Formation of intracellular vesicles within the Gram+ Lactococcus lactis induced by the overexpression of Caveolin-1ß.

BACKGROUND: Caveolae are invaginated plasma membrane domains of 50-100 nm in diameter involved in many important physiological functions in eukaryotic cells. They are composed of different proteins, including the membrane-embedded caveolins and the peripheric cavins. Caveolin-1 has already been expressed in various expression systems (E. coli, insect cells, Toxoplasma gondii, cell-free system), generating intracellular caveolin-enriched vesicles in E. coli, insect cells and T. gondii. These systems helped to understand the protein insertion within the membrane and its oligomerization. There is still need for fundamental insights into the formation of specific domains on membrane, the deformation of a biological membrane driven by caveolin-1, the organization of a caveolar coat, and the requirement of specific lipids and proteins during the process. The aim of this study was to test whether the heterologously expressed caveolin-1ß was able to induce the formation of intracellular vesicles within a Gram+ bacterium, Lactococcus lactis, since it displays a specific lipid composition different from E. coli and appears to emerge as a good alternative to E. coli for efficient overexpression of various membrane proteins. RESULTS: Recombinant bacteria transformed with the plasmid pNZ-HTC coding for the canine isoform of caveolin-1ß were shown to produce caveolin-1ß, in its functional oligomeric form, at a high expression level unexpected for an eukaryotic membrane protein. Electron microscopy revealed several intracellular vesicles from 30 to 60 nm, a size comparable to E. coli h-caveolae, beneath the plasma membrane of the overexpressing bacteria, showing that caveolin-1ß is sufficient to induce membrane vesiculation. Immunolabelling studies showed antibodies on such neo-formed intracellular vesicles, but none on plasma membrane. Density gradient fractionation allowed the correlation between detection of oligomers on Western blot and appearance of vesicles measurable by DLS, showing the requirement of caveolin-1ß oligomerization for vesicle formation. CONCLUSIONS: Lactococcus lactis cells can heterologously overexpress caveolin-1ß, generating caveolin-1ß enriched intracellular neo-formed vesicles. These vesicles might be useful for potential co-expression of membrane proteins of pharmaceutical interest for their simplified functional characterization.

[Diagnosis and treatment of cardiac transthyretin amyloidosis. Innovative therapy with tafamidis.] / Le médicament du mois. Diagnostic et traitement d'une amyloïdose cardiaque à transthyrétine. Thérapeutique innovante avec le tafamidis.

Cardiac amyloidosis is a rare and severe disease with worse prognosis than classic cardiac insufficiency. Transthyretin amyloïdosis is an underdiagnosed cause of amyloidosis. Technetium scintigraphy allows to confirm diagnosis of transthyretin amyloidosis with great specificity. A new hope is brought by tafamidis, a novel therapeutic option for this specific condition. This medication is the first one that proved a risk reduction in mortality among patients with cardiac amyloidosis in class NYHA I and II. In this article, we review across a clinical case the modalities for the diagnosis and treatment of transthyretin amyloidosis.

L'amyloïdose cardiaque est une maladie rare et sévère. En cas d'insuffisance cardiaque, le pronostic est pire que pour les autres étiologies. L'amyloïdose à transthyrétine est une des formes d'amyloïdose dont le diagnostic peut être posé avec une grande spécificité grâce à la scintigraphie au technétium. Une lueur d'espoir est apportée par l'arrivée du tafamidis, une nouvelle classe thérapeutique. Ce médicament est le premier à avoir démontré une réduction de mortalité parmi les patients en classe NYHA I et II. Dans cet article, nous décrivons, à partir d'un cas clinique, les démarches diagnostiques et thérapeutiques nécessaires à la prise en charge d'un patient présentant une insuffisance cardiaque sur amyloïdose à transthyrétine.

Magma pressure discharge induces very long period seismicity.

Volcano seismicity is one of the key parameters to understand magma dynamics of erupting volcanoes. However, the physical process at the origin of the resulting complex and broadband seismic signals remains unclear. Syn-eruptive very long period (VLP) seismic signals have been explained in terms of the sudden expansion of gas pockets rising in the liquid melt. Their origin is linked to a magma dynamics which triggers the explosive process occurring before the explosive onset. We provide evidence based on acoustic, thermal, and ground deformation data to demonstrate that VLP signals at Stromboli are generated at the top of the magma column mainly after the explosion onset. We show that VLP amplitude and duration scale with the eruptive flux which induces a decompression of 103-104 Pa involving the uppermost ~ 250 m of the feeding conduit. The seismic VLP source represents the final stage of a ~ 200 s long charge and discharge mechanism the magma column has to release excess gas accumulated at the base of a denser and degassed magma mush. The position of the VLP seismic source coincides with the centroid of the shallow mush plug and tracks elevation changes of the magma free surface.

[Structural or functional relationship between immunohematology and distribution - Which elements for controlling risks?] / Lien immunohématologie-délivrance structurel ou fonctionnel ­ Quels éléments pour la maîtrise des risques ?

OBJECTIVE: Transfusion safety is based on the availability of safe and compatible blood products at the right time and to the right patient, and requires close monitoring in order to detect possible incidents. The decree of June 20th 2018, which establishes the national blood transfusion's guiding plan, states that the organization that prevails throughout the national territory is built around an inseparable link between the implementation of erythrocyte immunohematology and the labile blood products delivery by authorised structures. METHOD: The article describes the two types of the link's organization, structural or functional, used to develop the comparative risk-benefit analysis. RESULTS: The structural link, which has fewer interfaces, reduces risk situations that lead to delays in release by default of a compatible product. The cases in which a functional link may have a greater benefit than the risks generated are those related to a geographical distance between the delivery site and the patient's place of care. In these cases, a functional link is possible provided that certain organizational points are mastered. CONCLUSION: The comparative analysis shows that the structural link is to be favoured since that the coherence of the patient's care and his care path is ensured. In certain situations, mainly geographical, the functional link can have a benefit that offsets the risks generated by the new interfaces; provided that the system is secured by a real tripartite collaboration between health care institution, biology laboratory and delivery site.

Surface plasmons in suspended graphene: launching with in-plane gold nanoantenna and propagation properties.

Graphene physics and plasmonics are two fields which, once combined, promise a variety of exciting applications. One of those applications is the integration of active nano-optoelectronic devices in electronic systems, using the fact that plasmons in graphene are tunable, highly confined and weakly damped. A crucial challenge remains before achieving these active devices: finding a platform enabling a high propagation of Graphene Plasmons Polaritons (GPPs). Suspended graphene presenting ultrahigh electron mobility has given rise to increasing interest. We numerically studied the plasmonic properties of suspended graphene. We propose a hybrid configuration and a set of conditions to launch graphene plasmons via an in-plane gold nanoantenna, for micrometric propagation of surface plasmons in suspended graphene. Finally, we propose a realistic optoelectronic device based on the use of suspended graphene.

Independent evaluation of tolerance of therapeutic plasma inactivated by amotosalen-HCl-UVA (Intercept ™) over a 5-year period of extensive delivery.

Amotosalen-HCl-UVA (AI) is a process to inactivate pathogens in therapeutic plasma (FFP). Tolerance is the main residual issue in FFP transfusion, and only large series observations are powered enough to identify significantly elevated levels of hazards. We report here on 15,133 new transfusions of AI-FFP, over the previously published 36,035, which in all represents one of the largest series observed by means of a highly standardized surveillance (51.168 observations). There is no noticeable difference in terms of tolerance of AI-FFP compared to 5875 transfusions of Quarantine (Q)-FFP. There was no significant difference in terms of advance events, between the two types of FFP (P = 0.98); further, no difference was recorded either when the total number of AI-FFP (51,168) was compared to the corresponding number of Q-FFP (5875; P = 0.62).

The relationship between grip strength and muscle mass (MM), inflammatory biomarkers and physical performance in community-dwelling very old persons.

The main consequence of the loss of MM and muscle strength is limitations of physical performance and disability in older people. It is unclear whether a decline in functional capacity results from the loss of MM and/or the qualitative impairment of the muscle tissue. The aim of our research was to investigate the relationship between physical performance and grip strength, inflammatory markers and MM in a population of community-dwelling very old persons. This study is a cross-sectional analysis within the BELFRAIL-study, a cohort study of subjects aged 80 years and older (n=567). MM was assessed by bioelectrical impedance. Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations were determined on fasting blood samples. Logistic regression analysis was build using a low physical performance level evaluated according to Short Physical Performance Battery (SPPB) (dependent variable) and grip strength, pro-inflammatory status and MM (independent variables) adjusted for age and for the total number of chronic diseases. Low SPPB scores were associated with grip strength scores for women (OR 0.86 (95% CI 0.77-0.96)), and for men (OR 0.89 (95% CI 0.81-0.96)). The relationships between low SPPB and MM or inflammatory profile were not significant. Our results show that low physical performance remains associated with low grip strength even after considering other risk factors for sarcopenia in the oldest old and support the hypothesis that low muscle strength is a better indicator than low MM. The role of an inflammatory component in the age-related loss of muscle strength and function could not be confirmed.

[Clinical case of the month. Tetanus still exists!]. / Le cas clinique du mois. Le tétanos existe toujours !

We report the dramatic story of a 81 year old patient admitted to the intensive care unit following the development of tetanus. This man, perfectly autonomous, used to workin his garden without anti-tetanus immunization coverage. In this article, we report the therapeutic management of tetanus. We emphasize the importance of vaccination which permits to avoid the disease, the mortality and morbidity of which remain high.

[Failures of the issue: how to improve?]. / Les défaillances de la délivrance: comment s'améliorer?

If they are not stopped before transfusion, distribution of blood components (BC) errors can have serious consequences for patients. The study of reported incidents of transfusion chain shows that the risk of failure is important, especially on the steps of patient selection in software, packing and giving the BC to transporter. The analysis of these problems most often state "human" error by misapplication of procedures. These errors are favored by systemic causes: many interfaces with numerous actors in the transfusion process, breaking between different information systems, stress of the emergency and lot of visual self-checks. Improvement may be proposed by a better the organization of the different tasks, by the ergonomic of the work, by improving distribution software and training operators to the management of the emergency. But things must be thought again by all the actors involved in the transfusion management of patients in order to reduce the risks associated with multiple interfaces.

[Clinical case of the month. Spontaneous hematoma and acquired hemophilia]. / Le cas clinique du mois. Hématomes spontanés et hémophilie acquise.

Acquired haemophilia is a rare disease, 50% of the cases are idiopathic. We report a case admitted in cardiology for spontaneous hematoma. Observation of isolated prolonged activated partial thromboplastin time (aPPT) without anticoagulation treatment and the absence of correction with normal plasma suggested diagnosis. Confirmation of inhibitors to FVIII allowed perfusions of activated prothrombin complex concentrates.

[2011 European guidelines for the management of cardiovascular diseases during pregnancy. Part II: management of hypertension]. / Recommandations Européennes 2011 pour la prise en charge des maladies cardiovasculaires pendant la grossesse. Partie 2: Prise en charge de l'hypertension artérielle.

In this article, we report the 2011 European guidelines on the management of cardiovascular diseases during pregnancy, with particular attention to the management of hypertension as hypertensive disorders are the most frequent cardiovascular complications in pregnancy.

[2011 European Society of Cardiology guidelines for the management of cardiovascular diseases during pregnancy. Part 1]. / Recommandations Européennes 2011 pour la prise en charge des maladies cardiovasculaires pendant la grossesse. Partie 1: valvulopathies et anticoagulation.

In this article, we describe the 2011 European guidelines on the management of cardiovascular diseases during pregnancy, with particular attention to the management of valvular heart disease and anticoagulation.We will also describe cardiologic conditions in which pregnancy is contraindicated and the preferred way of delivery.

Complex interactions between paternal and maternal effects: parental experience and age at reproduction affect fecundity and offspring performance in a butterfly.

Parental effects can greatly affect offspring performance and are thus expected to impact population dynamics and evolutionary trajectories. Most studies have focused on maternal effects, whereas fathers are also likely to influence offspring phenotype, for instance when males transfer nutrients to females during mating. Moreover, although the separate effects of maternal age and the environment have been documented as a source of parental effects in many species, their combined effects have not been investigated. In the present study, we analyzed the combined effects of maternal and paternal age at reproduction and a mobility treatment in stressful conditions on offspring performance in the butterfly Pieris brassicae. Both paternal and maternal effects affected progeny traits but always via interactions between age and mobility treatment. Moreover, parental effects shifted from male effects expressed at the larval stage to maternal effects at the adult stage. Indeed, egg survival until adult emergence significantly decreased with father age at mating only for fathers having experienced the mobility treatment, whereas offspring adult life span decreased with increasing mother age at laying only for females that did not experience the mobility treatment. Overall, our results demonstrate that both parents' phenotypes influence offspring performance through nongenetic effects, their relative contribution varying over the course of progeny's life.

[A left intraventricular mass]. / Le cas clinique du mois. A propos d'une masse intra-ventriculaire gauche.

We report the case of a 29-years-old male presenting with a large mass inserted at the hypokinetic apex of the left ventricle. Without any early regression under anticoagulant therapy and taking into account recent neurological manifestations, surgical extraction was decided. The mass corresponded to a chronic thrombus lying on a non-transmural myocardial necrosis. This case gives us the opportunity to review all causes of intracardiac masses.

Inter-island divergence within Drosophila mauritiana, a species of the D. simulans complex: Past history and/or speciation in progress?

Speciation with gene flow may be more common than generally thought, which makes detailed understanding of the extent and pattern of genetic divergence between geographically isolated populations useful. Species of the Drosophila simulans complex provide a good model for speciation and evolutionary studies, and hence understanding their population genetic structure will increase our understanding of the context in which speciation has occurred. Here, we describe genetic diversity and genetic differentiation of two distant populations of D. mauritiana (Mauritius and Rodrigues Islands) at mitochondrial and nuclear loci. We surveyed the two populations for their mitochondrial haplotypes, eight nuclear genes and 18 microsatellite loci. A new mitochondrial type is fixed in the Rodrigues population of D. mauritiana. The two populations are highly differentiated, their divergence appears relatively ancient (100,000 years) compared to the origin of the species, around 0.25MYA, and they exhibit very limited gene flow. However, they have similar levels of divergence from their sibling, D. simulans. Both nuclear genes and microsatellites revealed contrasting demographic histories between the two populations, expansion for the Mauritius population and stable population size for the Rodrigues Island population. The discovery of pronounced geographic structure within D. mauritiana combined to genetic structuring and low gene flow between the two island populations illuminates the evolutionary history of the species and clearly merits further attention in the broad context of speciation.

[Adherence to antiplatelet therapy in patients with coronary artery disease]. / Adhésion thérapeutique aux antiagrégants chez le patient coronarien.

Clinical benefit of antiplatelet therapy is established for cardiovascular disease and percutaneous coronary intervention (PCI). Dual antiplatelet therapy is used to optimize platelet inhibition. However, cardiovascular events still occur. Aspirin/clopidogrel resistance and poor compliance are the main factors implied in recurrent events. Compliance to dual antiplatelet therapy is particularly relevant during the first 6 months following acute coronary syndromes and PCI. Furthermore, several studies have shown association between antiplatelet resistance and poor compliance. Additionally, late (1 month to 1 year) and very late (> 1 year) stent thromboses are intimately linked to interruption of antiplatelet treatment. In this article we review the latest data about compliance, resistance and recommendations regarding antiplatelet therapy.

[Reorganization of blood watch and transfusion safety activities in the Marseille public hospital system in partnership between the French Blood Institute Alps Mediterranean Division (EFS AM)]. / Organisation de l'hémovigilance et de la sécurité transfusionnelle à l'assistance publique hôpitaux de Marseille (AP-HM): partenariat AP-HM - établissement français du sang Alpes-Méditerranée (EFS AM).

The Marseille public hospital system (APHM) has expressed its willingness to pool its services of immunohematology and delivery of labile blood products with those of the French blood institute Alps Mediterranean division (EFS AM). An agreement setting out the terms of this partnership was signed between the two parties. The users of the APHM and EFS AM blood watch wished to preserve the channels of distribution. Implementation of this reorganization has focused on ensuring transfusional safety, reinforcing harmonization of APHM practices, and finding ways to reduce costs. Despite joint information campaigns (to medical and paramedical personnel) carried out by the APHM and EFS AM blood watch, problems have arisen during start-up and adjustments have been necessary on both sides. The success of this project hinges on the involvement of the EFS AM in our transfusional practices, deployment of a system for diffusion of information, and consolidation of physical and human resources at the level of the APHM blood watch.

[Operational qualification of the computer-based information system and electronic data interchanges in a hospital blood bank]. / Qualification opérationnelle du système informatique d'un dépôt de sang et de ses échanges de données.

Since 1985, a Council Resolution defines a new approach to technical harmonization and standards. The directives resulting from this new approach establish the essential safety requirements with which products put on the market must conform, and which should therefore enjoy free movement throughout the European Union, owing to a presumption of conformity. However, if the manufacturer is responsible for the conformity of its product in terms of safety, it is the end-user who must make sure that its requirements for a specific use or a considered application are satisfied and that the product meets its needs. It is the objective of the procedure of validation, which calls upon protocols of qualification intended to show the aptitude of a material, a system, a device, of an installation, to meet the requirements of specified quality and safety. This concept of qualification applies to the data-processing software of the hospital blood banks. Only the stage of operational qualification will be developed here. It involves scenarios made up of test files which make it possible to check the electronic data interchanges between the hospital blood bank and the blood establishment (transmission of the results of analysis, transmission of the data of traceability), as well as the functions of assistance to the issuing of the labile blood products.