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Berlin Brandenburg

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  • 1
    In: Scientific Reports, 2015, Vol.5
    Description: The role of microglia in amyloid-β (Aβ) deposition is controversial. In the present study, an organotypic hippocampal slice culture (OHSC) system with an in vivo-like microglial-neuronal environment was used to investigate the potential contribution of microglia to Aβ plaque formation. We found that microglia ingested Aβ, thereby preventing plaque formation in OHSCs. Conversely, Aβ deposits formed rapidly in microglia-free wild-type slices. The capacity to prevent Aβ plaque formation was absent in forebrain microglia from young adult but not juvenile 5xFamilial Alzheimer's disease (FAD) mice. Since no loss of Aβ clearance capacity was observed in both wild-type and cerebellar microglia from 5xFAD animals, the high Aβ1-42 burden in the forebrain of 5xFAD animals likely underlies the exhaustion of microglial Aβ clearance capacity. These data may therefore explain why Aβ plaque formation has never been described in wild-type mice, and point to a beneficial role of microglia in AD pathology. We also describe a new method to study Aβ plaque formation in a cell culture setting.
    Keywords: Alzheimer Disease -- Pathology ; Amyloid Beta-Peptides -- Metabolism ; Hippocampus -- Pathology ; Microglia -- Pathology ; Peptide Fragments -- Metabolism ; Plaque, Amyloid -- Pathology ; Prosencephalon -- Pathology;
    ISSN: 20452322
    E-ISSN: 20452322
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  • 2
    Language: English
    In: Scientific Reports, 2015, Vol.5, pp.urn:issn:2045-2322
    Description: The role of microglia in amyloid-beta (A beta) deposition is controversial. In the present study, an organotypic hippocampal slice culture (OHSC) system with an in vivo-like microglial-neuronal environment was used to investigate the potential contribution of microglia to A beta plaque formation. We...
    Keywords: Alzheimers-Disease ; Transgenic Mice ; Mouse Models ; A-Beta ; Phagocytosis ; Expression ; Reveals ; Brain ; Cell ; Dysfunction
    ISSN: 2045-2322
    Source: NARCIS (National Academic Research and Collaborations Information System)
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  • 3
    Language: English
    In: Sci Rep, 2018, Vol.8(1), pp.4945-4945
    Description: We compared tiger shark (Galeocerdo cuvier) spatial behaviour among 4 Hawaiian Islands to evaluate whether local patterns of movement could explain higher numbers of shark bites seen around Maui than other islands. Our sample consisted of 96 electronically-tagged (satellite and acoustic transmitters) tiger sharks, individually tracked for up to 6 years. Most individuals showed fidelity to a specific ‘home’ island, but also swam between islands and sometimes ranged far (up to 1,400 km) offshore. Movements were primarily oriented to insular shelf habitat (0–200 m depth) in coastal waters, and individual sharks utilized core-structured home ranges within this habitat. Core utilization areas of large tiger sharks were closer to high-use ocean recreation sites around Maui, than around Oahu. Tiger sharks routinely visited shallow ocean recreation sites around Maui and were detected on more days overall at ocean recreation sites around Maui (62–80%) than Oahu (〈6%). Overall, our results suggest the extensive insular shelf surrounding Maui supports a fairly resident population of tiger sharks and also attracts visiting tiger sharks from elsewhere in Hawaii. Collectively these natural, habitat-driven spatial patterns may in-part explain why Maui has historically had more shark bites than other Hawaiian Islands.
    Keywords: Biology;
    ISSN: 2045-2322
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  • 4
    Language: English
    In: Sci Rep, 2017, Vol.7(1), pp.5585-5585
    Description: Aim of this study was to determine if perioperative hemodynamics have an impact on perioperative infarct volume and patients’ prognosis. 201 cases with surgery for a newly diagnosed or recurrent glioblastoma were retrospectively analyzed. Clinical data and perioperative hemodynamic parameters, blood tests and time of surgery were recorded. Postoperative infarct volume was quantitatively assessed by semiautomatic segmentation. Mean diastolic blood pressure (dBP) during surgery (rho −0.239, 95% CI −0.11 – −0.367, p = 0.017), liquid balance (rho 0.236, 95% CI 0.1–0.373, p = 0.017) and mean arterial pressure (MAP) during surgery (rho −0.206, 95% CI −0.07 – −0.34, p = 0.041) showed significant correlation to infarct volume. A rank regression model including also age and recurrent surgery as possible confounders revealed mean intraoperative dBP, liquid balance and length of surgery as independent factors for infarct volume. Univariate survival analysis showed mean intraoperative dBP and MAP as significant prognostic factors, length of surgery also remained as significant prognostic factor in a multivariate model. Perioperative close anesthesiologic monitoring of blood pressure and liquid balance is of high significance during brain tumor surgery and should be performed to prevent or minimize perioperative infarctions and to prolong survival.
    Keywords: Biology;
    ISSN: 2045-2322
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  • 5
    Language: English
    In: Sci Rep, 2018, Vol.8(1), pp.4561-4561
    Description: Recent studies suggested that postoperative hypoxia might trigger invasive tumor growth, resulting in diffuse/multifocal recurrence patterns. Aim of this study was to analyze distinct recurrence patterns and their association to postoperative infarct volume and outcome. 526 consecutive glioblastoma patients were analyzed, of which 129 met our inclusion criteria: initial tumor diagnosis, surgery, postoperative diffusion-weighted imaging and tumor recurrence during follow-up. Distinct patterns of contrast-enhancement at initial diagnosis and at first tumor recurrence (multifocal growth/progression, contact to dura/ventricle, ependymal spread, local/distant recurrence) were recorded by two blinded neuroradiologists. The association of radiological patterns to survival and postoperative infarct volume was analyzed by uni-/multivariate survival analyses and binary logistic regression analysis. With increasing postoperative infarct volume, patients were significantly more likely to develop multifocal recurrence, recurrence with contact to ventricle and contact to dura. Patients with multifocal recurrence (Hazard Ratio (HR) 1.99, P = 0.010) had significantly shorter OS, patients with recurrent tumor with contact to ventricle (HR 1.85, P = 0.036), ependymal spread (HR 2.97, P = 0.004) and distant recurrence (HR 1.75, P = 0.019) significantly shorter post-progression survival in multivariate analyses including well-established prognostic factors like age, Karnofsky Performance Score (KPS), therapy, extent of resection and patterns of primary tumors. Postoperative infarct volume might initiate hypoxia-mediated aggressive tumor growth resulting in multifocal and diffuse recurrence patterns and impaired survival.
    Keywords: Biology;
    ISSN: 2045-2322
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  • 6
    Language: English
    In: Scientific reports, 03 April 2018, Vol.8(1), pp.5527
    Description: Due to the highly invasive nature of Glioblastoma (GB), complete surgical resection is not feasible, while motile tumour cells are often associated with several specific brain structures that enhance treatment-resistance. Here, we investigate the therapeutic potential of Disulfiram and Carbenoxolone, that inhibit two distinct interactions between GB and the brain tissue microenvironment: stress-induced cell-matrix adhesion and gap junction mediated cell-cell communication, respectively. Increase in cell numbers of tumour-initiating cells, which are cultured in suspension as cell clusters, and adherent differentiated cells can be blocked to a similar extent by Carbenoxolone, as both cell populations form gap junctions, but the adherent differentiated cells are much more sensitive to Disulfiram treatment, which - via modulation of NF-κB signalling - interferes with cell-substrate adhesion. Interestingly, inducing adhesion in tumour-initiating cells without differentiating them does not sensitize for Disulfiram. Importantly, combining Disulfiram, Carbenoxolone and the standard chemotherapeutic drug Temozolomide reduces tumour size in an orthotopic mouse model. Isolating GB cells from their direct environment within the brain represents an important addition to current therapeutic approaches. The blockage of cellular interactions via the clinically relevant substances Disulfiram and Carbenoxolone, has distinct effects on different cell populations within a tumour, potentially reducing motility and/or resistance to apoptosis.
    Keywords: Brain Neoplasms -- Drug Therapy ; Carbenoxolone -- Pharmacology ; Disulfiram -- Pharmacology ; Glioblastoma -- Drug Therapy ; Neoplastic Stem Cells -- Drug Effects ; Tumor Microenvironment -- Drug Effects
    E-ISSN: 2045-2322
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  • 7
    Language: English
    In: Sci Rep, 2017, Vol.7(1), pp.9718-9718
    Description: Data-independent acquisition mass spectrometry promises higher performance in terms of quantification and reproducibility compared to data-dependent acquisition mass spectrometry methods. To enable high-accuracy quantification of Staphylococcus aureus proteins, we have developed a global ion library for data-independent acquisition approaches employing high-resolution time of flight or Orbitrap instruments for this human pathogen. We applied this ion library resource to investigate the time-resolved adaptation of S. aureus to the intracellular niche in human bronchial epithelial cells and in a murine pneumonia model. In epithelial cells, abundance changes for more than 400 S. aureus proteins were quantified, revealing, e.g., the precise temporal regulation of the SigB-dependent stress response and differential regulation of translation, fermentation, and amino acid biosynthesis. Using an in vivo murine pneumonia model, our data-independent acquisition quantification analysis revealed for the first time the in vivo proteome adaptation of S. aureus. From approximately 2.15 × 10  S. aureus cells, 578 proteins were identified. Increased abundance of proteins required for oxidative stress response, amino acid biosynthesis, and fermentation together with decreased abundance of ribosomal proteins and nucleotide reductase NrdEF was observed in post-infection samples compared to the pre-infection state.
    Keywords: Biology;
    ISSN: 2045-2322
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  • 8
    Language: English
    In: Scientific Reports, 01 June 2019, Vol.9(1), pp.1-9
    Description: Abstract This study was designed to assess risk factors for neurocognitive impairment in patients with benign intracranial lesions including tumors and vascular lesions. 74 patients (29 m, 51 f, mean age 54.4 years) with surgery for benign intracranial lesions were included in this prospective single-center study. Extensive neuropsychological testing was performed preoperatively, including tests for attention, memory and executive functions. Furthermore, headache and depression were assessed using the german version of the HDI (IBK) and the BDI-II. Multiple linear regression analyses of the percentile ranks (adjusted for age, sex and education) including the parameters age, Karnofsky Performance Status Scale (KPS), mood, pain and lesion size were performed to identify risk factors for cognitive impairment. Using the Mann-Whitney U test, the influence of hemisphere and type of lesion (tumor/vascular) was assessed. Posthoc Bonferroni correction was performed. Poorer neurocognitive functions were observed only in the category attention in patients with higher age (divided attention, WMS) and reduced KPS (WMS). Lesion volume, mood, pain, hemisphere or the type of the lesion (tumor, vascular) were not identified as risk factors for poorer neurocognitive functions in patients with benign intracranial lesions. Age and KPS are the main risk factors for poorer neurocognitive functions in the category attention in patients with benign intracranial lesions. Knowledge of these risk factors might be important to find appropriate therapy regimes to improve cognitive functions and quality of life.
    Keywords: Biology
    E-ISSN: 2045-2322
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