Alteration of Protein Levels during Influenza Virus H1N1 Infection in Host Cells: A Proteomic Survey of Host and Virus Reveals Differential Dynamics

We studied the dynamics of the proteome of influenza virus A/PR/8/34 (H1N1) infected Madin-Darby canine kidney cells up to 12 hours post infection by mass spectrometry based quantitative proteomics using the approach of stable isotope labeling by amino acids in cell culture (SILAC). We identified 1311 cell proteins and, apart from the proton channel M2, all major virus proteins. Based on their abundance two groups of virus proteins could be distinguished being in line with the function of the proteins in genesis and formation of new virions. Further, the data indicate a correlation between the amount of proteins synthesized and their previously determined copy number inside the viral particle. We employed bioinformatic approaches such as functional clustering, gene ontology, and pathway (KEGG) enrichment tests to uncover co-regulated cellular protein sets, assigned the individual subsets to their biological function, and determined their interrelation within the progression of viral infection. For the first time we are able to describe dynamic changes of the cellular and, of note, the viral proteome in a time dependent manner simultaneously. Through cluster analysis, time dependent patterns of protein abundances revealed highly dynamic up- and/or down-regulation processes. Taken together our study provides strong evidence that virus infection has a major impact on the cell status at the protein level.     

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The Intradermal Reaction in Amebiasis

Studies on the amebiasis skin test were carried out in Amerindians living on reserves of Northern Saskatchewan. Results indicate the skin test to be highly sensitive in patients with acute amebic dysentery and in individuals with a history of amebic disease. A high percentage of asymptomatic school children living on a reserve where amebic disease is of common occurrence were also skin reactors. In a similar group of school children living on a reserve where amebic disease had never been reported but where E. histolytica infection rates are high there were very few reactors. A control group of white adults living in a non-endemic area were uniformly negative to the skin test. A comparison with the indirect hemagglutination test showed a good general correlation, but the skin test proved to be more accurate in cases of acute amebic dysentery in children 5 years of age or under. The skin test appears to have potential as a diagnostic technique and may be of considerable value in defining endemic areas of amebic disease.     

Sphingolipids as modulators of membrane proteins

The diversity of the transmembranome of higher eukaryotes is matched by an enormous diversity of sphingolipid classes and molecular species. The intrinsic properties of sphingolipids are not only suited for orchestrating lateral architectures of biological membranes, but their molecular distinctions also allow for the evolution of protein motifs specifically recognising and interacting with individual lipids. Although various reports suggest a role of sphingolipids in membrane protein function, only a few cases have determined the specificity of these interactions. In this review we discuss examples of specific protein–sphingolipid interactions for which a modulator-like dependency on sphingolipids was assigned to specific proteins. These novel functions of sphingolipids in specific protein–lipid assemblies contribute to the complexity of the sphingolipid classes and other molecular species observed in animal cells. This article is part of a Special Issue entitled New Frontiers in Sphingolipid Biology.     

Induction of antibiotic specialized metabolism by co-culturing in a collection of phyllosphere bacteria

A diverse set of bacteria live on the above-ground parts of plants, composing the phyllosphere, and play important roles for plant health. Phyllosphere microbial communities assemble in a predictable manner and diverge from communities colonizing other plant organs or the soil. However, how these communities differ functionally remains obscure. We assembled a collection of 258 bacterial isolates representative of the most abundant taxa of the phyllosphere of Arabidopsis and a shared soil inoculum. We screened the collection for the production of metabolites that inhibit the growth of Gram-positive and Gram-negative bacteria either in isolation or in co-culture. We found that isolates capable of constitutive antibiotic production in monoculture were significantly enriched in the soil fraction. In contrast, the proportion of binary cultures resulting in the production of growth inhibitory compounds differed only marginally between the phyllosphere and soil fractions. This shows that the phyllosphere may be a rich resource for potentially novel molecules with antibiotic activity, but that production or activity is dependent upon induction by external signals or cues. Finally, we describe the isolation of antimicrobial acyloin metabolites from a binary culture of Arabidopsis phyllosphere isolates, which inhibit the growth of clinically relevant Acinetobacter baumannii.     

Costly Inheritance and the Persistence of Insecticide Resistance in Aedes aegypti Populations

Global emergence of arboviruses is a growing public health concern, since most of these diseases have no vaccine or prevention treatment available. In this scenario, vector control through the use of chemical insecticides is one of the most important prevention tools. Nevertheless, their effectiveness has been increasingly compromised by the development of strong resistance observed in field populations, even in spite of fitness costs usually associated to resistance. Using a stage-structured deterministic model parametrised for the Aedes aegypti—the main vector for dengue—we investigated the persistence of resistance by studying the time for a population which displays resistance to insecticide to revert to a susceptible population. By means of a comprehensive series of in-silico experiments, we studied this reversal time as a function of fitness costs and the initial presence of the resistance allele in the population. The resulting map provides both a guiding and a surveillance tool for public health officers to address the resistance situation of field populations. Application to field data from Brazil indicates that reversal can take, in some cases, decades even if fitness costs are not small. As by-products of this investigation, we were able to fit very simple formulas to the reversal times as a function of either cost or initial presence of the resistance allele. In addition, the in-silico experiments also showed that density dependent regulation plays an important role in the dynamics, slowing down the reversal process.     

Probabilistic Analysis of Pattern Formation in Monotonic Self-Assembly

Inspired by biological systems, self-assembly aims to construct complex structures. It functions through piece-wise, local interactions among component parts and has the potential to produce novel materials and devices at the nanoscale. Algorithmic self-assembly models the product of self-assembly as the output of some computational process, and attempts to control the process of assembly algorithmically. Though providing fundamental insights, these computational models have yet to fully account for the randomness that is inherent in experimental realizations, which tend to be based on trial and error methods. In order to develop a method of analysis that addresses experimental parameters, such as error and yield, this work focuses on the capability of assembly systems to produce a pre-determined set of target patterns, either accurately or perhaps only approximately. Self-assembly systems that assemble patterns that are similar to the targets in a significant percentage are “strong” assemblers. In addition, assemblers should predominantly produce target patterns, with a small percentage of errors or junk. These definitions approximate notions of yield and purity in chemistry and manufacturing. By combining these definitions, a criterion for efficient assembly is developed that can be used to compare the ability of different assembly systems to produce a given target set. Efficiency is a composite measure of the accuracy and purity of an assembler. Typical examples in algorithmic assembly are assessed in the context of these metrics. In addition to validating the method, they also provide some insight that might be used to guide experimentation. Finally, some general results are established that, for efficient assembly, imply that every target pattern is guaranteed to be assembled with a minimum common positive probability, regardless of its size, and that a trichotomy exists to characterize the global behavior of typical efficient, monotonic self-assembly systems in the literature.