A Metabolomic Approach to the Study of Wine Micro-Oxygenation

Wine micro-oxygenation is a globally used treatment and its effects were studied here by analysing by untargeted LC-MS the wine metabolomic fingerprint. Eight different procedural variations, marked by the addition of oxygen (four levels) and iron (two levels) were applied to Sangiovese wine, before and after malolactic fermentation

Diagnostic yield of next-generation sequencing in very early-onset inflammatory bowel diseases: a multicenter study (vol 12, pg 1104, 2021)

Transplantation and immunomodulatio

Regulation of LFA-1-mediated T cell adhesion by CD4

Contains fulltext : 27189___.PDF (publisher's version ) (Open Access

REGULATION OF T-HELPER-B-LYMPHOCYTE ADHESION THROUGH CD4-HLA CLASS-II INTERACTION

Antigen???independent adhesion of CD4+ T lymphocytes to Epstein???Barr virus (EBV)???transformed B cells is mediated by CD2/lymphocyte function???associated antigen (LFA)???3 and LFA???1/intracellular adhesion molecule (ICAM)???1. Although some anti???CD4 antibodies block the antigen???independent adhesion of CD4+ T lymphocytes, the CD4???HLA class II interaction does not appear to significantly contribute to the forces of cell adhesion since CD4+ T cells equally bind HLA class II+ and HLA class II??? mutant B cells. In addition, conjugates formed between CD4+ T cells and HLA class II??? B cells remain stable for at least 1 h while CD4+T/HLA class II+ B cell conjugate percentages promptly drop off. Down???regulation of CD4 or spontaneous low expression of CD4 also results in a persistance of conjugates formed with B cells. The role of the CD4???HLA class II interaction has been further studied by investigating the inhibitory effect of synthetic 12???mer peptides analogous to HLA class II and containing the Arg???Phe???Asp???Ser sequence conserved in the ??1 domain. These peptides were previously found to inhibit HLA class II???restricted T cell responses, this sequence being thought to be involved in CD4???HLA class II interaction. These peptides block conjugate formation of CD4+ resting T cells or clones but not of CD8+ T cells, by interacting with the T cells as shown by preincubation experiments. Down???regulation of CD4 or spontaneous low expression results in the loss of the inhibitory activity. The peptide???mediated inhibition is neutralized by a soluble dimeric CD4 molecule. Alteration within the Arg???Phe???Asp???Ser sequence results in a significant loss of inhibition. It is thus proposed that the CD4???HLA class II interaction negatively regulates antigen???independent adhesion of T cells, this interaction involving the highly conserved Arg???Phe???Asp???Ser sequence in the HLA class II ??1 sequence as a CD4???binding site

A steroidomic approach for biomarkers discovery in doping control.

Anti-doping authorities have high expectations of the athlete steroidal passport (ASP) for anabolic-androgenic steroids misuse detection. However, it is still limited to the monitoring of known well-established compounds and might greatly benefit from the discovery of new relevant biomarkers candidates. In this context, steroidomics opens the way to the untargeted simultaneous evaluation of a high number of compounds. Analytical platforms associating the performance of ultra-high pressure liquid chromatography (UHPLC) and the high mass-resolving power of quadrupole time-of-flight (QTOF) mass spectrometers are particularly adapted for such purpose. An untargeted steroidomic approach was proposed to analyse urine samples from a clinical trial for the discovery of relevant biomarkers of testosterone undecanoate oral intake. Automatic peak detection was performed and a filter of reference steroid metabolites mass-to-charge ratio (m/z) values was applied to the raw data to ensure the selection of a subset of steroid-related features. Chemometric tools were applied for the filtering and the analysis of UHPLC-QTOF-MS(E) data. Time kinetics could be assessed with N-way projections to latent structures discriminant analysis (N-PLS-DA) and a detection window was confirmed. Orthogonal projections to latent structures discriminant analysis (O-PLS-DA) classification models were evaluated in a second step to assess the predictive power of both known metabolites and unknown compounds. A shared and unique structure plot (SUS-plot) analysis was performed to select the most promising unknown candidates and receiver operating characteristic (ROC) curves were computed to assess specificity criteria applied in routine doping control. This approach underlined the pertinence to monitor both glucuronide and sulphate steroid conjugates and include them in the athletes passport, while promising biomarkers were also highlighted

A steroidomic approach for biomarkers discovery in doping control.

Anti-doping authorities have high expectations of the athlete steroidal passport (ASP) for anabolic-androgenic steroids misuse detection. However, it is still limited to the monitoring of known well-established compounds and might greatly benefit from the discovery of new relevant biomarkers candidates. In this context, steroidomics opens the way to the untargeted simultaneous evaluation of a high number of compounds. Analytical platforms associating the performance of ultra-high pressure liquid chromatography (UHPLC) and the high mass-resolving power of quadrupole time-of-flight (QTOF) mass spectrometers are particularly adapted for such purpose. An untargeted steroidomic approach was proposed to analyse urine samples from a clinical trial for the discovery of relevant biomarkers of testosterone undecanoate oral intake. Automatic peak detection was performed and a filter of reference steroid metabolites mass-to-charge ratio (m/z) values was applied to the raw data to ensure the selection of a subset of steroid-related features. Chemometric tools were applied for the filtering and the analysis of UHPLC-QTOF-MS(E) data. Time kinetics could be assessed with N-way projections to latent structures discriminant analysis (N-PLS-DA) and a detection window was confirmed. Orthogonal projections to latent structures discriminant analysis (O-PLS-DA) classification models were evaluated in a second step to assess the predictive power of both known metabolites and unknown compounds. A shared and unique structure plot (SUS-plot) analysis was performed to select the most promising unknown candidates and receiver operating characteristic (ROC) curves were computed to assess specificity criteria applied in routine doping control. This approach underlined the pertinence to monitor both glucuronide and sulphate steroid conjugates and include them in the athletes passport, while promising biomarkers were also highlighted