WorldWideScience

Sample records for visual pathway links

  1. Visual snow: A thalamocortical dysrhythmia of the visual pathway?

    Science.gov (United States)

    Lauschke, Jenny L; Plant, Gordon T; Fraser, Clare L

    2016-06-01

    In this paper we review the visual snow (VS) characteristics of a case cohort of 32 patients. History of symptoms and associated co-morbidities, ophthalmic examination, previous investigations and the results of intuitive colourimetry were collected and reviewed. VS symptoms follow a stereotypical description and are strongly associated with palinopsia, migraine and tinnitus, but also tremor. The condition is a chronic one and often results in misdiagnosis with psychiatric disorders or malingering. Colour filters, particularly in the yellow-blue colour spectrum, subjectively reduced symptoms of VS. There is neurobiological evidence for the syndrome of VS that links it with other disorders of visual and sensory processing such as migraine and tinnitus. Colour filters in the blue-yellow spectrum may alter the koniocellular pathway processing, which has a regulatory effect on background electroencephalographic rhythms, and may add weight to the hypothesis that VS is a thalamocortical dysrhythmia of the visual pathway. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Radical SAM, a novel protein superfamily linking unresolved steps in familiar biosynthetic pathways with radical mechanisms: functional characterization using new analysis and information visualization methods

    Science.gov (United States)

    Sofia, Heidi J.; Chen, Guang; Hetzler, Beth G.; Reyes-Spindola, Jorge F.; Miller, Nancy E.

    2001-01-01

    A novel protein superfamily with over 600 members was discovered by iterative profile searches and analyzed with powerful bioinformatics and information visualization methods. Evidence exists that these proteins generate a radical species by reductive cleavage of S-adenosylmethionine (SAM) through an unusual Fe-S center. The superfamily (named here Radical SAM) provides evidence that radical-based catalysis is important in a number of previously well- studied but unresolved biochemical pathways and reflects an ancient conserved mechanistic approach to difficult chemistries. Radical SAM proteins catalyze diverse reactions, including unusual methylations, isomerization, sulfur insertion, ring formation, anaerobic oxidation and protein radical formation. They function in DNA precursor, vitamin, cofactor, antibiotic and herbicide biosynthesis and in biodegradation pathways. One eukaryotic member is interferon-inducible and is considered a candidate drug target for osteoporosis; another is observed to bind the neuronal Cdk5 activator protein. Five defining members not previously recognized as homologs are lysine 2,3-aminomutase, biotin synthase, lipoic acid synthase and the activating enzymes for pyruvate formate-lyase and anaerobic ribonucleotide reductase. Two functional predictions for unknown proteins are made based on integrating other data types such as motif, domain, operon and biochemical pathway into an organized view of similarity relationships. PMID:11222759

  3. Neural pathways for visual speech perception.

    Science.gov (United States)

    Bernstein, Lynne E; Liebenthal, Einat

    2014-01-01

    This paper examines the questions, what levels of speech can be perceived visually, and how is visual speech represented by the brain? Review of the literature leads to the conclusions that every level of psycholinguistic speech structure (i.e., phonetic features, phonemes, syllables, words, and prosody) can be perceived visually, although individuals differ in their abilities to do so; and that there are visual modality-specific representations of speech qua speech in higher-level vision brain areas. That is, the visual system represents the modal patterns of visual speech. The suggestion that the auditory speech pathway receives and represents visual speech is examined in light of neuroimaging evidence on the auditory speech pathways. We outline the generally agreed-upon organization of the visual ventral and dorsal pathways and examine several types of visual processing that might be related to speech through those pathways, specifically, face and body, orthography, and sign language processing. In this context, we examine the visual speech processing literature, which reveals widespread diverse patterns of activity in posterior temporal cortices in response to visual speech stimuli. We outline a model of the visual and auditory speech pathways and make several suggestions: (1) The visual perception of speech relies on visual pathway representations of speech qua speech. (2) A proposed site of these representations, the temporal visual speech area (TVSA) has been demonstrated in posterior temporal cortex, ventral and posterior to multisensory posterior superior temporal sulcus (pSTS). (3) Given that visual speech has dynamic and configural features, its representations in feedforward visual pathways are expected to integrate these features, possibly in TVSA.

  4. Neural pathways for visual speech perception

    Directory of Open Access Journals (Sweden)

    Lynne E Bernstein

    2014-12-01

    Full Text Available This paper examines the questions, what levels of speech can be perceived visually, and how is visual speech represented by the brain? Review of the literature leads to the conclusions that every level of psycholinguistic speech structure (i.e., phonetic features, phonemes, syllables, words, and prosody can be perceived visually, although individuals differ in their abilities to do so; and that there are visual modality-specific representations of speech qua speech in higher-level vision brain areas. That is, the visual system represents the modal patterns of visual speech. The suggestion that the auditory speech pathway receives and represents visual speech is examined in light of neuroimaging evidence on the auditory speech pathways. We outline the generally agreed-upon organization of the visual ventral and dorsal pathways and examine several types of visual processing that might be related to speech through those pathways, specifically, face and body, orthography, and sign language processing. In this context, we examine the visual speech processing literature, which reveals widespread diverse patterns activity in posterior temporal cortices in response to visual speech stimuli. We outline a model of the visual and auditory speech pathways and make several suggestions: (1 The visual perception of speech relies on visual pathway representations of speech qua speech. (2 A proposed site of these representations, the temporal visual speech area (TVSA has been demonstrated in posterior temporal cortex, ventral and posterior to multisensory posterior superior temporal sulcus (pSTS. (3 Given that visual speech has dynamic and configural features, its representations in feedforward visual pathways are expected to integrate these features, possibly in TVSA.

  5. Neural pathways for visual speech perception

    Science.gov (United States)

    Bernstein, Lynne E.; Liebenthal, Einat

    2014-01-01

    This paper examines the questions, what levels of speech can be perceived visually, and how is visual speech represented by the brain? Review of the literature leads to the conclusions that every level of psycholinguistic speech structure (i.e., phonetic features, phonemes, syllables, words, and prosody) can be perceived visually, although individuals differ in their abilities to do so; and that there are visual modality-specific representations of speech qua speech in higher-level vision brain areas. That is, the visual system represents the modal patterns of visual speech. The suggestion that the auditory speech pathway receives and represents visual speech is examined in light of neuroimaging evidence on the auditory speech pathways. We outline the generally agreed-upon organization of the visual ventral and dorsal pathways and examine several types of visual processing that might be related to speech through those pathways, specifically, face and body, orthography, and sign language processing. In this context, we examine the visual speech processing literature, which reveals widespread diverse patterns of activity in posterior temporal cortices in response to visual speech stimuli. We outline a model of the visual and auditory speech pathways and make several suggestions: (1) The visual perception of speech relies on visual pathway representations of speech qua speech. (2) A proposed site of these representations, the temporal visual speech area (TVSA) has been demonstrated in posterior temporal cortex, ventral and posterior to multisensory posterior superior temporal sulcus (pSTS). (3) Given that visual speech has dynamic and configural features, its representations in feedforward visual pathways are expected to integrate these features, possibly in TVSA. PMID:25520611

  6. Loss of vision: imaging the visual pathways

    Energy Technology Data Exchange (ETDEWEB)

    Jaeger, H.R. [Institute of Neurology, Lysholm Department of Neuroradiology, London (United Kingdom)

    2005-03-01

    This is an overview of diseases presenting with visual impairment, which aims to provide an understanding of the anatomy and pathology of the visual pathways. It discusses the relevant clinical background and neuroimaging findings on CT and standard and advanced MRI of diseases affecting the globe; optic nerve/sheath complex; optic chiasm, tract and radiation; and visual cortex. The overview covers common tumours, trauma, inflammatory and vascular pathology, and conditions such as benign intracranial hypertension and posterior reversible leukoencephalopathy syndrome. (orig.)

  7. Visualizing Transmedia Networks: Links, Paths and Peripheries

    Science.gov (United States)

    Ruppel, Marc Nathaniel

    2012-01-01

    'Visualizing Transmedia Networks: Links, Paths and Peripheries' examines the increasingly complex rhetorical intersections between narrative and media ("old" and "new") in the creation of transmedia fictions, loosely defined as multisensory and multimodal stories told extensively across a diverse media set. In order…

  8. Intracranial pathology of the visual pathway

    Energy Technology Data Exchange (ETDEWEB)

    Mueller-Forell, W. E-mail: mueller-forell@neuroradio.klinik.uni-mainz.de

    2004-02-01

    Intracranial pathologies involving the visual pathway are manifold. Aligning to anatomy, the most frequent and/or most important extrinsic and intrinsic intracranial lesions are presented. Clinical symptoms and imaging characteristics of lesions of the sellar region are demonstrated in different imaging modalities. The extrinsic lesions mainly consist of pituitary adenomas, meningeomas, craniopharyngeomas and chordomas. In (asymptomatic and symptomatic) aneurysms, different neurological symptoms depend on the location of aneurysms of the circle of Willis. Intrinsic tumors as astrocytoma of any grade, ependymoma and primary CNS-lymphoma require the main pathology in the course of the visual pathway. Vascular and demyelinating diseases complete this overview of intracranial lesions.

  9. Multiple Pathways Linking Racism to Health Outcomes

    Science.gov (United States)

    Harrell, Camara Jules P.; Burford, Tanisha I.; Cage, Brandi N.; Nelson, Travette McNair; Shearon, Sheronda; Thompson, Adrian; Green, Steven

    2012-01-01

    This commentary discusses advances in the conceptual understanding of racism and selected research findings in the social neurosciences. The traditional stress and coping model holds that racism constitutes a source of aversive experiences that, when perceived by the individual, eventually lead to poor health outcomes. Current evidence points to additional psychophysiological pathways linking facets of racist environments with physiological reactions that contribute to disease. The alternative pathways emphasize prenatal experiences, subcortical emotional neural circuits, conscious and preconscious emotion regulation, perseverative cognitions, and negative affective states stemming from racist cognitive schemata. Recognition of these pathways challenges change agents to use an array of cognitive and self-controlling interventions in mitigating racism’s impact. Additionally, it charges policy makers to develop strategies that eliminate deep-seated structural aspects of racism in society. PMID:22518195

  10. Pathway-based visualization of cross-platform microarray datasets.

    Science.gov (United States)

    Wrzodek, Clemens; Eichner, Johannes; Zell, Andreas

    2012-12-01

    Traditionally, microarrays were almost exclusively used for the genome-wide analysis of differential gene expression. But nowadays, their scope of application has been extended to various genomic features, such as microRNAs (miRNAs), proteins and DNA methylation (DNAm). Most available methods for the visualization of these datasets are focused on individual platforms and are not capable of integratively visualizing multiple microarray datasets from cross-platform studies. Above all, there is a demand for methods that can visualize genomic features that are not directly linked to protein-coding genes, such as regulatory RNAs (e.g. miRNAs) and epigenetic alterations (e.g. DNAm), in a pathway-centred manner. We present a novel pathway-based visualization method that is especially suitable for the visualization of high-throughput datasets from multiple different microarray platforms that were used for the analysis of diverse genomic features in the same set of biological samples. The proposed methodology includes concepts for linking DNAm and miRNA expression datasets to canonical signalling and metabolic pathways. We further point out strategies for displaying data from multiple proteins and protein modifications corresponding to the same gene. Ultimately, we show how data from four distinct platform types (messenger RNA, miRNA, protein and DNAm arrays) can be integratively visualized in the context of canonical pathways. The described method is implemented as part of the InCroMAP application that is freely available at www.cogsys.cs.uni-tuebingen.de/software/InCroMAP. clemens.wrzodek@uni-tuebingen.de or andreas.zell@uni-tuebingen.de.

  11. Visual acuity and X-linked color blindness.

    Science.gov (United States)

    Jägle, Herbert; de Luca, Emanuela; Serey, Ludwig; Bach, Michael; Sharpe, Lindsay T

    2006-04-01

    Optimal sampling for visual acuity requires a fine array of cones with identical sensitivity. Thus, dichromats, whose inner fovea is made up of cones having the same spectral sensitivity, may have better than normal visual acuity. We investigated this by comparing the visual acuities of trichromats and X-linked dichromats, while taking into account the different molecular genetics underlying the disorder. Our subjects were age- and refraction-matched groups of normals (n=8) and X-linked dichromats (n=13). The dichromats (four protanopes and nine deuteranopes) were genotyped and classified according to whether they carried a single (n=6) or multiple (n=7) visual pigment genes on their X-chromosome. Visual acuity was measured in both eyes with the Freiburger Visual Acuity Test. Normal trichromats and ungenotyped dichromats do not significantly differ in visual acuity, nor do ungenotyped protanopes and deuteranopes. However, multi-gene dichromats, who possess more than one photopigment gene in the array, all of which encode for the same long- or middle-wavelength sensitive photopigment, have significantly higher visual acuity than either normal trichromats or dichromats who have only a single-gene. Multi-gene dichromats may benefit from a reduction in chromatic aberration and chromatic noise in the high acuity channel, normally a consequence of combining signals from different cone photoreceptor types and of cone-specific patterns of retinal image defocus and blur. Single-gene dichromats may not share in the advantage because of other molecular differences that influence the development of the retinal mosaic and/or its visual pathways.

  12. Linking Visualization and Understanding in Astronomy

    Science.gov (United States)

    Goodman, Alyssa A.

    2014-01-01

    In 1610, when Galileo pointed his small telescope at Jupiter, he drew sketches to record what he saw. After just a few nights of observing, he understood his sketches to be showing moons orbiting Jupiter. It was the visualization of Galileo's observations that led to his understanding of a clearly Sun-centered solar system, and to the revolution this understanding then caused. Similar stories can be found throughout the history of Astronomy, but visualization has never been so essential as it is today, when we find ourselves blessed with a larger wealth and diversity of data, per astronomer, than ever in the past. In this talk, I will focus on how modern tools for interactive “linked-view” visualization can be used to gain insight. Linked views, which dynamically update all open graphical displays of a data set (e.g. multiple graphs, tables and/or images) in response to user selection, are particularly important in dealing with so-called “high-dimensional data.” These dimensions need not be spatial, even though, e.g. in the case of radio spectral-line cubes or optical IFU data), they often are. Instead, “dimensions” should be thought of as any measured attribute of an observation or a simulation (e.g. time, intensity, velocity, temperature, etc.). The best linked-view visualization tools allow users to explore relationships amongst all the dimensions of their data, and to weave statistical and algorithmic approaches into the visualization process in real time. Particular tools and services will be highlighted in this talk, including: Glue (glueviz.org), the ADS All Sky Survey (adsass.org), WorldWide Telescope (worldwidetelescope.org), yt (yt-project.org), d3po (d3po.org), and a host of tools that can be interconnected via the SAMP message-passing architecture. The talk will conclude with a discussion of future challenges, including the need to educate astronomers about the value of visualization and its relationship to astrostatistics, and the need for

  13. Metabolic Pathways Visualization Skills Development by Undergraduate Students

    Science.gov (United States)

    dos Santos, Vanessa J. S. V.; Galembeck, Eduardo

    2015-01-01

    We have developed a metabolic pathways visualization skill test (MPVST) to gain greater insight into our students' abilities to comprehend the visual information presented in metabolic pathways diagrams. The test is able to discriminate students' visualization ability with respect to six specific visualization skills that we identified as key to…

  14. Visual pathway neurodegeneration winged by mitochondrial dysfunction.

    Science.gov (United States)

    Petzold, Axel; Nijland, Philip G; Balk, Lisanne J; Amorini, Angela Maria; Lazzarino, Giacomo; Wattjes, Mike P; Gasperini, Claudio; van der Valk, Paul; Tavazzi, Barbara; Lazzarino, Giuseppe; van Horssen, Jack

    2015-02-01

    To test for structural and functional contribution of mitochondrial dysfunction to neurodegeneration in multiple sclerosis (MS). A visual pathway model void of MS lesions was chosen in order to exclude neurodegeneration secondary to lesion related axonotmesis. A single-centre cohort study (230 MS patients, 63 controls). Spectral domain optical coherence tomography of the retina, 3T magnetic resonance imaging of the brain, spectrophotometric assessment of serum lactate levels. Postmortem immunohistochemistry. The visual pathway was void of MS lesions in 31 patients and 31 age-matched controls. Serum lactate was higher in MS compared to controls (P = 0.029). High serum lactate was structurally related to atrophy of the retinal nerve fiber layer at the optic disc (P = 0.041), macula (P = 0.025), and the macular ganglion cell complex (P = 0.041). High serum lactate was functionally related to poor color vision (P < 0.01), Expanded Disability Status Scale score (R = 0.37, P = 0.041), Guy's Neurological disability score (R = 0.38, P = 0.037), MS walking scale (R = 0.50, P = 0.009), upper limb motor function (R = 0.53, P = 0.002). Immunohistochemistry demonstrated increased astrocytic expression of a key lactate generating enzyme in MS lesions as well as profound vascular expression of monocarboxylate transporter-1, which is involved in lactate transport. This study provides structural, functional, and translational evidence for visual pathway neurodegeneration in MS related to mitochondrial dysfunction.

  15. Automatic vehicle classification using linked visual words

    Science.gov (United States)

    Watcharapinchai, Nattachai; Aramvith, Supavadee; Siddhichai, Supakorn

    2017-07-01

    An improvement in the method of automatic vehicle classification is investigated. The challenges are to correctly classify vehicles regardless of changes in illumination, differences in points of view of the camera, and variations in the types of vehicles. Our proposed appearance-based feature extraction algorithm is called linked visual words (LVWs) and is based on the existing technique bag-of-visual word (BoVW) with the addition of spatial information to improve accuracy of classification. In addition, to prevent over-fitting due to a large number of LVWs, four common sampling techniques with LVWs are investigated. Our results suggest that the sampling of LVWs using TF-IDF with grouping improved the accuracy of classification for the test dataset. In summary, the proposed system is able to classify nine types of vehicles and work with surveillance cameras in real-world scenarios. The classification accuracy of the proposed system is 5.58% and 4.27% higher on average for three datasets when compared with BoVW + SVM and Lenet-5, respectively.

  16. Developmental Reorganisation of Visual Motion Pathways

    Directory of Open Access Journals (Sweden)

    John Wattam-Bell

    2012-05-01

    Full Text Available In adults, visual form and motion activate independent networks of extrastriate areas which are roughly aligned with the ventral and dorsal streams, respectively. Using high-density steady-state ERPs, we have previously shown that the scalp topographies of infant form and motion responses are markedly different from those in adults, implying a substantial developmental reorganisation of the underlying cortical pathways. However, it is hard to discern the nature of this reorganisation from the ambiguous polarity and timing information available in steady-state ERPs. We have started to address this problem by measuring transient ERPs to motion onset. In adults, the transient ERP topography initially suggests activation of extrastriate cortex, but rapidly switches to a dominant focus over the occipital pole originating in V1 and/or V2. The infant ERP is similar to the initial phase of adult ERP, but lacks the sudden switch to a V1/V2-dominated topography. The implications of these results for the reorganisation of cortical motion pathways will be discussed, with particular focus on the idea that the adult V1/V2 component is mainly driven by feedback from extrastriate motion areas (eg, V5, and that these feedback signals are not present in the infant brain.

  17. Browsing and Visualization of Linked Environmental Data

    Science.gov (United States)

    Nikolaou, Charalampos; Kyzirakos, Kostis; Bereta, Konstantina; Dogani, Kallirroi; Koubarakis, Manolis

    2014-05-01

    RDF store Strabon (http://www.strabon.di.uoa.gr/) which, apart from querying geospatial information, can also be used to query both the valid time of a triple and user-defined time. With the aim of filling the aforementioned gaps and going beyond data exploration to map creation and sharing, we have designed and developed SexTant (http://sextant.di.uoa.gr/). SexTant can be used to produce thematic maps by layering spatiotemporal information which exists in a number of data sources ranging from standard SPARQL endpoints, to SPARQL endpoints following the standard GeoSPARQL defined by the Open Geospatial Consortium (OGC) for the modelling and querying of geospatial information, and other well-adopted geospatial file formats, such as KML and GeoJSON. In this work, we pick some real use cases from the environment domain to showcase the usefulness of SexTant to the environmental studies of a domain expert by presenting its browsing and visualization capabilities using a number of environmental datasets that we have published as linked data and also other geospatial data sources publicly available on the Web, such as KML files.

  18. Hierarchically organized layout for visualization of biochemical pathways.

    Science.gov (United States)

    Tsay, Jyh-Jong; Wu, Bo-Liang; Jeng, Yu-Sen

    2010-01-01

    Many complex pathways are described as hierarchical structures in which a pathway is recursively partitioned into several sub-pathways, and organized hierarchically as a tree. The hierarchical structure provides a natural way to visualize the global structure of a complex pathway. However, none of the previous research on pathway visualization explores the hierarchical structures provided by many complex pathways. In this paper, we aim to develop algorithms that can take advantages of hierarchical structures, and give layouts that explore the global structures as well as local structures of pathways. We present a new hierarchically organized layout algorithm to produce layouts for hierarchically organized pathways. Our algorithm first decomposes a complex pathway into sub-pathway groups along the hierarchical organization, and then partition each sub-pathway group into basic components. It then applies conventional layout algorithms, such as hierarchical layout and force-directed layout, to compute the layout of each basic component. Finally, component layouts are joined to form a final layout of the pathway. Our main contribution is the development of algorithms for decomposing pathways and joining layouts. Experiment shows that our algorithm is able to give comprehensible visualization for pathways with hierarchies, cycles as well as complex structures. It clearly renders the global component structures as well as the local structure in each component. In addition, it runs very fast, and gives better visualization for many examples from previous related research. 2009 Elsevier B.V. All rights reserved.

  19. Linking crowding, visual span, and reading.

    Science.gov (United States)

    He, Yingchen; Legge, Gordon E

    2017-09-01

    The visual span is hypothesized to be a sensory bottleneck on reading speed with crowding thought to be the major sensory factor limiting the size of the visual span. This proposed linkage between crowding, visual span, and reading speed is challenged by the finding that training to read crowded letters reduced crowding but did not improve reading speed (Chung, 2007). Here, we examined two properties of letter-recognition training that may influence the transfer to improved reading: the spatial arrangement of training stimuli and the presence of flankers. Three groups of nine young adults were trained with different configurations of letter stimuli at 10° in the lower visual field: a flanked-local group (flanked letters localized at one position), a flanked-distributed group (flanked letters distributed across different horizontal locations), and an isolated-distributed group (isolated and distributed letters). We found that distributed training, but not the presence of flankers, appears to be necessary for the training benefit to transfer to increased reading speed. Localized training may have biased attention to one specific, small area in the visual field, thereby failing to improve reading. We conclude that the visual span represents a sensory bottleneck on reading, but there may also be an attentional bottleneck. Reducing the impact of crowding can enlarge the visual span and can potentially facilitate reading, but not when adverse attentional bias is present. Our results clarify the association between crowding, visual span, and reading.

  20. BID links ferroptosis to mitochondrial cell death pathways

    NARCIS (Netherlands)

    Neitemeier, Sandra; Jelinek, Anja; Laino, Vincenzo; Hoffmann, Lena; Eisenbach, Ina; Eying, Roman; Ganjam, Goutham K; Dolga, Amalia M; Oppermann, Sina; Culmsee, Carsten

    2017-01-01

    Ferroptosis has been defined as an oxidative and iron-dependent pathway of regulated cell death that is distinct from caspase-dependent apoptosis and established pathways of death receptor-mediated regulated necrosis. While emerging evidence linked features of ferroptosis induced e.g. by

  1. The role of the retino-colliculo-extrastriate pathway in visual awareness and visual field recovery.

    Science.gov (United States)

    Bertini, Caterina; Grasso, Paolo A; Làdavas, Elisabetta

    2016-09-01

    Patients with visual field defects resulting from post-chiasmatic lesions experience loss of visual function in up to one half of their visual field, with consequent impairments in their daily life activities. Therefore, effective strategies for compensating for the visual field loss are of great clinical relevance. After lesions to the primary visual pathway -which conveys visual information from the retina to the lateral geniculate nucleus, the optic radiations and, then, to the striate cortex-an alternative visual pathway, which projects from the superior colliculus to the extrastriate cortex, is usually spared in patients with visual field defects. In the present review, evidence for spared functioning of this alternative pathway in patients with visual field defects will be presented, both in terms of residual visual abilities, without awareness, for stimuli presented in the blind field, and the ability to integrate unseen visual signals presented in the blind field with concurrent auditory stimuli. Crucially, this review will discuss how the spared retino-colliculo-extrastriate pathway might be a useful tool for compensating for the loss of visual perception. Accordingly, evidence for the compensatory effects of systematic multisensory audio-visual stimulation in patients with visual field defects will be reviewed. Copyright © 2016. Published by Elsevier Ltd.

  2. Sextant: Visualizing time-evolving linked geospatial data

    NARCIS (Netherlands)

    C. Nikolaou (Charalampos); K. Dogani (Kallirroi); K. Bereta (Konstantina); G. Garbis (George); M. Karpathiotakis (Manos); K. Kyzirakos (Konstantinos); M. Koubarakis (Manolis)

    2015-01-01

    textabstractThe linked open data cloud is constantly evolving as datasets get continuously updated with newer versions. As a result, representing, querying, and visualizing the temporal dimension of linked data is crucial. This is especially important for geospatial datasets that form the backbone

  3. Attentional effects in the visual pathways

    DEFF Research Database (Denmark)

    Bundesen, Claus; Larsen, Axel; Kyllingsbæk, Søren

    2002-01-01

    nucleus. Frontal activations were found in a region that seems implicated in visual short-term memory (posterior parts of the superior sulcus and the middle gyrus). The reverse, color-shape comparison showed bilateral increases in rCBF in the anterior cingulate gyri, superior frontal gyri, and superior...... and middle temporal gyri. The attentional effects found by the shape-color comparison in the thalamus and the primary visual cortex may have been generated by feedback signals preserving visual representations of selected stimuli in short-term memory....

  4. Alzheimer disease: functional abnormalities in the dorsal visual pathway.

    LENUS (Irish Health Repository)

    Bokde, Arun L W

    2012-02-01

    PURPOSE: To evaluate whether patients with Alzheimer disease (AD) have altered activation compared with age-matched healthy control (HC) subjects during a task that typically recruits the dorsal visual pathway. MATERIALS AND METHODS: The study was performed in accordance with the Declaration of Helsinki, with institutional ethics committee approval, and all subjects provided written informed consent. Two tasks were performed to investigate neural function: face matching and location matching. Twelve patients with mild AD and 14 age-matched HC subjects were included. Brain activation was measured by using functional magnetic resonance imaging. Group statistical analyses were based on a mixed-effects model corrected for multiple comparisons. RESULTS: Task performance was not statistically different between the two groups, and within groups there were no differences in task performance. In the HC group, the visual perception tasks selectively activated the visual pathways. Conversely in the AD group, there was no selective activation during performance of these same tasks. Along the dorsal visual pathway, the AD group recruited additional regions, primarily in the parietal and frontal lobes, for the location-matching task. There were no differences in activation between groups during the face-matching task. CONCLUSION: The increased activation in the AD group may represent a compensatory mechanism for decreased processing effectiveness in early visual areas of patients with AD. The findings support the idea that the dorsal visual pathway is more susceptible to putative AD-related neuropathologic changes than is the ventral visual pathway.

  5. Development of Network Analysis and Visualization System for KEGG Pathways

    Directory of Open Access Journals (Sweden)

    Dongmin Seo

    2015-07-01

    Full Text Available Big data refers to informationalization technology for extracting valuable information through the use and analysis of large-scale data and, based on that data, deriving plans for response or predicting changes. With the development of software and devices for next generation sequencing, a vast amount of bioinformatics data has been generated recently. Also, bioinformatics data based big-data technology is rising rapidly as a core technology by the bioinformatician, biologist and big-data scientist. KEGG pathway is bioinformatics data for understanding high-level functions and utilities of the biological system. However, KEGG pathway analysis requires a lot of time and effort because KEGG pathways are high volume and very diverse. In this paper, we proposed a network analysis and visualization system that crawl user interest KEGG pathways, construct a pathway network based on a hierarchy structure of pathways and visualize relations and interactions of pathways by clustering and selecting core pathways from the network. Finally, we construct a pathway network collected by starting with an Alzheimer’s disease pathway and show the results on clustering and selecting core pathways from the pathway network.

  6. Alterations of the visual pathways in congenital blindness

    DEFF Research Database (Denmark)

    Ptito, Maurice; Schneider, Fabien C G; Paulson, Olaf B

    2008-01-01

    We used whole brain MRI voxel-based morphometry (VBM) to study the anatomical organization of the visual system in congenitally blind (CB) adults. Eleven CB without a history of visual perception were compared with 21 age- and sex-matched normal-sighted controls (NS). CB showed significant atroph...... somatosensory or auditory inputs, suggesting a reorganization of the neural pathways that transmit sensory information to the visual cortex....

  7. Comparative study of visual pathways in owls (Aves: Strigiformes).

    Science.gov (United States)

    Gutiérrez-Ibáñez, Cristián; Iwaniuk, Andrew N; Lisney, Thomas J; Wylie, Douglas R

    2013-01-01

    Although they are usually regarded as nocturnal, owls exhibit a wide range of activity patterns, from strictly nocturnal, to crepuscular or cathemeral, to diurnal. Several studies have shown that these differences in the activity pattern are reflected in differences in eye morphology and retinal organization. Despite the evidence that differences in activity pattern among owl species are reflected in the peripheral visual system, there has been no attempt to correlate these differences with changes in the visual regions in the brain. In this study, we compare the relative size of nuclei in the main visual pathways in nine species of owl that exhibit a wide range of activity patterns. We found marked differences in the relative size of all visual structures among the species studied, both in the tectofugal and the thalamofugal pathway, as well in other retinorecipient nuclei, including the nucleus lentiformis mesencephali, the nucleus of the basal optic root and the nucleus geniculatus lateralis, pars ventralis. We show that the barn owl (Tyto alba), a species widely used in the study of the integration of visual and auditory processing, has reduced visual pathways compared to strigid owls. Our results also suggest there could be a trade-off between the relative size of visual pathways and auditory pathways, similar to that reported in mammals. Finally, our results show that although there is no relationship between activity pattern and the relative size of either the tectofugal or the thalamofugal pathway, there is a positive correlation between the relative size of both visual pathways and the relative number of cells in the retinal ganglion layer. Copyright © 2012 S. Karger AG, Basel.

  8. Learning Visual Design through Hypermedia: Pathways to Visual Literacy.

    Science.gov (United States)

    Lockee, Barbara; Hergert, Tom

    The interactive multimedia application described here attempts to provide learners and teachers with a common frame of reference for communicating about visual media. The system is based on a list of concepts related to composition, and illustrates those concepts with photographs, paintings, graphic designs, and motion picture scenes. The ability…

  9. The multiple sclerosis visual pathway cohort: understanding neurodegeneration in MS.

    Science.gov (United States)

    Martínez-Lapiscina, Elena H; Fraga-Pumar, Elena; Gabilondo, Iñigo; Martínez-Heras, Eloy; Torres-Torres, Ruben; Ortiz-Pérez, Santiago; Llufriu, Sara; Tercero, Ana; Andorra, Magi; Roca, Marc Figueras; Lampert, Erika; Zubizarreta, Irati; Saiz, Albert; Sanchez-Dalmau, Bernardo; Villoslada, Pablo

    2014-12-15

    Multiple Sclerosis (MS) is an immune-mediated disease of the Central Nervous System with two major underlying etiopathogenic processes: inflammation and neurodegeneration. The latter determines the prognosis of this disease. MS is the main cause of non-traumatic disability in middle-aged populations. The MS-VisualPath Cohort was set up to study the neurodegenerative component of MS using advanced imaging techniques by focusing on analysis of the visual pathway in a middle-aged MS population in Barcelona, Spain. We started the recruitment of patients in the early phase of MS in 2010 and it remains permanently open. All patients undergo a complete neurological and ophthalmological examination including measurements of physical and disability (Expanded Disability Status Scale; Multiple Sclerosis Functional Composite and neuropsychological tests), disease activity (relapses) and visual function testing (visual acuity, color vision and visual field). The MS-VisualPath protocol also assesses the presence of anxiety and depressive symptoms (Hospital Anxiety and Depression Scale), general quality of life (SF-36) and visual quality of life (25-Item National Eye Institute Visual Function Questionnaire with the 10-Item Neuro-Ophthalmic Supplement). In addition, the imaging protocol includes both retinal (Optical Coherence Tomography and Wide-Field Fundus Imaging) and brain imaging (Magnetic Resonance Imaging). Finally, multifocal Visual Evoked Potentials are used to perform neurophysiological assessment of the visual pathway. The analysis of the visual pathway with advance imaging and electrophysilogical tools in parallel with clinical information will provide significant and new knowledge regarding neurodegeneration in MS and provide new clinical and imaging biomarkers to help monitor disease progression in these patients.

  10. SexTant: Visualizing Time-Evolving Linked Geospatial Data

    NARCIS (Netherlands)

    K. Bereta (Konstantina); C. Nikolaou (Charalampos); M. Karpathiotakis (Manos); K. Kyzirakos (Konstantinos); M. Koubarakis (Manolis); E. Blomqvist; T. Groza

    2013-01-01

    htmlabstractWe present SexTant, a Web-based system for the visualization and exploration of time-evolving linked geospatial data and the creation, sharing, and collaborative editing of "temporally-enriched" thematic maps which are produced by combining dierent sources of such data.

  11. Emissions Scenario Portal for Visualization of Low Carbon Pathways

    Science.gov (United States)

    Friedrich, J.; Hennig, R. J.; Mountford, H.; Altamirano, J. C.; Ge, M.; Fransen, T.

    2016-12-01

    This proposal for a presentation is centered around a new project which is developed collaboratively by the World Resources Institute (WRI), Google Inc., and Deep Decarbonization Pathways Project (DDPP). The project aims to develop an online, open portal, the Emissions Scenario Portal (ESP),to enable users to easily visualize a range of future greenhouse gas emission pathways linked to different scenarios of economic and energy developments, drawing from a variety of modeling tools. It is targeted to users who are not modelling experts, but instead policy analysts or advisors, investment analysts, and similar who draw on modelled scenarios to inform their work, and who can benefit from better access to, and transparency around, the wide range of emerging scenarios on ambitious climate action. The ESP will provide information from scenarios in a visually appealing and easy-to-understand manner that enable these users to recognize the opportunities to reduce GHG emissions, the implications of the different scenarios, and the underlying assumptions. To facilitate the application of the portal and tools in policy dialogues, a series of country-specific and potentially sector-specific workshops with key decision-makers and analysts, supported by relevant analysis, will be organized by the key partners and also in broader collaboration with others who might wish to convene relevant groups around the information. This project will provide opportunities for modelers to increase their outreach and visibility in the public space and to directly interact with key audiences of emissions scenarios, such as policy analysts and advisors. The information displayed on the portal will cover a wide range of indicators, sectors and important scenario characteristics such as macroeconomic information, emission factors and policy as well as technology assumptions in order to facilitate comparison. These indicators have been selected based on existing standards (such as the IIASA AR5

  12. Visual Tracking With Convolutional Random Vector Functional Link Network.

    Science.gov (United States)

    Zhang, Le; Suganthan, Ponnuthurai Nagaratnam

    2017-10-01

    Deep neural network-based methods have recently achieved excellent performance in visual tracking task. As very few training samples are available in visual tracking task, those approaches rely heavily on extremely large auxiliary dataset such as ImageNet to pretrain the model. In order to address the discrepancy between the source domain (the auxiliary data) and the target domain (the object being tracked), they need to be finetuned during the tracking process. However, those methods suffer from sensitivity to the hyper-parameters such as learning rate, maximum number of epochs, size of mini-batch, and so on. Thus, it is worthy to investigate whether pretraining and fine tuning through conventional back-prop is essential for visual tracking. In this paper, we shed light on this line of research by proposing convolutional random vector functional link (CRVFL) neural network, which can be regarded as a marriage of the convolutional neural network and random vector functional link network, to simplify the visual tracking system. The parameters in the convolutional layer are randomly initialized and kept fixed. Only the parameters in the fully connected layer need to be learned. We further propose an elegant approach to update the tracker. In the widely used visual tracking benchmark, without any auxiliary data, a single CRVFL model achieves 79.0% with a threshold of 20 pixels for the precision plot. Moreover, an ensemble of CRVFL yields comparatively the best result of 86.3%.

  13. Detailed illustration of the visual field representation along the visual pathway to the primary visual cortex: a graphical summary.

    Science.gov (United States)

    Wärntges, Simone; Michelson, Georg

    2014-01-01

    In the literature, different graphic illustrations are available, which depict different parts of the visual pathway in relation to visual field sectors, to retinal sectors, the layers of the lateral geniculate nucleus (LGN), or sections of the primary visual cortex (V1). However, a complete overview is missing, which may be useful for a more precise differentiation of predominantly ophthalmological from intracerebral diseases. It may also be of interest to investigate additional intracerebral reasons that are involved in impaired vision of largely unknown pathophysiology. This work combines the scientific knowledge of partial graphics in one detailed illustration that allows exact follow-up of the neuronal connections from individual visual field sectors to the V1 areas. A selective search for peer-reviewed graphics of the visual pathway was performed in PubMed and Google Pictures. Sixteen different visual field sectors and their 16 corresponding retinal sectors were set in relation to 64 LGN sections and 20 areas of V1. Segmented cross-sectional areas of the optic nerve supplemented the graphical representation of the fiber orientation in relation to the visual field. The detailed illustration of the visual field projection along the visual pathway structures may facilitate a more precise calculation of correlations between morphological and functional measurements of ophthalmological and neuroradiological examinations. © 2013 S. Karger AG, Basel.

  14. Examining the Pathways Linking Chronic Sleep Restriction to Obesity

    Directory of Open Access Journals (Sweden)

    Christopher A. Magee

    2010-01-01

    Full Text Available A growing number of studies have identified chronic sleep restriction as a potential risk factor for obesity. This could have important implications for how obesity is prevented and managed, but current understanding of the processes linking chronic sleep restriction to obesity is incomplete. In this paper, we examined some of the pathways that could underlie the relationship between chronic sleep restriction and obesity. This involved exploring some of the potential environmental, health, behavioral, and sociodemographic determinants of chronic sleep restriction, which require further investigation in this context. Three pathways that could potentially link chronic sleep restriction to obesity were then examined: (1 altered neuroendocrine and metabolic function, (2 impaired glucose regulation, and (3 waking behavior. The selected pathways linking chronic sleep restriction to obesity reviewed in this paper are presented in a schematic representation; this may be used to guide future research in this area. This area of research is important because it may lead to more effective interventions and strategies to combat the present obesity epidemic.

  15. Dyslexia Linked to Visual Strengths Useful in Astronomy

    Science.gov (United States)

    Schneps, Matthew H.; Brockmole, J. R.; Rose, L. T.; Pomplun, M.; Sonnert, G.; Greenhill, L. J.

    2011-05-01

    Dyslexia is a hereditary neurological condition characterized by difficulties in reading, writing, and spelling. The fact that those with dyslexia include many accomplished scientists, including some recognized with a Nobel Prize, has prompted researchers to suggest that the neurology of dyslexia may predispose these individuals to advantages in visually-intensive domains such as science. Here, we report evidence of a link between dyslexia and abilities for visual processing useful in astronomy. First, we show that when images of natural scenes are Gaussian-blurred, so as to remove high-frequency detail (and resemble many astronomical images), college students with dyslexia significantly outperform those who are typical readers in learning the spatial contexts presented. Second, we show that when the threshold ability to detect radio signatures characteristic of black holes is measured in a laboratory simulation, astrophysicists with dyslexia significantly outperform those who are typical readers in this task when the visual periphery is important. In a third experiment, using eye-tracking technologies, we demonstrate that visual strategies significantly correlate with success in the black hole task, but that college students with dyslexia tend not to employ the strategies most likely to lead to success. Collectively, these studies suggest that dyslexia is linked to neurological advantages useful in astronomical careers, but that left to their own devices students with dyslexia may not benefit from these advantages without practice or training. These studies imply that many students who are struggling to read may find successful careers in astronomy or other fields that build on visual advantages linked to their reading disability, but that education and training may be vital in helping these students realize their strengths. This material is based upon work supported by the George E. Burch Fellowship (Smithsonian Institution) and the National Science Foundation

  16. Stress transgenerationally programs metabolic pathways linked to altered mental health.

    Science.gov (United States)

    Kiss, Douglas; Ambeskovic, Mirela; Montina, Tony; Metz, Gerlinde A S

    2016-12-01

    Stress is among the primary causes of mental health disorders, which are the most common reason for disability worldwide. The ubiquity of these disorders, and the costs associated with them, lends a sense of urgency to the efforts to improve prediction and prevention. Down-stream metabolic changes are highly feasible and accessible indicators of pathophysiological processes underlying mental health disorders. Here, we show that remote and cumulative ancestral stress programs central metabolic pathways linked to mental health disorders. The studies used a rat model consisting of a multigenerational stress lineage (the great-great-grandmother and each subsequent generation experienced stress during pregnancy) and a transgenerational stress lineage (only the great-great-grandmother was stressed during pregnancy). Urine samples were collected from adult male F4 offspring and analyzed using (1)H NMR spectroscopy. The results of variable importance analysis based on random variable combination were used for unsupervised multivariate principal component analysis and hierarchical clustering analysis, as well as metabolite set enrichment analysis (MSEA) and pathway analysis. We identified distinct metabolic profiles associated with the multigenerational and transgenerational stress phenotype, with consistent upregulation of hippurate and downregulation of tyrosine, threonine, and histamine. MSEA and pathway analysis showed that these metabolites are involved in catecholamine biosynthesis, immune responses, and microbial host interactions. The identification of metabolic signatures linked to ancestral programming assists in the discovery of gene targets for future studies of epigenetic regulation in pathogenic processes. Ultimately, this research can lead to biomarker discovery for better prediction and prevention of mental health disorders.

  17. Visual disability rates in a ten-year cohort of patients with anterior visual pathway meningiomas.

    Science.gov (United States)

    Bor-Shavit, Elite; Hammel, Naama; Nahum, Yoav; Rappaport, Zvi Harry; Stiebel-Kalish, Hadas

    2015-01-01

    To examine the visual outcome of anterior visual pathway meningioma (AVPM) patients followed for at least one year. Data were collected on demographics, clinical course and management. Visual disability was classified at the first and last examination as follows: I--no visual disability; II--mild visual defect in one eye; III--mild visual defect in both eyes; IV--loss of driver's license; V--legally blind. Eight-one AVPM patients had their tumor originate in the clinoid process in 23 (28%), sphenoid-wing area in 18 (22%), cavernous sinus in 15 (19%), tuberculum sellae in 8 (10%), and mixed in 17 (21%). On last examination, 46 patients (57%) had good visual acuity in one or both eyes (Class I or II) and 17 (21%) were mildly affected in both eyes. The rate of Class IV disability was 16%, and Class V disability was 6%. Attention needs to be addressed to the considerable proportion of patients with AVPM (22% in this study) who may lose their driver's license or become legally blind. Occupational therapists should play an important role in the multidisciplinary management of those patients to help them adapt to their new physical and social situation. Anterior visual pathway meningiomas (AVPMs) are commonly not life-threatening but they can lead to profound visual disability, especially when the tumor originates in the tuberculum sellae and cavernous sinus. Particular attention should be paid to visual acuity and visual field deficits, as these can profoundly affect the patient's quality of life including ability to drive and activities of daily living. The interdisciplinary management of patients with AVPM should include the neurosurgeon, neuro-ophthalmologist and occupational therapist. Also, early intervention by the occupational therapist can help patients adapt to their current physical and social situation and return to everyday tasks more rapidly.

  18. Exploring pathways linking greenspace to health: Theoretical and methodological guidance.

    Science.gov (United States)

    Markevych, Iana; Schoierer, Julia; Hartig, Terry; Chudnovsky, Alexandra; Hystad, Perry; Dzhambov, Angel M; de Vries, Sjerp; Triguero-Mas, Margarita; Brauer, Michael; Nieuwenhuijsen, Mark J; Lupp, Gerd; Richardson, Elizabeth A; Astell-Burt, Thomas; Dimitrova, Donka; Feng, Xiaoqi; Sadeh, Maya; Standl, Marie; Heinrich, Joachim; Fuertes, Elaine

    2017-10-01

    In a rapidly urbanizing world, many people have little contact with natural environments, which may affect health and well-being. Existing reviews generally conclude that residential greenspace is beneficial to health. However, the processes generating these benefits and how they can be best promoted remain unclear. During an Expert Workshop held in September 2016, the evidence linking greenspace and health was reviewed from a transdisciplinary standpoint, with a particular focus on potential underlying biopsychosocial pathways and how these can be explored and organized to support policy-relevant population health research. Potential pathways linking greenspace to health are here presented in three domains, which emphasize three general functions of greenspace: reducing harm (e.g. reducing exposure to air pollution, noise and heat), restoring capacities (e.g. attention restoration and physiological stress recovery) and building capacities (e.g. encouraging physical activity and facilitating social cohesion). Interrelations between among the three domains are also noted. Among several recommendations, future studies should: use greenspace and behavioural measures that are relevant to hypothesized pathways; include assessment of presence, access and use of greenspace; use longitudinal, interventional and (quasi)experimental study designs to assess causation; and include low and middle income countries given their absence in the existing literature. Cultural, climatic, geographic and other contextual factors also need further consideration. While the existing evidence affirms beneficial impacts of greenspace on health, much remains to be learned about the specific pathways and functional form of such relationships, and how these may vary by context, population groups and health outcomes. This Report provides guidance for further epidemiological research with the goal of creating new evidence upon which to develop policy recommendations. Copyright © 2017 Elsevier Inc

  19. Hexokinases link DJ-1 to the PINK1/parkin pathway.

    Science.gov (United States)

    Hauser, David N; Mamais, Adamantios; Conti, Melissa M; Primiani, Christopher T; Kumaran, Ravindran; Dillman, Allissa A; Langston, Rebekah G; Beilina, Alexandra; Garcia, Joseph H; Diaz-Ruiz, Alberto; Bernier, Michel; Fiesel, Fabienne C; Hou, Xu; Springer, Wolfdieter; Li, Yan; de Cabo, Rafael; Cookson, Mark R

    2017-09-29

    Early onset Parkinson's disease is caused by variants in PINK1, parkin, and DJ-1. PINK1 and parkin operate in pathways that preserve mitochondrial integrity, but the function of DJ-1 and how it relates to PINK1 and parkin is poorly understood. A series of unbiased high-content screens were used to analyze changes at the protein, RNA, and metabolite level in rodent brains lacking DJ-1. Results were validated using targeted approaches, and cellular assays were performed to probe the mechanisms involved. We find that in both rat and mouse brains, DJ-1 knockout results in an age-dependent accumulation of hexokinase 1 in the cytosol, away from its usual location at the mitochondria, with subsequent activation of the polyol pathway of glucose metabolism in vivo. Both in the brain and in cultured cells, DJ-1 deficiency is associated with accumulation of the phosphatase PTEN that antagonizes the kinase AKT. In cells, addition of an inhibitor of AKT (MK2206) or addition of a peptide to dissociate association of hexokinases from mitochondria both inhibit the PINK1/parkin pathway, which works to maintain mitochondrial integrity. Hexokinases are an important link between three major genetic causes of early onset Parkinson's disease. Because aging is associated with deregulated nutrient sensing, these results help explain why DJ-1 is associated with age-dependent disease.

  20. The influence of posterior visual pathway damage on visual information processing speed in multiple sclerosis.

    Science.gov (United States)

    Gabilondo, Iñigo; Rilo, Oiane; Ojeda, Natalia; Pena, Javier; Gómez-Gastiasoro, Ainara; Mendibe Bilbao, Mar; Rodríguez-Antigüedad, Alfredo; Cabrera, Alberto; Diez, Ibai; Ibarretxe-Bilbao, Naroa

    2017-08-01

    The injury of visual pathway and abnormalities of visual processing speed (VPS) are frequent in MS, but their association remains unexplored. To evaluate the impact of posterior visual pathway structural and functional integrity on VPS of MS patients. Cross-sectional study of 30 MS patients and 28 controls, evaluating the association of a VPS tests composite (Salthouse Perceptual Comparison test, Trail Making Test A and Symbol Digit Modalities Test) with 3T MRI visual cortex thickness, optic radiations (OR) diffusion tensor imaging indexes, and medial visual component (MVC) functional connectivity (FC) (MVC-MVC FC (iFC) and MVC-brain FC (eFC)) by linear regression, removing the effect of premorbid IQ, fatigue, and depression. V2 atrophy, lower OR fractional anisotropy (FA) and MVC FC significantly influenced VPS in MS (at none or lesser extent in controls), even after removing the effect of Expanded Disability Status Scale and previous optic neuritis (V2 ( r2 = 0.210): β = +0.366, p = 0.046; OR FA ( r2 = 0.243): β = +0.378, p = 0.034; MVC iFC, for example, left cuneus ( r2 = 0.450): β = -0.613, p < 0.001; MVC eFC, for example, right precuneus-postcentral gyrus ( r2 = 0.368): β = -0.466, p = 0.002). Posterior visual pathway integrity, structural (V2 thickness and OR FA) and functional (MVC FC), may explain respectively up to 24% and 45% of VPS variability in MS.

  1. Fatigue in chronic inflammation - a link to pain pathways.

    Science.gov (United States)

    Louati, Karine; Berenbaum, Francis

    2015-10-05

    Fatigue is a frequent symptom in several inflammatory diseases, particularly in rheumatic diseases. Elements of disease activity and cognitive and behavior aspects have been reported as causes of fatigue in patients with rheumatoid arthritis. Fatigue could be associated with activity of inflammatory rheumatism. Indeed, biologic agents targeting inflammatory cytokines are effective in fatigue. Fatigue is also associated with pain and depressive symptoms. Different pathways could be involved in fatigue and interact: the immune system with increased levels of pro-inflammatory cytokines (interleukin-1 and -6 and tumor necrosis factor alpha), dysregulation of the hypothalamic-pituitary-adrenal axis and neurological phenomena involving the central and autonomic nervous systems. A pro-inflammatory process could be involved in pain and behavioral symptoms. Inflammation could be a common link between fatigue, pain, and depression.

  2. Linking regional stakeholder scenarios and shared socioeconomic pathways

    DEFF Research Database (Denmark)

    Palazzo, Amanda; Vervoort, Joost M.; Mason-D'Croz, Daniel

    2017-01-01

    The climate change research community's shared socioeconomic pathways (SSPs) are a set of alternative global development scenarios focused on mitigation of and adaptation to climate change. To use these scenarios as a global context that is relevant for policy guidance at regional and national......-generated narratives and scenario trends and SSP assumptions. We present this process as an example of linking comparable scenarios across levels to increase coherence with global contexts, while presenting insights about the future of agriculture and food security under a range of future drivers including climate...... economy, West Africa remains a large consumer and producer of a selection of commodities. However, the growth in population coupled with rising incomes leads to increases in the region's imports. For West Africa, climate change is projected to have negative effects on both crop yields and grassland...

  3. Evolutionary bursts in Euphorbia (Euphorbiaceae) are linked with photosynthetic pathway.

    Science.gov (United States)

    Horn, James W; Xi, Zhenxiang; Riina, Ricarda; Peirson, Jess A; Yang, Ya; Dorsey, Brian L; Berry, Paul E; Davis, Charles C; Wurdack, Kenneth J

    2014-12-01

    The mid-Cenozoic decline of atmospheric CO2 levels that promoted global climate change was critical to shaping contemporary arid ecosystems. Within angiosperms, two CO2 -concentrating mechanisms (CCMs)-crassulacean acid metabolism (CAM) and C4 -evolved from the C3 photosynthetic pathway, enabling more efficient whole-plant function in such environments. Many angiosperm clades with CCMs are thought to have diversified rapidly due to Miocene aridification, but links between this climate change, CCM evolution, and increased net diversification rates (r) remain to be further understood. Euphorbia (∼2000 species) includes a diversity of CAM-using stem succulents, plus a single species-rich C4 subclade. We used ancestral state reconstructions with a dated molecular phylogeny to reveal that CCMs independently evolved 17-22 times in Euphorbia, principally from the Miocene onwards. Analyses assessing among-lineage variation in r identified eight Euphorbia subclades with significantly increased r, six of which have a close temporal relationship with a lineage-corresponding CCM origin. Our trait-dependent diversification analysis indicated that r of Euphorbia CCM lineages is approximately threefold greater than C3 lineages. Overall, these results suggest that CCM evolution in Euphorbia was likely an adaptive strategy that enabled the occupation of increased arid niche space accompanying Miocene expansion of arid ecosystems. These opportunities evidently facilitated recent, replicated bursts of diversification in Euphorbia. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

  4. PathText: a text mining integrator for biological pathway visualizations

    Science.gov (United States)

    Kemper, Brian; Matsuzaki, Takuya; Matsuoka, Yukiko; Tsuruoka, Yoshimasa; Kitano, Hiroaki; Ananiadou, Sophia; Tsujii, Jun'ichi

    2010-01-01

    Motivation: Metabolic and signaling pathways are an increasingly important part of organizing knowledge in systems biology. They serve to integrate collective interpretations of facts scattered throughout literature. Biologists construct a pathway by reading a large number of articles and interpreting them as a consistent network, but most of the models constructed currently lack direct links to those articles. Biologists who want to check the original articles have to spend substantial amounts of time to collect relevant articles and identify the sections relevant to the pathway. Furthermore, with the scientific literature expanding by several thousand papers per week, keeping a model relevant requires a continuous curation effort. In this article, we present a system designed to integrate a pathway visualizer, text mining systems and annotation tools into a seamless environment. This will enable biologists to freely move between parts of a pathway and relevant sections of articles, as well as identify relevant papers from large text bases. The system, PathText, is developed by Systems Biology Institute, Okinawa Institute of Science and Technology, National Centre for Text Mining (University of Manchester) and the University of Tokyo, and is being used by groups of biologists from these locations. Contact: brian@monrovian.com. PMID:20529930

  5. Customizable Visualizations with Formula-Linked Building Blocks

    DEFF Research Database (Denmark)

    Kuhail, Mohammad Amin; Lauesen, Søren

    . Visualization toolkits allow easier visualization creation in some cases, but customization and interaction are tedious. As an alternative, we developed uVis visualization tool that uses spreadsheet-like formulas to connect building blocks. uVis formulas can refer to building blocks and database tables. We...

  6. High Symmetry of Visual Acuity and Visual Fields in RPGR-Linked Retinitis Pigmentosa.

    Science.gov (United States)

    Bellingrath, Julia-Sophia; Ochakovski, G Alex; Seitz, Immanuel P; Kohl, Susanne; Zrenner, Eberhart; Hanig, Nicola; Prokisch, Holger; Weber, Bernhard H; Downes, Susan M; Ramsden, Simon; MacLaren, Robert E; Fischer, M Dominik

    2017-09-01

    Mutations in retinitis pigmentosa GTPase regulator (RPGR) cause 70% to 90% of X-linked retinitis pigmentosa (XLRP3) cases, making this gene a high-yield target for gene therapy. This study analyzed the utility of relevant clinical biomarkers to assess symmetry and rate of progression in XLRP3. A retrospective, cross-sectional analysis of 50 XLRP3 patients extracted clinical data including visual acuity (VA), visual fields (I4e and III4e targets), foveal thickness, and ERG data points alongside molecular genetic data. Symmetry was assessed by using linear regression analysis. Kaplan-Meier survival curves (KMCs) and generalized linear mixed model calculations were used to describe disease progression. Ninety-six percent of patients exhibited a rod-cone phenotype, and 4% a cone-rod phenotype. Open reading frame 15 (ORF15) was confirmed as a mutational hotspot within RPGR harboring 73% of exonic mutations. Significant variability, but no clear genotype-phenotype relationship, could be shown between mutations located in exons 1-14 versus ORF15. All biomarkers suggested a high degree of symmetry between eyes but demonstrated different estimates of disease progression. VA and foveal thickness, followed by perimetry III4e, were the most useful endpoints to evaluate progression. KMC estimates predicted a loss of 6/6 vision at a mean of 34 years (±2.9; 95% confidence interval). XLRP3 affects retinal structure and function symmetrically, supporting the use of the fellow eye as an internal control in interventional trials. VA and kinetic visual fields (III4e) seem promising functional outcome measures to assess disease progression. KMC analysis predicted the most severe decline in vision between the third and fourth decade of life.

  7. Dorsal visual pathway changes in patients with comitant extropia.

    Directory of Open Access Journals (Sweden)

    Xiaohe Yan

    Full Text Available BACKGROUND: Strabismus is a disorder in which the eyes are misaligned. Persistent strabismus can lead to stereopsis impairment. The effect of strabismus on human brain is not unclear. The present study is to investigate whether the brain white structures of comitant exotropia patients are impaired using combined T1-weighted imaging and diffusion tensor imaging (DTI. PRINCIPAL FINDINGS: Thirteen patients with comitant strabismus and twelve controls underwent magnetic resonance imaging (MRI with acquisition of T1-weighted and diffusion tensor images. T1-weighted images were used to analyze the change in volume of white matter using optimized voxel-based morphology (VBM and diffusion tensor images were used to detect the change in white matter fibers using voxel-based analysis of DTI in comitant extropia patients. VBM analysis showed that in adult strabismus, white matter volumes were smaller in the right middle occipital gyrus, right occipital lobe/cuneus, right supramarginal gyrus, right cingulate gyrus, right frontal lobe/sub-gyral, right inferior temporal gyrus, left parahippocampa gyrus, left cingulate gyrus, left occipital lobe/cuneus, left middle frontal gyrus, left inferior parietal lobule, and left postcentral gyrus, while no brain region with greater white matter volume was found. Voxel-based analysis of DTI showed lower fractional anisotropy (FA values in the right middle occipital gyrus and right supramarginal gyrus in strabismus patients, while brain region with increased FA value was found in the right inferior frontal gyrus. CONCLUSION: By combining VBM and voxel-based analysis of DTI results, the study suggests that the dorsal visual pathway was abnormal or impaired in patients with comitant exotropia.

  8. Visual advantage in deaf adults linked to retinal changes.

    Directory of Open Access Journals (Sweden)

    Charlotte Codina

    Full Text Available The altered sensory experience of profound early onset deafness provokes sometimes large scale neural reorganisations. In particular, auditory-visual cross-modal plasticity occurs, wherein redundant auditory cortex becomes recruited to vision. However, the effect of human deafness on neural structures involved in visual processing prior to the visual cortex has never been investigated, either in humans or animals. We investigated neural changes at the retina and optic nerve head in profoundly deaf (N = 14 and hearing (N = 15 adults using Optical Coherence Tomography (OCT, an in-vivo light interference method of quantifying retinal micro-structure. We compared retinal changes with behavioural results from the same deaf and hearing adults, measuring sensitivity in the peripheral visual field using Goldmann perimetry. Deaf adults had significantly larger neural rim areas, within the optic nerve head in comparison to hearing controls suggesting greater retinal ganglion cell number. Deaf adults also demonstrated significantly larger visual field areas (indicating greater peripheral sensitivity than controls. Furthermore, neural rim area was significantly correlated with visual field area in both deaf and hearing adults. Deaf adults also showed a significantly different pattern of retinal nerve fibre layer (RNFL distribution compared to controls. Significant correlations between the depth of the RNFL at the inferior-nasal peripapillary retina and the corresponding far temporal and superior temporal visual field areas (sensitivity were found. Our results show that cross-modal plasticity after early onset deafness may not be limited to the sensory cortices, noting specific retinal adaptations in early onset deaf adults which are significantly correlated with peripheral vision sensitivity.

  9. Altered white matter in early visual pathways of humans with amblyopia.

    Science.gov (United States)

    Allen, Brian; Spiegel, Daniel P; Thompson, Benjamin; Pestilli, Franco; Rokers, Bas

    2015-09-01

    Amblyopia is a visual disorder caused by poorly coordinated binocular input during development. Little is known about the impact of amblyopia on the white matter within the visual system. We studied the properties of six major visual white-matter pathways in a group of adults with amblyopia (n=10) and matched controls (n=10) using diffusion weighted imaging (DWI) and fiber tractography. While we did not find significant differences in diffusion properties in cortico-cortical pathways, patients with amblyopia exhibited increased mean diffusivity in thalamo-cortical visual pathways. These findings suggest that amblyopia may systematically alter the white matter properties of early visual pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Abnormal brain activation in neurofibromatosis type 1: a link between visual processing and the default mode network.

    Directory of Open Access Journals (Sweden)

    Inês R Violante

    Full Text Available Neurofibromatosis type 1 (NF1 is one of the most common single gene disorders affecting the human nervous system with a high incidence of cognitive deficits, particularly visuospatial. Nevertheless, neurophysiological alterations in low-level visual processing that could be relevant to explain the cognitive phenotype are poorly understood. Here we used functional magnetic resonance imaging (fMRI to study early cortical visual pathways in children and adults with NF1. We employed two distinct stimulus types differing in contrast and spatial and temporal frequencies to evoke relatively different activation of the magnocellular (M and parvocellular (P pathways. Hemodynamic responses were investigated in retinotopically-defined regions V1, V2 and V3 and then over the acquired cortical volume. Relative to matched control subjects, patients with NF1 showed deficient activation of the low-level visual cortex to both stimulus types. Importantly, this finding was observed for children and adults with NF1, indicating that low-level visual processing deficits do not ameliorate with age. Moreover, only during M-biased stimulation patients with NF1 failed to deactivate or even activated anterior and posterior midline regions of the default mode network. The observation that the magnocellular visual pathway is impaired in NF1 in early visual processing and is specifically associated with a deficient deactivation of the default mode network may provide a neural explanation for high-order cognitive deficits present in NF1, particularly visuospatial and attentional. A link between magnocellular and default mode network processing may generalize to neuropsychiatric disorders where such deficits have been separately identified.

  11. Two Visual Pathways in Primates Based on Sampling of Space: Exploitation and Exploration of Visual Information

    Science.gov (United States)

    Sheth, Bhavin R.; Young, Ryan

    2016-01-01

    Evidence is strong that the visual pathway is segregated into two distinct streams—ventral and dorsal. Two proposals theorize that the pathways are segregated in function: The ventral stream processes information about object identity, whereas the dorsal stream, according to one model, processes information about either object location, and according to another, is responsible in executing movements under visual control. The models are influential; however recent experimental evidence challenges them, e.g., the ventral stream is not solely responsible for object recognition; conversely, its function is not strictly limited to object vision; the dorsal stream is not responsible by itself for spatial vision or visuomotor control; conversely, its function extends beyond vision or visuomotor control. In their place, we suggest a robust dichotomy consisting of a ventral stream selectively sampling high-resolution/focal spaces, and a dorsal stream sampling nearly all of space with reduced foveal bias. The proposal hews closely to the theme of embodied cognition: Function arises as a consequence of an extant sensory underpinning. A continuous, not sharp, segregation based on function emerges, and carries with it an undercurrent of an exploitation-exploration dichotomy. Under this interpretation, cells of the ventral stream, which individually have more punctate receptive fields that generally include the fovea or parafovea, provide detailed information about object shapes and features and lead to the systematic exploitation of said information; cells of the dorsal stream, which individually have large receptive fields, contribute to visuospatial perception, provide information about the presence/absence of salient objects and their locations for novel exploration and subsequent exploitation by the ventral stream or, under certain conditions, the dorsal stream. We leverage the dichotomy to unify neuropsychological cases under a common umbrella, account for the increased

  12. Two visual pathways in primates based on sampling of space: exploitation and exploration of visual information

    Directory of Open Access Journals (Sweden)

    Bhavin Sheth

    2016-11-01

    Full Text Available Evidence is strong that the visual pathway is segregated into two distinct streams – ventral and dorsal. Two proposals theorize that the pathways are segregated in function: The ventral stream processes information about object identity, whereas the dorsal stream, according to one model, processes information about either object location, and according to another, is responsible in executing movements under visual control. The models are influential; however recent experimental evidence challenges them, e.gs. the ventral stream is not solely responsible for object recognition; conversely, its function is not strictly limited to object vision; the dorsal stream is not responsible by itself for spatial vision or visuomotor control; conversely, its function extends beyond vision or visuomotor control. In their place, we suggest a robust dichotomy consisting of a ventral stream selectively sampling high-resolution/focal spaces, and a dorsal stream sampling nearly all of space with reduced foveal bias. The proposal hews closely to the theme of embodied cognition: Function arises as a consequence of an extant sensory underpinning. A continuous, not sharp, segregation based on function emerges, and carries with it an undercurrent of an exploitation-exploration dichotomy. Under this interpretation, cells of the ventral stream, which individually have more punctate receptive fields that generally include the fovea or parafovea, provide detailed information about object shapes and features and lead to the systematic exploitation of said information; cells of the dorsal stream, which individually have large receptive fields, contribute to visuospatial perception, provide information about the presence/absence of salient objects and their locations for novel exploration and subsequent exploitation by the ventral stream or, under certain conditions, the dorsal stream. We leverage the dichotomy to unify neuropsychological cases under a common umbrella

  13. Building a Linked Learning Pathway: A Guide for Transforming High Schools for College and Career Success

    Science.gov (United States)

    Atterbury, Rob

    2014-01-01

    This guide provides an overview of a more robust online guide and toolkit available through ConnectEd Studios. It supplies a glimpse of the sequence of steps involved in creating a new Linked Learning pathway. This publication can help coaches, district leadership, and pathway teams gain an understanding of the overall process of designing and…

  14. A causal link between visual spatial attention and reading acquisition.

    Science.gov (United States)

    Franceschini, Sandro; Gori, Simone; Ruffino, Milena; Pedrolli, Katia; Facoetti, Andrea

    2012-05-08

    Reading is a unique, cognitive human skill crucial to life in modern societies, but, for about 10% of the children, learning to read is extremely difficult. They are affected by a neurodevelopmental disorder called dyslexia. Although impaired auditory and speech sound processing is widely assumed to characterize dyslexic individuals, emerging evidence suggests that dyslexia could arise from a more basic cross-modal letter-to-speech sound integration deficit. Letters have to be precisely selected from irrelevant and cluttering letters by rapid orienting of visual attention before the correct letter-to-speech sound integration applies. Here we ask whether prereading visual parietal-attention functioning may explain future reading emergence and development. The present 3 year longitudinal study shows that prereading attentional orienting--assessed by serial search performance and spatial cueing facilitation--captures future reading acquisition skills in grades 1 and 2 after controlling for age, nonverbal IQ, speech-sound processing, and nonalphabetic cross-modal mapping. Our findings provide the first evidence that visual spatial attention in preschoolers specifically predicts future reading acquisition, suggesting new approaches for early identification and efficient prevention of dyslexia. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Reduction of Interhemispheric Functional Connectivity in Sensorimotor and Visual Information Processing Pathways in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Xu Lang

    2016-01-01

    Conclusions: Interhemispheric functional connectivity in the sensorimotor and visual processing pathways was reduced in patients with schizophrenia, but this reduction was unrelated to the disease state; thus, this reduction may serve as a trait marker of schizophrenia.

  16. Visinets: a web-based pathway modeling and dynamic visualization tool

    National Research Council Canada - National Science Library

    Spychala, Jozef; Spychala, Pawel; Gomez, Shawn; Weinreb, Gabriel E

    2015-01-01

    In this report we describe a novel graphically oriented method for pathway modeling and a software package that allows for both modeling and visualization of biological networks in a user-friendly format...

  17. Visinets: A Web-Based Pathway Modeling and Dynamic Visualization Tool: e0123773

    National Research Council Canada - National Science Library

    Jozef Spychala; Pawel Spychala; Shawn Gomez; Gabriel E Weinreb

    2015-01-01

      In this report we describe a novel graphically oriented method for pathway modeling and a software package that allows for both modeling and visualization of biological networks in a user-friendly format...

  18. Common developmental pathways link tooth shape to regeneration

    Science.gov (United States)

    Fraser, Gareth J.; Bloomquist, Ryan F.; Streelman, J. Todd

    2013-01-01

    In many non-mammalian vertebrates, adult dentitions result from cyclical rounds of tooth regeneration wherein simple unicuspid teeth are replaced by more complex forms. Therefore and by contrast to mammalian models, the numerical majority of vertebrate teeth develop shape during the process of replacement. Here, we exploit the dental diversity of Lake Malawi cichlid fishes to ask how vertebrates generally replace their dentition and in turn how this process acts to influence resulting tooth morphologies. First, we used immunohistochemistry to chart organogenesis of continually replacing cichlid teeth and discovered an epithelial down-growth that initiates the replacement cycle via a labial proliferation bias. Next, we identified sets of co-expressed genes from common pathways active during de novo, lifelong tooth replacement and tooth morphogenesis. Of note, we found two distinct epithelial cell populations, expressing markers of dental competence and cell potency, which may be responsible for tooth regeneration. Related gene sets were simultaneously active in putative signaling centers associated with the differentiation of replacement teeth with complex shapes. Finally, we manipulated targeted pathways (BMP, FGF, Hh, Notch, Wnt/β-catenin) in vivo with small molecules and demonstrated dose-dependent effects on both tooth replacement and tooth shape. Our data suggest that the processes of tooth regeneration and tooth shape morphogenesis are integrated via a common set of molecular signals. This linkage has subsequently been lost or decoupled in mammalian dentitions where complex tooth shapes develop in first generation dentitions that lack the capacity for lifelong replacement. Our dissection of the molecular mechanics of vertebrate tooth replacement coupled to complex shape pinpoints aspects of odontogenesis that might be re-evolved in the lab to solve problems in regenerative dentistry. PMID:23422830

  19. Common developmental pathways link tooth shape to regeneration.

    Science.gov (United States)

    Fraser, Gareth J; Bloomquist, Ryan F; Streelman, J Todd

    2013-05-15

    In many non-mammalian vertebrates, adult dentitions result from cyclical rounds of tooth regeneration wherein simple unicuspid teeth are replaced by more complex forms. Therefore and by contrast to mammalian models, the numerical majority of vertebrate teeth develop shape during the process of replacement. Here, we exploit the dental diversity of Lake Malawi cichlid fishes to ask how vertebrates generally replace their dentition and in turn how this process acts to influence resulting tooth morphologies. First, we used immunohistochemistry to chart organogenesis of continually replacing cichlid teeth and discovered an epithelial down-growth that initiates the replacement cycle via a labial proliferation bias. Next, we identified sets of co-expressed genes from common pathways active during de novo, lifelong tooth replacement and tooth morphogenesis. Of note, we found two distinct epithelial cell populations, expressing markers of dental competence and cell potency, which may be responsible for tooth regeneration. Related gene sets were simultaneously active in putative signaling centers associated with the differentiation of replacement teeth with complex shapes. Finally, we manipulated targeted pathways (BMP, FGF, Hh, Notch, Wnt/β-catenin) in vivo with small molecules and demonstrated dose-dependent effects on both tooth replacement and tooth shape. Our data suggest that the processes of tooth regeneration and tooth shape morphogenesis are integrated via a common set of molecular signals. This linkage has subsequently been lost or decoupled in mammalian dentitions where complex tooth shapes develop in first generation dentitions that lack the capacity for lifelong replacement. Our dissection of the molecular mechanics of vertebrate tooth replacement coupled to complex shape pinpoints aspects of odontogenesis that might be re-evolved in the lab to solve problems in regenerative dentistry. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. BID links ferroptosis to mitochondrial cell death pathways

    Directory of Open Access Journals (Sweden)

    Sandra Neitemeier

    2017-08-01

    In the present study, we find that erastin-induced ferroptosis in neuronal cells was accompanied by BID transactivation to mitochondria, loss of mitochondrial membrane potential, enhanced mitochondrial fragmentation and reduced ATP levels. These hallmarks of mitochondrial demise are also established features of oxytosis, a paradigm of cell death induced by Xc- inhibition by millimolar concentrations of glutamate. Bid knockout using CRISPR/Cas9 approaches preserved mitochondrial integrity and function, and mediated neuroprotective effects against both, ferroptosis and oxytosis. Furthermore, the BID-inhibitor BI-6c9 inhibited erastin-induced ferroptosis, and, in turn, the ferroptosis inhibitors ferrostatin-1 and liproxstatin-1 prevented mitochondrial dysfunction and cell death in the paradigm of oxytosis. These findings show that mitochondrial transactivation of BID links ferroptosis to mitochondrial damage as the final execution step in this paradigm of oxidative cell death.

  1. Metabolic network visualization eliminating node redundance and preserving metabolic pathways

    Directory of Open Access Journals (Sweden)

    Sagot Marie-France

    2007-07-01

    Full Text Available Abstract Background The tools that are available to draw and to manipulate the representations of metabolism are usually restricted to metabolic pathways. This limitation becomes problematic when studying processes that span several pathways. The various attempts that have been made to draw genome-scale metabolic networks are confronted with two shortcomings: 1- they do not use contextual information which leads to dense, hard to interpret drawings, 2- they impose to fit to very constrained standards, which implies, in particular, duplicating nodes making topological analysis considerably more difficult. Results We propose a method, called MetaViz, which enables to draw a genome-scale metabolic network and that also takes into account its structuration into pathways. This method consists in two steps: a clustering step which addresses the pathway overlapping problem and a drawing step which consists in drawing the clustered graph and each cluster. Conclusion The method we propose is original and addresses new drawing issues arising from the no-duplication constraint. We do not propose a single drawing but rather several alternative ways of presenting metabolism depending on the pathway on which one wishes to focus. We believe that this provides a valuable tool to explore the pathway structure of metabolism.

  2. Escher: A Web Application for Building, Sharing, and Embedding Data-Rich Visualizations of Biological Pathways

    DEFF Research Database (Denmark)

    King, Zachary A.; Draeger, Andreas; Ebrahim, Ali

    2015-01-01

    draw pathways in a semi-automated way. Second, users can visualize data related to genes or proteins on the associated reactions and pathways, using rules that define which enzymes catalyze each reaction. Thus, users can identify trends in common genomic data types (e.g. RNA-Seq, proteomics, Ch...

  3. The ZEB1 pathway links glioblastoma initiation, invasion and chemoresistance.

    Science.gov (United States)

    Siebzehnrubl, Florian A; Silver, Daniel J; Tugertimur, Bugra; Deleyrolle, Loic P; Siebzehnrubl, Dorit; Sarkisian, Matthew R; Devers, Kelly G; Yachnis, Antony T; Kupper, Marius D; Neal, Daniel; Nabilsi, Nancy H; Kladde, Michael P; Suslov, Oleg; Brabletz, Simone; Brabletz, Thomas; Reynolds, Brent A; Steindler, Dennis A

    2013-08-01

    Glioblastoma remains one of the most lethal types of cancer, and is the most common brain tumour in adults. In particular, tumour recurrence after surgical resection and radiation invariably occurs regardless of aggressive chemotherapy. Here, we provide evidence that the transcription factor ZEB1 (zinc finger E-box binding homeobox 1) exerts simultaneous influence over invasion, chemoresistance and tumourigenesis in glioblastoma. ZEB1 is preferentially expressed in invasive glioblastoma cells, where the ZEB1-miR-200 feedback loop interconnects these processes through the downstream effectors ROBO1, c-MYB and MGMT. Moreover, ZEB1 expression in glioblastoma patients is predictive of shorter survival and poor Temozolomide response. Our findings indicate that this regulator of epithelial-mesenchymal transition orchestrates key features of cancer stem cells in malignant glioma and identify ROBO1, OLIG2, CD133 and MGMT as novel targets of the ZEB1 pathway. Thus, ZEB1 is an important candidate molecule for glioblastoma recurrence, a marker of invasive tumour cells and a potential therapeutic target, along with its downstream effectors. © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.

  4. Neuroplasticity Signaling Pathways Linked to the Pathophysiology of Schizophrenia

    Science.gov (United States)

    Balu, Darrick T.; Coyle, Joseph T.

    2010-01-01

    Schizophrenia is a severe mental illness that afflicts nearly 1% of the world's population. One of the cardinal pathological features of schizophrenia is perturbation in synaptic connectivity. Although the etiology of schizophrenia is unknown, it appears to be a developmental disorder involving the interaction of a potentially large number of risk genes, with no one gene producing a strong effect except rare, highly penetrant copy number variants. The purpose of this review is to detail how putative schizophrenia risk genes (DISC-1, neuregulin/ErbB4, dysbindin, Akt1, BDNF, and NMDA receptor) are involved in regulating neuroplasticity and how alterations in their expression may contribute to the disconnectivity observed in schizophrenia. Moreover, this review highlights how many of these risk genes converge to regulate common neurotransmitter systems and signaling pathways. Future studies aimed at elucidating the functions of these risk genes will provide new insights into the pathophysiology of schizophrenia and will likely lead to the nomination of novel therapeutic targets for restoring proper synaptic connectivity in the brain in schizophrenia and related disorders. PMID:20951727

  5. New tools for the visualization of biological pathways.

    Science.gov (United States)

    Ghosh, Tomojit; Ma, Xiaofeng; Kirby, Michael

    2018-01-01

    This paper presents several geometrically motivated techniques for the visualization of high-dimensional biological data sets. The Grassmann manifold provides a robust framework for measuring data similarity in a subspace context. Sparse radial basis function classification as a visualization technique leverages recent advances in radial basis function learning via convex optimization. In the spirit of deep belief networks, supervised centroid-encoding is proposed as a way to exploit class label information. These methods are compared to linear and nonlinear principal component analysis (autoencoders) in the context of data visualization; these approaches may perform poorly for visualization when the variance of the data is spread across more than three dimensions. In contrast, the proposed methods are shown to capture significant data structure in two or three dimensions, even when the information in the data lives in higher dimensional subspaces. To illustrate these ideas, the visualization techniques are applied to gene expression data sets that capture the host immune system's response to infection by the Ebola virus in non-human primate and collaborative cross mouse. Copyright © 2017. Published by Elsevier Inc.

  6. Linking Family Economic Hardship to Early Childhood Health: An Investigation of Mediating Pathways.

    Science.gov (United States)

    Hsu, Hui-Chin; Wickrama, Kandauda A S

    2015-12-01

    The underlying mechanisms through which family economic adversity influences child health are less understood. Taking a process-oriented approach, this study examined maternal mental health and investment in children, child health insurance, and child healthcare as mediators linking family economic hardship (FEH) to child health. A structural equation modeling was applied to test the hypothesized mediating model. After adjustment for sociodemographic risk factors, results revealed: (1) a significant direct path linking FEH to poor child health (effect size = .372), and (2) six significant mediating pathways (total effect size = .089). In two mediating pathways, exposures to FEH undermined mothers' mental health: in the first pathway poor maternal mental health led to decreased parental investment, which, in turn, contributed to poor child health, whereas in the second pathway the adverse effect of poor maternal mental health was cascaded through child unmet healthcare need, which resulted in poor child health. One pathway involved child insurance status, where the effect of FEH increased the likelihood to be uninsured, which led to unmet healthcare need, and, in turn, to poor health. Three pathways involved preventive care: in one pathway FEH contributed to poor preventive care, which led to unmet healthcare need and then to poor health; in the other two pathways where poor preventive care respectively gave rise to decreased investment in children or poor maternal mental health, which further contributed to poor child health. Results suggest that the association between FEH and children's health is mediated by multiple pathways.

  7. Escher: A Web Application for Building, Sharing, and Embedding Data-Rich Visualizations of Biological Pathways.

    Directory of Open Access Journals (Sweden)

    Zachary A King

    2015-08-01

    Full Text Available Escher is a web application for visualizing data on biological pathways. Three key features make Escher a uniquely effective tool for pathway visualization. First, users can rapidly design new pathway maps. Escher provides pathway suggestions based on user data and genome-scale models, so users can draw pathways in a semi-automated way. Second, users can visualize data related to genes or proteins on the associated reactions and pathways, using rules that define which enzymes catalyze each reaction. Thus, users can identify trends in common genomic data types (e.g. RNA-Seq, proteomics, ChIP--in conjunction with metabolite- and reaction-oriented data types (e.g. metabolomics, fluxomics. Third, Escher harnesses the strengths of web technologies (SVG, D3, developer tools so that visualizations can be rapidly adapted, extended, shared, and embedded. This paper provides examples of each of these features and explains how the development approach used for Escher can be used to guide the development of future visualization tools.

  8. Escher: A Web Application for Building, Sharing, and Embedding Data-Rich Visualizations of Biological Pathways.

    Science.gov (United States)

    King, Zachary A; Dräger, Andreas; Ebrahim, Ali; Sonnenschein, Nikolaus; Lewis, Nathan E; Palsson, Bernhard O

    2015-08-01

    Escher is a web application for visualizing data on biological pathways. Three key features make Escher a uniquely effective tool for pathway visualization. First, users can rapidly design new pathway maps. Escher provides pathway suggestions based on user data and genome-scale models, so users can draw pathways in a semi-automated way. Second, users can visualize data related to genes or proteins on the associated reactions and pathways, using rules that define which enzymes catalyze each reaction. Thus, users can identify trends in common genomic data types (e.g. RNA-Seq, proteomics, ChIP)--in conjunction with metabolite- and reaction-oriented data types (e.g. metabolomics, fluxomics). Third, Escher harnesses the strengths of web technologies (SVG, D3, developer tools) so that visualizations can be rapidly adapted, extended, shared, and embedded. This paper provides examples of each of these features and explains how the development approach used for Escher can be used to guide the development of future visualization tools.

  9. A Review of Pathway-Based Analysis Tools That Visualize Genetic Variants.

    Science.gov (United States)

    Cirillo, Elisa; Parnell, Laurence D; Evelo, Chris T

    2017-01-01

    Pathway analysis is a powerful method for data analysis in genomics, most often applied to gene expression analysis. It is also promising for single-nucleotide polymorphism (SNP) data analysis, such as genome-wide association study data, because it allows the interpretation of variants with respect to the biological processes in which the affected genes and proteins are involved. Such analyses support an interactive evaluation of the possible effects of variations on function, regulation or interaction of gene products. Current pathway analysis software often does not support data visualization of variants in pathways as an alternate method to interpret genetic association results, and specific statistical methods for pathway analysis of SNP data are not combined with these visualization features. In this review, we first describe the visualization options of the tools that were identified by a literature review, in order to provide insight for improvements in this developing field. Tool evaluation was performed using a computational epistatic dataset of gene-gene interactions for obesity risk. Next, we report the necessity to include in these tools statistical methods designed for the pathway-based analysis with SNP data, expressly aiming to define features for more comprehensive pathway-based analysis tools. We conclude by recognizing that pathway analysis of genetic variations data requires a sophisticated combination of the most useful and informative visual aspects of the various tools evaluated.

  10. Delayed early primary visual pathway development in premature infants: high density electrophysiological evidence.

    Directory of Open Access Journals (Sweden)

    Emmanuel Tremblay

    Full Text Available In the past decades, multiple studies have been interested in developmental patterns of the visual system in healthy infants. During the first year of life, differential maturational changes have been observed between the Magnocellular (P and the Parvocellular (P visual pathways. However, few studies investigated P and M system development in infants born prematurely. The aim of the present study was to characterize P and M system maturational differences between healthy preterm and fullterm infants through a critical period of visual maturation: the first year of life. Using a cross-sectional design, high-density electroencephalogram (EEG was recorded in 31 healthy preterms and 41 fullterm infants of 3, 6, or 12 months (corrected age for premature babies. Three visual stimulations varying in contrast and spatial frequency were presented to stimulate preferentially the M pathway, the P pathway, or both systems simultaneously during EEG recordings. Results from early visual evoked potentials in response to the stimulation that activates simultaneously both systems revealed longer N1 latencies and smaller P1 amplitudes in preterm infants compared to fullterms. Moreover, preterms showed longer N1 and P1 latencies in response to stimuli assessing the M pathway at 3 months. No differences between preterms and fullterms were found when using the preferential P system stimulation. In order to identify the cerebral generator of each visual response, distributed source analyses were computed in 12-month-old infants using LORETA. Source analysis demonstrated an activation of the parietal dorsal region in fullterm infants, in response to the preferential M pathway, which was not seen in the preterms. Overall, these findings suggest that the Magnocellular pathway development is affected in premature infants. Although our VEP results suggest that premature children overcome, at least partially, the visual developmental delay with time, source analyses reveal

  11. Delayed early primary visual pathway development in premature infants: high density electrophysiological evidence.

    Science.gov (United States)

    Tremblay, Emmanuel; Vannasing, Phetsamone; Roy, Marie-Sylvie; Lefebvre, Francine; Kombate, Damelan; Lassonde, Maryse; Lepore, Franco; McKerral, Michelle; Gallagher, Anne

    2014-01-01

    In the past decades, multiple studies have been interested in developmental patterns of the visual system in healthy infants. During the first year of life, differential maturational changes have been observed between the Magnocellular (P) and the Parvocellular (P) visual pathways. However, few studies investigated P and M system development in infants born prematurely. The aim of the present study was to characterize P and M system maturational differences between healthy preterm and fullterm infants through a critical period of visual maturation: the first year of life. Using a cross-sectional design, high-density electroencephalogram (EEG) was recorded in 31 healthy preterms and 41 fullterm infants of 3, 6, or 12 months (corrected age for premature babies). Three visual stimulations varying in contrast and spatial frequency were presented to stimulate preferentially the M pathway, the P pathway, or both systems simultaneously during EEG recordings. Results from early visual evoked potentials in response to the stimulation that activates simultaneously both systems revealed longer N1 latencies and smaller P1 amplitudes in preterm infants compared to fullterms. Moreover, preterms showed longer N1 and P1 latencies in response to stimuli assessing the M pathway at 3 months. No differences between preterms and fullterms were found when using the preferential P system stimulation. In order to identify the cerebral generator of each visual response, distributed source analyses were computed in 12-month-old infants using LORETA. Source analysis demonstrated an activation of the parietal dorsal region in fullterm infants, in response to the preferential M pathway, which was not seen in the preterms. Overall, these findings suggest that the Magnocellular pathway development is affected in premature infants. Although our VEP results suggest that premature children overcome, at least partially, the visual developmental delay with time, source analyses reveal abnormal brain

  12. Integrative pathways linking close family ties to health: A neurochemical perspective.

    Science.gov (United States)

    Uchino, Bert N; Way, Baldwin M

    2017-09-01

    The quality of one's familial life, for better or worse, has been linked to physical health. Such associations are evident across a number of acute and chronic conditions and highlight the widespread impact that close relationships have on physical health. However, the field currently lacks a complete understanding of the integrative biological pathways underlying the association between close relationships and disease risk. This article reviews the main peripheral biological and central nervous system pathways linking positive and negative familial relationship processes to physical health outcomes. It emphasizes the role of neurochemical pathways in mediating the influence of social relationships on health-relevant peripheral physiological systems using the oxytocin system as a model. Such neurochemical approaches are an important step toward a more integrative understanding of complex biological pathways and has novel theoretical and intervention implications. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  13. Visual arts training is linked to flexible attention to local and global levels of visual stimuli.

    Science.gov (United States)

    Chamberlain, Rebecca; Wagemans, Johan

    2015-10-01

    Observational drawing skill has been shown to be associated with the ability to focus on local visual details. It is unclear whether superior performance in local processing is indicative of the ability to attend to, and flexibly switch between, local and global levels of visual stimuli. It is also unknown whether these attentional enhancements remain specific to observational drawing skill or are a product of a wide range of artistic activities. The current study aimed to address these questions by testing if flexible visual processing predicts artistic group membership and observational drawing skill in a sample of first-year bachelor's degree art students (n=23) and non-art students (n=23). A pattern of local and global visual processing enhancements was found in relation to artistic group membership and drawing skill, with local processing ability found to be specifically related to individual differences in drawing skill. Enhanced global processing and more fluent switching between local and global levels of hierarchical stimuli predicted both drawing skill and artistic group membership, suggesting that these are beneficial attentional mechanisms for art-making in a range of domains. These findings support a top-down attentional model of artistic expertise and shed light on the domain specific and domain-general attentional enhancements induced by proficiency in the visual arts. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. DEPRIVATION AND STRABISMIC AMBLYOPIA: ABNORMALITIES IN GENICULOCORTICAL VISUAL PATHWAYS

    Directory of Open Access Journals (Sweden)

    S. V. Alekseenko

    2015-01-01

    Full Text Available Background: There are inconsistent data on the changes of functional performance in subcortical structures of visual system caused by early binocular vision impairment. Aim: To study neuronal functional activity of the dorsal lateral geniculate nucleus (LGNd in monocularly deprived cats and strabismic cats. Materials and methods: 4 cats with monocular convergent strabismus, 7 cats with monocular divergent strabismus, 3 monocularly deprived cats and 4 intact cats were studied. Histochemical method was used to detect cytochrome oxidase – the mitochondrial enzyme of respiratory chain correlating with neuronal functional activity. Optical density in ocular-specific layers A and A1 was measured on the images of stained LGNd sections, and the contrast was calculated. Results: Relative reduction of functional activity in the layers innervated from deprived and squinted eyes was demonstrated in LGNd bilaterally. In strabismic animals, the changes were observed only in the projection of the central part of the visual field, whereas in monocularly deprived animals the changes were in the projection of the whole visual field. Conclusion: These findings indicate differences between the mechanisms determining the development of strabismic and deprivation amblyopia. Thus, in amblyopia, preservation of peripheral stereoscopic vision is possible.

  15. Visual pathway impairment by pituitary adenomas: quantitative diagnostics by diffusion tensor imaging.

    Science.gov (United States)

    Lilja, Ylva; Gustafsson, Oscar; Ljungberg, Maria; Starck, Göran; Lindblom, Bertil; Skoglund, Thomas; Bergquist, Henrik; Jakobsson, Karl-Erik; Nilsson, Daniel

    2017-09-01

    OBJECTIVE Despite ample experience in surgical treatment of pituitary adenomas, little is known about objective indices that may reveal risk of visual impairment caused by tumor growth that leads to compression of the anterior visual pathways. This study aimed to explore diffusion tensor imaging (DTI) as a means for objective assessment of injury to the anterior visual pathways caused by pituitary adenomas. METHODS Twenty-three patients with pituitary adenomas, scheduled for transsphenoidal tumor resection, and 20 healthy control subjects were included in the study. A minimum suprasellar tumor extension of Grade 2-4, according to the SIPAP (suprasellar, infrasellar, parasellar, anterior, and posterior) scale, was required for inclusion. Neuroophthalmological examinations, conventional MRI, and DTI were completed in all subjects and were repeated 6 months after surgery. Quantitative assessment of chiasmal lift, visual field defect (VFD), and DTI parameters from the optic tracts was performed. Linear correlations, group comparisons, and prediction models were done in controls and patients. RESULTS Both the degree of VFD and chiasmal lift were significantly correlated with the radial diffusivity (r = 0.55, p visual pathways that were compressed by pituitary adenomas. The correlation between radial diffusivity and visual impairment may reflect a gradual demyelination in the visual pathways caused by an increased tumor effect. The low level of axial diffusivity found in the patient group may represent early atrophy in the visual pathways, detectable on DTI but not by conventional methods. DTI may provide objective data, detect early signs of injury, and be an additional diagnostic tool for determining indication for surgery in cases of pituitary adenomas.

  16. Integration of parallel mechanosensory and visual pathways resolved through sensory conflict.

    Science.gov (United States)

    Roth, Eatai; Hall, Robert W; Daniel, Thomas L; Sponberg, Simon

    2016-10-24

    The acquisition of information from parallel sensory pathways is a hallmark of coordinated movement in animals. Insect flight, for example, relies on both mechanosensory and visual pathways. Our challenge is to disentangle the relative contribution of each modality to the control of behavior. Toward this end, we show an experimental and analytical framework leveraging sensory conflict, a means for independently exciting and modeling separate sensory pathways within a multisensory behavior. As a model, we examine the hovering flower-feeding behavior in the hawkmoth Manduca sexta In the laboratory, moths feed from a robotically actuated two-part artificial flower that allows independent presentation of visual and mechanosensory cues. Freely flying moths track lateral flower motion stimuli in an assay spanning both coupled motion, in which visual and mechanosensory cues follow the same motion trajectory, and sensory conflict, in which the two sensory modalities encode different motion stimuli. Applying a frequency-domain system identification analysis, we find that the tracking behavior is, in fact, multisensory and arises from a linear summation of visual and mechanosensory pathways. The response dynamics are highly preserved across individuals, providing a model for predicting the response to novel multimodal stimuli. Surprisingly, we find that each pathway in and of itself is sufficient for driving tracking behavior. When multiple sensory pathways elicit strong behavioral responses, this parallel architecture furnishes robustness via redundancy.

  17. MRI of optic nerve and postchiasmal visual pathways and visual evoked potentials in secondary progressive multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Davies, M.B.; Hawkins, C.P. [School of Postgraduate Medicine, Keele Univ. (United Kingdom)]|[Department of Neurology and Neurophysiology, Royal Infirmary, Stoke-on-Trent (United Kingdom); Williams, R. [MRI Unit Cornwall House, Stoke-on-Trent (United Kingdom); Haq, N. [Department of Neurology, North Staffordshire Hospital, Stoke-on-Trent (United Kingdom); Pelosi, L. [Department of Neurology and Neurophysiology, Royal Infirmary, Stoke-on-Trent (United Kingdom)

    1998-12-01

    We studied the relationship between abnormalities shown by MRI and functional disturbances in the visual pathway as assessed by the visual evoked potential (VEP) in 25 patients with established multiple sclerosis (MS); only 4 of whom had a history of acute optic neuritis. Optic nerve MRI was abnormal in 19 (76 %) and is thus useful in detecting subclinical disease. Optic nerve total lesion length and area on the STIR sequence was found to correlate significantly with prolongation of the VEP latency. This may reflect a predominantly demyelinating rather than inflammatory origin for the signal change in the optic nerve. (orig.) With 5 figs., 1 tab., 25 refs.

  18. Feature-Specific Organization of Feedback Pathways in Mouse Visual Cortex.

    Science.gov (United States)

    Huh, Carey Y L; Peach, John P; Bennett, Corbett; Vega, Roxana M; Hestrin, Shaul

    2018-01-08

    Higher and lower cortical areas in the visual hierarchy are reciprocally connected [1]. Although much is known about how feedforward pathways shape receptive field properties of visual neurons, relatively little is known about the role of feedback pathways in visual processing. Feedback pathways are thought to carry top-down signals, including information about context (e.g., figure-ground segmentation and surround suppression) [2-5], and feedback has been demonstrated to sharpen orientation tuning of neurons in the primary visual cortex (V1) [6, 7]. However, the response characteristics of feedback neurons themselves and how feedback shapes V1 neurons' tuning for other features, such as spatial frequency (SF), remain largely unknown. Here, using a retrograde virus, targeted electrophysiological recordings, and optogenetic manipulations, we show that putatively feedback neurons in layer 5 (hereafter "L5 feedback") in higher visual areas, AL (anterolateral area) and PM (posteromedial area), display distinct visual properties in awake head-fixed mice. AL L5 feedback neurons prefer significantly lower SF (mean: 0.04 cycles per degree [cpd]) compared to PM L5 feedback neurons (0.15 cpd). Importantly, silencing AL L5 feedback reduced visual responses of V1 neurons preferring low SF (mean change in firing rate: -8.0%), whereas silencing PM L5 feedback suppressed responses of high-SF-preferring V1 neurons (-20.4%). These findings suggest that feedback connections from higher visual areas convey distinctly tuned visual inputs to V1 that serve to boost V1 neurons' responses to SF. Such like-to-like functional organization may represent an important feature of feedback pathways in sensory systems and in the nervous system in general. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Testing Pathways Linking Exposure to Community Violence and Sexual Behaviors Among African American Youth

    Science.gov (United States)

    Hotton, Anna L.; Neilands, Torsten B.

    2014-01-01

    Exposure to community violence and HIV sexual risks are two major public health concerns among youth. This study tests various pathways linking exposure to community violence and sexual behaviors among African American adolescents. Using a sample of 563 (61 % females) African American youth attending high school we examined whether problematic psychological symptoms, low school engagement, and/or negative perceptions of peer norms about safer sex functioned as pathways linking exposure to community violence and sexual behaviors. Major findings indicated that, for boys, the relationship between exposure to community violence and sexual début and sexual risk behaviors were linked by aggression. In addition, the relationship between exposure to community violence and sexual risk behaviors were linked by negative perceptions of peer attitudes about safer sex. For girls, the relationship between exposure to community violence and sexual début was linked by aggression and negative perceptions of peer attitudes about safer sex. These findings provide support for pathways linking exposure to community violence to sexual behaviors. PMID:24327295

  20. Testing pathways linking exposure to community violence and sexual behaviors among African American youth.

    Science.gov (United States)

    Voisin, Dexter R; Hotton, Anna L; Neilands, Torsten B

    2014-09-01

    Exposure to community violence and HIV sexual risks are two major public health concerns among youth. This study tests various pathways linking exposure to community violence and sexual behaviors among African American adolescents. Using a sample of 563 (61% females) African American youth attending high school we examined whether problematic psychological symptoms, low school engagement, and/or negative perceptions of peer norms about safer sex functioned as pathways linking exposure to community violence and sexual behaviors. Major findings indicated that, for boys, the relationship between exposure to community violence and sexual début and sexual risk behaviors were linked by aggression. In addition, the relationship between exposure to community violence and sexual risk behaviors were linked by negative perceptions of peer attitudes about safer sex. For girls, the relationship between exposure to community violence and sexual début was linked by aggression and negative perceptions of peer attitudes about safer sex. These findings provide support for pathways linking exposure to community violence to sexual behaviors.

  1. Linking fungal secondary metabolites and pathways to their genes in Aspergillus

    DEFF Research Database (Denmark)

    Petersen, Lene Maj

    . oryzae metabolites, however, revealed the chemical link between the two species. In two parallel projects, involving A. niger and A. aculeatus respectively, the polyketide 6-methyl salicylic acid (6-MSA), and corresponding biosynthetic pathways, were investigated. In A. niger, 6-MSA was converted...

  2. Centralized modularity of N-linked glycosylation pathways in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Pan-Jun Kim

    Full Text Available Glycosylation is a highly complex process to produce a diverse repertoire of cellular glycans that are attached to proteins and lipids. Glycans are involved in fundamental biological processes, including protein folding and clearance, cell proliferation and apoptosis, development, immune responses, and pathogenesis. One of the major types of glycans, N-linked glycans, is formed by sequential attachments of monosaccharides to proteins by a limited number of enzymes. Many of these enzymes can accept multiple N-linked glycans as substrates, thereby generating a large number of glycan intermediates and their intermingled pathways. Motivated by the quantitative methods developed in complex network research, we investigated the large-scale organization of such N-linked glycosylation pathways in mammalian cells. The N-linked glycosylation pathways are extremely modular, and are composed of cohesive topological modules that directly branch from a common upstream pathway of glycan synthesis. This unique structural property allows the glycan production between modules to be controlled by the upstream region. Although the enzymes act on multiple glycan substrates, indicating cross-talk between modules, the impact of the cross-talk on the module-specific enhancement of glycan synthesis may be confined within a moderate range by transcription-level control. The findings of the present study provide experimentally-testable predictions for glycosylation processes, and may be applicable to therapeutic glycoprotein engineering.

  3. Enabling global processing in simultanagnosia by psychophysical biasing of visual pathways

    OpenAIRE

    Thomas, Cibu; Kveraga, Kestutis; Huberle, Elisabeth; Karnath, Hans-Otto; Bar, Moshe

    2012-01-01

    A fundamental aspect of visual cognition is our disposition to see the ‘forest before the trees’. However, damage to the posterior parietal cortex, a critical brain region along the dorsal visual pathway, can produce a neurological disorder called simultanagnosia, characterized by a debilitating inability to perceive the ‘forest’ but not the ‘trees’ (i.e. impaired global processing despite intact local processing). This impairment in perceiving the global shape persists even though the ventra...

  4. Delayed Early Primary Visual Pathway Development in Premature Infants: High Density Electrophysiological Evidence

    OpenAIRE

    Emmanuel Tremblay; Phetsamone Vannasing; Marie-Sylvie Roy; Francine Lefebvre; Damelan Kombate; Maryse Lassonde; Franco Lepore; Michelle McKerral; Anne Gallagher

    2014-01-01

    In the past decades, multiple studies have been interested in developmental patterns of the visual system in healthy infants. During the first year of life, differential maturational changes have been observed between the Magnocellular (P) and the Parvocellular (P) visual pathways. However, few studies investigated P and M system development in infants born prematurely. The aim of the present study was to characterize P and M system maturational differences between healthy preterm and fullter...

  5. Enabling global processing in simultanagnosia by psychophysical biasing of visual pathways.

    Science.gov (United States)

    Thomas, Cibu; Kveraga, Kestutis; Huberle, Elisabeth; Karnath, Hans-Otto; Bar, Moshe

    2012-05-01

    A fundamental aspect of visual cognition is our disposition to see the 'forest before the trees'. However, damage to the posterior parietal cortex, a critical brain region along the dorsal visual pathway, can produce a neurological disorder called simultanagnosia, characterized by a debilitating inability to perceive the 'forest' but not the 'trees' (i.e. impaired global processing despite intact local processing). This impairment in perceiving the global shape persists even though the ventral visual pathway, the primary recognition pathway, is intact in these patients. Here, we enabled global processing in patients with simultanagnosia using a psychophysical technique, which allowed us to bias stimuli such that they are processed predominantly by the intact ventral visual pathway. Our findings reveal that the impairment in global processing that characterizes simultanagnosia stems from a disruption in the processing of low-spatial frequencies through the dorsal pathway. These findings advance our understanding of the relationship between visuospatial attention and perception and reveal the neural mechanism mediating the disposition to see the 'forest before the trees'.

  6. Spheres of Possibility: Linking Service-Learning and the Visual Arts

    Science.gov (United States)

    Jeffers, Carol S.

    2005-01-01

    This book began with the idea that it would describe a set of arts-based service-learning courses developed and implemented during the unique multi-year project, Linking Service-Learning and the Visual Arts. These courses, in photography, graphic design, ceramics, and art education were to be offered as models, perhaps, or better yet, as…

  7. Visual analytics of signalling pathways using time profiles.

    Science.gov (United States)

    Ma, David K G; Stolte, Christian; Kaur, Sandeep; Bain, Michael; O'Donoghue, Seán I

    2015-01-01

    Data visualisation is usually a crucial first step in analysing and exploring large-scale complex data. The visualisation of proteomics time-course data on post-translational modifications presents a particular challenge that is largely unmet by existing tools and methods. To this end, we present Minardo, a novel visualisation strategy tailored for such proteomics data, in which data layout is driven by both cellular topology and temporal order. In this work, we utilised the Minardo strategy to visualise a dataset showing phosphorylation events in response to insulin. We evaluated the visualisation together with experts in diabetes and obesity, which led to new insights into the insulin response pathway. Based on this success, we outline how this layout strategy could be automated into a web-based tool for visualising a broad range of proteomics time-course data. We also discuss how the approach could be extended to include protein 3D structure information, as well as higher dimensional data, such as a range of experimental conditions. We also discuss our entry of Minardo in the international DREAM8 competition.

  8. The trilateral link between anaesthesia, perioperative visual loss and Flammer syndrome.

    Science.gov (United States)

    Bojinova, Rossiana I; Konieczka, Katarzyna; Meyer, Peter; Todorova, Margarita G

    2016-02-04

    A variety of factors have been linked to perioperative visual loss during or directly after nonocular and ocular surgeries. Prolonged immobilization, biochemical factors and hemodynamic instability have been discussed as factors in the pathogenesis of this devastating complication. Perioperative visual loss in four consecutive patients, all featuring Flammer syndrome, is reported herein. To our knowledge, we present the first case series, which associates perioperative visual loss with Flammer syndrome. We assume that a low perfusion pressure, disturbed autoregulation of the ocular blood flow and altered drug sensitivity in such subjects, play significant role in the pathogenesis of this dreaded complication. We analysed the medical records of four consecutive patients with permanent perioperative visual loss and complemented our findings with additional history taking and clinical examinations. A variety of tests was performed, including colour Doppler ultrasonography of the retroocular vessels, static and dynamic retinal vessel analysis. The visual loss was unilateral in three patients and bilateral in one. An extensive review of published perioperative vision loss cases was conducted. All four patients were male Caucasians, and exhibited prominent signs and symptoms of Flammer syndrome. The visual loss originated from a propensity for unstable ocular blood flow, combined with hyperreactivity toward pharmacological stimuli, leading together to disturbed autoregulation of the blood supply, and subsequently - to ocular hypoxia. An identified intrinsic hypoperfusion diathesis was a crucial pathophysiologic link in all of the patients. Other, yet unknown systemic or local factors may also be involved in this process. A review of numerous publications of perioperative visual loss and our data, support our hypothesis for a novel pathophysiologic model and incorporate Flammer syndrome as a distinct risk factor for paradoxical visual loss, during nonocular and ocular

  9. Visual pathway-related horizontal reference plane for three-dimensional craniofacial analysis.

    Science.gov (United States)

    Kang, Y H; Kim, B C; Park, K R; Yon, J Y; Kim, H J; Tak, H J; Piao, Z; Kim, M K; Lee, S H

    2012-11-01

    To construct three-dimensional (3D) horizontal reference planes based on visual pathway and to determine their stability and reliability by analyzing the structural patterns of normal and dysmorphology for 3D craniofacial analysis. Thirty-six subjects with maxillofacial dysmorphology and malocclusion, and eight normal controls. MATERIALS AND METHODS POPULATION: On the 3D computed tomographic images of the subjects, the visual pathway-based planes, including the orbital axis plane (OAP), visual axis plane (VAP), and the optical axis plane (OpAP), were constructed and evaluated. The OAP, but not the VAP and OpAP, showed the ideal relationship between the midsagittal and posterior maxillary plane, and properly described the different patterns of maxillofacial dysmorphology with craniofacial plane 1 of Delaire's analysis and the occlusal plane. The proposed visual pathway-related horizontal reference planes, and in particular the OAP, seem to correctly express the visual axis and the position of the head in natural head position and can be used as a horizontal reference plane for the 3D analysis of craniofacial dysmorphology and anthropology. © 2012 John Wiley & Sons A/S.

  10. VISIBIOweb: visualization and layout services for BioPAX pathway models

    Science.gov (United States)

    Dilek, Alptug; Belviranli, Mehmet E.; Dogrusoz, Ugur

    2010-01-01

    With recent advancements in techniques for cellular data acquisition, information on cellular processes has been increasing at a dramatic rate. Visualization is critical to analyzing and interpreting complex information; representing cellular processes or pathways is no exception. VISIBIOweb is a free, open-source, web-based pathway visualization and layout service for pathway models in BioPAX format. With VISIBIOweb, one can obtain well-laid-out views of pathway models using the standard notation of the Systems Biology Graphical Notation (SBGN), and can embed such views within one's web pages as desired. Pathway views may be navigated using zoom and scroll tools; pathway object properties, including any external database references available in the data, may be inspected interactively. The automatic layout component of VISIBIOweb may also be accessed programmatically from other tools using Hypertext Transfer Protocol (HTTP). The web site is free and open to all users and there is no login requirement. It is available at: http://visibioweb.patika.org. PMID:20460470

  11. Exploring the Link between Visual Perception, Visual-Motor Integration, and Reading in Normal Developing and Impaired Children using DTVP-2.

    Science.gov (United States)

    Bellocchi, Stéphanie; Muneaux, Mathilde; Huau, Andréa; Lévêque, Yohana; Jover, Marianne; Ducrot, Stéphanie

    2017-08-01

    Reading is known to be primarily a linguistic task. However, to successfully decode written words, children also need to develop good visual-perception skills. Furthermore, motor skills are implicated in letter recognition and reading acquisition. Three studies have been designed to determine the link between reading, visual perception, and visual-motor integration using the Developmental Test of Visual Perception version 2 (DTVP-2). Study 1 tests how visual perception and visual-motor integration in kindergarten predict reading outcomes in Grade 1, in typical developing children. Study 2 is aimed at finding out if these skills can be seen as clinical markers in dyslexic children (DD). Study 3 determines if visual-motor integration and motor-reduced visual perception can distinguish DD children according to whether they exhibit or not developmental coordination disorder (DCD). Results showed that phonological awareness and visual-motor integration predicted reading outcomes one year later. DTVP-2 demonstrated similarities and differences in visual-motor integration and motor-reduced visual perception between children with DD, DCD, and both of these deficits. DTVP-2 is a suitable tool to investigate links between visual perception, visual-motor integration and reading, and to differentiate cognitive profiles of children with developmental disabilities (i.e. DD, DCD, and comorbid children). Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  12. The Kynurenine Pathway As a Novel Link between Allergy and the Gut Microbiome

    Directory of Open Access Journals (Sweden)

    Aaron P. Van der Leek

    2017-11-01

    Full Text Available In the past few decades, the indoleamine 2,3 dioxygenase (IDO subset of the kynurenine (KYN pathway of tryptophan (TRP metabolism has been the subject of much research in the area of immune tolerance. In this review, we aim to incorporate new findings on this pathway in relation to allergy and the gut microbiome, while providing a comprehensive overview of the pathway itself. Stimulated by interferon gamma, IDO acts as a tolerogenic, immunosuppressive enzyme to attenuate allergic responses by the induction of the KYN-IDO pathway, resultant depletion of TRP, and elevation in KYN metabolites. Acting through the aryl hydrocarbon receptor, KYN metabolites cause T-cell anergy and apoptosis, proliferation of Treg and Th17 cells, and deviation of the Th1/Th2 response, although the outcome is highly dependent on the microenvironment. Moreover, new evidence from germ-free mice and human infants shows that gut microbiota and breast milk are key in determining the functioning of the KYN-IDO pathway. As such, we recommend further research on how this pathway may be a critical link between the microbiome and development of allergy.

  13. A biological pathway linking inflammation and depression: activation of indoleamine 2,3-dioxygenase

    Directory of Open Access Journals (Sweden)

    Christmas DM

    2011-07-01

    Full Text Available David M Christmas, JP Potokar, Simon JC DaviesAcademic Unit of Psychiatry, School of Social and Community Medicine, University of Bristol, Bristol, UK A presentation relating to this manuscript was made by Dr David Christmas at the 9th International Meeting on Clinical Pharmacology in Psychiatry (9th IMCPP in Copenhagen, Denmark in September 2010Abstract: This article highlights the evidence linking depression to increased inflammatory drive and explores putative mechanisms for the association by reviewing both preclinical and clinical literature. The enzyme indoleamine 2,3-dioxygenase is induced by proinflammatory cytokines and may form a link between immune functioning and altered neurotransmission, which results in depression. Increased indoleamine 2,3-dioxygenase activity may cause both tryptophan depletion and increased neurotoxic metabolites of the kynurenine pathway, two alterations which have been hypothesized to cause depression. The tryptophan-kynurenine pathway is comprehensively described with a focus on the evidence linking metabolite alterations to depression. The use of immune-activated groups at high risk of depression have been used to explore these hypotheses; we focus on the studies involving chronic hepatitis C patients receiving interferon-alpha, an immune activating cytokine. Findings from this work have led to novel strategies for the future development of antidepressants including inhibition of indoleamine 2,3-dioxygenase, moderating the cytokines which activate it, or addressing other targets in the kynurenine pathway.Keywords: depression, inflammation, indoleamine 2,3-dioxygenase, kynurenine, serotonin, tryptophan

  14. HPIminer: A text mining system for building and visualizing human protein interaction networks and pathways.

    Science.gov (United States)

    Subramani, Suresh; Kalpana, Raja; Monickaraj, Pankaj Moses; Natarajan, Jeyakumar

    2015-04-01

    The knowledge on protein-protein interactions (PPI) and their related pathways are equally important to understand the biological functions of the living cell. Such information on human proteins is highly desirable to understand the mechanism of several diseases such as cancer, diabetes, and Alzheimer's disease. Because much of that information is buried in biomedical literature, an automated text mining system for visualizing human PPI and pathways is highly desirable. In this paper, we present HPIminer, a text mining system for visualizing human protein interactions and pathways from biomedical literature. HPIminer extracts human PPI information and PPI pairs from biomedical literature, and visualize their associated interactions, networks and pathways using two curated databases HPRD and KEGG. To our knowledge, HPIminer is the first system to build interaction networks from literature as well as curated databases. Further, the new interactions mined only from literature and not reported earlier in databases are highlighted as new. A comparative study with other similar tools shows that the resultant network is more informative and provides additional information on interacting proteins and their associated networks. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Quantitative Visualization of ChIP-chip Data by Using Linked Views

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Min-Yu; Weber, Gunther; Li, Xiao-Yong; Biggin, Mark; Hamann, Bernd

    2010-11-05

    Most analyses of ChIP-chip in vivo DNA binding have focused on qualitative descriptions of whether genomic regions are bound or not. There is increasing evidence, however, that factors bind in a highly overlapping manner to the same genomic regions and that it is quantitative differences in occupancy on these commonly bound regions that are the critical determinants of the different biological specificity of factors. As a result, it is critical to have a tool to facilitate the quantitative visualization of differences between transcription factors and the genomic regions they bind to understand each factor's unique roles in the network. We have developed a framework which combines several visualizations via brushing-and-linking to allow the user to interactively analyze and explore in vivo DNA binding data of multiple transcription factors. We describe these visualization types and also provide a discussion of biological examples in this paper.

  16. PANDA: pathway and annotation explorer for visualizing and interpreting gene-centric data.

    Science.gov (United States)

    Hart, Steven N; Moore, Raymond M; Zimmermann, Michael T; Oliver, Gavin R; Egan, Jan B; Bryce, Alan H; Kocher, Jean-Pierre A

    2015-01-01

    Objective. Bringing together genomics, transcriptomics, proteomics, and other -omics technologies is an important step towards developing highly personalized medicine. However, instrumentation has advances far beyond expectations and now we are able to generate data faster than it can be interpreted. Materials and Methods. We have developed PANDA (Pathway AND Annotation) Explorer, a visualization tool that integrates gene-level annotation in the context of biological pathways to help interpret complex data from disparate sources. PANDA is a web-based application that displays data in the context of well-studied pathways like KEGG, BioCarta, and PharmGKB. PANDA represents data/annotations as icons in the graph while maintaining the other data elements (i.e., other columns for the table of annotations). Custom pathways from underrepresented diseases can be imported when existing data sources are inadequate. PANDA also allows sharing annotations among collaborators. Results. In our first use case, we show how easy it is to view supplemental data from a manuscript in the context of a user's own data. Another use-case is provided describing how PANDA was leveraged to design a treatment strategy from the somatic variants found in the tumor of a patient with metastatic sarcomatoid renal cell carcinoma. Conclusion. PANDA facilitates the interpretation of gene-centric annotations by visually integrating this information with context of biological pathways. The application can be downloaded or used directly from our website: http://bioinformaticstools.mayo.edu/research/panda-viewer/.

  17. CLMSVault: A Software Suite for Protein Cross-Linking Mass-Spectrometry Data Analysis and Visualization.

    Science.gov (United States)

    Courcelles, Mathieu; Coulombe-Huntington, Jasmin; Cossette, Émilie; Gingras, Anne-Claude; Thibault, Pierre; Tyers, Mike

    2017-07-07

    Protein cross-linking mass spectrometry (CL-MS) enables the sensitive detection of protein interactions and the inference of protein complex topology. The detection of chemical cross-links between protein residues can identify intra- and interprotein contact sites or provide physical constraints for molecular modeling of protein structure. Recent innovations in cross-linker design, sample preparation, mass spectrometry, and software tools have significantly improved CL-MS approaches. Although a number of algorithms now exist for the identification of cross-linked peptides from mass spectral data, a dearth of user-friendly analysis tools represent a practical bottleneck to the broad adoption of the approach. To facilitate the analysis of CL-MS data, we developed CLMSVault, a software suite designed to leverage existing CL-MS algorithms and provide intuitive and flexible tools for cross-platform data interpretation. CLMSVault stores and combines complementary information obtained from different cross-linkers and search algorithms. CLMSVault provides filtering, comparison, and visualization tools to support CL-MS analyses and includes a workflow for label-free quantification of cross-linked peptides. An embedded 3D viewer enables the visualization of quantitative data and the mapping of cross-linked sites onto PDB structural models. We demonstrate the application of CLMSVault for the analysis of a noncovalent Cdc34-ubiquitin protein complex cross-linked under different conditions. CLMSVault is open-source software (available at https://gitlab.com/courcelm/clmsvault.git ), and a live demo is available at http://democlmsvault.tyerslab.com/ .

  18. Probing the magnocellular and parvocellular visual pathways in facial emotion perception in schizophrenia.

    Science.gov (United States)

    Jahshan, Carol; Wolf, Maor; Karbi, Yinnon; Shamir, Eyal; Rassovsky, Yuri

    2017-07-01

    Schizophrenia patients have well-established deficits in facial emotion perception, which contribute to their poor social functioning. A number of studies have related these deficits to a differential dysfunction in the magnocellular (M) versus parvocellular (P) visual pathway. We assessed 35 schizophrenia patients and 35 healthy individuals on an emotion identification task, in which facial stimuli were either unaltered (broad spatial frequency, BSF) or manipulated to contain only high (HSF) or low (LSF) spatial frequencies, thereby respectively biasing the visual system toward the P- or M- pathways. As expected, patients were less accurate and slower in recognizing emotions across all conditions, relative to controls. Performance was best in the BSF condition followed by the HSF and finally the LSF condition, in both groups. A significant group by spatial frequency interaction reflected a smaller magnitude of impairment in the HSF condition, compared to the other two conditions that preferentially engage the M-system. These findings are consistent with studies showing a differential M-pathway abnormality in schizophrenia with a less pronounced impairment in P-function. The current study suggests that patients have less difficulty extracting emotional content from faces when LSFs are attenuated and supports the need to remediate basic visual processing deficits in schizophrenia. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  19. Viral vector-mediated selective and reversible blockade of the pathway for visual orienting in mice

    Directory of Open Access Journals (Sweden)

    Tadashi eIsa

    2013-10-01

    Full Text Available Recently, by using a combination of two viral vectors, we developed a technique for pathway-selective and reversible synaptic transmission blockade, and successfully induced a behavioral deficit of dexterous hand movements in macaque monkeys by affecting a population of spinal interneurons. To explore the capacity of this technique to work in other pathways and species, and to obtain fundamental methodological information, we tried to block the crossed tecto-reticular pathway, which is known to control orienting responses to visual targets, in mice. A neuron-specific retrograde gene transfer vector with the gene encoding enhanced tetanus neurotoxin (eTeNT tagged with enhanced green fluorescent protein (EGFP under the control of a tetracycline responsive element was injected into the left medial pontine reticular formation. 7–17 days later, an adeno-associated viral vector with a highly efficient Tet-ON sequence, rtTAV16, was injected into the right superior colliculus. 5–9 weeks later, the daily administration of doxycycline (Dox was initiated. Visual orienting responses toward the left side were impaired 1 - 4 days after Dox administration. Anti-GFP immunohistochemistry revealed that a number of neurons in the intermediate and deep layers of the right superior colliculus were positively stained, indicating eTeNT expression. After the termination of Dox administration, the anti-GFP staining returned to the baseline level within 28 days. A second round of Dox administration, starting from 28 days after the termination of the first Dox administration, resulted in the reappearance of the behavioral impairment. These findings showed that pathway-selective and reversible blockade of synaptic transmission causes behavioral effects also in rodents, and that the crossed tecto-reticular pathway surely controls visual orienting behaviors.

  20. Design of a Novel Servo-motorized Laser Device for Visual Pathways Diseases Therapy

    Directory of Open Access Journals (Sweden)

    Carlos Ignacio Sarmiento

    2015-12-01

    Full Text Available We discuss a novel servo-motorized laser device and a research protocol for visual pathways diseases therapies. The proposed servo-mechanized laser device can be used for potential rehabilitation of patients with hemianopia, quadrantanopia, scotoma, and some types of cortical damages. The device uses a semi spherical structure where the visual stimulus will be shown inside, according to a previous stimuli therapy designed by an ophthalmologist or neurologist. The device uses a pair of servomotors (with torque=1.5kg, which controls the laser stimuli position for the internal therapy and another pair for external therapy. Using electronic tools such as microcontrollers along with miscellaneous electronic materials, combined with LabVIEW based interface, a control mechanism is developed for the new device. The proposed device is well suited to run various visual stimuli therapies. We outline the major design principles including the physical dimensions, laser device’s kinematical analysis and the corresponding software development.

  1. Genetic moderation of multiple pathways linking early cumulative socioeconomic adversity and young adults' cardiometabolic disease risk.

    Science.gov (United States)

    Wickrama, Kandauda A S; Lee, Tae Kyoung; O'Neal, Catherine Walker

    2017-05-23

    Recent research suggests that psychosocial resources and life stressors are mediating pathways explaining socioeconomic variation in young adults' health risks. However, less research has examined both these pathways simultaneously and their genetic moderation. A nationally representative sample of 11,030 respondents with prospective data collected over 13 years from the National Study of Adolescent to Adult Health was examined. First, the association between early cumulative socioeconomic adversity and young adults' (ages 25-34) cardiometabolic disease risk, as measured by 10 biomarkers, through psychosocial resources (educational attainment) and life stressors (accelerated transition to adulthood) was examined. Second, moderation of these pathways by the serotonin transporter linked polymorphic region gene (5-HTTLPR) was examined. There was evidence for the association between early socioeconomic adversity and young adults' cardiometabolic disease risk directly and indirectly through educational attainment and accelerated transitions. These direct and mediating pathways were amplified by the 5-HTTLPR polymorphism. These findings elucidate how early adversity can have an enduring influence on young adults' cardiometabolic disease risk directly and indirectly through psychosocial resources and life stressors and their genetic moderation. This information suggests that effective intervention and prevention programs should focus on early adversity, youth educational attainment, and their transition to young adulthood.

  2. Linking Biosynthetic Gene Clusters to their Metabolites via Pathway-Targeted Molecular Networking

    Science.gov (United States)

    Trautman, Eric P.; Crawford, Jason M.

    2016-01-01

    The connection of microbial biosynthetic gene clusters to the small molecule metabolites they encode is central to the discovery and characterization of new metabolic pathways with ecological and pharmacological potential. With increasing microbial genome sequence information being deposited into publicly available databases, it is clear that microbes have the coding capacity for many more biologically active small molecules than previously realized. Of increasing interest are the small molecules encoded by the human microbiome, as these metabolites likely mediate a variety of currently uncharacterized human-microbe interactions that influence health and disease. In this mini-review, we describe the ongoing biosynthetic, structural, and functional characterizations of the genotoxic colibactin pathway in gut bacteria as a thematic example of linking biosynthetic gene clusters to their metabolites. We also highlight other natural products that are produced through analogous biosynthetic logic and comment on some current disconnects between bioinformatics predictions and experimental structural characterizations. Lastly, we describe the use of pathway-targeted molecular networking as a tool to characterize secondary metabolic pathways within complex metabolomes and to aid in downstream metabolite structural elucidation efforts. PMID:26456470

  3. The Kynurenine Pathway: a Proposed Mechanism Linking Diabetes and Periodontal Disease in Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Rishabh Kapila

    2011-07-01

    Full Text Available Introduction: Diabetes mellitus is a metabolic disease characte-rized by dysregulation of carbohydrate, protein and lipid metabolism. Diabetes could result, in part, in activation of tryptophan metabolism. Diabetic patients are more susceptible to gingivitis and periodontitis than healthy subjects. The salivary kynurenine derivatives are also implicated in the onset and development of periodontal dis-ease in humans.The hypothesis: We propose that the tryptophan metabolites via kynurenine pathway may lead to diabetes and an increased severity of periodontal disease in diabetic patients, thus linking both diabetes and periodontal disease.Evaluation of the hypothesis: Tryptophan has been found in significant amount in saliva in diabetic individuals in some studies, particularly tryptophan metabolites like kynurenine and anthranilic acid. Moreover, altered tryptophan metabolism has also been reported in the onset of periodontal disease. Thus, this correlation between diabetes mellitus, periodontal disease and salivary tryptophan metabolite levels could be related to the impaired kynurenine pathway metabolism of tryptophan.

  4. Planarian Hh signaling regulates regeneration polarity and links Hh pathway evolution to cilia.

    Science.gov (United States)

    Rink, Jochen C; Gurley, Kyle A; Elliott, Sarah A; Sánchez Alvarado, Alejandro

    2009-12-04

    The Hedgehog (Hh) signaling pathway plays multiple essential roles during metazoan development, homeostasis, and disease. Although core protein components are highly conserved, the variations in Hh signal transduction mechanisms exhibited by existing model systems (Drosophila, fish, and mammals) are difficult to understand. We characterized the Hh pathway in planarians. Hh signaling is essential for establishing the anterior/posterior axis during regeneration by modulating wnt expression. Moreover, RNA interference methods to reduce signal transduction proteins Cos2/Kif27/Kif7, Fused, or Iguana do not result in detectable Hh signaling defects; however, these proteins are essential for planarian ciliogenesis. Our study expands the understanding of Hh signaling in the animal kingdom and suggests an ancestral mechanistic link between Hh signaling and the function of cilia.

  5. Functional overlap and regulatory links shape genetic interactions between signaling pathways.

    Science.gov (United States)

    van Wageningen, Sake; Kemmeren, Patrick; Lijnzaad, Philip; Margaritis, Thanasis; Benschop, Joris J; de Castro, Inês J; van Leenen, Dik; Groot Koerkamp, Marian J A; Ko, Cheuk W; Miles, Antony J; Brabers, Nathalie; Brok, Mariel O; Lenstra, Tineke L; Fiedler, Dorothea; Fokkens, Like; Aldecoa, Rodrigo; Apweiler, Eva; Taliadouros, Virginia; Sameith, Katrin; van de Pasch, Loes A L; van Hooff, Sander R; Bakker, Linda V; Krogan, Nevan J; Snel, Berend; Holstege, Frank C P

    2010-12-10

    To understand relationships between phosphorylation-based signaling pathways, we analyzed 150 deletion mutants of protein kinases and phosphatases in S. cerevisiae using DNA microarrays. Downstream changes in gene expression were treated as a phenotypic readout. Double mutants with synthetic genetic interactions were included to investigate genetic buffering relationships such as redundancy. Three types of genetic buffering relationships are identified: mixed epistasis, complete redundancy, and quantitative redundancy. In mixed epistasis, the most common buffering relationship, different gene sets respond in different epistatic ways. Mixed epistasis arises from pairs of regulators that have only partial overlap in function and that are coupled by additional regulatory links such as repression of one by the other. Such regulatory modules confer the ability to control different combinations of processes depending on condition or context. These properties likely contribute to the evolutionary maintenance of paralogs and indicate a way in which signaling pathways connect for multiprocess control. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Loom sensitive neurons link computation to action in the Drosophila visual system

    Science.gov (United States)

    de Vries, Saskia E. J.; Clandinin, Thomas R.

    2012-01-01

    Summary Background Many animals extract specific cues from rich visual scenes to guide appropriate behaviors. Such cues include visual motion signals produced both by self movement and by moving objects in the environment. The complexity of these signals requires neural circuits to link particular patterns of motion to specific behavioral responses. Results Through electrophysiological recordings, we characterize genetically identified neurons in the optic lobe of Drosophila that are specifically tuned to detect motion signals produced by looming objects on a collision course with the fly. Using a genetic manipulation to specifically silence these neurons, we demonstrate that signals from these cells are important for flies to efficiently initiate the loom escape response. Moreover, through targeted expression of Channelrhodopsin in these cells, in flies that are blind, we reveal that optogenetic stimulation of these neurons is typically sufficient to elicit escape, even in the absence of any visual stimulus. Conclusions In this compact nervous system, a small group of neurons that extract a specific visual cue from local motion inputs serve to trigger the ethologically appropriate behavioral response. PMID:22305754

  7. Linking Advanced Visualization and MATLAB for the Analysis of 3D Gene Expression Data

    Energy Technology Data Exchange (ETDEWEB)

    Ruebel, Oliver; Keranen, Soile V.E.; Biggin, Mark; Knowles, David W.; Weber, Gunther H.; Hagen, Hans; Hamann, Bernd; Bethel, E. Wes

    2011-03-30

    Three-dimensional gene expression PointCloud data generated by the Berkeley Drosophila Transcription Network Project (BDTNP) provides quantitative information about the spatial and temporal expression of genes in early Drosophila embryos at cellular resolution. The BDTNP team visualizes and analyzes Point-Cloud data using the software application PointCloudXplore (PCX). To maximize the impact of novel, complex data sets, such as PointClouds, the data needs to be accessible to biologists and comprehensible to developers of analysis functions. We address this challenge by linking PCX and Matlab via a dedicated interface, thereby providing biologists seamless access to advanced data analysis functions and giving bioinformatics researchers the opportunity to integrate their analysis directly into the visualization application. To demonstrate the usefulness of this approach, we computationally model parts of the expression pattern of the gene even skipped using a genetic algorithm implemented in Matlab and integrated into PCX via our Matlab interface.

  8. High CO2 Primes Plant Biotic Stress Defences through Redox-Linked Pathways1[OPEN

    Science.gov (United States)

    2016-01-01

    Industrial activities have caused tropospheric CO2 concentrations to increase over the last two centuries, a trend that is predicted to continue for at least the next several decades. Here, we report that growth of plants in a CO2-enriched environment activates responses that are central to defense against pathogenic attack. Salicylic acid accumulation was triggered by high-growth CO2 in Arabidopsis (Arabidopsis thaliana) and other plants such as bean (Phaseolus vulgaris). A detailed analysis in Arabidopsis revealed that elevated CO2 primes multiple defense pathways, leading to increased resistance to bacterial and fungal challenge. Analysis of gene-specific mutants provided no evidence that activation of plant defense pathways by high CO2 was caused by stomatal closure. Rather, the activation is partly linked to metabolic effects involving redox signaling. In support of this, genetic modification of redox components (glutathione contents and NADPH-generating enzymes) prevents full priming of the salicylic acid pathway and associated resistance by high CO2. The data point to a particularly influential role for the nonphosphorylating glyceraldehyde-3-phosphate dehydrogenase, a cytosolic enzyme whose role in plants remains unclear. Our observations add new information on relationships between high CO2 and oxidative signaling and provide novel insight into plant stress responses in conditions of increased CO2. PMID:27578552

  9. Neuronal Migration and Axonal Pathways Linked to Human Fetal Insular Development Revealed by Diffusion MR Tractography.

    Science.gov (United States)

    Das, Avilash; Takahashi, Emi

    2017-08-31

    The insula is a multimodal sensory integration structure that, in addition to serving as a gateway between somatosensory areas and limbic structures, plays a crucial role in autonomic nervous system function. While anatomical studies following the development of the insula have been conducted, currently, no studies have been published in human fetuses tracking the development of neuronal migration or of white matter tracts in the cortex. In this study, we aimed to follow the neuronal migration and subsequent maturation of axons in and around the insula in human fetal ages. Using high-angular resolution diffusion magnetic resonance imaging tractography, major white matter pathways to/from the insula and its surrounding operculum were identified at a number of time points during human gestation. Pathways likely linked to neuronal migration from the ventricular zone to the inferior frontal gyrus, superior temporal region, and the insular cortex were detected in the earliest gestational age studied (15 GW). Tractography reveals neuronal migration to areas surrounding the insula occurred at different time points. These results, in addition to demonstrating key time points for neuronal migration, suggest that neurons and axonal fiber pathways underlying the insula and its surrounding gyri mature differentially despite their relationship during cortical folding. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Jagged1 is the pathological link between Wnt and Notch pathways in colorectal cancer.

    Science.gov (United States)

    Rodilla, Verónica; Villanueva, Alberto; Obrador-Hevia, Antonia; Robert-Moreno, Alex; Fernández-Majada, Vanessa; Grilli, Andrea; López-Bigas, Nuria; Bellora, Nicolás; Albà, M Mar; Torres, Ferran; Duñach, Mireia; Sanjuan, Xavier; Gonzalez, Sara; Gridley, Thomas; Capella, Gabriel; Bigas, Anna; Espinosa, Lluís

    2009-04-14

    Notch has been linked to beta-catenin-dependent tumorigenesis; however, the mechanisms leading to Notch activation and the contribution of the Notch pathway to colorectal cancer is not yet understood. By microarray analysis, we have identified a group of genes downstream of Wnt/beta-catenin (down-regulated when blocking Wnt/beta-catenin) that are directly regulated by Notch (repressed by gamma-secretase inhibitors and up-regulated by active Notch1 in the absence of beta-catenin signaling). We demonstrate that Notch is downstream of Wnt in colorectal cancer cells through beta-catenin-mediated transcriptional activation of the Notch-ligand Jagged1. Consistently, expression of activated Notch1 partially reverts the effects of blocking Wnt/beta-catenin pathway in tumors implanted s.c. in nude mice. Crossing APC(Min/+) with Jagged1(+/Delta) mice is sufficient to significantly reduce the size of the polyps arising in the APC mutant background indicating that Notch is an essential modulator of tumorigenesis induced by nuclear beta-catenin. We show that this mechanism is operating in human tumors from Familial Adenomatous Polyposis patients. We conclude that Notch activation, accomplished by beta-catenin-mediated up-regulation of Jagged1, is required for tumorigenesis in the intestine. The Notch-specific genetic signature is sufficient to block differentiation and promote vasculogenesis in tumors whereas proliferation depends on both pathways.

  11. Functional characterization of Sporothrix schenckii glycosidases involved in the N-linked glycosylation pathway.

    Science.gov (United States)

    Lopes-Bezerra, Leila M; Lozoya-Pérez, Nancy E; López-Ramírez, Luz A; Martínez-Álvarez, José A; Teixeira, Marcus M; Felipe, Maria S S; Flores-Carreón, Arturo; Mora-Montes, Héctor M

    2015-01-01

    Protein glycosylation pathways are conserved metabolic processes in eukaryotic organisms and are required for cell fitness. In fungal pathogens, the N-linked glycosylation pathway is indispensable for proper cell wall composition and virulence. In Sporothrix schenckii sensu stricto, the causative agent of sporotrichosis, little is known about this glycosylation pathway. Here, using a genome-wide screening for putative members of the glycosyl hydrolase (CAZy - GH) families 47 and 63, which group enzymes involved in the processing step during N-linked glycan maturation, we found seven homologue genes belonging to family 47 and one to family 63. The eight genes were individually expressed in C. albicans null mutants lacking either MNS1 (for members of family 47) or CWH41 (for the member of family 63). Our results indicate that SsCWH41 is the functional ortholog of CaCWH41, whereas SsMNS1 is the functional ortholog of CaMNS1. The remaining genes of family 47 encode Golgi mannosidases and endoplasmic reticulum degradation-enhancing alpha-mannosidase-like proteins (EDEMs). Since these GH families gather proteins used as target for drugs to control cell growth, identification of these genes could help in the design of antifungals that could be used to treat sporotrichosis and other fungal diseases. In addition, to our knowledge, we are the first to report that Golgi mannosidases and EDEMs are expressed and characterized in yeast cells. © The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. A scalable architecture for extracting, aligning, linking, and visualizing multi-Int data

    Science.gov (United States)

    Knoblock, Craig A.; Szekely, Pedro

    2015-05-01

    An analyst today has a tremendous amount of data available, but each of the various data sources typically exists in their own silos, so an analyst has limited ability to see an integrated view of the data and has little or no access to contextual information that could help in understanding the data. We have developed the Domain-Insight Graph (DIG) system, an innovative architecture for extracting, aligning, linking, and visualizing massive amounts of domain-specific content from unstructured sources. Under the DARPA Memex program we have already successfully applied this architecture to multiple application domains, including the enormous international problem of human trafficking, where we extracted, aligned and linked data from 50 million online Web pages. DIG builds on our Karma data integration toolkit, which makes it easy to rapidly integrate structured data from a variety of sources, including databases, spreadsheets, XML, JSON, and Web services. The ability to integrate Web services allows Karma to pull in live data from the various social media sites, such as Twitter, Instagram, and OpenStreetMaps. DIG then indexes the integrated data and provides an easy to use interface for query, visualization, and analysis.

  13. Functional MRI Examination of Visual Pathways in Patients with Unilateral Optic Neuritis

    Directory of Open Access Journals (Sweden)

    Giulia Mascioli

    2012-01-01

    Full Text Available The relations between brain areas involved in vision were explored in 8 patients with unilateral acute optic neuritis using functional magnetic resonance imaging (fMRI and diffusion tensor imaging (DTI. In all patients monocular stimulation of affected and unaffected eye elicited significantly different activation foci in the primary visual cortex (V1, whereas the foci evoked in the middle temporal visual area (area V5 were similar in size and in delay of blood-oxygen-level-dependent response. DTI analysis documented lower white matter anisotropy values and reduced fibre reconstruction in the affected compared with the unaffected optic nerves. The preserved activation of area V5 observed in all our patients is an interesting finding that suggests the notion of a different sensitivity of the optic pathways to inflammatory changes.

  14. Higher integrity of the motor and visual pathways in long-term video-game players

    Directory of Open Access Journals (Sweden)

    Yang eZhang

    2015-03-01

    Full Text Available Long term video game players (VGPs have been reported to exhibit superior visual and motor skills compared with non-video-game controls (NVGCs. However, the neural basis underlying the enhanced behavioral performance remains largely unknown. To clarify this issue, the present study compared the whiter matter integrity within the corticospinal tracts (CST, the superior longitudinal fasciculus (SLF, the inferior longitudinal fasciculus (ILF, and the inferior fronto-occipital fasciculus (IFOF between the VGPs and the NVGCs using diffusion tensor imaging (DTI. Compared with the NVGCs, voxel-wise comparisons revealed significantly higher fractional anisotropy (FA value in some regions within the left CST, left SLF, bilateral ILF and IFOF in VGPs. Furthermore, higher FA value at the cerebral peduncle level of the left CST predicted faster response in visual attention task. These results suggested that the higher WM integrity in the motor and higher-tier visual pathways is associated with long-term video-game playing, which may contribute to the understanding of the neuromechanism of the effect of video game play on the motor and visual process performance.

  15. Higher integrity of the motor and visual pathways in long-term video game players.

    Science.gov (United States)

    Zhang, Yang; Du, Guijin; Yang, Yongxin; Qin, Wen; Li, Xiaodong; Zhang, Quan

    2015-01-01

    Long term video game players (VGPs) exhibit superior visual and motor skills compared with non-video game control subjects (NVGCs). However, the neural basis underlying the enhanced behavioral performance remains largely unknown. To clarify this issue, the present study compared the whiter matter integrity within the corticospinal tracts (CST), the superior longitudinal fasciculus (SLF), the inferior longitudinal fasciculus (ILF), and the inferior fronto-occipital fasciculus (IFOF) between the VGPs and the NVGCs using diffusion tensor imaging. Compared with the NVGCs, voxel-wise comparisons revealed significantly higher fractional anisotropy (FA) values in some regions within the left CST, left SLF, bilateral ILF, and IFOF in VGPs. Furthermore, higher FA values in the left CST at the level of cerebral peduncle predicted a faster response in visual attention tasks. These results suggest that higher white matter integrity in the motor and higher-tier visual pathways is associated with long-term video game playing, which may contribute to the understanding on how video game play influences motor and visual performance.

  16. A novel pathway for maytansinoid release from thioether linked antibody-drug conjugates (ADCs) under oxidative conditions.

    Science.gov (United States)

    Fishkin, Nathan; Maloney, Erin K; Chari, Ravi V J; Singh, Rajeeva

    2011-10-14

    A novel pathway for ex vivo maytansinoid release from thioether linked antibody maytansinoid conjugates (AMCs) upon incubation in human plasma has been identified. A thioether succinimide-linked AMC can undergo chemical oxidation followed by sulfoxide elimination under mild aqueous conditions (pH 5.5-7.5, 37 °C). Oxidized thioether-linked AMCs exhibit high, target-specific cytotoxicity toward cancer cells. This journal is © The Royal Society of Chemistry 2011

  17. Link Winds: A visual data analysis system and its application to the atmospheric ozone depletion problem

    Science.gov (United States)

    Jacobson, Allan S.; Berkin, Andrew L.

    1995-01-01

    The Linked Windows Interactive Data System (LinkWinds) is a prototype visual data exploration system resulting from a NASA Jet Propulsion Laboratory (JPL) program of research into the application of graphical methods for rapidly accessing, displaying, and analyzing large multi variate multidisciplinary data sets. Running under UNIX it is an integrated multi-application executing environment using a data-linking paradigm to dynamically interconnect and control multiple windows containing a variety of displays and manipulators. This paradigm, resulting in a system similar to a graphical spreadsheet, is not only a powerful method for organizing large amounts of data for analysis, but leads to a highly intuitive, easy-to-learn user interface. It provides great flexibility in rapidly interacting with large masses of complex data to detect trends, correlations, and anomalies. The system, containing an expanding suite of non-domain-specific applications, provides for the ingestion of a variety of data base formats and hard -copy output of all displays. Remote networked workstations running LinkWinds may be interconnected, providing a multiuser science environment (MUSE) for collaborative data exploration by a distributed science team. The system is being developed in close collaboration with investigators in a variety of science disciplines using both archived and real-time data. It is currently being used to support the Microwave Limb Sounder (MLS) in orbit aboard the Upper Atmosphere Research Satellite (UARS). This paper describes the application of LinkWinds to this data to rapidly detect features, such as the ozone hole configuration, and to analyze correlations between chemical constituents of the atmosphere.

  18. Fast and automatic activation of an abstract representation of money in the human ventral visual pathway.

    Directory of Open Access Journals (Sweden)

    Catherine Tallon-Baudry

    Full Text Available Money, when used as an incentive, activates the same neural circuits as rewards associated with physiological needs. However, unlike physiological rewards, monetary stimuli are cultural artifacts: how are monetary stimuli identified in the first place? How and when does the brain identify a valid coin, i.e. a disc of metal that is, by social agreement, endowed with monetary properties? We took advantage of the changes in the Euro area in 2002 to compare neural responses to valid coins (Euros, Australian Dollars with neural responses to invalid coins that have lost all monetary properties (French Francs, Finnish Marks. We show in magneto-encephalographic recordings, that the ventral visual pathway automatically distinguishes between valid and invalid coins, within only ∼150 ms. This automatic categorization operates as well on coins subjects were familiar with as on unfamiliar coins. No difference between neural responses to scrambled controls could be detected. These results could suggest the existence of a generic, all-purpose neural representation of money that is independent of experience. This finding is reminiscent of a central assumption in economics, money fungibility, or the fact that a unit of money is substitutable to another. From a neural point of view, our findings may indicate that the ventral visual pathway, a system previously thought to analyze visual features such as shape or color and to be influenced by daily experience, could also able to use conceptual attributes such as monetary validity to categorize familiar as well as unfamiliar visual objects. The symbolic abilities of the posterior fusiform region suggested here could constitute an efficient neural substrate to deal with culturally defined symbols, independently of experience, which probably fostered money's cultural emergence and success.

  19. Pathway collages: personalized multi-pathway diagrams.

    Science.gov (United States)

    Paley, Suzanne; O'Maille, Paul E; Weaver, Daniel; Karp, Peter D

    2016-12-13

    Metabolic pathway diagrams are a classical way of visualizing a linked cascade of biochemical reactions. However, to understand some biochemical situations, viewing a single pathway is insufficient, whereas viewing the entire metabolic network results in information overload. How do we enable scientists to rapidly construct personalized multi-pathway diagrams that depict a desired collection of interacting pathways that emphasize particular pathway interactions? We define software for constructing personalized multi-pathway diagrams called pathway-collages using a combination of manual and automatic layouts. The user specifies a set of pathways of interest for the collage from a Pathway/Genome Database. Layouts for the individual pathways are generated by the Pathway Tools software, and are sent to a Javascript Pathway Collage application implemented using Cytoscape.js. That application allows the user to re-position pathways; define connections between pathways; change visual style parameters; and paint metabolomics, gene expression, and reaction flux data onto the collage to obtain a desired multi-pathway diagram. We demonstrate the use of pathway collages in two application areas: a metabolomics study of pathogen drug response, and an Escherichia coli metabolic model. Pathway collages enable facile construction of personalized multi-pathway diagrams.

  20. Color vision versus pattern visual evoked potentials in the assessment of subclinical optic pathway involvement in multiple sclerosis

    OpenAIRE

    Gundogan, Fatih C.; Ahmet Tas; Salih Altun; Oguzhan Oz; Uzeyir Erdem; Gungor Sobaci

    2013-01-01

    Background: Optic pathway involvement in multiple sclerosis is frequently the initial sign in the disease process. In most clinical applications, pattern visual evoked potential (PVEP) is used in the assessment of optic pathway involvement. Objective: To question the value of PVEP against color vision assessment in the diagnosis of subclinical optic pathway involvement. Materials and Methods: This prospective, cross-sectional study included 20 multiple sclerosis patients without a history of ...

  1. Linking Adverse Outcome Pathways to Dynamic Energy Budgets: A Conceptual Model

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, Cheryl [Michigan State University, East Lansing; Nisbet, Roger [University of California Santa Barbara; Antczak, Philipp [University of Liverpool, UK; Reyero, Natalia [Army Corps of Engineers, Vicksburg; Gergs, Andre [Gaiac; Lika, Dina [University of Crete; Mathews, Teresa J. [ORNL; Muller, Eric [University of California, Santa Barbara; Nacci, Dianne [U.S. Environmental Protection Agency (EPA); Peace, Angela L. [ORNL; Remien, Chris [University of Idaho; Schulz, Irv [Pacific Northwest National Laboratory (PNNL); Watanabe, Karen [Arizona State University

    2018-02-01

    Ecological risk assessment quantifies the likelihood of undesirable impacts of stressors, primarily at high levels of biological organization. Data used to inform ecological risk assessments come primarily from tests on individual organisms or from suborganismal studies, indicating a disconnect between primary data and protection goals. We know how to relate individual responses to population dynamics using individual-based models, and there are emerging ideas on how to make connections to ecosystem services. However, there is no established methodology to connect effects seen at higher levels of biological organization with suborganismal dynamics, despite progress made in identifying Adverse Outcome Pathways (AOPs) that link molecular initiating events to ecologically relevant key events. This chapter is a product of a working group at the National Center for Mathematical and Biological Synthesis (NIMBioS) that assessed the feasibility of using dynamic energy budget (DEB) models of individual organisms as a “pivot” connecting suborganismal processes to higher level ecological processes. AOP models quantify explicit molecular, cellular or organ-level processes, but do not offer a route to linking sub-organismal damage to adverse effects on individual growth, reproduction, and survival, which can be propagated to the population level through individual-based models. DEB models describe these processes, but use abstract variables with undetermined connections to suborganismal biology. We propose linking DEB and quantitative AOP models by interpreting AOP key events as measures of damage-inducing processes in a DEB model. Here, we present a conceptual model for linking AOPs to DEB models and review existing modeling tools available for both AOP and DEB.

  2. Parallel neural pathways in higher visual centers of the Drosophila brain that mediate wavelength-specific behavior

    Directory of Open Access Journals (Sweden)

    Hideo eOtsuna

    2014-02-01

    Full Text Available Compared with connections between the retinae and primary visual centers, relatively less is known in both mammals and insects about the functional segregation of neural pathways connecting primary and higher centers of the visual processing cascade. Here, using the Drosophila visual system as a model, we demonstrate two levels of parallel computation in the pathways that connect primary visual centers of the optic lobe to computational circuits embedded within deeper centers in the central brain. We show that a seemingly simple achromatic behavior, namely phototaxis, is under the control of several independent pathways, each of which is responsible for navigation towards unique wavelengths. Silencing just one pathway is enough to disturb phototaxis towards one characteristic monochromatic source, whereas phototactic behavior towards white light is not affected. The response spectrum of each demonstrable pathway is different from that of individual photoreceptors, suggesting subtractive computations. A choice assay between two colors showed that these pathways are responsible for navigation towards, but not for the detection itself of, the monochromatic light. The present study provides novel insights about how visual information is separated and processed in parallel to achieve robust control of an innate behavior.

  3. Integrity of the Anterior Visual Pathway and Its Association with Ambulatory Performance in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Swathi Balantrapu

    2013-01-01

    Full Text Available Background. Retinal nerve fiber layer thickness and total macular volume (TMV represent markers of neuroaxonal degeneration within the anterior visual pathway that might correlate with ambulation in persons with multiple sclerosis (MS. Objective. This study examined the associations between and TMV with ambulatory parameters in MS. Methods. Fifty-eight MS patients underwent a neurological examination for generation of an expanded disability status scale (EDSS score and measurement of and TMV using optical coherence tomography (OCT. Participants completed the 6-minute walk (6MW and the timed 25-foot walk (T25FW. The associations were examined using generalized estimating equation models that accounted for within-patient, inter-eye correlations, and controlled for disease duration, EDSS score, and age. Results. was not significantly associated with 6MW or T25FW . TMV was significantly associated with 6MW and T25FW . The coefficients indicated that unit differences in 6MW (100 feet and T25FW (1 second were associated with 0.040 and −0.048 unit differences in TMV (mm3, respectively. Conclusion. Integrity of the anterior visual pathway, particularly TMV, might represent a noninvasive measure of neuroaxonal degeneration that is correlated with ambulatory function in MS.

  4. solQTL: a tool for QTL analysis, visualization and linking to genomes at SGN database

    Directory of Open Access Journals (Sweden)

    van der Knaap Esther

    2010-10-01

    Full Text Available Abstract Background A common approach to understanding the genetic basis of complex traits is through identification of associated quantitative trait loci (QTL. Fine mapping QTLs requires several generations of backcrosses and analysis of large populations, which is time-consuming and costly effort. Furthermore, as entire genomes are being sequenced and an increasing amount of genetic and expression data are being generated, a challenge remains: linking phenotypic variation to the underlying genomic variation. To identify candidate genes and understand the molecular basis underlying the phenotypic variation of traits, bioinformatic approaches are needed to exploit information such as genetic map, expression and whole genome sequence data of organisms in biological databases. Description The Sol Genomics Network (SGN, http://solgenomics.net is a primary repository for phenotypic, genetic, genomic, expression and metabolic data for the Solanaceae family and other related Asterids species and houses a variety of bioinformatics tools. SGN has implemented a new approach to QTL data organization, storage, analysis, and cross-links with other relevant data in internal and external databases. The new QTL module, solQTL, http://solgenomics.net/qtl/, employs a user-friendly web interface for uploading raw phenotype and genotype data to the database, R/QTL mapping software for on-the-fly QTL analysis and algorithms for online visualization and cross-referencing of QTLs to relevant datasets and tools such as the SGN Comparative Map Viewer and Genome Browser. Here, we describe the development of the solQTL module and demonstrate its application. Conclusions solQTL allows Solanaceae researchers to upload raw genotype and phenotype data to SGN, perform QTL analysis and dynamically cross-link to relevant genetic, expression and genome annotations. Exploration and synthesis of the relevant data is expected to help facilitate identification of candidate genes

  5. The inositol pyrophosphate synthesis pathway in Trypanosoma brucei is linked to polyphosphate synthesis in acidocalcisomes.

    Science.gov (United States)

    Cordeiro, Ciro D; Saiardi, Adolfo; Docampo, Roberto

    2017-10-01

    Inositol pyrophosphates are novel signaling molecules possessing high-energy pyrophosphate bonds and involved in a number of biological functions. Here, we report the correct identification and characterization of the kinases involved in the inositol pyrophosphate biosynthetic pathway in Trypanosoma brucei: inositol polyphosphate multikinase (TbIPMK), inositol pentakisphosphate 2-kinase (TbIP5K) and inositol hexakisphosphate kinase (TbIP6K). TbIP5K and TbIP6K were not identifiable by sequence alone and their activities were validated by enzymatic assays with the recombinant proteins or by their complementation of yeast mutants. We also analyzed T. brucei extracts for the presence of inositol phosphates using polyacrylamide gel electrophoresis and high-performance liquid chromatography. Interestingly, we could detect inositol phosphate (IP), inositol 4,5-bisphosphate (IP2 ), inositol 1,4,5-trisphosphate (IP3 ), and inositol hexakisphosphate (IP6 ) in T. brucei different stages. Bloodstream forms unable to produce inositol pyrophosphates, due to downregulation of TbIPMK expression by conditional knockout, have reduced levels of polyphosphate and altered acidocalcisomes. Our study links the inositol pyrophosphate pathway to the synthesis of polyphosphate in acidocalcisomes, and may lead to better understanding of these organisms and provide new targets for drug discovery. © 2017 John Wiley & Sons Ltd.

  6. Novel connections in plant organellar signalling link different stress responses and signalling pathways.

    Science.gov (United States)

    Kmiecik, Przemyslaw; Leonardelli, Manuela; Teige, Markus

    2016-06-01

    To coordinate growth, development and responses to environmental stimuli, plant cells need to communicate the metabolic state between different sub-compartments of the cell. This requires signalling pathways, including protein kinases, secondary messengers such as Ca(2+) ions or reactive oxygen species (ROS) as well as metabolites and plant hormones. The signalling networks involved have been intensively studied over recent decades and have been elaborated more or less in detail. However, it has become evident that these signalling networks are also tightly interconnected and often merge at common targets such as a distinct group of transcription factors, most prominently ABI4, which are amenable to regulation by phosphorylation, potentially also in a Ca(2+)- or ROS-dependent fashion. Moreover, the signalling pathways connect several organelles or subcellular compartments, not only in functional but also in physical terms, linking for example chloroplasts to the nucleus or peroxisomes to chloroplasts thereby enabling physical routes for signalling by metabolite exchange or even protein translocation. Here we briefly discuss these novel findings and try to connect them in order to point out the remaining questions and emerging developments in plant organellar signalling. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  7. A cortical-subcortical syntax pathway linking Broca's area and the striatum.

    Science.gov (United States)

    Teichmann, Marc; Rosso, Charlotte; Martini, Jean-Baptiste; Bloch, Isabelle; Brugières, Pierre; Duffau, Hugues; Lehéricy, Stéphane; Bachoud-Lévi, Anne-Catherine

    2015-06-01

    Combinatorial syntax has been shown to be underpinned by cortical key regions such as Broca's area and temporal cortices, and by subcortical structures such as the striatum. The cortical regions are connected via several cortico-to-cortical tracts impacting syntactic processing (e.g., the arcuate) but it remains unclear whether and how the striatum can be integrated into this cortex-centered syntax network. Here, we used a systematic stepwise approach to investigate the existence and syntactic function of an additional deep Broca-striatum pathway. We first asked 15 healthy controls and 12 patients with frontal/striatal lesions to perform three syntax tests. The results obtained were subjected to voxel-based lesion-symptom mapping (VLSM) to provide an anatomo-functional approximation of the pathway. The significant VLSM clusters were then overlapped with the probability maps of four cortico-cortical language tracts generated for 12 healthy participants (arcuate, extreme capsule fiber system, uncinate, aslant), including a probabilistic Broca-striatum tract. Finally, we carried out quantitative analyses of the relationship between the lesion load along the tracts and syntactic processing, by calculating tract-lesion overlap for each patient and analyzing the correlation with syntactic data. Our findings revealed a Broca-striatum tract linking BA45 with the left caudate head and overlapping with VLSM voxel clusters relating to complex syntax. The lesion load values for this tract were correlated with complex syntax scores, whereas no such correlation was observed for the other tracts. These results extend current syntax-network models, by adding a deep "Broca-caudate pathway," and are consistent with functional accounts of frontostriatal circuits. © 2015 Wiley Periodicals, Inc.

  8. Evidence against an X-linked visual loss susceptibility locus in Leber hereditary optic neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Chalmers, R.M.; Davis, M.B.; Sweeney, M.G.; Wood, N.W.; Harding, A.E. [Inst. of Neurology, London (United Kingdom)

    1996-07-01

    Pedigree analysis of British families with Leber hereditary optic neuropathy (LHON) closely fits a model in which a pathogenic mtDNA mutation interacts with an X-linked visual loss susceptibility locus (VLSL). This model predicts that 60% of affected females will show marked skewing of X inactivation. Linkage analysis in British and Italian families with genetically proven LHON has excluded the presence of such a VLSL over 169 cM of the X chromosome both when all families were analyzed together and when only families with the bp 11778 mutation were studied. Further, there was no excess skewing of X inactivation in affected females. There was no evidence for close linkage to three markers in the pseudoautosomal region of the sex chromosomes. The mechanism of incomplete penetrance and male predominance in LHON remains unclear. 27 refs., 1 fig., 3 tabs.

  9. Neural response to visual sexual cues in dopamine treatment-linked hypersexuality in Parkinson's disease.

    Science.gov (United States)

    Politis, Marios; Loane, Clare; Wu, Kit; O'Sullivan, Sean S; Woodhead, Zoe; Kiferle, Lorenzo; Lawrence, Andrew D; Lees, Andrew J; Piccini, Paola

    2013-02-01

    Hypersexuality with compulsive sexual behaviour is a significant source of morbidity for patients with Parkinson's disease receiving dopamine replacement therapies. We know relatively little about the pathophysiology of hypersexuality in Parkinson's disease, and it is unknown how visual sexual stimuli, similar to the portrayals of sexuality in the mainstream mass media may affect the brain and behaviour in such susceptible individuals. Here, we have studied a group of 12 patients with Parkinson's disease with hypersexuality using a functional magnetic resonance imaging block design exposing participants to both sexual, other reward-related and neutral visual cues. We hypothesized that exposure to visual sexual cues would trigger increased sexual desire in patients with Parkinson's disease with hypersexuality that would correspond to changes in brain activity in regions linked to dopaminergically stimulated sexual motivation. Patients with Parkinson's disease with hypersexuality were scanned ON and OFF dopamine drugs, and their results were compared with a group of 12 Parkinson's disease control patients without hypersexuality or other impulse control disorders. Exposure to sexual cues significantly increased sexual desire and hedonic responses in the Parkinson's disease hypersexuality group compared with the Parkinson's disease control patients. These behavioural changes corresponded to significant blood oxygen level-dependent signal changes in regions within limbic, paralimbic, temporal, occipital, somatosensory and prefrontal cortices that correspond to emotional, cognitive, autonomic, visual and motivational processes. The functional imaging data showed that the hypersexuality patients' increased sexual desire correlated with enhanced activations in the ventral striatum, and cingulate and orbitofrontal cortices. When the patients with Parkinson's disease with hypersexuality were OFF medication, the functional imaging data showed decreases in activation during

  10. Slm35 links mitochondrial stress response and longevity through TOR signaling pathway

    Science.gov (United States)

    Jose, L. Aguilar-Lopez; Laboy, Raymond; Fabiola, Jaimes-Miranda; Garay, Erika; Alexander, DeLuna; Funes, Soledad

    2016-01-01

    In most eukaryotic cells mitochondria are essential organelles involved in a great variety of cellular functions. One of the physiological processes linked to mitochondria is aging, a gradual process of damage accumulation that eventually promotes cell death. Aging depends on a balance between mitochondrial biogenesis, function and degradation. It has been previously shown that Tor1, Sch9 and Ras2 are activated in response to nutrient availability and regulate cell growth and division. A deficiency in any of these genes promotes lifespan extension and cell protection during oxidative and heat shock stress. In this work we report that in Saccharomyces cerevisiae, the uncharacterized mitochondrial protein Slm35 is functionally linked with the TOR signaling pathway. A Δtor1Δslm35 strain shows a severe decrease in lifespan and is unable to contend with oxidative and heat shock stresses. Specifically, this mutant shows decreased catalase activity indicating a misregulation of ROS scavenging mechanisms. In this study we show that Slm35 is also relevant for mitochondrial network dynamics and mitophagy. The results presented here suggest that Slm35 plays an important role connecting mitochondrial function with cytosolic responses and cell adaptation to stress and aging. PMID:27922823

  11. Rapid Processing of a Global Feature in the ON Visual Pathways of Behaving Monkeys

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    Jun Huang

    2017-08-01

    Full Text Available Visual objects are recognized by their features. Whereas, some features are based on simple components (i.e., local features, such as orientation of line segments, some features are based on the whole object (i.e., global features, such as an object having a hole in it. Over the past five decades, behavioral, physiological, anatomical, and computational studies have established a general model of vision, which starts from extracting local features in the lower visual pathways followed by a feature integration process that extracts global features in the higher visual pathways. This local-to-global model is successful in providing a unified account for a vast sets of perception experiments, but it fails to account for a set of experiments showing human visual systems' superior sensitivity to global features. Understanding the neural mechanisms underlying the “global-first” process will offer critical insights into new models of vision. The goal of the present study was to establish a non-human primate model of rapid processing of global features for elucidating the neural mechanisms underlying differential processing of global and local features. Monkeys were trained to make a saccade to a target in the black background, which was different from the distractors (white circle in color (e.g., red circle target, local features (e.g., white square target, a global feature (e.g., white ring with a hole target or their combinations (e.g., red square target. Contrary to the predictions of the prevailing local-to-global model, we found that (1 detecting a distinction or a change in the global feature was faster than detecting a distinction or a change in color or local features; (2 detecting a distinction in color was facilitated by a distinction in the global feature, but not in the local features; and (3 detecting the hole was interfered by the local features of the hole (e.g., white ring with a squared hole. These results suggest that monkey ON

  12. Linking cortical visual processing to viewing behaviour using fMRI

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    Jan-Bernard Cornelis Marsman

    2013-12-01

    Full Text Available One characteristic of natural visual behavior in humans is the frequent shifting of eye position. It has been argued that the characteristics of these eye movements can be used to distinguish between distinct modes of visual processing (Unema et al, 2005. These viewing modes would be distinguishable on the basis of the eye-movement parameters fixation duration and saccade amplitude and have been hypothesized to reflect the differential involvement of dorsal and ventral systems in saccade planning and information processing. According to this hypothesis, on the one hand, while in a pre-attentive or ambient mode, primarily scanning eye movements are made; in this mode fixation are relatively brief and saccades tends to be relatively large. On the other hand, in attentive focal mode, fixations last longer and saccades are relatively small, and result in viewing behaviour which could be described as detailed inspection. Thus far, no neuroscientific basis exists to support the idea that such distinct viewing modes are indeed linked to processing in distinct cortical regions. Here, we used fixation-based event-related (FIBER fMRI in combination with independent component analysis (ICA to investigate the neural correlates of these viewing modes. While we find robust eye-movement-related activations, our results do not support the theory that the above mentioned viewing modes modulate dorsal and ventral processing. Instead, further analyses revealed that eye-movement characteristics such as saccade amplitude and fixation duration did differentially modulate activity in three clusters in early, ventromedial and ventrolateral visual cortex. In summary, we conclude that evaluating viewing behaviour is crucial for unraveling cortical processing in natural vision.

  13. Anatomy of hierarchy: feedforward and feedback pathways in macaque visual cortex.

    Science.gov (United States)

    Markov, Nikola T; Vezoli, Julien; Chameau, Pascal; Falchier, Arnaud; Quilodran, René; Huissoud, Cyril; Lamy, Camille; Misery, Pierre; Giroud, Pascale; Ullman, Shimon; Barone, Pascal; Dehay, Colette; Knoblauch, Kenneth; Kennedy, Henry

    2014-01-01

    The laminar location of the cell bodies and terminals of interareal connections determines the hierarchical structural organization of the cortex and has been intensively studied. However, we still have only a rudimentary understanding of the connectional principles of feedforward (FF) and feedback (FB) pathways. Quantitative analysis of retrograde tracers was used to extend the notion that the laminar distribution of neurons interconnecting visual areas provides an index of hierarchical distance (percentage of supragranular labeled neurons [SLN]). We show that: 1) SLN values constrain models of cortical hierarchy, revealing previously unsuspected areal relations; 2) SLN reflects the operation of a combinatorial distance rule acting differentially on sets of connections between areas; 3) Supragranular layers contain highly segregated bottom-up and top-down streams, both of which exhibit point-to-point connectivity. This contrasts with the infragranular layers, which contain diffuse bottom-up and top-down streams; 4) Cell filling of the parent neurons of FF and FB pathways provides further evidence of compartmentalization; 5) FF pathways have higher weights, cross fewer hierarchical levels, and are less numerous than FB pathways. Taken together, the present results suggest that cortical hierarchies are built from supra- and infragranular counterstreams. This compartmentalized dual counterstream organization allows point-to-point connectivity in both bottom-up and top-down directions. Copyright © 2013 Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

  14. Ten_m3 regulates eye-specific patterning in the mammalian visual pathway and is required for binocular vision.

    Directory of Open Access Journals (Sweden)

    Catherine A Leamey

    2007-09-01

    Full Text Available Binocular vision requires an exquisite matching of projections from each eye to form a cohesive representation of the visual world. Eye-specific inputs are anatomically segregated, but in register in the visual thalamus, and overlap within the binocular region of primary visual cortex. Here, we show that the transmembrane protein Ten_m3 regulates the alignment of ipsilateral and contralateral projections. It is expressed in a gradient in the developing visual pathway, which is consistently highest in regions that represent dorsal visual field. Mice that lack Ten_m3 show profound abnormalities in mapping of ipsilateral, but not contralateral, projections, and exhibit pronounced deficits when performing visually mediated behavioural tasks. It is likely that the functional deficits arise from the interocular mismatch, because they are reversed by acute monocular inactivation. We conclude that Ten_m3 plays a key regulatory role in the development of aligned binocular maps, which are required for normal vision.

  15. Ventral aspect of the visual form pathway is not critical for the perception of biological motion

    Science.gov (United States)

    Gilaie-Dotan, Sharon; Saygin, Ayse Pinar; Lorenzi, Lauren J.; Rees, Geraint; Behrmann, Marlene

    2015-01-01

    Identifying the movements of those around us is fundamental for many daily activities, such as recognizing actions, detecting predators, and interacting with others socially. A key question concerns the neurobiological substrates underlying biological motion perception. Although the ventral “form” visual cortex is standardly activated by biologically moving stimuli, whether these activations are functionally critical for biological motion perception or are epiphenomenal remains unknown. To address this question, we examined whether focal damage to regions of the ventral visual cortex, resulting in significant deficits in form perception, adversely affects biological motion perception. Six patients with damage to the ventral cortex were tested with sensitive point-light display paradigms. All patients were able to recognize unmasked point-light displays and their perceptual thresholds were not significantly different from those of three different control groups, one of which comprised brain-damaged patients with spared ventral cortex (n > 50). Importantly, these six patients performed significantly better than patients with damage to regions critical for biological motion perception. To assess the necessary contribution of different regions in the ventral pathway to biological motion perception, we complement the behavioral findings with a fine-grained comparison between the lesion location and extent, and the cortical regions standardly implicated in biological motion processing. This analysis revealed that the ventral aspects of the form pathway (e.g., fusiform regions, ventral extrastriate body area) are not critical for biological motion perception. We hypothesize that the role of these ventral regions is to provide enhanced multiview/posture representations of the moving person rather than to represent biological motion perception per se. PMID:25583504

  16. The alexithymic brain: the neural pathways linking alexithymia to physical disorders

    Directory of Open Access Journals (Sweden)

    Kano Michiko

    2013-01-01

    Full Text Available Abstract Alexithymia is a personality trait characterized by difficulties in identifying and describing feelings and is associated with psychiatric and psychosomatic disorders. The mechanisms underlying the link between emotional dysregulation and psychosomatic disorders are unclear. Recent progress in neuroimaging has provided important information regarding emotional experience in alexithymia. We have conducted three brain imaging studies on alexithymia, which we describe herein. This article considers the role of emotion in the development of physical symptoms and discusses a possible pathway that we have identified in our neuroimaging studies linking alexithymia with psychosomatic disorders. In terms of socio-affective processing, alexithymics demonstrate lower reactivity in brain regions associated with emotion. Many studies have reported reduced activation in limbic areas (e.g., cingulate cortex, anterior insula, amygdala and the prefrontal cortex when alexithymics attempt to feel other people’s feelings or retrieve their own emotional episodes, compared to nonalexithymics. With respect to primitive emotional reactions such as the response to pain, alexithymics show amplified activity in areas considered to be involved in physical sensation. In addition to greater hormonal arousal responses in alexithymics during visceral pain, increased activity has been reported in the insula, anterior cingulate cortex, and midbrain. Moreover, in complex social situations, alexithymics may not be able to use feelings to guide their behavior appropriately. The Iowa gambling task (IGT was developed to assess decision-making processes based on emotion-guided evaluation. When alexithymics perform the IGT, they fail to learn an advantageous decision-making strategy and show reduced activity in the medial prefrontal cortex, a key area for successful performance of the IGT, and increased activity in the caudate, a region associated with impulsive choice. The

  17. Cortical damage in the posterior visual pathway in patients with sialidosis type 1.

    Science.gov (United States)

    Lu, Chin-Song; Ng, Shu-Hang; Lai, Szu-Chia; Kao, Ling-Yuh; Liu, Laura; Lin, Wey-Yil; Wu, Yi-Ming; Chen, Yao-Liang; Wang, Jiun-Jie

    2017-02-01

    In order to identify the cortical changes in patients with Sialidosis type 1, diffusion tensor imaging and resting state fMRI were acquired from 11 patients and 11 sex/age matched normal controls after clinical evaluations. The neuroimages from each participant were normalized and parcellated according to the Automatic Anatomical Labeling. Both the mean diffusivity and the corresponding functional connectivity were calculated from each cortical region. The white matter tract integrity was examined. The difference between patients and controls was examined using Student's t-test and between patients with either homozygous or heterozygous mutations by Mann-Whitney U test, both at a threshold of 0.05. Increased mean diffusivity throughout the brain can be noticed in the patients, together with a compromised white matter tracts integrity. The most severely affected cortical regions are in the occipital lobe. Decreased functional connectivity was from the temporal and occipital lobes to the hippocampus and parahippocampus. In contrast, connectivity from thalamus was enhanced. Diffused cortical atrophy with posterior focal lesions was noticed. We concluded that MRI observed functional changes in the posterior cortical pathways in the patients with Sialidosis. The observation might be related to the cortical blindness due to an altered neural network and a compromised visual pathway in the patients.

  18. Electrification pathways for Kenya-linking spatial electrification analysis and medium to long term energy planning

    Science.gov (United States)

    Moksnes, Nandi; Korkovelos, Alexandros; Mentis, Dimitrios; Howells, Mark

    2017-09-01

    In September 2015 UN announced 17 Sustainable Development goals (SDG) from which goal number 7 envisions universal access to modern energy services for all by 2030. In Kenya only about 46% of the population currently has access to electricity. This paper analyses hypothetical scenarios, and selected implications, investigating pathways that would allow the country to reach its electrification targets by 2030. Two modelling tools were used for the purposes of this study, namely OnSSET and OSeMOSYS. The tools were soft-linked in order to capture both the spatial and temporal dynamics of their nature. Two electricity demand scenarios were developed representing low and high end user consumption goals respectively. Indicatively, results show that geothermal, coal, hydro and natural gas would consist the optimal energy mix for the centralized national grid. However, in the case of the low demand scenario a high penetration of stand-alone systems is evident in the country, reaching out to approximately 47% of the electrified population. Increasing end user consumption leads to a shift in the optimal technology mix, with higher penetration of mini-grid technologies and grid extension.

  19. FANCD2 monoubiquitination provides a link between the HHR6 and FA-BRCA pathways.

    Science.gov (United States)

    Zhang, Jun; Zhao, Deping; Wang, Hong; Lin, Chia-Ju; Fei, Peiwen

    2008-02-01

    Fanconi Anemia (FA) is a rare genetic disease characterized by chromosome instability mostly resulting from an improper regulation of FANCD2 monoubiquitination. The E2 ubiquitin conjugating enzyme UBE2T along with a multi-protein E3 ubiquitin-ligase complex containing a catalytic subunit FANCL mediates monoubiquitination of FANCD2. However, the upstream events involved in regulating FANCD2 monoubiquitination remain unclear. Here we report that HHR6, human homologs of the yeast ubiquitin-conjugating enzyme Rad6, regulates FANCD2 monoubiquitination in a manner distinct from that of UBE2T. Indeed, although downregulation of HHR6 compromised FANCD2 monoubiquitination and overexpression of HHR6 enhanced FANCD2 monoubiquitination, HHR6 did not directly interact with FANCL. Cells deficient in HHR6, UBE2T or FANCL did, however, all exhibit similar sensitivities to the DNA crosslinking agent mitomycin C (MMC). As an HHR6-induced increase in oncogenic potential could be partially suppressed by co-expression of non-monoubiquitinated FANCD2, a tight regulation of appropriate levels of monoubiquitinated FANCD2 appears to play an important role in tumor suppression. Thus, these results provide further insights into the regulation of FANCD2 monoubiquitination as well as indicate a common link between the FA-BRCA and HHR6 pathways in the maintenance of genome integrity.

  20. Review of X-linked syndromes with arthrogryposis or early contractures-aid to diagnosis and pathway identification.

    Science.gov (United States)

    Hunter, Jesse M; Kiefer, Jeff; Balak, Christopher D; Jooma, Sonya; Ahearn, Mary Ellen; Hall, Judith G; Baumbach-Reardon, Lisa

    2015-05-01

    The following is a review of 50 X-linked syndromes and conditions associated with either arthrogryposis or other types of early contractures. These entities are categorized as those with known responsible gene mutations, those which are definitely X-linked, but the responsible gene has not been identified, and those suspected from family history to be X-linked. Several important ontology pathways for known disease genes have been identified and are discussed in relevance to clinical characteristics. Tables are included which help to identify distinguishing clinical features of each of the conditions. © 2015 Wiley Periodicals, Inc.

  1. Task relevance of emotional information affects anxiety-linked attention bias in visual search.

    Science.gov (United States)

    Dodd, Helen F; Vogt, Julia; Turkileri, Nilgun; Notebaert, Lies

    2017-01-01

    Task relevance affects emotional attention in healthy individuals. Here, we investigate whether the association between anxiety and attention bias is affected by the task relevance of emotion during an attention task. Participants completed two visual search tasks. In the emotion-irrelevant task, participants were asked to indicate whether a discrepant face in a crowd of neutral, middle-aged faces was old or young. Irrelevant to the task, target faces displayed angry, happy, or neutral expressions. In the emotion-relevant task, participants were asked to indicate whether a discrepant face in a crowd of middle-aged neutral faces was happy or angry (target faces also varied in age). Trait anxiety was not associated with attention in the emotion-relevant task. However, in the emotion-irrelevant task, trait anxiety was associated with a bias for angry over happy faces. These findings demonstrate that the task relevance of emotional information affects conclusions about the presence of an anxiety-linked attention bias. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. The cost of making an eye movement: A direct link between visual working memory and saccade execution.

    Science.gov (United States)

    Schut, Martijn J; Van der Stoep, Nathan; Postma, Albert; Van der Stigchel, Stefan

    2017-06-01

    To facilitate visual continuity across eye movements, the visual system must presaccadically acquire information about the future foveal image. Previous studies have indicated that visual working memory (VWM) affects saccade execution. However, the reverse relation, the effect of saccade execution on VWM load is less clear. To investigate the causal link between saccade execution and VWM, we combined a VWM task and a saccade task. Participants were instructed to remember one, two, or three shapes and performed either a No Saccade-, a Single Saccade- or a Dual (corrective) Saccade-task. The results indicate that items stored in VWM are reported less accurately if a single saccade-or a dual saccade-task is performed next to retaining items in VWM. Importantly, the loss of response accuracy for items retained in VWM by performing a saccade was similar to committing an extra item to VWM. In a second experiment, we observed no cost of executing a saccade for auditory working memory performance, indicating that executing a saccade exclusively taxes the VWM system. Our results suggest that the visual system presaccadically stores the upcoming retinal image, which has a similar VWM load as committing one extra item to memory and interferes with stored VWM content. After the saccade, the visual system can retrieve this item from VWM to evaluate saccade accuracy. Our results support the idea that VWM is a system which is directly linked to saccade execution and promotes visual continuity across saccades.

  3. Pathway analysis supports association of nonsyndromic cryptorchidism with genetic loci linked to cytoskeleton-dependent functions.

    Science.gov (United States)

    Barthold, Julia Spencer; Wang, Yanping; Kolon, Thomas F; Kollin, Claude; Nordenskjöld, Agneta; Olivant Fisher, Alicia; Figueroa, T Ernesto; BaniHani, Ahmad H; Hagerty, Jennifer A; Gonzaléz, Ricardo; Noh, Paul H; Chiavacci, Rosetta M; Harden, Kisha R; Abrams, Debra J; Kim, Cecilia E; Li, Jin; Hakonarson, Hakon; Devoto, Marcella

    2015-10-01

    What are the genetic loci that increase susceptibility to nonsyndromic cryptorchidism, or undescended testis? A genome-wide association study (GWAS) suggests that susceptibility to cryptorchidism is heterogeneous, with a subset of suggestive signals linked to cytoskeleton-dependent functions and syndromic forms of the disease. Population studies suggest moderate genetic risk of cryptorchidism and possible maternal and environmental contributions to risk. Previous candidate gene analyses have failed to identify a major associated locus, although variants in insulin-like 3 (INSL3), relaxin/insulin-like family peptide receptor 2 (RXFP2) and other hormonal pathway genes may increase risk in a small percentage of patients. This is a case-control GWAS of 844 boys with nonsyndromic cryptorchidism and 2718 control subjects without syndromes or genital anomalies, all of European ancestry. All boys with cryptorchidism were diagnosed and treated by a pediatric specialist. In the discovery phase, DNA was extracted from tissue or blood samples and genotyping performed using the Illumina HumanHap550 and Human610-Quad (Group 1) or OmniExpress (Group 2) platform. We imputed genotypes genome-wide, and combined single marker association results in meta-analyses for all cases and for secondary subphenotype analyses based on testis position, laterality and age, and defined genome-wide significance as P = 7 × 10(-9) to correct for multiple testing. Selected markers were genotyped in an independent replication group of European cases (n = 298) and controls (n = 324). We used several bioinformatics tools to analyze top (P Cytoskeleton-dependent molecular and cellular functions were prevalent in pathway analysis of suggestive signals, and may implicate loci encoding cytoskeletal proteins that participate in androgen receptor signaling. Genes linked to human syndromic cryptorchidism, including hypogonadotropic hypogonadism, and to hormone-responsive and/or differentially expressed genes

  4. cAMP-dependent proteolysis of GATA-6 is linked to JNK-signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ushijima, Hironori [Department of Molecular Biology, School of Pharmacy, Iwate Medical University, 2-1-1, Nishitokuta, Yahaba, Shiwagun, Iwate 028-3694 (Japan); Maeda, Masatomo, E-mail: mmaeda@iwate-med.ac.jp [Department of Molecular Biology, School of Pharmacy, Iwate Medical University, 2-1-1, Nishitokuta, Yahaba, Shiwagun, Iwate 028-3694 (Japan)

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer A JNK inhibitor SP600125 inhibited cAMP-dependent proteolysis of GATA-6. Black-Right-Pointing-Pointer Effect of a JNK activator anisomycin on the proteolysis was examined. Black-Right-Pointing-Pointer Anisomycin stimulated the export of nuclear GATA-6 into the cytoplasm. Black-Right-Pointing-Pointer JNK activated the CRM1 mediated nuclear export of GATA-6. Black-Right-Pointing-Pointer JNK further stimulated slowly the degradation of GATA-6 by cytoplasmic proteasomes. -- Abstract: A JNK inhibitor SP600125 inhibited cAMP-dependent proteolysis of GATA-6 by proteasomes around its IC50. We further examined the effects of SP600125 on the degradation of GATA-6 in detail, since an activator of JNK (anisomycin) is available. Interestingly, anisomycin immediately stimulated the export of nuclear GATA-6 into the cytoplasm, and then the cytoplasmic content of GATA-6 decreased slowly through degradation by proteasomes. Such an effect of anisomycin was inhibited by SP600125, indicating that the observed phenomenon might be linked to the JNK signaling pathway. The inhibitory effect of SP600125 could not be ascribed to the inhibition of PKA, since phosphorylation of CREB occurred in the presence of dbcAMP and SP600125. The nuclear export of GATA-6 was inhibited by leptomycin B, suggesting that CRM1-mediated export could be activated by anisomycin. Furthermore, it seems likely that the JNK activated by anisomycin may stimulate not only the nuclear export of GATA-6 through CRM1 but also the degradation of GATA-6 by cytoplasmic proteasomes. In contrast, A-kinase might activate only the latter process through JNK.

  5. Pathways linking health literacy, health beliefs, and cognition to medication adherence in older adults with asthma.

    Science.gov (United States)

    Soones, Tacara N; Lin, Jenny L; Wolf, Michael S; O'Conor, Rachel; Martynenko, Melissa; Wisnivesky, Juan P; Federman, Alex D

    2017-03-01

    Limited health literacy is associated with low adherence to asthma controller medications among older adults. We sought to describe the causal pathway linking health literacy to medication adherence by modeling asthma illness and medication beliefs as mediators. We recruited adults aged 60 years and older with asthma from hospital and community practices in New York, New York, and Chicago, Illinois. We measured health literacy and medication adherence using the Short Test of Functional Health Literacy in Adults and the Medication Adherence Rating Scale, respectively. We used validated instruments to assess asthma illness and medication beliefs. We assessed cognition using a cognitive battery. Using structural equation modeling, we modeled illness and medication beliefs as mediators of the relationship between health literacy and adherence while controlling for cognition. Our study included 433 patients with a mean age of 67 ± 6.8 years. The sample had 84% women, 31% non-Hispanic blacks, and 39% Hispanics. The 36% of patients with limited health literacy were more likely to have misconceptions about asthma (P medications (P adherence mediated by medications concerns (β = 0.033; P = .002). Neither medication necessity (β = 0.044; P = .138) nor illness beliefs (β = 0.007; P = .143) demonstrated a mediational role between health literacy and adherence. Interventions designed to improve asthma controller medication adherence in older adults may be enhanced by addressing concerns about medications in addition to using communication strategies appropriate for populations with limited health literacy and cognitive impairments. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  6. Modes of Effective Connectivity within Cortical Pathways Are Distinguished for Different Categories of Visual Context: An fMRI Study

    Directory of Open Access Journals (Sweden)

    Qiong Wu

    2017-05-01

    Full Text Available Context contributes to accurate and efficient information processing. To reveal the dynamics of the neural mechanisms that underlie the processing of visual contexts during the recognition of color, shape, and 3D structure of objects, we carried out functional magnetic resonance imaging (fMRI of subjects while judging the contextual validity of the three visual contexts. Our results demonstrated that the modes of effective connectivity in the cortical pathways, as well as the patterns of activation in these pathways, were dynamical depending on the nature of the visual contexts. While the fusiform gyrus, superior parietal lobe, and inferior prefrontal gyrus were activated by the three visual contexts, the temporal and parahippocampal gyrus/Amygdala (PHG/Amg cortices were activated only by the color context. We further carried out dynamic causal modeling (DCM analysis and revealed the nature of the effective connectivity involved in the three contextual information processing. DCM showed that there were dynamic connections and collaborations among the brain regions belonging to the previously identified ventral and dorsal visual pathways.

  7. Combinatorial high-throughput experimental and bioinformatic approach identifies molecular pathways linked with the sensitivity to anticancer target drugs.

    Science.gov (United States)

    Venkova, Larisa; Aliper, Alexander; Suntsova, Maria; Kholodenko, Roman; Shepelin, Denis; Borisov, Nicolas; Malakhova, Galina; Vasilov, Raif; Roumiantsev, Sergey; Zhavoronkov, Alex; Buzdin, Anton

    2015-09-29

    Effective choice of anticancer drugs is important problem of modern medicine. We developed a method termed OncoFinder for the analysis of new type of biomarkers reflecting activation of intracellular signaling and metabolic molecular pathways. These biomarkers may be linked with the sensitivity to anticancer drugs. In this study, we compared the experimental data obtained in our laboratory and in the Genomics of Drug Sensitivity in Cancer (GDS) project for testing response to anticancer drugs and transcriptomes of various human cell lines. The microarray-based profiling of transcriptomes was performed for the cell lines before the addition of drugs to the medium, and experimental growth inhibition curves were built for each drug, featuring characteristic IC50 values. We assayed here four target drugs - Pazopanib, Sorafenib, Sunitinib and Temsirolimus, and 238 different cell lines, of which 11 were profiled in our laboratory and 227 - in GDS project. Using the OncoFinder-processed transcriptomic data on ~600 molecular pathways, we identified pathways showing significant correlation between pathway activation strength (PAS) and IC50 values for these drugs. Correlations reflect relationships between response to drug and pathway activation features. We intersected the results and found molecular pathways significantly correlated in both our assay and GDS project. For most of these pathways, we generated molecular models of their interaction with known molecular target(s) of the respective drugs. For the first time, our study uncovered mechanisms underlying cancer cell response to drugs at the high-throughput molecular interactomic level.

  8. Concurrent audio-visual feedback for supporting drivers at intersections: A study using two linked driving simulators.

    Science.gov (United States)

    Houtenbos, M; de Winter, J C F; Hale, A R; Wieringa, P A; Hagenzieker, M P

    2017-04-01

    A large portion of road traffic crashes occur at intersections for the reason that drivers lack necessary visual information. This research examined the effects of an audio-visual display that provides real-time sonification and visualization of the speed and direction of another car approaching the crossroads on an intersecting road. The location of red blinking lights (left vs. right on the speedometer) and the lateral input direction of beeps (left vs. right ear in headphones) corresponded to the direction from where the other car approached, and the blink and beep rates were a function of the approaching car's speed. Two driving simulators were linked so that the participant and the experimenter drove in the same virtual world. Participants (N = 25) completed four sessions (two with the audio-visual display on, two with the audio-visual display off), each session consisting of 22 intersections at which the experimenter approached from the left or right and either maintained speed or slowed down. Compared to driving with the display off, the audio-visual display resulted in enhanced traffic efficiency (i.e., greater mean speed, less coasting) while not compromising safety (i.e., the time gap between the two vehicles was equivalent). A post-experiment questionnaire showed that the beeps were regarded as more useful than the lights. It is argued that the audio-visual display is a promising means of supporting drivers until fully automated driving is technically feasible. Copyright © 2016. Published by Elsevier Ltd.

  9. ERK pathway activation bidirectionally affects visual recognition memory and synaptic plasticity in the perirhinal cortex

    Directory of Open Access Journals (Sweden)

    Davide eSilingardi

    2011-12-01

    Full Text Available ERK 1,2 pathway mediates experience-dependent gene transcription in neurons and several studies have identified its pivotal role in experience-dependent synaptic plasticity and in forms of long term memory involving hippocampus, amygdala or striatum. The perirhinal cortex (PRHC plays an essential role in familiarity-based object recognition memory. It is still unknown whether ERK activation in PRHC is necessary for recognition memory consolidation. Most important, it is unknown whether by modulating the gain of the ERK pathway it is possible to bidirectionally affect visual recognition memory and PRHC synaptic plasticity.We have first pharmacologically blocked ERK activation in the PRHC of adult mice and found that this was sufficient to impair long term recognition memory in a familiarity-based task, the Object Recognition Task (ORT. We have then tested performance in the ORT in Ras-GRF1 knock-out (KO mice, which exhibit a reduced activation of ERK by neuronal activity, and in ERK1 KO mice, which have an increased activation of ERK2 and exhibit enhanced striatal plasticity and striatal mediated memory. We found that Ras-GRF1 KO mice have normal short-term memory but display a long term memory deficit; memory reconsolidation is also impaired. On the contrary, ERK1 KO mice exhibit a better performance than WT mice at 72 hour retention interval, suggesting a longer lasting recognition memory. In parallel with behavioural data, LTD was strongly reduced and LTP was significantly smaller in PRHC slices from Ras-GRF1 KO than in WT mice while enhanced LTP and LTD were found in PRHC slices from ERK1 KO mice.

  10. DMPD: Nuclear receptors in macrophages: a link between metabolism and inflammation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18022390 Nuclear receptors in macrophages: a link between metabolism and inflammati... Show Nuclear receptors in macrophages: a link between metabolism and inflammation. PubmedID 18022390 Title ...Nuclear receptors in macrophages: a link between metabolism and inflammation. Aut

  11. Frames as visual links between paintings and the museum environment: an analysis of statistical image properties

    Science.gov (United States)

    Redies, Christoph; Groß, Franziska

    2013-01-01

    Frames provide a visual link between artworks and their surround. We asked how image properties change as an observer zooms out from viewing a painting alone, to viewing the painting with its frame and, finally, the framed painting in its museum environment (museum scene). To address this question, we determined three higher-order image properties that are based on histograms of oriented luminance gradients. First, complexity was measured as the sum of the strengths of all gradients in the image. Second, we determined the self-similarity of histograms of the orientated gradients at different levels of spatial analysis. Third, we analyzed how much gradient strength varied across orientations (anisotropy). Results were obtained for three art museums that exhibited paintings from three major periods of Western art. In all three museums, the mean complexity of the frames was higher than that of the paintings or the museum scenes. Frames thus provide a barrier of complexity between the paintings and their exterior. By contrast, self-similarity and anisotropy values of images of framed paintings were intermediate between the images of the paintings and the museum scenes, i.e., the frames provided a transition between the paintings and their surround. We also observed differences between the three museums that may reflect modified frame usage in different art periods. For example, frames in the museum for 20th century art tended to be smaller and less complex than in the two other two museums that exhibit paintings from earlier art periods (13th–18th century and 19th century, respectively). Finally, we found that the three properties did not depend on the type of reproduction of the paintings (photographs in museums, scans from books or images from the Google Art Project). To the best of our knowledge, this study is the first to investigate the relation between frames and paintings by measuring physically defined, higher-order image properties. PMID:24265625

  12. Pediatric anterior visual pathway gliomas: trends in fluid and electrolyte dynamics and their management nuances.

    Science.gov (United States)

    Singh, Devesh K; Behari, Sanjay; Jaiswal, Awadhesh K; Sahu, Rabi N; Srivastava, Arun K; Mehrotra, Anant; Dabadgaon, Preeti

    2015-03-01

    Trends in pre- and postoperative fluid, electrolyte and osmolarity changes, and incidence of diabetes insipidus (DI) were assessed in pediatric patients with anterior visual pathway gliomas (AVPGs). Thirty-three patients with AVPGs (age electrolyte balance, serum osmolarity, and DI status were noted. Chi-square test compared clinical/endocrinological parameters, and unpaired T test evaluated mean daily water/electrolyte changes (p value 3 cm), hydrocephalus [(NHI: n = 7, 41.18 %; HI: n = 12, 75 %), endocrinopathies (p = 0.047), Na(+)/K(+) derangements, and preoperative DI (n = 8, p = 0.004)] were present in the group HI. Increased postoperative urine output (almost double in those with hypothalamic involvement) and hypernatremia/hyperkalemia were seen in group HI until the sixth postoperative day (p electrolyte disturbances. Strict vigilance over postoperative fluid balance is mandatory during the first postoperative week. Rapidly rising serial serum sodium values without increased urine output mandates immediate central venous pressure measurement to detect DI associated with dehydration.

  13. Ultrabroadband 2D electronic spectroscopy as a tool for direct visualization of pathways of energy flow

    Science.gov (United States)

    Son, Minjung; Schlau-Cohen, Gabriela S.

    2017-08-01

    Two-dimensional electronic spectroscopy (2DES) has emerged as an incisive tool for mapping out energy relaxation pathways in complex molecular systems by determining correlation maps between the excitation and emission frequencies. Its enhanced spectral as well as temporal resolution offer new insights into coupling and energy transfer between closely-spaced energy states, which are often hidden in a one-dimensional transient spectrum. However, a major drawback of the current 2DES technique is that the spectral window of detection is directly limited to the laser bandwidth used, which leads to an incomplete visualization of the full energy landscape of the system. As a solution to this limitation, we present an ultrabroadband 2DES apparatus utilizing a 8-fs, 185-nm bandwidth supercontinuum that covers the entire visible region. We demonstrate the utility of our setup by measuring the 2D spectra of laser dyes absorbing at different regions of the laser spectrum, and the major light-harvesting complex of spinach.

  14. Visualizing large, high-throughput datasets based on the cognitive representation of biological pathways

    Science.gov (United States)

    Nagel, Axel; Lohse, Marc; Bolger, Anthony; Stitt, Mark; Usadel, Björn

    2011-03-01

    The data explosion in the biological sciences has led to many novel challenges for the individual researcher. One of these is to interpret the sheer mass of data at hand. Typical high-throughput data sets from transcriptomic data can easily comprise hundred thousand data points. It is thus necessary to provide tools to interactively visualize these data sets in a way that aids in their interpretation. Thus we have developed the MAPMAN application. This application renders individual data points from different domains as different glyphs that are color coded to reflect underlying changes in the magnitude/abundance of the underlying data. In order to augment the human comprehensibility of the biologist domain experts these data are organized on meaningful pathway diagrams that the biologist has encountered numerous times. Using these representations together with a high level organization thus helps to quickly realize the main outcome of such a high throughput study and to further decide on additional tasks that should be performed to explore the data.

  15. Deep Learning Guided Partitioned Shape Model for Anterior Visual Pathway Segmentation.

    Science.gov (United States)

    Mansoor, Awais; Cerrolaza, Juan J; Idrees, Rabia; Biggs, Elijah; Alsharid, Mohammad A; Avery, Robert A; Linguraru, Marius George

    2016-08-01

    Analysis of cranial nerve systems, such as the anterior visual pathway (AVP), from MRI sequences is challenging due to their thin long architecture, structural variations along the path, and low contrast with adjacent anatomic structures. Segmentation of a pathologic AVP (e.g., with low-grade gliomas) poses additional challenges. In this work, we propose a fully automated partitioned shape model segmentation mechanism for AVP steered by multiple MRI sequences and deep learning features. Employing deep learning feature representation, this framework presents a joint partitioned statistical shape model able to deal with healthy and pathological AVP. The deep learning assistance is particularly useful in the poor contrast regions, such as optic tracts and pathological areas. Our main contributions are: 1) a fast and robust shape localization method using conditional space deep learning, 2) a volumetric multiscale curvelet transform-based intensity normalization method for robust statistical model, and 3) optimally partitioned statistical shape and appearance models based on regional shape variations for greater local flexibility. Our method was evaluated on MRI sequences obtained from 165 pediatric subjects. A mean Dice similarity coefficient of 0.779 was obtained for the segmentation of the entire AVP (optic nerve only =0.791 ) using the leave-one-out validation. Results demonstrated that the proposed localized shape and sparse appearance-based learning approach significantly outperforms current state-of-the-art segmentation approaches and is as robust as the manual segmentation.

  16. Long-term visual outcome after chemotherapy for optic pathway glioma in children: Site and age are strongly predictive.

    Science.gov (United States)

    Dodgshun, Andrew J; Elder, James E; Hansford, Jordan R; Sullivan, Michael J

    2015-12-01

    Optic pathway gliomas (OPGs) are commonly noted in pediatric oncology services. Radiotherapy is effective at controlling tumors, but has many undesirable late effects, especially in patients with neurofibromatosis. Chemotherapy is commonly used to preserve vision and delay or eliminate the need for radiotherapy. Despite visual threat being a common reason to initiate chemotherapy in patients with OPG, reports of visual outcome after chemotherapy are not common and reports of long-term visual outcome are even scarcer. In a single institution, all patients with OPG who had received chemotherapy or radiotherapy between 1996 and 2013 were identified from hospital databases. Visual, treatment, and radiological data were recorded. Categorized visual acuity was the primary outcome measure. Of 43 patients identified, visual data were available for 42 patients. Approximately 14% of patients experienced an improvement in visual acuity during therapy, 9% of patients experienced a deterioration, and the remainder were stable. At a mean follow-up of 78 months, 26% of patients were legally blind. Children aged children with OPG after treatment with chemotherapy is stability. This stability is maintained over the long term for >90% of children without these risk factors. © 2015 American Cancer Society.

  17. In Vivo Evaluation of the Visual Pathway in Streptozotocin-Induced Diabetes by Diffusion Tensor MRI and Contrast Enhanced MRI.

    Directory of Open Access Journals (Sweden)

    Swarupa Kancherla

    Full Text Available Visual function has been shown to deteriorate prior to the onset of retinopathy in some diabetic patients and experimental animal models. This suggests the involvement of the brain's visual system in the early stages of diabetes. In this study, we tested this hypothesis by examining the integrity of the visual pathway in a diabetic rat model using in vivo multi-modal magnetic resonance imaging (MRI. Ten-week-old Sprague-Dawley rats were divided into an experimental diabetic group by intraperitoneal injection of 65 mg/kg streptozotocin in 0.01 M citric acid, and a sham control group by intraperitoneal injection of citric acid only. One month later, diffusion tensor MRI (DTI was performed to examine the white matter integrity in the brain, followed by chromium-enhanced MRI of retinal integrity and manganese-enhanced MRI of anterograde manganese transport along the visual pathway. Prior to MRI experiments, the streptozotocin-induced diabetic rats showed significantly smaller weight gain and higher blood glucose level than the control rats. DTI revealed significantly lower fractional anisotropy and higher radial diffusivity in the prechiasmatic optic nerve of the diabetic rats compared to the control rats. No apparent difference was observed in the axial diffusivity of the optic nerve, the chromium enhancement in the retina, or the manganese enhancement in the lateral geniculate nucleus and superior colliculus between groups. Our results suggest that streptozotocin-induced diabetes leads to early injury in the optic nerve when no substantial change in retinal integrity or anterograde transport along the visual pathways was observed in MRI using contrast agent enhancement. DTI may be a useful tool for detecting and monitoring early pathophysiological changes in the visual system of experimental diabetes non-invasively.

  18. Aesthetics by numbers: Links between perceived texture qualities and computed visual texture properties

    NARCIS (Netherlands)

    Jacobs, R.H.A.H.; Haak, K.V.; Thumfart, S.; Renken, R.J.; Henson, B.; Cornelissen, F.W.

    2016-01-01

    Our world is filled with texture. For the human visual system, this is an important source of information for assessing environmental and material properties. Indeed - and presumably for this reason - the human visual system has regions dedicated to processing textures. Despite their abundance and

  19. Aesthetics by Numbers : Links between Perceived Texture Qualities and Computed Visual Texture Properties

    NARCIS (Netherlands)

    Jacobs, Richard H. A. H.; Haak, Koen V.; Thumfart, Stefan; Renken, Remco; Henson, Brian; Cornelissen, Frans W.

    2016-01-01

    Our world is filled with texture. For the human visual system, this is an important source of information for assessing environmental and material properties. Indeed-and presumably for this reason-the human visual system has regions dedicated to processing textures. Despite their abundance and

  20. Design and development of a linked open data-based health information representation and visualization system: potentials and preliminary evaluation.

    Science.gov (United States)

    Tilahun, Binyam; Kauppinen, Tomi; Keßler, Carsten; Fritz, Fleur

    2014-10-25

    Healthcare organizations around the world are challenged by pressures to reduce cost, improve coordination and outcome, and provide more with less. This requires effective planning and evidence-based practice by generating important information from available data. Thus, flexible and user-friendly ways to represent, query, and visualize health data becomes increasingly important. International organizations such as the World Health Organization (WHO) regularly publish vital data on priority health topics that can be utilized for public health policy and health service development. However, the data in most portals is displayed in either Excel or PDF formats, which makes information discovery and reuse difficult. Linked Open Data (LOD)-a new Semantic Web set of best practice of standards to publish and link heterogeneous data-can be applied to the representation and management of public level health data to alleviate such challenges. However, the technologies behind building LOD systems and their effectiveness for health data are yet to be assessed. The objective of this study is to evaluate whether Linked Data technologies are potential options for health information representation, visualization, and retrieval systems development and to identify the available tools and methodologies to build Linked Data-based health information systems. We used the Resource Description Framework (RDF) for data representation, Fuseki triple store for data storage, and Sgvizler for information visualization. Additionally, we integrated SPARQL query interface for interacting with the data. We primarily use the WHO health observatory dataset to test the system. All the data were represented using RDF and interlinked with other related datasets on the Web of Data using Silk-a link discovery framework for Web of Data. A preliminary usability assessment was conducted following the System Usability Scale (SUS) method. We developed an LOD-based health information representation, querying

  1. ProXL (Protein Cross-Linking Database): A Platform for Analysis, Visualization, and Sharing of Protein Cross-Linking Mass Spectrometry Data.

    Science.gov (United States)

    Riffle, Michael; Jaschob, Daniel; Zelter, Alex; Davis, Trisha N

    2016-08-05

    ProXL is a Web application and accompanying database designed for sharing, visualizing, and analyzing bottom-up protein cross-linking mass spectrometry data with an emphasis on structural analysis and quality control. ProXL is designed to be independent of any particular software pipeline. The import process is simplified by the use of the ProXL XML data format, which shields developers of data importers from the relative complexity of the relational database schema. The database and Web interfaces function equally well for any software pipeline and allow data from disparate pipelines to be merged and contrasted. ProXL includes robust public and private data sharing capabilities, including a project-based interface designed to ensure security and facilitate collaboration among multiple researchers. ProXL provides multiple interactive and highly dynamic data visualizations that facilitate structural-based analysis of the observed cross-links as well as quality control. ProXL is open-source, well-documented, and freely available at https://github.com/yeastrc/proxl-web-app .

  2. A novel link between the proteasome pathway and the signal transduction pathway of the Bone Morphogenetic Proteins (BMPs

    Directory of Open Access Journals (Sweden)

    Kim Richard H

    2002-06-01

    Full Text Available Abstract Background The intracellular signaling events of the Bone Morphogenetic Proteins (BMPs involve the R-Smad family members Smad1, Smad5, Smad8 and the Co-Smad, Smad4. Smads are currently considered to be DNA-binding transcriptional modulators and shown to recruit the master transcriptional co-activator CBP/p300 for transcriptional activation. SNIP1 is a recently discovered novel repressor of CBP/p300. Currently, the detailed molecular mechanisms that allow R-Smads and Co-Smad to co-operatively modulate transcription events are not fully understood. Results Here we report a novel physical and functional link between Smad1 and the 26S proteasome that contributes to Smad1- and Smad4-mediated transcriptional regulation. Smad1 forms a complex with a proteasome β subunit HsN3 and the ornithine decarboxylase antizyme (Az. The interaction is enhanced upon BMP type I receptor activation and occur prior to the incorporation of HsN3 into the mature 20S proteasome. Furthermore, BMPs trigger the translocation of Smad1, HsN3 and Az into the nucleus, where the novel CBP/p300 repressor protein SNIP1 is further recruited to Smad1/HsN3/Az complex and degraded in a Smad1-, Smad4- and Az-dependent fashion. The degradation of the CBP/p300 repressor SNIP1 is likely an essential step for Smad1-, Smad4-mediated transcriptional activation, since increased SNIP1 expression inhibits BMP-induced gene responses. Conclusions Our studies thus add two additional important functional partners of Smad1 into the signaling web of BMPs and also suggest a novel mechanism for Smad1 and Smad4 to co-modulate transcription via regulating proteasomal degradation of CBP/p300 repressor SNIP1.

  3. Ouabain, a cardiac glycoside, inhibits the Fanconi anemia/BRCA pathway activated by DNA interstrand cross-linking agents.

    Directory of Open Access Journals (Sweden)

    Dong Wha Jun

    Full Text Available Modulation of the DNA repair pathway is an emerging target for the development of anticancer drugs. DNA interstrand cross-links (ICLs, one of the most severe forms of DNA damage caused by anticancer drugs such as cisplatin and mitomycin C (MMC, activates the Fanconi anemia (FA/BRCA DNA repair pathway. Inhibition of the FA/BRCA pathway can enhance the cytotoxic effects of ICL-inducing anticancer drugs and can reduce anticancer drug resistance. To find FA/BRCA pathway inhibitory small molecules, we established a cell-based high-content screening method for quantitating the activation of the FA/BRCA pathway by measuring FANCD2 foci on DNA lesions and then applied our method to chemical screening. Using commercial LOPAC1280 chemical library screening, ouabain was identified as a competent FA/BRCA pathway inhibitory compound. Ouabain, a member of the cardiac glycoside family, binds to and inhibits Na(+/K(+-ATPase and has been used to treat heart disease for many years. We observed that ouabain, as well as other cardiac glycoside family members--digitoxin and digoxin--down-regulated FANCD2 and FANCI mRNA levels, reduced monoubiquitination of FANCD2, inhibited FANCD2 foci formation on DNA lesions, and abrogated cell cycle arrest induced by MMC treatment. These inhibitory activities of ouabain required p38 MAPK and were independent of cellular Ca(2+ ion increase or the drug uptake-inhibition effect of ouabain. Furthermore, we found that ouabain potentiated the cytotoxic effects of MMC in tumor cells. Taken together, we identified an additional effect of ouabain as a FA/BRCA pathway-inhibiting chemosensitization compound. The results of this study suggest that ouabain may serve as a chemosensitizer to ICL-inducing anticancer drugs.

  4. PDP-1 links the TGF-β and IIS pathways to regulate longevity, development, and metabolism.

    Directory of Open Access Journals (Sweden)

    Sri Devi Narasimhan

    2011-04-01

    Full Text Available The insulin/IGF-1 signaling (IIS pathway is a conserved regulator of longevity, development, and metabolism. In Caenorhabditis elegans IIS involves activation of DAF-2 (insulin/IGF-1 receptor tyrosine kinase, AGE-1 (PI 3-kinase, and additional downstream serine/threonine kinases that ultimately phosphorylate and negatively regulate the single FOXO transcription factor homolog DAF-16. Phosphatases help to maintain cellular signaling homeostasis by counterbalancing kinase activity. However, few phosphatases have been identified that negatively regulate the IIS pathway. Here we identify and characterize pdp-1 as a novel negative modulator of the IIS pathway. We show that PDP-1 regulates multiple outputs of IIS such as longevity, fat storage, and dauer diapause. In addition, PDP-1 promotes DAF-16 nuclear localization and transcriptional activity. Interestingly, genetic epistasis analyses place PDP-1 in the DAF-7/TGF-β signaling pathway, at the level of the R-SMAD proteins DAF-14 and DAF-8. Further investigation into how a component of TGF-β signaling affects multiple outputs of IIS/DAF-16, revealed extensive crosstalk between these two well-conserved signaling pathways. We find that PDP-1 modulates the expression of several insulin genes that are likely to feed into the IIS pathway to regulate DAF-16 activity. Importantly, dysregulation of IIS and TGF-β signaling has been implicated in diseases such as Type 2 Diabetes, obesity, and cancer. Our results may provide a new perspective in understanding of the regulation of these pathways under normal conditions and in the context of disease.

  5. Linking attentional processes and conceptual problem solving: Visual cues facilitate the automaticity of extracting relevant information from diagrams

    Directory of Open Access Journals (Sweden)

    Amy eRouinfar

    2014-09-01

    Full Text Available This study investigated links between lower-level visual attention processes and higher-level problem solving. This was done by overlaying visual cues on conceptual physics problem diagrams to direct participants’ attention to relevant areas to facilitate problem solving. Participants (N = 80 individually worked through four problem sets, each containing a diagram, while their eye movements were recorded. Each diagram contained regions that were relevant to solving the problem correctly and separate regions related to common incorrect responses. Problem sets contained an initial problem, six isomorphic training problems, and a transfer problem. The cued condition saw visual cues overlaid on the training problems. Participants’ verbal responses were used to determine their accuracy. The study produced two major findings. First, short duration visual cues can improve problem solving performance on a variety of insight physics problems, including transfer problems not sharing the surface features of the training problems, but instead sharing the underlying solution path. Thus, visual cues can facilitate re-representing a problem and overcoming impasse, enabling a correct solution. Importantly, these cueing effects on problem solving did not involve the solvers’ attention necessarily embodying the solution to the problem. Instead, the cueing effects were caused by solvers attending to and integrating relevant information in the problems into a solution path. Second, these short duration visual cues when administered repeatedly over multiple training problems resulted in participants becoming more efficient at extracting the relevant information on the transfer problem, showing that such cues can improve the automaticity with which solvers extract relevant information from a problem. Both of these results converge on the conclusion that lower-order visual processes driven by attentional cues can influence higher-order cognitive processes

  6. Color vision versus pattern visual evoked potentials in the assessment of subclinical optic pathway involvement in multiple sclerosis.

    Science.gov (United States)

    Gundogan, Fatih C; Tas, Ahmet; Altun, Salih; Oz, Oguzhan; Erdem, Uzeyir; Sobaci, Gungor

    2013-03-01

    Optic pathway involvement in multiple sclerosis is frequently the initial sign in the disease process. In most clinical applications, pattern visual evoked potential (PVEP) is used in the assessment of optic pathway involvement. To question the value of PVEP against color vision assessment in the diagnosis of subclinical optic pathway involvement. This prospective, cross-sectional study included 20 multiple sclerosis patients without a history of optic neuritis, and 20 healthy control subjects. Farnsworth-Munsell (FM) 100-Hue testing and PVEPs to 60-min arc and 15-min arc checks by using Roland-Consult RetiScan® system were performed. P 100 amplitude, P 100 latency in PVEP and total error scores (TES) in FM 100-Hue test were assessed. Expanded Disability Status Scale score and the time from diagnosis were 2.21 ± 2.53 (ranging from 0 to 7) and 4.1 ± 4.4 years. MS group showed significantly delayed P 100 latency for both checks (P 0.05 for all). 14 MS patients (70%) had an increased TESs in FM-100 Hue, 11 (55%) MS patients had delayed P 100 latency and 9 (45%) had reduced P 100 amplitude. The areas under the ROC curves were 0.944 for FM-100 Hue test, 0.753 for P 100 latency, and 0.173 for P 100 amplitude. Color vision testing seems to be more sensitive than PVEP in detecting subclinical visual pathway involvement in MS.

  7. Structure of mycobacterial maltokinase, the missing link in the essential GlgE-pathway.

    Science.gov (United States)

    Fraga, Joana; Maranha, Ana; Mendes, Vitor; Pereira, Pedro José Barbosa; Empadinhas, Nuno; Macedo-Ribeiro, Sandra

    2015-01-26

    A novel four-step pathway identified recently in mycobacteria channels trehalose to glycogen synthesis and is also likely involved in the biosynthesis of two other crucial polymers: intracellular methylglucose lipopolysaccharides and exposed capsular glucan. The structures of three of the intervening enzymes - GlgB, GlgE, and TreS - were recently reported, providing the first templates for rational drug design. Here we describe the structural characterization of the fourth enzyme of the pathway, mycobacterial maltokinase (Mak), uncovering a eukaryotic-like kinase (ELK) fold, similar to methylthioribose kinases and aminoglycoside phosphotransferases. The 1.15 Å structure of Mak in complex with a non-hydrolysable ATP analog reveals subtle structural rearrangements upon nucleotide binding in the cleft between the N- and the C-terminal lobes. Remarkably, this new family of ELKs has a novel N-terminal domain topologically resembling the cystatin family of protease inhibitors. By interfacing with and restraining the mobility of the phosphate-binding region of the N-terminal lobe, Mak's unusual N-terminal domain might regulate its phosphotransfer activity and represents the most likely anchoring point for TreS, the upstream enzyme in the pathway. By completing the gallery of atomic-detail models of an essential pathway, this structure opens new avenues for the rational design of alternative anti-tubercular compounds.

  8. A novel neuropeptide Y neuronal pathway linking energy state and reproductive behavior.

    Science.gov (United States)

    Muroi, Yoshikage; Ishii, Toshiaki

    2016-10-01

    Animals consume energy for reproduction, as well as survival. Excess or insufficient energy investment into reproduction, respectively, threatens the survival of parents or leads to the failure of reproduction. Management of energy consumption in reproduction is important, not only for the success of the process, but also for the survival of the parents. Reproductive behaviors, such as mating and parental behavior, are indispensable for achieving each event of reproduction including gametogamy, parturition, and lactation. Therefore, reproductive behavior is one of the important factors in managing energy consumption for reproduction. Orexigenic and anorexigenic molecules in the hypothalamus have been implicated in the regulation of reproductive functions. An orexigenic neuropeptide, neuropeptide Y (NPY), has been also implicated in the regulation of both reproduction and energy state of animals. In this review, we will first summarize the neuronal mechanism for regulating reproductive functions by orexigenic and anorexigenic molecules in the hypothalamus. Second, we will focus on the NPY neuronal pathways regulating reproductive behavior in the intra- and extra-hypothalamic brain areas. We will highlight the NPY neuronal pathway from the arcuate nucleus to the dorsal raphe nucleus as a novel extra-hypothalamic pathway for energy state-dependent regulation of reproductive behavior. Finally, we will propose a biological significance of the extra-hypothalamic NPY neuronal pathway, which plays an important role in the associative control of feeding and reproductive behaviors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Developmental Pathways Linking Externalizing Symptoms, Internalizing Symptoms, and Academic Competence to Adolescent Substance Use

    Science.gov (United States)

    Englund, Michelle M.; Siebenbruner, Jessica

    2012-01-01

    This study extends previous research investigating the developmental pathways predicting adolescent alcohol and marijuana use by examining the cascading effects of externalizing and internalizing symptoms and academic competence in the prediction of use and level of use of these substances in adolescence. Participants (N = 191) were drawn from a…

  10. Rare genomic variants link bipolar disorder to CREB regulated intracellular signaling pathways

    Directory of Open Access Journals (Sweden)

    Berit eKerner

    2013-11-01

    Full Text Available Bipolar disorder is a common, complex, and severe psychiatric disorder with cyclical disturbances of mood and a high suicide rate. Here, we describe a family with four siblings, three affected females and one unaffected male. The disease course was characterized by early-onset bipolar disorder and co-morbid anxiety spectrum disorders that followed the onset of bipolar disorder. Genetic risk factors were suggested by the early onset of the disease, the severe disease course, including multiple suicide attempts, and lack of adverse prenatal or early life events. In particular, drug and alcohol abuse did not contribute to the disease onset. Exome sequencing identified very rare, heterozygous, and likely protein-damaging variants in eight brain-expressed genes: IQUB, JMJD1C, GADD45A, GOLGB1, PLSCR5, VRK2, MESDC2, and FGGY. The variants were shared among all three affected family members but absent in the unaffected sibling and in more than 200 controls. The genes encode proteins with significant regulatory roles in the ERK/MAPK and CREB-regulated intracellular signaling pathways. These pathways are central to neuronal and synaptic plasticity, cognition, affect regulation and response to chronic stress. In addition, proteins in these pathways are the target of commonly used mood stabilizing drugs, such as tricyclic antidepressants, lithium and valproic acid. The combination of multiple rare, damaging mutations in these central pathways could lead to reduced resilience and increased vulnerability to stressful life events. Our results support a new model for psychiatric disorders, in which multiple rare, damaging mutations in genes functionally related to a common signaling pathway contribute to the manifestation of bipolar disorder.

  11. Xlink Analyzer: software for analysis and visualization of cross-linking data in the context of three-dimensional structures.

    Science.gov (United States)

    Kosinski, Jan; von Appen, Alexander; Ori, Alessandro; Karius, Kai; Müller, Christoph W; Beck, Martin

    2015-03-01

    Structural characterization of large multi-subunit protein complexes often requires integrating various experimental techniques. Cross-linking mass spectrometry (XL-MS) identifies proximal protein residues and thus is increasingly used to map protein interactions and determine the relative orientation of subunits within the structure of protein complexes. To fully adapt XL-MS as a structure characterization technique, we developed Xlink Analyzer, a software tool for visualization and analysis of XL-MS data in the context of the three-dimensional structures. Xlink Analyzer enables automatic visualization of cross-links, identifies cross-links violating spatial restraints, calculates violation statistics, maps chemically modified surfaces, and allows interactive manipulations that facilitate analysis of XL-MS data and aid designing new experiments. We demonstrate these features by mapping interaction sites within RNA polymerase I and the Rvb1/2 complex. Xlink Analyzer is implemented as a plugin to UCSF Chimera, a standard structural biology software tool, and thus enables seamless integration of XL-MS data with, e.g. fitting of X-ray structures to EM maps. Xlink Analyzer is available for download at http://www.beck.embl.de/XlinkAnalyzer.html. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Linking Automated Data Analysis and Visualization with Applications in Developmental Biology and High-Energy Physics

    Energy Technology Data Exchange (ETDEWEB)

    Ruebel, Oliver [Technical Univ. of Darmstadt (Germany)

    2009-11-20

    Knowledge discovery from large and complex collections of today's scientific datasets is a challenging task. With the ability to measure and simulate more processes at increasingly finer spatial and temporal scales, the increasing number of data dimensions and data objects is presenting tremendous challenges for data analysis and effective data exploration methods and tools. Researchers are overwhelmed with data and standard tools are often insufficient to enable effective data analysis and knowledge discovery. The main objective of this thesis is to provide important new capabilities to accelerate scientific knowledge discovery form large, complex, and multivariate scientific data. The research covered in this thesis addresses these scientific challenges using a combination of scientific visualization, information visualization, automated data analysis, and other enabling technologies, such as efficient data management. The effectiveness of the proposed analysis methods is demonstrated via applications in two distinct scientific research fields, namely developmental biology and high-energy physics.Advances in microscopy, image analysis, and embryo registration enable for the first time measurement of gene expression at cellular resolution for entire organisms. Analysis of high-dimensional spatial gene expression datasets is a challenging task. By integrating data clustering and visualization, analysis of complex, time-varying, spatial gene expression patterns and their formation becomes possible. The analysis framework MATLAB and the visualization have been integrated, making advanced analysis tools accessible to biologist and enabling bioinformatic researchers to directly integrate their analysis with the visualization. Laser wakefield particle accelerators (LWFAs) promise to be a new compact source of high-energy particles and radiation, with wide applications ranging from medicine to physics. To gain insight into the complex physical processes of particle

  13. Pathway Linking Patient-Centered Communication to Emotional Well-Being: Taking into Account Patient Satisfaction and Emotion Management.

    Science.gov (United States)

    Jiang, Shaohai

    2017-03-01

    In the United States, levels of emotional well-being remain low, with 40% of American adults reporting the experience of daily stress and excessive anxiety. The doctor-patient communication during medical encounters may play a significant role in improving people's emotional well-being. Based on Street and his colleagues' (2009) pathway mediation model linking communication to health outcomes, this paper illustrates a mechanism that underlies how patient-centered communication improves emotional well-being. The results showed that patient-centered communication had direct effects on emotional well-being. In addition to the direct effects, patient-centered communication also indirectly influenced emotional well-being, mediated by patient satisfaction and emotion management, supporting the partial mediation. The findings provide additional empirical evidence to the pathways from communication to health outcomes, one of the least developed areas of communication research, and also offer significant implications for the design of interventions to improve patients' emotional well-being.

  14. Hand Position Alters Vision by Biasing Processing through Different Visual Pathways

    Science.gov (United States)

    Gozli, Davood G.; West, Greg L.; Pratt, Jay

    2012-01-01

    The present study investigated the mechanisms responsible for the difference between visual processing of stimuli near and far from the observer's hands. The idea that objects near the hands are immediate candidates for action led us to hypothesize that vision near the hands would be biased toward the action-oriented magnocellular visual pathway…

  15. Population activity in the human dorsal pathway predicts the accuracy of visual motion detection.

    NARCIS (Netherlands)

    Donner, T.H.; Siegel, M.; Oostenveld, R.; Fries, P.; Bauer, M.; Engel, A.K.

    2007-01-01

    A person's ability to detect a weak visual target stimulus varies from one viewing to the next. We tested whether the trial-to-trial fluctuations of neural population activity in the human brain are related to the fluctuations of behavioral performance in a "yes-no" visual motion-detection task. We

  16. Treatment of one case of cerebral palsy combined with posterior visual pathway injury using autologous bone marrow mesenchymal stem cells.

    Science.gov (United States)

    Li, Min; Yu, Aixue; Zhang, Fangfang; Dai, Guanghui; Cheng, Hongbin; Wang, Xiaodong; An, Yihua

    2012-05-18

    Cerebral palsy is currently one of the major diseases that cause severe paralysis of the nervous system in children; approximately 9-30% of cerebral palsy patients are also visually impaired, for which no effective treatment is available. Bone marrow mesenchymal stem cells (BMSCs) have very strong self-renewal, proliferation, and pluripotent differentiation potentials. Therefore, autologous BMSC transplantation has become a novel method for treating cerebral palsy. An 11-year-old boy had a clear history of dystocia and asphyxia after birth; at the age of 6 months, the family members observed that his gaze roamed and noted that he displayed a lack of attention. A brain MRI examination at the age of 7 years showed that the child had cerebral palsy with visual impairment (i.e., posterior visual pathway injury). The patient was hospitalized for 20 days and was given four infusions of intravenous autologous BMSCs. Before transplantation and 1, 6, and 12 months after transplantation, a visual evoked potential test, an electrocardiogram, routine blood tests, and liver and kidney function tests were performed. The patient did not have any adverse reactions during hospitalization or postoperative follow-up. After discharge, the patient could walk more smoothly than he could before transplantation; furthermore, his vision significantly improved 6 months after transplantation, which was also supported by the electrophysiological examinations. The clinical application of BMSCs is effective for improving vision in a patient with cerebral palsy combined with visual impairment.

  17. Treatment of one case of cerebral palsy combined with posterior visual pathway injury using autologous bone marrow mesenchymal stem cells

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    Li Min

    2012-05-01

    Full Text Available Abstract Background Cerebral palsy is currently one of the major diseases that cause severe paralysis of the nervous system in children; approximately 9–30% of cerebral palsy patients are also visually impaired, for which no effective treatment is available. Bone marrow mesenchymal stem cells (BMSCs have very strong self-renewal, proliferation, and pluripotent differentiation potentials. Therefore, autologous BMSC transplantation has become a novel method for treating cerebral palsy. Methods An 11-year-old boy had a clear history of dystocia and asphyxia after birth; at the age of 6 months, the family members observed that his gaze roamed and noted that he displayed a lack of attention. A brain MRI examination at the age of 7 years showed that the child had cerebral palsy with visual impairment (i.e., posterior visual pathway injury. The patient was hospitalized for 20 days and was given four infusions of intravenous autologous BMSCs. Before transplantation and 1, 6, and 12 months after transplantation, a visual evoked potential test, an electrocardiogram, routine blood tests, and liver and kidney function tests were performed. Results The patient did not have any adverse reactions during hospitalization or postoperative follow-up. After discharge, the patient could walk more smoothly than he could before transplantation; furthermore, his vision significantly improved 6 months after transplantation, which was also supported by the electrophysiological examinations. Conclusions The clinical application of BMSCs is effective for improving vision in a patient with cerebral palsy combined with visual impairment.

  18. Linking Material Flow Analysis with Resilience Using Rice: A Case Study in Global, Visual MFA of a Key Food Product

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    Michal Monit

    2016-01-01

    Full Text Available This article uses the rice price crisis of 2007–2008 to show how material flow analysis (MFA can be combined with resilience research. After presentation of fundamental information and methods, resilience-related concepts are illustrated using graphical methods and MFA data. Herfindahl-Hirschman Index (HHI and node-link diagrams are used to highlight potential vulnerability hotspots and show response to, recovery from disturbance and adaptation following a disruption of the global rice market. The methods presented are especially useful in rapid screening for potential impact of supply-side disruptions, such as export restrictions or poor harvests. The article concludes by discussing other potential applications of the chosen approach and stressing the importance of visual communication in dissemination of results and cross-pollination between disciplines. All the data used in this study is available online, as interactive visualizations, at: http://ricestudyvis.weebly.com.

  19. Generate networks with power-law and exponential-law distributed degrees: with applications in link prediction of tumor pathways

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    WenJun Zhang

    2016-03-01

    Full Text Available In present study I proposed a method for generating biological networks based on power-law (p(x=x^(-a and exponential-law (p(x=e^(-ax distribution functions. Given the parameter of power-law or exponential-law distribution function, a, the algorithm generates an expected frequency distribution according to the given parameter, thereafter creates an adjacency matrix in which (practical frequency distribution of node degrees matches the expected frequency distribution. The results showed that power-law distribution function performs much better than exponential-law distribution function in generating networks. Using the revised algorithm, tumor related networks (pathways are simulated and predicted. The results prove that the algorithm is overall effective in predicting network links (14.6%-21.2%of correctly predicted links against 0.1%-3.4% of that for random assignments. Matlab codes of the algorithms are given also.

  20. Dynamic crossmodal links revealed by steady-state responses in auditory-visual divided attention

    NARCIS (Netherlands)

    de Jong, Ritske; Toffanin, Paolo; Harbers, Marten; Martens, Sander

    Frequency tagging has been often used to study intramodal attention but not intermodal attention. We used EEG and simultaneous frequency tagging of auditory and visual sources to study intermodal focused and divided attention in detection and discrimination performance. Divided-attention costs were

  1. Autism and the Artistic Imagination: The Link between Visual Thinking and Intelligence

    Science.gov (United States)

    Berube, Clair T.

    2007-01-01

    The author employs Howard Gardner's Theory of Multiple Intelligences to frame a discussion about the abilities of children on the Autism spectrum. Since children possess special gifts in visual/spatial areas, an argument is made to support this ability instead of "correcting" it into a more "normal" range. References from Dr. Temple Grandin's life…

  2. An editor for pathway drawing and data visualization in the Biopathways Workbench.

    Science.gov (United States)

    Byrnes, Robert W; Cotter, Dawn; Maer, Andreia; Li, Joshua; Nadeau, David; Subramaniam, Shankar

    2009-10-02

    Pathway models serve as the basis for much of systems biology. They are often built using programs designed for the purpose. Constructing new models generally requires simultaneous access to experimental data of diverse types, to databases of well-characterized biological compounds and molecular intermediates, and to reference model pathways. However, few if any software applications provide all such capabilities within a single user interface. The Pathway Editor is a program written in the Java programming language that allows de-novo pathway creation and downloading of LIPID MAPS (Lipid Metabolites and Pathways Strategy) and KEGG lipid metabolic pathways, and of measured time-dependent changes to lipid components of metabolism. Accessed through Java Web Start, the program downloads pathways from the LIPID MAPS Pathway database (Pathway) as well as from the LIPID MAPS web server http://www.lipidmaps.org. Data arises from metabolomic (lipidomic), microarray, and protein array experiments performed by the LIPID MAPS consortium of laboratories and is arranged by experiment. Facility is provided to create, connect, and annotate nodes and processes on a drawing panel with reference to database objects and time course data. Node and interaction layout as well as data display may be configured in pathway diagrams as desired. Users may extend diagrams, and may also read and write data and non-lipidomic KEGG pathways to and from files. Pathway diagrams in XML format, containing database identifiers referencing specific compounds and experiments, can be saved to a local file for subsequent use. The program is built upon a library of classes, referred to as the Biopathways Workbench, that convert between different file formats and database objects. An example of this feature is provided in the form of read/construct/write access to models in SBML (Systems Biology Markup Language) contained in the local file system. Inclusion of access to multiple experimental data types and

  3. An editor for pathway drawing and data visualization in the Biopathways Workbench

    Directory of Open Access Journals (Sweden)

    Li Joshua

    2009-10-01

    Full Text Available Abstract Background Pathway models serve as the basis for much of systems biology. They are often built using programs designed for the purpose. Constructing new models generally requires simultaneous access to experimental data of diverse types, to databases of well-characterized biological compounds and molecular intermediates, and to reference model pathways. However, few if any software applications provide all such capabilities within a single user interface. Results The Pathway Editor is a program written in the Java programming language that allows de-novo pathway creation and downloading of LIPID MAPS (Lipid Metabolites and Pathways Strategy and KEGG lipid metabolic pathways, and of measured time-dependent changes to lipid components of metabolism. Accessed through Java Web Start, the program downloads pathways from the LIPID MAPS Pathway database (Pathway as well as from the LIPID MAPS web server http://www.lipidmaps.org. Data arises from metabolomic (lipidomic, microarray, and protein array experiments performed by the LIPID MAPS consortium of laboratories and is arranged by experiment. Facility is provided to create, connect, and annotate nodes and processes on a drawing panel with reference to database objects and time course data. Node and interaction layout as well as data display may be configured in pathway diagrams as desired. Users may extend diagrams, and may also read and write data and non-lipidomic KEGG pathways to and from files. Pathway diagrams in XML format, containing database identifiers referencing specific compounds and experiments, can be saved to a local file for subsequent use. The program is built upon a library of classes, referred to as the Biopathways Workbench, that convert between different file formats and database objects. An example of this feature is provided in the form of read/construct/write access to models in SBML (Systems Biology Markup Language contained in the local file system. Conclusion

  4. Linking social change and developmental change: shifting pathways of human development.

    Science.gov (United States)

    Greenfield, Patricia M

    2009-03-01

    P. M. Greenfield's new theory of social change and human development aims to show how changing sociodemographic ecologies alter cultural values and learning environments and thereby shift developmental pathways. Worldwide sociodemographic trends include movement from rural residence, informal education at home, subsistence economy, and low-technology environments to urban residence, formal schooling, commerce, and high-technology environments. The former ecology is summarized by the German term Gemeinschaft ("community") and the latter by the German term Gesellschaft ("society"; Tönnies, 1887/1957). A review of empirical research demonstrates that, through adaptive processes, movement of any ecological variable in a Gesellschaft direction shifts cultural values in an individualistic direction and developmental pathways toward more independent social behavior and more abstract cognition--to give a few examples of the myriad behaviors that respond to these sociodemographic changes. In contrast, the (much less frequent) movement of any ecological variable in a Gemeinschaft direction is predicted to move cultural values and developmental pathways in the opposite direction. In conclusion, sociocultural environments are not static either in the developed or the developing world and therefore must be treated dynamically in developmental research.

  5. Source Water Flow Pathways In Forested, Mountain, Headwater Streams: A Link Between Sediment Movement Patterns And Stream Water Chemistry.

    Science.gov (United States)

    Martin, S.; Conklin, M. H.; Liu, F.

    2015-12-01

    Three years of continuous and discrete sediment and water quality data, from four forested, mountain, headwater catchments in the Sierra Nevada, is used to identify water sources, determine the importance of sub-surface flow pathways, detect any changes in source waters due to seasonal variation or drought, and link flow pathways with observed patterns of in-channel sediment movement within the study watersheds. Patterns in stream chemistry and turbidity point to infiltration as the dominant flow pathway within these catchments. Data support a flow pathway conceptual model in which precipitation water infiltrates into the shallow or deeper subsurface, increasing the hydraulic head of the water table and pushing pre-event water into the stream ahead of event water. Study catchments contain perennial streams and are characterized by a Mediterranean climate with a distinct wet and dry season. Sites are located in the rain-snow transition zone with snow making up 40 to 60 percent of average annual precipitation. Barring human disturbances such as logging/grazing (compaction) or fire (hydrophobicity), catchment soils have high infiltration capacities. Springs and seeps maintain baseflow during the summer low-flow season, and shifting chemical signals within the streams indicate the increased importance of sub-surface water sources during drought years. End-member mixing analysis was conducted to identify possible water end members. Turbidity hysteresis patterns described by previous studies show in-channel sources are dominant for discharge events year round, and there is no difference in fine sediment delivery to streams with or without a soil protecting layer of snow on the land surface. The dominance of sub-surface water sources and evidence for infiltration flow fits with turbidity data, as little material is reaching the stream due to erosive overland flow. An understanding of flow pathways provides a foundation for sustainable land use management in forested

  6. Selective optical control of synaptic transmission in the subcortical visual pathway by activation of viral vector-expressed halorhodopsin.

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    Katsuyuki Kaneda

    Full Text Available The superficial layer of the superior colliculus (sSC receives visual inputs via two different pathways: from the retina and the primary visual cortex. However, the functional significance of each input for the operation of the sSC circuit remains to be identified. As a first step toward understanding the functional role of each of these inputs, we developed an optogenetic method to specifically suppress the synaptic transmission in the retino-tectal pathway. We introduced enhanced halorhodopsin (eNpHR, a yellow light-sensitive, membrane-targeting chloride pump, into mouse retinal ganglion cells (RGCs by intravitreously injecting an adeno-associated virus serotype-2 vector carrying the CMV-eNpHR-EYFP construct. Several weeks after the injection, whole-cell recordings made from sSC neurons in slice preparations revealed that yellow laser illumination of the eNpHR-expressing retino-tectal axons, putatively synapsing onto the recorded cells, effectively inhibited EPSCs evoked by electrical stimulation of the optic nerve layer. We also showed that sSC spike activities elicited by visual stimulation were significantly reduced by laser illumination of the sSC in anesthetized mice. These results indicate that photo-activation of eNpHR expressed in RGC axons enables selective blockade of retino-tectal synaptic transmission. The method established here can most likely be applied to a variety of brain regions for studying the function of individual inputs to these regions.

  7. Conceptual disorganization weakens links in cognitive pathways: Disentangling neurocognition, social cognition, and metacognition in schizophrenia.

    Science.gov (United States)

    Minor, Kyle S; Marggraf, Matthew P; Davis, Beshaun J; Luther, Lauren; Vohs, Jenifer L; Buck, Kelly D; Lysaker, Paul H

    2015-12-01

    Disentangling links between neurocognition, social cognition, and metacognition offers the potential to improve interventions for these cognitive processes. Disorganized symptoms have shown promise for explaining the limiting relationship that neurocognition holds with both social cognition and metacognition. In this study, primary aims included: 1) testing whether conceptual disorganization, a specific disorganized symptom, moderated relationships between cognitive processes, and 2) examining the level of conceptual disorganization necessary for links between cognitive processes to break down. To accomplish these aims, comprehensive assessments of conceptual disorganization, neurocognition, social cognition, and metacognition were administered to 67 people with schizophrenia-spectrum disorders. We found that conceptual disorganization significantly moderated the relationship between neurocognition and metacognition, with links between cognitive processes weakening when conceptual disorganization is present even at minimal levels of severity. There was no evidence that conceptual disorganization-or any other specific disorganized symptom-drove the limiting relationship of neurocognition on social cognition. Based on our findings, conceptual disorganization appears to be a critical piece of the puzzle when disentangling the relationship between neurocognition and metacognition. Roles of specific disorganized symptoms in the neurocognition - social cognition relationship were less clear. Findings from this study suggest that disorganized symptoms are an important treatment consideration when aiming to improve cognitive impairments. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. An EcologicalVisual Exploration Tool to Support the Analysis of Visual Processing Pathways in Children with Autism Spectrum Disorders

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    Dario Cazzato

    2017-12-01

    Full Text Available Recent improvements in the field of assistive technologies have led to innovative solutions aiming at increasing the capabilities of people with disability, helping them in daily activities with applications that span from cognitive impairments to developmental disabilities. In particular, in the case of Autism Spectrum Disorder (ASD, the need to obtain active feedback in order to extract subsequently meaningful data becomes of fundamental importance. In this work, a study about the possibility of understanding the visual exploration in children with ASD is presented. In order to obtain an automatic evaluation, an algorithm for free (i.e., without constraints, nor using additional hardware, infrared (IR light sources or other intrusive methods gaze estimation is employed. Furthermore, no initial calibration is required. It allows the user to freely rotate the head in the field of view of the sensor, and it is insensitive to the presence of eyeglasses, hats or particular hairstyles. These relaxations of the constraints make this technique particularly suitable to be used in the critical context of autism, where the child is certainly not inclined to employ invasive devices, nor to collaborate during calibration procedures.The evaluation of children’s gaze trajectories through the proposed solution is presented for the purpose of an Early Start Denver Model (ESDM program built on the child’s spontaneous interests and game choice delivered in a natural setting.

  9. Aesthetics by numbers:Links between perceived texture qualities and computed visual texture properties

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    Richard Henrikus Augustinus Hubertus Jacobs

    2016-07-01

    Full Text Available Our world is filled with texture. For the human visual system, this is an important source of information for assessing environmental and material properties. Indeed – and presumably for this reason– the human visual system has regions dedicated to processing textures. Despite their abundance and apparent relevance, only recently the relationships between texture features and high-level judgments have captured the interest of mainstream science, despite long-standing indications for such relationships. In this study, we explore such relationships, as these might be used to predict perceived texture qualities. This is relevant, not only from a psychological/neuroscience perspective, but also for more applied fields such as design, architecture, and the visual arts. In two separate experiments, observers judged various qualities of visual textures such as beauty, roughness, naturalness, elegance, and complexity. Based on factor analysis, we find that in both experiments, ~75% of the variability in the judgments could be explained by a two-dimensional space, with axes that are closely aligned to the beauty and roughness judgments. That a two-dimensional judgment space suffices to capture most of the variability in the perceived texture qualities suggests that observers use a relatively limited set of internal scales on which to base various judgments, including aesthetic ones.Finally, for both of these judgments, we determined the relationship with a large number of texture features computed for each of the texture stimuli. We find that the presence of lower spatial frequencies, oblique orientations, higher intensity variation, higher saturation, and redness correlates with higher beauty ratings. Features that captured image intensity and uniformity correlated with roughness ratings. Therefore, a number of computational texture features are predictive of these judgments. This suggests that perceived texture qualities – including the aesthetic

  10. The Fanconi anemia pathway: Repairing the link between DNA damage and squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Romick-Rosendale, Lindsey E. [Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children' s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229 (United States); Lui, Vivian W.Y.; Grandis, Jennifer R. [Department of Otolaryngology, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Wells, Susanne I., E-mail: Susanne.Wells@cchmc.org [Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children' s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229 (United States)

    2013-03-15

    Fanconi anemia (FA) is a rare inherited recessive disease caused by mutations in one of fifteen genes known to encode FA pathway components. In response to DNA damage, nuclear FA proteins associate into high molecular weight complexes through a cascade of post-translational modifications and physical interactions, followed by the repair of damaged DNA. Hematopoietic cells are particularly sensitive to the loss of these interactions, and bone marrow failure occurs almost universally in FA patients. FA as a disease is further characterized by cancer susceptibility, which highlights the importance of the FA pathway in tumor suppression, and will be the focus of this review. Acute myeloid leukemia is the most common cancer type, often subsequent to bone marrow failure. However, FA patients are also at an extreme risk of squamous cell carcinoma (SCC) of the head and neck and gynecological tract, with an even greater incidence in those individuals who have received a bone marrow transplant and recovered from hematopoietic disease. FA tumor suppression in hematopoietic versus epithelial compartments could be mechanistically similar or distinct. Definition of compartment specific FA activities is now critical to assess the effects of today's bone marrow failure treatments on tomorrow's solid tumor development. It is our hope that current therapies can then be optimized to decrease the risk of malignant transformation in both hematopoietic and epithelial cells. Here we review our current understanding of the mechanisms of action of the Fanconi anemia pathway as it contributes to stress responses, DNA repair and squamous cell carcinoma susceptibility.

  11. Potential biological pathways linking Type-D personality and poor health: A cross-sectional investigation.

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    Vera K Jandackova

    Full Text Available Type-D personality, defined as a combination of high negative affect and high social isolation, has been associated with poor health outcomes. However, pathways underlying this association are largely unknown. We investigated the relationship between Type-D personality and several biological and behavioral pathways including the autonomic nervous system, the immune system, glucose regulation and sleep in a large, apparently healthy sample.Data from a total of 646 respondents (age 41.6±11.5, 12,2% women were available for analysis. Persons with Type-D (negative affect and social isolation score ≥10 were contrasted with those without Type-D. Measures of plasma fibrinogen levels, white blood cell count, high sensitivity C-reactive protein, fasting plasma glucose (FPG, cholesterol, high-density and low-density lipoprotein, glycated hemoglobin (HbA1c, creatinine, triglycerides, and albumin were derived from fasting blood samples. Urine norepinephrine and free cortisol were determined by high-performance liquid chromatography. Time-domain heart rate variability (HRV measures were calculated for the 24hr recording period and for nighttime separately.Persons with Type-D had higher HbA1c, FPG, and fibrinogen, and lower nighttime HRV than those without Type-D, suggesting worse glycemic control, systemic inflammation and poorer autonomic nervous system modulation in Type-D persons. In addition, those with Type-D reported less social support and greater sleep difficulties while no group differences were observed for alcohol and cigarette consumption, physical activity and body mass index.Findings provide some of the first evidence for multiple possible biological and behavioral pathways between Type-D personality and increased morbidity and mortality.

  12. Parallel pathways from whisker and visual sensory cortices to distinct frontal regions of mouse neocortex.

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    Sreenivasan, Varun; Kyriakatos, Alexandros; Mateo, Celine; Jaeger, Dieter; Petersen, Carl C H

    2017-07-01

    The spatial organization of mouse frontal cortex is poorly understood. Here, we used voltage-sensitive dye to image electrical activity in the dorsal cortex of awake head-restrained mice. Whisker-deflection evoked the earliest sensory response in a localized region of primary somatosensory cortex and visual stimulation evoked the earliest responses in a localized region of primary visual cortex. Over the next milliseconds, the initial sensory response spread within the respective primary sensory cortex and into the surrounding higher order sensory cortices. In addition, secondary hotspots in the frontal cortex were evoked by whisker and visual stimulation, with the frontal hotspot for whisker deflection being more anterior and lateral compared to the frontal hotspot evoked by visual stimulation. Investigating axonal projections, we found that the somatosensory whisker cortex and the visual cortex directly innervated frontal cortex, with visual cortex axons innervating a region medial and posterior to the innervation from somatosensory cortex, consistent with the location of sensory responses in frontal cortex. In turn, the axonal outputs of these two frontal cortical areas innervate distinct regions of striatum, superior colliculus, and brainstem. Sensory input, therefore, appears to map onto modality-specific regions of frontal cortex, perhaps participating in distinct sensorimotor transformations, and directing distinct motor outputs.

  13. Insulin/glucose induces natriuretic peptide clearance receptor in human adipocytes: a metabolic link with the cardiac natriuretic pathway.

    Science.gov (United States)

    Bordicchia, M; Ceresiani, M; Pavani, M; Minardi, D; Polito, M; Wabitsch, M; Cannone, V; Burnett, J C; Dessì-Fulgheri, P; Sarzani, R

    2016-07-01

    Cardiac natriuretic peptides (NP) are involved in cardiorenal regulation and in lipolysis. The NP activity is largely dependent on the ratio between the signaling receptor NPRA and the clearance receptor NPRC. Lipolysis increases when NPRC is reduced by starving or very-low-calorie diet. On the contrary, insulin is an antilipolytic hormone that increases sodium retention, suggesting a possible functional link with NP. We examined the insulin-mediated regulation of NP receptors in differentiated human adipocytes and tested the association of NP receptor expression in visceral adipose tissue (VAT) with metabolic profiles of patients undergoing renal surgery. Differentiated human adipocytes from VAT and Simpson-Golabi-Behmel Syndrome (SGBS) adipocyte cell line were treated with insulin in the presence of high-glucose or low-glucose media to study NP receptors and insulin/glucose-regulated pathways. Fasting blood samples and VAT samples were taken from patients on the day of renal surgery. We observed a potent insulin-mediated and glucose-dependent upregulation of NPRC, through the phosphatidylinositol 3-kinase pathway, associated with lower lipolysis in differentiated adipocytes. No effect was observed on NPRA. Low-glucose medium, used to simulate in vivo starving conditions, hampered the insulin effect on NPRC through modulation of insulin/glucose-regulated pathways, allowing atrial natriuretic peptide to induce lipolysis and thermogenic genes. An expression ratio in favor of NPRC in adipose tissue was associated with higher fasting insulinemia, HOMA-IR, and atherogenic lipid levels. Insulin/glucose-dependent NPRC induction in adipocytes might be a key factor linking hyperinsulinemia, metabolic syndrome, and higher blood pressure by reducing NP effects on adipocytes. Copyright © 2016 the American Physiological Society.

  14. The aspartate-family pathway of plants: linking production of essential amino acids with energy and stress regulation.

    Science.gov (United States)

    Galili, Gad

    2011-02-01

    The Asp family pathway of plants is highly important from a nutritional standpoint because it leads to the synthesis of the four essential amino acids Lys, Thr, Met and Ile. These amino acids are not synthesized by human and its monogastric livestock and should be supplemented in their diets. Among the Asp-family amino acids, Lys is considered as the nutritionally most important essential amino acid because its level is most limiting in cereal grains, representing the largest source of plant foods and feeds worldwide. Metabolic engineering approaches led to significant increase in Lys level in seeds by enhancing its synthesis and reducing its catabolism. However, results from the model plant Arabidopsis showed that this approach may retard seed germination due to a major negative effect on the levels of a number of TCA cycle metabolites that associate with cellular energy. In the present review, we discuss the regulatory metabolic link of the Asp-family pathway with the TCA cycle and its biological significance upon exposure to stress conditions that cause energy deprivation. In addition, we also discuss how deep understanding of the regulatory metabolic link of the Asp-family pathway with energy and stress regulation can be used to improve Lys level in seeds of important crop species, minimizing the interference with the cellular energy status and plant-stress interaction. This review thus provides an example showing how deep understanding the inter-regulation of metabolism with plant stress physiology can lead to successful nutritional improvements with minimal negative effect on plant growth and response to stressful environments.

  15. Saccharomyces cerevisiae KTR4, KTR5 and KTR7 encode mannosyltransferases differentially involved in the N- and O-linked glycosylation pathways.

    Science.gov (United States)

    Hernández, Nahúm V; López-Ramírez, Luz A; Díaz-Jiménez, Diana F; Mellado-Mojica, Erika; Martínez-Duncker, Iván; López, Mercedes G; Mora-Montes, Héctor M

    2017-10-01

    Saccharomyces cerevisiae is a model to understand basic aspects of protein glycosylation pathways. Although these metabolic routes have been thoroughly studied, there are still knowledge gaps; among them, the role of the MNT1/KRE2 gene family. This family is composed of nine members, with only six functionally characterized. The enzymes Ktr1, Ktr3, and Mnt1/Kre2 have overlapping activities in both O-linked and N-linked glycan synthesis; while Ktr2 and Yur1 participate exclusively in the elongation of the N-linked glycan outer chain. KTR6 encodes for a phosphomannosyltransferase that synthesizes the cell wall phosphomannan. Here, we aimed to establish the functional role of KTR4, KTR5 and KTR7 in the protein glycosylation pathways, by using heterologous complementation in Candida albicans null mutants lacking members of the MNT1/KRE2 gene family. The three S. cerevisiae genes restored defects in the C. albicans N-linked glycosylation pathway. KTR5 and KTR7 partially complemented a C. albicans null mutant with defects in the synthesis of O-linked glycans, and only KTR4 fully elongated the O-linked glycans like wild-type cells. Therefore, our results suggest that the three genes have a redundant activity in the S. cerevisiae N-linked glycosylation pathway, but KTR4 plays a major role in O-linked glycan synthesis. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  16. Color vision versus pattern visual evoked potentials in the assessment of subclinical optic pathway involvement in multiple sclerosis

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    Fatih C Gundogan

    2013-01-01

    Full Text Available Background: Optic pathway involvement in multiple sclerosis is frequently the initial sign in the disease process. In most clinical applications, pattern visual evoked potential (PVEP is used in the assessment of optic pathway involvement. Objective: To question the value of PVEP against color vision assessment in the diagnosis of subclinical optic pathway involvement. Materials and Methods: This prospective, cross-sectional study included 20 multiple sclerosis patients without a history of optic neuritis, and 20 healthy control subjects. Farnsworth-Munsell (FM 100-Hue testing and PVEPs to 60-min arc and 15-min arc checks by using Roland-Consult RetiScan® system were performed. P 100 amplitude, P 100 latency in PVEP and total error scores (TES in FM 100-Hue test were assessed. Results: Expanded Disability Status Scale score and the time from diagnosis were 2.21 ± 2.53 (ranging from 0 to 7 and 4.1 ± 4.4 years. MS group showed significantly delayed P 100 latency for both checks (P 0.05 for all. 14 MS patients (70% had an increased TESs in FM-100 Hue, 11 (55% MS patients had delayed P 100 latency and 9 (45% had reduced P 100 amplitude. The areas under the ROC curves were 0.944 for FM-100 Hue test, 0.753 for P 100 latency, and 0.173 for P 100 amplitude. Conclusions: Color vision testing seems to be more sensitive than PVEP in detecting subclinical visual pathway involvement in MS.

  17. Psychoneuroimmunology in pregnancy: immune pathways linking stress with maternal health, adverse birth outcomes, and fetal development.

    Science.gov (United States)

    Christian, Lisa M

    2012-01-01

    It is well-established that psychological stress promotes immune dysregulation in nonpregnant humans and animals. Stress promotes inflammation, impairs antibody responses to vaccination, slows wound healing, and suppresses cell-mediated immune function. Importantly, the immune system changes substantially to support healthy pregnancy, with attenuation of inflammatory responses and impairment of cell-mediated immunity. This adaptation is postulated to protect the fetus from rejection by the maternal immune system. Thus, stress-induced immune dysregulation during pregnancy has unique implications for both maternal and fetal health, particularly preterm birth. However, very limited research has examined stress-immune relationships in pregnancy. The application of psychoneuroimmunology research models to the perinatal period holds great promise for elucidating biological pathways by which stress may affect adverse pregnancy outcomes, maternal health, and fetal development. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Linking Cognitive and Visual Perceptual Decline in Healthy Aging: The Information Degradation Hypothesis

    Science.gov (United States)

    Monge, Zachary A.; Madden, David J.

    2016-01-01

    Several hypotheses attempt to explain the relation between cognitive and perceptual decline in aging (e.g., common-cause, sensory deprivation, cognitive load on perception, information degradation). Unfortunately, the majority of past studies examining this association have used correlational analyses, not allowing for these hypotheses to be tested sufficiently. This correlational issue is especially relevant for the information degradation hypothesis, which states that degraded perceptual signal inputs, resulting from either age-related neurobiological processes (e.g., retinal degeneration) or experimental manipulations (e.g., reduced visual contrast), lead to errors in perceptual processing, which in turn may affect non-perceptual, higher-order cognitive processes. Even though the majority of studies examining the relation between age-related cognitive and perceptual decline have been correlational, we reviewed several studies demonstrating that visual manipulations affect both younger and older adults’ cognitive performance, supporting the information degradation hypothesis and contradicting implications of other hypotheses (e.g., common-cause, sensory deprivation, cognitive load on perception). The reviewed evidence indicates the necessity to further examine the information degradation hypothesis in order to identify mechanisms underlying age-related cognitive decline. PMID:27484869

  19. Multimodal neuroimaging evidence linking memory and attention systems during visual search cued by context.

    Science.gov (United States)

    Kasper, Ryan W; Grafton, Scott T; Eckstein, Miguel P; Giesbrecht, Barry

    2015-03-01

    Visual search can be facilitated by the learning of spatial configurations that predict the location of a target among distractors. Neuropsychological and functional magnetic resonance imaging (fMRI) evidence implicates the medial temporal lobe (MTL) memory system in this contextual cueing effect, and electroencephalography (EEG) studies have identified the involvement of visual cortical regions related to attention. This work investigated two questions: (1) how memory and attention systems are related in contextual cueing; and (2) how these systems are involved in both short- and long-term contextual learning. In one session, EEG and fMRI data were acquired simultaneously in a contextual cueing task. In a second session conducted 1 week later, EEG data were recorded in isolation. The fMRI results revealed MTL contextual modulations that were correlated with short- and long-term behavioral context enhancements and attention-related effects measured with EEG. An fMRI-seeded EEG source analysis revealed that the MTL contributed the most variance to the variability in the attention enhancements measured with EEG. These results support the notion that memory and attention systems interact to facilitate search when spatial context is implicitly learned. © 2015 New York Academy of Sciences.

  20. Changing visual perspective changes processing style: A distinct pathway by which imagery guides cognition.

    Science.gov (United States)

    Shaeffer, Eric M; Libby, Lisa K; Eibach, Richard P

    2015-06-01

    Action images can be depicted either from the actor's first-person or an observer's third-person visual perspective. This research demonstrates that visual perspective of action imagery influences the extent to which people process actions abstractly. Two experiments presented photographs of everyday actions, manipulating their visual perspective (first-person vs. third-person), holding constant the scope and objects depicted. Subsequently, participants interpreted actions unrelated to the images. Across both experiments, viewing third-person (vs. first-person) photographs caused participants to construe the unrelated actions more abstractly. This carryover effect demonstrates a shift in processing style, sheds light on an underlying mechanism of perspective effects, and suggests that imagery is a more versatile cognitive tool than traditionally assumed. (c) 2015 APA, all rights reserved).

  1. Membrane-to-nucleus signaling links insulin-like growth factor-1- and stem cell factor-activated pathways.

    Directory of Open Access Journals (Sweden)

    Yujiro Hayashi

    Full Text Available Stem cell factor (mouse: Kitl, human: KITLG and insulin-like growth factor-1 (IGF1, acting via KIT and IGF1 receptor (IGF1R, respectively, are critical for the development and integrity of several tissues. Autocrine/paracrine KITLG-KIT and IGF1-IGF1R signaling are also activated in several cancers including gastrointestinal stromal tumors (GIST, the most common sarcoma. In murine gastric muscles, IGF1 promotes Kitl-dependent development of interstitial cells of Cajal (ICC, the non-neoplastic counterpart of GIST, suggesting cooperation between these pathways. Here, we report a novel mechanism linking IGF1-IGF1R and KITLG-KIT signaling in both normal and neoplastic cells. In murine gastric muscles, the microenvironment for ICC and GIST, human hepatic stellate cells (LX-2, a model for cancer niches, and GIST cells, IGF1 stimulated Kitl/KITLG protein and mRNA expression and promoter activity by activating several signaling pathways including AKT-mediated glycogen synthase kinase-3β inhibition (GSK3i. GSK3i alone also stimulated Kitl/KITLG expression without activating mitogenic pathways. Both IGF1 and GSK3i induced chromatin-level changes favoring transcriptional activation at the Kitl promoter including increased histone H3/H4 acetylation and H3 lysine (K 4 methylation, reduced H3K9 and H3K27 methylation and reduced occupancy by the H3K27 methyltransferase EZH2. By pharmacological or RNA interference-mediated inhibition of chromatin modifiers we demonstrated that these changes have the predicted impact on KITLG expression. KITLG knock-down and immunoneutralization inhibited the proliferation of GIST cells expressing wild-type KIT, signifying oncogenic autocrine/paracrine KITLG-KIT signaling. We conclude that membrane-to-nucleus signaling involving GSK3i establishes a previously unrecognized link between the IGF1-IGF1R and KITLG-KIT pathways, which is active in both physiologic and oncogenic contexts and can be exploited for therapeutic purposes.

  2. Developmental Pathways for Social Understanding: Linking Social Cognition to Social Contexts

    Directory of Open Access Journals (Sweden)

    Kimberly eBrink

    2015-05-01

    Full Text Available Contemporary research, often with looking-time tasks, reveals that infants possess foundational understandings of their social worlds. However, few studies have examined how these early social cognitions relate to the child’s social interactions and behavior in early development. Does an early understanding of the social world relate to how an infant interacts with his or her parents? Do early social interactions along with social-cognitive understandings in infancy predict later preschool social competencies? In the current paper, we propose a theory in which children’s later social behaviors and their understanding of the social world depend on the integration of early social understanding and experiences in infancy. We review several of our studies, as well as other research, that directly examine the pathways between these competencies to support a hypothesized network of relations between social-cognitive development and social-interactive behaviors in the development from infancy to childhood. In total, these findings reveal differences in infant social competences that both track the developmental trajectory of infants’ understanding of people over the first years of life and provide external validation for the large body of social-cognitive findings emerging from laboratory looking-time paradigms.

  3. Dental fluorosis linked to degassing of Ambrym volcano, Vanuatu: a novel exposure pathway.

    Science.gov (United States)

    Allibone, Rachel; Cronin, Shane J; Charley, Douglas T; Neall, Vince E; Stewart, Robert B; Oppenheimer, Clive

    2012-04-01

    Ambrym in Vanuatu is a persistently degassing island volcano whose inhabitants harvest rainwater for their potable water needs. The findings from this study indicate that dental fluorosis is prevalent in the population due to fluoride contamination of rainwater by the volcanic plume. A dental survey was undertaken of 835 children aged 6-18 years using the Dean's Index of Fluorosis. Prevalence of dental fluorosis was found to be 96% in the target area of West Ambrym, 71% in North Ambrym, and 61% in Southeast Ambrym. This spatial distribution appears to reflect the prevailing winds and rainfall patterns on the island. Severe cases were predominantly in West Ambrym, the most arid part of the island, and the most commonly affected by the volcanic plume. Over 50 km downwind, on a portion of Malakula Island, the dental fluorosis prevalence was 85%, with 36% prevalence on Tongoa Island, an area rarely affected by volcanic emissions. Drinking water samples from West Ambrym contained fluoride levels from 0.7 to 9.5 ppm F (average 4.2 ppm F, n = 158) with 99% exceeding the recommended concentration of 1.0 ppm F. The pathway of fluoride-enriched rainwater impacting upon human health as identified in this study has not previously been recognised in the aetiology of fluorosis. This is an important consideration for populations in the vicinity of degassing volcanoes, particularly where rainwater comprises the primary potable water supply for humans or animals.

  4. SINs and SOMs: Neural microcircuits for size tuning in the zebrafish and mouse visual pathway.

    Directory of Open Access Journals (Sweden)

    Alison J. Barker

    2013-05-01

    Full Text Available In many animals, a fast and reliable circuit for discriminating between predator-sized objects and edible (prey-sized objects is necessary for survival. How are receptive fields in visual brain areas organized to extract information about size? Recent studies from the zebrafish optic tectum and the mouse visual cortex suggest de novo shaping of receptive fields by subtypes of inhibitory neurons. Del Bene et al. (2010 describe a population of GABAergic neurons in the zebrafish optic tectum (Superficial Interneurons, SINs that are necessary for size filtering during prey capture. Adesnik et al. (2012 describe a somatostatin-expressing interneuron population (SOMs that confers surround suppression on layer II/III pyramidal cells in mouse V1. Strikingly both the SINs and the SOMs, display size-dependent response properties. Increasing visual stimulus size increases excitatory input to these neurons. Dampening SIN or SOM activity alters tuning of neighboring circuits such that they lose preference for small objects. Both results provide exciting evidence for mechanisms of size filtering in visual circuits. Here we review the roles of the SINs and the SOMs and speculate on the similarity of such spatial filters across species.

  5. A Visual Pathway for Looming-Evoked Escape in Larval Zebrafish.

    Science.gov (United States)

    Temizer, Incinur; Donovan, Joseph C; Baier, Herwig; Semmelhack, Julia L

    2015-07-20

    Avoiding the strike of an approaching predator requires rapid visual detection of a looming object, followed by a directed escape maneuver. While looming-sensitive neurons have been discovered in various animal species, the relative importance of stimulus features that are extracted by the visual system is still unclear. Furthermore, the neural mechanisms that compute object approach are largely unknown. We found that a virtual looming stimulus, i.e., a dark expanding disk on a bright background, reliably evoked rapid escape movements. Related stimuli, such as dimming, receding, or bright looming objects, were substantially less effective, and angular size was a critical determinant of escape initiation. Two-photon calcium imaging in retinal ganglion cell (RGC) axons revealed three retinorecipient areas that responded robustly to looming stimuli. One of these areas, the optic tectum, is innervated by a subset of RGC axons that respond selectively to looming stimuli. Laser-induced lesions of the tectal neuropil impaired the behavior. Our findings demonstrate a visually mediated escape behavior in zebrafish larvae exposed to objects approaching on a collision course. This response is sensitive to spatiotemporal parameters of the looming stimulus. Our data indicate that a subset of RGC axons within the tectum responds selectively to features of looming stimuli and that this input is necessary for visually evoked escape. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. The Role of the Magnocellular Visual Pathway in the Attentional Blink

    Science.gov (United States)

    Stuart, Geoffrey W.; Lambeth, Sandra E.; Day, Ross H.; Gould, Ian C.; Castles, Anne E.

    2012-01-01

    Visual attention has temporal limitations. In the attentional blink (AB) a stream of stimuli such as letters or digits are presented to a participant on a computer monitor at a rapid rate. Embedded in the stream are two targets that the participant must try to identify. Identification of the second target is severely impaired if it is presented…

  7. Genetic enhancement of visual learning by activation of protein kinase C pathways in small groups of rat cortical neurons.

    Science.gov (United States)

    Zhang, Guo-Rong; Wang, Xiaodan; Kong, Lingxin; Lu, Xiu-Gui; Lee, Brian; Liu, Meng; Sun, Mei; Franklin, Corinna; Cook, Robert G; Geller, Alfred I

    2005-09-14

    Although learning and memory theories hypothesize that memories are encoded by specific circuits, it has proven difficult to localize learning within a cortical area. Neural network theories predict that activation of a small fraction of the neurons in a circuit can activate that circuit. Consequently, altering the physiology of a small group of neurons might potentiate a specific circuit and enhance learning, thereby localizing learning to that circuit. In this study, we activated protein kinase C (PKC) pathways in small groups of neurons in rat postrhinal (POR) cortex. We microinjected helper virus-free herpes simplex virus vectors that expressed a constitutively active PKC into POR cortex. This PKC was expressed predominantly in glutamatergic and GABAergic neurons in POR cortex. This intervention increased phosphorylation of five PKC substrates that play critical roles in neurotransmitter release (GAP-43 and dynamin) or glutamatergic neurotransmission (specific subunits of AMPA or NMDA receptors and myristoylated alanine-rich C kinase substrate). Additionally, activation of PKC pathways in cultured cortical neurons supported activation-dependent increases in release of glutamate and GABA. This intervention enhanced the learning rate and accuracy of visual object discriminations. In individual rats, the numbers of transfected neurons positively correlated with this learning. During learning, neuronal activity was increased in neurons proximal to the transfected neurons. These results demonstrate that potentiating small groups of glutamatergic and GABAergic neurons in POR cortex enhances visual object learning. More generally, these results suggest that learning can be mediated by specific cortical circuits.

  8. Apoptotic Pathways Linked to Endocrine System as Potential Therapeutic Targets for Benign Prostatic Hyperplasia.

    Science.gov (United States)

    Minutoli, Letteria; Rinaldi, Mariagrazia; Marini, Herbert; Irrera, Natasha; Crea, Giovanni; Lorenzini, Cesare; Puzzolo, Domenico; Valenti, Andrea; Pisani, Antonina; Adamo, Elena B; Altavilla, Domenica; Squadrito, Francesco; Micali, Antonio

    2016-08-11

    Benign prostatic hyperplasia (BPH) is a chronic condition common in older men that can result in bothersome lower urinary tract symptoms. The molecular mechanisms and networks underlying the development and the progression of the disease are still far from being fully understood. BPH results from smooth muscle cell and epithelial cell proliferation, primarily within the transition zone of the prostate. Apoptosis and inflammation play important roles in the control of cell growth and in the maintenance of tissue homeostasis. Disturbances in molecular mechanisms of apoptosis machinery have been linked to BPH. Increased levels of the glycoprotein Dickkopf-related protein 3 in BPH cause an inhibition of the apoptosis machinery through a reduction in B cell lymphoma (Bcl)-2 associated X protein (Bax) expression. Inhibitors of apoptosis proteins influence cell death by direct inhibition of caspases and modulation of the transcription factor nuclear factor-κB. Current pharmacotherapy targets either the static component of BPH, including finasteride and dutasteride, or the dynamic component of BPH, including α-adrenoceptor antagonists such as tamsulosin and alfuzosin. Both these classes of drugs significantly interfere with the apoptosis machinery. Furthermore, phytotherapic supplements and new drugs may also modulate several molecular steps of apoptosis.

  9. Apoptotic Pathways Linked to Endocrine System as Potential Therapeutic Targets for Benign Prostatic Hyperplasia

    Directory of Open Access Journals (Sweden)

    Letteria Minutoli

    2016-08-01

    Full Text Available Benign prostatic hyperplasia (BPH is a chronic condition common in older men that can result in bothersome lower urinary tract symptoms. The molecular mechanisms and networks underlying the development and the progression of the disease are still far from being fully understood. BPH results from smooth muscle cell and epithelial cell proliferation, primarily within the transition zone of the prostate. Apoptosis and inflammation play important roles in the control of cell growth and in the maintenance of tissue homeostasis. Disturbances in molecular mechanisms of apoptosis machinery have been linked to BPH. Increased levels of the glycoprotein Dickkopf-related protein 3 in BPH cause an inhibition of the apoptosis machinery through a reduction in B cell lymphoma (Bcl-2 associated X protein (Bax expression. Inhibitors of apoptosis proteins influence cell death by direct inhibition of caspases and modulation of the transcription factor nuclear factor-κB. Current pharmacotherapy targets either the static component of BPH, including finasteride and dutasteride, or the dynamic component of BPH, including α-adrenoceptor antagonists such as tamsulosin and alfuzosin. Both these classes of drugs significantly interfere with the apoptosis machinery. Furthermore, phytotherapic supplements and new drugs may also modulate several molecular steps of apoptosis.

  10. FDA Facilitated Regulatory Pathways : Visualizing Their Characteristics, Development, and Authorization Timelines

    NARCIS (Netherlands)

    Liberti, Lawrence; Bujar, Magda; Breckenridge, Alasdair; Hoekman, Jarno; McAuslane, Neil; Stolk, Pieter; Leufkens, Bert

    2017-01-01

    The US Food and Drug Administration (FDA) has four facilitated regulatory pathways (FRPs): Fast Track (FT), Breakthrough Therapy (BTD), Priority Review (PR), and Accelerated Approval (AA). Only PR specifies an expedited review timeline (6 months). We sought to determine to what extent the

  11. The photosensor protein Ppr of Rhodocista centenaria is linked to the chemotaxis signalling pathway

    Directory of Open Access Journals (Sweden)

    Kiefer Dorothee

    2010-11-01

    Full Text Available Abstract Background Rhodocista centenaria is a phototrophic α-proteobacterium exhibiting a phototactic behaviour visible as colony movement on agar plates directed to red light. As many phototrophic purple bacteria R. centenaria possesses a soluble photoactive yellow protein (Pyp. It exists as a long fusion protein, designated Ppr, consisting of three domains, the Pyp domain, a putative bilin binding domain (Bbd and a histidine kinase domain (Pph. The Ppr protein is involved in the regulation of polyketide synthesis but it is still unclear, how this is connected to phototaxis and chemotaxis. Results To elucidate the possible role of Ppr and Pph in the chemotactic network we studied the interaction with chemotactic proteins in vitro as well as in vivo. Matrix-assisted coelution experiments were performed to study the possible communication of the different putative binding partners. The kinase domain of the Ppr protein was found to interact with the chemotactic linker protein CheW. The formation of this complex was clearly ATP-dependent. Further results indicated that the Pph histidine kinase domain and CheW may form a complex with the chemotactic kinase CheAY suggesting a role of Ppr in the chemotaxis signalling pathway. In addition, when Ppr or Pph were expressed in Escherichia coli, the chemotactic response of the cells was dramatically affected. Conclusions The Ppr protein of Rhodocista centenaria directly interacts with the chemotactic protein CheW. This suggests a role of the Ppr protein in the regulation of the chemotactic response in addition to its role in chalcone synthesis.

  12. Streptococcus pyogenes Malate Degradation Pathway Links pH Regulation and Virulence

    Science.gov (United States)

    Paluscio, Elyse

    2015-01-01

    The ability of Streptococcus pyogenes to infect different niches within its human host most likely relies on its ability to utilize alternative carbon sources. In examining this question, we discovered that all sequenced S. pyogenes strains possess the genes for the malic enzyme (ME) pathway, which allows malate to be used as a supplemental carbon source for growth. ME is comprised of four genes in two adjacent operons, with the regulatory two-component MaeKR required for expression of genes encoding a malate permease (maeP) and malic enzyme (maeE). Analysis of transcription indicated that expression of maeP and maeE is induced by both malate and low pH, and induction in response to both cues is dependent on the MaeK sensor kinase. Furthermore, both maePE and maeKR are repressed by glucose, which occurs via a CcpA-independent mechanism. Additionally, malate utilization requires the PTS transporter EI enzyme (PtsI), as a PtsI– mutant fails to express the ME genes and is unable to utilize malate. Virulence of selected ME mutants was assessed in a murine model of soft tissue infection. MaeP–, MaeK–, and MaeR– mutants were attenuated for virulence, whereas a MaeE– mutant showed enhanced virulence compared to that of the wild type. Taken together, these data show that ME contributes to S. pyogenes' carbon source repertory, that malate utilization is a highly regulated process, and that a single regulator controls ME expression in response to diverse signals. Furthermore, malate uptake and utilization contribute to the adaptive pH response, and ME can influence the outcome of infection. PMID:25583521

  13. Developmental pathways linking childhood temperament with antisocial behavior and substance use in adolescence: Explanatory mechanisms in the peer environment.

    Science.gov (United States)

    Buil, J Marieke; van Lier, Pol A C; Brendgen, Mara R; Koot, Hans M; Vitaro, Frank

    2017-06-01

    This study investigated 3 developmental pathways involving the peer environment that may explain how certain temperamental dispositions in childhood may become manifested in later antisocial behavior and substance use. A total of 411 (52% boys) Canadian children were followed annually from ages 6 to 15 years. The study tested whether the temperamental traits approach, negative reactivity and attention (assessed at ages 6-7 years), were associated with overt antisocial behavior, covert antisocial behavior and illicit substance use (assessed at ages 14-15 years), via poor social preference among peers, inflated social self-perception and antisocial behavior of peer-group affiliates (assessed throughout ages 8-13 years). Results indicated that negative reactivity was indirectly associated with overt antisocial behavior and substance use via poor social preference. Specifically, negative reactivity in earlier childhood predicted poor social preference in later childhood and early adolescence. This poor social standing among peers, in turn, predicted more engagement in overt antisocial behavior but less substance use in later adolescence. Over and above the influence of social preference, negative reactivity predicted engagement in all 3 outcomes via children's antisocial behavior in childhood and early adolescence. Inflated social self-perception and antisocial behavior of peer-group affiliates did not mediate the link between temperament and the outcomes under scrutiny. No sex differences in developmental pathways from temperament to the outcomes were found. To further our understanding of the developmental link between childhood temperament and later antisocial behavior and substance use, we need to recognize the role of peer environmental factors, specifically poor preference among peers. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  14. Visual acuity, crowding, and stereo-vision are linked in children with and without amblyopia.

    Science.gov (United States)

    Greenwood, John A; Tailor, Vijay K; Sloper, John J; Simmers, Anita J; Bex, Peter J; Dakin, Steven C

    2012-11-15

    During development, the presence of strabismus and anisometropia frequently leads to amblyopia, a visual disorder characterized by interocular acuity differences. Although additional deficits in contrast sensitivity, crowding (the impaired recognition of closely spaced objects), and stereoacuity are common, the relationship between these abilities is unclear. We measured the covariation between these four abilities in children 4 to 9 years of age (n = 72) with strabismus, anisometropia, or mixed strabismus/anisometropia, and unaffected controls. Children reported the orientation of a target (a modified "Pac-Man," similar to Landolt-C stimuli) using four "ghosts" as references. Using a modified staircase procedure we measured threshold size (acuity), contrast detection, foveal crowding (the minimum separation between target and ghost-flankers supporting accurate identification), and stereoacuity (with random-dot stereogram ghosts). Group averages revealed significant interocular differences (IODs) in acuity for all three clinical groups (0.2-0.3 log minutes), and significant crowding IODs for the strabismic and mixed groups (0.6 and 0.4°, respectively). Nonetheless, crowding IODs were correlated with acuity IODs in all four groups (r values between 0.43 and 0.59 and P stereo-blindness (most common in strabismic and mixed groups) was associated with a significant increase in IODs for both acuity and crowding (each P stereo-vision. We suggest that the deficits derived from strabismus and anisometropia lay along a continuum with abilities observed during normal development.

  15. Pathways to Identity. Using Visualization to Aid Law Enforcement in Identification Tasks

    Energy Technology Data Exchange (ETDEWEB)

    Bruce, Joseph R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Scholtz, Jean [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hodges, Duncan [Univ. of Oxford (United Kingdom); Emanuel, Lia [Univ. of Bath (United Kingdom); Stanton Fraser, Danae [Univ. of Bath (United Kingdom); Creese, Sadie [Univ. of Oxford (United Kingdom); Love, Oriana J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2014-09-18

    The nature of identity has changed dramatically in recent years and has grown in complexity. Identities are defined in multiple domains: biological and psychological elements strongly contribute, but biographical and cyber elements also are necessary to complete the picture. Law enforcement is beginning to adjust to these changes, recognizing identity’s importance in criminal justice. The SuperIdentity project seeks to aid law enforcement officials in their identification tasks through research of techniques for discovering identity traits, generation of statistical models of identity and analysis of identity traits through visualization. We present use cases compiled through user interviews in multiple fields, including law enforcement, and describe the modeling and visualization tools design to aid in those use cases.

  16. Pathways to Identity: Aiding Law Enforcement in Identification Tasks With Visual Analytics

    Energy Technology Data Exchange (ETDEWEB)

    Bruce, Joseph R.; Scholtz, Jean; Hodges, Duncan; Emanuel, Lia; Stanton-Fraser, Danae; Creese, Sadie; Love, Oriana J.

    2014-09-18

    The nature of identity has changed dramatically in recent years, and has grown in complexity. Identities are defined in multiple domains: biological and psychological elements strongly contribute, but also biographical and cyber elements are necessary to complete the picture. Law enforcement is beginning to adjust to these changes, recognizing its importance in criminal justice. The SuperIdentity project seeks to aid law enforcement officials in their identification tasks through research of techniques for discovering identity traits, generation of statistical models of identity and analysis of identity traits through visualization. We present use cases compiled through user interviews in multiple fields, including law enforcement, as well as the modeling and visualization tools design to aid in those use cases.

  17. Linking regional stakeholder scenarios and shared socioeconomic pathways: Quantified West African food and climate futures in a global context.

    Science.gov (United States)

    Palazzo, Amanda; Vervoort, Joost M; Mason-D'Croz, Daniel; Rutting, Lucas; Havlík, Petr; Islam, Shahnila; Bayala, Jules; Valin, Hugo; Kadi Kadi, Hamé Abdou; Thornton, Philip; Zougmore, Robert

    2017-07-01

    The climate change research community's shared socioeconomic pathways (SSPs) are a set of alternative global development scenarios focused on mitigation of and adaptation to climate change. To use these scenarios as a global context that is relevant for policy guidance at regional and national levels, they have to be connected to an exploration of drivers and challenges informed by regional expertise. In this paper, we present scenarios for West Africa developed by regional stakeholders and quantified using two global economic models, GLOBIOM and IMPACT, in interaction with stakeholder-generated narratives and scenario trends and SSP assumptions. We present this process as an example of linking comparable scenarios across levels to increase coherence with global contexts, while presenting insights about the future of agriculture and food security under a range of future drivers including climate change. In these scenarios, strong economic development increases food security and agricultural development. The latter increases crop and livestock productivity leading to an expansion of agricultural area within the region while reducing the land expansion burden elsewhere. In the context of a global economy, West Africa remains a large consumer and producer of a selection of commodities. However, the growth in population coupled with rising incomes leads to increases in the region's imports. For West Africa, climate change is projected to have negative effects on both crop yields and grassland productivity, and a lack of investment may exacerbate these effects. Linking multi-stakeholder regional scenarios to the global SSPs ensures scenarios that are regionally appropriate and useful for policy development as evidenced in the case study, while allowing for a critical link to global contexts.

  18. Evaluation of Mixed-Mode Data-Link Communications for NextGen 4DT and Equivalent Visual Surface Operations

    Science.gov (United States)

    Prinzel, Lawrence J., III; Shelton, Kevin J.; Jones, Denise R.; Allamandola, Angela S.; Arthur, Jarvis, J., III; Bailey, Randall E.

    2010-01-01

    By 2025, U.S. air traffic is predicted to increase 3-fold and may strain the current air traffic management system, which may not be able to accommodate this growth. In response to this challenge, a revolutionary new concept has been proposed for U.S. aviation operations, termed the Next Generation Air Transportation System or NextGen. Many key capabilities are being identified to enable NextGen, including the use of data-link communications. Because NextGen represents a radically different approach to air traffic management and requires a dramatic shift in the tasks, roles, and responsibilities for the flight deck, there are numerous research issues and challenges that must be overcome to ensure a safe, sustainable air transportation system. Flight deck display and crew-vehicle interaction concepts are being developed that proactively investigate and overcome potential technology and safety barriers that might otherwise constrain the full realization of NextGen. The paper describes simulation research examining data-link communications during 4DT and equivalent visual surface operations.

  19. Visualization of oxytocin release that mediates paired pulse facilitation in hypothalamic pathways to brainstem autonomic neurons.

    Directory of Open Access Journals (Sweden)

    Ramón A Piñol

    Full Text Available Recent work has shown that oxytocin is involved in more than lactation and uterine contraction. The paraventricular nucleus of the hypothalamus (PVN contains neuroendocrine neurons that control the release of hormones, including vasopressin and oxytocin. Other populations of PVN neurons do not release hormones, but rather project to and release neurotransmitters onto other neurons in the CNS involved in fluid retention, thermoregulation, sexual behavior and responses to stress. Activation of oxytocin receptors can be cardioprotective and reduces the adverse cardiovascular consequences of anxiety and stress, yet how oxytocin can affect heart rate and cardiac function is unknown. While anatomical work has shown the presence of peptides, including oxytocin, in the projections from the PVN to parasympathetic nuclei, electrophysiological studies to date have only demonstrated release of glutamate and activation of fast ligand gated receptors in these pathways. In this study, using rats, we directly show, using sniffer CHO cells that express oxytocin receptors and the Ca2+ indicator R-GECO, that optogenetic activation of channelrhodopsin-2 (ChR2 expressing PVN fibers in the brainstem activates oxytocin receptors in the dorsomotor nucleus of the vagus (DMNV. We also demonstrate that while a single photoactivation of PVN terminals only activates glutamatergic receptors in brainstem cardiac vagal neurons (CVNs, neurons that dominate the neural control of heart rate, both the paired pulse facilitation, and sustained enhancement of glutamate release in this pathway is mediated by activation of oxytocin receptors. Our results provide direct evidence that a pathway from the PVN likely releases oxytocin and enhances short-term plasticity of this critical autonomic connection.

  20. Visualizing functional pathways in the human brain using correlation tensors and magnetic resonance imaging.

    Science.gov (United States)

    Ding, Zhaohua; Xu, Ran; Bailey, Stephen K; Wu, Tung-Lin; Morgan, Victoria L; Cutting, Laurie E; Anderson, Adam W; Gore, John C

    2016-01-01

    Functional magnetic resonance imaging usually detects changes in blood oxygenation level dependent (BOLD) signals from T2*-sensitive acquisitions, and is most effective in detecting activity in brain cortex which is irrigated by rich vasculature to meet high metabolic demands. We recently demonstrated that MRI signals from T2*-sensitive acquisitions in a resting state exhibit structure-specific temporal correlations along white matter tracts. In this report we validate our preliminary findings and introduce spatio-temporal functional correlation tensors to characterize the directional preferences of temporal correlations in MRI signals acquired at rest. The results bear a remarkable similarity to data obtained by diffusion tensor imaging but without any diffusion-encoding gradients. Just as in gray matter, temporal correlations in resting state signals may reflect intrinsic synchronizations of neural activity in white matter. Here we demonstrate that functional correlation tensors are able to visualize long range white matter tracts as well as short range sub-cortical fibers imaged at rest, and that evoked functional activities alter these structures and enhance the visualization of relevant neural circuitry. Furthermore, we explore the biophysical mechanisms underlying these phenomena by comparing pulse sequences, which suggest that white matter signal variations are consistent with hemodynamic (BOLD) changes associated with neural activity. These results suggest new ways to evaluate MRI signal changes within white matter. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. STAT1-dependent expression of energy metabolic pathways links tumour growth and radioresistance to the Warburg effect.

    Science.gov (United States)

    Pitroda, Sean P; Wakim, Bassam T; Sood, Ravi F; Beveridge, Mara G; Beckett, Michael A; MacDermed, Dhara M; Weichselbaum, Ralph R; Khodarev, Nikolai N

    2009-11-05

    The Signal Transducer and Activator of Transcription 1 (STAT1) has traditionally been regarded as a transmitter of interferon signaling and a pro-apoptotic tumour suppressor. Recent data have identified new functions of STAT1 associated with tumourigenesis and resistance to genotoxic stress, including ionizing radiation (IR) and chemotherapy. To investigate the mechanisms contributing to the tumourigenic functions of STAT1, we performed a combined transcriptomic-proteomic expressional analysis and found that STAT1 is associated with regulation of energy metabolism with potential implication in the Warburg effect. We generated a stable knockdown of STAT1 in the SCC61 human squamous cell carcinoma cell line, established tumour xenografts in athymic mice, and compared transcriptomic and proteomic profiles of STAT1 wild-type (WT) and knockdown (KD) untreated or irradiated (IR) tumours. Transcriptional profiling was based on Affymetrix Human GeneChip(R) Gene 1.0 ST microarrays. Proteomes were determined from the tandem mass spectrometry (MS/MS) data by searching against the human subset of the UniProt database. Data were analysed using Significance Analysis of Microarrays for ribonucleic acid and Visualize software for proteins. Functional analysis was performed with Ingenuity Pathway Analysis with statistical significance measured by Fisher's exact test. Knockdown of STAT1 led to significant growth suppression in untreated tumours and radio sensitization of irradiated tumours. These changes were accompanied by alterations in the expression of genes and proteins of glycolysis/gluconeogenesis (GG), the citrate cycle (CC) and oxidative phosphorylation (OP). Of these pathways, GG had the most concordant changes in gene and protein expression and demonstrated a STAT1-dependent expression of genes and proteins consistent with tumour-specific glycolysis. In addition, IR drastically suppressed the GG pathway in STAT1 KD tumours without significant change in STAT1 WT tumours

  2. STAT1-dependent expression of energy metabolic pathways links tumour growth and radioresistance to the Warburg effect

    Directory of Open Access Journals (Sweden)

    MacDermed Dhara M

    2009-11-01

    Full Text Available Abstract Background The Signal Transducer and Activator of Transcription 1 (STAT1 has traditionally been regarded as a transmitter of interferon signaling and a pro-apoptotic tumour suppressor. Recent data have identified new functions of STAT1 associated with tumourigenesis and resistance to genotoxic stress, including ionizing radiation (IR and chemotherapy. To investigate the mechanisms contributing to the tumourigenic functions of STAT1, we performed a combined transcriptomic-proteomic expressional analysis and found that STAT1 is associated with regulation of energy metabolism with potential implication in the Warburg effect. Methods We generated a stable knockdown of STAT1 in the SCC61 human squamous cell carcinoma cell line, established tumour xenografts in athymic mice, and compared transcriptomic and proteomic profiles of STAT1 wild-type (WT and knockdown (KD untreated or irradiated (IR tumours. Transcriptional profiling was based on Affymetrix Human GeneChip® Gene 1.0 ST microarrays. Proteomes were determined from the tandem mass spectrometry (MS/MS data by searching against the human subset of the UniProt database. Data were analysed using Significance Analysis of Microarrays for ribonucleic acid and Visualize software for proteins. Functional analysis was performed with Ingenuity Pathway Analysis with statistical significance measured by Fisher's exact test. Results Knockdown of STAT1 led to significant growth suppression in untreated tumours and radio sensitization of irradiated tumours. These changes were accompanied by alterations in the expression of genes and proteins of glycolysis/gluconeogenesis (GG, the citrate cycle (CC and oxidative phosphorylation (OP. Of these pathways, GG had the most concordant changes in gene and protein expression and demonstrated a STAT1-dependent expression of genes and proteins consistent with tumour-specific glycolysis. In addition, IR drastically suppressed the GG pathway in STAT1 KD tumours

  3. A role for the CAMKK pathway in visual object recognition memory.

    Science.gov (United States)

    Tinsley, Chris J; Narduzzo, Katherine E; Brown, Malcolm W; Warburton, E Clea

    2012-03-01

    The role of the CAMKK pathway in object recognition memory was investigated. Rats' performance in a preferential object recognition test was examined after local infusion into the perirhinal cortex of the CAMKK inhibitor STO-609. STO-609 infused either before or immediately after acquisition impaired memory tested after a 24 h but not a 20-min delay. Memory was not impaired when STO-609 was infused 20 min after acquisition. The expression of a downstream reaction product of CAMKK was measured by immunohistochemical staining for phospho-CAMKI(Thr177) at 10, 40, 70, and 100 min following the viewing of novel and familiar images of objects. Processing familiar images resulted in more pCAMKI stained neurons in the perirhinal cortex than processing novel images at the 10- and 40-min delays. Prior infusion of STO-609 caused a reduction in pCAMKI stained neurons in response to viewing either novel or familiar images, consistent with its role as an inhibitor of CAMKK. The results establish that the CAMKK pathway within the perirhinal cortex is important for the consolidation of object recognition memory. The activation of pCAMKI after acquisition is earlier than previously reported for pCAMKII. Copyright © 2011 Wiley Periodicals, Inc.

  4. Myelin repair by Schwann cells in the regenerating goldfish visual pathway: regional patterns revealed by X-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Nona, S.N.; Stafford, C.A.; Cronly-Dillon, J.R. (Manchester Univ. (United Kingdom). Inst. of Science and Technology); Duncan, A. (Guy' s Hospital, London (United Kingdom). Dept. of Anatomy); Scholes, J. (University Coll., London (United Kingdom))

    1994-07-01

    In the regenerating goldfish optic nerves, Schwann cells of unknown origin reliably infiltrate the lesion site forming a band of peripheral-type myelinating tissue by 1-2 months, sharply demarcated form the adjacent new CNS myelin. To investigate this effect, we have interfered with cell proliferation by locally X-irradiating the fish visual pathway 24 h after the lesion. As assayed by immunohistochemistry and EM, irradiation retards until 6 months formation of new myelin by Schwann cells at the lesion site, and virtually abolishes oligodendrocyte myelination distally, but has little or no effect on nerve fibre regrowth. Optic nerve astrocyte processes normally fail to re-infiltrate the lesion, but re-occupy it after irradiation, suggesting that they are normally excluded by early cell proliferation at this site. Moreover, scattered myelinating Schwann cells also appear in the oligodendrocyte-depleted distal optic nerve after irradiation, although only as far as the optic tract. (Author).

  5. Measuring Connectivity in the Primary Visual Pathway in Human Albinism Using Diffusion Tensor Imaging and Tractography.

    Science.gov (United States)

    Grigorian, Anahit; McKetton, Larissa; Schneider, Keith A

    2016-08-11

    In albinism, the number of ipsilaterally projecting retinal ganglion cells (RGCs) is significantly reduced. The retina and optic chiasm have been proposed as candidate sites for misrouting. Since a correlation between the number of lateral geniculate nucleus (LGN) relay neurons and LGN size has been shown, and based on previously reported reductions in LGN volumes in human albinism, we suggest that fiber projections from LGN to the primary visual cortex (V1) are also reduced. Studying structural differences in the visual system of albinism can improve the understanding of the mechanism of misrouting and subsequent clinical applications. Diffusion data and tractography are useful for mapping the OR (optic radiation). This manuscript describes two algorithms for OR reconstruction in order to compare brain connectivity in albinism and controls.An MRI scanner with a 32-channel head coil was used to acquire structural scans. A T1-weighted 3D-MPRAGE sequence with 1 mm(3) isotropic voxel size was used to generate high-resolution images for V1 segmentation. Multiple proton density (PD) weighted images were acquired coronally for right and left LGN localization. Diffusion tensor imaging (DTI) scans were acquired with 64 diffusion directions. Both deterministic and probabilistic tracking methods were run and compared, with LGN as the seed mask and V1 as the target mask. Though DTI provides relatively poor spatial resolution, and accurate delineation of OR may be challenging due to its low fiber density, tractography has been shown to be advantageous both in research and clinically. Tract based spatial statistics (TBSS) revealed areas of significantly reduced white matter integrity within the OR in patients with albinism compared to controls. Pairwise comparisons revealed a significant reduction in LGN to V1 connectivity in albinism compared to controls. Comparing both tracking algorithms revealed common findings, strengthening the reliability of the technique.

  6. Targeting Allergen to FcγRI Reveals a Novel Th2 Regulatory Pathway Linked to TSLP Receptor

    Science.gov (United States)

    Hulse, Kathryn E.; Reefer, Amanda J.; Engelhard, Victor H.; Patrie, James T.; Ziegler, Steven F.; Chapman, Martin D.; Woodfolk, Judith A.

    2009-01-01

    Background The molecule H22-Fel d 1, which targets cat allergen to FcγRI on dendritic cells, has the potential to treat cat allergy owing to its T-cell modulatory properties. Objective To investigate whether the T-cell response induced by H22-Fel d 1 is altered in the presence of the Th2-promoting cytokine, TSLP. Methods Studies were performed in cat-allergic subjects with and without atopic dermatitis. Monocyte-derived dendritic cells were primed with H22-Fel d 1 in the presence or absence of TSLP and the resulting T-cell cytokine repertoire was analyzed by flow cytometry. The capacity for H22-Fel d 1 to modulate TSLP receptor expression on dendritic cells was examined by flow cytometry in the presence or absence of inhibitors of Fc receptor signaling molecules. Results Surprisingly, TSLP alone was a weak inducer of Th2 responses irrespective of atopic status; however, dendritic cells co-primed with TSLP and H22-Fel d 1 selectively and synergistically amplified Th2 responses in highly atopic subjects. This effect was OX40 ligand-independent pointing to an unconventional TSLP-mediated pathway. Expression of TSLP receptor was upregulated on atopic dendritic cells primed with H22-Fel d 1 through a pathway regulated by FcγRI-associated signaling components, including src related tyrosine kinases and Syk, as well as the downstream molecule, PI3-kinase. Inhibition of TSLP receptor upregulation triggered by H22-Fel d 1 blocked TSLP-mediated Th2 responses. Conclusion Discovery of a novel Th2 regulatory pathway linking FcγRI signaling to TSLP receptor upregulation and consequent TSLP-mediated effects questions the validity of receptor-targeted allergen vaccines. Clinical Implications This study establishes a pivotal role for Fc receptor ligation in promoting TSLP-mediated Th2 responses associated with allergic disease. Capsule Summary Atopic dendritic cells are equipped to efficiently upregulate TSLP receptor upon Fc receptor ligation by allergen. These findings suggest

  7. Visual Outcomes After SMILE, LASEK, and LASEK Combined With Corneal Collagen Cross-Linking for High Myopic Correction.

    Science.gov (United States)

    Hyun, Sangyoon; Lee, Seongjun; Kim, Jae-Hyung

    2017-04-01

    To compare the visual and refractive outcomes of small-incision lenticule extraction (SMILE), laser-assisted subepithelial keratomileusis (LASEK), and LASEK combined with corneal collagen cross-linking (LASEK-CXL) surgery for high-degree myopia. Medical records of patients with spherical equivalent (SE) greater than -6.00 diopters (D) treated with SMILE, LASEK, and LASEK-CXL were reviewed. Uncorrected distance visual acuity (UCVA), SE, and corneal haze were followed up in the 3 groups for 6 months. The SMILE group included 69 eyes, the LASEK group included 61 eyes, and the LASEK-CXL group included 40 eyes. At 6 months postoperatively, there were no statistically significant differences in UCVA between the SMILE, LASEK, and LASEK-CXL groups (logMAR 0.00 ± 0.00, 0.01 ± 0.08, and 0.01 ± 0.08, respectively, P = 0.69). The averages of the absolute value of SE were 0.34 ± 0.25 D, 0.50 ± 0.36 D, and 0.42 ± 0.34 D in the SMILE, LASEK, and LASEK-CXL groups, respectively (P = 0.04). The percentages of the patients with a postoperative residual refractive error within ±0.50 D were 84% in the SMILE group, 65% in the LASEK group, and 76% in the LASEK-CXL group. The percentages of the patients with greater than 20/25 postoperative UCVA were 100%, 91%, and 95%, respectively. SMILE produced no postoperative corneal haze. However, 18% of patients treated with LASEK and 25% of those treated with LASEK-CXL had corneal haze at 6 months postoperatively. SMILE, LASEK, and LASEK-CXL surgery appear to be safe and effective for high-degree myopic correction. However, the SMILE group had no haze and fewer induction of some higher-order aberrations compared with the LASEK and LASEK-CXL groups.

  8. Pharmacological inhibition of nicotinamide phosphoribosyltransferase/visfatin enzymatic activity identifies a new inflammatory pathway linked to NAD.

    Directory of Open Access Journals (Sweden)

    Nathalie Busso

    Full Text Available Nicotinamide phosphoribosyltransferase (NAMPT, also known as visfatin, is the rate-limiting enzyme in the salvage pathway of NAD biosynthesis from nicotinamide. Since its expression is upregulated during inflammation, NAMPT represents a novel clinical biomarker in acute lung injury, rheumatoid arthritis, and Crohn's disease. However, its role in disease progression remains unknown. We report here that NAMPT is a key player in inflammatory arthritis. Increased expression of NAMPT was confirmed in mice with collagen-induced arthritis, both in serum and in the arthritic paw. Importantly, a specific competitive inhibitor of NAMPT effectively reduced arthritis severity with comparable activity to etanercept, and decreased pro-inflammatory cytokine secretion in affected joints. Moreover, NAMPT inhibition reduced intracellular NAD concentration in inflammatory cells and circulating TNFalpha levels during endotoxemia in mice. In vitro pharmacological inhibition of NAMPT reduced the intracellular concentration of NAD and pro-inflammatory cytokine secretion by inflammatory cells. Thus, NAMPT links NAD metabolism to inflammatory cytokine secretion by leukocytes, and its inhibition might therefore have therapeutic efficacy in immune-mediated inflammatory disorders.

  9. Elaboration of the Visual Pathways from the Study of War-Related Cranial Injuries: The Period from the Russo-Japanese War to World War I.

    Science.gov (United States)

    Lanska, Douglas J

    2016-01-01

    As a result of the wars in the early 20th century, elaboration of the visual pathways was greatly facilitated by the meticulous study of visual defects in soldiers who had suffered focal injuries to the visual cortex. Using relatively crude techniques, often under difficult wartime circumstances, investigators successfully mapped key features of the visual pathways. Studies during the Russo- Japanese War (1904-1905) by Tatsuji Inouye (1881-1976) and during World War I by Gordon Holmes (1876-1965), William Lister (1868-1944), and others produced increasingly refined retinotopic maps of the primary visual cortex, which were later supported and refined by studies during and after World War II. Studies by George Riddoch (1888-1947) during World War I also demonstrated that some patients could still perceive motion despite blindness caused by damage to their visual cortex and helped to establish the concept of functional partitioning of visual processes in the occipital cortex. © 2016 S. Karger AG, Basel.

  10. Atlas and feature based 3D pathway visualization enhancement for skull base pre-operative fast planning from head CT

    Science.gov (United States)

    Aghdasi, Nava; Li, Yangming; Berens, Angelique; Moe, Kris S.; Bly, Randall A.; Hannaford, Blake

    2015-03-01

    Minimally invasive neuroendoscopic surgery provides an alternative to open craniotomy for many skull base lesions. These techniques provides a great benefit to the patient through shorter ICU stays, decreased post-operative pain and quicker return to baseline function. However, density of critical neurovascular structures at the skull base makes planning for these procedures highly complex. Furthermore, additional surgical portals are often used to improve visualization and instrument access, which adds to the complexity of pre-operative planning. Surgical approach planning is currently limited and typically involves review of 2D axial, coronal, and sagittal CT and MRI images. In addition, skull base surgeons manually change the visualization effect to review all possible approaches to the target lesion and achieve an optimal surgical plan. This cumbersome process relies heavily on surgeon experience and it does not allow for 3D visualization. In this paper, we describe a rapid pre-operative planning system for skull base surgery using the following two novel concepts: importance-based highlight and mobile portal. With this innovation, critical areas in the 3D CT model are highlighted based on segmentation results. Mobile portals allow surgeons to review multiple potential entry portals in real-time with improved visualization of critical structures located inside the pathway. To achieve this we used the following methods: (1) novel bone-only atlases were manually generated, (2) orbits and the center of the skull serve as features to quickly pre-align the patient's scan with the atlas, (3) deformable registration technique was used for fine alignment, (4) surgical importance was assigned to each voxel according to a surgical dictionary, and (5) pre-defined transfer function was applied to the processed data to highlight important structures. The proposed idea was fully implemented as independent planning software and additional data are used for verification and

  11. Concurrent audio-visual feedback for supporting drivers at intersections : a study using two linked driving simulators.

    NARCIS (Netherlands)

    Houtenbos, M. Winter, J.C.F. de Hale, A.R. Wieringa, P.A. & Hagenzieker, M.P.

    2016-01-01

    A large portion of road traffic crashes occur at intersections for the reason that drivers lack necessary visual information. This research examined the effects of an audio-visual display that provides real-time sonification and visualization of the speed and direction of another car approaching the

  12. Decreased activation along the dorsal visual pathway after a 3-month treatment with galantamine in mild Alzheimer disease: a functional magnetic resonance imaging study.

    Science.gov (United States)

    Bokde, Arun L W; Karmann, Michaela; Teipel, Stefan J; Born, Christine; Lieb, Martin; Reiser, Maximilian F; Möller, Hans-Jürgen; Hampel, Harald

    2009-04-01

    Visual perception has been shown to be altered in Alzheimer disease (AD) patients, and it is associated with decreased cognitive function. Galantamine is an active cholinergic agent, which has been shown to lead to improved cognition in mild to moderate AD patients. This study examined brain activation in a group of mild AD patients after a 3-month open-label treatment with galantamine. The objective was to examine the changes in brain activation due to treatment. There were 2 tasks to visual perception. The first task was a face-matching task to test the activation along the ventral visual pathway, and the second task was a location-matching task to test neuronal function along the dorsal pathway. Brain activation was measured using functional magnetic resonance imaging. There were 5 mild AD patients in the study. There were no differences in the task performance and in the cognitive scores of the Consortium to Establish a Registry for Alzheimer's Disease battery before and after treatment. In the location-matching task, we found a statistically significant decrease in activation along the dorsal visual pathway after galantamine treatment. A previous study found that AD patients had higher activation in the location-matching task compared with healthy controls. There were no differences in activation for the face-matching task after treatment. Our data indicate that treatment with galantamine leads to more efficient visual processing of stimuli or changes the compensatory mechanism in the AD patients. A visual perception task recruiting the dorsal visual system may be useful as a biomarker of treatment effects.

  13. Elevated C-Reactive Protein in Children from Risky Neighborhoods: Evidence for a Stress Pathway Linking Neighborhoods and Inflammation in Children

    OpenAIRE

    Broyles, Stephanie T.; Staiano, Amanda E.; Drazba, Kathryn T.; Gupta, Alok K.; Sothern, Melinda; Katzmarzyk, Peter T.

    2012-01-01

    BACKGROUND: Childhood socioeconomic status is linked to adult cardiovascular disease and disease risk. One proposed pathway involves inflammation due to exposure to a stress-inducing neighborhood environment. Whether CRP, a marker of systemic inflammation, is associated with stressful neighborhood conditions among children is unknown. METHODS AND RESULTS: The sample included 385 children 5-18 years of age from 255 households and 101 census tracts. Multilevel logistic regression analyses compa...

  14. XIAP, a cellular member of the inhibitor of apoptosis protein family, links the receptors to TAB1-TAK1 in the BMP signaling pathway.

    Science.gov (United States)

    Yamaguchi, K; Nagai, S; Ninomiya-Tsuji, J; Nishita, M; Tamai, K; Irie, K; Ueno, N; Nishida, E; Shibuya, H; Matsumoto, K

    1999-01-01

    Signals elicited by transforming growth factor-beta (TGF-beta) superfamily ligands are generated following the formation of heteromeric receptor complexes consisting of type I and type II receptors. TAK1, a member of the MAP kinase kinase kinase family, and its activator, TAB1, participate in the bone morphogenetic protein (BMP) signaling pathway involved in mesoderm induction and patterning in early Xenopus embryos. However, the events leading from receptor activation to TAK1 activation remain to be identified. A yeast interaction screen was used to search for proteins that function in the pathway linking the receptors and TAB1-TAK1. The human X-chromosome-linked inhibitor of apoptosis protein (XIAP) was isolated as a TAB1-binding protein. XIAP associated not only with TAB1 but also with the BMP receptors in mammalian cells. Injection of XIAP mRNA into dorsal blastomeres enhanced the ventralization of Xenopus embryos in a TAB1-TAK1-dependent manner. Furthermore, a truncated form of XIAP lacking the TAB1-binding domain partially blocked the expression of ventral mesodermal marker genes induced by a constitutively active BMP type I receptor. These results suggest that XIAP participates in the BMP signaling pathway as a positive regulator linking the BMP receptors and TAB1-TAK1. PMID:9878061

  15. Developmental Dyslexia: Exploring How Much Phonological and Visual Attention Span Disorders Are Linked to Simultaneous Auditory Processing Deficits

    Science.gov (United States)

    Lallier, Marie; Donnadieu, Sophie; Valdois, Sylviane

    2013-01-01

    The simultaneous auditory processing skills of 17 dyslexic children and 17 skilled readers were measured using a dichotic listening task. Results showed that the dyslexic children exhibited difficulties reporting syllabic material when presented simultaneously. As a measure of simultaneous visual processing, visual attention span skills were…

  16. Dose-Response Modeling of the Visual Pathway Tolerance to Single-Fraction and Hypofractionated Stereotactic Radiosurgery.

    Science.gov (United States)

    Hiniker, Susan M; Modlin, Leslie A; Choi, Clara Y; Atalar, Banu; Seiger, Kira; Binkley, Michael S; Harris, Jeremy P; Liao, Yaping Joyce; Fischbein, Nancy; Wang, Lei; Ho, Anthony; Lo, Anthony; Chang, Steven D; Harsh, Griffith R; Gibbs, Iris C; Hancock, Steven L; Li, Gordon; Adler, John R; Soltys, Scott G

    2016-04-01

    Patients with tumors adjacent to the optic nerves and chiasm are frequently not candidates for single-fraction stereotactic radiosurgery (SRS) due to concern for radiation-induced optic neuropathy. However, these patients have been successfully treated with hypofractionated SRS over 2-5 days, though dose constraints have not yet been well defined. We reviewed the literature on optic tolerance to radiation and constructed a dose-response model for visual pathway tolerance to SRS delivered in 1-5 fractions. We analyzed optic nerve and chiasm dose-volume histogram (DVH) data from perioptic tumors, defined as those within 3mm of the optic nerves or chiasm, treated with SRS from 2000-2013 at our institution. Tumors with subsequent local progression were excluded from the primary analysis of vision outcome. A total of 262 evaluable cases (26 with malignant and 236 with benign tumors) with visual field and clinical outcomes were analyzed. Median patient follow-up was 37 months (range: 2-142 months). The median number of fractions was 3 (1 fraction n = 47, 2 fraction n = 28, 3 fraction n = 111, 4 fraction n = 10, and 5 fraction n = 66); doses were converted to 3-fraction equivalent doses with the linear quadratic model using α/β = 2Gy prior to modeling. Optic structure dose parameters analyzed included Dmin, Dmedian, Dmean, Dmax, V30Gy, V25Gy, V20Gy, V15Gy, V10Gy, V5Gy, D50%, D10%, D5%, D1%, D1cc, D0.50cc, D0.25cc, D0.20cc, D0.10cc, D0.05cc, D0.03cc. From the plan DVHs, a maximum-likelihood parameter fitting of the probit dose-response model was performed using DVH Evaluator software. The 68% CIs, corresponding to one standard deviation, were calculated using the profile likelihood method. Of the 262 analyzed, 2 (0.8%) patients experienced common terminology criteria for adverse events grade 4 vision loss in one eye, defined as vision of 20/200 or worse in the affected eye. One of these patients had received 2 previous courses of radiotherapy to the optic structures

  17. Daily visual stimulation in the critical period enhances multiple aspects of vision through BDNF-mediated pathways in the mouse retina.

    Science.gov (United States)

    Mui, Amanda M; Yang, Victoria; Aung, Moe H; Fu, Jieming; Adekunle, Adewumi N; Prall, Brian C; Sidhu, Curran S; Park, Han Na; Boatright, Jeffrey H; Iuvone, P Michael; Pardue, Machelle T

    2018-01-01

    Visual experience during the critical period modulates visual development such that deprivation causes visual impairments while stimulation induces enhancements. This study aimed to determine whether visual stimulation in the form of daily optomotor response (OMR) testing during the mouse critical period (1) improves aspects of visual function, (2) involves retinal mechanisms and (3) is mediated by brain derived neurotrophic factor (BDNF) and dopamine (DA) signaling pathways. We tested spatial frequency thresholds in C57BL/6J mice daily from postnatal days 16 to 23 (P16 to P23) using OMR testing. Daily OMR-treated mice were compared to littermate controls that were placed in the OMR chamber without moving gratings. Contrast sensitivity thresholds, electroretinograms (ERGs), visual evoked potentials, and pattern ERGs were acquired at P21. To determine the role of BDNF signaling, a TrkB receptor antagonist (ANA-12) was systemically injected 2 hours prior to OMR testing in another cohort of mice. BDNF immunohistochemistry was performed on retina and brain sections. Retinal DA levels were measured using high-performance liquid chromatography. Daily OMR testing enhanced spatial frequency thresholds and contrast sensitivity compared to controls. OMR-treated mice also had improved rod-driven ERG oscillatory potential response times, greater BDNF immunoreactivity in the retinal ganglion cell layer, and increased retinal DA content compared to controls. VEPs and pattern ERGs were unchanged. Systemic delivery of ANA-12 attenuated OMR-induced visual enhancements. Daily OMR testing during the critical period leads to general visual function improvements accompanied by increased DA and BDNF in the retina, with this process being requisitely mediated by TrkB activation. These results suggest that novel combination therapies involving visual stimulation and using both behavioral and molecular approaches may benefit degenerative retinal diseases or amblyopia.

  18. C-fos induction in forebrain areas of two different visual pathways during consolidation of sexual imprinting in the zebra finch (Taeniopygia guttata).

    Science.gov (United States)

    Sadananda, Monika; Bischof, Hans-Joachim

    2006-10-16

    Two forebrain areas in the hyperpallium apicale and in the lateral nidopallium of isolated male zebra finches are highly active (2-deoxyglucose technique) on exposure to females for the first time, that is first courtship. These areas also demonstrate enhanced neuronal plasticity when screened with c-fos immunocytochemistry. Both are areas involved in the processing of visual information conveyed by the two major visual pathways in birds, strengthening our hypothesis that courtship in the zebra finch is a visually guided behaviour. First courtship and chased birds show enhanced c-fos induction in the hyperpallial area, which could represent neuronal activity reflecting changes in the immediate environment. The enhanced expression of fos in first courtship birds in lateral nidopallial neurons indicates imminent long-lasting changes at the synaptic level that form the substrate for imprinting, a stable form of learning in birds.

  19. Abnormal regional spontaneous neural activity in visual pathway in retinal detachment patients: a resting-state functional MRI study

    Directory of Open Access Journals (Sweden)

    Huang X

    2017-11-01

    Full Text Available Xin Huang,1,2,* Dan Li,3,* Hai-Jun Li,3 Yu-Lin Zhong,1 Shelby Freeberg,4 Jing Bao,1 Xian-Jun Zeng,3 Yi Shao1 1Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute, Nanchang, Jiangxi, People’s Republic of China; 2Department of Ophthalmology, Eye Center, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 4Department of Ophthalmology, University of Florida, Gainesville, FL, USA *These authors contributed equally to this work Objective: The aim of the study was to investigate changes of brain neural homogeneity in retinal detachment (RD patients using the regional homogeneity (ReHo method to understand their relationships with clinical features. Materials and methods: A total of 30 patients with RD (16 men and 14 women, and 30 healthy controls (HCs (16 men and 14 women closely matched in age and sex were recruited. Resting-state functional magnetic resonance imaging scans were performed for all subjects. The ReHo method was used to investigate the brain regional neural homogeneity. Patients with RD were distinguished from HCs by receiver operating characteristic curve. The relationships between the mean ReHo signal values in many brain regions and clinical features in RD patients were calculated by Pearson correlation analysis. Results: Compared with HCs, RD patients had significantly decreased ReHo values in the right occipital lobe, right superior temporal gyrus, bilateral cuneus and left middle frontal gyrus. Moreover, we found that the mean ReHo signal of the bilateral cuneus showed positive relationships with the duration of the RD (r=0.392, P=0.032. Conclusion: The RD patients showed brain neural homogeneity dysfunction in the visual pathway, which may underline the pathological mechanism

  20. Linking regional stakeholder scenarios and shared socioeconomic pathways: Quantified West African food and climate futures in a global context

    NARCIS (Netherlands)

    Palazzo, Amanda; Vervoort, Joost M.; Mason-D’Croz, Daniel; Rutting, Lucas; Havlík, Petr; Islam, Shahnila; Bayala, Jules; Valin, Hugo; Kadi Kadi, Hamé Abdou; Thornton, Philip; Zougmore, Robert

    2017-01-01

    The climate change research community’s shared socioeconomic pathways (SSPs) are a set of alternative global development scenarios focused on mitigation of and adaptation to climate change. To use these scenarios as a global context that is relevant for policy guidance at regional and national

  1. Hedonic tone and activation in the mood-creativity link: towards a dual pathway to creativity model

    NARCIS (Netherlands)

    de Dreu, C.K.W.; Baas, M.; Nijstad, B.A.

    2008-01-01

    To understand when and why mood states influence creativity, the authors developed and tested a dual pathway to creativity model; creative fluency (number of ideas or insights) and originality (novelty) are functions of cognitive flexibility, persistence, or some combination thereof. Invoking work

  2. Hedonic tone and activation level in the mood-creativity link : Toward a dual pathway to creativity model

    NARCIS (Netherlands)

    De Dreu, Carsten K. W.; Baas, Matthijs; Nijstad, Bernard A.

    To understand when and why mood states influence creativity, the authors developed and tested a dual pathway to creativity model; creative fluency (number of ideas or insights) and originality (novelty) are functions of cognitive flexibility, persistence, or some combination thereof. Invoking work

  3. Completing the Link between Exposure Science and Toxicology for Improved Environmental Health Decision Making: The Aggregate Exposure Pathway Framework

    Energy Technology Data Exchange (ETDEWEB)

    Teeguarden, Justin G.; Tan, Yu-Mei; Edwards, Stephen W.; Leonard, Jeremy A.; Anderson, Kim A.; Corley, Richard A.; Kile, Molly L.; Simonich, Staci M.; Stone, David; Tanguay, Robert L.; Waters, Katrina M.; Harper, Stacey L.; Williams, David E.

    2016-05-03

    Driven by major scientific advances in analytical methods, biomonitoring, and computational exposure assessment, and a newly articulated vision for a greater impact in public health, the field of exposure science is undergoing a rapid transition from a field of observation to a field of prediction. Deployment of an organizational and predictive framework for exposure science analogous to the computationally enabled “systems approaches” used in the biological sciences is a necessary step in this evolution. Here we propose the aggregate exposure pathway (AEP) concept as the natural and complementary companion in the exposure sciences to the adverse outcome pathway (AOP) concept in the toxicological sciences. The AEP framework offers an intuitive approach to successful organization of exposure science data within individual units of prediction common to the field, setting the stage for exposure forecasting. Looking farther ahead, we envision direct linkages between aggregate exposure pathway and adverse outcome pathways, completing the source to outcome continuum and setting the stage for more efficient integration of exposure science and toxicity testing information. Together these frameworks form and inform a decision making framework with the flexibility for risk-based, hazard-based or exposure-based decisions.

  4. Impact of Raised Serum Cobalt Levels From Recalled Articular Surface Replacement Hip Prostheses on the Visual Pathway.

    Science.gov (United States)

    Unsworth-Smith, Timothy; Khan, Jane C; Khan, Riaz J K; Chelva, Enid; Lim, Caroline Ann; Haebich, Samantha; Trevenen, Michelle L

    2017-10-01

    The articular surface replacement (ASR) was recalled in 2010 because of higher than expected revision rates. Patients reported symptoms of neurologic dysfunction including poor vision. This cohort study, using objective measurements, aimed to establish whether a higher incidence of visual function defects exists in ASR patients. Thirty-three ASR patients and 33 non-ASR controls (control 1) were recruited. Data were compared with normative population data from the visual electrophysiology database (control 2). Patients underwent investigations for serum cobalt levels, psychophysical visual tests, and extensive electrophysiological visual testing. After excluding 2 subjects with pre-existing eye disease, data from 33 ASR patients were compared with the 2 control cohorts. The median serum cobalt level in the ASR group (median, 52 nmol/L [interquartile range, 14-151 nmol/L]) was significantly higher than that in the control 1 cohort (median, 7 nmol/L [interquartile range, 5-14 nmol/L]; P visual-evoked potential latency was significantly longer in the ASR group compared with those in the control 2 cohort (P = .0201). There were no statistical differences in visual acuity. A statistically significant disturbance in visual electrophysiology was found in the ASR group when compared with the control groups. These differences did not translate to identifiable clinical visual deficits. Orthopedic surgeons need to be aware of the possibility of visual dysfunction in patients with ASR and other metal-on-metal hip arthroplasties; however, routine visual testing is not recommended. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Bullying perpetration and victimization as externalizing and internalizing pathways: A retrospective study linking parenting styles and self-esteem to depression, alcohol use, and alcohol-related problems

    Science.gov (United States)

    Patock-Peckham, Julie A; Medina, Mia; Terrell, Nathan; Belton, Daniel; King, Kevin M

    2016-01-01

    Emerging research suggests significant positive associations between bullying and substance use behaviors. However, these studies typically focused either on the link between substance use and bullying perpetration or victimization, and few have conceptualized bullying perpetration and/or victimization as mediators. In this study, we simultaneously tested past bullying perpetration and victimization as mediational pathways from retrospective report of parenting styles and global self-esteem to current depressive symptoms, alcohol use and alcohol-related problems. Data were collected from a college sample of 419 drinkers. Mediation effects were conducted using a bias-corrected bootstrap technique in structural equation modeling. Two-path mediation analyses indicated that mother and father authoritativeness were protective against bully victimization and depression through higher self-esteem. Conversely, having a permissive or authoritarian mother was positively linked to bullying perpetration, which in turn was associated with increased alcohol use, and to a lesser degree, more alcohol-related problems. Mother authoritarianism was associated with alcohol-related problems through depressive symptoms. Three-path mediation analyses suggested a trend in which individuals with higher self-esteem were less likely to report alcohol-related problems through lower levels of bullying victimization and depression. Results suggested that bullying perpetration and victimization may respectively serve as externalizing and internalizing pathways through which parenting styles and self-esteem are linked to depression and alcohol-related outcomes. The present study identified multiple modifiable precursors of, and mediational pathways to, alcohol-related problems which could guide the development and implementation of prevention programs targeting problematic alcohol use. PMID:26757486

  6. Bullying Perpetration and Victimization as Externalizing and Internalizing Pathways: A Retrospective Study Linking Parenting Styles and Self-Esteem to Depression, Alcohol Use, and Alcohol-Related Problems.

    Science.gov (United States)

    Luk, Jeremy W; Patock-Peckham, Julie A; Medina, Mia; Terrell, Nathan; Belton, Daniel; King, Kevin M

    2016-01-02

    Emerging research suggests significant positive associations between bullying and substance use behaviors. However, these studies typically focused either on the link between substance use and bullying perpetration or victimization, and few have conceptualized bullying perpetration and/or victimization as mediators. In this study, we simultaneously tested past bullying perpetration and victimization as mediational pathways from retrospective report of parenting styles and global self-esteem to current depressive symptoms, alcohol use, and alcohol-related problems. Data were collected from a college sample of 419 drinkers. Mediation effects were conducted using a bias-corrected bootstrap technique within a structural equation modeling framework. Two-path mediation analyses indicated that mother and father authoritativeness were protective against bully victimization and depression through higher self-esteem. Conversely, having a permissive or authoritarian mother was positively linked to bullying perpetration, which in turn, was associated with increased alcohol use, and to a lesser degree, more alcohol-related problems. Mother authoritarianism was associated with alcohol-related problems through depressive symptoms. Three-path mediation analyses suggested a trend in which individuals with higher self-esteem were less likely to report alcohol-related problems through lower levels of bullying victimization and depression. Results suggested that bullying perpetration and victimization may, respectively, serve as externalizing and internalizing pathways through which parenting styles and self-esteem are linked to depression and alcohol-related outcomes. The present study identified multiple modifiable precursors of, and mediational pathways to, alcohol-related problems which could guide the development and implementation of prevention programs targeting problematic alcohol use.

  7. Ion-pairing liquid chromatography-tandem mass spectrometry-based quantification of uridine diphosphate-linked intermediates in the Staphylococcus aureus cell wall biosynthesis pathway.

    Science.gov (United States)

    Vemula, Harika; Bobba, Sudheer; Putty, Sandeep; Barbara, Joanna E; Gutheil, William G

    2014-11-15

    Bacterial cell wall biosynthesis is the target of several antibiotics and is of interest as a target for new inhibitor development. The cytoplasmic steps of this pathway involve a series of uridine diphosphate (UDP)-linked peptidoglycan intermediates. Quantification of these intermediates is essential for studies of current agents targeting this pathway and for the development of new agents targeting this pathway. In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for quantification of these intermediates in Staphylococcus aureus. To address the problem of poor retention of UDP-linked intermediates on reverse phase media, an ion-pairing (IP) approach using N,N-dimethylhexylamine was developed. MS/MS detection in negative mode was optimized for UDP-GlcNAc, UDP-MurNAc, UDP-MurNAc-L-Ala, UDP-MurNAc-L-Ala-D-Glu, UDP-MurNAc-L-Ala-D-Glu-L-Lys, and UDP-MurNAc-L-Ala-D-Glu-L-Lys-D-Ala-D-Ala. The lower limits of quantification (LLOQs) for these analytes were 1.8, 1.0, 0.8, 2.2, 0.6, and 0.5 pmol, respectively, which correspond to LLOQs of 6, 3, 3, 7, 2, and 2 nmol/g bacteria, respectively. This method was demonstrated for quantification of in vivo levels of these intermediates from S. aureus (0.3mg dry weight analyzed) treated with fosfomycin, D-boroAla, D-cycloserine, and vancomycin. Metabolite accumulation is consistent with the known targets of these antibiotics and indicates potential regulatory loops within this pathway. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Pathways to Adolescents' Flourishing: Linking Self-Control Skills and Positivity Ratio through Social Support

    Science.gov (United States)

    Orkibi, Hod; Hamama, Liat; Gavriel-Fried, Belle; Ronen, Tammie

    2018-01-01

    This study focused on the ability to experience a high ratio of positive to negative emotions in 807 Israeli adolescents aged 12 to 15 years (50% girls). While considering possible gender differences, we tested a model positing that adolescents' self-control skills would link to their positivity ratio and indirectly through perceived social…

  9. Genetic link between Cabeza, a Drosophila homologue of Fused in Sarcoma (FUS), and the EGFR signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Shimamura, Mai; Kyotani, Akane [Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585 (Japan); Insect Biomedical Research Center, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585 (Japan); Azuma, Yumiko [Department of Neurology, Kyoto Prefectural University of Medicine, 465 Kajii-cho,Kamigyo-ku, Kyoto 602-8566 (Japan); Yoshida, Hideki; Binh Nguyen, Thanh [Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585 (Japan); Insect Biomedical Research Center, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585 (Japan); Mizuta, Ikuko; Yoshida, Tomokatsu; Mizuno, Toshiki [Department of Neurology, Kyoto Prefectural University of Medicine, 465 Kajii-cho,Kamigyo-ku, Kyoto 602-8566 (Japan); Nakagawa, Masanori [North Medical Center, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566 (Japan); Tokuda, Takahiko, E-mail: ttokuda@koto.kpu-m.ac.jp [Department of Neurology, Kyoto Prefectural University of Medicine, 465 Kajii-cho,Kamigyo-ku, Kyoto 602-8566 (Japan); Department of Molecular Pathobiology of Brain Diseases, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566 (Japan); Yamaguchi, Masamitsu, E-mail: myamaguc@kit.ac.jp [Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585 (Japan); Insect Biomedical Research Center, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585 (Japan)

    2014-08-01

    Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that causes progressive muscular weakness. Fused in Sarcoma (FUS) that has been identified in familial ALS is an RNA binding protein that is normally localized in the nucleus. However, its function in vivo is not fully understood. Drosophila has Cabeza (Caz) as a FUS homologue and specific knockdown of Caz in the eye imaginal disc and pupal retina using a GMR-GAL4 driver was here found to induce an abnormal morphology of the adult compound eyes, a rough eye phenotype. This was partially suppressed by expression of the apoptosis inhibitor P35. Knockdown of Caz exerted no apparent effect on differentiation of photoreceptor cells. However, immunostaining with an antibody to Cut that marks cone cells revealed fusion of these and ommatidia of pupal retinae. These results indicate that Caz knockdown induces apoptosis and also inhibits differentiation of cone cells, resulting in abnormal eye morphology in adults. Mutation in EGFR pathway-related genes, such as rhomboid-1, rhomboid-3 and mirror suppressed the rough eye phenotype induced by Caz knockdown. Moreover, the rhomboid-1 mutation rescued the fusion of cone cells and ommatidia observed in Caz knockdown flies. The results suggest that Caz negatively regulates the EGFR signaling pathway required for determination of cone cell fate in Drosophila. - Highlights: • Knockdown of Cabeza induced rough eye phenotype. • Knockdown of Cabeza induced fusion of cone cells in pupal retinae. • Knockdown of Cabeza induced apoptosis in pupal retinae. • Mutation in EGFR pathway-related genes suppressed the rough eye phenotype. • Cabeza may negatively regulate the EGFR pathway.

  10. A proposed biosynthetic pathway of picrosides linked through the detection of biochemical intermediates in the endangered medicinal herb Picrorhiza kurroa.

    Science.gov (United States)

    Kumar, Varun; Sood, Hemant; Sharma, Manu; Chauhan, Rajinder Singh

    2013-01-01

    Picrorhiza kurroa Royle ex Benth is an important medicinal herb used in the preparation of several herbal drug formulations due to the presence of picroside-I (P-I) and picroside-II (P-II) along with other iridoid-glucosides derivatives. The endangered status of P. kurroa coupled with lack of information on biosynthesis of P-I and P-II necessitate deciphering the biosynthetic pathway for picrosides. LC with electrospray ionisation (ESI) and quadrupole time of flight combined with MS/MS was used to detect intermediates and assemble the picrosides biosynthetic pathway in P. kurroa. The presence of catalpol and aucubin, the major backbone structures of picrosides, along with intermediate metabolites boschnaloside, bartsioside and mussaenosidic acid, was confirmed in ESI negative mode with pseudomolecular ion peaks, that is, m/z 361, m/z 343, m/z 345, m/z 329 and m/z 375 ions and their fragmentation patterns. The picrosides biosynthetic pathway is expected to provide a reliable platform towards understanding the molecular components (genes/enzymes) of P-I and P-II biosynthesis in P. kurroa for their eventual utilisation in various applications. Copyright © 2013 John Wiley & Sons, Ltd.

  11. Linking the X3D Pathway to Integral Field Spectrographs: YSNR 1E 0102.2-7219 in the SMC as a Case Study

    Science.gov (United States)

    Vogt, Frédéric P. A.; Seitenzahl, Ivo R.; Dopita, Michael A.; Ruiter, Ashley J.

    2017-05-01

    The concept of the x3d pathway was introduced by Vogt et al. as a new approach to sharing and publishing three-dimensional structures interactively in online scientific journals. The core characteristics of the x3d pathway are that: (1) it does not rely on specific software, but rather a file format (x3d), (2) it can be implemented using fully open-source tools, and (3) article readers can access the interactive models using most main stream web browsers without the need for any additional plugins. In this article, we further demonstrate the potential of the x3d pathway to visualize data sets from optical integral field spectrographs. We use recent observations of the oxygen-rich young supernova remnant 1E 0102.2-7219 in the Small Magellanic Cloud to implement additional x3dom tools & techniques and expand the range of interactions that can be offered to article readers. In particular, we present a set of javascript functions allowing the creation and interactive handling of clip planes, effectively allowing users to take measurements of distances and angles directly from the interactive model itself.

  12. Neuroinflammation and J2 prostaglandins: linking impairment of the ubiquitin-proteasome pathway and mitochondria to neurodegeneration

    Directory of Open Access Journals (Sweden)

    Maria Emilia Figueiredo-Pereira

    2015-01-01

    Full Text Available The immune response of the CNS is a defense mechanism activated upon injury to initiate repair mechanisms while chronic over-activation of the CNS immune system (termed neuroinflammation may exacerbate injury. The latter is implicated in a variety of neurological and neurodegenerative disorders such as Alzheimer and Parkinson diseases, amyotrophic lateral sclerosis, multiple sclerosis, traumatic brain injury, HIV dementia and prion diseases. Cyclooxygenases (COX -1 and COX-2, which are key enzymes in the conversion of arachidonic acid into bioactive prostanoids, play a central role in the inflammatory cascade. J2 prostaglandins are endogenous toxic products of cyclooxygenases, and because their levels are significantly increased upon brain injury, they are actively involved in neuronal dysfunction induced by pro-inflammatory stimuli. In this review, we highlight the mechanisms by which J2 prostaglandins (1 exert their actions, (2 potentially contribute to the transition from acute to chronic inflammation and to the spreading of neuropathology, (3 disturb the ubiquitin-proteasome pathway and mitochondrial function, and (4 contribute to neurodegenerative disorders such as Alzheimer and Parkinson diseases, and amyotrophic lateral sclerosis, as well as stroke, traumatic brain injury, and demyelination in Krabbe disease. We conclude by discussing the therapeutic potential of targeting the J2 prostaglandin pathway to prevent/delay neurodegeneration associated with neuroinflammation. In this context, we suggest a shift from the traditional view that cyclooxygenases are the most appropriate targets to treat neuroinflammation, to the notion that J2 prostaglandin pathways and other neurotoxic prostaglandins downstream from cyclooxygenases, would offer significant benefits as more effective therapeutic targets to treat chronic neurodegenerative diseases, while minimizing adverse side effects.

  13. Linking genome content to biofuel production yields: a meta-analysis of major catabolic pathways among select H2 and ethanol-producing bacteria.

    Science.gov (United States)

    Carere, Carlo R; Rydzak, Thomas; Verbeke, Tobin J; Cicek, Nazim; Levin, David B; Sparling, Richard

    2012-12-18

    on H2 production in organisms that do not encode ethanol producing pathways, they do influence reduced end-product yields in those that do. Here we show that composition of genes encoding pathways involved in pyruvate catabolism and end-product synthesis pathways can be used to approximate potential end-product distribution patterns. We have identified a number of genetic biomarkers for streamlining ethanol and H2 producing capabilities. By linking genome content, reaction thermodynamics, and end-product yields, we offer potential targets for optimization of either ethanol or H2 yields through metabolic engineering.

  14. Starvation-Dependent Regulation of Golgi Quality Control Links the TOR Signaling and Vacuolar Protein Sorting Pathways

    Directory of Open Access Journals (Sweden)

    Niv Dobzinski

    2015-09-01

    Full Text Available Upon amino acid (AA starvation and TOR inactivation, plasma-membrane-localized permeases rapidly undergo ubiquitination and internalization via the vacuolar protein sorting/multivesicular body (VPS-MVB pathway and are degraded in the yeast vacuole. We now show that specific Golgi proteins are also directed to the vacuole under these conditions as part of a Golgi quality-control (GQC process. The degradation of GQC substrates is dependent upon ubiquitination by the defective-for-SREBP-cleavage (DSC complex, which was identified via genetic screening and includes the Tul1 E3 ligase. Using a model GQC substrate, GFP-tagged Yif1, we show that vacuolar targeting necessitates upregulation of the VPS pathway via proteasome-mediated degradation of the initial endosomal sorting complex required for transport, ESCRT-0, but not downstream ESCRT components. Thus, early cellular responses to starvation include the targeting of specific Golgi proteins for degradation, a phenomenon reminiscent of the inactivation of BTN1, the yeast Batten disease gene ortholog.

  15. The Nuclear Factor κB pathway: A link to the immune system in the radiation response.

    Science.gov (United States)

    Hellweg, Christine E

    2015-11-28

    Exposure to ionizing radiation modulates immune responses in a complex dose-dependent pattern, with possible anti-inflammatory effects in the low dose range, expression of pro-inflammatory cytokines at moderate doses and immunosuppression after exposure to higher doses due to precursor cell death together with concomitant exacerbated innate immune responses. A central regulator in the immune system is the transcription factor Nuclear Factor κB (NF-κB). NF-κB is involved in the regulation of cellular survival, immune responses and inflammation, resulting in eminent importance in cancerogenesis. After exposure to ionizing radiation, NF-κB activation is initially triggered by ATM which is activated by DNA double strand breaks. Together with the NF-κB essential modulator (NEMO), it serves as a nucleoplasmic shuttle. The pathway converges with the classical NF-κB pathway at IκB kinase (IKK) complex activation. Resulting cytokine expression can activate NF-κB in a positive feed forward loop. Danger signals released from dying cells can activate NF-κB via Toll-like receptors (TLRs). The resulting immune activation can be beneficial or detrimental. In the low dose range, pro- and anticancerogenic effects are possible. In the radiotherapy-relevant dose range, tolerogenic immune responses should be avoided, and an anti-tumor immune response might be supported by TLR agonists activating NF-κB. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Functional assessment of the visual pathway with multifocal visual evoked potentials, and their relationship with disability in patients with multiple sclerosis.

    Science.gov (United States)

    Blanco, Román; Pérez-Rico, Consuelo; Puertas-Muñoz, Inmaculada; Ayuso-Peralta, Lucía; Boquete, Luciano; Arévalo-Serrano, Juan

    2014-02-01

    To objectively evaluate the visual function, and the relationship between disability and optic nerve dysfunction, in patients with multiple sclerosis (MS) and optic neuritis (ON), using multifocal visual evoked potentials (mfVEP). This observational, cross-sectional study assessed 28 consecutive patients with clinically definite MS, according to the McDonald criteria, and 19 age-matched healthy subjects. Disability was recorded using the Expanded Disability Status Scale (EDSS) score. The patients' mfVEP were compared to their clinical, psychophysical (Humphrey perimetry) and structural (optic coherence tomography (OCT)) diagnostic test data. We observed a significant agreement between mfVEP amplitude and Humphrey perimetry/OCT in MS-ON eyes, and between mfVEP amplitude and OCT in MS but non-ON eyes. We found significant differences in EDSS score between patients with abnormal and normal mfVEP amplitudes. Abnormal mfVEP amplitude defects (from interocular and monocular probability analysis) were found in 67.9% and 73.7% of the MS-ON and MS-non-ON group eyes, respectively. Delayed mfVEP latencies (interocular and monocular probability analysis) were seen in 70.3% and 73.7% of the MS-ON and MS-non-ON groups, respectively. We found a significant relationship between mfVEP amplitude and disease severity, as measured by EDSS score, that suggested there is a role for mfVEP amplitude as a functional biomarker of axonal loss in MS.

  17. Visual Hallucinations as Incidental Negative Effects of Virtual Reality on Parkinson’s Disease Patients: A Link with Neurodegeneration?

    Directory of Open Access Journals (Sweden)

    Giovanni Albani

    2015-01-01

    Full Text Available We followed up a series of 23 Parkinson’s disease (PD patients who had performed an immersive virtual reality (VR protocol eight years before. On that occasion, six patients incidentally described visual hallucinations (VH with occurrences of images not included in the virtual environment. Curiously, in the following years, only these patients reported the appearance of VH later in their clinical history, while the rest of the group did not. Even considering the limited sample size, we may argue that VR immersive systems can induce unpleasant effects in PD patients who are predisposed to a cognitive impairment.

  18. Linking Material Flow Analysis with Resilience Using Rice: A Case Study in Global, Visual MFA of a Key Food Product

    OpenAIRE

    Michal Monit; André Pina; Paulo Ferrão

    2016-01-01

    This article uses the rice price crisis of 2007–2008 to show how material flow analysis (MFA) can be combined with resilience research. After presentation of fundamental information and methods, resilience-related concepts are illustrated using graphical methods and MFA data. Herfindahl-Hirschman Index (HHI) and node-link diagrams are used to highlight potential vulnerability hotspots and show response to, recovery from disturbance and adaptation following a disruption of the global rice mark...

  19. Lung Cancer Cell Line Screen Links Fanconi Anemia/BRCA Pathway Defects to Increased Relative Biological Effectiveness of Proton Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Qi; Ghosh, Priyanjali; Magpayo, Nicole [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Testa, Mauro; Tang, Shikui [Division of Radiation Physics, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Gheorghiu, Liliana [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Biggs, Peter; Paganetti, Harald [Division of Radiation Physics, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Efstathiou, Jason A. [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Lu, Hsiao-Ming [Division of Radiation Physics, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Held, Kathryn D. [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Willers, Henning, E-mail: hwillers@mgh.harvard.edu [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2015-04-01

    Purpose: Growing knowledge of genomic heterogeneity in cancer, especially when it results in altered DNA damage responses, requires re-examination of the generic relative biological effectiveness (RBE) of 1.1 of protons. Methods and Materials: For determination of cellular radiosensitivity, we irradiated 17 lung cancer cell lines at the mid-spread-out Bragg peak of a clinical proton beam (linear energy transfer, 2.5 keV/μm). For comparison, 250-kVp X rays and {sup 137}Cs γ-rays were used. To estimate the RBE of protons relative to {sup 60}Co (Co60eq), we assigned an RBE(Co60Eq) of 1.1 to X rays to correct the physical dose measured. Standard DNA repair foci assays were used to monitor damage responses. FANCD2 was depleted using RNA interference. Results: Five lung cancer cell lines (29.4%) exhibited reduced clonogenic survival after proton irradiation compared with X-irradiation with the same physical doses. This was confirmed in a 3-dimensional sphere assay. Corresponding proton RBE(Co60Eq) estimates were statistically significantly different from 1.1 (P≤.05): 1.31 to 1.77 (for a survival fraction of 0.5). In 3 of these lines, increased RBE was correlated with alterations in the Fanconi anemia (FA)/BRCA pathway of DNA repair. In Calu-6 cells, the data pointed toward an FA pathway defect, leading to a previously unreported persistence of proton-induced RAD51 foci. The FA/BRCA-defective cells displayed a 25% increase in the size of subnuclear 53BP1 foci 18 hours after proton irradiation. Conclusions: Our cell line screen has revealed variations in proton RBE that are partly due to FA/BRCA pathway defects, suggesting that the use of a generic RBE for cancers should be revisited. We propose that functional biomarkers, such as size of residual 53BP1 foci, may be used to identify cancers with increased sensitivity to proton radiation.

  20. Hedonic tone and activation level in the mood-creativity link: toward a dual pathway to creativity model.

    Science.gov (United States)

    De Dreu, Carsten K W; Baas, Matthijs; Nijstad, Bernard A

    2008-05-01

    To understand when and why mood states influence creativity, the authors developed and tested a dual pathway to creativity model; creative fluency (number of ideas or insights) and originality (novelty) are functions of cognitive flexibility, persistence, or some combination thereof. Invoking work on arousal, psychophysiological processes, and working memory capacity, the authors argue that activating moods (e.g., angry, fearful, happy, elated) lead to more creative fluency and originality than do deactivating moods (e.g., sad, depressed, relaxed, serene). Furthermore, activating moods influence creative fluency and originality because of enhanced cognitive flexibility when tone is positive and because of enhanced persistence when tone is negative. Four studies with different mood manipulations and operationalizations of creativity (e.g., brainstorming, category inclusion tasks, gestalt completion tests) support the model. (c) 2008 APA, all rights reserved

  1. Biomarkers of effect in endocrine disruption: how to link a functional assay to an adverse outcome pathway

    Directory of Open Access Journals (Sweden)

    Stefano Lorenzetti

    2015-06-01

    Full Text Available The development of in vitro testing strategies may achieve a cost-effective generation of comprehensive datasets on a large number of chemicals, according to the requirements of the European Regulation REACH. Much emphasis is placed on in vitro methods based on subcellular mechanisms (e.g., nuclear receptor interaction, but it is necessary to define the predictive value of molecular or biochemical changes within an adverse outcome pathway (AOP. AOP pivots on the description of the flow from a molecular initiating event through a cascade of intermediate events needed to produce a specific adverse effect at organism level: downstream responses at cell level are, therefore, essential to define an AOP. Several in vitro assays are based on human cell lines representative of endocrine-targeted tissues (e.g., prostate and on functional biomarkers of clinical relevance (e.g., PSA secretion in human prostate epithelial cells. We discuss the implementation of such functional biomarkers in the AOP context.

  2. Pathways Linking Adverse Childhood Experiences to Cigarette Smoking Among Young Black Men: a Prospective Analysis of the Role of Sleep Problems and Delayed Reward Discounting.

    Science.gov (United States)

    Oshri, Assaf; Kogan, Steven; Liu, Sihong; Sweet, Lawrence; Mackillop, James

    2017-05-12

    African American men experience increases in smoking during the young adult transition. Exposure to childhood adversity, a risk factor which disproportionately affects African American men, has been identified as a robust precursor to health risk behavior in general and cigarette smoking in particular. The intermediate mechanisms that transmit the influence of early adversity to smoking behavior are not well understood. We tested a model of the escalation of smoking behaviors among young adult African American men, investigating sleep disturbance and delayed reward discounting as intermediate factors linking adverse childhood experiences with smoking. Hypotheses were tested with three waves of data (M age-T1 = 20.34, M age-T2 = 21.92, M age-T3 = 23.02) from 505 African American men living in rural counties in South Georgia. Men provided self-report data on their adverse childhood experiences, sleep problems, and smoking behavior using audio-assisted computer self-interviews. Men also completed a computer-based delayed reward discounting task. Structural equation modeling analyses supported our hypotheses: Adverse childhood experiences predicted poor sleep adequacy, which forecast increases in delayed reward discounting; discounting, in turn, predicted increased smoking. Significant indirect pathways were detected linking adversity to discounting via sleep adequacy and linking sleep adequacy to smoking via discounting. Prevention and intervention researchers can draw on these findings to develop programs that focus on sleep adequacy to reduce smoking in African American men exposed to childhood adversity.

  3. Sleep as a Mediator in the Pathway Linking Environmental Factors to Hypertension: A Review of the Literature

    Directory of Open Access Journals (Sweden)

    Oluwaseun A. Akinseye

    2015-01-01

    Full Text Available Environmental factors, such as noise exposure and air pollution, are associated with hypertension. These environmental factors also affect sleep quality. Given the growing evidence linking sleep quality with hypertension, the purpose of this review is to investigate the role of sleep as a key mediator in the association between hypertension and environmental factors. Through this narrative review of the extant literature, we highlight that poor sleep quality mediates the relationship between environmental factors and hypertension. The conceptual model proposed in this review offers opportunities to address healthcare disparities in hypertension among African Americans by highlighting the disparate impact that the predictors (environmental factors and mediator (sleep have on the African-American community. Understanding the impact of these factors is crucial since the main outcome variable (hypertension severely burdens the African-American community.

  4. Plant Aquaporin AtPIP1;4 Links Apoplastic H2O2 Induction to Disease Immunity Pathways.

    Science.gov (United States)

    Tian, Shan; Wang, Xiaobing; Li, Ping; Wang, Hao; Ji, Hongtao; Xie, Junyi; Qiu, Qinglei; Shen, Dan; Dong, Hansong

    2016-07-01

    Hydrogen peroxide (H2O2) is a stable component of reactive oxygen species, and its production in plants represents the successful recognition of pathogen infection and pathogen-associated molecular patterns (PAMPs). This production of H2O2 is typically apoplastic but is subsequently associated with intracellular immunity pathways that regulate disease resistance, such as systemic acquired resistance and PAMP-triggered immunity. Here, we elucidate that an Arabidopsis (Arabidopsis thaliana) aquaporin (i.e. the plasma membrane intrinsic protein AtPIP1;4) acts to close the cytological distance between H2O2 production and functional performance. Expression of the AtPIP1;4 gene in plant leaves is inducible by a bacterial pathogen, and the expression accompanies H2O2 accumulation in the cytoplasm. Under de novo expression conditions, AtPIP1;4 is able to mediate the translocation of externally applied H2O2 into the cytoplasm of yeast (Saccharomyces cerevisiae) cells. In plant cells treated with H2O2, AtPIP1;4 functions as an effective facilitator of H2O2 transport across plasma membranes and mediates the translocation of externally applied H2O2 from the apoplast to the cytoplasm. The H2O2-transport role of AtPIP1;4 is essentially required for the cytoplasmic import of apoplastic H2O2 induced by the bacterial pathogen and two typical PAMPs in the absence of induced production of intracellular H2O2 As a consequence, cytoplasmic H2O2 quantities increase substantially while systemic acquired resistance and PAMP-triggered immunity are activated to repress the bacterial pathogenicity. By contrast, loss-of-function mutation at the AtPIP1;4 gene locus not only nullifies the cytoplasmic import of pathogen- and PAMP-induced apoplastic H2O2 but also cancels the subsequent immune responses, suggesting a pivotal role of AtPIP1;4 in apocytoplastic signal transduction in immunity pathways. © 2016 American Society of Plant Biologists. All Rights Reserved.

  5. Integrated analysis of oral tongue squamous cell carcinoma identifies key variants and pathways linked to risk habits, HPV, clinical parameters and tumor recurrence [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Neeraja Krishnan

    2015-11-01

    Full Text Available Oral tongue squamous cell carcinomas (OTSCC are a homogeneous group of tumors characterized by aggressive behavior, early spread to lymph nodes and a higher rate of regional failure. Additionally, the incidence of OTSCC among younger population (<50yrs is on the rise; many of whom lack the typical associated risk factors of alcohol and/or tobacco exposure. We present data on single nucleotide variations (SNVs, indels, regions with loss of heterozygosity (LOH, and copy number variations (CNVs from fifty-paired oral tongue primary tumors and link the significant somatic variants with clinical parameters, epidemiological factors including human papilloma virus (HPV infection and tumor recurrence. Apart from the frequent somatic variants harbored in TP53, CASP8, RASA1, NOTCH and CDKN2A genes, significant amplifications and/or deletions were detected in chromosomes 6-9, and 11 in the tumors. Variants in CASP8 and CDKN2A were mutually exclusive. CDKN2A, PIK3CA, RASA1 and DMD variants were exclusively linked to smoking, chewing, HPV infection and tumor stage. We also performed a whole-genome gene expression study that identified matrix metalloproteases to be highly expressed in tumors and linked pathways involving arachidonic acid and NF-k-B to habits and distant metastasis, respectively. Functional knockdown studies in cell lines demonstrated the role of CASP8 in a HPV-negative OTSCC cell line. Finally, we identified a 38-gene minimal signature that predicts tumor recurrence using an ensemble machine-learning method. Taken together, this study links molecular signatures to various clinical and epidemiological factors in a homogeneous tumor population with a relatively high HPV prevalence.

  6. Corona cell RNA sequencing from individual oocytes revealed transcripts and pathways linked to euploid oocyte competence and live birth.

    Science.gov (United States)

    Parks, Jason C; Patton, Alyssa L; McCallie, Blair R; Griffin, Darren K; Schoolcraft, William B; Katz-Jaffe, Mandy G

    2016-05-01

    Corona cells surround the oocyte and maintain a close relationship through transzonal processes and gap junctions, and may be used to assess oocyte competence. In this study, the corona cell transcriptome of individual cumulus oocyte complexes (COCs) was investigated. Isolated corona cells were collected from COCs that developed into euploid blastocysts and were transferred in a subsequent frozen embryo transfer. Ten corona cell samples underwent RNA-sequencing to generate unique gene expression profiles. Live birth was compared with negative implantation after the transfer of a euploid blastocyst using bioinformatics and statistical analysis. Individual corona cell samples produced a mean of 21.2 million sequence reads, and 307 differentially expressed transcrpits (P corona cell transcriptome was successfully generated using RNA-sequencing. Key genes and signalling pathways were identified in association with implantation outcome after the transfer of a euploid blastocyst in a frozen embryo transfer. These data could provide novel biomarkers for the non-invasive assessment of embryo viability. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  7. Quantitative proteomics links metabolic pathways to specific developmental stages of the plant-pathogenic oomycete Phytophthora capsici.

    Science.gov (United States)

    Pang, Zhili; Srivastava, Vaibhav; Liu, Xili; Bulone, Vincent

    2017-04-01

    The oomycete Phytophthora capsici is a plant pathogen responsible for important losses to vegetable production worldwide. Its asexual reproduction plays an important role in the rapid propagation and spread of the disease in the field. A global proteomics study was conducted to compare two key asexual life stages of P. capsici, i.e. the mycelium and cysts, to identify stage-specific biochemical processes. A total of 1200 proteins was identified using qualitative and quantitative proteomics. The transcript abundance of some of the enriched proteins was also analysed by quantitative real-time polymerase chain reaction. Seventy-three proteins exhibited different levels of abundance between the mycelium and cysts. The proteins enriched in the mycelium are mainly associated with glycolysis, the tricarboxylic acid (or citric acid) cycle and the pentose phosphate pathway, providing the energy required for the biosynthesis of cellular building blocks and hyphal growth. In contrast, the proteins that are predominant in cysts are essentially involved in fatty acid degradation, suggesting that the early infection stage of the pathogen relies primarily on fatty acid degradation for energy production. The data provide a better understanding of P. capsici biology and suggest potential metabolic targets at the two different developmental stages for disease control. © 2016 BSPP AND JOHN WILEY & SONS LTD.

  8. Link Analysis

    Science.gov (United States)

    Donoho, Steve

    Link analysis is a collection of techniques that operate on data that can be represented as nodes and links. This chapter surveys a variety of techniques including subgraph matching, finding cliques and K-plexes, maximizing spread of influence, visualization, finding hubs and authorities, and combining with traditional techniques (classification, clustering, etc). It also surveys applications including social network analysis, viral marketing, Internet search, fraud detection, and crime prevention.

  9. Attenuated lipotoxicity and apoptosis is linked to exogenous and endogenous augmenter of liver regeneration by different pathways

    Science.gov (United States)

    Lupke, Madeleine; Ibrahim, Sara; Buechler, Christa; Lorenz, Julia; Ruemmele, Petra; Hofmann, Ute; Melter, Michael; Dayoub, Rania

    2017-01-01

    Nonalcoholic fatty liver disease (NAFLD) covers a spectrum from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. Free fatty acids (FFA) induce steatosis and lipo-toxicity and correlate with severity of NAFLD. In this study we aimed to investigate the role of exogenous and endogenous ALR (augmenter of liver regeneration) for FFA induced ER (endoplasmatic reticulum) -stress and lipoapoptosis. Primary human hepatocytes or hepatoma cells either treated with recombinant human ALR (rhALR, 15kDa) or expressing short form ALR (sfALR, 15kDa) were incubated with palmitic acid (PA) and analyzed for lipo-toxicity, -apoptosis, activation of ER-stress response pathways, triacylglycerides (TAG), mRNA and protein expression of lipid metabolizing genes. Both, exogenous rhALR and cytosolic sfALR reduced PA induced caspase 3 activity and Bax protein expression and therefore lipotoxicity. Endogenous sfALR but not rhALR treatment lowered TAG levels, diminished activation of ER-stress mediators C-Jun N-terminal kinase (JNK), X-box binding protein-1 (XBP1) and proapoptotic transcription factor C/EBP-homologous protein (CHOP), and reduced death receptor 5 protein expression. Cellular ALR exerts its lipid lowering and anti-apoptotic actions by enhancing FABP1, which binds toxic FFA, increasing mitochondrial β-oxidation by elevating the mitochondrial FFA transporter CPT1α, and decreasing ELOVL6, which delivers toxic FFA metabolites. We found reduced hepatic mRNA levels of ALR in a high fat diet mouse model, and of ALR and FOXA2, a transcription factor inducing ALR expression, in human steatotic as well as NASH liver samples, which may explain increased lipid deposition and reduced β-oxidation in NASH patients. Present study shows that exogenous and endogenous ALR reduce PA induced lipoapoptosis. Furthermore, cytosolic sfALR changes mRNA and protein expression of genes regulating lipid metabolism, reduces ER-stress finally impeding progression of NASH. PMID:28877220

  10. Visual agnosia.

    Science.gov (United States)

    Álvarez, R; Masjuan, J

    2016-03-01

    Visual agnosia is defined as an impairment of object recognition, in the absence of visual acuity or cognitive dysfunction that would explain this impairment. This condition is caused by lesions in the visual association cortex, sparing primary visual cortex. There are 2 main pathways that process visual information: the ventral stream, tasked with object recognition, and the dorsal stream, in charge of locating objects in space. Visual agnosia can therefore be divided into 2 major groups depending on which of the two streams is damaged. The aim of this article is to conduct a narrative review of the various visual agnosia syndromes, including recent developments in a number of these syndromes. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  11. The space - time - cube and the display of large movement data sets: the link between visualization strategies and cartographic design guidelines

    DEFF Research Database (Denmark)

    Kveladze, Irma; Kraak, Menno-Jan

    2011-01-01

    one should not only consider the nature of the data, but also the purpose of the particular phase of the workflow. To verify the above approach the visualization strategies and design guidelines are applied in a different use cases. The cases include: • The annotated space-time path A travel log...... is the Space-Time-cube (STC). The last decades the interest in this representation has increased considerable because of the technological opportunities. Despite the many domains where the STC is used, it is still unclear what the full possibilities and limitations of this graphic representation are. Its three...... consisting of a trajectory based on different modes of transport, with linked annotations. The challenge is to deal different scales and annotations. • The historical movement data The event ‘Napoleons march to Moscow’ contains fifteen space-time paths (STP) with attribute information. Challenge is to answer...

  12. Evidence against an X-linked locus close to DXS7 determining visual loss susceptibility in British and Italian families with Leber hereditary optic neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Sweeney, M.G.; Davis, M.B.; Lashwood, A.; Brockington, M.; Harding, A.E. (Institute of Neurology, Queen Square, London (United Kingdom)); Toscano, A. (Clinica Neurologica, Messina (Italy))

    1992-10-01

    Leber hereditary optic neuropathy (LHON) is associated with mutations of mtDNA, but two features of LHON pedigrees are not explicable solely on the basis of mitochondrial inheritance. There is a large excess of affected males, and not all males at risk develop the disease. These observations could be explained by the existence of an X-linked visual loss susceptibility gene. This hypothesis was supported by linkage studies in Finland, placing the susceptibility locus at DXS7, with a maximum lod score of 2.48 at a recombination fraction of 0. Linkage studies in 1 Italian and 12 British families with LHON, analyzed either together or separately depending on the associated mtDNA mutation, have excluded the presence of such a locus from an interval of about 30 cM around DXS7 in these kindreds, with a total lod score of -26.51 at a recombination fraction of 0. 17 refs., 2 figs., 1 tab.

  13. The cycad genotoxin MAM modulates brain cellular pathways involved in neurodegenerative disease and cancer in a DNA damage-linked manner.

    Directory of Open Access Journals (Sweden)

    Glen E Kisby

    Full Text Available Methylazoxymethanol (MAM, the genotoxic metabolite of the cycad azoxyglucoside cycasin, induces genetic alterations in bacteria, yeast, plants, insects and mammalian cells, but adult nerve cells are thought to be unaffected. We show that the brains of adult C57BL6 wild-type mice treated with a single systemic dose of MAM acetate display DNA damage (O⁶-methyldeoxyguanosine lesions, O⁶-mG that remains constant up to 7 days post-treatment. By contrast, MAM-treated mice lacking a functional gene encoding the DNA repair enzyme O⁶-mG DNA methyltransferase (MGMT showed elevated O⁶-mG DNA damage starting at 48 hours post-treatment. The DNA damage was linked to changes in the expression of genes in cell-signaling pathways associated with cancer, human neurodegenerative disease, and neurodevelopmental disorders. These data are consistent with the established developmental neurotoxic and carcinogenic properties of MAM in rodents. They also support the hypothesis that early-life exposure to MAM-glucoside (cycasin has an etiological association with a declining, prototypical neurodegenerative disease seen in Guam, Japan, and New Guinea populations that formerly used the neurotoxic cycad plant for food or medicine, or both. These findings suggest environmental genotoxins, specifically MAM, target common pathways involved in neurodegeneration and cancer, the outcome depending on whether the cell can divide (cancer or not (neurodegeneration. Exposure to MAM-related environmental genotoxins may have relevance to the etiology of related tauopathies, notably, Alzheimer's disease.

  14. Pathways to policy: Lessons learned in multisectoral collaboration for physical activity and built environment policy development from the Coalitions Linking Action and Science for Prevention (CLASP) initiative.

    Science.gov (United States)

    Politis, Christopher E; Mowat, David L; Keen, Deb

    2017-06-16

    The Canadian Partnership Against Cancer funded 12 large-scale knowledge to action cancer and chronic disease prevention projects between 2009 and 2016 through the Coalitions Linking Action and Science for Prevention (CLASP) initiative. Two projects, Healthy Canada by Design (HCBD) and Children's Mobility, Health and Happiness (CMHH), developed policies to address physical activity and the built environment through a multisectoral approach. A qualitative analysis involving a review of 183 knowledge products and 8 key informant interviews was conducted to understand what policy changes occurred, and the underlying critical success factors, through these projects. Both projects worked at the local level to change physical activity and built environment policy in 203 sites, including municipalities and schools. Both projects brought multisectoral expertise (e.g., public health, land use planning, transportation engineering, education, etc.) together to inform the development of local healthy public policy in the areas of land use, transportation and school travel planning. Through the qualitative analysis of the knowledge products and key informant interviews, 163 policies were attributed to HCBD and CMHH work. Fourteen "pathways to policy" were identified as critical success factors facilitating and accelerating the development and implementation of physical activity and built environment policy. Of the 14 pathways to policy, 8 had a focus on multisectoral collaboration. The lessons learned from the CLASP experience could support enhanced multisectoral collaborations to accelerate the development and implementation of physical activity and built environment policy in new jurisdictions across Canada and internationally.

  15. Elevated C-reactive protein in children from risky neighborhoods: evidence for a stress pathway linking neighborhoods and inflammation in children.

    Science.gov (United States)

    Broyles, Stephanie T; Staiano, Amanda E; Drazba, Kathryn T; Gupta, Alok K; Sothern, Melinda; Katzmarzyk, Peter T

    2012-01-01

    Childhood socioeconomic status is linked to adult cardiovascular disease and disease risk. One proposed pathway involves inflammation due to exposure to a stress-inducing neighborhood environment. Whether CRP, a marker of systemic inflammation, is associated with stressful neighborhood conditions among children is unknown. The sample included 385 children 5-18 years of age from 255 households and 101 census tracts. Multilevel logistic regression analyses compared children and adolescents with CRP levels >3 mg/L to those with levels ≤ 3 mg/L across neighborhood environments. Among children living in neighborhoods (census tracts) in the upper tertile of poverty or crime, 18.6% had elevated CRP levels, in contrast to 7.9% of children living in neighborhoods with lower levels of poverty and crime. Children from neighborhoods with the highest levels of either crime or poverty had 2.7 (95% CI: 1.2-6.2) times the odds of having elevated CRP levels when compared to children from other neighborhoods, independent of adiposity, demographic and behavioral differences. Children living in neighborhoods with high levels of poverty or crime had elevated CRP levels compared to children from other neighborhoods. This result is consistent with a psychosocial pathway favoring early development of cardiovascular risk that involves chronic stress from exposure to socially- and physically-disordered neighborhoods characteristic of poverty.

  16. Elevated C-reactive protein in children from risky neighborhoods: evidence for a stress pathway linking neighborhoods and inflammation in children.

    Directory of Open Access Journals (Sweden)

    Stephanie T Broyles

    Full Text Available BACKGROUND: Childhood socioeconomic status is linked to adult cardiovascular disease and disease risk. One proposed pathway involves inflammation due to exposure to a stress-inducing neighborhood environment. Whether CRP, a marker of systemic inflammation, is associated with stressful neighborhood conditions among children is unknown. METHODS AND RESULTS: The sample included 385 children 5-18 years of age from 255 households and 101 census tracts. Multilevel logistic regression analyses compared children and adolescents with CRP levels >3 mg/L to those with levels ≤ 3 mg/L across neighborhood environments. Among children living in neighborhoods (census tracts in the upper tertile of poverty or crime, 18.6% had elevated CRP levels, in contrast to 7.9% of children living in neighborhoods with lower levels of poverty and crime. Children from neighborhoods with the highest levels of either crime or poverty had 2.7 (95% CI: 1.2-6.2 times the odds of having elevated CRP levels when compared to children from other neighborhoods, independent of adiposity, demographic and behavioral differences. CONCLUSIONS: Children living in neighborhoods with high levels of poverty or crime had elevated CRP levels compared to children from other neighborhoods. This result is consistent with a psychosocial pathway favoring early development of cardiovascular risk that involves chronic stress from exposure to socially- and physically-disordered neighborhoods characteristic of poverty.

  17. The Nuclear Factor kappaB Pathway: A Link to the Immune System in the Radiation Response

    Science.gov (United States)

    Hellweg, Christine; Baumstark-Khan, Christa; Reitz, Guenther; Chishti, Arif Ali; Koch, Kristina; Manchanda, Kashish

    Understanding the cellular radiation response is an essential prerequisite for the risk assessment of astronauts’ space radiation exposure during long-term space missions and for effective countermeasure development. In addition to the space radiation effects, other environmental factors during space missions such as microgravity have profound effects on the body, e.g. suppression of the innate and acquired immune response. Exposure to ionizing radiation modulates immune responses in a complex dose-dependent pattern, with possible anti-inflammatory effects in the low dose range, expression of pro-inflammatory cytokines at moderate doses and immunosuppression after exposure to higher doses due to precursor cell death together with concomitant exacerbated innate immune responses. A central regulator in the immune system is the transcription factor Nuclear Factor kB (NF-kappaB). In this work, the role of NF-kappaB in the cellular response to space relevant radiation qualities was analyzed. It was shown with a recombinant human NF-kappaB reporter cell line that heavy ions with a linear energy transfer (LET) of 100-300 keV/µm have a nine times higher potential to activate the NF-kappaB pathway compared to X-rays (150 kV). ATM was essential for NF-kappaB activation in response to X-rays and heavy ions. Knockdown of the NF-kappaB subunit RelA (p65) resulted in higher sensitivity towards X-rays. Reverse Transcriptase real-time quantitative PCR (RT-qPCR) experiments showed that after exposure to radiation, NF-kappaB predominantly upregulates genes involved in intercellular communication processes, especially genes coding for chemokines, suggesting an important contribution of NF-kappaB in the molecular profile of the reaction to radiation, which can comprise features of inflammation and wound healing processes. This is process is strictly NF-kappaB dependent as this response is completely absent in RelA knockdown cells. These results show that the role of NF-kappaB in

  18. PRO40 is a scaffold protein of the cell wall integrity pathway, linking the MAP kinase module to the upstream activator protein kinase C.

    Directory of Open Access Journals (Sweden)

    Ines Teichert

    2014-09-01

    Full Text Available Mitogen-activated protein kinase (MAPK pathways are crucial signaling instruments in eukaryotes. Most ascomycetes possess three MAPK modules that are involved in key developmental processes like sexual propagation or pathogenesis. However, the regulation of these modules by adapters or scaffolds is largely unknown. Here, we studied the function of the cell wall integrity (CWI MAPK module in the model fungus Sordaria macrospora. Using a forward genetic approach, we found that sterile mutant pro30 has a mutated mik1 gene that encodes the MAPK kinase kinase (MAPKKK of the proposed CWI pathway. We generated single deletion mutants lacking MAPKKK MIK1, MAPK kinase (MAPKK MEK1, or MAPK MAK1 and found them all to be sterile, cell fusion-deficient and highly impaired in vegetative growth and cell wall stress response. By searching for MEK1 interaction partners via tandem affinity purification and mass spectrometry, we identified previously characterized developmental protein PRO40 as a MEK1 interaction partner. Although fungal PRO40 homologs have been implicated in diverse developmental processes, their molecular function is currently unknown. Extensive affinity purification, mass spectrometry, and yeast two-hybrid experiments showed that PRO40 is able to bind MIK1, MEK1, and the upstream activator protein kinase C (PKC1. We further found that the PRO40 N-terminal disordered region and the central region encompassing a WW interaction domain are sufficient to govern interaction with MEK1. Most importantly, time- and stress-dependent phosphorylation studies showed that PRO40 is required for MAK1 activity. The sum of our results implies that PRO40 is a scaffold protein for the CWI pathway, linking the MAPK module to the upstream activator PKC1. Our data provide important insights into the mechanistic role of a protein that has been implicated in sexual and asexual development, cell fusion, symbiosis, and pathogenicity in different fungal systems.

  19. Targeting allergen to FcgammaRI reveals a novel T(H)2 regulatory pathway linked to thymic stromal lymphopoietin receptor.

    Science.gov (United States)

    Hulse, Kathryn E; Reefer, Amanda J; Engelhard, Victor H; Patrie, James T; Ziegler, Steven F; Chapman, Martin D; Woodfolk, Judith A

    2010-01-01

    The molecule H22-Fel d 1, which targets cat allergen to FcgammaRI on dendritic cells (DCs), has the potential to treat cat allergy because of its T-cell modulatory properties. We sought to investigate whether the T-cell response induced by H22-Fel d 1 is altered in the presence of the T(H)2-promoting cytokine thymic stromal lymphopoietin (TSLP). Studies were performed in subjects with cat allergy with and without atopic dermatitis. Monocyte-derived DCs were primed with H22-Fel d 1 in the presence or absence of TSLP, and the resulting T-cell cytokine repertoire was analyzed by flow cytometry. The capacity for H22-Fel d 1 to modulate TSLP receptor expression on DCs was examined by flow cytometry in the presence or absence of inhibitors of Fc receptor signaling molecules. Surprisingly, TSLP alone was a weak inducer of T(H)2 responses irrespective of atopic status; however, DCs coprimed with TSLP and H22-Fel d 1 selectively and synergistically amplified T(H)2 responses in highly atopic subjects. This effect was OX40 ligand independent, pointing to an unconventional TSLP-mediated pathway. Expression of TSLP receptor was upregulated on atopic DCs primed with H22-Fel d 1 through a pathway regulated by FcgammaRI-associated signaling components, including src-related tyrosine kinases and Syk, as well as the downstream molecule phosphoinositide 3-kinase. Inhibition of TSLP receptor upregulation triggered by H22-Fel d 1 blocked TSLP-mediated T(H)2 responses. Discovery of a novel T(H)2 regulatory pathway linking FcgammaRI signaling to TSLP receptor upregulation and consequent TSLP-mediated effects questions the validity of receptor-targeted allergen vaccines. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  20. Evidence that the Entamoeba histolytica Mitochondrial Carrier Family Links Mitosomal and Cytosolic Pathways through Exchange of 3'-Phosphoadenosine 5'-Phosphosulfate and ATP.

    Science.gov (United States)

    Mi-ichi, Fumika; Nozawa, Akira; Yoshida, Hiroki; Tozawa, Yuzuru; Nozaki, Tomoyoshi

    2015-11-01

    Entamoeba histolytica, a microaerophilic protozoan parasite, possesses mitosomes. Mitosomes are mitochondrion-related organelles that have largely lost typical mitochondrial functions, such as those involved in the tricarboxylic acid cycle and oxidative phosphorylation. The biological roles of Entamoeba mitosomes have been a long-standing enigma. We previously demonstrated that sulfate activation, which is not generally compartmentalized to mitochondria, is a major function of E. histolytica mitosomes. Sulfate activation cooperates with cytosolic enzymes, i.e., sulfotransferases (SULTs), for the synthesis of sulfolipids, one of which is cholesteryl sulfate. Notably, cholesteryl sulfate plays an important role in encystation, an essential process in the Entamoeba life cycle. These findings identified a biological role for Entamoeba mitosomes; however, they simultaneously raised a new issue concerning how the reactions of the pathway, separated by the mitosomal membranes, cooperate. Here, we demonstrated that the E. histolytica mitochondrial carrier family (EhMCF) has the capacity to exchange 3'-phosphoadenosine 5'-phosphosulfate (PAPS) with ATP. We also confirmed the cytosolic localization of all the E. histolytica SULTs, suggesting that in Entamoeba, PAPS, which is produced through mitosomal sulfate activation, is translocated to the cytosol and becomes a substrate for SULTs. In contrast, ATP, which is produced through cytosolic pathways, is translocated into the mitosomes and is a necessary substrate for sulfate activation. Taking our findings collectively, we suggest that EhMCF functions as a PAPS/ATP antiporter and plays a crucial role in linking the mitosomal sulfate activation pathway to cytosolic SULTs for the production of sulfolipids. Copyright © 2015 Mi-ichi et al.

  1. SARS Coronavirus Papain-Like Protease Inhibits the TLR7 Signaling Pathway through Removing Lys63-Linked Polyubiquitination of TRAF3 and TRAF6.

    Science.gov (United States)

    Li, Shih-Wen; Wang, Ching-Ying; Jou, Yu-Jen; Huang, Su-Hua; Hsiao, Li-Hsin; Wan, Lei; Lin, Ying-Ju; Kung, Szu-Hao; Lin, Cheng-Wen

    2016-05-05

    Severe acute respiratory syndrome coronavirus (SARS-CoV) papain-like protease (PLPro) reportedly inhibits the production of type I interferons (IFNs) and pro-inflammatory cytokines in Toll-like receptor 3 (TLR3) and retinoic acid-inducible gene 1 (RIG-I) pathways. The study investigated the inhibitory effect and its antagonistic mechanism of SARS-CoV PLPro on TLR7-mediated cytokine production. TLR7 agonist (imiquimod (IMQ)) concentration-dependently induced activation of ISRE-, NF-κB- and AP-1-luciferase reporters, as well as the production of IFN-α, IFN-β, TNF-α, IL-6 and IL-8 in human promonocyte cells. However, SARS-CoV PLPro significantly inhibited IMQ-induced cytokine production through suppressing the activation of transcription factors IRF-3, NF-κB and AP-1. Western blot analysis with anti-Lys48 and anti-Lys63 ubiquitin antibodies indicated the SARS-CoV PLPro removed Lys63-linked ubiquitin chains of TRAF3 and TRAF6, but not Lys48-linked ubiquitin chains in un-treated and treated cells. The decrease in the activated state of TRAF3 and TRAF6 correlated with the inactivation of TBK1 in response to IMQ by PLPro. The results revealed that the antagonism of SARS-CoV PLPro on TLR7-mediated innate immunity was associated with the negative regulation of TRAF3/6-TBK1-IRF3/NF-κB/AP1 signals.

  2. The Quest for Converting Biorenewable Bifunctional α-Methylene-γ-butyrolactone into Degradable and Recyclable Polyester: Controlling Vinyl-Addition/Ring-Opening/Cross-Linking Pathways

    KAUST Repository

    Tang, Xiaoyan

    2016-10-04

    α-Methylene-γ-butyrolactone (MBL), a naturally occurring and biomass-sourced bifunctional monomer, contains both a highly reactive exocyclic C═C bond and a highly stable five-membered γ-butyrolactone ring. Thus, all previous work led to exclusive vinyl-addition polymerization (VAP) product P(MBL)VAP. Now, this work reverses this conventional chemoselectivity to enable the first ring-opening polymerization (ROP) of MBL, thereby producing exclusively unsaturated polyester P(MBL)ROP with Mn up to 21.0 kg/mol. This elusive goal was achieved through uncovering the thermodynamic, catalytic, and processing conditions. A third reaction pathway has also been discovered, which is a crossover propagation between VAP and ROP processes, thus affording cross-linked polymer P(MBL)CLP. The formation of the three types of polymers, P(MBL)VAP, P(MBL)CLP, and P(MBL)ROP, can be readily controlled by adjusting the catalyst (La)/initiator (ROH) ratio, which is determined by the unique chemoselectivity of the La–X (X = OR, NR2, R) group. The resulting P(MBL)ROP is degradable and can be readily postfunctionalized into cross-linked or thiolated materials but, more remarkably, can also be fully recycled back to its monomer thermochemically. Computational studies provided the theoretical basis for, and a mechanistic understanding of, the three different polymerization processes and the origin of the chemoselectivity.

  3. Visual Detection of Canine Parvovirus Based on Loop-Mediated Isothermal Amplification Combined with Enzyme-Linked Immunosorbent Assay and with Lateral Flow Dipstick

    Science.gov (United States)

    SUN, Yu-Ling; YEN, Chon-Ho; TU, Ching-Fu

    2013-01-01

    ABSTRACT Loop-mediated isothermal amplification (LAMP) combined with enzyme-linked immunosorbent assay (LAMP–ELISA) and with lateral flow dipstick (LAMP–LFD) are rapid, sensitive and specific methods for the visual detection of clinical pathogens. In this study, LAMP–ELISA and LAMP–LFD were developed for the visual detection of canine parvovirus (CPV). For LAMP, a set of four primers (biotin-labeled forward inner primers) was designed to specifically amplify a region of the VP2 gene of CPV. The optimum time and temperature for LAMP were 60 min and 65°C, respectively. The specific capture oligonucleotide probes, biotin-labeled CPV probe for LAMP–ELISA and fluorescein isothiocyanate-labeled CPV probe for LAMP–LFD were also designed for hybridization with LAMP amplicons on streptavidin-coated wells and LFD strips, respectively. For the comparison of detection sensitivity, conventional PCR and LAMP for CPV detection were also performed. The CPV detection limits by PCR, PCR–ELISA, LAMP, LAMP–ELISA and LAMP–LFD were 102, 102, 10−1, 10−1 and 10−1 TCID50/ml, respectively. In tests using artificially contaminated dog fecal samples, the samples with CPV inoculation levels of ≥1 TCID50/ml gave positive results by both LAMP–ELISA and LAMP–LFD. Our data indicated that both LAMP–ELISA and LAMP–LFD are promising as rapid, sensitive and specific methods for an efficient diagnosis of CPV infection. PMID:24334855

  4. Data-link and surface map traffic intent displays for NextGen 4DT and equivalent visual surface operations

    Science.gov (United States)

    Shelton, Kevin J.; Prinzel, Lawrence (Lance) J., III; Arthur, Jarvis (Trey) J., III; Jones, Denise R.; Allamandola, Angela S.; Bailey, Randall E.

    2009-05-01

    By 2025, U.S. air traffic is predicted to increase 3-fold and may strain the current air traffic management system, which may not be able to accommodate this growth. In response to this challenge, a consortium of industry, academia and government agencies have proposed a revolutionary new concept for U.S. aviation operations, termed the Next Generation Air Transportation System or "NextGen". Many key capabilities are being identified to enable NextGen, including the concept of "net-centric" operations whereby each aircraft and air services provider shares information to allow real-time adaptability to ever-changing factors such as weather, traffic, flight trajectories, and security. Data-link is likely to be the primary source of communication in NextGen. Because NextGen represents a radically different approach to air traffic management and requires a dramatic shift in the tasks, roles, and responsibilities for the flight deck, there are numerous research issues and challenges that must be overcome to ensure a safe, sustainable air transportation system. Flight deck display and crew-vehicle interaction concepts are being developed that proactively investigate and overcome potential technology and safety barriers that might otherwise constrain the full realization of NextGen.

  5. Visualizing Changes in Cdkn1c Expression Links Early-Life Adversity to Imprint Mis-regulation in Adults

    Directory of Open Access Journals (Sweden)

    Mathew Van de Pette

    2017-01-01

    Full Text Available Imprinted genes are regulated according to parental origin and can influence embryonic growth and metabolism and confer disease susceptibility. Here, we designed sensitive allele-specific reporters to non-invasively monitor imprinted Cdkn1c expression in mice and showed that expression was modulated by environmental factors encountered in utero. Acute exposure to chromatin-modifying drugs resulted in de-repression of paternally inherited (silent Cdkn1c alleles in embryos that was temporary and resolved after birth. In contrast, deprivation of maternal dietary protein in utero provoked permanent de-repression of imprinted Cdkn1c expression that was sustained into adulthood and occurred through a folate-dependent mechanism of DNA methylation loss. Given the function of imprinted genes in regulating behavior and metabolic processes in adults, these results establish imprinting deregulation as a credible mechanism linking early-life adversity to later-life outcomes. Furthermore, Cdkn1c-luciferase mice offer non-invasive tools to identify factors that disrupt epigenetic processes and strategies to limit their long-term impact.

  6. Aircraft dynamics, wind tunnel testing, and CFD flow visualization of two linked UAVs flying at close proximity

    Science.gov (United States)

    Cuji, Edgar A.; Lukaczyk, Trent W.; Garcia, Ephrahim

    2010-04-01

    This paper presents an analysis of close proximity aerodynamics and aircraft dynamics of two Linked UAVs. As the UAVs approach each other for wingtip docking there will be strong aerodynamic coupling between their wings tips. Lifting line and Computational Fluid Dynamics (CFD) simulation as well as wind tunnel testing of close proximity effects on lift, drag, roll, pitch and yaw moments for two UAV wings has been performed. The proximity aerodynamics effects between the UAVs wings were analyzed as a function of its relative position in all three directions. A look-up library of aerodynamic forces and moments for relative positions and angles of attack between the two UAVs has been developed. In this study we examined how the close proximity aerodynamics affects the dynamics and stability of the UAVs. The aircraft dynamics analysis is done in Simulink, which will include the close proximity aerodynamic look-up library. An aerodynamic disturbance intensity field will be generated, utilizing both simulation and wind tunnel data, to determine a trajectory for the two UAVs to approach each other for docking.

  7. GLAMM: Genome-Linked Application for Metabolic Maps

    Energy Technology Data Exchange (ETDEWEB)

    Bates, John; Chivian, Dylan; Arkin, Adam

    2011-05-29

    The Genome-Linked Application for Metabolic Maps (GLAMM) is a unified web interface for visualizing metabolic networks, reconstructing metabolic networks from annotated genome data, visualizing experimental data in the context of metabolic networks, and investigating the construction of novel, transgenic pathways. This simple, user-friendly interface is tightly integrated with the comparative genomics tools of MicrobesOnline. GLAMM is available for free to the scientific community at glamm.lbl.gov.

  8. CellPublisher: a web platform for the intuitive visualization and sharing of metabolic, signalling and regulatory pathways.

    Science.gov (United States)

    Flórez, Lope A; Lammers, Christoph R; Michna, Raphael; Stülke, Jörg

    2010-12-01

    Systems biology relies increasingly on collaborations between several groups with different expertise. Therefore, the systems biology community is adopting standards that allow effective communication of concepts, as well as transmission and processing of pathway information. The Systems Biology Graphical Notation (SBGN) is a graphical language for biological pathways that has both a biological as well as a computational meaning. The program CellDesigner allows the codification of biological phenomena in an SBGN compliant form. CellPublisher is a web server that allows the conversion of CellDesigner files to web-based navigatable diagrams based on the user interface of Google maps. Thus, CellPublisher complements CellDesigner by facilitating the understanding of complex diagrams and by providing the possibility to share any CellDesigner diagram online with collaborators and get their feedback. Due to the intuitive interface of the online diagrams, CellPublisher serves as a basis for discovery of novel properties of the modelled networks. The freely available web server and the documentation can be accessed at: http://cellpublisher.gobics.de/. The source code and the offline version for Microsoft Windows are freely available at http://sourceforge.net/projects/cellpublisher/. jstuelk@gwdg.de Supplementary data are available at Bioinformatics online.

  9. S.E. Mitchell Vascular Anomalies Flow Chart (SEMVAFC): a visual pathway combining clinical and imaging findings for classification of soft-tissue vascular anomalies.

    Science.gov (United States)

    Tekes, A; Koshy, J; Kalayci, T O; Puttgen, K; Cohen, B; Redett, R; Mitchell, S E

    2014-05-01

    Classification of vascular anomalies (VAs) is challenging due to overlapping clinical symptoms, confusing terminology in the literature and unfamiliarity with this complex entity. It is important to recognize that VAs include two distinct entities, vascular tumours (VTs) and vascular malformations (VaMs). In this article, we describe SE Mitchell Vascular Anomalies Flow Chart (SEMVAFC), which arises from a multidisciplinary approach that incorporates clinical symptoms, physical examination and magnetic resonance imaging (MRI) findings to establish International Society for the Study of Vascular Anomalies (ISSVA)-based classification of the VAs. SEMVAFC provides a clear visual pathway for physicians to accurately diagnose Vas, which is important as treatment, management, and prognosis differ between VTs and VaMs. Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  10. Medications influencing central cholinergic pathways affect fixation stability, saccadic response time and associated eye movement dynamics during a temporally-cued visual reaction time task.

    Science.gov (United States)

    Naicker, Preshanta; Anoopkumar-Dukie, Shailendra; Grant, Gary D; Modenese, Luca; Kavanagh, Justin J

    2017-02-01

    Anticholinergic medications largely exert their effects due to actions on the muscarinic receptor, which mediates the functions of acetylcholine in the peripheral and central nervous systems. In the central nervous system, acetylcholine plays an important role in the modulation of movement. This study investigated the effects of over-the-counter medications with varying degrees of central anticholinergic properties on fixation stability, saccadic response time and the dynamics associated with this eye movement during a temporally-cued visual reaction time task, in order to establish the significance of central cholinergic pathways in influencing eye movements during reaction time tasks. Twenty-two participants were recruited into the placebo-controlled, human double-blind, four-way crossover investigation. Eye tracking technology recorded eye movements while participants reacted to visual stimuli following temporally informative and uninformative cues. The task was performed pre-ingestion as well as 0.5 and 2 h post-ingestion of promethazine hydrochloride (strong centrally acting anticholinergic), hyoscine hydrobromide (moderate centrally acting anticholinergic), hyoscine butylbromide (anticholinergic devoid of central properties) and a placebo. Promethazine decreased fixation stability during the reaction time task. In addition, promethazine was the only drug to increase saccadic response time during temporally informative and uninformative cued trials, whereby effects on response time were more pronounced following temporally informative cues. Promethazine also decreased saccadic amplitude and increased saccadic duration during the temporally-cued reaction time task. Collectively, the results of the study highlight the significant role that central cholinergic pathways play in the control of eye movements during tasks that involve stimulus identification and motor responses following temporal cues.

  11. Virtual reality presurgical planning for cerebral gliomas adjacent to motor pathways in an integrated 3-D stereoscopic visualization of structural MRI and DTI tractography.

    Science.gov (United States)

    Qiu, Tian-ming; Zhang, Yi; Wu, Jin-Song; Tang, Wei-Jun; Zhao, Yao; Pan, Zhi-Guang; Mao, Ying; Zhou, Liang-Fu

    2010-11-01

    Resection of gliomas invading primary motor cortex and subcortical motor pathway is difficult in both surgical decision-making and functional outcome prediction. In this study, magnetic resonance (MR) diffusion tensor imaging (DTI) data were used to perform tractography to visualize pyramidal tract (PT) along its whole length in a stereoscopic virtual reality (VR) environment. The potential value of its clinical application was evaluated. Both three-dimensional (3-D) magnetic resonance imaging (MRI) and DTI datasets were obtained from 45 eligible patients with suspected cerebral gliomas and then transferred to the VR system (Dextroscope; Volume Interactions Pte. Ltd., Singapore). The cortex and tumor were segmented and reconstructed via MRI, respectively, while the tractographic PTs were reconstructed via DTI. All those were presented in a stereoscopic 3-D display synchronously, for the purpose of patient-specific presurgical planning and surgical simulation in each case. The relationship between increasing amplitude of the number of effective fibers of PT (EPT) at affected sides and the patients' Karnofsky Performance Scale (KPS) at 6 months was addressed out. In VR presurgical planning for gliomas, surgery was aided by stereoscopic 3-D visualizing the relative position of the PTs and a tumor. There was no significant difference between pre- and postsurgical EPT in this population. A positive relationship was proved between EPT increasing amplitude and 6-month KPS. 3-D stereoscopic visualization of tractography in this VR environment enhances the operators to well understand the anatomic information of intra-axial tumor contours and adjacent PT, results in surgical trajectory optimization initially, and maximal safe tumor resection finally. In accordance to the EPT increasing amplitude, surgeon can predict the long-term motor functional outcome.

  12. Candidate pathways linking inducible nitric oxide synthase to a basal-like transcription pattern and tumor progression in human breast cancer.

    Science.gov (United States)

    Ambs, Stefan; Glynn, Sharon A

    2011-02-15

    Inducible nitric oxide synthase (NOS2) is an inflammation responsive enzyme (EC 1.14.13.39) that is induced during acute and chronic inflammation and tissue injury as part of the host defense and wound healing process. NOS2 up-regulation leads to increased nitric oxide (NO) production, the means by which this enzyme can initiate NO-dependent signal transduction, influence the redox state of cells and induce modifications of proteins, lipids, and DNA. Aberrant expression of NOS2 has been observed in many types of human tumors. In breast cancer, increased NOS2 is associated with markers of poor outcome and decreased survival. Growth factor and cytokine signaling, tissue remodeling, NF-kB activation, and hypoxia are candidate mechanisms that induce NOS2 in tumor epithelial and tumor-infiltrating cells. NOS2 induction will trigger the release of variable amounts of NO into the tumor microenvironment and can activate oncogenic pathways, including the Akt, epidermal growth factor receptor and c-Myc signaling pathways, and stimulate tumor microvascularization. Constitutively increased NO levels may also select for mutant p53 cells to overcome the tumor suppressor function of NO-activated wild-type p53. More recent findings suggest that NO induces stem cell-like tumor characteristics in breast cancer. In this review, we will discuss the effects of NO in tumor biology and disease progression with an emphasis on breast cancer, and will examine the mechanisms that link increased NO to a basal-like transcription pattern in human breast tumors and poor disease outcome.

  13. Magnolol Affects Cellular Proliferation, Polyamine Biosynthesis and Catabolism-Linked Protein Expression and Associated Cellular Signaling Pathways in Human Prostate Cancer Cells in vitro

    Directory of Open Access Journals (Sweden)

    Brendan T. McKeown

    2015-01-01

    Full Text Available Background: Prostate cancer is the most commonly diagnosed form of cancer in men in Canada and the United States. Both genetic and environmental factors contribute to the development and progression of many cancers, including prostate cancer. Context and purpose of this study: This study investigated the effects of magnolol, a compound found in the roots and bark of the magnolia tree Magnolia officinalis, on cellular proliferation and proliferation-linked activities of PC3 human prostate cancer cells in vitro. Results: PC3 cells exposed to magnolol at a concentration of 80 μM for 6 hours exhibited decreased protein expression of ornithine decarboxylase, a key regulator in polyamine biosynthesis, as well as affecting the expression of other proteins involved in polyamine biosynthesis and catabolism. Furthermore, protein expression of the R2 subunit of ribonucleotide reductase, a key regulatory protein associated with DNA synthesis, was significantly decreased. Finally, the MAPK (mitogen-activated protein kinase, PI3K (phosphatidylinositol 3-kinase, NFκB (nuclear factor of kappa-light-chain-enhancer of activated B cells and AP-1 (activator protein 1 cellular signaling pathways were assayed to determine which, if any, of these pathways magnolol exposure would alter. Protein expressions of p-JNK-1 and c-jun were significantly increased while p-p38, JNK-1/2, PI3Kp85, p-PI3Kp85, p-Akt, NFκBp65, p-IκBα and IκBα protein expressions were significantly decreased. Conclusions: These alterations further support the anti-proliferative effects of magnolol on PC3 human prostate cancer cells in vitro and suggest that magnolol may have potential as a novel anti-prostate cancer agent.

  14. Perception of biological motion in visual agnosia

    National Research Council Canada - National Science Library

    Huberle, Elisabeth; Rupek, Paul; Lappe, Markus; Karnath, Hans-Otto

    2012-01-01

    ...") visual information processing pathway. Patients with brain damage of the ventral pathway typically present with signs of visual agnosia, the inability to identify and discriminate objects by visual exploration, but show normal perception...

  15. Genome Expression Pathway Analysis Tool – Analysis and visualization of microarray gene expression data under genomic, proteomic and metabolic context

    Directory of Open Access Journals (Sweden)

    Engelmann Julia C

    2007-06-01

    Full Text Available Abstract Background Regulation of gene expression is relevant to many areas of biology and medicine, in the study of treatments, diseases, and developmental stages. Microarrays can be used to measure the expression level of thousands of mRNAs at the same time, allowing insight into or comparison of different cellular conditions. The data derived out of microarray experiments is highly dimensional and often noisy, and interpretation of the results can get intricate. Although programs for the statistical analysis of microarray data exist, most of them lack an integration of analysis results and biological interpretation. Results We have developed GEPAT, Genome Expression Pathway Analysis Tool, offering an analysis of gene expression data under genomic, proteomic and metabolic context. We provide an integration of statistical methods for data import and data analysis together with a biological interpretation for subsets of probes or single probes on the chip. GEPAT imports various types of oligonucleotide and cDNA array data formats. Different normalization methods can be applied to the data, afterwards data annotation is performed. After import, GEPAT offers various statistical data analysis methods, as hierarchical, k-means and PCA clustering, a linear model based t-test or chromosomal profile comparison. The results of the analysis can be interpreted by enrichment of biological terms, pathway analysis or interaction networks. Different biological databases are included, to give various information for each probe on the chip. GEPAT offers no linear work flow, but allows the usage of any subset of probes and samples as a start for a new data analysis. GEPAT relies on established data analysis packages, offers a modular approach for an easy extension, and can be run on a computer grid to allow a large number of users. It is freely available under the LGPL open source license for academic and commercial users at http

  16. The dynamics of individual nucleosomes controls the chromatin condensation pathway: direct atomic force microscopy visualization of variant chromatin.

    Science.gov (United States)

    Montel, Fabien; Menoni, Hervé; Castelnovo, Martin; Bednar, Jan; Dimitrov, Stefan; Angelov, Dimitar; Faivre-Moskalenko, Cendrine

    2009-07-22

    Chromatin organization and dynamics is studied at scales ranging from single nucleosome to nucleosomal array by using a unique combination of biochemical assays, single molecule imaging technique, and numerical modeling. We show that a subtle modification in the nucleosome structure induced by the histone variant H2A.Bbd drastically modifies the higher order organization of the nucleosomal arrays. Importantly, as directly visualized by atomic force microscopy, conventional H2A nucleosomal arrays exhibit specific local organization, in contrast to H2A.Bbd arrays, which show "beads on a string" structure. The combination of systematic image analysis and theoretical modeling allows a quantitative description relating the observed gross structural changes of the arrays to their local organization. Our results suggest strongly that higher-order organization of H1-free nucleosomal arrays is determined mainly by the fluctuation properties of individual nucleosomes. Moreover, numerical simulations suggest the existence of attractive interactions between nucleosomes to provide the degree of compaction observed for conventional chromatin fibers.

  17. Nucleophilic cross-linked, dextran coated iron oxide nanoparticles as basis for molecular imaging: synthesis, characterization, visualization and comparison with previous product.

    Science.gov (United States)

    Borny, Robert; Lechleitner, Thomas; Schmiedinger, Thomas; Hermann, Martin; Tessadri, Richard; Redhammer, Günther; Neumüller, Josef; Kerjaschki, Dontscho; Berzaczy, Gundula; Erman, Gürkan; Popovic, Martin; Lammer, Johannes; Funovics, Martin

    2015-01-01

    We present a new synthesis protocol for a multivalent, multimodality, nucleophilic nanoparticle ideal for in vivo imaging. Stability requirements necessitated covalent cross-linking of the carbohydrate cage, easy functionalization the introduction of sterically accessible amine groups. The new protocol aimed at more uniform particle size, less clustering and superior magnetic properties compared with commercial nanoparticles. Particles were precipitated from Fe(2+) and Fe(3+) in the presence of 10 kDa dextran monodispersed from the aerosol phase. Cross-linking was achieved with epichlorhydrin, nuclophilication with NH3, purification with ultrafiltration and dialysis. Particles and a commercial product (Rienso®, Takeda Pharma) underwent physicochemical characterizations. Biocompatibility was assessed by Resazurin on LLC-PK1 cells; the internalization rate was measured for three cell lines (HAEC, HASMC, HT29). Core size was 5.61 ± 1.25 nm; hydrodynamic size was 49.56 ± 11.73 nm. The number of sterically accessible amine groups averaged 9.9. The cores showed cubic magnetite structure. Values of r1 and r2 were 10.9 and 148.17 mM(-1) s(-1). Cellular viability was unchanged after incubation. Introduction of aerosol phase dextran resulted in a reduction of the overall hydrodynamic diameter and a narrower size distribution of the synthesized particles. Electron tomography visualized for the first time the postulated 'hairy layer' of the dextran coating and enabled the measurement of the overall diameter of 100.2 ± 7.92 nm. The resulting nanoparticle is biocompatible, functionalizable and detectable at nanomolar concentrations with MRI and optical imaging. It can potentially serve as a platform for multimodal molecular imaging and targeted therapy approaches. Copyright © 2014 John Wiley & Sons, Ltd.

  18. A Redox-Active, Compact Molecule for Cross-Linking Amyloidogenic Peptides into Nontoxic, Off-Pathway Aggregates: In Vitro and In Vivo Efficacy and Molecular Mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Derrick, Jeffrey S.; Kerr, Richard A.; Nam, Younwoo; Oh, Shin Bi; Lee, Hyuck Jin; Earnest, Kaylin G.; Suh, Nayoung; Peck, Kristy L.; Ozbil, Mehmet; Korshavn, Kyle J.; Ramamoorthy, Ayyalusamy; Prabhakar, Rajeev; Merino, Edward J.; Shearer, Jason; Lee, Joo-Yong; Ruotolo, Brandon T.; Lim, Mi Hee

    2015-11-25

    Chemical reagents targeting and controlling amyloidogenic peptides have received much attention for helping identify their roles in the pathogenesis of protein-misfolding disorders. Herein, we report a novel strategy for redirecting amyloidogenic peptides into nontoxic, off-pathway aggregates, which utilizes redox properties of a small molecule (DMPD, N,N-dimethyl-p-phenylenediamine) to trigger covalent adduct formation with the peptide. In addition, for the first time, biochemical, biophysical, and molecular dynamics simulation studies have been performed to demonstrate a mechanistic understanding for such an interaction between a small molecule (DMPD) and amyloid-β (Aβ) and its subsequent anti-amyloidogenic activity, which, upon its transformation, generates ligand–peptide adducts via primary amine-dependent intramolecular cross-linking correlated with structural compaction. Furthermore, in vivo efficacy of DMPD toward amyloid pathology and cognitive impairment was evaluated employing 5xFAD mice of Alzheimer’s disease (AD). Such a small molecule (DMPD) is indicated to noticeably reduce the overall cerebral amyloid load of soluble Aβ forms and amyloid deposits as well as significantly improve cognitive defects in the AD mouse model. Overall, our in vitro and in vivo studies of DMPD toward Aβ with the first molecular-level mechanistic investigations present the feasibility of developing new, innovative approaches that employ redox-active compounds without the structural complexity as next-generation chemical tools for amyloid management.

  19. A Kinase Anchoring Protein 9 Is a Novel Myosin VI Binding Partner That Links Myosin VI with the PKA Pathway in Myogenic Cells

    Directory of Open Access Journals (Sweden)

    Justyna Karolczak

    2015-01-01

    Full Text Available Myosin VI (MVI is a unique motor protein moving towards the minus end of actin filaments unlike other known myosins. Its important role has recently been postulated for striated muscle and myogenic cells. Since MVI functions through interactions of C-terminal globular tail (GT domain with tissue specific partners, we performed a search for MVI partners in myoblasts and myotubes using affinity chromatography with GST-tagged MVI-GT domain as a bait. A kinase anchoring protein 9 (AKAP9, a regulator of PKA activity, was identified by means of mass spectrometry as a possible MVI interacting partner both in undifferentiated and differentiating myoblasts and in myotubes. Coimmunoprecipitation and proximity ligation assay confirmed that both proteins could interact. MVI and AKAP9 colocalized at Rab5 containing early endosomes. Similarly to MVI, the amount of AKAP9 decreased during myoblast differentiation. However, in MVI-depleted cells, both cAMP and PKA levels were increased and a change in the MVI motor-dependent AKAP9 distribution was observed. Moreover, we found that PKA phosphorylated MVI-GT domain, thus implying functional relevance of MVI-AKAP9 interaction. We postulate that this novel interaction linking MVI with the PKA pathway could be important for targeting AKAP9-PKA complex within cells and/or providing PKA to phosphorylate MVI tail domain.

  20. Molecular pathways

    DEFF Research Database (Denmark)

    Cox, Thomas R; Erler, Janine Terra

    2014-01-01

    that 45% of deaths in the developed world are linked to fibrotic disease. Fibrosis and cancer are known to be inextricably linked; however, we are only just beginning to understand the common and overlapping molecular pathways between the two. Here, we discuss what is known about the intersection...... of fibrosis and cancer, with a focus on cancer metastasis, and highlight some of the exciting new potential clinical targets that are emerging from analysis of the molecular pathways associated with these two devastating diseases. Clin Cancer Res; 20(14); 3637-43. ©2014 AACR....

  1. Direct Visualization of RNA-DNA Primer Removal from Okazaki Fragments Provides Support for Flap Cleavage and Exonucleolytic Pathways in Eukaryotic Cells.

    Science.gov (United States)

    Liu, Bochao; Hu, Jiazhi; Wang, Jingna; Kong, Daochun

    2017-03-24

    During DNA replication in eukaryotic cells, short single-stranded DNA segments known as Okazaki fragments are first synthesized on the lagging strand. The Okazaki fragments originate from ∼35-nucleotide-long RNA-DNA primers. After Okazaki fragment synthesis, these primers must be removed to allow fragment joining into a continuous lagging strand. To date, the models of enzymatic machinery that removes the RNA-DNA primers have come almost exclusively from biochemical reconstitution studies and some genetic interaction assays, and there is little direct evidence to confirm these models. One obstacle to elucidating Okazaki fragment processing has been the lack of methods that can directly examine primer removal in vivo In this study, we developed an electron microscopy assay that can visualize nucleotide flap structures on DNA replication forks in fission yeast ( Schizosaccharomyces pombe ). With this assay, we first demonstrated the generation of flap structures during Okazaki fragment processing in vivo The mean and median lengths of the flaps in wild-type cells were ∼51 and ∼41 nucleotides, respectively. We also used yeast mutants to investigate the impact of deleting key DNA replication nucleases on these flap structures. Our results provided direct in vivo evidence for a previously proposed flap cleavage pathway and the critical function of Dna2 and Fen1 in cleaving these flaps. In addition, we found evidence for another previously proposed exonucleolytic pathway involving RNA-DNA primer digestion by exonucleases RNase H2 and Exo1. Taken together, our observations suggest a dual mechanism for Okazaki fragment maturation in lagging strand synthesis and establish a new strategy for interrogation of this fascinating process. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Visual Impairment, Including Blindness

    Science.gov (United States)

    ... Who Knows What? (log-in required) Select Page Visual Impairment, Including Blindness Mar 31, 2017 Links updated, ... doesn’t wear his glasses. Back to top Visual Impairments in Children Vision is one of our ...

  3. The Visual System

    Medline Plus

    Full Text Available ... USAJobs Home > NEI for Kids > The Visual System All About Vision About the Eye Ask a Scientist ... Tricks Links to More Information Optical Illusions Printables The Visual System Ever wonder how your eyes work? ...

  4. Visualization of Social Networks

    NARCIS (Netherlands)

    Boertjes, E.M.; Kotterink, B.; Jager, E.J.

    2011-01-01

    Current visualizations of social networks are mostly some form of node-link diagram. Depending on the type of social network, this can be some treevisualization with a strict hierarchical structure or a more generic network visualization.

  5. Formal modeling and analysis of the hexosamine biosynthetic pathway: role of O-linked N-acetylglucosamine transferase in oncogenesis and cancer progression

    Directory of Open Access Journals (Sweden)

    Muhammad Tariq Saeed

    2016-09-01

    Full Text Available The alteration of glucose metabolism, through increased uptake of glucose and glutamine addiction, is essential to cancer cell growth and invasion. Increased flux of glucose through the Hexosamine Biosynthetic Pathway (HBP drives increased cellular O-GlcNAcylation (hyper-O-GlcNAcylation and contributes to cancer progression by regulating key oncogenes. However, the association between hyper-O-GlcNAcylation and activation of these oncogenes remains poorly characterized. Here, we implement a qualitative modeling framework to analyze the role of the Biological Regulatory Network in HBP activation and its potential effects on key oncogenes. Experimental observations are encoded in a temporal language format and model checking is applied to infer the model parameters and qualitative model construction. Using this model, we discover step-wise genetic alterations that promote cancer development and invasion due to an increase in glycolytic flux, and reveal critical trajectories involved in cancer progression. We compute delay constraints to reveal important associations between the production and degradation rates of proteins. O-linked N-acetylglucosamine transferase (OGT, an enzyme used for addition of O-GlcNAc during O-GlcNAcylation, is identified as a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc. Silencing of the OGT and c-Myc loop decreases glycolytic flux and leads to programmed cell death. Results of network analyses also identify a significant cycle that highlights the role of p53-Mdm2 circuit oscillations in cancer recovery and homeostasis. Together, our findings suggest that the OGT and c-Myc feedback loop is critical in tumor progression, and targeting these mediators may provide a mechanism-based therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer.

  6. Formal modeling and analysis of the hexosamine biosynthetic pathway: role of O-linked N-acetylglucosamine transferase in oncogenesis and cancer progression.

    Science.gov (United States)

    Saeed, Muhammad Tariq; Ahmad, Jamil; Kanwal, Shahzina; Holowatyj, Andreana N; Sheikh, Iftikhar A; Zafar Paracha, Rehan; Shafi, Aamir; Siddiqa, Amnah; Bibi, Zurah; Khan, Mukaram; Ali, Amjad

    2016-01-01

    The alteration of glucose metabolism, through increased uptake of glucose and glutamine addiction, is essential to cancer cell growth and invasion. Increased flux of glucose through the Hexosamine Biosynthetic Pathway (HBP) drives increased cellular O-GlcNAcylation (hyper-O-GlcNAcylation) and contributes to cancer progression by regulating key oncogenes. However, the association between hyper-O-GlcNAcylation and activation of these oncogenes remains poorly characterized. Here, we implement a qualitative modeling framework to analyze the role of the Biological Regulatory Network in HBP activation and its potential effects on key oncogenes. Experimental observations are encoded in a temporal language format and model checking is applied to infer the model parameters and qualitative model construction. Using this model, we discover step-wise genetic alterations that promote cancer development and invasion due to an increase in glycolytic flux, and reveal critical trajectories involved in cancer progression. We compute delay constraints to reveal important associations between the production and degradation rates of proteins. O-linked N-acetylglucosamine transferase (OGT), an enzyme used for addition of O-GlcNAc during O-GlcNAcylation, is identified as a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc. Silencing of the OGT and c-Myc loop decreases glycolytic flux and leads to programmed cell death. Results of network analyses also identify a significant cycle that highlights the role of p53-Mdm2 circuit oscillations in cancer recovery and homeostasis. Together, our findings suggest that the OGT and c-Myc feedback loop is critical in tumor progression, and targeting these mediators may provide a mechanism-based therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer.

  7. DMPD: Toll-like receptor 3: a link between toll-like receptor, interferon and viruses. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15031527 Toll-like receptor 3: a link between toll-like receptor, interferon and virus... (.csml) Show Toll-like receptor 3: a link between toll-like receptor, interferon and viruses. PubmedID 1503...1527 Title Toll-like receptor 3: a link between toll-like receptor, interferon and virus

  8. Identification of intergenic trans-regulatory RNAs containing a disease-linked SNP sequence and targeting cell cycle progression/differentiation pathways in multiple common human disorders.

    Science.gov (United States)

    Glinskii, Anna B; Ma, Jun; Ma, Shuang; Grant, Denise; Lim, Chang-Uk; Sell, Stewart; Glinsky, Gennadi V

    2009-12-01

    Meta-analysis of genomic coordinates of SNP variations identified in genome-wide association studies (GWAS) of up to 712,253 samples (comprising 221,158 disease cases, 322,862 controls, and 168,233 case/control subjects of obesity GWAS) reveals that 39% of SNPs associated with 22 common human disorders are located within intergenic regions. Chromatin-state maps based on H3K4me3-H3K36me3 signatures show that many intergenic disease-linked SNPs are located within the boundaries of the K4-K36 domains, suggesting that SNP-harboring genomic regions are transcribed. Here we report identification of 13 trans-regulatory RNAs (transRNAs) 100 to 200 nucleotides in length containing intergenic SNP sequences associated with Crohn's disease, rheumatoid arthritis, type 1 diabetes, vitiligo, hypertension and multiple types of epithelial malignancies (prostate, breast, ovarian and colorectal cancers). We demonstrate that NALP1 loci intergenic SNP sequence, rs2670660, is expressed in human cells and may contribute to clinical manifestations of autoimmune and autoimflammatory phenotypes by generating distinct allelic variants of transRNAs. Stable expression of allele-specific sense and anti-sense variants of transRNAs markedly alters cellular behavior, affect cell cycle progression, and interfere with monocyte/macrophage transdifferentiation. On a molecular level, forced expression of allele-specific sense and anti-sense variants of transRNAs asserts allele-specific genome-wide effects on abundance of hundreds microRNAs and mRNAs. Using lentiviral gene transfer, microarray and Q-RT-PCR technologies, we identify rs2670660 allele-specific gene expression signatures (GES) which appear useful for detecting the activated states of innate immunity/inflammasome pathways in approximately 700 clinical samples from 185 control subjects and 350 patients diagnosed with nine common human disorders, including Crohn's disease, ulcerative colitis, rheumatoid arthritis, Huntington disease, autism

  9. Visual memory profile in 22q11.2 microdeletion syndrome: are there differences in performance and neurobiological substrates between tasks linked to ventral and dorsal visual brain structures? A cross-sectional and longitudinal study.

    Science.gov (United States)

    Bostelmann, Mathilde; Schneider, Maude; Padula, Maria Carmela; Maeder, Johanna; Schaer, Marie; Scariati, Elisa; Debbané, Martin; Glaser, Bronwyn; Menghetti, Sarah; Eliez, Stephan

    2016-01-01

    Children affected by the 22q11.2 deletion syndrome (22q11.2DS) have a specific neuropsychological profile with strengths and weaknesses in several cognitive domains. Specifically, previous evidence has shown that patients with 22q11.2DS have more difficulties memorizing faces and visual-object characteristics of stimuli. In contrast, they have better performance in visuo-spatial memory tasks. The first focus of this study was to replicate these results in a larger sample of patients affected with 22q11.2DS and using a range of memory tasks. Moreover, we analyzed if the deficits were related to brain morphology in the structures typically underlying these abilities (ventral and dorsal visual streams). Finally, since the longitudinal development of visual memory is not clearly characterized in 22q11.2DS, we investigated its evolution from childhood to adolescence. Seventy-one patients with 22q11.2DS and 49 control individuals aged between 9 and 16 years completed the Benton Visual Retention Test (BVRT) and specific subtests assessing visual memory from the Children's Memory Scale (CMS). The BVRT was used to compute spatial and object memory errors. For the CMS, specific subtests were classified into ventral, dorsal, and mixed subtests. Longitudinal data were obtained from a subset of 26 patients and 22 control individuals. Cross-sectional results showed that patients with 22q11.2DS were impaired in all visual memory measures, with stronger deficits in visual-object memory and memory of faces, compared to visuo-spatial memory. No correlations between morphological brain impairments and visual memory were found in patients with 22q11.2DS. Longitudinal findings revealed that participants with 22q11.2DS made more object memory errors than spatial memory errors at baseline. This difference was no longer significant at follow-up. Individuals with 22q11.2DS have impairments in visual memory abilities, with more pronounced difficulties in memorizing faces and visual

  10. Visualizing post genomics data-sets on customized pathway maps by ProMeTra – aeration-dependent gene expression and metabolism of Corynebacterium glutamicum as an example

    Directory of Open Access Journals (Sweden)

    Hüser Andrea T

    2009-08-01

    Full Text Available Abstract Background The rapid progress of post-genomic analyses, such as transcriptomics, proteomics, and metabolomics has resulted in the generation of large amounts of quantitative data covering and connecting the complete cascade from genotype to phenotype for individual organisms. Various benefits can be achieved when these "Omics" data are integrated, such as the identification of unknown gene functions or the elucidation of regulatory networks of whole organisms. In order to be able to obtain deeper insights in the generated datasets, it is of utmost importance to present the data to the researcher in an intuitive, integrated, and knowledge-based environment. Therefore, various visualization paradigms have been established during the last years. The visualization of "Omics" data using metabolic pathway maps is intuitive and has been applied in various software tools. It has become obvious that the application of web-based and user driven software tools has great potential and benefits from the use of open and standardized formats for the description of pathways. Results In order to combine datasets from heterogeneous "Omics" sources, we present the web-based ProMeTra system that visualizes and combines datasets from transcriptomics, proteomics, and metabolomics on user defined metabolic pathway maps. Therefore, structured exchange of data with our "Omics" applications Emma 2, Qupe and MeltDB is employed. Enriched SVG images or animations are generated and can be obtained via the user friendly web interface. To demonstrate the functionality of ProMeTra, we use quantitative data obtained during a fermentation experiment of the L-lysine producing strain Corynebacterium glutamicum DM1730. During fermentation, oxygen supply was switched off in order to perturb the system and observe its reaction. At six different time points, transcript abundances, intracellular metabolite pools, as well as extracellular glucose, lactate, and L-lysine levels

  11. Acting without seeing: Eye movements reveal visual processing without awareness Miriam Spering & Marisa Carrasco

    Science.gov (United States)

    Spering, Miriam; Carrasco, Marisa

    2015-01-01

    Visual perception and eye movements are considered to be tightly linked. Diverse fields, ranging from developmental psychology to computer science, utilize eye tracking to measure visual perception. However, this prevailing view has been challenged by recent behavioral studies. We review converging evidence revealing dissociations between the contents of perceptual awareness and different types of eye movements. Such dissociations reveal situations in which eye movements are sensitive to particular visual features that fail to modulate perceptual reports. We also discuss neurophysiological, neuroimaging and clinical studies supporting the role of subcortical pathways for visual processing without awareness. Our review links awareness to perceptual-eye movement dissociations and furthers our understanding of the brain pathways underlying vision and movement with and without awareness. PMID:25765322

  12. Pathways and trajectories linking housing instability and poor health among low-income women experiencing intimate partner violence (IPV): Toward a conceptual framework.

    Science.gov (United States)

    Daoud, Nihaya; Matheson, Flora I; Pedersen, Cheryl; Hamilton-Wright, Sarah; Minh, Anita; Zhang, Janice; O'Campo, Patricia

    2016-01-01

    We used grounded theory to understand pathways and trajectories to housing instability (HI) and poor health among low-income women with experiences of intimate partner violence (IPV). We conducted in-depth interviews during 2010-11 with forty-one women (ages 18-45 years) living in Ontario, Canada. All women reported depressive symptoms in combination with other health problems. In addition to the direct pathway of IPV to poor health, thematic analysis revealed an indirect multi-tiered pathway with complex trajectories among IPV, HI, and poor health. These trajectories included material HI (homelessness, high mobility, evictions, problems paying rent, hiding, and landlord discrimination), psychological HI (feeling unsafe, low self-esteem, and poor control), and social trajectories (financial problems, loss of employment, income, or social networks, and leaving school). These trajectories elevated stress and decreased self-care (unhealthy behaviors, substance abuse, and reduced medical compliance) and exacerbated poor health already compromised by IPV. Depending on her specific context, each woman experienced these pathways and trajectories differently. Moreover, the women's experiences differed across three time periods: before, immediately after, and long after leaving an abusive relationship. Finally, we found that for these women, achieving stable housing was crucial for stabilizing their health.

  13. Suicides in Visually Impaired Persons: A Nation-Wide Register-Linked Study from Finland Based on Thirty Years of Data

    Science.gov (United States)

    Meyer-Rochow, Victor Benno; Hakko, Helinä; Ojamo, Matti; Uusitalo, Hannu; Timonen, Markku

    2015-01-01

    Focusing on seasonality, gender, age, and suicide methods a Finnish nation-wide cohort-based study was carried out to compare suicide data between sighted, visually-impaired (WHO impairment level I-II, i.e., visual acuity >0.05, but blind (WHO impairment level III-V, i.e., visual acuity blind. Mortality was significantly increased in the visually impaired (SMR = 1.3; 95% CI 1.07–1.61), but in gender-stratified analyses the increase only affected males (1.34; 95% CI = 1.06–1.70) and not females (1.24; 95% CI 0.82–1.88). Age-stratified analyses identified blind males of working age rather than older men (as in the general population) as a high risk group that requires particular attention. The statistically significant spring suicide peak in blind subjects mirrors that of sighted victims and its possible cause in the blind is discussed. PMID:26509899

  14. Phosphatase and tensin homologue/protein kinase B pathway linked to motor neuron survival in human superoxide dismutase 1-related amyotrophic lateral sclerosis.

    Science.gov (United States)

    Kirby, Janine; Ning, Ke; Ferraiuolo, Laura; Heath, Paul R; Ismail, Azza; Kuo, Su-Wei; Valori, Chiara F; Cox, Laura; Sharrack, Basil; Wharton, Stephen B; Ince, Paul G; Shaw, Pamela J; Azzouz, Mimoun

    2011-02-01

    Gene expression profiling has been used previously with spinal cord homogenates and laser capture microdissected motor neurons to determine the mechanisms involved in neurodegeneration in amyotrophic lateral sclerosis. However, while cellular and animal model work has focused on superoxide dismutase 1-related amyotrophic lateral sclerosis, the transcriptional profile of human mutant superoxide dismutase 1 motor neurons has remained undiscovered. The aim of this study was to apply gene expression profiling to laser captured motor neurons from human superoxide dismutase 1-related amyotrophic lateral sclerosis and neurologically normal control cases, in order to determine those pathways dysregulated in human superoxide dismutase 1-related neurodegeneration and to establish potential pathways suitable for therapeutic intervention. Identified targets were then validated in cultured cell models using lentiviral vectors to manipulate the expression of key genes. Microarray analysis identified 1170 differentially expressed genes in spinal cord motor neurons from superoxide dismutase 1-related amyotrophic lateral sclerosis, compared with controls. These genes encoded for proteins in multiple functional categories, including those involved in cell survival and cell death. Further analysis determined that multiple genes involved in the phosphatidylinositol-3 kinase signalling cascade were differentially expressed in motor neurons that survived the disease process. Functional experiments in cultured cells and primary motor neurons demonstrate that manipulating this pathway by reducing the expression of a single upstream target, the negative phosphatidylinositol-3 kinase regulator phosphatase and tensin homology, promotes a marked pro-survival effect. Therefore, these data indicate that proteins in the phosphatidylinositol-3 kinase pathway could represent a target for therapeutic manipulation in motor neuron degeneration.

  15. Sorghum bmr6 mutant analysis demonstrates that a shared MYB1 transcription factor binding site in the promoter links the expression of genes in related pathways.

    Science.gov (United States)

    Li, Jieqin; Wang, Lihua; Zhan, Qiuwen; Liu, Yanlong; Fu, Bisheng; Wang, Chunming

    2013-11-01

    Sorghum is not only an important cereal crop but also a biofuel crop. The sorghum brown midrib mutant 6 (bmr6) has a reduced lignin content in the cell walls and vascular tissues, which could potentially be advantageous for cellulosic biofuel production. Meanwhile, both dry matter yield and plant height were decreased in the bmr6 mutant. To identify genes affected in the mutant, differential gene expression analysis was performed for bmr6 and the wild type. As a result, a total of 1,052 differentially expressed genes were detected between the two samples, of which 166 genes were downregulated and 886 genes were upregulated. Five hundred seventy-nine of the 1,052 differentially expressed genes could be assigned to 154 documented pathways. These pathways mainly included primary and secondary metabolism. Therefore, mutation of the bmr6 gene, which impaired the biosynthesis of lignin, ultimately affected the expression of these genes associated with the growth and development of sorghum. Except for the bmr6 gene, 11 key enzyme genes of monolignols biosynthesis were upregulated. Promoter analysis identified that these genes have common MYB sites. It revealed that a feedback mechanism existed in the pathway and a MYB1 transcription factor (Sb02g031190) could associate with the upregulation of these genes in sorghum. In this study, we investigated gene expressions at a global level in sorghum bmr6 mutant and provided valuable insights into the mechanisms of lignin biosynthesis.

  16. Visualization analysis and design

    CERN Document Server

    Munzner, Tamara

    2015-01-01

    Visualization Analysis and Design provides a systematic, comprehensive framework for thinking about visualization in terms of principles and design choices. The book features a unified approach encompassing information visualization techniques for abstract data, scientific visualization techniques for spatial data, and visual analytics techniques for interweaving data transformation and analysis with interactive visual exploration. It emphasizes the careful validation of effectiveness and the consideration of function before form. The book breaks down visualization design according to three questions: what data users need to see, why users need to carry out their tasks, and how the visual representations proposed can be constructed and manipulated. It walks readers through the use of space and color to visually encode data in a view, the trade-offs between changing a single view and using multiple linked views, and the ways to reduce the amount of data shown in each view. The book concludes with six case stu...

  17. Applications of Lexical Link Analysis Web Service for Large-Scale Automation, Validation, Discovery, Visualization, and Real-Time Program-Awareness

    Science.gov (United States)

    2012-04-30

    closeness of the systems in comparison can be visually examined or examined using the Quadratic Assignment Procedure ( QAP ; Hubert & Schultz, 1976, e.g...Comparing Two Time Periods Figure 16. QAP Correlation via UCINET Each node, or word hub, represents a system feature, and each color refers to the...Systems Experimentation, Naval Postgraduate School BACK-UP SLIDES Statistical Test Example: QAP Correlation Quadratic Assignment Procedure [ QAP

  18. A protein–protein interaction network linking the energy-sensor kinase SnRK1 to multiple signaling pathways in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Madlen Nietzsche

    2016-04-01

    Full Text Available In plants, the sucrose non-fermenting (SNF1-related protein kinase 1 (SnRK1 represents a central integrator of low energy signaling and acclimation towards many environmental stress responses. Although SnRK1 acts as a convergent point for many different environmental and metabolic signals to control growth and development, it is currently unknown how these many different signals could be translated into a cell-type or stimulus specific response since many components of SnRK1-regulated signaling pathways remain unidentified. Recently, we have demonstrated that proteins containing a domain of unknown function (DUF 581 interact with the catalytic α subunits of SnRK1 (AKIN10/11 from Arabidopsis thaliana and could potentially act as mediators conferring tissue- and stimulus-type specific differences in SnRK1 regulation. To further extend the SnRK1 signaling network in plants, we systematically screened for novel DUF581 interaction partners using the yeast two-hybrid system. A deep and exhaustive screening identified 17 interacting partners for 10 of the DUF581 proteins tested. Many of these novel interaction partners are implicated in cellular processes previously associated with SnRK1 signaling. Furthermore, we mined publicly available interaction data to identify additional DUF581 interacting proteins. A protein–protein interaction network resulting from our studies suggests connections between SnRK1 signaling and other central signaling pathways involved in growth regulation and environmental responses. These include TOR and MAP-kinase signaling as well as hormonal pathways. The resulting protein–protein interaction network promises to be effective in generating hypotheses to study the precise mechanisms SnRK1 signaling on a functional level.

  19. A feed-forward circuit linking wingless, fat-dachsous signaling, and the warts-hippo pathway to Drosophila wing growth.

    Directory of Open Access Journals (Sweden)

    Myriam Zecca

    Full Text Available During development, the Drosophila wing primordium undergoes a dramatic increase in cell number and mass under the control of the long-range morphogens Wingless (Wg, a Wnt and Decapentaplegic (Dpp, a BMP. This process depends in part on the capacity of wing cells to recruit neighboring, non-wing cells into the wing primordium. Wing cells are defined by activity of the selector gene vestigial (vg and recruitment entails the production of a vg-dependent "feed-forward signal" that acts together with morphogen to induce vg expression in neighboring non-wing cells. Here, we identify the protocadherins Fat (Ft and Dachsous (Ds, the Warts-Hippo tumor suppressor pathway, and the transcriptional co-activator Yorkie (Yki, a YES associated protein, or YAP as components of the feed-forward signaling mechanism, and we show how this mechanism promotes wing growth in response to Wg. We find that vg generates the feed-forward signal by creating a steep differential in Ft-Ds signaling between wing and non-wing cells. This differential down-regulates Warts-Hippo pathway activity in non-wing cells, leading to a burst of Yki activity and the induction of vg in response to Wg. We posit that Wg propels wing growth at least in part by fueling a wave front of Ft-Ds signaling that propagates vg expression from one cell to the next.

  20. The Visual System

    Medline Plus

    Full Text Available ... Glossary The Visual System Your Eyes’ Natural Defenses Eye Health and Safety First Aid Tips Healthy Vision Tips Protective Eyewear Sports and Your Eyes Fun Stuff Cool Eye Tricks Links to More ...

  1. The Visual System

    Medline Plus

    Full Text Available ... USAJobs Home > NEI for Kids > The Visual System All About Vision About the Eye Ask a Scientist Video ... Vision Tips Protective Eyewear Sports and Your Eyes Fun Stuff Cool Eye Tricks Links to More Information ...

  2. The Visual System

    Medline Plus

    Full Text Available ... Tricks Links to More Information Optical Illusions Printables The Visual System Ever wonder how your eyes work? ... able to see the world around you. Did You Know? On average, you blink about 15 to ...

  3. Whole-Exome Sequencing in a South American Cohort Links ALDH1A3, FOXN1 and Retinoic Acid Regulation Pathways to Autism Spectrum Disorders.

    Science.gov (United States)

    Moreno-Ramos, Oscar A; Olivares, Ana María; Haider, Neena B; de Autismo, Liga Colombiana; Lattig, María Claudia

    2015-01-01

    Autism spectrum disorders (ASDs) are a range of complex neurodevelopmental conditions principally characterized by dysfunctions linked to mental development. Previous studies have shown that there are more than 1000 genes likely involved in ASD, expressed mainly in brain and highly interconnected among them. We applied whole exome sequencing in Colombian-South American trios. Two missense novel SNVs were found in the same child: ALDH1A3 (RefSeq NM_000693: c.1514T>C (p.I505T)) and FOXN1 (RefSeq NM_003593: c.146C>T (p.S49L)). Gene expression studies reveal that Aldh1a3 and Foxn1 are expressed in ~E13.5 mouse embryonic brain, as well as in adult piriform cortex (PC; ~P30). Conserved Retinoic Acid Response Elements (RAREs) upstream of human ALDH1A3 and FOXN1 and in mouse Aldh1a3 and Foxn1 genes were revealed using bioinformatic approximation. Chromatin immunoprecipitation (ChIP) assay using Retinoid Acid Receptor B (Rarb) as the immunoprecipitation target suggests RA regulation of Aldh1a3 and Foxn1 in mice. Our results frame a possible link of RA regulation in brain to ASD etiology, and a feasible non-additive effect of two apparently unrelated variants in ALDH1A3 and FOXN1 recognizing that every result given by next generation sequencing should be cautiously analyzed, as it might be an incidental finding.

  4. Age-related effects of triphenyl phosphite-induced delayed neuropathy on central visual pathways in the European ferret (Mustela putorius furo).

    Science.gov (United States)

    Tanaka, D; Bursian, S J; Aulerich, R J

    1994-05-01

    The objective of this study was to investigate the relationship between the maturation of visual system neurons and the onset of their susceptibility to triphenyl phosphite (TPP)-induced delayed neurotoxicity in the European ferret. We administered single subcutaneous doses of TPP (1184 mg/kg body wt) to 1- to 10-week-old ferret kits to assess the effects on connections and neurons of the developing lateral geniculate thalamic nucleus (LGN) and primary visual cortex. Brains were processed with a modified Fink-Heimer silver-impregnation method. Axonal and terminal degeneration were first noted in the LGN of kits injected at 5 weeks of age. The severity of the degeneration increased in kits injected at later ages and reached adult densities and configurations in ferrets injected at 10 weeks of age. Degenerating neuronal cell bodies were also present in the LGN of kits injected at 7 weeks of age and older. In the visual cortex, axonal and terminal degeneration were consistently present in kits injected at 8 weeks of age and attained adult-like densities in kits injected at 10 weeks of age. Previous studies have reported that the ferret visual system appears to reach anatomical maturity (as defined by mature LGN lamination patterns, the location and density of axon terminals originating from neurons in the retina and LGN, and the migration and synaptic connections of cortical neurons) by 4-5 weeks of age. A temporal comparison of these normal developmental data with the degeneration data obtained in the present study suggests that immature neurons in the visual system of the ferret are not susceptible to TPP-induced delayed neurotoxicity but only become so after they have achieved some degree of maturity. Whether the LGN neurons undergoing degeneration are directly affected by TPP or are showing a transneuronal response to loss of afferent input remains unresolved.

  5. Visual rehabilitation in low-moderate keratoconus:intracorneal ring segment implantation followed by same-day topography-guided photorefractive keratectomy and collagen cross linking

    Directory of Open Access Journals (Sweden)

    Ferial M. Zeraid

    2014-10-01

    Full Text Available AIM:To present the results of same-day topography-guided photorefractive keratectomy (TG-PRK and corneal collagen crosslinking (CXL after previous intrastromal corneal ring segment (ISCR implantation for keratoconus.METHODS:An experimental clinical study on twenty-one eyes of 19 patients aged 27.1±6.6y (range 19-43y, with low to moderate keratoconus who were selected to undergo customized TG-PRK immediately followed by same-day CXL, 9mo after ISCR implantation in a university ophthalmology clinic. Refraction, uncorrected distance visual acuities (UDVA and corrected distance visual acuities (CDVA, keratometry (K values, central corneal thickness (CCT and coma were assessed 3mo after TG-PRK and CXL.RESULTS:After TG-PRK/CXL:the mean UDVA (logMAR improved significantly from 0.66±0.41 to 0.20±0.25 (P<0.05; Kflat value decreased from:48.44±3.66 D to 43.71±1.95 D; Ksteep value decreased from 45.61±2.40 D to 41.56±2.05 D; Kaverage also decreased from 47.00±2.66 D to 42.42±2.07 D (P<0.05 for all. The mean sphere and cylinder decreased significantly post-surgery from, -3.10±2.99 D to -0.11±0.93 D and from -3.68±1.53 to -1.11±0.75 D respectively, while the CDVA, CCT and coma showed no significant changes. Compared to post-ISCR, significant reductions (P<0.05 or all in all K values, sphere and cylinder were observed after TG-PRK/CXL.CONCLUSION:Same-day combined topography-guided PRK and corneal crosslinking following placement of ISCR is a safe and potentially effective option in treating low-moderate keratoconus. It significantly improves all visual acuity, reduced keratometry, sphere and astigmatism, but causes no change in central corneal thickness and coma.

  6. Evidence from auditory and visual event-related potential (ERP) studies of deviance detection (MMN and vMMN) linking predictive coding theories and perceptual object representations.

    Science.gov (United States)

    Winkler, István; Czigler, István

    2012-02-01

    Predictive coding theories posit that the perceptual system is structured as a hierarchically organized set of generative models with increasingly general models at higher levels. The difference between model predictions and the actual input (prediction error) drives model selection and adaptation processes minimizing the prediction error. Event-related brain potentials elicited by sensory deviance are thought to reflect the processing of prediction error at an intermediate level in the hierarchy. We review evidence from auditory and visual studies of deviance detection suggesting that the memory representations inferred from these studies meet the criteria set for perceptual object representations. Based on this evidence we then argue that these perceptual object representations are closely related to the generative models assumed by predictive coding theories. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. cPath: open source software for collecting, storing, and querying biological pathways

    Directory of Open Access Journals (Sweden)

    Gross Benjamin E

    2006-11-01

    Full Text Available Abstract Background Biological pathways, including metabolic pathways, protein interaction networks, signal transduction pathways, and gene regulatory networks, are currently represented in over 220 diverse databases. These data are crucial for the study of specific biological processes, including human diseases. Standard exchange formats for pathway information, such as BioPAX, CellML, SBML and PSI-MI, enable convenient collection of this data for biological research, but mechanisms for common storage and communication are required. Results We have developed cPath, an open source database and web application for collecting, storing, and querying biological pathway data. cPath makes it easy to aggregate custom pathway data sets available in standard exchange formats from multiple databases, present pathway data to biologists via a customizable web interface, and export pathway data via a web service to third-party software, such as Cytoscape, for visualization and analysis. cPath is software only, and does not include new pathway information. Key features include: a built-in identifier mapping service for linking identical interactors and linking to external resources; built-in support for PSI-MI and BioPAX standard pathway exchange formats; a web service interface for searching and retrieving pathway data sets; and thorough documentation. The cPath software is freely available under the LGPL open source license for academic and commercial use. Conclusion cPath is a robust, scalable, modular, professional-grade software platform for collecting, storing, and querying biological pathways. It can serve as the core data handling component in information systems for pathway visualization, analysis and modeling.

  8. A novel pathway links oxidative stress to loss of insulin growth factor-2 (IGF2 imprinting through NF-κB activation.

    Directory of Open Access Journals (Sweden)

    Bing Yang

    Full Text Available Genomic imprinting is the allele-specific expression of a gene based on parental origin. Loss of imprinting(LOI of Insulin-like Growth Factor 2 (IGF2 during aging is important in tumorigenesis, yet the regulatory mechanisms driving this event are largely unknown. In this study oxidative stress, measured by increased NF-κB activity, induces LOI in both cancerous and noncancerous human prostate cells. Decreased expression of the enhancer-blocking element CCCTC-binding factor(CTCF results in reduced binding of CTCF to the H19-ICR (imprint control region, a major factor in the allelic silencing of IGF2. This ICR then develops increased DNA methylation. Assays identify a recruitment of the canonical pathway proteins NF-κB p65 and p50 to the CTCF promoter associated with the co-repressor HDAC1 explaining gene repression. An IκBα super-repressor blocks oxidative stress-induced activation of NF-κB and IGF2 imprinting is maintained. In vivo experiments using IκBα mutant mice with continuous NF-κB activation demonstrate increased IGF2 LOI further confirming a central role for canonical NF-κB signaling. We conclude CTCF plays a central role in mediating the effects of NF-κB activation that result in altered imprinting both in vitro and in vivo. This novel finding connects inflammation found in aging prostate tissues with the altered epigenetic landscape.

  9. A Disulfide Bond-forming Machine Is Linked to the Sortase-mediated Pilus Assembly Pathway in the Gram-positive Bacterium Actinomyces oris.

    Science.gov (United States)

    Reardon-Robinson, Melissa E; Osipiuk, Jerzy; Chang, Chungyu; Wu, Chenggang; Jooya, Neda; Joachimiak, Andrzej; Das, Asis; Ton-That, Hung

    2015-08-28

    Export of cell surface pilins in Gram-positive bacteria likely occurs by the translocation of unfolded precursor polypeptides; however, how the unfolded pilins gain their native conformation is presently unknown. Here, we present physiological studies to demonstrate that the FimA pilin of Actinomyces oris contains two disulfide bonds. Alanine substitution of cysteine residues forming the C-terminal disulfide bridge abrogates pilus assembly, in turn eliminating biofilm formation and polymicrobial interaction. Transposon mutagenesis of A. oris yielded a mutant defective in adherence to Streptococcus oralis, and revealed the essential role of a vitamin K epoxide reductase (VKOR) gene in pilus assembly. Targeted deletion of vkor results in the same defects, which are rescued by ectopic expression of VKOR, but not a mutant containing an alanine substitution in its conserved CXXC motif. Depletion of mdbA, which encodes a membrane-bound thiol-disulfide oxidoreductase, abrogates pilus assembly and alters cell morphology. Remarkably, overexpression of MdbA or a counterpart from Corynebacterium diphtheriae, rescues the Δvkor mutant. By alkylation assays, we demonstrate that VKOR is required for MdbA reoxidation. Furthermore, crystallographic studies reveal that A. oris MdbA harbors a thioredoxin-like fold with the conserved CXXC active site. Consistently, each MdbA enzyme catalyzes proper disulfide bond formation within FimA in vitro that requires the catalytic CXXC motif. Because the majority of signal peptide-containing proteins encoded by A. oris possess multiple Cys residues, we propose that MdbA and VKOR constitute a major folding machine for the secretome of this organism. This oxidative protein folding pathway may be a common feature in Actinobacteria. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Explaining the pathway from familial and peer social support to disordered eating: Is body dissatisfaction the link for male and female adolescents?

    Science.gov (United States)

    Kirsch, Alexandra C; Shapiro, Jenna B; Conley, Colleen S; Heinrichs, Gretchen

    2016-08-01

    This study examined if familial and peer social support longitudinally predicted disordered eating for late adolescents in the transitional first year of college, and if body dissatisfaction mediated this relation. Gender differences between support types and disordered eating, and body dissatisfaction as a mediator, were also examined. 651 late adolescent males and females (Mage=18.47) completed measures of social support at the end of the first semester of college and of disordered eating and body image approximately five months later, at the end of the first year. Lower levels of familial social support prospectively predicted greater disordered eating, but not greater body dissatisfaction, and lower levels of peer social support prospectively predicted greater body dissatisfaction but not greater disordered eating, above and beyond the other type of social support type, prior levels of body dissatisfaction, disordered eating, and BMI. Body dissatisfaction did not mediate the relation between familial social support and disordered eating; however, it did significantly mediate the non-significant relation between peer social support and disordered eating, which was further moderated by gender. These findings suggest that parental social support remains a significant predictor of disordered eating for late adolescents even after they transition to college, and has a stronger relation to disordered eating than peer support. In contrast, peer social support seems to be especially linked to feelings of body dissatisfaction and may be an avenue for intervention of this type of negative self-perception that is a risk factor for later disordered eating. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Ro60-associated single-stranded RNA links inflammation with fetal cardiac fibrosis via ligation of TLRs: a novel pathway to autoimmune-associated heart block.

    Science.gov (United States)

    Clancy, Robert M; Alvarez, David; Komissarova, Elena; Barrat, Franck J; Swartz, Jordan; Buyon, Jill P

    2010-02-15

    Activation of TLR by ssRNA after FcgammaR-mediated phagocytosis of immune complexes (IC) may be relevant in autoimmune-associated congenital heart block (CHB) where the obligate factor is a maternal anti-SSA/Ro Ab and the fetal factors, protein/RNA on an apoptotic cardiocyte and infiltrating macrophages. This study addressed the hypothesis that Ro60-associated ssRNAs link macrophage activation to fibrosis via TLR engagement. Both macrophage transfection with noncoding ssRNA that bind Ro60 and an IC generated by incubation of Ro60-ssRNA with an IgG fraction from a CHB mother or affinity purified anti-Ro60 significantly increased TNF-alpha secretion, an effect not observed using control RNAs or normal IgG. Dependence on TLR was supported by the significant inhibition of TNF-alpha release by IRS661 and chloroquine. The requirement for FcgammaRIIIa-mediated delivery was provided by inhibition with an anti-CD16a Ab. Fibrosis markers were noticeably increased in fetal cardiac fibroblasts after incubation with supernatants generated from macrophages transfected with ssRNA or incubated with the IC. Supernatants generated from macrophages with ssRNA in the presence of IRS661 or chloroquine did not cause fibrosis. In a CHB heart, but not a healthy heart, TLR7 immunostaining was localized to a region near the atrioventricular groove at a site enriched in mononuclear cells and fibrosis. These data support a novel injury model in CHB, whereby endogenous ligand, Ro60-associated ssRNA, forges a nexus between TLR ligation and fibrosis instigated by binding of anti-Ro Abs to the target protein likely accessible via apoptosis.

  12. Pathways linking car transport for young adults and the public health in Northern Ireland: a qualitative study to inform the evaluation of graduated driver licensing

    Directory of Open Access Journals (Sweden)

    Nicola Christie

    2017-06-01

    licensed and general population; and impact on transport exclusion. We suggest an important pathway will be change in social norms around offering and accepting lifts and to risk-taking. The growing adoption of in-car telematics will have implications for future GDL programmes and for evaluation.

  13. Pathways linking car transport for young adults and the public health in Northern Ireland: a qualitative study to inform the evaluation of graduated driver licensing.

    Science.gov (United States)

    Christie, Nicola; Steinbach, Rebecca; Green, Judith; Mullan, M Patricia; Prior, Lindsay

    2017-06-07

    suggest an important pathway will be change in social norms around offering and accepting lifts and to risk-taking. The growing adoption of in-car telematics will have implications for future GDL programmes and for evaluation.

  14. International Practice in Care Provision for Post-stroke Visual Impairment.

    Science.gov (United States)

    Rowe, Fiona J

    2017-09-01

    This study sought to explore the practice of orthoptists internationally in care provision for poststroke visual impairment. Survey questions were developed and piloted with clinicians, academics, and users. Questions addressed types of visual problems, how these were identified, treated, and followed up, care pathways in use, links with other professions, and referral options. The survey was approved by the institutional ethical committee. The survey was accessed via a web link that was circulated through the International Orthoptic Association member professional organisations to orthoptists. Completed electronic surveys were obtained from 299 individuals. About one-third (35.5%) of orthoptists saw patients within 2 weeks of stroke onset and over half (55.5%) by 1 month post stroke. Stroke survivors were routinely assessed by 87%; over three-quarters in eye clinics. Screening tools were used by 11%. Validated tests were used for assessment of visual acuity (76.5%), visual field (68.2%), eye movement (80.9%), binocular vision (77.9%), and visual function (55.8%). Visual problems suspected by family or professionals were high (86.6%). Typical overall follow-up period of vision care was less than 3 months. Designated care pathways for stroke survivors with visual problems were used by 56.9% of orthoptists. Information on visual impairment was provided by 85.9% of orthoptists. In international orthoptic practice, there is general agreement on assessment and management of visual impairment in stroke populations. More than half of orthoptists reported seeing stroke survivors within 1 month of the stroke onset, typically in eye clinics. There was a high use of validated tests of visual acuity, visual fields, ocular motility, and binocular vision. Similarly there was high use of established treatment options including prisms, occlusion, compensatory strategies, and oculomotor training, appropriately targeted at specific types of visual conditions/symptoms. This

  15. Characterization of a Population with Visual, Auditory, Speech and Motor Disabilities, for Their Linking to Undergraduate Programs at a University in Colombia

    Directory of Open Access Journals (Sweden)

    Luz Myrian Rojas-Rojas

    2017-10-01

    Full Text Available This article presents the results of an unpublished research project whose objective was to characterize a population with visual, hearing, speech and motor disabilities. The research quantified potential users of the programs offered by the Faculty of Distance Education (FESAD at the Pedagogical and Technological University of Colombia (UPTC. It had an exploratory-descriptive methodological design with random sampling. Surveys were applied to young high school students and adult bachelors by using Braille system and a digital sign language translator. For data analysis, a quantitative statistical method was implemented. The results showed that, from young bachelors, 53% were women, 51% adults were men; 57% of young people were between 18 and 21 years old, 47% of adults were between 22 and 30 years old, and 65% of adult bachelors did not work. From the preferred university careers to study, a 28% of young people preferred engineering; 21%, economic and administrative sciences; 15%, arts; and 13%, education sciences. 27% of adult bachelors preferred engineering; 18%, economic and administrative sciences; and 15%, education sciences. 85% of youth and 71% of adult bachelors were deaf. It is concluded that there is a vulnerable population with disabilities and with an obvious lack of opportunities to access higher education. FESAD has trained teachers in designing an integrated and inclusive curriculum for the development of labor skills. FESAD also has technical and technological resources to take care of this population. It is recommended to boost higher education policies for social inclusion in Colombia, and conduct new studies on causes and effects to design and implement programs that apply these policies.

  16. Axonal tracing of the normal and regenerating visual pathway of mouse, rat, frog, and fish using manganese-enhanced MRI (MEMRI).

    Science.gov (United States)

    Sandvig, Axel; Sandvig, Ioanna; Berry, Martin; Olsen, Øystein; Pedersen, Tina Bugge; Brekken, Christian; Thuen, Marte

    2011-09-01

    To assess optic nerve (ON) regeneration after injury by applying manganese-enhanced MRI (MEMRI) in a study of comparative physiology between nonregenerating rat and mouse species and regenerating frog and fish species. The normal visual projections of rats, mice, frogs, and fish was visualized by intravitreal MnCl(2) injection followed by MRI. Rats and mice with ON crush (ONC) were divided into nonregenerating (ONC only), and regenerating animals with peripheral nerve graft (ONC+PNG; rats) or lens injury (ONC+LI; mice) and monitored by MEMRI at 1 and 20 days post-lesion (dpl). Frog and fish with ON transection (ONT) were monitored by MEMRI up to 6 months postlesion (mpl). Signal intensity profiles of the Mn(2+)-enhanced ON were consistent with ON regeneration in the ONC+PNG and ONC+LI rat and mice groups, respectively, compared with the nonregenerating ONC groups. Furthermore, signal intensity profiles of the Mn(2+)-enhanced ON obtained between 1 mpl and 6 mpl in the fish and frog groups, respectively, were consistent with spontaneous, complete ON regeneration. Taken together, these results demonstrate that MEMRI is a viable method for serial, in vivo monitoring of normal, induced, and spontaneously regenerating optic nerve axons in different species. Copyright © 2011 Wiley-Liss, Inc.

  17. The link in Linking

    Science.gov (United States)

    Caldwell, Jane C; Chiale, Pablo A; Gonzalez, Mario D; Baranchuk, Adrian

    2013-01-01

    We present 2 cases of the slow-fast form of AVNRT with initially narrow QRS complexes followed by sudden unexpected transition to persistently wide QRS complexes due to aberrant intraventricular conduction. Introduction of a properly timed extrastimulus in one case and critical oscillations in cycle length due to short-long coupling in the second case set the stage for the initial bundle branch block. However, persistence of the aberrancy pattern once the initial event abated was maintained by the "linking" phenomenon. Delayed, retrograde concealed activation from the contralateral bundle branch perpetuated the initial bundle branch block. PMID:23840106

  18. Visualization in modern cartography

    CERN Document Server

    MacEachren, AM

    1994-01-01

    Visualization in Modern Cartography explores links between the centuries-old discipline of cartography and today's revolutionary developments in scientific visualization. The book has three main goals: (1) to pass on design and symbolization expertise to the scientific visualization community - information that comes from centuries of pre-computer visualization by cartographers, and their more recent experiences with computerizing the discipline; (2) to help cartographers cope with the dramatic shift from print cartography to a dynamic virtual cartography for which their role is changing from

  19. Visual Impairment

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Visual Impairment KidsHealth / For Teens / Visual Impairment What's in ... with the brain, making vision impossible. What Is Visual Impairment? Many people have some type of visual ...

  20. Visual field

    Science.gov (United States)

    Perimetry; Tangent screen exam; Automated perimetry exam; Goldmann visual field exam; Humphrey visual field exam ... Confrontation visual field exam. This is a quick and basic check of the visual field. The health care provider ...

  1. Delayed visual maturation: pupillary responses implicate subcortical and cortical visual systems.

    Science.gov (United States)

    Cocker, K D; Moseley, M J; Stirling, H F; Fielder, A R

    1998-03-01

    Vision in very early infancy is probably subserved by subcortical pathways, with many cortical processes only fully emerging by 3 months of age. The improvement of vision in delayed visual maturation (DVM) occurs around this time, and this has given rise to the suggestion that the condition may have a subcortical basis that resolves with the appearance of cortical function. To explore further the role of cortical and subcortical visual systems in DVM we studied the visual development in identical twins, one of whom had type 1b DVM. Two non-invasive methods of investigating visual pathway function were employed: the acuity card procedure (a behavioural response) and luminance and grating pupillometry. While the former reflects both subcortical and cortical function and can be detected at birth, pupil responses to gratings reflect cortical activity alone and normally become measurable at 1 month of age. Development of both behavioural and pupillary responses was delayed in DVM, indicating that although the underlying defect is primarily subcortical, secondarily it delays the emergence of cortically mediated responses. The observed rapidity of improvement--over a very few days and within a narrow age range--suggests a discrete rather than a widespread structural abnormality, the improvement of which is closely linked to postmenstrual age.

  2. Vision and visualization.

    Science.gov (United States)

    Wade, Nicholas J

    2008-01-01

    The art of visual communication is not restricted to the fine arts. Scientists also apply art in communicating their ideas graphically. Diagrams of anatomical structures, like the eye and visual pathways, and figures displaying specific visual phenomena have assisted in the communication of visual ideas for centuries. It is often the case that the development of a discipline can be traced through graphical representations and this is explored here in the context of concepts of visual science. As with any science, vision can be subdivided in a variety of ways. The classification adopted is in terms of optics, anatomy, and visual phenomena; each of these can in turn be further subdivided. Optics can be considered in terms of the nature of light and its transmission through the eye. Understanding of the gross anatomy of the eye and visual pathways was initially dependent upon the skills of the anatomist whereas microanatomy relied to a large extent on the instruments that could resolve cellular detail, allied to the observational skills of the microscopist. Visual phenomena could often be displayed on the printed page, although novel instruments expanded the scope of seeing, particularly in the nineteenth century.

  3. Linked Partitions and Linked Cycles

    OpenAIRE

    Chen, William Y. C.; Wu, Susan Y. J.; Yan, Catherine H.

    2006-01-01

    The notion of noncrossing linked partition arose from the study of certain transforms in free probability theory. It is known that the number of noncrossing linked partitions of [n+1] is equal to the n-th large Schroder number $r_n$, which counts the number of Schroder paths. In this paper we give a bijective proof of this result. Then we introduce the structures of linked partitions and linked cycles. We present various combinatorial properties of noncrossing linked partitions, linked partit...

  4. Diffusion MRI properties of the human uncinate fasciculus correlate with the ability to learn visual associations.

    Science.gov (United States)

    Thomas, Cibu; Avram, Alexandru; Pierpaoli, Carlo; Baker, Chris

    2015-11-01

    The uncinate fasciculus (UF) is a cortico-cortico white matter pathway that links the anterior temporal and the orbitofrontal cortex (OFC). In the monkey, transection of the UF causes significant impairments in learning conditional visual-visual associations, while object discrimination remains intact, suggesting an important role for the UF in mediating the learning of complex visual associations. Whether this functional role extends to the human UF has not been tested directly. Here, we used diffusion tensor magnetic resonance imaging (dMRI) and behavioral experiments to examine the relation between learning visual associations and the structural properties of the human UF. In a group of healthy adults, we segmented the UF and the inferior longitudinal fasciculus (ILF) and derived dMRI measures of the structural properties of the two pathways. We also used a behavioral experiment adapted from the monkey studies to characterize the ability of these individuals to learn to associate a person's face with a group of specific scenes (conditional visual-visual association). We then tested whether the variability in the dMRI measures of the two pathways correlated with variability in the ability to rapidly learn the face-place associations. Our study suggests that in the human, the left UF may be important for mediating the rapid learning of conditional visual-visual associations whereas the right UF may play an important role in the immediate retrieval of visual-visual associations. These results provide preliminary evidence suggesting similarities and differences in the functional role of the UF in monkeys compared to humans. The findings presented here contribute to our understanding of the functional role of the UF in humans and the functional neuroanatomy of the brain networks involved in visual cognition. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Radiation-induced mitotic cell death and glioblastoma radioresistance: a new regulating pathway controlled by integrin-linked kinase, hypoxia-inducible factor 1 alpha and survivin in U87 cells.

    Science.gov (United States)

    Lanvin, Olivia; Monferran, Sylvie; Delmas, Caroline; Couderc, Bettina; Toulas, Christine; Cohen-Jonathan-Moyal, Elizabeth

    2013-09-01

    We have previously shown that integrin-linked kinase (ILK) regulates U87 glioblastoma cell radioresistance by modulating the main radiation-induced cell death mechanism in solid tumours, the mitotic cell death. To decipher the biological pathways involved in these mechanisms, we constructed a U87 glioblastoma cell model expressing an inducible shRNA directed against ILK (U87shILK). We then demonstrated that silencing ILK enhanced radiation-induced centrosome overduplication, leading to radiation-induced mitotic cell death. In this model, ionising radiations induce hypoxia-inducible factor 1 alpha (HIF-1α) stabilisation which is inhibited by silencing ILK. Moreover, silencing HIF-1α in U87 cells reduced the surviving fraction after 2 Gy irradiation by increasing cell sensitivity to radiation-induced mitotic cell death and centrosome amplification. Because it is known that HIF-1α controls survivin expression, we then looked at the ILK silencing effect on survivin expression. We show that survivin expression is decreased in U87shILK cells. Furthermore, treating U87 cells with the specific survivin suppressor YM155 significantly increased the percentage of giant multinucleated cells, centrosomal overduplication and thus U87 cell radiosensitivity. In consequence, we decipher here a new pathway of glioma radioresistance via the regulation of radiation-induced centrosome duplication and therefore mitotic cell death by ILK, HIF-1α and survivin. This work identifies new targets in glioblastoma with the intention of radiosensitising these highly radioresistant tumours. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Application of fMRI to obesity research: differences in reward pathway activation measured with fMRI BOLD during visual presentation of high and low calorie foods

    Science.gov (United States)

    Tsao, Sinchai; Adam, Tanja C.; Goran, Michael I.; Singh, Manbir

    2012-03-01

    The factors behind the neural mechanisms that motivate food choice and obesity are not well known. Furthermore, it is not known when these neural mechanisms develop and how they are influenced by both genetic and environmental factors. This study uses fMRI together with clinical data to shed light on the aforementioned questions by investigating how appetite-related activation in the brain changes with low versus high caloric foods in pre-pubescent girls. Previous studies have shown that obese adults have less striatal D2 receptors and thus reduced Dopamine (DA) signaling leading to the reward-deficit theory of obesity. However, overeating in itself reduces D2 receptor density, D2 sensitivity and thus reward sensitivity. The results of this study will show how early these neural mechanisms develop and what effect the drastic endocrinological changes during puberty has on these mechanisms. Our preliminary results showed increased activations in the Putamen, Insula, Thalamus and Hippocampus when looking at activations where High Calorie > Low Calorie. When comparing High Calorie > Control and Low Calorie > Control, the High > Control test showed increased significant activation in the frontal lobe. The Low > Control also yielded significant activation in the Left and Right Fusiform Gyrus, which did not appear in the High > Control test. These results indicate that the reward pathway activations previously shown in post-puberty and adults are present in pre-pubescent teens. These results may suggest that some of the preferential neural mechanisms of reward are already present pre-puberty.

  7. Building maps from maps in primary visual cortex.

    Science.gov (United States)

    Nauhaus, Ian; Nielsen, Kristina J

    2014-02-01

    Neurons in the visual system respond to more complex and holistic features at each new stage of processing. Often, these features are organized into continuous maps. Could there be a fundamental link between continuous maps and functional hierarchies? Here, we review recent studies regarding V1 maps providing some of the most noteworthy advances in our understanding of how and why maps exist. In particular, we focus on the common theme that some maps are inherited from the input of parallel pathways, which are then intimately linked to the emergence of new functional properties and their corresponding maps. These results on V1 maps may prove to be a unifying framework for hierarchical representations in the visual cortex. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Implicit integration in a case of integrative visual agnosia.

    Science.gov (United States)

    Aviezer, Hillel; Landau, Ayelet N; Robertson, Lynn C; Peterson, Mary A; Soroker, Nachum; Sacher, Yaron; Bonneh, Yoram; Bentin, Shlomo

    2007-05-15

    We present a case (SE) with integrative visual agnosia following ischemic stroke affecting the right dorsal and the left ventral pathways of the visual system. Despite his inability to identify global hierarchical letters [Navon, D. (1977). Forest before trees: The precedence of global features in visual perception. Cognitive Psychology, 9, 353-383], and his dense object agnosia, SE showed normal global-to-local interference when responding to local letters in Navon hierarchical stimuli and significant picture-word identity priming in a semantic decision task for words. Since priming was absent if these features were scrambled, it stands to reason that these effects were not due to priming by distinctive features. The contrast between priming effects induced by coherent and scrambled stimuli is consistent with implicit but not explicit integration of features into a unified whole. We went on to show that possible/impossible object decisions were facilitated by words in a word-picture priming task, suggesting that prompts could activate perceptually integrated images in a backward fashion. We conclude that the absence of SE's ability to identify visual objects except through tedious serial construction reflects a deficit in accessing an integrated visual representation through bottom-up visual processing alone. However, top-down generated images can help activate these visual representations through semantic links.

  9. Exploring pathways linking greenspace to health

    NARCIS (Netherlands)

    Markevych, Iana; Schoierer, Julia; Hartig, Terry; Chudnovsky, Alexandra; Hystad, Perry; Dzhambov, Angel M.; Vries, de Sjerp; Triguero-Mas, Margarita; Brauer, Michael; Nieuwenhuijsen, Mark J.; Lupp, Gerd; Richardson, Elizabeth A.; Astell-Burt, Thomas; Dimitrova, Donka; Feng, Xiaoqi; Sadeh, Maya; Standl, Marie; Heinrich, Joachim; Fuertes, Elaine

    2017-01-01

    Background In a rapidly urbanizing world, many people have little contact with natural environments, which may affect health and well-being. Existing reviews generally conclude that residential greenspace is beneficial to health. However, the processes generating these benefits and how they can

  10. Molecular pathways linking metabolic inflammation and thermogenesis.

    OpenAIRE

    Solinas Giovanni

    2012-01-01

    Obesity is caused by chronic positive energy balance because of higher energy intake relative to energy expenditure. Thermogenesis the capacity of an organism to produce heat is an important component of energy expenditure. Thus targeting the molecular mechanisms controlling thermogenesis could be an effective strategy for the prevention or treatment of obesity. Thermogenesis is modulated by three major factors: environmental temperature nutrient quantity and quality and by systemic inflammat...

  11. Molecular pathways linking metabolic inflammation and thermogenesis

    OpenAIRE

    Solinas, Giovanni

    2013-01-01

    Obesity is caused by chronic positive energy balance because of higher energy intake relative to energy expenditure. Thermogenesis, the capacity of an organism to produce heat, is an important component of energy expenditure. Thus targeting the molecular mechanisms controlling thermogenesis could be an effective strategy for the prevention or treatment of obesity. Thermogenesis is modulated by three major factors: environmental temperature, nutrient quantity and quality, and by systemic infla...

  12. Visual Semiotics & Uncertainty Visualization: An Empirical Study.

    Science.gov (United States)

    MacEachren, A M; Roth, R E; O'Brien, J; Li, B; Swingley, D; Gahegan, M

    2012-12-01

    This paper presents two linked empirical studies focused on uncertainty visualization. The experiments are framed from two conceptual perspectives. First, a typology of uncertainty is used to delineate kinds of uncertainty matched with space, time, and attribute components of data. Second, concepts from visual semiotics are applied to characterize the kind of visual signification that is appropriate for representing those different categories of uncertainty. This framework guided the two experiments reported here. The first addresses representation intuitiveness, considering both visual variables and iconicity of representation. The second addresses relative performance of the most intuitive abstract and iconic representations of uncertainty on a map reading task. Combined results suggest initial guidelines for representing uncertainty and discussion focuses on practical applicability of results.

  13. Estrone sulfate source of estrone and estradiol formation in isolated human hair roots: identification of a pathway linked to hair growth phase and subject to site-, gender-, and age-related modulations.

    Science.gov (United States)

    Wehner, Gabriele; Schweikert, Hans-Udo

    2014-04-01

    The present study investigated the metabolism of estrone sulfate into bioactive estrogens in the human hair root, including the effects of hair growth phase, anatomical site, gender, and age. Healthy male (n = 18) and female (n = 20) subjects were investigated. Growing (anagen) and resting (telogen) hair roots were collected from selected scalp and body sites. Estrone sulfate metabolism in the hair root yielded substantial levels of estrone and estradiol. Estrogen synthesis exceeded that associated with aromatization of androgens in a previous study. In subjects hair was lower in men than in women. Comparable levels of estrogen formation were observed in 1) male and female axillary and pubic hair and 2) male beard hair. These levels were higher than the estrogen levels detected in the in scalp hair of men hair from all body sites, the capacity to form estrone from estrone sulfate remained unaffected, whereas the ability to form estradiol decreased by 62% and 86% in men and women, respectively. Estrogen formation from estrone sulfate in sexually dimorphic hair is linked to the hair growth phase and is subject to gender- and age-related modulations. The magnitude of the in situ estrogen synthesis from estrone sulfate and the selective arrest of estradiol synthesis at the end of the hair cycle suggest that this pathway plays a crucial role in the regulation of human hair growth.

  14. A simpler primate brain: the visual system of the marmoset monkey

    Directory of Open Access Journals (Sweden)

    Samuel Gavan Solomon

    2014-08-01

    Full Text Available Humans are diurnal primates with high visual acuity at the centre of gaze. Although primates share many similarities in the organisation of their visual centres with other mammals, and even other species of vertebrates, their visual pathways also show unique features, particularly with respect to the organization of the cerebral cortex. Therefore, in order to understand some aspects of human visual function, we need to study non-human primate brains. Which species is the most appropriate model? Macaque monkeys, the most widely used non-human primates, are not an optimal choice in many practical respects. For example, much of the macaque cerebral cortex is buried within sulci, and is therefore inaccessible to many imaging techniques, and the postnatal development and lifespan of macaques are prohibitively long for many studies of brain maturation, plasticity and ageing. In these and several other respects the marmoset, a small New World monkey, represents a more appropriate choice. Here we review the visual pathways of the marmoset, highlighting recent work that brings these advantages into focus, and identify where additional work needs to be done to link marmoset brain organisation to that of macaques and humans. We will argue that the marmoset monkey provides a good subject for studies of a complex visual system, which will likely allow an important bridge linking experiments in animal models to humans.

  15. Aspects of ontology visualization and integration

    NARCIS (Netherlands)

    Dmitrieva, Joelia Borisovna

    2011-01-01

    In this thesis we will describe and discuss methodologies for ontology visualization and integration. Two visualization methods will be elaborated. In one method the ontology is visualized with the node-link technique, and with the other method the ontology is visualized with the containment

  16. Visual cognition in social insects.

    Science.gov (United States)

    Avarguès-Weber, Aurore; Deisig, Nina; Giurfa, Martin

    2011-01-01

    Visual learning admits different levels of complexity, from the formation of a simple associative link between a visual stimulus and its outcome, to more sophisticated performances, such as object categorization or rules learning, that allow flexible responses beyond simple forms of learning. Not surprisingly, higher-order forms of visual learning have been studied primarily in vertebrates with larger brains, while simple visual learning has been the focus in animals with small brains such as insects. This dichotomy has recently changed as studies on visual learning in social insects have shown that these animals can master extremely sophisticated tasks. Here we review a spectrum of visual learning forms in social insects, from color and pattern learning, visual attention, and top-down image recognition, to interindividual recognition, conditional discrimination, category learning, and rule extraction. We analyze the necessity and sufficiency of simple associations to account for complex visual learning in Hymenoptera and discuss possible neural mechanisms underlying these visual performances.

  17. Scandinavian links

    DEFF Research Database (Denmark)

    Matthiessen, Christian Wichmann; Knowles, Richard D.

    2014-01-01

    The European Round Table of Industrialists identified in the 1980ies 14 missing links in the transportation network of the continent. Three of them were found around the Danish island of Zealand. One link is within the nation, the other two are between nations. One link connects heavy economic....... They concentrate traffic flows and create strong transport corridors. They are the basis of new regional development regimes. “Ferries connect systems, fixed links unite systems”....

  18. Distinct acute zones for visual stimuli in different visual tasks in Drosophila.

    Directory of Open Access Journals (Sweden)

    Xing Yang

    Full Text Available The fruit fly Drosophila melanogaster has a sophisticated visual system and exhibits complex visual behaviors. Visual responses, vision processing and higher cognitive processes in Drosophila have been studied extensively. However, little is known about whether the retinal location of visual stimuli can affect fruit fly performance in various visual tasks. We tested the response of wild-type Berlin flies to visual stimuli at several vertical locations. Three paradigms were used in our study: visual operant conditioning, visual object fixation and optomotor response. We observed an acute zone for visual feature memorization in the upper visual field when visual patterns were presented with a black background. However, when a white background was used, the acute zone was in the lower visual field. Similar to visual feature memorization, the best locations for visual object fixation and optomotor response to a single moving stripe were in the lower visual field with a white background and the upper visual field with a black background. The preferred location for the optomotor response to moving gratings was around the equator of the visual field. Our results suggest that different visual processing pathways are involved in different visual tasks and that there is a certain degree of overlap between the pathways for visual feature memorization, visual object fixation and optomotor response.

  19. Houdini for Astrophysical Visualization

    Science.gov (United States)

    Naiman, J. P.; Borkiewicz, Kalina; Christensen, A. J.

    2017-05-01

    The rapid growth in scale and complexity of both computational and observational astrophysics over the past decade necessitates efficient and intuitive methods for examining and visualizing large data sets. Here, we discuss some newly developed tools used to import and manipulate astrophysical data into the three-dimensional visual effects software, Houdini. This software is widely used by visual effects artists, but a recently implemented Python API now allows astronomers to more easily use Houdini as a visualization tool. This paper includes a description of features, workflow, and various example visualizations. The project website, www.ytini.com, is aimed at a scientific audience and contains Houdini tutorials and links to the Python script Bitbucket repository to simplify the process of importing and rendering astrophysical data.

  20. Visual electrophysiology in children

    Directory of Open Access Journals (Sweden)

    Jelka Brecelj

    2005-10-01

    Full Text Available Background: Electrophysiological assessment of vision in children helps to recognise abnormal development of the visual system when it is still susceptible to medication and eventual correction. Visual electrophysiology provides information about the function of the retina (retinal pigment epithelium, cone and rod receptors, bipolar, amacrine, and ganglion cells, optic nerve, chiasmal and postchiasmal visual pathway, and visual cortex.Methods: Electroretinograms (ERG and visual evoked potentials (VEP are recorded non-invasively; in infants are recorded simultaneously ERG with skin electrodes, while in older children separately ERG with HK loop electrode in accordance with ISCEV (International Society for Clinical Electrophysiology of Vision recommendations.Results: Clinical and electrophysiological changes in children with nystagmus, Leber’s congenital amaurosis, achromatopsia, congenital stationary night blindness, progressive retinal dystrophies, optic nerve hypoplasia, albinism, achiasmia, optic neuritis and visual pathway tumours are presented.Conclusions: Electrophysiological tests can help to indicate the nature and the location of dysfunction in unclear ophthalmological and/or neurological cases.

  1. PathwayAccess: CellDesigner plugins for pathway databases.

    Science.gov (United States)

    Van Hemert, John L; Dickerson, Julie A

    2010-09-15

    CellDesigner provides a user-friendly interface for graphical biochemical pathway description. Many pathway databases are not directly exportable to CellDesigner models. PathwayAccess is an extensible suite of CellDesigner plugins, which connect CellDesigner directly to pathway databases using respective Java application programming interfaces. The process is streamlined for creating new PathwayAccess plugins for specific pathway databases. Three PathwayAccess plugins, MetNetAccess, BioCycAccess and ReactomeAccess, directly connect CellDesigner to the pathway databases MetNetDB, BioCyc and Reactome. PathwayAccess plugins enable CellDesigner users to expose pathway data to analytical CellDesigner functions, curate their pathway databases and visually integrate pathway data from different databases using standard Systems Biology Markup Language and Systems Biology Graphical Notation. Implemented in Java, PathwayAccess plugins run with CellDesigner version 4.0.1 and were tested on Ubuntu Linux, Windows XP and 7, and MacOSX. Source code, binaries, documentation and video walkthroughs are freely available at http://vrac.iastate.edu/~jlv.

  2. Operative Links

    DEFF Research Database (Denmark)

    Wistoft, Karen; Højlund, Holger

    2012-01-01

    educational goals, learning content, or value clarification. Health pedagogy is often a matter of retrospective rationalization rather than the starting point of planning. Health and risk behaviour approaches override health educational approaches. Conclusions: Operational links between health education......, health professionalism, and management strategies pose the foremost challenge. Operational links indicates cooperative levels that facilitate a creative and innovative effort across traditional professional boundaries. It is proposed that such links are supported by network structures, shared semantics...

  3. Assessment of visual disability using visual evoked potentials.

    Science.gov (United States)

    Jeon, Jihoon; Oh, Seiyul; Kyung, Sungeun

    2012-08-06

    The purpose of this study is to validate the use of visual evoked potential (VEP) to objectively quantify visual acuity in normal and amblyopic patients, and determine if it is possible to predict visual acuity in disability assessment to register visual pathway lesions. A retrospective chart review was conducted of patients diagnosed with normal vision, unilateral amblyopia, optic neuritis, and visual disability who visited the university medical center for registration from March 2007 to October 2009. The study included 20 normal subjects (20 right eyes: 10 females, 10 males, ages 9-42 years), 18 unilateral amblyopic patients (18 amblyopic eyes, ages 19-36 years), 19 optic neuritis patients (19 eyes: ages 9-71 years), and 10 patients with visual disability having visual pathway lesions. Amplitude and latencies were analyzed and correlations with visual acuity (logMAR) were derived from 20 normal and 18 amblyopic subjects. Correlation of VEP amplitude and visual acuity (logMAR) of 19 optic neuritis patients confirmed relationships between visual acuity and amplitude. We calculated the objective visual acuity (logMAR) of 16 eyes from 10 patients to diagnose the presence or absence of visual disability using relations derived from 20 normal and 18 amblyopic eyes. Linear regression analyses between amplitude of pattern visual evoked potentials and visual acuity (logMAR) of 38 eyes from normal (right eyes) and amblyopic (amblyopic eyes) subjects were significant [y = -0.072x + 1.22, x: VEP amplitude, y: visual acuity (logMAR)]. There were no significant differences between visual acuity prediction values, which substituted amplitude values of 19 eyes with optic neuritis into function. We calculated the objective visual acuity of 16 eyes of 10 patients to diagnose the presence or absence of visual disability using relations of y = -0.072x + 1.22 (-0.072). This resulted in a prediction reference of visual acuity associated with malingering vs. real

  4. Assessment of visual disability using visual evoked potentials

    Directory of Open Access Journals (Sweden)

    Jeon Jihoon

    2012-08-01

    Full Text Available Abstract Background The purpose of this study is to validate the use of visual evoked potential (VEP to objectively quantify visual acuity in normal and amblyopic patients, and determine if it is possible to predict visual acuity in disability assessment to register visual pathway lesions. Methods A retrospective chart review was conducted of patients diagnosed with normal vision, unilateral amblyopia, optic neuritis, and visual disability who visited the university medical center for registration from March 2007 to October 2009. The study included 20 normal subjects (20 right eyes: 10 females, 10 males, ages 9–42 years, 18 unilateral amblyopic patients (18 amblyopic eyes, ages 19–36 years, 19 optic neuritis patients (19 eyes: ages 9–71 years, and 10 patients with visual disability having visual pathway lesions. Amplitude and latencies were analyzed and correlations with visual acuity (logMAR were derived from 20 normal and 18 amblyopic subjects. Correlation of VEP amplitude and visual acuity (logMAR of 19 optic neuritis patients confirmed relationships between visual acuity and amplitude. We calculated the objective visual acuity (logMAR of 16 eyes from 10 patients to diagnose the presence or absence of visual disability using relations derived from 20 normal and 18 amblyopic eyes. Results Linear regression analyses between amplitude of pattern visual evoked potentials and visual acuity (logMAR of 38 eyes from normal (right eyes and amblyopic (amblyopic eyes subjects were significant [y = −0.072x + 1.22, x: VEP amplitude, y: visual acuity (logMAR]. There were no significant differences between visual acuity prediction values, which substituted amplitude values of 19 eyes with optic neuritis into function. We calculated the objective visual acuity of 16 eyes of 10 patients to diagnose the presence or absence of visual disability using relations of y = −0.072x + 1.22 (−0.072. This resulted in a prediction

  5. The Visual System

    Medline Plus

    Full Text Available ... Fun Stuff Cool Eye Tricks Links to More Information Optical Illusions Printables The Visual System Ever wonder how your eyes work? Watch this video to learn how you’re able to see the world around you. Did ... on Social Media Information in Spanish (Información en español) Website, Social Media ...

  6. The Visual System

    Medline Plus

    Full Text Available ... System Your Eyes’ Natural Defenses Eye Health and Safety First Aid Tips Healthy Vision Tips Protective Eyewear Sports and Your Eyes Fun Stuff Cool Eye Tricks Links to More Information Optical Illusions Printables The Visual System Ever wonder how your eyes work? Watch this video to learn how you’re ...

  7. The Visual System

    Medline Plus

    Full Text Available ... Fun Stuff Cool Eye Tricks Links to More Information Optical Illusions Printables The Visual System Ever wonder how your eyes work? Watch this video to learn how you’re able to see the world around you. Did You Know? On ... on Social Media Information in Spanish (Información en español) Website, Social Media ...

  8. Visual art and visual perception

    NARCIS (Netherlands)

    Koenderink, Jan J.

    2015-01-01

    Visual art and visual perception ‘Visual art’ has become a minor cul-de-sac orthogonal to THE ART of the museum directors and billionaire collectors. THE ART is conceptual, instead of visual. Among its cherished items are the tins of artist’s shit (Piero Manzoni, 1961, Merda d’Artista) “worth their

  9. Are Deaf Students Visual Learners?

    Science.gov (United States)

    Marschark, Marc; Morrison, Carolyn; Lukomski, Jennifer; Borgna, Georgianna; Convertino, Carol

    2013-01-01

    It is frequently assumed that by virtue of their hearing losses, deaf students are visual learners. Deaf individuals have some visual-spatial advantages relative to hearing individuals, but most have been linked to use of sign language rather than auditory deprivation. How such cognitive differences might affect academic performance has been…

  10. MAPT and PAICE: Tools for time series and single time point transcriptionist visualization and knowledge discovery.

    Science.gov (United States)

    Hosseini, Parsa; Tremblay, Arianne; Matthews, Benjamin F; Alkharouf, Nadim W

    2012-01-01

    With the advent of next-generation sequencing, -omics fields such as transcriptomics have experienced increases in data throughput on the order of magnitudes. In terms of analyzing and visually representing these huge datasets, an intuitive and computationally tractable approach is to map quantified transcript expression onto biochemical pathways while employing datamining and visualization principles to accelerate knowledge discovery. We present two cross-platform tools: MAPT (Mapping and Analysis of Pathways through Time) and PAICE (Pathway Analysis and Integrated Coloring of Experiments), an easy to use analysis suite to facilitate time series and single time point transcriptomics analysis. In unison, MAPT and PAICE serve as a visual workbench for transcriptomics knowledge discovery, data-mining and functional annotation. Both PAICE and MAPT are two distinct but yet inextricably linked tools. The former is specifically designed to map EC accessions onto KEGG pathways while handling multiple gene copies, detection-call analysis, as well as UN/annotated EC accessions lacking quantifiable expression. The latter tool integrates PAICE datasets to drive visualization, annotation, and data-mining. The database is available for free at http://sourceforge.net/projects/paice/http://sourceforge.net/projects/mapt/

  11. Processing Of Visual Information In Primate Brains

    Science.gov (United States)

    Anderson, Charles H.; Van Essen, David C.

    1991-01-01

    Report reviews and analyzes information-processing strategies and pathways in primate retina and visual cortex. Of interest both in biological fields and in such related computational fields as artificial neural networks. Focuses on data from macaque, which has superb visual system similar to that of humans. Authors stress concept of "good engineering" in understanding visual system.

  12. Flow visualization

    CERN Document Server

    Merzkirch, Wolfgang

    1974-01-01

    Flow Visualization describes the most widely used methods for visualizing flows. Flow visualization evaluates certain properties of a flow field directly accessible to visual perception. Organized into five chapters, this book first presents the methods that create a visible flow pattern that could be investigated by visual inspection, such as simple dye and density-sensitive visualization methods. It then deals with the application of electron beams and streaming birefringence. Optical methods for compressible flows, hydraulic analogy, and high-speed photography are discussed in other cha

  13. Principles of visual attention

    DEFF Research Database (Denmark)

    Bundesen, Claus; Habekost, Thomas

    The nature of attention is one of the oldest and most central problems in psychology. A huge amount of research has been produced on this subject in the last half century, especially on attention in the visual modality, but a general explanation has remained elusive. Many still view attention...... research as a field that is fundamentally fragmented. This book takes a different perspective and presents a unified theory of visual attention: the TVA model. The TVA model explains the many aspects of visual attention by just two mechanisms for selection of information: filtering and pigeonholing....... These mechanisms are described in a set of simple equations, which allow TVA to mathematically model a large number of classical results in the attention literature. The theory explains psychological and neuroscientific findings by the same equations; TVA is a complete theory of visual attention, linking mind...

  14. Pathways with PathWhiz.

    Science.gov (United States)

    Pon, Allison; Jewison, Timothy; Su, Yilu; Liang, Yongjie; Knox, Craig; Maciejewski, Adam; Wilson, Michael; Wishart, David S

    2015-07-01

    PathWhiz (http://smpdb.ca/pathwhiz) is a web server designed to create colourful, visually pleasing and biologically accurate pathway diagrams that are both machine-readable and interactive. As a web server, PathWhiz is accessible from almost any place and compatible with essentially any operating system. It also houses a public library of pathways and pathway components that can be easily viewed and expanded upon by its users. PathWhiz allows users to readily generate biologically complex pathways by using a specially designed drawing palette to quickly render metabolites (including automated structure generation), proteins (including quaternary structures, covalent modifications and cofactors), nucleic acids, membranes, subcellular structures, cells, tissues and organs. Both small-molecule and protein/gene pathways can be constructed by combining multiple pathway processes such as reactions, interactions, binding events and transport activities. PathWhiz's pathway replication and propagation functions allow for existing pathways to be used to create new pathways or for existing pathways to be automatically propagated across species. PathWhiz pathways can be saved in BioPAX, SBGN-ML and SBML data exchange formats, as well as PNG, PWML, HTML image map or SVG images that can be viewed offline or explored using PathWhiz's interactive viewer. PathWhiz has been used to generate over 700 pathway diagrams for a number of popular databases including HMDB, DrugBank and SMPDB. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. Cartographic visualization

    NARCIS (Netherlands)

    Kraak, M.J.; Wright, James D.

    2015-01-01

    The cartographic visualization process, based on the statement “How do I say what to whom, and is it effective?” is explained for both presenting and exploring spatiotemporal data. The visualization environment and required functionality are described

  16. Neural correlates of visualizations of concrete and abstract words in preschool children: A developmental embodied approach

    Directory of Open Access Journals (Sweden)

    Amedeo eD'angiulli

    2015-06-01

    Full Text Available The neural correlates of visualization underlying word comprehension were examined in preschool children. On each trial, a concrete or abstract word was delivered binaurally (part 1: post-auditory visualization, followed by a four-picture array (a target plus three distractors (part 2: matching visualization. Children were to select the picture matching the word they heard in part 1. Event-Related Potentials (ERPs locked to each stimulus presentation and task interval were averaged over sets of trials of increasing word abstractness. ERP time-course during both parts of the task showed that early activity (i.e. < 300 ms was predominant in response to concrete words, while activity in response to abstract words became evident only at intermediate (i.e. 300-699 ms and late (i.e. 700-1000 ms ERP intervals. Specifically, ERP topography showed that while early activity during post-auditory visualization was linked to left temporo-parietal areas for concrete words, early activity during matching visualization occurred mostly in occipito-parietal areas for concrete words, but more anteriorly in centro-parietal areas for abstract words. In intermediate ERPs, post-auditory visualization coincided with parieto-occipital and parieto-frontal activity in response to both concrete and abstract words, while in matching visualization a parieto-central activity was common to both types of words. In the late ERPs for both types of words, the post-auditory visualization involved right-hemispheric activity following a post-anterior pathway sequence: occipital, parietal and temporal areas; conversely, matching visualization involved left-hemispheric activity following an ant-posterior pathway sequence: frontal, temporal, parietal and occipital areas. These results suggest that, similarly for concrete and abstract words, meaning in young children depends on variably complex visualization processes integrating visuo-auditory experiences and supramodal embodying

  17. Making Memories: The Development of Long-Term Visual Knowledge in Children with Visual Agnosia

    OpenAIRE

    Tiziana Metitieri; Carmen Barba; Simona Pellacani; Maria Pia Viggiano; Renzo Guerrini

    2013-01-01

    There are few reports about the effects of perinatal acquired brain lesions on the development of visual perception. These studies demonstrate nonseverely impaired visual-spatial abilities and preserved visual memory. Longitudinal data analyzing the effects of compromised perceptions on long-term visual knowledge in agnosics are limited to lesions having occurred in adulthood. The study of children with focal lesions of the visual pathways provides a unique opportunity to assess the developme...

  18. Linked data

    NARCIS (Netherlands)

    Koster, L.

    2011-01-01

    Semantisch web, linked data, web 3.0… Het zijn allemaal termen die vaak door elkaar worden gebruikt. Onterecht vindt Lukas Koster van de Universiteit van Amsterdam. Wat houden die begrippen nu eigenlijk in?

  19. Visual Scripting.

    Science.gov (United States)

    Halas, John

    Visual scripting is the coordination of words with pictures in sequence. This book presents the methods and viewpoints on visual scripting of fourteen film makers, from nine countries, who are involved in animated cinema; it contains concise examples of how a storybook and preproduction script can be prepared in visual terms; and it includes a…

  20. Effects of Visual Cortex Activation on the Nociceptive Blink Reflex in Healthy Subjects

    Science.gov (United States)

    Sava, Simona L.; de Pasqua, Victor; Magis, Delphine; Schoenen, Jean

    2014-01-01

    Bright light can cause excessive visual discomfort, referred to as photophobia. The precise mechanisms linking luminance to the trigeminal nociceptive system supposed to mediate this discomfort are not known. To address this issue in healthy human subjects we modulated differentially visual cortex activity by repetitive transcranial magnetic stimulation (rTMS) or flash light stimulation, and studied the effect on supraorbital pain thresholds and the nociceptive-specific blink reflex (nBR). Low frequency rTMS that inhibits the underlying cortex, significantly decreased pain thresholds, increased the 1st nBR block ipsi- and contralaterally and potentiated habituation contralaterally. After high frequency or sham rTMS over the visual cortex, and rMS over the right greater occipital nerve we found no significant change. By contrast, excitatory flash light stimulation increased pain thresholds, decreased the 1st nBR block of ipsi- and contralaterally and increased habituation contralaterally. Our data demonstrate in healthy subjects a functional relation between the visual cortex and the trigeminal nociceptive system, as assessed by the nociceptive blink reflex. The results argue in favour of a top-down inhibitory pathway from the visual areas to trigemino-cervical nociceptors. We postulate that in normal conditions this visuo-trigeminal inhibitory pathway may avoid disturbance of vision by too frequent blinking and that hypoactivity of the visual cortex for pathological reasons may promote headache and photophobia. PMID:24936654

  1. Data visualization

    CERN Document Server

    Azzam, Tarek

    2013-01-01

    Do you communicate data and information to stakeholders? In Part 1, we introduce recent developments in the quantitative and qualitative data visualization field and provide a historical perspective on data visualization, its potential role in evaluation practice, and future directions. Part 2 delivers concrete suggestions for optimally using data visualization in evaluation, as well as suggestions for best practices in data visualization design. It focuses on specific quantitative and qualitative data visualization approaches that include data dashboards, graphic recording, and geographic information systems (GIS). Readers will get a step-by-step process for designing an effective data dashboard system for programs and organizations, and various suggestions to improve their utility.

  2. Quantized Visual Awareness

    Directory of Open Access Journals (Sweden)

    W Alexander Escobar

    2013-11-01

    Full Text Available The proposed model holds that, at its most fundamental level, visual awareness is quantized. That is to say that visual awareness arises as individual bits of awareness through the action of neural circuits with hundreds to thousands of neurons in at least the human striate cortex. Circuits with specific topologies will reproducibly result in visual awareness that correspond to basic aspects of vision like color, motion and depth. These quanta of awareness (qualia are produced by the feedforward sweep that occurs through the geniculocortical pathway but are not integrated into a conscious experience until recurrent processing from centers like V4 or V5 select the appropriate qualia being produced in V1 to create a percept. The model proposed here has the potential to shift the focus of the search for visual awareness to the level of microcircuits and these likely exist across the kingdom Animalia. Thus establishing qualia as the fundamental nature of visual awareness will not only provide a deeper understanding of awareness, but also allow for a more quantitative understanding of the evolution of visual awareness throughout the animal kingdom.

  3. Visual loss after orthopedic procedures.

    Science.gov (United States)

    Kaeser, Pierre-François; Borruat, François-Xavier

    2011-02-01

    Perioperative visual loss (PVL) is a very rare and unpredictable complication of surgery performed at distance from the visual pathways, mostly after spine or cardiac procedures. We report 6 consecutive patients with PVL after routine orthopedic procedures (osteosynthesis for complex fracture of the femur [2], total hip arthroplasty [2], hip prosthesis arthroplasty [1], bilateral simultaneous total knee arthroplasty [1]) and reviewed the literature on the subject. An ischemic optic neuropathy was diagnosed in all cases, and visual loss was bilateral in 5 of 6 patients. Partial visual improvement occurred in only 3 of 11 eyes. No specific therapy is available for PVL. Postoperative visual disturbances should prompt without delay an ophthalmic evaluation because emergent correction of anemia, systemic hypotension, or hypovolemia might improve visual prognosis of PVL. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Visual handicap in children.

    Science.gov (United States)

    Bull, M; Evans, P J; Maclean, H

    1982-05-01

    Vision is the primary mode of learning and if it is absent or impaired, other pathways must be stimulated. The range of appropriate services available to visually handicapped children is explained in relation to the school run by the Royal Victorian Institution for the Blind in Melbourne. A period of residential education may be needed for children with multiple impairment. Those whose handicap is primarily visual can usually live at home and have their education integrated with that of their normal peers. Home-based services and parent support systems for preschool and kindergarten age children are outlined. To be successful, they require sharing confidential medical and education information. The school provides a major input to a discussion group of all professionals dealing with such children. Information from the group includes the causes, and educational implications of visual handicap in Victorian children. The commonest pathologies are macular problems and congenital cataract.

  5. GABA predicts visual intelligence.

    Science.gov (United States)

    Cook, Emily; Hammett, Stephen T; Larsson, Jonas

    2016-10-06

    Early psychological researchers proposed a link between intelligence and low-level perceptual performance. It was recently suggested that this link is driven by individual variations in the ability to suppress irrelevant information, evidenced by the observation of strong correlations between perceptual surround suppression and cognitive performance. However, the neural mechanisms underlying such a link remain unclear. A candidate mechanism is neural inhibition by gamma-aminobutyric acid (GABA), but direct experimental support for GABA-mediated inhibition underlying suppression is inconsistent. Here we report evidence consistent with a global suppressive mechanism involving GABA underlying the link between sensory performance and intelligence. We measured visual cortical GABA concentration, visuo-spatial intelligence and visual surround suppression in a group of healthy adults. Levels of GABA were strongly predictive of both intelligence and surround suppression, with higher levels of intelligence associated with higher levels of GABA and stronger surround suppression. These results indicate that GABA-mediated neural inhibition may be a key factor determining cognitive performance and suggests a physiological mechanism linking surround suppression and intelligence. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  6. Changes in visual object recognition precede the shape bias in early noun learning

    Directory of Open Access Journals (Sweden)

    Meagan N Yee

    2012-12-01

    Full Text Available Two of the most formidable skills that characterize human beings are language and our prowess in visual object recognition. They may also be developmentally intertwined. Two experiments, a large sample cross-sectional study and a smaller sample 6-month longitudinal study of 18- 24 month olds tested a hypothesized developmental link between changes in the visual object representation and noun learning. Previous findings in visual object recognition indicate that children’s ability to recognize common basic level categories from sparse structural shape representations of object shape emerges between the ages of 18 and 24 months, is related to noun vocabulary size, and is lacking in children with language delay. Other research shows that in artificial noun learning tasks, during this same developmental period, young children systematically generalize object names by shape, that this shape bias predicts future noun learning, and is lacking in children with language delay. The two experiments examine the developmental relation between visual object recognition and the shape bias for the first time. The results show that developmental changes in visual object recognition systematically preceded the emergence of the shape bias. The results suggest a developmental pathway in which early changes in visual object recognition that are themselves linked to category learning enable the discovery of higher-order regularities in category structure and thus the shape bias in novel noun learning tasks. The proposed developmental pathway has implications for understanding the role of specific experience in the development of both visual object recognition and the shape bias in early noun learning.

  7. METAGRAPH VISUALIZATION METHOD

    Directory of Open Access Journals (Sweden)

    O. S. Kryvenko

    2014-05-01

    Full Text Available Analysis of visualization techniques for various types of graphs is done. Conclusion about the relevance of method development for metagraph visualizing is made. The paper deals with issues that arise when solving the problem of metagraph visualization, such as: the placement of nodes that belong to metavertices and do not belong to them, figures intersection of metavertices. These problems are exemplified. Criteria are proposed for the final image to be considered coherent, understandable for users and corresponding to a predetermined metagraph. The problem of metagraph visualization is posed. The method based on the principles of force algorithms is proposed for the problem solving. The rules for forces between metagraph nodes are defined in the framework of the method. These forces depend on nodes type between which they are performed and the presence of edges between them. This method does not involve human intervention during the formation of the image, thus saving time at frequent changes that require rebuilding of the image. The resulting image gives the possibility to portray clearly the entities of the subject area and the links between them. Graphical analysis methods can be applied to the image. Areas for the future researches are identified. They are: minimization of the number of edges intersections and the area occupied by the resulting image. Results of the modified visualization method can improve the visual metagraph representation.

  8. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... projects/learn-link-drugs-hiv . 120x90 460x80 486x60 Social Media Send the message to young people and ... Daytona Beach Film Festival Big Mini Film Festival Visual AIDS Bus Boys and Poets Sistahs Getting Real ...

  9. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... with NIDA : Facebook LinkedIn Twitter YouTube Flickr RSS Menu Home Drugs of Abuse Commonly Abused Drugs Charts ... Daytona Beach Film Festival Big Mini Film Festival Visual AIDS Bus Boys and Poets Sistahs Getting Real ...

  10. Visual Sedimentation

    OpenAIRE

    Huron, Samuel; Vuillemot, Romain; Fekete, Jean-Daniel

    2013-01-01

    International audience; We introduce Visual Sedimentation, a novel design metaphor for visualizing data streams directly inspired by the physical process of sedimentation. Visualizing data streams (e. g., Tweets, RSS, Emails) is challenging as incoming data arrive at unpredictable rates and have to remain readable. For data streams, clearly expressing chronological order while avoiding clutter, and keeping aging data visible, are important. The metaphor is drawn from the real-world sedimentat...

  11. Visualization Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Evaluates and improves the operational effectiveness of existing and emerging electronic warfare systems. By analyzing and visualizing simulation results...

  12. Are Deaf Students Visual Learners?

    Science.gov (United States)

    Marschark, Marc; Morrison, Carolyn; Lukomski, Jennifer; Borgna, Georgianna; Convertino, Carol

    2013-01-01

    It is frequently assumed that by virtue of their hearing losses, deaf students are visual learners. Deaf individuals have some visual-spatial advantages relative to hearing individuals, but most have been are linked to use of sign language rather than auditory deprivation. How such cognitive differences might affect academic performance has been investigated only rarely. This study examined relations among deaf college students’ language and visual-spatial abilities, mathematics problem solving, and hearing thresholds. Results extended some previous findings and clarified others. Contrary to what might be expected, hearing students exhibited visual-spatial skills equal to or better than deaf students. Scores on a Spatial Relations task were associated with better mathematics problem solving. Relations among the several variables, however, suggested that deaf students are no more likely to be visual learners than hearing students and that their visual-spatial skill may be related more to their hearing than to sign language skills. PMID:23750095

  13. KeyPathwayMinerWeb

    DEFF Research Database (Denmark)

    List, Markus; Alcaraz, Nicolas; Dissing-Hansen, Martin

    2016-01-01

    such as data integration, input of background knowledge, batch runs for parameter optimization and visualization of extracted pathways. In addition to an intuitive web interface, we also implemented a RESTful API that now enables other online developers to integrate network enrichment as a web service......We present KeyPathwayMinerWeb, the first online platform for de novo pathway enrichment analysis directly in the browser. Given a biological interaction network (e.g. protein-protein interactions) and a series of molecular profiles derived from one or multiple OMICS studies (gene expression...

  14. Visual search

    NARCIS (Netherlands)

    Toet, A.; Bijl, P.

    2003-01-01

    Visual search, with or without the aid of optical or electro-optical instruments, plays a significant role in various types of military and civilian operations (e.g., reconnaissance, surveillance, and search and rescue). Advance knowledge of human visual search and target acquisition performance is

  15. Visual Education

    DEFF Research Database (Denmark)

    Buhl, Mie; Flensborg, Ingelise

    2010-01-01

    The intrinsic breadth of various types of images creates new possibilities and challenges for visual education. The digital media have moved the boundaries between images and other kinds of modalities (e.g. writing, speech and sound) and have augmented the possibilities for integrating the functi......The intrinsic breadth of various types of images creates new possibilities and challenges for visual education. The digital media have moved the boundaries between images and other kinds of modalities (e.g. writing, speech and sound) and have augmented the possibilities for integrating...... to emerge in the interlocutory space of a global visual repertoire and diverse local interpretations. The two perspectives represent challenges for future visual education which require visual competences, not only within the arts but also within the subjects of natural sciences, social sciences, languages...

  16. Flow, affect and visual creativity.

    Science.gov (United States)

    Cseh, Genevieve M; Phillips, Louise H; Pearson, David G

    2015-01-01

    Flow (being in the zone) is purported to have positive consequences in terms of affect and performance; however, there is no empirical evidence about these links in visual creativity. Positive affect often--but inconsistently--facilitates creativity, and both may be linked to experiencing flow. This study aimed to determine relationships between these variables within visual creativity. Participants performed the creative mental synthesis task to simulate the creative process. Affect change (pre- vs. post-task) and flow were measured via questionnaires. The creativity of synthesis drawings was rated objectively and subjectively by judges. Findings empirically demonstrate that flow is related to affect improvement during visual creativity. Affect change was linked to productivity and self-rated creativity, but no other objective or subjective performance measures. Flow was unrelated to all external performance measures but was highly correlated with self-rated creativity; flow may therefore motivate perseverance towards eventual excellence rather than provide direct cognitive enhancement.

  17. Revolutionary Pathways

    DEFF Research Database (Denmark)

    Colgan, Jeff; Lucas, Edward

    2017-01-01

    How much and in what ways do individual leaders matter for international politics? This article sheds new light on these questions by considering the consequences of domestic revolutions in international relations. We argue that revolutions have international effects due to two separate pathways......, one associated with the event and one associated with the new leader's administration. In the first pathway, a revolutionary event disrupts established relationships and perceptions, creating uncertainty both within the state and abroad. In the second pathway, revolutions put individuals into office...... who are more willing to challenge the status quo and who have publicly committed to a sustained shift in policies during their administration. These two distinct pathways suggest that the important question about revolutions is not whether leaders or events matter most but rather the conditions under...

  18. Visual exploration across biomedical databases.

    Science.gov (United States)

    Lieberman, Michael D; Taheri, Sima; Guo, Huimin; Mirrashed, Fatemeh; Yahav, Inbal; Aris, Aleks; Shneiderman, Ben

    2011-01-01

    Though biomedical research often draws on knowledge from a wide variety of fields, few visualization methods for biomedical data incorporate meaningful cross-database exploration. A new approach is offered for visualizing and exploring a query-based subset of multiple heterogeneous biomedical databases. Databases are modeled as an entity-relation graph containing nodes (database records) and links (relationships between records). Users specify a keyword search string to retrieve an initial set of nodes, and then explore intra- and interdatabase links. Results are visualized with user-defined semantic substrates to take advantage of the rich set of attributes usually present in biomedical data. Comments from domain experts indicate that this visualization method is potentially advantageous for biomedical knowledge exploration.

  19. Stroke pathways.

    Science.gov (United States)

    Venketasubramanian, N

    2001-07-01

    Stroke pathways are task-orientated structured multidisciplinary care plans which detail essential steps and interventions during the period of care of a "typical" stroke patient. Pathway development and implementation are best achieved by an appointed champion leading a multidisciplinary team of health care workers and administrators, who will also be the end users of the pathway. Pathway development involves reviews of existing clinical practice guidelines and pathways, followed by documentation, interdigitation and prioritization of care requirements at different time points in the various spheres, taking into consideration local philosophies and practices. These spheres could include investigations, pharmacologic treatment, rehabilitative therapy, nursing measures, and patient education. This would result in evidence-based holistic quality care, wide support base, efficient service provision, reduced costs and length of stay, less practice variation, improved communication among disciplines, enhanced patient-staff relationship, ease of audit and research opportunities. Components of the pathway could include a patient summary sheet, multidisciplinary record of the various activities structured on a day-to-day basis, sign-off columns for staff responsible for performing those activity, variance sheet, and separate protocols for specific issues. Implementation requires training of users, pilot runs, feedback, regular revisions, monitoring of compliance, and analysis of variances. Widespread implementation of pathways may be hindered by lack of support, and concerns about increased time requirements and costs, stifling of innovation, restriction of application of clinical judgement, lack of applicability to all patients, misuse and legal issues. However, a well-designed pathway will ensure quality care in a cost-efficient manner, benefiting the patient, carer and the health care service.

  20. Visualizing Data Patterns with Micromaps

    CERN Document Server

    Carr, Daniel B

    2010-01-01

    After more than 15 years of development drawing on research in cognitive psychology, statistical graphics, computer science, and cartography, micromap designs are becoming part of mainstream statistical visualizations. Bringing together the research of two leaders in this field, "Visualizing Data Patterns with Micromaps" presents the many design variations and applications of micromaps, which link statistical information to an organized set of small maps. This full-color book helps readers simultaneously explore the statistical and geographic patterns in their data. After illustratin

  1. Interactive online brain shape visualization

    Directory of Open Access Journals (Sweden)

    Anisha Keshavan

    2017-02-01

    Full Text Available The open-source Mindboggle package improves the labeling and morphometry estimates of brain imaging data. At the 2015 Brainhack event, we developed a web-based, interactive, brain shape visualization of Mindboggle outputs. The application links a 3D brain visualization with boxplots that describe shape measures across a selected cortical label. The code is freely available at http://www.github.com/akeshavan/roygbiv and a demo is online at http://roygbiv.mindboggle.info.

  2. Visual cognition.

    Science.gov (United States)

    Cavanagh, Patrick

    2011-07-01

    Visual cognition, high-level vision, mid-level vision and top-down processing all refer to decision-based scene analyses that combine prior knowledge with retinal input to generate representations. The label "visual cognition" is little used at present, but research and experiments on mid- and high-level, inference-based vision have flourished, becoming in the 21st century a significant, if often understated part, of current vision research. How does visual cognition work? What are its moving parts? This paper reviews the origins and architecture of visual cognition and briefly describes some work in the areas of routines, attention, surfaces, objects, and events (motion, causality, and agency). Most vision scientists avoid being too explicit when presenting concepts about visual cognition, having learned that explicit models invite easy criticism. What we see in the literature is ample evidence for visual cognition, but few or only cautious attempts to detail how it might work. This is the great unfinished business of vision research: at some point we will be done with characterizing how the visual system measures the world and we will have to return to the question of how vision constructs models of objects, surfaces, scenes, and events. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Enhanced visual motion perception in major depressive disorder.

    Science.gov (United States)

    Golomb, Julie D; McDavitt, Jenika R B; Ruf, Barbara M; Chen, Jason I; Saricicek, Aybala; Maloney, Kathleen H; Hu, Jian; Chun, Marvin M; Bhagwagar, Zubin

    2009-07-15

    Major depressive disorder (MDD) is a mood disorder that is not traditionally considered to affect the visual system. However, recent findings have reported decreased cortical levels of the inhibitory neurotransmitter GABA in occipital cortex. To explore possible functional consequences of MDD on visual processing, we applied a psychophysical visual motion processing task in which healthy young adults typically exhibit impaired perceptual discrimination of large high-contrast stimuli. It has been suggested that this phenomenon, spatial suppression, is mediated by GABAergic center-surround antagonism in visual pathways. Based on previous findings linking MDD to occipital GABA dysfunction, we hypothesized that MDD patients would exhibit decreased spatial suppression, leading to the counterintuitive hypothesis of better psychophysical performance. Indeed, motion perception for typically suppressed stimuli was enhanced in patients with MDD compared with age-matched controls. Furthermore, the degree of spatial suppression correlated with an individual's illness load; patients with greater lifetime duration of depression exhibited the least spatial suppression and performed the best in the high-contrast motion discrimination task. Notably, this decrease in spatial suppression persisted beyond recovery and without the confound of acute illness or treatment; all patients had been clinically recovered and unmedicated for several months at the time of testing, suggesting that depression has ubiquitous consequences that may persist long after mood symptoms have receded. This finding raises the possibility that spatial suppression may represent a sensitive endophenotypic marker of trait vulnerability in MDD.

  4. Dancing links

    OpenAIRE

    Knuth, Donald E.

    2000-01-01

    The author presents two tricks to accelerate depth-first search algorithms for a class of combinatorial puzzle problems, such as tiling a tray by a fixed set of polyominoes. The first trick is to implement each assumption of the search with reversible local operations on doubly linked lists. By this trick, every step of the search affects the data incrementally. The second trick is to add a ghost square that represents the identity of each polyomino. Thus puts the rule that each polyomino be ...

  5. Visual cognition

    OpenAIRE

    Cavanagh, Patrick

    2011-01-01

    Visual cognition, high-level vision, mid-level vision and top-down processing all refer to decision-based scene analyses that combine prior knowledge with retinal input to generate representations. The label “visual cognition” is little used at present, but research and experiments on mid- and high-level, inference-based vision have flourished, becoming in the 21st century a significant, if often understated part, of current vision research. How does visual cognition work? What are its moving...

  6. Visual agnosia and focal brain injury.

    Science.gov (United States)

    Martinaud, O

    Visual agnosia encompasses all disorders of visual recognition within a selective visual modality not due to an impairment of elementary visual processing or other cognitive deficit. Based on a sequential dichotomy between the perceptual and memory systems, two different categories of visual object agnosia are usually considered: 'apperceptive agnosia' and 'associative agnosia'. Impaired visual recognition within a single category of stimuli is also reported in: (i) visual object agnosia of the ventral pathway, such as prosopagnosia (for faces), pure alexia (for words), or topographagnosia (for landmarks); (ii) visual spatial agnosia of the dorsal pathway, such as cerebral akinetopsia (for movement), or orientation agnosia (for the placement of objects in space). Focal brain injuries provide a unique opportunity to better understand regional brain function, particularly with the use of effective statistical approaches such as voxel-based lesion-symptom mapping (VLSM). The aim of the present work was twofold: (i) to review the various agnosia categories according to the traditional visual dual-pathway model; and (ii) to better assess the anatomical network underlying visual recognition through lesion-mapping studies correlating neuroanatomical and clinical outcomes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Linking assumptions in amblyopia

    Science.gov (United States)

    LEVI, DENNIS M.

    2017-01-01

    Over the last 35 years or so, there has been substantial progress in revealing and characterizing the many interesting and sometimes mysterious sensory abnormalities that accompany amblyopia. A goal of many of the studies has been to try to make the link between the sensory losses and the underlying neural losses, resulting in several hypotheses about the site, nature, and cause of amblyopia. This article reviews some of these hypotheses, and the assumptions that link the sensory losses to specific physiological alterations in the brain. Despite intensive study, it turns out to be quite difficult to make a simple linking hypothesis, at least at the level of single neurons, and the locus of the sensory loss remains elusive. It is now clear that the simplest notion—that reduced contrast sensitivity of neurons in cortical area V1 explains the reduction in contrast sensitivity—is too simplistic. Considerations of noise, noise correlations, pooling, and the weighting of information also play a critically important role in making perceptual decisions, and our current models of amblyopia do not adequately take these into account. Indeed, although the reduction of contrast sensitivity is generally considered to reflect “early” neural changes, it seems plausible that it reflects changes at many stages of visual processing. PMID:23879956

  8. Visual Confidence.

    Science.gov (United States)

    Mamassian, Pascal

    2016-10-14

    Visual confidence refers to an observer's ability to judge the accuracy of her perceptual decisions. Even though confidence judgments have been recorded since the early days of psychophysics, only recently have they been recognized as essential for a deeper understanding of visual perception. The reluctance to study visual confidence may have come in part from obtaining convincing experimental evidence in favor of metacognitive abilities rather than just perceptual sensitivity. Some effort has thus been dedicated to offer different experimental paradigms to study visual confidence in humans and nonhuman animals. To understand the origins of confidence judgments, investigators have developed two competing frameworks. The approach based on signal decision theory is popular but fails to account for response times. In contrast, the approach based on accumulation of evidence models naturally includes the dynamics of perceptual decisions. These models can explain a range of results, including the apparently paradoxical dissociation between performance and confidence that is sometimes observed.

  9. Visual cognition

    Energy Technology Data Exchange (ETDEWEB)

    Pinker, S.

    1985-01-01

    This book consists of essays covering issues in visual cognition presenting experimental techniques from cognitive psychology, methods of modeling cognitive processes on computers from artificial intelligence, and methods of studying brain organization from neuropsychology. Topics considered include: parts of recognition; visual routines; upward direction; mental rotation, and discrimination of left and right turns in maps; individual differences in mental imagery, computational analysis and the neurological basis of mental imagery: componental analysis.

  10. Which visual functions depend on intermediate visual regions? Insights from a case of developmental visual form agnosia.

    Science.gov (United States)

    Gilaie-Dotan, Sharon

    2016-03-01

    A key question in visual neuroscience is the causal link between specific brain areas and perceptual functions; which regions are necessary for which visual functions? While the contribution of primary visual cortex and high-level visual regions to visual perception has been extensively investigated, the contribution of intermediate visual areas (e.g. V2/V3) to visual processes remains unclear. Here I review more than 20 visual functions (early, mid, and high-level) of LG, a developmental visual agnosic and prosopagnosic young adult, whose intermediate visual regions function in a significantly abnormal fashion as revealed through extensive fMRI and ERP investigations. While expectedly, some of LG's visual functions are significantly impaired, some of his visual functions are surprisingly normal (e.g. stereopsis, color, reading, biological motion). During the period of eight-year testing described here, LG trained on a perceptual learning paradigm that was successful in improving some but not all of his visual functions. Following LG's visual performance and taking into account additional findings in the field, I propose a framework for how different visual areas contribute to different visual functions, with an emphasis on intermediate visual regions. Thus, although rewiring and plasticity in the brain can occur during development to overcome and compensate for hindering developmental factors, LG's case seems to indicate that some visual functions are much less dependent on strict hierarchical flow than others, and can develop normally in spite of abnormal mid-level visual areas, thereby probably less dependent on intermediate visual regions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Visualizing water

    Science.gov (United States)

    Baart, F.; van Gils, A.; Hagenaars, G.; Donchyts, G.; Eisemann, E.; van Velzen, J. W.

    2016-12-01

    A compelling visualization is captivating, beautiful and narrative. Here we show how melding the skills of computer graphics, art, statistics, and environmental modeling can be used to generate innovative, attractive and very informative visualizations. We focus on the topic of visualizing forecasts and measurements of water (water level, waves, currents, density, and salinity). For the field of computer graphics and arts, water is an important topic because it occurs in many natural scenes. For environmental modeling and statistics, water is an important topic because the water is essential for transport, a healthy environment, fruitful agriculture, and a safe environment.The different disciplines take different approaches to visualizing water. In computer graphics, one focusses on creating water as realistic looking as possible. The focus on realistic perception (versus the focus on the physical balance pursued by environmental scientists) resulted in fascinating renderings, as seen in recent games and movies. Visualization techniques for statistical results have benefited from the advancement in design and journalism, resulting in enthralling infographics. The field of environmental modeling has absorbed advances in contemporary cartography as seen in the latest interactive data-driven maps. We systematically review the design emerging types of water visualizations. The examples that we analyze range from dynamically animated forecasts, interactive paintings, infographics, modern cartography to web-based photorealistic rendering. By characterizing the intended audience, the design choices, the scales (e.g. time, space), and the explorability we provide a set of guidelines and genres. The unique contributions of the different fields show how the innovations in the current state of the art of water visualization have benefited from inter-disciplinary collaborations.

  12. The Reactome pathway Knowledgebase.

    Science.gov (United States)

    Fabregat, Antonio; Sidiropoulos, Konstantinos; Garapati, Phani; Gillespie, Marc; Hausmann, Kerstin; Haw, Robin; Jassal, Bijay; Jupe, Steven; Korninger, Florian; McKay, Sheldon; Matthews, Lisa; May, Bruce; Milacic, Marija; Rothfels, Karen; Shamovsky, Veronica; Webber, Marissa; Weiser, Joel; Williams, Mark; Wu, Guanming; Stein, Lincoln; Hermjakob, Henning; D'Eustachio, Peter

    2016-01-04

    The Reactome Knowledgebase (www.reactome.org) provides molecular details of signal transduction, transport, DNA replication, metabolism and other cellular processes as an ordered network of molecular transformations-an extended version of a classic metabolic map, in a single consistent data model. Reactome functions both as an archive of biological processes and as a tool for discovering unexpected functional relationships in data such as gene expression pattern surveys or somatic mutation catalogues from tumour cells. Over the last two years we redeveloped major components of the Reactome web interface to improve usability, responsiveness and data visualization. A new pathway diagram viewer provides a faster, clearer interface and smooth zooming from the entire reaction network to the details of individual reactions. Tool performance for analysis of user datasets has been substantially improved, now generating detailed results for genome-wide expression datasets within seconds. The analysis module can now be accessed through a RESTFul interface, facilitating its inclusion in third party applications. A new overview module allows the visualization of analysis results on a genome-wide Reactome pathway hierarchy using a single screen page. The search interface now provides auto-completion as well as a faceted search to narrow result lists efficiently. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. Pathways of lateral spreading.

    Science.gov (United States)

    Jacobi, U; Schanzer, S; Weigmann, H-J; Patzelt, A; Vergou, T; Sterry, W; Lademann, J

    2011-01-01

    In the case of topically applied substances, usually both lateral spreading and competitive penetration into the skin occur in parallel. In the present study, the pathways of lateral spreading were studied quantitatively and visually. The local distribution and lateral spreading of the UV filter substance butyl methoxydibenzoylmethane applied in an o/w emulsion was studied on the forearm and the back. The tape stripping procedure was used to determine the recovery rates inside and outside the area of application. The skin characteristics of transepidermal water loss, pH value, hydration of the stratum corneum and sebum rate were determined at both anatomic sites. Photography and laser scanning microscopy were used to visually investigate the lateral spreading of topically applied dyes. On the back, a preferred direction of lateral spreading parallel to the body axis was observed. This result was caused by differences in the network of furrows. The furrows functioned as a pathway for lateral spreading, whereas the follicles formed a reservoir for the topically applied substance. Copyright © 2011 S. Karger AG, Basel.

  14. Visual comparison for information visualization

    KAUST Repository

    Gleicher, M.

    2011-09-07

    Data analysis often involves the comparison of complex objects. With the ever increasing amounts and complexity of data, the demand for systems to help with these comparisons is also growing. Increasingly, information visualization tools support such comparisons explicitly, beyond simply allowing a viewer to examine each object individually. In this paper, we argue that the design of information visualizations of complex objects can, and should, be studied in general, that is independently of what those objects are. As a first step in developing this general understanding of comparison, we propose a general taxonomy of visual designs for comparison that groups designs into three basic categories, which can be combined. To clarify the taxonomy and validate its completeness, we provide a survey of work in information visualization related to comparison. Although we find a great diversity of systems and approaches, we see that all designs are assembled from the building blocks of juxtaposition, superposition and explicit encodings. This initial exploration shows the power of our model, and suggests future challenges in developing a general understanding of comparative visualization and facilitating the development of more comparative visualization tools. © The Author(s) 2011.

  15. Visual stability.

    Science.gov (United States)

    Melcher, David

    2011-02-27

    Our vision remains stable even though the movements of our eyes, head and bodies create a motion pattern on the retina. One of the most important, yet basic, feats of the visual system is to correctly determine whether this retinal motion is owing to real movement in the world or rather our own self-movement. This problem has occupied many great thinkers, such as Descartes and Helmholtz, at least since the time of Alhazen. This theme issue brings together leading researchers from animal neurophysiology, clinical neurology, psychophysics and cognitive neuroscience to summarize the state of the art in the study of visual stability. Recently, there has been significant progress in understanding the limits of visual stability in humans and in identifying many of the brain circuits involved in maintaining a stable percept of the world. Clinical studies and new experimental methods, such as transcranial magnetic stimulation, now make it possible to test the causal role of different brain regions in creating visual stability and also allow us to measure the consequences when the mechanisms of visual stability break down.

  16. How can audiovisual pathways enhance the temporal resolution of time-compressed speech in blind subjects?

    Directory of Open Access Journals (Sweden)

    Ingo eHertrich

    2013-08-01

    Full Text Available In blind people, the visual channel cannot assist face-to-face communication via lipreading or visual prosody. Nevertheless, the visual system may enhance the evaluation of auditory information due to its cross-links to (1 the auditory system, (2 supramodal representations, and (3 frontal action-related areas. Apart from feedback or top-down support of, for example, the processing of spatial or phonological representations, experimental data have shown that the visual system can impact auditory perception at more basic computational stages such as temporal resolution. For example, blind as compared to sighted subjects are more resistant against backward masking, and this ability appears to be associated with activity in visual cortex. Regarding the comprehension of continuous speech, blind subjects can learn to use accelerated text-to-speech systems for "reading" texts at ultra-fast speaking rates (> 16 syllables/s, exceeding by far the normal range of 6 syllables/s. An fMRI study has shown that this ability, among other brain regions, significantly covaries with BOLD responses in bilateral pulvinar, right visual cortex, and left supplementary motor area. Furthermore, magnetoencephalographic (MEG measurements revealed a particular component in right occipital cortex phase-locked to the syllable onsets of accelerated speech. In sighted people, the "bottleneck" for understanding time-compressed speech seems related to a demand for buffering phonological material and is, presumably, linked to frontal brain structures. On the other hand, the neurophysiological correlates of functions overcoming this bottleneck, seem to depend upon early visual cortex activity. The present Hypothesis and Theory paper outlines a model that aims at binding these data together, based on early cross-modal pathways that are already known from various audiovisual experiments considering cross-modal adjustments in space, time, and object recognition.

  17. How can audiovisual pathways enhance the temporal resolution of time-compressed speech in blind subjects?

    Science.gov (United States)

    Hertrich, Ingo; Dietrich, Susanne; Ackermann, Hermann

    2013-01-01

    In blind people, the visual channel cannot assist face-to-face communication via lipreading or visual prosody. Nevertheless, the visual system may enhance the evaluation of auditory information due to its cross-links to (1) the auditory system, (2) supramodal representations, and (3) frontal action-related areas. Apart from feedback or top-down support of, for example, the processing of spatial or phonological representations, experimental data have shown that the visual system can impact auditory perception at more basic computational stages such as temporal signal resolution. For example, blind as compared to sighted subjects are more resistant against backward masking, and this ability appears to be associated with activity in visual cortex. Regarding the comprehension of continuous speech, blind subjects can learn to use accelerated text-to-speech systems for "reading" texts at ultra-fast speaking rates (>16 syllables/s), exceeding by far the normal range of 6 syllables/s. A functional magnetic resonance imaging study has shown that this ability, among other brain regions, significantly covaries with BOLD responses in bilateral pulvinar, right visual cortex, and left supplementary motor area. Furthermore, magnetoencephalographic measurements revealed a particular component in right occipital cortex phase-locked to the syllable onsets of accelerated speech. In sighted people, the "bottleneck" for understanding time-compressed speech seems related to higher demands for buffering phonological material and is, presumably, linked to frontal brain structures. On the other hand, the neurophysiological correlates of functions overcoming this bottleneck, seem to depend upon early visual cortex activity. The present Hypothesis and Theory paper outlines a model that aims at binding these data together, based on early cross-modal pathways that are already known from various audiovisual experiments on cross-modal adjustments during space, time, and object recognition.

  18. Visual cognition

    Energy Technology Data Exchange (ETDEWEB)

    Pinker, S.

    1985-01-01

    This collection of research papers on visual cognition first appeared as a special issue of Cognition: International Journal of Cognitive Science. The study of visual cognition has seen enormous progress in the past decade, bringing important advances in our understanding of shape perception, visual imagery, and mental maps. Many of these discoveries are the result of converging investigations in different areas, such as cognitive and perceptual psychology, artificial intelligence, and neuropsychology. This volume is intended to highlight a sample of work at the cutting edge of this research area for the benefit of students and researchers in a variety of disciplines. The tutorial introduction that begins the volume is designed to help the nonspecialist reader bridge the gap between the contemporary research reported here and earlier textbook introductions or literature reviews.

  19. Visualizations as Projection Devices

    DEFF Research Database (Denmark)

    Harty, Chris; Holm Jacobsen, Peter; Tryggestad, Kjell

    connected to create projections of a future perfect, yet integral to this process a number of concerns emerges in the processes of designing and constructing the new hospital. These emergent concerns, in turn, have practical implications for the management of complex hospital construction projects......The aim of this paper is to inquire into the role of project visualizations in shaping healthcare spaces and practices. The study draws upon an ethnographic field study from a large on-going hospital construction project in Denmark, and focuses on the early phases of on-boarding the design team...... schedule for the hospital construction project. The study reveals how the visualizations are dynamically developed and linked to each other and their role in facilitating both control and innovation in project work and clinical work at the hospital. The paper contributes to our understanding of the active...

  20. A visualization architecture for intelligence analysis

    Science.gov (United States)

    Keahey, T. Alan; Eick, Stephen G.

    2004-06-01

    This paper describes the design and construction of a new visualization system for collections of heterogeneous information for intelligence analysis. The system has several novel features that taken together provide a highly modular and reusable framework for creating linked visual metaphors. The system leverages modern web technologies such as XML DOM and Schemas to create an expressive and powerful system. Examples of this are the ability to use the structure of the information being visualized (as expressed in an XML schema) to directly generate the object oriented code for manipulating that information, and the use of static and dynamic binding facilities for creating mappings between internal information items and visualization components. The resulting system blurs the distinction between information visualization and the World Wide Web. It is very modular and flexible, and supports rapid iteration and refinement of input data sources as well as interoperability with other information schemas. New linked visual metaphors can easily be added to the framework as required.

  1. Are Worry and Rumination Specific Pathways Linking Neuroticism and Symptoms of Anxiety and Depression in Patients with Generalized Anxiety Disorder, Major Depressive Disorder and Mixed Anxiety-Depressive Disorder?

    Directory of Open Access Journals (Sweden)

    Hipólito Merino

    Full Text Available This study examines the relationships between neuroticism (higher-order vulnerability factor, the cognitive styles of worry, brooding and reflection (second-order vulnerability factors and symptoms of anxiety and depression in three groups of patients: patients with Generalized Anxiety Disorder (GAD, with Major Depressive Disorder (MDD and with Mixed Anxiety-Depressive Disorder (MADD. One hundred and thirty four patients completed a battery of questionnaires including measures of neuroticism, worry, rumination (brooding and reflection, anxiety and depression. Multiple mediation analyses indicate that worry may act as a mediating mechanism linking neuroticism and anxiety symptoms in the three diagnostic groups, whereas brooding-rumination may play a mediating role between neuroticism and depressive symptoms in patients with MDD and MADD and, with less certainty, in patients with GAD. Overall, our findings suggest that neuroticism may increase the risk of anxious and depressive symptoms via specific links involving either worry or brooding, respectively, and that both worry and brooding may operate in the three groups examined, irrespectively of whether anxiety or depression are the main emotions or whether they coexist without any clear predominance; consequently, we hypothesize the existence of "specific transdiagnostic" mechanisms.

  2. Are Worry and Rumination Specific Pathways Linking Neuroticism and Symptoms of Anxiety and Depression in Patients with Generalized Anxiety Disorder, Major Depressive Disorder and Mixed Anxiety-Depressive Disorder?

    Science.gov (United States)

    Merino, Hipólito; Senra, Carmen; Ferreiro, Fátima

    2016-01-01

    This study examines the relationships between neuroticism (higher-order vulnerability factor), the cognitive styles of worry, brooding and reflection (second-order vulnerability factors) and symptoms of anxiety and depression in three groups of patients: patients with Generalized Anxiety Disorder (GAD), with Major Depressive Disorder (MDD) and with Mixed Anxiety-Depressive Disorder (MADD). One hundred and thirty four patients completed a battery of questionnaires including measures of neuroticism, worry, rumination (brooding and reflection), anxiety and depression. Multiple mediation analyses indicate that worry may act as a mediating mechanism linking neuroticism and anxiety symptoms in the three diagnostic groups, whereas brooding-rumination may play a mediating role between neuroticism and depressive symptoms in patients with MDD and MADD and, with less certainty, in patients with GAD. Overall, our findings suggest that neuroticism may increase the risk of anxious and depressive symptoms via specific links involving either worry or brooding, respectively, and that both worry and brooding may operate in the three groups examined, irrespectively of whether anxiety or depression are the main emotions or whether they coexist without any clear predominance; consequently, we hypothesize the existence of "specific transdiagnostic" mechanisms.

  3. Detection of the dominant direction of information flow and feedback links in densely interconnected regulatory networks

    Directory of Open Access Journals (Sweden)

    Ispolatov Iaroslav

    2008-10-01

    Full Text Available Abstract Background Finding the dominant direction of flow of information in densely interconnected regulatory or signaling networks is required in many applications in computational biology and neuroscience. This is achieved by first identifying and removing links which close up feedback loops in the original network and hierarchically arranging nodes in the remaining network. In mathematical language this corresponds to a problem of making a graph acyclic by removing as few links as possible and thus altering the original graph in the least possible way. The exact solution of this problem requires enumeration of all cycles and combinations of removed links, which, as an NP-hard problem, is computationally prohibitive even for modest-size networks. Results We introduce and compare two approximate numerical algorithms for solving this problem: the probabilistic one based on a simulated annealing of the hierarchical layout of the network which minimizes the number of "backward" links going from lower to higher hierarchical levels, and the deterministic, "greedy" algorithm that sequentially cuts the links that participate in the largest number of feedback cycles. We find that the annealing algorithm outperforms the deterministic one in terms of speed, memory requirement, and the actual number of removed links. To further improve a visual perception of the layout produced by the annealing algorithm, we perform an additional minimization of the length of hierarchical links while keeping the number of anti-hierarchical links at their minimum. The annealing algorithm is then tested on several examples of regulatory and signaling networks/pathways operating in human cells. Conclusion The proposed annealing algorithm is powerful enough to performs often optimal layouts of protein networks in whole organisms, consisting of around ~104 nodes and ~105 links, while the applicability of the greedy algorithm is limited to individual pathways with ~100

  4. Traffic Visualization

    DEFF Research Database (Denmark)

    Picozzi, Matteo; Verdezoto, Nervo; Pouke, Matti

    2013-01-01

    techniques to give a rapid overview of traffic data. We illustrate our approach as a case study for traffic visualization systems, using datasets from the city of Oulu that can be extended to other city planning activities. We also report the feedback of real users (traffic management employees, traffic police...

  5. Visualizing inequality

    Science.gov (United States)

    Eliazar, Iddo

    2016-07-01

    The study of socioeconomic inequality is of substantial importance, scientific and general alike. The graphic visualization of inequality is commonly conveyed by Lorenz curves. While Lorenz curves are a highly effective statistical tool for quantifying the distribution of wealth in human societies, they are less effective a tool for the visual depiction of socioeconomic inequality. This paper introduces an alternative to Lorenz curves-the hill curves. On the one hand, the hill curves are a potent scientific tool: they provide detailed scans of the rich-poor gaps in human societies under consideration, and are capable of accommodating infinitely many degrees of freedom. On the other hand, the hill curves are a powerful infographic tool: they visualize inequality in a most vivid and tangible way, with no quantitative skills that are required in order to grasp the visualization. The application of hill curves extends far beyond socioeconomic inequality. Indeed, the hill curves are highly effective 'hyperspectral' measures of statistical variability that are applicable in the context of size distributions at large. This paper establishes the notion of hill curves, analyzes them, and describes their application in the context of general size distributions.

  6. CathaCyc, a metabolic pathway database built from Catharanthus roseus RNA-Seq data.

    Science.gov (United States)

    Van Moerkercke, Alex; Fabris, Michele; Pollier, Jacob; Baart, Gino J E; Rombauts, Stephane; Hasnain, Ghulam; Rischer, Heiko; Memelink, Johan; Oksman-Caldentey, Kirsi-Marja; Goossens, Alain

    2013-05-01

    The medicinal plant Madagascar periwinkle (Catharanthus roseus) synthesizes numerous terpenoid indole alkaloids (TIAs), such as the anticancer drugs vinblastine and vincristine. The TIA pathway operates in a complex metabolic network that steers plant growth and survival. Pathway databases and metabolic networks reconstructed from 'omics' sequence data can help to discover missing enzymes, study metabolic pathway evolution and, ultimately, engineer metabolic pathways. To date, such databases have mainly been built for model plant species with sequenced genomes. Although genome sequence data are not available for most medicinal plant species, next-generation sequencing is now extensively employed to create comprehensive medicinal plant transcriptome sequence resources. Here we report on the construction of CathaCyc, a detailed metabolic pathway database, from C. roseus RNA-Seq data sets. CathaCyc (version 1.0) contains 390 pathways with 1,347 assigned enzymes and spans primary and secondary metabolism. Curation of the pathways linked with the synthesis of TIAs and triterpenoids, their primary metabolic precursors, and their elicitors, the jasmonate hormones, demonstrated that RNA-Seq resources are suitable for the construction of pathway databases. CathaCyc is accessible online (http://www.cathacyc.org) and offers a range of tools for the visualization and analysis of metabolic networks and 'omics' data. Overlay with expression data from publicly available RNA-Seq resources demonstrated that two well-characterized C. roseus terpenoid pathways, those of TIAs and triterpenoids, are subject to distinct regulation by both developmental and environmental cues. We anticipate that databases such as CathaCyc will become key to the study and exploitation of the metabolism of medicinal plants.

  7. Confrontation visual field testing in routine ophthalmic practice ...

    African Journals Online (AJOL)

    Background: Visual field testing, aids in detecting, localizing and monitoring diseases of the visual pathway. Early detection may help to preserve the patient's sight or life. In some situations, standard perimetry may not be possible. Aim: To highlight the relevance of confrontation visual field testing (CVF) in routine ...

  8. Transformation of visual direction requires the cognitive visual system

    Science.gov (United States)

    Bridgeman, Bruce

    2001-06-01

    We differentiate a cognitive branch of the visual system form a sensorimotor branch with the Roelofs effect, a perception that a target's position is biased in the direction opposite the offset of a surrounding fame. When a small fixed target is presented inside a frame that is offset to one side, normal humans perceive the target to be deviated in the direction opposite the frame's offset. They can still jab the target accurately, however, even though it is perceptually mislocalized. This dissociation indicates that motor coordinates are coded in a 'sensorimotor', possibly dorsal, pathway containing visual information that can be inconsistent with perceived information in a 'cognitive', possibly ventral pathway. Lack of a Roelofs effect indicates use of information in the sensorimotor pathway, independent from perception. We ask whether the sensorimotor pathway can handle a transformation of target position, in an anti-jabbing task analogous to anti-saccade tasks: the observer jabs a position symmetrically opposite the target's position, relative to the midline of the head. A 1 deg left or right. Observers were to jab the symmetrically opposite position as soon as the target disappeared. The result was a large and consistent Roelofs effect for an open-loop motor task, indicating that information from the cognitive pathway must be used to perform this task.

  9. The structure of inter-individual differences in visual ability: Evidence from the general population and synaesthesia.

    Science.gov (United States)

    Ward, Jamie; Rothen, Nicolas; Chang, Acer; Kanai, Ryota

    2017-12-01

    This study considers how inter-individual differences in visual ability are structured. Visual ability could be a single entity (along the lines of general intelligence, or 'g'), or could be structured according to major anatomical or physiological pathways (dorsal v. ventral streams; magno- v. parvo-cellular systems); or may be a finer-grained mosaic of abilities. To test this, we employed seven visual psychophysical tests (generating 16 measures) on a large (100+) sample of neurotypical participants. A Varimax-rotated PCA (Principal Component Analysis) revealed a two-factor solution that broadly corresponds to a high and low spatial frequency division (consistent with a magno/parvo distinction). Over and above this, two measures (temporal order judgments; gain in contrast sensitivity) correlated with most others, and loaded on both factors, suggesting that they tap broad visual processing demands. These analyses open up further possibilities for exploring the genetic and neuroscientific foundations of differences in visual ability. The tests were also run on a group of individuals with different types of visually-based synaesthesia, given that previous research have suggested they possess a distinct profile of visual abilities. Synaesthesia was linked to enhanced processing of colour and shape/curvature information (amongst others), that may relate to differences in V4 in this group. In conclusion, individual differences in vision are both striking and meaningful, despite our difficulty to imagine seeing the world any differently. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. The Visual Agnosias and Related Disorders.

    Science.gov (United States)

    Haque, Sameen; Vaphiades, Michael S; Lueck, Christian J

    2017-09-22

    There are many disorders of higher visual processing that result from damage to specific areas of the cerebral cortex that have a specific role in processing certain aspects (modalities) of vision. These can be grouped into those that affect the ventral, or "what?", pathway (e.g., object agnosia, cerebral achromatopsia, prosopagnosia, topographagnosia, and pure alexia), and those that affect the dorsal, or "where?", pathway (e.g., akinetopsia, simultanagnosia, and optic ataxia). This article reviews pertinent literature, concentrating on recent developments in basic science research and studies of individual patients. An overview of the current understanding of higher cerebral visual processing is followed by a discussion of the various disorders listed above. There has been considerable progress in the understanding of how the extrastriate visual cortex is organized, specifically in relation to functionally specialized visual areas. This permits a better understanding of the individual visual agnosias resulting from damage to these areas.

  11. MEG reveals a fast pathway from somatosensory cortex to occipital areas via posterior parietal cortex in a blind subject

    Directory of Open Access Journals (Sweden)

    Andreas A Ioannides

    2013-08-01

    Full Text Available Cross-modal activity in visual cortex of blind subjects has been reported during performance of variety of non-visual tasks. A key unanswered question is through which pathways non-visual inputs are funneled to the visual cortex. Here we used tomographic analysis of single trial magnetoencephalography (MEG data recorded from one congenitally blind and two sighted subjects after stimulation of the left and right median nerves at three intensities: below sensory threshold, above sensory threshold and above motor threshold; the last sufficient to produce thumb twitching. We identified reproducible brain responses in the primary somatosensory (S1 and motor (M1 cortices at around 20 ms post-stimulus, which were very similar in sighted and blind subjects. Time-frequency analysis revealed strong 45 to 70 Hz activity at latencies of 20 to 50 ms in S1 and M1, and posterior parietal cortex Brodmann areas (BA 7 and 40, which compared to lower frequencies, were substantially more pronounced in the blind than the sighted subjects. Critically, at frequencies from α-band up to 100 Hz we found clear, strong and widespread responses in the visual cortex of the blind subject, which increased with the intensity of the somatosensory stimuli. Time-delayed mutual information (MI revealed that in blind subject the stimulus information is funneled from the early somatosensory to visual cortex through posterior parietal BA 7 and 40, projecting first to visual areas V5 and V3, and eventually V1. The flow of information through this pathway occured in stages characterized by convergence of activations into specific cortical regions. In sighted subjects, no linked activity was found that led from the somatosensory to the visual cortex through any of the studied brain regions. These results provide the first evidence from MEG that in blind subjects, tactile information is routed from primary somatosensory to occipital cortex via the posterior parietal cortex.

  12. MEG reveals a fast pathway from somatosensory cortex to occipital areas via posterior parietal cortex in a blind subject.

    Science.gov (United States)

    Ioannides, Andreas A; Liu, Lichan; Poghosyan, Vahe; Saridis, George A; Gjedde, Albert; Ptito, Maurice; Kupers, Ron

    2013-01-01

    Cross-modal activity in visual cortex of blind subjects has been reported during performance of variety of non-visual tasks. A key unanswered question is through which pathways non-visual inputs are funneled to the visual cortex. Here we used tomographic analysis of single trial magnetoencephalography (MEG) data recorded from one congenitally blind and two sighted subjects after stimulation of the left and right median nerves at three intensities: below sensory threshold, above sensory threshold and above motor threshold; the last sufficient to produce thumb twitching. We identified reproducible brain responses in the primary somatosensory (S1) and motor (M1) cortices at around 20 ms post-stimulus, which were very similar in sighted and blind subjects. Time-frequency analysis revealed strong 45-70 Hz activity at latencies of 20-50 ms in S1 and M1, and posterior parietal cortex Brodmann areas (BA) 7 and 40, which compared to lower frequencies, were substantially more pronounced in the blind than the sighted subjects. Critically, at frequencies from α-band up to 100 Hz we found clear, strong, and widespread responses in the visual cortex of the blind subject, which increased with the intensity of the somatosensory stimuli. Time-delayed mutual information (MI) revealed that in blind subject the stimulus information is funneled from the early somatosensory to visual cortex through posterior parietal BA 7 and 40, projecting first to visual areas V5 and V3, and eventually V1. The flow of information through this pathway occurred in stages characterized by convergence of activations into specific cortical regions. In sighted subjects, no linked activity was found that led from the somatosensory to the visual cortex through any of the studied brain regions. These results provide the first evidence from MEG that in blind subjects, tactile information is routed from primary somatosensory to occipital cortex via the posterior parietal cortex.

  13. Hydrogen peroxide inhibits transforming growth factor-β1-induced cell cycle arrest by promoting Smad3 linker phosphorylation through activation of Akt-ERK1/2-linked signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jiyeon; Park, Seong Ji; Jo, Eun Ji [Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Lee, Hui-Young [Department of Internal Medicine, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Hong, Suntaek [Laboratory of Cancer Cell Biology, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 406-840 (Korea, Republic of); Kim, Seong-Jin [CHA Cancer Institute, CHA University of Medicine and Science, Seoul 135-081 (Korea, Republic of); Kim, Byung-Chul, E-mail: bckim@kangwon.ac.kr [Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 200-701 (Korea, Republic of)

    2013-06-14

    Highlights: •H{sub 2}O{sub 2} inhibits TGF-β1-induced cell cycle arrest. •H{sub 2}O{sub 2} induces Smad3 linker phosphorylation through Akt-ERK1/2 pathway. •H{sub 2}O{sub 2}-mediated suppression of TGF-β signal requires Smad3 linker phosphorylation. •This is a first report about interplay between H{sub 2}O{sub 2} and growth inhibition pathway. -- Abstract: Hydrogen peroxide (H{sub 2}O{sub 2}) functions as a second messenger in growth factor receptor-mediated intracellular signaling cascade and is tumorigenic by virtue of its ability to promote cell proliferation; however, the mechanisms underlying the growth stimulatory action of H{sub 2}O{sub 2} are less understood. Here we report an important mechanism for antagonistic effects of H{sub 2}O{sub 2} on growth inhibitory response to transforming growth factor-β1 (TGF-β1). In Mv1Lu and HepG2 cells, pretreatment of H{sub 2}O{sub 2} (0.05–0.2 mM) completely blocked TGF-β1-mediated induction of p15{sup INK4B} expression and increase of its promoter activity. Interestingly, H{sub 2}O{sub 2} selectively suppressed the transcriptional activation potential of Smad3, not Smad2, in the absence of effects on TGF-β1-induced phosphorylation of the COOH-tail SSXS motif of Smad3 and its nuclear translocation. Mechanism studies showed that H{sub 2}O{sub 2} increases the phosphorylation of Smad3 at the middle linker region in a concentration- and time-dependent manner and this effect is mediated by activation of extracellular signal-activated kinase 1/2 through Akt. Furthermore, expression of a mutant Smad3 in which linker phosphorylation sites were ablated significantly abrogated the inhibitory effects of H{sub 2}O{sub 2} on TGF-β1-induced increase of p15{sup INK4B}-Luc reporter activity and blockade of cell cycle progression from G1 to S phase. These findings for the first time define H{sub 2}O{sub 2} as a signaling molecule that modulate Smad3 linker phosphorylation and its transcriptional activity, thus providing

  14. Visual-vestibular processing deficits in mild traumatic brain injury.

    Science.gov (United States)

    Wright, W G; Tierney, R T; McDevitt, J

    2017-01-01

    The search for reliable and valid signs and symptoms of mild traumatic brain injury (mTBI), commonly synonymous with concussion, has lead to a growing body of evidence that individuals with long-lasting, unremitting impairments often experience visual and vestibular symptoms, such as dizziness, postural and gait disturbances. Investigate the role of visual-vestibular processing deficits following concussion. A number of clinically accepted vestibular, oculomotor, and balance assessments as well as a novel virtual reality (VR)-based balance assessment device were used to assess adults with post-acute concussion (n = 14) in comparison to a healthy age-matched cohort (n = 58). Significant between-group differences were found with the VR-based balance device (p = 0.001), with dynamic visual motion emerging as the most discriminating balance condition. The symptom reports collected after performing the oculomotor and vestibular tests: rapid alternating horizontal eye saccades, optokinetic stimulation, and gaze stabilization, were all sensitive to health status (p vestibular tasks most closely linked to spatial and self-motion perception had the greatest discriminatory outcomes. The current findings suggest that mesencephalic and parieto-occipital centers and pathways may be involved in concussion.

  15. Sex-linked recessive

    Science.gov (United States)

    Inheritance - sex-linked recessive; Genetics - sex-linked recessive; X-linked recessive ... X-linked recessive diseases most often occur in males. Males have only one X chromosome. A single recessive gene ...

  16. Sex-linked dominant

    Science.gov (United States)

    Inheritance - sex-linked dominant; Genetics - sex-linked dominant; X-linked dominant; Y-linked dominant ... can be either an autosomal chromosome or a sex chromosome. It also depends on whether the trait ...

  17. Heat Shock Protein HSP27 Secretion by Ovarian Cancer Cells Is Linked to Intracellular Expression Levels, Occurs Independently of the Endoplasmic Reticulum Pathway and HSP27’s Phosphorylation Status, and Is Mediated by Exosome Liberation

    Directory of Open Access Journals (Sweden)

    Matthias B. Stope

    2017-01-01

    Full Text Available The heat shock protein HSP27 has been correlated in ovarian cancer (OC patients with aggressiveness and chemoresistance and, therefore, represents a promising potential biomarker for OC diagnosis, prognosis, and treatment response. Notably, secretion of soluble HSP27 has been described by a few cell types and may take place as well in OC cells. Therefore, we studied HSP27 secretion mechanisms under diverse cellular conditions in an OC cell model system. Secretion of HSP27 was characterized after overexpression of HSP27 by transfected plasmids and after heat shock. Intra- and extracellular HSP27 amounts were assessed by Western blotting and ELISA. Protein secretion was blocked by brefeldin A and the impact of the HSP27 phosphorylation status was analyzed overexpressing HSP27 phosphomutants. The present study demonstrated that HSP27 secretion by OVCAR-3 and SK-OV-3 cells depends on intracellular HSP27 concentrations. Moreover, HSP27 secretion is independent of the endoplasmic reticulum secretory pathway and HSP27 phosphorylation. Notably, analysis of OC cell-born exosomes not only confirmed the concentration-dependent correlation of HSP27 expression and secretion but also demonstrated a concentration-dependent incorporation of HSP27 protein into exosomes. Thus, secreted HSP27 may become more important as an extracellular factor which controls the tumor microenvironment and might be a noninvasive biomarker.

  18. Y-box Binding Protein-1 Is Part of a Complex Molecular Network Linking ΔNp63α to the PI3K/akt Pathway in Cutaneous Squamous Cell Carcinoma.

    Science.gov (United States)

    Troiano, Annaelena; Lomoriello, Irene Schiano; di Martino, Orsola; Fusco, Sabato; Pollice, Alessandra; Vivo, Maria; La Mantia, Girolama; Calabrò, Viola

    2015-09-01

    Cutaneous squamous cell carcinomas (SCCs) typically lack somatic oncogene-activating mutations and most of them contain p53 mutations. However, the presence of p53 mutations in skin premalignant lesions suggests that these represent early events during tumor progression and additional alterations may be required for SCC development. SCC cells frequently express high levels of ΔNp63α and Y-box binding 1 (YB-1 or YBX1) oncoproteins. Here, we show that knockdown of YB-1 in spontaneously immortalized HaCaT and non-metastatic SCC011 cells led to a dramatic decrease of ΔNp63α, cell detachment and death. In highly metastatic SCC022 cells, instead, YB-1 silencing induces PI3K/AKT signaling hyperactivation which counteracts the effect of YB-1 depletion and promotes cell survival. In summary, our results unveil a functional cross-talk between YB-1, ΔNp63α and the PI3K/AKT pathway critically governing survival of squamous carcinoma cells. © 2015 Wiley Periodicals, Inc.

  19. Do visual illusions probe the visual brain? Illusions in action without a dorsal visual stream.

    Science.gov (United States)

    Coello, Yann; Danckert, James; Blangero, Annabelle; Rossetti, Yves

    2007-04-09

    Visual illusions have been shown to affect perceptual judgements more so than motor behaviour, which was interpreted as evidence for a functional division of labour within the visual system. The dominant perception-action theory argues that perception involves a holistic processing of visual objects or scenes, performed within the ventral, inferior temporal cortex. Conversely, visuomotor action involves the processing of the 3D relationship between the goal of the action and the body, performed predominantly within the dorsal, posterior parietal cortex. We explored the effect of well-known visual illusions (a size-contrast illusion and the induced Roelofs effect) in a patient (IG) suffering bilateral lesions of the dorsal visual stream. According to the perception-action theory, IG's perceptual judgements and control of actions should rely on the intact ventral stream and hence should both be sensitive to visual illusions. The finding that IG performed similarly to controls in three different illusory contexts argues against such expectations and shows, furthermore, that the dorsal stream does not control all aspects of visuomotor behaviour. Assuming that the patient's dorsal stream visuomotor system is fully lesioned, these results suggest that her visually guided action can be planned and executed independently of the dorsal pathways, possibly through the inferior parietal lobule.

  20. Designing pathways

    DEFF Research Database (Denmark)

    2010-01-01

    The theoretical background in this chapter is organizational studies and especially theories about design and design processes in organizations. The concept of design is defined as a particular kind of work aimed at making arrangements in order to change existing situations into desired ones....... The illustrative case example is the introduction of clinical pathways in a psychiatric department. The contribution to a general core of design research is the development of the concept of design work and a critical discussion of the role of technological rules in design work....

  1. Visualizing Transformation

    DEFF Research Database (Denmark)

    Pedersen, Pia

    2012-01-01

    the finished charts as a starting point and then going back to the beginning; furthermore, this inquiry presents a novel approach to clarifying the process by designing symbols and diagrams. It will be demonstrated that transformation offers an improved approach to data visualization. The message in the chart...... is not preformed, but formed through the process of transformation; this means that the purpose of transformation is not the styling of charts with pictograms, but rather creating a meaningful message. The contribution of this paper is an elaborated understanding of the process of transformation...... design. Recently transformation has attracted renewed interest because of the book The Transformer written by Robin Kinross and Marie Neurath. My on-going research project, summarized in this paper, identifies and depicts the essential principles of data visualization underlying the process...

  2. Visualizing Progress

    Science.gov (United States)

    2000-01-01

    Reality Capture Technologies, Inc. is a spinoff company from Ames Research Center. Offering e-business solutions for optimizing management, design and production processes, RCT uses visual collaboration environments (VCEs) such as those used to prepare the Mars Pathfinder mission.The product, 4-D Reality Framework, allows multiple users from different locations to manage and share data. The insurance industry is one targeted commercial application for this technology.

  3. Making memories: the development of long-term visual knowledge in children with visual agnosia.

    Science.gov (United States)

    Metitieri, Tiziana; Barba, Carmen; Pellacani, Simona; Viggiano, Maria Pia; Guerrini, Renzo

    2013-01-01

    There are few reports about the effects of perinatal acquired brain lesions on the development of visual perception. These studies demonstrate nonseverely impaired visual-spatial abilities and preserved visual memory. Longitudinal data analyzing the effects of compromised perceptions on long-term visual knowledge in agnosics are limited to lesions having occurred in adulthood. The study of children with focal lesions of the visual pathways provides a unique opportunity to assess the development of visual memory when perceptual input is degraded. We assessed visual recognition and visual memory in three children with lesions to the visual cortex having occurred in early infancy. We then explored the time course of visual memory impairment in two of them at 2  years and 3.7  years from the initial assessment. All children exhibited apperceptive visual agnosia and visual memory impairment. We observed a longitudinal improvement of visual memory modulated by the structural properties of objects. Our findings indicate that processing of degraded perceptions from birth results in impoverished memories. The dynamic interaction between perception and memory during development might modulate the long-term construction of visual representations, resulting in less severe impairment.

  4. Making Memories: The Development of Long-Term Visual Knowledge in Children with Visual Agnosia

    Directory of Open Access Journals (Sweden)

    Tiziana Metitieri

    2013-01-01

    Full Text Available There are few reports about the effects of perinatal acquired brain lesions on the development of visual perception. These studies demonstrate nonseverely impaired visual-spatial abilities and preserved visual memory. Longitudinal data analyzing the effects of compromised perceptions on long-term visual knowledge in agnosics are limited to lesions having occurred in adulthood. The study of children with focal lesions of the visual pathways provides a unique opportunity to assess the development of visual memory when perceptual input is degraded. We assessed visual recognition and visual memory in three children with lesions to the visual cortex having occurred in early infancy. We then explored the time course of visual memory impairment in two of them at 2 years and 3.7 years from the initial assessment. All children exhibited apperceptive visual agnosia and visual memory impairment. We observed a longitudinal improvement of visual memory modulated by the structural properties of objects. Our findings indicate that processing of degraded perceptions from birth results in impoverished memories. The dynamic interaction between perception and memory during development might modulate the long-term construction of visual representations, resulting in less severe impairment.

  5. Visualizing thought.

    Science.gov (United States)

    Tversky, Barbara

    2011-07-01

    Depictive expressions of thought predate written language by thousands of years. They have evolved in communities through a kind of informal user testing that has refined them. Analyzing common visual communications reveals consistencies that illuminate how people think as well as guide design; the process can be brought into the laboratory and accelerated. Like language, visual communications abstract and schematize; unlike language, they use properties of the page (e.g., proximity and place: center, horizontal/up-down, vertical/left-right) and the marks on it (e.g., dots, lines, arrows, boxes, blobs, likenesses, symbols) to convey meanings. The visual expressions of these meanings (e.g., individual, category, order, relation, correspondence, continuum, hierarchy) have analogs in language, gesture, and especially in the patterns that are created when people design the world around them, arranging things into piles and rows and hierarchies and arrays, spatial-abstraction-action interconnections termed spractions. The designed world is a diagram. Copyright © 2010 Cognitive Science Society, Inc.

  6. Personalized visual aesthetics

    Science.gov (United States)

    Vessel, Edward A.; Stahl, Jonathan; Maurer, Natalia; Denker, Alexander; Starr, G. G.

    2014-02-01

    How is visual information linked to aesthetic experience, and what factors determine whether an individual finds a particular visual experience pleasing? We have previously shown that individuals' aesthetic responses are not determined by objective image features but are instead a function of internal, subjective factors that are shaped by a viewers' personal experience. Yet for many classes of stimuli, culturally shared semantic associations give rise to similar aesthetic taste across people. In this paper, we investigated factors that govern whether a set of observers will agree in which images are preferred, or will instead exhibit more "personalized" aesthetic preferences. In a series of experiments, observers were asked to make aesthetic judgments for different categories of visual stimuli that are commonly evaluated in an aesthetic manner (faces, natural landscapes, architecture or artwork). By measuring agreement across observers, this method was able to reveal instances of highly individualistic preferences. We found that observers showed high agreement on their preferences for images of faces and landscapes, but much lower agreement for images of artwork and architecture. In addition, we found higher agreement for heterosexual males making judgments of beautiful female faces than of beautiful male faces. These results suggest that preferences for stimulus categories that carry evolutionary significance (landscapes and faces) come to rely on similar information across individuals, whereas preferences for artifacts of human culture such as architecture and artwork, which have fewer basic-level category distinctions and reduced behavioral relevance, rely on a more personalized set of attributes.

  7. Visual rehabilitation: visual scanning, multisensory stimulation and vision restoration trainings

    Directory of Open Access Journals (Sweden)

    Neil M. Dundon

    2015-07-01

    Full Text Available Neuropsychological training methods of visual rehabilitation for homonymous vision loss caused by postchiasmatic damage fall into two fundamental paradigms: compensation and restoration. Existing methods can be classified into three groups: Visual Scanning Training (VST, Audio-Visual Scanning Training (AViST and Vision Restoration Training (VRT. VST and AViST aim at compensating vision loss by training eye scanning movements, whereas VRT aims at improving lost vision by activating residual visual functions by training light detection and discrimination of visual stimuli. This review discusses the rationale underlying these paradigms and summarizes the available evidence with respect to treatment efficacy. The issues raised in our review should help guide clinical care and stimulate new ideas for future research uncovering the underlying neural correlates of the different treatment paradigms. We propose that both local within-system interactions (i.e., relying on plasticity within peri-lesional spared tissue and changes in more global between-system networks (i.e., recruiting alternative visual pathways contribute to both vision restoration and compensatory rehabilitation that ultimately have implications for the rehabilitation of cognitive functions.

  8. Auditory and visual interhemispheric communication in musicians and non-musicians.

    Science.gov (United States)

    Woelfle, Rebecca; Grahn, Jessica A

    2013-01-01

    The corpus callosum (CC) is a brain structure composed of axon fibres linking the right and left hemispheres. Musical training is associated with larger midsagittal cross-sectional area of the CC, suggesting that interhemispheric communication may be faster in musicians. Here we compared interhemispheric transmission times (ITTs) for musicians and non-musicians. ITT was measured by comparing simple reaction times to stimuli presented to the same hemisphere that controlled a button-press response (uncrossed reaction time), or to the contralateral hemisphere (crossed reaction time). Both visual and auditory stimuli were tested. We predicted that the crossed-uncrossed difference (CUD) for musicians would be smaller than for non-musicians as a result of faster interhemispheric transfer times. We did not expect a difference in CUDs between the visual and auditory modalities for either musicians or non-musicians, as previous work indicates that interhemispheric transfer may happen through the genu of the CC, which contains motor fibres rather than sensory fibres. There were no significant differences in CUDs between musicians and non-musicians. However, auditory CUDs were significantly smaller than visual CUDs. Although this auditory-visual difference was larger in musicians than non-musicians, the interaction between modality and musical training was not significant. Therefore, although musical training does not significantly affect ITT, the crossing of auditory information between hemispheres appears to be faster than visual information, perhaps because subcortical pathways play a greater role for auditory interhemispheric transfer.

  9. Auditory and visual interhemispheric communication in musicians and non-musicians.

    Directory of Open Access Journals (Sweden)

    Rebecca Woelfle

    Full Text Available The corpus callosum (CC is a brain structure composed of axon fibres linking the right and left hemispheres. Musical training is associated with larger midsagittal cross-sectional area of the CC, suggesting that interhemispheric communication may be faster in musicians. Here we compared interhemispheric transmission times (ITTs for musicians and non-musicians. ITT was measured by comparing simple reaction times to stimuli presented to the same hemisphere that controlled a button-press response (uncrossed reaction time, or to the contralateral hemisphere (crossed reaction time. Both visual and auditory stimuli were tested. We predicted that the crossed-uncrossed difference (CUD for musicians would be smaller than for non-musicians as a result of faster interhemispheric transfer times. We did not expect a difference in CUDs between the visual and auditory modalities for either musicians or non-musicians, as previous work indicates that interhemispheric transfer may happen through the genu of the CC, which contains motor fibres rather than sensory fibres. There were no significant differences in CUDs between musicians and non-musicians. However, auditory CUDs were significantly smaller than visual CUDs. Although this auditory-visual difference was larger in musicians than non-musicians, the interaction between modality and musical training was not significant. Therefore, although musical training does not significantly affect ITT, the crossing of auditory information between hemispheres appears to be faster than visual information, perhaps because subcortical pathways play a greater role for auditory interhemispheric transfer.

  10. The Pathway Tools cellular overview diagram and Omics Viewer

    OpenAIRE

    Paley, Suzanne M.; Karp, Peter D.

    2006-01-01

    The Pathway Tools cellular overview diagram is a visual representation of the biochemical network of an organism. The overview is automatically created from a Pathway/Genome Database describing that organism. The cellular overview includes metabolic, transport and signaling pathways, and other membrane and periplasmic proteins. Pathway Tools supports interrogation and exploration of cellular biochemical networks through the overview diagram. Furthermore, a software component called the Omics ...

  11. Visual cognition

    National Research Council Canada - National Science Library

    Cavanagh, Patrick

    2011-01-01

    ... is unified in our mind even if not in the image. The construction of these entities is the task of visual cognition and, in almost all cases, each construct is a choice among an infinity of possibilities, chosen based on likelihood, bias, or a whim, but chosen by rejecting other valid competitors. The entities are not limited to static surfaces or structures but also include dynamic structures that only emerge over time – from dots that appear to be walking like a human or a moon orbiting a planet, to the...

  12. Linked alternating forms and linked symplectic Grassmannians

    OpenAIRE

    Osserman, Brian; Bigas, Montserrat Teixidor I.

    2011-01-01

    Motivated by applications to higher-rank Brill-Noether theory and the Bertram-Feinberg-Mukai conjecture, we introduce the concepts of linked alternating and linked symplectic forms on a chain of vector bundles, and show that the linked symplectic Grassmannians parametrizing chains of subbundles isotropic for a given linked symplectic form has good dimensional behavior analogous to that of the classical symplectic Grassmannian.

  13. Visual coherence for large-scale line-plot visualizations

    KAUST Repository

    Muigg, Philipp

    2011-06-01

    Displaying a large number of lines within a limited amount of screen space is a task that is common to many different classes of visualization techniques such as time-series visualizations, parallel coordinates, link-node diagrams, and phase-space diagrams. This paper addresses the challenging problems of cluttering and overdraw inherent to such visualizations. We generate a 2x2 tensor field during line rasterization that encodes the distribution of line orientations through each image pixel. Anisotropic diffusion of a noise texture is then used to generate a dense, coherent visualization of line orientation. In order to represent features of different scales, we employ a multi-resolution representation of the tensor field. The resulting technique can easily be applied to a wide variety of line-based visualizations. We demonstrate this for parallel coordinates, a time-series visualization, and a phase-space diagram. Furthermore, we demonstrate how to integrate a focus+context approach by incorporating a second tensor field. Our approach achieves interactive rendering performance for large data sets containing millions of data items, due to its image-based nature and ease of implementation on GPUs. Simulation results from computational fluid dynamics are used to evaluate the performance and usefulness of the proposed method. © 2011 The Author(s).

  14. Structural Variability within Frontoparietal Networks and Individual Differences in Attentional Functions: An Approach Using the Theory of Visual Attention.

    Science.gov (United States)

    Chechlacz, Magdalena; Gillebert, Celine R; Vangkilde, Signe A; Petersen, Anders; Humphreys, Glyn W

    2015-07-29

    Visuospatial attention allows us to select and act upon a subset of behaviorally relevant visual stimuli while ignoring distraction. Bundesen's theory of visual attention (TVA) (Bundesen, 1990) offers a quantitative analysis of the different facets of attention within a unitary model and provides a powerful analytic framework for understanding individual differences in attentional functions. Visuospatial attention is contingent upon large networks, distributed across both hemispheres, consisting of several cortical areas interconnected by long-association frontoparietal pathways, including three branches of the superior longitudinal fasciculus (SLF I-III) and the inferior fronto-occipital fasciculus (IFOF). Here we examine whether structural variability within human frontoparietal networks mediates differences in attention abilities as assessed by the TVA. Structural measures were based on spherical deconvolution and tractography-derived indices of tract volume and hindrance-modulated orientational anisotropy (HMOA). Individual differences in visual short-term memory (VSTM) were linked to variability in the microstructure (HMOA) of SLF II, SLF III, and IFOF within the right hemisphere. Moreover, VSTM and speed of information processing were linked to hemispheric lateralization within the IFOF. Differences in spatial bias were mediated by both variability in microstructure and volume of the right SLF II. Our data indicate that the microstructural and macrostrucutral organization of white matter pathways differentially contributes to both the anatomical lateralization of frontoparietal attentional networks and to individual differences in attentional functions. We conclude that individual differences in VSTM capacity, processing speed, and spatial bias, as assessed by TVA, link to variability in structural organization within frontoparietal pathways. Copyright © 2015 Chechlacz et al.

  15. Psychophysical evidence for impaired Magno, Parvo, and Konio-cellular pathways in dyslexic children

    Directory of Open Access Journals (Sweden)

    Khazar Ahmadi

    2015-01-01

    Conclusion: We may suggest that dyslexic subjects might suffer from both magnocellular and parvocellular deficits. Moreover, our results show partial impairment of the koniocellular pathway. Thus, dyslexia might be associated with deficits in all three visual pathways.

  16. How information visualization novices construct visualizations.

    Science.gov (United States)

    Grammel, Lars; Tory, Melanie; Storey, Margaret-Anne

    2010-01-01

    It remains challenging for information visualization novices to rapidly construct visualizations during exploratory data analysis. We conducted an exploratory laboratory study in which information visualization novices explored fictitious sales data by communicating visualization specifications to a human mediator, who rapidly constructed the visualizations using commercial visualization software. We found that three activities were central to the iterative visualization construction process: data attribute selection, visual template selection, and visual mapping specification. The major barriers faced by the participants were translating questions into data attributes, designing visual mappings, and interpreting the visualizations. Partial specification was common, and the participants used simple heuristics and preferred visualizations they were already familiar with, such as bar, line and pie charts. We derived abstract models from our observations that describe barriers in the data exploration process and uncovered how information visualization novices think about visualization specifications. Our findings support the need for tools that suggest potential visualizations and support iterative refinement, that provide explanations and help with learning, and that are tightly integrated into tool support for the overall visual analytics process.

  17. Body image, visual working memory and visual mental imagery.

    Science.gov (United States)

    Darling, Stephen; Uytman, Clare; Allen, Richard J; Havelka, Jelena; Pearson, David G

    2015-01-01

    Body dissatisfaction (BD) is a highly prevalent feature amongst females in society, with the majority of individuals regarding themselves to be overweight compared to their personal ideal, and very few self-describing as underweight. To date, explanations of this dramatic pattern have centred on extrinsic social and media factors, or intrinsic factors connected to individuals' knowledge and belief structures regarding eating and body shape, with little research examining links between BD and basic cognitive mechanisms. This paper reports a correlational study in which visual and executive cognitive processes that could potentially impact on BD were assessed. Visual memory span and self-rated visual imagery were found to be predictive of BD, alongside a measure of inhibition derived from the Stroop task. In contrast, spatial memory and global precedence were not related to BD. Results are interpreted with reference to the influential multi-component model of working memory.

  18. Body image, visual working memory and visual mental imagery

    Directory of Open Access Journals (Sweden)

    Stephen Darling

    2015-02-01

    Full Text Available Body dissatisfaction (BD is a highly prevalent feature amongst females in society, with the majority of individuals regarding themselves to be overweight compared to their personal ideal, and very few self-describing as underweight. To date, explanations of this dramatic pattern have centred on extrinsic social and media factors, or intrinsic factors connected to individuals’ knowledge and belief structures regarding eating and body shape, with little research examining links between BD and basic cognitive mechanisms. This paper reports a correlational study in which visual and executive cognitive processes that could potentially impact on BD were assessed. Visual memory span and self-rated visual imagery were found to be predictive of BD, alongside a measure of inhibition derived from the Stroop task. In contrast, spatial memory and global precedence were not related to BD. Results are interpreted with reference to the influential multi-component model of working memory.

  19. Remaining visual field and preserved subjective visual functioning prevent mental distress in patients with visual field defects

    Directory of Open Access Journals (Sweden)

    Carolin eGall

    2013-09-01

    Full Text Available Background: Patients with visual field defects after visual pathway lesion may experience reduced vision-related quality of life (vrQoL. It has not been clarified how vrQoL impairments contribute to vision-related mental distress.Methods: 108 subjects with visual field defects caused by optic neuropathies (age M=57.6; SD=13.7 years answered the National Eye Institute Visual-Functioning Questionnaire (NEI-VFQ for vrQoL and the SF-12 Short Form Health Survey for health-related quality of life (hrQoL. A ten item composite of NEI-VFQ visual functioning and five items of mental health symptoms due to vision problems were subjected to Rasch analysis. The test battery comprised static and High Resolution Perimetry (HRP. Regression and path analysis were used to investigate associations between QoL, mental distress and perimetry results.Results: A higher level of visual functioning was associated with monocular impairment and a larger remaining visual field compared to binocular impairment. Subjective visual functioning but not visual field parameters predicted mental health symptoms due to vision problems which was the only variable associated with the SF-12 mental component score. The SF-12 physical component score was less strongly associated with mental health symptoms due to vision problems. Here, reaction time in HRP and mean threshold in perimetry were additional significant variables. Path analysis revealed a significant path of remaining visual field via visual functioning on mental health. Conclusions: Subjective consequences of visual impairments in everyday life impact mental health rather than objective visual function loss as measured by perimetry. Since a higher extent of vrQoL was related to lower levels of mental distress, the maintenance of vrQoL could reduce and prevent mental distress due to vision problems. Patients with persisting visual field defects may benefit from neuropsychological rehabilitation and supportive therapies.

  20. Visual analytics in scalable visualization environments

    OpenAIRE

    Yamaoka, So

    2011-01-01

    Visual analytics is an interdisciplinary field that facilitates the analysis of the large volume of data through interactive visual interface. This dissertation focuses on the development of visual analytics techniques in scalable visualization environments. These scalable visualization environments offer a high-resolution, integrated virtual space, as well as a wide-open physical space that affords collaborative user interaction. At the same time, the sheer scale of these environments poses ...

  1. Visualization rhetoric: framing effects in narrative visualization.

    Science.gov (United States)

    Hullman, Jessica; Diakopoulos, Nicholas

    2011-12-01

    Narrative visualizations combine conventions of communicative and exploratory information visualization to convey an intended story. We demonstrate visualization rhetoric as an analytical framework for understanding how design techniques that prioritize particular interpretations in visualizations that "tell a story" can significantly affect end-user interpretation. We draw a parallel between narrative visualization interpretation and evidence from framing studies in political messaging, decision-making, and literary studies. Devices for understanding the rhetorical nature of narrative information visualizations are presented, informed by the rigorous application of concepts from critical theory, semiotics, journalism, and political theory. We draw attention to how design tactics represent additions or omissions of information at various levels-the data, visual representation, textual annotations, and interactivity-and how visualizations denote and connote phenomena with reference to unstated viewing conventions and codes. Classes of rhetorical techniques identified via a systematic analysis of recent narrative visualizations are presented, and characterized according to their rhetorical contribution to the visualization. We describe how designers and researchers can benefit from the potentially positive aspects of visualization rhetoric in designing engaging, layered narrative visualizations and how our framework can shed light on how a visualization design prioritizes specific interpretations. We identify areas where future inquiry into visualization rhetoric can improve understanding of visualization interpretation. © 2011 IEEE

  2. Time Course of Competition for Visual Processing Resources between Emotional Pictures and Foreground Task

    National Research Council Canada - National Science Library

    Müller, Matthias M; Andersen, Søren K; Keil, Andreas

    2008-01-01

    .... The present study used an electrophysiological approach for continuously measuring the time course of competition for processing resources in the visual pathway arising from emotionally salient...

  3. Sketchy Rendering for Information Visualization.

    Science.gov (United States)

    Wood, J; Isenberg, P; Isenberg, T; Dykes, J; Boukhelifa, N; Slingsby, A

    2012-12-01

    We present and evaluate a framework for constructing sketchy style information visualizations that mimic data graphics drawn by hand. We provide an alternative renderer for the Processing graphics environment that redefines core drawing primitives including line, polygon and ellipse rendering. These primitives allow higher-level graphical features such as bar charts, line charts, treemaps and node-link diagrams to be drawn in a sketchy style with a specified degree of sketchiness. The framework is designed to be easily integrated into existing visualization implementations with minimal programming modification or design effort. We show examples of use for statistical graphics, conveying spatial imprecision and for enhancing aesthetic and narrative qualities of visualization. We evaluate user perception of sketchiness of areal features through a series of stimulus-response tests in order to assess users' ability to place sketchiness on a ratio scale, and to estimate area. Results suggest relative area judgment is compromised by sketchy rendering and that its influence is dependent on the shape being rendered. They show that degree of sketchiness may be judged on an ordinal scale but that its judgement varies strongly between individuals. We evaluate higher-level impacts of sketchiness through user testing of scenarios that encourage user engagement with data visualization and willingness to critique visualization design. Results suggest that where a visualization is clearly sketchy, engagement may be increased and that attitudes to participating in visualization annotation are more positive. The results of our work have implications for effective information visualization design that go beyond the traditional role of sketching as a tool for prototyping or its use for an indication of general uncertainty.

  4. Human factors experiments for data link : interim report 1

    Science.gov (United States)

    1972-11-01

    This report discusses three experiments aimed at providing information pertinent to the Data Link Operational Experiments Program. Section 1. describes the evaluation of the WIDCOM, a visual display, and a voice synthesizer for providing ATC informat...

  5. Recovery from optic neuritis: an ROI-based analysis of LGN and visual cortical areas

    DEFF Research Database (Denmark)

    Korsholm, Kirsten; Madsen, Kristoffer Hougaard; Frederiksen, Jette L

    2007-01-01

    and neuronal plasticity in the cortical and subcortical visual pathways. To assess where recovery takes place along the visual pathway, visual activation was studied in the lateral geniculate nucleus (LGN), the main thalamic relay nucleus in the visual pathway and in three areas of the visual cortex...... the affected and unaffected eye diminished during recovery, and after 180 days the difference was no longer significant (P = 0.59). The decreased difference during recovery was mainly due to an increase in the fMRI signal when stimulating the affected eye, but included a component of a decreasing fMRI signal...

  6. Functional and structural comparison of visual lateralization in birds – similar but still different

    Directory of Open Access Journals (Sweden)

    Martina eManns

    2014-03-01

    Full Text Available Vertebrate brains display physiological and anatomical left-right differences, which are related to hemispheric dominances for specific functions. Functional lateralizations likely rely on structural left-right differences in intra- and interhemispheric connectivity patterns that develop in tight gene-environment interactions. The visual systems of chickens and pigeons show that asymmetrical light stimulation during ontogeny induces a dominance of the left hemisphere for visuomotor control that is paralleled by projection asymmetries within the ascending visual pathways. But structural asymmetries vary essentially between both species concerning the affected pathway (thalamo- vs. tectofugal system, constancy of effects (transient vs. permanent, and the hemisphere receiving stronger bilateral input (right vs. left. These discrepancies suggest that at least two aspects of visual processes are influenced by asymmetric light stimulation: 1. Visuomotor dominance develops within the ontogenetically stronger stimulated hemisphere but not necessarily in the one receiving stronger bottom-up input. As a secondary consequence of asymmetrical light experience, lateralized top-down mechanisms play a critical role in the emergence of hemispheric dominance. 2. Ontogenetic light experiences may affect the dominant use of left- and right-hemispheric strategies. Evidences from social and spatial cognition tasks indicate that chickens rely more on a right-hemispheric global strategy whereas pigeons display a dominance of the left hemisphere. Thus, behavioural asymmetries are linked to a stronger bilateral input to the right hemisphere in chickens but to the left one in pigeons. The degree of bilateral visual input may determine the dominant visual processing strategy when redundant encoding is possible. This analysis supports that environmental stimulation affects the balance between hemispheric-specific processing by lateralized interactions of bottom-up and top

  7. The role of human ventral visual cortex in motion perception

    Science.gov (United States)

    Saygin, Ayse P.; Lorenzi, Lauren J.; Egan, Ryan; Rees, Geraint; Behrmann, Marlene

    2013-01-01

    Visual motion perception is fundamental to many aspects of visual perception. Visual motion perception has long been associated with the dorsal (parietal) pathway and the involvement of the ventral ‘form’ (temporal) visual pathway has not been considered critical for normal motion perception. Here, we evaluated this view by examining whether circumscribed damage to ventral visual cortex impaired motion perception. The perception of motion in basic, non-form tasks (motion coherence and motion detection) and complex structure-from-motion, for a wide range of motion speeds, all centrally displayed, was assessed in five patients with a circumscribed lesion to either the right or left ventral visual pathway. Patients with a right, but not with a left, ventral visual lesion displayed widespread impairments in central motion perception even for non-form motion, for both slow and for fast speeds, and this held true independent of the integrity of areas MT/V5, V3A or parietal regions. In contrast with the traditional view in which only the dorsal visual stream is critical for motion perception, these novel findings implicate a more distributed circuit in which the integrity of the right ventral visual pathway is also necessary even for the perception of non-form motion. PMID:23983030

  8. Visualizing Entropy

    Science.gov (United States)

    Lechner, Joseph H.

    1999-10-01

    This report describes two classroom activities that help students visualize the abstract concept of entropy and apply the second law of thermodynamics to real situations. (i) A sealed "rainbow tube" contains six smaller vessels, each filled with a different brightly colored solution (low entropy). When the tube is inverted, the solutions mix together and react to form an amorphous precipitate (high entropy). The change from low entropy to high entropy is irreversible as long as the tube remains sealed. (ii) When U.S. currency is withdrawn from circulation, intact bills (low entropy) are shredded into small fragments (high entropy). Shredding is quick and easy; the reverse process is clearly nonspontaneous. It is theoretically possible, but it is time-consuming and energy-intensive, to reassemble one bill from a pile that contains fragments of hundreds of bills. We calculate the probability P of drawing pieces of only one specific bill from a mixture containing one pound of bills, each shredded into n fragments. This result can be related to Boltzmann's entropy formula S?=klnW.

  9. Visualization-by-Sketching: An Artist's Interface for Creating Multivariate Time-Varying Data Visualizations.

    Science.gov (United States)

    Schroeder, David; Keefe, Daniel F

    2016-01-01

    We present Visualization-by-Sketching, a direct-manipulation user interface for designing new data visualizations. The goals are twofold: First, make the process of creating real, animated, data-driven visualizations of complex information more accessible to artists, graphic designers, and other visual experts with traditional, non-technical training. Second, support and enhance the role of human creativity in visualization design, enabling visual experimentation and workflows similar to what is possible with traditional artistic media. The approach is to conceive of visualization design as a combination of processes that are already closely linked with visual creativity: sketching, digital painting, image editing, and reacting to exemplars. Rather than studying and tweaking low-level algorithms and their parameters, designers create new visualizations by painting directly on top of a digital data canvas, sketching data glyphs, and arranging and blending together multiple layers of animated 2D graphics. This requires new algorithms and techniques to interpret painterly user input relative to data "under" the canvas, balance artistic freedom with the need to produce accurate data visualizations, and interactively explore large (e.g., terabyte-sized) multivariate datasets. Results demonstrate a variety of multivariate data visualization techniques can be rapidly recreated using the interface. More importantly, results and feedback from artists support the potential for interfaces in this style to attract new, creative users to the challenging task of designing more effective data visualizations and to help these users stay "in the creative zone" as they work.

  10. Ontology-enriched Visualization of Human Anatomy

    Energy Technology Data Exchange (ETDEWEB)

    Pouchard, LC

    2005-12-20

    The project focuses on the problem of presenting a human anatomical 3D model associated with other types of human systemic information ranging from physiological to anatomical information while navigating the 3D model. We propose a solution that integrates a visual 3D interface and navigation features with the display of structured information contained in an ontology of anatomy where the structures of the human body are formally and semantically linked. The displayed and annotated anatomy serves as a visual entry point into a patient's anatomy, medical indicators and other information. The ontology of medical information provides labeling to the highlighted anatomical parts in the 3D display. Because of the logical organization and links between anatomical objects found in the ontology and associated 3D model, the analysis of a structure by a physician is greatly enhanced. Navigation within the 3D visualization and between this visualization and objects representing anatomical concepts within the model is also featured.

  11. Identifying and characterising cerebral visual impairment in children: a review

    National Research Council Canada - National Science Library

    Philip, Swetha Sara; Dutton, Gordon N

    2014-01-01

    .... This can be isolated or accompany anterior visual pathway dysfunction. It is a major cause of low vision in children in the developed and developing world due to increasing survival in paediatric and neonatal care...

  12. LinkED: A Novel Methodology for Publishing Linked Enterprise Data

    Directory of Open Access Journals (Sweden)

    Shreyas Suresh Rao

    2017-01-01

    Full Text Available Semantic Web technologies have redefined and strengthened the Enterprise-Web interoperability over the last decade. Linked Open Data (LOD refers to a set of best practices that empower enterprises to publish and interlink their data using existing ontologies on the World Wide Web. Current research in LOD focuses on expert search, the creation of unified information space and augmentation of core data from an enterprise context. However, existing approaches for publication of enterprise data as LOD are domain-specific, ad-hoc and suffer from lack of uniform representation across domains. The paper proposes a novel methodology called LinkED that contributes towards LOD literature in two ways: (a streamlines the publishing process through five stages of cleaning, triplification, interlinking, storage and visualization; (b addresses the latest challenges in LOD publication, namely: inadequate links, inconsistencies in the quality of the dataset and replicability of the LOD publication process. Further, the methodology is demonstrated via the publication of digital repository data as LOD in a university setting, which is evaluated based on two semantic standards: Five-Star model and data quality metrics. Overall, the paper provides a generic LOD publication process that is applicable across various domains such as healthcare, e-governance, banking, and tourism, to name a few.

  13. Linked data management

    CERN Document Server

    Hose, Katja; Schenkel, Ralf

    2014-01-01

    Linked Data Management presents techniques for querying and managing Linked Data that is available on today’s Web. The book shows how the abundance of Linked Data can serve as fertile ground for research and commercial applications. The text focuses on aspects of managing large-scale collections of Linked Data. It offers a detailed introduction to Linked Data and related standards, including the main principles distinguishing Linked Data from standard database technology. Chapters also describe how to generate links between datasets and explain the overall architecture of data integration systems based on Linked Data. A large part of the text is devoted to query processing in different setups. After presenting methods to publish relational data as Linked Data and efficient centralized processing, the book explores lookup-based, distributed, and parallel solutions. It then addresses advanced topics, such as reasoning, and discusses work related to read-write Linked Data for system interoperation. Desp...

  14. Usher syndrome: molecular links of pathogenesis, proteins and pathways.

    NARCIS (Netherlands)

    Kremer, H.; Wijk, E. van; Marker, T.; Wolfrum, U.; Roepman, R.

    2006-01-01

    Usher syndrome is the most common form of deaf-blindness. The syndrome is both clinically and genetically heterogeneous, and to date, eight causative genes have been identified. The proteins encoded by these genes are part of a dynamic protein complex that is present in hair cells of the inner ear

  15. Pathways linking obesity to health-related quality of life.

    Science.gov (United States)

    Park, Sangshin

    2017-08-01

    Obesity is a well-recognized risk factor for impaired health-related quality of life (HRQOL). Nevertheless, few studies have investigated the mechanisms underlying the obesity-HRQOL associations. In this study, we explored potential mediators of the associations between obesity and HRQOL. Body mass index (BMI), an indicator of obesity, and HRQOL data were available for the 34,565 individuals 20 years of age and older participating in the cross-sectional Korea National Health and Nutrition Examination Survey 2007-2012. HRQOL was measured by the EuroQol five-dimension descriptive system. Path analysis was performed to assess the contributions of obesity-related diseases and self-rated health (SRH) on the relationships between obesity and HRQOL. In men, obesity was negatively associated with HRQOL through diabetes mellitus, hypertension, and dyslipidemia and positively associated with HRQOL through SRH. These opposite indirect effects offset one another and produced a non-significant association between obesity and HRQOL in men. However, in women, obesity was directly associated with HRQOL and indirectly associated with HRQOL through diabetes mellitus and SRH. Since these associations were in the same negative direction, the negative obesity-HRQOL association was clearly observed in women. Obesity was negatively associated with HRQOL through obesity-related diseases in both genders. However, in men, the positive association between obesity and SRH resulted in a non-significant association of obesity with HRQOL.

  16. Pathways for shared prosperity: Understanding the links between ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... 11 projects addressing barriers to women's economic empowerment and gender gaps in earnings and productivity. GrOW will also support a cluster of four projects looking at the intersection of economic growth and women's economic empowerment. This project is among them, selected through a global competitive call.

  17. Integrating Mechanisms for Insulin Resistance: Common Threads and Missing Links

    Science.gov (United States)

    Samuel, Varman T.; Shulman, Gerald I.

    2012-01-01

    Insulin resistance is a complex metabolic disorder that defies a single etiological pathway. Accumulation of ectopic lipid metabolites, activation of the unfolded protein response (UPR) pathway and innate immune pathways have all been implicated in the pathogenesis of insulin resistance. However, these pathways are also closely linked to changes in fatty acid uptake, lipogenesis, and energy expenditure that can impact ectopic lipid deposition. Ultimately, accumulation of specific lipid metabolites (diacylglycerols