Overcoming class II-linked non-responsiveness to hepatitis B vaccine

This work shows that class II-linked humoral lack of response to an antigen can be overcome by joint immunization with the antigen and a T-helper cell determinant (TDh) well recognized by class II molecules of a non-responder individual. Thus, SJL/J mice (H-2s), which are non-responders to the S region of hepatitis B virus surface antigen (HBsAg), were rendered responders by joint immunization with a recombinant surface antigen, only composed of the S region, and a short synthetic TDh peptide well recognized by the H-2s restriction. By contrast, when this peptide is not recognized as TDh, as in B10M mice (H-2f restricted and also non-responders to the S region), no humoral response could be induced against the S region. These results have important implications for therapy and vaccination against hepatitis B virus as well as in enhancing the immunogenicity of other antigens

Enhancement of peptide immunogenicity by insertion of a cathepsin B cleavage site between determinants recognized by B and T cells

The insertion of two lysine residues (cleavage sites of cathepsin B) at the boundary of a peptide recognized by B cells (BD) and a class-II- presentable sequence (TDh) enhanced the anti-BD antibody induction capacity of this type of peptide construct, as well as production of IL2. It is postulated that these lysines generate a neoprocessable site which helps in release of the TDh moiety from the construct, enabling its presentation to class II molecules, an essential step in clonal expansion of the antibody-producing B cell after internalization of the construct via the BD moiety

Electrodeposition of sizeable and compositionally tunable rhodium-iron nanoparticles and their activity toward hydrogen evolution reaction

Rh-Fe nanoparticles (NPs) with variable Rh/Fe ratios have been obtained by direct current electrodeposition onto Au-metalized Si/Ti substrates from an electrolyte containing Rh(III) and Fe(III) chloride salts. NP mean diameter could be varied in the range of 20-80 nm by playing with the applied current density (-j = 0.5-2 mA cm-2) and deposition times (t = 200-3200 s). NPs were very well adhered to the substrate and became progressively enriched in Fe as the absolute value of the current density increased. X-ray photoelectron spectroscopy analyses revealed that the NPs are mostly metallic. The oxygen signal detected at surface level is relatively high but reduces down to less than 1 at% after 1 min Ar ions sputtering. The as-deposited Rh-Fe NPs are active toward hydrogen evolution reaction in alkaline medium. Different values of the onset potential for water reduction have been observed depending on the j and t values applied for NPs growth. Cycling stability tests reveal that NPs do not suffer from excessive deterioration of their electrocatalytic activity with time

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND: Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVE: We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS: We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 ± 19.2 years) recruited from 29 international centers. RESULTS: At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% ± 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of ≤35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS: MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 +/- 19.2 years) recruited from 29 international centers. RESULTS At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% +/- 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of <= 35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

Influence of fluoride content and pH on corrosion and tribocorrosion behaviour of Ti13Nb13Zr alloy in oral environment

© 2015 Elsevier Ltd. CpTi and Ti6Al4V alloy are the most widely used materials for implant application, but the release of toxic elements (. e.g. Al and V) and the so-called stress-shielding effect are still a concern. In recent years, β and near-. β titanium alloys have been developed, which overcome these issues with reduced modulus of elasticity and biocompatible alloying elements. However, literature is scarce studying the tribocorrosion behaviour of these alloys for dental implantology. The present work studies the tribocorrosion behaviour of the near-. β Ti13Nb13Zr alloy in oral environment, using CpTi4 for comparison purposes. To that end, the influence of the pH and fluoride concentration in artificial saliva was analysed. Reciprocating sliding corrosion tests were carried out under open circuit potential and potentiostatic conditions. Results reveal a negative influence of the increase of fluoride concentration and the acidified artificial saliva on the material degradation. Moreover, some light has been shed on the different tribocorrosion mechanisms of Ti13Nb13Zr and CpTi4 in simulated oral environment.This work was partially supported by Basque Department of Economic Development and Competitivity, S-PE13MU016, and Spanish Ministry of Economy and Competitivity, MAT2013-48224-C2-1-R-MUNSUTI.Peer Reviewe

Electrodeposition of sizeable and compositionally tunable rhodium-iron nanoparticles and their activity toward hydrogen evolution reaction

Rh-Fe nanoparticles (NPs) with variable Rh/Fe ratios have been obtained by direct current electrodeposition onto Au-metalized Si/Ti substrates from an electrolyte containing Rh(III) and Fe(III) chloride salts. NP mean diameter could be varied in the range of 20-80 nm by playing with the applied current density (-j = 0.5-2 mA cm-2) and deposition times (t = 200-3200 s). NPs were very well adhered to the substrate and became progressively enriched in Fe as the absolute value of the current density increased. X-ray photoelectron spectroscopy analyses revealed that the NPs are mostly metallic. The oxygen signal detected at surface level is relatively high but reduces down to less than 1 at% after 1 min Ar ions sputtering. The as-deposited Rh-Fe NPs are active toward hydrogen evolution reaction in alkaline medium. Different values of the onset potential for water reduction have been observed depending on the j and t values applied for NPs growth. Cycling stability tests reveal that NPs do not suffer from excessive deterioration of their electrocatalytic activity with time

Insights on the amino acid side-chain interactions of a synthetic T-cell determinant

The effect of single amino acid substitutions at positions 18 and 20 on the T-cell determinant (TD) character of peptide p12-26 from lambda repressor protein and on its recognition by a monoclonal antibody was studied by means of 40 synthetic peptides of a length of 15 amino acids. ELISA competition experiments showed that the identity of amino acid at position 20 is very important for antibody recognition, whereas that of amino acid at position 18 is much less important. In contrast, both Leu 18 and Ala 20 are important residues in defining the TD character of peptide p12-26. The most tolerated replacements, ordered in increasing disrupting power are: Ala 20 by Cys, Ser or Gly and Leu 18 by Ile or Val. Any other amino acid replacement completely abolishes the TD capacity of peptide p12-26. The peptides used in this study were synthesized using a multiple solid-phase peptide synthesizer newly designed. Their purity was very high as shown by amino acid sequence experiments