Quantifying information transfer by protein domains: Analysis of the Fyn SH2 domain structure

Background  

Efficient communication between distant sites within a protein is essential for cooperative biological response. Although often associated with large allosteric movements, more subtle changes in protein dynamics can also induce long-range correlations. However, an appropriate formalism that directly relates protein structural dynamics to information exchange between functional sites is still lacking.     

Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells

Background

Highly pathogenic avian influenza (HPAI) H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease.

Aim

To study influenza A (H5N1) virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease.

Methods

We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces.

Results

We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our data suggests that viremia, secondary to, for example, gastro-intestinal infection, can potentially lead to infection of the lung. HPAI H5N1 virus was a more potent inducer of cytokines (e.g. IP-10, RANTES, IL-6) in comparison to H1N1 virus in alveolar epithelial cells, and these virus-induced chemokines were secreted onto both the apical and basolateral aspects of the polarized alveolar epithelium.

Conclusion

The predilection of viruses for different routes of entry and egress from the infected cell is important in understanding the pathogenesis of influenza H5N1 infection and may help unravel the pathogenesis of human H5N1 disease.     

ETISEQ – an algorithm for automated elution time ion sequencing of concurrently fragmented peptides for mass spectrometry-based proteomics

Background  

Concurrent peptide fragmentation (i.e. shotgun CID, parallel CID or MS^E) has emerged as an alternative to data-dependent acquisition in generating peptide fragmentation data in LC-MS/MS proteomics experiments. Concurrent peptide fragmentation data acquisition has been shown to be advantageous over data-dependent acquisition by providing greater detection dynamic range and providing more accurate quantitative information. Nevertheless, concurrent peptide fragmentation data acquisition remains to be widely adopted due to the lack of published algorithms designed specifically to process or interpret such data acquired on any mass spectrometer.     

A comparison of spatially explicit landscape representation methods and their relationship to stream condition

1. Biodiversity, water quality and ecosystem processes in streams are known to be influenced by the terrestrial landscape over a range of spatial and temporal scales. Lumped attributes (i.e. per cent land use) are often used to characterise the condition of the catchment; however, they are not spatially explicit and do not account for the disproportionate influence of land located near the stream or connected by overland flow. 2. We compared seven landscape representation metrics to determine whether accounting for the spatial proximity and hydrological effects of land use can be used to account for additional variability in indicators of stream ecosystem health. The landscape metrics included the following: a lumped metric, four inverse‐distance‐weighted (IDW) metrics based on distance to the stream or survey site and two modified IDW metrics that also accounted for the level of hydrologic activity (HA‐IDW). Ecosystem health data were obtained from the Ecological Health Monitoring Programme in Southeast Queensland, Australia and included measures of fish, invertebrates, physicochemistry and nutrients collected during two seasons over 4 years. Linear models were fitted to the stream indicators and landscape metrics, by season, and compared using an information‐theoretic approach. 3. Although no single metric was most suitable for modelling all stream indicators, lumped metrics rarely performed as well as other metric types. Metrics based on proximity to the stream (IDW and HA‐IDW) were more suitable for modelling fish indicators, while the HA‐IDW metric based on proximity to the survey site generally outperformed others for invertebrates, irrespective of season. There was consistent support for metrics based on proximity to the survey site (IDW or HA‐IDW) for all physicochemical indicators during the dry season, while a HA‐IDW metric based on proximity to the stream was suitable for five of the six physicochemical indicators in the post‐wet season. Only one nutrient indicator was tested and results showed that catchment area had a significant effect on the relationship between land use metrics and algal stable isotope ratios in both seasons. 4. Spatially explicit methods of landscape representation can clearly improve the predictive ability of many empirical models currently used to study the relationship between landscape, habitat and stream condition. A comparison of different metrics may provide clues about causal pathways and mechanistic processes behind correlative relationships and could be used to target restoration efforts strategically.     

胞间连丝：共质体运输的动态通道

胞间连丝作为一种细胞质结构将相邻的细胞连系起来而形成植物的共质体。胞间连丝通过调控许多离子和分子的共质体运输而广泛地参与植物的生命活动。胞间连丝的主要构成部分是细胞质膜、连丝小管、以及位于二之间的环层细胞质。这三都很容易在电子显微镜下观察到。细胞骨架的成分（肌动蛋白和肌球蛋白）起到稳定胞间连丝的作用。同时,钙结合蛋白可能具有调节间连丝功能的作用。在胞间连丝里,环层细胞质为大多数溶质提供共质体运输的通道,而有些 共质体运输则可能是通过连丝小管的内腔、连丝小管的壳层、甚或是细胞质膜来实现的。共质体可以细分为数个区块,它们各自允许不同大小的分子（从低于1000到高于10000道尔顿）通过。从发生上看,胞间连丝可以是初生的,也可以是次生的。前是伴随着新细胞壁的形成则产生的,而后则是在已有的细胞壁上产生的。胞间连丝的动态性质还表现在它们的频率是处于变化之中,这是由于组织或植物整体的发育和生理状态决定的。虽然共质体运输的基本形式是扩散,但胞间连丝对于某些离子和分子却是选择性的。在病毒感染细胞时,病毒的移动蛋白作用于胞间连丝的受体蛋白,结果,胞间连丝被显地扩张（其机理尚不清楚）。于是,病毒的移动蛋白连同与之结合在一起的病毒基因组进入毗邻的健康细胞。一些植物源性的蛋白质也能够通过胞间连丝来运输;推测其方式类似于病毒的移动蛋白。有些植物蛋白质本身就是信号分子,它们调节分化和其他活动。与此相反,还有一些植物蛋白质的共质体运输并不是通过特异的方式来实现的。     

Potential habitat dependence in deposition rate of presumptive annual lines in shells of the bivalve Protothaca staminea

Although repeating depositional features in shells of bivalve molluscs continue to be used in ecology and paleoecology to age individual specimens and thereby provide a potentially powerful tool for geochronological reconstruction of past events, few studies actually test the basic assumptions of growth line analysis: (1) that line deposition is truly periodic and (2) that the length of the period is one year. Recapture of marked individuals of the bivalve Protothaca staminea after 12 or 24 months in field plots in two habitats of Mugu Lagoon (California, U.S.A.) suggests a habitat-specific pattern of deposition of the major growth lines previously assumed to be annual. External (surface) and internal (cross-sectional) growth lines were in excellent agreement on any given specimen and showed that each specimen from a muddy-sand environment deposited a single annual line over 12 months, whereas all but one specimen from a clean-sand environment deposited several more major growth lines than predicted from the numbers of years of additional growth. Although more frequent handling or natural disturbance in the higher-energy, clean-sand habitat may explain these differences, the results demand caution in extrapolating tests of annual periodicity in growth line deposition across species or even across habitats for a single species.     

Unpredictability in the facultative association between larvae of Euphilotes enoptes (Lepidoptera: Lycaenidae) and ants

Larvae of the lycaenid butterfly, Euphilotes enoptes , are facultatively associated with ants. To determine whether variation in this association is predictable, I documented the proportion of larvae tended by ants and the identity of those ants over a three-year period in two study areas in central Washington state. Each study area contained numerous patches of Eriogonum compositum , the sole host plant of E. enoptes in this region. Using complete censuses and random subsampling, I estimated the dispersion and densities of E. enoptes larvae occupying each patch. The results of these observations indicated significant spatial and temporal variation in the identities of ants tending larvae and the frequency of ant attendance. In addition, early instar larvae were tended less frequently and by smaller ant species, than fourth instar larvae. Although larvae were aggregated at two spatial scales: individual plants within a patch and individual inflorescences on a plant, attendance rates did not vary consistently with aggregation size at either scale. Similarly, attendance rates were independent of the patch-wide density of larvae. I discuss the potential sources of such unpredictable variation and its implications for the evolution of further specialization in this facultative association.     

Growth response of subalpine fir (Abies lasiocarpa) to climate in the Olympic Mountains, Washington, USA

Growth response of subalpine fir (Abies lasiocarpa) to climate was studied across its local geographical and elevation range in the Olympic Mountains, Washington. A dendroecological analysis of subalpine fir across a range of elevations (1350-1850 m) and annual precipitation (125-350 cm y^?1), was used to compare environmental factors affecting growth. Climate-growth relationships were explored using Pearson product-moment correlation coefficients; partial correlation analysis was used to assess relationships among site chronologies and climatic variables. Radial growth is negatively correlated with winter precipitation at high elevation and wet sites, but not at low and middle elevation dry sites. Growth is positively correlated with current growing season temperature at all sites; however, growth is negatively correlated with previous year August temperature, indicating that climate affects growth in subsequent years. Positive correlations between growth and summer precipitation during the growing season at low and middle elevation dry sites suggest that soil moisture is partially limiting to growth on these sites. If the climate of the Pacific Northwest becomes warmer and drier, then subalpine fir growth may increase at high elevation and wet sites, but may decrease at lower elevation dry sites in the Olympic Mountains. However, the growth response of subalpine fir to potentially rapid climate change will not be uniform because subalpine fir grows over a wide range of topographic features, habitats, and local climates at different geographical scales. A comparison of growth response to current growing season temperature suggests that the temperature-related growth response of subalpine fir is not adequately described by the parabolic curve used in JABOWA-based models.     

Rapid evolution of goat and sheep globin genes following gene duplication

Statistical analyses of DNA sequences of globin genes (beta A, beta C, and gamma) from goat and sheep (including new sequence information for the second intron of sheep beta A and gamma, kindly provided by A. Davis and A. W. Nienhuis) indicate that the rates of nonsynonymous substitution in these genes have been greatly accelerated following the gene duplication separating gamma and the ancestor of beta A and beta C and the gene duplication separating beta A and beta C. In both cases the acceleration was apparently due to relaxation of purifying selection (functional constraints) rather than advantageous mutations because acceleration occurred only in less important parts of the beta globin chain. The rates of nonsynonymous substitution in these genes are estimated to be about 2.3 x 10(-9) per site per year, which is three times higher than that for the divergence between human beta and mouse beta major globin genes. Our analyses further suggest that the rate of synonymous substitution in functional genes and the rate of substitution in pseudogenes are approximately equal and are between 2.8 x 10(-9) and 5.0 x 10(-9) and that the rate of substitution in introns is about 3.0 x 10(-9). The divergence time between beta A and beta C and that between gamma and the beta A-beta C pair are about 12 and 30 million years, respectively. The proportion of transition mutations is estimated to be 64%, two times higher than expected under random mutation but considerably lower than the 96% estimated for animal mitochondrial DNA.      

Chemical Composition of the Epidermal, Hypodermal, Endodermal and Intervening Cortical Cell Walls of Various Plant Roots

A survey of chemical modifications in the cells of the epidermis,hypodermis, cortical parenchyma and endodermis in roots of 27plant species was performed. Cortical parenchyma walls weregenerally free of modifying substances whereas the walls ofthe epidermis, hypodermis and endodermis were usually modifiedby the presence of lipids, phenols, suberin or lignin. In mostcases, wall-modifying components could be detected within 5mm of the root apex. lipids, phenols, suberin, lignin, ferulic acid, root, epidermis, hypodermis, cortex, endodermis, cell wall