Search

Allograft Inflammatory Factor1 (AIF1), alias ionized calcium-binding adapter molecule 1 (IBA1), is a highly conserved Ca2+-binding cytokine that has been identified as a key regulator of the immune response in vertebrates. AIF1 is highly expressed in activated macrophages during inflammatory responses, thus representing an accurate indicator of macrophage activation in the body and a pathogenic factor in several inflammatory diseases. Proteins of the AIF1 superfamily are also present in invertebrates, from sponges to echinoderms. Here, we describe the Paracentrotus lividus Aif-1, which encodes a predicted protein of 151 amino acids with high similarity to vertebrate AIF1. In the common sea urchin, molecular and immunocytochemical analyses showed the constitutive expression of Aif-1 in the coelomocytes. Aif-1 localizes in the perinuclear area of amoebocytes and inside the granules of red cells, but it is not present in vibratile cells and colorless spherula cells. Moreover, significant increase of P. lividus Aif-1 expression, at both mRNA and protein level, are observed in coelomocytes after Gram+ bacterial challenge. BLAST searches across Echinoderm databases resulted in identification of orthologous proteins from 24 species (8 sea urchins, 1 brittle star, 12 starfishes and 3 sea cucumbers). Among these, P. lividus Aif-1 shared a high identity with several species, e.g., 85.4% with the sea urchin Strongylocentrotus purpuratus, 60.9% with the brittle star Ophiocoma echinata, 59.6% with the starfish Achantaster planci, and 52.3% with the sea cucumber Apostichopus japonicus. Our study on P. lividus Aif-1 will contribute to elucidate AIF1 function along the evolutionary scale and to consolidate the key evolutionary position of echinoderms throughout metazoans with respect to the common immune paths.

International audience; In Mammals, microglial cells are considered as the resident immune cells in central nervous system (CNS). Many studies demonstrated that, after injury, these cells are activated and recruited at the lesion site. Leech microglia present a similar pattern of microglial activation and migration upon experimental lesion of CNS. This activation is associated with the release of a large amount of extracellular vesicles (EVs). We collected EVs released by microglia primary culture and compared two different protocols of isolation: one with differential ultracentrifugation (UC) and one using an additional Optiprep™ Density Gradient (ODG) ultracentrifugation. Nanoparticles tracking analysis (NTA) and transmission electron microscopy (TEM) were used to assess vesicles size and morphology. The protein content of isolated EVs was assessed by mass spectrometry approaches. Results showed the presence of EV-specific proteins in both procedures. The extensive proteomic analysis of each single ODG fractions confirmed the efficiency of this protocol in limiting the presence of co-isolated proteins aggregates and other membranous particles during vesicles isolation. The present study permitted for the first time the characterisation of microglial EV protein content in an annelid model. Interestingly, an important amount of proteins found in leech vesicles was previously described in EV-specific databases. Finally, purified EVs were assessed for neurotrophic activity and promote neurites outgrowth on primary cultured neurons.

The presentation talks about LVAD implantation and outcomes among patients with Duchenne Muscular Dystrophy and end-stage heart failure.

In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produced long-lasting behavioral alterations such as social withdrawal and cognitive impairment in the social interaction test and in the novel object recognition test, respectively. At molecular level, an increased cannabinoid receptor type-1 (CB1) mRNA and protein expression which might be due to a reduction in DNA methylation at gene promoter in the prefrontal cortex (PFC), coincided with deficits in the social interaction test and in the novel object recognition test in MAM rats. Both schizophrenia-like phenotype and altered transcriptional regulation of CB1 receptors were reversed by peripubertal treatment (from PND 19 to PND 39) with the non-psychotropic phytocannabinoid cannabidiol (30 mg/kg/day), or, in part, by treatment with the cannabinoid CB1 receptor antagonist/inverse agonist AM251 (0.5 mg/kg/day), but not with haloperidol (0.6 mg/kg/day). These results suggest that early treatment with cannabidiol may prevent both the appearance of schizophrenia-like deficits as well as CB1 alterations in the PFC at adulthood, supporting that peripubertal cannabidiol treatment might be protective against MAM insult.