French Institute of Health and Medical Research

About: French Institute of Health and Medical Research is a government organization based out in Paris, France. It is known for research contribution in the topics: Population & Receptor. The organization has 109367 authors who have published 174236 publications receiving 8365503 citations.

Mitochondrio-nuclear translocation of AIF in apoptosis and necrosis

Abstract: Apoptosis inducing factor (AIF) is a novel apoptotic effector protein that induces chromatin condensation and large-scale (∼50 kbp) DNA fragmentation when added to purified nuclei in vitro. Confocal and electron microscopy reveal that, in normal cells, AIF is strictly confined to mitochondria and thus colocalizes with heat shock protein 60 (hsp60). On induction of apoptosis by staurosporin, c-Myc, etoposide, or ceramide, AIF (but not hsp60) translocates to the nucleus. This suggests that only the outer mitochondrial membrane (which retains AIF in the intermembrane space) but not the inner membrane (which retains hsp60 in the matrix) becomes protein permeable. The mitochondrio-nuclear redistribution of AIF is prevented by a Bcl-2 protein specifically targeted to mitochondrial membranes. The pan-caspase inhibitor Z-VAD.fmk does not prevent the staurosporin-induced translocation of AIF, although it does inhibit oligonucleosomal DNA fragmentation and arrests chromatin condensation at an early stage. ATP deple...

Krox-20 controls myelination in the peripheral nervous system.

Abstract: The molecular mechanisms controlling the process of myelination by Schwann cells remain elusive, despite recent progress in the identification and characterization of genes encoding myelin components (reviewed in ref. 1). We have created a null allele in the mouse Krox-20 gene, which encodes a zinc-finger transcription factor, by in-frame insertion of the Escherichia coli lacZ gene, and have shown that hindbrain segmentation is affected in Krox-20-/- embryos. We demonstrate here that Krox-20 is also activated in Schwann cells before the onset of myelination and that its disruption blocks Schwann cells at an early stage in their differentiation, thus preventing myelination in the peripheral nervous system. In Krox-20-/- mice, Schwann cells wrap their cytoplasmic processes only one and a half turns around the axon, and although they express the early myelin marker, myelin-associated glycoprotein, late myelin gene products are absent, including those for protein zero and myelin basic protein. Therefore Krox-20 is likely to control a set of genes required for completion of myelination in the peripheral nervous system.

Antimicrobial activity of mucosal-associated invariant T cells

Abstract: Mucosal-associated invariant T lymphocytes (MAIT lymphocytes) are characterized by two evolutionarily conserved features: an invariant T cell antigen receptor (TCR) alpha-chain and restriction by the major histocompatibility complex (MHC)-related protein MR1. Here we show that MAIT cells were activated by cells infected with various strains of bacteria and yeast, but not cells infected with virus, in both humans and mice. This activation required cognate interaction between the invariant TCR and MR1, which can present a bacteria-derived ligand. In humans, we observed considerably fewer MAIT cells in blood from patients with bacterial infections such as tuberculosis. In the mouse, MAIT cells protected against infection by Mycobacterium abscessus or Escherichia coli. Thus, MAIT cells are evolutionarily conserved innate-like lymphocytes that sense and help fight off microbial infection.

Transcription of the dystrophin gene in human muscle and non-muscle tissues

Abstract: The gene that is defective in patients with Duchenne and Becker muscular dystrophy consists of about 60 short exons scattered along a gigantic DNA region that spans some 2 megabase pairs1,2. The encoded protein, dystrophin, was recently characterized as a component of muscle intracellular membranes of low abundance3,4. The dystrophin messenger RNA is difficult to study in both normal and pathological tissue specimens because it is large (14 kilobases) and scarce (0.01–0.001% of total muscle mRNA)2. We report here that efficient in vitro co-amplifications of the mRNAs of the dystrophin gene and of a reporter gene, aldolase A, by the poly-merase chain reaction procedure5 enables us to obtain a quantitative estimate of the dystrophin gene transcript. A processed, transcribed segment was thus detected in 13 different human tissues. It ranged from 0.02–0.12% of total mRNA in skeletal muscle to 25,000 times less in lymphoblastoid cells.