The interaction between the measles virus nucleoprotein and the Interferon Regulator Factor 3 relies on a specific cellular environment

<p>Abstract</p> <p>Background</p> <p>The genome of measles virus consists of a non-segmented single-stranded RNA molecule of negative polarity, which is encapsidated by the viral nucleoprotein (N) within a helical nucleocapsid. The N protein possesses an intrinsically disordered C-terminal domain (aa 401–525, N_TAIL) that is exposed at the surface of the viral nucleopcapsid. Thanks to its flexible nature, N_TAILinteracts with several viral and cellular partners. Among these latter, the Interferon Regulator Factor 3 (IRF-3) has been reported to interact with N, with the interaction having been mapped to the regulatory domain of IRF-3 and to N_TAIL. This interaction was described to lead to the phosphorylation-dependent activation of IRF-3, and to the ensuing activation of the pro-immune cytokine RANTES gene.</p> <p>Results</p> <p>After confirming the reciprocal ability of IRF-3 and N to be co-immunoprecipitated in 293T cells, we thoroughly investigated the N_TAIL-IRF-3 interaction using a recombinant, monomeric form of the regulatory domain of IRF-3. Using a large panel of spectroscopic approaches, including circular dichroism, fluorescence spectroscopy, nuclear magnetic resonance and electron paramagnetic resonance spectroscopy, we failed to detect any direct interaction between IRF-3 and either full-length N or N_TAILunder conditions where these latter interact with the C-terminal X domain of the viral phosphoprotein. Furthermore, such interaction was neither detected in <it>E. coli </it>nor in a yeast two hybrid assay.</p> <p>Conclusion</p> <p>Altogether, these data support the requirement for a specific cellular environment, such as that provided by 293T human cells, for the N_TAIL-IRF-3 interaction to occur. This dependence from a specific cellular context likely reflects the requirement for a human or mammalian cellular co-factor.</p

Assistive technologies to address capabilities of people with dementia: from research to practice

Assistive technologies (AT) became pervasive and virtually present in all our life domains. They can be either an enabler or an obstacle leading to social exclusion. The Fondation Médéric Alzheimer gathered international experts of dementia care, with backgrounds in biomedical, human and social sciences, to analyse how AT can address the capabilities of people with dementia, on the basis of their needs. Discussion covered the unmet needs of people with dementia, the domains of daily life activities where AT can provide help to people with dementia, the enabling and empowering impact of technology to improve their safety and wellbeing, barriers and limits of use, technology assessment, ethical and legal issues. The capability approach (possible freedom) appears particularly relevant in person-centered dementia care and technology development. The focus is not on the solution, rather on what the person can do with it: seeing dementia as disability, with technology as an enabler to promote capabilities of the person, provides a useful framework for both research and practice. This article summarizes how these concepts took momentum in professional practice and public policies in the past fifteen years (2000-2015), discusses current issues in the design, development and economic model of AT for people with dementia, and covers how these technologies are being used and assessed

Impact of early enteral versus parenteral nutrition on mortality in patients requiring mechanical ventilation and catecholamines: study protocol for a randomized controlled trial (NUTRIREA-2)

BACKGROUND: Nutritional support is crucial to the management of patients receiving invasive mechanical ventilation (IMV) and the most commonly prescribed treatment in intensive care units (ICUs). International guidelines consistently indicate that enteral nutrition (EN) should be preferred over parenteral nutrition (PN) whenever possible and started as early as possible. However, no adequately designed study has evaluated whether a specific nutritional modality is associated with decreased mortality. The primary goal of this trial is to assess the hypothesis that early first-line EN, as compared to early first-line PN, decreases day 28 all-cause mortality in patients receiving IMV and vasoactive drugs for shock. METHODS/DESIGN: The NUTRIREA-2 study is a multicenter, open-label, parallel-group, randomized controlled trial comparing early PN versus early EN in critically ill patients requiring IMV for an expected duration of at least 48 hours, combined with vasoactive drugs, for shock. Patients will be allocated at random to first-line PN for at least 72 hours or to first-line EN. In both groups, nutritional support will be started within 24 hours after IMV initiation. Calorie targets will be 20 to 25 kcal/kg/day during the first week, then 25 to 30 kcal/kg/day thereafter. Patients receiving PN may be switched to EN after at least 72 hours in the event of shock resolution (no vasoactive drugs for 24 consecutive hours and arterial lactic acid level below 2 mmol/L). On day 7, all patients receiving PN and having no contraindications to EN will be switched to EN. In both groups, supplemental PN may be added to EN after day 7 in patients with persistent intolerance to EN and inadequate calorie intake. We plan to recruit 2,854 patients at 44 participating ICUs. DISCUSSION: The NUTRIREA-2 study is the first large randomized controlled trial designed to assess the hypothesis that early EN improves survival compared to early PN in ICU patients. Enrollment started on 22 March 2013 and is expected to end in November 2015. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01802099 (registered 27 February 2013)

Artificial wetlands on the Rhône River: a comparative approach to investigate their evolution and hydro-sedimentary functioning

International audienc

Le suicide en Haute-Normandie

Hacpille Lucie, Villet Hervé, Arros Pascal, Babouin Corinne, Comble Gérard, Marec Yannick, Tailleux Patrick, Vaguet Alain. Le suicide en Haute-Normandie. In: Études Normandes, 39e année, n°4, 1990. Prospective et aménagement - une société en mouvement. pp. 64-78

Transvaginal treatment of anterior and apical genital prolapses using an Ultra lightweight mesh: Restorelle® Direct Fix™. A retrospective study on feasibility and morbidity

International audienceBACKGROUND:Vaginal mesh safety information is limited, especially concerning single incision techniques using ultra lightweight meshes for the treatment of anterior pelvic organ prolapse (POP).OBJECTIVE:To determine the intraoperative and postoperative complication rates after anterior POP repair involving an ultralight mesh (19g/m2): Restorelle® Direct Fix™.METHODS:A case series of 218 consecutive patients, operated on between January 2013 and December 2016 in ten tertiary and secondary care centres, was retrospectively analyzed. Eligible patients had POP vaginal repair (recurrent or not) planned with anterior Restorelle® Direct Fix™ mesh (with or without posterior mesh). Surgical complications were graded using the Clavien-Dindo classification.RESULTS:Intraoperative complications were bladder wound (0.5%), rectal wound (0.5%), ureteral injuries (0.9%). 98.2% of the patient did not have per operative complications. We observed one fail of procedure. Early complications mainly included urinary retention (8.7%) urinary tract infections (5.5%) and haematoma (2.7%). One haematoma required surgical treatment and another, embolization. 80.7% of the patient did not have complications during hospitalization and 80.3% did not have complication at the follow up visit. None of the analyzed factors (age, body mass index, surgical history, grade of prolapse or concomitant procedure) was significantly associated with the risk of perioperative complications. A total of 2.8% patients had grade III complications according Clavien Dindo. None had grade IV or V.CONCLUSIONS:This multicentre case-series on the early experience of the use of anterior Restorelle® Direct Fix™ mesh showed a satisfactory technical feasibility and a low rate of grade III complications according Clavien Dindo. Long term studies are necessary to assess anterior Restorelle® Direct Fix™ mesh performances and to appraise patient satisfaction feedback

Broad Range Amino Acid Specificity of RNA-dependent Lipid Remodeling by Multiple Peptide Resistance Factors*

Aminoacylphosphatidylglycerol synthases (aaPGSs) are multiple peptide resistance factors that transfer amino acids from aminoacyl-tRNAs to phosphatidylglycerol (PG) in the cytoplasmic membrane. Aminoacylation of PG is used by bacteria to decrease the net negative charge of the cell envelope, diminishing affinity for charged molecules and allowing for adaptation to environmental changes. Lys-PGS, which transfers lysine to PG, is essential for the virulence of certain pathogens, providing resistance to both host cationic antimicrobial peptides and therapeutic antibiotics. Ala-PGS was also recently described, but little is known about the possible activities of other members of the highly diverse aaPGS family of proteins. Systematic deletion of the predicted membrane-inserted domains of several aaPGSs revealed that the carboxyl-terminal hydrophilic domain alone is sufficient for aminoacylphosphatidylglycerol transferase catalytic activity. In contrast to previously characterized aaPGSs, the Enterococcus faecium enzyme used an expanded repertoire of amino acids to modify PG with Ala, Arg, or Lys. Reexamination of previously characterized aaPGSs also revealed broader than anticipated substrate specificity, for example Bacillus subtilis Lys-PGS was shown to also catalyze Ala-PG synthesis. The relaxed substrate specificities of these aaPGSs allows for more elaborate remodeling of membrane lipids than previously thought, potentially providing bacteria that harbor these enzymes resistance to a broad spectrum of antibiotics and environmental stresses