Antibody Vh Repertoire Differences between Resolving and Chronically Evolving Hepatitis C Virus Infections

Despite the production of neutralizing antibodies to hepatitis C virus (HCV), many patients fail to clear the virus and instead develop chronic infection and long-term complications. To understand how HCV infection perturbs the antibody repertoire and to identify molecular features of antibody genes associated with either viral clearance or chronic infection, we sequenced the V(D)J region of naïve and memory B cells of 6 persons who spontaneously resolved an HCV infection (SR), 9 patients with a newly diagnosed chronically evolving infection (CE), and 7 healthy donors. In both naïve and memory B cells, the frequency of use of particular antibody gene subfamilies and segments varied among the three clinical groups, especially between SR and CE. Compared to CE, SR antibody genes used fewer VH, D and JH gene segments in naïve B cells and fewer VH segments in memory B cells. SR and CE groups significantly differed in the frequency of use of 7 gene segments in naïve B cell clones and 3 gene segments in memory clones. The nucleotide mutation rates were similar among groups, but the pattern of replacement and silent mutations in memory B cell clones indicated greater antigen selection in SR than CE. Greater clonal evolution of SR than CE memory B cells was revealed by analysis of phylogenetic trees and CDR3 lengths. Pauciclonality of the peripheral memory B cell population is a distinguishing feature of persons who spontaneously resolved an HCV infection. This finding, previously considered characteristic only of patients with HCV-associated lymphoproliferative disorders, suggests that the B cell clones potentially involved in clearance of the virus may also be those susceptible to abnormal expansion

Immune Responses Elicited in Tertiary Lymphoid Tissues Display Distinctive Features

During chronic inflammation, immune effectors progressively organize themselves into a functional tertiary lymphoid tissue (TLT) within the targeted organ. TLT has been observed in a wide range of chronic inflammatory conditions but its pathophysiological significance remains unknown. We used the rat aortic interposition model in which a TLT has been evidenced in the adventitia of chronically rejected allografts one month after transplantation. The immune responses elicited in adventitial TLT and those taking place in spleen and draining lymph nodes (LN) were compared in terms of antibody production, T cell activation and repertoire perturbations. The anti-MHC humoral response was more intense and more diverse in TLT. This difference was associated with an increased percentage of activated CD4+ T cells and a symmetric reduction of regulatory T cell subsets. Moreover, TCR repertoire perturbations in TLT were not only increased and different from the common pattern observed in spleen and LN but also “stochastic,” since each recipient displayed a specific pattern. We propose that the abnormal activation of CD4+ T cells promotes the development of an exaggerated pathogenic immune humoral response in TLT. Preliminary findings suggest that this phenomenon i) is due to a defective immune regulation in this non-professional inflammatory-induced lymphoid tissue, and ii) also occurs in human chronically rejected grafts

When Patient Involvement and Collaborations between Patient Organisations and Healthcare Institutions May Overcom Issues Of Collective Advocacy and Representation

0info:eu-repo/semantics/publishe

Revisiting the thermodynamic modelling of type I gas–hydroquinone clathrates

ACLInternational audienceUnder specific pressure and temperature conditions, certain gaseous species can be engaged in a host lattice of hydroquinone molecules, forming a supramolecular entity called a gas hydroquinone clathrate. This study is devoted to the thermodynamic modelling of type I hydroquinone clathrates. The gases considered in this work are argon, krypton, xenon, methane, nitrogen, oxygen and hydrogen sulphide. The basic van der Waals and Platteeuw model, which is, for example, not able to predict well the phase equilibrium properties of such clathrates at high temperature, is modified and extended by considering first the solubility of the guest in solid HQ and then the mutual interactions between the gaseous molecules inside the clathrate structure (i.e. guest–guest interactions). Other improvements of the basic theory, such as the choice of the reference state, are proposed, and a unique set of thermodynamic parameters valid for all the studied guests are finally calculated. Very good agreement is obtained between the model predictions and the experimental data available in the literature. Our results clearly demonstrate that the highest level of theory is necessary to describe well both the triphasic equilibrium line (where the HQ clathrate, the native hydroquinone HQα and the gas coexist), the occupancy of the guest in the clathrate, and the intercalation enthalpy

A crystalline σ complex of copper

cited By 27International audienceOver the last decades, our understanding of σ-bond activation at transition metals has progressed considerably from both fundamental and synthetic points of view thanks to the preparation and characterization of a variety of σ complexes. Here we report the synthesis and structural analysis of the first σ complex involving a coinage metal. The copper(I) complex 2 derived from the diphosphine-disilane [Ph2P(C 6H4)Me2Si-SiMe2(C6H 4)PPh2] (1) has been isolated and crystallographically characterized. The coordination of the Si-Si σ bond to copper was thoroughly analyzed by quantum-chemical methods. © 2011 American Chemical Society

Synthetic, Cyclovoltammetric, and UV-Photoelectron Spectroscopic Studies of 2,3-Dihydro-1H-1,3,2-diazaboroles and 1,3,2-Diazaborolidines

Weber L, Domke I, Greschner W, Miqueu K, Chrostowska A, Baylere P. Synthetic, Cyclovoltammetric, and UV-Photoelectron Spectroscopic Studies of 2,3-Dihydro-1H-1,3,2-diazaboroles and 1,3,2-Diazaborolidines. Organometallics. 2005;24(22):5455-5463.The oxidation potentials E-ox of a series of 2,3-dihydro-1H-1,3,2-diazaboroles (BuNCH)-Bu-t=CHN(Bu-t)BR (1a-i) and of the corresponding saturated 1,3,2-diazaborolidines 2a (R = NH2)2b (OMe), 2c (Me), 2d (NMe2), 2e (H), 2f (SMe), 2g (SnMe3) 2h (Br), 2i (CN) were determined by cyclovoltammetry in CH2Cl2 solution. The potentials E-ox of the irreversible electrochemical oxidations range from E-ox = -288 mV (1a) to 752 mV (1i). In contrast to this, E-ox of the corresponding diazaborolidines are anodically shifted by 260 mV (1d, 2d) to 752 mV (1b, 2b) and vary from 280 mV (2a) to 1164 mV (2i). Gas-phase photoelectron spectra of representatives of both series of compounds were recorded and assessed by density functional calculations. The first ionization potentials of the 2,3-dihydro-1H-1,3,2-diazaboroles range in the series 1c (7.1 eV) < If (7.3 eV) < 1e = 1h (7.4 eV) < 1i (7.7 eV). They differ by less than 0.3 eV from the first ionization potentials determined for the saturated analogues [1st IP for 2c (7.3 eV) < 2e = 2f (7.4 eV) < 2h (7.7 eV)]

Activation of a σ-SnSn bond at copper, followed by double addition to an alkyne

cited By 19International audienceMany synthetically useful copper-catalyzed transformations involve the activation of apolar or weakly polar σ-bonds (E-H and E-E′ bonds, with E = C, B, Si, Sn, etc.). Yet, little is known so far about the associated elementary steps, and it is highly desirable to gain better knowledge regarding the way σ-bonds can be activated by copper to help further development in this area. To this end, we became interested in investigating the coordination and activation of apolar or weakly polar σ-bonds at copper using chelating assistance. Here we report investigations of gold and copper complexes deriving from the diphosphine-stannane [Ph2P(o-C6H 4)Me2Sn-SnMe2(o-C6H 4)PPh2] 1. The σ-SnSn bond of 1 readily undergoes oxidative addition at both gold and copper, giving bis(stannyl) Au+ and Cu+ complexes 2 and 3. Coordination of 1 to CuBr leads to the neutral complex 4 which features more σ-SnSn complex character. The ability of complex 3 to undergo insertion reactions with alkynes was then examined. With methyl propiolate, a clean reaction occurred, and the bis-stannylated alkene copper complex 5 was isolated. The structures of ligand 1 and complexes 2-5 have been unambiguously determined by multinuclear NMR spectroscopy and crystallography. These results substantiate the ability of copper to promote the addition of apolar σ-bonds to CC multiple bonds via a 2e redox sequence and draw thereby an unprecedented parallel with the group 10 metals. © 2013 American Chemical Society

Determination of the Global Phase Behavior of THF + CH4, +CO2, and + H2O Binary Mixtures using the SAFT-VR Approach.

COMInternational audienc

Organic Clathrates for Novel Phase Change Materials.

AFFInternational audienc