The human secretome

The proteins secreted by human cells (collectively referred to as the secretome) are important not only for the basic understanding of human biology but also for the identification of potential targets for future diagnostics and therapies. Here, we present a comprehensive analysis of proteins predicted to be secreted in human cells, which provides information about their final localization in the human body, including the proteins actively secreted to peripheral blood. The analysis suggests that a large number of the proteins of the secretome are not secreted out of the cell, but instead are retained intracellularly, whereas another large group of proteins were identified that are predicted to be retained locally at the tissue of expression and not secreted into the blood. Proteins detected in the human blood by mass spectrometry-based proteomics and antibody-based immuno-assays are also presented with estimates of their concentrations in the blood. The results are presented in an updated version 19 of the Human Protein Atlas in which each gene encoding a secretome protein is annotated to provide an open-access knowledge resource of the human secretome, including body-wide expression data, spatial localization data down to the single-cell and subcellular levels, and data about the presence of proteins that are detectable in the blood

Affinity Proteomic Profiling of Plasma, Cerebrospinal Fluid, and Brain Tissue within Multiple Sclerosis

Cet article est basé sur une correspondance inédite (1844-1846) entre une femme suisse de la haute société et son médecin, Antoine Despine. La patiente fut soignée à Aix-les-Bains, en Savoie, par les eaux, l’électrothérapie et le magnétisme animal. Cette correspondance est située dans le contexte historique des controverses de l’époque sur le magnétisme animal et, plus précisément, des théories, des pratiques et du style thérapeutique de Despine. L’article s’attache au personnage féminin et il montre comment la relation patient-thérapeute est en interrelation avec un groupe plus large d’adeptes du magnétisme.This article is based on an unpublished correspondence (1844-1846) between an upper-class Swiss woman and her physician, Antoine Despine. The patient was treated in Aix-les-Bains in Savoy by spa water, electrotherapy and mesmerism. This correspondence is situated within an historical context including controversies of that time on animal magnetism and, more precisely, Despine’s theories, practices and therapeutic style. The article focuses on the female character and analyses how the patient-therapist relationship interplays with a larger group of followers of animal magnetism

Somatic progenitor cell vulnerability to mitochondrial DNA mutagenesis underlies progeroid phenotypes in Polg mutator mice

Somatic stem cell (SSC) dysfunction is typical for different progeroid phenotypes in mice with genomic DNA repair defects. MtDNA mutagenesis in mice with defective Polg exonuclease activity also leads to progeroid symptoms, by an unknown mechanism. We found that Polg-Mutator mice had neural (NSC) and hematopoietic progenitor (HPC) dysfunction already from embryogenesis. NSC self-renewal was decreased in vitro, and quiescent NSC amounts were reduced in vivo. HPCs showed abnormal lineage differentiation leading to anemia and lymphopenia. N-acetyl-L-cysteine treatment rescued both NSC and HPC abnormalities, suggesting that subtle ROS/redox changes, induced by mtDNA mutagenesis, modulate SSC function. Our results show that mtDNA mutagenesis affected SSC function early but manifested as respiratory chain deficiency in nondividing tissues in old age. Deletor mice, having mtDNA deletions in postmitotic cells and no progeria, had normal SSCs. We propose that SSC compartment is sensitive to mtDNA mutagenesis, and that mitochondrial dysfunction in SSCs can underlie progeroid manifestations