O2 Level Controls Hematopoietic Circulating Progenitor Cells Differentiation into Endothelial or Smooth Muscle Cells

BACKGROUND:Recent studies showed that progenitor cells could differentiate into mature vascular cells. The main physiological factors implicated in cell differentiation are specific growth factors. We hypothesized that simply by varying the oxygen content, progenitor cells can be differentiated either in mature endothelial cells (ECs) or contractile smooth muscle cells (SMCs) while keeping exactly the same culture medium. METHODOLOGY/PRINCIPAL FINDINGS:Mononuclear cells were isolated by density gradient were cultivated under hypoxic (5% O2) or normoxic (21% O2) environment. Differentiated cells characterization was performed by confocal microscopy examination and flow cytometry analyses. The phenotype stability over a longer time period was also performed. The morphological examination of the confluent obtained cells after several weeks (between 2 and 4 weeks) showed two distinct morphologies: cobblestone shape in normoxia and a spindle like shape in hypoxia. The cell characterization showed that cobblestone cells were positive to ECs markers while spindle like shape cells were positive to contractile SMCs markers. Moreover, after several further amplification (until 3(rd) passage) in hypoxic or normoxic conditions of the previously differentiated SMC, immunofluorescence studies showed that more than 80% cells continued to express SMCs markers whatever the cell environmental culture conditions with a higher contractile markers expression compared to control (aorta SMCs) signature of phenotype stability. CONCLUSION/SIGNIFICANCE:We demonstrate in this paper that in vitro culture of peripheral blood mononuclear cells with specific angiogenic growth factors under hypoxic conditions leads to SMCs differentiation into a contractile phenotype, signature of their physiological state. Moreover after amplification, the differentiated SMC did not reverse and keep their contractile phenotype after the 3rd passage performed under hypoxic and normoxic conditions. These aspects are of the highest importance for tissue engineering strategies. These results highlight also the determinant role of the tissue environment in the differentiation process of vascular progenitor cells

Malarial Hemozoin Is a Nalp3 Inflammasome Activating Danger Signal

BACKGROUND: Characteristic symptoms of malaria include recurrent fever attacks and neurodegeneration, signs that are also found in patients with a hyperactive Nalp3 inflammasome. Plasmodium species produce a crystal called hemozoin that is generated by detoxification of heme after hemoglobin degradation in infected red blood cells. Thus, we hypothesized that hemozoin could activate the Nalp3 inflammasome, due to its particulate nature reminiscent of other inflammasome-activating agents. METHODOLOGY/PRINCIPAL FINDINGS: We found that hemozoin acts as a proinflammatory danger signal that activates the Nalp3 inflammasome, causing the release of IL-1beta. Similar to other Nalp3-activating particles, hemozoin activity is blocked by inhibiting phagocytosis, K(+) efflux and NADPH oxidase. In vivo, intraperitoneal injection of hemozoin results in acute peritonitis, which is impaired in Nalp3-, caspase-1- and IL-1R-deficient mice. Likewise, the pathogenesis of cerebral malaria is dampened in Nalp3-deficient mice infected with Plasmodium berghei sporozoites, while parasitemia remains unchanged. SIGNIFICANCE/CONCLUSIONS: The potent pro-inflammatory effect of hemozoin through inflammasome activation may possibly be implicated in plasmodium-associated pathologies such as cerebral malaria

Malarial Hemozoin Is a Nalp3 Inflammasome Activating Danger Signal

BACKGROUND: Characteristic symptoms of malaria include recurrent fever attacks and neurodegeneration, signs that are also found in patients with a hyperactive Nalp3 inflammasome. Plasmodium species produce a crystal called hemozoin that is generated by detoxification of heme after hemoglobin degradation in infected red blood cells. Thus, we hypothesized that hemozoin could activate the Nalp3 inflammasome, due to its particulate nature reminiscent of other inflammasome-activating agents. METHODOLOGY/PRINCIPAL FINDINGS: We found that hemozoin acts as a proinflammatory danger signal that activates the Nalp3 inflammasome, causing the release of IL-1beta. Similar to other Nalp3-activating particles, hemozoin activity is blocked by inhibiting phagocytosis, K(+) efflux and NADPH oxidase. In vivo, intraperitoneal injection of hemozoin results in acute peritonitis, which is impaired in Nalp3-, caspase-1- and IL-1R-deficient mice. Likewise, the pathogenesis of cerebral malaria is dampened in Nalp3-deficient mice infected with Plasmodium berghei sporozoites, while parasitemia remains unchanged. SIGNIFICANCE/CONCLUSIONS: The potent pro-inflammatory effect of hemozoin through inflammasome activation may possibly be implicated in plasmodium-associated pathologies such as cerebral malaria

Terrestrial Very-Long-Baseline Atom Interferometry : summary of the second workshop

This summary of the second Terrestrial Very-Long-Baseline Atom Interferometry (TVLBAI) Workshop provides a comprehensive overview of our meeting held in London in April 2024 (Second Terrestrial Very-Long-Baseline Atom Interferometry Workshop, Imperial College, April 2024), building on the initial discussions during the inaugural workshop held at CERN in March 2023 (First Terrestrial Very-Long-Baseline Atom Interferometry Workshop, CERN, March 2023). Like the summary of the first workshop (Abend et al. in AVS Quantum Sci. 6:024701, 2024), this document records a critical milestone for the international atom interferometry community. It documents our concerted efforts to evaluate progress, address emerging challenges, and refine strategic directions for future large-scale atom interferometry projects. Our commitment to collaboration is manifested by the integration of diverse expertise and the coordination of international resources, all aimed at advancing the frontiers of atom interferometry physics and technology, as set out in a Memorandum of Understanding signed by over 50 institutions (Memorandum of Understanding for the Terrestrial Very Long Baseline Atom Interferometer Study)

Autobiography

In this email exchange, Jean-Christophe Menu inveighs against the deterioration of comics autobiography into a formulaic ‘genre’. Fabrice Neaud maintains that the autobiographical enterprise is necessarily a dangerous undertaking in which a precarious subject comes into being, unlike the ‘proximate’ autobiography featuring a ready-made persona in search of peer approval. He employs a Darwinist evolutionary metaphor to demonstrate the colonisation of the ecological niche that houses comics autobiography by an ‘autobiography-lite’ better adapted to the market. He details the criticisms that have been made of his work (‘egotistical’, or formally over-conservative) and laments the tendency to equate artless scribbles with ‘sincerity’. Menu regrets that a distanced and selective portrayal of family life can be read as invasive of privacy, with devastating legal consequences.</jats:p

Autobiography

In this email exchange, Jean-Christophe Menu inveighs against the deterioration of comics autobiography into a formulaic ‘genre’. Fabrice Neaud maintains that the autobiographical enterprise is necessarily a dangerous undertaking in which a precarious subject comes into being, unlike the ‘proximate’ autobiography featuring a ready-made persona in search of peer approval. He employs a Darwinist evolutionary metaphor to demonstrate the colonisation of the ecological niche that houses comics autobiography by an ‘autobiography-lite’ better adapted to the market. He details the criticisms that have been made of his work (‘egotistical’, or formally over-conservative) and laments the tendency to equate artless scribbles with ‘sincerity’. Menu regrets that a distanced and selective portrayal of family life can be read as invasive of privacy, with devastating legal consequences.</jats:p

Du contrôle de la tête au contrôle de la main (études en environnement gravito-inertiel)

AIX-MARSEILLE2-BU Sci.Luminy (130552106) / SudocTOULON-BU Centrale (830622101) / SudocSudocFranceF

Head positioning control in a gravito-inertial field and in normal gravity

The way in which the head is controlled in roll was investigated by dissociating the body axis and the gravito-inertial force orientation. Seated subjects (N = 8) were requested to align their head with their trunk, 30° to the left, 30° to the right or with the gravito-inertial vector, before, during (Per Rotation), after off-center rotation and on a tilted chair without rotation (Tilted). The gravito-inertial vector angle during rotation and the chair tilt angle were identical (17°). The subjects were either in total darkness or facing a visual frame that was fixed to the trunk. Both final error and within-subject variability of head positioning increased when the body axis and the gravito-inertial vector were dissociated (Per Rotation and Tilted). However, the behavior was different depending on whether the subjects were in the Tilted or Per Rotation conditions. The presentation of the visual frame reduced the within-subject variability and modified the perception of the gravito-inertial vector's orientation on the tilted chair. As head positioning with respect to the body and sensing of the gravito-inertial vector are modified when body axis and gravito-inertial vector orientation are dissociated, the observed decrease in performance while executing motor tasks in a gravito-inertial field may be at least in part attributed to the inaccurate sensing of head position.</jats:p