279 research outputs found

    Early phenology and growth trait variation in closely related European pine species

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    Closely related taxa occupying different environments are valuable systems for studying evolution. In this study, we examined differences in early phenology (bud set, bud burst) and early growth in a common garden trial of closely related pine species: Pinus sylvestris, P. mugo, and P. uncinata. Seeds for the trial were sourced from populations across the ranges of each species in Europe. Over first 4 years of development, clear differences were observed between species, while the most significant intraspecific differentiation was observed among plants from P. sylvestris populations from continental European locations. Trait differences within P. sylvestris were highly correlated with altitude and latitude of the site of origin. Meanwhile, P. mugo populations from the Carpathians had the earliest bud set and bud flush compared to other populations of the species. Overall, populations from the P. mugo complex from heterogeneous mountain environments and P. sylvestris from the Scottish Highlands showed the highest within-population variation for the focal traits. Although the three species have been shown to be genetically highly similar, this study reveals large differences in key adaptive traits both among and within species

    Spectroscopy of Heavy Mesons Expanded in 1/m_Q

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    Operating just once with the naive Foldy-Wouthuysen-Tani transformation on the relativistic Fermi-Yang equation for QqˉQ\bar q bound states described by the semi-relativistic Hamiltonian which includes Coulomb-like as well as confining scalar potentials, we have calculated heavy meson mass spectra of D and B together with higher spin states. Based on the formulation recently proposed, their masses and wave functions are expanded up to the second order in 1/mQ1/m_Q with a heavy quark mass mQm_Q and the lowest order equation is examined carefully to obtain a complete set of eigenfunctions for the Schr\"odinger equation. Heavy quark effective theory parameters, Λˉ\bar\Lambda, λ1\lambda_1, and λ2\lambda_2, are also determined at the first and second order in 1/mQ1/m_Q.Comment: 49 pages, 5 epsf figure

    Stellar structure and compact objects before 1940: Towards relativistic astrophysics

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    Since the mid-1920s, different strands of research used stars as "physics laboratories" for investigating the nature of matter under extreme densities and pressures, impossible to realize on Earth. To trace this process this paper is following the evolution of the concept of a dense core in stars, which was important both for an understanding of stellar evolution and as a testing ground for the fast-evolving field of nuclear physics. In spite of the divide between physicists and astrophysicists, some key actors working in the cross-fertilized soil of overlapping but different scientific cultures formulated models and tentative theories that gradually evolved into more realistic and structured astrophysical objects. These investigations culminated in the first contact with general relativity in 1939, when J. Robert Oppenheimer and his students George Volkoff and Hartland Snyder systematically applied the theory to the dense core of a collapsing neutron star. This pioneering application of Einstein's theory to an astrophysical compact object can be regarded as a milestone in the path eventually leading to the emergence of relativistic astrophysics in the early 1960s.Comment: 83 pages, 4 figures, submitted to the European Physical Journal

    Treating childhood pneumonia in hard-to-reach areas: A model-based comparison of mobile clinics and community-based care

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    BACKGROUND: Where hard-to-access populations (such as those living in insecure areas) lack access to basic health services, relief agencies, donors, and ministries of health face a dilemma in selecting the most effective intervention strategy. This paper uses a decision mathematical model to estimate the relative effectiveness of two alternative strategies, mobile clinics and fixed community-based health services, for antibiotic treatment of childhood pneumonia, the world's leading cause of child mortality. METHODS: A "Markov cycle tree" cohort model was developed in Excel with Visual Basic to compare the number of deaths from pneumonia in children aged 1 to 59 months expected under three scenarios: 1) No curative services available, 2) Curative services provided by a highly-skilled but intermittent mobile clinic, and 3) Curative services provided by a low-skilled community health post. Parameter values were informed by literature and expert interviews. Probabilistic sensitivity analyses were conducted for several plausible scenarios. RESULTS: We estimated median pneumonia-specific under-5 mortality rates of 0.51 (95% credible interval: 0.49 to 0.541) deaths per 10,000 child-days without treatment, 0.45 (95% CI: 0.43 to 0.48) with weekly mobile clinics, and 0.31 (95% CI: 0.29 to 0.32) with CHWs in fixed health posts. Sensitivity analyses found the fixed strategy superior, except when mobile clinics visited communities daily, where rates of care-seeking were substantially higher at mobile clinics than fixed posts, or where several variables simultaneously differed substantially from our baseline assumptions. CONCLUSIONS: Current evidence does not support the hypothesis that mobile clinics are more effective than CHWs. A CHW strategy therefore warrants consideration in high-mortality, hard-to-access areas. Uncertainty remains, and parameter values may vary across contexts, but the model allows preliminary findings to be updated as new or context-specific evidence becomes available. Decision analytic modelling can guide needed field-based research efforts in hard-to-access areas and offer evidence-based insights for decision-makers

    In vitro nuclear interactome of the HIV-1 Tat protein

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    <p>Abstract</p> <p>Background</p> <p>One facet of the complexity underlying the biology of HIV-1 resides not only in its limited number of viral proteins, but in the extensive repertoire of cellular proteins they interact with and their higher-order assembly. HIV-1 encodes the regulatory protein Tat (86–101aa), which is essential for HIV-1 replication and primarily orchestrates HIV-1 provirus transcriptional regulation. Previous studies have demonstrated that Tat function is highly dependent on specific interactions with a range of cellular proteins. However they can only partially account for the intricate molecular mechanisms underlying the dynamics of proviral gene expression. To obtain a comprehensive nuclear interaction map of Tat in T-cells, we have designed a proteomic strategy based on affinity chromatography coupled with mass spectrometry.</p> <p>Results</p> <p>Our approach resulted in the identification of a total of 183 candidates as Tat nuclear partners, 90% of which have not been previously characterised. Subsequently we applied <it>in silico </it>analysis, to validate and characterise our dataset which revealed that the Tat nuclear interactome exhibits unique signature(s). First, motif composition analysis highlighted that our dataset is enriched for domains mediating protein, RNA and DNA interactions, and helicase and ATPase activities. Secondly, functional classification and network reconstruction clearly depicted Tat as a polyvalent protein adaptor and positioned Tat at the nexus of a densely interconnected interaction network involved in a range of biological processes which included gene expression regulation, RNA biogenesis, chromatin structure, chromosome organisation, DNA replication and nuclear architecture.</p> <p>Conclusion</p> <p>We have completed the <it>in vitro </it>Tat nuclear interactome and have highlighted its modular network properties and particularly those involved in the coordination of gene expression by Tat. Ultimately, the highly specialised set of molecular interactions identified will provide a framework to further advance our understanding of the mechanisms of HIV-1 proviral gene silencing and activation.</p

    Microbiome to Brain:Unravelling the Multidirectional Axes of Communication

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    The gut microbiome plays a crucial role in host physiology. Disruption of its community structure and function can have wide-ranging effects making it critical to understand exactly how the interactive dialogue between the host and its microbiota is regulated to maintain homeostasis. An array of multidirectional signalling molecules is clearly involved in the host-microbiome communication. This interactive signalling not only impacts the gastrointestinal tract, where the majority of microbiota resides, but also extends to affect other host systems including the brain and liver as well as the microbiome itself. Understanding the mechanistic principles of this inter-kingdom signalling is fundamental to unravelling how our supraorganism function to maintain wellbeing, subsequently opening up new avenues for microbiome manipulation to favour desirable mental health outcome

    Reinforcement, Dopamine and Rodent Models in Drug Development for ADHD

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