Nutrient Niche Space of Clostridium difficile Across Susceptible Microbiomes and the Impact of Infection on Metabolism of the Murine Cecal Microbiota

The nosocomial pathogen Clostridium difficile causes an antibiotic-associated diarrheal disease, and largest single cause of hospital-acquired infection as well as gastroenteritis-associated death in the United States. The connection with prior antibiotic therapy is due to the collateral damage induced by these drugs on the community of indigenous bacteria that reside along the gastrointestinal tract. In its healthy state, the gut microbiota prevents the establishment of C. difficile in the gut through the intrinsic property known as colonization resistance. Following a perturbation, like exposure to antibiotics, this community becomes susceptible to colonization by the pathogen and subsequent disease. Most antibiotic classes have been associated with C. difficile infection (CDI) susceptibility; many leading to distinct community structures with unique metabolic profiles stemming from variation in bacterial targets of action. Additionally, a subset of these antibiotics are more closely associated with recurrent or persistent infection. In this thesis I demonstrate that certain susceptible gut communities are more permissive of long-term C. difficile colonization, and that the pathogen has a disproportionate effect on the metabolic activity of communities where persistence occurs. Taxonomic analyses of altered gene expression revealed that this effect consistently impact minority bacterial genera of the community across infection groups. In order to measure the adaptive capacity of C. difficile to these diverse environments, I also generated a genomic/transcriptomic-enabled metabolic modeling platform to assess the differences in nutrient preference of C. difficile across different community contexts. This revealed the pathogen inhabited distinct nutrient niche spaces across susceptible gut environments. My dissertation work has strong implications in future research of targeted pre- and probiotic therapies that mitigate primary or established C. difficile colonization from the gastrointestinal tract.PHDMicrobiology & ImmunologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/138521/1/mljenior_1.pd

Observation and Modeling of Traffic Operations at Intersections in Malfunction Flash Mode

When a traffic signals malfunction monitoring unit detects a problem with a traffic signal such as the simultaneous display of green indications to conflicting movements or loss of power to some signal heads, the signal is automatically placed into flash mode as a safety precaution. Signals can have either red/red malfunction flash mode or yellow/red malfunction flash mode, and the mode cannot change by time of day or day of week. This study analyzed traffic operation at 34 instances of yellow/red malfunction flash and 9 instances of red/red malfunction flash in the Atlanta, Georgia area. Many of these instances were during high volume periods. A high level of driver confusion exists at malfunction flash intersections. The rate at which through major street drivers (i.e. those facing a flashing yellow signal) stopped exceeded 75 percent at some yellow/red flash intersections. This creates a safety hazard for other major street drivers who are not expecting vehicles to stop, and for minor street drivers who cannot tell what type of control is being presented to cross traffic or do not understand that vehicles are not required to stop when approaching a flashing yellow indication. Furthermore, high stopping rates at a flashing yellow signal eliminate many of the operational benefits that yellow/red flash is assumed to have over red/red flash. Based on the findings of this study, the use of red/red flash should be the primary flash mode and possibly used exclusively. Requiring all vehicles to stop will improve safety conditions and not have large operational impacts at intersections where a majority of major street vehicles are already stopping at a flashing yellow signal. Yellow/red flash may be an acceptable malfunction flash mode at the intersection of a very large street and a very small street, but additional measures would be required at these intersections to address potential driver confusion.M.S.Committee Chair: Hunter, Michael; Committee Member: Meyer, Michael; Committee Member: Rodgers, Michae

PEDAGOGIAS DECOLONIAIS EM PERFORMANCE

Práticas educativas em performance têm se tornado uma área em construção cada vez mais potente no campo da arte-educação. Diversas abordagens são possí­veis neste sentido tendo em vista a amplitude da temática. Voltamos nossa atenção para o potencial decolonial de tais processos. Encontrando aí­ um rico território em que os sujeitos possam construir conhecimento coletivamente, experimentar a si próprios, vivenciar e educar a si mesmos, baseados em um cultivo de si, que passa necessariamente pelo corpo de cada ser, que traz, como matéria, a singularidade de cada um em suas vivências e experiências próprias e únicas. Nesse sentido, olhamos para o corpo como algo central no processo decolonial, não o corpo de uma pessoa qualquer, sem idade, raça, nacionalidade, gênero, sexualidade, classe social, mas reconhecendo suas especificidades, seu lugar único de fala. Nos posicionamos assim em uma perspectiva interseccional, que reflete sobre as múltiplas camadas de opressão que nos formam e deformam, reflexos da colonialidade do poder, do ser, do saber, do corpo, do imaginário, que nos foram impostos, e que ainda repercutem em nossa carne

PEDAGOGIAS DECOLONIAIS EM PERFORMANCE

Práticas educativas em performance têm se tornado uma área em construção cada vez mais potente no campo da arte-educação. Diversas abordagens são possíveis neste sentido tendo em vista a amplitude da temática. Voltamos nossa atenção para o potencial decolonial de tais processos. Encontrando aí um rico território em que os sujeitos possam construir conhecimento coletivamente, experimentar a si próprios, vivenciar e educar a si mesmos, baseados em um cultivo de si, que passa necessariamente pelo corpo de cada ser, que traz, como matéria, a singularidade de cada um em suas vivências e experiências próprias e únicas. Nesse sentido, olhamos para o corpo como algo central no processo decolonial, não o corpo de uma pessoa qualquer, sem idade, raça, nacionalidade, gênero, sexualidade, classe social, mas reconhecendo suas especificidades, seu lugar único de fala. Nos posicionamos assim em uma perspectiva interseccional, que reflete sobre as múltiplas camadas de opressão que nos formam e deformam, reflexos da colonialidade do poder, do ser, do saber, do corpo, do imaginário, que nos foram impostos, e que ainda repercutem em nossa carne

Effects of mixed metals in the sediment on DNA damage and lipid peroxidation in the gills of Poecilia reticulata

O presente estudo avaliou os efeitos da mistura de metais, essa mistura foi composta por cobre, chumbo, mercúrio e zinco, no sedimento contaminado (spiking) sobre danos em DNA e peroxidação lipídica nas brânquias do peixe Poecilia reticulata através de biomarcadores de efeito, em dois níveis de contaminação: baixa e moderada, sendo que os valores de guia para contaminar os sedimentos com metais foram baseados na resolução do CONAMA 454 que regulamenta a caracterização de sedimentos a serem dragados. Os níveis baixos ou moderado de concentração da mistura de metais não afetaram de maneira significativa os danos em DNA. Porém para LPO foi possível observar um padrão crescente com a contaminação no período de 3 dias, e em períodos maiores de exposição foi possível observar que houve uma supercompensação. São necessários mais estudos e análises que trabalhem com outras respostas de biomarcadores de defesas antioxidantes para desvendar os mecanismos empregados nesta supercompensação.The present study evaluated the effects of the mixture of metals, this mixture was composed of copper, lead, mercury and zinc, in the contaminated sediment (spiking) on ​​DNA damage and lipid peroxidation in the gills of the fish Poecilia reticulata through effect biomarkers, in two levels of contamination: low and moderate, and the guide values ​​for contaminating the sediments with metals were based on the resolution of CONAMA 454 which regulates the characterization of sediments to be dredged. Low or moderate concentration levels of the metal mixture did not significantly affect DNA damage. However, for LPO it was possible to observe an increasing pattern with the contamination in a period of 3 days, and in longer periods of exposure it was possible to observe that there was an overcompensation. More studies and analyzes that work with other responses of antioxidant defense biomarkers are needed to unravel the mechanisms used in this supercompensation

Quantifying cumulative phenotypic and genomic evidence for procedural generation of metabolic network reconstructions.

Genome-scale metabolic network reconstructions (GENREs) are valuable tools for understanding microbial metabolism. The process of automatically generating GENREs includes identifying metabolic reactions supported by sufficient genomic evidence to generate a draft metabolic network. The draft GENRE is then gapfilled with additional reactions in order to recapitulate specific growth phenotypes as indicated with associated experimental data. Previous methods have implemented absolute mapping thresholds for the reactions automatically included in draft GENREs; however, there is growing evidence that integrating annotation evidence in a continuous form can improve model accuracy. There is a need for flexibility in the structure of GENREs to better account for uncertainty in biological data, unknown regulatory mechanisms, and context-specificity associated with data inputs. To address this issue, we present a novel method that provides a framework for quantifying combined genomic, biochemical, and phenotypic evidence for each biochemical reaction during automated GENRE construction. Our method, Constraint-based Analysis Yielding reaction Usage across metabolic Networks (CANYUNs), generates accurate GENREs with a quantitative metric for the cumulative evidence for each reaction included in the network. The structuring of CANYUNs allows for the simultaneous integration of three data inputs while maintaining all supporting evidence for biochemical reactions that may be active in an organism. CANYUNs is designed to maximize the utility of experimental and annotation datasets and to ultimately assist in the curation of the reference datasets used for the automatic construction of metabolic networks. We validated CANYUNs by generating an E. coli K-12 model and compared it to the manually curated reconstruction iML1515. Finally, we demonstrated the use of CANYUNs to build a model by generating an E. coli Nissle CANYUNs model using novel phenotypic data that we collected. This method may address key challenges for the procedural construction of metabolic networks by leveraging uncertainty and redundancy in biological data