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  • 1
    Publication Date: 2018-10-23
    Description: Enterovirus D68 (EV-D68) belongs to the picornavirus family and was first isolated in CA, USA, in 1962. EV-D68 can cause severe cranial nerve system damage such as flaccid paralysis and acute respiratory diseases such as pneumonia. There are currently no efficient therapeutic methods or effective prophylactics. In this study, we isolated the mAb A6-1 from an EV-D68–infected rhesus macaque ( Macaca mulatta ) and found that the Ab provided effective protection in EV-D68 intranasally infected suckling mice. We observed that A6-1 bound to the DE loop of EV-D68 VP1 and interfered with the interaction between the EV-D68 virus and α2,6-linked sialic acids of the host cell. The production of A6-1 and its Ab properties present a bridging study for EV-D68 vaccine design and provide a tool for analyzing the process by which Abs can inhibit EV-D68 infection.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 2
    Publication Date: 2018-11-22
    Description: A trimer-of-hairpins motif has been identified in triggering virus-cell fusion within a variety of viral envelopes. Chemically manipulating such a motif represents current repertoire of viral fusion inhibitors. Here, we report that triterpenoids, a class of natural products, antagonize this trimer-of-hairpins via its constitutive heptad repeat-2 (HR2), a prevalent α-helical coil in class I viral fusion proteins. Triterpenoids inhibit the entry of Ebola, Marburg, HIV, and influenza A viruses with distinct structure-activity relationships. Specifically, triterpenoid probes capture the viral envelope via photocrosslinking HR2. Profiling the Ebola HR2-triterpenoid interactions using amino acid substitution, surface plasmon resonance, and nuclear magnetic resonance revealed six residues accessible to triterpenoids, leading to wrapping of the hydrophobic helix and blocking of the HR1-HR2 interaction critical in the trimer-of-hairpins formation. This finding was also observed in the envelopes of HIV and influenza A viruses and might potentially extend to a broader variety of viruses, providing a mechanistic insight into triterpenoid-mediated modulation of viral fusion.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 3
    Publication Date: 2018-05-02
    Description: The serine/threonine kinase Polo-like kinase 1 (Plk1) plays a pivotal role in cell proliferation and has been validated as a promising anticancer drug target. However, very limited success has been achieved in clinical applications using existing Plk1 inhibitors, due to lack of sufficient specificity toward Plk1. To develop a novel Plk1 inhibitor with high selectivity and efficacy, we designed and synthesized a pyrrole-imidazole polyamide–Hoechst conjugate, PIP3, targeted to specific DNA sequence in the PLK1 promoter. PIP3 could specifically inhibit the cell cycle–regulated Plk1 expression and consequently retard tumor cell growth. Cancer cells treated with PIP3 exhibited severe mitotic defects and increased apoptosis, whereas normal cells were not affected by PIP3 treatment. Furthermore, subcutaneous injection of PIP3 into mice bearing human cancer xenografts induced significant tumor growth suppression with low host toxicity. Therefore, PIP3 exhibits the potential as an effective agent for targeted cancer therapy. Mol Cancer Ther; 17(5); 988–1002. ©2018 AACR .
    Print ISSN: 1535-7163
    Electronic ISSN: 1538-8514
    Topics: Medicine
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  • 4
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    German Medical Science; Düsseldorf, Köln
    In:  International Conference on SARS - one year after the (first) outbreak; 20040508-20040511; Lübeck; DOC04sars8.06 /20040526/
    Publication Date: 2004-05-26
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 5
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    German Medical Science; Düsseldorf, Köln
    In:  International Conference on SARS - one year after the (first) outbreak; 20040508-20040511; Lübeck; DOC04sarsP4.04 /20040526/
    Publication Date: 2004-05-26
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 6
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    German Medical Science; Düsseldorf, Köln
    In:  International Conference on SARS - one year after the (first) outbreak; 20040508-20040511; Lübeck; DOC04sarsP4.03 /20040526/
    Publication Date: 2004-05-26
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 7
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  GMS Ophthalmology Cases; VOL: 4; DOC03 /20140417/
    Publication Date: 2014-04-18
    Description: A healthy 12 month old infant without significant medical history presented with left eye redness for one week. Ophthalmic examination showed elevated intraocular pressure with iris neovascularization in the affected eye with increased optic nerve cupping. Scleral depression revealed a ciliary body mass in the supratemporal quadrant. A large, non-pigmented, vascular mass was noted; biopsy results showed multilayered cords, tubules, and sheets resembling primitive medullary epithelium arising from the ciliary body. The patient was diagnosed with medulloepithelioma. The patient underwent enucleation of the affected eye. Medulloepithelioma is a rare but important cause of neovascular glaucoma in the pediatric population. This case will focus on the characteristics of medulloepthelioma and the differential diagnosis for a non-pigmented ciliary body mass in a child.
    Keywords: ciliary body ; medulloepithelioma ; neovascular glaucoma ; ddc: 610
    Language: English
    Type: article
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  • 8
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  24. Jahrestagung der Deutschen Gesellschaft für Arterioskleroseforschung; 20100318-20100320; Blaubeuren; DOC10dgaf05 /20110323/
    Publication Date: 2011-03-23
    Description: Nitric oxide (NO) produced by the endothelial NO synthase (eNOS) represents a vasoprotective principle. Cardiovascular diseases are associated with decreased NO bioavailability and eNOS uncoupling (i.e., uncoupling of oxygen reduction from NO synthesis in eNOS). An uncoupled eNOS produces superoxide instead of NO. Therefore, compounds that increase eNOS protein levels are only beneficial when guaranteeing eNOS functionality. Recently, we have found compounds that maintain eNOS functionality in disease, and, at the same time, upregulate expression of the enzyme. Midostaurin upregulates eNOS expression through PKC-independent mechanisms and reduces NADPH oxidase expression via PKC inhibition. Oxidative stress-mediated oxidation of tetrahydrobiopterin (BH4), the essential eNOS cofactor, is likely to be a major cause for eNOS uncoupling. By reducing NADPH oxidase-mediated oxidative stress, midostaurin reverses eNOS uncoupling in spontaneously hypertensive rats and in atherosclerosis-prone apolipoprotein E knockout (apoE-KO) mice, which is associated with NO-mediated vasodilation and blood pressure reduction. AVE9488 and AVE3085 are two small-molecular weight eNOS transcription enhancers. Both compounds stimulate eNOS transcription in endothelial cells in vitro and in vascular tissues in vivo. Importantly, treatment of apoE-KO mice with AVE9488 enhances vascular BH4 levels and reverses eNOS uncoupling. In apoE-KO mice, but not in eNOS-knockout mice, treatment with AVE9488 reduces cuff-induced neointima formation. A 12-week treatment with AVE9488 or AVE3085 reduces atherosclerotic plaque formation in apoE-KO mice, but not in apoE/eNOS-double knockout mice. Also resveratrol reverses eNOS uncoupling and enhances eNOS expression. In conclusion, compounds combining eNOS upregulation with eNOS recoupling may have therapeutic potential for cardiovascular diseases.
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 9
    Keywords: PROTEINS ; INFECTION ; CARCINOGENESIS ; antibody ; ADENOCARCINOMAS ; multiplex serology ; CAGA ; ERADICATION ; SHANGHAI WOMENS HEALTH
    Abstract: Background: Helicobacter pylori is the leading risk factor for gastric cancer, yet only a fraction of infected individuals ever develop neoplasia. Methods: To identify potential predictive biomarkers, we assessed the association of 15 antibodies to H. pylori proteins and gastric cancer in a nested case-control study. Blood levels of antibodies were assessed using multiplex serology for 226 incident cases and 451 matched controls from the Shanghai Men's Health Study. ORs and 95% confidence intervals (CI) were calculated using conditional logistic regression. Results: Seropositivity to four (Omp, HP0305, HyuA, and HpaA) proteins was associated with a 1.5- to 3-fold increased risk for gastric cancer. When exCIuding cases diagnosed within 2 years of study enrollment, seropositivity to two additional proteins (CagA and VacA) showed significant associations with risk. Compared with individuals with three or fewer seropositive results to the six virulent proteins identified in this population, individuals with four to five seropositive results were at a 2-fold increased risk (OR, 2.08; 95% CI, 1.31-3.30) and individuals seropositive to all six proteins had a 3.5-fold increase in risk (OR, 3.49; 95% CI, 2.00-6.11) for gastric cancer. Among individuals diagnosed at least 2 years after study enrollment, these associations were even stronger (ORs, 2.79 and 4.16, respectively). Conclusions: Increasing number of seropositives to six H. pylori proteins may be a risk marker for distal gastric cancer in China. Impact: In a population with a 90% prevalence of CagA-positive H. pylori infection, assessment of additional virulent H. pylori proteins might better identify individuals at high risk for gastric cancer.
    Type of Publication: Journal article published
    PubMed ID: 23035179
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  • 10
    Keywords: REDUCTION ; PATTERNS ; DATABASE ; SECONDARY STRUCTURE ; OXIDATION ; AMINO-ACID-COMPOSITION ; INTRINSICALLY UNSTRUCTURED PROTEINS ; CONNECTIVITY ; WEB SERVER ; CYSTEINES
    Abstract: Protein disulfide bond is formed during post-translational modifications, and has been implicated in various physiological and pathological processes. Proper localization of disulfide bonds also facilitates the prediction of protein three-dimensional (3D) structure. However, it is both time-consuming and labor-intensive using conventional experimental approaches to determine disulfide bonds, especially for large-scale data sets. Since there are also some limitations for disulfide bond prediction based on 3D structure features, developing sequence-based, convenient and fast-speed computational methods for both inter- and intra-chain disulfide bond prediction is necessary. In this study, we developed a computational method for both types of disulfide bond prediction based on maximum relevance and minimum redundancy (mRMR) method followed by incremental feature selection (IFS), with nearest neighbor algorithm as its prediction model. Features of sequence conservation, residual disorder, and amino acid factor are used for inter-chain disulfide bond prediction. And in addition to these features, sequential distance between a pair of cysteines is also used for intra-chain disulfide bond prediction. Our approach achieves a prediction accuracy of 0.8702 for inter-chain disulfide bond prediction using 128 features and 0.9219 for intra-chain disulfide bond prediction using 261 features. Analysis of optimal feature set indicated key features and key sites for the disulfide bond formation. Interestingly, comparison of top features between interand intra-chain disulfide bonds revealed the similarities and differences of the mechanisms of forming these two types of disulfide bonds, which might help understand more of the mechanisms and provide clues to further experimental studies in this research field.
    Type of Publication: Journal article published
    PubMed ID: 22591475
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