The orthology of HLA-E and H2-Qa1 is hidden by their concerted evolution with other MHC class I molecules

BACKGROUND: Whether MHC molecules undergo concerted evolution or not has been the subject of a long-standing debate. RESULTS: By comparing sequences of eight functional homologues of HLA-E from primates and rodents with those of MHC class Ia molecules from the same eight species, we find that different portions of MHC class I molecules undergo different patterns of evolution. By focusing our analyses sequentially on these various portions, we have obtained clear evidence for concerted evolution of MHC class I molecules, suggesting the occurrence of extensive interallelic and intergenic exchanges. Intra-species homogenisation of sequences is particularly noticeable at the level of exon 4, which codes for the α3 domain, but our results suggest that homogenisation also concerns certain residues of the α1–α2 codomain that lie outside the antigen recognition site. CONCLUSION: A model is presented in which Darwinian selective pressures due to pathogens could, at the same time, favour diversification of MHC class Ia molecules and promote concerted evolution of separate loci by spreading advantageous motifs arising by mutations in individual MHC molecules to other alleles and to other loci of the MHC region. This would also allow MHC molecules to co-evolve with the proteins with which they interact to fulfil their functions of antigen presentation and regulation of NK cell activity. One of the raisons d'être of the MHC may therefore be to favour at the same time both diversification of MHC class Ia molecules and homogenisation of the whole pool of MHC class I molecules (Ia and Ib) involved in antigen presentation. REVIEWERS: This article was reviewed by Stephan Beck, Lutz Walter and Pierre Pontarotti

Independence of first- and second-order memories in newborn rabbits.

WOS:000291649400006International audienceThe mammary pheromone promotes the acquisition of novel odorants (CS1) in newborn rabbits. Here, experiments pinpoint that CS1 becomes able to support neonatal learning of other odorants (CS2). We therefore evaluated whether these first- and second-order memories remained dependent after reactivation. Amnesia induced after CS2 recall selectively blocked this memory, when recall and amnesia of CS1 left the souvenir of CS2 safe; this finding partially differed from results obtained in adult mammals. Thus, in this model of neonatal appetitive odor learning, second-order memory seems to depend on first-order memory for its formation but not for its maintenance

Micro-confinement of bacteria into w/o emulsion droplets for rapid detection and enumeration

International audienceToday, rapid detection and identification of bacteria in microbiological diagnosis is a major issue. Reference methods usually rely on growth of microorganisms, with the drawback of lengthy time-to-result. The method provides global information on a clonal population that is known to be inhomogeneous relative to metabolic states and activities. Therefore, there may be a significant advantage of methods that allow characterisation of individual bacteria from a large population, both for test time reduction and the clinical value of the characterisation. We report here a method for rapid detection and real-time monitoring of the metabolic activities of single bacteria. Water-in-oil emulsions were used to encapsulate single Escherichia coli cells into picolitre (pL)-sized microreactor droplets. The glucuronidase activity in each droplet was monitored using the fluorogenic reporter molecule MUG (4-methylumbelliferyl- - d-glucuronide) coupled to time-lapse fluorescence imaging of the droplets. Such bacterial confinement provides several major advantages. (1) Enzymatic activities of a large number of single bacterium-containing droplet could be monitored simultaneously, allowing the full characterisation of metabolic heterogeneity in a clonal population. We monitored glucuronidase enzymatic activity and growth over ∼200 single bacteria over a 24-h period. (2) Micro-confinement of cells in small volumes allows rapid accumulation of the fluorescent metabolite, hence decreasing the detection time. Independent of the initial concentration of bacteria in the sample, detection of the presence of bacteria could be achieved in less than 2 h. (3) Considering the random distribution of bacteria in droplets, this method allowed rapid and reliable enumeration of bacteria in the initial sample. Overall, the results of this study showed that confinement of bacterial cells increased the effective concentration of fluorescent metabolites leading to rapid (2 h) detection of the fluorescent metabolites, thus significantly reducing time to numeration

Characterisation of RT1-E2, a multigenic family of highly conserved rat non-classical MHC class I molecules initially identified in cells from immunoprivileged sites

BACKGROUND: So-called "immunoprivileged sites" are tissues or organs where slow allograft rejection correlates with low levels of expression of MHC class I molecules. Whilst classical class I molecules are recognised by cytotoxic T lymphocytes (CTL), some MHC class I molecules are called "non-classical" because they exhibit low polymorphism and are not widely expressed. These last years, several studies have shown that these can play different, more specialised roles than their classical counterparts. In the course of efforts to characterise MHC class I expression in rat cells obtained from immunoprivileged sites such as the central nervous system or the placenta, a new family of non-classical MHC class I molecules, which we have named RT1-E2, has been uncovered. RESULTS: Members of the RT1-E2 family are all highly homologous to one another, and the number of RT1-E2 loci varies from one to four per MHC haplotype among the six rat strains studied so far, with some loci predicted to give rise to soluble molecules. The RT1(n )MHC haplotype (found in BN rats) carries a single RT1-E2 locus, which lies in the RT1-C/E region of the MHC and displays the typical exon-intron organisation and promoter features seen in other rat MHC class I genes. We present evidence that: i) RT1-E2 molecules can be detected at the surface of transfected mouse L cells and simian COS-7 cells, albeit at low levels; ii) their transport to the cell surface is dependent on a functional TAP transporter. In L cells, their transport is also hindered by protease inhibitors, brefeldin A and monensin. CONCLUSIONS: These findings suggest that RT1-E2 molecules probably associate with ligands of peptidic nature. The high homology between the RT1-E2 molecules isolated from divergent rat MHC haplotypes is particularly striking at the level of their extra-cellular portions. Compared to other class I molecules, this suggests that RT1-E2 molecules may associate with well defined sets of ligands. Several characteristics point to a certain similarity to the mouse H2-Qa2 and human HLA-G molecules

Coloured coatings for glazing of active solar thermal façades by reactive magnetron sputtering

For building integration of solar-powered energy systems, aesthetic aspects play an important role. Covering a standard solar collector with a coloured glazing, opaque to the human eye but highly transparent to solar energy, permits a perfect architectural integration of solar thermal panels into glazed building façades. The thermal energy produced can be used for both solar heating and cooling, as well as for domestic hot water. The principle of the coloured appearance is based on interference in the thin-film coating on the reverse side of the cover glass. Different interference filters based on nano-composite materials deposited by the solgel method were presented at CISBAT 2007 [1]. Currently, we are developing new plasma-deposition processes, which are more suitable for industrial large-scale production. A new state-of-the-art ultra-high vacuum (UHV) system for magnetron sputtering deposition of novel nano-composite solar coatings has recently been designed, constructed, and installed at the Solar Energy and Building Physics Laboratory (LESO-PB). Up to five different magnetron sources can be used simultaneously, in reactive and non-reactive mode. The geometric configuration of the chamber has been optimised for best film homogeneity and allows the deposition on substrates up to 100 mm in diameter. The optical and electronic properties of thin films are closely interrelated and highly relevant for solar coatings. Photoelectron spectroscopy provides information on the coating structure, the deposited material and its chemical state inside the coating, as well as the nature of the interface between different layers. A system for ESCA analysis (Electron Spectroscopy for Chemical Analysis) has recently been installed and put into operation at LESO-PB. By ellipsometry and spectrophotometry, we can determine exactly the different optical properties of the coating, such as layer thickness, refractive index, or absorption coefficient. This provides best conditions for highly efficient research and development on new materials for further optimisation of the coloured interference filters. First results have been obtained with our new experimental infrastructure and will be presented in this contribution

Severe pain management in the emergency department: patient pathway as a new factor associated with IV morphine prescription

BackgroundAcross the world, 25–29% of the population suffer from pain. Pain is the most frequent reason for an emergency department (ED) visit. This symptom is involved in approximately 70% of all ED visits. The effective management of acute pain with adequate analgesia remains a challenge, especially for severe pain. Intravenous (IV) morphine protocols are currently indicated. These protocols are based on patient-reported scores, most often after an immediate evaluation of pain intensity at triage. However, they are not systematically prescribed. This aspect could be explained by the fact that physicians individualize opioid pain management for each patient and each care pathway to determine the best benefit–risk balance. Few data are available regarding bedside organizational factors involved in this phenomenon.ObjectiveThis study aimed to analyze the organizational factors associated with no IV morphine prescription in a standardized context of opioid management in a tertiary-care ED.MethodsA 3-month prospective study with a case–control design was conducted in a French university hospital ED. This study focused on factors associated with protocol avoidance despite a visual analog scale (VAS) ≥60 or a numeric rating scale (NRS) ≥6 at triage. Pain components, physician characteristics, patient epidemiologic characteristics, and care pathways were considered. Qualitative variables (percentages) were compared using Fisher’s exact test or the chi-squared tests. Student’s t-test was used to compare continuous variables. The results were expressed as means with their standard deviation (SD). Factors associated with morphine avoidance were identified by logistic regression.ResultsA total of 204 patients were included in this study. A total of 46 cases (IV morphine) and 158 controls (IV morphine avoidance) were compared (3:1 ratio). Pain patterns and patient’s epidemiologic characteristics were not associated with an IV morphine prescription. Regarding NRS intervals, the results suggest a practice disconnected from the patient’s initial self-report. IV morphine avoidance was significantly associated with care pathways. A significant difference between the IV morphine group and the IV morphine avoidance group was observed for “self-referral” [adjusted odds ratio (aOR): 5.11, 95% CIs: 2.32–12.18, p < 0.0001] and patients’ trajectories (Fisher’s exact test; p < 0.0001), suggesting IV morphine avoidance in ambulatory pathways. In addition, “junior physician grade” was associated with IV morphine avoidance (aOR: 2.35, 95% CIs: 1.09–5.25, p = 0.03), but physician gender was not.ConclusionThis bedside case–control study highlights that IV morphine avoidance in the ED could be associated with ambulatory pathways. It confirms the decreased choice of “NRS-only” IV morphine protocols for all patients, including non-trauma patterns. Modern pain education should propose new tools for pain evaluation that integrate the heterogeneity of ED pathways

Innovative Solution for Building Integrated Photovoltaics

Among the main challenges of our century, the climate change and the need of diversification of the energy sources are of most importance. Renewable energies undoubtedly have an important role to play, photovoltaic (PV) electricity being especially well suited to face these energy challenges. However, the current integration of PV panels often comes without architectural consideration. In this context, the Archinsolar project [1] aims to develop a new generation of photovoltaic elements based on silicon thin films technologies (amorphous and micromorph), ultra-reliable and manufacturable at a very low cost, allowing a unique architectural integration, respectful of the bui lt environment and overall landscape. Here we will present our new developments on innovative PV elements including colored PV panels and a solar tile using a composite back-structure

Magnetism of CoPd self-organized alloy clusters on Au(111)

Magnetic properties of gold-encapsulated CoxPd1-x self-organized nano-clusters on Au(111) are analyzed by x-ray magnetic circular dichroism for x = 0.5, 0.7, and 1.0. The clusters are superparamagnetic with a blocking temperature decreasing with increasing Pd concentration, due to a reduction of the out-of-plane anisotropy strength. No magnetic moment is detected on Pd in these clusters, within the detection limit, contrary to thick CoPd films. Both reduction of anisotropy and vanishing Pd moment are attributed to strain. (C) 2013 AIP Publishing LLC