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1.
Separation between primary and secondary lymphoid organs is a universal feature in jawed vertebrates. Strikingly, oncostatin M (OM)-transgenic mice present massive extrathymic T cell development, localized exclusively in the lymph nodes (LN). According to the prevailing paradigm, the thymus is the main source of T lymphocytes in gnathostomes mainly because thymic epithelial cells have a unique ability to support early steps in T cell development. It is therefore remarkable that productive T cell development occurs in the OM(+) LN, despite the absence of epithelial cells. The present study shows that in the OM(+) LN: 1) MHC class I expression strictly on hemopoietic cells is sufficient to support the development of a diversified repertoire of CD8 T cells; 2) the efficiency of positive selection of specific TCR-transgenic T cells is not the same as in the thymus; 3) negative selection is very effective, despite the lack of an organized thymic-like medulla. Furthermore, our data suggest that extrathymic T lymphocytes developing in the OM(+) LN undergo extensive postselection expansion because they live in the microenvironment in which they were positively selected. This work illustrates how the division of labor between primary and secondary lymphoid organs influences the repertoire and homeostasis of T lymphocytes. 相似文献
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Koura Jessica Manneh Rima Belarbi Rafik El Khoury Vanessa El Bachawati Makram 《The International Journal of Life Cycle Assessment》2020,25(3):423-442
The International Journal of Life Cycle Assessment - Vegetative roofs (VRs) are fully planted roof spaces that offer aesthetic view, storm water management, sound insulation, energy savings, and... 相似文献
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Ahmad I Hoessli DC Walker-Nasir E Choudhary MI Rafik SM Shakoori AR;Nasir-ud-Din 《Journal of cellular biochemistry》2006,99(3):706-718
Protein functions are determined by their three-dimensional structures and the folded 3-D structure is in turn governed by the primary structure and post-translational modifications the protein undergoes during synthesis and transport. Defining protein functions in vivo in the cellular and extracellular environments is made very difficult in the presence of other molecules. However, the modifications taking place during and after protein folding are determined by the modification potential of amino acids and not by the primary structure or sequence. These post-translational modifications, like phosphorylation and O-linked N-acetylglucosamine (O-GlcNAc) modifications, are dynamic and result in temporary conformational changes that regulate many functions of the protein. Computer-assisted studies can help determining protein functions by assessing the modification potentials of a given protein. Integrins are important membrane receptors involved in bi-directional (outside-in and inside-out) signaling events. The beta3 integrin family, including, alpha(IIb)beta3 and alpha(v)beta3, has been studied for its role in platelet aggregation during clot formation and clot retraction based on hydroxyl group modification by phosphate and GlcNAc on Ser, Thr, or Tyr and their interplay on Ser and Thr in the cytoplasmic domain of the beta3 subunit. An antagonistic role of phosphate and GlcNAc interplay at Thr758 for controlling both inside-out and outside-in signaling events is proposed. Additionally, interplay of GlcNAc and phosphate at Ser752 has been proposed to control activation and inactivation of integrin-associated Src kinases. This study describes the multifunctional behavior of integrins based on their modification potential at hydroxyl groups of amino acids as a source of interplay. 相似文献
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Samira Riabi Rafik Harrath Imed Gaaloul Lamjed Bouslama Dorsaf Nasri Mahjoub Aouni Sylvie Pillet Bruno Pozzetto 《Journal of biomedical science》2014,21(1):50
Background
Decay Accelerating Factor (DAF) and Coxsackievirus-Adenovirus Receptor (CAR) have been identified as cellular receptors for Coxsackie B viruses (CV-B). The aim of this study is to elucidate the different binding properties of CV-B serotypes and to find out if there are any amino acid changes that could be associated to the different phenotypes.Twenty clinical CV-B isolates were tested on CaCo-2 cell line using anti-DAF (BRIC216) and anti-CAR (RmcB) antibodies. CV-B3 Nancy prototype strain and a recombinant strain (Rec, CV-B3/B4) were tested in parallel. The P1 genomic region of 12 CV-B isolates from different serotypes was sequenced and the Trans-Epithelial Electrical Resistance (TEER) along with the virus growth cycle was measured.Results
Infectivity assays revealed clear differences between CV-B isolates with regard to their interactions with DAF and CAR. All tested CV-B isolates showed an absolute requirement for CAR but varied in their binding to DAF. We also reported that for some isolates of CV-B, DAF attachment was not adapted. Genetic analysis of the P1 region detected multiple differences in the deduced amino acid sequences.Conclusion
Within a given serotype, variations exist in the capacity of virus isolates to bind to specific receptors, and variants with different additional ligands may arise during infection in humans as well as in tissue culture. 相似文献6.
Prostate cancer (PCa) formation has been reported to be associated with androgen. Two key steps in the sex steroid synthesis are mediated by the enzyme cytochrome P450c 17α which is encoded in the CYP17 gene. The A2 allele of the CYP17 gene has been thought to be associated with increased functional activity of this steroidogenic enzyme. Consequently, the A2 allele has been examined as a biomarker of individual susceptibility to hormone-related diseases among men. We prospectively assessed the association between the A2 allele of CYP17 and PCa risk among 125 cases and 125 controls in a case–control study. Our aim was to investigate whether a polymorphism of CYP17 gene could be used as a genetic marker for associating PCa. The result revealed a significant association between the CYP17 polymorphic genotypes and PCa. Therefore, CYP17 gene polymorphism is likely contributed to the pathogenesis of PCa but not to disease severity. 相似文献
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Rafik Karmali Nicole Nijs-DeWolf Ingo Beyer Geoffrey N. Hendy Pierre Bergmann 《In vitro cellular & developmental biology. Animal》1999,35(5):296-298
Summary When fetal rat long bones are incubated in the presence of 10−8
M 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], steady-state parathyroid hormone-related peptide (PTHrP) mRNA levels are decreased. This decrease is temporary: it is observed
as soon as after 3 h of exposure and reaches a nadir after 6 h. At that time, PTHrP mRNA levels are significantly lower in
the experimental than in the control bones. However the inhibitory effect vanishes after 24 h, despite continuous exposure
to 1,25(OH)2D3 for even 48 h. This is the first report showing that PTHrP mRNA expression can be regulated in rat fetal long bones in vitro
by 1,25(OH)2D3. 相似文献
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Rafik Menasria Nicolas Boivin Manon Lebel Jocelyne Piret Jean Gosselin Guy Boivin 《Journal of virology》2013,87(13):7301-7308
Toll-like receptors (TLRs) and RNA helicases (RLHs) are important cell sensors involved in the immunological control of viral infections through production of type I interferon (IFN). The impact of a deficiency in the TRIF and IPS-1 adaptor proteins, respectively, implicated in TLR3 and RLH signaling pathways, was investigated during herpes simplex virus 1 (HSV-1) encephalitis. TRIF−/−, IPS-1−/−, and C57BL/6 wild-type (WT) mice were infected intranasally with 7.5 × 105 PFU of HSV-1. Mice were monitored for neurological signs and survival over 20 days. Groups of mice were sacrificed on days 3, 5, 7, 9, and 11 postinfection for determination of brain viral replication by quantitative PCR (qPCR), plaque assay, and immunohistochemistry and for alpha/beta interferon (IFN-α/β) levels and phosphorylation of interferon regulatory factors 3 and 7 (IRF-3 and -7) in brain homogenates by enzyme-linked immunosorbent assay (ELISA) and Western blotting, respectively. TRIF−/− and IPS-1−/− mice had higher mortality rates than WT mice (P = 0.02 and P = 0.09, respectively). Viral antigens were more disseminated throughout the brain, correlating with a significant increase in brain viral load for TRIF−/− (days 5 to 9) and IPS-1−/− (days 7 and 9) mice compared to results for the WT. IFN-β production was reduced in brain homogenates of TRIF−/− and IPS-1−/− mice on day 5 compared to results for the WT, whereas IFN-α levels were increased on day 7 in TRIF−/− mice. Phosphorylation levels of IRF-3 and IRF-7 were decreased in TRIF−/− and IPS-1−/− mice, respectively. These data suggest that both the TRIF and IPS-1 signaling pathways are important for the control of HSV replication in the brain and survival through IFN-β production. 相似文献
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Karaman R 《Bioorganic chemistry》2009,37(1):11-142
AM1 semi-empirical molecular orbital and ab initio HF at the 6-31G level calculations for the lactonization processes of 12 different hydroxy acids (1a-1l) which differ in their structural features have been conducted. The calculations obtained reveal the following: (1) The rate-limiting step in the lactonization process is formation of a tetrahedral intermediate and not its collapse as was previously reported. (2) The rate-limiting step in both the acid-catalyzed and uncatalyzed lactonization is composed of two successive steps: approach of the hydroxyl toward the carbonyl carbon until it reaches a distance of 1.4 -1.5 Å, followed by proton transfer from the ether-type oxygen to one of the hydroxyls in the tetrahedral intermediate. Calculations of the activation energies for formation of the tetrahedral intermediate in the 12 hydroxy acids studied indicate: (1) A linear relationship exists between the change in enthalpic energy (E) and the ratio of the attack angle (nucleophilic-oxygen/carbonyl-carbon/αλπηα-carbon) to the distance (nucleophilic-oxygen/carbonyl-carbon) termed α/r; (2) The slope (S) of E vs. α/r plots depend on the nature of the hydroxy acids. Furthermore, plots of S values against the experimental rate values (log kexp) show a linear correlation with a high correlation coefficient. The combined results suggest that hydroxy acids with low S values have high kexp values due to enthalpic proximity effects. 相似文献
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Marina P. Borisova Rafik A. Brutyan Lev N. Ermishkin 《The Journal of membrane biology》1986,90(1):13-20
Summary Zero current potential and conductance of ionic channels formed by polyene antibiotic amphotericin B in a lipid bilayer were studied in various electrolyte solutions. Nonpermeant magnesium and sulphate ions were used to independently vary the concentration of monovalent anions and cations as well as to maintain the high ionic strength of the two solutions separated by the membrane. Under certain conditions the channels select very strongly for anions over cations. They are permeable to small inorganic anions. However, in the absence of these anions the channels are practically impermeable to any cation. In the presence of a permeant anion the contribution of monovalent cations to channel conductance grows with an increase in the anion concentration. The ratio of cation-to-anion permeability coefficients is independent of the membrane potential and cation concentration, but it does depend linearly on the sum of concentrations of a permeant anion in the two solutions. These results are accounted for on the assumption that a cation can enter only an anion-occupied channel to form an ionic pair at the center of the channel. The cation is also assumed to slip past the anion and then to leave the channel for the opposite solution. This model with only few parameters can quantitatively describe the concentration dependences of conductance and zero current potential under various conditions. 相似文献