228 research outputs found

    A circadian zip code guides leukocyte homing

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    Circadian rhythms are important for organisms to anticipate predictable environmental changes. Evidence indicates that the oscillation of murine blood numbers is closely related to the lighting schedule. However, the dynamics and the mechanisms of the migration of leukocyte subsets over 24 hours are unknown. Here, we could show that that numbers of circulating leucocyte subsets exhibit circadian rhythms in murine blood, which was regulated by rhythmic homing, with a co-contribution of both microenvironmental and leukocyte-autonomous oscillations. We identified leukocyte and vascular bed specific surface expression oscillations of adhesion molecules and chemokine receptors over 24 hours. To test the relevance of these oscillations, functional blocking experiments using antibodies or functional blockers directed against pro-migratory molecules were performed. Our data indicate the adhesion molecules CD11a, CD49d and L-selectin and the chemokine receptor CXCR4 on the leukocyte side, as well as VCAM-1 and ICAM-1 on the endothelial side to be important in the rhythmic recruitment process of leukocyte subsets. A stronger blocking effect targeting these molecules was found at night for leukocyte subsets. In the homing experiments, we found donor leukocytes preferentially migrated to organs at night, and that the recruitment process of different leukocyte subsets to various organs could be blocked by distinct inhibitors. We exposed the role of circadian genes in the rhythmic recruitment process using B-cell and myeloid-cell-specific knockouts of the circadian gene Bmal1, which demonstrated altered expression levels of specific oscillatory molecules and leukocyte numbers in tissues, suggesting that rhythmicity in these factors may be directly regulated by the circadian clock. Furthermore, we detected inverse oscillation patterns of human blood cell numbers compared to murine cells as well as of the expression levels of CXCR4 on leukocyte subsets. Together, our data demonstrate that circadian genes control a rhythmic leukocyte- and tissue-specific molecular signature in the expression of pro-migratory factors, which allows for the recruitment of select leukocyte subsets at distinct times

    A circadian zip code guides leukocyte homing

    Get PDF
    Circadian rhythms are important for organisms to anticipate predictable environmental changes. Evidence indicates that the oscillation of murine blood numbers is closely related to the lighting schedule. However, the dynamics and the mechanisms of the migration of leukocyte subsets over 24 hours are unknown. Here, we could show that that numbers of circulating leucocyte subsets exhibit circadian rhythms in murine blood, which was regulated by rhythmic homing, with a co-contribution of both microenvironmental and leukocyte-autonomous oscillations. We identified leukocyte and vascular bed specific surface expression oscillations of adhesion molecules and chemokine receptors over 24 hours. To test the relevance of these oscillations, functional blocking experiments using antibodies or functional blockers directed against pro-migratory molecules were performed. Our data indicate the adhesion molecules CD11a, CD49d and L-selectin and the chemokine receptor CXCR4 on the leukocyte side, as well as VCAM-1 and ICAM-1 on the endothelial side to be important in the rhythmic recruitment process of leukocyte subsets. A stronger blocking effect targeting these molecules was found at night for leukocyte subsets. In the homing experiments, we found donor leukocytes preferentially migrated to organs at night, and that the recruitment process of different leukocyte subsets to various organs could be blocked by distinct inhibitors. We exposed the role of circadian genes in the rhythmic recruitment process using B-cell and myeloid-cell-specific knockouts of the circadian gene Bmal1, which demonstrated altered expression levels of specific oscillatory molecules and leukocyte numbers in tissues, suggesting that rhythmicity in these factors may be directly regulated by the circadian clock. Furthermore, we detected inverse oscillation patterns of human blood cell numbers compared to murine cells as well as of the expression levels of CXCR4 on leukocyte subsets. Together, our data demonstrate that circadian genes control a rhythmic leukocyte- and tissue-specific molecular signature in the expression of pro-migratory factors, which allows for the recruitment of select leukocyte subsets at distinct times

    Constrained capacity of MIMO Rayleigh fading channels

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    In this thesis channel capacity of a special type of multiple-input multiple-output (MIMO) Rayleigh fading channels is studied, where the transmitters are subject to a finite phase-shift keying (PSK) input alphabet. The constraint on the input alphabet makes an analytical solution for the capacity beyond reach. However we are able to simplify the final expression, which requires a single expectation and thus can be evaluated easily through simulation. To facilitate simulations, analytical expressions are derived for the eigenvalues and eigenvectors of a covariance matrix involved in the simplified capacity expression. The simplified expression is used to provide some good approximations to the capacity at low signal-to-noise ratios (SNRs). Involved in derivation of the capacity is the capacity-achieving input distribution. It is proved that a uniform prior distribution is capacity achieving. We also show that it is the only capacity-achieving distribution for our channel model. On top of that we generalize the uniqueness case for an input distribution to a broader range of channels

    Genetic Evolution and Molecular Selection of the HE Gene of Influenza C Virus

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    Influenza C virus (ICV) was first identified in humans and swine, but recently also in cattle, indicating a wider host range and potential threat to both the livestock industry and public health than was originally anticipated. The ICV hemagglutinin-esterase (HE) glycoprotein has multiple functions in the viral replication cycle and is the major determinant of antigenicity. Here, we developed a comparative approach integrating genetics, molecular selection analysis, and structural biology to identify the codon usage and adaptive evolution of ICV. We show that ICV can be classified into six lineages, consistent with previous studies. The HE gene has a low codon usage bias, which may facilitate ICV replication by reducing competition during evolution. Natural selection, dinucleotide composition, and mutation pressure shape the codon usage patterns of the ICV HE gene, with natural selection being the most important factor. Codon adaptation index (CAI) and relative codon deoptimization index (RCDI) analysis revealed that the greatest adaption of ICV was to humans, followed by cattle and swine. Additionally, similarity index (SiD) analysis revealed that swine exerted a stronger evolutionary pressure on ICV than humans, which is considered the primary reservoir. Furthermore, a similar tendency was also observed in the M gene. Of note, we found HE residues 176, 194, and 198 to be under positive selection, which may be the result of escape from antibody responses. Our study provides useful information on the genetic evolution of ICV from a new perspective that can help devise prevention and control strategies

    Reductive dehalogenation of 1,3-dichloropropane by a [Ni(tetramethylcyclam)]Br2-Nafion modified electrode

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    International audienceDechlorination reaction of 1,3-dichloropropane, a contaminant solvent, was investigated by electrochemical reduction in aqueous medium using a Ni(tmc)Br2 complex, known as effective catalyst in dehalogenation reactions. The catalytic activity of the complex was first investigated by cyclic voltammetry and flow homogeneous redox catalysis using a graphite felt as working electrode. A total degradation of 1,3-dichloropropane was obtained after 5 h of electrolysis with a substrate/catalyst ratio of 2.3. The concentration of chloride ions determined by ion chromatography analysis showed a dechlorination yield of 98%. The complex was then immobilized on the graphite felt electrode in a Nafion® film. Flow heterogeneous catalytic reduction of 1,3-dichloropropane was then carried out with the [Ni(tmc)]Br2-modified Nafion® electrode. GC analyses underlined the total degradation of the substrate in only 3.5 h with a substrate/catalyst ratio of 100. A dechlorination yield of 80% was obtained, as seen with ion chromatography analyses of chloride ion. Comparison of both homogeneous and heterogeneous reactions highlighted the interest of the [Ni(tmc)]Br2-modified Nafion® electrode that led to a higher stability of the catalyst with a turnover number of 180 and a higher current efficiency
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