The study of biodiversity spans many disciplines and includes data pertaining to species distributions and abundances, genetic sequences, trait measurements, and ecological niches, complemented by ...information on collection and measurement protocols. A review of the current landscape of metadata standards and ontologies in biodiversity science suggests that existing standards such as the Darwin Core terminology are inadequate for describing biodiversity data in a semantically meaningful and computationally useful way. Existing ontologies, such as the Gene Ontology and others in the Open Biological and Biomedical Ontologies (OBO) Foundry library, provide a semantic structure but lack many of the necessary terms to describe biodiversity data in all its dimensions. In this paper, we describe the motivation for and ongoing development of a new Biological Collections Ontology, the Environment Ontology, and the Population and Community Ontology. These ontologies share the aim of improving data aggregation and integration across the biodiversity domain and can be used to describe physical samples and sampling processes (for example, collection, extraction, and preservation techniques), as well as biodiversity observations that involve no physical sampling. Together they encompass studies of: 1) individual organisms, including voucher specimens from ecological studies and museum specimens, 2) bulk or environmental samples (e.g., gut contents, soil, water) that include DNA, other molecules, and potentially many organisms, especially microbes, and 3) survey-based ecological observations. We discuss how these ontologies can be applied to biodiversity use cases that span genetic, organismal, and ecosystem levels of organization. We argue that if adopted as a standard and rigorously applied and enriched by the biodiversity community, these ontologies would significantly reduce barriers to data discovery, integration, and exchange among biodiversity resources and researchers.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Using satellite remote sensing, this study aims to assess the validity of upscaling ground‐based structural observations of small valley glaciers, to larger‐scale ice masses that are too vast or ...inaccessible for field‐study or ground‐truthing. Focusing on four adjacent valley glaciers on Bylot Island, Nunavut, Arctic Canada, we establish that ground‐based structural observations from two smaller (Stagnation and Fountain Glaciers) can be used to interpret the structures visible in optical satellite imagery in two much larger glaciers (Aktineq and Sermilik Glaciers). All the glaciers investigated have prominent longitudinal lineations, which are interpreted from ground observations to be longitudinal foliation. Other structures that were identified include primary stratification, crevasses, crevasse traces, and thrust‐faults. Strong longitudinal foliation is concentrated at flow‐unit boundaries, with differential ablation of ice facies commonly resulting in a ridge‐and‐furrow supraglacial topography that controls supraglacial streams and debris concentrations. Consequently, areas of strong foliation appear darker than areas of weak foliation in satellite imagery. As coarser resolution imagery is utilized to map large‐scale ice masses, sub‐pixel structural information is lost. Individual lineations mapped in coarser resolution imagery therefore probably comprise groups of clustered foliation at the sub‐pixel scale. Lateral narrowing measurements and calculated one‐dimensional strain across zones of longitudinal foliation are assessed as a tool for identifying large‐scale surface strain patterns, in particular large‐scale pure shear regimes. These one‐dimensional strain measurements suggest that flow‐unit boundaries are areas that undergo considerable cumulative strains. The upscaling approach used here can be applied to the largest ice masses, notably the Antarctic Ice Sheet.
In this study, the validity of upscaling ground‐based structural glaciological observations to inaccessible larger‐scale ice masses through satellite remote sensing is assessed. Coarser resolution imagery, commonly used for mapping large spatial areas, clusters information at the sub‐pixel scale, resulting in visible features that comprise groups of structures with individual dimensions less than the image resolution. Nevertheless, remote sensing‐based studies remain valid as wide‐scale dynamic information is shown to be preserved in the clustered structures.
X-linked Dystonia-Parkinsonism (XDP) is a Mendelian neurodegenerative disease that is endemic to the Philippines and is associated with a founder haplotype. We integrated multiple genome and ...transcriptome assembly technologies to narrow the causal mutation to the TAF1 locus, which included a SINE-VNTR-Alu (SVA) retrotransposition into intron 32 of the gene. Transcriptome analyses identified decreased expression of the canonical cTAF1 transcript among XDP probands, and de novo assembly across multiple pluripotent stem-cell-derived neuronal lineages discovered aberrant TAF1 transcription that involved alternative splicing and intron retention (IR) in proximity to the SVA that was anti-correlated with overall TAF1 expression. CRISPR/Cas9 excision of the SVA rescued this XDP-specific transcriptional signature and normalized TAF1 expression in probands. These data suggest an SVA-mediated aberrant transcriptional mechanism associated with XDP and may provide a roadmap for layered technologies and integrated assembly-based analyses for other unsolved Mendelian disorders.
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•Genome assembly narrows the causal XDP locus to TAF1•An XDP-specific SVA insertion causes intron retention and reduced expression of TAF1•CRISPR/Cas9 excision of SVA rescues aberrant splicing and TAF1 expression in XDP•Expression profiling implicates neurodevelopment and dystonia pathways in XDP
A Mendelian form of dystonia arises from altered splicing and intron retention within a general transcription factor.
The insulin receptor (IR) and the homologous Type 1 insulin-like growth factor receptor (IGF-1R) are cell-surface tyrosine kinase receptors that effect signaling within the respective pathways of ...glucose metabolism and normal human growth. While ligand binding to these receptors is assumed to result in a structural transition within the receptor ectodomain that then effects signal transduction across the cell membrane, little is known about the molecular detail of these events. Presented here are small-angle X-ray scattering data obtained from the IR and IGF-1R ectodomains in solution. We show that, in solution, the ectodomains of IR and IGF-1R have a domain disposition that is very similar to that seen in the crystal structure of the ectodomain of IR, despite the constituent domains being in relatively sparse contact and potentially mobile. We also show that the IGF-1R ectodomain is capable of binding up to three molecules of IGF-1 in solution, with surprisingly little apparent change in relative domain disposition compared to the apo form. While the observed 3:1 ligand-binding stoichiometry appears to contradict earlier explanations of the absence of a bell-shaped dose–response curve for IGF-1R in ligand displacement assays, it is readily understood in the context of the harmonic oscillator model of the negative cooperativity of ligand binding to IGF-1R. Taken together, our findings suggest that the structural movements within these receptors upon ligand binding are small and are possibly limited to local rotation of domains.
The forkhead transcription factor gene
FOXC1 (formerly
FKHL7) is responsible for a number of glaucoma phenotypes in families in which the disease maps to 6p25, although mutations have not been found ...in all families in which the disease maps to this region. In a large pedigree with iris hypoplasia and glaucoma mapping to 6p25 (peak LOD score 6.20 recombination fraction 0 at D6S967), no
FOXC1 mutations were detected by direct sequencing. However, genotyping with microsatellite repeat markers suggested the presence of a chromosomal duplication that segregated with the disease phenotype. The duplication was confirmed in affected individuals by FISH with markers encompassing
FOXC1. These results provide evidence of gene duplication causing developmental disease in humans, with increased gene dosage of either
FOXC1 or other, as yet unknown genes within the duplicated segment being the probable mechanism responsible for the phenotype.
Summary Many patients with asthma remain symptomatic with impaired airway function on inhaled steroids. This study investigates the relationship between the clinical effect seen in response to ...additional treatment and the effect on airway inflammatory indices. Seventy-five adult asthmatic patients, incompletely controlled on 800 mcg budesonide/day, were randomised following a 4 week run-in period, to a double-blind, multi-centre controlled clinical trial of doubling inhaled corticosteroid (budesonide 1600 mcg/day) or adding 10 mg montelukast for 12 weeks. Induced sputum was collected at baseline and end of treatment and analysed for eosinophil and neutrophil percentages, leukotrienes C 4 , D 4 and E 4 , IL-8, Eosinophil Cationic Protein (ECP) and histamine. Sputum evidence of inflammation ( ⩾ 2.0 % eosinophils) was seen in only 29% of these patients and the percentage of eosinophils and other markers of airway inflammation did not change over the study period in either treatment group. There were significant improvements in am PEF (montelukast: 31.7 L/min, budesonide: 32.3 L/min) and quality of life with both treatments. We conclude that while both treatments showed similar improvements in lung function and quality of life, there was no evidence from these sputum markers measured that the effects were mediated via a reduction in airway inflammation or that the level of pre-treatment markers was associated with outcome.
The meniscus is a fibrocartilaginous tissue uniquely adapted to enable load transmission in the knee. Although the meniscus was once considered a useless remnant of joint formation, removal of all or ...part of the meniscus initiates osteoarthritis. Surgical repair methods focus on fragment stabilization or biologic enhancement of healing. An alternative approach based on tissue-engineering principles involves the development of new materials for implantation. Our meniscus tissue-engineering efforts aim to recapitulate the architectural features and mechanical anisotropies essential to native tissue function. We use a novel scaffold production technology called electrospinning, in which organized three-dimensional arrays of ultrafine biodegradable fibers are generated. Using these scaffolds as micropatterns for directed growth, we have generated constructs with mechanical properties and architectural features comparable to native meniscus. This review details our progress and outlines the remaining hurdles that must be addressed to translate this work into clinical implementation.
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