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  • 1
    Publication Date: 2014-12-20
    Description: Multivalent molecules with repetitive structures including bacterial capsular polysaccharides and viral capsids elicit antibody responses through B cell receptor (BCR) crosslinking in the absence of T cell help. We report that immunization with these T cell-independent type 2 (TI-2) antigens causes up-regulation of endogenous retrovirus (ERV) RNAs in antigen-specific mouse B cells. These RNAs are detected via a mitochondrial antiviral signaling protein (MAVS)-dependent RNA sensing pathway or reverse-transcribed and detected via the cGAS-cGAMP-STING pathway, triggering a second, sustained wave of signaling that promotes specific immunoglobulin M production. Deficiency of both MAVS and cGAS, or treatment of MAVS-deficient mice with reverse transcriptase inhibitors, dramatically inhibits TI-2 antibody responses. These findings suggest that ERV and two innate sensing pathways that detect them are integral components of the TI-2 B cell signaling apparatus.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391621/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391621/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zeng, Ming -- Hu, Zeping -- Shi, Xiaolei -- Li, Xiaohong -- Zhan, Xiaoming -- Li, Xiao-Dong -- Wang, Jianhui -- Choi, Jin Huk -- Wang, Kuan-wen -- Purrington, Tiana -- Tang, Miao -- Fina, Maggy -- DeBerardinis, Ralph J -- Moresco, Eva Marie Y -- Pedersen, Gabriel -- McInerney, Gerald M -- Karlsson Hedestam, Gunilla B -- Chen, Zhijian J -- Beutler, Bruce -- P01 AI070167/AI/NIAID NIH HHS/ -- R01 AI093967/AI/NIAID NIH HHS/ -- R01 CA157996/CA/NCI NIH HHS/ -- U19 AI100627/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Dec 19;346(6216):1486-92. doi: 10.1126/science.346.6216.1486.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8502, USA. ; Department of Pediatrics and Children's Medical Center Research Institute, and McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8502, USA. ; Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8502, USA. Howard Hughes Medical Institute, Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9148, USA. ; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels vag 16, SE-171 77 Stockholm, Sweden. ; Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8502, USA. Bruce.Beutler@UTSouthwestern.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25525240" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/genetics/*immunology ; Animals ; Antibody Formation ; Antigens, T-Independent/*immunology ; B-Lymphocytes/*immunology ; Cytosol/immunology ; DNA/immunology ; Endogenous Retroviruses/genetics/*immunology ; Lymphocyte Activation ; Membrane Proteins/immunology ; Mice ; Mice, Inbred C57BL ; NF-kappa B/metabolism ; Nucleotides, Cyclic/immunology ; Nucleotidyltransferases/genetics/*immunology ; RNA, Viral/genetics/*immunology ; Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2018-08-07
    Description: Nonalcoholic steatohepatitis (NASH) is the progressive stage of nonalcoholic fatty liver disease that may ultimately lead to cirrhosis and liver cancer, and there are few therapeutic options for its treatment. Glycyrrhizin (GL), extracted from the traditional Chinese medicine liquorice, has potent hepatoprotective effects in both preclinical animal models and in humans. However, little is currently known about its effects and mechanisms in treating NASH. To explore the effects of GL on NASH, GL or its active metabolite glycyrrhetinic acid (GA) was administered to mice treated with a methionine- and choline-deficient (MCD) diet-induced NASH model, and histologic and biochemical analyses were used to measure the degree of lipid disruption, liver inflammation, and fibrosis. GL significantly improved MCD diet-induced hepatic steatosis, inflammation, and fibrosis and inhibited activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome. GL significantly attenuated serum bile acid accumulation in MCD diet-fed mice partially by restoring inflammation-mediated hepatic farnesoid X receptor inhibition. In Raw 264.7 macrophage cells, both GL and GA inhibited deoxycholic acid–induced NLRP3 inflammasome-associated inflammation. Notably, both intraperitoneal injection of GL’s active metabolite GA and oral administration of GL prevented NASH in mice, indicating that GL may attenuate NASH via its active metabolite GA. These results reveal that GL, via restoration of bile acid homeostasis and inhibition of inflammatory injury, can be a therapeutic option for treatment of NASH.
    Print ISSN: 0090-9556
    Electronic ISSN: 1521-009X
    Topics: Chemistry and Pharmacology , Medicine
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  • 3
    ISSN: 1432-1440
    Keywords: Key words Potassium channel ; Two P domains ; TOK1 ; d-ORK1 ; HOHO1 ; h-TPKC1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A new superfamily of K+ channels has emerged in the past 2 years. Notable for possessing two pore-forming P domains in each subunit, members of the superfamily have been recognized through phylogeny from micro-organisms to humans. Four subfamilies of two P domain channels have been isolated thus far; among these are the first cloned examples of outward rectifier and open rectifier (or leak) K+ channels. The two P domain K+ channels offer a new perspective from which to glimpse the molecular basis for function and dysfunction of K+-selective ion channels.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1435-5663
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Technology
    Notes: Abstract The vibration of machine tools during machining adversely affects machining accuracy and tool life, and therefore must be minimized. The cutting forces for stable turning are generally known to be random, and hence excite all the resonance modes. Of all these modes, those that generate relative motions between a cutting tool and a workpiece are of concern. This paper presents a new approach for designing an optimal damper to minimize the relative vibration between the cutting tool and workpiece during stable machining. An approximate normal mode method is employed to calculate the response of a machine tool system with nonproportional damping subject to random excitation. The major advantage of this method is that it reduces the amount of computation greatly for higher-order systems when responses have to be calculated repeatedly in the process of optimization. An optimal design procedure is presented based on a representative lumped parameter model that can be constructed by using existing experimental or analytical techniques. The two-step optimization procedure based on the modified pattern search and univariate search effectively leads the numerical solution to the global minimun irrespectively of initial values even under the existence of many local minima.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The use, transportation, and storage of the hazardous gas, arsine, raise serious safety issues. Consequently, there is considerable interest in the generation of arsine on demand from less hazardous substances. We report the first use of in situ generated arsine for III-V epitaxy. The gas has been generated electrochemically at an arsenic cathode in an aqueous electrolyte and used to supply a hydride vapor phase epitaxy reactor. InGaAs/InP test structures were grown on InP substrates and were similar to comparison structures grown using tank arsine. Recessed-gate enhanced Schottky metal-semiconductor field-effect transistors were fabricated and exhibited well-behaved current-voltage characteristics.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Various types of InP-based semiconductor lasers, Fabry–Perot (FP), and distributed feedback (DFB), in different wavelength regions of 1.3, 1.48, and 1.55 μm have been subjected to human-body-model electrostatic discharge (ESD) testing. The reverse V-I characteristics of these diode lasers were found to be generally most sensitive in detecting ESD damage than the forward characteristics (e.g., threshold current) of the laser. The laser ESD failure voltages were much lower for the reverse than the forward polarity and DFB lasers were found to be more vulnerable to ESD than FP lasers. The failure mechanism was found to be due to localized melting—a thermal effect—in both polarities of ESD testing. We also report the study of the latent ESD effects on the long-term aging rates of semiconductor lasers.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0005-2736
    Keywords: Magnetic field ; Potassium ion channel, ATP-sensitive ; Single-channel conductance
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 51 (1996), S. 87-94 
    ISSN: 0006-3592
    Keywords: cross-inhibition ; phenol ; glucose ; biodegradation kinetics ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The kinetics of utilization of glucose, phenol, and their mixtures by Pseudomonas putida (ATCC 17514) were studied with a continuously aerated, jacketed batch reactor operating at 28°C and pH 7.2. It was found that when glucose is the sole carbon and energy source, the culture utilizes it following Monod kinetics. When phenol is the sole carbon and energy source, the culture biodegrades it following Andrews (inhibitory) kinetics. When both glucose and phenol are present in the medium, the culture uses them simultaneously but with lower specific rates. Reduction of the specific substrate utilization rates indicates that the two substances are involved in a cross-inhibitory pattern which can be classified as uncompetitive. The values of the kinetic interaction constants suggest that glucose inhibits the specific rate of phenol removal much more than phenol inhibits the specific rate of glucose utilization. The results suggest that substitutable substrates which are dissimilar in origin and molecular structure may be involved in an uncompetitive cross-inhibitory interaction when they are simultaneously removed. It is also concluded that the use of easily degradable substrates may not enhance the per-unit amount of biomass removal of compounds which are classified as toxic. A general classification of kinetic interactions between substitutable resources is proposed. © 1996 John Wiley & Sons, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 9
    Publication Date: 2018-06-23
    Description: Introduction Acute lymphoblastic leukaemia is the most common paediatric cancer. Survivors of childhood acute lymphoblastic leukaemia (SALL) are at risk of obesity and related cardiometabolic diseases including type 2 diabetes, hypertension, stroke and cardiovascular events. Therefore, it is important to address obesity in this population as this may help mitigate future cardiometabolic comorbidities. In this systematic review, we aim to assess current treatment strategies including lifestyle interventions, pharmacotherapy and bariatric surgery to manage overweight and obesity in SALL. Methods and analysis We will search the following databases for primary studies: CINAHL, SPORTDiscus, EMBASE, MEDLINE, PsycINFO, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. In addition, unpublished primary studies will be searched in ClinicalTrials.gov as well as conference proceedings, presentations, abstracts, editorials and ProQuest Dissertations and Theses A&I. Reviewers will perform title, abstract, and full-text screening as well as data abstraction and risk of bias assessment independently with a third reviewer to be consulted to resolve disagreements. Searches will be run and updated through May 1st, 2018. The overall quality of the evidence will be determined using the Grading of Recommendations, Assessment, Development, and Evaluation criteria for each outcome. A meta-analysis will be performed if two studies deploying similar interventions, populations, and design and outcomes are identified. Ethics and dissemination As individual patient data will not be included, we do not require ethics approval. This review will be published in a peer-reviewed journal. PROSPERO registration number CRD42016051031.
    Keywords: Open access, Diabetes and Endocrinology
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 10
    Publication Date: 2018-12-08
    Description: The temperature-sensitive and calcium-permeable transient receptor potential vanilloid 3 (TRPV3) channel abundantly expressed in keratinocytes plays important functions in skin physiology. Dysfunctional gain-of-function TRPV3 gene mutations cause genetic Olmsted syndrome characterized by periorificial keratoderma, palmoplantar keratoderma, inflammation, and severe itching, which suggests that pharmacological inhibition of overactive TRPV3 function may be beneficial in treating pruritus or skin disorders. To test this hypothesis, we identified natural compound forsythoside B as a TRPV3 inhibitor through screening of human embryonic kidney 293 (HEK293) cells expressing human TRPV3 channels in a calcium fluorescent assay. Whole-cell patch-clamp recordings of HEK293 cells expressing TRPV3 confirmed that forsythoside B selectively inhibited the channel current activated by agonist 2-aminoethoxydiphenyl borate (50 µ M) in a dose-dependent fashion, with an IC 50 value of 6.7 ± 0.7 μ M. In vivo evaluation of scratching behavior demonstrated that pharmacological inhibition of TRPV3 by forsythoside B significantly attenuated acute itch induced by either the TRPV3 agonist carvacrol or the pruritogen histamine, as well as chronic itch induced by acetone-ether-water in a mouse model of dry skin. Furthermore, forsythoside B was able to prevent the death of HEK293 cells or native human immortalized nontumorigenic keratinocyte cells from human keratinocytes expressing a gain-of-function TRPV3 G573S mutant or in the presence of the TRPV3 agonist carvacrol. Taken together, our findings demonstrate the crucial role of TRPV3 in pruritus and keratinocyte toxicity; thus, specific inhibition of overactive TRPV3 by natural forsythoside B may possess therapeutic potential for treatment of chronic pruritus, skin allergy, or inflammation-related skin diseases.
    Print ISSN: 0022-3565
    Electronic ISSN: 1521-0103
    Topics: Medicine
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