223 research outputs found

    Modelling North American palaeo-subglacial lakes and their meltwater drainage pathways

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    This paper presents predictions of palaeo-subglacial lakes and their drainage pathways beneath the North American Ice Sheet during the last glaciation. We utilise data on the current topography and seafloor bathymetry, and elevation models of the ice- and ground-surface topography from data-calibrated glaciological modelling to calculate the hydraulic potential surface at the ice-sheets bed. Given that specific ice-surface elevations are only known from modelled outputs, and thus contain significant uncertainty, we utilise many such outputs to examine where on the bed that subglacial lakes are likely to have occurred. Our analysis demonstrates the potential for subglacial lake genesis, particularly beneath the former Cordilleran Ice Sheet; along the suture zone between the Laurentide and Cordilleran ice sheets; in Hudson Bay; in the Great Lake basins and deep trenches of the Canadian Archipelago. During the Last Glacial Maximum we suggest that at least 1000km of meltwater could have been stored subglacially. As the ice-sheet and the bed evolved subglacial lakes repeatedly formed and emptied, particularly in Hudson Bay and the suture zone between the Laurentide and Cordilleran ice sheets where lakes were characteristically broad and shallow (<10m deep). In contrast, the Cordilleran Ice Sheet was characterised by deep (up to ~90m) and persistent lake genesis. Significantly, similar distributions and modes of predicted subglacial lakes are obtained irrespective of the model or model run, which suggests the results are robust. Subglacial meltwater drainage varied between stable networks, typically associated with strong topographic controls, and convoluted networks that underwent considerable dynamism, including repeated meltwater network capture. These lake likelihood predictions could usefully form targets for detailed field and remote investigations and we hypothesise and explore the potential that numerous deposits and spillways previously interpreted as arising from ice-marginal lakes may have emanated from their subglacial cousins. © 2013 The Authors

    Alignment of Biological Sequences with Jalview

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    In this chapter, we introduce core functionality of the Jalview interactive platform for the creation, analysis, and publication of multiple sequence alignments. A workflow is described based on Jalview's core functions: from data import to figure generation, including import of alignment reliability scores from T-Coffee and use of Jalview from the command line. The accompanying notes provide background information on the underlying methods and discuss additional options for working with Jalview to perform multiple sequence alignment, functional site analysis, and publication of alignments on the web

    The periodic topography of ice stream beds: Insights from the Fourier spectra of mega-scale glacial lineations

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    Ice stream bed topography contains key evidence for the ways ice streams interact with, and are potentially controlled by, their beds. Here we present the first application of two-dimensional Fourier analysis to 22 marine and terrestrial topographies from 5 regions in Antarctica and Canada, with and without mega-scale glacial lineations (MSGLs). We find that the topography of MSGL-rich ice stream sedimentary beds is characterized by multiple, periodic wavelengths between 300 and 1200 m and amplitudes from decimeters to a few meters. This periodic topography is consistent with the idea that instability is a key element to the formation of MSGL bedforms. Dominant wavelengths vary among locations and, on one paleo ice stream bed, increase along the direction of ice flow by 1.7 ± 0.52% km−1. We suggest that these changes are likely to reflect pattern evolution via downstream wavelength coarsening, even under potentially steady ice stream geometry and flow conditions. The amplitude of MSGLs is smaller than that of other fluvial and glacial topographies but within the same order of magnitude. However, MSGLs are a striking component of ice stream beds because the topographic amplitude of features not aligned with ice flow is reduced by an order of magnitude relative to those oriented with the flow direction. This study represents the first attempt to automatically derive the spectral signatures of MSGLs. It highlights the plausibility of identifying these landform assemblages using automated techniques and provides a benchmark for numerical models of ice stream flow and subglacial landscape evolution.The research was funded by the NE/J004766/1 UK NERC New Investigator and a SAGES 728 PECRE grants awarded to MS

    Crystal structure of human XLF/Cernunnos reveals unexpected differences from XRCC4 with implications for NHEJ

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    The recently characterised 299-residue human XLF/Cernunnos protein plays a crucial role in DNA repair by non-homologous end joining (NHEJ) and interacts with the XRCC4–DNA Ligase IV complex. Here, we report the crystal structure of the XLF (1–233) homodimer at 2.3 Å resolution, confirming the predicted structural similarity to XRCC4. The XLF coiled-coil, however, is shorter than that of XRCC4 and undergoes an unexpected reverse in direction giving rise to a short distorted four helical bundle and a C-terminal helical structure wedged between the coiled-coil and head domain. The existence of a dimer as the major species is confirmed by size-exclusion chromatography, analytical ultracentrifugation, small-angle X-ray scattering and other biophysical methods. We show that the XLF structure is not easily compatible with a proposed XRCC4:XLF heterodimer. However, we demonstrate interactions between dimers of XLF and XRCC4 by surface plasmon resonance and analyse these in terms of surface properties, amino-acid conservation and mutations in immunodeficient patients. Our data are most consistent with head-to-head interactions in a 2:2:1 XRCC4:XLF:Ligase IV complex

    Activating mutations of the GNAQ gene: a frequent event in primary melanocytic neoplasms of the central nervous system

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    Primary melanocytic neoplasms of the central nervous system (CNS) are uncommon neoplasms derived from melanocytes that normally can be found in the leptomeninges. They cover a spectrum of malignancy grades ranging from low-grade melanocytomas to lesions of intermediate malignancy and overtly malignant melanomas. Characteristic genetic alterations in this group of neoplasms have not yet been identified. Using direct sequencing, we investigated 19 primary melanocytic lesions of the CNS (12 melanocytomas, 3 intermediate-grade melanocytomas, and 4 melanomas) for hotspot oncogenic mutations commonly found in melanocytic tumors of the skin (BRAF, NRAS, and HRAS genes) and uvea (GNAQ gene). Somatic mutations in the GNAQ gene at codon 209, resulting in constitutive activation of GNAQ, were detected in 7/19 (37%) tumors, including 6/12 melanocytomas, 0/3 intermediate-grade melanocytomas, and 1/4 melanomas. These GNAQ-mutated tumors were predominantly located around the spinal cord (6/7). One melanoma carried a BRAF point mutation that is frequently found in cutaneous melanomas (c.1799 T>A, p.V600E), raising the question whether this is a metastatic rather than a primary tumor. No HRAS or NRAS mutations were detected. We conclude that somatic mutations in the GNAQ gene at codon 209 are a frequent event in primary melanocytic neoplasms of the CNS. This finding provides new insight in the pathogenesis of these lesions and suggests that GNAQ-dependent mitogen-activated kinase signaling is a promising therapeutic target in these tumors. The prognostic and predictive value of GNAQ mutations in primary melanocytic lesions of the CNS needs to be determined in future studies

    Spillway-Induced Salmon Head Injury Triggers the Generation of Brain αII-Spectrin Breakdown Product Biomarkers Similar to Mammalian Traumatic Brain Injury

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    Recent advances in biomedical research have resulted in the development of specific biomarkers for diagnostic testing of disease condition or physiological risk. Of specific interest are αII-spectrin breakdown products (SBDPs), which are produced by proteolytic events in traumatic brain injury and have been used as biomarkers to predict the severity of injury in humans and other mammalian brain injury models. This study describes and demonstrates the successful use of antibody-based mammalian SBDP biomarkers to detect head injury in migrating juvenile Chinook salmon (Oncorhynchus tshawytscha) that have been injured during passage through high-energy hydraulic environments present in spillways under different operational configurations. Mortality and injury assessment techniques currently measure only near-term direct mortality and easily observable acute injury. Injury-based biomarkers may serve as a quantitative indicator of subacute physical injury and recovery, and aid hydropower operators in evaluation of safest passage configuration and operation actions for migrating juvenile salmonids. We describe a novel application of SBDP biomarkers for head injury for migrating salmon. To our knowledge, this is the first documented cross-over use of a human molecular biomarker in a wildlife and operational risk management scenario

    Supervised multivariate analysis of sequence groups to identify specificity determining residues

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    <p>Abstract</p> <p>Background</p> <p>Proteins that evolve from a common ancestor can change functionality over time, and it is important to be able identify residues that cause this change. In this paper we show how a supervised multivariate statistical method, Between Group Analysis (BGA), can be used to identify these residues from families of proteins with different substrate specifities using multiple sequence alignments.</p> <p>Results</p> <p>We demonstrate the usefulness of this method on three different test cases. Two of these test cases, the Lactate/Malate dehydrogenase family and Nucleotidyl Cyclases, consist of two functional groups. The other family, Serine Proteases consists of three groups. BGA was used to analyse and visualise these three families using two different encoding schemes for the amino acids.</p> <p>Conclusion</p> <p>This overall combination of methods in this paper is powerful and flexible while being computationally very fast and simple. BGA is especially useful because it can be used to analyse any number of functional classes. In the examples we used in this paper, we have only used 2 or 3 classes for demonstration purposes but any number can be used and visualised.</p

    Screen-based media use clusters are related to other activity behaviours and health indicators in adolescents

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    Background: Screen-based media (SBM) occupy a considerable portion of young peoples’ discretionary leisure time. The aim of this paper was to investigate whether distinct clusters of SBM use exist, and if so, to examine the relationship of any identified clusters with other activity/sedentary behaviours and physical and mental health indicators.Methods: The data for this study come from 643 adolescents, aged 14 years, who were participating in the longitudinal Western Australian Pregnancy Cohort (Raine) Study through May 2003 to June 2006. Time spent on SBM, phone use and reading was assessed using the Multimedia Activity Recall for Children and Adults. Height, weight, muscle strength were measured at a clinic visit and the adolescents also completed questionnaires on their physical activity and psychosocial health. Latent class analysis (LCA) was used to analyse groupings of SBM use.Results: Three clusters of SBM use were found; C1 ‘instrumental computer users’ (high email use, general computer use), C2 ‘multi-modal e-gamers’ (both high console and computer game use) and C3 ‘computer e-gamers’ (high computer game use only). Television viewing was moderately high amongst all the clusters. C2 males took fewer steps than their male peers in C1 and C3 (-13,787/week, 95% CI: -4619 to -22957, p = 0.003 and -14,806, 95% CI: -5,306 to -24,305, p = 0.002) and recorded less MVPA than the C1 males (-3.5 h, 95% CI: -1.0 to -5.9, p = 0.005). There was no difference in activity levels between females in clusters C1 and C3.Conclusion: SBM use by adolescents did cluster and these clusters related differently to activity/sedentary behaviours and both physical and psychosocial health indicators. It is clear that SBM use is not a single construct and future research needs to take consideration of this if it intends to understand the impact SBM has on health

    TRY plant trait database - enhanced coverage and open access

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    Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives
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