) swimming speeds provide a robust, repeatable relative measure of swimming speed that can serve as a useful surrogate for other measures of swimming performance. Here we collate and make available one the most comprehensive datasets on U-crit swimming abilities of tropical marine fish larvae and pelagic juveniles, most of which are reef associated as adults. The dataset includes U-crit speed measurements for settlement stage fishes across a large range of species and families obtained mostly from field specimens collected in light traps and crest nets; and the development of swimming abilities throughout ontogeny for a range of species using reared larvae. In nearly all instances, the size of the individual was available, and in many cases, data include other morphological measurements (e.g. “propulsive area”) useful for predicting swimming capacity. We hope these data prove useful for further studies of larval swimming performance and other broader syntheses

Influence of stigma, sociodemographic and clinical characteristics on mental health-related service use and associated costs among young people in the United Kingdom

This study examined the influence of stigma, psychopathology, and sociodemographic characteristics on mental health-related service use and costs related to service use in a cohort of young people in the UK. Using data from a community sample of young people aged 9–17 years and their caregivers, we assessed 407 young people’s use of services due to mental health problems, young people’s psychopathology, demographic characteristics, maternal education and caregivers’ stigma-related beliefs. Unit costs related to services were gathered from national annual compendia and other widely used sources. We assessed predictors of service use through logistic regression analysis and developed generalised linear models to identify factors associated with costs of mental health-related service utilisation. Persistent psychopathology, socioeconomic disadvantage, and low caregiver intended stigma-related behaviour were associated with increased likelihood of service use among young people. Older age and socioeconomic disadvantage were associated with increased costs. Different factors influenced contact with services and the cost associated with their use — persistent psychopathology and socioeconomic disadvantage increased, and caregivers’ intended stigma-related behaviour decreased the likelihood of using services, whereas socioeconomic disadvantage and older age were associated with increased costs. Social determinants of mental health problems play an important role in the use and costs of different types of mental health-related services for young people. Discordance between drivers of service use and costs implies that young people who are more likely to access services due to mental health problems do not necessarily receive care at the intensity they need

The Precarious Health of Young Mexican American Men in South Texas, Cameron County Hispanic Cohort, 2004–2015

Introduction Hispanic men have higher rates of illness and death from various chronic conditions than do non-Hispanic men. We aimed to characterize the health of Mexican American men living on the US–Mexico border in South Texas and elucidate indications of chronic disease in young men. Methods We sampled all male participants from the Cameron County Hispanic Cohort, an ongoing population-based cohort of Mexican Americans in Brownsville, Texas. We calculated descriptive statistics and stratified the sample into 3 age groups to estimate the prevalence of sociodemographic, behavioral, and clinical factors by age group and evaluated differences between age groups. Results Obesity prevalence was approximately 50% across all age groups (P = .83). Diabetes prevalence was high overall (26.8%), and 16.9% (95% confidence interval [CI], 10.1%–23.8%) of men younger than 35 had diabetes. More than 70% of these young men had elevated liver enzymes, and mean values of aspartate aminotransferase were significantly higher in younger men (45.0 u/L; 95% CI, 39.5–50.6 u/L) than in both older age groups. Less than 20% of young men had any form of health insurance. Current smoking was higher in young men than in men in the other groups, and the rate was higher than the national prevalence of current smoking among Hispanic men. Conclusions We suggest a need for obesity and diabetes prevention programs and smoking cessation programs for men in this region. Opportunities exist to expand current intervention programs and tailor them to better reach this vulnerable population of young Hispanic men. Elevated liver enzymes in men younger than 35 suggest a substantial burden of liver abnormalities, a finding that warrants further study

The Dictyostelium genome encodes numerous RasGEFs with multiple biological roles

BACKGROUND: Dictyostelium discoideum is a eukaryote with a simple lifestyle and a relatively small genome whose sequence has been fully determined. It is widely used for studies on cell signaling, movement and multicellular development. Ras guanine-nucleotide exchange factors (RasGEFs) are the proteins that activate Ras and thus lie near the top of many signaling pathways. They are particularly important for signaling in development and chemotaxis in many organisms, including Dictyostelium. RESULTS: We have searched the genome for sequences encoding RasGEFs. Despite its relative simplicity, we find that the Dictyostelium genome encodes at least 25 RasGEFs, with a few other genes encoding only parts of the RasGEF consensus domains. All appear to be expressed at some point in development. The 25 genes include a wide variety of domain structures, most of which have not been seen in other organisms. The LisH domain, which is associated with microtubule binding, is seen particularly frequently; other domains that confer interactions with the cytoskeleton are also common. Disruption of a sample of the novel genes reveals that many have clear phenotypes, including altered morphology and defects in chemotaxis, slug phototaxis and thermotaxis. CONCLUSION: These results suggest that the unexpectedly large number of RasGEF genes reflects an evolutionary expansion of the range of Ras signaling rather than functional redundancy or the presence of multiple pseudogenes

Moyo Vol. X N 2

Million, Chris. Editor\u27s Letter . 4. Kaczur, Erin. Why It Sucks to be Human: I Would Like to Change My Casing, Not My Underwear . 5. Dunson, Jim and Tom Hankinson. MoYummy: Our Staff Connoisseurs Hit the Spots That Hit the Spot . 6. Fisher, Dan. Happy, O Monk, Is Thy Shadow! A No Pluses, No Minuses Memory of a Spiritual Friend . 10. Reuss, Liz. Who is S/He? Leslie Feinberg Interview Inspires Introspection . 11. Marston, Jennifer. MoYo Millenium Picks: Ghandi Can Forget it . 12. Bungard, Chris. Pop The Cork on Ireland. Strictly No Drinking Stritly Ignored . 13. Wilson, Kalyn. Pagans in print: The Craft--So Much more Than Sabrina . 14. Mallinger, Adam. DU Press Release Revisited . 16. Zellner, Kelli. Denison University\u27s Campus Compact--Myth or Reality? DU\u27s Bubble, Burst . 17. Hankinson, Tom. Bureaucracy--Friend of the Common man. An Explication Rather Than an Expletive . 18. The TasyPaycheck. A Very Tasty Quiz: The Denison Social Hierarchy - Do You Cut it? 20. Mong, Derek. The Armpit Epiphany . 21. Curry, Kim. Hot Child in The City: An Unaccustomed look Back from a Big Apple Intern . 22. Million, Chris. Their Last Chance! 32. Kovach, Steve. Risk-y Business: Strategies for Getting More enjoyment Out of World Conquest . 34