A computational framework for influenza antigenic cartography

Influenza viruses have been responsible for large losses of lives around the world and continue to present a great public health challenge. Antigenic characterization based on hemagglutination inhibition (HI) assay is one of the routine procedures for influenza vaccine strain selection. However, HI assay is only a crude experiment reflecting the antigenic correlations among testing antigens (viruses) and reference antisera (antibodies). Moreover, antigenic characterization is usually based on more than one HI dataset. The combination of multiple datasets results in an incomplete HI matrix with many unobserved entries. This paper proposes a new computational framework for constructing an influenza antigenic cartography from this incomplete matrix, which we refer to as Matrix Completion-Multidimensional Scaling (MC-MDS). In this approach, we first reconstruct the HI matrices with viruses and antibodies using low-rank matrix completion, and then generate the two-dimensional antigenic cartography using multidimensional scaling. Moreover, for influenza HI tables with herd immunity effect (such as those from Human influenza viruses), we propose a temporal model to reduce the inherent temporal bias of HI tables caused by herd immunity. By applying our method in HI datasets containing H3N2 influenza A viruses isolated from 1968 to 2003, we identified eleven clusters of antigenic variants, representing all major antigenic drift events in these 36 years. Our results showed that both the completed HI matrix and the antigenic cartography obtained via MC-MDS are useful in identifying influenza antigenic variants and thus can be used to facilitate influenza vaccine strain selection. The webserver is available at http://sysbio.cvm.msstate.edu/AntigenMap.     

A flexible hierarchical framework for improving inference in area-referenced environmental health studies

Study designs where data have been aggregated by geographical areas are popular in environmental epidemiology. These studies are commonly based on administrative databases and, providing a complete spatial coverage, are particularly appealing to make inference on the entire population. However, the resulting estimates are often biased and difficult to interpret due to unmeasured confounders, which typically are not available from routinely collected data. We propose a framework to improve inference drawn from such studies exploiting information derived from individual-level survey data. The latter are summarized in an area-level scalar score by mimicking at ecological level the well-known propensity score methodology. The literature on propensity score for confounding adjustment is mainly based on individual-level studies and assumes a binary exposure variable. Here, we generalize its use to cope with area-referenced studies characterized by a continuous exposure. Our approach is based upon Bayesian hierarchical structures specified into a two-stage design: (i) geolocated individual-level data from survey samples are up-scaled at ecological level, then the latter are used to estimate a generalized ecological propensity score (EPS) in the in-sample areas; (ii) the generalized EPS is imputed in the out-of-sample areas under different assumptions about the missingness mechanisms, then it is included into the ecological regression, linking the exposure of interest to the health outcome. This delivers area-level risk estimates, which allow a fuller adjustment for confounding than traditional areal studies. The methodology is illustrated by using simulations and a case study investigating the risk of lung cancer mortality associated with nitrogen dioxide in England (UK).     

A role for accessibility to self-peptide-self-MHC complexes in intrathymic negative selection

Whether intrathymic-positive and -negative selection of conventional alpha beta T cells occur in anatomically distinct sites is a matter of debate. By using a system composed of two distinct immune receptors, the Y-Ae mAb and the 1H3.1 (V alpha 1/V beta 6) TCR, both directed against the 52--68 fragment of the I-E alpha-chain (E alpha 52--68) bound to I-A(b), we examined the occurrence of negative selection imposed in vivo by a self-peptide-self-MHC class II complex with differential tissue expression. 1H3.1 TCR-transgenic (Tg) mice were bred to mice having an I-E alpha transgene with expression directed to all MHC class II-positive cells, restricted to thymic epithelial cells, or restricted to B cells, dendritic cells, and medullary thymic epithelial cells. All 1H3.1 TCR/I-E alpha double-Tg mice revealed a severely diminished thymic cellularity. Their lymph node cells were depleted of V beta 6(+)CD4(+) cells and were unresponsive to E alpha 52--68 in vitro. The absolute number of CD4(+)CD8(+) thymocytes was drastically reduced in all combinations, indicating that negative selection caused by an endogenously expressed self-determinant can effectively occur in the thymic cortex in vivo. Moreover, both cortical epithelial cells and, interestingly, the few cortical dendritic cells were able to support negative selection of CD4(+)CD8(+) thymocytes, albeit with a distinct efficiency. Collectively, these observations support a model where, in addition to the avidity of the thymocyte/stromal cell interaction, in vivo negative selection of autoreactive TCR-Tg T cells is determined by accessibility to self-peptide-self-MHC complexes regardless of the anatomical site.     

The enzymatic degradation of algal cell walls: a useful approach for improving protein accessibility?

With protein contents higher than 20% (dry weight), some red or green seaweeds are potential sources of commercially useful plant proteins. However, the presence of anionic or neutral polysaccharides in large quantities in the cell wall strongly hinders the solubilization of proteins during the application of classical extraction procedures. A present this limits the study and industrial use of seaweed proteins. This short paper is a discussion about the use of enzymes degrading the cell wall polysaccharides as an alternative method to improve the extraction and the solubilization of algal proteins. This revised version was published online in July 2006 with corrections to the Cover Date.     

A generic method for assignment of reliability scores applied to solvent accessibility predictions

Background  

Estimation of the reliability of specific real value predictions is nontrivial and the efficacy of this is often questionable. It is important to know if you can trust a given prediction and therefore the best methods associate a prediction with a reliability score or index. For discrete qualitative predictions, the reliability is conventionally estimated as the difference between output scores of selected classes. Such an approach is not feasible for methods that predict a biological feature as a single real value rather than a classification. As a solution to this challenge, we have implemented a method that predicts the relative surface accessibility of an amino acid and simultaneously predicts the reliability for each prediction, in the form of a Z-score.     

Molecular cartography of globular proteins with application to antigenic sites

A method, molecular cartography, is introduced as a way to quantitate the topographic structure of a protein surface. The method is applied to the problem of antigenic determinants, and it is used to examine local and global topography of reported antigenic regions on the surface of myoglobin and lysozyme. In nine antigenic sites taken from the literature and studied in detail, no local property was found in sites that was not also found in remaining regions of the surface. However, a strong correlation was found between antigenic sites and regions of the surface that are globally exposed. This finding suggests that global exposure of the protein surface may play a primary role in determining the antigenic structure of the protein. Molecular cartography may be useful in other instances of protein–protein interactions such as those between proteolytic enzymes and their substrates.     

Dynamic multiple-target tracing to probe spatiotemporal cartography of cell membranes

Although the highly dynamic and mosaic organization of the plasma membrane is well-recognized, depicting a resolved, global view of this organization remains challenging. We present an analytical single-particle tracking (SPT) method and tool, multiple-target tracing (MTT), that takes advantage of the high spatial resolution provided by single-fluorophore sensitivity. MTT can be used to generate dynamic maps at high densities of tracked particles, thereby providing global representation of molecular dynamics in cell membranes. Deflation by subtracting detected peaks allows detection of lower-intensity peaks. We exhaustively detected particles using MTT, with performance reaching theoretical limits, and then reconnected trajectories integrating the statistical information from past trajectories. We demonstrate the potential of this method by applying it to the epidermal growth factor receptor (EGFR) labeled with quantum dots (Qdots), in the plasma membrane of live cells. We anticipate the use of MTT to explore molecular dynamics and interactions at the cell membrane.     

A serotonergic axon-cilium synapse drives nuclear signaling to alter chromatin accessibility

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The C-terminal region of E1A: a molecular tool for cellular cartography

The adenovirus E1A proteins function via protein-protein interactions. By making many connections with the cellular protein network, individual modules of this virally encoded hub reprogram numerous aspects of cell function and behavior. Although many of these interactions have been thoroughly studied, those mediated by the C-terminal region of E1A are less well understood. This review focuses on how this region of E1A affects cell cycle progression, apoptosis, senescence, transformation, and conversion of cells to an epithelial state through interactions with CTBP1/2, DYRK1A/B, FOXK1/2, and importin-α. Furthermore, novel potential pathways that the C-terminus of E1A influences through these connections with the cellular interaction network are discussed.     

Solvent accessibility to flavin in oxynitrilase

Oxynitrilase containing 2-thioFAD [C(2) = S] in place of FAD exhibits catalytic activity similar to that of native enzyme. Reaction of methyl methanethiolsulfonate with 2-thioFAD bound to oxynitrilase results in the formation of the corresponding flavin disulfide [C(2)-SSCH3]. Normal flavin [C(2) = O] is formed by reacting 2-thioFAD oxynitrilase with m-chloroperoxybenzoate or H2O2. Both reactions proceed via a spectrally detectable flavin 2-S-oxide intermediate [C(2) = S+-O-], but sizable amounts of this intermediate accumulate only in the m-chloroperoxybenzoate reaction (about 40%). While similar reactions have been reported with free 2-thioflavin, kinetic and other data indicate that the oxynitrilase reactions occur with intact enzyme. This shows that the 2-position of the pyrimidine ring in the bound coenzyme is accessible to solvent. The data are consistent with previous studies on the reaction of peroxides with oxynitrilase-bound 5-deazaFAD which show that the pyrimidine ring is accessible at position 4. Analogous studies indicate that the pyrimidine ring is buried in the case of flavin bound to lactate oxidase, since the data indicate that both positions 2 and 4 are inaccessible to solvent.     

The legacy of human use in Amazonian palm communities along environmental and accessibility gradients

Aim

Palms are iconic and dominant elements of neotropical forests. In the Amazon region, palms have been used and managed by humans for food, material, medicine and other purposes for millennia. It is, however, debated to what extent the structure of modern palm communities reflects long-term human modification. Here, we investigate the complex interplay of ecological and societal factors that influence the distributions of both human-used and non-used palms in western Amazonia.

Location

Amazonia.

Time period

Present.

Major taxa studied

Palms (Arecaceae).

Methods

We used Bayesian hierarchical joint species distribution models to predict the distributions and environmental niche dimensions of 78 western Amazonian species, and to explore their relationships with their diversity of human uses and with specific uses (food, construction and medicine). The models were parameterized with a comprehensive set of field- and satellite-derived environmental predictors.

Results

Our results suggest that a combination of ecological and anthropogenic factors drive the present-day distributions of Amazonian palms. The modelled ecological niches of the species revealed use-related species-sorting along soil, climatic, accessibility and drainage gradients. We found peaks in the proportions of useful palms and their diversity of uses in fertile soils, close to rivers, and on floodplains. These are habitats favourable for human settlement, although they harbour naturally restricted palm species pools. We also found a negative correlation between predicted palm species richness and number of human uses across western Amazonia.

Main conclusions

Soil characteristics, accessibility, and species pool size all contribute to defining palm–human relationships. At the basin scale, the signature of human use on palm communities was predicted to be stronger in the species-poor south-west than in central-western Amazonia. Overall, we conclude that environmental conditions have influenced modern Amazonian palm distributions both directly and indirectly, by regulating human settlement patterns and natural resource use over extended time periods.     

Gas-discharge method for improving the environmental characteristics of the atmosphere (In memory of G.A. Askar'yan)

The possibility of improving the environmental characteristics of the atmosphere with the help of freely localized microwave discharges is analyzed. Theoretical and experimental studies devoted to cleaning the troposphere of ozone-destroying pollutants and creating an artificial ozone layer in the stratosphere are reviewed. Results from the studies of the possibility of the plasmochemical utilization of the accumulated chlorofluorocarbons, capable of depleting the ozone layer, are presented. The results of theoretical and experimental modeling are used to predict the plasmochemical consequences of creating artificial ionized regions in the atmosphere for the purpose of long-range radio and TV communication.     

基于CVM的黄河三角洲城市噪声环境质量改善的居民支付意愿研究

运用CVM和统计分析方法,调查了黄河三角洲城市噪声环境质量改善居民的支付意愿,得出愿意为城市噪声质量改善支付部分金钱的占71.3%,支付额平均为3.64元/(月.人);性别和教育程度对居民支付意愿均无显著影响,年龄、月收入和噪声影响程度对居民支付意愿均呈显著的正相关关系,职业对支付意愿有显著影响,但变化规律不明显。性别和噪声影响程度对支付水平无显著影响,年龄和教育程度对支付水平均呈显著负相关关系,职业和月收入对支付水平呈显著正相关关系。     

A theory for environmental systems

A theory for environmental systems is defined on the basis of two elements, termed ‘environmental unity’ and ‘behavior’. Environmental systems are regarded as non-living systems, each one related with only one biological system. We construct a material-energetic environmental diagram, which is introduced in terms of the theory of categories, thereby giving rise to a new categoryE. By means of two biological conditions, and the definition of static property of the biological system (related to its own environment), a set of theorems is obtained, exhibiting mathematical consequences for the represented theory.