Resistance to antibody neutralization in HIV-2 infection occurs in late stage disease and is associated with X4 tropism

This is a non-final version of an article published in final form in AIDS. 28 November 2012 - Volume 26 - Issue 18 - p 2275–2284Objectives: To characterize the nature and dynamics of the neutralizing antibody (NAb) response and escape in chronically HIV-2 infected patients.Methods: Twenty-eight chronically infected adults were studied over a period of 1-4 years. The neutralizing activity of plasma IgG antibodies against autologous and heterologous primary isolates was analyzed using a standard assay in TZM-bl cells. Coreceptor usage was determined in GHOST cells. The sequence and predicted 3Dstructure of the C2V3C3 Env region were determined for all isolates.Results: Only 50% of the patients consistently produced IgG NAbs to autologous and contemporaneous virus isolates. In contrast, 96% of the patients produced IgG antibodies that neutralized at least two isolates of a panel of six heterologous R5 isolates. Breadth and potency of the neutralizing antibodies were positively associated with the number of CD4+ T cells and with the titer and avidity of C2V3C3-specific binding IgG antibodies. X4 isolates were obtained only from late stage disease patients and were fully resistant to neutralization. The V3 loop of X4 viruses was longer, had a higher net charge and differed markedly in secondary structure compared to R5 viruses.Conclusions: Most HIV-2 patients infected with R5 isolates produce C2V3C3-specific neutralizing antibodies whose potency and breadth decreases as the disease progresses. Resistance to antibody neutralization occurs in late stage disease and is usually associated with X4 viral tropism and major changes in V3 sequence and conformation. Our studies support a model of HIV-2 pathogenesis in which the neutralizing antibodies play a central role and have clear implications for the vaccine field.Fundação para a Ciência e Tecnologia, Portuga

Sequential conformational transitions and α-helical supercoiling regulate a sensor histidine kinase

Sensor histidine kinases are central to sensing in bacteria and in plants. They usually contain sensor, linker, and kinase modules and the structure of many of these components is known. However, it is unclear how the kinase module is structurally regulated. Here, we use nano- to millisecond time- resolved X-ray scattering to visualize the solution structural changes that occur when the light-sensitive model histidine kinase YF1 is activated by blue light. We find that the coiled coil linker and the attached histidine kinase domains undergo a left handed rotation within microseconds. In a much slower second step, the kinase domains rearrange internally. This structural mechanism presents a template for signal transduction in sensor histidine kinases

A Nearly Optimal Algorithm for covering the interior of an Art Gallery

The problem of locating visual sensors can be often modeled as 2D Art Gallery problems. In particular, tasks such as surveillance require observing the interior of a polygonal environment (interior covering, IC), while for inspection or image based rendering observing the boundary (edge covering, EC) is sufficient. Both problems are NP-hard, and no technique is known for transforming one problem into the other. Recently, an incremental algorithm for EC has been proposed, and its near-optimality has been demonstrated experimentally. In this paper we show that, with some modification, the algorithm is nearly optimal also for IC. The algorithm has been implemented and tested over several hundreds of random polygons with and without holes. The cardinality of the solutions provided is very near to, or coincident with, a polygon-specific lower bound, and then suboptimal or optimal. In addition, our algorithm has been compared, for all the test polygons, with recent heuristic sensor location algorithms. In all cases, the cardinality of the set of guards provided by our algorithm was less than or equal to that of the set computed by the other algorithms. An enhanced version of the algorithm, also taking into account range and incidence constraints, has also been implemente

Self Consistent Molecular Field Theory for Packing in Classical Liquids

Building on a quasi-chemical formulation of solution theory, this paper proposes a self consistent molecular field theory for packing problems in classical liquids, and tests the theoretical predictions for the excess chemical potential of the hard sphere fluid. Results are given for the self consistent molecular fields obtained, and for the probabilities of occupancy of a molecular observation volume. For this system, the excess chemical potential predicted is as accurate as the most accurate prior theories, particularly the scaled particle (Percus-Yevick compressibility) theory. It is argued that the present approach is particularly simple, and should provide a basis for a molecular-scale description of more complex solutions.Comment: 6 pages and 5 figure

Meaningful, Motivating Library Lessons that Matter to Students in Grade Four

The purpose of this project was to develop a meaningful, motivating library curriculum to increase student learning in literacy for students in grade four. Current literature and research on the roles of the teacher-librarian, information literacy instruction, reading advocacy, specifically literature guidance and appreciation, and motivation were explored. A yearlong library curriculum map was created addressing topics and methods found to be effective in the review of current research. The library curriculum was aligned with the Marysville School District Elementary Library Curriculum Guide for Grade Four, the Washington State Grade Level Expectations in Reading, the Washington State Essential Learnings in Writing and Communication, and the Information Literacy Standards for Student Learning

Electrochemical Characterization of Clean Shape-Controlled Pt Nanoparticles Prepared in Presence of Oleylamine/Oleic Acid

A collection of shape-controlled Pt nanoparticles has been prepared using two different and previously described methodologies, both using oleylamine/oleic acid as capping material/solvent. A new decontamination protocol is presented to effectively clean the surface of the different nanoparticles thus allowing a full exposure of their surface area and consequently to make the most of their surface structure dependent reactivity. Subsequently, the clean shape-controlled Pt nanoparticles have been electrochemically characterized and their electrocatalytic properties evaluated towards some surface structure reactions of interest. The results indicate that the full characterization of the surface structure cannot be done exclusively by the available microscopy techniques, since it is very difficult to determine the presence of surface defects. Additional surface characterization probes, such as those provided by electrochemical surface sensitive reactions, have been used to assess the surface structure of the samples.This work has been financially supported by the MICINN (Feder) of Spain and Generalitat Valencia through Projects CTQ2013-44083-P and PROMETEOII/2014/013, respectively

In the Spotlight: Joel Bjorling, Jussi Bjorling Anecdotes

I first heard about Jussi Bjorling from my parents. Though I never met him in person, he was always fondly remembered. We had his records at home, and my parents heard him sing at the Shrine Mosque in Peoria, Illinois

Your Vocal Problem: Advice from Jussi Bjorling

In a rather unusual article which appeared in 1950, Jussi responded to questions on vocal problems; unfortunately, we do not have the name of the magazine in which the article originally appeared