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This chapter examines how phylogenetic diversity changes across spatial and temporal gradients. Spatial ecophylogenetic patterns can reveal how different processes shape ecological communities. Metacommunity ecology reinvigorated the search for general mechanisms that create diversity and structural differences among communities, and by using phylogenetic patterns we can understand how shared traits and evolution inform community differences. The chapter first considers phylobetadiversity as a measure of phylogenetic turnover before discussing two types of phylobetadiversity metrics, diversity partitioning and pairwise distances. It also analyzes the influence of spatial scale on phylogenetic patterns, focusing on the scale dependency of phylogenetic patterns, and concludes with an overview of phylogenetic diversity–area relationships.

This chapter examines the logic of null modeling for phylogenetic tests. Developing null expectations for community phylogenetic patterns from randomization procedures is the cornerstone for many ecophylogenetic analysis. The chapter advocates an approach that explicitly considers multiple randomizations to better understand what aspects of community and phylogenetic structure determine observed patterns. It first provides a brief historical overview of randomization tests in ecology, focusing on two important academic conflicts that highlight the need for using randomizations in ecological analysis: the first relates to species–genus ratios and competition between close relatives, and the second deals with co-occurrence patterns and competitive coexistence. It then explains how community data and phylogenetic data can be randomized, taking into account randomizations to test trait data, altering the phylogenetic tree, and other randomizations and inference issues. It also discusses some important considerations for constructing the species pool to be used in the randomization tests.

This chapter reviews the history of the use of phylogenetics in ecology, beginning with a discussion of early attempts to classify the diversity of life and the development of evolutionary theory. In particular, it examines how early taxonomists, starting with Carl Linnaeus, have grouped species by similarity in their traits and how early ecologists and biologists such as Charles Darwin recognized the importance of relatedness in influencing ecological interactions and species distributions. The chapter proceeds by focusing on the introduction of the neutral theory of biodiversity into mainstream ecology and the development of the niche-based model of community assembly. It also considers how some ecologists questioned the relevance of phylogenetic corrections for ecology and concludes by analyzing the emergence of ecological phylogenetics or ecophylogenetics.

This book has explored the major methods and concepts in the field of ecophylogenetics. It has considered many of the common statistics and metrics used by ecologists when testing ecophylogenetic hypotheses at both small and large scales. The power of this approach is predicated on the assumption that phylogeny provides information on the evolutionary history of traits that cannot be inferred simply from community data. This concluding chapter reviews some of the advances that have been made in terms of predicting ecology from evolutionary patterns, combining trait and phylogenetic information, and developing a more predictive science of climate change and the biology of species invasions. It also discusses several possible trajectories for ecophylogenetic analyses in the future that will be important in moving the field forward. Finally, it looks at the benefits of a synthesis between ecology and evolution.

This is the first book to critically review the application of phylogenetic methods in ecology, and it serves as a primer to working ecologists and students of ecology wishing to understand these methods. The book demonstrates how phylogenetic information is transforming ecology by offering fresh ways to estimate the similarities and differences among species, and by providing deeper, evolutionary-based insights on species distributions, coexistence, and niche partitioning. It examines this emerging area's explosive growth, allowing for this new body of hypotheses testing. It systematically looks at all the main areas of current ecophylogenetic methodology, testing, and inference. Each chapter covers a unique topic, emphasizes key assumptions, and introduces the appropriate statistical methods and null models required for testing phylogenetically informed hypotheses. The applications presented throughout are supported and connected by examples relying on real-world data that have been analyzed using the open-source programming language, R. Showing how phylogenetic methods are shedding light on fundamental ecological questions related to species coexistence, conservation, and global change, the book will interest anyone who thinks that evolution might be important in their data.

This chapter examines the use of phylogenetic methods to explain macroevolutionary trends in speciation, extinction, and the distribution of phylogenetic diversity across space and through time. The diversity of life is unevenly distributed across the globe. Species richness tends to be higher at lower latitudes and elevations, and the distribution of life forms also varies across space. For example, Foster's rule suggests that on islands small species evolve to become bigger, while large species evolve to become smaller. Equally, the distribution of evolutionary history shows large spatial variation, reflecting the histories of speciation, extinction, and dispersal. This chapter first considers how large, global phylogenies make it possible to map the distribution of phylogenetic diversity and develop a conservation strategy to maximize coverage of the tree of life. It then discusses the variation in diversification across spatiotemporal gradients and shows that phylogenetic diversity covaries significantly with taxonomic richness.

This chapter discusses the use of phylogenetic distances to infer mechanisms of ecological assembly. Mechanisms influencing patterns of community assembly act on the ecological similarities and differences of organisms, and not on the number of species. Phylogenetic patterns of relatedness have provided an especially useful and popular approach to quantifying expected species ecological differences for examining community assembly. Over the past decade, phylogenetic information has been widely used in community assembly studies to test a basic set of hypotheses about the relatedness of co-occurring species. This chapter considers two kinds of metrics employing phylogenetic information: those that examine patterns of relatedness by measuring phylogenetic distances among species, and those that provide an index of phylodiversity within an assemblage by accounting for the distribution of or evenness in edge lengths.

In the presence of cycloheximide (CHX) to inhibit protein synthesis, a high concentration of staurosporine (STS) induces almost all cells in explant cultures of 8/8 types of newborn mouse organs and 3/3 types of adult mouse organs to die with the characteristic features of apoptosis. Eggs and blastomeres also die in this way when treated with STS and CHX, although they are less sensitive to this treatment than trophectoderm or inner cell mass cells whose sensitivity resembles that of other developing cells. Human red blood cells are exceptional in being completely resistant to treatment with STS and CHX. As (STS plus CHX)-induced cell deaths have been shown to display the characteristic features of programmed cell death (PCD), we conclude that all mammalian nucleated cells are capable of undergoing PCD and constitutively express all the proteins required to do so. It seems that the machinery for PCD is in place and ready to run, even though its activation often depends on new RNA and protein synthesis.

Prominent among the various types of cell that differentiate from the trophectoderm of the mouse blastocyst are trophoblastic giant cells. Repeated endoreduplication of the genome accompanies the growth of these cells, which have been shown to be polytene rather than polyploid. Early stages in giant transformation have been examined, mainly in the mural trophectoderm of the implanting blastocyst which gives rise to the primary trophoblastic giant cells. One confusing issue is whether these early stages include the onset of endoreduplication of the genome. This issue has been addressed in the present study by comparing the DNA content of nuclei in isolated trophectoderm and ICM tissue rather than, as previously, by relating measurements on air-dry preparations of entire blastocysts to those of adult liver. The results, particularly those from delayed and reactivated blastocysts, show that genome endoreduplication is not an obligatory early event in the transformation of mural trophectoderm cells.

The skeletal muscle proteins, dysferlin (DYSF) and myoferlin (MYOF) have been demonstrated by mass spectrometry to be present in the apical syncytiotrophoblast of the human placenta, where they may play a role in membrane repair. Immunohistochemistry and immunoblotting were performed on placental samples to localize and quantify DYSF and MYOF in first trimester, term and pathological pregnancies. Here, we show that placental DYSF and MYOF are reduced in labour but only MYOF is elevated in cases of intrauterine growth restriction (IUGR) and pre-eclampsia, relative to Caesarean section controls. In term villous explants cultured for 24 h, DYSF levels decreased, compared to T(0) controls, while MYOF levels remained static. Additionally, trophoblastic BeWo cells show reduced levels of DYSF but unchanged levels of MYOF under conditions of oxidative stress, while DYSF levels in microparticles isolated from the supernatant increase. These findings suggest that DYSF but not MYOF plays a pivotal role in membrane repair mechanisms in the human placenta and that dysferlin microparticles could potentially represent a novel biomarker for pre-eclampsia. Ethical approval: Samples were collected with informed written consent of the patients and Local Research Committee approval. Conflict of interest: none declared.

The joint use of phylogenetic trees and ecological data has proven useful for many aspects of ecology. However, there are a multitude of phylo-diversity metrics with complex interdependencies and mathematical redundancies (the so-called ‘jungle’ of metrics). Several recentpapers have been trying to ‘map’ this jungle but appear at a first glance to contradict each other. We suggest that these contradictory results are in fact complementary and reflect two approaches to understand diversity metrics: the first focuses on general mathematical properties,the second focuses on assessing metric performance in relation to particular questions.In this manuscript, we discuss the complementarity of the two approaches and in particular how recent papers fit into this categorisation.

Phylogenetic Generalized Least Square (PGLS) is the tool of choice among phylogenetic comparative methods to measure the correlation between species features such as morphological and life-history traits or niche characteristics. In its usual form, it assumes that the residual variation follows a homogenous model of evolution across the branches of the phylogenetic tree. Since a homogenous model of evolution is unlikely to be realistic in nature, we explored the robustness of the phylogenetic regression when this assumption is violated. We did so by simulating a set of traits under various heterogeneous models of evolution, and evaluating the statistical performance (type I error [the percentage of tests based on samples that incorrectly rejected a true null hypothesis] and power [the percentage of tests that correctly rejected a false null hypothesis]) of classical phylogenetic regression. We found that PGLS has good power but unacceptable type I error rates. This finding is important since this method has been increasingly used in comparative analyses over the last decade. To address this issue, we propose a simple solution based on transforming the underlying variance-covariance matrix to adjust for model heterogeneity within PGLS. We suggest that heterogeneous rates of evolution might be particularly prevalent in large phylogenetic trees, while most current approaches assume a homogenous rate of evolution. Our analysis demonstrates that overlooking rate heterogeneity can result in inflated type I errors, thus misleading comparative analyses. We show that it is possible to correct for this bias even when the underlying model of evolution is not known a priori.

Muscle activity detected by surface electromyography sensors can be affected by several factors, one of which is the location of sensor placement. The objective of this study is to determine how the location of the sensors affect the amplitudes and timing of muscle activity measured by the sensors during regular walking. A surface electromyography sensor placed on the vastus lateralis according to SENIAM guidelines was considered the “gold standard”. It appeared that sensors placed along the same muscle fibers showed less variability in muscle signal amplitude and timing compared to sensors located medially and laterally.

Identifying drivers of infectious disease patterns and impacts at the broadest scales of organisation is one of the most crucial challenges for modern science, yet answers to many fundamental questions remain elusive. These include what factors commonly facilitate transmission of pathogens to novel host species, what drives variation in immune investment among host species, and more generally what drives global patterns of parasite diversity and distribution? Here we consider how the perspectives and tools of macroecology, a field that investigates patterns and processes at broad spatial, temporal and taxonomic scales, are expanding scientific understanding of global infectious disease ecology. In particular, emerging approaches are providing new insights about scaling properties across all living taxa, and new strategies for mapping pathogen biodiversity and infection risk. Ultimately, macroecology is establishing a framework to more accurately predict global patterns of infectious disease distribution and emergence.

Introduction Atherosclerosis is the underlying cause of cardiovascular disease that leads to more global mortalities each year than any other ailment. Consumption of active food ingredients such as phytosterols, omega-3 polyunsaturated fatty acids and flavanols are known to impart beneficial effects on cardiovascular disease although the combined actions of such agents in atherosclerosis is poorly understood. The aim of this study was to screen a nutritional supplement containing each of these active components for its anti-atherosclerotic effect on macrophages in vitro. Results The supplement attenuated the expression of intercellular adhesion molecule-1 and macrophage chemoattractant protein-1 in human and murine macrophages at physiologically relevant doses. The migratory capacity of human monocytes was also hindered, possibly mediated by eicosapentaenoic acid and catechin, while the ability of foam cells to efflux cholesterol was improved. The polarisation of murine macrophages towards a pro-inflammatory phenotype was also attenuated by the supplement. Conclusion The formulation was able to hinder multiple key steps of atherosclerosis development in vitro by inhibiting monocyte recruitment, foam cell formation and macrophage polarisation towards an inflammatory phenotype. This is the first time a combination these ingredients has been shown to elicit such effects and supports its further study in preclinical in vivo models.

A high-density sample mount has been developed for efficient goniometer-based sample delivery at synchrotron and XFEL sources., Higher throughput methods to mount and collect data from multiple small and radiation-sensitive crystals are important to support challenging structural investigations using microfocus synchrotron beamlines. Furthermore, efficient sample-delivery methods are essential to carry out productive femtosecond crystallography experiments at X-ray free-electron laser (XFEL) sources such as the Linac Coherent Light Source (LCLS). To address these needs, a high-density sample grid useful as a scaffold for both crystal growth and diffraction data collection has been developed and utilized for efficient goniometer-based sample delivery at synchrotron and XFEL sources. A single grid contains 75 mounting ports and fits inside an SSRL cassette or uni-puck storage container. The use of grids with an SSRL cassette expands the cassette capacity up to 7200 samples. Grids may also be covered with a polymer film or sleeve for efficient room-temperature data collection from multiple samples. New automated routines have been incorporated into the Blu-Ice/DCSS experimental control system to support grids, including semi-automated grid alignment, fully automated positioning of grid ports, rastering and automated data collection. Specialized tools have been developed to support crystallization experiments on grids, including a universal adaptor, which allows grids to be filled by commercial liquid-handling robots, as well as incubation chambers, which support vapor-diffusion and lipidic cubic phase crystallization experiments. Experiments in which crystals were loaded into grids or grown on grids using liquid-handling robots and incubation chambers are described. Crystals were screened at LCLS-XPP and SSRL BL12-2 at room temperature and cryogenic temperatures.

Disparate ecological datasets are often organized into databases post hoc and then analyzed and interpreted in ways that may diverge from the purposes of the original data collections. Few studies, however, have attempted to quantify how biases inherent in these data (for example, species richness, replication, climate) affect their suitability for addressing broad scientific questions, especially in under-represented systems (for example, deserts, tropical forests) and wild communities. Here, we quantitatively compare the sensitivity of species first flowering and leafing dates to spring warmth in two phenological databases from the Northern Hemisphere. One—PEP725—has high replication within and across sites, but has low species diversity and spans a limited climate gradient. The other—NECTAR—includes many more species and a wider range of climates, but has fewer sites and low replication of species across sites. PEP725, despite low species diversity and relatively low seasonality, accurately captures the magnitude and seasonality of warming responses at climatically similar NECTAR sites, with most species showing earlier phenological events in response to warming. In NECTAR, the prevalence of temperature responders significantly declines with increasing mean annual temperature, a pattern that cannot be detected across the limited climate gradient spanned by the PEP725 flowering and leafing data. Our results showcase broad areas of agreement between the two databases, despite significant differences in species richness and geographic coverage, while also noting areas where including data across broader climate gradients may provide added value. Such comparisons help to identify gaps in our observations and knowledge base that can be addressed by ongoing monitoring and research efforts. Resolving these issues will be critical for improving predictions in understudied and under-sampled systems outside of the temperature seasonal mid-latitudes.

Calanus finmarchicus stage-C5 and C. hyperboreus stage-C4 diapausing in Scotian Shelfbasins are high-quality food sources because they are abundant and high inenergy content. When combined, these two variables are informative for quantify-ing energy density, carrying capacity and energy transfer in marine ecosystems.However, measuring energy content directly can be difficult and expensive. Here,we present energy (caloric) content estimates for two co-located diapausingcopepod species; C. finmarchicus C5 and C. hyperboreus C4 collected during late-summer when their energy content is at or near the annual maximum. We thendevelop several practical energy content calibrations, each designed to estimateenergy content using simple measures of Calanus spp. body size or weight. Weight-specific energy content (energy quality, kJ g

Aim At broad geographical scales, species richness is a product of three basic processes: speciation, extinction and migration. However, determining which of these processes predominates is a major challenge. Whilst palaeontological studies can provide information on speciation and extinction rates, data are frequently lacking. Here we use a recent dated phylogenetic tree of mammals to explore the relative importance of these three processes in structuring present-day richness gradients. Location The global terrestrial biosphere. Methods We combine macroecological data with phylogenetic methods more typically used in community ecology to describe the phylogenetic history of regional faunas. Using simulations, we explore two simple phylogenetic metrics, the mean and variance in the pairwise distances between taxa, and describe their relationship to phylogenetic tree topology. We then use these two metrics to characterize the evolutionary relationships among mammal species assemblages across the terrestrial biome. Results We show that the mean and variance in the pairwise distances describe phylogenetic tree topology well, but are less sensitive to phylogenetic uncertainty than more direct measures of tree shape. We find the phylogeny for South American mammals is imbalanced and ‘stemmy’ (long branches towards the root), consistent with recent diversification within evolutionarily disparate lineages. In contrast, the phylogeny for African mammals is balanced and ‘tippy’ (long branches towards the tips), more consistent with the slow accumulation of diversity over long times, reflecting the Old World origin of many mammal clades. Main conclusions We show that phylogeny can accurately capture biogeographical processes operating at broad spatial scales and over long time periods. Our results support inferences from the fossil record – that the New World tropics are a diversity cradle whereas the Old World tropics are a museum of old diversity.

SummaryPlasminogen is the proenzyme precursor of the primary fibrinolytic protease plasmin. Circulating plasminogen, which comprises a Pan-apple (PAp) domain, five kringle domains (KR1-5), and a serine protease (SP) domain, adopts a closed, activation-resistant conformation. The kringle domains mediate interactions with fibrin clots and cell-surface receptors. These interactions trigger plasminogen to adopt an open form that can be cleaved and converted to plasmin by tissue-type and urokinase-type plasminogen activators. Here, the structure of closed plasminogen reveals that the PAp and SP domains, together with chloride ions, maintain the closed conformation through interactions with the kringle array. Differences in glycosylation alter the position of KR3, although in all structures the loop cleaved by plasminogen activators is inaccessible. The ligand-binding site of KR1 is exposed and likely governs proenzyme recruitment to targets. Furthermore, analysis of our structure suggests that KR5 peeling away from the PAp domain may initiate plasminogen conformational change.

The tendency for more closely related species to share similar traits and ecological strategies can be explained by their longer shared evolutionary histories and represents phylogenetic conservatism. How strongly species traits co-vary with phylogeny can significantly impact how we analyze cross-species data and can influence our interpretation of assembly rules in the rapidly expanding field of community phylogenetics. Phylogenetic conservatism is typically quantified by analyzing the distribution of species values on the phylogenetic tree that connects them. Many phylogenetic approaches, however, assume a completely sampled phylogeny: while we have good estimates of deeper phylogenetic relationships for many species-rich groups, such as birds and flowering plants, we often lack information on more recent interspecific relationships (i.e., within a genus). A common solution has been to represent these relationships as polytomies on trees using taxonomy as a guide. Here we show that such trees can dramatically inflate estimates of phylogenetic conservatism quantified using S. P. Blomberg et al.'s K statistic. Using simulations, we show that even randomly generated traits can appear to be phylogenetically conserved on poorly resolved trees. We provide a simple rarefaction-based solution that can reliably retrieve unbiased estimates of K, and we illustrate our method using data on first flowering times from Thoreau's woods (Concord, Massachusetts, USA).

The repeated independent evolution of similar features in divergent lineages, a process known as convergent evolution, has long been a source of fascination for both naturalists and evolutionary biologists. Until recently, this active area of research had been focused principally on the evolution of physical characteristics associated with novel traits (e.g. the independent evolution of wings in birds, bats and pterosaurs). This article is protected by copyright. All rights reserved

Part of the latest SAMPL challenge was to predict how a small fragment library of 500 commercially available compounds would bind to a protein target. In order to assess the modellers’ work, a reasonably comprehensive set of data was collected using a number of techniques. These included surface plasmon resonance, isothermal titration calorimetry, protein crystallization and protein crystallography. Using these techniques we could determine the kinetics of fragment binding, the energy of binding, how this affects the ability of the target to crystallize, and when the fragment did bind, the pose or orientation of binding. Both the final data set and all of the raw images have been made available to the community for scrutiny and further work. This overview sets out to give the parameters of the experiments done and what might be done differently for future studies.

The Gouldian Finch (Erythrura gouldiae) has experienced significant decline in population and the extent of its range over the past 40 years, which has generally been attributed to the availability of suitable foraging habitat. Less research, however, has investigated the suitability or availability of breeding habitat of the species. Gouldian Finches are obligate cavity nesters, and a recent study has shown that they select nest-sites non-randomly based on structural characteristics of the cavity. Here we investigated the relative effects of different environmental factors on the spatial distribution of Gouldian Finch nests at two different scales. At the broader, landscape scale (over ~60 km2), the strongest predictor of nesting density at a site was the abundance of suitable nest-sites. At the finer scale (~1 km2), no single factor explained the variation in location of nest-sites. Gouldian Finches require areas of habitat characterised by high densities of suitable nest-sites (tree-cavities). Within these patches, individuals are potentially selecting nest-sites based on the morphometry of cavities rather than landscape features such as topography, vegetation or proximity to water. Our findings should be integrated with studies of feeding and habitat requirements in the non-breeding season, with the aim of constructing holistic and predictive habitat-suitability models for this endangered species.

Pathogens must steal iron from their hosts to establish infection. In mammals, hemoglobin (Hb) represents the largest reservoir of iron, and pathogens express Hb-binding proteins to access this source. Here, we show how one of the commonest and most significant human pathogens, Staphylococcus aureus, captures Hb as the first step of an iron-scavenging pathway. The x-ray crystal structure of Hb bound to a domain from the Isd (iron-regulated surface determinant) protein, IsdH, is the first structure of a Hb capture complex to be determined. Surface mutations in Hb that reduce binding to the Hb-receptor limit the capacity of S. aureus to utilize Hb as an iron source, suggesting that Hb sequence is a factor in host susceptibility to infection. The demonstration that pathogens make highly specific recognition complexes with Hb raises the possibility of developing inhibitors of Hb binding as antibacterial agents. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

Forecasting how species and ecosystems will respond to climate change has been a major aim of ecology in recent years. Much of this research has focused on phenology – the timing of life-history events. Phenology has well-demonstrated links to climate, from genetic to landscape scales; yet our ability to explain and predict variation in phenology across species, habitats and time remains poor. Here, we outline how merging approaches from ecology, climate science and evolutionary biology can advance research on phenological responses to climate variability. Using insight into seasonal and interannual climate variability combined with niche theory and community phylogenetics, we develop a predictive approach for species’ reponses to changing climate. Our approach predicts that species occupying higher latitudes or the early growing season should be most sensitive to climate and have the most phylogenetically conserved phenologies. We further predict that temperate species will respond to climate change by shifting in time, while tropical species will respond by shifting space, or by evolving. Although we focus here on plant phenology, our approach is broadly applicable to ecological research of plant responses to climate variability.

A prototype device was developed to allow individuals to hear ultrasound reflections off environmental obstacles. Previous studies have shown that this device allows for better distance judgement than audition and allows for effective passage through the centreline of apertures. The purpose of this research was to evaluate audification as a method to localise direct sound sources as compared to audition.In an anechoic environment, participants localised point-sound sources for three conditions: auditory, audified ultrasound with receivers facing laterally, and audified ultrasound with receivers facing forward.Azimuth localisation was similar within a range of -35° to 35° in front of the participant among all conditions. At the periphery, -70° and 70°, audified ultrasound was more accurate than audition for novice participants. No difference was evident in user elevation accuracy for these signals among the different conditions.Audification of ultrasound can be effective for localising point-source sounds in the azimuth direction, but more evidence is required to evaluate accuracy in the vertical direction. [Box: see text].

Within most terrestrial groups of animals, including mammals, species richness varies along two axes of environmental variation, representing energy availability and plant productivity. This relationship has led to a search for mechanistic links between climate and diversity. Explanations have traditionally focused on single mechanisms, such as variation in environmental carrying capacity or evolutionary rates. Consensus, though, has proved difficult to achieve and there is growing appreciation that geographical patterns of species richness are a product of many interacting factors including biogeographic history and biological traits. Here, we review some current hypotheses on the causes of gradients in mammal richness and range sizes since the two quantities are intimately linked. We then present novel analyses using recent datasets to explore the structure of the environment–richness relationship for mammals. Specifically, we consider the impact of glaciation on present day mammalian diversity gradients. We conclude that not only are multiple processes important in structuring diversity gradients, but also that different processes predominate in different places.

Numerous evolutionary studies have sought to explain the distribution of diversity across the limbs of the tree of life. At the same time, ecological studies have sought to explain differences in diversity and relative abundance within and among ecological communities. Traditionally, these patterns have been considered separately, but models that consider processes operating at the level of individuals, such as neutral biodiversity theory (NBT), can provide a link between them. Here, we compare evolutionary dynamics across a suite of NBT models. We show that NBT can yield phylogenetic tree topologies with imbalance closely resembling empirical observations. In general, metacommunities that exhibit greater disparity in abundance are characterized by more imbalanced phylogenetic trees. However, NBT fails to capture the tempo of diversification as represented by the distribution of branching events through time. We suggest that population-level processes might therefore help explain the asymmetry of phylogenetic trees, but that tree shape might mislead estimates of evolutionary rates unless the diversification process is modeled explicitly.

Natural killer cells and cytotoxic T lymphocytes accomplish the critically important function of killing virus-infected and neoplastic cells. They do this by releasing the pore-forming protein perforin and granzyme proteases from cytoplasmic granules into the cleft formed between the abutting killer and target cell membranes. Perforin, a 67-kilodalton multidomain protein, oligomerizes to form pores that deliver the pro-apoptopic granzymes into the cytosol of the target cell. The importance of perforin is highlighted by the fatal consequences of congenital perforin deficiency, with more than 50 different perforin mutations linked to familial haemophagocytic lymphohistiocytosis (type 2 FHL). Here we elucidate the mechanism of perforin pore formation by determining the X-ray crystal structure of monomeric murine perforin, together with a cryo-electron microscopy reconstruction of the entire perforin pore. Perforin is a thin 'key-shaped' molecule, comprising an amino-terminal membrane attack complex perforin-like (MACPF)/cholesterol dependent cytolysin (CDC) domain followed by an epidermal growth factor (EGF) domain that, together with the extreme carboxy-terminal sequence, forms a central shelf-like structure. A C-terminal C2 domain mediates initial, Ca(2+)-dependent membrane binding. Most unexpectedly, however, electron microscopy reveals that the orientation of the perforin MACPF domain in the pore is inside-out relative to the subunit arrangement in CDCs. These data reveal remarkable flexibility in the mechanism of action of the conserved MACPF/CDC fold and provide new insights into how related immune defence molecules such as complement proteins assemble into pores.

Cell surface pili are polymeric protein assemblies that enable bacteria to adhere to surfaces and to specific host tissues. The pili expressed by Gram-positive bacteria constitute a unique paradigm in which sortase-mediated covalent linkages join successive pilin subunits like beads on a string. These pili are formed from two or three distinct types of pilin subunit, typically encoded in small gene clusters, often with their cognate sortases. In Group A streptococci (GAS), a major pilin forms the polymeric backbone, whereas two minor pilins are located at the tip and the base. Here, we report the 1.9-Å resolution crystal structure of the GAS basal pilin FctB, revealing an immunoglobulin (Ig)-like N-terminal domain with an extended proline-rich tail. Unexpected structural homology between the FctB Ig-like domain and the N-terminal domain of the GAS shaft pilin helps explain the use of the same sortase for polymerization of the shaft and its attachment to FctB. It also enabled the identification, from mass spectral data, of the lysine residue involved in the covalent linkage of FctB to the shaft. The proline-rich tail forms a polyproline-II helix that appears to be a common feature of the basal (cell wall-anchoring) pilins. Together, our results indicate distinct structural elements in the pilin proteins that play a role in selecting for the appropriate sortases and thereby help orchestrate the ordered assembly of the pilus.

Aim In an era of global habitat loss and species extinction, conservation biology is increasingly becoming a science of triage. A key approach has been the designation of global biodiversity hotspots – areas of high species richness and endemism – prioritizing regions that are disproportionately valuable. However, traditional hotspot approaches leave absent information on species evolutionary histories. We argue that prioritizing the preservation of evolutionary diversity is one way to maximize genotypic and functional diversity, providing ecosystems with the greatest number of options for dealing with an uncertain future. Location Global. Methods We review methods for encapsulating phylogenetic diversity and distinctiveness and provide an illustration of how phylogenetic metrics can be extended to include data on geographical rarity and inform conservation prioritization at biogeographic scales. Results Abundance-weighted metrics of evolutionary diversity can be used to simultaneously prioritize populations, species, habitats and biogeographical regions. Main conclusion Policy makers need to know where scarce conservation funds should be focused to maximize gains and minimize the loss of biological diversity. By incorporating these evolutionary diversity metrics into prioritization schemes, managers can better quantify the valuation of different regions based on evolutionary information.

Many of the most virulent emerging infectious diseases in humans, e.g., AIDS and Ebola, are zoonotic, having shifted from wildlife populations. Critical questions for predicting disease emergence are: (1) what determines when and where a disease will first cross from one species to another, and (2) which factors facilitate emergence after a successful host shift. In wild primates, infectious diseases most often are shared between species that are closely related and inhabit the same geographic region. Therefore, humans may be most vulnerable to diseases from the great apes, which include chimpanzees and gorillas, because these species represent our closest relatives. Geographic overlap may provide the opportunity for cross-species transmission, but successful infection and establishment will be determined by the biology of both the host and pathogen. We extrapolate the evolutionary relationship between pathogen sharing and divergence time between primate species to generate “hotspot” maps, highlighting regions where the risk of disease transfer between wild primates and from wild primates to humans is greatest. We find that central Africa and Amazonia are hotspots for cross-species transmission events between wild primates, due to a high diversity of closely related primate species. Hotspots of host shifts to humans will be most likely in the forests of central and west Africa, where humans come into frequent contact with their wild primate relatives. These areas also are likely to sustain a novel epidemic due to their rapidly growing human populations, close proximity to apes, and population centers with high density and contact rates among individuals.

Edwardsite, Cu3Cd2(SO4)2(OH)6·4H2O, is a new mineral from the Block 14 Opencut, Broken Hill, New South Wales, Australia. It occurs as druses of tabular and bladed crystals up to 0.06 mm in size, associated with niedermayrite and christelite. Edwardsite is pale blue, transparent with vitreous lustre and has excellent cleavage parallel to {100}. Density was not measured but the calculated density, from the empirical formula, is 3.53 g cm–3and the Mohs hardness is ∼3. Optically, it is biaxial negative with α ∼ 1.74, β = 1.762(4), γ ∼ 1.77 and 2Vcalc.∼ +62°. The optical orientation is X =b, Y ∼a, Z ∼c. Electron microprobe analysis gave (wt.%): CdO 32.43, CuO 28.06, ZnO 2.26, FeO 0.08, SO320.35, H2Ocalc.(from crystal-structure analysis) 14.14, totalling 99.32. The empirical formula, calculated on the basis of 18 oxygen atoms is Cu2.77Cd1.98Zn0.22Fe0.01(SO4)2.00(OH)5.95·4.06H2O. Edwardsite is monoclinic, space groupP21/c, witha= 10.863(2) Å,b= 13.129(3) Å,c= 11.169(2) Å, β = 113.04(3)°,V= 1465.9(5) Å3(single-crystal data) andZ= 4. The eight strongest lines in the powder diffraction pattern are [d(Å), (I/I0), (hkl)]: 9.991, (90), (100); 5.001, (90), (200, 21); 4.591, (45), (20); 3.332, (60), (300, 032); 3.005, (30), (03); 2.824, (40), (2); 2.769, (55), (20, 042, 10); 2.670, (45), (2). The crystal structure was determined by direct methods and refined toR1 = 3.21% using 1904 observed reflections withFo> 4σ(Fo) collected using synchrotron X-ray radiation (λ = 0.773418 Å). The structure is based on infinite sheets of edge-sharing Cuϕ6(ϕ: O2–, OH) octahedra and Cdϕ7(ϕ: O2–, H2O) polyhedra parallel to (100). The sheets are decorated on both sides by corner-sharing (SO4) tetrahedra, which also corner-link to isolated Cdϕ6octahedra, thus connecting adjacent sheets. Moderate-strong to weak hydrogen bonding provides additional linkage between sheets.

Aim The purpose of this study was to systematically review published evidence on the development, use, and effectiveness of devices and technologies that enable or enhance self-directed computer access by individuals with cerebral palsy (CP). Methods Nine electronic databases were searched using keywords ‘computer’, ‘software’, ‘spastic’, ‘athetoid’, and ‘cerebral palsy’; the reference lists of articles thus identified were also searched. Thirty articles were selected for review, with 23 reports of development and usability testing of devices and seven evaluations of algorithms to increase computer recognition of input and cursor movements. Results Twenty-four studies had fewer than 10 participants with CP, with a wide age range of 5 to 77 years. Computer task performance was usually tested, but only three groups sought participant feedback on ease and comfort of use. International standards exist to evaluate effectiveness of non-keyboard devices, but only one group undertook this testing. None of the study designs were higher than American Academy for Cerebral Palsy and Developmental Medicine level IV. Interpretation Access solutions for individuals with CP are in the early stages of development. Future work should include assessment of end-user comfort, effort, and performance as well as design features. Engaging users and therapists when designing and evaluating technologies to enhance computer access may increase acceptance and improve performance.

To provide an experimental basis for a comprehensive molecular modeling evaluation study, 500 fragments from the Maybridge fragment library were soaked into crystals of bovine pancreatic trypsin and the structures determined by X-ray crystallography. The soaking experiments were performed in both single and pooled aliquots to determine if combination of fragments is an appropriate strategy. A further set of data was obtained from co-crystallizing the pooled fragments with the protein. X-ray diffraction data were collected on approximately 1000 crystals at the Australian Synchrotron, and these data were subsequently processed, and the preliminary analysis was performed with a custom software application (Jigsaw), which combines available software packages for structure solution and analysis.

Transport regulators are examining the feasibility of requiring the adoption of takeoff performance monitoring systems in certain circumstances. Recent advances in the development of aircraft landing and takeoff performance monitoring systems have shown the feasibility of a cockpit instrument that could aid significantly in the decision making process during the most critical phases of flight, provided that the information can be effectively visualized. The design and construction of a cockpit interface to communicate the information in a timely and efficient manner has now been completed. The resulting Thrust and Braking Indicator/Advisor (TABI/A) integrates a visual display with audible advice.

Individuals with functional blindness must often use assistive aids to enable effective locomotion. To date, such devices do not provide effective information about obstacles above waist height, or are too cumbersome to have gained widespread adoption. This paper presents the development of a device that provides a user with pronounced Doppler echoes obtained by direct down-conversion of ultrasound. This system provides acoustic flow that is evident upon initiation of travel and can be used to visualise the environment and detect environmental obstacles. The prototype version was human-tested for localisation, distance estimation, and aperture passage. From this initial study, a refined, compact system has been developed that is currently undergoing testing.

This research identified differences in the ability to determine distance using audible echolocation relative to audified ultrasound echoes with receivers mounted laterally and forward. In an anechoic environment, participants walked toward a stationary “wall” and provided an indication of perceived distance from the wall. Once the judgement was made, the participant walked to the location of the wall to provide an opportunity to recalibrate for future trials. At closer distances, no differences were observed among conditions, but at farther distances the results from the audified ultrasound were more accurate. The orientation of the receivers in the outward direction provided for better results overall in the judgement of distance to environmental obstacles.

A species' range can be a proxy for its ecological well-being. Species with small and shrinking range distributions are particularly vulnerable to extinction. Future climate change scenarios are predicted to affect species' geographical extents, but data on how species' distributions respond to changing climate are largely anecdotal, and our understanding of the determinants and limits to species geographic ranges is surprisingly poor. Here we show that mammal species in more historically variable environments have larger geographical ranges. However, the relationship between range size and long-term climate trends cannot be explained by variation in our estimates of habitat specificity. We suggest that large oscillations in Quaternary temperatures may have shaped the contemporary distribution of range sizes via the selective extirpation of small-ranged species during glacial expansion and/or recolonization by good dispersers after glacial retreats. The effect of current climate change on species' distributions and extinctions may therefore be determined by the geographical coincidence between historical and future climate scenarios, the "mesh size" of the extinction/dispersal filter imposed by past climate change, and whether similar ecological and evolutionary responses to historical climatic change are appropriate in an increasingly transformed and fragmented landscape.

Enzymes from the de novo purine biosynthetic pathway have been exploited for the development of anti-cancer drugs, and represent novel targets for anti-bacterial drug development. In Mycobacterium tuberculosis, the cause of tuberculosis, this pathway has been identified as essential for growth and survival. The structure of M. tuberculosis PurN (MtPurN) has been determined in complex with magnesium and iodide at 1.30 A resolution, and with cofactor analogue, 5-methyltetrahydrofolate (5MTHF) at 2.2 A resolution. The structure shows a Rossmann-type fold that is very similar to the known structures of the human and E. coli PurN proteins. In contrast, MtPurN forms a dimer that is quite different from that formed by the Escherichia coli PurN, and which suggests a mechanism whereby communication could take place between the two active sites. Differences are seen in two active site loops and in the binding mode of the 5MTHF cofactor analogue between the two MtPurN molecules of the dimer. A binding site for halide ions is found in the dimer interface, and bound magnesium and iodide ions in the active site suggest sites that might be exploited in potential drug discovery strategies.

Increasing atmospheric carbon dioxide levels are causing ocean acidification, compromising the ability of some marine organisms to build and maintain support structures. An analysis of mussels from a submarine volcano setting with natural low-pH conditions shows low shell thicknesses and growth rates, but survival over up to four decades. Increasing atmospheric carbon dioxide levels are causing ocean acidification1,2, compromising the ability of some marine organisms to build and maintain support structures3 as the equilibrium state of inorganic carbon moves away from calcium carbonate4. Few marine organisms tolerate conditions where ocean pH falls significantly below today’s value of about 8.1 and aragonite and calcite saturation values below 1 (refs 5, 6). Here we report dense clusters of the vent mussel Bathymodiolus brevior in natural conditions of pH values between 5.36 and 7.29 on northwest Eifuku volcano, Mariana arc, where liquid carbon dioxide and hydrogen sulphide emerge in a hydrothermal setting. We find that both shell thickness and daily growth increments in shells from northwest Eifuku are only about half those recorded from mussels living in water with pH>7.8. Low pH may therefore also be implicated in metabolic impairment7. We identify four-decade-old mussels, but suggest that the mussels can survive for so long only if their protective shell covering remains intact: crabs that could expose the underlying calcium carbonate to dissolution are absent from this setting. The mussels’ ability to precipitate shells in such low-pH conditions is remarkable. Nevertheless, the vulnerability of molluscs to predators is likely to increase in a future ocean with low pH.

Phylogenies describe the origins and history of species. However, they can also help to predict species' fates and so can be useful tools for managing the future of biodiversity. This article starts by sketching how phylogenetic, geographic, and trait information can be combined to elucidate present mammalian diversity patterns and how they arose. Recent diversification rates and standing diversity show different geographic patterns, indicating that cradles of diversity have moved over time. Patterns in extinction risk reflect both biological differences among mammalian lineages and differences in threat intensity among regions. Phylogenetic comparative analyses indicate that for small-bodied mammals, extinction risk is governed mostly by where the species live and the intensity of the threats, whereas for large-bodied mammals, ecological differences also play an important role. This modeling approach identifies species whose intrinsic biology renders them particularly vulnerable to increased human pressure. We outline how the approach might be extended to consider future trends in anthropogenic drivers, to identify likely future battlegrounds of mammalian conservation, and the likely casualties. This framework could help to highlight consequences of choosing among different future climatic and socioeconomic scenarios. We end by discussing priority-setting, showing how alternative currencies for diversity can suggest very different priorities. We argue that aiming to maximize long-term evolutionary responses is inappropriate, that conservation planning needs to consider costs as well as benefits, and that proactive conservation of largely intact systems should be part of a balanced strategy.

The current infrafamilial taxonomy of the Iridaceae recognizes four subfamilies; Isophysidoideae (1: 1); Nivenioideae (6: ca. 92), Iridoideae (29: 890), and Crocoideae (29: 1032). Phylogenetic analyses of sequences of five plastid DNA regions, rbcL, rps4, trnL–F, matK, and rps16, confirm most aspects of this classification and the evolutionary patterns that they imply, importantly the sisiter relationship of Isophysidoideae to the remainder of the family and the monophyly of Iridoideae. Subfamily Nivenioideae is, however, paraphyletic; Crocoideae is consistently found nested within it, sister to the core Nivenioideae, the woody Klattia, Nivenia, and Witsenia. This clade is sister to Aristea, which in turn is sister to the Madagascan Geosiris, and then to the Australasian Patersonia. We treat Aristea, Geosiris, and Patersonia as separate subfamilies, Aristeoideae and the new Geosiridaceae and Patersonioideae, rendering Nivenioideae and Crocoideae monophyletic. The alternative, uniting a widely circumscribed Nivenioideae and Crocoideae, seems undesirable because Nivenioideae have none of the numerous synapomorphies of Crocoideae, and that subfamily includes more than half the total species of Iridaceae. Main synapomorphies of Crocoideae are: pollen operculate; exine perforate; ovule campylotropous; root xylem vessels with simple perforations; rootstock a corm; inflorescence usually a spike; plants deciduous. Four more derived features of Crocoideae are shared only with core Nivenioideae: flowers long-lived; perianth tube well developed; flowers sessile; and septal nectaries present. The genera of the latter subfamily are evergreen shrubs, have monocot-type secondary growth, tangentially flattened seeds, and the inflorescence unit is a binate rhipidium. The latter feature unites core Nivenioideae with Aristea, Geosiris, and Patersonia, which have fugaceous flowers and, with few exceptions, a blue perianth. Molecular-based phylogenetic trees using sequences from five plastid DNA regions now show discrete generic clusters within Crocoideae and Iridoideae, the foundation for the tribal classification. The five tribe classification of Iridoideae, initially based on morphological characters and subsequently supported by a four plastid DNA region sequence analysis, continues to receive support using additional DNA sequences. Application of molecular clock techniques to our phylogeny indicates that the Iridaceae differentiated in the late Cretaceous and diverged from the next most closely related family, Doryanthaceae circa 82 mya, thus during the Campanian. The Tasmanian Isophysis is the only extant member of the clade sister to the remainder of the Iridaceae, from which it may have diverged 66 mya, in the Maastrichtian. The generic phylogeny shows the proximal clades of the family are all Australasian, which corroborates past hypotheses that the Iridaceae originated in Antarctica-Australasia, although its subsequent radiation occurred elsewhere, notably in southern Africa and temperate and highland South America at the end of the Eocene or later.

In natural systems, host species are often co-infected by multiple pathogen species, and recent work has suggested that many pathogens can infect a wide range of host species. An important question therefore is what determines the host range of a pathogen and the community of pathogens found within a given host species. Using primates as a model, we show that infectious diseases are more often shared between species that are closely related and inhabit the same geographical region. We find that host relatedness is the best overall predictor of whether two host species share the same pathogens. A higher frequency of pathogen host shifts between close relatives or inheritance of pathogens from a common ancestor may explain this result. For viruses, geographical overlap among neighbouring primate hosts is more important in determining host range. We suggest this is because rapid evolution within viral lineages allows host jumps across larger evolutionary distances. We also show that the phylogenetic pattern of pathogen sharing with humans is the same as that between wild primates. For humans, this means we share a higher proportion of pathogens with the great apes, including chimpanzees and gorillas, because these species are our closest relatives.

We used the largest DNA-based phylogeny of flowering plants to date to evaluate the importance of energy vs. past climate change in predicting global patterns in diversification. Relative diversification rates increased towards the equator, suggesting that differences in per-lineage net diversification may be an important component of the latitudinal diversity gradient. The amplitude of Quaternary climate oscillations experienced by families explained variation in diversification equally well compared to contemporary energy measures, and energy and climate change measures were intercorrelated, making it difficult to reject either as a causal mechanism. Many putative mechanisms linking diversification to energy availability do not apply to plants, whereas the climate change mechanism has more support. We also present the first global map of angiosperm diversification, showing that, after correcting for family range-size, tropical diversification rates were fastest for clades currently in regions with high endemic species richness outside the main lowland rainforest areas.

This paper discusses the pilot testing of an auditory interface designed to increase navigational ability of visually impaired individuals. Sonar devices have been developed to increase preview distances, but these have gained limited acceptance as they lack an easily interpreted interface. This paper presents usability testing of an auditory prototype interface developed using the work domain analysis of ecological interface design (EID). An interface design that provides the user with sufficient preview to avoid obstacles may offer more environmental information than the single tones of the current designs.

One of the biggest challenges for conservation biology is to provide conservation planners with ways to prioritize effort. Much attention has been focused on biodiversity hotspots. However, the conservation of evolutionary process is now also acknowledged as a priority in the face of global change. Phylogenetic diversity (PD) is a biodiversity index that measures the length of evolutionary pathways that connect a given set of taxa. PD therefore identifies sets of taxa that maximize the accumulation of 'feature diversity'. Recent studies, however, concluded that taxon richness is a good surrogate for PD. Here we show taxon richness to be decoupled from PD, using a biome-wide phylogenetic analysis of the flora of an undisputed biodiversity hotspot--the Cape of South Africa. We demonstrate that this decoupling has real-world importance for conservation planning. Finally, using a database of medicinal and economic plant use, we demonstrate that PD protection is the best strategy for preserving feature diversity in the Cape. We should be able to use PD to identify those key regions that maximize future options, both for the continuing evolution of life on Earth and for the benefit of society.

Co-occurring species might be morphologically similar because they are adapted to the same environment, or morphologically dissimilar to minimize competition. We use sister species comparisons to evaluate the relationship between morphological disparity and regional patterns of co-occurrence across carnivores. Up to 63% of the variation in range overlap can be explained by morphological divergence in dentition. Species that differ more in carnassial tooth length overlap more in their geographical range. Carnassials are the primary teeth associated with food processing, and hence difference in carnassial size may be a good indicator of difference in resource use. We suggest this pattern is consistent with competition in sympatry driving ecological character displacement, or competitive exclusion among ecologically similar species. Our study uses newly available data on global distributions, morphology and phylogeny, and is the first to demonstrate a close relationship between morphological disparity and co-occurrence at a regional scale encompassing multiple communities.