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  • 1
    Publication Date: 2023-12-21
    Description: CD4+ T lymphocytes play an essential role in host defense against bacterial, parasitic and viral infections. During infection, under the influence of intrinsic signals received through peptide-MHC/TCR interactions and extrinsic signals provided by pathogen-conditioned dendritic and other accessory cells, CD4+ T cells proliferate and differentiate into specialized T helper (Th) effectors, which produce distinct sets of cytokines tailored to combat a specific class of microbes. The concept of CD4+ T cell multi-functionality was developed after the seminal discovery of Th1 and Th2 cells nearly 30 years ago. Although the Th1/Th2 paradigm has successfully withstood the test of time, in the past decade additional Th subsets (Th17, Tfh, Th22, Th9) have been identified. Similarly, single cell analyses of cytokines and master transcriptional factors have revealed that, at the population level, CD4+ T cell responses are far more heterogeneous than initially anticipated. While some of the checkpoints in Th cell specification have been identified, recent studies of transcriptional and epigenetic regulation have uncovered a significant flexibility during the course CD4+ T lymphocyte polarization. In addition, Th cells expressing cytokines with counteracting functions, as a measure of self-regulation, display yet another level of diversity. Understanding the mechanisms that control the balance between stability vs. plasticity of Th effectors both at the time of initiation of immune response and during development of CD4 T cell memory is critical for the rational design of better vaccines and new immunotherapeutic strategies. This research topic will cover current views on Th cell development, with a focus on the mechanisms that govern differentiation, function and regulation of effector Th cells in the context of microbial infections.
    Keywords: R5-920 ; RC581-607 ; Infection ; Dendritic Cells ; Cytokines ; Immunoregulation ; CD4 lymphocytes ; Memory ; long noncoding RNA ; Macrophages ; Metabolism ; Th1 Th2 ; bic Book Industry Communication::M Medicine
    Language: English
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  • 2
    Publication Date: 2019
    Description: 〈p〉Fucosylated glycoconjugates are involved in a variety of physiological and pathological processes. However, economical production of fucosylated drugs and prebiotic supplements has been hampered by the poor catalytic efficiency of fucosyltransferases. Here, we developed a fluorescence-activated cell sorting system that enables the ultrahigh-throughput screening (〉10〈sup〉7〈/sup〉 mutants/hour) of such enzymes and designed a companion strategy to assess the screening performance of the system. After three rounds of directed evolution, a mutant M32 of the α1,3-FucT from 〈i〉Helicobacter pylori〈/i〉 was identified with 6- and 14-fold increases in catalytic efficiency (〈i〉k〈/i〉〈sub〉cat〈/sub〉/〈i〉K〈/i〉〈sub〉m〈/sub〉) for the synthesis of Lewis x and 3'-fucosyllactose, respectively. The structure of the M32 mutant revealed that the S45F mutation generates a clamp-like structure that appears to improve binding of the galactopyranose ring of the acceptor substrate. Moreover, molecular dynamic simulations reveal that helix α5, is more mobile in the M32 mutant, possibly explaining its high fucosylation activity.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 3
    Publication Date: 2016-09-17
    Description: Clostridium difficile infection (CDI) is the most common cause of antibiotic-associated diarrhea and colitis in developed countries. The disease is mainly mediated via two major exotoxins TcdA and TcdB secreted by the bacterium. We have previously developed a novel, potently neutralizing, tetravalent and bispecific heavy-chain-only single domain (V H H) antibody to both TcdA and TcdB (designated as ABA) that reverses fulminant CDI in mice. Since ABA has a short serum half-life, in this study a replication-deficient recombinant adenovirus expressing ABA was generated and the long-lasting expression of functional ABA was demonstrated in vitro and in vivo . Mice transduced with one dose of the adenovirus displayed high levels of serum ABA for more than1 month and were fully protected against systemic toxin challenges. More importantly, the ABA delivered by the adenovirus protected mice from both primary and recurrent CDI. Thus, replication-deficient adenoviral vector may be used to deliver neutralizing antibodies against the toxins in order to prevent CDI and recurrence.
    Print ISSN: 0928-8244
    Topics: Biology , Medicine
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  • 4
    Publication Date: 2013-02-02
    Description: The peer churn rate in the peer-to-peer (P2P) video-on-demand streaming service is much higher than in the P2P live streaming service, which makes the data scheduling problem more challenging. First, the available upload bandwidth information used in the data scheduling scheme is often inaccurate due to the peer churn, which lets a peer make bad scheduling decisions and leads to load imbalance. The higher peer churn makes this problem worse. Secondly, the higher peer churn exacerbates the bandwidth contention problem which occurs between a newly joined peer and some already-existing peers. To tackle the above two challenges, we propose an event-driven high-priority first data scheduling scheme, called EHPF scheme. To tackle the first challenge, we design a piggyback mechanism based on the event-driven mechanism. To tackle the second challenge, we design a priority calculation strategy to differentiate the requests from the newly joined peers and those from the already-existing peers, and use the high-priority first policy to allocate the upload bandwidths of peers. Through simulations and a real environment experiment, we demonstrate that the EHPF scheme outperforms the periodical data scheduling scheme in terms of startup delay, streaming quality and load balancing.
    Print ISSN: 0010-4620
    Electronic ISSN: 1460-2067
    Topics: Computer Science
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  • 5
    Publication Date: 2016-02-28
    Description: In this paper, we proposed an interesting method to test the dual supermassive black hole model for active galactic nucleus (AGN) with double-peaked narrow [O  iii ] lines (double-peaked narrow emitters) through their broad optical Balmer line properties. Under the dual supermassive black hole model for double-peaked narrow emitters, we could expect statistically smaller virial black hole masses estimated by observed broad Balmer line properties than true black hole masses (total masses of central two black holes). Then, we compare the virial black hole masses between a sample of 37 double-peaked narrow emitters with broad Balmer lines and samples of Sloan Digital Sky Survey selected normal broad line AGN with single-peaked [O  iii ] lines. However, we can find clearly statistically larger calculated virial black hole masses for the 37 broad line AGN with double-peaked [O  iii ] lines than for samples of normal broad line AGN. Therefore, we give our conclusion that the dual supermassive black hole model is probably not statistically preferred to the double-peaked narrow emitters, and more efforts should be necessary to carefully find candidates for dual supermassive black holes by observed double-peaked narrow emission lines.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 6
    Publication Date: 2016-01-15
    Description: In this Letter, we checked spectral properties of the well-known narrow line Seyfert I Mrk142, in order to try to find effects of narrow line variability on BLR radius of Mrk142 which is an outlier in the R–L plane. Although, no improvement can be found on BLR radius, apparent narrow line variability can be confirmed in Mrk142. Using the public spectra collected from the Lick AGN Monitoring Project, the spectral scaling method based on assumption of constant [O iii ] line is first checked by examining broad and narrow emission line properties. We find that with the application of the spectral scaling method, there is a strong correlation between the [O iii ] line flux and the [O iii ] line width, but weaker correlations between the broad Hα flux and the broad Hβ flux, and between the broad Hα flux and the continuum emission at 5100 Å. The results indicate that the assumption of constant [O iii ] line is not preferred, and caution should be exercised when applying the spectral scaling calibration method. And then, we can find a strong correlation between the [O iii ] line flux and the continuum emission at 5100 Å, which indicates apparent short-term variability of the [O iii ] line in Mrk142 over about two months.
    Print ISSN: 1745-3925
    Electronic ISSN: 1745-3933
    Topics: Physics
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  • 7
    Publication Date: 2012-06-06
    Description: Cerium oxide-doped ZnFe 2 O 4 sorbents supported on modified semi-coke (MSC) were prepared to improve the desulfurization efficiency of zinc ferrites. The sulfidation tests of the ZnFe 2 O 4 /MSC sorbents with and without Ce were carried out using a fixed-bed reactor at 450 °C. The effect of the CeO 2 /ZnFe 2 O 4 molar ratio of the sorbents on the sulfur capacity was studied. The characteristics of the sorbents were analyzed by X-ray diffraction, N 2 adsorption, scanning electron microscopy and X-ray photoelectron spectroscopy. The results showed that cerium oxide could greatly improve the desulfurization reactivity of the ZnFe 2 O 4 /MSC sorbents. The molar ratio of Ce to Zn and Fe influences the desulfurization reactivity, and a good sulfur capacity of the sorbent can be obtained with a Ce/Zn/Fe ratio of 4:4:1. It was also found that the addition of CeO 2 could enlarge the surface area and the pore volume, thus improving the dispersion of active components. Ce doping results in an increment of the oxygen adsorbed on the sorbent surface, which facilitates the adsorption of H 2 S. The Ce ions could act as carriers of the oxidation and reduction reactions and the oxygen transfer could be accelerated during the desulfurization process of coal gas. Cerium oxide-doped ZnFe 2 O 4 sorbents supported on modified semi-coke were prepared to improve the desulfurization efficiency of zinc ferrites. The addition of CeO 2 enlarges the surface area and the pore volume and improves the dispersion of active components. The increased amount of oxygen adsorbed on the sorbent surface induced by Ce doping facilitates the adsorption of H 2 S.
    Print ISSN: 0930-7516
    Electronic ISSN: 1521-4125
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Published by Wiley
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  • 8
    Publication Date: 2011-04-28
    Description: : Major and trace element, including REE, concentrations of the Doushantuo cap carbonate ( c . 635 Ma) in South China show enrichment in Fe, Mn and redox-sensitive elements and slightly negative Ce anomalies, indicating anoxic environments during cap carbonate precipitation. High Fe T /Al ratios but very low concentration of extractable pyrites suggest ferruginous rather than euxinic conditions. The REE + Y patterns of samples show enrichment of heavy REE (HREE), positive Eu anomalies and positive Y anomalies, implying a hydrothermal origin for elevated concentration of Fe, Mn and redox-sensitive elements. The results suggest that ferruginous Ediacaran oceans may have rooted from hydrothermally induced iron accumulation in severely glaciated Cryogenian oceans.
    Print ISSN: 0016-7649
    Topics: Geosciences
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  • 9
    Publication Date: 2014-11-12
    Description: Nitric oxide (NO), an active signaling molecule in plants, is involved in numerous physiological processes and adaptive responses to environmental stresses. Under high-salt conditions, plants accumulate NO quickly, and reorganize Na+ and K+ contents. However, the molecular connection between NO and ion homeostasis is largely unknown. Here, we report that...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 10
    Publication Date: 2014-11-20
    Description: Solenopsis invicta and Solenopsis richteri are two closely related invasive ants native to South America. Despite their similarity in biology and behavior, S. invicta is a more successful invasive species. Toxic tolerance has been found to be important to the success of some invasive species. Esterases play a crucial role in toxic tolerance of insects. Hence, we hypothesized that the more invasive S. invicta would have a higher esterase activity than S. richteri. Esterase activities were measured for workers and male and female alates of both ant species using α-naphthyl acetate and β-naphthyl acetate as substrates. Esterase activities in S. invicta were always significantly higher than those in S. richteri supporting our hypothesis. In S. invicta, male alates had the highest esterase activities followed by workers then female alates for both substrates. In S. richetri, for α-naphthyl acetate, male alates had the highest activity followed by female alates then workers, while for β-naphthyl acetate, female alates had the highest activity followed by male alates then workers. For workers, S. richteri showed significantly higher levels of variation about the mean esterase activity than S. invicta. However, S. invicta showed significantly higher levels of variation in both female and male alates. Scientific Reports 4 doi: 10.1038/srep07112
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
    Published by Springer Nature
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