Maturation of West Nile virus modulates sensitivity to antibody-mediated neutralization

West Nile virions incorporate 180 envelope (E) proteins that orchestrate the process of virus entry and are the primary target of neutralizing antibodies. The E proteins of newly synthesized West Nile virus (WNV) are organized into trimeric spikes composed of pre-membrane (prM) and E protein heterodimers. During egress, immature virions undergo a protease-mediated cleavage of prM that results in a reorganization of E protein into the pseudo-icosahedral arrangement characteristic of mature virions. While cleavage of prM is a required step in the virus life cycle, complete maturation is not required for infectivity and infectious virions may be heterogeneous with respect to the extent of prM cleavage. In this study, we demonstrate that virion maturation impacts the sensitivity of WNV to antibody-mediated neutralization. Complete maturation results in a significant reduction in sensitivity to neutralization by antibodies specific for poorly accessible epitopes that comprise a major component of the human antibody response following WNV infection or vaccination. This reduction in neutralization sensitivity reflects a decrease in the accessibility of epitopes on virions to levels that fall below a threshold required for neutralization. Thus, in addition to a role in facilitating viral entry, changes in E protein arrangement associated with maturation modulate neutralization sensitivity and introduce an additional layer of complexity into humoral immunity against WNV

Is The Mobile Phone Technology Feasible For Effective Monitoring Of Defecation Practices In Ghana? The Case Of A Peri-Urban District In Ghana

Abstract: Background: The world leaders have decided to increase the sanitation coverage in areas of with poor access and monitor the progress. However, data collection via existing paper-based monitoring and evaluation (M & E) survey tools has limitations, including the approach used in Ghana. Therefore, there is the need to test new innovative M & E tools for monitoring sanitation practices. Objective: To compare a mobile phone short messaging service (SMS) M & E survey tool with a paper based format in a rapidly expanding peri-urban setting of Prampram, Ghana. Methods: Four hundred and fifty-eight adults with access to a mobile phone were purposely selected. Next, they were randomly assigned to the group using SMS or the group reporting on sanitation practices through a paper-based survey method. Respondents were asked to answer 5 questions on sanitation practices once every quarter over a one-year period. Non-responders were interviewed to ascertain reasons for non-response. A subset of 227 respondents were interviewed to obtain information on acceptability, ease of use and level of privacy of the two M & E survey tools. Results: Respondents from this study, found the mobile phone SMS M & E survey tool to be feasible although the tool was unacceptable, not user friendly and offered a low level of privacy as compared to the paper tool. Conclusions: The mobile phone SMS M & E tool cannot replace paper-based tool for sanitation M & E in Ghana. Further studies could examine alternative mobile phone applications, for example the use of pictorial mobile phone technology for data collection among lowliteracy populations

Wirkung der Maßnahmen der Bundesregierung innerhalb der Zielarchitektur zum Umbau der Energieversorgung

Um die weitere Entwicklung der Energiewende zu gestalten, wurde mit dem Ersten Fortschrittsbericht zur Energiewende eine Strukturierung der verschiedenen Energiewendeziele nach Sektoren und Kategorien vorgenommen und in eine Hierarchie nach Strategie- und Steuerungsebene gebracht. Diese Strukturierung der Ziele wird in dieser Studie (und auch darüber hinaus) als Zielarchitektur bezeichnet. In der vorliegenden Studie werden die Wirkungen der Instrumente innerhalb der Zielarchitektur und ihr Zusammenspiel zur Erreichung der energiepolitischen Ziele analysiert. Auf Basis der erzielten Ergebnisse wird die Zielarchitektur im Hinblick auf die Erreichung der energie- und klimapolitischen Ziele sowie einer weiteren Optimierung der Energiewende hin untersucht. Dabei sollen insbesondere anhand der beiden Leitkriterien Kosteneffizienz und Systemintegration mögliche Korridore für Steuerungsziele wie auch Flexibilisierungsoptionen der Ziele identifiziert werden

Catalytic Mechanism and Efficiency of Methane Oxidation by Hg(II) in Sulfuric Acid and Comparison to Radical Initiated Conditions

Methane conversion to methyl bisulfate by Hg^(II)(SO_4) in sulfuric acid is an example of fast and selective alkane oxidation catalysis. Dichotomous mechanisms involving C–H activation and electron transfer have been proposed based on experiments. Radical oxidation pathways have also been proposed for some reaction conditions. Hg^(II) is also of significant interest because as a d^(10) transition metal it is similar to d^(10) main-group metals that also oxidize alkanes. Density-functional calculations are presented that use both implicit and a mixture of implicit/explicit solvent models for the complete Hg_(II) catalytic cycle of methane oxidation to methyl bisulfate. These calculations are consistent with experiment and reveal that methane is functionalized to methyl bisulfate by a C–H activation and reductive metal alkyl functionalization mechanism. This reaction pathway is lower in energy than both electron transfer and proton-coupled electron transfer pathways. After methane C–H functionalization, catalysis is completed by conversion of the proposed resting state, [Hg^I(HSO_4)]_2, into Hg^0 followed by Hg^0 to Hg^(II) oxidation induced by SO_3 from dehydration of sulfuric acid. This catalytic cycle is efficient because in sulfuric acid the Hg^(II)/Hg^0 potential results in a moderate free energy barrier for oxidation (∼40 kcal/mol) and Hg^(II) is electrophilic enough to induce barriers of <40 kcal/mol for C–H activation and reductive metal alkyl functionalization. Comparison of Hg^(II) to Tl^(III) shows that while C–H activation and reductive metal alkyl functionalization have reasonable barriers for Tl^(III), the oxidation of Tl^I to Tl^(III) has a significantly larger barrier than Hg^0 to Hg^(II) oxidation and therefore Tl^(III) is not catalytic in sulfuric acid. Comparison of Hg^(II) to Cd^(II) and Zn^(II) reveals that while M^0 to M^(II) oxidation and C–H activation are feasible for these first-row and second-row transition metals, reductive metal alkyl functionalization barriers are very large and catalysis is not feasible. Calculations are also presented that outline the mechanism and energy landscape for radical-initiated (K_2S_2O_8) methane oxidation to methanesulfonic acid in sulfuric acid

Mps1 Phosphorylation of Dam1 Couples Kinetochores to Microtubule Plus Ends at Metaphase

Duplicated chromosomes are equally segregated to daughter cells by a bipolar mitotic spindle during cell division. By metaphase, sister chromatids are coupled to microtubule (MT) plus ends from opposite poles of the bipolar spindle via kinetochores. Here we describe a phosphorylation event that promotes the coupling of kinetochores to microtubule plus ends

Physician Awareness of Drug Cost: A Systematic Review

From a review of data from 24 studies, Michael Allan and colleagues conclude that doctors often underestimate the price of expensive drugs and overestimate the price of those that are inexpensive