206 research outputs found

    It Takes a Library to Support Distance Learners

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    Wallace Library\u27s philosophy is to create and provide resources and services that will support all users. Consequently, distance learners and distance faculty have a plethora of online resources available to them, some of which is pushed out, saving time and effort for the library user. The evolvement of Wallace\u27s online resources is continuous, focused on the student or professor\u27s research need from a geographic distance

    Toxicity of Volatile Methylated Species of Bismuth, Arsenic, Tin, and Mercury in Mammalian Cells In Vitro

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    The biochemical transformation of mercury, tin, arsenic and bismuth through formation of volatile alkylated species performs a fundamental role in determining the environmental processing of these elements. While the toxicity of inorganic forms of most of these compounds are well documented (e.g., arsenic, mercury) and some of them are of relatively low toxicity (e.g., tin, bismuth), the more lipid-soluble organometals can be highly toxic. In the present study we investigated the cyto- and genotoxicity of five volatile metal(loid) compounds: trimethylbismuth, dimethylarsenic iodide, trimethylarsine, tetramethyltin, and dimethylmercury. As far as we know, this is the first study investigating the toxicity of volatile metal(loid) compounds in vitro. Our results showed that dimethylmercury was most toxic to all three used cell lines (CHO-9 cells, CaCo, Hep-G2) followed by dimethylarsenic iodide. Tetramethyltin was the least toxic compound; however, the toxicity was also dependend upon the cell type. Human colon cells (CaCo) were most susceptible to the toxicity of the volatile compounds compared to the other cell lines. We conclude from our study that volatile metal(loid) compounds can be toxic to mammalian cells already at very low concentrations but the toxicity depends upon the metal(loid) species and the exposed cell type

    Chrysotile effects on human lung cell carcinoma in culture: 3-D reconstruction and DNA quantification by image analysis

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    <p>Abstract</p> <p>Background</p> <p>Chrysotile is considered less harmful to human health than other types of asbestos fibers. Its clearance from the lung is faster and, in comparison to amphibole forms of asbestos, chrysotile asbestos fail to accumulate in the lung tissue due to a mechanism involving fibers fragmentation in short pieces. Short exposure to chrysotile has not been associated with any histopathological alteration of lung tissue.</p> <p>Methods</p> <p>The present work focuses on the association of small chrysotile fibers with interphasic and mitotic human lung cancer cells in culture, using for analyses confocal laser scanning microscopy and 3D reconstructions. The main goal was to perform the analysis of abnormalities in mitosis of fibers-containing cells as well as to quantify nuclear DNA content of treated cells during their recovery in fiber-free culture medium.</p> <p>Results</p> <p>HK2 cells treated with chrysotile for 48 h and recovered in additional periods of 24, 48 and 72 h in normal medium showed increased frequency of multinucleated and apoptotic cells. DNA ploidy of the cells submitted to the same chrysotile treatment schedules showed enhanced aneuploidy values. The results were consistent with the high frequency of multipolar spindles observed and with the presence of fibers in the intercellular bridge during cytokinesis.</p> <p>Conclusion</p> <p>The present data show that 48 h chrysotile exposure can cause centrosome amplification, apoptosis and aneuploid cell formation even when long periods of recovery were provided. Internalized fibers seem to interact with the chromatin during mitosis, and they could also interfere in cytokinesis, leading to cytokinesis failure which forms aneuploid or multinucleated cells with centrosome amplification.</p

    Coordination of sustainable financing for evidence-based youth mental health treatments: Protocol for development and evaluation of the fiscal mapping process

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    BACKGROUND: Sustained delivery of evidence-based treatments (EBTs) is essential to addressing the public health and economic impacts of youth mental health problems, but is complicated by the limited and fragmented funding available to youth mental health service agencies (hereafter, service agencies ). Strategic planning tools are needed that can guide these service agencies in their coordination of sustainable funding for EBTs. This protocol describes a mixed-methods research project designed to (1) develop and (2) evaluate our novel fiscal mapping process that guides strategic planning efforts to finance the sustainment of EBTs in youth mental health services. METHOD: Participants will be 48 expert stakeholder participants, including representatives from ten service agencies and their partners from funding agencies (various public and private sources) and intermediary organizations (which provide guidance and support on the delivery of specific EBTs). Aim 1 is to develop the fiscal mapping process: a multi-step, structured tool that guides service agencies in selecting the optimal combination of strategies for financing their EBT sustainment efforts. We will adapt the fiscal mapping process from an established intervention mapping process and will incorporate an existing compilation of 23 financing strategies. We will then engage participants in a modified Delphi exercise to achieve consensus on the fiscal mapping process steps and gather information that can inform the selection of strategies. Aim 2 is to evaluate preliminary impacts of the fiscal mapping process on service agencies\u27 EBT sustainment capacities (i.e., structures and processes that support sustainment) and outcomes (e.g., intentions to sustain). The ten agencies will pilot test the fiscal mapping process. We will evaluate how the fiscal mapping process impacts EBT sustainment capacities and outcomes using a comparative case study approach, incorporating data from focus groups and document review. After pilot testing, the stakeholder participants will conceptualize the process and outcomes of fiscal mapping in a participatory modeling exercise to help inform future use and evaluation of the tool. DISCUSSION: This project will generate the fiscal mapping process, which will facilitate the coordination of an array of financing strategies to sustain EBTs in community youth mental health services. This tool will promote the sustainment of youth-focused EBTs

    Step-by-step design of proteins for small molecule interaction: a review on recent milestones

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    Protein design is the field of synthetic biology that aims at developing de-novo custom made proteins and peptides for specific applications. Despite exploring an ambitious goal, recent computational advances in both hardware and software technologies have paved the way to high-throughput screening and detailed design of novel folds and improved functionalities. Modern advances in the field of protein design for small molecule targeting are described in this review, organized in a step-by-step fashion: from the conception of a new or upgraded active binding site, to scaffold design, sequence optimization and experimental expression of the custom protein. In each step, contemporary examples are described, and state-of-the art software is briefly explored.publishe

    The Fate of Chrysotile-Induced Multipolar Mitosis and Aneuploid Population in Cultured Lung Cancer Cells

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    Chrysotile is one of the six types of asbestos, and it is the only one that can still be commercialized in many countries. Exposure to other types of asbestos has been associated with serious diseases, such as lung carcinomas and pleural mesotheliomas. The association of chrysotile exposure with disease is controversial. However, in vitro studies show the mutagenic potential of chrysotile, which can induce DNA and cell damage. The present work aimed to analyze alterations in lung small cell carcinoma cultures after 48 h of chrysotile exposure, followed by 2, 4 and 8 days of recovery in fiber-free culture medium. Some alterations, such as aneuploid cell formation, increased number of cells in G2/M phase and cells in multipolar mitosis were observed even after 8 days of recovery. The presence of chrysotile fibers in the cell cultures was detected and cell morphology was observed by laser scanning confocal microscopy. After 4 and 8 days of recovery, only a few chrysotile fragments were present in some cells, and the cellular morphology was similar to that of control cells. Cells transfected with the GFP-tagged α-tubulin plasmid were treated with chrysotile for 24 or 48 h and cells in multipolar mitosis were observed by time-lapse microscopy. Fates of these cells were established: retention in metaphase, cell death, progression through M phase generating more than two daughter cells or cell fusion during telophase or cytokinesis. Some of them were related to the formation of aneuploid cells and cells with abnormal number of centrosomes

    Expression and Differential Responsiveness of Central Nervous System Glial Cell Populations to the Acute Phase Protein Serum Amyloid A

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    Acute-phase response is a systemic reaction to environmental/inflammatory insults and involves hepatic production of acute-phase proteins, including serum amyloid A (SAA). Extrahepatically, SAA immunoreactivity is found in axonal myelin sheaths of cortex in Alzheimer's disease and multiple sclerosis (MS), although its cellular origin is unclear. We examined the responses of cultured rat cortical astrocytes, microglia and oligodendrocyte precursor cells (OPCs) to master pro-inflammatory cytokine tumour necrosis factor (TNF)-\u3b1 and lipopolysaccaride (LPS). TNF-\u3b1 time-dependently increased Saa1 (but not Saa3) mRNA expression in purified microglia, enriched astrocytes, and OPCs (as did LPS for microglia and astrocytes). Astrocytes depleted of microglia were markedly less responsive to TNF-\u3b1 and LPS, even after re-addition of microglia. Microglia and enriched astrocytes showed complementary Saa1 expression profiles following TNF-\u3b1 or LPS challenge, being higher in microglia with TNF-\u3b1 and higher in astrocytes with LPS. Recombinant human apo-SAA stimulated production of both inflammatory mediators and its own mRNA in microglia and enriched, but not microglia-depleted astrocytes. Co-ultramicronized palmitoylethanolamide/luteolin, an established anti-inflammatory/neuroprotective agent, reduced Saa1 expression in OPCs subjected to TNF-\u3b1 treatment. These last data, together with past findings suggest that co-ultramicronized palmitoylethanolamide/luteolin may be a novel approach in the treatment of inflammatory demyelinating disorders like MS

    IgE Mediated Autoallergy against Thyroid Peroxidase – A Novel Pathomechanism of Chronic Spontaneous Urticaria?

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    Chronic spontaneous urticaria (csU), which is characterized by recurrent episodes of mast cell-driven wheal and flare-type skin reactions, is often associated with elevated total IgE levels and thyroid autoimmunity. We speculate that some csU patients express IgE autoantibodies against thyroid antigens such as thyroid peroxidase (TPO), which could bind to skin mast cells and induce their activation.We developed and used a site-directed human IgE capture ELISA to quantify IgE-anti-TPO. We used this assay and investigated csU patients (n = 478) and healthy control subjects (n = 127) for IgE-anti-TPO and then assessed IgE-anti-TPO-positive and -negative csU patients for clinical and serological differences. ( = 61%, IgE-anti-TPO: median 6.67, interquartile range 5.39–8.24). IgE-anti-TPO-positive and -negative csU patients had very similar distributions of age and gender as well as disease activity and duration. IgE-anti-TPO-positive csU patients exhibited significantly higher IgG-anti-TPO levels and lymphocyte counts as well as decreased C4 complement levels.Our findings show that a sizeable subgroup of csU patients expresses IgE antibodies against thyroid peroxidase. These autoantibodies could cause “autoallergic” mast cell activation, a novel pathomechanism of chronic spontaneous urticaria
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