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At least 433 records · Page 24Linked to original sources

The locus of repetition priming of spoken word production.

Naming of a pictured object is substantially facilitated when the name has recently been produced in response to a definition or read aloud. The first experiment shows this to be so when over one hundred trials have intervened, and when the subjects can name the pictures quickly and accurately in the absence of priming. The locus of the effect must be in lexicalization processes subsequent to picture identification and is unlikely to be mediated by recovery of an episodic trace. Two further experiments show that prior production of a homophone of the object's name is not an effective prime, (although slower responses are somewhat facilitated when the homophones are spelled the same). Hence the facilitation observed for repeated production of the same word cannot be associated with the repetition of the phonological form per se. We conclude that the facilitation must be associated with retrieval of the semantic specification or the process of mapping of that specification to its associated phonological representation.

Adolescent↗

Finding the Missing Link between Landscape Structure and Population Dynamics: A Spatially Explicit Perspective.

We construct and explore a general modeling framework that allows for a systematic investigation of the impact of changes in landscape structure on population dynamics. The essential parts of the framework are a landscape generator with independent control over landscape composition and physiognomy, an individual-based spatially explicit population model that simulates population dynamics within heterogeneous landscapes, and scale-dependent landscape indices that depict the essential aspects of landscape that interact with dispersal and demographic processes. Landscape maps are represented by a grid of [Formula: see text] cells and consist of good-quality, poor-quality, or uninhabitable matrix habitat cells. The population model was shaped in accordance to the biology of European brown bears (Ursus arctos), and demographic parameters were adjusted to yield a source-sink configuration. Results obtained with the spatially explicit model do not confirm results of earlier nonspatial source-sink models where addition of sink habitat resulted in a decrease of total population size because of dilution of high-quality habitat. Our landscape indices, which describe scale-dependent correlation between and within habitat types, were able to explain variations in variables of population dynamics (mean number of females with sink home ranges, mean number of females with source home ranges, and mean dispersal distance) caused by different landscape structure. When landscape structure changed, changes in these variables generally followed the corresponding change of an appropriate landscape index in a linear way. Our general approach incorporates source-sink dynamics as well as metapopulation dynamics, and the population model can easily be modified for other species groups.

habitat connectivity↗

Retinoic acid synthesis in the postnatal mouse brain marks distinct developmental stages and functional systems.

Retinoic acid (RA) affects development and function of the brain, but little is known about how much is made locally and where it is distributed. To identify RA-sensitive neural processes, we mapped the RA-synthesizing retinaldehyde dehydrogenases (RALDHs) during postnatal brain formation of the mouse. High and stable RALDH expressions mark the basal ganglia, olfactory bulbs, hippocampus and auditory afferents as major sites of RA actions in the functional brain. During the early postnatal period, transient and very high RALDH3 expressions distinguish two developmental events: (i) the colonization of the nucleus accumbens and the olfactory bulbs by neuronal precursors and (ii) the maturation of selected parts of the cerebral cortex. In the cortex, RALDH3 is transiently activated in postmigratory layer II/III neurons during formation of their dendritic arbors and it is transported in their axons across the corpus callosum. RALDH3-expressing cortical regions include most of the limbic lobe, with strongest expression in the anterior cingulate cortex, medial and lateral secondary visual cortices, auditory cortical areas, the secondary motor cortex and some association areas. The transient cortical expression points to a brief RA-critical period during differentiation of the cortical network that serves in the coordination of sensory-motor activity with emotional and recently learned information.

Aldehyde Oxidoreductases↗

Organizational re-engineering using systems modelling: rediscovering the physics of the health service.

This paper explores the general role of systems modelling and its specific use in the UK National Health Service for providing a balanced overview of change management which links organizational structure, strategy, and process. The maps and modelling tools of the method are described, together with an outline of how they can be used to simulate and test alternative interventions in complex organizations and to create a management focus on generic insights, accelerated business learning, and improved financial performance. A case study involving the use of systems modelling at the interface between the health service and community care is presented as a specific example of the method in action.

Community Health Services↗

A novel bipartite splicing enhancer modulates the differential processing of the human fibronectin EDA exon.

EDA is a facultative type III homology of human fibronectin encoded by an alternative spliced exon. The EDA+ and EDA- mRNA forms show a cell type specific distribution with their relative proportion varying during development, aging and oncogenic transformation. We have previously demonstrated that an 81 bp nucleotide sequence within the exon itself is essential for differential RNA processing. Fine mapping of cis acting elements within this region has been carried out to identify possible target sites for the modulation of alternative splicing. There are at least two short nucleotide sequences involved. Element A (GAAGAAGA) is a positive modulator for the recognition of the exon, its deletion results in constitutive exclusion of the EDA exon. Element B (CAAGG) is a negative modulator for exon recognition, its deletion results in constitutive inclusion of the EDA exon. This bipartite structure of the splicing enhancer is a novel feature of the mammalian exons.

Alternative Splicing↗

Desynchronization in coupled systems with quasiperiodic driving

We describe the development of coexisting attractors in coupled quasiperiodically forced maps. The process of loss of complete synchronization in the systems, which individually demonstrates strange nonchaotic behavior, is studied. With this process, the complex structure of the basin of attraction is observed.

Journal Article↗

The Uppsala Electron-Density Server.

The Uppsala Electron Density Server (EDS; http://eds.bmc.uu.se/) is a web-based facility that provides access to electron-density maps and statistics concerning the fit of crystal structures and their maps. Maps are available for approximately 87% of the crystallographic Protein Data Bank (PDB) entries for which structure factors have been deposited and for which straightforward map calculations succeed in reproducing the published R value to within five percentage points. Here, an account is provided of the methods that are used to generate the information contained in the server. Some of the problems that are encountered in the map-generation process as well as some spin-offs of the project are also discussed.

Computational Biology↗

Distribution of functional glutamate and GABA receptors on hippocampal pyramidal cells and interneurons.

The distribution of functional neurotransmitter receptors is an important determinant of neuronal information processing. To map the location of functional glutamate and GABA receptors on individual hippocampal neurons, we photolyzed "caged" glutamate and GABA while measuring the electrical currents resulting from activation of these receptors. Responses to uncaged neurotransmitters were spatially nonuniform and varied according to the type of receptor and type of neuron. Every region of CA1 pyramidal cells responded to glutamate and GABA, but glutamate and GABA receptors increased in density along the length of their distal dendrites. Similar gradients of glutamate receptors were found in stratum radiatum interneurons, while GABA responses were detectable only in the perisomatic region of these interneurons. These regional variations in receptor distribution indicate the selective targeting of receptors on central neurons and may reflect a mechanism for local regulation of synaptic efficacy.

2-Amino-5-phosphonovalerate↗

Scintigraphic assessment of regional cardiac adrenergic innervation.

To assess the feasibility of noninvasively imaging the regional distribution of myocardial sympathetic innervation, we evaluated the distribution of sympathetic nerve endings, using 123I metaiodobenzylguanidine (MIBG), and compared this with the distribution of myocardial perfusion, using 201Tl. Twenty dogs were studied: 11 after regional denervation, and nine as controls. Regional denervation was done by left stellate ganglion removal, right stellate ganglion removal, and application of phenol to the epicardial surface. Computer-processed functional maps displayed the relative distribution of MIBG and thallium in multiple projections in vivo and excised heart slices in all animals. In six animals, dual isotope emission computed tomograms were acquired in vivo. Tissue samples taken from innervated and denervated regions of the MIBG images were analyzed for norepinephrine content to validate image findings. Normal controls showed homogeneous and parallel distributions of MIBG and thallium in the major left ventricular mass. In the left stellectomized hearts, MIBG was reduced relative to thallium in the posterior left ventricle; whereas in right stellectomized hearts, reduced MIBG was in the anterior left ventricle. Phenol-painted hearts showed a broad area of decreased MIBG extending beyond the area of phenol application. In both stellectomized and phenol-painted hearts, thallium distribution remained homogeneous and normal. Norepinephrine content was greater in regions showing normal MIBG (550 +/- 223 ng/g) compared with regions showing reduced MIBG (39 +/- 44 ng/g) (p less than 0.001), confirming regional denervation. Combined MIBG-thallium functional maps display the regional distribution of sympathetic innervation. This new ability to noninvasively map the distribution of sympathetic nerves with simultaneous comparison to regional perfusion may provide important new insights into mechanisms, whereby an imbalance in sympathetic activity may relate to clinical disorders.

3-Iodobenzylguanidine↗

Hi5+: systematic development of a family intervention to increase fruit and vegetable intake.

This article describes the development of a peer-led home-based intervention to increase fruit and vegetable (FV) intake and family interaction among fourth graders and their families. Hi5+ intervention content and delivery strategies were developed using two complementary processes: cognitive mapping (CM), a consumer-based approach to identifying salient issues, and intervention mapping (IM), a comprehensive planning model. Step 1 involved creating plans to guide the design, implementation, and evaluation of Hi5+. We delineated our performance objectives and then prioritized those determinants we felt were most salient and changeable. Step 2 involved selecting and utilizing cognitive and behavioral theory constructs to develop intervention methods and strategies. Step 3 involved designing and pilot testing the instructional materials and other intervention components. Step 4 entailed developing plans for program adoption and implementation, while the final step (Step 5) involved creating a comprehensive evaluation plan. Implications of this multistep approach to intervention development are discussed.

Adult↗

Improving the accuracy of protein secondary structure prediction using structural alignment.

BACKGROUND: The accuracy of protein secondary structure prediction has steadily improved over the past 30 years. Now many secondary structure prediction methods routinely achieve an accuracy (Q3) of about 75%. We believe this accuracy could be further improved by including structure (as opposed to sequence) database comparisons as part of the prediction process. Indeed, given the large size of the Protein Data Bank (>35,000 sequences), the probability of a newly identified sequence having a structural homologue is actually quite high. RESULTS: We have developed a method that performs structure-based sequence alignments as part of the secondary structure prediction process. By mapping the structure of a known homologue (sequence ID >25%) onto the query protein's sequence, it is possible to predict at least a portion of that query protein's secondary structure. By integrating this structural alignment approach with conventional (sequence-based) secondary structure methods and then combining it with a "jury-of-experts" system to generate a consensus result, it is possible to attain very high prediction accuracy. Using a sequence-unique test set of 1644 proteins from EVA, this new method achieves an average Q3 score of 81.3%. Extensive testing indicates this is approximately 4-5% better than any other method currently available. Assessments using non sequence-unique test sets (typical of those used in proteome annotation or structural genomics) indicate that this new method can achieve a Q3 score approaching 88%. CONCLUSION: By using both sequence and structure databases and by exploiting the latest techniques in machine learning it is possible to routinely predict protein secondary structure with an accuracy well above 80%. A program and web server, called PROTEUS, that performs these secondary structure predictions is accessible at http://wishart.biology.ualberta.ca/proteus. For high throughput or batch sequence analyses, the PROTEUS programs, databases (and server) can be downloaded and run locally.

Algorithms↗

Voxel-based detection of white matter abnormalities in mild Alzheimer disease.

OBJECTIVE: To detect white matter abnormalities in patients with mild Alzheimer disease (AD) by diffusion tensor imaging and to determine their topographic relationship with gray matter atrophy. METHODS: Thirteen patients with mild AD and 16 normal age-matched volunteers underwent diffusion tensor imaging and three-dimensional spoiled gradient-recalled sequence scanning. Voxel-based morphometry was conducted to detect regions of gray matter atrophy in the AD group relative to the control group. Fractional anisotropy (FA) maps were processed using SPM2 to make voxel-wise comparison of anisotropy in whole brain between the two groups. The relationship between locations of abnormalities in the white and gray matter was examined. RESULTS: Significant reductions in anisotropy were found in the white matter of both medial temporal lobes, bilateral temporal stems, bilateral superior longitudinal fasciculi, bilateral internal capsules, and cerebral peduncles, as well as the white matter of left middle temporal gyrus and right superior parietal lobule, the body and genu of the corpus callosum, and the right lateral capsule in patients with AD. Although the decrease in FA was consistent with cortical volumetric reduction in both temporal lobes, the widespread involvement of bilateral superior longitudinal fasciculi was dominant in these white matter findings. CONCLUSIONS: Voxel-wise comparison of whole-brain anisotropy revealed widely distributed disintegration of white matter in mild Alzheimer disease (AD). The white matter shows a different pattern of degeneration from gray matter and may be an independent factor in the progress of AD.

Aged↗

Quantitative flow analysis around aquatic animals using laser sheet particle image velocimetry

Two alternative particle image velocimetry (PIV) methods have been developed, applying laser light sheet illumination of particle-seeded flows around marine organisms. Successive video images, recorded perpendicular to a light sheet parallel to the main stream, were digitized and processed to map the flow velocity in two-dimensional planes. In particle tracking velocimetry (PTV), displacements of single particles in two subsequent images were determined semi-automatically, resulting in flow diagrams consisting of non-uniformly distributed velocity vectors. Application of grid-cell averaging resulted in flow field diagrams with uniform vector distribution. In sub-image correlation PIV (SCPIV), repetitive convolution filtering of small sub-areas of two subsequent images resulted in automatic determination of cross-correlation peaks, yielding flow field diagrams with regularly spaced velocity vectors. In both PTV and SCPIV, missing values, caused by incomplete particle displacement information in some areas of the images or due to rejection of some erroneous vectors by the vector validation procedure, were interpolated using a two-dimensional spline interpolation technique. The resultant vector flow fields were used to study the spatial distribution of velocity, spatial acceleration, vorticity, strain and shear. These flow fields could also be used to test for flow in the third dimension by studying the divergence, and to detect the presence and location of vortices. The results offer detailed quantitative descriptions of the flow morphology and can be used to assess dissipated energy. The versatile character of the technique makes it applicable to a wide range of fluid mechanical subjects within biological research. So far it has been successfully applied to map the flow around swimming copepods, fish larvae and juvenile fish and the ventilation current of a tube-living shrimp.

Journal Article↗

Phase-stepped gauge block interferometry using a frequency-tunable visible laser diode.

Frequency changes induced by bias or temperature modulation of injection diode lasers can provide an economical and effective method of applying phase-stepping interferometry to optical metrology. However, the intrinsic frequency instability of these devices limits their use in gauge block interferometry where precise and repeatable phase steps must be maintained simultaneously on two discontinuous surfaces and over relatively long path lengths. We demonstrate a method using a visible injection diode laser, the frequency of which is locked by using a Fabry-Perot interferometer. Small changes to the length of the Fabry-Perot interferometer shift the frequency of the laser producing proportional and repeatable phase steps to the gauge block interferogram. This method has been successfully implemented with a Fizeau-type gauge block interferometer with a phase measurement resolution of 0.005 lambda. The phase data are then processed to map the surface form of gauge blocks up to 100 mm in length and to objectively assess surface shape parameters.

Journal Article↗

B-cell signal transduction: tyrosine phosphorylation, kinase activity, and calcium mobilization.

Signal transduction by the B-cell antigen receptor (BCR) regulates development, survival, and clonal expansion of B cells. The BCR complex comprises the membrane-bound immunoglobulin molecule and the Ig-alpha/Ig-beta heterodimer, and was shown to form oligomeric structures. Antigen-mediated engagement of the BCR results in the tyrosine phosphorylation of multiple signaling proteins leading to calcium mobilization and the activation of downstream serine/threonine kinases as well as transcription factors. In pervanadate (PV)-treated B cells, comparable pathways are activated on expression of the BCR, indicating that the BCR can signal in an antigen-independent fashion as well. In this chapter, we describe the analysis of antigen-dependent and -independent tyrosine phosphorylation events as well as a method to study calcium mobilization from differentially stimulated B cells. Furthermore, we emphasize the use of phospho-specific antibodies (Abs) and low-molecular-weight enzyme inhibitors in the process of mapping BCR-activated signaling pathways as well as determining activation states of signaling proteins.

Animals↗

Mitogen activated protein (MAP) kinases: development of ATP and non-ATP dependent inhibitors.

Extracellular signals regulate most of the body's physiological functions through the MAP kinase signaling pathways. These MAP kinase signaling pathways are normally under tight regulation such that activation and inactivation occurs only when needed. However, aberrant regulation observed with naturally occurring mutations in specific signaling proteins often results in constitutive activation of the MAP kinases and is involved in several pathophysiological conditions, such as cancer, neurodegeneration, and inflammation. As such, much effort has been expended to develop inhibitory molecules of the MAP kinase signaling pathways. Several compounds have been identified that inhibit MAP kinase signaling by targeting receptors or other proteins upstream of the MAP kinases. The development of specific inhibitors of the MAP kinases themselves has been less successful and only a few compounds, which interfere with ATP binding, have been identified. A common problem with kinase inhibitors that compete with ATP binding is their lack of specificity. Thus, alternative approaches to inhibit MAP kinase function are being sought. The MAP kinase proteins contain docking domains that direct the interactions with a variety of substrate proteins. Using the 3-dimensional structure of MAP kinases and computer modeling, molecules that target specific docking domains and selectively disrupt substrate interactions are being developed. This non-ATP interfering approach may allow the selective inhibition of MAP kinase substrates involved in disease processes while preserving MAP kinase functions associated with normal cells.

Adenosine Triphosphate↗

Serial movement timing and musical experience.

Musicians and non-musicians were compared on a serial movement-timing task incorporating six continuous 11-cm segments. The serial pattern was structured for both spatial and temporal symmetry. There were seven subjects in each group and 50 test trials were analyzed for timing error. The non-musicians were less accurate and more variable for certain parts of the pattern. The findings supported the view that musical practice can assist the process of mapping internal representations of serial relations to novel spatio-temporal patterns of movement.

Adult↗

Identification of new proteins in follicular fluid from mature human follicles by direct sample rehydration method of two-dimensional polyacrylamide gel electrophoresis.

Human follicular fluid (HFF) includes various biologically active proteins which can affect follicle growth and oocyte fertilization. Thus far, these proteins from mature follicles in human follicular fluid have been poorly characterized. Here, two-dimensional polyacrylamide gel electrophoresis (2-DE) with matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) was used to identify new proteins in HFF. Mature follicular fluids were obtained from five females after oocyte collection during in vitro fertilization (IVF). We directly rehydrated HFF samples, obtained high-resolution 2-DE maps, and processed them for 2-DE and MALDI-MS. One hundred eighty spots were detected and 10 of these spots were identified. By the 2-DE database, six of them had been reported, as proteins already existing in HFF. Hormone sensitive lipase (HSL), Unnamed protein product 1 (UPP1), Unnamed protein product 2 (UPP2), and apolipoprotein A-IV precursor were newly detected. HSL and apolipoprotein A-IV participate in lipid metabolism. UPP1 has a homology with selenocysteine lyase. We found by RT-PCR that these genes are expressed from human primary granulosa cells. The proteins identified here may emerge as potential candidates for specific functions during folliculogenesis, hormone secretion regulation, or oocyte maturation. Further functional analysis of these proteins is necessitated to determine their biological implications.

Adult↗