Giant lobelias exemplify convergent evolution

Giant lobeliads on tropical mountains in East Africa and Hawaii have highly unusual, giant-rosette growth forms that appear to be convergent on each other and on those of several independently evolved groups of Asteraceae and other families. A recent phylogenetic analysis by Antonelli, based on sequencing the widest selection of lobeliads to date, raises doubts about this paradigmatic example of convergent evolution. Here I address the kinds of evidence needed to test for convergent evolution and argue that the analysis by Antonelli fails on four points. Antonelli's analysis makes several important contributions to our understanding of lobeliad evolution and geographic spread, but his claim regarding convergence appears to be invalid. Giant lobeliads in Hawaii and Africa represent paradigmatic examples of convergent evolution

Speciation Along Environmental Gradients

Traditional discussions of speciation are based on geographical patterns of species ranges. In allopatric speciation, long-term geographical isolation generates reproductively isolated and spatially segregated descendant species. In the absence of geographical barriers, diversification is hindered by gene flow. Yet a growing body of phylogenetic and experimental data suggests that closely related species often occur in sympatry or have adjacent ranges in regions over which environmental changes are gradual and do not prevent gene flow. Theory has identified a variety of evolutionary processes that can result in speciation under sympatric conditions, with some recent advances concentrating on the phenomenon of evolutionary branching. Here we establish a link between geographical patterns and ecological processes of speciation by studying evolutionary branching in spatially structured populations. We show that along an environmental gradient, evolutionary branching can occur much more easily than in non-spatial models. This facilitation is most pronounced for gradients of intermediate slope. Moreover, spatial evolutionary branching readily generates patterns of spatial segregation and abutment between the emerging species. Our results highlight the importance of local processes of adaptive divergence for geographical patterns of speciation, and caution against pitfalls of inferring past speciation processes from present biogeographical patterns

First Neutrino Observations from the Sudbury Neutrino Observatory

The first neutrino observations from the Sudbury Neutrino Observatory are presented from preliminary analyses. Based on energy, direction and location, the data in the region of interest appear to be dominated by 8B solar neutrinos, detected by the charged current reaction on deuterium and elastic scattering from electrons, with very little background. Measurements of radioactive backgrounds indicate that the measurement of all active neutrino types via the neutral current reaction on deuterium will be possible with small systematic uncertainties. Quantitative results for the fluxes observed with these reactions will be provided when further calibrations have been completed.Comment: Latex, 7 pages, 10 figures, Invited paper at Neutrino 2000 Conference, Sudbury, Canada, June 16-21, 2000 to be published in the Proceeding

The HOPE fixation technique - a promising alternative to common prostate cancer biobanking approaches

<p>Abstract</p> <p>Background</p> <p>The availability of well-annotated prostate tissue samples through biobanks is key for research. Whereas fresh-frozen tissue is well suited for a broad spectrum of molecular analyses, its storage and handling is complex and cost-intensive. Formalin-fixed paraffin-embedded specimens (FFPE) are easy to handle and economic to store, but their applicability for molecular methods is restricted. The recently introduced Hepes-glutamic acid-buffer mediated Organic solvent Protection Effect (HOPE) is a promising alternative, which might have the potential to unite the benefits of FFPE and fresh-frozen specimen. Aim of the study was to compare HOPE-fixed, FFPE and fresh-frozen bio-specimens for their accessibility for diagnostic and research purposes.</p> <p>Methods</p> <p>10 prostate cancer samples were each preserved with HOPE, formalin, and liquid nitrogen and studied with in-situ and molecular methods. Samples were H&E stained, and assessed by immunohistochemistry (i.e. PSA, GOLPH2, p63) and FISH (i.e. <it>ERG </it>rearrangement). We assessed DNA integrity by PCR, using control genes ranging from 100 to 600 bp amplicon size. RNA integrity was assessed through qRT-PCR on three housekeeping genes (TBP, GAPDH, β-actin). Protein expression was analysed by performing western blot analysis using GOLPH2 and PSA antibodies.</p> <p>Results</p> <p>Of the HOPE samples, morphologic quality of H&E sections, immunohistochemical staining, and the FISH assay was at least equal to FFPE tissue, and significantly better than the fresh-frozen specimens. DNA, RNA, and protein analysis of HOPE samples provided similar results as compared to fresh-frozen specimens. As expected, FFPE-samples were inferior for most of the molecular analyses.</p> <p>Conclusions</p> <p>This is the first study, comparatively assessing the suitability of these fixation methods for diagnostic and research utilization. Overall, HOPE-fixed bio-specimens combine the benefits of FFPE- and fresh-frozen samples. Results of this study have the potential to expand on contemporary prostate tissue biobanking approaches and can serve as a model for other organs and tumors.</p

Network Models of TEM β-Lactamase Mutations Coevolving under Antibiotic Selection Show Modular Structure and Anticipate Evolutionary Trajectories

Understanding how novel functions evolve (genetic adaptation) is a critical goal of evolutionary biology. Among asexual organisms, genetic adaptation involves multiple mutations that frequently interact in a non-linear fashion (epistasis). Non-linear interactions pose a formidable challenge for the computational prediction of mutation effects. Here we use the recent evolution of β-lactamase under antibiotic selection as a model for genetic adaptation. We build a network of coevolving residues (possible functional interactions), in which nodes are mutant residue positions and links represent two positions found mutated together in the same sequence. Most often these pairs occur in the setting of more complex mutants. Focusing on extended-spectrum resistant sequences, we use network-theoretical tools to identify triple mutant trajectories of likely special significance for adaptation. We extrapolate evolutionary paths (n = 3) that increase resistance and that are longer than the units used to build the network (n = 2). These paths consist of a limited number of residue positions and are enriched for known triple mutant combinations that increase cefotaxime resistance. We find that the pairs of residues used to build the network frequently decrease resistance compared to their corresponding singlets. This is a surprising result, given that their coevolution suggests a selective advantage. Thus, β-lactamase adaptation is highly epistatic. Our method can identify triplets that increase resistance despite the underlying rugged fitness landscape and has the unique ability to make predictions by placing each mutant residue position in its functional context. Our approach requires only sequence information, sufficient genetic diversity, and discrete selective pressures. Thus, it can be used to analyze recent evolutionary events, where coevolution analysis methods that use phylogeny or statistical coupling are not possible. Improving our ability to assess evolutionary trajectories will help predict the evolution of clinically relevant genes and aid in protein design

Measuring persistence of implementation: QUERI Series

As more quality improvement programs are implemented to achieve gains in performance, the need to evaluate their lasting effects has become increasingly evident. However, such long-term follow-up evaluations are scarce in healthcare implementation science, being largely relegated to the "need for further research" section of most project write-ups. This article explores the variety of conceptualizations of implementation sustainability, as well as behavioral and organizational factors that influence the maintenance of gains. It highlights the finer points of design considerations and draws on our own experiences with measuring sustainability, framed within the rich theoretical and empirical contributions of others. In addition, recommendations are made for designing sustainability analyses

A critical analysis of the cycles of physical activity policy in England

BACKGROUND: There has been increasing focus on the importance of national policy to address population levels of physical inactivity. Components of a comprehensive national physical activity policy framework include: 1) national recommendations on physical activity levels; 2) setting population goals and targets; 3) surveillance or health monitoring systems; and 4) public education. The aim of the current paper was to analyse the policy actions which have addressed each of these elements in England and to identify areas of progress and remaining challenges.  METHODS: A literature search was undertaken to identify past and present documents relevant to physical activity policy in England. Each document was analysed to identify content relevant to the four key elements of policy which formed the focus of the current research.  RESULTS: Physical activity recommendations are an area where England has demonstrated a robust scientific approach and good practice; however, the physical activity campaigns in England have not been sufficiently sustained to achieve changes in social norms and behaviour. The setting of physical activity targets has been unrealistic and continuous changes to national surveillance measures have presented challenges for monitoring trends over time.  CONCLUSIONS: Overall, physical activity policy in England has fluctuated over the past two decades. The variations and cycles in policy reflect some of the challenges in implementing and sustaining physical activity policy in the face of political changes, changes in government direction, and changing opportunities to profile active lifestyles

Discovery of a Non-Peptidic Inhibitor of West Nile Virus NS3 Protease by High-Throughput Docking

An estimated 2.5 billion people are at risk of diseases caused by dengue and West Nile virus. As of today, there are neither vaccines to prevent nor drugs to cure the severe infections caused by these viruses. The NS3 protease is one of the most promising targets for drug development against West Nile virus because it is an essential enzyme for viral replication and because success has been demonstrated with the closely related hepatitis C virus protease. We have discovered a small molecule that inhibits the NS3 protease of West Nile virus by computer-aided high-throughput docking, and validated it using three experimental techniques. The inhibitor has potential to be developed to a drug candidate to combat West Nile virus infections

Institutional shared resources and translational cancer research

The development and maintenance of adequate shared infrastructures is considered a major goal for academic centers promoting translational research programs. Among infrastructures favoring translational research, centralized facilities characterized by shared, multidisciplinary use of expensive laboratory instrumentation, or by complex computer hardware and software and/or by high professional skills are necessary to maintain or improve institutional scientific competitiveness. The success or failure of a shared resource program also depends on the choice of appropriate institutional policies and requires an effective institutional governance regarding decisions on staffing, existence and composition of advisory committees, policies and of defined mechanisms of reporting, budgeting and financial support of each resource. Shared Resources represent a widely diffused model to sustain cancer research; in fact, web sites from an impressive number of research Institutes and Universities in the U.S. contain pages dedicated to the SR that have been established in each Center, making a complete view of the situation impossible. However, a nation-wide overview of how Cancer Centers develop SR programs is available on the web site for NCI-designated Cancer Centers in the U.S., while in Europe, information is available for individual Cancer centers. This article will briefly summarize the institutional policies, the organizational needs, the characteristics, scientific aims, and future developments of SRs necessary to develop effective translational research programs in oncology

Implications of the Plastid Genome Sequence of Typha (Typhaceae, Poales) for Understanding Genome Evolution in Poaceae

Plastid genomes of the grasses (Poaceae) are unusual in their organization and rates of sequence evolution. There has been a recent surge in the availability of grass plastid genome sequences, but a comprehensive comparative analysis of genome evolution has not been performed that includes any related families in the Poales. We report on the plastid genome of Typha latifolia, the first non-grass Poales sequenced to date, and we present comparisons of genome organization and sequence evolution within Poales. Our results confirm that grass plastid genomes exhibit acceleration in both genomic rearrangements and nucleotide substitutions. Poaceae have multiple structural rearrangements, including three inversions, three genes losses (accD, ycf1, ycf2), intron losses in two genes (clpP, rpoC1), and expansion of the inverted repeat (IR) into both large and small single-copy regions. These rearrangements are restricted to the Poaceae, and IR expansion into the small single-copy region correlates with the phylogeny of the family. Comparisons of 73 protein-coding genes for 47 angiosperms including nine Poaceae genera confirm that the branch leading to Poaceae has significantly accelerated rates of change relative to other monocots and angiosperms. Furthermore, rates of sequence evolution within grasses are lower, indicating a deceleration during diversification of the family. Overall there is a strong correlation between accelerated rates of genomic rearrangements and nucleotide substitutions in Poaceae, a phenomenon that has been noted recently throughout angiosperms. The cause of the correlation is unknown, but faulty DNA repair has been suggested in other systems including bacterial and animal mitochondrial genomes