360 research outputs found

    Postfledging Survival, Movements, and Dispersal of Ring Ouzels (Turdus torquatus)

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    We thank Invercauld Estate for cooperation with access to Glen Clunie. S. Redpath, J. Wilson, and S. Roos provided valuable comments on the manuscript. This study was funded by the Royal Society for the Protection of Birds, Scottish Natural Heritage, and the Cairngorms National Park Authority. J.L.L. was supported by the Natural Environment Research Council.Peer reviewedPublisher PD

    The protective effects of plasma gelsolin on stroke outcome in rats

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    <p>Abstract</p> <p>Background</p> <p>To date, recombinant tissue plasminogen activator (rtPA) is the only approved drug for ischemic stroke. It is intravenously administered functioning as a thrombolytic agent and is used to obtain reperfusion of the affected area of the brain. Excitotoxicity, inflammation and apoptosis are all involved in delayed neuronal death following stroke and offer multiple opportunities to intervene with neuroprotective agents. Gelsolin (GSN) is an actin- and calcium-binding protein mediating the disassembly of actin filaments and activity of calcium channels. It also functions as a regulator of apoptosis and inflammatory responses. This study tests the hypothesis that increasing the concentration of the form of GSN known as plasma GSN (pGSN) near an infarct will provide neuroprotection following ischemic stroke.</p> <p>Methods</p> <p>We induced middle cerebral artery occlusion (MCAO) in male rats via intracranial injection of endothelin-1 (ET-1), a potent vasoconstrictor, and then treated with local delivery of pGSN. Whole brain laser Doppler perfusion imaging was performed through the skull to assess MCAO effectiveness. Cylinder and vibrissae tests evaluated sensorimotor function before and 72 h after MCAO. Infarct volumes were examined 72 h after MCAO via 2, 3, 5-triphenyltetrazolium chloride (TTC) assay.</p> <p>Results</p> <p>Estimates of relative cerebral perfusion were significantly decreased in all groups receiving MCAO with no differences detected between treatments. Despite equivalent initial strokes, the infarct volume of the pGSN treatment group was significantly reduced compared with the untreated MCAO rats at 72 h. ET-1 induced significant deficits in both cylinder and vibrissae tests while pGSN significantly limited these deficits.</p> <p>Conclusion</p> <p>Gelsolin could be a promising drug for protection against neurodegeneration following ischemic stroke.</p

    Application of DEN refinement and automated model building to a difficult case of molecular-replacement phasing: the structure of a putative succinyl-diaminopimelate desuccinylase from Corynebacterium glutamicum.

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    Phasing by molecular replacement remains difficult for targets that are far from the search model or in situations where the crystal diffracts only weakly or to low resolution. Here, the process of determining and refining the structure of Cgl1109, a putative succinyl-diaminopimelate desuccinylase from Corynebacterium glutamicum, at ∼3 Å resolution is described using a combination of homology modeling with MODELLER, molecular-replacement phasing with Phaser, deformable elastic network (DEN) refinement and automated model building using AutoBuild in a semi-automated fashion, followed by final refinement cycles with phenix.refine and Coot. This difficult molecular-replacement case illustrates the power of including DEN restraints derived from a starting model to guide the movements of the model during refinement. The resulting improved model phases provide better starting points for automated model building and produce more significant difference peaks in anomalous difference Fourier maps to locate anomalous scatterers than does standard refinement. This example also illustrates a current limitation of automated procedures that require manual adjustment of local sequence misalignments between the homology model and the target sequence

    Preferential dust sources: a geomorphological classification designed for use in global dust-cycle models

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    We present a simple theoretical land-surface classification that can be used to determine the location and temporal behaviour of preferential sources of terrestrial dust emissions. The classification also provides information about the likely nature of the sediments, their erodibility and the likelihood that they will generate emissions under given conditions. The scheme is based on the dual notions of geomorphic type and connectivity between geomorphic units. We demonstrate that the scheme can be used to map potential modern-day dust sources in the Chihuahuan Desert, the Lake Eyre Basin and the Taklamakan. Through comparison with observed dust emissions, we show that the scheme provides a reasonable prediction of areas of emission in the Chihuahuan Desert and in the Lake Eyre Basin. The classification is also applied to point source data from the Sahara to enable comparison of the relative importance of different land surfaces for dust emissions. We indicate how the scheme could be used to provide an improved characterisation of preferential dust sources in global dust-cycle models

    Structure of the first representative of Pfam family PF04016 (DUF364) reveals enolase and Rossmann-like folds that combine to form a unique active site with a possible role in heavy-metal chelation.

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    The crystal structure of Dhaf4260 from Desulfitobacterium hafniense DCB-2 was determined by single-wavelength anomalous diffraction (SAD) to a resolution of 2.01 Å using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). This protein structure is the first representative of the PF04016 (DUF364) Pfam family and reveals a novel combination of two well known domains (an enolase N-terminal-like fold followed by a Rossmann-like domain). Structural and bioinformatic analyses reveal partial similarities to Rossmann-like methyltransferases, with residues from the enolase-like fold combining to form a unique active site that is likely to be involved in the condensation or hydrolysis of molecules implicated in the synthesis of flavins, pterins or other siderophores. The genome context of Dhaf4260 and homologs additionally supports a role in heavy-metal chelation

    Machine learning of neuroimaging for assisted diagnosis of cognitive impairment and dementia: A systematic review

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    pp. 519-535Los métodos avanzados de aprendizaje automático pueden ayudar a identificar el riesgo de demencia de la neuroimagen, pero su precisión hasta la fecha no está clara. Revisamos sistemáticamente la literatura, desde 2006 hasta finales de 2016, para los estudios de aprendizaje automático que diferencian el envejecimiento saludable de la demencia de varios tipos, evaluamos la calidad del estudio y comparamos la precisión en diferentes límites de enfermedades. De los 111 estudios relevantes, la mayoría evaluó la enfermedad de Alzheimer en comparación con los controles sanos, utilizando datos de la Iniciativa de neuroimagen AD, máquinas de vectores de soporte y solo secuencias ponderadas en T1. La precisión fue más alta para diferenciar la enfermedad de Alzheimer de los controles sanos y pobre para diferenciar los controles sanos versus deterioro cognitivo leve versus enfermedad de Alzheimer o conversores de deterioro cognitivo leve versus no conversores. La precisión aumentó con los tipos de datos combinados, pero no con la fuente de datos, el tamaño de la muestra o el método de aprendizaje automático. El aprendizaje automático todavía no distingue categorías de enfermedades clínicamente relevantes. Los conjuntos de datos más diversos, las combinaciones de diferentes tipos de datos y la estrecha integración clínica del aprendizaje automático ayudarían a avanzar en este campo.S

    Evaluating a complex research capacity-building intervention: reflections on an evaluation of the African Institutions Initiative

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    Increasing policy demand for realist evaluations of research and capacity-building programmes reflects a recognition of the management, governance and impact gains that can result from evaluation. However, the evidence base on how to successfully implement realist evaluations of complex interventions in international development efforts is scarce. We know little about the associated merits, limitations and ways to mitigate challenges. There is a need for reflective work which considers the methodology in context. This paper shares learning from the experience of conducting a realist, theory-of-change driven evaluation of the African Institutions Initiative, a Wellcome Trust funded programme which aimed to build sustainable health research capacity in Africa at institutional and network levels, across seven research consortia. We reflect on the key challenges experienced throughout the evaluation and recommend ways of managing them, highlight opportunities and critical success factors associated with this evaluation approach, as well as elaborate on alternative evaluation approaches

    Structure of a putative NTP pyrophosphohydrolase: YP_001813558.1 from Exiguobacterium sibiricum 255-15.

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    The crystal structure of a putative NTPase, YP_001813558.1 from Exiguobacterium sibiricum 255-15 (PF09934, DUF2166) was determined to 1.78 Å resolution. YP_001813558.1 and its homologs (dimeric dUTPases, MazG proteins and HisE-encoded phosphoribosyl ATP pyrophosphohydrolases) form a superfamily of all-α-helical NTP pyrophosphatases. In dimeric dUTPase-like proteins, a central four-helix bundle forms the active site. However, in YP_001813558.1, an unexpected intertwined swapping of two of the helices that compose the conserved helix bundle results in a `linked dimer' that has not previously been observed for this family. Interestingly, despite this novel mode of dimerization, the metal-binding site for divalent cations, such as magnesium, that are essential for NTPase activity is still conserved. Furthermore, the active-site residues that are involved in sugar binding of the NTPs are also conserved when compared with other α-helical NTPases, but those that recognize the nucleotide bases are not conserved, suggesting a different substrate specificity
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