67 research outputs found

    Spermidine/spermine N1-acetyltransferase specifically binds to the integrin α9 subunit cytoplasmic domain and enhances cell migration

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    The integrin α9β1 is expressed on migrating cells, such as leukocytes, and binds to multiple ligands that are present at sites of tissue injury and inflammation. α9β1, like the structurally related integrin α4β1, mediates accelerated cell migration, an effect that depends on the α9 cytoplasmic domain. α4β1 enhances migration through reversible binding to the adapter protein, paxillin, but α9β1-dependent migration is paxillin independent. Using yeast two-hybrid screening, we identified the polyamine catabolizing enzyme spermidine/spermine N1-acetyltransferase (SSAT) as a specific binding partner of the α9 cytoplasmic domain. Overexpression of SSAT increased α9β1-mediated migration, and small interfering RNA knockdown of SSAT inhibited this migration without affecting cell adhesion or migration that was mediated by other integrin cytoplasmic domains. The enzyme activity of SSAT is critical for this effect, because a catalytically inactive version did not enhance migration. We conclude that SSAT directly binds to the α9 cytoplasmic domain and mediates α9-dependent enhancement of cell migration, presumably by localized effects on acetylation of polyamines or of unidentified substrates

    Dysfunctional Tissue Correlates of Unrelated Naming Errors in Acute Left Hemisphere Stroke

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    Most naming error lesion-symptom mapping (LSM) studies have focused on semantic and/or phonological errors. Anomic individuals also produce unrelated word errors, which may be linked to semantic or modality-independent lexical deficits. To investigate the neural underpinnings of rarely-studied unrelated errors, we conducted LSM analyses in 100 individuals hospitalised with a left hemisphere stroke who completed imaging protocols and language assessments. We used least absolute shrinkage and selection operator regression to capture relationships between naming errors and dysfunctional brain tissue metrics (regional damage or hypoperfusion in vascular territories) in two groups: participants with and without impaired single-word auditory comprehension. Hypoperfusion—particularly within the parietal lobe—was an important error predictor, especially for the unimpaired group. In both groups, higher unrelated error proportions were associated with primarily ventral stream damage, the language route critical for processing meaning. Nonetheless, brain metrics implicated in unrelated errors were distinct from semantic error correlates

    Rapid Multi-Locus Sequence Typing Using Microfluidic Biochips

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    sequencing of 6–8 housekeeping loci to assign unique sequence types. In this work we adapted MLST to a rapid microfluidics platform in order to enhance speed and reduce laboratory labor time. isolated in this study from one location in Rockville, Maryland (0.04 substitutions per site) was found to be as great as the global collection of isolates.Biogeographical investigation of pathogens is only one of a panoply of possible applications of microfluidics based MLST; others include microbiologic forensics, biothreat identification, and rapid characterization of human clinical samples

    Childhood IQ and survival to 79: Follow-up of 94% of the Scottish Mental Survey 1947.

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    Objective To extend previous literature that suggests higher IQ in youth is associated with living longer. Previous studies have been unable to assess reliably whether the effect differs across sexes and ages of death, and whether the effect is graded across different levels of IQ. Methods We test IQ-survival associations in 94% of the near-entire population born in Scotland in 1936 who took an IQ test at age 11 (n = 70,805) and were traced in a 68-year follow-up. Results Higher IQ at age 11 years was associated with a lower risk of death (HR = 0.80, 95% CI = 0.79, 0.81). The decline in risk across categories of IQ scores was graded across the full range with the effect slightly stronger in women (HR = 0.79, 95% CI = 0.77, 0.80) than in men (HR = 0.82, 95% CI = 0.81, 0.84). Higher IQ had a significantly stronger association with death before and including age 65 (HR = 0.76, 95% CI = 0.74, 0.77) than in those participants who died at an older age (HR = 0.79, 95% CI = 0.78, 0.80). Conclusions Higher childhood IQ is associated with lower risk of all-cause mortality in both men and women. This is the only near-entire population study to date that examines the association between childhood IQ and mortality across most of the human life course

    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

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Quantifying fracture geometry with X-ray tomography: Technique of Iterative Local Thresholding (TILT) for 3D image segmentation

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    This paper presents a new method—the Technique of Iterative Local Thresholding (TILT)—for processing 3D X-ray computed tomography (xCT) images for visualization and quantification of rock fractures. The TILT method includes the following advancements. First, custom masks are generated by a fracture-dilation procedure, which significantly amplifies the fracture signal on the intensity histogram used for local thresholding. Second, TILT is particularly well suited for fracture characterization in granular rocks because the multi-scale Hessian fracture (MHF) filter has been incorporated to distinguish fractures from pores in the rock matrix. Third, TILT wraps the thresholding and fracture isolation steps in an optimized iterative routine for binary segmentation, minimizing human intervention and enabling automated processing of large 3D datasets. As an illustrative example, we applied TILT to 3D xCT images of reacted and unreacted fractured limestone cores. Other segmentation methods were also applied to provide insights regarding variability in image processing. The results show that TILT significantly enhanced separability of grayscale intensities, outperformed the other methods in automation, and was successful in isolating fractures from the porous rock matrix. Because the other methods are more likely to misclassify fracture edges as void and/or have limited capacity in distinguishing fractures from pores, those methods estimated larger fracture volumes (up to 80 %), surface areas (up to 60 %), and roughness (up to a factor of 2). These differences in fracture geometry would lead to significant disparities in hydraulic permeability predictions, as determined by 2D flow simulations

    A História da Alimentação: balizas historiográficas

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    Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema
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