Structural insights into Clostridium perfringens delta toxin pore formation

Clostridium perfringens Delta toxin is one of the three hemolysin-like proteins produced by C. perfringens type C and possibly type B strains. One of the others, NetB, has been shown to be the major cause of Avian Nectrotic Enteritis, which following the reduction in use of antibiotics as growth promoters, has become an emerging disease of industrial poultry. Delta toxin itself is cytotoxic to the wide range of human and animal macrophages and platelets that present GM2 ganglioside on their membranes. It has sequence similarity with Staphylococcus aureus β-pore forming toxins and is expected to heptamerize and form pores in the lipid bilayer of host cell membranes. Nevertheless, its exact mode of action remains undetermined. Here we report the 2.4 Å crystal structure of monomeric Delta toxin. The superposition of this structure with the structure of the phospholipid-bound F component of S. aureus leucocidin (LukF) revealed that the glycerol molecules bound to Delta toxin and the phospholipids in LukF are accommodated in the same hydrophobic clefts, corresponding to where the toxin is expected to latch onto the membrane, though the binding sites show significant differences. From structure-based sequence alignment with the known structure of staphylococcal α-hemolysin, a model of the Delta toxin pore form has been built. Using electron microscopy, we have validated our model and characterized the Delta toxin pore on liposomes. These results highlight both similarities and differences in the mechanism of Delta toxin (and by extension NetB) cytotoxicity from that of the staphylococcal pore-forming toxins

In Antisynthetase Syndrome, ACPA Are Associated With Severe and Erosive Arthritis: An Overlapping Rheumatoid Arthritis and Antisynthetase Syndrome

International audienceAbstract: Anticitrullinated peptide/protein antibodies (ACPA), which are highly specific for rheumatoid arthritis (RA), may be found in some patients with other systemic autoimmune diseases. The clinical significance of ACPA in patients with antisynthetase syndrome (ASS), a systemic disease characterized by the association of myositis, interstitial lung disease, polyarthralgia, and/or polyarthritis, has not yet been evaluated with regard to phenotype, prognosis, and response to treatment. ACPA-positive ASS patients were first identified among a French multicenter registry of patients with ASS. Additionally, all French rheumatology and internal medicine practitioners registered on the Club Rhumatismes et Inflammation web site were asked to report their observations of ASS patients with ACPA. The 17 collected patients were retrospectively studied using a standardized questionnaire and compared with 34 unselected ACPA-negative ASS patients in a case–control study. All ACPA-positive ASS patients suffered from arthritis versus 41% in the control group (P 7-year mean follow-up, extra-articular outcomes and survival were not different. ACPA-positive ASS patients showed an overlapping RA–ASS syndrome, were at high risk of refractory erosive arthritis, and might experience ASS flare when treated with antitumor necrosis factor drugs. In contrast, other biologics such as anti-CD20 mAb were effective in this context, without worsening systemic involvements

Evolution de la composition en polyamines des baies de raisin au cours du processus d'infection par Botrytis cinerea

Evolution of polyamine composition in grape berries during infection with Botrytis cinereaPolyamines are growth regulators occurring naturally in grapevine(Vitis vinifera L.) and pathogenic fungi, e.g. Botrytis cinerea. Investigation of polyamines of in vitro-grown Botrytis cinerea mycelium and infected berries has shown modifications in the metabolism of the berries which are directly related to the development of the fungi in the berries. The abnormal polyamine concentrations in infected berries appear to be of fungal origin for free polyamines and of plant origin for conjugated polyamines. The specific role of each type of polyamine is discussed with regard to the host-parasite relation.

Real-time navigation by fluorescence-based enhanced reality for precise estimation of future anastomotic site in digestive surgery.

Fluorescence-based enhanced reality (FLER) is a technique to evaluate intestinal perfusion based on the elaboration of the Indocyanine Green fluorescence signal. The aim of the study was to assess FLER's performances in evaluating perfusion in an animal model of long-lasting intestinal ischemia. An ischemic segment was created in 18 small bowel loops in 6 pigs. After 2 h (n = 6), 4 h (n = 6), and 6 h (n = 6), loops were evaluated clinically and by FLER to delineate five regions of interest (ROIs): ischemic zone (ROI 1), presumed viable margins (ROI 2a-2b), and vascularized areas (3a-3b). Capillary lactates were measured to compare clinical vs. FLER assessment. Basal (V 0 ) and maximal (V max) mitochondrial respiration rates were determined according to FLER. Lactates (mmol/L) at clinically identified resection lines were significantly higher when compared to those identified by FLER (2.43 ± 0.95 vs. 1.55 ± 0.33 p = 0.02) after 4 h of ischemia. Lactates at 2 h at ROI 1 were 5.45 ± 2.44 vs. 1.9 ± 0.6 (2a-2b; p < 0.0001) vs. 1.2 ± 0.3 (3a-3b; p < 0.0001). At 4 h, lactates were 4.36 ± 1.32 (ROI 1) vs. 1.83 ± 0.81 (2a-2b; p < 0.0001) vs. 1.35 ± 0.67 (3a-3b; p < 0.0001). At 6 h, lactates were 4.16 ± 2.55 vs. 1.8 ± 1.2 vs. 1.45 ± 0.83 at ROI 1 vs. 2a--2b (p = 0.013) vs. 3a-3b (p = 0.0035). Mean V 0 and V max (pmolO2/second/mg of tissue) were significantly impaired after 4 and 6 h at ROI 1 (V 0 (4h) = 34.83 ± 10.39; V max (4h) = 76.6 ± 29.09; V 0 (6h) = 44.1 ± 12.37 and V max (6h) = 116.1 ± 40.1) when compared to 2a--2b (V 0 (4h) = 67.1 ± 17.47 p = 0.00039; V max (4h) = 146.8 ± 55.47 p = 0.0054; V 0 (6h) = 63.9 ± 28.99 p = 0.03; V max (6h) = 167.2 ± 56.96 p = 0.01). V 0 and V max were significantly higher at 3a-3b. FLER may identify the future anastomotic site even after repetitive assessments and long-standing bowel ischemia

Evidentiality, egophoricity and engagement

The expression of knowledge in language (i.e. epistemicity) consists of a number of distinct notions and proposed categories that are only partly related to a well explored forms like epistemic modals. The aim of the volume is therefore to contribute to the ongoing exploration of epistemic marking systems in lesser-documented languages from the Americas, Papua New Guinea, and Central Asia from the perspective of language description and cross-linguistic comparison. As the title of the volume suggests, part of this exploration consists of situating already established notions (such as evidentiality) with the diversity of systems found in individual languages. Epistemic forms that feature in the present volume include ones that signal how speakers claim knowledge based on perceptual-cognitive access (evidentials); the speaker’s involvement as a basis for claiming epistemic authority (egophorics); the distribution of knowledge between the speech-participants where the speaker signals assumptions about the addressee’s knowledge of an event as either shared, or non-shared with the speaker (engagement marking).  &nbsp

Evidentiality, egophoricity and engagement

The expression of knowledge in language (i.e. epistemicity) consists of a number of distinct notions and proposed categories that are only partly related to a well explored forms like epistemic modals. The aim of the volume is therefore to contribute to the ongoing exploration of epistemic marking systems in lesser-documented languages from the Americas, Papua New Guinea, and Central Asia from the perspective of language description and cross-linguistic comparison. As the title of the volume suggests, part of this exploration consists of situating already established notions (such as evidentiality) with the diversity of systems found in individual languages. Epistemic forms that feature in the present volume include ones that signal how speakers claim knowledge based on perceptual-cognitive access (evidentials); the speaker’s involvement as a basis for claiming epistemic authority (egophorics); the distribution of knowledge between the speech-participants where the speaker signals assumptions about the addressee’s knowledge of an event as either shared, or non-shared with the speaker (engagement marking).  &nbsp

Evidentiality, egophoricity and engagement

The expression of knowledge in language (i.e. epistemicity) consists of a number of distinct notions and proposed categories that are only partly related to a well explored forms like epistemic modals. The aim of the volume is therefore to contribute to the ongoing exploration of epistemic marking systems in lesser-documented languages from the Americas, Papua New Guinea, and Central Asia from the perspective of language description and cross-linguistic comparison. As the title of the volume suggests, part of this exploration consists of situating already established notions (such as evidentiality) with the diversity of systems found in individual languages. Epistemic forms that feature in the present volume include ones that signal how speakers claim knowledge based on perceptual-cognitive access (evidentials); the speaker’s involvement as a basis for claiming epistemic authority (egophorics); the distribution of knowledge between the speech-participants where the speaker signals assumptions about the addressee’s knowledge of an event as either shared, or non-shared with the speaker (engagement marking).  &nbsp