The viral transmembrane superfamily: possible divergence of Arenavirus and Filovirus glycoproteins from a common RNA virus ancestor

BackgroundRecent studies of viral entry proteins from influenza, measles, human immunodeficiency virus, type 1 (HIV-1), and Ebola virus have shown, first with molecular modeling, and then X-ray crystallographic or other biophysical studies, that these disparate viruses share a coiled-coil type of entry protein.ResultsStructural models of the transmembrane glycoproteins (GP-2) of the Arenaviruses, lymphochoriomeningitis virus (LCMV) and Lassa fever virus, are presented, based on consistent structural propensities despite variation in the amino acid sequence. The principal features of the model, a hydrophobic amino terminus, and two antiparallel helices separated by a glycosylated, antigenic apex, are common to a number of otherwise disparate families of enveloped RNA viruses. Within the first amphipathic helix, demonstrable by circular dichroism of a peptide fragment, there is a highly conserved heptad repeat pattern proposed to mediate multimerization by coiled-coil interactions. The amino terminal 18 amino acids are 28% identical and 50% highly similar to the corresponding region of Ebola, a member of the Filovirus family. Within the second, charged helix just prior to membrane insertion there is also high similarity over the central 18 amino acids in corresponding regions of Lassa and Ebola, which may be further related to the similar region of HIV-1 defining a potent antiviral peptide analogue.ConclusionsThese findings indicate a common pattern of structure and function among viral transmembrane fusion proteins from a number of virus families. Such a pattern may define a viral transmembrane superfamily that evolved from a common precursor eons ago

In our own backyard: urban health inequities and Aboriginal experiences of neighbourhood life, social capital and racism.

This report is about Aboriginal and Torres Strait Islander people who live in urban areas. Thus it contributes to filling the gap in literature and knowledge about the health and everyday life experience of urban Indigenous peoples.This study, the Adelaide Aboriginal and Torres Strait Islander Health (AATSIH) project, was funded by the National Health and Medical Research Council (NHMRC) and focused on neighbourhood life, social capital, experiences of racism and health. This was a ‘companion’ project to another NHMRC project (the General Location and Health project (the General L&H project) – see Baum, Ziersch, Zhang et al, 2007) that explored neighbourhood life and social capital for the general population in four contrasting socio-economic areas in Adelaide

Mechanisms of Groucho-mediated repression revealed by genome-wide analysis of Groucho binding and activity

Antibody validation (A) Chromatin isolated and sheared exactly as for the ChIP-seq analysis was subjected to immunoprecipitation with the indicated amounts (in μl) of affinity purified antibody against the Gro GP domain used for the ChIP-seq analysis, and then probed in a western blot with both an anti-Gro monoclonal antibody (mAb) or the anti-GP antibody. The band indicated by the asterisk is a cross-reacting protein that is recognized in the western blot but that is not efficiently immunoprecipitated by the anti-GP antibody. Ab HC – antibody heavy chain. (B) Heat map showing overlap (Jacard similarity coefficient [96]) between the peaks called in the duplicate ChIP-seq experiments at each time point. (C) Representative genome browser tracts comparing duplicate ChIP-seq experiments. (D and E) Comparison of Gro binding patterns obtained by ChIP-seq using our anti-GP antibody with that obtained by ChIP-chip (0–12 hr embryos; modENCODE #597) and ChIP-seq (white pre-pupae; modENCODE #4981) using independently derived antibodies [40]. (PDF 588 kb

Viewing America’s energy future in three dimensions

The future of the US energy infrastructure is a major and urgent challenge for our society. This monograph was stimulated by a report of the National Academies' Committee on America's Energy Future, America's Energy Future: Technology and Transformation, Summary Edition, 2009. The report pointed out the critical but poorly understood and little explored role of societal considerations in determining the fate of national energy policies and programs. In our efforts to respond to those concerns, we have examined the thesis that the three major dimensions of the energy challenge—technology, economics, and societal—are overlapping, interactive, and inseparable; therefore, they can be understood only when considered simultaneously and discussed in terms of their interactions. Correspondingly, this monograph describes energy technologies in the context of their economic and societal contexts, energy economics in their technological and societal contexts, and the societal aspects of energy in their technological and economic contexts. The monograph then identifies social science–driven research opportunities pertaining to America’s energy challenge, with the hope that the proposed research will help not only overcome the societal barriers identified by the National Academies' report, but also harness societal forces in developing a rational energy future

Damage control operations in non-trauma patients: defining criteria for the staged rapid source control laparotomy in emergency general surgery

Abstract Background The staged laparotomy in the operative management of emergency general surgery (EGS) patients is an extension of trauma surgeons operating on this population. Indications for its application, however, are not well defined, and are currently based on the lethal triad used in physiologically-decompensated trauma patients. This study sought to determine the acute indications for the staged, rapid source control laparotomy (RSCL) in EGS patients. Methods All EGS patients undergoing emergent staged RSCL and non-RSCL over 3 years were studied. Demographics, physiologic parameters, perioperative variables, outcomes, and survival were compared. Logistic regression models determined the influence of physiologic parameters on mortality and postoperative complications. EGS-RSCL indications were defined. Results 215 EGS patients underwent emergent laparotomy; 53 (25 %) were staged RSCL. In the 53 patients who underwent a staged RSCL based on the lethal triad, adjusted multivariable regression analysis shows that when used alone, no component of the lethal triad independently improved survival. Staged RSCL may decrease mortality in patients with preoperative severe sepsis / septic shock, and an elevated lactate (≥3); acidosis (pH ≤ 7.25); elderly (≥70); male gender; and multiple comorbidities (≥3). Of the 162 non-RSCL emergent laparotomies, 27 (17 %) required unplanned re-explorations; of these, 17 (63 %) had sepsis preoperatively and 9 (33 %) died. Conclusions The acute physiologic indicators that help guide operative decisions in trauma may not confer a similar survival advantage in EGS. To replace the lethal triad, criteria for application of the staged RSCL in EGS need to be defined. Based on these results, the indications should include severe sepsis / septic shock, lactate, acidosis, gender, age, and pre-existing comorbidities. When correctly applied, the staged RSCL may help to improve survival in decompensated EGS patients

Using genetic variation and environmental risk factor data to identify individuals at high risk for age-related macular degeneration

A major goal of personalized medicine is to pre-symptomatically identify individuals at high risk for disease using knowledge of each individual's particular genetic profile and constellation of environmental risk factors. With the identification of several well-replicated risk factors for age-related macular degeneration (AMD), the leading cause of legal blindness in older adults, this previously unreachable goal is beginning to seem less elusive. However, recently developed algorithms have either been much less accurate than expected, given the strong effects of the identified risk factors, or have not been applied to independent datasets, leaving unknown how well they would perform in the population at large. We sought to increase accuracy by using novel modeling strategies, including multifactor dimensionality reduction (MDR) and grammatical evolution of neural networks (GENN), in addition to the traditional logistic regression approach. Furthermore, we rigorously designed and tested our models in three distinct datasets: a Vanderbilt-Miami (VM) clinic-based case-control dataset, a VM family dataset, and the population-based Age-related Maculopathy Ancillary (ARMA) Study cohort. Using a consensus approach to combine the results from logistic regression and GENN models, our algorithm was successful in differentiating between high- and low-risk groups (sensitivity 77.0%, specificity 74.1%). In the ARMA cohort, the positive and negative predictive values were 63.3% and 70.7%, respectively. We expect that future efforts to refine this algorithm by increasing the sample size available for model building, including novel susceptibility factors as they are discovered, and by calibrating the model for diverse populations will improve accuracy

Benefit Analysis of IGBT Power Device Simulation Modeling

The National Institute of Standards and Technology’s Electronic and Electrical Engineering Laboratory (NIST/EEEL) program supports the development of mathematical models for several classes of semiconductor devices. This study presents the results from a microeconomic impact assessment of the development of mathematical models for the design of insulated-gate bipolar transistor (IGBT) semiconductor power devices. NIST/EEEL’s IGBT mathematical modeling program (referred to as the NIST IGBT modeling program) has led to significant economic benefits. These benefits include: improvements in R&D efficiency, decreases in transaction costs, decreases in production costs, and improvements in product quality. NIST’s activities have affected software companies, IGBT device manufacturers, and manufacturers of products that employ IGBTs (referred to as applications manufacturers). Software companies have incorporated NIST’s mathematical models into their commercial simulation modeling software. Device manufacturers, such as Harris Semiconductors and International Rectifier, and applications manufacturers, such as Ford Motor Company and General Electric, use this software to design electrical systems employing IGBTs. IGBTs are used in a wide range of applications, such as automotive ignition systems and adjustable speed drives. In the absence of NIST’s activities, industry experts stated that the availability of IGBT simulation modeling software “would have been delayed, and the modeling software developed would not have been as accurate.” This study quantifies the economic benefits associated with improvements in R&D efficiency and reductions in transaction costs. In addition, the study identifies and qualitatively describes the impact of the NIST IGBT modeling program on production costs and quality and performance of final products employing IGBTs