Mutation of a Single Residue Renders Human Tetherin Resistant to HIV-1 Vpu-Mediated Depletion

The recently identified restriction factor tetherin/BST-2/CD317 is an interferon-inducible trans-membrane protein that restricts HIV-1 particle release in the absence of the HIV-1 countermeasure viral protein U (Vpu). It is known that Tantalus monkey CV1 cells can be rendered non-permissive to HIV-1 release upon stimulation with type 1 interferon, despite the presence of Vpu, suggesting species-specific sensitivity of tetherin proteins to viral countermeasures such as Vpu. Here we demonstrate that Tantalus monkey tetherin restricts HIV-1 by nearly two orders of magnitude, but in contrast to human tetherin the Tantalus protein is insensitive to HIV-1 Vpu. We have investigated tetherin''s sensitivity to Vpu using positive selection analyses, seeking evidence for evolutionary conflict between tetherin and viral countermeasures. We provide evidence that tetherin has undergone positive selection during primate evolution. Mutation of a single amino acid (showing evidence of positive selection) in the trans-membrane cap of human tetherin to that in Tantalus monkey (T45I) substantially impacts on sensitivity to HIV-1 Vpu, but not on antiviral activity. Finally, we provide evidence that cellular steady state levels of tetherin are substantially reduced by Vpu, and that the T45I mutation abrogates this effect. This study provides evidence that tetherin is important in protecting mammals against viral infection, and that the HIV-1 Vpu–mediated countermeasure is specifically adapted to act against human tetherin. It also emphasizes the power of selection analyses to illuminate the molecular details of host–virus interactions. This work suggests that tetherin binding agents might protect it from viral encoded countermeasures and thus make powerful antivirals.     

DataStager: scalable data staging services for petascale applications

Known challenges for petascale machines are that (1) the costs of I/O for high performance applications can be substantial, especially for output tasks like checkpointing, and (2) noise from I/O actions can inject undesirable delays into the runtimes of such codes on individual compute nodes. This paper introduces the flexible ‘DataStager’ framework for data staging and alternative services within that jointly address (1) and (2). Data staging services moving output data from compute nodes to staging or I/O nodes prior to storage are used to reduce I/O overheads on applications’ total processing times, and explicit management of data staging offers reduced perturbation when extracting output data from a petascale machine’s compute partition. Experimental evaluations of DataStager on the Cray XT machine at Oak Ridge National Laboratory establish both the necessity of intelligent data staging and the high performance of our approach, using the GTC fusion modeling code and benchmarks running on 1000+ processors.     

A mark-recapture population estimate for invasive silver carp (<Emphasis Type="Italic">Hypophthalmichthys molitrix</Emphasis>) in the La Grange Reach,Illinois River

Invasive silver carp (Hypophthalmichthys molitrix) populations have expanded greatly in the Upper Mississippi River System (UMRS) since their introduction in the early 1970s. We conducted a Chapman-modified, continuous Schnabel mark-recapture population and biomass estimate for silver carp (106–901 mm) in the La Grange reach, Illinois River during 2007–2008. We estimated a total of 328,192 (95% CI 231,226–484,474) silver carp (2,544 per river km 1,792–3,756) comprising 705 (95% CI; 496–1,040) metric tons of biomass (5.5 metric tons per river km 3.8–8.1). Long Term Resource Monitoring Program (LTRMP) data from the La Grange reach showed an exponential increase in silver carp catches since 1998, with an intrinsic rate of increase approaching 84%. In 2008, silver carp comprised about 51% of the total LTRMP annual fish collection. To our knowledge, this large river reach may contain the greatest ambient densities of wild silver carp in the world. Our findings provide a target for reduction efforts and also emphasize the importance of the La Grange reach as a source population for potential expansion of the species to the Laurentian Great Lakes.     

Expanding horizons for herbaceous ecosystem restoration: the Grassy Groundcover Restoration Project

Summary The Grassy Groundcover Restoration Project (GGRP) has sown thirteen 1 ha plots of species‐rich grassland or herbaceous understorey in previously weedy agricultural paddocks in a range of rural locations across southern and western Victoria, Australia. The sown plots are intended as both experimental trials and ‘core’ areas for the restoration of herbaceous communities native to these regions. Approximately 200 species were grown in Seed Production Areas (SPAs) and successfully sown in the field. Species were most successfully established on areas that were scalped prior to seeding, and least successful on plots that were pre‐treated with 1, 2 or 3 years of traditional herbicide weed control. Weed presence was lowest in scalped plots and highest in non‐scalped plots. Long‐term monitoring will be required to understand the development trajectories and degree of persistence of the sown communities, but in the shorter term (3–6 years of post‐seeding) an average of 80% of sown species have established and remain as adult populations. Surveys indicate that in scalped plots (n = 130) vegetation composition, structure and quality has been maintained. Conversely, composition, structure and quality have declined markedly in non‐scalped plots (n = 130). Formal surveys and field observations have also revealed that all sites provide a range of habitats which have been colonized by fauna from a variety of trophic levels. The implications of building on these trials to realize complex grassy ecosystem restoration at larger scales are discussed including the securing of sufficient quantities of high‐quality seed, the use of mechanized broad‐scale direct‐seeding techniques and the effectiveness of using complex mixtures of species early in the restoration cycle.     

Comparison of watershed disturbance predictive models for stream benthic macroinvertebrates for three distinct ecoregions in western US

The successful use of macroinvertebrates as indicators of stream condition in bioassessments has led to heightened interest throughout the scientific community in the prediction of stream condition. For example, predictive models are increasingly being developed that use measures of watershed disturbance, including urban and agricultural land-use, as explanatory variables to predict various metrics of biological condition such as richness, tolerance, percent predators, index of biotic integrity, functional species traits, or even ordination axes scores. Our primary intent was to determine if effective models could be developed using watershed characteristics of disturbance to predict macroinvertebrate metrics among disparate and widely separated ecoregions. We aggregated macroinvertebrate data from universities and state and federal agencies in order to assemble stream data sets of high enough density appropriate for modeling in three distinct ecoregions in Oregon and California. Extensive review and quality assurance of macroinvertebrate sampling protocols, laboratory subsample counts and taxonomic resolution was completed to assure data comparability. We used widely available digital coverages of land-use and land-cover data summarized at the watershed and riparian scale as explanatory variables to predict macroinvertebrate metrics commonly used by state resource managers to assess stream condition. The “best” multiple linear regression models from each region required only two or three explanatory variables to model macroinvertebrate metrics and explained 41–74% of the variation. In each region the best model contained some measure of urban and/or agricultural land-use, yet often the model was improved by including a natural explanatory variable such as mean annual precipitation or mean watershed slope. Two macroinvertebrate metrics were common among all three regions, the metric that summarizes the richness of tolerant macroinvertebrates (RICHTOL) and some form of EPT (Ephemeroptera, Plecoptera, and Trichoptera) richness. Best models were developed for the same two invertebrate metrics even though the geographic regions reflect distinct differences in precipitation, geology, elevation, slope, population density, and land-use. With further development, models like these can be used to elicit better causal linkages to stream biological attributes or condition and can be used by researchers or managers to predict biological indicators of stream condition at unsampled sites.     

Triaminotriazine DNA helicase inhibitors with antibacterial activity

Screening of a chemical library in a DNA helicase assay involving the Pseudomonas aeruginosa DnaB helicase provided a triaminotriazine inhibitor with good antibacterial activity but associated cytotoxicity toward mammalian cells. Synthesis of analogs provided a few inhibitors that retained antibacterial activity and demonstrated a significant reduction in cytotoxicity. The impact of serum and initial investigations toward a mode of action highlight several features of this class of compounds as antibacterials.     

Comparative phylogeography of woodland reptiles in California: repeated patterns of cladogenesis and population expansion

The ultimate goal of comparative phylogeographical analyses is to infer processes of diversification from contemporary geographical patterns of genetic diversity. When such studies are employed across diverse groups in an array of communities, it may be difficult to discover common evolutionary and ecological processes associated with diversification. In order to identify taxa that have responded in a similar fashion to historical events, we conducted comparative phylogeographical analyses on a phylogenetically and ecologically limited set of taxa. Here, we focus on a group of squamate reptiles (snakes and lizards) that share similar ecological requirements and generally occupy the same communities in the western USA. At a gross level, deep genetic division in Contia tenuis, Diadophis punctatus, Elgaria multicarinata, the Charina bottae complex, and Lampropeltis zonata are often concordant in the Transverse Ranges, the Monterey Bay and Sacramento-San Joaquin Delta region, and the southern Sierra Nevada in California. Molecular clock estimates suggest that major phyletic breaks within many of these taxa roughly coincide temporally, and may correspond to important geological events. Furthermore, significant congruence between the phylogeographies of E. multicarinata and L. zonata suggests that the succession of vicariance and dispersal events in these species progressed in concert. Such congruence suggests that E. multicarinata and L. zonata have occupied the same communities through time. However, across our entire multi-taxon data set, the sequence of branching events rarely match between sympatric taxa, indicating the importance of subtle differences in life history features as well as random processes in creating unique genetic patterns. Lastly, coalescent and noncoalescent estimates of population expansion suggest that populations in the more southerly distributed clades of C. tenuis, D. punctatus, E. multicarinata, and L. zonata have been stable, while populations in more northerly clades appear to have recently expanded. This concerted demographic response is consistent with palaeontological data and previous phylogeographical work that suggests that woodland habitat has become more restricted in southern California, but more widespread in the North during Holocene warming. Future phylogeographical work focusing on allied and ecologically associated taxa may add insight into the ecological and evolutionary processes that yield current patterns of genetic diversity.     

Structural stabilization of CNS synapses during postnatal development in rat cortex

CNS synapses are produced rapidly upon pre- and post-synaptic recruitment. However, their composition is known to change during development and we reasoned that this may be reflected in the gross biochemical properties of synapses. We found synaptic structure in adult cortical synaptosomes to be resistant to digestion with trypsin in the presence and absence of calcium ions, contrasting with previous observations. We evaluated the divalent cation dependence and trypsin sensitivities of synapses using synaptosomes from different developmental stages. In contrast to adult synapses, at postnatal day (P) 10 EDTA treatment eliminated approximately 60% of the synapses, and trypsin and EDTA, together, eliminated all junctions. Trypsinization in the presence of calcium eliminated approximately 60% of the junctions at P10. By P35, all synapses were calcium independent, whereas full trypsin resistance was not attained until P49. To compare the calcium dependence and trypsin sensitivity of synapses in another region of the adult brain, we examined synapses from adult (P50) hippocampus. Adult hippocampus maintained a population of synapses that resembled that of P35 cortex. Our results show that synapses are modified over a long time period in the developing cortex. We propose a model in which the addition of synergistic calcium-dependent and -independent adhesive systems stabilize synapses.