193 research outputs found

    Pennsylvania Folklife Vol. 13, No. 4

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    • Stoneware: Stepchild of Early Pottery • The Days of Auld Lang Syne • Grout-Kootch, Coldframe, and Hotbed • Memories of Three Spring Farm • Folk Festival Program • Saffron Cookery • My Childhood Games • Western Pennsylvania Epitaphshttps://digitalcommons.ursinus.edu/pafolklifemag/1016/thumbnail.jp

    Phenotypic Variation and Bistable Switching in Bacteria

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    Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

    The Polyamine Inhibitor Alpha-Difluoromethylornithine Modulates Hippocampus-Dependent Function after Single and Combined Injuries

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    Exposure to uncontrolled irradiation in a radiologic terrorism scenario, a natural disaster or a nuclear battlefield, will likely be concomitantly superimposed on other types of injury, such as trauma. In the central nervous system, radiation combined injury (RCI) involving irradiation and traumatic brain injury may have a multifaceted character. This may entail cellular and molecular changes that are associated with cognitive performance, including changes in neurogenesis and the expression of the plasticity-related immediate early gene Arc. Because traumatic stimuli initiate a characteristic early increase in polyamine metabolism, we hypothesized that treatment with the polyamine inhibitor alpha-difluoromethylornithine (DFMO) would reduce the adverse effects of single or combined injury on hippocampus structure and function. Hippocampal dependent cognitive impairments were quantified with the Morris water maze and showed that DFMO effectively reversed cognitive impairments after all injuries, particularly traumatic brain injury. Similar results were seen with respect to the expression of Arc protein, but not neurogenesis. Given that polyamines have been found to modulate inflammatory responses in the brain we also assessed the numbers of total and newly born activated microglia, and found reduced numbers of newly born cells. While the mechanisms responsible for the improvement in cognition after DFMO treatment are not yet clear, the present study provides new and compelling data regarding the potential use of DFMO as a potential countermeasure against the adverse effects of single or combined injury

    A mitotic recombination map proximal to the APC locus on chromosome 5q and assessment of influences on colorectal cancer risk

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    Mitotic recombination is important for inactivating tumour suppressor genes by copy-neutral loss of heterozygosity (LOH). Although meiotic recombination maps are plentiful, little is known about mitotic recombination. The APC gene (chr5q21) is mutated in most colorectal tumours and its usual mode of LOH is mitotic recombination.

    Immunopurification of Pathological Prion Protein Aggregates

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    Background: Prion diseases are fatal neurodegenerative disorders that can arise sporadically, be genetically inherited or acquired through infection. The key event in these diseases is misfolding of the cellular prion protein (PrP) into a pathogenic isoform that is rich in β-sheet structure. This conformational change may result in the formation of PrP, the prion isoform of PrP, which propagates itself by imprinting its aberrant conformation onto PrP molecules. A great deal of effort has been devoted to developing protocols for purifying PrP for structural studies, and testing its biological properties. Most procedures rely on protease digestion, allowing efficient purification of PrP27-30, the protease-resistant core of PrP. However, protease treatment cannot be used to isolate abnormal forms of PrP lacking conventional protease resistance, such as those found in several genetic and atypical sporadic cases. Principal Findings: We developed a method for purifying pathological PrP molecules based on sequential centrifugation and immunoprecipitation with a monoclonal antibody selective for aggregated PrP. With this procedure we purified full-length PrP and mutant PrP aggregates at electrophoretic homogeneity. PrP purified from prion-infected mice was able to seed misfolding of PrP in a protein misfolding cyclic amplification reaction, and mutant PrP aggregates from transgenic mice were toxic to cultured neurons. Significance: The immunopurification protocol described here isolates biologically active forms of aggregated PrP. These preparations may be useful for investigating the structural and chemico-physical properties of infectious and neurotoxic PrP aggregates

    Optic disc classification by the Heidelberg Retina Tomograph and by physicians with varying experience of glaucoma

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    PurposeTo compare the diagnostic accuracy of the Heidelberg Retina Tomograph's (HRT) Moorfields regression analysis (MRA) and glaucoma probability score (GPS) with that of subjective grading of optic disc photographs performed by ophthalmologists with varying experience of glaucoma and by ophthalmology residents.MethodsDigitized disc photographs and HRT images from 97 glaucoma patients with visual field defects and 138 healthy individuals were classified as either within normal limits (WNL), borderline (BL), or outside normal limits (ONL). Sensitivity and specificity were compared for MRA, GPS, and the physicians. Analyses were also made according to disc size and for advanced visual field loss.ResultsForty-five physicians participated. When BL results were regarded as normal, sensitivity was significantly higher (P<5%) for both MRA and GPS compared with the average physician, 87%, 79%, and 62%, respectively. Specificity ranged from 86% for MRA to 97% for general ophthalmologists, but the differences were not significant. In eyes with small discs, sensitivity was 75% for MRA, 60% for the average doctor, and 25% for GPS; in eyes with large discs, sensitivity was 100% for both GPS and MRA, but only 68% for physicians.ConclusionOur results suggest that sensitivity of MRA is superior to that of the average physician, but not that of glaucoma experts. MRA correctly classified all eyes with advanced glaucoma and showed the best sensitivity in eyes with small optic discs
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