Insights from Amphioxus into the Evolution of Vertebrate Cartilage

Central to the story of vertebrate evolution is the origin of the vertebrate head, a problem difficult to approach using paleontology and comparative morphology due to a lack of unambiguous intermediate forms. Embryologically, much of the vertebrate head is derived from two ectodermal tissues, the neural crest and cranial placodes. Recent work in protochordates suggests the first chordates possessed migratory neural tube cells with some features of neural crest cells. However, it is unclear how and when these cells acquired the ability to form cellular cartilage, a cell type unique to vertebrates. It has been variously proposed that the neural crest acquired chondrogenic ability by recruiting proto-chondrogenic gene programs deployed in the neural tube, pharynx, and notochord. To test these hypotheses we examined the expression of 11 amphioxus orthologs of genes involved in neural crest chondrogenesis. Consistent with cellular cartilage as a vertebrate novelty, we find that no single amphioxus tissue co-expresses all or most of these genes. However, most are variously co-expressed in mesodermal derivatives. Our results suggest that neural crest-derived cartilage evolved by serial cooption of genes which functioned primitively in mesoderm

Reinforcement learning or active inference?

This paper questions the need for reinforcement learning or control theory when optimising behaviour. We show that it is fairly simple to teach an agent complicated and adaptive behaviours using a free-energy formulation of perception. In this formulation, agents adjust their internal states and sampling of the environment to minimize their free-energy. Such agents learn causal structure in the environment and sample it in an adaptive and self-supervised fashion. This results in behavioural policies that reproduce those optimised by reinforcement learning and dynamic programming. Critically, we do not need to invoke the notion of reward, value or utility. We illustrate these points by solving a benchmark problem in dynamic programming; namely the mountain-car problem, using active perception or inference under the free-energy principle. The ensuing proof-of-concept may be important because the free-energy formulation furnishes a unified account of both action and perception and may speak to a reappraisal of the role of dopamine in the brain

Recovery and resilience of tropical forests after disturbance

The time taken for forested tropical ecosystems to re-establish post-disturbance is of widespread interest. Yet to date there has been no comparative study across tropical biomes to determine rates of forest re-growth, and how they vary through space and time. Here we present results from a meta-analysis of palaeoecological records that use fossil pollen as a proxy for vegetation change over the past 20,000 years. A total of 283 forest disturbance and recovery events, reported in 71 studies, are identified across four tropical regions. Results indicate that forests in Central America and Africa generally recover faster from past disturbances than those in South America and Asia, as do forests exposed to natural large infrequent disturbances compared with post-climatic and human impacts. Results also demonstrate that increasing frequency of disturbance events at a site through time elevates recovery rates, indicating a degree of resilience in forests exposed to recurrent past disturbance

Model-selection-based approach for calculating cellular multiplicity of infection during virus colonization of multi-cellular hosts

The cellular multiplicity of infection (MOI) is a key parameter for describing the interactions between virions and cells, predicting the dynamics of mixed-genotype infections, and understanding virus evolution. Two recent studies have reported in vivo MOI estimates for Tobacco mosaic virus (TMV) and Cauliflower mosaic virus (CaMV), using sophisticated approaches to measure the distribution of two virus variants over host cells. Although the experimental approaches were similar, the studies employed different definitions of MOI and estimation methods. Here, new model-selection-based methods for calculating MOI were developed. Seven alternative models for predicting MOI were formulated that incorporate an increasing number of parameters. For both datasets the best-supported model included spatial segregation of virus variants over time, and to a lesser extent aggregation of virus-infected cells was also implicated. Three methods for MOI estimation were then compared: the two previously reported methods and the best-supported model. For CaMV data, all three methods gave comparable results. For TMV data, the previously reported methods both predicted low MOI values (range: 1.04-1.23) over time, whereas the best-supported model predicted a wider range of MOI values (range: 1.01-2.10) and an increase in MOI over time. Model selection can therefore identify suitable alternative MOI models and suggest key mechanisms affecting the frequency of coinfected cells. For the TMV data, this leads to appreciable differences in estimated MOI values.This work was supported by grant BFU2012-30805 (SFE) and by 'Juan de la Cierva' postdoctoral contract JCI-2011-10379 (MPZ) from the Spanish Secretaria de Estado de Investigacion, Desarrollo e Innovacion. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Zwart, MP.; Tromas ., N.; Elena Fito, SF. (2013). Model-selection-based approach for calculating cellular multiplicity of infection during virus colonization of multi-cellular hosts. PLoS ONE. 8:64657-64657. https://doi.org/10.1371/journal.pone.0064657S64657646578Froissart, R., Wilke, C. O., Montville, R., Remold, S. K., Chao, L., & Turner, P. E. (2004). Co-infection Weakens Selection Against Epistatic Mutations in RNA Viruses. Genetics, 168(1), 9-19. doi:10.1534/genetics.104.030205Miyashita, S., & Kishino, H. (2009). Estimation of the Size of Genetic Bottlenecks in Cell-to-Cell Movement of Soil-Borne Wheat Mosaic Virus and the Possible Role of the Bottlenecks in Speeding Up Selection of Variations in trans-Acting Genes or Elements. Journal of Virology, 84(4), 1828-1837. doi:10.1128/jvi.01890-09Taylor, D. R., Zeyl, C., & Cooke, E. (2002). Conflicting levels of selection in the accumulation of mitochondrial defects inSaccharomycescerevisiae. Proceedings of the National Academy of Sciences, 99(6), 3690-3694. doi:10.1073/pnas.072660299Turner, P. E., & Chao, L. (1999). Prisoner’s dilemma in an RNA virus. Nature, 398(6726), 441-443. doi:10.1038/18913Turner, P. E., & Chao, L. (2003). Escape from Prisoner’s Dilemma in RNA Phage Φ6. The American Naturalist, 161(3), 497-505. doi:10.1086/367880Zwart, M. P., Erro, E., van Oers, M. M., de Visser, J. A. G. M., & Vlak, J. M. (2008). Low multiplicity of infection in vivo results in purifying selection against baculovirus deletion mutants. Journal of General Virology, 89(5), 1220-1224. doi:10.1099/vir.0.83645-0Godfray, H. C. J., O’reilly, D. R., & Briggs, C. J. (1997). A model of Nucleopolyhedrovirus (NPV) population genetics applied to co–occlusion and the spread of the few Polyhedra (FP) phenotype. Proceedings of the Royal Society of London. Series B: Biological Sciences, 264(1380), 315-322. doi:10.1098/rspb.1997.0045Bull, J. C., Godfray, H. C. J., & O’Reilly, D. R. (2001). Persistence of an Occlusion-Negative Recombinant Nucleopolyhedrovirus in Trichoplusia ni Indicates High Multiplicity of Cellular Infection. Applied and Environmental Microbiology, 67(11), 5204-5209. doi:10.1128/aem.67.11.5204-5209.2001Gonzalez-Jara, P., Fraile, A., Canto, T., & Garcia-Arenal, F. (2009). The Multiplicity of Infection of a Plant Virus Varies during Colonization of Its Eukaryotic Host. Journal of Virology, 83(15), 7487-7494. doi:10.1128/jvi.00636-09Gutiérrez, S., Yvon, M., Thébaud, G., Monsion, B., Michalakis, Y., & Blanc, S. (2010). Dynamics of the Multiplicity of Cellular Infection in a Plant Virus. PLoS Pathogens, 6(9), e1001113. doi:10.1371/journal.ppat.1001113Morra, M. R., & Petty, I. T. D. (2000). Tissue Specificity of Geminivirus Infection Is Genetically Determined. The Plant Cell, 12(11), 2259-2270. doi:10.1105/tpc.12.11.2259Silva, M. S., Goldbach, R. W., van Lent, J. W. M., & Wellink, J. (2002). Phloem loading and unloading of Cowpea mosaic virus in Vigna unguiculata. Journal of General Virology, 83(6), 1493-1504. doi:10.1099/0022-1317-83-6-1493Sokal RR, Rohlf FJ (1995) Biometry, 3rd edition. New York: W.H. Freeman and Co. 887 p.Zwart, M. P., Hemerik, L., Cory, J. S., de Visser, J. A. G. M., Bianchi, F. J. J. A., Van Oers, M. M., … Van der Werf, W. (2009). An experimental test of the independent action hypothesis in virus–insect pathosystems. Proceedings of the Royal Society B: Biological Sciences, 276(1665), 2233-2242. doi:10.1098/rspb.2009.0064Dietrich, C. (2003). Fluorescent labelling reveals spatial separation of potyvirus populations in mixed infected Nicotiana benthamiana plants. Journal of General Virology, 84(10), 2871-2876. doi:10.1099/vir.0.19245-0Zwart, M. P., Daròs, J.-A., & Elena, S. F. (2011). One Is Enough: In Vivo Effective Population Size Is Dose-Dependent for a Plant RNA Virus. PLoS Pathogens, 7(7), e1002122. doi:10.1371/journal.ppat.1002122Lafforgue, G., Tromas, N., Elena, S. F., & Zwart, M. P. (2012). Dynamics of the Establishment of Systemic Potyvirus Infection: Independent yet Cumulative Action of Primary Infection Sites. Journal of Virology, 86(23), 12912-12922. doi:10.1128/jvi.02207-12Dolja, V. V., McBride, H. J., & Carrington, J. C. (1992). Tagging of plant potyvirus replication and movement by insertion of beta-glucuronidase into the viral polyprotein. Proceedings of the National Academy of Sciences, 89(21), 10208-10212. doi:10.1073/pnas.89.21.10208Van der Werf, W., Hemerik, L., Vlak, J. M., & Zwart, M. P. (2011). Heterogeneous Host Susceptibility Enhances Prevalence of Mixed-Genotype Micro-Parasite Infections. PLoS Computational Biology, 7(6), e1002097. doi:10.1371/journal.pcbi.1002097Barlow, N. D. (1991). A Spatially Aggregated Disease/Host Model for Bovine Tb in New Zealand Possum Populations. The Journal of Applied Ecology, 28(3), 777. doi:10.2307/2404207Barlow, N. D. (2000). Non-linear transmission and simple models for bovine tuberculosis. Journal of Animal Ecology, 69(4), 703-713. doi:10.1046/j.1365-2656.2000.00428.xR Core Team (2012) R: A Language and Environment for Statistical Computing. Vienna: R Foundation for Statistical Computing.Olkin I, Gleser LJ, Derman C. (1994) Probability Models and Applications, 2nd ed. New York: Macmillan. 575 p

Kinetic Analysis of Substrate Utilization by Native and TNAP-, NPP1-, or PHOSPHO1-Deficient Matrix Vesicles

During the process of endochondral bone formation, chondrocytes and osteoblasts mineralize their extracellular matrix by promoting the formation of hydroxyapatite seed crystals in the sheltered interior of membrane-limited matrix vesicles (MVs). Here, we have studied phosphosubstrate catalysis by osteoblast-derived MVs at physiologic pH, analyzing the hydrolysis of ATP, ADP, and PPi by isolated wild-type (WT) as well as TNAP-, NPP1- and PHOSPHO1-deficient MVs. Comparison of the catalytic efficiencies identified ATP as the main substrate hydrolyzed by WT MVs. The lack of TNAP had the most pronounced effect on the hydrolysis of all physiologic substrates. The lack of PHOSPHO1 affected ATP hydrolysis via a secondary reduction in the levels of TNAP in PHOSPHO1-deficient MVs. The lack of NPP1 did not significantly affect the kinetic parameters of hydrolysis when compared with WT MVs for any of the substrates. We conclude that TNAP is the enzyme that hydrolyzes both ATP and PPi in the MV compartment. NPP1 does not have a major role in PPi generation from ATP at the level of MVs, in contrast to its accepted role on the surface of the osteoblasts and chondrocytes, but rather acts as a phosphatase in the absence of TNAP. © 2010 American Society for Bone and Mineral Research

Measurement of the branching fraction and CP content for the decay B(0) -> D(*+)D(*-)

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APS.We report a measurement of the branching fraction of the decay B0→D*+D*- and of the CP-odd component of its final state using the BABAR detector. With data corresponding to an integrated luminosity of 20.4  fb-1 collected at the Υ(4S) resonance during 1999–2000, we have reconstructed 38 candidate signal events in the mode B0→D*+D*- with an estimated background of 6.2±0.5 events. From these events, we determine the branching fraction to be B(B0→D*+D*-)=[8.3±1.6(stat)±1.2(syst)]×10-4. The measured CP-odd fraction of the final state is 0.22±0.18(stat)±0.03(syst).This work is supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the A.P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications

Measurement of D-s(+) and D-s(*+) production in B meson decays and from continuum e(+)e(-) annihilation at √s=10.6 GeV

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APSNew measurements of Ds+ and Ds*+ meson production rates from B decays and from qq̅ continuum events near the Υ(4S) resonance are presented. Using 20.8 fb-1 of data on the Υ(4S) resonance and 2.6 fb-1 off-resonance, we find the inclusive branching fractions B(B⃗Ds+X)=(10.93±0.19±0.58±2.73)% and B(B⃗Ds*+X)=(7.9±0.8±0.7±2.0)%, where the first error is statistical, the second is systematic, and the third is due to the Ds+→φπ+ branching fraction uncertainty. The production cross sections σ(e+e-→Ds+X)×B(Ds+→φπ+)=7.55±0.20±0.34pb and σ(e+e-→Ds*±X)×B(Ds+→φπ+)=5.8±0.7±0.5pb are measured at center-of-mass energies about 40 MeV below the Υ(4S) mass. The branching fractions ΣB(B⃗Ds(*)+D(*))=(5.07±0.14±0.30±1.27)% and ΣB(B⃗Ds*+D(*))=(4.1±0.2±0.4±1.0)% are determined from the Ds(*)+ momentum spectra. The mass difference m(Ds+)-m(D+)=98.4±0.1±0.3MeV/c2 is also measured.This work was supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the Swiss NSF, A. P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation

A systematic review of the effectiveness of self-management interventions in people with multiple sclerosis at improving depression, anxiety and quality of life.

BACKGROUND: Self-management interventions have become increasingly popular in the management of long-term health conditions; however, little is known about their impact on psychological well-being in people with Multiple Sclerosis (MS). PURPOSE: To examine the effectiveness of self-management interventions on improving depression, anxiety and health related quality of life in people with MS. METHOD: A structured literature search was conducted for the years 2000 to 2016. The review process followed the PRISMA guidelines, and is registered with PROSPERO (no. CRD42016033925). RESULTS: The review identified 10 RCT trials that fulfilled selection criteria and quality appraisal. Self-management interventions improved health-related quality of life in 6 out of 7 studies, with some evidence of improvement in depression and anxiety symptoms. CONCLUSION: Although the results are promising more robust evaluation is required in order to determine the effectiveness of self-management interventions on depression, anxiety and quality of life in people with MS. Evaluation of the data was impeded by a number of methodological issues including incomplete content and delivery information for the intervention and the exclusion of participants representing the disease spectrum. Recommendations are made for service development and research quality improvement

New Disturbing Trend in Antimicrobial Resistance of Gram-Negative Pathogens

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