The human homologue of Caenorhabditis elegans CED-6 specifically promotes phagocytosis of apoptotic cells

AbstractA key feature of the process of programmed cell death (apoptosis) is the efficiency with which the dying cells are recognized and engulfed by phagocytes [1]. Apoptotic cells are rapidly cleared either by neighbouring cells acting as semi-professional phagocytes or by experts of the macrophage line, so that an inflammatory response is avoided [2]. The Caenorhabditis elegans gene ced-6 is required for efficient engulfment of apoptotic cells [3] and is one of a group of genes that define two partially redundant parallel pathways for the engulfment process [4,5]. These pathways may be conserved across evolution, as two other engulfment genes have human homologues. A CED-5 homologue is part of a human CrkII–DOCK180–Rac signaling pathway proposed to mediate cytoskeletal reorganization [6–8] and a CED-7 homologue is similar to the ABC transporters [9,10]. Here, we report the cloning and characterization of human CED-6, a human homologue of C. elegans CED-6. The 34 kDa hCED-6 protein is expressed in most tissues, some human cancer cells, and in primary human macrophages. We developed an assay that quantitates the phagocytic activity of mammalian macrophages: the number of apoptotic cells that have been internalized is measured by the uptake of lacZ-positive apoptotic cells by adherent transgenic macrophages. The results of this assay demonstrate that overexpression of hCED-6 promotes phagocytosis only of apoptotic cells and suggest that hCED-6 is the mammalian orthologue of C. elegans CED-6 and is a part of a highly conserved pathway that specifically mediates the phagocytosis of apoptotic cells

In the land of pharma : a qualitative analysis of the reputational discourse of the pharmaceutical industry

The pharmaceutical industry has been battling a negative reputation and has been confronted with accusations such as putting profits before patients and manipulating clinical trial results. In this study, we focus on how pharmaceutical companies address what we define as the Bad Pharma discourse. Drawing on interviews, press releases, corporate documentation and ethnographic fieldwork, we analyse the main themes that are used by the Belgian pharmaceutical industry to construct its reputational discourse, and we focus on how this discourse is shaped by the Bad Pharma discourse. Our results illustrate that on the one hand, the industry contests the Bad Pharma discourse by generating an alternative discourse. On the other hand, they also partly embrace and reframe this Bad Pharma discourse. This way, current societal debates are entextualised in the reputational discourses of the pharmaceutical industry

Petroselinic acid purification and its use for the fermentation of new sophorolipids

Petroselinic acid, a positional isomer of oleic acid, was isolated from the vegetable oil of Coriandrum sativum fruits. This uncommon fatty acid was subsequently used as substrate for sophorolipid fermentation with a Starmerella bombicola lactone esterase overexpression (oe sble) strain. A petroselinic acid based diacetylated sophorolipid lactone was obtained in high purity without incorporation of de novo synthesized fatty acids such as oleic acid. A total production of 40 g/L was obtained. The petroselinic acid based sophorolipid lactone was subsequently hydrolyzed towards the petroselinic acid based sophorolipid acid. For both compounds, their critical micelle concentration (CMC) and corresponding surface tension were compared to their oleic acid based counterparts. Both petroselinic acid based sophorolipids displayed a much lower CMC value than their oleic acid based counterparts, although their minimal surface tension was the same. Besides, the sophorolipid fermentation product was chemically modified towards a novel C12 sophorolipid aldehyde. This derivative constitutes an interesting building block for further modification towards new-to-nature sophorolipids with high potential for self-assembly applications

Means and covariance functions for geostatistical compositional data: an axiomatic approach

This work focuses on the characterization of the central tendency of a sample of compositional data. It provides new results about theoretical properties of means and covariance functions for compositional data, with an axiomatic perspective. Original results that shed new light on the geostatistical modeling of compositional data are presented. As a first result, it is shown that the weighted arithmetic mean is the only central tendency characteristic satisfying a small set of axioms, namely continuity, reflexivity and marginal stability. Moreover, this set of axioms also implies that the weights must be identical for all parts of the composition. This result has deep consequences on the spatial multivariate covariance modeling of compositional data. In a geostatistical setting, it is shown as a second result that the proportional model of covariance functions (i.e., the product of a covariance matrix and a single correlation function) is the only model that provides identical kriging weights for all components of the compositional data. As a consequence of these two results, the proportional model of covariance function is the only covariance model compatible with reflexivity and marginal stability

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Multi-messenger Observations of a Binary Neutron Star Merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ∼ 1.7 {{s}} with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of {40}-8+8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 {M}ȯ . An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ∼ 40 {{Mpc}}) less than 11 hours after the merger by the One-Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ∼10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ∼ 9 and ∼ 16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC 4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta.</p

unc-53 controls longitudinal migration in C-elegans.

International audienceCell migration and outgrowth are thought to be based on analogous mechanisms that require repeated cycles of process extension, reading and integration of multiple directional signals, followed by stabilisation in a preferred direction, and renewed extension. We have characterised a C. elegans gene, unc-53, that appears to act cell autonomously in the migration and outgrowth of muscles, axons and excretory canals. Abrogation of unc-53 function disrupts anteroposterior outgrowth in those cells that normally express the gene. Conversely, overexpression of unc-53 in bodywall muscles leads to exaggerated outgrowth. UNC-53 is a novel protein conserved in vertebrates that contains putative SH3- and actin-binding sites. unc-53 interacts genetically with sem-5 and we demonstrated a direct interaction in vitro between UNC-53 and the SH2-SH3 adaptor protein SEM-5/GRB2. Thus, unc-53 is involved in longitudinal navigation and might act by linking extracellular guidance cues to the intracellular cytoskeleton

In the Land of Pharma: a thematic analysis of the corporate communication of the pharmaceutical industry

Over the past decade, the pharmaceutical industry has been battling a negative reputation and has been confronted with accusations, such as putting profits for patients and manipulating clinical trial results. In this study, we focus on how pharmaceutical companies use corporate communication as a strategic tool to battle, what we define as, “the Bad Pharma discourse”. Drawing on interviews, press releases, corporate documentation, and ethnographic fieldwork, we analyse the main themes that are used by the industry to construct its corporate reputation discourse and focus on how this discourse interacts with other discourses. Our results illustrate that on the one hand the industry contests the Bad Pharma discourse by generating an alternative discourse. On the other hand, they also partly embrace and reframe this Bad Pharma discourse. Therefore, we argue that corporate communication can be perceived as a never-ending struggle over meaning with other discourses