The response of AM transcription to exposure to conidia is expected to provide information about the mechanism by which these cells prevent conidial germination and therefore invasive aspergillosis.
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View SamplesStudies using yeast have advanced our understanding of both replicative and chronological aging, leading to the discovery of longevity genes that have homologues in higher eukaryotes. Chronological lifespan in yeast is conventionally defined as the lifespan of a non-dividing cell. To date, this parameter has only been estimated under calorically restricted (CR) conditions, mimicked by starvation. Since post-mitotic cells in higher eukaryotes are rarely calorically-restricted, we sought to develop an alternative experimental system where non-dividing yeast would age chronologically, in the presence of excess nutrients. We report here on a system wherein alginate-encapsulated yeast are packed in a pH- and temperature-controlled bioreactor, then continuously fed non-limiting substrate for extended periods of time. We present demographic, physiological and genomic evidence indicating that after ~120 hrs, immobilized cells cease dividing, remain metabolically very active and retain >95% viability for periods of 17 days. Over the same time interval, starved planktonic cells, cultured using the same media, and also controlled for temperature and pH, retained < 1 % viability in both aerobic and anaerobic cultures,. Unlike planktonic yeast, continuously-fed immobilized cells hyper-accumulate glycogen. FACS analysis of SYTOX green-stained yeast confirms that immobilized cells completely arrest within 5 days of culture, and unlike starving planktonic cells, remain free thereafter of replicative stress and are non-apoptotic. This unusual state is supported by a global gene expression profile that is stable over time, repeatable across replicate experiments, and altogether distinct from planktonic cells cultured in the presence and absence of limiting nutrients. DNA expression profiling, performed here for the very first time on immobilized cells, reveals that glycolytic genes and their trans-acting regulatory elements are upregulated, as are genes involved in remodeling the cell wall and resisting stress; by contrast, many genes that promote cell cycle progression and carry out oxidative metabolism are repressed. Stress resistance transcription factor MSN4 and its upstream effector RIM15 are conspicuously upregulated in the immobilized state, suggesting that nutrient-sensing pathways may play a role in cell viability and longevity when yeast are immobilized and placed in prolonged culture under calorically-unrestricted conditions. The cell cycle arrest in the immobilized state is mediated by RIM 15. Over the time-course of our experiments, well-fed, non-diving immobilized cells do not appear to age.
Uncoupling reproduction from metabolism extends chronological lifespan in yeast.
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The Pseudomonas aeruginosa PAO1 Two-Component Regulator CarSR Regulates Calcium Homeostasis and Calcium-Induced Virulence Factor Production through Its Regulatory Targets CarO and CarP.
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View SamplesThe response to the presence of the ncpBVDV-infected PI or TI fetus is expected to provide information on the impact of the PI fetus on the immune response of the dam
Persistent fetal infection with bovine viral diarrhea virus differentially affects maternal blood cell signal transduction pathways.
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View SamplesStaphylococcus aureus produces the cyclic dipeptides tyrvalin and phevalin (aureusimine A and B, respectively).
Phevalin (aureusimine B) production by Staphylococcus aureus biofilm and impacts on human keratinocyte gene expression.
Specimen part, Treatment
View SamplesType I IFN-signaling suppresses an excessive IFN-{gamma} response and prevents lung damage and chronic inflammation following Pneumocystis (PC)-infection and clearance in CD4 T cell-competent mice.
Type-I IFN signaling suppresses an excessive IFN-gamma response and thus prevents lung damage and chronic inflammation during Pneumocystis (PC) clearance in CD4 T cell-competent mice.
Specimen part
View SamplesGenetic disruption of thioredoxin reductase 1 protects against acetaminophen (APAP) toxicity.
A Txnrd1-dependent metabolic switch alters hepatic lipogenesis, glycogen storage, and detoxification.
Sex, Specimen part
View SamplesPulmonary hypertension (PH) is a disease of diverse etiology. While primary PH can develop in the absence of prior disease, PH more commonly develops in conjunction with other pulmonary pathologies. We previously reported a mouse model in which PH occurs as a sequelae of Pneumocystis infection in the context of transient CD4 depletion. Here, we demonstrate that instead of the expected Th2 pathways, the Th1 cytokine IFN- was essential for the development of PH, as wild type mice developed PH, but not IFN- knockout mice.
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Specimen part
View SamplesPseudomonas aeruginosa evolving in the cystic fibrosis (CF) lung encounters selection via iron-limitation, antibiotics, immune system effectors and other microbes. Standing genetic variation, which depends on rates of horizontal gene transfer (HGT) and mutation supply, controls response to challenges. HGT may increase if new clones successfully invade, while mutator strains increase new mutations. We sought to ascertain genomic signatures of invasion and whether, in the absence of novel invasion, mutator-containing P. aeruginosa populations from chronically infected CF lung are more genetically variable than nonmutator populations. Forty-nine strains from 14 patients treated over three years at Necker Childrens Hospital in Paris were phenotyped for antibiotic resistance, mucoidy and mutator status, and then genotyped by rep-PCR, PFGE and MLST analysis. Overall, strains exhibited greater genetic similarity within patients than among patients, with initial and terminal clones differing markedly between series, indicating unrelated clones independently established infections and resisted invasions that might enlarge genetic variation by sexual recombination. Mutator series were more likely to be multiply antibiotic-resistant, but were no more genetically variable at the single nucleotide level. DNA microarray analyses of bacterial genomes in two longitudinal series of equal duration, one containing and one lacking mutators, revealed both series conspicuously lack genes encoding proteins involved in attachment, motility and amino acid biosynthesis. The mutator series also contained fewer genes hybridizing to canonical PAO1 genome sequences. These data suggest genetic variation arising from mutators may be limited in scope, transient in nature or not easily resolved by fingerprinting, MLST or comparative genomic analyses.
No associated publication
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Contribution of stress responses to antibiotic tolerance in Pseudomonas aeruginosa biofilms.
No sample metadata fields
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