Parasites or Cohabitants: Cruel Omnipresent Usurpers or Creative “Éminences Grises”?

This paper presents many types of interplays between parasites and the host, showing the history of parasites, the effects of parasites on the outcome of wars, invasions, migrations, and on the development of numerous regions of the globe, and the impact of parasitic diseases on the society and on the course of human evolution. It also emphasizes the pressing need to change the look at the parasitism phenomenon, proposing that the term “cohabitant” is more accurate than parasite, because every living being, from bacteria to mammals, is a consortium of living beings in the pangenome. Even the term parasitology should be replaced by cohabitology because there is no parasite alone and host alone: both together compose a new adaptive system: the parasitized-host or the cohabitant-cohabited being. It also suggests switching the old paradigm based on attrition and destruction, to a new one founded on adaptation and living together

Dynamics of glycine receptor insertion in the neuronal plasma membrane

The exocytosis site of newly synthesized glycine receptor was defined by means of a morphological assay to characterize its export from the trans-Golgi Network to the plasma membrane. This was achieved by expressing in transfected neurons an alpha1 subunit bearing an N-terminal tag selectively cleavable from outside the cell by thrombin. This was combined with a transient temperature-induced block of exocytic transport that creates a synchronized exocytic wave. Immunofluorescence microscopy analysis of the cell surface appearance of newly synthesized receptor revealed that exocytosis mainly occurred at nonsynaptic sites in the cell body and the initial portion of dendrites. At the time of cell surface insertion, the receptors existed as discrete clusters. Quantitative analysis showed that glycine receptor clusters are stable in size and subsequently appeared in more distal dendritic regions. This localization resulted from diffusion in the plasma membrane and not from exocytosis of transport vesicles directed to dendrites. Kinetic analysis established a direct substrate-product relationship between pools of somatic and dendritic receptors. This indicated that clusters represent intermediates between newly synthesized and synaptic receptors. These results support a diffusion-retention model for the formation of receptor-enriched postsynaptic domains and not that of a vectorial intracellular targeting to synapses

AMBER/VLTI high spectral resolution observations of the Brγ\gamma emitting region in HD 98922. A compact disc wind launched from the inner disc region

We analyse the main physical parameters and the circumstellar environment of the young Herbig Be star HD 98922. We present AMBER/VLTI high spectral resolution (R =12000) interferometric observations across the Br$\gamma$ line, accompanied by UVES high-resolution spectroscopy and SINFONI-AO assisted near-infrared integral field spectroscopic data. To interpret our observations, we develop a magneto-centrifugally driven disc-wind model. Our analysis of the UVES spectrum shows that HD 98922 is a young (~5x10^5 yr) Herbig Be star (SpT=B9V), located at a distance of 440(+60-50) pc, with a mass accretion rate of ~9+/-3x10^(-7) M_sun yr^(-1). SINFONI K-band AO-assisted imaging shows a spatially resolved circumstellar disc-like region (~140 AU in diameter) with asymmetric brightness distribution. Our AMBER/VLTI UT observations indicate that the Br$\gamma$ emitting region (radius ~0.31+/-0.04 AU) is smaller than the continuum emitting region (inner dust radius ~0.7+/-0.2 AU), showing significant non-zero V-shaped differential phases (i.e. non S-shaped, as expected for a rotating disc). The value of the continuum-corrected pure Br$\gamma$ line visibility at the longest baseline (89 m) is ~0.8+/-0.1, i.e. the Br$\gamma$ emitting region is partially resolved. Our modelling suggests that the observed Br$\gamma$ line-emitting region mainly originates from a disc wind with a half opening angle of 30deg, and with a mass-loss rate of ~2x10(-7) M_sun yr^(-1). The observed V-shaped differential phases are reliably reproduced by combining a simple asymmetric continuum disc model with our Br$\gamma$ disc-wind model. The Br$\gamma$ emission of HD 98922 can be modelled with a disc wind that is able to approximately reproduce all interferometric observations if we assume that the intensity distribution of the dust continuum disc is asymmetric.Comment: Accepted for publication on Astronomy \& Astrophysics. High resolution figures published on the main journal (see Astronomy & Astrophysics: Forthcoming) or at www.researchgate.net/profile/Alessio_Caratti_o_Garatti/publication

Identification, characterization and localization of chagasin, a tight-binding cysteine protease inhibitor in Trypanosoma cruzi

Lysosomal cysteine proteases from mammalian cells and plants are regulated by endogenous tight-binding inhibitors from the cystatin superfamily. The presence of cystatin-like inhibitors in lower eukaryotes such as protozoan parasites has not yet been demonstrated, although these cells express large quantities of cysteine proteases and may also count on endogenous inhibitors to regulate cellular proteolysis. Trypanosoma cruzi, the causative agent of Chagas heart disease, is a relevant model to explore this possibility because these intracellular parasites rely on their major lysosomal cysteine protease (cruzipain) to invade and multiply in mammalian host cells. Here we report the isolation, biochemical characterization, developmental stage distribution and subcellular localization of chagasin, an endogenous cysteine protease inhibitor in T. cruzi. We used high temperature induced denaturation to isolate a heat-stable cruzipain-binding protein (apparent molecular mass, 12 kDa) from epimastigote lysates. This protein was subsequently characterized as a tight-binding and reversible inhibitor of papain-like cysteine proteases. Immunoblotting indicated that the expression of chagasin is developmentally regulated and inversely correlated with that of cruzipain. Gold-labeled antibodies localized chagasin to the flagellar pocket and cytoplasmic vesicles of trypomastigotes and to the cell surface of amastigotes. Binding assays performed by probing living parasites with fluorescein (FITC)-cruzipain or FITC-chagasin revealed the presence of both inhibitor and protease at the cell surface of amastigotes. The intersection of chagasin and cruzipain trafficking pathways may represent a checkpoint for downstream regulation of proteolysis in trypanosomatid protozoa

Dose effect activity of ferrocifen-loaded lipid nanocapsules on a 9L-glioma model

Ferrociphenol (Fc-diOH) is a new molecule belonging to the fast-growing family of organometallic anti-cancer drugs. In a previous study, we showed promising in vivo results obtained after the intratumoural subcutaneous administration of the new drug-carrier system Fc-diOH-LNCs on a 9L-glioma model. To further increase the dose of this lipophilic entity, we have created a series of prodrugs of Fc-diOH. The phenol groups were protected by either an acetyl (Fc-diAc) or by the long fatty-acid chain of a palmitate (Fc-diPal). LNCs loaded with Fc-diOH prodrugs have to be activated in situ by enzymatic hydrolysis. We show here that the protection of diphenol groups with palmitoyl results in the loss of Fc-diOH in vitro activity, probably due to a lack of in situ hydrolysis. On the contrary, protection with an acetate group does not affect the strong, in vitro, antiproliferative effect of ferrocifen-loaded-LNCs neither the reduction of tumour volume observed on an ectopic model, confirming that acetate is easily cleaved by cell hydrolases. Moreover, the cytostatic activity of Fc-diOH-LNCs is confirmed on an orthotopic glioma model since the difference in survival time between the infusion of 0.36 mg/rat Fc-diOH-LNCs and blank LNCs is statistically significant. By using LNCs or Labrafac to carry the drug, a dose-effect ranging from 0.005 to 2.5mg of Fc-diOH per animal can be evidenced