Comprehensive linker-scanning mutagenesis of the hepatitis C virus E1 and E2 envelope glycoproteins reveals new structure–function relationships

Despite extensive research, many details about the structure and functions of hepatitis C virus (HCV) glycoproteins E1 and E2 are not fully understood, and their crystal structure remains to be determined. We applied linker-scanning mutagenesis to generate a panel of 34 mutants, each containing an insertion of 5 aa at a random position within the E1E2 sequence. The mutated glycoproteins were analysed by using a range of assays to identify regions critical for maintaining protein conformation, E1E2 complex assembly, CD81 receptor binding, membrane fusion and infectivity. The results, while supporting previously published data, provide several interesting new findings. Firstly, insertion at amino acid 587 or 596 reduced E1E2 heterodimerization without affecting reactivity with some conformation-sensitive mAbs or with CD81, thus implicating these residues in glycoprotein assembly. Secondly, insertions within a conserved region of E2, between amino acid residues 611 and 631, severely disrupted protein conformation and abrogated binding of all conformation-sensitive antibodies, suggesting that the structural integrity of this region is critical for the correct folding of E2. Thirdly, an insertion at Leu-682 specifically affected membrane fusion, providing direct evidence that the membrane-proximal ‘stem’ of E2 is involved in the fusion mechanism. Overall, our results show that the HCV glycoproteins generally do not tolerate insertions and that there are a very limited number of sites that can be changed without dramatic loss of function. Nevertheless, we identified two E2 insertion mutants, at amino acid residues 408 and 577, that were infectious in the murine leukemia virus-based HCV pseudoparticle system

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

Nitric Acid Particles in Cold Thick Ice Clouds Observed at Global Scale: Link with Lightning, Temperature, and Upper Tropospheric Water Vapor

Signatures of nitric acid particles (NAP) in cold thick ice clouds have been derived from satellite observations. Most NAP are detected in the Tropics (9 to 20% of clouds with T less than 202.5 K). Higher occurrences were found in the rare mid-latitudes very cold clouds. NAP occurrence increases as cloud temperature decreases and NAP are more numerous in January than July. Comparisons of NAP and lightning distributions show that lightning is the main source of the NOx, which forms NAP in cold clouds. Qualitative comparisons of NAP with upper tropospheric humidity distributions suggest that NAP play a role in the dehydration of the upper troposphere when the tropopause is colder than 195K

Multi-resolution image analysis for vehicle detection

Proceeding of: Second Iberian Conference, IbPRIA 2005, Estoril, Portugal, June 7-9, 2005Computer Vision can provide a great deal of assistance to Intelligent Vehicles. In this paper an Advanced Driver Assistance Systems for Vehicle Detection is presented. A geometric model of the vehicle is defined where its energy function includes information of the shape and symmetry of the vehicle and the shadow it produces. A genetic algorithm finds the optimum parameter values. As the algorithm receives information from a road detection module some geometric restrictions can be applied. A multi-resolution approach is used to speed up the algorithm and work in realtime. Examples of real images are shown to validate the algorithm.Publicad

What Else is Revealed by Order-Revealing Encryption?

The security of order-revealing encryption (ORE) has been unclear since its invention. Dataset characteristics for which ORE is especially insecure have been identified, such as small message spaces and low-entropy distributions. On the other hand, properties like one-wayness on uniformly-distributed datasets have been proved for ORE constructions. This work shows that more plaintext information can be extracted from ORE ciphertexts than was previously thought. We identify two issues: First, we show that when multiple columns of correlated data are encrypted with ORE, attacks can use the encrypted columns together to reveal more information than prior attacks could extract from the columns individually. Second, we apply known attacks, and develop new attacks, to show that the \emph{leakage} of concrete ORE schemes on non-uniform data leads to more accurate plaintext recovery than is suggested by the security theorems which only dealt with uniform inputs

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

Anaesthetic management of people with multiple sclerosis.

There is a lack of published guidelines on the management of patients with multiple sclerosis (MS) undergoing procedures that require anaesthesia and respective advice is largely based on retrospective studies or case reports. The aim of this paper is to provide recommendations for anaesthetists and neurologists for the management of patients with MS requiring anaesthesia. This review covers issues related to the anaesthetic management of patients with MS, with a focus on preoperative assessment, choice of anaesthetic techniques and agents, side-effects of drugs used during anaesthesia and their potential impact on the disease evolution, drug interactions that may occur, and the need to use monitoring devices. A systematic PubMed research was performed to retrieve relevant articles