Blocking TGF-β signaling pathway preserves mitochondrial proteostasis and reduces early activation of PDGFRβ+ pericytes in aristolochic acid induced acute kidney injury in wistar male rats

The platelet-derived growth factor receptor β (PDGFRβ)+ perivascular cell activation becomes increasingly recognized as a main source of scar-associated kidney myofibroblasts and recently emerged as a new cellular therapeutic target.In this regard, we first confirmed the presence of PDGFRβ+ perivascular cells in a human case of end-stage aristolochic acid nephropathy (AAN) and thereafter we focused on the early fibrosis events of transforming growth factor β (TGFβ) inhibition in a rat model of AAN.Neutralizing anti-TGFβ antibody (1D11) and its control isotype (13C4) were administered (5 mg/kg, i.p.) at Days -1, 0, 2 and 4; AA (15 mg/kg, sc) was injected daily.At Day 5, 1D11 significantly suppressed p-Smad2/3 signaling pathway improving renal function impairment, reduced the score of acute tubular necrosis, peritubular capillaritis, interstitial inflammation and neoangiogenesis. 1D11 markedly decreased interstitial edema, disruption of tubular basement membrane loss of brush border, cytoplasmic edema and organelle ultrastructure alterations (mitochondrial disruption and endoplasmic reticulum edema) in proximal tubular epithelial cells. Moreover, 1D11 significantly inhibited p-PERK activation and attenuated dysregulation of unfolded protein response (UPR) pathways, endoplasmic reticulum and mitochondrial proteostasis in vivo and in vitro.The early inhibition of p-Smad2/3 signaling pathway improved acute renal function impairment, partially prevented epithelial-endothelial axis activation by maintaining PTEC proteostasis and reduced early PDGFRβ+ pericytes-derived myofibroblasts accumulation

Forward Masking Estimated by Signal Detection Theory Analysis of Neuronal Responses in Primary Auditory Cortex

Psychophysical forward masking is an increase in threshold of detection of a sound (probe) when it is preceded by another sound (masker). This is reminiscent of the reduction in neuronal responses to a sound following prior stimulation. Studies in the auditory nerve and cochlear nucleus using signal detection theory techniques to derive neuronal thresholds showed that in centrally projecting neurons, increases in masked thresholds were significantly smaller than the changes measured psychophysically. Larger threshold shifts have been reported in the inferior colliculus of awake marmoset. The present study investigated the magnitude of forward masking in primary auditory cortical neurons of anaesthetised guinea-pigs. Responses of cortical neurons to unmasked and forward masked tones were measured and probe detection thresholds estimated using signal detection theory methods. Threshold shifts were larger than in the auditory nerve, cochlear nucleus and inferior colliculus. The larger threshold shifts suggest that central, and probably cortical, processes contribute to forward masking. However, although methodological differences make comparisons difficult, the threshold shifts in cortical neurons were, in contrast to subcortical nuclei, actually larger than those observed psychophysically. Masking was largely attributable to a reduction in the responses to the probe, rather than either a persistence of the masker responses or an increase in the variability of probe responses

Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort

Characterization of different viruses infecting the marine harmful algal bloom species Phaeocystis globosa

AbstractTwelve lytic viruses (PgV) infecting the marine unicellular eukaryotic harmful algal bloom species Phaeocystis globosa were isolated from the southern North Sea in 2000–2001 and partially characterized. All PgV isolates shared common phenotypic features with other algal viruses belonging to the family Phycodnaviridae and could be categorized in four different groups. Two main groups (PgV Group I and II) were discriminated based on particle size (150 and 100 nm respectively), genome size (466 and 177 kb) and structural protein composition. The lytic cycle showed a latent period of 10 h for PgV Group I and latent periods of 12 h and 16 h for PgV Group IIA and IIB. Host specificity and temperature sensitivity finally defined a fourth group (PgV Group IIC). Our results imply that viral infection plays an important role not only in P. globosa dynamics but also in the diversity of both host and virus community

: SIMPLES PARASITES OU ACTEURS MAJEURS DES ÉCOSYSTÈMES AQUATIQUES ?

National audienceLes virus n’en finissent pas de nous fasciner et de nous faire peur, du fait de leur caractère pathogène pour les plantes et les animaux. Dans les mers et les océans, ils sont des acteurs majeurs du fonctionnement des écosystèmes. Les virus constituent l’entité biologique la plus petite, la plus abondante et la plus diversifiée connue à ce jour en milieu marin, où ils exercent de multiples fonctions. Outre leur rôle dans la mortalité cellulaire et la redistribution de la matière, les virus sont aussi un puissant vecteur d’évolution de leurs hôtes et représentent une source majeure de diversité génétique, riche de découvertes pour la recherche fondamentale et appliquée. Cet ouvrage a pour but de mettre en lumière une communauté biologique invisible et essentielle pour comprendre et expliquer le fonctionnement des océans. Les auteurs, spécialistes de l’écologie et de l’évolution des virus aquatiques, montrent de quelle façon les virus régulent les écosystèmes microbiens, à la base des chaînes alimentaires des océans, et comment leur action pourrait, le cas échéant, agir sur le climat. Cet ouvrage est destiné aux étudiants en sciences de la vie et de la Terre, enseignants, chercheurs et universitaires, ainsi qu’au grand public intéressé par le sujet des virus et des océans