Unraveling the molecular basis of subunit specificity in P pilus assembly by mass spectrometry

P pili are multisubunit fibers essential for the attachment of uropathogenic Escherichia coli to the kidney. These fibers are formed by the noncovalent assembly of six different homologous subunit types in an array that is strictly defined in terms of both the number and order of each subunit type. Assembly occurs through a mechanism termed “donor-strand exchange (DSE)” in which an N-terminal extension (Nte) of one subunit donates a β-strand to an adjacent subunit, completing its Ig fold. Despite structural determination of the different subunits, the mechanism determining specificity of subunit ordering in pilus assembly remained unclear. Here, we have used noncovalent mass spectrometry to monitor DSE between all 30 possible pairs of P pilus subunits and their Ntes. We demonstrate a striking correlation between the natural order of subunits in pili and their ability to undergo DSE in vitro. The results reveal insights into the molecular mechanism by which subunit ordering during the assembly of this complex is achieved

New pandemics: HIV and AIDS, HCV and chronic hepatitis, Influenza virus and flu

New pandemics are a serious threat to the health of the entire world. They are essentially of viral origin and spread at large speed. A meeting on this topic was held in Lyon, France, within the XIXth Jacques Cartier Symposia, a series of France-Québec meetings held every year. New findings on HIV and AIDS, on HCV and chronic hepatitis, and an update on influenza virus and flu were covered during this meeting on December 4 and 5, 2006. Aspects of viral structure, virus-host interactions, antiviral defenses, drugs and vaccinations, and epidemiological aspects were discussed for HIV and HCV. Old and recent data on the flu epidemics ended this meeting.The meeting sponsors were the Centre Jacques Cartier, the Agence Nationale de Recherches sur le SIDA et les hépatites (ANRS) France, the Ecole Normale Supérieure en Sciences de Lyon, The Réseau SIDA et Maladies Infectieuses from the Fond de la Recherche en Santé du Québec (FRSQ), The Institut de Recherches Cliniques de Montréal (IRCM), Boehringer Ingelheim, Sanofi Aventis, ViroChem Pharma and Merck Frosst. The authors thank the speakers for their meeting abstracts and comments that helped writing this review

Benchmarking clear-sky reflectances

Accurate calculations of shortwave reflectances in clear-sky aerosol-laden atmospheres are necessary for various applications in atmospheric sciences. However, computational cost becomes increasingly important for some applications such as data assimilation of top-of-atmosphere reflectances in models of atmospheric composition. This study aims to provide a benchmark that can help in assessing these two requirements in combination. We describe a protocol and input data for 44 080 cases involving various solar and viewing geometries, four different surfaces (one oceanic bidirectional reflectance function and three albedo values for a Lambertian surface), eight aerosol optical depths, five wavelengths, and four aerosol types. We first consider two models relying on the discrete ordinate method: VLIDORT (in vector and scalar configurations) and DISORT (scalar configuration only). We use VLIDORT in its vector configuration as a reference model and quantify the loss of accuracy due to (i) neglecting the effect of polarization in DISORT and VLIDORT (scalar) models and (ii) decreasing the number of streams in DISORT. We further test two other models: the 6SV2 model, relying on the successive orders of scattering method, and Forward-Lobe Two-Stream Radiance Model (FLOTSAM), a new model under development by two of the authors. Typical mean fractional errors of 2.8 % and 2.4 % for 6SV2 and FLOTSAM are found, respectively. Computational cost depends on the input parameters but also on the code implementation and application as some models solve the radiative transfer equations for a range of geometries while others do not. All necessary input and output data are provided as a Supplement as a potential resource for interested developers and users of radiative transfer models

Verrucous Carcinoma of the Vulva: A Case Report and Review of the Literature.

Verrucous carcinoma of the vulva is a rare lesion (1). Affecting essentially postmenopausal women, this lesion is a distinct and particular entity in vulval carcinoma classification and its scalability is uncertain and unpredictable. Here, we present a case concerning a 48-year-old patient, without follow-up after a condyloma acuminate of the vulva (large left lip). The origin of this case will be discussed in this article. The treatment decided was only surgical. A review of literature shows the rarity of this lesion of the female genital tract

Shortwave radiative forcing and efficiency of key aerosol types using AERONET data

The shortwave radiative forcing (Δ<i>F</i>) and the radiative forcing efficiency (Δ<i>F</i><sup>eff</sup>) of natural and anthropogenic aerosols have been analyzed using estimates of radiation both at the Top (TOA) and at the Bottom Of Atmosphere (BOA) modeled based on AERONET aerosol retrievals. Six main types of atmospheric aerosols have been compared (desert mineral dust, biomass burning, urban-industrial, continental background, oceanic and free troposphere) in similar observational conditions (i.e., for solar zenith angles between 55° and 65°) in order to compare the nearly same solar geometry. The instantaneous Δ<i>F</i> averages obtained vary from −122 ± 37 Wm<sup>−2</sup> (aerosol optical depth, AOD, at 0.55 μm, 0.85 ± 0.45) at the BOA for the mixture of desert mineral dust and biomass burning aerosols in West Africa and −42 ± 22 Wm<sup>−2</sup> (AOD = 0.9 ± 0.5) at the TOA for the pure mineral dust also in this region up to −6 ± 3 Wm<sup>−2</sup> and −4 ± 2 Wm<sup>−2</sup> (AOD = 0.03 ± 0.02) at the BOA and the TOA, respectively, for free troposphere conditions. This last result may be taken as reference on a global scale. Furthermore, we observe that the more absorbing aerosols are overall more efficient at the BOA in contrast to at the TOA, where they backscatter less solar energy into the space. The analysis of the radiative balance at the TOA shows that, together with the amount of aerosols and their absorptive capacity, it is essential to consider the surface albedo of the region on which they are. Thus, we document that in regions with high surface reflectivity (deserts and snow conditions) atmospheric aerosols lead to a warming of the Earth-atmosphere system

An adenovirus-derived protein: A novel candidate for anti-diabetic drug development

© 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). Aims Exposure to human adenovirus Ad36 is causatively and correlatively linked with better glycemic control in animals and humans, respectively. Although the anti-hyperglycemic property of Ad36 may offer some therapeutic potential, it is impractical to use an infectious agent for therapeutic benefit. Cell-based studies identified that Ad36 enhances cellular glucose disposal via its E4orf1 protein. Ability to improve glycemic control in vivo is a critical prerequisite for further investigating the therapeutic potential of E4orf1. Therefore, the aim of this study was to determine the ability of E4orf1 to improve glycemic control independent of insulin despite high fat diet. Materials & Methods 8-9wk old male C57BL/6J mice fed a high-fat diet (60% kcal) were injected with a retrovirus plasmid expressing E4orf1, or a null vector (Control). Glycemic control was determined by glucose and insulin tolerance test. Islet cell size, amount of insulin and glucagon were determined in formalin-fixed pancreas. Rat insulinoma cell line (832/13) was infected with E4orf1 or control to determine changes in glucose stimulated insulin secretion. Protein from flash frozen adipose tissue depots, liver and muscle was used to determine molecular signaling by western blotting. Results In multiple experiments, retrovirus-mediated E4orf1 expression in C57BL/6J mice significantly and reproducibly improved glucose excursion following a glucose load despite a high fat diet (60% energy). Importantly, E4orf1 improved glucose clearance without increasing insulin sensitivity, production or secretion, underscoring its insulin-independent effect. E4orf1 modulated molecular signaling in mice tissue, which included greater protein abundance of adiponectin, p-AKT and Glucose transporter Glu4. Conclusions This study provides the proof of concept for translational development of E4orf1 as a potential anti-diabetic agent. High fat intake and impaired insulin signaling are often associated with obesity, diabetes and insulin resistance. Hence, the ability of E4orf1 to improve glycemic control despite high fat diet and independent of insulin, is particularly attractive

Cloud thermodynamic phase inferred from merged POLDER and MODIS data

International audienceThe global spatial and diurnal distribution of cloud properties is a key issue for understanding the hydrological cycle, and critical for advancing efforts to improve numerical weather models and general circulation models. Satellite data provides the best way of gaining insight into global cloud properties. In particular, the determination of cloud thermodynamic phase is a critical first step in the process of inferring cloud optical and microphysical properties from satellite measurements. It is important that cloud phase be derived together with an estimate of the confidence of this determination, so that this information can be included with subsequent retrievals (optical thickness, effective particle radius, and ice/liquid water content). In this study, we combine three different and well documented approaches for inferring cloud phase into a single algorithm. The algorithm is applied to data obtained by the MODIS (MODerate resolution Imaging Spectroradiometer) and POLDER3 (Polarization and Directionality of the Earth Reflectance) instruments. It is shown that this synergistic algorithm can be used routinely to derive cloud phase along with an index that helps to discriminate ambiguous phase from confident phase cases. The resulting product provides a semi-continuous confidence index ranging from confident liquid to confident ice instead of the usual discrete classification of liquid phase, ice phase, mixed phase (potential combination of ice and liquid particles), or simply unknown phase clouds. This approach is expected to be useful for cloud assimilation and modeling efforts while providing more insight into the global cloud properties derived from satellite data