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  • 1
    Online Resource
    Online Resource
    Basel :S. Karger AG,
    Keywords: Electronic books.
    Type of Medium: Online Resource
    Pages: 1 online resource (203 pages)
    Edition: 1st ed.
    ISBN: 9783318011746
    Series Statement: Chemical Immunology and Allergy Series ; v.86
    Language: English
    Note: Cover -- Contents -- Preface -- Antimicrobial Peptides: Basic Features and Clinical Relevance -- Antimicrobial Peptides in Drosophila: Structures, Activities and Gene Regulation -- Abstract -- Introduction -- Drosophila Defensin, An Anti-Gram-Positive Peptide -- The Antifungal Drosomycin -- Antifungal Peptide -- Metchnikowin, A Cysteine-Free Drosophila Antifungal Peptide -- Cecropins, alpha-Helical Peptides Largely Distributed in Higher Insect Orders -- Drosocin, An Anti-Gram-Negative O-Glycopeptide -- Diptericin, An Anti-Gram-Negative O-Glycopeptide -- Attacins, Large Polypeptides with Antibacterial Properties -- MPAC, the Drosophila Attacin C Pro-Domain with Antibacterial Properties -- Rel Proteins Control Expression of Antimicrobial Peptide Genes -- The Toll and IMD Pathways Control Inducible Expression of AMP Genes -- Other Signaling Pathways Activated during the Drosophila Immune Response -- Hemocytes in the Drosophila Immune Response -- Epithelial Responses in Drosophila -- Concluding Remarks -- Acknowledgements -- References -- Antimicrobial Peptides in Human Skin -- Abstract -- Introduction -- beta-Defensins -- Human beta-Defensin-2 -- Human beta-Defensin-3 -- Human beta-Defensin-1 -- Human beta-Defensin-4 -- Cathelicidin LL-37 -- Serine Protease Inhibitors Antileukoprotease and Elafin -- Dermcidin -- Adrenomedullin -- Neutrophil Gelatinase-Associated Lipocalin -- RNase 7 -- Skin Disease Implications -- Conclusion -- References -- Human Defensins in Crohn's Disease -- Abstract -- Introduction -- Epidemiology: The Role of Hygiene -- Pathophysiology: The Role of Luminal and Mucosal Bacteria -- Defensin Expression and Regulation in the Healthy Intestinal Tract -- Defensins and Inflammatory Bowel Diseases -- NOD2, A Peptidoglycan Receptor and Defensin Expression -- Toll-Like Receptors and Their Expression in Inflammatory Bowel Diseases. , Therapy: The Role of Antibiotics and Probiotics -- Concluding Remarks -- Acknowledgements -- References -- Antimicrobial Peptides in Lung Inflammation -- Abstract -- Introduction -- AMPs Are Expressed in the Respiratory Tract -- Host Defense in the Airways -- AMPs in the Human Lung -- Regulation of the AMPs in the Lung -- Functions of AMPs in the Respiratory Tract -- Antimicrobial Activity -- Inflammation, Angiogenesis, and Cell Function -- Role of AMPs in Pulmonary Disease -- Pneumonia and Tuberculosis -- Cystic Fibrosis and Diffuse Panbronchiolitis -- Asthma and Chronic Obstructive Pulmonary Disease -- Adult Respiratory Distress Syndrome -- Pulmonary Fibrosis and Sarcoidosis -- Conclusions -- Acknowledgement -- References -- Reciprocal Interactions of Host Cells and Microbes -- Bacterial Evasion of Innate Defense at Epithelial Linings -- Abstract -- How to Circumvent Physical Removal from Body Surfaces -- Overcome Space and Nutrient Deprivation -- Resisting the Low-pH Defense Barrier -- Avoid Protease Mediated Destruction and Opsonization -- Evade Recognition and Cell Activation -- Withstand Targeted Destruction -- Active Penetration of the Epithelial Cell Barrier -- Acknowledgements -- References -- Recognition of Bacterial Products by Toll-Like Receptors -- Abstract -- Mammalian Toll-Like Receptors and Their Ligands -- Extracellular Recognition of TLR Ligands -- TLR4 -- TLR2, TLR2/TLR1, and TLR2/TLR6 -- TLR10 -- TLR5 -- TLR11 -- Intracellular Recognition of TLR Ligands -- TLR3 -- TLR7/TLR8 -- TLR9 -- Conclusion -- References -- TLR Signalling and the Function of Dendritic Cells -- Abstract -- Introduction -- What Are Toll-Like Receptors? -- Toll-Like Receptors Recognize Various Molecules -- Signalling Pathway of TLRs -- MyD88-Dependent Pathway -- MyD88-Independent Pathway -- TIRAP/Mal -- TRIF -- TRAM -- The Role of TLR Family in the Host Defence. , TLRs Stimulate DCs to Induce T Cell Activation -- LPS-Stimulated MyD88-Deficient DCs -- DC Subset-Dependent Cytokine Production -- Conclusion -- References -- Contribution of T Cells to Epithelial Defense -- Immunosurveillance by gama/deltaT Cells: Focus on the Murine System -- Abstract -- TCRgamadelta+ Intraepithelial Lymphocytes -- Immunoprotective Roles of gamadelta T Cells in the Tissues -- Immunoregulatory Roles of Local gamadelta T Cells -- gamadelta+ T Cells and Tumor Surveillance -- gamadelta+ T Cell Regulation of Epithelial Malignancy -- From gamadelta Cell Biology in Mice to Immunosurveillance in Humans -- Immunological Mechanisms Highlighted by gamadelta Cells - Towards the Clinic -- References -- gamadelta T Cells Link Innate and Adaptive Immune Responses -- Abstract -- Introduction -- Vgama9/Vdelta2 T Cells -- Vgama9/Vdelta2 T Cells Are Expanded by Various Microbes -- Vgama9/Vdelta2 T Cells Are Activated by Non-Peptide Antigens -- Non-Mevalonate Pathway Intermediates Are the Most Potent Vgama9/Vdelta2 Activators -- Alkylamines Activate Vgama9/Vdelta2 T Cells -- N-Bisphosphonates Stimulate Vgama9/Vdelta2 T Cells -- Vgama9/Vdelta2 T Cells Can Kill Bacteria within Hours after Activation -- The Vgama9/Vdelta2 TCR Repertoire Is Shaped by Non-Peptide Antigens -- Vgama9/Vdelta2 T Cells and Tumor Surveillance -- Activation of Vgama9/Vdelta2 T Cells as a Therapeutic Approach in Tumor Treatment: From Bench to Bedside -- Vdelta1 Cells -- Vdelta1 T Cells Are the Dominant gamma/delta T Cell Population at Mucosal Surfaces -- Vdelta1 T Cells Are Activated by MICA/B -- Vdelta1 T Cells Are Activated by Glycolipids Presented by CD1 -- Lipid Extracts from Gram-Negative Bacteria Indirectly Stimulate Vdelta1T Cells -- TCR Repertoire of Vdelta1 T Cells -- The Role of Vdelta1 T Cells in Microbial Infections -- The Role of Vdelta1 T Cells in Tumor Recognition. , Migration and Homing of gamma/delta T cells -- Chemokine Expression of Peripheral gamma/delta T cells -- gamma/delta T Cells Can Be Polarized into TH1/TH2 Cells -- Chemokine Expression of Mucosal gamma/delta T Cells -- gamma/delta T Cells Can Have Immunosuppressive and Anti-Inflammatory Activities -- Expression of Toll-Like Receptors -- Concluding Remarks -- References -- Author Index -- Subject Index -- A -- B -- C -- D -- E -- F -- G -- H -- I -- L -- M -- N -- P -- R -- S -- T -- Y.
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  • 2
    Publication Date: 2015-07-09
    Print ISSN: 1045-2249
    Electronic ISSN: 1465-7279
    Topics: Biology
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  • 3
    Publication Date: 2013-01-03
    Description: The spectra of several high-redshift ( z 〉 6) quasars have shown indications for a Gunn–Peterson (GP) damping wing, suggesting a substantial mean neutral hydrogen fraction ( $\bar{x}_{\rm H\,{\scriptscriptstyle I}}^{\rm IGM}\gtrsim 0.03$ ) in the z 6 intergalactic medium (IGM). However, previous analyses assumed that the IGM was uniformly ionized outside of the quasar’s H  ii region. Here we relax this assumption and model patchy reionization scenarios for a range of IGM and quasar parameters. Compared to uniform reionization, patchy reionization imprints a different average damping wing profile with an associated sightline-to-sightline scatter. We quantify the impact of these differences on the inferred $\bar{x}_{\rm H\,{\scriptscriptstyle I}}^{\rm IGM}$ , by fitting the spectra of three quasars: SDSS J1148+5251 ( z = 6.4189), J1030+0524 ( z = 6.308) and J1623+3112 ( z = 6.247). We find that the best-fitting values of $\bar{x}_{\rm H\,{\scriptscriptstyle I}}^{\rm IGM}$ in the patchy models agree well with the uniform case. More importantly, we confirm that the observed spectra favour the presence of a GP damping wing, with peak likelihoods decreasing by factors of few–10 when the spectra are modelled without a damping wing. We also find that the Lyα absorption spectra, by themselves, cannot distinguish the damping wing in a relatively neutral IGM from a damping wing in a highly ionized IGM, caused either by an isolated neutral patch or by a damped Lyα absorber (DLA). However, neutral patches in a highly ionized universe ( $\bar{x}_{\rm H\,{\scriptscriptstyle I}}^{\rm IGM}\lesssim 10^{-2}$ ) and DLAs with the large required column densities ( $N_{\rm H\,{\small I}}\gtrsim {\rm { few}}\times 10^{20}{\rm { cm}^{-2}}$ ) are both rare. As a result, when we include reasonable prior probabilities for the line of sight (LOS) to intercept either a neutral patch or a DLA at the required distance of ~ 40-60 comoving Mpc away from the quasar, we find strong lower limits on the neutral fraction in the IGM, $\bar{x}_{\rm H\,{\scriptscriptstyle I}}^{\rm IGM}\gtrsim 0.1$ (at 95 per cent confidence). This supports earlier claims that a substantial global fraction of hydrogen in the z 6 IGM is in neutral form.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 4
    Publication Date: 2012-09-06
    Description: Nonpigmented Yersinia pestis ( pgm ) strains are defective in scavenging host iron and have been used in live-attenuated vaccines to combat plague epidemics. Recently, a Y. pestis pgm strain was isolated from a researcher with hereditary hemochromatosis who died from laboratory-acquired plague. We used hemojuvelin-knockout ( Hjv –/– ) mice to examine whether iron-storage disease restores the virulence defects of nonpigmented Y. pestis . Unlike wild-type mice, Hjv –/– mice developed lethal plague when challenged with Y. pestis pgm strains. Immunization of Hjv –/– mice with a subunit vaccine that blocks Y. pestis type III secretion generated protection against plague. Thus, individuals with hereditary hemochromatosis may be protected with subunit vaccines but should not be exposed to live-attenuated plague vaccines.
    Print ISSN: 0022-1899
    Electronic ISSN: 1537-6613
    Topics: Medicine
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  • 5
    Publication Date: 2016-02-16
    Description: We employed a semi-Markov multistate model for the simultaneous analysis of various endpoints describing the course of breast cancer. Results were compared with those from standard analyses using a Cox proportional hazards model. We included 3,012 patients with invasive breast cancer newly diagnosed between 2001 and 2005 who were recruited in Germany for a population-based study, the Mamma Carcinoma Risk Factor Investigation (MARIE Study), and prospectively followed up until the end of 2009. Locoregional recurrence and distant metastasis were included as intermediate states, and deaths from breast cancer, secondary cancer, and other causes were included as competing absorbing states. Tumor characteristics were significantly associated with all breast cancer–related endpoints. Nodal involvement was significantly related to local recurrence but more strongly related to distant metastases. Smoking was significantly associated with mortality from second cancers and other causes, whereas menopausal hormone use was significantly associated with reduced distant metastasis and death from causes other than cancer. The presence of cardiovascular disease at diagnosis was solely associated with mortality from other causes. Compared with separate Cox models, multistate models allow for dissection of prognostic factors and intermediate events in the analysis of cause-specific mortality and can yield new insights into disease progression and associated pathways.
    Print ISSN: 0002-9262
    Electronic ISSN: 1476-6256
    Topics: Medicine
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  • 6
    Publication Date: 2012-08-15
    Description: Aims Dynamic three-dimensional-cardiac magnetic resonance (3D-CMR) perfusion proved highly diagnostic for the detection of angiographically defined coronary artery disease (CAD) and has been used to assess the efficacy of coronary stenting procedures. The present study aimed to relate significant coronary lesions as assessed by fractional flow reserve (FFR) to the volume of myocardial hypoenhancement on 3D-CMR adenosine stress perfusion imaging and to define the inter-study reproducibility of stress inducible 3D-CMR hypoperfusion. Methods and results A total of 120 patients with known or suspected CAD were examined in two CMR centres using 1.5 T systems. The protocol included cine imaging, 3D-CMR perfusion during adenosine infusion, and at rest followed by delayed enhancement (DE) imaging. Fractional flow reserve was recorded in epicardial coronary arteries and side branches with ≥2 mm luminal diameter and 〉40% severity stenosis (pathologic FFR 〈 0.75). Twenty-five patients underwent an identical repeat CMR examination for the determination of inter-study reproducibility of 3D-CMR perfusion deficits induced by adenosine. Three-dimensional CMR perfusion scans were visually classified as pathologic if one or more segments showed an inducible perfusion deficit in the absence of DE. Myocardial ischaemic burden (MIB) was measured by segmentation of the area of inducible hypoenhancement and normalized to left ventricular myocardial volume (MIB, %). Three-dimensional CMR perfusion resulted in a sensitivity, specificity, and diagnostic accuracy of 90, 82, and 87%, respectively. Substantial concordance was found for inter-study reproducibility [Lin's correlation coefficient: 0.98 (95% confidence interval: 0.96–0.99)]. Conclusion Three-dimensional CMR stress perfusion provided high diagnostic accuracy for the detection of functionally significant CAD. Myocardial ischaemic burden measurements were highly reproducible and allowed the assessment of CAD severity.
    Print ISSN: 0195-668X
    Electronic ISSN: 1522-9645
    Topics: Medicine
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  • 7
    Publication Date: 2014-04-29
    Description: Potassium (K + )-uptake transport proteins present in prokaryote and eukaryote cells are categorized into two classes; Trk/Ktr/HKT, K + channel, and Kdp belong to the same superfamily, whereas the remaining K + -uptake family, Kup/HAK/KT has no homology to the others, and neither its membrane topology nor crucial residues for K + uptake have been identified. We examined the topology of Kup from Escherichia coli . Results from the reporter fusion and cysteine labeling assays support a model with 12 membrane-spanning domains. A model for proton-coupled K + uptake mediated by Kup has been proposed. However, this study did not show any stimulation of Kup activity at low pH and any evidence of involvement of the three His in Kup-mediated K + uptake. Moreover, replacement of all four cysteines of Kup with serine did not abolish K + transport activity. To gain insight on crucial residues of Kup-mediated K + uptake activity, we focused on acidic residues in the predicted external and transmembrane regions, and identified four residues in the membrane regions required for K + uptake activity. This is different from no membrane-localized acidic residues essential for Trk/Ktr/HKTs, K + channels and Kdp. Taken together, these results demonstrate that Kup belongs to a distinct type of K + transport system.
    Print ISSN: 0021-924X
    Electronic ISSN: 1756-2651
    Topics: Biology , Chemistry and Pharmacology
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