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  • 1
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Science Ltd
    Scandinavian journal of immunology 53 (2001), S. 0 
    ISSN: 1365-3083
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Morphological and functional heterogeneity of the splenic macrophage (Mφ) population was studied in Leishmania donovani (LD) infected BALB/c mice. On a discontinuous percoll gradient two distinct Mφ populations were separated. They differed significantly in size as evident from Scanning Electron Microscopy (SEM). Morphologically, the bigger Mφ (LM) showed surface projections, whereas the smaller Mφ (SM) was round. As regards the antigen-presenting abilities, the LM of infected animals showed defective antigen-presenting abilities at a later stage of the disease, i.e. 6 months post infection (6I-LM) but not earlier, whereas the SM population remained functionally intact throughout the course of the infection. Further, the 6I-LM showed a much enhanced Ad status as compared to their controls. Interestingly, both the 6I-LM and the control set showed a comparable level of binding of a known Ad restricted peptide. Despite the presence of sufficient Ad molecules and the ability to bind the appropriate peptide, 6I-LM were unable to stimulate peptide specific T-cell hybridoma. Further, the 6I-LM showed an increase in membrane fluidity and distorted morphology with membrane fissure and blebs as evident from SEM. It is possible that an increase in the membrane fluidity may lead to the defective antigen-presenting ability of 6I-LM. Thus, the LD infection functionally keep the 6I-LM out of antigen presentation and this may contribute to the defective cell mediated immune response in leishmaniasis.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    ISSN: 1365-3083
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: The expression of chemokines and chemokine receptors was studied in Leishmania donovani (LD)-infected human mononuclear phagocytes and the human monocytic cell line THP1. Our studies showed that LD infection caused the upregulation of three β chemokines (macrophage inflammatory protein-1 alpha (MIP-1α), MIP-1β and RANTES (regulated on activation normal T cell expressed and secreted)), one α chemokine (interleukin-8 (IL-8)) and the CC chemokine receptor 5 (CCR5) but not CCR1, as evident from reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. The CCR5 upregulation in human mononuclear phagocytes and THP1 cells was also evident by confocal microscopy. The possible association of such upregulation in relation to Leishmania and human immunodeficiency virus (HIV) coinfection was discussed.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Science Ltd
    International journal of dermatology 39 (2000), S. 0 
    ISSN: 1365-4632
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Science Ltd
    International journal of dermatology 43 (2004), S. 0 
    ISSN: 1365-4632
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Tetracyclines (TCN) were introduced in 1948 as broad-spectrum antibiotics that may be used in the treatment of many common infections in children and adults. One of the side-effects of tetracyclines is incorporation into tissues that are calcifying at the time of their administration. They have the ability to chelate calcium ions and to be incorporated into teeth, cartilage and bone, resulting in discoloration of both the primary and permanent dentitions. This permanent discoloration varies from yellow or gray to brown depending on the dose or the type of the drug received in relation to body weight. Minocycline hydrochloride, a semisynthetic derivative of tetracycline often used for the treatment of acne, has been shown to cause pigmentation of a variety of tissues including skin, thyroid, nails, sclera, teeth, conjunctiva and bone. Adult-onset tooth discoloration following long-term ingestion of tetracycline and minocycline has also been reported. The remarkable side-effect of minocycline on the oral cavity is the singular occurrence of “black bones”, “black or green roots” and blue-gray to gray hue darkening of the crowns of permanent teeth. The prevalence of tetracycline and minocycline staining is 3–6%. The mechanism of minocycline staining is still unknown. Most of the reviewed literature consisted of case reports; longitudinal clinical trials are necessary to provide more information on the prevalence, severity, etiology and clinical presentation of tetracycline and TCN-derivative staining in the adult population.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    ISSN: 1365-2486
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Biologie , Energietechnik , Geographie
    Notizen: Two experiments assessed the effect of current and elevated levels of ultravioletB (UV-B) radiation on forage crop production. The effect of current levels of UV-B radiation was assessed by comparing the growth of eight cultivars of four legume and four grass species for three growing seasons (1994–96) under simulated sward conditions in the field. An exclusion system using cellulose diacetate or polyester covers provided comparable growing conditions for the plants, except for the presence or absence of ambient UV-B radiation, respectively. The second experiment studied the effect of elevated levels of UV-B on eight cultivars of two legume and two grass species in the greenhouse under simulated sward conditions. Natural lighting with sufficient supplemental light was used to provide ideal growing conditions for a 16-h day length. Separate sets of UV lights were installed to provide UV-B levels at approximately the same intensity as would be found in mid summer, and 33% and 66% more than this value. A fourth treatment consisted of removing UV-B radiation by using a polyester filter. Plant production was measured in both experiments. In 1994, field herbage yields from all young grass and legume seedlings were not significantly affected by the exclusion of ambient UV-B radiation, with the exception of alfalfa. Intra-specific variations with alfalfa yields were found for reduced levels of UV-B radiation. In general, these trends persisted as stands matured during two post seeding years. In the second experiment, no significant differences were observed for all tested species with increasing levels of UV-B radiation, except with some alfalfa cultivars and one birdsfoot trefoil cultivar. Collectively, these results demonstrate that in the northern latitudes young and mature plants of the studied species are resistant to current and potentially higher levels of solar UV-B radiation, with the exception of some alfalfa cultivars. The yield of these cultivars increased under enhanced levels of UV-B radiation in the greenhouse and decreased when UV-B was excluded in the field.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Science Ltd
    International journal of dermatology 39 (2000), S. 0 
    ISSN: 1365-4632
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: In November 1997, approximately 1 year before being evaluated at the Mayo Clinic, Rochester, a 63-year-old woman presented with erosive tongue lesions that were diagnosed by her physician as oral lichen planus. The lesions responded well to 3 months of treatment with systemic and topical corticosteroids and topical antiyeast medication. She stopped taking the medications and had a relapse. A few months after the oral lesions developed, her left eyelid became ptotic. Results of magnetic resonance imaging of her brain were normal, and the ptosis resolved spontaneously after 2 weeks. One year later, her right eyelid began to droop, and the results of edrophonium testing were positive. She was prescribed prednisone, 30 mg daily, and pyridostigmine, as needed. The ptosis improved, but never fully resolved. Radiography revealed a left ‘‘thyroid nodule,’' but computed tomography did not show a mediastinal mass. She was advised to have the ‘‘nodule’' removed surgically and came to the Mayo Clinic, Rochester, for a second opinion.Her medical history was significant for the following: tinnitus, glaucoma, early bilateral cataracts, and long-standing hypertension, for which she took losartan, 50 mg twice daily. Other medications included: prednisone, 30 mg daily; pyridostigmine as needed; famotidine, 40 mg daily; and eyedrops for glaucoma. She denied any history of hyperthyroidism or hypothyroidism, head and neck irradiation, family history of thyroid disease, or diplopia. Hepatitis serologic studies revealed hepatitis B exposure and recovery, hepatitis C immunity, and a previous hepatitis A viral infection.On examination at the Mayo Clinic, Rochester, an erosive hypertrophic plaque was noted on the posterior dorsal half of the tongue, and vesicles and erythematous erosions on the hard and soft palates ( 〈link href="#f2.1"〉Fig. 1a). A lace-like white pattern was seen on the buccal mucosa bilaterally, and a small erosive patch on the left buccal mucosa ( 〈link href="#f2.1b"〉Fig. 1b). Ocular and nasal mucous membranes were normal in appearance, and there were no pertinent skin findings. Dermatopathologic examination of an excisional biopsy specimen from the left dorsum of the tongue demonstrated an ulcer with epitheliomatous hyperplasia and a granulomatous reaction, presumably due to yeast infection. Silver staining showed hyphae and yeast at the base of the tongue ulcer. The results of the direct immunofluorescence study were negative and revealed no lichenoid changes on hematoxylin and eosin staining. Indirect immunofluorescence testing of the serum revealed a 1 : 80 titer of basement membrane zone antibodies, reflecting pemphigoid. This test was positive on repeat study. Salt-split skin on monkey esophagus revealed an epidermal pattern of basement membrane zone antibodies. Treatment included fluocinonide gel applied to the involved areas four times daily and oral antiyeast therapy (fluconazole, 200 mg once daily by mouth) while the rest of the evaluation was being completed.〈figure xml:id="f2.1"〉1(a)〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD035-2:IJD_035_2_f1a"/〉Erosive hypertrophic tongue plaque.〈figure xml:id="f2.1b"〉 (b)  〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD035-2:IJD_035_2_f1b"/〉Erosive patch on the buccal mucosa.As part of the evaluation of the ptosis, a myasthenia gravis antibody panel was performed. It revealed the following abnormalities: striated muscle antibody at 1 : 480 (reference range, 〈1 : 60), acetylcholine receptor binding antibody at 6.33 nmol/L (reference range, ≤ 0.02 nmol/L), acetylcholine receptor blocking antibody at 31% (reference range, 0–25%), and acetylcholine receptor modulating antibody at 100% (reference range, 0–20%), suggesting thymoma. Treatment included pyridostigmine, 30–45 mg 3–4 times daily, to control the myasthenia symptoms, while the ill-defined neck mass was being evaluated.A mildly enlarged thyroid was noted on physical examination. Hematology panel revealed thyroid-stimulating hormone (TSH) levels in the low normal range; the thyroid microsomal antibody was normal. Chest radiography showed minor tracheal deviation, and a previous computed tomogram showed what appeared to be a 3-cm enlarged mass in the thyroid. Ultrasonographically guided thyroid biopsy did not show malignancy, but a benign mesenchymal-type tumor was found and surgical excision was planned. Intraoperatively, a thymoma of the left cervical thymic tongue was found.At 6 months' follow-up, the ptosis and oral mucosal lesions had improved significantly, although she continued topical corticosteroid therapy intermittently for minor erosive oral disease.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    Publikationsdatum: 2013-06-02
    Beschreibung: Comparative functional genomics studies the evolution of biological processes by analyzing functional data, such as gene expression profiles, across species. A major challenge is to compare profiles collected in a complex phylogeny. Here, we present Arboretum, a novel scalable computational algorithm that integrates expression data from multiple species with species and gene phylogenies to infer modules of coexpressed genes in extant species and their evolutionary histories. We also develop new, generally applicable measures of conservation and divergence in gene regulatory modules to assess the impact of changes in gene content and expression on module evolution. We used Arboretum to study the evolution of the transcriptional response to heat shock in eight species of Ascomycota fungi and to reconstruct modules of the ancestral environmental stress response (ESR). We found substantial conservation in the stress response across species and in the reconstructed components of the ancestral ESR modules. The greatest divergence was in the most induced stress, primarily through module expansion. The divergence of the heat stress response exceeds that observed in the response to glucose depletion in the same species. Arboretum and its associated analyses provide a comprehensive framework to systematically study regulatory evolution of condition-specific responses.
    Digitale ISSN: 1549-5469
    Thema: Biologie , Medizin
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    Publikationsdatum: 2017-07-06
    Beschreibung: Changes in chromatin state play important roles in cell fate transitions. Current computational approaches to analyze chromatin modifications across multiple cell types do not model how the cell types are related on a lineage or over time . To overcome this limitation, we developed a method called Chromatin Module INference on Trees (CMINT), a probabilistic clustering approach to systematically capture chromatin state dynamics across multiple cell types. Compared to existing approaches, CMINT can handle complex lineage topologies, capture higher quality clusters, and reliably detect chromatin transitions between cell types. We applied CMINT to gain novel insights in two complex processes: reprogramming to induced pluripotent stem cells (iPSCs) and hematopoiesis. In reprogramming, chromatin changes could occur without large gene expression changes, different combinations of activating marks were associated with specific reprogramming factors, there was an order of acquisition of chromatin marks at pluripotency loci, and multivalent states (comprising previously undetermined combinations of activating and repressive histone modifications) were enriched for CTCF. In the hematopoietic system, we defined critical decision points in the lineage tree, identified regulatory elements that were enriched in cell-type–specific regions, and found that the underlying chromatin state was achieved by specific erasure of preexisting chromatin marks in the precursor cell or by de novo assembly. Our method provides a systematic approach to model the dynamics of chromatin state to provide novel insights into the relationships among cell types in diverse cell-fate specification processes.
    Digitale ISSN: 1549-5469
    Thema: Biologie , Medizin
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    Publikationsdatum: 2012-07-03
    Beschreibung: Gaining insights on gene regulation from large-scale functional data sets is a grand challenge in systems biology. In this article, we develop and apply methods for transcriptional regulatory network inference from diverse functional genomics data sets and demonstrate their value for gene function and gene expression prediction. We formulate the network inference problem in a machine-learning framework and use both supervised and unsupervised methods to predict regulatory edges by integrating transcription factor (TF) binding, evolutionarily conserved sequence motifs, gene expression, and chromatin modification data sets as input features. Applying these methods to Drosophila melanogaster, we predict ~300,000 regulatory edges in a network of ~600 TFs and 12,000 target genes. We validate our predictions using known regulatory interactions, gene functional annotations, tissue-specific expression, protein–protein interactions, and three-dimensional maps of chromosome conformation. We use the inferred network to identify putative functions for hundreds of previously uncharacterized genes, including many in nervous system development, which are independently confirmed based on their tissue-specific expression patterns. Last, we use the regulatory network to predict target gene expression levels as a function of TF expression, and find significantly higher predictive power for integrative networks than for motif or ChIP-based networks. Our work reveals the complementarity between physical evidence of regulatory interactions (TF binding, motif conservation) and functional evidence (coordinated expression or chromatin patterns) and demonstrates the power of data integration for network inference and studies of gene regulation at the systems level.
    Digitale ISSN: 1549-5469
    Thema: Biologie , Medizin
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    Publikationsdatum: 2012-12-02
    Beschreibung: The order of genes in eukaryotic genomes has generally been assumed to be neutral, since gene order is largely scrambled over evolutionary time. Only a handful of exceptional examples are known, typically involving deeply conserved clusters of tandemly duplicated genes (e.g., Hox genes and histones). Here we report the first systematic survey of microsynteny conservation across metazoans, utilizing 17 genome sequences. We identified nearly 600 pairs of unrelated genes that have remained tightly physically linked in diverse lineages across over 600 million years of evolution. Integrating sequence conservation, gene expression data, gene function, epigenetic marks, and other genomic features, we provide extensive evidence that many conserved ancient linkages involve (1) the coordinated transcription of neighboring genes, or (2) genomic regulatory blocks (GRBs) in which transcriptional enhancers controlling developmental genes are contained within nearby bystander genes. In addition, we generated ChIP-seq data for key histone modifications in zebrafish embryos, which provided further evidence of putative GRBs in embryonic development. Finally, using chromosome conformation capture (3C) assays and stable transgenic experiments, we demonstrate that enhancers within bystander genes drive the expression of genes such as Otx and Islet , critical regulators of central nervous system development across bilaterians. These results suggest that ancient genomic functional associations are far more common than previously thought—involving ~12% of the ancestral bilaterian genome—and that cis -regulatory constraints are crucial in determining metazoan genome architecture.
    Digitale ISSN: 1549-5469
    Thema: Biologie , Medizin
    Standort Signatur Einschränkungen Verfügbarkeit
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