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Sample records for identifies cortical sites

  1. Intra-operative multi-site stimulation: Expanding methodology for cortical brain mapping of language functions.

    Science.gov (United States)

    Gonen, Tal; Gazit, Tomer; Korn, Akiva; Kirschner, Adi; Perry, Daniella; Hendler, Talma; Ram, Zvi

    2017-01-01

    Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping.

  2. SitesIdentify: a protein functional site prediction tool

    Directory of Open Access Journals (Sweden)

    Doig Andrew J

    2009-11-01

    Full Text Available Abstract Background The rate of protein structures being deposited in the Protein Data Bank surpasses the capacity to experimentally characterise them and therefore computational methods to analyse these structures have become increasingly important. Identifying the region of the protein most likely to be involved in function is useful in order to gain information about its potential role. There are many available approaches to predict functional site, but many are not made available via a publicly-accessible application. Results Here we present a functional site prediction tool (SitesIdentify, based on combining sequence conservation information with geometry-based cleft identification, that is freely available via a web-server. We have shown that SitesIdentify compares favourably to other functional site prediction tools in a comparison of seven methods on a non-redundant set of 237 enzymes with annotated active sites. Conclusion SitesIdentify is able to produce comparable accuracy in predicting functional sites to its closest available counterpart, but in addition achieves improved accuracy for proteins with few characterised homologues. SitesIdentify is available via a webserver at http://www.manchester.ac.uk/bioinformatics/sitesidentify/

  3. Identifying suitable sites for Florida panther reintroduction

    Science.gov (United States)

    Thatcher, Cindy A.; van Manen, Frank T.; Clark, Joseph D.

    2006-01-01

    A major objective of the 1995 Florida Panther (Puma concolor cory) Recovery Plan is the establishment of 2 additional panther populations within the historic range. Our goal was to identify prospective sites for Florida panther reintroduction within the historic range based on quantitative landscape assessments. First, we delineated 86 panther home ranges using telemetry data collected from 1981 to 2001 in south Florida to develop a Mahalanobis distance (D2) habitat model, using 4 anthropogenic variables and 3 landscape variables mapped at a 500-m resolution. From that analysis, we identified 9 potential reintroduction sites of sufficient size to support a panther population. We then developed a similar D2 model at a higher spatial resolution to quantify the area of favorable panther habitat at each site. To address potential for the population to expand, we calculated the amount of favorable habitat adjacent to each prospective reintroduction site within a range of dispersal distances of female panthers. We then added those totals to the contiguous patches to estimate the total amount of effective panther habitat at each site. Finally, we developed an expert-assisted model to rank and incorporate potentially important habitat variables that were not appropriate for our empirical analysis (e.g., area of public lands, livestock density). Anthropogenic factors heavily influenced both the landscape and the expert-assisted models. Of the 9 areas we identified, the Okefenokee National Wildlife Refuge, Ozark National Forest, and Felsenthal National Wildlife Refuge regions had the highest combination of effective habitat area and expert opinion scores. Sensitivity analyses indicated that variability among key model parameters did not affect the high ranking of those sites. Those sites should be considered as starting points for the field evaluation of potential reintroduction sites.

  4. Cortical GABA markers identify a molecular subtype of psychotic and bipolar disorders.

    Science.gov (United States)

    Volk, D W; Sampson, A R; Zhang, Y; Edelson, J R; Lewis, D A

    2016-09-01

    Deficits in gamma aminobutyric acid (GABA) neuron-related markers, including the GABA-synthesizing enzyme GAD67, the calcium-binding protein parvalbumin, the neuropeptide somatostatin, and the transcription factor Lhx6, are most pronounced in a subset of schizophrenia subjects identified as having a 'low GABA marker' (LGM) molecular phenotype. Furthermore, schizophrenia shares degrees of genetic liability, clinical features and cortical circuitry abnormalities with schizoaffective disorder and bipolar disorder. Therefore, we determined the extent to which a similar LGM molecular phenotype may also exist in subjects with these disorders. Transcript levels for GAD67, parvalbumin, somatostatin, and Lhx6 were quantified using quantitative PCR in prefrontal cortex area 9 of 184 subjects with a diagnosis of schizophrenia (n = 39), schizoaffective disorder (n = 23) or bipolar disorder (n = 35), or with a confirmed absence of any psychiatric diagnoses (n = 87). A blinded clustering approach was employed to determine the presence of a LGM molecular phenotype across all subjects. Approximately 49% of the subjects with schizophrenia, 48% of the subjects with schizoaffective disorder, and 29% of the subjects with bipolar disorder, but only 5% of unaffected subjects, clustered in the cortical LGM molecular phenotype. These findings support the characterization of psychotic and bipolar disorders by cortical molecular phenotype which may help elucidate more pathophysiologically informed and personalized medications.

  5. Differential alterations of cortical glutamatergic binding sites in senile dementia of the Alzheimer type

    International Nuclear Information System (INIS)

    Chalmers, D.T.; Dewar, D.; Graham, D.I.; Brooks, D.N.; McCulloch, J.

    1990-01-01

    Involvement of cortical glutamatergic mechanisms in senile dementia of the Alzheimer type (SDAT) has been investigated with quantitative ligand-binding autoradiography. The distribution and density of Na(+)-dependent glutamate uptake sites and glutamate receptor subtypes--kainate, quisqualate, and N-methyl-D-aspartate--were measured in adjacent sections of frontal cortex obtained postmortem from six patients with SDAT and six age-matched controls. The number of senile plaques was determined in the same brain region. Binding of D-[3H]aspartate to Na(+)-dependent uptake sites was reduced by approximately 40% throughout SDAT frontal cortex relative to controls, indicating a general loss of glutamatergic presynaptic terminals. [3H]Kainate receptor binding was significantly increased by approximately 70% in deep layers of SDAT frontal cortex compared with controls, whereas this binding was unaltered in superficial laminae. There was a positive correlation (r = 0.914) between kainate binding and senile plaque number in deep cortical layers. Quisqualate receptors, as assessed by 2-amino-3-hydroxy-5-[3H]methylisoxazole-4-propionic acid binding, were unaltered in SDAT frontal cortex compared with controls. There was a small reduction (25%) in N-methyl-D-aspartate-sensitive [3H]glutamate binding only in superficial cortical layers of SDAT brains relative to control subjects. [3H]Glutamate binding in SDAT subjects was unrelated to senile plaque number in superficial cortical layers (r = 0.104). These results indicate that in the presence of cortical glutamatergic terminal loss in SDAT plastic alterations occur in some glutamate receptor subtypes but not in others

  6. Neuroanatomical phenotypes in mental illness: identifying convergent and divergent cortical phenotypes across autism, ADHD and schizophrenia.

    Science.gov (United States)

    Park, Min Tae M; Raznahan, Armin; Shaw, Philip; Gogtay, Nitin; Lerch, Jason P; Chakravarty, M Mallar

    2018-05-01

    There is evidence suggesting neuropsychiatric disorders share genomic, cognitive and clinical features. Here, we ask if autism-spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD) and schizophrenia share neuroanatomical variations. First, we used measures of cortical anatomy to estimate spatial overlap of neuroanatomical variation using univariate methods. Next, we developed a novel methodology to determine whether cortical deficits specifically target or are "enriched" within functional resting-state networks. We found cortical anomalies were preferentially enriched across functional networks rather than clustering spatially. Specifically, cortical thickness showed significant enrichment between patients with ASD and those with ADHD in the default mode network, between patients with ASD and those with schizophrenia in the frontoparietal and limbic networks, and between patients with ADHD and those with schizophrenia in the ventral attention network. Networks enriched in cortical thickness anomalies were also strongly represented in functional MRI results (Neurosynth; r = 0.64, p = 0.032). We did not account for variable symptom dimensions and severity in patient populations, and our cross-sectional design prevented longitudinal analyses of developmental trajectories. These findings suggest that common deficits across neuropsychiatric disorders cannot simply be characterized as arising out of local changes in cortical grey matter, but rather as entities of both local and systemic alterations targeting brain networks.

  7. The Posterior Cerebral Artery and its Main Cortical Branches Identified with Noninvasive Transcranial Color-Coded Duplex Sonography.

    Science.gov (United States)

    Frid, P E; Schreiber, S J; Pade, O; Doepp, F; Valdueza, J

    2015-11-01

    To differentiate PCA segments and cortical branches by means of transcranial color-coded duplex sonography (TCCD) and to measure flow parameters at rest and during visual stimulation. 60 healthy subjects with a good acoustic temporal bone window were examined. The main stem of the PCA (P1, P2 and P3) and 4 main cortical branches - the anterior temporal artery (ATA), the occipital temporal artery (OTA), the parietooccipital artery (POA) and the calcarine artery (CA) - were assessed using an axial transtemporal approach. Systolic and diastolic blood flow velocities (BFVs) were recorded at rest and during visual stimulation. Identification of the P1 segment of the PCA was successful in 97.5% (117/120) of cases. The P2 and P3 segments were visualized in all cases. The 4 main cortical branches could be identified to varying degrees: ATA in 88%, OTA in 96%, POA in 69% and CA in 62%. There was an evoked flow response in the P2 main stem and in all cortical branches. The most pronounced increase in diastolic/systolic BFV after visual stimulation test was seen in the CA (42%/35%), followed by P2 (30%/24%), the POA (27%/27%), the OTA (16%/13%) and the ATA (9%/8%). Insonation through the temporal bone window with TCCD confidently allows the assessment of the P1 to P3 segments of the PCA as well as the 2 proximal branches, the ATA and the OTA. An ultrasound-based classification of PCA anatomy and its cortical branches may be used as a noninvasive method for the evaluation of posterior circulation pathology.

  8. A tool for identifying potential Eucalyptus nitens seed orchard sites ...

    African Journals Online (AJOL)

    Shy seed production in orchards of Eucalyptus nitens is a major barrier to the deployment of genetic gain in South African plantations. A machine learning method was used to identify optimal sites for the establishment of E. nitens seed orchards within the plantation forestry landscape of the summer rainfall region of South ...

  9. Identifying Cortical Lateralization of Speech Processing in Infants Using Near-Infrared Spectroscopy

    Science.gov (United States)

    Bortfeld, Heather; Fava, Eswen; Boas, David A.

    2010-01-01

    We investigate the utility of near-infrared spectroscopy (NIRS) as an alternative technique for studying infant speech processing. NIRS is an optical imaging technology that uses relative changes in total hemoglobin concentration and oxygenation as an indicator of neural activation. Procedurally, NIRS has the advantage over more common methods (e.g., fMRI) in that it can be used to study the neural responses of behaviorally active infants. Older infants (aged 6–9 months) were allowed to sit on their caretakers’ laps during stimulus presentation to determine relative differences in focal activity in the temporal region of the brain during speech processing. Results revealed a dissociation of sensory-specific processing in two cortical regions, the left and right temporal lobes. These findings are consistent with those obtained using other neurophysiological methods and point to the utility of NIRS as a means of establishing neural correlates of language development in older (and more active) infants. PMID:19142766

  10. Dynamic brain glucose metabolism identifies anti-correlated cortical-cerebellar networks at rest.

    Science.gov (United States)

    Tomasi, Dardo G; Shokri-Kojori, Ehsan; Wiers, Corinde E; Kim, Sunny W; Demiral, Şukru B; Cabrera, Elizabeth A; Lindgren, Elsa; Miller, Gregg; Wang, Gene-Jack; Volkow, Nora D

    2017-12-01

    It remains unclear whether resting state functional magnetic resonance imaging (rfMRI) networks are associated with underlying synchrony in energy demand, as measured by dynamic 2-deoxy-2-[ 18 F]fluoroglucose (FDG) positron emission tomography (PET). We measured absolute glucose metabolism, temporal metabolic connectivity (t-MC) and rfMRI patterns in 53 healthy participants at rest. Twenty-two rfMRI networks emerged from group independent component analysis (gICA). In contrast, only two anti-correlated t-MC emerged from FDG-PET time series using gICA or seed-voxel correlations; one included frontal, parietal and temporal cortices, the other included the cerebellum and medial temporal regions. Whereas cerebellum, thalamus, globus pallidus and calcarine cortex arose as the strongest t-MC hubs, the precuneus and visual cortex arose as the strongest rfMRI hubs. The strength of the t-MC linearly increased with the metabolic rate of glucose suggesting that t-MC measures are strongly associated with the energy demand of the brain tissue, and could reflect regional differences in glucose metabolism, counterbalanced metabolic network demand, and/or differential time-varying delivery of FDG. The mismatch between metabolic and functional connectivity patterns computed as a function of time could reflect differences in the temporal characteristics of glucose metabolism as measured with PET-FDG and brain activation as measured with rfMRI.

  11. Immunocytochemistry and fluorescence imaging efficiently identify individual neurons with CRISPR/Cas9-mediated gene disruption in primary cortical cultures.

    Science.gov (United States)

    Tsunematsu, Hiroto; Uyeda, Akiko; Yamamoto, Nobuhiko; Sugo, Noriyuki

    2017-08-01

    CRISPR/Cas9 system is a powerful method to investigate the role of genes by introducing a mutation selectively and efficiently to specific genome positions in cell and animal lines. However, in primary neuron cultures, this method is affected by the issue that the effectiveness of CRISPR/Cas9 is different in each neuron. Here, we report an easy, quick and reliable method to identify mutants induced by the CRISPR/Cas9 system at a single neuron level, using immunocytochemistry (ICC) and fluorescence imaging. Dissociated cortical cells were transfected with CRISPR/Cas9 plasmids targeting the transcription factor cAMP-response element binding protein (CREB). Fluorescence ICC with CREB antibody and quantitative analysis of fluorescence intensity demonstrated that CREB expression disappeared in a fraction of the transfected neurons. The downstream FOS expression was also decreased in accordance with suppressed CREB expression. Moreover, dendritic arborization was decreased in the transfected neurons which lacked CREB immunoreactivity. Detection of protein expression is efficient to identify individual postmitotic neurons with CRISPR/Cas9-mediated gene disruption in primary cortical cultures. The present method composed of CRISPR/Cas9 system, ICC and fluorescence imaging is applicable to study the function of various genes at a single-neuron level.

  12. Identifying potential kidney donors using social networking web sites.

    Science.gov (United States)

    Chang, Alexander; Anderson, Emily E; Turner, Hang T; Shoham, David; Hou, Susan H; Grams, Morgan

    2013-01-01

    Social networking sites like Facebook may be a powerful tool for increasing rates of live kidney donation. They allow for wide dissemination of information and discussion and could lessen anxiety associated with a face-to-face request for donation. However, sparse data exist on the use of social media for this purpose. We searched Facebook, the most popular social networking site, for publicly available English-language pages seeking kidney donors for a specific individual, abstracting information on the potential recipient, characteristics of the page itself, and whether potential donors were tested. In the 91 pages meeting inclusion criteria, the mean age of potential recipients was 37 (range: 2-69); 88% were US residents. Other posted information included the individual's photograph (76%), blood type (64%), cause of kidney disease (43%), and location (71%). Thirty-two percent of pages reported having potential donors tested, and 10% reported receiving a live-donor kidney transplant. Those reporting donor testing shared more potential recipient characteristics, provided more information about transplantation, and had higher page traffic. Facebook is already being used to identify potential kidney donors. Future studies should focus on how to safely, ethically, and effectively use social networking sites to inform potential donors and potentially expand live kidney donation. © 2013 John Wiley & Sons A/S.

  13. Catalytic site identification—a web server to identify catalytic site structural matches throughout PDB

    Science.gov (United States)

    Kirshner, Daniel A.; Nilmeier, Jerome P.; Lightstone, Felice C.

    2013-01-01

    The catalytic site identification web server provides the innovative capability to find structural matches to a user-specified catalytic site among all Protein Data Bank proteins rapidly (in less than a minute). The server also can examine a user-specified protein structure or model to identify structural matches to a library of catalytic sites. Finally, the server provides a database of pre-calculated matches between all Protein Data Bank proteins and the library of catalytic sites. The database has been used to derive a set of hypothesized novel enzymatic function annotations. In all cases, matches and putative binding sites (protein structure and surfaces) can be visualized interactively online. The website can be accessed at http://catsid.llnl.gov. PMID:23680785

  14. Identifying high dose activities in industrial site radiography

    International Nuclear Information System (INIS)

    Heaton, B.

    2000-01-01

    Although the radiation doses received by industrial radiographers in the UK have progressively fallen over the last few years, with most now receiving less than 1 mSv/y, a few still receive, relative to the rest, much higher doses. As a percentage of all radiographers the number stays surprisingly constant from year to year. This paper describes a survey to identify the work causing these doses and suggest possible solutions. The UK Central Index of Dose Information was interrogated to identify the industrial radiography companies having staff (not necessarily the same person) with doses of greater than 5mSv/y in the last three years for which information was available. This was 15 in total. The people on the staff receiving these doses were identified and a questionnaire sent to the companies concerned requesting information about their work. A general questionnaire about the operation of the company was also included. With the agreement of the company these questionnaires were followed up by a visit to the company to interviews a number of the management and the radiographers if available. Both groups were generally very open about their problems and every discussion had a positive outcome. Several areas of work/reasons for the doses have been identified. These are: pipeline radiography, ultra sound radiographers working on nuclear reactors, complex plant work often with several teams in the area, inability to retreat from the wind out equipment due to height or access problems, site pressure to not follow the best practices and a lack of appreciation when a dose was being received or, alternatively, carelessness. Some o these problem areas are very difficult to resolve. However ways in which the Health and Safety can help influence the doses have been identified together with practical suggestions radiographers could adopt. These will be reported. (author)

  15. Non-Invasive Brain Stimulation to Enhance Upper Limb Motor Practice Poststroke: A Model for Selection of Cortical Site

    Directory of Open Access Journals (Sweden)

    Michelle L. Harris-Love

    2017-05-01

    Full Text Available Motor practice is an essential part of upper limb motor recovery following stroke. To be effective, it must be intensive with a high number of repetitions. Despite the time and effort required, gains made from practice alone are often relatively limited, and substantial residual impairment remains. Using non-invasive brain stimulation to modulate cortical excitability prior to practice could enhance the effects of practice and provide greater returns on the investment of time and effort. However, determining which cortical area to target is not trivial. The implications of relevant conceptual frameworks such as Interhemispheric Competition and Bimodal Balance Recovery are discussed. In addition, we introduce the STAC (Structural reserve, Task Attributes, Connectivity framework, which incorporates patient-, site-, and task-specific factors. An example is provided of how this framework can assist in selecting a cortical region to target for priming prior to reaching practice poststroke. We suggest that this expanded patient-, site-, and task-specific approach provides a useful model for guiding the development of more successful approaches to neuromodulation for enhancing motor recovery after stroke.

  16. Identifying Key Factors Relevant for Base Camp Siting

    Science.gov (United States)

    2017-12-01

    centers. 3.2.6.3 Religious and historical sites Respecting sacred sites helps build rapport with the host nation. 3.2.6.4 Local infrastructure...churches, mosques, national libraries, hospitals, cemeteries, historical ruins, religious sites, cultural areas, and other protected sites...controlled and protected wells. • Electricity: town engineer • Academic: government and religious leaders • Trash: private business (local

  17. Screening with an NMNAT2-MSD platform identifies small molecules that modulate NMNAT2 levels in cortical neurons.

    Science.gov (United States)

    Ali, Yousuf O; Bradley, Gillian; Lu, Hui-Chen

    2017-03-07

    Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a key neuronal maintenance factor and provides potent neuroprotection in numerous preclinical models of neurological disorders. NMNAT2 is significantly reduced in Alzheimer's, Huntington's, Parkinson's diseases. Here we developed a Meso Scale Discovery (MSD)-based screening platform to quantify endogenous NMNAT2 in cortical neurons. The high sensitivity and large dynamic range of this NMNAT2-MSD platform allowed us to screen the Sigma LOPAC library consisting of 1280 compounds. This library had a 2.89% hit rate, with 24 NMNAT2 positive and 13 negative modulators identified. Western analysis was conducted to validate and determine the dose-dependency of identified modulators. Caffeine, one identified NMNAT2 positive-modulator, when systemically administered restored NMNAT2 expression in rTg4510 tauopathy mice to normal levels. We confirmed in a cell culture model that four selected positive-modulators exerted NMNAT2-specific neuroprotection against vincristine-induced cell death while four selected NMNAT2 negative modulators reduced neuronal viability in an NMNAT2-dependent manner. Many of the identified NMNAT2 positive modulators are predicted to increase cAMP concentration, suggesting that neuronal NMNAT2 levels are tightly regulated by cAMP signaling. Taken together, our findings indicate that the NMNAT2-MSD platform provides a sensitive phenotypic screen to detect NMNAT2 in neurons.

  18. Benefits of mineralized bone cortical allograft for immediate implant placement in extraction sites: an in vivo study in dogs.

    Science.gov (United States)

    Orti, Valérie; Bousquet, Philippe; Tramini, Paul; Gaitan, Cesar; Mertens, Brenda; Cuisinier, Frédéric

    2016-10-01

    The aim of the present study was to evaluate the effectiveness of using a mineralized bone cortical allograft (MBCA), with or without a resorbable collagenous membrane derived from bovine pericardium, on alveolar bone remodeling after immediate implant placement in a dog model. Six mongrel dogs were included. The test and control sites were randomly selected. Four biradicular premolars were extracted from the mandible. In control sites, implants without an allograft or membrane were placed immediately in the fresh extraction sockets. In the test sites, an MBCA was placed to fill the gap between the bone socket wall and implant, with or without a resorbable collagenous membrane. Specimens were collected after 1 and 3 months. The amount of residual particles and new bone quality were evaluated by histomorphometry. Few residual graft particles were observed to be closely embedded in the new bone without any contact with the implant surface. The allograft combined with a resorbable collagen membrane limited the resorption of the buccal wall in height and width. The histological quality of the new bone was equivalent to that of the original bone. The MBCA improved the quality of new bone formation, with few residual particles observed at 3 months. The preliminary results of this animal study indicate a real benefit in obtaining new bone as well as in enhancing osseointegration due to the high resorbability of cortical allograft particles, in comparison to the results of xenografts or other biomaterials (mineralized or demineralized cancellous allografts) that have been presented in the literature. Furthermore, the use of an MBCA combined with a collagen membrane in extraction and immediate implant placement limited the extent of post-extraction resorption.

  19. Methods and systems for identifying ligand-protein binding sites

    KAUST Repository

    Gao, Xin

    2016-05-06

    The invention provides a novel integrated structure and system-based approach for drug target prediction that enables the large-scale discovery of new targets for existing drugs Novel computer-readable storage media and computer systems are also provided. Methods and systems of the invention use novel sequence order-independent structure alignment, hierarchical clustering, and probabilistic sequence similarity techniques to construct a probabilistic pocket ensemble (PPE) that captures even promiscuous structural features of different binding sites for a drug on known targets. The drug\\'s PPE is combined with an approximation of the drug delivery profile to facilitate large-scale prediction of novel drug- protein interactions with several applications to biological research and drug development.

  20. Identifying suitable piercement salt domes for nuclear waste storage sites

    International Nuclear Information System (INIS)

    Kehle, R.; e.

    1980-08-01

    Piercement salt domes of the northern interior salt basins of the Gulf of Mexico are being considered as permanent storage sites for both nuclear and chemically toxic wastes. The suitable domes are stable and inactive, having reached their final evolutionary configuration at least 30 million years ago. They are buried to depths far below the level to which erosion will penetrate during the prescribed storage period and are not subject to possible future reactivation. The salt cores of these domes are themselves impermeable, permitting neither the entry nor exit of ground water or other unwanted materials. In part, a stable dome may be recognized by its present geometric configuration, but conclusive proof depends on establishing its evolutionary state. The evolutionary state of a dome is obtained by reconstructing the growth history of the dome as revealed by the configuration of sedimentary strata in a large area (commonly 3,000 square miles or more) surrounding the dome. A high quality, multifold CDP reflection seismic profile across a candidate dome will provide much of the necessary information when integrated with available subsurface control. Additional seismic profiles may be required to confirm an apparent configuration of the surrounding strata and an interpreted evolutionary history. High frequency seismic data collected in the near vicinity of a dome are also needed as a supplement to the CDP data to permit accurate depiction of the configuration of shallow strata. Such data must be tied to shallow drill hole control to confirm the geologic age at which dome growth ceased. If it is determined that a dome reached a terminal configuration many millions of years ago, such a dome is incapable of reactivation and thus constitutes a stable storage site for nuclear wastes

  1. Integrating microRNA and mRNA expression profiles of neuronal progenitors to identify regulatory networks underlying the onset of cortical neurogenesis

    Directory of Open Access Journals (Sweden)

    Barker Jeffery L

    2009-08-01

    Full Text Available Abstract Background Cortical development is a complex process that includes sequential generation of neuronal progenitors, which proliferate and migrate to form the stratified layers of the developing cortex. To identify the individual microRNAs (miRNAs and mRNAs that may regulate the genetic network guiding the earliest phase of cortical development, the expression profiles of rat neuronal progenitors obtained at embryonic day 11 (E11, E12 and E13 were analyzed. Results Neuronal progenitors were purified from telencephalic dissociates by a positive-selection strategy featuring surface labeling with tetanus-toxin and cholera-toxin followed by fluorescence-activated cell sorting. Microarray analyses revealed the fractions of miRNAs and mRNAs that were up-regulated or down-regulated in these neuronal progenitors at the beginning of cortical development. Nearly half of the dynamically expressed miRNAs were negatively correlated with the expression of their predicted target mRNAs. Conclusion These data support a regulatory role for miRNAs during the transition from neuronal progenitors into the earliest differentiating cortical neurons. In addition, by supplying a robust data set in which miRNA and mRNA profiles originate from the same purified cell type, this empirical study may facilitate the development of new algorithms to integrate various "-omics" data sets.

  2. Mass spectrometry identifies multiple organophosphorylated sites on tubulin

    International Nuclear Information System (INIS)

    Grigoryan, Hasmik; Schopfer, Lawrence M.; Peeples, Eric S.; Duysen, Ellen G.; Grigoryan, Marine; Thompson, Charles M.; Lockridge, Oksana

    2009-01-01

    Acute toxicity of organophosphorus poisons (OP) is explained by inhibition of acetylcholinesterase in nerve synapses. Low-dose effects are hypothesized to result from modification of other proteins, whose identity is not yet established. The goal of the present work was to obtain information that would make it possible to identify tubulin as a target of OP exposure. Tubulin was selected for study because live mice injected with a nontoxic dose of a biotinylated organophosphorus agent appeared to have OP-labeled tubulin in brain as determined by binding to avidin beads and mass spectrometry. The experiments with live mice were not conclusive because binding to avidin beads could be nonspecific. To be convincing, it is necessary to find and characterize the OP-labeled tubulin peptide. The search for OP-labeled tubulin peptides was begun by identifying residues capable of making a covalent bond with OP. Pure bovine tubulin (0.012 mM) was treated with 0.01-0.5 mM chlorpyrifos oxon for 24 h at 37 o C in pH 8.3 buffer. The identity of labeled amino acids and percent labeling was determined by mass spectrometry. Chlorpyrifos oxon bound covalently to tyrosines 83, 103, 108, 161, 224, 262, 272, 357, and 399 in bovine alpha tubulin, and to tyrosines 50, 51, 59, 106, 159, 281, 310, and 340 in bovine beta tubulin. The most reactive were tyrosine 83 in alpha and tyrosine 281 in beta tubulin. In the presence of 1 mM GTP, percent labeling increased 2-fold. Based on the crystal structure of the tubulin heterodimer (PDB 1jff) tyrosines 83 and 281 are well exposed to solvent. In conclusion seventeen tyrosines in tubulin have the potential to covalently bind chlorpyrifos oxon. These results will be useful when searching for OP-labeled tubulin in live animals.

  3. Target and identify: triazene linker helps identify azidation sites of labelled proteins via click and cleave strategy.

    Science.gov (United States)

    Lohse, Jonas; Schindl, Alexandra; Danda, Natasha; Williams, Chris P; Kramer, Karl; Kuster, Bernhard; Witte, Martin D; Médard, Guillaume

    2017-10-31

    A method for identifying probe modification of proteins via tandem mass spectrometry was developed. Azide bearing molecules are immobilized on functionalised sepharose beads via copper catalysed Huisgen-type click chemistry and selectively released under acidic conditions by chemical cleavage of the triazene linkage. We applied this method to identify the modification site of targeted-diazotransfer on BirA.

  4. Central site monitoring: results from a test of accuracy in identifying trials and sites failing Food and Drug Administration inspection.

    Science.gov (United States)

    Lindblad, Anne S; Manukyan, Zorayr; Purohit-Sheth, Tejashri; Gensler, Gary; Okwesili, Paul; Meeker-O'Connell, Ann; Ball, Leslie; Marler, John R

    2014-04-01

    Site monitoring and source document verification account for 15%-30% of clinical trial costs. An alternative is to streamline site monitoring to focus on correcting trial-specific risks identified by central data monitoring. This risk-based approach could preserve or even improve the quality of clinical trial data and human subject protection compared to site monitoring focused primarily on source document verification. To determine whether a central review by statisticians using data submitted to the Food and Drug Administration (FDA) by clinical trial sponsors can identify problem sites and trials that failed FDA site inspections. An independent Analysis Center (AC) analyzed data from four anonymous new drug applications (NDAs) where FDA had performed site inspections overseen by FDA's Office of Scientific Investigations (OSI). FDA team members in the OSI chose the four NDAs from among all NDAs with data in Study Data Tabulation Model (SDTM) format. Two of the NDAs had data that OSI had deemed unreliable in support of the application after FDA site inspections identified serious data integrity problems. The other two NDAs had clinical data that OSI deemed reliable after site inspections. At the outset, the AC knew only that the experimental design specified two NDAs with significant problems. FDA gave the AC no information about which NDAs had problems, how many sites were inspected, or how many were found to have problems until after the AC analysis was complete. The AC evaluated randomization balance, enrollment patterns, study visit scheduling, variability of reported data, and last digit reference. The AC classified sites as 'High Concern', 'Moderate Concern', 'Mild Concern', or 'No Concern'. The AC correctly identified the two NDAs with data deemed unreliable by OSI. In addition, central data analysis correctly identified 5 of 6 (83%) sites for which FDA recommended rejection of data and 13 of 15 sites (87%) for which any regulatory deviations were

  5. The mouse cortical meninges are the site of immune responses to many different pathogens, and are accessible to intravital imaging.

    Science.gov (United States)

    Coles, Jonathan A; Stewart-Hutchinson, Phillip J; Myburgh, Elmarie; Brewer, James M

    2017-08-15

    A wide range of viral and microbial infections are known to cause meningitis, and there is evidence that the meninges are the gateway to pathogenic invasion of the brain parenchyma. Hence observation of these regions has wide application to understanding host-pathogen interactions. Interactions between pathogens and cells of the immune response can be modified by changes in their environment, such as suppression of the flow of blood and lymph, and, particularly in the case of the meninges, with their unsupported membranes, invasive dissection can alter the tissue architecture. For these reasons, intravital imaging through the unperforated skull is the method of choice. We give a protocol for a simple method of two-photon microscopy through the thinned cortical skull of the anesthetized mouse to enable real-time imaging with sub-micron resolution through the meninges and into the superficial brain parenchyma. In reporter mice in which selected cell types express fluorescent proteins, imaging after infection with fluorescent pathogens (lymphocytic choriomeningitis virus, Trypanosoma brucei or Plasmodium berghei) has shown strong recruitment to the cortical meninges of immune cells, including neutrophils, T cells, and putative dendritic cells and macrophages. Without special labeling, the boundaries between the dura mater, the leptomeninx, and the parenchyma are not directly visualized in intravital two-photon microscopy, but other landmarks and characteristics, which we illustrate, allow the researcher to identify the compartment being imaged. While most infectious meningitides are localized mainly in the dura mater, others involve recruitment of immune cells to the leptomeninx. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Use of Anisotropy, 3D Segmented Atlas, and Computational Analysis to Identify Gray Matter Subcortical Lesions Common to Concussive Injury from Different Sites on the Cortex.

    Directory of Open Access Journals (Sweden)

    Praveen Kulkarni

    Full Text Available Traumatic brain injury (TBI can occur anywhere along the cortical mantel. While the cortical contusions may be random and disparate in their locations, the clinical outcomes are often similar and difficult to explain. Thus a question that arises is, do concussions at different sites on the cortex affect similar subcortical brain regions? To address this question we used a fluid percussion model to concuss the right caudal or rostral cortices in rats. Five days later, diffusion tensor MRI data were acquired for indices of anisotropy (IA for use in a novel method of analysis to detect changes in gray matter microarchitecture. IA values from over 20,000 voxels were registered into a 3D segmented, annotated rat atlas covering 150 brain areas. Comparisons between left and right hemispheres revealed a small population of subcortical sites with altered IA values. Rostral and caudal concussions were of striking similarity in the impacted subcortical locations, particularly the central nucleus of the amygdala, laterodorsal thalamus, and hippocampal complex. Subsequent immunohistochemical analysis of these sites showed significant neuroinflammation. This study presents three significant findings that advance our understanding and evaluation of TBI: 1 the introduction of a new method to identify highly localized disturbances in discrete gray matter, subcortical brain nuclei without postmortem histology, 2 the use of this method to demonstrate that separate injuries to the rostral and caudal cortex produce the same subcortical, disturbances, and 3 the central nucleus of the amygdala, critical in the regulation of emotion, is vulnerable to concussion.

  7. Shifts of Gamma Phase across Primary Visual Cortical Sites Reflect Dynamic Stimulus-Modulated Information Transfer.

    Science.gov (United States)

    Besserve, Michel; Lowe, Scott C; Logothetis, Nikos K; Schölkopf, Bernhard; Panzeri, Stefano

    2015-01-01

    Distributed neural processing likely entails the capability of networks to reconfigure dynamically the directionality and strength of their functional connections. Yet, the neural mechanisms that may allow such dynamic routing of the information flow are not yet fully understood. We investigated the role of gamma band (50-80 Hz) oscillations in transient modulations of communication among neural populations by using measures of direction-specific causal information transfer. We found that the local phase of gamma-band rhythmic activity exerted a stimulus-modulated and spatially-asymmetric directed effect on the firing rate of spatially separated populations within the primary visual cortex. The relationships between gamma phases at different sites (phase shifts) could be described as a stimulus-modulated gamma-band wave propagating along the spatial directions with the largest information transfer. We observed transient stimulus-related changes in the spatial configuration of phases (compatible with changes in direction of gamma wave propagation) accompanied by a relative increase of the amount of information flowing along the instantaneous direction of the gamma wave. These effects were specific to the gamma-band and suggest that the time-varying relationships between gamma phases at different locations mark, and possibly causally mediate, the dynamic reconfiguration of functional connections.

  8. Benchmark data for identifying N6-methyladenosine sites in the Saccharomyces cerevisiae genome

    Directory of Open Access Journals (Sweden)

    Wei Chen

    2015-12-01

    Full Text Available This data article contains the benchmark dataset for training and testing iRNA-Methyl, a web-server predictor for identifying N6-methyladenosine sites in RNA (Chen et al., 2015 [15]. It can also be used to develop other predictors for identifying N6-methyladenosine sites in the Saccharomyces cerevisiae genome.

  9. Evidentiary requirements to identify potentially acceptable sites (PAS) in crystalline rock

    International Nuclear Information System (INIS)

    Comella, P.A.; Smith, B.H.

    1985-01-01

    This report contains information on the evidentiary requirements to identify potentially acceptable sites in crystalline rock for waste disposal. Topics addressed include: chronology, key regulatory assumptions, statutory framework for identifying potentially acceptable sites, application of 10 disqualifiers, consideration of favorable and potentially adverse conditions, a composite favorability analysis, and a proposed outline for PAS identification decision document

  10. Regulatory O-GlcNAcylation sites on FoxO1 are yet to be identified

    Energy Technology Data Exchange (ETDEWEB)

    Fardini, Yann [INSERM, U1016, Institut Cochin, Paris (France); CNRS, UMR8104, Paris (France); Université Paris Descartes, Sorbonne Paris Cité, Paris (France); Perez-Cervera, Yobana [Structural and Functional Glycobiology Unit, Lille 1 University, CNRS (UMR 8576), IFR 117, Villeneuve d' Ascq (France); Facultad de Odontología, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca (Mexico); Camoin, Luc [INSERM, U1068, CRCM, Marseille Protéomique IBiSA, Marseille, F-13009 (France); Institut Paoli-Calmettes Team, Cell Polarity, Cell Signaling and Cancer, Marseille, F-13009 (France); Aix-Marseille Université, F-13284, Marseille (France); CNRS, UMR7258, CRCM, Marseille, F-13009 (France); Pagesy, Patrick [INSERM, U1016, Institut Cochin, Paris (France); CNRS, UMR8104, Paris (France); Université Paris Descartes, Sorbonne Paris Cité, Paris (France); Lefebvre, Tony [Structural and Functional Glycobiology Unit, Lille 1 University, CNRS (UMR 8576), IFR 117, Villeneuve d' Ascq (France); Issad, Tarik, E-mail: tarik.issad@inserm.fr [INSERM, U1016, Institut Cochin, Paris (France); CNRS, UMR8104, Paris (France); Université Paris Descartes, Sorbonne Paris Cité, Paris (France)

    2015-06-26

    O-GlcNAcylation is a reversible post-translational modification that regulates cytosolic and nuclear proteins. We and others previously demonstrated that FoxO1 is O-GlcNAcylated in different cell types, resulting in an increase in its transcriptional activity. Four O-GlcNAcylation sites were identified in human FOXO1 but directed mutagenesis of each site individually had modest (T317) or no effect (S550, T648, S654) on its O-GlcNAcylation status and transcriptional activity. Moreover, the consequences of mutating all four sites had not been investigated. In the present work, we mutated these sites in the mouse Foxo1 and found that mutation of all four sites did not decrease Foxo1 O-GlcNAcylation status and transcriptional activity, and would even tend to increase them. In an attempt to identify other O-GlcNAcylation sites, we immunoprecipitated wild-type O-GlcNAcylated Foxo1 and analysed the tryptic digest peptides by mass spectrometry using High-energy Collisional Dissociation. We identified T646 as a new O-GlcNAcylation site on Foxo1. However, site directed mutagenesis of this site individually or together with all four previously identified residues did not impair Foxo1 O-GlcNAcylation and transcriptional activity. These results suggest that residues important for the control of Foxo1 activity by O-GlcNAcylation still remain to be identified. - Highlights: • We mutate four previously identified O-GlcNAcylation sites on Foxo1. • Unexpectedly, these mutations do not reduce Foxo1 O-GlcNAcylation. • These mutation do not reduce Foxo1 transcriptional activity. • We identify a new O-GlcNAcylation site on Foxo1 by mass spectrometry. • Mutation of this site increases Foxo1 transcriptional activity.

  11. Regulatory O-GlcNAcylation sites on FoxO1 are yet to be identified

    International Nuclear Information System (INIS)

    Fardini, Yann; Perez-Cervera, Yobana; Camoin, Luc; Pagesy, Patrick; Lefebvre, Tony; Issad, Tarik

    2015-01-01

    O-GlcNAcylation is a reversible post-translational modification that regulates cytosolic and nuclear proteins. We and others previously demonstrated that FoxO1 is O-GlcNAcylated in different cell types, resulting in an increase in its transcriptional activity. Four O-GlcNAcylation sites were identified in human FOXO1 but directed mutagenesis of each site individually had modest (T317) or no effect (S550, T648, S654) on its O-GlcNAcylation status and transcriptional activity. Moreover, the consequences of mutating all four sites had not been investigated. In the present work, we mutated these sites in the mouse Foxo1 and found that mutation of all four sites did not decrease Foxo1 O-GlcNAcylation status and transcriptional activity, and would even tend to increase them. In an attempt to identify other O-GlcNAcylation sites, we immunoprecipitated wild-type O-GlcNAcylated Foxo1 and analysed the tryptic digest peptides by mass spectrometry using High-energy Collisional Dissociation. We identified T646 as a new O-GlcNAcylation site on Foxo1. However, site directed mutagenesis of this site individually or together with all four previously identified residues did not impair Foxo1 O-GlcNAcylation and transcriptional activity. These results suggest that residues important for the control of Foxo1 activity by O-GlcNAcylation still remain to be identified. - Highlights: • We mutate four previously identified O-GlcNAcylation sites on Foxo1. • Unexpectedly, these mutations do not reduce Foxo1 O-GlcNAcylation. • These mutation do not reduce Foxo1 transcriptional activity. • We identify a new O-GlcNAcylation site on Foxo1 by mass spectrometry. • Mutation of this site increases Foxo1 transcriptional activity

  12. Under What Assumptions Do Site-by-Treatment Instruments Identify Average Causal Effects?

    Science.gov (United States)

    Reardon, Sean F.; Raudenbush, Stephen W.

    2013-01-01

    The increasing availability of data from multi-site randomized trials provides a potential opportunity to use instrumental variables methods to study the effects of multiple hypothesized mediators of the effect of a treatment. We derive nine assumptions needed to identify the effects of multiple mediators when using site-by-treatment interactions…

  13. Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA.

    Directory of Open Access Journals (Sweden)

    Orr Ashenberg

    2017-03-01

    Full Text Available The innate-immune restriction factor MxA inhibits influenza replication by targeting the viral nucleoprotein (NP. Human influenza virus is more resistant than avian influenza virus to inhibition by human MxA, and prior work has compared human and avian viral strains to identify amino-acid differences in NP that affect sensitivity to MxA. However, this strategy is limited to identifying sites in NP where mutations that affect MxA sensitivity have fixed during the small number of documented zoonotic transmissions of influenza to humans. Here we use an unbiased deep mutational scanning approach to quantify how all single amino-acid mutations to NP affect MxA sensitivity in the context of replication-competent virus. We both identify new sites in NP where mutations affect MxA resistance and re-identify mutations known to have increased MxA resistance during historical adaptations of influenza to humans. Most of the sites where mutations have the greatest effect are almost completely conserved across all influenza A viruses, and the amino acids at these sites confer relatively high resistance to MxA. These sites cluster in regions of NP that appear to be important for its recognition by MxA. Overall, our work systematically identifies the sites in influenza nucleoprotein where mutations affect sensitivity to MxA. We also demonstrate a powerful new strategy for identifying regions of viral proteins that affect inhibition by host factors.

  14. GASS-WEB: a web server for identifying enzyme active sites based on genetic algorithms.

    Science.gov (United States)

    Moraes, João P A; Pappa, Gisele L; Pires, Douglas E V; Izidoro, Sandro C

    2017-07-03

    Enzyme active sites are important and conserved functional regions of proteins whose identification can be an invaluable step toward protein function prediction. Most of the existing methods for this task are based on active site similarity and present limitations including performing only exact matches on template residues, template size restraints, despite not being capable of finding inter-domain active sites. To fill this gap, we proposed GASS-WEB, a user-friendly web server that uses GASS (Genetic Active Site Search), a method based on an evolutionary algorithm to search for similar active sites in proteins. GASS-WEB can be used under two different scenarios: (i) given a protein of interest, to match a set of specific active site templates; or (ii) given an active site template, looking for it in a database of protein structures. The method has shown to be very effective on a range of experiments and was able to correctly identify >90% of the catalogued active sites from the Catalytic Site Atlas. It also managed to achieve a Matthew correlation coefficient of 0.63 using the Critical Assessment of protein Structure Prediction (CASP 10) dataset. In our analysis, GASS was ranking fourth among 18 methods. GASS-WEB is freely available at http://gass.unifei.edu.br/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. Site-matched assessment of structural and tissue properties of cortical bone using scanning acoustic microscopy and synchrotron radiation μCT

    International Nuclear Information System (INIS)

    Raum, K; Leguerney, I; Chandelier, F; Talmant, M; Saied, A; Peyrin, F; Laugier, P

    2006-01-01

    200 MHz scanning acoustic microscopy (SAM) and synchrotron radiation μCT (SR-μCT) were used to assess microstructural parameters and tissue properties in site-matched regions of interest in cortical bone. Anterior and postero-lateral regions of ten cross sections from human cortical radius were explored. Structural parameters, including diameter and number of Haversian canals per cortical area (Ca.Dm, N.Ca/Ar) and porosity Po were assessed with both methods using a custom-developed image fusion and analysis software. Acoustic impedance Z and degree of mineralization of bone DMB were extracted separately for osteonal and interstitial tissues from the fused images. Structural parameter estimations obtained from radiographic and acoustic images were almost identical. DMB and impedance values were in the range between 0.77 and 1.28 g cm -3 and 5.13 and 12.1 Mrayl, respectively. Interindividual and regional variations were observed, whereas the strongest difference was found between osteonal and interstitial tissues (Z: 7.2 ± 1.1 Mrayl versus 9.3 ± 1.0 Mrayl, DMB: 1.06 ± 0.07 g cm -3 versus 1.16 ± 0.05 g cm -3 , paired t-test, p 2 = 0.174, p -4 ) and for the pooled (osteonal and interstitial) data. The regression of the pooled osteonal and interstitial tissue data follows a second-order polynomial (R 2 = 0.39, p -4 ). Both modalities fulfil the requirement for a simultaneous evaluation of cortical bone microstructure and material properties at the tissue level. While SAM inspection is limited to the evaluation of carefully prepared sample surfaces, SR-μCT provides volumetric information on the tissue without substantial preparation requirements. However, SAM provides a quantitative estimate of elastic properties at the tissue level that cannot be captured by SR-μCT

  16. Toward identifying the next generation of superfund and hazardous waste site contaminants.

    Science.gov (United States)

    Ela, Wendell P; Sedlak, David L; Barlaz, Morton A; Henry, Heather F; Muir, Derek C G; Swackhamer, Deborah L; Weber, Eric J; Arnold, Robert G; Ferguson, P Lee; Field, Jennifer A; Furlong, Edward T; Giesy, John P; Halden, Rolf U; Henry, Tala; Hites, Ronald A; Hornbuckle, Keri C; Howard, Philip H; Luthy, Richard G; Meyer, Anita K; Sáez, A Eduardo; Vom Saal, Frederick S; Vulpe, Chris D; Wiesner, Mark R

    2011-01-01

    This commentary evolved from a workshop sponsored by the National Institute of Environmental Health Sciences titled "Superfund Contaminants: The Next Generation" held in Tucson, Arizona, in August 2009. All the authors were workshop participants. Our aim was to initiate a dynamic, adaptable process for identifying contaminants of emerging concern (CECs) that are likely to be found in future hazardous waste sites, and to identify the gaps in primary research that cause uncertainty in determining future hazardous waste site contaminants. Superfund-relevant CECs can be characterized by specific attributes: They are persistent, bioaccumulative, toxic, occur in large quantities, and have localized accumulation with a likelihood of exposure. Although still under development and incompletely applied, methods to quantify these attributes can assist in winnowing down the list of candidates from the universe of potential CECs. Unfortunately, significant research gaps exist in detection and quantification, environmental fate and transport, health and risk assessment, and site exploration and remediation for CECs. Addressing these gaps is prerequisite to a preventive approach to generating and managing hazardous waste sites. A need exists for a carefully considered and orchestrated expansion of programmatic and research efforts to identify, evaluate, and manage CECs of hazardous waste site relevance, including developing an evolving list of priority CECs, intensifying the identification and monitoring of likely sites of present or future accumulation of CECs, and implementing efforts that focus on a holistic approach to prevention.

  17. Positron emission tomography studies of neuronal activity patterns during sensory and cognitive stimulations in Alzheimer's disease. A study of cortical attention sites in man

    International Nuclear Information System (INIS)

    Johannsen, Peter

    1997-01-01

    This Ph.D.-thesis describes different subtypes of attention, models for the organization of attention, and the attention deficits in Alzheimer's disease. The experimental part of the study is based on studies of sustained and divided attention to two different sensory modalities; a visual checkerboard stimulation reversing at 7 Hz, and a 110 Hz vibrotactile stimulation of the right hand in a group of healthy elderly subjects (n = 16) age-matched with a group of patients with mild to moderate Alzheimer's disease (n = 16). The cortical activations during the attention tasks have been mapped using O-15-water and positron emission tomography (PET) measurements of regional cerebral blood flow (rCBF) during rest and during performance of an attention task. After anatomical standardization and averaging over subjects, activation foci were assessed by a t-statistical evaluation of the differences of rCBF maps acquired before and during the execution of the attention tasks. The rCBF deficits in the Alzheimer patients were compared to rCBF pattern in the healthy elderly and assessed statistically on a voxel-by-voxel basis, revealing a distinct and localized pattern of rCBF deficits extending from the hippocampal area along the longitudinal fascicle to the temporo-parietal cortices with further deficits in the frontal regions. The resting rCBF deficits are distributed with the same pattern as described in neuropathological studies of lesions in Alzheimer's disease. In the healthy elderly, both sustained and divided attention elicited activation of the right inferior parietal lobule (Brodmann Area 19/40) and the right middle frontal gyrus (Brodmann Area 46). Divided attention favored activation of the right middle frontal gyrus and sustained attention activation of the right inferior parietal lobule. Both the frontal and the parietal attention sites were active during attention to both the visual and the vibrotactile stimuli. These results support a network hypothesis of

  18. Positron emission tomography studies of neuronal activity patterns during sensory and cognitive stimulations in Alzheimer`s disease. A study of cortical attention sites in man

    Energy Technology Data Exchange (ETDEWEB)

    Johannsen, Peter

    1997-12-31

    This Ph.D.-thesis describes different subtypes of attention, models for the organization of attention, and the attention deficits in Alzheimer`s disease. The experimental part of the study is based on studies of sustained and divided attention to two different sensory modalities; a visual checkerboard stimulation reversing at 7 Hz, and a 110 Hz vibrotactile stimulation of the right hand in a group of healthy elderly subjects (n = 16) age-matched with a group of patients with mild to moderate Alzheimer`s disease (n = 16). The cortical activations during the attention tasks have been mapped using O-15-water and positron emission tomography (PET) measurements of regional cerebral blood flow (rCBF) during rest and during performance of an attention task. After anatomical standardization and averaging over subjects, activation foci were assessed by a t-statistical evaluation of the differences of rCBF maps acquired before and during the execution of the attention tasks. The rCBF deficits in the Alzheimer patients were compared to rCBF pattern in the healthy elderly and assessed statistically on a voxel-by-voxel basis, revealing a distinct and localized pattern of rCBF deficits extending from the hippocampal area along the longitudinal fascicle to the temporo-parietal cortices with further deficits in the frontal regions. The resting rCBF deficits are distributed with the same pattern as described in neuropathological studies of lesions in Alzheimer`s disease. In the healthy elderly, both sustained and divided attention elicited activation of the right inferior parietal lobule (Brodmann Area 19/40) and the right middle frontal gyrus (Brodmann Area 46). Divided attention favored activation of the right middle frontal gyrus and sustained attention activation of the right inferior parietal lobule. Both the frontal and the parietal attention sites were active during attention to both the visual and the vibrotactile stimuli. These results support a network hypothesis of

  19. Identifying diabetes knowledge network nodes as sites for a diabetes prevention program.

    Science.gov (United States)

    Gesler, Wilbert M; Arcury, Thomas A; Skelly, Anne H; Nash, Sally; Soward, April; Dougherty, Molly

    2006-12-01

    This paper reports on the methods used and results of a study that identified specific places within a community that have the potential to be sites for a diabetes prevention program. These sites, termed diabetes knowledge network nodes (DKNNs), are based on the concept of socio-spatial knowledge networks (SSKNs), the web of social relationships within which people obtain knowledge about type 2 diabetes. The target population for the study was working poor African Americans, Latinos, and European Americans of both sexes in a small rural southern town who had not been diagnosed with diabetes. Information was collected from a sample of 121 respondents on the places they visited in carrying out their daily activities. Data on number of visits to specific sites, degree of familiarity with these sites, and ratings of sites as places to receive diabetes information were used to develop three categories of DKNNs for six subgroups based on ethnicity and sex. Primary potential sites of importance to one or more subgroups included churches, grocery stores, drugstores, the local library, a beauty salon, laundromats, a community service agency, and a branch of the County Health Department. Secondary potential sites included gas stations, restaurants, banks, and post offices. Latent potential sites included three medical facilities. Most of the DKNNs were located either in the downtown area or in one of two shopping areas along the most used highway that passed through the town. The procedures used in this study can be generalized to other communities and prevention programs for other chronic diseases.

  20. SABER: a computational method for identifying active sites for new reactions.

    Science.gov (United States)

    Nosrati, Geoffrey R; Houk, K N

    2012-05-01

    A software suite, SABER (Selection of Active/Binding sites for Enzyme Redesign), has been developed for the analysis of atomic geometries in protein structures, using a geometric hashing algorithm (Barker and Thornton, Bioinformatics 2003;19:1644-1649). SABER is used to explore the Protein Data Bank (PDB) to locate proteins with a specific 3D arrangement of catalytic groups to identify active sites that might be redesigned to catalyze new reactions. As a proof-of-principle test, SABER was used to identify enzymes that have the same catalytic group arrangement present in o-succinyl benzoate synthase (OSBS). Among the highest-scoring scaffolds identified by the SABER search for enzymes with the same catalytic group arrangement as OSBS were L-Ala D/L-Glu epimerase (AEE) and muconate lactonizing enzyme II (MLE), both of which have been redesigned to become effective OSBS catalysts, demonstrated by experiments. Next, we used SABER to search for naturally existing active sites in the PDB with catalytic groups similar to those present in the designed Kemp elimination enzyme KE07. From over 2000 geometric matches to the KE07 active site, SABER identified 23 matches that corresponded to residues from known active sites. The best of these matches, with a 0.28 Å catalytic atom RMSD to KE07, was then redesigned to be compatible with the Kemp elimination using RosettaDesign. We also used SABER to search for potential Kemp eliminases using a theozyme predicted to provide a greater rate acceleration than the active site of KE07, and used Rosetta to create a design based on the proteins identified. Copyright © 2012 The Protein Society.

  1. Evaluation of potential regulatory elements identified as DNase I hypersensitive sites in the CFTR gene

    DEFF Research Database (Denmark)

    Phylactides, M.; Rowntree, R.; Nuthall, H.

    2002-01-01

    hypersensitive sites (DHS) within the locus. We previously identified at least 12 clusters of DHS across the CFTR gene and here further evaluate DHS in introns 2,3,10,16,17a, 18, 20 and 21 to assess their functional importance in regulation of CFTR gene expression. Transient transfections of enhancer/reporter...

  2. Identifying protein phosphorylation sites with kinase substrate specificity on human viruses.

    Directory of Open Access Journals (Sweden)

    Neil Arvin Bretaña

    Full Text Available Viruses infect humans and progress inside the body leading to various diseases and complications. The phosphorylation of viral proteins catalyzed by host kinases plays crucial regulatory roles in enhancing replication and inhibition of normal host-cell functions. Due to its biological importance, there is a desire to identify the protein phosphorylation sites on human viruses. However, the use of mass spectrometry-based experiments is proven to be expensive and labor-intensive. Furthermore, previous studies which have identified phosphorylation sites in human viruses do not include the investigation of the responsible kinases. Thus, we are motivated to propose a new method to identify protein phosphorylation sites with its kinase substrate specificity on human viruses. The experimentally verified phosphorylation data were extracted from virPTM--a database containing 301 experimentally verified phosphorylation data on 104 human kinase-phosphorylated virus proteins. In an attempt to investigate kinase substrate specificities in viral protein phosphorylation sites, maximal dependence decomposition (MDD is employed to cluster a large set of phosphorylation data into subgroups containing significantly conserved motifs. The experimental human phosphorylation sites are collected from Phospho.ELM, grouped according to its kinase annotation, and compared with the virus MDD clusters. This investigation identifies human kinases such as CK2, PKB, CDK, and MAPK as potential kinases for catalyzing virus protein substrates as confirmed by published literature. Profile hidden Markov model is then applied to learn a predictive model for each subgroup. A five-fold cross validation evaluation on the MDD-clustered HMMs yields an average accuracy of 84.93% for Serine, and 78.05% for Threonine. Furthermore, an independent testing data collected from UniProtKB and Phospho.ELM is used to make a comparison of predictive performance on three popular kinase

  3. Identifying protein phosphorylation sites with kinase substrate specificity on human viruses.

    Science.gov (United States)

    Bretaña, Neil Arvin; Lu, Cheng-Tsung; Chiang, Chiu-Yun; Su, Min-Gang; Huang, Kai-Yao; Lee, Tzong-Yi; Weng, Shun-Long

    2012-01-01

    Viruses infect humans and progress inside the body leading to various diseases and complications. The phosphorylation of viral proteins catalyzed by host kinases plays crucial regulatory roles in enhancing replication and inhibition of normal host-cell functions. Due to its biological importance, there is a desire to identify the protein phosphorylation sites on human viruses. However, the use of mass spectrometry-based experiments is proven to be expensive and labor-intensive. Furthermore, previous studies which have identified phosphorylation sites in human viruses do not include the investigation of the responsible kinases. Thus, we are motivated to propose a new method to identify protein phosphorylation sites with its kinase substrate specificity on human viruses. The experimentally verified phosphorylation data were extracted from virPTM--a database containing 301 experimentally verified phosphorylation data on 104 human kinase-phosphorylated virus proteins. In an attempt to investigate kinase substrate specificities in viral protein phosphorylation sites, maximal dependence decomposition (MDD) is employed to cluster a large set of phosphorylation data into subgroups containing significantly conserved motifs. The experimental human phosphorylation sites are collected from Phospho.ELM, grouped according to its kinase annotation, and compared with the virus MDD clusters. This investigation identifies human kinases such as CK2, PKB, CDK, and MAPK as potential kinases for catalyzing virus protein substrates as confirmed by published literature. Profile hidden Markov model is then applied to learn a predictive model for each subgroup. A five-fold cross validation evaluation on the MDD-clustered HMMs yields an average accuracy of 84.93% for Serine, and 78.05% for Threonine. Furthermore, an independent testing data collected from UniProtKB and Phospho.ELM is used to make a comparison of predictive performance on three popular kinase-specific phosphorylation site

  4. Identifying potential surface water sampling sites for emerging chemical pollutants in Gauteng Province, South Africa

    OpenAIRE

    Petersen, F; Dabrowski, JM; Forbes, PBC

    2017-01-01

    Emerging chemical pollutants (ECPs) are defined as new chemicals which do not have a regulatory status, but which may have an adverse effect on human health and the environment. The occurrence and concentrations of ECPs in South African water bodies are largely unknown, so monitoring is required in order to determine the potential threat that these ECPs may pose. Relevant surface water sampling sites in the Gauteng Province of South Africa were identified utilising a geographic information sy...

  5. A model-based approach to identify binding sites in CLIP-Seq data.

    Directory of Open Access Journals (Sweden)

    Tao Wang

    Full Text Available Cross-linking immunoprecipitation coupled with high-throughput sequencing (CLIP-Seq has made it possible to identify the targeting sites of RNA-binding proteins in various cell culture systems and tissue types on a genome-wide scale. Here we present a novel model-based approach (MiClip to identify high-confidence protein-RNA binding sites from CLIP-seq datasets. This approach assigns a probability score for each potential binding site to help prioritize subsequent validation experiments. The MiClip algorithm has been tested in both HITS-CLIP and PAR-CLIP datasets. In the HITS-CLIP dataset, the signal/noise ratios of miRNA seed motif enrichment produced by the MiClip approach are between 17% and 301% higher than those by the ad hoc method for the top 10 most enriched miRNAs. In the PAR-CLIP dataset, the MiClip approach can identify ∼50% more validated binding targets than the original ad hoc method and two recently published methods. To facilitate the application of the algorithm, we have released an R package, MiClip (http://cran.r-project.org/web/packages/MiClip/index.html, and a public web-based graphical user interface software (http://galaxy.qbrc.org/tool_runner?tool_id=mi_clip for customized analysis.

  6. Hon-yaku: a biology-driven Bayesian methodology for identifying translation initiation sites in prokaryotes

    Directory of Open Access Journals (Sweden)

    de Hoon Michiel JL

    2007-02-01

    Full Text Available Abstract Background Computational prediction methods are currently used to identify genes in prokaryote genomes. However, identification of the correct translation initiation sites remains a difficult task. Accurate translation initiation sites (TISs are important not only for the annotation of unknown proteins but also for the prediction of operons, promoters, and small non-coding RNA genes, as this typically makes use of the intergenic distance. A further problem is that most existing methods are optimized for Escherichia coli data sets; applying these methods to newly sequenced bacterial genomes may not result in an equivalent level of accuracy. Results Based on a biological representation of the translation process, we applied Bayesian statistics to create a score function for predicting translation initiation sites. In contrast to existing programs, our combination of methods uses supervised learning to optimally use the set of known translation initiation sites. We combined the Ribosome Binding Site (RBS sequence, the distance between the translation initiation site and the RBS sequence, the base composition of the start codon, the nucleotide composition (A-rich sequences following start codons, and the expected distribution of the protein length in a Bayesian scoring function. To further increase the prediction accuracy, we also took into account the operon orientation. The outcome of the procedure achieved a prediction accuracy of 93.2% in 858 E. coli genes from the EcoGene data set and 92.7% accuracy in a data set of 1243 Bacillus subtilis 'non-y' genes. We confirmed the performance in the GC-rich Gamma-Proteobacteria Herminiimonas arsenicoxydans, Pseudomonas aeruginosa, and Burkholderia pseudomallei K96243. Conclusion Hon-yaku, being based on a careful choice of elements important in translation, improved the prediction accuracy in B. subtilis data sets and other bacteria except for E. coli. We believe that most remaining

  7. 2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size.

    Science.gov (United States)

    Otani, Tomoki; Marchetto, Maria C; Gage, Fred H; Simons, Benjamin D; Livesey, Frederick J

    2016-04-07

    Variation in cerebral cortex size and complexity is thought to contribute to differences in cognitive ability between humans and other animals. Here we compare cortical progenitor cell output in humans and three nonhuman primates using directed differentiation of pluripotent stem cells (PSCs) in adherent two-dimensional (2D) and organoid three-dimensional (3D) culture systems. Clonal lineage analysis showed that primate cortical progenitors proliferate for a protracted period of time, during which they generate early-born neurons, in contrast to rodents, where this expansion phase largely ceases before neurogenesis begins. The extent of this additional cortical progenitor expansion differs among primates, leading to differences in the number of neurons generated by each progenitor cell. We found that this mechanism for controlling cortical size is regulated cell autonomously in culture, suggesting that primate cerebral cortex size is regulated at least in part at the level of individual cortical progenitor cell clonal output. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Common integration sites of published datasets identified using a graph-based framework

    Directory of Open Access Journals (Sweden)

    Alessandro Vasciaveo

    2016-01-01

    Full Text Available With next-generation sequencing, the genomic data available for the characterization of integration sites (IS has dramatically increased. At present, in a single experiment, several thousand viral integration genome targets can be investigated to define genomic hot spots. In a previous article, we renovated a formal CIS analysis based on a rigid fixed window demarcation into a more stretchy definition grounded on graphs. Here, we present a selection of supporting data related to the graph-based framework (GBF from our previous article, in which a collection of common integration sites (CIS was identified on six published datasets. In this work, we will focus on two datasets, ISRTCGD and ISHIV, which have been previously discussed. Moreover, we show in more detail the workflow design that originates the datasets.

  9. A method of identifying social structures in siting regions for deep geological repositories in Switzerland

    International Nuclear Information System (INIS)

    Brander, Simone

    2010-09-01

    Acceptance is a key element in the site selection process for deep geological repositories for high-level and low and intermediate-level radioactive waste in Switzerland. Participation requirements such as comprehensive negotiation issues and adequate resources have thus been defined by the Swiss Federal Office of Energy (SFOE). In 2008, on the basis of technical criteria Nagra (National Cooperative for the Disposal of Radioactive Waste) proposed several potential areas for deep geological repositories. The number of potential areas will be narrowed down within the next few years. All municipalities within the planning perimeter (the area in which surface facilities can be realised) are affected and form the siting region. In order to ensure that the local population have their say in the forthcoming discussions, regional participation bodies including all municipalities within a siting region are being set up by the SFOE. Regional participation ensures that local interests, needs and values are taken into account in the site selection process. Assembling the regional participation bodies is therefore of great importance. Before such bodies can be formed, however, the various interests, needs and values have to be identified, and special attention has to be paid to long-term interests of future generations, as well as to non-organised and under-represented interests. According to the concept of proportional representation, the interests, needs and values that are identified and weighted by the local population are to be represented in the regional participation procedure. The aim of this study is to share a method of mapping existing social structures in a defined geographical area. This involves a combination of an analysis of socio-economic statistical data and qualitative and quantitative social research methods

  10. SNOSite: exploiting maximal dependence decomposition to identify cysteine S-nitrosylation with substrate site specificity.

    Directory of Open Access Journals (Sweden)

    Tzong-Yi Lee

    Full Text Available S-nitrosylation, the covalent attachment of a nitric oxide to (NO the sulfur atom of cysteine, is a selective and reversible protein post-translational modification (PTM that regulates protein activity, localization, and stability. Despite its implication in the regulation of protein functions and cell signaling, the substrate specificity of cysteine S-nitrosylation remains unknown. Based on a total of 586 experimentally identified S-nitrosylation sites from SNAP/L-cysteine-stimulated mouse endothelial cells, this work presents an informatics investigation on S-nitrosylation sites including structural factors such as the flanking amino acids composition, the accessible surface area (ASA and physicochemical properties, i.e. positive charge and side chain interaction parameter. Due to the difficulty to obtain the conserved motifs by conventional motif analysis, maximal dependence decomposition (MDD has been applied to obtain statistically significant conserved motifs. Support vector machine (SVM is applied to generate predictive model for each MDD-clustered motif. According to five-fold cross-validation, the MDD-clustered SVMs could achieve an accuracy of 0.902, and provides a promising performance in an independent test set. The effectiveness of the model was demonstrated on the correct identification of previously reported S-nitrosylation sites of Bos taurus dimethylarginine dimethylaminohydrolase 1 (DDAH1 and human hemoglobin subunit beta (HBB. Finally, the MDD-clustered model was adopted to construct an effective web-based tool, named SNOSite (http://csb.cse.yzu.edu.tw/SNOSite/, for identifying S-nitrosylation sites on the uncharacterized protein sequences.

  11. GSHSite: exploiting an iteratively statistical method to identify s-glutathionylation sites with substrate specificity.

    Directory of Open Access Journals (Sweden)

    Yi-Ju Chen

    Full Text Available S-glutathionylation, the covalent attachment of a glutathione (GSH to the sulfur atom of cysteine, is a selective and reversible protein post-translational modification (PTM that regulates protein activity, localization, and stability. Despite its implication in the regulation of protein functions and cell signaling, the substrate specificity of cysteine S-glutathionylation remains unknown. Based on a total of 1783 experimentally identified S-glutathionylation sites from mouse macrophages, this work presents an informatics investigation on S-glutathionylation sites including structural factors such as the flanking amino acids composition and the accessible surface area (ASA. TwoSampleLogo presents that positively charged amino acids flanking the S-glutathionylated cysteine may influence the formation of S-glutathionylation in closed three-dimensional environment. A statistical method is further applied to iteratively detect the conserved substrate motifs with statistical significance. Support vector machine (SVM is then applied to generate predictive model considering the substrate motifs. According to five-fold cross-validation, the SVMs trained with substrate motifs could achieve an enhanced sensitivity, specificity, and accuracy, and provides a promising performance in an independent test set. The effectiveness of the proposed method is demonstrated by the correct identification of previously reported S-glutathionylation sites of mouse thioredoxin (TXN and human protein tyrosine phosphatase 1b (PTP1B. Finally, the constructed models are adopted to implement an effective web-based tool, named GSHSite (http://csb.cse.yzu.edu.tw/GSHSite/, for identifying uncharacterized GSH substrate sites on the protein sequences.

  12. Computerized analysis of the 12-lead electrocardiogram to identify epicardial ventricular tachycardia exit sites.

    Science.gov (United States)

    Yokokawa, Miki; Jung, Dae Yon; Joseph, Kim K; Hero, Alfred O; Morady, Fred; Bogun, Frank

    2014-11-01

    Twelve-lead electrocardiogram (ECG) criteria for epicardial ventricular tachycardia (VT) origins have been described. In patients with structural heart disease, the ability to predict an epicardial origin based on QRS morphology is limited and has been investigated only for limited regions in the heart. The purpose of this study was to determine whether a computerized algorithm is able to accurately differentiate epicardial vs endocardial origins of ventricular arrhythmias. Endocardial and epicardial pace-mapping were performed in 43 patients at 3277 sites. The 12-lead ECGs were digitized and analyzed using a mixture of gaussian model (MoG) to assess whether the algorithm was able to identify an epicardial vs endocardial origin of the paced rhythm. The MoG computerized algorithm was compared to algorithms published in prior reports. The computerized algorithm correctly differentiated epicardial vs endocardial pacing sites for 80% of the sites compared to an accuracy of 42% to 66% of other described criteria. The accuracy was higher in patients without structural heart disease than in those with structural heart disease (94% vs 80%, P = .0004) and for right bundle branch block (82%) compared to left bundle branch block morphologies (79%, P = .001). Validation studies showed the accuracy for VT exit sites to be 84%. A computerized algorithm was able to accurately differentiate the majority of epicardial vs endocardial pace-mapping sites. The algorithm is not region specific and performed best in patients without structural heart disease and with VTs having a right bundle branch block morphology. Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  13. Challenges in identifying sites climatically matched to the native ranges of animal invaders

    Science.gov (United States)

    Rodda, G.H.; Jarnevich, C.S.; Reed, R.N.

    2011-01-01

    Background: Species distribution models are often used to characterize a species' native range climate, so as to identify sites elsewhere in the world that may be climatically similar and therefore at risk of invasion by the species. This endeavor provoked intense public controversy over recent attempts to model areas at risk of invasion by the Indian Python (Python molurus). We evaluated a number of MaxEnt models on this species to assess MaxEnt's utility for vertebrate climate matching. Methodology/Principal Findings: Overall, we found MaxEnt models to be very sensitive to modeling choices and selection of input localities and background regions. As used, MaxEnt invoked minimal protections against data dredging, multi-collinearity of explanatory axes, and overfitting. As used, MaxEnt endeavored to identify a single ideal climate, whereas different climatic considerations may determine range boundaries in different parts of the native range. MaxEnt was extremely sensitive to both the choice of background locations for the python, and to selection of presence points: inclusion of just four erroneous localities was responsible for Pyron et al.'s conclusion that no additional portions of the U.S. mainland were at risk of python invasion. When used with default settings, MaxEnt overfit the realized climate space, identifying models with about 60 parameters, about five times the number of parameters justifiable when optimized on the basis of Akaike's Information Criterion. Conclusions/Significance: When used with default settings, MaxEnt may not be an appropriate vehicle for identifying all sites at risk of colonization. Model instability and dearth of protections against overfitting, multi-collinearity, and data dredging may combine with a failure to distinguish fundamental from realized climate envelopes to produce models of limited utility. A priori identification of biologically realistic model structure, combined with computational protections against these

  14. Challenges in identifying sites climatically matched to the native ranges of animal invaders.

    Directory of Open Access Journals (Sweden)

    Gordon H Rodda

    Full Text Available BACKGROUND: Species distribution models are often used to characterize a species' native range climate, so as to identify sites elsewhere in the world that may be climatically similar and therefore at risk of invasion by the species. This endeavor provoked intense public controversy over recent attempts to model areas at risk of invasion by the Indian Python (Python molurus. We evaluated a number of MaxEnt models on this species to assess MaxEnt's utility for vertebrate climate matching. METHODOLOGY/PRINCIPAL FINDINGS: Overall, we found MaxEnt models to be very sensitive to modeling choices and selection of input localities and background regions. As used, MaxEnt invoked minimal protections against data dredging, multi-collinearity of explanatory axes, and overfitting. As used, MaxEnt endeavored to identify a single ideal climate, whereas different climatic considerations may determine range boundaries in different parts of the native range. MaxEnt was extremely sensitive to both the choice of background locations for the python, and to selection of presence points: inclusion of just four erroneous localities was responsible for Pyron et al.'s conclusion that no additional portions of the U.S. mainland were at risk of python invasion. When used with default settings, MaxEnt overfit the realized climate space, identifying models with about 60 parameters, about five times the number of parameters justifiable when optimized on the basis of Akaike's Information Criterion. CONCLUSIONS/SIGNIFICANCE: When used with default settings, MaxEnt may not be an appropriate vehicle for identifying all sites at risk of colonization. Model instability and dearth of protections against overfitting, multi-collinearity, and data dredging may combine with a failure to distinguish fundamental from realized climate envelopes to produce models of limited utility. A priori identification of biologically realistic model structure, combined with computational protections

  15. Challenges in identifying sites climatically matched to the native ranges of animal invaders.

    Science.gov (United States)

    Rodda, Gordon H; Jarnevich, Catherine S; Reed, Robert N

    2011-02-09

    Species distribution models are often used to characterize a species' native range climate, so as to identify sites elsewhere in the world that may be climatically similar and therefore at risk of invasion by the species. This endeavor provoked intense public controversy over recent attempts to model areas at risk of invasion by the Indian Python (Python molurus). We evaluated a number of MaxEnt models on this species to assess MaxEnt's utility for vertebrate climate matching. Overall, we found MaxEnt models to be very sensitive to modeling choices and selection of input localities and background regions. As used, MaxEnt invoked minimal protections against data dredging, multi-collinearity of explanatory axes, and overfitting. As used, MaxEnt endeavored to identify a single ideal climate, whereas different climatic considerations may determine range boundaries in different parts of the native range. MaxEnt was extremely sensitive to both the choice of background locations for the python, and to selection of presence points: inclusion of just four erroneous localities was responsible for Pyron et al.'s conclusion that no additional portions of the U.S. mainland were at risk of python invasion. When used with default settings, MaxEnt overfit the realized climate space, identifying models with about 60 parameters, about five times the number of parameters justifiable when optimized on the basis of Akaike's Information Criterion. When used with default settings, MaxEnt may not be an appropriate vehicle for identifying all sites at risk of colonization. Model instability and dearth of protections against overfitting, multi-collinearity, and data dredging may combine with a failure to distinguish fundamental from realized climate envelopes to produce models of limited utility. A priori identification of biologically realistic model structure, combined with computational protections against these statistical problems, may produce more robust models of invasion risk.

  16. The indications and donor-site morbidity of tibial cortical strut autografts in the management of defects in long bones.

    Science.gov (United States)

    Lauthe, O; Soubeyrand, M; Babinet, A; Dumaine, V; Anract, P; Biau, D J

    2018-05-01

    Aims The primary aim of this study was to determine the morbidity of a tibial strut autograft and characterize the rate of bony union following its use. Patients and Methods We retrospectively assessed a series of 104 patients from a single centre who were treated with a tibial strut autograft of > 5 cm in length. A total of 30 had a segmental reconstruction with continuity of bone, 27 had a segmental reconstruction without continuity of bone, 29 had an arthrodesis and 18 had a nonunion. Donor-site morbidity was defined as any event that required a modification of the postoperative management. Union was assessed clinically and radiologically at a median of 36 months (IQR, 14 to 74). Results Donor-site morbidity occurred in four patients (4%; 95% confidence interval (CI) 1 to 10). One patient had a stress fracture of the tibia, which healed with a varus deformity, requiring an osteotomy. Two patients required evacuation of a haematoma and one developed anterior compartment syndrome which required fasciotomies. The cumulative probability of union was 90% (95% CI 80 to 96) at five years. The type of reconstruction (p = 0.018), continuity of bone (p = 0.006) and length of tibial graft (p = 0.037) were associated with the time to union. Conclusion The tibial strut autograft has a low risk of morbidity and provides adequate bone stock for treating various defects of long bones. Cite this article: Bone Joint J 2018;100-B:667-74.

  17. Using questions sent to an Ask-A-Scientist site to identify children's interests in science

    Science.gov (United States)

    Baram-Tsabari, Ayelet; Sethi, Ricky J.; Bry, Lynn; Yarden, Anat

    2006-11-01

    Interest is a powerful motivator; nonetheless, science educators often lack the necessary information to make use of the power of student-specific interests in the reform process of science curricula. This study suggests a novel methodology, which might be helpful in identifying such interests - using children's self-generated questions as an indication of their scientific interests. In this research, children's interests were measured by analyzing 1555 science-related questions submitted to an international Ask-A-Scientist Internet site. The analysis indicated that the popularity of certain topics varies with age and gender. Significant differences were found between children's spontaneous (intrinsically motivated) and school-related (extrinsically motivated) interests. Surprisingly, girls contributed most of the questions to the sample; however, the number of American girls dropped upon entering senior high school. We also found significant differences between girls' and boys' interests, with girls generally preferring biological topics. The two genders kept to their stereotypic fields of interest, in both their school-related and spontaneous questions. Children's science interests, as inferred from questions to Web sites, could ultimately inform classroom science teaching. This methodology extends the context in which children's interests can be investigated.

  18. Identifying malaria hotspots in Keur Soce health and demographic surveillance site in context of low transmission.

    Science.gov (United States)

    Ndiath, Mansour; Faye, Babacar; Cisse, Badara; Ndiaye, Jean Louis; Gomis, Jules François; Dia, Anta Tal; Gaye, Oumar

    2014-11-24

    Malaria is major public health problem in Senegal. In some parts of the country, it occurs almost permanently with a seasonal increase during the rainy season. There is evidence to suggest that the prevalence of malaria in Senegal has decreased considerably during the past few years. Recent data from the Senegalese National Malaria Control Programme (NMCP) indicates that the number of malaria cases decrease from 1,500,000 in 2006 to 174,339 in 2010. With the decline of malaria morbidity in Senegal, the characterization of the new epidemiological profile of this disease is crucial for public health decision makers. SaTScan™ software using the Kulldorf method of retrospective space-time permutation and the Bernoulli purely spatial model was used to identify malaria clusters using confirmed malaria cases in 74 villages. ArcMAp was used to map malaria hotspots. Logistic regression was used to investigate risk factors for malaria hotspots in Keur Soce health and demographic surveillance site. A total of 1,614 individuals in 440 randomly selected households were enrolled. The overall malaria prevalence was 12%. The malaria prevalence during the study period varied from less than 2% to more than 25% from one village to another. The results showed also that rooms located between 50 m to 100 m away from livestock holding place [adjusted O.R = 0.7, P = 0.044, 95% C.I (1.02 - 7.42)], bed net use [adjusted O.R = 1.2, P = 0.024, 95% C.I (1.02 -1.48)], are good predictors for malaria hotspots in the Keur Soce health and demographic surveillance site. The socio economic status of the household also predicted on hotspots patterns. The less poor household are 30% less likely to be classified as malaria hotspots area compared to the poorest household [adjusted O.R = 0.7, P = 0.014, 95% C.I (0.47 - 0.91)]. The study investigated risk factors for malaria hotspots in small communities in the Keur Soce site. The result showed considerable variation of malaria

  19. Identifying functional transcription factor binding sites in yeast by considering their positional preference in the promoters.

    Directory of Open Access Journals (Sweden)

    Fu-Jou Lai

    Full Text Available Transcription factor binding site (TFBS identification plays an important role in deciphering gene regulatory codes. With comprehensive knowledge of TFBSs, one can understand molecular mechanisms of gene regulation. In the recent decades, various computational approaches have been proposed to predict TFBSs in the genome. The TFBS dataset of a TF generated by each algorithm is a ranked list of predicted TFBSs of that TF, where top ranked TFBSs are statistically significant ones. However, whether these statistically significant TFBSs are functional (i.e. biologically relevant is still unknown. Here we develop a post-processor, called the functional propensity calculator (FPC, to assign a functional propensity to each TFBS in the existing computationally predicted TFBS datasets. It is known that functional TFBSs reveal strong positional preference towards the transcriptional start site (TSS. This motivates us to take TFBS position relative to the TSS as the key idea in building our FPC. Based on our calculated functional propensities, the TFBSs of a TF in the original TFBS dataset could be reordered, where top ranked TFBSs are now the ones with high functional propensities. To validate the biological significance of our results, we perform three published statistical tests to assess the enrichment of Gene Ontology (GO terms, the enrichment of physical protein-protein interactions, and the tendency of being co-expressed. The top ranked TFBSs in our reordered TFBS dataset outperform the top ranked TFBSs in the original TFBS dataset, justifying the effectiveness of our post-processor in extracting functional TFBSs from the original TFBS dataset. More importantly, assigning functional propensities to putative TFBSs enables biologists to easily identify which TFBSs in the promoter of interest are likely to be biologically relevant and are good candidates to do further detailed experimental investigation. The FPC is implemented as a web tool at http://santiago.ee.ncku.edu.tw/FPC/.

  20. A spatial modeling approach to identify potential butternut restoration sites in Mammoth Cave National Park

    Science.gov (United States)

    Thompson, L.M.; Van Manen, F.T.; Schlarbaum, S.E.; DePoy, M.

    2006-01-01

    Incorporation of disease resistance is nearly complete for several important North American hardwood species threatened by exotic fungal diseases. The next important step toward species restoration would be to develop reliable tools to delineate ideal restoration sites on a landscape scale. We integrated spatial modeling and remote sensing techniques to delineate potential restoration sites for Butternut (Juglans cinerea L.) trees, a hardwood species being decimated by an exotic fungus, in Mammoth Cave National Park (MCNP), Kentucky. We first developed a multivariate habitat model to determine optimum Butternut habitats within MCNP. Habitat characteristics of 54 known Butternut locations were used in combination with eight topographic and land use data layers to calculate an index of habitat suitability based on Mahalanobis distance (D2). We used a bootstrapping technique to test the reliability of model predictions. Based on a threshold value for the D2 statistic, 75.9% of the Butternut locations were correctly classified, indicating that the habitat model performed well. Because Butternut seedlings require extensive amounts of sunlight to become established, we used canopy cover data to refine our delineation of favorable areas for Butternut restoration. Areas with the most favorable conditions to establish Butternut seedlings were limited to 291.6 ha. Our study provides a useful reference on the amount and location of favorable Butternut habitat in MCNP and can be used to identify priority areas for future Butternut restoration. Given the availability of relevant habitat layers and accurate location records, our approach can be applied to other tree species and areas. ?? 2006 Society for Ecological Restoration International.

  1. Rigorous Screening Technology for Identifying Suitable CO2 Storage Sites II

    Energy Technology Data Exchange (ETDEWEB)

    George J. Koperna Jr.; Vello A. Kuuskraa; David E. Riestenberg; Aiysha Sultana; Tyler Van Leeuwen

    2009-06-01

    This report serves as the final technical report and users manual for the 'Rigorous Screening Technology for Identifying Suitable CO2 Storage Sites II SBIR project. Advanced Resources International has developed a screening tool by which users can technically screen, assess the storage capacity and quantify the costs of CO2 storage in four types of CO2 storage reservoirs. These include CO2-enhanced oil recovery reservoirs, depleted oil and gas fields (non-enhanced oil recovery candidates), deep coal seems that are amenable to CO2-enhanced methane recovery, and saline reservoirs. The screening function assessed whether the reservoir could likely serve as a safe, long-term CO2 storage reservoir. The storage capacity assessment uses rigorous reservoir simulation models to determine the timing, ultimate storage capacity, and potential for enhanced hydrocarbon recovery. Finally, the economic assessment function determines both the field-level and pipeline (transportation) costs for CO2 sequestration in a given reservoir. The screening tool has been peer reviewed at an Electrical Power Research Institute (EPRI) technical meeting in March 2009. A number of useful observations and recommendations emerged from the Workshop on the costs of CO2 transport and storage that could be readily incorporated into a commercial version of the Screening Tool in a Phase III SBIR.

  2. Dipeptide frequency/bias analysis identifies conserved sites of nonrandomness shared by cysteine-rich motifs.

    Science.gov (United States)

    Campion, S R; Ameen, A S; Lai, L; King, J M; Munzenmaier, T N

    2001-08-15

    This report describes the application of a simple computational tool, AAPAIR.TAB, for the systematic analysis of the cysteine-rich EGF, Sushi, and Laminin motif/sequence families at the two-amino acid level. Automated dipeptide frequency/bias analysis detects preferences in the distribution of amino acids in established protein families, by determining which "ordered dipeptides" occur most frequently in comprehensive motif-specific sequence data sets. Graphic display of the dipeptide frequency/bias data revealed family-specific preferences for certain dipeptides, but more importantly detected a shared preference for employment of the ordered dipeptides Gly-Tyr (GY) and Gly-Phe (GF) in all three protein families. The dipeptide Asn-Gly (NG) also exhibited high-frequency and bias in the EGF and Sushi motif families, whereas Asn-Thr (NT) was distinguished in the Laminin family. Evaluation of the distribution of dipeptides identified by frequency/bias analysis subsequently revealed the highly restricted localization of the G(F/Y) and N(G/T) sequence elements at two separate sites of extreme conservation in the consensus sequence of all three sequence families. The similar employment of the high-frequency/bias dipeptides in three distinct protein sequence families was further correlated with the concurrence of these shared molecular determinants at similar positions within the distinctive scaffolds of three structurally divergent, but similarly employed, motif modules.

  3. Provocative Endoscopy to Identify Bleeding Site in Upper Gastrointestinal Bleeding: A Novel Approach in Transarterial Embolization.

    Science.gov (United States)

    Kamo, Minobu; Fuwa, Sokun; Fukuda, Katsuyuki; Fujita, Yoshiyuki; Kurihara, Yasuyuki

    2016-07-01

    This report describes a novel approach to endoscopically induce bleeding by removing a clot from the bleeding site during angiography for upper gastrointestinal (UGI) hemorrhage. This procedure enabled accurate identification of the bleeding site, allowing for successful targeted embolization despite a negative initial angiogram. Provocative endoscopy may be a feasible and useful option for angiography of obscure bleeding sites in patients with UGI arterial hemorrhage. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

  4. Identifying the most productive breeding sites for malaria mosquitoes in The Gambia

    NARCIS (Netherlands)

    Fillinger, U.; Sombroek, H.; Majambere, S.; Loon, van E.; Takken, W.; Lindsay, S.W.

    2009-01-01

    Background: Ideally larval control activities should be targeted at sites that generate the most adult vectors, thereby reducing operational costs. Despite the plethora of potential mosquito breeding sites found in the floodplains of the Gambia River, about 150 km from its mouth, during the rainy

  5. Application of Geophysical Techniques in Identifying UNE Signatures at Semipalatinsk Test Site (for OSI Purposes)

    Science.gov (United States)

    Belyashov, A.; Shaitorov, V.; Yefremov, M.

    2014-03-01

    This article describes geological and geophysical studies of an underground nuclear explosion area in one of the boreholes at the Semipalatinsk test site in Kazakhstan. During these studies, the typical elements of mechanical impact of the underground explosion on the host medium—fracturing of rock, spall zones, faults, cracks, etc., were observed. This information supplements to the database of underground nuclear explosion phenomenology and can be applied in fulfilling on-site inspection tasks under the Comprehensive Nuclear-Test-Ban Treaty.

  6. Identifying the Tunneling Site in Strong-Field Ionization of H_{2}^{+}.

    Science.gov (United States)

    Liu, Kunlong; Barth, Ingo

    2017-12-15

    The tunneling site of the electron in a molecule exposed to a strong laser field determines the initial position of the ionizing electron and, as a result, has a large impact on the subsequent ultrafast electron dynamics on the polyatomic Coulomb potential. Here, the tunneling site of the electron of H_{2}^{+} ionized by a strong circularly polarized (CP) laser pulse is studied by numerically solving the time-dependent Schrödinger equation. We show that the electron removed from the down-field site is directly driven away by the CP field and the lateral photoelectron momentum distribution (LPMD) exhibits a Gaussian-like distribution, whereas the corresponding LPMD of the electron removed from the up-field site differs from the Gaussian shape due to the Coulomb focusing and scattering by the down-field core. Our current study presents the direct evidence clarifying a long-standing controversy over the tunneling site in H_{2}^{+} and raises the important role of the tunneling site in strong-field molecular ionization.

  7. Refinement of a Method for Identifying Probable Archaeological Sites from Remotely Sensed Data

    Science.gov (United States)

    Tilton, James C.; Comer, Douglas C.; Priebe, Carey E.; Sussman, Daniel; Chen, Li

    2012-01-01

    To facilitate locating archaeological sites before they are compromised or destroyed, we are developing approaches for generating maps of probable archaeological sites, through detecting subtle anomalies in vegetative cover, soil chemistry, and soil moisture by analyzing remotely sensed data from multiple sources. We previously reported some success in this effort with a statistical analysis of slope, radar, and Ikonos data (including tasseled cap and NDVI transforms) with Student's t-test. We report here on new developments in our work, performing an analysis of 8-band multispectral Worldview-2 data. The Worldview-2 analysis begins by computing medians and median absolute deviations for the pixels in various annuli around each site of interest on the 28 band difference ratios. We then use principle components analysis followed by linear discriminant analysis to train a classifier which assigns a posterior probability that a location is an archaeological site. We tested the procedure using leave-one-out cross validation with a second leave-one-out step to choose parameters on a 9,859x23,000 subset of the WorldView-2 data over the western portion of Ft. Irwin, CA, USA. We used 100 known non-sites and trained one classifier for lithic sites (n=33) and one classifier for habitation sites (n=16). We then analyzed convex combinations of scores from the Archaeological Predictive Model (APM) and our scores. We found that that the combined scores had a higher area under the ROC curve than either individual method, indicating that including WorldView-2 data in analysis improved the predictive power of the provided APM.

  8. Biological data warehousing system for identifying transcriptional regulatory sites from gene expressions of microarray data.

    Science.gov (United States)

    Tsou, Ann-Ping; Sun, Yi-Ming; Liu, Chia-Lin; Huang, Hsien-Da; Horng, Jorng-Tzong; Tsai, Meng-Feng; Liu, Baw-Juine

    2006-07-01

    Identification of transcriptional regulatory sites plays an important role in the investigation of gene regulation. For this propose, we designed and implemented a data warehouse to integrate multiple heterogeneous biological data sources with data types such as text-file, XML, image, MySQL database model, and Oracle database model. The utility of the biological data warehouse in predicting transcriptional regulatory sites of coregulated genes was explored using a synexpression group derived from a microarray study. Both of the binding sites of known transcription factors and predicted over-represented (OR) oligonucleotides were demonstrated for the gene group. The potential biological roles of both known nucleotides and one OR nucleotide were demonstrated using bioassays. Therefore, the results from the wet-lab experiments reinforce the power and utility of the data warehouse as an approach to the genome-wide search for important transcription regulatory elements that are the key to many complex biological systems.

  9. Web-based Tool Identifies and Quantifies Potential Cost Savings Measures at the Hanford Site

    International Nuclear Information System (INIS)

    Renevitz, Marisa J.; Peschong, Jon C.; Charboneau, Briant L.; Simpson, Brett C.

    2014-01-01

    The Technical Improvement system is an approachable web-based tool that is available to Hanford DOE staff, site contractors, and general support service contractors as part of the baseline optimization effort underway at the Hanford Site. Finding and implementing technical improvements are a large part of DOE's cost savings efforts. The Technical Improvement dashboard is a key tool for brainstorming and monitoring the progress of submitted baseline optimization and potential cost/schedule efficiencies. The dashboard is accessible to users over the Hanford Local Area Network (HLAN) and provides a highly visual and straightforward status to management on the ideas provided, alleviating the need for resource intensive weekly and monthly reviews

  10. Superfund TIO videos. Set A. Identifying PRPS. Removal process: Removal site evaluation. Part 2. Audio-Visual

    International Nuclear Information System (INIS)

    1990-01-01

    The videotape is divided into three sections. Section 1 details the liability of Potentially Responsible Parties (PRPs) and describes the four classes of PRPs: current owners and operators, former owners and operators, generators, and transporters (if they selected the site). Section 2 lists the goals of the Potentially Responsible Party (PRP) search and explains how to identify key players during the PRP search. How to plan and conduct the PRP search is also outlined. Section 3 outlines the steps involved in conducting a removal site evaluation. A discussion of when to conduct a removal preliminary assessment, a removal site inspection, and an Engineering Evaluation/Cost Analysis (EE/AC) also is covered

  11. Enhanced down regulation of cortical ±-propranolol sensitive [3H]-DHA binding sites by co-administration of DMI and 5-HT1A partial agonist gepirone

    International Nuclear Information System (INIS)

    Geissler, M.A.; Yocca, F.D.

    1990-01-01

    The putative interrelationship between the noradrenergic and serotonergic systems has been supported by numerous studies. Recently, Dudley et al. (1989) demonstrated significant down regulation of cortical β-adrenergic receptors by co-administration of desipramine (DMI), a norepinephrine uptake inhibitor, and the full 5-HT 1A agonist 8-OH-DPAT. To this end, the effects of acute and chronic (4 and 14 day) administration of DMI, gepirone, a selective 5-HT 1A post-synaptic partial agonist, as well as a combination of the two, on cortical (±)-propranolol sensitive [ 3 H]-DHA binding sites were examined in rats. Down regulation was apparent after 4 and 14 day treatment with DMI. However, this was not the case with gepirone. Of particular importance is the demonstration of a greater magnitude of down regulation with co-administration of a greater magnitude of down regulation with co-administration of DMI and gepirone. These results suggests that alteration in rat cortical (±)-propranolol sensitive [ 3 H]-DHA binding sites by noradrenergic uptake inhibitors can be further modulated by selective partial agonist activity at central 5-HT 1A postsynaptic receptors. Further data on the co-administration of DMI and BMY 7378 (7,9-dioxo-8-[2-(4-o-methoxyphenylpiperazinyl)ethyl]-8-azaspiro[4,5]decane dihydrochloride), a weak partial agonist at postsynaptic 5-HT 1A receptors, are also presented

  12. FANCD2 binding identifies conserved fragile sites at large transcribed genes in avian cells

    DEFF Research Database (Denmark)

    Pentzold, Constanze; Shah, Shiraz Ali; Hansen, Niels Richard

    2018-01-01

    Common Chromosomal Fragile Sites (CFSs) are specific genomic regions prone to form breaks on metaphase chromosomes in response to replication stress. Moreover, CFSs are mutational hotspots in cancer genomes, showing that the mutational mechanisms that operate at CFSs are highly active in cancer c...

  13. Ligand-bound Structures and Site-directed Mutagenesis Identify the Acceptor and Secondary Binding Sites of Streptomyces coelicolor Maltosyltransferase GlgE*

    Science.gov (United States)

    Syson, Karl; Stevenson, Clare E. M.; Miah, Farzana; Barclay, J. Elaine; Tang, Minhong; Gorelik, Andrii; Rashid, Abdul M.; Lawson, David M.; Bornemann, Stephen

    2016-01-01

    GlgE is a maltosyltransferase involved in α-glucan biosynthesis in bacteria that has been genetically validated as a target for tuberculosis therapies. Crystals of the Mycobacterium tuberculosis enzyme diffract at low resolution so most structural studies have been with the very similar Streptomyces coelicolor GlgE isoform 1. Although the donor binding site for α-maltose 1-phosphate had been previously structurally defined, the acceptor site had not. Using mutagenesis, kinetics, and protein crystallography of the S. coelicolor enzyme, we have now identified the +1 to +6 subsites of the acceptor/product, which overlap with the known cyclodextrin binding site. The sugar residues in the acceptor subsites +1 to +5 are oriented such that they disfavor the binding of malto-oligosaccharides that bear branches at their 6-positions, consistent with the known acceptor chain specificity of GlgE. A secondary binding site remote from the catalytic center was identified that is distinct from one reported for the M. tuberculosis enzyme. This new site is capable of binding a branched α-glucan and is most likely involved in guiding acceptors toward the donor site because its disruption kinetically compromises the ability of GlgE to extend polymeric substrates. However, disruption of this site, which is conserved in the Streptomyces venezuelae GlgE enzyme, did not affect the growth of S. venezuelae or the structure of the polymeric product. The acceptor subsites +1 to +4 in the S. coelicolor enzyme are well conserved in the M. tuberculosis enzyme so their identification could help inform the design of inhibitors with therapeutic potential. PMID:27531751

  14. Neuropeptide Y binding sites in rat brain identified with purified neuropeptide Y-I125

    International Nuclear Information System (INIS)

    Walker, M.W.; Miller, R.J.

    1986-01-01

    Neuropeptide Y (NPY) is a widely distributed neuronally localized peptide with 36 amino acids, 5 of which are tyrosines. The authors wished to investigate the properties of specific receptors for NPY. They therefore labeled the tyrosines with I125 using chloramine T and then purified the peptide using HPLC. A single mono-iodinated species of NPY which yielded > 85% specific binding in rat forebrain synaptosomes was selected as the ligand for all subsequent experiments. A time course of binding showed that equilibrium conditions were reached in 60 minutes at 21 0 C. Scatchard plots revealed a single class of binding sites with a Kd and a Bmax of 3 x 10-10 M and 28 pmol/mg, respectively. Competition binding with unlabeled NPY showed 50% displacement of bound ligand at 1 x 10-10 M NPY. Competition binding with rat pancreatic polypeptide (RPP), a homologous peptide possessing little NPY-like activity, showed 50% displacement of bound ligand at 2 x 10 -7 M RPP. No binding was observed on F-11 or PC12 neuronal cell lines, or on HSWP fibroblast cells. They conclude that NPY-I125 purified to homogeneity with HPLC is a highly selective ligand for NPY receptor sites. They are currently investigating such sites in brain, gut, and other tissues

  15. Guide for Identifying and Converting High-Potential Petroleum Brownfield Sites to Alternative Fuel Stations

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, C.; Hettinger, D.; Mosey, G.

    2011-05-01

    Former gasoline stations that are now classified as brownfields can be good sites to sell alternative fuels because they are in locations that are convenient to vehicles and they may be seeking a new source of income. However, their success as alternative fueling stations is highly dependent on location-specific criteria. First, this report outlines what these criteria are, how to prioritize them, and then applies that assessment framework to five of the most popular alternative fuels--electricity, natural gas, hydrogen, ethanol, and biodiesel. The second part of this report delves into the criteria and tools used to assess an alternative fuel retail site at the local level. It does this through two case studies of converting former gasoline stations in the Seattle-Eugene area into electric charge stations. The third part of this report addresses steps to be taken after the specific site has been selected. This includes choosing and installing the recharging equipment, which includes steps to take in the permitting process and key players to include.

  16. Calcium-dependent depletion zones in the cortical microtubule array coincide with sites of, but do not regulate, wall ingrowth papillae deposition in epidermal transfer cells

    Science.gov (United States)

    Zhang, Hui-ming; Talbot, Mark J.; McCurdy, David W.; Patrick, John W.; Offler, Christina E.

    2015-01-01

    Trans-differentiation to a transfer-cell morphology is characterized by the localized deposition of wall ingrowth papillae that protrude into the cytosol. Whether the cortical microtubule array directs wall ingrowth papillae formation was investigated using a Vicia faba cotyledon culture system in which their adaxial epidermal cells were spontaneously induced to trans-differentiate to transfer cells. During deposition of wall ingrowth papillae, the aligned cortical microtubule arrays in precursor epidermal cells were reorganized into a randomized array characterized by circular depletion zones. Concurrence of the temporal appearance, spatial pattern, and size of depletion zones and wall ingrowth papillae was consistent with each papilla occupying a depletion zone. Surprisingly, microtubules appeared not to regulate construction of wall ingrowth papillae, as neither depolymerization nor stabilization of cortical microtubules changed their deposition pattern or morphology. Moreover, the size and spatial pattern of depletion zones was unaltered when the formation of wall ingrowth papillae was blocked by inhibiting cellulose biosynthesis. In contrast, the depletion zones were absent when the cytosolic calcium plumes, responsible for directing wall ingrowth papillae formation, were blocked or dissipated. Thus, we conclude that the depletion zones within the cortical microtubule array result from localized depolymerization of microtubules initiated by elevated cytosolic Ca2+ levels at loci where wall ingrowth papillae are deposited. The physiological significance of the depletion zones as a mechanism to accommodate the construction of wall ingrowth papillae without compromising maintenance of the plasma membrane–microtubule inter-relationship is discussed. PMID:26136268

  17. Gradient temperature Raman spectroscopy identifies flexible sites in proline and alanine peptides

    Science.gov (United States)

    Continuous thermo dynamic Raman spectroscopy (TDRS) applies the temperature gradients utilized in differential scanning calorimetry (DSC) to Raman spectroscopy, providing a straightforward technique to identify molecular rearrangements that occur just prior to phase transitions. Herein we apply TDRS...

  18. COSMID: A Web-based Tool for Identifying and Validating CRISPR/Cas Off-target Sites

    Directory of Open Access Journals (Sweden)

    Thomas J Cradick

    2014-01-01

    Full Text Available Precise genome editing using engineered nucleases can significantly facilitate biological studies and disease treatment. In particular, clustered regularly interspaced short palindromic repeats (CRISPR with CRISPR-associated (Cas proteins are a potentially powerful tool for modifying a genome by targeted cleavage of DNA sequences complementary to designed guide strand RNAs. Although CRISPR/Cas systems can have on-target cleavage rates close to the transfection rates, they may also have relatively high off-target cleavage at similar genomic sites that contain one or more base pair mismatches, and insertions or deletions relative to the guide strand. We have developed a bioinformatics-based tool, COSMID (CRISPR Off-target Sites with Mismatches, Insertions, and Deletions that searches genomes for potential off-target sites (http://crispr.bme.gatech.edu. Based on the user-supplied guide strand and input parameters, COSMID identifies potential off-target sites with the specified number of mismatched bases and insertions or deletions when compared with the guide strand. For each site, amplification primers optimal for the chosen application are also given as output. This ranked-list of potential off-target sites assists the choice and evaluation of intended target sites, thus helping the design of CRISPR/Cas systems with minimal off-target effects, as well as the identification and quantification of CRISPR/Cas induced off-target cleavage in cells.

  19. A preliminary guidebook for identifying stratigraphic contacts at the Nevada Test Site

    International Nuclear Information System (INIS)

    Pawloski, G.A.; McKague, H.L.; Wagoner, J.L.; McKinnis, W.B.

    1992-01-01

    Lithologic variation, regional depositional trends, and the lack of written guidelines have resulted in inconsistencies in the recognition of stratigraphic contacts in drill holes at the Nevada Test Site (NTS). Stratigraphic identification, based on mineralogy of discrete samples, can be augmented by geophysical logs and downhole movies to more accurately and consistently locate contacts between units. Criteria are established for locating the base of the Pahute Mesa ash-flow tuff, the top of the Ammonia Tanks ash-flow tuff, the top of the Ammonia Tanks bedded tuff, and the top and the base of the Rainier Mesa Tuff

  20. A Study Identifying Causes of Construction Waste Production and Applying Safety Management on Construction Site

    Directory of Open Access Journals (Sweden)

    Ali Asghar Najafpoor

    2014-09-01

    Full Text Available Background and purpose: In a recent century, the amount of construction waste has increased significantly. Although the building industry has a considerable role in the development of a society, it is regarded as an environmentally destructive. Source reduction is the highest goal in the waste management hierarchy and is in priority. It also has economic benefits by reducing costs associated with transportation, disposal or recycling of wastes. The present study is aimed to identify activities generating the wastes in design, transportation and storage and procurement of building materials. Materials and Methods: This was questionnaire survey. A total of 94 professionals in the construction industry were attended in this study. To determine the validity and reliability of the instrument, content validity method and Cronbach’s alpha coefficient (0.79 were used. Data were analyzed using SPSS for Windows. Frequencies, percentage, mean and standard deviation were determined in this research. Results: The results showed that handling and storage have been chosen as the most causative factor of waste production in construction activity. Improper material storage was identified major factor in producing waste in handling and storage phase. Usage of low-quality material in design stage and material price changes in procurement were recognized as major causes of waste production in these stages. Conclusion: All studied phases in this research were identified as causative factors in producing of waste. Identifying causes of construction waste production will help us decide better how to control this sort of wastes.

  1. Calcium-dependent depletion zones in the cortical microtubule array coincide with sites of, but do not regulate, wall ingrowth papillae deposition in epidermal transfer cells.

    Science.gov (United States)

    Zhang, Hui-ming; Talbot, Mark J; McCurdy, David W; Patrick, John W; Offler, Christina E

    2015-09-01

    Trans-differentiation to a transfer-cell morphology is characterized by the localized deposition of wall ingrowth papillae that protrude into the cytosol. Whether the cortical microtubule array directs wall ingrowth papillae formation was investigated using a Vicia faba cotyledon culture system in which their adaxial epidermal cells were spontaneously induced to trans-differentiate to transfer cells. During deposition of wall ingrowth papillae, the aligned cortical microtubule arrays in precursor epidermal cells were reorganized into a randomized array characterized by circular depletion zones. Concurrence of the temporal appearance, spatial pattern, and size of depletion zones and wall ingrowth papillae was consistent with each papilla occupying a depletion zone. Surprisingly, microtubules appeared not to regulate construction of wall ingrowth papillae, as neither depolymerization nor stabilization of cortical microtubules changed their deposition pattern or morphology. Moreover, the size and spatial pattern of depletion zones was unaltered when the formation of wall ingrowth papillae was blocked by inhibiting cellulose biosynthesis. In contrast, the depletion zones were absent when the cytosolic calcium plumes, responsible for directing wall ingrowth papillae formation, were blocked or dissipated. Thus, we conclude that the depletion zones within the cortical microtubule array result from localized depolymerization of microtubules initiated by elevated cytosolic Ca(2+) levels at loci where wall ingrowth papillae are deposited. The physiological significance of the depletion zones as a mechanism to accommodate the construction of wall ingrowth papillae without compromising maintenance of the plasma membrane-microtubule inter-relationship is discussed. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  2. Identifying opportune landing sites in degraded visual environments with terrain and cultural databases

    Science.gov (United States)

    Moody, Marc; Fisher, Robert; Little, J. Kristin

    2014-06-01

    Boeing has developed a degraded visual environment navigational aid that is flying on the Boeing AH-6 light attack helicopter. The navigational aid is a two dimensional software digital map underlay generated by the Boeing™ Geospatial Embedded Mapping Software (GEMS) and fully integrated with the operational flight program. The page format on the aircraft's multi function displays (MFD) is termed the Approach page. The existing work utilizes Digital Terrain Elevation Data (DTED) and OpenGL ES 2.0 graphics capabilities to compute the pertinent graphics underlay entirely on the graphics processor unit (GPU) within the AH-6 mission computer. The next release will incorporate cultural databases containing Digital Vertical Obstructions (DVO) to warn the crew of towers, buildings, and power lines when choosing an opportune landing site. Future IRAD will include Light Detection and Ranging (LIDAR) point cloud generating sensors to provide 2D and 3D synthetic vision on the final approach to the landing zone. Collision detection with respect to terrain, cultural, and point cloud datasets may be used to further augment the crew warning system. The techniques for creating the digital map underlay leverage the GPU almost entirely, making this solution viable on most embedded mission computing systems with an OpenGL ES 2.0 capable GPU. This paper focuses on the AH-6 crew interface process for determining a landing zone and flying the aircraft to it.

  3. A bioinformatics approach for identifying transgene insertion sites using whole genome sequencing data.

    Science.gov (United States)

    Park, Doori; Park, Su-Hyun; Ban, Yong Wook; Kim, Youn Shic; Park, Kyoung-Cheul; Kim, Nam-Soo; Kim, Ju-Kon; Choi, Ik-Young

    2017-08-15

    Genetically modified crops (GM crops) have been developed to improve the agricultural traits of modern crop cultivars. Safety assessments of GM crops are of paramount importance in research at developmental stages and before releasing transgenic plants into the marketplace. Sequencing technology is developing rapidly, with higher output and labor efficiencies, and will eventually replace existing methods for the molecular characterization of genetically modified organisms. To detect the transgenic insertion locations in the three GM rice gnomes, Illumina sequencing reads are mapped and classified to the rice genome and plasmid sequence. The both mapped reads are classified to characterize the junction site between plant and transgene sequence by sequence alignment. Herein, we present a next generation sequencing (NGS)-based molecular characterization method, using transgenic rice plants SNU-Bt9-5, SNU-Bt9-30, and SNU-Bt9-109. Specifically, using bioinformatics tools, we detected the precise insertion locations and copy numbers of transfer DNA, genetic rearrangements, and the absence of backbone sequences, which were equivalent to results obtained from Southern blot analyses. NGS methods have been suggested as an effective means of characterizing and detecting transgenic insertion locations in genomes. Our results demonstrate the use of a combination of NGS technology and bioinformatics approaches that offers cost- and time-effective methods for assessing the safety of transgenic plants.

  4. Cortical plasticity as a new endpoint measurement for chronic pain

    Directory of Open Access Journals (Sweden)

    Zhuo Min

    2011-07-01

    Full Text Available Abstract Animal models of chronic pain are widely used to investigate basic mechanisms of chronic pain and to evaluate potential novel drugs for treating chronic pain. Among the different criteria used to measure chronic pain, behavioral responses are commonly used as the end point measurements. However, not all chronic pain conditions can be easily measured by behavioral responses such as the headache, phantom pain and pain related to spinal cord injury. Here I propose that cortical indexes, that indicate neuronal plastic changes in pain-related cortical areas, can be used as endpoint measurements for chronic pain. Such cortical indexes are not only useful for those chronic pain conditions where a suitable animal model is lacking, but also serve as additional screening methods for potential drugs to treat chronic pain in humans. These cortical indexes are activity-dependent immediate early genes, electrophysiological identified plastic changes and biochemical assays of signaling proteins. It can be used to evaluate novel analgesic compounds that may act at peripheral or spinal sites. I hope that these new cortical endpoint measurements will facilitate our search for new, and more effective, pain medicines, and help to reduce false lead drug targets.

  5. Mesoscale Biotransformations of Uranium: Identifying Sites and Strategies where Reductive Immobilization is Practical

    International Nuclear Information System (INIS)

    Tetsu K. Tokunaga; Jiamin Wan; Terry C. Hazen; Mary K. Firestone; Eoin Brodie; Yongman Kim; Rebecca Daly

    2006-01-01

    Bioreduction of U in contaminated sediments is an attractive strategy because of its low cost, and because of short-term studies supporting its feasibility. However, any in-situ immobilization approach for U will require assurance of either permanent fixation, or of very low release rates into the biosphere. Our previous long-term (2 years) laboratory experiments have shown that organic carbon (OC) based U(VI) bioreduction to UO2 can be transient even under sustained reducing (methanogenic) conditions. The biogeochemical processes underlying this finding urgently need to be understood. The current research is designed to identify mechanisms responsible for anaerobic U oxidation, and identify conditions that will support long-term stability of bioreduced U. We are investigating: (1) effects of OC concentration and supply rate on remobilization of bioreduced U, (2) the roles of Fe- and Mn-oxides as potential U oxidants in sediments, and (3) the role of microorganisms in U reoxidation, and (4) influences of pH on U(IV)/U(VI) redox equilibrium

  6. FIGIFIGO as a tool to characterize and identify planetary analogue sites

    Science.gov (United States)

    Gritsevich, M.; Peltoniemi, J.; Hakala, T.; Muinonen, K.

    2014-07-01

    We present an overview of the Finnish Geodetic Institute's field goniospectrometer (FIGIFIGO) and highlight its usability to study extraterrestrial analogues on the Earth. The design concept of this custom-made instrument has been proved to have a number of advantages, such as a well-adopted user-friendly interface, a high level of automation, and excellent suitability for field measurements within a wide range of weather conditions. It is perfect for collection of reference data on a given target in natural undisturbed (and well-recorded for further data interpretation) conditions. The instrument communicates via a controlled computer with an implemented simple and user-friendly interface. This allows users to easily set up optional parameters at the beginning of the measurement series. Thus a number of details may be modified, such as the initial position of the sensor, the range and speed of further automated zenith turns, and length of the turnable arm holding the selected optics (including an option for a computer-turned linear polarizer) above the target. The assembly and operation of the instrument are fast and efficient in both laboratory and field conditions. It is battery powered and easily portable, including possible transportation by plane, car, boat, or sledge. The system includes a sky camera to detect the goniometer orientation and a pyranometer to monitor the actual illumination conditions. A fine-tune mirror is used for spatial correction of the optics footprint. Recent calibration of the system has significantly increased the measurement robustness and data reliability, and has provided the operators with information on how to operate the instrument in the most efficient and accurate way. Measurement campaigns are organized frequently and significant amount of reference data has been already collected. The identification of new planetary analogue sites and characterization of known ones using FIGIFIGO could offer new possibilities and provide

  7. Identifying sites of replication initiation in yeast chromosomes: looking for origins in all the right places.

    Science.gov (United States)

    van Brabant, A J; Hunt, S Y; Fangman, W L; Brewer, B J

    1998-06-01

    DNA fragments that contain an active origin of replication generate bubble-shaped replication intermediates with diverging forks. We describe two methods that use two-dimensional (2-D) agarose gel electrophoresis along with DNA sequence information to identify replication origins in natural and artificial Saccharomyces cerevisiae chromosomes. The first method uses 2-D gels of overlapping DNA fragments to locate an active chromosomal replication origin within a region known to confer autonomous replication on a plasmid. A variant form of 2-D gels can be used to determine the direction of fork movement, and the second method uses this technique to find restriction fragments that are replicated by diverging forks, indicating that a bidirectional replication origin is located between the two fragments. Either of these two methods can be applied to the analysis of any genomic region for which there is DNA sequence information or an adequate restriction map.

  8. Cortical visual impairment

    OpenAIRE

    Koželj, Urša

    2013-01-01

    In this thesis we discuss cortical visual impairment, diagnosis that is in the developed world in first place, since 20 percent of children with blindness or low vision are diagnosed with it. The objectives of the thesis are to define cortical visual impairment and the definition of characters suggestive of the cortical visual impairment as well as to search for causes that affect the growing diagnosis of cortical visual impairment. There are a lot of signs of cortical visual impairment. ...

  9. Focal cortical dysplasia – review

    International Nuclear Information System (INIS)

    Kabat, Joanna; Król, Przemysław

    2012-01-01

    Focal cortical dysplasia is a malformation of cortical development, which is the most common cause of medically refractory epilepsy in the pediatric population and the second/third most common etiology of medically intractable seizures in adults. Both genetic and acquired factors are involved in the pathogenesis of cortical dysplasia. Numerous classifications of the complex structural abnormalities of focal cortical dysplasia have been proposed – from Taylor et al. in 1971 to the last modification of Palmini classification made by Blumcke in 2011. In general, three types of cortical dysplasia are recognized. Type I focal cortical dysplasia with mild symptomatic expression and late onset, is more often seen in adults, with changes present in the temporal lobe. Clinical symptoms are more severe in type II of cortical dysplasia usually seen in children. In this type, more extensive changes occur outside the temporal lobe with predilection for the frontal lobes. New type III is one of the above dysplasias with associated another principal lesion as hippocampal sclerosis, tumor, vascular malformation or acquired pathology during early life. Brain MRI imaging shows abnormalities in the majority of type II dysplasias and in only some of type I cortical dysplasias. The most common findings on MRI imaging include: focal cortical thickening or thinning, areas of focal brain atrophy, blurring of the gray-white junction, increased signal on T2- and FLAIR-weighted images in the gray and subcortical white matter often tapering toward the ventricle. On the basis of the MRI findings, it is possible to differentiate between type I and type II cortical dysplasia. A complete resection of the epileptogenic zone is required for seizure-free life. MRI imaging is very helpful to identify those patients who are likely to benefit from surgical treatment in a group of patients with drug-resistant epilepsy. However, in type I cortical dysplasia, MR imaging is often normal, and also in both

  10. Small molecule inhibitors of the LEDGF site of human immunodeficiency virus integrase identified by fragment screening and structure based design.

    Directory of Open Access Journals (Sweden)

    Thomas S Peat

    Full Text Available A fragment-based screen against human immunodeficiency virus type 1 (HIV integrase led to a number of compounds that bound to the lens epithelium derived growth factor (LEDGF binding site of the integrase catalytic core domain. We determined the crystallographic structures of complexes of the HIV integrase catalytic core domain for 10 of these compounds and quantitated the binding by surface plasmon resonance. We demonstrate that the compounds inhibit the interaction of LEDGF with HIV integrase in a proximity AlphaScreen assay, an assay for the LEDGF enhancement of HIV integrase strand transfer and in a cell based assay. The compounds identified represent a potential framework for the development of a new series of HIV integrase inhibitors that do not bind to the catalytic site of the enzyme.

  11. GIS and Multi Criteria Decision Method Based Approach of Identifying Appropriate Landfill Sites for the City Of Chittagong

    Directory of Open Access Journals (Sweden)

    M. Ali Ashraf

    2015-02-01

    were identified initially. Out of these sites four were found to be most appropriate and suitable for use as landfill. DOI: http://dx.doi.org/10.3126/ije.v4i1.12174International Journal of Environment Volume-4, Issue-1, Dec-Feb 2014/15, page: 1-15  

  12. Using the Textpresso Site-Specific Recombinases Web server to identify Cre expressing mouse strains and floxed alleles.

    Science.gov (United States)

    Condie, Brian G; Urbanski, William M

    2014-01-01

    Effective tools for searching the biomedical literature are essential for identifying reagents or mouse strains as well as for effective experimental design and informed interpretation of experimental results. We have built the Textpresso Site Specific Recombinases (Textpresso SSR) Web server to enable researchers who use mice to perform in-depth searches of a rapidly growing and complex part of the mouse literature. Our Textpresso Web server provides an interface for searching the full text of most of the peer-reviewed publications that report the characterization or use of mouse strains that express Cre or Flp recombinase. The database also contains most of the publications that describe the characterization or analysis of strains carrying conditional alleles or transgenes that can be inactivated or activated by site-specific recombinases such as Cre or Flp. Textpresso SSR complements the existing online databases that catalog Cre and Flp expression patterns by providing a unique online interface for the in-depth text mining of the site specific recombinase literature.

  13. Cortical Visual Impairment

    Science.gov (United States)

    ... resolves by one year of life. Is “cortical blindness” the same thing as CVI? Cortical blindness is ... What visual characteristics are associated with CVI? • Distinct color preferences • Variable level of vision loss, often demonstrating ...

  14. Using transcranial magnetic stimulation of the undamaged brain to identify lesion sites that predict language outcome after stroke.

    Science.gov (United States)

    Lorca-Puls, Diego L; Gajardo-Vidal, Andrea; Seghier, Mohamed L; Leff, Alexander P; Sethi, Varun; Prejawa, Susan; Hope, Thomas M H; Devlin, Joseph T; Price, Cathy J

    2017-06-01

    Transcranial magnetic stimulation focused on either the left anterior supramarginal gyrus or opercular part of the left inferior frontal gyrus has been reported to transiently impair the ability to perform phonological more than semantic tasks. Here we tested whether phonological processing abilities were also impaired following lesions to these regions in right-handed, English speaking adults, who were investigated at least 1 year after a left-hemisphere stroke. When our regions of interest were limited to 0.5 cm3 of grey matter centred around sites that had been identified with transcranial magnetic stimulation-based functional localization, phonological impairments were observed in 74% (40/54) of patients with damage to the regions and 21% (21/100) of patients sparing these regions. This classification accuracy was better than that observed when using regions of interest centred on activation sites in previous functional magnetic resonance imaging studies of phonological processing, or transcranial magnetic stimulation sites that did not use functional localization. New regions of interest were generated by redefining the borders of each of the transcranial magnetic stimulation sites to include areas that were consistently damaged in the patients with phonological impairments. This increased the incidence of phonological impairments in the presence of damage to 85% (46/54) and also reduced the incidence of phonological impairments in the absence of damage to 15% (15/100). The difference in phonological processing abilities between those with and without damage to these 'transcranial magnetic stimulation-guided' regions remained highly significant even after controlling for the effect of lesion size. The classification accuracy of the transcranial magnetic stimulation-guided regions was validated in a second sample of 108 patients and found to be better than that for (i) functional magnetic resonance imaging-guided regions; (ii) a region identified from an

  15. A Prospective Comparison of 18F-FDG PET/CT and CT as Diagnostic Tools to Identify the Primary Tumor Site in Patients with Extracervical Carcinoma of Unknown Primary Site

    DEFF Research Database (Denmark)

    Moller, Anne Kirstine H; Loft, Annika; Berthelsen, Anne K

    2012-01-01

    that the same set of criteria were used for classification of patients, that is, either as CUP patients or patients with a suggested primary tumor site. The independently obtained suggestions of primary tumor sites using PET/CT and CT were correlated with the SR to reach a consensus regarding true-positive (TP......), true-negative, false-negative, and false-positive results.Results. SR identified a primary tumor site in 66 CUP patients (48.9%). PET/CT identified 38 TP primary tumor sites and CT identified 43 TP primary tumor sites. No statistically significant differences were observed between (18)F-FDG PET...

  16. Identifying strategic sites for Green-Infrastructures (GI) to manage stormwater in a miscellaneous use urban African watershed

    Science.gov (United States)

    Selker, J. S.; Kahsai, S. K.

    2017-12-01

    Green Infrastructure (GI) or Low impact development (LID), is a land use planning and design approach with the objective of mitigating land development impacts to the environment, and is ever more looked to as a way to lessen runoff and pollutant loading to receiving water bodies. Broad-scale approaches for siting GI/LID have been developed for agricultural watersheds, but are rare for urban watersheds, largely due to greater land use complexity. And it is even more challenging when it comes to Urban Africa due to the combination of poor data quality, rapid and unplanned development, and civic institutions unable to reliably carry out regular maintenance. We present a spacio-temporal simulation-based approach to identify an optimal prioritization of sites for GI/LID based on DEM, land use and land cover. Optimization used is a multi-objective optimization tool along with an urban storm water management model (SWMM) to identify the most cost-effective combination of LID/GI. This was applied to an urban watershed in NW Kampala, Lubigi Catchment (notorious for being heavily flooded every year), with a miscellaneous use watershed in Uganda, as a case-study to demonstrate the approach.

  17. Genome-wide screens for in vivo Tinman binding sites identify cardiac enhancers with diverse functional architectures.

    Directory of Open Access Journals (Sweden)

    Hong Jin

    Full Text Available The NK homeodomain factor Tinman is a crucial regulator of early mesoderm patterning and, together with the GATA factor Pannier and the Dorsocross T-box factors, serves as one of the key cardiogenic factors during specification and differentiation of heart cells. Although the basic framework of regulatory interactions driving heart development has been worked out, only about a dozen genes involved in heart development have been designated as direct Tinman target genes to date, and detailed information about the functional architectures of their cardiac enhancers is lacking. We have used immunoprecipitation of chromatin (ChIP from embryos at two different stages of early cardiogenesis to obtain a global overview of the sequences bound by Tinman in vivo and their linked genes. Our data from the analysis of ~50 sequences with high Tinman occupancy show that the majority of such sequences act as enhancers in various mesodermal tissues in which Tinman is active. All of the dorsal mesodermal and cardiac enhancers, but not some of the others, require tinman function. The cardiac enhancers feature diverse arrangements of binding motifs for Tinman, Pannier, and Dorsocross. By employing these cardiac and non-cardiac enhancers in machine learning approaches, we identify a novel motif, termed CEE, as a classifier for cardiac enhancers. In vivo assays for the requirement of the binding motifs of Tinman, Pannier, and Dorsocross, as well as the CEE motifs in a set of cardiac enhancers, show that the Tinman sites are essential in all but one of the tested enhancers; although on occasion they can be functionally redundant with Dorsocross sites. The enhancers differ widely with respect to their requirement for Pannier, Dorsocross, and CEE sites, which we ascribe to their different position in the regulatory circuitry, their distinct temporal and spatial activities during cardiogenesis, and functional redundancies among different factor binding sites.

  18. Selection of Inhibitor-Resistant Viral Potassium Channels Identifies a Selectivity Filter Site that Affects Barium and Amantadine Block

    Science.gov (United States)

    Fujiwara, Yuichiro; Arrigoni, Cristina; Domigan, Courtney; Ferrara, Giuseppina; Pantoja, Carlos; Thiel, Gerhard; Moroni, Anna; Minor, Daniel L.

    2009-01-01

    Background Understanding the interactions between ion channels and blockers remains an important goal that has implications for delineating the basic mechanisms of ion channel function and for the discovery and development of ion channel directed drugs. Methodology/Principal Findings We used genetic selection methods to probe the interaction of two ion channel blockers, barium and amantadine, with the miniature viral potassium channel Kcv. Selection for Kcv mutants that were resistant to either blocker identified a mutant bearing multiple changes that was resistant to both. Implementation of a PCR shuffling and backcrossing procedure uncovered that the blocker resistance could be attributed to a single change, T63S, at a position that is likely to form the binding site for the inner ion in the selectivity filter (site 4). A combination of electrophysiological and biochemical assays revealed a distinct difference in the ability of the mutant channel to interact with the blockers. Studies of the analogous mutation in the mammalian inward rectifier Kir2.1 show that the T→S mutation affects barium block as well as the stability of the conductive state. Comparison of the effects of similar barium resistant mutations in Kcv and Kir2.1 shows that neighboring amino acids in the Kcv selectivity filter affect blocker binding. Conclusions/Significance The data support the idea that permeant ions have an integral role in stabilizing potassium channel structure, suggest that both barium and amantadine act at a similar site, and demonstrate how genetic selections can be used to map blocker binding sites and reveal mechanistic features. PMID:19834614

  19. Repeated mapping of cortical language sites by preoperative navigated transcranial magnetic stimulation compared to repeated intraoperative DCS mapping in awake craniotomy

    Science.gov (United States)

    2014-01-01

    Background Repetitive navigated transcranial magnetic stimulation (rTMS) was recently described for mapping of human language areas. However, its capability of detecting language plasticity in brain tumor patients was not proven up to now. Thus, this study was designed to evaluate such data in order to compare rTMS language mapping to language mapping during repeated awake surgery during follow-up in patients suffering from language-eloquent gliomas. Methods Three right-handed patients with left-sided gliomas (2 opercular glioblastomas, 1 astrocytoma WHO grade III of the angular gyrus) underwent preoperative language mapping by rTMS as well as intraoperative language mapping provided via direct cortical stimulation (DCS) for initial as well as for repeated Resection 7, 10, and 15 months later. Results Overall, preoperative rTMS was able to elicit clear language errors in all mappings. A good correlation between initial rTMS and DCS results was observed. As a consequence of brain plasticity, initial DCS and rTMS findings only corresponded with the results obtained during the second examination in one out of three patients thus suggesting changes of language organization in two of our three patients. Conclusions This report points out the usefulness but also the limitations of preoperative rTMS language mapping to detect plastic changes in language function or for long-term follow-up prior to DCS even in recurrent gliomas. However, DCS still has to be regarded as gold standard. PMID:24479694

  20. Prospective detection of cortical dysplasia on clinical MRI in pediatric intractable epilepsy

    Energy Technology Data Exchange (ETDEWEB)

    Radhakrishnan, Rupa; Leach, James L.; Gelfand, Michael J. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Mangano, Francesco T. [Cincinnati Children' s Hospital Medical Center, Department of Neurosurgery, Cincinnati, OH (United States); Rozhkov, Leonid; Greiner, Hansel M. [Cincinnati Children' s Hospital Medical Center, Department of Neurology, Comprehensive Epilepsy Treatment Center, Cincinnati, OH (United States); Miles, Lili [Cincinnati Children' s Hospital Medical Center, Department of Pathology, Cincinnati, OH (United States)

    2016-09-15

    Cortical dysplasia is the most common cause of pediatric refractory epilepsy. MRI detection of epileptogenic lesion is associated with good postsurgical outcome. Additional electrophysiological information is suggested to be helpful in localization of cortical dysplasia. Educational measures were taken to increase the awareness of cortical dysplasia at our institution in the context of a recent International League Against Epilepsy (ILAE 2011) classification of cortical dysplasia. To determine changes in the rate of prospective identification of cortical dysplasia on an initial radiology report and also evaluate the benefit of MRI review as part of a multidisciplinary epilepsy conference in identifying previously overlooked MRI findings. We retrospectively evaluated surgically treated children with refractory epilepsy from 2007 to 2014 with cortical dysplasia on histopathology. We analyzed the initial radiology report, preoperative MRI interpretation at multidisciplinary epilepsy conference and subsequent retrospective MRI review with knowledge of the resection site. We recorded additional electrophysiological data and the presence of lobar concordance with the MRI findings. Of 78 children (44 MRI lesional) evaluated, 18 had initially overlooked MRI findings. Comparing 2007-2010 to 2011-2014, there was improvement in the rate of overlooked findings on the initial radiology report (54% vs. 13% of lesional cases, respectively; P = 0.008). The majority (72%) were identified at a multidisciplinary conference with lobar concordance of findings with at least one additional electrophysiological investigation in 89%. Awareness of current classification schemes of cortical dysplasia and image review in the context of a multidisciplinary conference can lead to improved MRI detection of cortical dysplasia in children. (orig.)

  1. Prospective detection of cortical dysplasia on clinical MRI in pediatric intractable epilepsy

    International Nuclear Information System (INIS)

    Radhakrishnan, Rupa; Leach, James L.; Gelfand, Michael J.; Mangano, Francesco T.; Rozhkov, Leonid; Greiner, Hansel M.; Miles, Lili

    2016-01-01

    Cortical dysplasia is the most common cause of pediatric refractory epilepsy. MRI detection of epileptogenic lesion is associated with good postsurgical outcome. Additional electrophysiological information is suggested to be helpful in localization of cortical dysplasia. Educational measures were taken to increase the awareness of cortical dysplasia at our institution in the context of a recent International League Against Epilepsy (ILAE 2011) classification of cortical dysplasia. To determine changes in the rate of prospective identification of cortical dysplasia on an initial radiology report and also evaluate the benefit of MRI review as part of a multidisciplinary epilepsy conference in identifying previously overlooked MRI findings. We retrospectively evaluated surgically treated children with refractory epilepsy from 2007 to 2014 with cortical dysplasia on histopathology. We analyzed the initial radiology report, preoperative MRI interpretation at multidisciplinary epilepsy conference and subsequent retrospective MRI review with knowledge of the resection site. We recorded additional electrophysiological data and the presence of lobar concordance with the MRI findings. Of 78 children (44 MRI lesional) evaluated, 18 had initially overlooked MRI findings. Comparing 2007-2010 to 2011-2014, there was improvement in the rate of overlooked findings on the initial radiology report (54% vs. 13% of lesional cases, respectively; P = 0.008). The majority (72%) were identified at a multidisciplinary conference with lobar concordance of findings with at least one additional electrophysiological investigation in 89%. Awareness of current classification schemes of cortical dysplasia and image review in the context of a multidisciplinary conference can lead to improved MRI detection of cortical dysplasia in children. (orig.)

  2. A GIS-based approach for identifying potential runoff harvesting sites in the Thukela River basin, South Africa

    Science.gov (United States)

    de Winnaar, G.; Jewitt, G. P. W.; Horan, M.

    Water scarce countries such as South Africa are subject to various hydrological constraints which can often be attributed to poor rainfall partitioning, particularly within resource poor farming communities that are reliant on rainfed agriculture. Recent initiatives to address this have shifted focus to explore more efficient alternatives to water supply and the recognition of numerous opportunities to implement runoff harvesting as a means to supplement water availability. However, increasing the implementation of runoff harvesting, without encountering unintended impacts on downstream hydrological and ecological systems, requires better understanding of the hydrologic and environmental impacts at catchment scale. In this paper the representation of spatial variations in landscape characteristics such as soil, land use, rainfall and slope information is shown to be an important step in identifying potential runoff harvesting sites, after which modelling the hydrological response in catchments where extensive runoff harvesting is being considered can be performed and likely impacts assessed. Geographic information systems (GIS) was utilised as an integrating tool to store, analyse and manage spatial information and when linked to hydrological response models, provided a rational means to facilitate decision making by providing catchment level identification, planning and assessment of runoff harvesting sites as illustrated by a case study at the Potshini catchment, a small sub-catchment in the Thukela River basin, South Africa. Through the linked GIS, potential runoff harvesting sites are identified relative to areas that concentrate runoff and where the stored water will be appropriately distributed. Based on GIS analysis it was found that 17% percent of the Potshini catchment area has a high potential for generating surface runoff, whereas an analysis of all factors which influence the location of such systems, shows that 18% is highly suitable for runoff

  3. An evaluation of applicability of seismic refraction method in identifying shallow archaeological features A case study at archaeological site

    Science.gov (United States)

    Jahangardi, Morteza; Hafezi Moghaddas, Naser; Keivan Hosseini, Sayyed; Garazhian, Omran

    2015-04-01

    We applied the seismic refraction method at archaeological site, Tepe Damghani located in Sabzevar, NE of Iran, in order to determine the structures of archaeological interests. This pre-historical site has special conditions with respect to geographical location and geomorphological setting, so it is an urban archaeological site, and in recent years it has been used as an agricultural field. In spring and summer of 2012, the third season of archaeological excavation was carried out. Test trenches of excavations in this site revealed that cultural layers were often disturbed adversely due to human activities such as farming and road construction in recent years. Conditions of archaeological cultural layers in southern and eastern parts of Tepe are slightly better, for instance, in test trench 3×3 m²1S03, third test trench excavated in the southern part of Tepe, an adobe in situ architectural structure was discovered that likely belongs to cultural features of a complex with 5 graves. After conclusion of the third season of archaeological excavation, all of the test trenches were filled with the same soil of excavated test trenches. Seismic refraction method was applied with12 channels of P geophones in three lines with a geophone interval of 0.5 meter and a 1.5 meter distance between profiles on test trench 1S03. The goal of this operation was evaluation of applicability of seismic method in identification of archaeological features, especially adobe wall structures. Processing of seismic data was done with the seismic software, SiesImager. Results were presented in the form of seismic section for every profile, so that identification of adobe wall structures was achieved hardly. This could be due to that adobe wall had been built with the same materials of the natural surrounding earth. Thus, there is a low contrast and it has an inappropriate effect on seismic processing and identifying of archaeological features. Hence the result could be that application of

  4. TSSer: an automated method to identify transcription start sites in prokaryotic genomes from differential RNA sequencing data.

    Science.gov (United States)

    Jorjani, Hadi; Zavolan, Mihaela

    2014-04-01

    Accurate identification of transcription start sites (TSSs) is an essential step in the analysis of transcription regulatory networks. In higher eukaryotes, the capped analysis of gene expression technology enabled comprehensive annotation of TSSs in genomes such as those of mice and humans. In bacteria, an equivalent approach, termed differential RNA sequencing (dRNA-seq), has recently been proposed, but the application of this approach to a large number of genomes is hindered by the paucity of computational analysis methods. With few exceptions, when the method has been used, annotation of TSSs has been largely done manually. In this work, we present a computational method called 'TSSer' that enables the automatic inference of TSSs from dRNA-seq data. The method rests on a probabilistic framework for identifying both genomic positions that are preferentially enriched in the dRNA-seq data as well as preferentially captured relative to neighboring genomic regions. Evaluating our approach for TSS calling on several publicly available datasets, we find that TSSer achieves high consistency with the curated lists of annotated TSSs, but identifies many additional TSSs. Therefore, TSSer can accelerate genome-wide identification of TSSs in bacterial genomes and can aid in further characterization of bacterial transcription regulatory networks. TSSer is freely available under GPL license at http://www.clipz.unibas.ch/TSSer/index.php

  5. SVM-based prediction of propeptide cleavage sites in spider toxins identifies toxin innovation in an Australian tarantula.

    Directory of Open Access Journals (Sweden)

    Emily S W Wong

    Full Text Available Spider neurotoxins are commonly used as pharmacological tools and are a popular source of novel compounds with therapeutic and agrochemical potential. Since venom peptides are inherently toxic, the host spider must employ strategies to avoid adverse effects prior to venom use. It is partly for this reason that most spider toxins encode a protective proregion that upon enzymatic cleavage is excised from the mature peptide. In order to identify the mature toxin sequence directly from toxin transcripts, without resorting to protein sequencing, the propeptide cleavage site in the toxin precursor must be predicted bioinformatically. We evaluated different machine learning strategies (support vector machines, hidden Markov model and decision tree and developed an algorithm (SpiderP for prediction of propeptide cleavage sites in spider toxins. Our strategy uses a support vector machine (SVM framework that combines both local and global sequence information. Our method is superior or comparable to current tools for prediction of propeptide sequences in spider toxins. Evaluation of the SVM method on an independent test set of known toxin sequences yielded 96% sensitivity and 100% specificity. Furthermore, we sequenced five novel peptides (not used to train the final predictor from the venom of the Australian tarantula Selenotypus plumipes to test the accuracy of the predictor and found 80% sensitivity and 99.6% 8-mer specificity. Finally, we used the predictor together with homology information to predict and characterize seven groups of novel toxins from the deeply sequenced venom gland transcriptome of S. plumipes, which revealed structural complexity and innovations in the evolution of the toxins. The precursor prediction tool (SpiderP is freely available on ArachnoServer (http://www.arachnoserver.org/spiderP.html, a web portal to a comprehensive relational database of spider toxins. All training data, test data, and scripts used are available from

  6. Identifying and Further Understanding the Role of Bacteria and Archaea in a Basic Mine Drainage Remediation Site in Tanoma, PA

    Science.gov (United States)

    Sharp, G.; Mount, G.

    2017-12-01

    Acid mine drainage pollutes over 3000 miles of streams and ground water in Pennsylvania alone, and in response many solutions have been developed to counteract the effects of acidic mine drainage. It is estimated by USGS that restoring these watersheds would cost 5 billion-15 billion in total. As economic conditions place limits on expenditures, cost effective means of remediation will be of critical importance. One such method is passive bioremediation, and in the case of metal contamination, self-sustaining oxygenation. Our location of interest is the Tanoma Acid Mine Drainage engineered wetland near Tanoma, Pennsylvania. It is estimated that up to 5,000 gallons per minute is currently being discharged into the site. While most local remediation sites are acidic (pH bioremediation in more neutral pH setting (pH of 5.5-7.5). In this study, we look to further understand biologic, chemical, and hydrologic controls that contribute to the efficiency of the wetland. Our research will focus on the spatial and temporal distribution of biomass through the wetland system as well as changes in water and soil chemistry. Local biofilm (Leptothrix discophora ) are an important part of the remediation process, using iron from the water as an energy source. The bacteria reduce the iron content of the water, precipitating it onto the pond bed as Terraced Iron Formations (TIF). Terraces iron formations (TIF's) are correlated with localized biofilm-archaea densities where archaea thrive in iron rich sediments. By determining bacteria densities in the wetland through gram stain analysis, we can further understand their role in terraced iron formation creation, find localized TIF's that occur, and correlate methane production due to archaea in that location. Mapping TIF locations and identifying bacteria densities will help determine the bioremediation effects on the overall efficiency of iron reduction throughout the Tanoma AMD passive remediation system.

  7. Isthmus sites identified by Ripple Mapping are usually anatomically stable: A novel method to guide atrial substrate ablation?

    Science.gov (United States)

    Luther, Vishal; Qureshi, Norman; Lim, Phang Boon; Koa-Wing, Michael; Jamil-Copley, Shahnaz; Ng, Fu Siong; Whinnett, Zachary; Davies, D Wyn; Peters, Nicholas S; Kanagaratnam, Prapa; Linton, Nick

    2018-03-01

    Postablation reentrant ATs depend upon conducting isthmuses bordered by scar. Bipolar voltage maps highlight scar as sites of low voltage, but the voltage amplitude of an electrogram depends upon the myocardial activation sequence. Furthermore, a voltage threshold that defines atrial scar is unknown. We used Ripple Mapping (RM) to test whether these isthmuses were anatomically fixed between different activation vectors and atrial rates. We studied post-AF ablation ATs where >1 rhythm was mapped. Multipolar catheters were used with CARTO Confidense for high-density mapping. RM visualized the pattern of activation, and the voltage threshold below which no activation was seen. Isthmuses were characterized at this threshold between maps for each patient. Ten patients were studied (Map 1 was AT1; Map 2: sinus 1/10, LA paced 2/10, AT2 with reverse CS activation 3/10; AT2 CL difference 50 ± 30 ms). Point density was similar between maps (Map 1: 2,589 ± 1,330; Map 2: 2,214 ± 1,384; P  =  0.31). RM activation threshold was 0.16 ± 0.08 mV. Thirty-one isthmuses were identified in Map 1 (median 3 per map; width 27 ± 15 mm; 7 anterior; 6 roof; 8 mitral; 9 septal; 1 posterior). Importantly, 7 of 31 (23%) isthmuses were unexpectedly identified within regions without prior ablation. AT1 was treated following ablation of 11/31 (35%) isthmuses. Of the remaining 20 isthmuses, 14 of 16 isthmuses (88%) were consistent between the two maps (four were inadequately mapped). Wavefront collision caused variation in low voltage distribution in 2 of 16 (12%). The distribution of isthmuses and nonconducting tissue within the ablated left atrium, as defined by RM, appear concordant between rhythms. This could guide a substrate ablative approach. © 2018 Wiley Periodicals, Inc.

  8. Novel colchicine-site binders with a cyclohexanedione scaffold identified through a ligand-based virtual screening approach.

    Science.gov (United States)

    Canela, María-Dolores; Pérez-Pérez, María-Jesús; Noppen, Sam; Sáez-Calvo, Gonzalo; Díaz, J Fernando; Camarasa, María-José; Liekens, Sandra; Priego, Eva-María

    2014-05-22

    Vascular disrupting agents (VDAs) constitute an innovative anticancer therapy that targets the tumor endothelium, leading to tumor necrosis. Our approach for the identification of new VDAs has relied on a ligand 3-D shape similarity virtual screening (VS) approach using the ROCS program as the VS tool and as query colchicine and TN-16, which both bind the α,β-tubulin dimer. One of the hits identified, using TN-16 as query, has been explored by the synthesis of its structural analogues, leading to 2-(1-((2-methoxyphenyl)amino)ethylidene)-5-phenylcyclohexane-1,3-dione (compound 16c) with an IC50 = 0.09 ± 0.01 μM in HMEC-1 and BAEC, being 100-fold more potent than the initial hit. Compound 16c caused cell cycle arrest in the G2/M phase and interacted with the colchicine-binding site in tubulin, as confirmed by a competition assay with N,N'-ethylenebis(iodoacetamide) and by fluorescence spectroscopy. Moreover, 16c destroyed an established endothelial tubular network at 1 μM and inhibited the migration and invasion of human breast carcinoma cells at 0.4 μM. In conclusion, our approach has led to a new chemotype of promising antiproliferative compounds with antimitotic and potential VDA properties.

  9. Cortical areas involved in Arabic number reading.

    Science.gov (United States)

    Roux, F-E; Lubrano, V; Lauwers-Cances, V; Giussani, C; Démonet, J-F

    2008-01-15

    Distinct functional pathways for processing words and numbers have been hypothesized from the observation of dissociated impairments of these categories in brain-damaged patients. We aimed to identify the cortical areas involved in Arabic number reading process in patients operated on for various brain lesions. Direct cortical electrostimulation was prospectively used in 60 brain mappings. We used object naming and two reading tasks: alphabetic script (sentences and number words) and Arabic number reading. Cortical areas involved in Arabic number reading were identified according to location, type of interference, and distinctness from areas associated with other language tasks. Arabic number reading was sustained by small cortical areas, often extremely well localized (area (Brodmann area 45), the anterior part of the dominant supramarginal gyrus (Brodmann area 40; p area (Brodmann area 37; p areas.

  10. Cortical bone metastases

    International Nuclear Information System (INIS)

    Davis, T.M. Jr.; Rogers, L.F.; Hendrix, R.W.

    1986-01-01

    Twenty-five cases of bone metastases involving the cortex alone are reviewed. Seven patients had primary lung carcinoma, while 18 had primary tumors not previously reported to produce cortical bone metastases (tumors of the breast, kidney, pancreas, adenocarcinoma of unknown origin, multiple myeloma). Radiographically, these cortical lesions were well circumscribed, osteolytic, and produced soft-tissue swelling and occasional periosteal reaction. A recurrent pattern of metadiaphyseal involvement of the long bones of the lower extremity (particularly the femur) was noted, and is discussed. Findings reported in the literature, review, pathophysiology, and the role of skeletal radiographs, bone scans, and CT scans in evaluating cortical bone metastases are addressed

  11. Differences in cortical coding of heat evoked pain beyond the perceived intensity: an fMRI and EEG study.

    Science.gov (United States)

    Haefeli, Jenny; Freund, Patrick; Kramer, John L K; Blum, Julia; Luechinger, Roger; Curt, Armin

    2014-04-01

    Imaging studies have identified a wide network of brain areas activated by nociceptive stimuli and revealed differences in somatotopic representation of highly distinct stimulation sites (foot vs. hand) in the primary (S1) and secondary (S2) somatosensory cortices. Somatotopic organization between adjacent dermatomes and differences in cortical coding of similarly perceived nociceptive stimulation are less well studied. Here, cortical processing following contact heat nociceptive stimulation of cervical (C4, C6, and C8) and trunk (T10) dermatomes were recorded in 20 healthy subjects using functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Stimulation of T10 compared with the C6 and C8 revealed significant higher response intensity in the left S1 (contralateral) and the right S2 (ipsilateral) even when the perceived pain was equal between stimulation sites. Accordingly, contact heat evoked potentials following stimulation of T10 showed significantly higher N2P2 amplitudes compared to C6 and C8. Adjacent dermatomes did not reveal a distinct somatotopical representation. Within the assessed cervical and trunk dermatomes, nociceptive cortical processing to heat differs significantly in magnitude even when controlling for pain perception. This study provides evidence that controlling for pain perception is not sufficient to compare directly the magnitude of cortical processing [blood oxygen level dependence (BOLD) response and amplitude of evoked potentials] between body sites. Copyright © 2013 Wiley Periodicals, Inc.

  12. Autosomal dominant cortical tremor, myoclonus and epilepsy.

    Science.gov (United States)

    Striano, Pasquale; Zara, Federico

    2016-09-01

    The term 'cortical tremor' was first introduced by Ikeda and colleagues to indicate a postural and action-induced shivering movement of the hands which mimics essential tremor, but presents with the electrophysiological findings of cortical reflex myoclonus. The association between autosomal dominant cortical tremor, myoclonus and epilepsy (ADCME) was first recognized in Japanese families and is now increasingly reported worldwide, although it is described using different acronyms (BAFME, FAME, FEME, FCTE and others). The disease usually takes a benign course, although drug-resistant focal seizures or slight intellectual disability occur in some cases. Moreover, a worsening of cortical tremor and myoclonus is common in advanced age. Although not yet recognized by the International League Against Epilepsy (ILAE), this is a well-delineated epilepsy syndrome with remarkable features that clearly distinguishes it from other myoclonus epilepsies. Moreover, genetic studies of these families show heterogeneity and different susceptible chromosomal loci have been identified.

  13. Simulations of hydrogen sorption in rht-MOF-1: identifying the binding sites through explicit polarization and quantum rotation calculations

    KAUST Repository

    Pham, Tony

    2014-01-01

    Grand canonical Monte Carlo (GCMC) simulations of hydrogen sorption were performed in rht-MOF-1, a metal-organic framework (MOF) that consists of isophthalate groups joined by copper paddlewheel clusters and Cu3O trimers through tetrazolate moeities. This is a charged rht-MOF that contains extra-framework nitrate counterions within the material. For the simulations performed herein, excellent agreement with experiment was achieved for the simulated hydrogen sorption isotherms and calculated isosteric heat of adsorption, Qst, values only when using a polarizable potential. Thermodynamic agreement is demonstrated via comparing to experimental isotherms and binding sites are revealed by combining simulation and inelastic neutron scattering (INS) data. Simulations involving explicit many-body polarization interactions assisted in the determination of the binding sites in rht-MOF-1 through the distribution of the induced dipoles that led to strong adsorbate interactions. Four distinct hydrogen sorption sites were determined from the polarization distribution: the nitrate ions located in the corners of the truncated tetrahedral cages, the Cu2+ ions of the paddlewheels that project into the truncated tetrahedral and truncated octahedral cages (Cu1 ions), the Cu2+ ions of the Cu3O trimers (Cu3 ions), and the sides of the paddlewheels in the cuboctahedral cage. The simulations revealed that the initial sorption sites for hydrogen in rht-MOF-1 are the nitrate ions; this site corresponds to the high initial Qst value for hydrogen (9.5 kJ mol-1) in the MOF. The radial distribution functions, g(r), about the Cu2+ ions at various loadings revealed that the Cu1 ions are the preferred open-metal sorption sites for hydrogen at low loading, while the Cu3 ions become occupied at higher loadings. The validation of the aforementioned sorption sites in rht-MOF-1 was confirmed by calculating the two-dimensional quantum rotational levels about each site and comparing the levels to the

  14. Cortical and trabecular bone microstructure did not recover at weight-bearing skeletal sites and progressively deteriorated at non-weight-bearing sites during the year following international space station missions

    NARCIS (Netherlands)

    Vico, L.; van Rietbergen, B.; Vilayphiou, N.; Linossier, M.T.; Locrelle, H.; Normand, M.; Zouch, M.; Gerbaix, M.; Bonnet, N.; Novikov, V.; Thomas, T.; Vassilieva, G.

    2017-01-01

    Risk for premature osteoporosis is a major health concern in astronauts and cosmonauts; the reversibility of the bone lost at the weight-bearing bone sites is not established, although it is suspected to take longer than the mission length. The bone three-dimensional structure and strength that

  15. Determining the cortical target of transcranial magnetic stimulation.

    Science.gov (United States)

    Thielscher, A; Wichmann, F A

    2009-10-01

    Determining the cortical region that is effectively targeted by TMS to induce a reproducible behavioral effect is a non-trivial problem. In mapping experiments, a grid of coil positions is used to systematically assess the TMS effect on, e.g. muscle responses or error rates. The center-of-mass (CoM) of the response distribution is projected onto the cortex to determine the likely target site, implicitly assuming the existence of a single, contiguous target. The mapping results, however, often contain several local maxima. These could either stem from measurement noise, or hint towards a distributed target region. Critically, the calculation of a CoM, by design, treats multiple maxima as if they were noise. Here, a stringent hierarchical sigmoidal model fitting approach is developed that determines the cortical target(s) from TMS mapping based on electric field calculations. Monte-Carlo simulations are used to assess the significance and the goodness-of-fit of the sigmoidal fits, and to obtain confidence regions around the calculated targets. The approach was applied to mapping data on visual suppression (N=7). In all subjects, we reliably identified two or three neighboring targets commonly contributing to the suppression effect (average distance+/-SD: 7.7+/-2.3 mm). This demonstrates that (i) the assumption of a single CoM is not generally valid and (ii) the combination of TMS mapping with the fitting approach has a cortical resolution of TMS.

  16. RED: A Java-MySQL Software for Identifying and Visualizing RNA Editing Sites Using Rule-Based and Statistical Filters.

    Directory of Open Access Journals (Sweden)

    Yongmei Sun

    Full Text Available RNA editing is one of the post- or co-transcriptional processes that can lead to amino acid substitutions in protein sequences, alternative pre-mRNA splicing, and changes in gene expression levels. Although several methods have been suggested to identify RNA editing sites, there remains challenges to be addressed in distinguishing true RNA editing sites from its counterparts on genome and technical artifacts. In addition, there lacks a software framework to identify and visualize potential RNA editing sites. Here, we presented a software - 'RED' (RNA Editing sites Detector - for the identification of RNA editing sites by integrating multiple rule-based and statistical filters. The potential RNA editing sites can be visualized at the genome and the site levels by graphical user interface (GUI. To improve performance, we used MySQL database management system (DBMS for high-throughput data storage and query. We demonstrated the validity and utility of RED by identifying the presence and absence of C→U RNA-editing sites experimentally validated, in comparison with REDItools, a command line tool to perform high-throughput investigation of RNA editing. In an analysis of a sample data-set with 28 experimentally validated C→U RNA editing sites, RED had sensitivity and specificity of 0.64 and 0.5. In comparison, REDItools had a better sensitivity (0.75 but similar specificity (0.5. RED is an easy-to-use, platform-independent Java-based software, and can be applied to RNA-seq data without or with DNA sequencing data. The package is freely available under the GPLv3 license at http://github.com/REDetector/RED or https://sourceforge.net/projects/redetector.

  17. RED: A Java-MySQL Software for Identifying and Visualizing RNA Editing Sites Using Rule-Based and Statistical Filters.

    Science.gov (United States)

    Sun, Yongmei; Li, Xing; Wu, Di; Pan, Qi; Ji, Yuefeng; Ren, Hong; Ding, Keyue

    2016-01-01

    RNA editing is one of the post- or co-transcriptional processes that can lead to amino acid substitutions in protein sequences, alternative pre-mRNA splicing, and changes in gene expression levels. Although several methods have been suggested to identify RNA editing sites, there remains challenges to be addressed in distinguishing true RNA editing sites from its counterparts on genome and technical artifacts. In addition, there lacks a software framework to identify and visualize potential RNA editing sites. Here, we presented a software - 'RED' (RNA Editing sites Detector) - for the identification of RNA editing sites by integrating multiple rule-based and statistical filters. The potential RNA editing sites can be visualized at the genome and the site levels by graphical user interface (GUI). To improve performance, we used MySQL database management system (DBMS) for high-throughput data storage and query. We demonstrated the validity and utility of RED by identifying the presence and absence of C→U RNA-editing sites experimentally validated, in comparison with REDItools, a command line tool to perform high-throughput investigation of RNA editing. In an analysis of a sample data-set with 28 experimentally validated C→U RNA editing sites, RED had sensitivity and specificity of 0.64 and 0.5. In comparison, REDItools had a better sensitivity (0.75) but similar specificity (0.5). RED is an easy-to-use, platform-independent Java-based software, and can be applied to RNA-seq data without or with DNA sequencing data. The package is freely available under the GPLv3 license at http://github.com/REDetector/RED or https://sourceforge.net/projects/redetector.

  18. Towards identifying the active sites on RuO2(110) in catalyzing oxygen evolution  

    DEFF Research Database (Denmark)

    Rao, Reshma R.; Kolb, Manuel J.; Halck, Niels Bendtsen

    2017-01-01

    While the surface atomic structure of RuO2 has been well studied in ultra high vacuum, much less is known about the interaction between water and RuO2 in aqueous solution. In this work, in situ surface X-ray scattering measurements combined with density functional theory (DFT) were used to determ......While the surface atomic structure of RuO2 has been well studied in ultra high vacuum, much less is known about the interaction between water and RuO2 in aqueous solution. In this work, in situ surface X-ray scattering measurements combined with density functional theory (DFT) were used...... on the coordinatively unsaturated Ru sites (CUS) and hydrogen adsorbed to the bridging oxygen sites. At potentials relevant to the oxygen evolution reaction (OER), an –OO species on the Ru CUS sites was detected, which was stabilized by a neighboring –OH group on the Ru CUS or bridge site. Combining potential...

  19. Pairwise comparisons of ten porcine tissues identify differential transcriptional regulation at the gene, isoform, promoter and transcription start site level

    DEFF Research Database (Denmark)

    Farajzadeh, Leila; Hornshøj, Henrik; Momeni, Jamal

    2013-01-01

    , isoform, and transcription start site (TSS), and promoter level showed that several of the genes differed at all four levels. Interestingly, these genes were mainly annotated to the "electron transport chain" and neuronal differentiation, emphasizing that "tissue important" genes are regulated at several...

  20. Applying the 5 WHYs to Identify Root Causes to Non-completions in On-Site Construction

    DEFF Research Database (Denmark)

    Lindhard, Søren Munch

    2014-01-01

    from mistakes. A central part of the control framework Last Planner System is to identify not completed activities to identify root causes and to learn. One tool to investigate root causes is the 5 WHYs approach. The 5 WHYs approach has been applied in a case study research to analysis the root cause...

  1. Model outputs for each hotspot site to identify the likely environmental, economic and social effects of proposed remediation strategies

    DEFF Research Database (Denmark)

    Fleskens, Luuk; Irvine, Brian; Kirkby, Mike

    2012-01-01

    Portuguese sites) a fire severity index under current conditions and under different technologies. The DESMICE model is informed by WB3 WOCAT database records, economic WB4 experimental results, additionally requested data on spatial variability of costs and benefits, and secondary data. It applies spatially...... multiple stakeholders in very different contexts into the modelling process, in order to enhance both the realism and relevance of outputs for policy and practice; b) site-selection modelling is being applied to land degradation mitigation to enable landscape-scale assessments of the most economically....... Biophysical models (e.g. PESERA) should be able to separate immediate and gradual aspects. Ongoing degradation in the without case is not yet implicitly considered. Analysis of robustness to climatic variability and prices is also essential. Finally, factors such as attitude towards conservation and risk...

  2. Pairwise comparisons of ten porcine tissues identify differential transcriptional regulation at the gene, isoform, promoter and transcription start site level

    International Nuclear Information System (INIS)

    Farajzadeh, Leila; Hornshøj, Henrik; Momeni, Jamal; Thomsen, Bo; Larsen, Knud; Hedegaard, Jakob; Bendixen, Christian; Madsen, Lone Bruhn

    2013-01-01

    Highlights: •Transcriptome sequencing yielded 223 mill porcine RNA-seq reads, and 59,000 transcribed locations. •Establishment of unique transcription profiles for ten porcine tissues including four brain tissues. •Comparison of transcription profiles at gene, isoform, promoter and transcription start site level. •Highlights a high level of regulation of neuro-related genes at both gene, isoform, and TSS level. •Our results emphasize the pig as a valuable animal model with respect to human biological issues. -- Abstract: The transcriptome is the absolute set of transcripts in a tissue or cell at the time of sampling. In this study RNA-Seq is employed to enable the differential analysis of the transcriptome profile for ten porcine tissues in order to evaluate differences between the tissues at the gene and isoform expression level, together with an analysis of variation in transcription start sites, promoter usage, and splicing. Totally, 223 million RNA fragments were sequenced leading to the identification of 59,930 transcribed gene locations and 290,936 transcript variants using Cufflinks with similarity to approximately 13,899 annotated human genes. Pairwise analysis of tissues for differential expression at the gene level showed that the smallest differences were between tissues originating from the porcine brain. Interestingly, the relative level of differential expression at the isoform level did generally not vary between tissue contrasts. Furthermore, analysis of differential promoter usage between tissues, revealed a proportionally higher variation between cerebellum (CBE) versus frontal cortex and cerebellum versus hypothalamus (HYP) than in the remaining comparisons. In addition, the comparison of differential transcription start sites showed that the number of these sites is generally increased in comparisons including hypothalamus in contrast to other pairwise assessments. A comprehensive analysis of one of the tissue contrasts, i

  3. Background noise exerts diverse effects on the cortical encoding of foreground sounds.

    Science.gov (United States)

    Malone, B J; Heiser, Marc A; Beitel, Ralph E; Schreiner, Christoph E

    2017-08-01

    In natural listening conditions, many sounds must be detected and identified in the context of competing sound sources, which function as background noise. Traditionally, noise is thought to degrade the cortical representation of sounds by suppressing responses and increasing response variability. However, recent studies of neural network models and brain slices have shown that background synaptic noise can improve the detection of signals. Because acoustic noise affects the synaptic background activity of cortical networks, it may improve the cortical responses to signals. We used spike train decoding techniques to determine the functional effects of a continuous white noise background on the responses of clusters of neurons in auditory cortex to foreground signals, specifically frequency-modulated sweeps (FMs) of different velocities, directions, and amplitudes. Whereas the addition of noise progressively suppressed the FM responses of some cortical sites in the core fields with decreasing signal-to-noise ratios (SNRs), the stimulus representation remained robust or was even significantly enhanced at specific SNRs in many others. Even though the background noise level was typically not explicitly encoded in cortical responses, significant information about noise context could be decoded from cortical responses on the basis of how the neural representation of the foreground sweeps was affected. These findings demonstrate significant diversity in signal in noise processing even within the core auditory fields that could support noise-robust hearing across a wide range of listening conditions. NEW & NOTEWORTHY The ability to detect and discriminate sounds in background noise is critical for our ability to communicate. The neural basis of robust perceptual performance in noise is not well understood. We identified neuronal populations in core auditory cortex of squirrel monkeys that differ in how they process foreground signals in background noise and that may

  4. Dynamic Causal Modeling of the Cortical Responses to Wrist Perturbations

    Directory of Open Access Journals (Sweden)

    Yuan Yang

    2017-09-01

    Full Text Available Mechanical perturbations applied to the wrist joint typically evoke a stereotypical sequence of cortical and muscle responses. The early cortical responses (<100 ms are thought be involved in the “rapid” transcortical reaction to the perturbation while the late cortical responses (>100 ms are related to the “slow” transcortical reaction. Although previous studies indicated that both responses involve the primary motor cortex, it remains unclear if both responses are engaged by the same effective connectivity in the cortical network. To answer this question, we investigated the effective connectivity cortical network after a “ramp-and-hold” mechanical perturbation, in both the early (<100 ms and late (>100 ms periods, using dynamic causal modeling. Ramp-and-hold perturbations were applied to the wrist joint while the subject maintained an isometric wrist flexion. Cortical activity was recorded using a 128-channel electroencephalogram (EEG. We investigated how the perturbation modulated the effective connectivity for the early and late periods. Bayesian model comparisons suggested that different effective connectivity networks are engaged in these two periods. For the early period, we found that only a few cortico-cortical connections were modulated, while more complicated connectivity was identified in the cortical network during the late period with multiple modulated cortico-cortical connections. The limited early cortical network likely allows for a rapid muscle response without involving high-level cognitive processes, while the complexity of the late network may facilitate coordinated responses.

  5. Newly identified essential amino acid residues affecting ^8-sphingolipid desaturase activity revealed by site-directed mutagenesis

    Science.gov (United States)

    In order to identify amino acid residues crucial for the enzymatic activity of ^8-sphingolipid desaturases, a sequence comparison was performed among ^8-sphingolipid desaturases and ^6-fatty acid desaturase from various plants. In addition to the known conserved cytb5 (cytochrome b5) HPGG motif and...

  6. Partial digestion with restriction enzymes of ultraviolet-irradiated human genomic DNA: a method for identifying restriction site polymorphisms

    International Nuclear Information System (INIS)

    Nobile, C.; Romeo, G.

    1988-01-01

    A method for partial digestion of total human DNA with restriction enzymes has been developed on the basis of a principle already utilized by P.A. Whittaker and E. Southern for the analysis of phage lambda recombinants. Total human DNA irradiated with uv light of 254 nm is partially digested by restriction enzymes that recognize sequences containing adjacent thymidines because of TT dimer formation. The products resulting from partial digestion of specific genomic regions are detected in Southern blots by genomic-unique DNA probes with high reproducibility. This procedure is rapid and simple to perform because the same conditions of uv irradiation are used for different enzymes and probes. It is shown that restriction site polymorphisms occurring in the genomic regions analyzed are recognized by the allelic partial digest patterns they determine

  7. Diet of pumas (Puma concolor) in Sonora, Mexico, as determined by GPS kill sites and molecular identified scat, with comments on jaguar (Panthera onca) diet

    Science.gov (United States)

    Cassaigne, Ivonne; Medellin, Rodrigo A.; Thompson, Ron W.; Culver, Melanie; Ochoa, Alexander; Vargas, Karla; Childs, Jack L.; Sanderson, Jim; List, Rurik; Torres-Gomez, Armando

    2016-01-01

    We documented puma (Puma concolor) and jaguar (Panthera onca) prey consumption in northeastern Sonora, Mexico, by investigating global positioning system cluster sites (n = 220), and conducting molecular analyses of scat (n = 116) collected between 2011 and 2013. We used camera trap data (n = 8,976 camera days) to estimate relative abundances of pumas and jaguars. Deer (Odocoileus virginianus) was the most frequent prey for puma found at kill sites (67%) and identified from scat (74%), although based on relative numbers of prey consumed, deer represented 45% and lagomorphs 20% of the proportion of all individuals eaten. A variety of small prey (weighing Sonora.

  8. Mapping cortical mesoscopic networks of single spiking cortical or sub-cortical neurons.

    Science.gov (United States)

    Xiao, Dongsheng; Vanni, Matthieu P; Mitelut, Catalin C; Chan, Allen W; LeDue, Jeffrey M; Xie, Yicheng; Chen, Andrew Cn; Swindale, Nicholas V; Murphy, Timothy H

    2017-02-04

    Understanding the basis of brain function requires knowledge of cortical operations over wide-spatial scales, but also within the context of single neurons. In vivo, wide-field GCaMP imaging and sub-cortical/cortical cellular electrophysiology were used in mice to investigate relationships between spontaneous single neuron spiking and mesoscopic cortical activity. We make use of a rich set of cortical activity motifs that are present in spontaneous activity in anesthetized and awake animals. A mesoscale spike-triggered averaging procedure allowed the identification of motifs that are preferentially linked to individual spiking neurons by employing genetically targeted indicators of neuronal activity. Thalamic neurons predicted and reported specific cycles of wide-scale cortical inhibition/excitation. In contrast, spike-triggered maps derived from single cortical neurons yielded spatio-temporal maps expected for regional cortical consensus function. This approach can define network relationships between any point source of neuronal spiking and mesoscale cortical maps.

  9. A strategy for interaction site prediction between phospho-binding modules and their partners identified from proteomic data.

    Science.gov (United States)

    Aucher, Willy; Becker, Emmanuelle; Ma, Emilie; Miron, Simona; Martel, Arnaud; Ochsenbein, Françoise; Marsolier-Kergoat, Marie-Claude; Guerois, Raphaël

    2010-12-01

    Small and large scale proteomic technologies are providing a wealth of potential interactions between proteins bearing phospho-recognition modules and their substrates. Resulting interaction maps reveal such a dense network of interactions that the functional dissection and understanding of these networks often require to break specific interactions while keeping the rest intact. Here, we developed a computational strategy, called STRIP, to predict the precise interaction site involved in an interaction with a phospho-recognition module. The method was validated by a two-hybrid screen carried out using the ForkHead Associated (FHA)1 domain of Rad53, a key protein of Saccharomyces cerevisiae DNA checkpoint, as a bait. In this screen we detected 11 partners, including Cdc7 and Cdc45, essential components of the DNA replication machinery. FHA domains are phospho-threonine binding modules and the threonines involved in both interactions could be predicted using the STRIP strategy. The threonines T484 and T189 in Cdc7 and Cdc45, respectively, were mutated and loss of binding could be monitored experimentally with the full-length proteins. The method was further tested for the analysis of 63 known Rad53 binding partners and provided several key insights regarding the threonines likely involved in these interactions. The STRIP method relies on a combination of conservation, phosphorylation likelihood, and binding specificity criteria and can be accessed via a web interface at http://biodev.extra.cea.fr/strip/.

  10. A Strategy for Interaction Site Prediction between Phospho-binding Modules and their Partners Identified from Proteomic Data*

    Science.gov (United States)

    Aucher, Willy; Becker, Emmanuelle; Ma, Emilie; Miron, Simona; Martel, Arnaud; Ochsenbein, Françoise; Marsolier-Kergoat, Marie-Claude; Guerois, Raphaël

    2010-01-01

    Small and large scale proteomic technologies are providing a wealth of potential interactions between proteins bearing phospho-recognition modules and their substrates. Resulting interaction maps reveal such a dense network of interactions that the functional dissection and understanding of these networks often require to break specific interactions while keeping the rest intact. Here, we developed a computational strategy, called STRIP, to predict the precise interaction site involved in an interaction with a phospho-recognition module. The method was validated by a two-hybrid screen carried out using the ForkHead Associated (FHA)1 domain of Rad53, a key protein of Saccharomyces cerevisiae DNA checkpoint, as a bait. In this screen we detected 11 partners, including Cdc7 and Cdc45, essential components of the DNA replication machinery. FHA domains are phospho-threonine binding modules and the threonines involved in both interactions could be predicted using the STRIP strategy. The threonines T484 and T189 in Cdc7 and Cdc45, respectively, were mutated and loss of binding could be monitored experimentally with the full-length proteins. The method was further tested for the analysis of 63 known Rad53 binding partners and provided several key insights regarding the threonines likely involved in these interactions. The STRIP method relies on a combination of conservation, phosphorylation likelihood, and binding specificity criteria and can be accessed via a web interface at http://biodev.extra.cea.fr/strip/. PMID:20733106

  11. Surgical site infection prevention: a survey to identify the gap between evidence and practice in University of Toronto teaching hospitals.

    Science.gov (United States)

    Eskicioglu, Cagla; Gagliardi, Anna R; Fenech, Darlene S; Forbes, Shawn S; McKenzie, Marg; McLeod, Robin S; Nathens, Avery B

    2012-08-01

    A gap exists between the best evidence and practice with regards to surgical site infection (SSI) prevention. Awareness of evidence is the first step in knowledge translation. A web-based survey was distributed to 59 general surgeons and 68 residents at University of Toronto teaching hospitals. Five domains pertaining to SSI prevention with questions addressing knowledge of prevention strategies, efficacy of antibiotics, strategies for changing practice and barriers to implementation of SSI prevention strategies were investigated. Seventy-six individuals (60%) responded. More than 90% of respondents stated there was evidence for antibiotic prophylaxis and perioperative normothermia and reported use of these strategies. There was a discrepancy in the perceived evidence for and the self-reported use of perioperative hyperoxia, omission of hair removal and bowel preparation. Eighty-three percent of respondents felt that consulting published guidelines is important in making decisions regarding antibiotics. There was also a discrepancy between what respondents felt were important strategies to ensure timely administration of antibiotics and what strategies were in place. Checklists, standardized orders, protocols and formal surveillance programs were rated most highly by 75%-90% of respondents, but less than 50% stated that these strategies were in place at their institutions. Broad-reaching initiatives that increase surgeon and trainee awareness and implementation of multifaceted hospital strategies that engage residents and attending surgeons are needed to change practice.

  12. Trajectories of cortical surface area and cortical volume maturation in normal brain development

    Directory of Open Access Journals (Sweden)

    Simon Ducharme

    2015-12-01

    Full Text Available This is a report of developmental trajectories of cortical surface area and cortical volume in the NIH MRI Study of Normal Brain Development. The quality-controlled sample included 384 individual typically-developing subjects with repeated scanning (1–3 per subject, total scans n=753 from 4.9 to 22.3 years of age. The best-fit model (cubic, quadratic, or first-order linear was identified at each vertex using mixed-effects models, with statistical correction for multiple comparisons using random field theory. Analyses were performed with and without controlling for total brain volume. These data are provided for reference and comparison with other databases. Further discussion and interpretation on cortical developmental trajectories can be found in the associated Ducharme et al.׳s article “Trajectories of cortical thickness maturation in normal brain development – the importance of quality control procedures” (Ducharme et al., 2015 [1].

  13. Cortical myoclonus and cerebellar pathology

    NARCIS (Netherlands)

    Tijssen, MAJ; Thom, M; Ellison, DW; Wilkins, P; Barnes, D; Thompson, PD; Brown, P

    2000-01-01

    Objective To study the electrophysiologic and pathologic findings in three patients with cortical myoclonus. In two patients the myoclonic ataxic syndrome was associated with proven celiac disease. Background: The pathologic findings in conditions associated with cortical myoclonus commonly involve

  14. Cortical myoclonus and cerebellar pathology

    NARCIS (Netherlands)

    Tijssen, M. A.; Thom, M.; Ellison, D. W.; Wilkins, P.; Barnes, D.; Thompson, P. D.; Brown, P.

    2000-01-01

    OBJECTIVE: To study the electrophysiologic and pathologic findings in three patients with cortical myoclonus. In two patients the myoclonic ataxic syndrome was associated with proven celiac disease. BACKGROUND: The pathologic findings in conditions associated with cortical myoclonus commonly involve

  15. Application of multiple tracers (SF6 and chloride) to identify the transport by characteristics of contaminant at two separate contaminated sites

    Science.gov (United States)

    Lee, K. K.; Lee, S. S.; Kim, H. H.; Koh, E. H.; Kim, M. O.; Lee, K.; Kim, H. J.

    2016-12-01

    Multiple tracers were applied for source and pathway detection at two different sites. CO2 gas injected in the subsurface for a shallow-depth CO2 injection and leak test can be regarded as a potential contaminant source. Therefore, it is necessary to identify the migration pattern of CO2 gas. Also, at a DNAPL contaminated site, it is important to figure out the characteristics of plume evolution from the source zone. In this study, multiple tracers (SF6 and chloride) were used to evaluate the applicability of volatile and non-volatile tracers and to identify the characteristics of contaminant transport at each CO2 injection and leak test site and DNAPL contaminated site. Firstly, at the CO2 test site, multiple tracers were used to perform the single well push-drift-pull tracer test at total 3 specific depth zones. As results of tests, volatile and non-volatile tracers showed different mass recovery percentage. Most of chloride mass was recovered but less than half of SF6 mass was recovered due to volatile property. This means that only gaseous SF6 leak out to unsaturated zone. However, breakthrough curves of both tracers indicated similar peak time, effective porosity, and regional groundwater velocity. Also, at both contaminated sites, natural gradient tracer tests were performed with multiple tracers. With the results of natural gradient tracer test, it was possible to confirm the applicability of multiple tracers and to understand the contaminant transport in highly heterogeneous aquifer systems through the long-term monitoring of tracers. Acknowledgement: financial support was provided by the R&D Project on Environmental Management of Geologic CO2 Storage)" from the KEITI (Project Number: 2014001810003) and Korea Ministry of Environment as "The GAIA project (2014000540010)".

  16. Cortical thickness patterns as state biomarker of anorexia nervosa.

    Science.gov (United States)

    Lavagnino, Luca; Mwangi, Benson; Cao, Bo; Shott, Megan E; Soares, Jair C; Frank, Guido K W

    2018-03-01

    Only few studies have investigated cortical thickness in anorexia nervosa (AN), and it is unclear whether patterns of altered cortical thickness can be identified as biomarkers for AN. Cortical thickness was measured in 19 adult women with restricting-type AN, 24 individuals recovered from restricting-type AN (REC-AN) and 24 healthy controls. Those individuals with current or recovered from AN had previously shown altered regional cortical volumes across orbitofrontal cortex and insula. A linear relevance vector machine-learning algorithm estimated patterns of regional thickness across 24 subdivisions of those regions. Region-based analysis showed higher cortical thickness in AN and REC-AN, compared to controls, in the right medial orbital (olfactory) sulcus, and greater cortical thickness for short insular gyri in REC-AN versus controls bilaterally. The machine-learning algorithm identified a pattern of relatively higher right orbital, right insular and left middle frontal cortical thickness, but lower left orbital, right middle and inferior frontal, and bilateral superior frontal cortical thickness specific to AN versus controls (74% specificity and 74% sensitivity, χ 2 p < .004); predicted probabilities differed significantly between AN and controls (p < .023). No pattern significantly distinguished the REC-AN group from controls. Higher cortical thickness in medial orbitofrontal cortex and insula probably contributes to higher gray matter volume in AN in those regions. The machine-learning algorithm identified a mixed pattern of mostly higher orbital and insular, but relatively lower superior frontal cortical thickness in individuals with current AN. These novel results suggest that regional cortical thickness patterns could be state markers for AN. © 2018 Wiley Periodicals, Inc.

  17. Paradiaphyseal calcific tendinitis with cortical bone erosion.

    Science.gov (United States)

    Fritz, P; Bardin, T; Laredo, J D; Ziza, J M; D'Anglejan, G; Lansaman, J; Bucki, B; Forest, M; Kuntz, D

    1994-05-01

    To determine the clinical, radiologic, and histologic features of calcific tendinitis with cortical bone erosion. The records of 6 patients with paradiaphyseal calcific tendinitis and adjacent bone cortex erosion were reviewed. Calcific tendinitis involved the linea aspera in 4 patients, the bicipital groove in 1 patient, and the deltoid insertion in another. Calcium deposits were associated with cortical bone erosions, revealed on plain radiographs in 4 patients and computed tomography scans in 2. Bone scans were performed in 2 patients and showed local hyperfixation of the isotope. In 4 patients, suspicion of a neoplasm led to a biopsy. Calcium deposits appeared to be surrounded by a foreign body reaction with numerous giant cells. Apatite crystals were identified by transmission electron microscopy and elemental analysis in 1 surgical sample. Paradiaphyseal calcific tendinitis with cortical bone erosion is an uncommon presentation of apatite deposition disease.

  18. Cerebellar motor learning: when is cortical plasticity not enough?

    Directory of Open Access Journals (Sweden)

    John Porrill

    2007-10-01

    Full Text Available Classical Marr-Albus theories of cerebellar learning employ only cortical sites of plasticity. However, tests of these theories using adaptive calibration of the vestibulo-ocular reflex (VOR have indicated plasticity in both cerebellar cortex and the brainstem. To resolve this long-standing conflict, we attempted to identify the computational role of the brainstem site, by using an adaptive filter version of the cerebellar microcircuit to model VOR calibration for changes in the oculomotor plant. With only cortical plasticity, introducing a realistic delay in the retinal-slip error signal of 100 ms prevented learning at frequencies higher than 2.5 Hz, although the VOR itself is accurate up to at least 25 Hz. However, the introduction of an additional brainstem site of plasticity, driven by the correlation between cerebellar and vestibular inputs, overcame the 2.5 Hz limitation and allowed learning of accurate high-frequency gains. This "cortex-first" learning mechanism is consistent with a wide variety of evidence concerning the role of the flocculus in VOR calibration, and complements rather than replaces the previously proposed "brainstem-first" mechanism that operates when ocular tracking mechanisms are effective. These results (i describe a process whereby information originally learnt in one area of the brain (cerebellar cortex can be transferred and expressed in another (brainstem, and (ii indicate for the first time why a brainstem site of plasticity is actually required by Marr-Albus type models when high-frequency gains must be learned in the presence of error delay.

  19. Transcranial magnetic stimulation in patients with early cortical dementia: A pilot study

    Directory of Open Access Journals (Sweden)

    Thomas Gregor Issac

    2013-01-01

    Full Text Available Context: The diagnostic accuracy of the currently available tools carries poor sensitivity resulting in significant delay in specific diagnosis of cortical dementias. Considering the properties of default mode networking of the brain it is highly probable that specific changes may be seen in frontotemporal dementias (FTDs and Alzheimer′s disease sufficiently early. Aim: The aim of this study is to look for changes in Transcranial Magnetic Stimulation (TMS in cortical dementia. Materials and Methods: Evaluated with a single pulse TMS with the figure of eight coil and recorded from right first dorsal interossei (FDI. Resting Motor Threshold (RMT was estimated on the opposite motor cortex (T1. Second site of stimulation was cervical spine at C7-T2. Central motor conduction time (CMCT is equal toT1-T2.Silent Period (SP identified by applying TMS pulse to contracting FDI. Conclusions: RMT was reduced in seven out of eight Alzheimer′s dementias. CMCT was in the upper limit of normal in both patients with FTD. The most consistent observation was that SP was reduced and there were escape discharges noticed during the SP suggesting increased cortical excitability and decreased cortical inhibition. This suggests probable early asymptomatic changes in the gamma-aminobutyric acid (GABA nergic and cholinergic system is taking place. This if confirmed may give some insight into early diagnosis and therapeutic role of GABA agonists in these disorders.

  20. Transcranial magnetic stimulation in patients with early cortical dementia: A pilot study.

    Science.gov (United States)

    Issac, Thomas Gregor; Chandra, S R; Nagaraju, B C

    2013-10-01

    The diagnostic accuracy of the currently available tools carries poor sensitivity resulting in significant delay in specific diagnosis of cortical dementias. Considering the properties of default mode networking of the brain it is highly probable that specific changes may be seen in frontotemporal dementias (FTDs) and Alzheimer's disease sufficiently early. The aim of this study is to look for changes in Transcranial Magnetic Stimulation (TMS) in cortical dementia. Evaluated with a single pulse TMS with the figure of eight coil and recorded from right first dorsal interossei (FDI). Resting Motor Threshold (RMT) was estimated on the opposite motor cortex (T1). Second site of stimulation was cervical spine at C7-T2. Central motor conduction time (CMCT) is equal toT1-T2. Silent Period (SP) identified by applying TMS pulse to contracting FDI. RMT was reduced in seven out of eight Alzheimer's dementias. CMCT was in the upper limit of normal in both patients with FTD. The most consistent observation was that SP was reduced and there were escape discharges noticed during the SP suggesting increased cortical excitability and decreased cortical inhibition. This suggests probable early asymptomatic changes in the gamma-aminobutyric acid (GABA) nergic and cholinergic system is taking place. This if confirmed may give some insight into early diagnosis and therapeutic role of GABA agonists in these disorders.

  1. Cortical injury in multiple sclerosis; the role of the immune system

    Directory of Open Access Journals (Sweden)

    Walker Caroline A

    2011-12-01

    Full Text Available Abstract The easily identifiable, ubiquitous demyelination and neuronal damage that occurs within the cerebral white matter of patients with multiple sclerosis (MS has been the subject of extensive study. Accordingly, MS has historically been described as a disease of the white matter. Recently, the cerebral cortex (gray matter of patients with MS has been recognized as an additional and major site of disease pathogenesis. This acknowledgement of cortical tissue damage is due, in part, to more powerful MRI that allows detection of such injury and to focused neuropathology-based investigations. Cortical tissue damage has been associated with inflammation that is less pronounced to that which is associated with damage in the white matter. There is, however, emerging evidence that suggests cortical damage can be closely associated with robust inflammation not only in the parenchyma, but also in the neighboring meninges. This manuscript will highlight the current knowledge of inflammation associated with cortical tissue injury. Historical literature along with contemporary work that focuses on both the absence and presence of inflammation in the cerebral cortex and in the cerebral meninges will be reviewed.

  2. SCS-CN and GIS-based approach for identifying potential water harvesting sites in the Kali Watershed, Mahi River Basin, India

    Science.gov (United States)

    Ramakrishnan, D.; Bandyopadhyay, A.; Kusuma, K. N.

    2009-08-01

    The Kali sub-watershed is situated in the semi-arid region of Gujarat, India and forms a part of the Mahi River Watershed. This watershed receives an average annual rainfall of 900mm mainly between July and September. Due to high runoff potential, evapo-transpiration and poor infiltration, drought like situation prevails in this area from December to June almost every year. In this paper, augmentation of water resource is proposed by construction of runoff harvesting structures like check dam, percolation pond, farm pond, well and subsurface dyke. The site suitability for different water harvesting structures is determined by considering spatially varying parameters like runoff potential, slope, fracture pattern and micro-watershed area. GIS is utilised as a tool to store, analyse and integrate spatial and attribute information pertaining to runoff, slope, drainage and fracture. The runoff derived by SCS-CN method is a function of runoff potential which can be expressed in terms of runoff coefficient (ratio between the runoff and rainfall) which can be classified into three classes, viz., high (>40%), moderate (20-40%) and low (<20%). In addition to IMSD, FAO specifications for water harvesting/recharging structures, parameters such as effective storage, rock mass permeability are herein considered to augment effective storage. Using the overlay and decision tree concepts in GIS, potential water harvesting sites are identified. The derived sites are field investigated for suitability and implementation. In all, the accuracy of the site selection at implementation level varies from 80-100%.

  3. A triad of lys12, lys41, arg78 spatial domain, a novel identified heparin binding site on tat protein, facilitates tat-driven cell adhesion.

    Directory of Open Access Journals (Sweden)

    Jing Ai

    Full Text Available Tat protein, released by HIV-infected cells, has a battery of important biological effects leading to distinct AIDS-associated pathologies. Cell surface heparan sulfate protoglycans (HSPGs have been accepted as endogenous Tat receptors, and the Tat basic domain has been identified as the heparin binding site. However, findings that deletion or substitution of the basic domain inhibits but does not completely eliminate Tat-heparin interactions suggest that the basic domain is not the sole Tat heparin binding site. In the current study, an approach integrating computational modeling, mutagenesis, biophysical and cell-based assays was used to elucidate a novel, high affinity heparin-binding site: a Lys12, Lys41, Arg78 (KKR spatial domain. This domain was also found to facilitate Tat-driven β1 integrin activation, producing subsequent SLK cell adhesion in an HSPG-dependent manner, but was not involved in Tat internalization. The identification of this new heparin binding site may foster further insight into the nature of Tat-heparin interactions and subsequent biological functions, facilitating the rational design of new therapeutics against Tat-mediated pathological events.

  4. Computational Characterization of Small Molecules Binding to the Human XPF Active Site and Virtual Screening to Identify Potential New DNA Repair Inhibitors Targeting the ERCC1-XPF Endonuclease

    Directory of Open Access Journals (Sweden)

    Francesco Gentile

    2018-04-01

    Full Text Available The DNA excision repair protein ERCC-1-DNA repair endonuclease XPF (ERCC1-XPF is a heterodimeric endonuclease essential for the nucleotide excision repair (NER DNA repair pathway. Although its activity is required to maintain genome integrity in healthy cells, ERCC1-XPF can counteract the effect of DNA-damaging therapies such as platinum-based chemotherapy in cancer cells. Therefore, a promising approach to enhance the effect of these therapies is to combine their use with small molecules, which can inhibit the repair mechanisms in cancer cells. Currently, there are no structures available for the catalytic site of the human ERCC1-XPF, which performs the metal-mediated cleavage of a DNA damaged strand at 5′. We adopted a homology modeling strategy to build a structural model of the human XPF nuclease domain which contained the active site and to extract dominant conformations of the domain using molecular dynamics simulations followed by clustering of the trajectory. We investigated the binding modes of known small molecule inhibitors targeting the active site to build a pharmacophore model. We then performed a virtual screening of the ZINC Is Not Commercial 15 (ZINC15 database to identify new ERCC1-XPF endonuclease inhibitors. Our work provides structural insights regarding the binding mode of small molecules targeting the ERCC1-XPF active site that can be used to rationally optimize such compounds. We also propose a set of new potential DNA repair inhibitors to be considered for combination cancer therapy strategies.

  5. Initial direct comparison of 99mTc-TOC and 99mTc-TATE in identifying sites of disease in patients with proven GEP NETs.

    Science.gov (United States)

    Cwikla, Jaroslaw B; Mikolajczak, Renata; Pawlak, Dariusz; Buscombe, John R; Nasierowska-Guttmejer, Anna; Bator, Andrzej; Maecke, Helmut R; Walecki, Jerzy

    2008-07-01

    The imaging of neuroendocrine tumors has become one of the most significant areas in nuclear oncology. In an attempt to provide high-quality imaging and possible sensitivity at a reduced cost, time, and radiation dose, several (99m)Tc agents have been proposed. The aim of this initial study was to compare the tumor uptake and biodistribution of 2 new 6-hydrazinopyridine-3-carboxylic acid (HYNIC)-derivatized Tyr(3)-octreotide analogs, (99m)Tc-[HYNIC,Tyr(3)]octreotide ((99m)Tc-TOC) and (99m)Tc-[HYNIC,Tyr(3),Thr(8)]octreotide ((99m)Tc-TATE), in patients with somatostatin receptor-expressing tumors. Each of 12 patients with proven gastrointestinal pancreatic neuroendocrine tumors received a mean activity of 520 MBq of (99m)Tc-TOC and (99m)Tc-TATE. Scintigraphy with both tracers was performed 3-4 h after their injection using standard whole-body and SPECT imaging. The images were reviewed subjectively by 2 readers, who reported tumor uptake lesion by lesion. Both radiotracers demonstrated concordance between the results in 7 patients (58%). In total, 110 sites of disease were identified with (99m)Tc-TOC, compared with 115 with (99m)Tc-TATE. There was 1 case in which (99m)Tc-TOC identified sites of disease not seen on (99m)Tc-TATE imaging but 4 cases in which some sites of disease were seen with (99m)Tc-TATE and not (99m)Tc-TOC. In this initial study, both tracers seem to show similar sites of tumor, with (99m)Tc-TATE having a slight edge in the total number of lesions seen, especially in lymph node metastases.

  6. Exome Sequencing Identified a Splice Site Mutation in FHL1 that Causes Uruguay Syndrome, an X-Linked Disorder With Skeletal Muscle Hypertrophy and Premature Cardiac Death.

    Science.gov (United States)

    Xue, Yuan; Schoser, Benedikt; Rao, Aliz R; Quadrelli, Roberto; Vaglio, Alicia; Rupp, Verena; Beichler, Christine; Nelson, Stanley F; Schapacher-Tilp, Gudrun; Windpassinger, Christian; Wilcox, William R

    2016-04-01

    Previously, we reported a rare X-linked disorder, Uruguay syndrome in a single family. The main features are pugilistic facies, skeletal deformities, and muscular hypertrophy despite a lack of exercise and cardiac ventricular hypertrophy leading to premature death. An ≈19 Mb critical region on X chromosome was identified through identity-by-descent analysis of 3 affected males. Exome sequencing was conducted on one affected male to identify the disease-causing gene and variant. A splice site variant (c.502-2A>G) in the FHL1 gene was highly suspicious among other candidate genes and variants. FHL1A is the predominant isoform of FHL1 in cardiac and skeletal muscle. Sequencing cDNA showed the splice site variant led to skipping of exons 6 of the FHL1A isoform, equivalent to the FHL1C isoform. Targeted analysis showed that this splice site variant cosegregated with disease in the family. Western blot and immunohistochemical analysis of muscle from the proband showed a significant decrease in protein expression of FHL1A. Real-time polymerase chain reaction analysis of different isoforms of FHL1 demonstrated that the FHL1C is markedly increased. Mutations in the FHL1 gene have been reported in disorders with skeletal and cardiac myopathy but none has the skeletal or facial phenotype seen in patients with Uruguay syndrome. Our data suggest that a novel FHL1 splice site variant results in the absence of FHL1A and the abundance of FHL1C, which may contribute to the complex and severe phenotype. Mutation screening of the FHL1 gene should be considered for patients with uncharacterized myopathies and cardiomyopathies. © 2016 American Heart Association, Inc.

  7. Rhodium(II) Proximity-Labeling Identifies a Novel Target Site on STAT3 for Inhibitors with Potent Anti-Leukemia Activity.

    Science.gov (United States)

    Minus, Matthew B; Liu, Wei; Vohidov, Farrukh; Kasembeli, Moses M; Long, Xin; Krueger, Michael J; Stevens, Alexandra; Kolosov, Mikhail I; Tweardy, David J; Sison, Edward Allan R; Redell, Michele S; Ball, Zachary T

    2015-10-26

    Nearly 40 % of children with acute myeloid leukemia (AML) suffer relapse arising from chemoresistance, often involving upregulation of the oncoprotein STAT3 (signal transducer and activator of transcription 3). Herein, rhodium(II)-catalyzed, proximity-driven modification identifies the STAT3 coiled-coil domain (CCD) as a novel ligand-binding site, and we describe a new naphthalene sulfonamide inhibitor that targets the CCD, blocks STAT3 function, and halts its disease-promoting effects in vitro, in tumor growth models, and in a leukemia mouse model, validating this new therapeutic target for resistant AML. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Identifying the Infection Control Areas Requiring Modifications in Thoracic Surgery Units: Results of a Two-Year Surveillance of Surgical Site Infections in Hospitals in Southern Poland.

    Science.gov (United States)

    Dubiel, Grzegorz; Rogoziński, Paweł; Żaloudik, Elżbieta; Bruliński, Krzysztof; Różańska, Anna; Wójkowska-Mach, Jadwiga

    2017-10-01

    Surgical site infection (SSI) is considered to be a priority in infection control. The objective of this study is the analysis of results of active targeted surveillance conducted over a two-year period in the Department of Thoracic Surgery at the Pulmonology and Thoracic Surgery Center in Bystra, in southern Poland. The retrospective analysis was carried out on the basis of results of active monitoring of SSI in the 45-bed Department of Thoracic Surgery at the Pulmonology and Thoracic Surgery Center in Bystra between April 1, 2014 and April 30, 2016. Surgical site infections were identified based on the definitions of the European Centre for Disease Prevention and Control (ECDC) taking into account the time of symptom onset, specifically, whether the symptoms occurred within 30 d after the surgical procedure. Detection of SSI relied on daily inspection of incisions by a trained nurse, analysis of medical and nursing entries in the computer system, and analysis of all results of microbiologic tests taken in the unit and in the operating room. In the study period, data were collected regarding 1,387 treatment procedures meeting the registration criteria. Forty cases of SSI were detected yielding an incidence rate of 3%. Most cases (55%) were found in the course of hospitalization and 45% were detected after the patient's discharge. The SSIs were classified as follows: superficial, 37.5%; deep infections, 7.5%; and organ/space infection, 55%. Among patients who were diagnosed with SSI, most were male (77.5%). For patients with an American Society of Anesthesiologists (ASA) score I-II the incidence rate was 2%; ASA score III or more, 3.7%. The incidence rate varied from 0.3% in clean surgical site to 6.5% in clean-contaminated site. The study validated the usefulness of targeted surveillance in monitoring SSIs in patients hospitalized in thoracic surgery departments. Surgical site infection surveillance identified areas of care requiring modifications, namely

  9. Brain cortical characteristics of lifetime cognitive ageing.

    Science.gov (United States)

    Cox, Simon R; Bastin, Mark E; Ritchie, Stuart J; Dickie, David Alexander; Liewald, Dave C; Muñoz Maniega, Susana; Redmond, Paul; Royle, Natalie A; Pattie, Alison; Valdés Hernández, Maria; Corley, Janie; Aribisala, Benjamin S; McIntosh, Andrew M; Wardlaw, Joanna M; Deary, Ian J

    2018-01-01

    Regional cortical brain volume is the product of surface area and thickness. These measures exhibit partially distinct trajectories of change across the brain's cortex in older age, but it is unclear which cortical characteristics at which loci are sensitive to cognitive ageing differences. We examine associations between change in intelligence from age 11 to 73 years and regional cortical volume, surface area, and thickness measured at age 73 years in 568 community-dwelling older adults, all born in 1936. A relative positive change in intelligence from 11 to 73 was associated with larger volume and surface area in selective frontal, temporal, parietal, and occipital regions (r cognitive ageing and a thinner cortex for any region. Interestingly, thickness and surface area were phenotypically independent across bilateral lateral temporal loci, whose surface area was significantly related to change in intelligence. These findings suggest that associations between regional cortical volume and cognitive ageing differences are predominantly driven by surface area rather than thickness among healthy older adults. Regional brain surface area has been relatively underexplored, and is a potentially informative biomarker for identifying determinants of cognitive ageing differences.

  10. Altered Regional Brain Cortical Thickness in Pediatric Obstructive Sleep Apnea

    Directory of Open Access Journals (Sweden)

    Paul M. Macey

    2018-01-01

    Full Text Available RationaleObstructive sleep apnea (OSA affects 2–5% of all children and is associated with cognitive and behavioral deficits, resulting in poor school performance. These psychological deficits may arise from brain injury, as seen in preliminary findings of lower gray matter volume among pediatric OSA patients. However, the psychological deficits in OSA are closely related to functions in the cortex, and such brain areas have not been specifically assessed. The objective was to determine whether cortical thickness, a marker of possible brain injury, is altered in children with OSA.MethodsWe examined regional brain cortical thicknesses using high-resolution T1-weighted magnetic resonance images in 16 pediatric OSA patients (8 males; mean age ± SD = 8.4 ± 1.2 years; mean apnea/hypopnea index ± SD = 11 ± 6 events/h and 138 controls (8.3 ± 1.1 years; 62 male; 138 subjects from the NIH Pediatric MRI database to identify cortical thickness differences in pediatric OSA subjects.ResultsCortical thinning occurred in multiple regions including the superior frontal, ventral medial prefrontal, and superior parietal cortices. The left side showed greater thinning in the superior frontal cortex. Cortical thickening was observed in bilateral precentral gyrus, mid-to-posterior insular cortices, and left central gyrus, as well as right anterior insula cortex.ConclusionChanges in cortical thickness are present in children with OSA and likely indicate disruption to neural developmental processes, including maturational patterns of cortical volume increases and synaptic pruning. Regions with thicker cortices may reflect inflammation or astrocyte activation. Both the thinning and thickening associated with OSA in children may contribute to the cognitive and behavioral dysfunction frequently found in the condition.

  11. In Silico Analysis of Gene Expression Network Components Underlying Pigmentation Phenotypes in the Python Identified Evolutionarily Conserved Clusters of Transcription Factor Binding Sites

    Directory of Open Access Journals (Sweden)

    Kristopher J. L. Irizarry

    2016-01-01

    Full Text Available Color variation provides the opportunity to investigate the genetic basis of evolution and selection. Reptiles are less studied than mammals. Comparative genomics approaches allow for knowledge gained in one species to be leveraged for use in another species. We describe a comparative vertebrate analysis of conserved regulatory modules in pythons aimed at assessing bioinformatics evidence that transcription factors important in mammalian pigmentation phenotypes may also be important in python pigmentation phenotypes. We identified 23 python orthologs of mammalian genes associated with variation in coat color phenotypes for which we assessed the extent of pairwise protein sequence identity between pythons and mouse, dog, horse, cow, chicken, anole lizard, and garter snake. We next identified a set of melanocyte/pigment associated transcription factors (CREB, FOXD3, LEF-1, MITF, POU3F2, and USF-1 that exhibit relatively conserved sequence similarity within their DNA binding regions across species based on orthologous alignments across multiple species. Finally, we identified 27 evolutionarily conserved clusters of transcription factor binding sites within ~200-nucleotide intervals of the 1500-nucleotide upstream regions of AIM1, DCT, MC1R, MITF, MLANA, OA1, PMEL, RAB27A, and TYR from Python bivittatus. Our results provide insight into pigment phenotypes in pythons.

  12. No Association between Cortical Gyrification or Intrinsic Curvature and Attention-deficit/Hyperactivity Disorder in Adolescents and Young Adults

    Directory of Open Access Journals (Sweden)

    Natalie J. Forde

    2017-04-01

    Full Text Available Magnetic resonance imaging (MRI studies have highlighted subcortical, cortical, and structural connectivity abnormalities associated with attention-deficit/hyperactivity disorder (ADHD. Gyrification investigations of the cortex have been inconsistent and largely negative, potentially due to a lack of sensitivity of the previously used morphological parameters. The innovative approach of applying intrinsic curvature analysis, which is predictive of gyrification pattern, to the cortical surface applied herein allowed us greater sensitivity to determine whether the structural connectivity abnormalities thus far identified at a centimeter scale also occur at a millimeter scale within the cortical surface. This could help identify neurodevelopmental processes that contribute to ADHD. Structural MRI datasets from the NeuroIMAGE project were used [n = 306 ADHD, n = 164 controls, and n = 148 healthy siblings of individuals with ADHD (age in years, mean(sd; 17.2 (3.4, 16.8 (3.2, and 17.7 (3.8, respectively]. Reconstructions of the cortical surfaces were computed with FreeSurfer. Intrinsic curvature (taken as a marker of millimeter-scale surface connectivity and local gyrification index were calculated for each point on the surface (vertex with Caret and FreeSurfer, respectively. Intrinsic curvature skew and mean local gyrification index were extracted per region; frontal, parietal, temporal, occipital, cingulate, and insula. A generalized additive model was used to compare the trajectory of these measures between groups over age, with sex, scanner site, total surface area of hemisphere, and familiality accounted for. After correcting for sex, scanner site, and total surface area no group differences were found in the developmental trajectory of intrinsic curvature or local gyrification index. Despite the increased sensitivity of intrinsic curvature, compared to gyrification measures, to subtle morphological abnormalities of the cortical surface we found

  13. Mass spectrometry and site-directed mutagenesis identify several autophosphorylated residues required for the activity of PrkC, a Ser/Thr kinase from Bacillus subtilis

    DEFF Research Database (Denmark)

    Madec, Edwige; Stensballe, Allan; Kjellström, Sven

    2003-01-01

    We have shown recently that PrkC, which is involved in developmental processes in Bacillus subtilis, is a Ser/Thr kinase with features of the receptor kinase family of eukaryotic Hanks kinases. In this study, we expressed and purified from Escherichia coli the cytoplasmic domain of PrkC containing...... the kinase and a short juxtamembrane region. This fragment, which we designate PrkCc, undergoes autophosphorylation in E.coli. PrkCc is further autophosphorylated in vitro, apparently through a trans-kinase, intermolecular reaction. PrkC also displays kinase activity with myelin basic protein. Using high...... mass accuracy electrospray tandem mass spectrometry (LC-MS/MS) and nanoelectrospray tandem mass spectrometry, we identified seven phosphorylated threonine and one serine residue in PrkCc. All the corresponding residues were replaced by systematic site-directed mutagenesis and the purified mutant...

  14. Site-Mutation of Hydrophobic Core Residues Synchronically Poise Super Interleukin 2 for Signaling: Identifying Distant Structural Effects through Affordable Computations

    Directory of Open Access Journals (Sweden)

    Longcan Mei

    2018-03-01

    Full Text Available A superkine variant of interleukin-2 with six site mutations away from the binding interface developed from the yeast display technique has been previously characterized as undergoing a distal structure alteration which is responsible for its super-potency and provides an elegant case study with which to get insight about how to utilize allosteric effect to achieve desirable protein functions. By examining the dynamic network and the allosteric pathways related to those mutated residues using various computational approaches, we found that nanosecond time scale all-atom molecular dynamics simulations can identify the dynamic network as efficient as an ensemble algorithm. The differentiated pathways for the six core residues form a dynamic network that outlines the area of structure alteration. The results offer potentials of using affordable computing power to predict allosteric structure of mutants in knowledge-based mutagenesis.

  15. Structure-guided approach identifies a novel class of HIV-1 ribonuclease H inhibitors: binding mode insights through magnesium complexation and site-directed mutagenesis studies

    DEFF Research Database (Denmark)

    Poongavanam, Vasanthanathan; Corona, Angela; Steinmann, Casper

    2018-01-01

    is a long and expensive process that can be speeded up by in silico methods. In the present study, a structure-guided screening is coupled with a similarity-based search on the Specs database to identify a new class of HIV-1 RNase H inhibitors. Out of the 45 compounds selected for experimental testing, 15...... inhibited the RNase H function below 100 μM with three hits exhibiting IC50 values active compound, AA, inhibits HIV-1 RNase H with an IC50 of 5.1 μM and exhibits a Mg-independent mode of inhibition. Site-directed mutagenesis studies provide valuable insight into the binding mode of newly...

  16. Dominant mutations in S. cerevisiae PMS1 identify the Mlh1-Pms1 endonuclease active site and an exonuclease 1-independent mismatch repair pathway.

    Directory of Open Access Journals (Sweden)

    Catherine E Smith

    2013-10-01

    Full Text Available Lynch syndrome (hereditary nonpolypsis colorectal cancer or HNPCC is a common cancer predisposition syndrome. Predisposition to cancer in this syndrome results from increased accumulation of mutations due to defective mismatch repair (MMR caused by a mutation in one of the mismatch repair genes MLH1, MSH2, MSH6 or PMS2/scPMS1. To better understand the function of Mlh1-Pms1 in MMR, we used Saccharomyces cerevisiae to identify six pms1 mutations (pms1-G683E, pms1-C817R, pms1-C848S, pms1-H850R, pms1-H703A and pms1-E707A that were weakly dominant in wild-type cells, which surprisingly caused a strong MMR defect when present on low copy plasmids in an exo1Δ mutant. Molecular modeling showed these mutations caused amino acid substitutions in the metal coordination pocket of the Pms1 endonuclease active site and biochemical studies showed that they inactivated the endonuclease activity. This model of Mlh1-Pms1 suggested that the Mlh1-FERC motif contributes to the endonuclease active site. Consistent with this, the mlh1-E767stp mutation caused both MMR and endonuclease defects similar to those caused by the dominant pms1 mutations whereas mutations affecting the predicted metal coordinating residue Mlh1-C769 had no effect. These studies establish that the Mlh1-Pms1 endonuclease is required for MMR in a previously uncharacterized Exo1-independent MMR pathway.

  17. Dominant mutations in S. cerevisiae PMS1 identify the Mlh1-Pms1 endonuclease active site and an exonuclease 1-independent mismatch repair pathway.

    Science.gov (United States)

    Smith, Catherine E; Mendillo, Marc L; Bowen, Nikki; Hombauer, Hans; Campbell, Christopher S; Desai, Arshad; Putnam, Christopher D; Kolodner, Richard D

    2013-10-01

    Lynch syndrome (hereditary nonpolypsis colorectal cancer or HNPCC) is a common cancer predisposition syndrome. Predisposition to cancer in this syndrome results from increased accumulation of mutations due to defective mismatch repair (MMR) caused by a mutation in one of the mismatch repair genes MLH1, MSH2, MSH6 or PMS2/scPMS1. To better understand the function of Mlh1-Pms1 in MMR, we used Saccharomyces cerevisiae to identify six pms1 mutations (pms1-G683E, pms1-C817R, pms1-C848S, pms1-H850R, pms1-H703A and pms1-E707A) that were weakly dominant in wild-type cells, which surprisingly caused a strong MMR defect when present on low copy plasmids in an exo1Δ mutant. Molecular modeling showed these mutations caused amino acid substitutions in the metal coordination pocket of the Pms1 endonuclease active site and biochemical studies showed that they inactivated the endonuclease activity. This model of Mlh1-Pms1 suggested that the Mlh1-FERC motif contributes to the endonuclease active site. Consistent with this, the mlh1-E767stp mutation caused both MMR and endonuclease defects similar to those caused by the dominant pms1 mutations whereas mutations affecting the predicted metal coordinating residue Mlh1-C769 had no effect. These studies establish that the Mlh1-Pms1 endonuclease is required for MMR in a previously uncharacterized Exo1-independent MMR pathway.

  18. Radiation Therapy Deficiencies Identified During On-Site Dosimetry Visits by the Imaging and Radiation Oncology Core Houston Quality Assurance Center.

    Science.gov (United States)

    Kry, Stephen F; Dromgoole, Lainy; Alvarez, Paola; Leif, Jessica; Molineu, Andrea; Taylor, Paige; Followill, David S

    2017-12-01

    To review the dosimetric, mechanical, and programmatic deficiencies most frequently observed during on-site visits of radiation therapy facilities by the Imaging and Radiation Oncology Core Quality Assurance Center in Houston (IROC Houston). The findings of IROC Houston between 2000 and 2014, including 409 institutions and 1020 linear accelerators (linacs), were compiled. On-site evaluations by IROC Houston include verification of absolute calibration (tolerance of ±3%), relative dosimetric review (tolerances of ±2% between treatment planning system [TPS] calculation and measurement), mechanical evaluation (including multileaf collimator and kilovoltage-megavoltage isocenter evaluation against Task Group [TG]-142 tolerances), and general programmatic review (including institutional quality assurance program vs TG-40 and TG-142). An average of 3.1 deficiencies was identified at each institution visited, a number that has decreased slightly with time. The most common errors are tabulated and include TG-40/TG-142 compliance (82% of institutions were deficient), small field size output factors (59% of institutions had errors ≥3%), and wedge factors (33% of institutions had errors ≥3%). Dosimetric errors of ≥10%, including in beam calibration, were seen at many institutions. There is substantial room for improvement of both dosimetric and programmatic issues in radiation therapy, which should be a high priority for the medical physics community. Particularly relevant was suboptimal beam modeling in the TPS and a corresponding failure to detect these errors by not including TPS data in the linac quality assurance process. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Cortico-cortical communication dynamics

    Directory of Open Access Journals (Sweden)

    Per E Roland

    2014-05-01

    Full Text Available IIn principle, cortico-cortical communication dynamics is simple: neurons in one cortical area communicate by sending action potentials that release glutamate and excite their target neurons in other cortical areas. In practice, knowledge about cortico-cortical communication dynamics is minute. One reason is that no current technique can capture the fast spatio-temporal cortico-cortical evolution of action potential transmission and membrane conductances with sufficient spatial resolution. A combination of optogenetics and monosynaptic tracing with virus can reveal the spatio-temporal cortico-cortical dynamics of specific neurons and their targets, but does not reveal how the dynamics evolves under natural conditions. Spontaneous ongoing action potentials also spread across cortical areas and are difficult to separate from structured evoked and intrinsic brain activity such as thinking. At a certain state of evolution, the dynamics may engage larger populations of neurons to drive the brain to decisions, percepts and behaviors. For example, successfully evolving dynamics to sensory transients can appear at the mesoscopic scale revealing how the transient is perceived. As a consequence of these methodological and conceptual difficulties, studies in this field comprise a wide range of computational models, large-scale measurements (e.g., by MEG, EEG, and a combination of invasive measurements in animal experiments. Further obstacles and challenges of studying cortico-cortical communication dynamics are outlined in this critical review.

  20. Retrosplenial cortical thinning as a possible major contributor for cognitive impairment in HIV patients

    International Nuclear Information System (INIS)

    Shin, Na-Young; Hong, Jinwoo; Yoon, Uicheul; Choi, Jun Yong; Lee, Seung-Koo; Lim, Soo Mee

    2017-01-01

    To identify brain cortical regions relevant to HIV-associated neurocognitive disorder (HAND) in HIV patients. HIV patients with HAND (n = 10), those with intact cognition (HIV-IC; n = 12), and age-matched, seronegative controls (n = 11) were recruited. All participants were male and underwent 3-dimensional T1-weighted imaging. Both vertex-wise and region of interest (ROI) analyses were performed to analyse cortical thickness. Compared to controls, both HIV-IC and HAND showed decreased cortical thickness mainly in the bilateral primary sensorimotor areas, extending to the prefrontal and parietal cortices. When directly comparing HIV-IC and HAND, HAND showed cortical thinning in the left retrosplenial cortex, left dorsolateral prefrontal cortex, left inferior parietal lobule, bilateral superior medial prefrontal cortices, right temporoparietal junction and left hippocampus, and cortical thickening in the left middle occipital cortex. Left retrosplenial cortical thinning showed significant correlation with slower information processing, declined verbal memory and executive function, and impaired fine motor skills. This study supports previous research suggesting the selective vulnerability of the primary sensorimotor cortices and associations between cortical thinning in the prefrontal and parietal cortices and cognitive impairment in HIV-infected patients. Furthermore, for the first time, we propose retrosplenial cortical thinning as a possible major contributor to HIV-associated cognitive impairment. (orig.)

  1. Retrosplenial cortical thinning as a possible major contributor for cognitive impairment in HIV patients

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Na-Young [The Catholic University of Korea, Department of Radiology, College of Medicine, Seoul (Korea, Republic of); Hong, Jinwoo; Yoon, Uicheul [Catholic University of Daegu, Department of Biomedical Engineering, College of Health and Medical Science, Gyeongsan-si, Gyeongbuk (Korea, Republic of); Choi, Jun Yong [Yonsei University College of Medicine, Department of Internal Medicine and AIDS Research Institute, Seoul (Korea, Republic of); Lee, Seung-Koo [Yonsei University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Lim, Soo Mee [Ewha Womans University, School of Medicine, Department of Radiology, Seoul (Korea, Republic of)

    2017-11-15

    To identify brain cortical regions relevant to HIV-associated neurocognitive disorder (HAND) in HIV patients. HIV patients with HAND (n = 10), those with intact cognition (HIV-IC; n = 12), and age-matched, seronegative controls (n = 11) were recruited. All participants were male and underwent 3-dimensional T1-weighted imaging. Both vertex-wise and region of interest (ROI) analyses were performed to analyse cortical thickness. Compared to controls, both HIV-IC and HAND showed decreased cortical thickness mainly in the bilateral primary sensorimotor areas, extending to the prefrontal and parietal cortices. When directly comparing HIV-IC and HAND, HAND showed cortical thinning in the left retrosplenial cortex, left dorsolateral prefrontal cortex, left inferior parietal lobule, bilateral superior medial prefrontal cortices, right temporoparietal junction and left hippocampus, and cortical thickening in the left middle occipital cortex. Left retrosplenial cortical thinning showed significant correlation with slower information processing, declined verbal memory and executive function, and impaired fine motor skills. This study supports previous research suggesting the selective vulnerability of the primary sensorimotor cortices and associations between cortical thinning in the prefrontal and parietal cortices and cognitive impairment in HIV-infected patients. Furthermore, for the first time, we propose retrosplenial cortical thinning as a possible major contributor to HIV-associated cognitive impairment. (orig.)

  2. Quantitative in vivo analyses reveal calcium-dependent phosphorylation sites and identifies a novel component of the Toxoplasma invasion motor complex.

    Directory of Open Access Journals (Sweden)

    Thomas Nebl

    2011-09-01

    Full Text Available Apicomplexan parasites depend on the invasion of host cells for survival and proliferation. Calcium-dependent signaling pathways appear to be essential for micronemal release and gliding motility, yet the target of activated kinases remains largely unknown. We have characterized calcium-dependent phosphorylation events during Toxoplasma host cell invasion. Stimulation of live tachyzoites with Ca²⁺-mobilizing drugs leads to phosphorylation of numerous parasite proteins, as shown by differential 2-DE display of ³²[P]-labeled protein extracts. Multi-dimensional Protein Identification Technology (MudPIT identified ∼546 phosphorylation sites on over 300 Toxoplasma proteins, including 10 sites on the actomyosin invasion motor. Using a Stable Isotope of Amino Acids in Culture (SILAC-based quantitative LC-MS/MS analyses we monitored changes in the abundance and phosphorylation of the invasion motor complex and defined Ca²⁺-dependent phosphorylation patterns on three of its components--GAP45, MLC1 and MyoA. Furthermore, calcium-dependent phosphorylation of six residues across GAP45, MLC1 and MyoA is correlated with invasion motor activity. By analyzing proteins that appear to associate more strongly with the invasion motor upon calcium stimulation we have also identified a novel 15-kDa Calmodulin-like protein that likely represents the MyoA Essential Light Chain of the Toxoplasma invasion motor. This suggests that invasion motor activity could be regulated not only by phosphorylation but also by the direct binding of calcium ions to this new component.

  3. Multi-species comparative analysis of the equine ACE gene identifies a highly conserved potential transcription factor binding site in intron 16.

    Science.gov (United States)

    Hamilton, Natasha A; Tammen, Imke; Raadsma, Herman W

    2013-01-01

    Angiotensin converting enzyme (ACE) is essential for control of blood pressure. The human ACE gene contains an intronic Alu indel (I/D) polymorphism that has been associated with variation in serum enzyme levels, although the functional mechanism has not been identified. The polymorphism has also been associated with cardiovascular disease, type II diabetes, renal disease and elite athleticism. We have characterized the ACE gene in horses of breeds selected for differing physical abilities. The equine gene has a similar structure to that of all known mammalian ACE genes. Nine common single nucleotide polymorphisms (SNPs) discovered in pooled DNA were found to be inherited in nine haplotypes. Three of these SNPs were located in intron 16, homologous to that containing the Alu polymorphism in the human. A highly conserved 18 bp sequence, also within that intron, was identified as being a potential binding site for the transcription factors Oct-1, HFH-1 and HNF-3β, and lies within a larger area of higher than normal homology. This putative regulatory element may contribute to regulation of the documented inter-individual variation in human circulating enzyme levels, for which a functional mechanism is yet to be defined. Two equine SNPs occurred within the conserved area in intron 16, although neither of them disrupted the putative binding site. We propose a possible regulatory mechanism of the ACE gene in mammalian species which was previously unknown. This advance will allow further analysis leading to a better understanding of the mechanisms underpinning the associations seen between the human Alu polymorphism and enzyme levels, cardiovascular disease states and elite athleticism.

  4. Multi-species comparative analysis of the equine ACE gene identifies a highly conserved potential transcription factor binding site in intron 16.

    Directory of Open Access Journals (Sweden)

    Natasha A Hamilton

    Full Text Available Angiotensin converting enzyme (ACE is essential for control of blood pressure. The human ACE gene contains an intronic Alu indel (I/D polymorphism that has been associated with variation in serum enzyme levels, although the functional mechanism has not been identified. The polymorphism has also been associated with cardiovascular disease, type II diabetes, renal disease and elite athleticism. We have characterized the ACE gene in horses of breeds selected for differing physical abilities. The equine gene has a similar structure to that of all known mammalian ACE genes. Nine common single nucleotide polymorphisms (SNPs discovered in pooled DNA were found to be inherited in nine haplotypes. Three of these SNPs were located in intron 16, homologous to that containing the Alu polymorphism in the human. A highly conserved 18 bp sequence, also within that intron, was identified as being a potential binding site for the transcription factors Oct-1, HFH-1 and HNF-3β, and lies within a larger area of higher than normal homology. This putative regulatory element may contribute to regulation of the documented inter-individual variation in human circulating enzyme levels, for which a functional mechanism is yet to be defined. Two equine SNPs occurred within the conserved area in intron 16, although neither of them disrupted the putative binding site. We propose a possible regulatory mechanism of the ACE gene in mammalian species which was previously unknown. This advance will allow further analysis leading to a better understanding of the mechanisms underpinning the associations seen between the human Alu polymorphism and enzyme levels, cardiovascular disease states and elite athleticism.

  5. Monoclonal antibody OKB7, which identifies the 14OKd complement receptor type 2 (CR/sub 2/), also identifies a 72Kd secreted fragment of CR/sub 2/ that contains the C3d-binding site

    Energy Technology Data Exchange (ETDEWEB)

    Myones, B.L.; Ross, G.D.

    1986-03-05

    CR/sub 2/ is a 140-145Kd glycoprotein expressed on B lymphocytes which binds both C3d and Epstein-Barr virus (EBV). OKB7, an IgG/sub 2a/ monoclonal antibody to CR/sub 2/, blocks C3d and EBV binding, while HB-5, another monoclonal IgG/sub 2a/ anti-CR/sub 2/, does not. A 72Kd C3d-binding glycoprotein (gp72), isolated from Raji cell media, was previously thought to be CR/sub 2/ because a polyclonal rabbit anti-gp72 inhibited EC3d rosettes. ELISA assay demonstrated that OKB7, but not HB-5, bound to purified gp72 fixed to microtiter wells. Insoluble and soluble gp72 blocked Raji cell uptake of /sup 125/I-labeled OKB7, but not labeled anti-B2 or HB-5. Rabbit anti-gp72 immunoprecipitated bands at 140Kd and 72Kd from /sup 125/I-labelled and solubilized B cell membranes. Culture media from Raji cells grown in the presence /sup 3/H-labeled amino acids was sequentially immunoprecipitated by irrelevant antibody, OKB7, and HB-5. A single 72Kd radiolabeled band was demonstrated only with OKB7, and this was identical to that produced by the immunoprecipitation of /sup 125/I-labeled gp72 with rabbit anti-gp72. Thus, OKB7, which identifies the 140Kd CR/sub 2/ molecule, also identifies a 72Kd shed fragment of CR/sub 2/ isolated from Raji cell media, which contains the C3d-binding site.

  6. Monoclonal antibody OKB7, which identifies the 14OKd complement receptor type 2 (CR2), also identifies a 72Kd secreted fragment of CR2 that contains the C3d-binding site

    International Nuclear Information System (INIS)

    Myones, B.L.; Ross, G.D.

    1986-01-01

    CR 2 is a 140-145Kd glycoprotein expressed on B lymphocytes which binds both C3d and Epstein-Barr virus (EBV). OKB7, an IgG/sub 2a/ monoclonal antibody to CR 2 , blocks C3d and EBV binding, while HB-5, another monoclonal IgG/sub 2a/ anti-CR 2 , does not. A 72Kd C3d-binding glycoprotein (gp72), isolated from Raji cell media, was previously thought to be CR 2 because a polyclonal rabbit anti-gp72 inhibited EC3d rosettes. ELISA assay demonstrated that OKB7, but not HB-5, bound to purified gp72 fixed to microtiter wells. Insoluble and soluble gp72 blocked Raji cell uptake of 125 I-labeled OKB7, but not labeled anti-B2 or HB-5. Rabbit anti-gp72 immunoprecipitated bands at 140Kd and 72Kd from 125 I-labelled and solubilized B cell membranes. Culture media from Raji cells grown in the presence 3 H-labeled amino acids was sequentially immunoprecipitated by irrelevant antibody, OKB7, and HB-5. A single 72Kd radiolabeled band was demonstrated only with OKB7, and this was identical to that produced by the immunoprecipitation of 125 I-labeled gp72 with rabbit anti-gp72. Thus, OKB7, which identifies the 140Kd CR 2 molecule, also identifies a 72Kd shed fragment of CR 2 isolated from Raji cell media, which contains the C3d-binding site

  7. Progressive posterior cortical dysfunction

    Directory of Open Access Journals (Sweden)

    Fábio Henrique de Gobbi Porto

    Full Text Available Abstract Progressive posterior cortical dysfunction (PPCD is an insidious syndrome characterized by prominent disorders of higher visual processing. It affects both dorsal (occipito-parietal and ventral (occipito-temporal pathways, disturbing visuospatial processing and visual recognition, respectively. We report a case of a 67-year-old woman presenting with progressive impairment of visual functions. Neurologic examination showed agraphia, alexia, hemispatial neglect (left side visual extinction, complete Balint's syndrome and visual agnosia. Magnetic resonance imaging showed circumscribed atrophy involving the bilateral parieto-occipital regions, slightly more predominant to the right . Our aim was to describe a case of this syndrome, to present a video showing the main abnormalities, and to discuss this unusual presentation of dementia. We believe this article can contribute by improving the recognition of PPCD.

  8. Progressive posterior cortical dysfunction

    Science.gov (United States)

    Porto, Fábio Henrique de Gobbi; Machado, Gislaine Cristina Lopes; Morillo, Lilian Schafirovits; Brucki, Sonia Maria Dozzi

    2010-01-01

    Progressive posterior cortical dysfunction (PPCD) is an insidious syndrome characterized by prominent disorders of higher visual processing. It affects both dorsal (occipito-parietal) and ventral (occipito-temporal) pathways, disturbing visuospatial processing and visual recognition, respectively. We report a case of a 67-year-old woman presenting with progressive impairment of visual functions. Neurologic examination showed agraphia, alexia, hemispatial neglect (left side visual extinction), complete Balint’s syndrome and visual agnosia. Magnetic resonance imaging showed circumscribed atrophy involving the bilateral parieto-occipital regions, slightly more predominant to the right. Our aim was to describe a case of this syndrome, to present a video showing the main abnormalities, and to discuss this unusual presentation of dementia. We believe this article can contribute by improving the recognition of PPCD. PMID:29213665

  9. Modeling cortical circuits.

    Energy Technology Data Exchange (ETDEWEB)

    Rohrer, Brandon Robinson; Rothganger, Fredrick H.; Verzi, Stephen J.; Xavier, Patrick Gordon

    2010-09-01

    The neocortex is perhaps the highest region of the human brain, where audio and visual perception takes place along with many important cognitive functions. An important research goal is to describe the mechanisms implemented by the neocortex. There is an apparent regularity in the structure of the neocortex [Brodmann 1909, Mountcastle 1957] which may help simplify this task. The work reported here addresses the problem of how to describe the putative repeated units ('cortical circuits') in a manner that is easily understood and manipulated, with the long-term goal of developing a mathematical and algorithmic description of their function. The approach is to reduce each algorithm to an enhanced perceptron-like structure and describe its computation using difference equations. We organize this algorithmic processing into larger structures based on physiological observations, and implement key modeling concepts in software which runs on parallel computing hardware.

  10. A 1.4-Billion Pixel Map of the Seafloor: BOEM's Mission to Visualize Dynamic Geology and Identify Natural Seep Sites in the Gulf of Mexico

    Science.gov (United States)

    Kramer, K.; Shedd, W. W.

    2017-12-01

    In May, 2017, the U.S. Department of the Interior's Bureau of Ocean Energy Management (BOEM) published a high-resolution seafloor map of the northern Gulf of Mexico region. The new map, derived from 3-D seismic surveys, provides the scientific community with enhanced resolution and reveals previously undiscovered and poorly resolved geologic features of the continental slope, salt minibasin province, abyssal plain, Mississippi Fan, and the Florida Shelf and Escarpment. It becomes an even more powerful scientific tool when paired with BOEM's public database of 35,000 seafloor features, identifying natural hydrocarbon seeps, hard grounds, mud volcanoes, sediment flows, pockmarks, slumps, and many others. BOEM has mapped the Gulf of Mexico seafloor since 1998 in a regulatory mission to identify natural oil and gas seeps and protect the coral and chemosynthetic communities growing at those sites. The nineteen-year mapping effort, still ongoing, resulted in the creation of the 1.4-billion pixel map and the seafloor features database. With these tools and continual collaboration with academia, professional scientific institutions, and the offshore energy industry, BOEM will continue to incorporate new data to update and expand these two resources on a regular basis. They can be downloaded for free from BOEM's website at https://www.boem.gov/Gulf-of-Mexico-Deepwater-Bathymetry/ and https://www.boem.gov/Seismic-Water-Bottom-Anomalies-Map-Gallery/.

  11. Identifying key controls on the behavior of an acidic-U(VI) plume in the Savannah River Site using reactive transport modeling.

    Science.gov (United States)

    Bea, Sergio A; Wainwright, Haruko; Spycher, Nicolas; Faybishenko, Boris; Hubbard, Susan S; Denham, Miles E

    2013-08-01

    Acidic low-level waste radioactive waste solutions were discharged to three unlined seepage basins at the F-Area of the Department of Energy (DOE) Savannah River Site (SRS), South Carolina, USA, from 1955 through 1989. Despite many years of active remediation, the groundwater remains acidic and contaminated with significant levels of U(VI) and other radionuclides. Monitored Natural Attenuation (MNA) is a desired closure strategy for the site, based on the premise that regional flow of clean background groundwater will eventually neutralize the groundwater acidity, immobilizing U(VI) through adsorption. An in situ treatment system is currently in place to accelerate this in the downgradient portion of the plume and similar measures could be taken upgradient if necessary. Understanding the long-term pH and U(VI) adsorption behavior at the site is critical to assess feasibility of MNA along with the in-situ remediation treatments. This paper presents a reactive transport (RT) model and uncertainty quantification (UQ) analyses to explore key controls on the U(VI)-plume evolution and long-term mobility at this site. Two-dimensional numerical RT simulations are run including the saturated and unsaturated (vadose) zones, U(VI) and H(+) adsorption (surface complexation) onto sediments, dissolution and precipitation of Al and Fe minerals, and key hydrodynamic processes are considered. UQ techniques are applied using a new open-source tool that is part of the developing ASCEM reactive transport modeling and analysis framework to: (1) identify the complex physical and geochemical processes that control the U(VI) plume migration in the pH range where the plume is highly mobile, (2) evaluate those physical and geochemical parameters that are most controlling, and (3) predict the future plume evolution constrained by historical, chemical and hydrological data. The RT simulation results show a good agreement with the observed historical pH and concentrations of U(VI), nitrates

  12. Extensive cortical rewiring after brain injury.

    Science.gov (United States)

    Dancause, Numa; Barbay, Scott; Frost, Shawn B; Plautz, Erik J; Chen, Daofen; Zoubina, Elena V; Stowe, Ann M; Nudo, Randolph J

    2005-11-02

    Previously, we showed that the ventral premotor cortex (PMv) underwent neurophysiological remodeling after injury to the primary motor cortex (M1). In the present study, we examined cortical connections of PMv after such lesions. The neuroanatomical tract tracer biotinylated dextran amine was injected into the PMv hand area at least 5 months after ischemic injury to the M1 hand area. Comparison of labeling patterns between experimental and control animals demonstrated extensive proliferation of novel PMv terminal fields and the appearance of retrogradely labeled cell bodies within area 1/2 of the primary somatosensory cortex after M1 injury. Furthermore, evidence was found for alterations in the trajectory of PMv intracortical axons near the site of the lesion. The results suggest that M1 injury results in axonal sprouting near the ischemic injury and the establishment of novel connections within a distant target. These results support the hypothesis that, after a cortical injury, such as occurs after stroke, cortical areas distant from the injury undergo major neuroanatomical reorganization. Our results reveal an extraordinary anatomical rewiring capacity in the adult CNS after injury that may potentially play a role in recovery.

  13. Neuregulin 3 Mediates Cortical Plate Invasion and Laminar Allocation of GABAergic Interneurons

    Directory of Open Access Journals (Sweden)

    Giorgia Bartolini

    2017-01-01

    Full Text Available Neural circuits in the cerebral cortex consist of excitatory pyramidal cells and inhibitory interneurons. These two main classes of cortical neurons follow largely different genetic programs, yet they assemble into highly specialized circuits during development following a very precise choreography. Previous studies have shown that signals produced by pyramidal cells influence the migration of cortical interneurons, but the molecular nature of these factors has remained elusive. Here, we identified Neuregulin 3 (Nrg3 as a chemoattractive factor expressed by developing pyramidal cells that guides the allocation of cortical interneurons in the developing cortical plate. Gain- and loss-of-function approaches reveal that Nrg3 modulates the migration of interneurons into the cortical plate in a process that is dependent on the tyrosine kinase receptor ErbB4. Perturbation of Nrg3 signaling in conditional mutants leads to abnormal lamination of cortical interneurons. Nrg3 is therefore a critical mediator in the assembly of cortical inhibitory circuits.

  14. Antigenic Fingerprinting following Primary RSV Infection in Young Children Identifies Novel Antigenic Sites and Reveals Unlinked Evolution of Human Antibody Repertoires to Fusion and Attachment Glycoproteins.

    Directory of Open Access Journals (Sweden)

    Sandra Fuentes

    2016-04-01

    Full Text Available Respiratory Syncytial Virus (RSV is the major cause of pneumonia among infants. Here we elucidated the antibody repertoire following primary RSV infection and traced its evolution through adolescence and adulthood. Whole genome-fragment phage display libraries (GFPDL expressing linear and conformational epitopes in the RSV fusion protein (F and attachment protein (G were used for unbiased epitope profiling of infant sera prior to and following RSV infection. F-GFPDL analyses demonstrated modest changes in the anti-F epitope repertoires post-RSV infection, while G-GFPDL analyses revealed 100-fold increase in number of bound phages. The G-reactive epitopes spanned the N- and C-terminus of the G ectodomain, along with increased reactivity to the central conserved domain (CCD. Panels of F and G antigenic sites were synthesized to evaluate sera from young children (<2 yr, adolescents (14-18 yr and adults (30-45 yr in SPR real-time kinetics assays. A steady increase in RSV-F epitope repertoires from young children to adults was observed using peptides and F proteins. Importantly, several novel epitopes were identified in pre-fusion F and an immunodominant epitope in the F-p27. In all age groups, antibody binding to pre-fusion F was 2-3 folds higher than to post-fusion form. For RSV-G, antibody responses were high following early RSV infection in children, but declined significantly in adults, using either G proteins or peptides. This study identified unlinked evolution of anti-F and anti G responses and supportive evidence for immune pressure driven evolution of RSV-G. These findings could help development of effective countermeasures including vaccines.

  15. Use of a scenario-development procedure to identify potentially disruptive scenarios, Greater Confinement Disposal facility, Area 5, Nevada Test Site

    International Nuclear Information System (INIS)

    Guzowski, R.V.; Sandia National Labs., Albuquerque, NM

    1994-01-01

    The Greater Confinement Disposal (GCD) facility includes four boreholes that contain transuranic (TRLT) waste. Presence of the TRU waste means that this facility must comply with the US Environmental Protection Agency's Environmental Radiation Protection Standards for Management and Disposal of Spent Nuclear Fuel, High-Level and Transuranic Waste-Final Rule 40 CFR Part 191. To comply with the Containment Requirements of this rule, all potentially disruptive events and processes, and by implication all potentially disruptive combinations of events and processes (scenarios), must be identified for possible inclusion in performance assessments. Screening of the FEPs identified four events for scenario development: exploratory drilling for natural resources, drilling withdrawal wells, irrigation, and subsidence. Recent environmental-isotope analyses of the vadose zone suggest that radionuclide transport from the boreholes to the water table by infiltration is not a feasible transport mechanism within the time frame of regulatory concern. For this reason, the event of drilling withdrawal wells was merged with exploratory drilling for resources. The descriptions of the remaining three events were modified slightly to aid in estimation of event probabilities and consequence analyses. The three events are: exploratory drilling for resources penetrates a TRU borehole, irrigation occurs at the Radioactive Waste Management Site (RWMS), and subsidence occurs at the RWMS. Use of a logic diagram with these three events resulted in the construction of eight scenarios, including base-case (undisturbed) conditions. Screening these scenarios at this stage of scenario development was beyond the scope of this task. Based on the implementation assumptions, this scenario-development procedure produced a comprehensive set of mutually exclusive scenarios that are reproducible and auditable for use in GCD performance assessments

  16. Cortical thickness differences between bipolar depression and major depressive disorder.

    Science.gov (United States)

    Lan, Martin J; Chhetry, Binod Thapa; Oquendo, Maria A; Sublette, M Elizabeth; Sullivan, Gregory; Mann, J John; Parsey, Ramin V

    2014-06-01

    Bipolar disorder (BD) is a psychiatric disorder with high morbidity and mortality that cannot be distinguished from major depressive disorder (MDD) until the first manic episode. A biomarker able to differentiate BD and MDD could help clinicians avoid risks of treating BD with antidepressants without mood stabilizers. Cortical thickness differences were assessed using magnetic resonance imaging in BD depressed patients (n = 18), MDD depressed patients (n = 56), and healthy volunteers (HVs) (n = 54). A general linear model identified clusters of cortical thickness difference between diagnostic groups. Compared to the HV group, the BD group had decreased cortical thickness in six regions, after controlling for age and sex, located within the frontal and parietal lobes, and the posterior cingulate cortex. Mean cortical thickness changes in clusters ranged from 7.6 to 9.6% (cluster-wise p-values from 1.0 e-4 to 0.037). When compared to MDD, three clusters of lower cortical thickness in BD were identified that overlapped with clusters that differentiated the BD and HV groups. Mean cortical thickness changes in the clusters ranged from 7.5 to 8.2% (cluster-wise p-values from 1.0 e-4 to 0.023). The difference in cortical thickness was more pronounced when the subgroup of subjects with bipolar I disorder (BD-I) was compared to the MDD group. Cortical thickness patterns were distinct between BD and MDD. These results are a step toward developing an imaging test to differentiate the two disorders. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Can osseous landmarks in the distal medial humerus be used to identify the attachment sites of ligaments and tendons: paleopathologic-anatomic imaging study in cadavers

    Energy Technology Data Exchange (ETDEWEB)

    Buck, Florian M. [Veterans Administration Medical Center, Department of Radiology, San Diego, CA (United States); Institut fuer Diagnostische Radiologie, Uniklinik Balgrist, Zurich (Switzerland); Zoner, Cristiane S.; Cardoso, Fabiano; Gheno, Ramon; Nico, Marcelo A.C.; Trudell, Debra J.; Resnick, Donald [Veterans Administration Medical Center, Department of Radiology, San Diego, CA (United States); Randall, Tori D. [San Diego Museum of Man, Physical Anthropology, San Diego, CA (United States)

    2010-09-15

    To describe osseous landmarks that allow identification of the attachments of the ligaments and tendons in the distal medial aspect of the humerus. Reliable osseous landmarks in the distal medial aspect of the humerus were identified in 34 well-preserved specimens from a paleopathologic collection. These osseous landmarks were then sought in magnetic resonance (MR) images of ten cadaveric elbow specimens so that the ease of their visualization and optimal imaging plane could be assessed. To assign these osseous landmarks to specific attachments of the tendons and ligaments in the distal medial humerus, we cut the specimens in slices and photographed and examined them. Subsequently, the prevalence of these osseous landmarks as well as the attachment sites of the tendons and ligaments in this location was determined. We determined ten reliable osseous landmarks in the distal medial aspect of the humerus, their prevalence and ease of identification, and their relationship to the attachments of the tendons and ligaments at the medial distal humerus. It is possible to use osseous landmarks at the distal medial humerus to facilitate identification of the different attachments of tendons and ligaments when MR images of the elbow are assessed. (orig.)

  18. Classification of Cortical Brain Malformations

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2008-03-01

    Full Text Available Clinical, radiological, and genetic classifications of 113 cases of malformations of cortical development (MCD were evaluated at the Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.

  19. Spatial integration and cortical dynamics.

    Science.gov (United States)

    Gilbert, C D; Das, A; Ito, M; Kapadia, M; Westheimer, G

    1996-01-23

    Cells in adult primary visual cortex are capable of integrating information over much larger portions of the visual field than was originally thought. Moreover, their receptive field properties can be altered by the context within which local features are presented and by changes in visual experience. The substrate for both spatial integration and cortical plasticity is likely to be found in a plexus of long-range horizontal connections, formed by cortical pyramidal cells, which link cells within each cortical area over distances of 6-8 mm. The relationship between horizontal connections and cortical functional architecture suggests a role in visual segmentation and spatial integration. The distribution of lateral interactions within striate cortex was visualized with optical recording, and their functional consequences were explored by using comparable stimuli in human psychophysical experiments and in recordings from alert monkeys. They may represent the substrate for perceptual phenomena such as illusory contours, surface fill-in, and contour saliency. The dynamic nature of receptive field properties and cortical architecture has been seen over time scales ranging from seconds to months. One can induce a remapping of the topography of visual cortex by making focal binocular retinal lesions. Shorter-term plasticity of cortical receptive fields was observed following brief periods of visual stimulation. The mechanisms involved entailed, for the short-term changes, altering the effectiveness of existing cortical connections, and for the long-term changes, sprouting of axon collaterals and synaptogenesis. The mutability of cortical function implies a continual process of calibration and normalization of the perception of visual attributes that is dependent on sensory experience throughout adulthood and might further represent the mechanism of perceptual learning.

  20. Spatial integration and cortical dynamics.

    OpenAIRE

    Gilbert, C D; Das, A; Ito, M; Kapadia, M; Westheimer, G

    1996-01-01

    Cells in adult primary visual cortex are capable of integrating information over much larger portions of the visual field than was originally thought. Moreover, their receptive field properties can be altered by the context within which local features are presented and by changes in visual experience. The substrate for both spatial integration and cortical plasticity is likely to be found in a plexus of long-range horizontal connections, formed by cortical pyramidal cells, which link cells wi...

  1. Viability of dielectrophoretically trapped neuronal cortical cells in culture

    NARCIS (Netherlands)

    Heida, Tjitske; Vulto, P; Rutten, Wim; Marani, Enrico

    2001-01-01

    Negative dielectrophoretic trapping of neural cells is an efficient way to position neural cells on the electrode sites of planar micro-electrode arrays. The preservation of viability of the neural cells is essential for this approach. This study investigates the viability of postnatal cortical rat

  2. Relative contributions of intracortical and thalamo-cortical processes in the generation of alpha rhythms, revealed by partial coherence analysis

    NARCIS (Netherlands)

    Lopes da Silva, F.H.; Vos, J.E.; Mooibroek, J.; Rotterdam, A. van

    1980-01-01

    The thalamo-cortical relationships of alpha rhythms have been analysed in dogs using partial coherence function analysis. The objective was to clarify how far the large intracortical coherence commonly recorded between different cortical sites could depend on a common thalamic site. It was found

  3. Basic visual function and cortical thickness patterns in posterior cortical atrophy.

    Science.gov (United States)

    Lehmann, Manja; Barnes, Josephine; Ridgway, Gerard R; Wattam-Bell, John; Warrington, Elizabeth K; Fox, Nick C; Crutch, Sebastian J

    2011-09-01

    Posterior cortical atrophy (PCA) is characterized by a progressive decline in higher-visual object and space processing, but the extent to which these deficits are underpinned by basic visual impairments is unknown. This study aimed to assess basic and higher-order visual deficits in 21 PCA patients. Basic visual skills including form detection and discrimination, color discrimination, motion coherence, and point localization were measured, and associations and dissociations between specific basic visual functions and measures of higher-order object and space perception were identified. All participants showed impairment in at least one aspect of basic visual processing. However, a number of dissociations between basic visual skills indicated a heterogeneous pattern of visual impairment among the PCA patients. Furthermore, basic visual impairments were associated with particular higher-order object and space perception deficits, but not with nonvisual parietal tasks, suggesting the specific involvement of visual networks in PCA. Cortical thickness analysis revealed trends toward lower cortical thickness in occipitotemporal (ventral) and occipitoparietal (dorsal) regions in patients with visuoperceptual and visuospatial deficits, respectively. However, there was also a lot of overlap in their patterns of cortical thinning. These findings suggest that different presentations of PCA represent points in a continuum of phenotypical variation.

  4. Hiperostosis cortical infantil

    Directory of Open Access Journals (Sweden)

    Salvador Javier Santos Medina

    2015-04-01

    Full Text Available La enfermedad de Caffey, o hiperostosis cortical infantil, es una rara enfermedad ósea autolimitada, que aparece de preferencia en lactantes con signos inespecíficos sistémicos; el más relevante es la reacción subperióstica e hiperostosis en varios huesos del cuerpo, con predilección en el 75-80 % de los casos por la mandíbula. Su pronóstico es bueno, la mayoría no deja secuelas. El propósito del presente trabajo es describir las características clínicas, presentes en un lactante de cinco meses de edad, atendido en el Hospital Pediátrico Provincial “Mártires de Las Tunas” con este diagnóstico, quien ingresó en el servicio de miscelánea B por una celulitis facial. Presentaba aumento de volumen en la región geniana izquierda, febrícola e inapetencia. Se impuso tratamiento con cefazolina y se egresó a los siete días. Acudió nuevamente con tumefacción blanda y difusa de ambas hemicaras, irritabilidad y fiebre. Se interconsultó con cirugía maxilofacial, se indicaron estudios sanguíneos y radiológicos. Se diagnosticó como enfermedad de Caffey, basado en la edad del niño, tumefacción facial sin signos inflamatorios agudos e hiperostosis en ambas corticales mandibulares a la radiografía AP mandíbula; unido a anemia ligera, leucocitosis y eritrosedimentación acelerada. El paciente se trató sintomáticamente y con antinflamatorios no esteroideos. Esta rara entidad se debe tener presente en casos de niños y lactantes con irritabilidad y fiebre inespecífica

  5. Energy infrastructure of the United States and projected siting needs: Scoping ideas, identifying issues and options. Draft report of the Department of Energy Working Group on Energy Facility Siting to the Secretary

    Energy Technology Data Exchange (ETDEWEB)

    1993-12-01

    A Department of Energy (DOE) Working Group on Energy Facility Siting, chaired by the Policy Office with membership from the major program and staff offices of the Department, reviewed data regarding energy service needs, infrastructure requirements, and constraints to siting. The Working Group found that the expeditious siting of energy facilities has important economic, energy, and environmental implications for key Administration priorities.

  6. High FDG uptake areas on pre-radiotherapy PET/CT identify preferential sites of local relapse after chemoradiotherapy for locally advanced oesophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Calais, Jeremie; Lemarignier, Charles; Vera, Pierre [Henri Becquerel Cancer Center and Rouen University Hospital, Nuclear Medicine Department, Rouen (France); University of Rouen, QuantIF-LITIS (Equipe d' Accueil 4108-FR CNRS 3638), Faculty of Medicine, Rouen (France); Dubray, Bernard [University of Rouen, QuantIF-LITIS (Equipe d' Accueil 4108-FR CNRS 3638), Faculty of Medicine, Rouen (France); Centre Henri Becquerel and Rouen University Hospital, Department of Radiotherapy and Medical Physics, Rouen (France); Nkhali, Lamyaa; Thureau, Sebastien; Modzelewski, Romain; Gardin, Isabelle [Henri Becquerel Cancer Center and Rouen University Hospital, Nuclear Medicine Department, Rouen (France); University of Rouen, QuantIF-LITIS (Equipe d' Accueil 4108-FR CNRS 3638), Faculty of Medicine, Rouen (France); Centre Henri Becquerel and Rouen University Hospital, Department of Radiotherapy and Medical Physics, Rouen (France); Di Fiore, Frederic [Rouen University Hospital, Department of Gastroenterology, Rouen (France); Rouen University Hospital, Department of Oncology, Henri Becquerel Cancer Center, IRON, Rouen (France); Michel, Pierre [Rouen University Hospital, Department of Gastroenterology, Rouen (France)

    2015-05-01

    The high failure rates in the radiotherapy (RT) target volume suggest that patients with locally advanced oesophageal cancer (LAOC) would benefit from increased total RT doses. High 2-deoxy-2-[{sup 18}F]fluoro-D-glucose (FDG) uptake (hotspot) on pre-RT FDG positron emission tomography (PET)/CT has been reported to identify intra-tumour sites at increased risk of relapse after RT in non-small cell lung cancer and in rectal cancer. Our aim was to confirm these observations in patients with LAOC and to determine the optimal maximum standardized uptake value (SUV{sub max}) threshold to delineate smaller RT target volumes that would facilitate RT dose escalation without impaired tolerance. The study included 98 consecutive patients with LAOC treated by chemoradiotherapy (CRT). All patients underwent FDG PET/CT at initial staging and during systematic follow-up in a single institution. FDG PET/CT acquisitions were coregistered on the initial CT scan. Various subvolumes within the initial tumour (30, 40, 50, 60, 70, 80 and 90 % SUV{sub max} thresholds) and in the subsequent local recurrence (LR, 40 and 90 % SUV{sub max} thresholds) were pasted on the initial CT scan and compared[Dice, Jaccard, overlap fraction (OF), common volume/baseline volume, common volume/recurrent volume]. Thirty-five patients had LR. The initial metabolic tumour volume was significantly higher in LR tumours than in the locally controlled tumours (mean 25.4 vs 14.2 cc; p = 0.002). The subvolumes delineated on initial PET/CT with a 30-60 % SUV{sub max} threshold were in good agreement with the recurrent volume at 40 % SUV{sub max} (OF = 0.60-0.80). The subvolumes delineated on initial PET/CT with a 30-60 % SUV{sub max} threshold were in good to excellent agreement with the core volume (90 % SUV{sub max}) of the relapse (common volume/recurrent volume and OF indices 0.61-0.89). High FDG uptake on pretreatment PET/CT identifies tumour subvolumes that are at greater risk of recurrence after CRT in

  7. The Decline of Laparoendoscopic Single-Site Surgery: A Survey of the Endourological Society to Identify Shortcomings and Guidance for Future Directions.

    Science.gov (United States)

    Sorokin, Igor; Canvasser, Noah E; Irwin, Brian; Autorino, Riccardo; Liatsikos, Evangelos N; Cadeddu, Jeffrey A; Rane, Abhay

    2017-10-01

    To analyze the most recent temporal trends in the adoption of urologic laparoendoscopic single-site (LESS), to identify the perceived limitations associated with its decline, and to determine factors that might revive the role of LESS in the field of minimally invasive urologic surgery. A 15 question survey was created and sent to members of the Endourological Society in September 2016. Only members who performed LESS procedures in practice were asked to respond. In total, 106 urologists responded to the survey. Most of the respondents were from the United States (35%) and worked in an academic hospital (84.9%). Standard LESS was the most popular approach (78.1%), while 14.3% used robotics, and 7.6% used both. 2009 marked the most popular year to perform the initial (27.6%) and the majority (20%) of LESS procedures. The most common LESS procedure was a radical/simple nephrectomy (51%) followed by pyeloplasty (17.3%). In the past 12 months, 60% of respondents had performed no LESS procedures. Compared to conventional laparoscopy, respondents only believed cosmesis to be better, however, this enthusiasm waned over time. Worsening shifts in enthusiasm for LESS also occurred with patient desire, marketability, cost, safety, and robotic adaptability. The highest rated factor to help LESS regain popularity was a new robotic platform. The decline of LESS is apparent, with few urologists continuing to perform procedures attributed to multiple factors. The availability of a purpose-built robotic platform and better instrumentation might translate into a renewed future interest of LESS.

  8. Analysis of 30 putative BRCA1 splicing mutations in hereditary breast and ovarian cancer families identifies exonic splice site mutations that escape in silico prediction.

    Directory of Open Access Journals (Sweden)

    Barbara Wappenschmidt

    Full Text Available Screening for pathogenic mutations in breast and ovarian cancer genes such as BRCA1/2, CHEK2 and RAD51C is common practice for individuals from high-risk families. However, test results may be ambiguous due to the presence of unclassified variants (UCV in the concurrent absence of clearly cancer-predisposing mutations. Especially the presence of intronic or exonic variants within these genes that possibly affect proper pre-mRNA processing poses a challenge as their functional implications are not immediately apparent. Therefore, it appears necessary to characterize potential splicing UCV and to develop appropriate classification tools. We investigated 30 distinct BRCA1 variants, both intronic and exonic, regarding their spliceogenic potential by commonly used in silico prediction algorithms (HSF, MaxEntScan along with in vitro transcript analyses. A total of 25 variants were identified spliceogenic, either causing/enhancing exon skipping or activation of cryptic splice sites, or both. Except from a single intronic variant causing minor effects on BRCA1 pre-mRNA processing in our analyses, 23 out of 24 intronic variants were correctly predicted by MaxEntScan, while HSF was less accurate in this cohort. Among the 6 exonic variants analyzed, 4 severely impair correct pre-mRNA processing, while the remaining two have partial effects. In contrast to the intronic alterations investigated, only half of the spliceogenic exonic variants were correctly predicted by HSF and/or MaxEntScan. These data support the idea that exonic splicing mutations are commonly disease-causing and concurrently prone to escape in silico prediction, hence necessitating experimental in vitro splicing analysis.

  9. Post-genome wide association studies and functional analyses identify association of MPP7 gene variants with site-specific bone mineral density.

    Science.gov (United States)

    Xiao, Su-Mei; Kung, Annie Wai Chee; Gao, Yi; Lau, Kam-Shing; Ma, Alvin; Zhang, Zhen-Lin; Liu, Jian-Min; Xia, Wiebo; He, Jin-Wei; Zhao, Lin; Nie, Min; Fu, Wei-Zhen; Zhang, Min-Jia; Sun, Jing; Kwan, Johnny S H; Tso, Gloria Hoi Wan; Dai, Zhi-Jie; Cheung, Ching-Lung; Bow, Cora H; Leung, Anskar Yu Hung; Tan, Kathryn Choon Beng; Sham, Pak Chung

    2012-04-01

    Our previous genome-wide association study (GWAS) in a Hong Kong Southern Chinese population with extreme bone mineral density (BMD) scores revealed suggestive association with MPP7, which ranked second after JAG1 as a candidate gene for BMD. To follow-up this suggestive signal, we replicated the top single-nucleotide polymorphism rs4317882 of MPP7 in three additional independent Asian-descent samples (n= 2684). The association of rs4317882 reached the genome-wide significance in the meta-analysis of all available subjects (P(meta)= 4.58 × 10(-8), n= 4204). Site heterogeneity was observed, with a larger effect on spine than hip BMD. Further functional studies in a zebrafish model revealed that vertebral bone mass was lower in an mpp7 knock-down model compared with the wide-type (P= 9.64 × 10(-4), n= 21). In addition, MPP7 was found to have constitutive expression in human bone-derived cells during osteogenesis. Immunostaining of murine MC3T3-E1 cells revealed that the Mpp7 protein is localized in the plasma membrane and intracytoplasmic compartment of osteoblasts. In an assessment of the function of identified variants, an electrophoretic mobility shift assay demonstrated the binding of transcriptional factor GATA2 to the risk allele 'A' but not the 'G' allele of rs4317882. An mRNA expression study in human peripheral blood mononuclear cells confirmed that the low BMD-related allele 'A' of rs4317882 was associated with lower MPP7 expression (P= 9.07 × 10(-3), n= 135). Our data suggest a genetic and functional association of MPP7 with BMD variation.

  10. The cortical representation of sensory inputs arising from bone.

    Science.gov (United States)

    Ivanusic, Jason J; Sahai, Vineet; Mahns, David A

    2009-05-07

    In the present study, we show that sensory information from bone reaches the discriminative areas of the somatosensory cortices by electrically stimulating the nerve to the cat humerus and recording evoked potentials on the surface of the primary (SI) and secondary (SII) somatosensory cortex. The SI focus was located over the rostral part of the postcruciate cortex, caudal to the lateral aspect of the cruciate sulcus. The SII focus was identified on the anterior ectosylvian gyrus, lateral to the suprasylvian sulcus. These foci were located adjacent to, or within areas that responded to stimulation of the median, ulnar and/or musculocutaneous nerves. The latency (6-11 ms) to onset of cortical responses in SI and SII were indistinguishable (unpaired t-test; P>0.05), and were consistent with activation of A delta fibers in the peripheral nerve. The amplitudes of the cortical responses were graded as a function of stimulus intensity, and may reflect a mechanism for intensity coding. We did not observe long latency cortical responses (50-300 ms) that would be consistent with C fiber activation in the peripheral nerve, and provide evidence that this may be attributable to inhibition of cortical responsiveness following the initial A delta response. Our finding of discrete, short latency evoked potentials (presumably of A delta origin) in the primary and secondary somatosensory cortices, following stimulation of a nerve innervating bone, may reflect a mechanism for the discriminative component of bone pain.

  11. Longitudinal course of cortical thickness decline in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Schuster, Christina; Kasper, Elisabeth; Machts, Judith; Bittner, Daniel; Kaufmann, Jörn; Benecke, Reiner; Teipel, Stefan; Vielhaber, Stefan; Prudlo, Johannes

    2014-10-01

    To determine longitudinal rates of cortical atrophy in classical Amyotrophic lateral sclerosis (ALS) and ALS variants. Rates of cortical thinning were determined between 2 scans, 3-15 months apart, in 77 ALS patients: 51 classical, 12 upper motor neuron (UMN), and 14 lower motor neuron (LMN) ALS variants. Cortical thickness at the first assessment was compared with 60 healthy controls matched by age and gender. Atrophy rates were compared between patient sub-groups and correlated with disease duration, progression, and severity. Using a cross-sectional analysis, we found a significant difference in cortical thickness between ALS patients and controls in the motor and extra-motor areas (left medial orbito frontal gyrus, left inferior parietal gyrus, bilateral insular cortex, right fusiform gyrus, bilateral precuneus). Using a longitudinal analysis, we found a significant decline of cortical thickness in frontal, temporal, and parietal regions over the course of the study in ALS patients. Effects were independent of the clinical subtype, with exception of the precentral gyrus (p gyrus, the UMN-dominant subjects exhibited intermediate rates of atrophy, and the classical ALS patients exhibited no such change. Atrophy of the precentral gyrus in classical ALS indicates a floor effect at the first assessment, resulting in a lack of further atrophy over time. Structural loss of the precentral gyrus appears to be an early sign of classical ALS. Over time, patterns of cortical thinning in extra-motor areas can be identified in ALS, regardless of the phenotype.

  12. The cortical signature of amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Federica Agosta

    Full Text Available The aim of this study was to explore the pattern of regional cortical thickness in patients with non-familial amyotrophic lateral sclerosis (ALS and to investigate whether cortical thinning is associated with disease progression rate. Cortical thickness analysis was performed in 44 ALS patients and 26 healthy controls. Group differences in cortical thickness and the age-by-group effects were assessed using vertex-by-vertex and multivariate linear models. The discriminatory ability of MRI variables in distinguishing patients from controls was estimated using the Concordance Statistics (C-statistic within logistic regression analyses. Correlations between cortical thickness measures and disease progression rate were tested using the Pearson coefficient. Relative to controls, ALS patients showed a bilateral cortical thinning of the primary motor, prefrontal and ventral frontal cortices, cingulate gyrus, insula, superior and inferior temporal and parietal regions, and medial and lateral occipital areas. There was a significant age-by-group effect in the sensorimotor cortices bilaterally, suggesting a stronger association between age and cortical thinning in ALS patients compared to controls. The mean cortical thickness of the sensorimotor cortices distinguished patients with ALS from controls (C-statistic ≥ 0.74. Cortical thinning of the left sensorimotor cortices was related to a faster clinical progression (r = -0.33, p = 0.03. Cortical thickness measurements allowed the detection and quantification of motor and extramotor involvement in patients with ALS. Cortical thinning of the precentral gyrus might offer a marker of upper motor neuron involvement and disease progression.

  13. The cortical signature of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Agosta, Federica; Valsasina, Paola; Riva, Nilo; Copetti, Massimiliano; Messina, Maria Josè; Prelle, Alessandro; Comi, Giancarlo; Filippi, Massimo

    2012-01-01

    The aim of this study was to explore the pattern of regional cortical thickness in patients with non-familial amyotrophic lateral sclerosis (ALS) and to investigate whether cortical thinning is associated with disease progression rate. Cortical thickness analysis was performed in 44 ALS patients and 26 healthy controls. Group differences in cortical thickness and the age-by-group effects were assessed using vertex-by-vertex and multivariate linear models. The discriminatory ability of MRI variables in distinguishing patients from controls was estimated using the Concordance Statistics (C-statistic) within logistic regression analyses. Correlations between cortical thickness measures and disease progression rate were tested using the Pearson coefficient. Relative to controls, ALS patients showed a bilateral cortical thinning of the primary motor, prefrontal and ventral frontal cortices, cingulate gyrus, insula, superior and inferior temporal and parietal regions, and medial and lateral occipital areas. There was a significant age-by-group effect in the sensorimotor cortices bilaterally, suggesting a stronger association between age and cortical thinning in ALS patients compared to controls. The mean cortical thickness of the sensorimotor cortices distinguished patients with ALS from controls (C-statistic ≥ 0.74). Cortical thinning of the left sensorimotor cortices was related to a faster clinical progression (r = -0.33, p = 0.03). Cortical thickness measurements allowed the detection and quantification of motor and extramotor involvement in patients with ALS. Cortical thinning of the precentral gyrus might offer a marker of upper motor neuron involvement and disease progression.

  14. Cortical tremor: a variant of cortical reflex myoclonus.

    Science.gov (United States)

    Ikeda, A; Kakigi, R; Funai, N; Neshige, R; Kuroda, Y; Shibasaki, H

    1990-10-01

    Two patients with action tremor that was thought to originate in the cerebral cortex showed fine shivering-like finger twitching provoked mainly by action and posture. Surface EMG showed relatively rhythmic discharge at a rate of about 9 Hz, which resembled essential tremor. However, electrophysiologic studies revealed giant somatosensory evoked potentials (SEPs) with enhanced long-loop reflex and premovement cortical spike by the jerk-locked averaging method. Treatment with beta-blocker showed no effect, but anticonvulsants such as clonazepam, valproate, and primidone were effective to suppress the tremor and the amplitude of SEPs. We call this involuntary movement "cortical tremor," which is in fact a variant of cortical reflex myoclonus.

  15. Trade-off of cerebello-cortical and cortico-cortical functional networks for planning in 6-year-old children.

    Science.gov (United States)

    Kipping, Judy A; Margulies, Daniel S; Eickhoff, Simon B; Lee, Annie; Qiu, Anqi

    2018-05-03

    Childhood is a critical period for the development of cognitive planning. There is a lack of knowledge on its neural mechanisms in children. This study aimed to examine cerebello-cortical and cortico-cortical functional connectivity in association with planning skills in 6-year-olds (n = 76). We identified the cerebello-cortical and cortico-cortical functional networks related to cognitive planning using activation likelihood estimation (ALE) meta-analysis on existing functional imaging studies on spatial planning, and data-driven independent component analysis (ICA) of children's resting-state functional MRI (rs-fMRI). We investigated associations of cerebello-cortical and cortico-cortical functional connectivity with planning ability in 6-year-olds, as assessed using the Stockings of Cambridge task. Long-range functional connectivity of two cerebellar networks (lobules VI and lateral VIIa) with the prefrontal and premotor cortex were greater in children with poorer planning ability. In contrast, cortico-cortical association networks were not associated with the performance of planning in children. These results highlighted the key contribution of the lateral cerebello-frontal functional connectivity, but not cortico-cortical association functional connectivity, for planning ability in 6-year-olds. Our results suggested that brain adaptation to the acquisition of planning ability during childhood is partially achieved through the engagement of the cerebello-cortical functional connectivity. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Cerebellar Shaping of Motor Cortical Firing Is Correlated with Timing of Motor Actions

    Directory of Open Access Journals (Sweden)

    Abdulraheem Nashef

    2018-05-01

    Full Text Available Summary: In higher mammals, motor timing is considered to be dictated by cerebellar control of motor cortical activity, relayed through the cerebellar-thalamo-cortical (CTC system. Nonetheless, the way cerebellar information is integrated with motor cortical commands and affects their temporal properties remains unclear. To address this issue, we activated the CTC system in primates and found that it efficiently recruits motor cortical cells; however, the cortical response was dominated by prolonged inhibition that imposed a directional activation across the motor cortex. During task performance, cortical cells that integrated CTC information fired synchronous bursts at movement onset. These cells expressed a stronger correlation with reaction time than non-CTC cells. Thus, the excitation-inhibition interplay triggered by the CTC system facilitates transient recruitment of a cortical subnetwork at movement onset. The CTC system may shape neural firing to produce the required profile to initiate movements and thus plays a pivotal role in timing motor actions. : Nashef et al. identified a motor cortical subnetwork recruited by cerebellar volley that was transiently synchronized at movement onset. Cerebellar control of cortical firing was dominated by inhibition that shaped task-related firing of neurons and may dictate motor timing. Keywords: motor control, primates, cerebellar-thalamo-cortical, synchrony, noise correlation, reaction time

  17. Cholinergic systems are essential for late-stage maturation and refinement of motor cortical circuits

    Science.gov (United States)

    Ramanathan, Dhakshin S.; Conner, James M.; Anilkumar, Arjun A.

    2014-01-01

    Previous studies reported that early postnatal cholinergic lesions severely perturb early cortical development, impairing neuronal cortical migration and the formation of cortical dendrites and synapses. These severe effects of early postnatal cholinergic lesions preclude our ability to understand the contribution of cholinergic systems to the later-stage maturation of topographic cortical representations. To study cholinergic mechanisms contributing to the later maturation of motor cortical circuits, we first characterized the temporal course of cortical motor map development and maturation in rats. In this study, we focused our attention on the maturation of cortical motor representations after postnatal day 25 (PND 25), a time after neuronal migration has been accomplished and cortical volume has reached adult size. We found significant maturation of cortical motor representations after this time, including both an expansion of forelimb representations in motor cortex and a shift from proximal to distal forelimb representations to an extent unexplainable by simple volume enlargement of the neocortex. Specific cholinergic lesions placed at PND 24 impaired enlargement of distal forelimb representations in particular and markedly reduced the ability to learn skilled motor tasks as adults. These results identify a novel and essential role for cholinergic systems in the late refinement and maturation of cortical circuits. Dysfunctions in this system may constitute a mechanism of late-onset neurodevelopmental disorders such as Rett syndrome and schizophrenia. PMID:25505106

  18. Direct cortical hemodynamic mapping of somatotopy of pig nostril sensation by functional near-infrared cortical imaging (fNCI).

    Science.gov (United States)

    Uga, Minako; Saito, Toshiyuki; Sano, Toshifumi; Yokota, Hidenori; Oguro, Keiji; Rizki, Edmi Edison; Mizutani, Tsutomu; Katura, Takusige; Dan, Ippeita; Watanabe, Eiju

    2014-05-01

    Functional near-infrared spectroscopy (fNIRS) is a neuroimaging technique for the noninvasive monitoring of human brain activation states utilizing the coupling between neural activity and regional cerebral hemodynamics. Illuminators and detectors, together constituting optodes, are placed on the scalp, but due to the presence of head tissues, an inter-optode distance of more than 2.5cm is necessary to detect cortical signals. Although direct cortical monitoring with fNIRS has been pursued, a high-resolution visualization of hemodynamic changes associated with sensory, motor and cognitive neural responses directly from the cortical surface has yet to be realized. To acquire robust information on the hemodynamics of the cortex, devoid of signal complications in transcranial measurement, we devised a functional near-infrared cortical imaging (fNCI) technique. Here we demonstrate the first direct functional measurement of temporal and spatial patterns of cortical hemodynamics using the fNCI technique. For fNCI, inter-optode distance was set at 5mm, and light leakage from illuminators was prevented by a special optode holder made of a light-shielding rubber sheet. fNCI successfully detected the somatotopy of pig nostril sensation, as assessed in comparison with concurrent and sequential somatosensory-evoked potential (SEP) measurements on the same stimulation sites. Accordingly, the fNCI system realized a direct cortical hemodynamic measurement with a spatial resolution comparable to that of SEP mapping on the rostral region of the pig brain. This study provides an important initial step toward realizing functional cortical hemodynamic monitoring during neurosurgery of human brains. Copyright © 2014. Published by Elsevier Inc.

  19. Horizontal integration and cortical dynamics.

    Science.gov (United States)

    Gilbert, C D

    1992-07-01

    We have discussed several results that lead to a view that cells in the visual system are endowed with dynamic properties, influenced by context, expectation, and long-term modifications of the cortical network. These observations will be important for understanding how neuronal ensembles produce a system that perceives, remembers, and adapts to injury. The advantage to being able to observe changes at early stages in a sensory pathway is that one may be able to understand the way in which neuronal ensembles encode and represent images at the level of their receptive field properties, of cortical topographies, and of the patterns of connections between cells participating in a network.

  20. Is cortical bone hip? What determines cortical bone properties?

    Science.gov (United States)

    Epstein, Sol

    2007-07-01

    Increased bone turnover may produce a disturbance in bone structure which may result in fracture. In cortical bone, both reduction in turnover and increase in hip bone mineral density (BMD) may be necessary to decrease hip fracture risk and may require relatively greater proportionate changes than for trabecular bone. It should also be noted that increased porosity produces disproportionate reduction in bone strength, and studies have shown that increased cortical porosity and decreased cortical thickness are associated with hip fracture. Continued studies for determining the causes of bone strength and deterioration show distinct promise. Osteocyte viability has been observed to be an indicator of bone strength, with viability as the result of maintaining physiological levels of loading and osteocyte apoptosis as the result of a decrease in loading. Osteocyte apoptosis and decrease are major factors in the bone loss and fracture associated with aging. Both the osteocyte and periosteal cell layer are assuming greater importance in the process of maintaining skeletal integrity as our knowledge of these cells expand, as well being a target for pharmacological agents to reduce fracture especially in cortical bone. The bisphosphonate alendronate has been seen to have a positive effect on cortical bone by allowing customary periosteal growth, while reducing the rate of endocortical bone remodeling and slowing bone loss from the endocortical surface. Risedronate treatment effects were attributed to decrease in bone resorption and thus a decrease in fracture risk. Ibandronate has been seen to increase BMD as the spine and femur as well as a reduced incidence of new vertebral fractures and non vertebral on subset post hoc analysis. And treatment with the anabolic agent PTH(1-34) documented modeling and remodelling of quiescent and active bone surfaces. Receptor activator of nuclear factor kappa B ligand (RANKL) plays a key role in bone destruction, and the human monoclonal

  1. Comparative assessment of environmental and socio-economic impacts of disposal of radioactive waste by shallow burial at sites identified by Nirex

    International Nuclear Information System (INIS)

    Gordon, A.E.M.; Morrow, A.J.; Watson, S.R.

    1987-09-01

    This case study tested two methodologies, comparative assessment and multi-attribute value analysis, on repository site selection. Problems affecting their application stemmed from incomplete baseline and proposed project data and from the impacts being essentially indistinguishable between sites. The latter meant that initial screening was not possible and subsequent screening became arbitrary. The large number of impacts which had to be retained made handling difficult and meaningful rating under comparative assessment was virtually impossible without introducing implicit weightings and adjusting the scale. Multi-attribute value analysis, whilst the more data demanding of the two methodologies, has a greater capability for handling the impacts. Clearly, the limitations on what data can realistically be collected must be taken into account when the evaluation methodology is designed. Ideally a draft methodology should be applied to one site and modified as need be before used for the formal assessment. (author)

  2. Aging and Cortical Mechanisms of Speech Perception in Noise

    Science.gov (United States)

    Wong, Patrick C. M.; Jin, James Xumin; Gunasekera, Geshri M.; Abel, Rebekah; Lee, Edward R.; Dhar, Sumitrajit

    2009-01-01

    Spoken language processing in noisy environments, a hallmark of the human brain, is subject to age-related decline, even when peripheral hearing might be intact. The present study examines the cortical cerebral hemodynamics (measured by fMRI) associated with such processing in the aging brain. Younger and older subjects identified single words in…

  3. One Size Fits All? Slow Cortical Potentials Neurofeedback: A Review

    Science.gov (United States)

    Mayer, Kerstin; Wyckoff, Sarah N.; Strehl, Ute

    2013-01-01

    Objective: The intent of this manuscript was to review all published studies on slow cortical potentials (SCP) neurofeedback for the treatment of ADHD, with emphasis on neurophysiological rationale, study design, protocol, outcomes, and limitations. Method: For review, PubMed, MEDLINE, ERIC, and Google Scholar searches identified six studies and…

  4. Osteocyte lacunar properties in rat cortical bone

    DEFF Research Database (Denmark)

    Bach-Gansmo, Fiona Linnea; Weaver, James C.; Jensen, Mads Hartmann

    2015-01-01

    Recently, the roles of osteocytes in bone maintenance have gained increasing attention. Osteocytes reside in lacunae that are interconnected by canaliculi resulting in a vast cellular network within the mineralized bone matrix. As the structure of the lacuno-canalicular network is highly connected......-species but also inter-site variation in lacunar properties. Here, osteocyte lacunae in rat cortical bone have been studied using synchrotron radiation micro computed tomography (SR μCT) and backscattered electron (BE) microscopy. Quantitative lacunar geometric characteristics are reported based on the synchrotron...... radiation data, differentiating between circumferential lamellar bone and a central, more disordered bone type. From these studies, no significant differences were found in lacunar volumes between lamellar and central bone, whereas significant differences in lacunar orientation, shape and density values...

  5. Low cortical bone density measured by computed tomography in children and adolescents with untreated hyperthyroidism.

    Science.gov (United States)

    Numbenjapon, Nawaporn; Costin, Gertrude; Gilsanz, Vicente; Pitukcheewanont, Pisit

    2007-05-01

    To determine whether increased thyroid hormones levels have an effect on various bone components (cortical vs cancellous bone). The anthropometric and 3-dimensional quantitative computed tomography (CT) bone measurements, including bone density (BD), cross-sectional area (CSA) of the lumbar spine and femur, and cortical bone area (CBA) of the femur, of 18 children and adolescents with untreated hyperthyroidism were reviewed and compared with those of age-, sex-, and ethnicity-matched historical controls. No significant differences in height, weight, body mass index (BMI), or pubertal staging between patients and controls were found. Cortical BD was significantly lower (P hyperthyroidism compared with historical controls. After adjusting for weight and height, no difference in femur CSA between hyperthyroid children and historical controls was evident. No significant correlations among thyroid hormone levels, antithyroid antibody levels, and cortical BD values were found. As determined by CT, cortical bone is the preferential site of bone loss in children and adolescents with untreated hyperthyroidism.

  6. Retinoic acid from the meninges regulates cortical neuron generation.

    Science.gov (United States)

    Siegenthaler, Julie A; Ashique, Amir M; Zarbalis, Konstantinos; Patterson, Katelin P; Hecht, Jonathan H; Kane, Maureen A; Folias, Alexandra E; Choe, Youngshik; May, Scott R; Kume, Tsutomu; Napoli, Joseph L; Peterson, Andrew S; Pleasure, Samuel J

    2009-10-30

    Extrinsic signals controlling generation of neocortical neurons during embryonic life have been difficult to identify. In this study we demonstrate that the dorsal forebrain meninges communicate with the adjacent radial glial endfeet and influence cortical development. We took advantage of Foxc1 mutant mice with defects in forebrain meningeal formation. Foxc1 dosage and loss of meninges correlated with a dramatic reduction in both neuron and intermediate progenitor production and elongation of the neuroepithelium. Several types of experiments demonstrate that retinoic acid (RA) is the key component of this secreted activity. In addition, Rdh10- and Raldh2-expressing cells in the dorsal meninges were either reduced or absent in the Foxc1 mutants, and Rdh10 mutants had a cortical phenotype similar to the Foxc1 null mutants. Lastly, in utero RA treatment rescued the cortical phenotype in Foxc1 mutants. These results establish RA as a potent, meningeal-derived cue required for successful corticogenesis.

  7. TargetM6A: Identifying N6-Methyladenosine Sites From RNA Sequences via Position-Specific Nucleotide Propensities and a Support Vector Machine.

    Science.gov (United States)

    Li, Guang-Qing; Liu, Zi; Shen, Hong-Bin; Yu, Dong-Jun

    2016-10-01

    As one of the most ubiquitous post-transcriptional modifications of RNA, N 6 -methyladenosine ( [Formula: see text]) plays an essential role in many vital biological processes. The identification of [Formula: see text] sites in RNAs is significantly important for both basic biomedical research and practical drug development. In this study, we designed a computational-based method, called TargetM6A, to rapidly and accurately target [Formula: see text] sites solely from the primary RNA sequences. Two new features, i.e., position-specific nucleotide/dinucleotide propensities (PSNP/PSDP), are introduced and combined with the traditional nucleotide composition (NC) feature to formulate RNA sequences. The extracted features are further optimized to obtain a much more compact and discriminative feature subset by applying an incremental feature selection (IFS) procedure. Based on the optimized feature subset, we trained TargetM6A on the training dataset with a support vector machine (SVM) as the prediction engine. We compared the proposed TargetM6A method with existing methods for predicting [Formula: see text] sites by performing stringent jackknife tests and independent validation tests on benchmark datasets. The experimental results show that the proposed TargetM6A method outperformed the existing methods for predicting [Formula: see text] sites and remarkably improved the prediction performances, with MCC = 0.526 and AUC = 0.818. We also provided a user-friendly web server for TargetM6A, which is publicly accessible for academic use at http://csbio.njust.edu.cn/bioinf/TargetM6A.

  8. Hydrous ferric oxide: evaluation of Cd-HFO surface complexation models combining Cd(K) EXAFS data, potentiometric titration results, and surface site structures identified from mineralogical knowledge.

    Science.gov (United States)

    Spadini, Lorenzo; Schindler, Paul W; Charlet, Laurent; Manceau, Alain; Vala Ragnarsdottir, K

    2003-10-01

    The surface properties of ferrihydrite were studied by combining wet chemical data, Cd(K) EXAFS data, and a surface structure and protonation model of the ferrihydrite surface. Acid-base titration experiments and Cd(II)-ferrihydrite sorption experiments were performed within 3titration data could be adequately modeled by triple bond Fe- OH(2)(+1/2)-H(+)triple bond Fe-OH(-1/2),logk((int))=-8.29, assuming the existence of a unique intrinsic microscopic constant, logk((int)), and consequently the existence of a single significant type of acid-base reactive functional groups. The surface structure model indicates that these groups are terminal water groups. The Cd(II) data were modeled assuming the existence of a single reactive site. The model fits the data set at low Cd(II) concentration and up to 50% surface coverage. At high coverage more Cd(II) ions than predicted are adsorbed, which is indicative of the existence of a second type of site of lower affinity. This agrees with the surface structure and protonation model developed, which indicates comparable concentrations of high- and low-affinity sites. The model further shows that for each class of low- and high-affinity sites there exists a variety of corresponding Cd surface complex structure, depending on the model crystal faces on which the complexes develop. Generally, high-affinity surface structures have surface coordinations of 3 and 4, as compared to 1 and 2 for low-affinity surface structures.

  9. Cortical-Cortical Interactions And Sensory Information Processing in Autism

    Science.gov (United States)

    2008-04-30

    significant development for disseminating the results of biomedical research in our lifetime." Sir Paul Nurse , Cancer Research UK Your research papers...of the evidence for local cortical over-connectivity is anecdotal. Belmonte and colleagues suggested the co-morbidity with epilepsy that is highly...Tomma-Halme J, Lahti-Nuuttila P, Service E, Virsu V: Rate of information segregation in developmentally dyslexic children . Brain Lang 2000, 75:66-81

  10. Adolescent cortical thickness pre- and post marijuana and alcohol initiation.

    Science.gov (United States)

    Jacobus, Joanna; Castro, Norma; Squeglia, Lindsay M; Meloy, M J; Brumback, Ty; Huestis, Marilyn A; Tapert, Susan F

    Cortical thickness abnormalities have been identified in youth using both alcohol and marijuana. However, limited studies have followed individuals pre- and post initiation of alcohol and marijuana use to help identify to what extent discrepancies in structural brain integrity are pre-existing or substance-related. Adolescents (N=69) were followed from ages 13 (pre-initiation of substance use, baseline) to ages 19 (post-initiation, follow-up). Three subgroups were identified, participants that initiated alcohol use (ALC, n=23, >20 alcohol use episodes), those that initiated both alcohol and marijuana use (ALC+MJ, n=23, >50 marijuana use episodes) and individuals that did not initiate either substance regularly by follow-up (CON, n=23, marijuana use episodes). All adolescents underwent neurocognitive testing, neuroimaging, and substance use and mental health interviews. Significant group by time interactions and main effects on cortical thickness estimates were identified for 18 cortical regions spanning the left and right hemisphere (pseffect, in cortical thickness by follow-up for individuals who have not initiated regular substance use or alcohol use only by age 19; modest between-group differences were identified at baseline in several cortical regions (ALC and CON>ALC+MJ). Minimal neurocognitive differences were observed in this sample. Findings suggest pre-existing neural differences prior to marijuana use may contribute to initiation of use and observed neural outcomes. Marijuana use may also interfere with thinning trajectories that contribute to morphological differences in young adulthood that are often observed in cross-sectional studies of heavy marijuana users. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Longitudinal changes in cortical thickness in autism and typical development.

    Science.gov (United States)

    Zielinski, Brandon A; Prigge, Molly B D; Nielsen, Jared A; Froehlich, Alyson L; Abildskov, Tracy J; Anderson, Jeffrey S; Fletcher, P Thomas; Zygmunt, Kristen M; Travers, Brittany G; Lange, Nicholas; Alexander, Andrew L; Bigler, Erin D; Lainhart, Janet E

    2014-06-01

    The natural history of brain growth in autism spectrum disorders remains unclear. Cross-sectional studies have identified regional abnormalities in brain volume and cortical thickness in autism, although substantial discrepancies have been reported. Preliminary longitudinal studies using two time points and small samples have identified specific regional differences in cortical thickness in the disorder. To clarify age-related trajectories of cortical development, we examined longitudinal changes in cortical thickness within a large mixed cross-sectional and longitudinal sample of autistic subjects and age- and gender-matched typically developing controls. Three hundred and forty-five magnetic resonance imaging scans were examined from 97 males with autism (mean age = 16.8 years; range 3-36 years) and 60 males with typical development (mean age = 18 years; range 4-39 years), with an average interscan interval of 2.6 years. FreeSurfer image analysis software was used to parcellate the cortex into 34 regions of interest per hemisphere and to calculate mean cortical thickness for each region. Longitudinal linear mixed effects models were used to further characterize these findings and identify regions with between-group differences in longitudinal age-related trajectories. Using mean age at time of first scan as a reference (15 years), differences were observed in bilateral inferior frontal gyrus, pars opercularis and pars triangularis, right caudal middle frontal and left rostral middle frontal regions, and left frontal pole. However, group differences in cortical thickness varied by developmental stage, and were influenced by IQ. Differences in age-related trajectories emerged in bilateral parietal and occipital regions (postcentral gyrus, cuneus, lingual gyrus, pericalcarine cortex), left frontal regions (pars opercularis, rostral middle frontal and frontal pole), left supramarginal gyrus, and right transverse temporal gyrus, superior parietal lobule, and

  12. Scaling Up Cortical Control Inhibits Pain

    Directory of Open Access Journals (Sweden)

    Jahrane Dale

    2018-05-01

    Full Text Available Summary: Acute pain evokes protective neural and behavioral responses. Chronic pain, however, disrupts normal nociceptive processing. The prefrontal cortex (PFC is known to exert top-down regulation of sensory inputs; unfortunately, how individual PFC neurons respond to an acute pain signal is not well characterized. We found that neurons in the prelimbic region of the PFC increased firing rates of the neurons after noxious stimulations in free-moving rats. Chronic pain, however, suppressed both basal spontaneous and pain-evoked firing rates. Furthermore, we identified a linear correlation between basal and evoked firing rates of PFC neurons, whereby a decrease in basal firing leads to a nearly 2-fold reduction in pain-evoked response in chronic pain states. In contrast, enhancing basal PFC activity with low-frequency optogenetic stimulation scaled up prefrontal outputs to inhibit pain. These results demonstrate a cortical gain control system for nociceptive regulation and establish scaling up prefrontal outputs as an effective neuromodulation strategy to inhibit pain. : Dale et al. find that acute pain increases activity levels in the prefrontal cortex. Chronic pain reduces both basal spontaneous and pain-evoked activity in this region, whereas neurostimulation to restore basal activities can in turn enhance nociception-evoked prefrontal activities to inhibit pain. Keywords: chronic pain, neuromodulation, prefrontal cortex, PFC, cortical gain control

  13. A Retrospective Study on Indian Population to evaluate Cortical Bone Thickness in Maxilla and Mandible using Computed Tomography Images

    Directory of Open Access Journals (Sweden)

    Jeegar Ketan Vakil

    2014-01-01

    Conclusion: Mini-implants have gained considerable popularity due to their low cost, effectiveness, clinical management and stability. Among the factors related to microimplant stability, bone density and cortical bone thickness appear to be critical for successful placement. This study will provide knowledge of cortical bone thickness in various areas which can guide the clinicians in selecting the placement site.

  14. Zic deficiency in the cortical marginal zone and meninges results in cortical lamination defects resembling those in type II lissencephaly.

    Science.gov (United States)

    Inoue, Takashi; Ogawa, Masaharu; Mikoshiba, Katsuhiko; Aruga, Jun

    2008-04-30

    The formation of the highly organized cortical structure depends on the production and correct placement of the appropriate number and types of neurons. The Zic family of zinc-finger transcription factors plays essential roles in regulating the proliferation and differentiation of neuronal progenitors in the medial forebrain and the cerebellum. Examination of the expression of Zic genes demonstrated that Zic1, Zic2, and Zic3 were expressed by the progenitor cells in the septum and cortical hem, the sites of generation of the Cajal-Retzius (CR) cells. Immunohistochemical studies have revealed that Zic proteins were abundantly expressed in the meningeal cells and that the majority of the CR cells distributed in the medial and dorsal cortex also expressed Zic proteins in the mid-late embryonic and postnatal cortical marginal zones. During embryonic cortical development, Zic1/Zic3 double-mutant and hypomorphic Zic2 mutant mice showed a reduction in the number of CR cells in the rostral cortex, whereas the cell number remained unaffected in the caudal cortex. These mutants also showed mislocalization of the CR cells and cortical lamination defects, resembling the changes noted in type II (cobblestone) lissencephaly, throughout the brain. In the Zic1/3 mutant, reduced proliferation of the meningeal cells was observed before the thinner and disrupted organization of the pial basement membrane (BM) with reduced expression of the BM components and the meningeal cell-derived secretory factor. These defects correlated with the changes in the end feet morphology of the radial glial cells. These findings indicate that the Zic genes play critical roles in cortical development through regulating the proliferation of meningeal cells and the pial BM assembly.

  15. Imprinting and recalling cortical ensembles.

    Science.gov (United States)

    Carrillo-Reid, Luis; Yang, Weijian; Bando, Yuki; Peterka, Darcy S; Yuste, Rafael

    2016-08-12

    Neuronal ensembles are coactive groups of neurons that may represent building blocks of cortical circuits. These ensembles could be formed by Hebbian plasticity, whereby synapses between coactive neurons are strengthened. Here we report that repetitive activation with two-photon optogenetics of neuronal populations from ensembles in the visual cortex of awake mice builds neuronal ensembles that recur spontaneously after being imprinted and do not disrupt preexisting ones. Moreover, imprinted ensembles can be recalled by single- cell stimulation and remain coactive on consecutive days. Our results demonstrate the persistent reconfiguration of cortical circuits by two-photon optogenetics into neuronal ensembles that can perform pattern completion. Copyright © 2016, American Association for the Advancement of Science.

  16. Right anterior cingulate cortical thickness and bilateral striatal volume correlate with child behavior checklist aggressive behavior scores in healthy children.

    Science.gov (United States)

    Ducharme, Simon; Hudziak, James J; Botteron, Kelly N; Ganjavi, Hooman; Lepage, Claude; Collins, D Louis; Albaugh, Matthew D; Evans, Alan C; Karama, Sherif

    2011-08-01

    The anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and basal ganglia have been implicated in pathological aggression. This study aimed at identifying neuroanatomical correlates of impulsive aggression in healthy children. Data from 193 representative 6- to 18-year-old healthy children were obtained from the National Institutes of Health Magnetic Resonance Imaging Study of Normal Brain Development after a blinded quality control. Cortical thickness and subcortical volumes were obtained with automated software. Aggression levels were measured with the Aggressive Behavior scale (AGG) of the Child Behavior Checklist. AGG scores were regressed against cortical thickness and basal ganglia volumes using first- and second-order linear models while controlling for age, gender, scanner site, and total brain volume. Gender by AGG interactions were analyzed. There were positive associations between bilateral striatal volumes and AGG scores (right: r = .238, p = .001; left: r = .188, p = .01). A significant association was found with right ACC and subgenual ACC cortical thickness in a second-order linear model (p right ACC cortex. An AGG by gender interaction trend was found in bilateral OFC and ACC associations with AGG scores. This study shows the existence of relationships between impulsive aggression in healthy children and the structure of the striatum and right ACC. It also suggests the existence of gender-specific patterns of association in OFC/ACC gray matter. These results may guide research on oppositional-defiant and conduct disorders. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  17. Adrenal medullary regulation of rat renal cortical adrenergic receptors

    International Nuclear Information System (INIS)

    Sundaresan, P.R.; Guarnaccia, M.M.; Izzo, J.L. Jr.

    1987-01-01

    The role of the adrenal medulla in the regulation of renal cortical adrenergic receptors was investigated in renal cortical particular fractions from control rats and rats 6 wk after adrenal demedullation. The specific binding of [ 3 H]prazosin, [ 3 H]rauwolscine, and [ 125 I]iodocyanopindolol were used to quantitate α 1 -, α 2 -, and β-adrenergic receptors, respectively. Adrenal demedullation increased the concentration of all three groups of renal adrenergic receptors; maximal number of binding sites (B max , per milligram membrane protein) for α 1 -, and α 2 -, and β-adrenergic receptors were increased by 22, 18.5, and 25%, respectively. No differences were found in the equilibrium dissociation constants (K D ) for any of the radioligands. Plasma corticosterone and plasma and renal norepinephrine levels were unchanged, whereas plasma epinephrine was decreased 72% by adrenal demedullation, renal cortical epinephrine was not detectable in control or demedullated animals. The results suggest that, in the physiological state, the adrenal medulla modulates the number of renal cortical adrenergic receptors, presumably through the actions of a circulating factor such as epinephrine

  18. [Schizophrenia and cortical GABA neurotransmission].

    Science.gov (United States)

    Hashimoto, Takanori; Matsubara, Takuro; Lewis, David A

    2010-01-01

    -synaptic GABA-A receptors. Our recent analyses demonstrated that this pattern exists across diverse cortical areas including the prefrontal, anterior cingulate, primary motor, and primary visual cortices. GABA neurotransmission by PV-containing and SST-containing neurons is important for the generation of cortical oscillatory activities in the gamma (30-100 Hz) and theta (4-7 Hz) bands, respectively. These oscillatory activities have been proposed to play critical roles in regulating the efficiency of information transfer between neurons and neuronal networks in the cortex. Altered cortical GABA neurotransmission appears to contribute to disturbances in diverse functions through affecting the generation of cortical oscillations in schizophrenia.

  19. Functional MRI study of cerebral cortical activation during volitional swallowing

    International Nuclear Information System (INIS)

    Wakasa, Toru; Aiga, Hideki; Yanagi, Yoshinobu; Kawai, Noriko; Sugimoto, Tomosada; Kuboki, Takuo; Kishi, Kanji

    2002-01-01

    The purpose of this study was to investigate the somatotropic distribution and lateralization of motor and sensory cortical activity during swallowing in healthy adult human subjects using functional MR imaging. Nine healthy right-handed adult volunteers (6 men, 3 women; ages 22-38) were examined. Their cortical activities were evoked by having them swallow, five times, a small bolus of water (3 ml) supplied through a plastic catheter. As a positive control, the subjects performed five repetitions of right-handed grasping tasks. Blood oxygenation level-dependent images were obtained using a 1.5 Tesla MR system (Magnetom Vision, Siemens Germany; repetition time/echo time (TR/TE)=0.96/0.66, flip angle (FA)=90 deg). T1 weighted anatomical images were obtained for the same slices in each subject. Cerebral activity was observed most notably in the primary motor cortex and primary somatosensory cortex, followed by the premotor cortex, anterior cingulate cortex, frontal operculum, and insula. The hand-grasping task activated relatively superior parts of the primary motor and somatosensory cortices. The swallowing task, on the other hand, activated the inferior parts of the pre- and postcentral gyri. The hand-grasping activation of motor and sensory cortices was localized absolutely on the contralateral side, whereas swallowing activated the motor cortex either bilaterally or unilaterally. Swallowing activated the sensory cortex almost always bilaterally. This study suggested that fMRI could be used to identify the specific areas of cortical activation caused by various tasks, and to differentiate the locations of cortical activation between tasks. (author)

  20. Functional MRI study of cerebral cortical activation during volitional swallowing

    Energy Technology Data Exchange (ETDEWEB)

    Wakasa, Toru; Aiga, Hideki; Yanagi, Yoshinobu; Kawai, Noriko; Sugimoto, Tomosada; Kuboki, Takuo; Kishi, Kanji [Okayama Univ. (Japan). Graduate School of Medicine and Dentistry

    2002-12-01

    The purpose of this study was to investigate the somatotropic distribution and lateralization of motor and sensory cortical activity during swallowing in healthy adult human subjects using functional MR imaging. Nine healthy right-handed adult volunteers (6 men, 3 women; ages 22-38) were examined. Their cortical activities were evoked by having them swallow, five times, a small bolus of water (3 ml) supplied through a plastic catheter. As a positive control, the subjects performed five repetitions of right-handed grasping tasks. Blood oxygenation level-dependent images were obtained using a 1.5 Tesla MR system (Magnetom Vision, Siemens Germany; repetition time/echo time (TR/TE)=0.96/0.66, flip angle (FA)=90 deg). T1 weighted anatomical images were obtained for the same slices in each subject. Cerebral activity was observed most notably in the primary motor cortex and primary somatosensory cortex, followed by the premotor cortex, anterior cingulate cortex, frontal operculum, and insula. The hand-grasping task activated relatively superior parts of the primary motor and somatosensory cortices. The swallowing task, on the other hand, activated the inferior parts of the pre- and postcentral gyri. The hand-grasping activation of motor and sensory cortices was localized absolutely on the contralateral side, whereas swallowing activated the motor cortex either bilaterally or unilaterally. Swallowing activated the sensory cortex almost always bilaterally. This study suggested that fMRI could be used to identify the specific areas of cortical activation caused by various tasks, and to differentiate the locations of cortical activation between tasks. (author)

  1. Swine cortical and cancellous bone: histomorphometric and densitometric characterisation

    Directory of Open Access Journals (Sweden)

    Maria Elena Andreis

    2017-06-01

    Full Text Available Introduction: Swine bone morphology, composition and remodelling are similar to humans’, therefore they are considered good models in bone-related research. They have been used for several studies involving bone growth, bone and cartilage fractures and femoral head osteonecrosis. Nevertheless, the literature about pig normal bone features is incomplete. This work aims to fill the literature gaps on the microarchitecture and Bone Mineral Density (BMD of swine femoral diaphysis and distal epiphysis and tibial plateau and diaphysis. Materials and methods: Five hind limbs were collected from slaughtered 80-100 kg pigs. Microscopic analysis of cortical and cancellous bone from middle/distal femur and proximal/middle tibia was performed to determine basic histomorphometric parameters at different sites. Dual-energy X-Rays Absorptiometry was also employed to evaluate BMD. ANOVA and correlation between BMD, bone area (BA and cortical thickness were performed. Results and discussion: Diaphyseal cortical bone was mostly plexiform both in the tibia and the femur; primary/secondary osteons without clear organization were also found. Mean values for bone area, bone perimeter, trabecular width, number and separation and BMD at different anatomical sites were defined. No significant difference was found for these values at different anatomical sites. BMD proved to be positively correlated with cortical thickness (r=0,80; p<0,01. Despite the small sample size, these results seem homogeneous. They could therefore represent reference values for normal bone parameters in pigs. Applied anatomy and regenerative medicine, in fact, demand very precise information about bone micromorphology, composition and density to provide reliable indication in bone substitutes building. Moreover, since the interpretation of bone abnormalities is based on mastering normal bone characteristics, the definition of reference parameters is mandatory to avoid misinterpretation and

  2. Mutational analysis of the EMCV 2A protein identifies a nuclear localization signal and an eIF4E binding site

    International Nuclear Information System (INIS)

    Groppo, Rachel; Brown, Bradley A.; Palmenberg, Ann C.

    2011-01-01

    Cardioviruses have a unique 2A protein (143 aa). During genome translation, the encephalomyocarditis virus (EMCV) 2A is released through a ribosome skipping event mitigated through C-terminal 2A sequences and by subsequent N-terminal reaction with viral 3C pro . Although viral replication is cytoplasmic, mature 2A accumulates in nucleoli shortly after infection. Some protein also transiently associates with cytoplasmic 40S ribosomal subunits, an activity contributing to inhibition of cellular cap-dependent translation. Cardiovirus sequences predict an eIF4E binding site (aa 126-134) and a nuclear localization signal (NLS, aa 91-102), within 2A, both of which are functional during EMCV infection. Point mutations preventing eIF4E:2A interactions gave small-plaque phenotype viruses, but still inhibited cellular cap-dependent translation. Deletions within the NLS motif relocalized 2A to the cytoplasm and abrogated the inhibition of cap-dependent translation. A fusion protein linking the 2A NLS to eGFP was sufficient to redirect the reporter to the nucleus but not into nucleoli.

  3. Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120.

    Science.gov (United States)

    deCamp, Allan C; Rolland, Morgane; Edlefsen, Paul T; Sanders-Buell, Eric; Hall, Breana; Magaret, Craig A; Fiore-Gartland, Andrew J; Juraska, Michal; Carpp, Lindsay N; Karuna, Shelly T; Bose, Meera; LePore, Steven; Miller, Shana; O'Sullivan, Annemarie; Poltavee, Kultida; Bai, Hongjun; Dommaraju, Kalpana; Zhao, Hong; Wong, Kim; Chen, Lennie; Ahmed, Hasan; Goodman, Derrick; Tay, Matthew Z; Gottardo, Raphael; Koup, Richard A; Bailer, Robert; Mascola, John R; Graham, Barney S; Roederer, Mario; O'Connell, Robert J; Michael, Nelson L; Robb, Merlin L; Adams, Elizabeth; D'Souza, Patricia; Kublin, James; Corey, Lawrence; Geraghty, Daniel E; Frahm, Nicole; Tomaras, Georgia D; McElrath, M Juliana; Frenkel, Lisa; Styrchak, Sheila; Tovanabutra, Sodsai; Sobieszczyk, Magdalena E; Hammer, Scott M; Kim, Jerome H; Mullins, James I; Gilbert, Peter B

    2017-01-01

    Although the HVTN 505 DNA/recombinant adenovirus type 5 vector HIV-1 vaccine trial showed no overall efficacy, analysis of breakthrough HIV-1 sequences in participants can help determine whether vaccine-induced immune responses impacted viruses that caused infection. We analyzed 480 HIV-1 genomes sampled from 27 vaccine and 20 placebo recipients and found that intra-host HIV-1 diversity was significantly lower in vaccine recipients (P ≤ 0.04, Q-values ≤ 0.09) in Gag, Pol, Vif and envelope glycoprotein gp120 (Env-gp120). Furthermore, Env-gp120 sequences from vaccine recipients were significantly more distant from the subtype B vaccine insert than sequences from placebo recipients (P = 0.01, Q-value = 0.12). These vaccine effects were associated with signatures mapping to CD4 binding site and CD4-induced monoclonal antibody footprints. These results suggest either (i) no vaccine efficacy to block acquisition of any viral genotype but vaccine-accelerated Env evolution post-acquisition; or (ii) vaccine efficacy against HIV-1s with Env sequences closest to the vaccine insert combined with increased acquisition due to other factors, potentially including the vaccine vector.

  4. Tandem affinity purification of histones, coupled to mass spectrometry, identifies associated proteins and new sites of post-translational modification in Saccharomyces cerevisiae.

    Science.gov (United States)

    Valero, M Luz; Sendra, Ramon; Pamblanco, Mercè

    2016-03-16

    Histones and their post-translational modifications contribute to regulating fundamental biological processes in all eukaryotic cells. We have applied a conventional tandem affinity purification strategy to histones H3 and H4 of the yeast Saccharomyces cerevisiae. Mass spectrometry analysis of the co-purified proteins revealed multiple associated proteins, including core histones, which indicates that tagged histones may be incorporated to the nucleosome particle. Among the many other co-isolated proteins there are histone chaperones, elements of chromatin remodeling, of nucleosome assembly/disassembly, and of histone modification complexes. The histone chaperone Rtt106p, two members of chromatin assembly FACT complex and Psh1p, an ubiquitin ligase, were the most abundant proteins obtained with both H3-TAP and H4-TAP, regardless of the cell extraction medium stringency. Our mass spectrometry analyses have also revealed numerous novel post-translational modifications, including 30 new chemical modifications in histones, mainly by ubiquitination. We have discovered not only new sites of ubiquitination but that, besides lysine, also serine and threonine residues are targets of ubiquitination on yeast histones. Our results show the standard tandem affinity purification procedure is suitable for application to yeast histones, in order to isolate and characterize histone-binding proteins and post-translational modifications, avoiding the bias caused by histone purification from a chromatin-enriched fraction. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. The human dorsal premotor cortex facilitates the excitability of ipsilateral primary motor cortex via a short latency cortico-cortical route

    DEFF Research Database (Denmark)

    Groppa, Sergiu; Schlaak, Boris H; Münchau, Alexander

    2012-01-01

    In non-human primates, invasive tracing and electrostimulation studies have identified strong ipsilateral cortico-cortical connections between dorsal premotor- (PMd) and the primary motor cortex (M1(HAND) ). Here, we applied dual-site transcranial magnetic stimulation (dsTMS) to left PMd and M1......(HAND) through specifically designed minicoils to selectively probe ipsilateral PMd-to-M1(HAND) connectivity in humans. A suprathreshold test stimulus (TS) was applied to M1(HAND) producing a motor evoked potential (MEP) of about 0.5 mV in the relaxed right first dorsal interosseus muscle (FDI......) facilitation did not change as a function of CS intensity. Even at higher intensities, the CS alone failed to elicit a MEP or a cortical silent period in the pre-activated FDI, excluding a direct spread of excitation from PMd to M1(HAND). No MEP facilitation was present while CS was applied rostrally over...

  6. Growth and Age-Related Abnormalities in Cortical Structure and Fracture Risk

    Directory of Open Access Journals (Sweden)

    Ego Seeman

    2015-12-01

    Full Text Available Vertebral fractures and trabecular bone loss have dominated thinking and research into the pathogenesis and the structural basis of bone fragility during the last 70 years. However, 80% of all fractures are non-vertebral and occur at regions assembled using large amounts of cortical bone; only 20% of fractures are vertebral. Moreover, ~80% of the skeleton is cortical and ~70% of all bone loss is cortical even though trabecular bone is lost more rapidly than cortical bone. Bone is lost because remodelling becomes unbalanced after midlife. Most cortical bone loss occurs by intracortical, not endocortical remodelling. Each remodelling event removes more bone than deposited enlarging existing canals which eventually coalesce eroding and thinning the cortex from 'within.' Thus, there is a need to study the decay of cortical as well as trabecular bone, and to develop drugs that restore the strength of both types of bone. It is now possible to accurately quantify cortical porosity and trabecular decay in vivo. The challenges still to be met are to determine whether measurement of porosity identifies persons at risk for fracture, whether this approach is compliments information obtained using bone densitometry, and whether changes in cortical porosity and other microstructural traits have the sensitivity to serve as surrogates of treatment success or failure.

  7. Use of geographic information systems (GIS to identify adequate sites for cultivation of the seaweed Gracilaria birdiae in Rio Grande do Norte, Northeastern Brazil

    Directory of Open Access Journals (Sweden)

    Flavo E. S. de Sousa

    2012-06-01

    Full Text Available This study was designed to select potential areas for cultivation of the seaweed Gracilaria birdiae Plastino & E.C. Oliveira (Gracilariales, Rhodophyta on the coast of Rio Grande do Norte state, Brazil. The Geographic Information System (GIS and multi-criteria evaluation (MCE were used to identify the most suitable areas. The Analytical Hierarchical Process (AHP was applied to establish MCE weights, thereby generating viable areas for species cultivation. From a total of 3316.82 ha, around 53.67% (1780.06 ha were indicated as highly suitable areas, 40.93% (1357.58 ha as moderately suitable and 5.40% (179.18 ha as scarcely suitable for seaweed cultivation. Seven areas (1084.62 ha are located on the northern coast and 20 (2232.20 ha on the eastern coast. The results show that GIS can be used as an effective instrument for selecting seaweed cultivation areas.

  8. MRI of focal cortical dysplasia

    International Nuclear Information System (INIS)

    Lee, B.C.P.; Hatfield, G.A.; Bourgeois, B.; Park, T.S.

    1998-01-01

    We studied nine cases of focal cortical dysplasia (FCD) by MRI, with surface-rendered 3D reconstructions. One case was also examined using single-voxel proton MR spectroscopy (MRS). The histological features were reviewed and correlated with the MRI findings. The gyri affected by FCD were enlarged and the signal of the cortex was slightly increased on T1-weighted images. The gray-white junction was indistinct. Signal from the subcortical white matter was decreased on T1- and increased on T2-weighted images in most cases. Contrast enhancement was seen in two cases. Proton MRS showed a spectrum identical to that of normal brain. (orig.) (orig.)

  9. Acute hepatic encephalopathy with diffuse cortical lesions

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, S.M.; Spreer, J.; Schumacher, M. [Section of Neuroradiology, Univ. of Freiburg (Germany); Els, T. [Dept. of Neurology, University of Freiburg (Germany)

    2001-07-01

    Acute hepatic encephalopathy is a poorly defined syndrome of heterogeneous aetiology. We report a 49-year-old woman with alcoholic cirrhosis and hereditary haemorrhagic telangiectasia who developed acute hepatic coma induced by severe gastrointestinal bleeding. Laboratory analysis revealed excessively elevated blood ammonia. MRI showed lesions compatible with chronic hepatic encephalopathy and widespread cortical signal change sparing the perirolandic and occipital cortex. The cortical lesions resembled those of hypoxic brain damage and were interpreted as acute toxic cortical laminar necrosis. (orig.)

  10. Communication and Wiring in the Cortical Connectome

    Directory of Open Access Journals (Sweden)

    Julian eBudd

    2012-10-01

    Full Text Available In cerebral cortex, the huge mass of axonal wiring that carries information between near and distant neurons is thought to provide the neural substrate for cognitive and perceptual function. The goal of mapping the connectivity of cortical axons at different spatial scales, the cortical connectome, is to trace the paths of information flow in cerebral cortex. To appreciate the relationship between the connectome and cortical function, we need to discover the nature and purpose of the wiring principles underlying cortical connectivity. A popular explanation has been that axonal length is strictly minimized both within and between cortical regions. In contrast, we have hypothesized the existence of a multi-scale principle of cortical wiring where to optimise communication there is a trade-off between spatial (construction and temporal (routing costs. Here, using recent evidence concerning cortical spatial networks we critically evaluate this hypothesis at neuron, local circuit, and pathway scales. We report three main conclusions. First, the axonal and dendritic arbor morphology of single neocortical neurons may be governed by a similar wiring principle, one that balances the conservation of cellular material and conduction delay. Second, the same principle may be observed for fibre tracts connecting cortical regions. Third, the absence of sufficient local circuit data currently prohibits any meaningful assessment of the hypothesis at this scale of cortical organization. To avoid neglecting neuron and microcircuit levels of cortical organization, the connectome framework should incorporate more morphological description. In addition, structural analyses of temporal cost for cortical circuits should take account of both axonal conduction and neuronal integration delays, which appear mostly of the same order of magnitude. We conclude the hypothesized trade-off between spatial and temporal costs may potentially offer a powerful explanation for

  11. Acute hepatic encephalopathy with diffuse cortical lesions

    International Nuclear Information System (INIS)

    Arnold, S.M.; Spreer, J.; Schumacher, M.; Els, T.

    2001-01-01

    Acute hepatic encephalopathy is a poorly defined syndrome of heterogeneous aetiology. We report a 49-year-old woman with alcoholic cirrhosis and hereditary haemorrhagic telangiectasia who developed acute hepatic coma induced by severe gastrointestinal bleeding. Laboratory analysis revealed excessively elevated blood ammonia. MRI showed lesions compatible with chronic hepatic encephalopathy and widespread cortical signal change sparing the perirolandic and occipital cortex. The cortical lesions resembled those of hypoxic brain damage and were interpreted as acute toxic cortical laminar necrosis. (orig.)

  12. Obstructive sleep apnea and cortical thickness in females and males.

    Science.gov (United States)

    Macey, Paul M; Haris, Natasha; Kumar, Rajesh; Thomas, M Albert; Woo, Mary A; Harper, Ronald M

    2018-01-01

    Obstructive sleep apnea (OSA) affects approximately 10% of adults, and alters brain gray and white matter. Psychological and physiological symptoms of the disorder are sex-specific, perhaps related to greater injury occurs in female than male patients in white matter. Our objective was to identify influences of OSA separated by sex on cortical gray matter. We assessed cortical thickness in 48 mild-severe OSA patients (mean age±std[range] = 46.5±9.0[30.8-62.7] years; apnea-hypopnea index = 32.6±21.1[6-102] events/hour; 12 female, 36 male; OSA severity: 5 mild, 18 moderate, 25 severe) and 62 controls (mean age = 47.7±8.9[30.9-65.8] years; 22 female, 40 male). All OSA patients were recently-diagnosed via polysomnography, and control subjects screened and a subset assessed with sleep studies. We used high-resolution magnetic resonance imaging to identify OSA-related cortical thinning, based on a model with condition and sex as independent variables. OSA and OSA-by-sex interaction effects were assessed (Pfrontal lobe in female OSA vs. all other groups. Significant thinning within the pre- and post-central gyri and the superior temporal gyrus, extending into the insula, appeared between the general OSA populations vs. control subjects. No areas showed increased thickness in OSA vs. controls or positive female OSA interaction effects. Reduced cortical thickness likely represents tissue atrophy from long term injury, including death of neurons and supporting glia from repeated intermittent hypoxic exposure in OSA, although disease comordities may also contribute to thinning. Lack of polysomnography in all control subjects means results may be confounded by undiagnosed OSA. The greater cortical injury in cognitive areas of female OSA patients may underlie enhanced symptoms in that group. The thinning associated with OSA in male and females OSA patients may contribute to autonomic dysregulation and impaired upper airway sensori-motor function.

  13. Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis

    Science.gov (United States)

    Malhotra, Deepti; Portales-Casamar, Elodie; Singh, Anju; Srivastava, Siddhartha; Arenillas, David; Happel, Christine; Shyr, Casper; Wakabayashi, Nobunao; Kensler, Thomas W.; Wasserman, Wyeth W.; Biswal, Shyam

    2010-01-01

    The Nrf2 (nuclear factor E2 p45-related factor 2) transcription factor responds to diverse oxidative and electrophilic environmental stresses by circumventing repression by Keap1, translocating to the nucleus, and activating cytoprotective genes. Nrf2 responses provide protection against chemical carcinogenesis, chronic inflammation, neurodegeneration, emphysema, asthma and sepsis in murine models. Nrf2 regulates the expression of a plethora of genes that detoxify oxidants and electrophiles and repair or remove damaged macromolecules, such as through proteasomal processing. However, many direct targets of Nrf2 remain undefined. Here, mouse embryonic fibroblasts (MEF) with either constitutive nuclear accumulation (Keap1−/−) or depletion (Nrf2−/−) of Nrf2 were utilized to perform chromatin-immunoprecipitation with parallel sequencing (ChIP-Seq) and global transcription profiling. This unique Nrf2 ChIP-Seq dataset is highly enriched for Nrf2-binding motifs. Integrating ChIP-Seq and microarray analyses, we identified 645 basal and 654 inducible direct targets of Nrf2, with 244 genes at the intersection. Modulated pathways in stress response and cell proliferation distinguish the inducible and basal programs. Results were confirmed in an in vivo stress model of cigarette smoke-exposed mice. This study reveals global circuitry of the Nrf2 stress response emphasizing Nrf2 as a central node in cell survival response. PMID:20460467

  14. SLEEP AND OLFACTORY CORTICAL PLASTICITY

    Directory of Open Access Journals (Sweden)

    Dylan eBarnes

    2014-04-01

    Full Text Available In many systems, sleep plays a vital role in memory consolidation and synaptic homeostasis. These processes together help store information of biological significance and reset synaptic circuits to facilitate acquisition of information in the future. In this review, we describe recent evidence of sleep-dependent changes in olfactory system structure and function which contribute to odor memory and perception. During slow-wave sleep, the piriform cortex becomes hypo-responsive to odor stimulation and instead displays sharp-wave activity similar to that observed within the hippocampal formation. Furthermore, the functional connectivity between the piriform cortex and other cortical and limbic regions is enhanced during slow-wave sleep compared to waking. This combination of conditions may allow odor memory consolidation to occur during a state of reduced external interference and facilitate association of odor memories with stored hedonic and contextual cues. Evidence consistent with sleep-dependent odor replay within olfactory cortical circuits is presented. These data suggest that both the strength and precision of odor memories is sleep-dependent. The work further emphasizes the critical role of synaptic plasticity and memory in not only odor memory but also basic odor perception. The work also suggests a possible link between sleep disturbances that are frequently co-morbid with a wide range of pathologies including Alzheimer’s disease, schizophrenia and depression and the known olfactory impairments associated with those disorders.

  15. Cortical representations of communication sounds.

    Science.gov (United States)

    Heiser, Marc A; Cheung, Steven W

    2008-10-01

    This review summarizes recent research into cortical processing of vocalizations in animals and humans. There has been a resurgent interest in this topic accompanied by an increased number of studies using animal models with complex vocalizations and new methods in human brain imaging. Recent results from such studies are discussed. Experiments have begun to reveal the bilateral cortical fields involved in communication sound processing and the transformations of neural representations that occur among those fields. Advances have also been made in understanding the neuronal basis of interaction between developmental exposures and behavioral experiences with vocalization perception. Exposure to sounds during the developmental period produces large effects on brain responses, as do a variety of specific trained tasks in adults. Studies have also uncovered a neural link between the motor production of vocalizations and the representation of vocalizations in cortex. Parallel experiments in humans and animals are answering important questions about vocalization processing in the central nervous system. This dual approach promises to reveal microscopic, mesoscopic, and macroscopic principles of large-scale dynamic interactions between brain regions that underlie the complex phenomenon of vocalization perception. Such advances will yield a greater understanding of the causes, consequences, and treatment of disorders related to speech processing.

  16. rab3 mediates cortical granule exocytosis in the sea urchin egg.

    Science.gov (United States)

    Conner, S; Wessel, G M

    1998-11-15

    Egg activation at fertilization in the sea urchin results in the exocytosis of approximately 15,000 cortical granules that are docked at the plasma membrane. Previously, we reported that several integral membrane proteins modeled in the SNARE hypothesis, synaptotagmin, VAMP, and syntaxin, in addition to a small GTPase of the ras superfamily, rab3, were present on cortical granules (Conner, S., Leaf, D., and Wessel, G., Mol. Reprod. Dev. 48, 1-13, 1997). Here we report that rab3 is associated with cortical granules throughout oogenesis, during cortical granule translocation, and while docked at the egg plasma membrane. Following cortical granule exocytosis, however, rab3 reassociates with a different population of vesicles, at least some of which are of endocytic origin. Because of its selective association with cortical granules in eggs and oocytes, we hypothesize that rab3 functions in cortical granule exocytosis. To test this hypothesis, we used a strategy of interfering with rab3 function by peptide competition with its effector domain, a conserved region within specific rab types. We first identified the effector domain sequence in Lytechinus variegatus eggs and find the sequence 94% identical to the effector domain of rab3 in Stronglocentrotus purpuratus. Then, with synthetic peptides to different regions of the rab3 protein, we find that cortical granule exocytosis is inhibited in eggs injected with effector domain peptides, but not with peptides from the hypervariable region or with a scrambled effector peptide. Additionally, effector-peptide-injected eggs injected with IP3 are blocked in their ability to exocytose cortical granules, suggesting that the inhibition is directly on the membrane fusion event and not the result of interference with the signal transduction mechanism leading to calcium release. We interpret these results to mean that rab3 functions in the regulation of cortical granule exocytosis following vesicle docking. Copyright 1998 Academic

  17. ASYMMETRY OF SOMATOSENSORY CORTICAL PLASTICITY IN PATIENT WITH BILATERAL CARPAL TUNNEL SYNDROME

    Directory of Open Access Journals (Sweden)

    Hikmat Hadoush

    2017-09-01

    Full Text Available Background: Following peripheral nerve lesion, the adult somatosensory system showedcortical reorganizational abilities.Previous studies identified the digits' somatotopy map changes and somatosensory cortical plasticity in response to the Carpal Tunnel Syndrome (CTS that affected the dominant hand only. Objective: Answering the remained question is that what the extent of the cortical plasticity would be in left and right somatosensory cortices in response to CTS affecting the right and left hands simultaneously. Methods: Cortical representations activated by tactile stimulation of median nerve (index and ulnar nerve (little of both dominant and non-dominant hands were evaluated by Magnetoencephalography (MEG systemfor healthy participants and patient with bilateral moderate CTS. index – little fingers'somatotopy map and inter-digit cortical distance was then mapped and calculated for each participant on the real MRI data and the 3D brain surface image. Results: in healthy participants, index – little inter-digit somatosensory cortical distance of right hand (dominant was significantly larger than the index – little inter-digitsomatosensory cortical distance of left hand (11.2±2.1mm vs.7.0±2.9mm, P = 0.006. However, in patient with bilateral CTS, the index – little inter-digit somatosensory cortical distance of righthand (dominant was significantly smaller than the index – little inter-digit somatosensory cortical distance of left hand (5.8mm vs. 7.4mm. Conclusion: our data could be interpreted as the hand use – dependency served more median nerve – cortical territory from the ulnar nerve invasion in the right somatotopy map (left hand than the left somatotopy map of the right hand.

  18. Value of renal cortical scintigraphy in children with acute pyelonephritis

    International Nuclear Information System (INIS)

    Paul, A.K.; Miah, M.S.R.; Rahman, H.A.; Hasan, M.H.

    2004-01-01

    Purpose: Acute pyelonephritis is a major cause of morbidity in children with urinary tract infection and can result in irreversible renal scarring leading to hypertension and end-stage renal disease. Tc-99m-dimercaptosuccinic acid (DMSA) scintigraphy is the imaging modality of choice for the detection of acute pyelonephhfis and renal scarfing. This study evaluated the importance of renal cortical scintigraphy to identify children at risk from renal damage due to acute pyelonephritis. Methods: Forty-nine children (ages 9 months to 11 years) with urinary tract infection having positive urine culture were studied. A DMSA scan was performed within 72 hours of receiving antibiotic during acute infection. Single or multiple areas of varying degrees of diminished cortical uptake or diffusely decreased uptake in an enlarged kidney was considered for the diagnosis of acute pyelonephrifis. Follow-up scintigraphy was done at 6 months of initial scan in children with acute pyelonephritis documented by DMSA scan. Renal scarring was considered if the affected kidney shows cortical thinning or focal cortical defect with loss of volume or become small kidney. Children with known renal tract abnormalities were excluded from the study. RESULTS: Twenty-seven children (55%) wine considered acute pyelonephritis by DMSA scintigraphy and the abnormality was bilateral in 17(63%) cases and unilateral in 10(37%) cases. Among these 44 abnormal kidneys, scintigraphy showed solitary defect in 29 kidneys, multiple defects in 6 kidneys and diffuse decreased uptake in 9 kidneys. Of them, twenty children were available for follow-up evaluation and scintigraphy demonstrated complete recovery in 21 of 34 (62%) kidneys and renal scarfing in 13 of 34 (38%) kidneys. Renal scarring was found in 5 of 7 kidneys (71%) with diffuse decreased uptake, 2 of 5 kidneys (40%) with multiple cortical defect and 6 of 22 (27%) with single focal detect. Conclusion: The scintigraphic pattern of acute pyelonephritis

  19. Response of cortical bone to antiresorptive treatment

    DEFF Research Database (Denmark)

    Hyldstrup, Lars; Jørgensen, J T; Sørensen, T K

    2001-01-01

    of the spine, hip, and forearm. Longitudinal changes in bone densitometry were compared with changes captured by DXR: BMD evaluated by DXR (BMDDXR), cortical thickness of the second metacarpal (CTMC2), and porosity of cortical bone. The expected annual postmenopausal reduction in BMD in the control group...... treatment regimens used in the prevention of osteoporosis....

  20. Low serum vitamin D is associated with higher cortical porosity in elderly men.

    Science.gov (United States)

    Sundh, D; Mellström, D; Ljunggren, Ö; Karlsson, M K; Ohlsson, C; Nilsson, M; Nilsson, A G; Lorentzon, M

    2016-11-01

    Bone loss at peripheral sites in the elderly is mainly cortical and involves increased cortical porosity. However, an association between bone loss at these sites and 25-hydroxyvitamin D has not been reported. To investigate the association between serum levels of 25-hydroxyvitamin D, bone microstructure and areal bone mineral density (BMD) in elderly men. A population-based cohort of 444 elderly men (mean ± SD age 80.2 ± 3.5 years) was investigated. Bone microstructure was measured by high-resolution peripheral quantitative computed tomography, areal BMD by dual-energy X-ray absorptiometry and serum 25-hydroxyvitamin D and parathyroid hormone levels by immunoassay. Mean cortical porosity at the distal tibia was 14.7% higher (12.5 ± 4.3% vs. 10.9 ± 4.1%, P vitamin D levels compared to the highest. In men with vitamin D deficiency (6.8 pmol L -1 )], cortical porosity was 17.2% higher than in vitamin D-sufficient men (P vitamin D supplementation and parathyroid hormone showed that 25-hydroxyvitamin D independently predicted cortical porosity (standardized β = -0.110, R 2 = 1.1%, P = 0.024), area (β = 0.123, R 2 = 1.4%, P = 0.007) and cortical volumetric BMD (β = 0.125, R 2 = 1.4%, P = 0.007) of the tibia as well as areal BMD of the femoral neck (β = 0.102, R 2 = 0.9%, P = 0.04). Serum vitamin D is associated with cortical porosity, area and density, indicating that bone fragility as a result of low vitamin D could be due to changes in cortical bone microstructure and geometry. © 2016 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

  1. Perceptual learning and adult cortical plasticity.

    Science.gov (United States)

    Gilbert, Charles D; Li, Wu; Piech, Valentin

    2009-06-15

    The visual cortex retains the capacity for experience-dependent changes, or plasticity, of cortical function and cortical circuitry, throughout life. These changes constitute the mechanism of perceptual learning in normal visual experience and in recovery of function after CNS damage. Such plasticity can be seen at multiple stages in the visual pathway, including primary visual cortex. The manifestation of the functional changes associated with perceptual learning involve both long term modification of cortical circuits during the course of learning, and short term dynamics in the functional properties of cortical neurons. These dynamics are subject to top-down influences of attention, expectation and perceptual task. As a consequence, each cortical area is an adaptive processor, altering its function in accordance to immediate perceptual demands.

  2. Adult Pilomyxoid Astrocytoma Mimicking a Cortical Brain Tumor: MR Imaging Findings

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Jong Chang; Weon, Young Cheol; Suh, Jae Hee; Kim, Young; Hwang, Jae Cheol [Ulsan University Hospital, Ulsan (Korea, Republic of)

    2010-08-15

    A pilomyxoid astrocytoma (PMA) is a recently identified low-grade neoplasm that was previously classified as a pilocytic astrocytoma (PA), yet demonstrates unique histological features and more aggressive behavior. Although a PMA is generally a tumor of early childhood and typically occurs in the hypothalamic/chiasmatic region, it can mimic cortical tumors, especially in adults. We report the MR findings of a PMA presenting as a cortical brain tumor in an adult with neurofibromatosis 1 (NF1)

  3. Cortical Integration of Audio-Visual Information

    Science.gov (United States)

    Vander Wyk, Brent C.; Ramsay, Gordon J.; Hudac, Caitlin M.; Jones, Warren; Lin, David; Klin, Ami; Lee, Su Mei; Pelphrey, Kevin A.

    2013-01-01

    We investigated the neural basis of audio-visual processing in speech and non-speech stimuli. Physically identical auditory stimuli (speech and sinusoidal tones) and visual stimuli (animated circles and ellipses) were used in this fMRI experiment. Relative to unimodal stimuli, each of the multimodal conjunctions showed increased activation in largely non-overlapping areas. The conjunction of Ellipse and Speech, which most resembles naturalistic audiovisual speech, showed higher activation in the right inferior frontal gyrus, fusiform gyri, left posterior superior temporal sulcus, and lateral occipital cortex. The conjunction of Circle and Tone, an arbitrary audio-visual pairing with no speech association, activated middle temporal gyri and lateral occipital cortex. The conjunction of Circle and Speech showed activation in lateral occipital cortex, and the conjunction of Ellipse and Tone did not show increased activation relative to unimodal stimuli. Further analysis revealed that middle temporal regions, although identified as multimodal only in the Circle-Tone condition, were more strongly active to Ellipse-Speech or Circle-Speech, but regions that were identified as multimodal for Ellipse-Speech were always strongest for Ellipse-Speech. Our results suggest that combinations of auditory and visual stimuli may together be processed by different cortical networks, depending on the extent to which speech or non-speech percepts are evoked. PMID:20709442

  4. Identifying unstable sites on logging roads

    Science.gov (United States)

    R. M. Rice; J. Lewis

    1986-01-01

    Logging roads are an important source of forestry-related erosion. The amount of erosion on a forest road is determined by the interaction between how the road is constructed and maintained and the environment in which it is built. The roads in this study were constructed with large bulldozers, and most excavated material was sidecast. The roads studied were...

  5. Hearing with Two Ears: Evidence for Cortical Binaural Interaction during Auditory Processing.

    Science.gov (United States)

    Henkin, Yael; Yaar-Soffer, Yifat; Givon, Lihi; Hildesheimer, Minka

    2015-04-01

    Integration of information presented to the two ears has been shown to manifest in binaural interaction components (BICs) that occur along the ascending auditory pathways. In humans, BICs have been studied predominantly at the brainstem and thalamocortical levels; however, understanding of higher cortically driven mechanisms of binaural hearing is limited. To explore whether BICs are evident in auditory event-related potentials (AERPs) during the advanced perceptual and postperceptual stages of cortical processing. The AERPs N1, P3, and a late negative component (LNC) were recorded from multiple site electrodes while participants performed an oddball discrimination task that consisted of natural speech syllables (/ka/ vs. /ta/) that differed by place-of-articulation. Participants were instructed to respond to the target stimulus (/ta/) while performing the task in three listening conditions: monaural right, monaural left, and binaural. Fifteen (21-32 yr) young adults (6 females) with normal hearing sensitivity. By subtracting the response to target stimuli elicited in the binaural condition from the sum of responses elicited in the monaural right and left conditions, the BIC waveform was derived and the latencies and amplitudes of the components were measured. The maximal interaction was calculated by dividing BIC amplitude by the summed right and left response amplitudes. In addition, the latencies and amplitudes of the AERPs to target stimuli elicited in the monaural right, monaural left, and binaural listening conditions were measured and subjected to analysis of variance with repeated measures testing the effect of listening condition and laterality. Three consecutive BICs were identified at a mean latency of 129, 406, and 554 msec, and were labeled N1-BIC, P3-BIC, and LNC-BIC, respectively. Maximal interaction increased significantly with progression of auditory processing from perceptual to postperceptual stages and amounted to 51%, 55%, and 75% of the sum of

  6. Quantifying cortical surface harmonic deformation with stereovision during open cranial neurosurgery

    Science.gov (United States)

    Ji, Songbai; Fan, Xiaoyao; Roberts, David W.; Paulsen, Keith D.

    2012-02-01

    Cortical surface harmonic motion during open cranial neurosurgery is well observed in image-guided neurosurgery. Recently, we quantified cortical surface deformation noninvasively with synchronized blood pressure pulsation (BPP) from a sequence of stereo image pairs using optical flow motion tracking. With three subjects, we found the average cortical surface displacement can reach more than 1 mm and in-plane principal strains of up to 7% relative to the first image pair. In addition, the temporal changes in deformation and strain were in concert with BPP and patient respiration [1]. However, because deformation was essentially computed relative to an arbitrary reference, comparing cortical surface deformation at different times was not possible. In this study, we extend the technique developed earlier by establishing a more reliable reference profile of the cortical surface for each sequence of stereo image acquisitions. Specifically, fast Fourier transform (FFT) was applied to the dynamic cortical surface deformation, and the fundamental frequencies corresponding to patient respiration and BPP were identified, which were used to determine the number of image acquisitions for use in averaging cortical surface images. This technique is important because it potentially allows in vivo characterization of soft tissue biomechanical properties using intraoperative stereovision and motion tracking.

  7. Is the Alzheimer's disease cortical thickness signature a biological marker for memory?

    Science.gov (United States)

    Busovaca, Edgar; Zimmerman, Molly E; Meier, Irene B; Griffith, Erica Y; Grieve, Stuart M; Korgaonkar, Mayuresh S; Williams, Leanne M; Brickman, Adam M

    2016-06-01

    Recent work suggests that analysis of the cortical thickness in key brain regions can be used to identify individuals at greatest risk for development of Alzheimer's disease (AD). It is unclear to what extent this "signature" is a biological marker of normal memory function - the primary cognitive domain affected by AD. We examined the relationship between the AD signature biomarker and memory functioning in a group of neurologically healthy young and older adults. Cortical thickness measurements and neuropsychological evaluations were obtained in 110 adults (age range 21-78, mean = 46) drawn from the Brain Resource International Database. The cohort was divided into young adult (n = 64, age 21-50) and older adult (n = 46, age 51-78) groups. Cortical thickness analysis was performed with FreeSurfer, and the average cortical thickness extracted from the eight regions that comprise the AD signature. Mean AD-signature cortical thickness was positively associated with performance on the delayed free recall trial of a list learning task and this relationship did not differ between younger and older adults. Mean AD-signature cortical thickness was not associated with performance on a test of psychomotor speed, as a control task, in either group. The results suggest that the AD signature cortical thickness is a marker for memory functioning across the adult lifespan.

  8. DREAM mediates cAMP-dependent, Ca2+-induced stimulation of GFAP gene expression and regulates cortical astrogliogenesis.

    Science.gov (United States)

    Cebolla, Beatriz; Fernández-Pérez, Antonio; Perea, Gertrudis; Araque, Alfonso; Vallejo, Mario

    2008-06-25

    In the developing mouse brain, once the generation of neurons is mostly completed during the prenatal period, precisely coordinated signals act on competent neural precursors to direct their differentiation into astrocytes, which occurs mostly after birth. Among these signals, those provided by neurotrophic cytokines and bone morphogenetic proteins appear to have a key role in triggering the neurogenic to gliogenic switch and in regulating astrocyte numbers. In addition, we have reported previously that the neurotrophic peptide pituitary adenylate cyclase-activating polypeptide (PACAP) is able to promote astrocyte differentiation of cortical precursors via activation of a cAMP-dependent pathway. Signals acting on progenitor cells of the developing cortex to generate astrocytes activate glial fibrillary acidic protein (GFAP) gene expression, but the transcriptional mechanisms that regulate this activation are unclear. Here, we identify the previously known transcriptional repressor downstream regulatory element antagonist modulator (DREAM) as an activator of GFAP gene expression. We found that DREAM occupies specific sites on the GFAP promoter before and after differentiation is initiated by exposure of cortical progenitor cells to PACAP. PACAP raises intracellular calcium concentration via a mechanism that requires cAMP, and DREAM-mediated transactivation of the GFAP gene requires the integrity of calcium-binding domains. Cortical progenitor cells from dream(-/-) mice fail to express GFAP in response to PACAP. Moreover, the neonatal cortex of dream(-/-) mice exhibits a reduced number of astrocytes and increased number of neurons. These results identify the PACAP-cAMP-Ca(2+)-DREAM cascade as a new pathway to activate GFAP gene expression during astrocyte differentiation.

  9. Environmental Modeling, The Natural Filter Wetland Priority layers identify priority wetland restoration sites by subwatershed. Land use, hydrology, soil, and landscape characteristics were analyzed to rank opportunities with high nutrient removal potential., Published in 2014, Smaller than 1:100000 scale, Maryland Department of Natural Resources (DNR).

    Data.gov (United States)

    NSGIC Education | GIS Inventory — Environmental Modeling dataset current as of 2014. The Natural Filter Wetland Priority layers identify priority wetland restoration sites by subwatershed. Land use,...

  10. Ocean Disposal Site Monitoring

    Science.gov (United States)

    EPA is responsible for managing all designated ocean disposal sites. Surveys are conducted to identify appropriate locations for ocean disposal sites and to monitor the impacts of regulated dumping at the disposal sites.

  11. Promoting Your Web Site.

    Science.gov (United States)

    Raeder, Aggi

    1997-01-01

    Discussion of ways to promote sites on the World Wide Web focuses on how search engines work and how they retrieve and identify sites. Appropriate Web links for submitting new sites and for Internet marketing are included. (LRW)

  12. Cortical feedback control of olfactory bulb circuits.

    Science.gov (United States)

    Boyd, Alison M; Sturgill, James F; Poo, Cindy; Isaacson, Jeffry S

    2012-12-20

    Olfactory cortex pyramidal cells integrate sensory input from olfactory bulb mitral and tufted (M/T) cells and project axons back to the bulb. However, the impact of cortical feedback projections on olfactory bulb circuits is unclear. Here, we selectively express channelrhodopsin-2 in olfactory cortex pyramidal cells and show that cortical feedback projections excite diverse populations of bulb interneurons. Activation of cortical fibers directly excites GABAergic granule cells, which in turn inhibit M/T cells. However, we show that cortical inputs preferentially target short axon cells that drive feedforward inhibition of granule cells. In vivo, activation of olfactory cortex that only weakly affects spontaneous M/T cell firing strongly gates odor-evoked M/T cell responses: cortical activity suppresses odor-evoked excitation and enhances odor-evoked inhibition. Together, these results indicate that although cortical projections have diverse actions on olfactory bulb microcircuits, the net effect of cortical feedback on M/T cells is an amplification of odor-evoked inhibition. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Discrimination of cortical laminae using MEG.

    Science.gov (United States)

    Troebinger, Luzia; López, José David; Lutti, Antoine; Bestmann, Sven; Barnes, Gareth

    2014-11-15

    Typically MEG source reconstruction is used to estimate the distribution of current flow on a single anatomically derived cortical surface model. In this study we use two such models representing superficial and deep cortical laminae. We establish how well we can discriminate between these two different cortical layer models based on the same MEG data in the presence of different levels of co-registration noise, Signal-to-Noise Ratio (SNR) and cortical patch size. We demonstrate that it is possible to make a distinction between superficial and deep cortical laminae for levels of co-registration noise of less than 2mm translation and 2° rotation at SNR > 11 dB. We also show that an incorrect estimate of cortical patch size will tend to bias layer estimates. We then use a 3D printed head-cast (Troebinger et al., 2014) to achieve comparable levels of co-registration noise, in an auditory evoked response paradigm, and show that it is possible to discriminate between these cortical layer models in real data. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Functional Cortical Network in Alpha Band Correlates with Social Bargaining

    Science.gov (United States)

    Billeke, Pablo; Zamorano, Francisco; Chavez, Mario; Cosmelli, Diego; Aboitiz, Francisco

    2014-01-01

    Solving demanding tasks requires fast and flexible coordination among different brain areas. Everyday examples of this are the social dilemmas in which goals tend to clash, requiring one to weigh alternative courses of action in limited time. In spite of this fact, there are few studies that directly address the dynamics of flexible brain network integration during social interaction. To study the preceding, we carried out EEG recordings while subjects played a repeated version of the Ultimatum Game in both human (social) and computer (non-social) conditions. We found phase synchrony (inter-site-phase-clustering) modulation in alpha band that was specific to the human condition and independent of power modulation. The strength and patterns of the inter-site-phase-clustering of the cortical networks were also modulated, and these modulations were mainly in frontal and parietal regions. Moreover, changes in the individuals’ alpha network structure correlated with the risk of the offers made only in social conditions. This correlation was independent of changes in power and inter-site-phase-clustering strength. Our results indicate that, when subjects believe they are participating in a social interaction, a specific modulation of functional cortical networks in alpha band takes place, suggesting that phase synchrony of alpha oscillations could serve as a mechanism by which different brain areas flexibly interact in order to adapt ongoing behavior in socially demanding contexts. PMID:25286240

  15. Paediatric post-traumatic cortical defects of the distal radius

    International Nuclear Information System (INIS)

    Roach, Richard T.; Summers, Bruce N.; Cassar-Pullicino, Victor

    2002-01-01

    Paediatric post-traumatic cortical defects, although rare, are predominately seen affecting the distal radius following a greenstick or torus fracture. We review the literature and present a further two cases supported by CT and MRI. Images from an acute greenstick fracture are also presented to help understand the pathogenesis. Defects are typically solitary on plain radiographs and are usually noticed late, proximal to the site of compression. They are non-expansile in an otherwise healthy child. CT and MRI may reveal smaller multiple subperiosteal defects. Typical defects require no further management other than reassurance and advice that they may occasionally cause discomfort but resolve with time. (orig.)

  16. Exploring the influence of EGCG on the β-sheet-rich oligomers of human islet amyloid polypeptide (hIAPP1-37 and identifying its possible binding sites from molecular dynamics simulation.

    Directory of Open Access Journals (Sweden)

    Qianqian Wang

    Full Text Available EGCG possesses the ability of disaggregating the existing amyloid fibrils which were associated with many age-related degenerative diseases. However, the molecular mechanism of EGCG to disaggregate these fibrils is poorly known. In this work, to study the influence of EGCG on the full-length human islet amyloid polypeptide 1-37 (hIAPP1-37 oligomers, molecular dynamics simulations of hIAPP1-37 pentamer and decamer with EGCG were performed, respectively. The obtained results indicate that EGCG indeed destabilized the hIAPP1-37 oligomers. The nematic order parameter and secondary structure calculations coupled with the free-energy landscape indicate that EGCG broke the initial ordered pattern of two polymers, greatly reduced their β-sheet content and enlarged their conformational space. On this basis, three possible target sites were identified with the binding capacity order of S1>S2>S3. After a deeper analysis of each site, we found that S1 was the most possible site on which residues B-Ile26/Ala25, A-Phe23, B/C-Leu27 and E-Tyr37 played an important role for their binding. The proposal of this molecular mechanism can not only provide a prospective interaction figure between EGCG and β-sheet-rich fibrils of hIAPP1-37, but also is useful for further discovering other potential inhibitors.

  17. Associations between cortical thickness and general intelligence in children, adolescents and young adults

    Science.gov (United States)

    Menary, Kyle; Collins, Paul F.; Porter, James N.; Muetzel, Ryan; Olson, Elizabeth A.; Kumar, Vipin; Steinbach, Michael; Lim, Kelvin O.; Luciana, Monica

    2013-01-01

    Neuroimaging research indicates that human intellectual ability is related to brain structure including the thickness of the cerebral cortex. Most studies indicate that general intelligence is positively associated with cortical thickness in areas of association cortex distributed throughout both brain hemispheres. In this study, we performed a cortical thickness mapping analysis on data from 182 healthy typically developing males and females ages 9 to 24 years to identify correlates of general intelligence (g) scores. To determine if these correlates also mediate associations of specific cognitive abilities with cortical thickness, we regressed specific cognitive test scores on g scores and analyzed the residuals with respect to cortical thickness. The effect of age on the association between cortical thickness and intelligence was examined. We found a widely distributed pattern of positive associations between cortical thickness and g scores, as derived from the first unrotated principal factor of a factor analysis of Wechsler Abbreviated Scale of Intelligence (WASI) subtest scores. After WASI specific cognitive subtest scores were regressed on g factor scores, the residual score variances did not correlate significantly with cortical thickness in the full sample with age covaried. When participants were grouped at the age median, significant positive associations of cortical thickness were obtained in the older group for g-residualized scores on Block Design (a measure of visual-motor integrative processing) while significant negative associations of cortical thickness were observed in the younger group for g-residualized Vocabulary scores. These results regarding correlates of general intelligence are concordant with the existing literature, while the findings from younger versus older subgroups have implications for future research on brain structural correlates of specific cognitive abilities, as well as the cognitive domain specificity of behavioral

  18. Rapid Identification of Cortical Motor Areas in Rodents by High-Frequency Automatic Cortical Stimulation and Novel Motor Threshold Algorithm

    Directory of Open Access Journals (Sweden)

    Mitsuaki Takemi

    2017-10-01

    Full Text Available Cortical stimulation mapping is a valuable tool to test the functional organization of the motor cortex in both basic neurophysiology (e.g., elucidating the process of motor plasticity and clinical practice (e.g., before resecting brain tumors involving the motor cortex. However, compilation of motor maps based on the motor threshold (MT requires a large number of cortical stimulations and is therefore time consuming. Shortening the time for mapping may reduce stress on the subjects and unveil short-term plasticity mechanisms. In this study, we aimed to establish a cortical stimulation mapping procedure in which the time needed to identify a motor area is reduced to the order of minutes without compromising reliability. We developed an automatic motor mapping system that applies epidural cortical surface stimulations (CSSs through one-by-one of 32 micro-electrocorticographic electrodes while examining the muscles represented in a cortical region. The next stimulus intensity was selected according to previously evoked electromyographic responses in a closed-loop fashion. CSS was repeated at 4 Hz and electromyographic responses were submitted to a newly proposed algorithm estimating the MT with smaller number of stimuli with respect to traditional approaches. The results showed that in all tested rats (n = 12 the motor area maps identified by our novel mapping procedure (novel MT algorithm and 4-Hz CSS significantly correlated with the maps achieved by the conventional MT algorithm with 1-Hz CSS. The reliability of the both mapping methods was very high (intraclass correlation coefficients ≧0.8, while the time needed for the mapping was one-twelfth shorter with the novel method. Furthermore, the motor maps assessed by intracortical microstimulation and the novel CSS mapping procedure in two rats were compared and were also significantly correlated. Our novel mapping procedure that determined a cortical motor area within a few minutes could help

  19. Reye's syndrome with cortical laminar necrosis: MRI

    International Nuclear Information System (INIS)

    Kinoshita, T.; Takahashi, S.; Ishii, K.; Higano, S.; Matsumoto, K.; Sakamoto, K.; Haginoya, K.; Iinuma, K.

    1996-01-01

    Serial MRI findings are described in two patients with Reye's syndrome, demonstrating diffuse cortical and white matter changes. In the acute stage, T2-weighted images showed subtle but definite laminar high signal and contrast-enhanced T1-weighted images laminar enhancement, along the entire cerebral cortex bilaterally. In the chronic stage, unenhanced T1-weighted images showed diffuse cortical laminar high signal. These characteristic MRI features seemed very similar to those of laminar cortical necrosis in hypoxic brain damage. MRI also displayed delayed white matter changes with cerebral atrophy. (orig.)

  20. Cortical heterotopia in Aicardi's syndrome - CT findings

    International Nuclear Information System (INIS)

    Besenski, N.; Bosnjak, V.; Ligutic, I.; Marusic-Della Marina, B.

    1988-01-01

    The case of 5-month-old female infant with Aicardi's syndrome is presented. The main clinical features were severe developmental retardation and intractable epileptic seizures. Ophthalmoscopic examination revealed pathognomonic choriorethinopathy. Ultrasonic examination of the brain detected agenesis of the corpus callosum, whereas CT showed a coexisting malformation of the brain, i.e. cortical heterotopia of the gray matter. Agenesis of the corpus callosum is an entity well-recognized by sonography. However, ultrasonography is an insufficient modality for the visualization of cortical heterotopia which is common to all cases of Aicardi's syndrome. Therefore, in cases of suspected Aicardi's syndrome CT is recommended, as it enables the diagnosis of cortical heterotopia. (orig.)

  1. Identification of sumoylation sites in CCDC6, the first identified RET partner gene in papillary thyroid carcinoma, uncovers a mode of regulating CCDC6 function on CREB1 transcriptional activity.

    Directory of Open Access Journals (Sweden)

    Chiara Luise

    Full Text Available CCDC6 was originally identified in chimeric genes as caused by chromosomal translocation involving the RET protooncogene in some thyroid tumors. Recognised as a 65 kDa pro-apoptotic phosphoprotein, CCDC6 has been enrolled as an ATM substrate that contribute to protect genome integrity by modulating PP4c activity in response to genotoxic stress. Recently, CCDC6 has been identified as a repressor of CREB1-dependent transcription. Sumoylation has emerged as an important mechanism in transcriptional control. Here, we report the identification and characterization of three sites of sumoylation in CCDC6 (K74, K266 and K424 which are highly conserved in vertebrates. We demonstrate that the post-translational modifications by SUMO2 constrain most of the CCDC6 protein in the cytosol and affect its functional interaction with CREB1 with a decrease of CCDC6 repressive function on CREB1 transcriptional activity. Indeed, the impairment of functional outcome of sumoylated CCDC6 is obtained knocking down all three the sumoylation sites. Interestingly, in thyroid cells the SUMO2-mediated CCDC6 post-translational modifications are induced by Forskolin, a cAMP analog. Signal transduction via the cAMP pathway is known to be ubiquitous and represents a major line of communication between many organisms and their environment. We believe that CCDC6 could be an important player in the dynamics of cAMP signaling by fine regulating CREB1 transcriptional activity in normal and transformed thyroid cells.

  2. O-GlcNAcPRED-II: an integrated classification algorithm for identifying O-GlcNAcylation sites based on fuzzy undersampling and a K-means PCA oversampling technique.

    Science.gov (United States)

    Jia, Cangzhi; Zuo, Yun; Zou, Quan; Hancock, John

    2018-02-06

    Protein O-GlcNAcylation (O-GlcNAc) is an important post-translational modification of serine (S)/threonine (T) residues that involves multiple molecular and cellular processes. Recent studies have suggested that abnormal O-G1cNAcylation causes many diseases, such as cancer and various neurodegenerative diseases. With the available protein O-G1cNAcylation sites experimentally verified, it is highly desired to develop automated methods to rapidly and effectively identify O-G1cNAcylation sites. Although some computational methods have been proposed, their performance has been unsatisfactory, particularly in terms of prediction sensitivity. In this study, we developed an ensemble model O-GlcNAcPRED-II to identify potential O-G1cNAcylation sites. A K-means principal component analysis oversampling technique (KPCA) and fuzzy undersampling method (FUS) were first proposed and incorporated to reduce the proportion of the original positive and negative training samples. Then, rotation forest, a type of classifier-integrated system, was adopted to divide the eight types of feature space into several subsets using four sub-classifiers: random forest, k-nearest neighbour, naive Bayesian and support vector machine. We observed that O-GlcNAcPRED-II achieved a sensitivity of 81.05%, specificity of 95.91%, accuracy of 91.43% and Matthew's correlation coefficient of 0.7928 for five-fold cross-validation run 10 times. Additionally, the results obtained by O-GlcNAcPRED-II on two independent datasets also indicated that the proposed predictor outperformed five published prediction tools. http://121.42.167.206/OGlcPred/. cangzhijia@dlmu.edu.cn or zouquan@nclab.net. © The Author (2018). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  3. Sensory experience regulates cortical inhibition by inducing IGF1 in VIP neurons.

    Science.gov (United States)

    Mardinly, A R; Spiegel, I; Patrizi, A; Centofante, E; Bazinet, J E; Tzeng, C P; Mandel-Brehm, C; Harmin, D A; Adesnik, H; Fagiolini, M; Greenberg, M E

    2016-03-17

    Inhibitory neurons regulate the adaptation of neural circuits to sensory experience, but the molecular mechanisms by which experience controls the connectivity between different types of inhibitory neuron to regulate cortical plasticity are largely unknown. Here we show that exposure of dark-housed mice to light induces a gene program in cortical vasoactive intestinal peptide (VIP)-expressing neurons that is markedly distinct from that induced in excitatory neurons and other subtypes of inhibitory neuron. We identify Igf1 as one of several activity-regulated genes that are specific to VIP neurons, and demonstrate that IGF1 functions cell-autonomously in VIP neurons to increase inhibitory synaptic input onto these neurons. Our findings further suggest that in cortical VIP neurons, experience-dependent gene transcription regulates visual acuity by activating the expression of IGF1, thus promoting the inhibition of disinhibitory neurons and affecting inhibition onto cortical pyramidal neurons.

  4. Learning-enhanced coupling between ripple oscillations in association cortices and hippocampus.

    Science.gov (United States)

    Khodagholy, Dion; Gelinas, Jennifer N; Buzsáki, György

    2017-10-20

    Consolidation of declarative memories requires hippocampal-neocortical communication. Although experimental evidence supports the role of sharp-wave ripples in transferring hippocampal information to the neocortex, the exact cortical destinations and the physiological mechanisms of such transfer are not known. We used a conducting polymer-based conformable microelectrode array (NeuroGrid) to record local field potentials and neural spiking across the dorsal cortical surface of the rat brain, combined with silicon probe recordings in the hippocampus, to identify candidate physiological patterns. Parietal, midline, and prefrontal, but not primary cortical areas, displayed localized ripple (100 to 150 hertz) oscillations during sleep, concurrent with hippocampal ripples. Coupling between hippocampal and neocortical ripples was strengthened during sleep following learning. These findings suggest that ripple-ripple coupling supports hippocampal-association cortical transfer of memory traces. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  5. Biomechanics of far cortical locking.

    Science.gov (United States)

    Bottlang, Michael; Feist, Florian

    2011-02-01

    The development of far cortical locking (FCL) was motivated by a conundrum: locked plating constructs provide inherently rigid stabilization, yet they should facilitate biologic fixation and secondary bone healing that relies on flexible fixation to stimulate callus formation. Recent studies have confirmed that the high stiffness of standard locked plating constructs can suppress interfragmentary motion to a level that is insufficient to reliably promote secondary fracture healing by callus formation. Furthermore, rigid locking screws cause an uneven stress distribution that may lead to stress fracture at the end screw and stress shielding under the plate. This review summarizes four key features of FCL constructs that have been shown to enhance fixation and healing of fractures: flexible fixation, load distribution, progressive stiffening, and parallel interfragmentary motion. Specifically, flexible fixation provided by FCL reduces the stiffness of a locked plating construct by 80% to 88% to actively promote callus proliferation similar to an external fixator. Load is evenly distributed between FCL screws to mitigate stress risers at the end screw. Progressive stiffening occurs by near cortex support of FCL screws and provides additional support under elevated loading. Finally, parallel interfragmentary motion by the S-shaped flexion of FCL screws promotes symmetric callus formation. In combination, these features of FCL constructs have been shown to induce more callus and to yield significantly stronger and more consistent healing compared with standard locked plating constructs. As such, FCL constructs function as true internal fixators by replicating the biomechanical behavior and biologic healing response of external fixators.

  6. Human cortical areas involved in perception of surface glossiness.

    Science.gov (United States)

    Wada, Atsushi; Sakano, Yuichi; Ando, Hiroshi

    2014-09-01

    Glossiness is the visual appearance of an object's surface as defined by its surface reflectance properties. Despite its ecological importance, little is known about the neural substrates underlying its perception. In this study, we performed the first human neuroimaging experiments that directly investigated where the processing of glossiness resides in the visual cortex. First, we investigated the cortical regions that were more activated by observing high glossiness compared with low glossiness, where the effects of simple luminance and luminance contrast were dissociated by controlling the illumination conditions (Experiment 1). As cortical regions that may be related to the processing of glossiness, V2, V3, hV4, VO-1, VO-2, collateral sulcus (CoS), LO-1, and V3A/B were identified, which also showed significant correlation with the perceived level of glossiness. This result is consistent with the recent monkey studies that identified selective neural response to glossiness in the ventral visual pathway, except for V3A/B in the dorsal visual pathway, whose involvement in the processing of glossiness could be specific to the human visual system. Second, we investigated the cortical regions that were modulated by selective attention to glossiness (Experiment 2). The visual areas that showed higher activation to attention to glossiness than that to either form or orientation were identified as right hV4, right VO-2, and right V3A/B, which were commonly identified in Experiment 1. The results indicate that these commonly identified visual areas in the human visual cortex may play important roles in glossiness perception. Copyright © 2014. Published by Elsevier Inc.

  7. Perceptual incongruence influences bistability and cortical activation

    NARCIS (Netherlands)

    Brouwer, G.J.; Tong, F.; Hagoort, P.; van Ee, R.

    2009-01-01

    We employed a parametric psychophysical design in combination with functional imaging to examine the influence of metric changes in perceptual incongruence on perceptual alternation rates and cortical responses. Subjects viewed a bistable stimulus defined by incongruent depth cues; bistability

  8. Cortical electrophysiological network dynamics of feedback learning

    NARCIS (Netherlands)

    Cohen, M.X.; Wilmes, K.A.; van de Vijver, I.

    2011-01-01

    Understanding the neurophysiological mechanisms of learning is important for both fundamental and clinical neuroscience. We present a neurophysiologically inspired framework for understanding cortical mechanisms of feedback-guided learning. This framework is based on dynamic changes in systems-level

  9. The Diversity of Cortical Inhibitory Synapses

    Directory of Open Access Journals (Sweden)

    Yoshiyuki eKubota

    2016-04-01

    Full Text Available The most typical and well known inhibitory action in the cortical microcircuit is a strong inhibition on the target neuron by axo-somatic synapses. However, it has become clear that synaptic inhibition in the cortex is much more diverse and complicated. Firstly, at least ten or more inhibitory non-pyramidal cell subtypes engage in diverse inhibitory functions to produce the elaborate activity characteristic of the different cortical states. Each distinct non-pyramidal cell subtype has its own independent inhibitory function. Secondly, the inhibitory synapses innervate different neuronal domains, such as axons, spines, dendrites and soma, and their IPSP size is not uniform. Thus cortical inhibition is highly complex, with a wide variety of anatomical and physiological modes. Moreover, the functional significance of the various inhibitory synapse innervation styles and their unique structural dynamic behaviors differ from those of excitatory synapses. In this review, we summarize our current understanding of the inhibitory mechanisms of the cortical microcircuit.

  10. Cortical modulation of the nucleus of the optic tract in the rabbit.

    Science.gov (United States)

    Pettorossi, V E; Troiani, D

    1983-09-01

    We analyzed in rabbits the relationships between the temporooccipital nystagmogenic cortex (NGC)--the region sited at the border between cortical areas 17, 21, and 22--and the nucleus of the optic tract (NOT). Two experimental approaches were used: (a) eye movement analysis before and after electrolytic lesion of the NOT region provided an indication of the importance of the NOT for the interaction between the ocular nystagmus elicited by natural optokinetic stimulation (OKN) and the nystagmus evoked by electrical stimulation of the nystagmogenic area; (b) NOT direction-selective and velocity-sensitive units were tested with single shock or repetitive electrical stimulation of the nystagmogenic region. Single-shock stimulation evoked single or multiple spikes in 50% of NOT units analyzed and repetitive stimuli induced prolonged facilitation and inhibitory rebounds in 70% of the units tested. Comparison of orthodromic activation latencies of the NOT cells (3.2 and 6.1 ms) after cortical stimulation and of antidromic activation latencies of cortical nystagmogenic units (2.6 ms) after NOT shocks, suggested monosynaptic as well as polysynaptic connections between the temporooccipital cortex and the NOT. The existence of such cortical-NOT linkage indicates that the NOT is intercalated between the cortex and the oculomotor centers and represents the most probable site of interaction of the cortical nystagmus pathway with the optokinetic reflex arc.

  11. Extent of cortical involvement in amyotrophic lateral sclerosis--an analysis based on cortical thickness.

    Science.gov (United States)

    Thorns, Johannes; Jansma, Henk; Peschel, Thomas; Grosskreutz, Julian; Mohammadi, Bahram; Dengler, Reinhard; Münte, Thomas F

    2013-10-18

    Besides the defining involvement of upper and lower motor neurons, the involvement of extramotor structures has been increasingly acknowledged in amyotrophic lateral sclerosis (ALS). Here we investigated a group of 14 mildly to moderately affected ALS patients and 14 age-matched healthy control participants using cortical thickness analysis. Cortical thickness was determined from high resolution 3D T1 magnetic resonance images and involved semiautomatic segmentation in grey and white matter, cortical alignment and determination of thickness using the Laplace method. In addition to a whole-cortex analysis a region of interest approach was applied. ALS patients showed regions of significant cortical thinning in the pre- and postcentral gyri bilaterally. Further regions of cortical thinning included superior and inferior parietal lobule, angular and supramarginal gyrus, insula, superior frontal, temporal and occipital regions, thus further substantiating extramotor involvement in ALS. A relationship between cortical thickness of the right superior frontal cortex and clinical severity (assessed by the ALS functional rating scale) was also demonstrated. Cortical thickness is reduced in ALS not only in motor areas but in widespread non-motor cortical areas. Cortical thickness is related to clinical severity.

  12. Cortical oscillations modulated by congruent and incongruent audiovisual stimuli.

    Science.gov (United States)

    Herdman, A T; Fujioka, T; Chau, W; Ross, B; Pantev, C; Picton, T W

    2004-11-30

    Congruent or incongruent grapheme-phoneme stimuli are easily perceived as one or two linguistic objects. The main objective of this study was to investigate the changes in cortical oscillations that reflect the processing of congruent and incongruent audiovisual stimuli. Graphemes were Japanese Hiragana characters for four different vowels (/a/, /o/, /u/, and /i/). They were presented simultaneously with their corresponding phonemes (congruent) or non-corresponding phonemes (incongruent) to native-speaking Japanese participants. Participants' reaction times to the congruent audiovisual stimuli were significantly faster by 57 ms as compared to reaction times to incongruent stimuli. We recorded the brain responses for each condition using a whole-head magnetoencephalograph (MEG). A novel approach to analysing MEG data, called synthetic aperture magnetometry (SAM), was used to identify event-related changes in cortical oscillations involved in audiovisual processing. The SAM contrast between congruent and incongruent responses revealed greater event-related desynchonization (8-16 Hz) bilaterally in the occipital lobes and greater event-related synchronization (4-8 Hz) in the left transverse temporal gyrus. Results from this study further support the concept of interactions between the auditory and visual sensory cortices in multi-sensory processing of audiovisual objects.

  13. Cortico-Cortical Receptive Field Estimates in Human Visual Cortex

    Directory of Open Access Journals (Sweden)

    Koen V Haak

    2012-05-01

    Full Text Available Human visual cortex comprises many visual areas that contain a map of the visual field (Wandell et al 2007, Neuron 56, 366–383. These visual field maps can be identified readily in individual subjects with functional magnetic resonance imaging (fMRI during experimental sessions that last less than an hour (Wandell and Winawer 2011, Vis Res 718–737. Hence, visual field mapping with fMRI has been, and still is, a heavily used technique to examine the organisation of both normal and abnormal human visual cortex (Haak et al 2011, ACNR, 11(3, 20–21. However, visual field mapping cannot reveal every aspect of human visual cortex organisation. For example, the information processed within a visual field map arrives from somewhere and is sent to somewhere, and visual field mapping does not derive these input/output relationships. Here, we describe a new, model-based analysis for estimating the dependence between signals in distinct cortical regions using functional magnetic resonance imaging (fMRI data. Just as a stimulus-referred receptive field predicts the neural response as a function of the stimulus contrast, the neural-referred receptive field predicts the neural response as a function of responses elsewhere in the nervous system. When applied to two cortical regions, this function can be called the cortico-cortical receptive field (CCRF. We model the CCRF as a Gaussian-weighted region on the cortical surface and apply the model to data from both stimulus-driven and resting-state experimental conditions in visual cortex.

  14. Mapping auditory core, lateral belt, and parabelt cortices in the human superior temporal gyrus

    DEFF Research Database (Denmark)

    Sweet, Robert A; Dorph-Petersen, Karl-Anton; Lewis, David A

    2005-01-01

    The goal of the present study was to determine whether the architectonic criteria used to identify the core, lateral belt, and parabelt auditory cortices in macaque monkeys (Macaca fascicularis) could be used to identify homologous regions in humans (Homo sapiens). Current evidence indicates...

  15. Exome Sequencing Identifies a Novel LMNA Splice-Site Mutation and Multigenic Heterozygosity of Potential Modifiers in a Family with Sick Sinus Syndrome, Dilated Cardiomyopathy, and Sudden Cardiac Death.

    Directory of Open Access Journals (Sweden)

    Michael V Zaragoza

    Full Text Available The goals are to understand the primary genetic mechanisms that cause Sick Sinus Syndrome and to identify potential modifiers that may result in intrafamilial variability within a multigenerational family. The proband is a 63-year-old male with a family history of individuals (>10 with sinus node dysfunction, ventricular arrhythmia, cardiomyopathy, heart failure, and sudden death. We used exome sequencing of a single individual to identify a novel LMNA mutation and demonstrated the importance of Sanger validation and family studies when evaluating candidates. After initial single-gene studies were negative, we conducted exome sequencing for the proband which produced 9 gigabases of sequencing data. Bioinformatics analysis showed 94% of the reads mapped to the reference and identified 128,563 unique variants with 108,795 (85% located in 16,319 genes of 19,056 target genes. We discovered multiple variants in known arrhythmia, cardiomyopathy, or ion channel associated genes that may serve as potential modifiers in disease expression. To identify candidate mutations, we focused on ~2,000 variants located in 237 genes of 283 known arrhythmia, cardiomyopathy, or ion channel associated genes. We filtered the candidates to 41 variants in 33 genes using zygosity, protein impact, database searches, and clinical association. Only 21 of 41 (51% variants were validated by Sanger sequencing. We selected nine confirmed variants with minor allele frequencies G, a novel heterozygous splice-site mutation as the primary mutation with rare or novel variants in HCN4, MYBPC3, PKP4, TMPO, TTN, DMPK and KCNJ10 as potential modifiers and a mechanism consistent with haploinsufficiency.

  16. Electrocorticographic Temporal Alteration Mapping: A Clinical Technique for Mapping the Motor Cortex with Movement-Related Cortical Potentials

    Directory of Open Access Journals (Sweden)

    Zehan Wu

    2017-06-01

    Full Text Available We propose electrocorticographic temporal alteration mapping (ETAM for motor cortex mapping by utilizing movement-related cortical potentials (MRCPs within the low-frequency band [0.05-3] Hz. This MRCP waveform-based temporal domain approach was compared with the state-of-the-art electrocorticographic frequency alteration mapping (EFAM, which is based on frequency spectrum dynamics. Five patients (two epilepsy cases and three tumor cases were enrolled in the study. Each patient underwent intraoperative direct electrocortical stimulation (DECS procedure for motor cortex localization. Moreover, the patients were required to perform simple brisk wrist extension task during awake craniotomy surgery. Cross-validation results showed that the proposed ETAM method had high sensitivity (81.8% and specificity (94.3% in identifying sites which exhibited positive DECS motor responses. Moreover, although the sensitivity of the ETAM and EFAM approaches was not significantly different, ETAM had greater specificity compared with EFAM (94.3 vs. 86.1%. These results indicate that for the intraoperative functional brain mapping, ETAM is a promising novel approach for motor cortex localization with the potential to reduce the need for cortical electrical stimulation.

  17. Assessment of cortical and sub-cortical function in neonates by electrophysiological monitoring

    NARCIS (Netherlands)

    Jennekens, W.

    2012-01-01

    The aim of this thesis was the assessment of cortical and sub-cortical function in neonates by electrophysiological monitoring, i.e. to evaluate the function of the neonatal cortex and brainstem through quantitative analysis of signals readily available in the NICU. These signals include

  18. Osmosis in Cortical Collecting Tubules

    Science.gov (United States)

    Schafer, James A.; Troutman, Susan L.; Andreoli, Thomas E.

    1974-01-01

    The present experiments were designed to evaluate the effects of varying the osmolality of luminal solutions on the antidiuretic hormone (ADH)-independent water and solute permeability properties of isolated rabbit cortical collecting tubules. In the absence of ADH, the osmotic water permeability coefficient (cm s–1) Pfl→b, computed from volume flows from hypotonic lumen to isotonic bath, was 20 ± 4 x 10–4 (SEM); the value of Pfb→l in the absence of ADH, computed from volume flows from isotonic bath to hypertonic lumen, was 88 ± 15 x 10–4 cm s–1. We also measured apparent urea permeability coefficients (cm s–1) from 14C-urea fluxes from lumen to bath (P DDurea l→b) and from bath to lumen (P DDurea b→l). For hypotonic luminal solutions and isotonic bathing solutions, P DDurea l→b was 0.045 ± 0.004 x 10–4 and was unaffected by ADH. The ADH-independent values of P DDurea l→b and P urea b→l were, respectively, 0.216 ± 0.022 x 10–4 cm s–1 and 0.033 ± 0.002 x 10–4 cm s–1 for isotonic bathing solutions and luminal solutions made hypertonic with urea, i.e., there was an absolute increase in urea permeability and asymmetry of urea fluxes. Significantly, P DDurea l→b did not rise when luminal hypertonicity was produced by sucrose; and, bathing fluid hypertonicity did not alter tubular permeability to water or to urea. We interpret these data to indicate that luminal hypertonicity increased the leakiness of tight junctions to water and urea but not sucrose. Since the value of Pfb→l in the absence of ADH, when tight junctions were open to urea, was approximately half of the value of Pfl→b in the presence of ADH, when tight junctions were closed to urea, we conclude that tight junctions are negligible paracellular shunts for lumen to bath osmosis with ADH. These findings, together with those in the preceding paper, are discussed in terms of a solubility-diffusion model for water permeation in which ADH increases water solubility in

  19. Cortical Photostimulation Technology for Vision Prosthesis

    Science.gov (United States)

    2017-05-01

    Milestone Brain tissue harvest completed 12 ongoing (15%) *When obstacles arose during the synthesis of oxNI-Glu, we prepared an alternative caged...photostimulation, which permits better penetration into brain tissue. Characterization of the properties of oxNI-Glu, most important being photolysis kinetics and...Name Patrick O. Kanold Project Role Site P.I. at Univ. of Maryland, College Park Researcher identifier eRA Commons: Pkanold Person months worked 1

  20. Structural and functional evaluation of cortical motor areas in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Cosottini, Mirco; Pesaresi, Ilaria; Piazza, Selina; Diciotti, Stefano; Cecchi, Paolo; Fabbri, Serena; Carlesi, Cecilia; Mascalchi, Mario; Siciliano, Gabriele

    2012-03-01

    The structural and functional data gathered with Magnetic Resonance Imaging (MRI) techniques about the brain cortical motor damage in Amyotrophic Lateral Sclerosis (ALS) are controversial. In fact some structural MRI studies showed foci of gray matter (GM) atrophy in the precentral gyrus, even in the early stage, while others did not. Most functional MRI (fMRI) studies in ALS reported hyperactivation of extra-primary motor cortices, while contradictory results were obtained on the activation of the primary motor cortex. We aimed to investigate the cortical motor circuitries in ALS patients by a combined structural and functional approach. Twenty patients with definite ALS and 16 healthy subjects underwent a structural examination with acquisition of a 3D T1-weighted sequence and fMRI examination during a maximal force handgrip task executed with the right-hand, the left-hand and with both hands simultaneously. The T1-weighted images were analyzed with Voxel-Based Morphometry (VBM) that showed several clusters of reduced cortical GM in ALS patients compared to controls including the pre and postcentral gyri, the superior, middle and inferior frontal gyri, the supplementary motor area, the superior and inferior parietal cortices and the temporal lobe, bilaterally but more extensive on the right side. In ALS patients a significant hypoactivation of the primary sensory motor cortex and frontal dorsal premotor areas as compared to controls was observed. The hypoactivated areas matched with foci of cortical atrophy demonstrated by VBM. The fMRI analysis also showed an enhanced activation in the ventral premotor frontal areas and in the parietal cortex pertaining to the fronto-parietal motor circuit which paralleled with disease progression rate and matched with cortical regions of atrophy. The hyperactivation of the fronto-parietal circuit was asymmetric and prevalent in the left hemisphere. VBM and fMRI identified structural and functional markers of an extended

  1. Decreased prefrontal cortical dopamine transmission in alcoholism.

    Science.gov (United States)

    Narendran, Rajesh; Mason, Neale Scott; Paris, Jennifer; Himes, Michael L; Douaihy, Antoine B; Frankle, W Gordon

    2014-08-01

    Basic studies have demonstrated that optimal levels of prefrontal cortical dopamine are critical to various executive functions such as working memory, attention, inhibitory control, and risk/reward decisions, all of which are impaired in addictive disorders such as alcoholism. Based on this and imaging studies of alcoholism that have demonstrated less dopamine in the striatum, the authors hypothesized decreased dopamine transmission in the prefrontal cortex in persons with alcohol dependence. To test this hypothesis, amphetamine and [11C]FLB 457 positron emission tomography were used to measure cortical dopamine transmission in 21 recently abstinent persons with alcohol dependence and 21 matched healthy comparison subjects. [11C]FLB 457 binding potential, specific compared to nondisplaceable uptake (BPND), was measured in subjects with kinetic analysis using the arterial input function both before and after 0.5 mg kg-1 of d-amphetamine. Amphetamine-induced displacement of [11C]FLB 457 binding potential (ΔBPND) was significantly smaller in the cortical regions in the alcohol-dependent group compared with the healthy comparison group. Cortical regions that demonstrated lower dopamine transmission in the alcohol-dependent group included the dorsolateral prefrontal cortex, medial prefrontal cortex, orbital frontal cortex, temporal cortex, and medial temporal lobe. The results of this study, for the first time, unambiguously demonstrate decreased dopamine transmission in the cortex in alcoholism. Further research is necessary to understand the clinical relevance of decreased cortical dopamine as to whether it is related to impaired executive function, relapse, and outcome in alcoholism.

  2. Role of peripheral quantitative computed tomography in identifying disuse osteoporosis in paraplegia

    International Nuclear Information System (INIS)

    Coupaud, Sylvie; McLean, Alan N.; Allan, David B.

    2009-01-01

    Disuse osteoporosis is a major long-term health consequence of spinal cord injury (SCI) that still needs to be addressed. Its management in SCI should begin with accurate diagnosis, followed by targeted treatments in the most vulnerable subgroups. We present data quantifying disuse osteoporosis in a cross-section of the Scottish paraplegic population to identify subgroups with lowest bone mineral density (BMD). Forty-seven people with chronic SCI at levels T2-L2 were scanned using peripheral quantitative computed tomography at four tibial sites and two femoral sites, at the Queen Elizabeth National Spinal Injuries Unit, Glasgow (UK). At the distal epiphyses, trabecular BMD (BMDtrab), total BMD, total bone cross-sectional area (CSA) and bone mineral content (BMC) were determined. In the diaphyses, cortical BMD, total bone CSA, cortical CSA and BMC were calculated. Bone, muscle and fat CSAs were estimated in the lower leg and thigh. BMDtrab decreased exponentially with time since injury at different rates in the tibia and femur. At most sites, female paraplegics had significantly lower BMC, total bone CSA and muscle CSA than male paraplegics. Subjects with lumbar SCI tended to have lower bone values and smaller muscle CSAs than in thoracic SCI. At the distal epiphyses of the tibia and femur, there is generally a rapid and extensive reduction in BMDtrab after SCI. Female subjects, and those with lumbar SCI, tend to have lower bone values than males or those with thoracic SCI, respectively. (orig.)

  3. Role of peripheral quantitative computed tomography in identifying disuse osteoporosis in paraplegia

    Energy Technology Data Exchange (ETDEWEB)

    Coupaud, Sylvie [University of Glasgow, Centre for Rehabilitation Engineering, Department of Mechanical Engineering, Glasgow (United Kingdom); Southern General Hospital, Queen Elizabeth National Spinal Injuries Unit, Glasgow (United Kingdom); McLean, Alan N.; Allan, David B. [Southern General Hospital, Queen Elizabeth National Spinal Injuries Unit, Glasgow (United Kingdom)

    2009-10-15

    Disuse osteoporosis is a major long-term health consequence of spinal cord injury (SCI) that still needs to be addressed. Its management in SCI should begin with accurate diagnosis, followed by targeted treatments in the most vulnerable subgroups. We present data quantifying disuse osteoporosis in a cross-section of the Scottish paraplegic population to identify subgroups with lowest bone mineral density (BMD). Forty-seven people with chronic SCI at levels T2-L2 were scanned using peripheral quantitative computed tomography at four tibial sites and two femoral sites, at the Queen Elizabeth National Spinal Injuries Unit, Glasgow (UK). At the distal epiphyses, trabecular BMD (BMDtrab), total BMD, total bone cross-sectional area (CSA) and bone mineral content (BMC) were determined. In the diaphyses, cortical BMD, total bone CSA, cortical CSA and BMC were calculated. Bone, muscle and fat CSAs were estimated in the lower leg and thigh. BMDtrab decreased exponentially with time since injury at different rates in the tibia and femur. At most sites, female paraplegics had significantly lower BMC, total bone CSA and muscle CSA than male paraplegics. Subjects with lumbar SCI tended to have lower bone values and smaller muscle CSAs than in thoracic SCI. At the distal epiphyses of the tibia and femur, there is generally a rapid and extensive reduction in BMDtrab after SCI. Female subjects, and those with lumbar SCI, tend to have lower bone values than males or those with thoracic SCI, respectively. (orig.)

  4. Qualia could arise from information processing in local cortical networks.

    Science.gov (United States)

    Orpwood, Roger

    2013-01-01

    Re-entrant feedback, either within sensory cortex or arising from prefrontal areas, has been strongly linked to the emergence of consciousness, both in theoretical and experimental work. This idea, together with evidence for local micro-consciousness, suggests the generation of qualia could in some way result from local network activity under re-entrant activation. This paper explores the possibility by examining the processing of information by local cortical networks. It highlights the difference between the information structure (how the information is physically embodied), and the information message (what the information is about). It focuses on the network's ability to recognize information structures amongst its inputs under conditions of extensive local feedback, and to then assign information messages to those structures. It is shown that if the re-entrant feedback enables the network to achieve an attractor state, then the message assigned in any given pass of information through the network is a representation of the message assigned in the previous pass-through of information. Based on this ability the paper argues that as information is repeatedly cycled through the network, the information message that is assigned evolves from a recognition of what the input structure is, to what it is like, to how it appears, to how it seems. It could enable individual networks to be the site of qualia generation. The paper goes on to show networks in cortical layers 2/3 and 5a have the connectivity required for the behavior proposed, and reviews some evidence for a link between such local cortical cyclic activity and conscious percepts. It concludes with some predictions based on the theory discussed.

  5. PET in malformations of cortical development

    International Nuclear Information System (INIS)

    Bouilleret, V.; O'Brien, T.J.; Bouilleret, V.; Bouilleret, V.; Chiron, C.; Chiron, C.

    2009-01-01

    Within the group of malformations of cortical development, focal cortical dysplasia (FCD) are an increasingly recognized cause of intractable epilepsy that can be cured by surgery. The success of cortical resection for intractable epilepsy is highly dependent on the accurate pre-surgical delineation of the regions responsible for generating seizures. [ 18 F]-FDG PET, which images cerebral metabolism studying brain glucose uptake, is the most established functional imaging modality in the evaluation of patients with epilepsy. The aim of this article is to review [ 18 F]-FDG PET usefulness as a pre-surgical tool in the evaluation of medically refractory partial epilepsy. It has an established place in assisting in the localisation and definition of FCD in patients with no lesion, or only a subtle abnormality, on MRI. The role of FDG-PET in defining the extent of the surgical resection is still uncertain and needs to be the focus of future research. (authors)

  6. Reduced cortical thickness in gambling disorder

    DEFF Research Database (Denmark)

    Grant, Jon E; Odlaug, Brian Lawrence; Chamberlain, Samuel R

    2015-01-01

    with significant reductions (average 15.8-19.9 %) in cortical thickness, versus controls, predominantly in right frontal cortical regions. Pronounced right frontal morphometric brain abnormalities occur in gambling disorder, supporting neurobiological overlap with substance disorders and its recent......Gambling disorder has recently been recognized as a prototype 'behavioral addiction' by virtue of its inclusion in the DSM-5 category of 'Substance-Related and Addictive Disorders.' Despite its newly acquired status and prevalence rate of 1-3 % globally, relatively little is known regarding...... the neurobiology of this disorder. The aim of this study was to explore cortical morphometry in untreated gambling disorder, for the first time. Subjects with gambling disorder (N = 16) free from current psychotropic medication or psychiatric comorbidities, and healthy controls (N = 17), were entered...

  7. MicroRNA-338 Attenuates Cortical Neuronal Outgrowth by Modulating the Expression of Axon Guidance Genes.

    Science.gov (United States)

    Kos, Aron; Klein-Gunnewiek, Teun; Meinhardt, Julia; Loohuis, Nikkie F M Olde; van Bokhoven, Hans; Kaplan, Barry B; Martens, Gerard J; Kolk, Sharon M; Aschrafi, Armaz

    2017-07-01

    MicroRNAs (miRs) are small non-coding RNAs that confer robustness to gene networks through post-transcriptional gene regulation. Previously, we identified miR-338 as a modulator of axonal outgrowth in sympathetic neurons. In the current study, we examined the role of miR-338 in the development of cortical neurons and uncovered its downstream mRNA targets. Long-term inhibition of miR-338 during neuronal differentiation resulted in reduced dendritic complexity and altered dendritic spine morphology. Furthermore, monitoring axon outgrowth in cortical cells revealed that miR-338 overexpression decreased, whereas inhibition of miR-338 increased axonal length. To identify gene targets mediating the observed phenotype, we inhibited miR-338 in cortical neurons and performed whole-transcriptome analysis. Pathway analysis revealed that miR-338 modulates a subset of transcripts involved in the axonal guidance machinery by means of direct and indirect gene targeting. Collectively, our results implicate miR-338 as a novel regulator of cortical neuronal maturation by fine-tuning the expression of gene networks governing cortical outgrowth.

  8. Cortical atrophy rates in Alzheimer's patients and subjects with mild cognitive impairment from the AddNeuroMed data collection

    DEFF Research Database (Denmark)

    Eskildsen, Simon Fristed; Westman, Eric; Gwadry-Sridhar, Femida

    2010-01-01

    Background: The AddNeuroMed project is a multi-centre European project which aims to identify biomarkers in Alzheimer's disease (AD). In this study we measured the rate of cortical atrophy in AD patients, subjects with mild cognitive impairment (MCI), and healthy controls (HC) using MRI. Methods...... quality control for both the acquisition and image processing were included in the study. Cortical thickness was measured using FACE (fast accurate cortex extraction) and averaged within main lobes using a stereotaxic atlas. Atrophy rates were calculated as percent decrease in cortical thickness and rate...

  9. Rasmussen's encephalitis presenting as focal cortical dysplasia

    Directory of Open Access Journals (Sweden)

    D.J. O'Rourke

    2014-01-01

    Full Text Available Rasmussen's encephalitis is a rare syndrome characterized by intractable seizures, often associated with epilepsia partialis continua and symptoms of progressive hemispheric dysfunction. Seizures are usually the hallmark of presentation, but antiepileptic drug treatment fails in most patients and is ineffective against epilepsia partialis continua, which often requires surgical intervention. Co-occurrence of focal cortical dysplasia has only rarely been described and may have implications regarding pathophysiology and management. We describe a rare case of dual pathology of Rasmussen's encephalitis presenting as a focal cortical dysplasia (FCD and discuss the literature on this topic.

  10. Rasmussen's encephalitis presenting as focal cortical dysplasia

    Science.gov (United States)

    O'Rourke, D.J.; Bergin, A.; Rotenberg, A.; Peters, J.; Gorman, M.; Poduri, A.; Cryan, J.; Lidov, H.; Madsen, J.; Harini, C.

    2014-01-01

    Rasmussen's encephalitis is a rare syndrome characterized by intractable seizures, often associated with epilepsia partialis continua and symptoms of progressive hemispheric dysfunction. Seizures are usually the hallmark of presentation, but antiepileptic drug treatment fails in most patients and is ineffective against epilepsia partialis continua, which often requires surgical intervention. Co-occurrence of focal cortical dysplasia has only rarely been described and may have implications regarding pathophysiology and management. We describe a rare case of dual pathology of Rasmussen's encephalitis presenting as a focal cortical dysplasia (FCD) and discuss the literature on this topic. PMID:25667877

  11. Cortical Networks for Visual Self-Recognition

    Science.gov (United States)

    Sugiura, Motoaki

    This paper briefly reviews recent developments regarding the brain mechanisms of visual self-recognition. A special cognitive mechanism for visual self-recognition has been postulated based on behavioral and neuropsychological evidence, but its neural substrate remains controversial. Recent functional imaging studies suggest that multiple cortical mechanisms play self-specific roles during visual self-recognition, reconciling the existing controversy. Respective roles for the left occipitotemporal, right parietal, and frontal cortices in symbolic, visuospatial, and conceptual aspects of self-representation have been proposed.

  12. Cortical networks for visual self-recognition

    International Nuclear Information System (INIS)

    Sugiura, Motoaki

    2007-01-01

    This paper briefly reviews recent developments regarding the brain mechanisms of visual self-recognition. A special cognitive mechanism for visual self-recognition has been postulated based on behavioral and neuropsychological evidence, but its neural substrate remains controversial. Recent functional imaging studies suggest that multiple cortical mechanisms play self-specific roles during visual self-recognition, reconciling the existing controversy. Respective roles for the left occipitotemporal, right parietal, and frontal cortices in symbolic, visuospatial, and conceptual aspects of self-representation have been proposed. (author)

  13. Mu opioid receptor binding sites in human brain

    International Nuclear Information System (INIS)

    Pilapil, C.; Welner, S.; Magnan, J.; Zamir, N.; Quirion, R.

    1986-01-01

    Our experiments focused on the examination of the distribution of mu opioid receptor binding sites in normal human brain using the highly selective ligand [ 3 H]DAGO, in both membrane binding assay and in vitro receptor autoradiography. Mu opioid binding sites are very discretely distributed in human brain with high densities of sites found in the posterior amygdala, caudate, putamen, hypothalamus and certain cortical areas. Moreover the autoradiographic distribution of [ 3 H]DAGO binding sites clearly reveals the discrete lamination (layers I and III-IV) of mu sites in cortical areas

  14. Comparing the influence of crestal cortical bone and sinus floor cortical bone in posterior maxilla bi-cortical dental implantation: a three-dimensional finite element analysis.

    Science.gov (United States)

    Yan, Xu; Zhang, Xinwen; Chi, Weichao; Ai, Hongjun; Wu, Lin

    2015-05-01

    This study aimed to compare the influence of alveolar ridge cortical bone and sinus floor cortical bone in sinus areabi-cortical dental implantation by means of 3D finite element analysis. Three-dimensional finite element (FE) models in a posterior maxillary region with sinus membrane and the same height of alveolar ridge of 10 mm were generated according to the anatomical data of the sinus area. They were either with fixed thickness of crestal cortical bone and variable thickness of sinus floor cortical bone or vice versa. Ten models were assumed to be under immediate loading or conventional loading. The standard implant model based on the Nobel Biocare implant system was created via computer-aided design software. All materials were assumed to be isotropic and linearly elastic. An inclined force of 129 N was applied. Von Mises stress mainly concentrated on the surface of crestal cortical bone around the implant neck. For all the models, both the axial and buccolingual resonance frequencies of conventional loading were higher than those of immediate loading; however, the difference is less than 5%. The results showed that bi-cortical implant in sinus area increased the stability of the implant, especially for immediately loading implantation. The thickness of both crestal cortical bone and sinus floor cortical bone influenced implant micromotion and stress distribution; however, crestal cortical bone may be more important than sinus floor cortical bone.

  15. Electrophysiological and pathological study of focal cortical dysplasia

    International Nuclear Information System (INIS)

    Hodozuka, Akira; Hashizume, Kiyotaka; Hayashi, Yoshimitsu; Tanaka, Tatsuya

    2008-01-01

    Clinical and experimental studies on focal cortical dysplasia (FCD) were carried out. For the experimental study, an experimental FCD model of rats was developed. Twenty Wistar rats at 0-2 days after birth were used for the study. Kainic acid (KA) solution was injected stereotaxically into medial and lateral sites of the sensori-motor cortex. Bipolar electrodes were inserted. The behavior of the rats and electroencephalography (EEG) were recorded using a digital video-EEG monitoring system. After observation periods of 1, 2 and 6 months, the rats were perfused for pathological study. FCD was observed adjacent to the site of KA injection in all rats more than one month after the injection. EEG recording demonstrated focal spike discharges in and around the site of injection. However, clinical seizure was not observed. Pathological studies showed decrease in gamma aminobutyric acid (GABA)-A receptors and increase in GABA-B receptors not only in the lesion but also in perilesional areas. Fifteen surgical cases of FCD with intractable epilepsy were included in the clinical study. Neuro-imaging studies including high-resolution MRI and single photon emission computed tomography (SPECT) were performed. Conventional EEG studies demonstrated focal EEG abnormalities with epileptic phenomena. At surgery, intraoperative electrocorticography (ECoG) was performed in order to localize epileptic foci under neuroleptanalgesia. Fourteen patients showed epileptiform discharges on preresection ECoG. All foci in non-eloquent areas were resected. Pathological studies including immunohistochemical staining were performed, and characteristics of the FCD in relation to EEG findings were analyzed. Electrophysiological examination revealed epileptogenecity not only in the lesions but also in perilesional areas. In the lesions, immunohistochemical studies showed decrease in GABA-A receptors and increase in GABA-B receptors in both the lesions and perilesional areas, but N

  16. Signal transfer within a cultured asymmetric cortical neuron circuit.

    Science.gov (United States)

    Isomura, Takuya; Shimba, Kenta; Takayama, Yuzo; Takeuchi, Akimasa; Kotani, Kiyoshi; Jimbo, Yasuhiko

    2015-12-01

    Simplified neuronal circuits are required for investigating information representation in nervous systems and for validating theoretical neural network models. Here, we developed patterned neuronal circuits using micro fabricated devices, comprising a micro-well array bonded to a microelectrode-array substrate. The micro-well array consisted of micrometre-scale wells connected by tunnels, all contained within a silicone slab called a micro-chamber. The design of the micro-chamber confined somata to the wells and allowed axons to grow through the tunnels bidirectionally but with a designed, unidirectional bias. We guided axons into the point of the arrow structure where one of the two tunnel entrances is located, making that the preferred direction. When rat cortical neurons were cultured in the wells, their axons grew through the tunnels and connected to neurons in adjoining wells. Unidirectional burst transfers and other asymmetric signal-propagation phenomena were observed via the substrate-embedded electrodes. Seventy-nine percent of burst transfers were in the forward direction. We also observed rapid propagation of activity from sites of local electrical stimulation, and significant effects of inhibitory synapse blockade on bursting activity. These results suggest that this simple, substrate-controlled neuronal circuit can be applied to develop in vitro models of the function of cortical microcircuits or deep neural networks, better to elucidate the laws governing the dynamics of neuronal networks.

  17. Language experience enhances early cortical pitch-dependent responses

    Science.gov (United States)

    Krishnan, Ananthanarayan; Gandour, Jackson T.; Ananthakrishnan, Saradha; Vijayaraghavan, Venkatakrishnan

    2014-01-01

    Pitch processing at cortical and subcortical stages of processing is shaped by language experience. We recently demonstrated that specific components of the cortical pitch response (CPR) index the more rapidly-changing portions of the high rising Tone 2 of Mandarin Chinese, in addition to marking pitch onset and sound offset. In this study, we examine how language experience (Mandarin vs. English) shapes the processing of different temporal attributes of pitch reflected in the CPR components using stimuli representative of within-category variants of Tone 2. Results showed that the magnitude of CPR components (Na-Pb and Pb-Nb) and the correlation between these two components and pitch acceleration were stronger for the Chinese listeners compared to English listeners for stimuli that fell within the range of Tone 2 citation forms. Discriminant function analysis revealed that the Na-Pb component was more than twice as important as Pb-Nb in grouping listeners by language affiliation. In addition, a stronger stimulus-dependent, rightward asymmetry was observed for the Chinese group at the temporal, but not frontal, electrode sites. This finding may reflect selective recruitment of experience-dependent, pitch-specific mechanisms in right auditory cortex to extract more complex, time-varying pitch patterns. Taken together, these findings suggest that long-term language experience shapes early sensory level processing of pitch in the auditory cortex, and that the sensitivity of the CPR may vary depending on the relative linguistic importance of specific temporal attributes of dynamic pitch. PMID:25506127

  18. Signal transfer within a cultured asymmetric cortical neuron circuit

    Science.gov (United States)

    Isomura, Takuya; Shimba, Kenta; Takayama, Yuzo; Takeuchi, Akimasa; Kotani, Kiyoshi; Jimbo, Yasuhiko

    2015-12-01

    Objective. Simplified neuronal circuits are required for investigating information representation in nervous systems and for validating theoretical neural network models. Here, we developed patterned neuronal circuits using micro fabricated devices, comprising a micro-well array bonded to a microelectrode-array substrate. Approach. The micro-well array consisted of micrometre-scale wells connected by tunnels, all contained within a silicone slab called a micro-chamber. The design of the micro-chamber confined somata to the wells and allowed axons to grow through the tunnels bidirectionally but with a designed, unidirectional bias. We guided axons into the point of the arrow structure where one of the two tunnel entrances is located, making that the preferred direction. Main results. When rat cortical neurons were cultured in the wells, their axons grew through the tunnels and connected to neurons in adjoining wells. Unidirectional burst transfers and other asymmetric signal-propagation phenomena were observed via the substrate-embedded electrodes. Seventy-nine percent of burst transfers were in the forward direction. We also observed rapid propagation of activity from sites of local electrical stimulation, and significant effects of inhibitory synapse blockade on bursting activity. Significance. These results suggest that this simple, substrate-controlled neuronal circuit can be applied to develop in vitro models of the function of cortical microcircuits or deep neural networks, better to elucidate the laws governing the dynamics of neuronal networks.

  19. Methomyl poisoning presenting with decorticate posture and cortical blindness.

    Science.gov (United States)

    Lin, Chih-Ming

    2014-01-17

    Methomyl is a potent pesticide that is widely used in the field of agriculture. The systemic toxic effects of methomyl have been well described. However, the neurological effects of methomyl intoxication are not well understood. In this study, we report a 61-year-old Taiwanese man sent to our emergency department because of altered mental status. His family stated that he had consumed liquid methomyl in a suicide attempt. He was provided cardiopulmonary resuscitation because of unstable vital signs. He was then sent to an intensive care unit for close observation. On the second day of admission, he regained consciousness but exhibited irregular limb and torso posture. On the sixth day, he started to complain of blurred vision. An ophthalmologist was consulted but no obvious abnormalities could be identified. On suspicion of cerebral disease, a neurologist was consulted. Further examination revealed cortical blindness and decorticate posture. Cerebral magnetic resonance imaging (MRI) was arranged, which identified bilateral occipital regions lesions. The patient was administered normal saline and treated with aspirin and piracetam for 3 weeks in hospital. During the treatment period, his symptom of cortical blindness resolved, whereas his decorticate posture was refractory. Follow-up brain MRI results supported our clinical observations by indicating the disappearance of the bilateral occipital lesions and symmetrical putaminal high signal abnormalities. In this article, we briefly discuss the possible mechanisms underlying the cerebral effects of methomyl poisoning. Our study can provide clinicians with information on the manifestations of methomyl intoxication and an appropriate treatment direction.

  20. Methomyl poisoning presenting with decorticate posture and cortical blindness

    Directory of Open Access Journals (Sweden)

    Chih-Ming Lin

    2014-02-01

    Full Text Available Methomyl is a potent pesticide that is widely used in the field of agriculture. The systemic toxic effects of methomyl have been well described. However, the neurological effects of methomyl intoxication are not well understood. In this study, we report a 61-year-old Taiwanese man sent to our emergency department because of altered mental status. His family stated that he had consumed liquid methomyl in a suicide attempt. He was provided cardiopulmonary resuscitation because of unstable vital signs. He was then sent to an intensive care unit for close observation. On the second day of admission, he regained consciousness but exhibited irregular limb and torso posture. On the sixth day, he started to complain of blurred vision. An ophthalmologist was consulted but no obvious abnormalities could be identified. On suspicion of cerebral disease, a neurologist was consulted. Further examination revealed cortical blindness and decorticate posture. Cerebral magnetic resonance imaging (MRI was arranged, which identified bilateral occipital regions lesions. The patient was administered normal saline and treated with aspirin and piracetam for 3 weeks in hospital. During the treatment period, his symptom of cortical blindness resolved, whereas his decorticate posture was refractory. Follow-up brain MRI results supported our clinical observations by indicating the disappearance of the bilateral occipital lesions and symmetrical putaminal high signal abnormalities. In this article, we briefly discuss the possible mechanisms underlying the cerebral effects of methomyl poisoning. Our study can provide clinicians with information on the manifestations of methomyl intoxication and an appropriate treatment direction.

  1. Environmental Modeling, The Buffer Priority layers for Nitrogen Removal identify priority forest/grass buffer sites by subwatershed. Land use, hydrology, soil, and landscape characteristics were analyzed to rank opportunities with high nitrogen removal potential., Published in 2014, Smaller than 1:100000 scale, Maryland Department of Natural Resources (DNR).

    Data.gov (United States)

    NSGIC Education | GIS Inventory — Environmental Modeling dataset current as of 2014. The Buffer Priority layers for Nitrogen Removal identify priority forest/grass buffer sites by subwatershed. Land...

  2. Delineation of cortical pathology in multiple sclerosis using multi-surface magnetization transfer ratio imaging

    Directory of Open Access Journals (Sweden)

    David A. Rudko

    2016-01-01

    Full Text Available The purpose of our study was to evaluate the utility of measurements of cortical surface magnetization transfer ratio (csMTR on the inner, mid and outer cortical boundaries as clinically accessible biomarkers of cortical gray matter pathology in multiple sclerosis (MS. Twenty-five MS patients and 12 matched controls were recruited from the MS Clinic of the Montreal Neurological Institute. Anatomical and magnetization transfer ratio (MTR images were acquired using 3 Tesla MRI at baseline and two-year time-points. MTR maps were smoothed along meshes representing the inner, mid and outer neocortical boundaries. To evaluate csMTR reductions suggestive of sub-pial demyelination in MS patients, a mixed model analysis was carried out at both the individual vertex level and in anatomically parcellated brain regions. Our results demonstrate that focal areas of csMTR reduction are most prevalent along the outer cortical surface in the superior temporal and posterior cingulate cortices, as well as in the cuneus and precentral gyrus. Additionally, age regression analysis identified that reductions of csMTR in MS patients increase with age but appear to hit a plateau in the outer caudal anterior cingulate, as well as in the precentral and postcentral cortex. After correction for the naturally occurring gradient in cortical MTR, the difference in csMTR between the inner and outer cortex in focal areas in the brains of MS patients correlated with clinical disability. Overall, our findings support multi-surface analysis of csMTR as a sensitive marker of cortical sub-pial abnormality indicative of demyelination in MS patients.

  3. Simplified Classification of Focal Cortical Dysplasia

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-09-01

    Full Text Available Sections of cortex from 52 of 224 (23% patients with cortical dysplasia, operated on for drug-resistant partial epilepsy, were retrospectively re-examined histologically at Niguarda Hospital, and Istituto Nazionale Neurologico ‘C. Besta’, Milan, Italy.

  4. Stroke rehabilitation using noninvasive cortical stimulation: aphasia.

    Science.gov (United States)

    Mylius, Veit; Zouari, Hela G; Ayache, Samar S; Farhat, Wassim H; Lefaucheur, Jean-Pascal

    2012-08-01

    Poststroke aphasia results from the lesion of cortical areas involved in the motor production of speech (Broca's aphasia) or in the semantic aspects of language comprehension (Wernicke's aphasia). Such lesions produce an important reorganization of speech/language-specific brain networks due to an imbalance between cortical facilitation and inhibition. In fact, functional recovery is associated with changes in the excitability of the damaged neural structures and their connections. Two main mechanisms are involved in poststroke aphasia recovery: the recruitment of perilesional regions of the left hemisphere in case of small lesion and the acquisition of language processing ability in homotopic areas of the nondominant right hemisphere when left hemispheric language abilities are permanently lost. There is some evidence that noninvasive cortical stimulation, especially when combined with language therapy or other therapeutic approaches, can promote aphasia recovery. Cortical stimulation was mainly used to either increase perilesional excitability or reduce contralesional activity based on the concept of reciprocal inhibition and maladaptive plasticity. However, recent studies also showed some positive effects of the reinforcement of neural activities in the contralateral right hemisphere, based on the potential compensatory role of the nondominant hemisphere in stroke recovery.

  5. Neuroimaging of malformation of cortical development

    International Nuclear Information System (INIS)

    Zlatareva, D.; Hadjidekov, V.; Tournev, I.; Rossi, A.

    2012-01-01

    Malformations of cortical development (MCD) are heterogeneous group of disease which result from disruption of 3 main stages of cortical development.The common clinical presentation is refractory epilepsy and or developmental delay. The aim of this paper is to describe and analyze magnetic resonance (MR) findings and to present protocol for examination. We analyze MR findings in 17 patients with MCD. The average age was 12,1 year (from 2 months - 57 years). The main indications from reference physician are epilepsy and developmental delay. In 12 patients 1.5T MR was performed, and in 5 - 0.5T. Subependymal heterotopias was found in 6 patients, focal cortical dysplasia - 3. polymicrogyria - 3, schizencephaly - 2, hemimegalencephaly -1, lizencephaly -1, tuberous sclerosis -1. The most common MCD are heterotopias, focal cortical dysplasia, polymicrogyria. schizencephaiy, pachygyria and lizencephaly. In our study the number of patients is not big enough to make a conclusion about frequency of the forms of MCD and our goal is to analyze MR findings which are not well studied in our country. MRI is the method of choice for diagnosis of MCD. The protocol should be different from routine brain protocol to interpret the images with good quality and not miss the pathology. Knowledge of MR findings in MCD would help for genetic counselling in some cases or can predict prognosis in some patients. (authors)

  6. Response variability in balanced cortical networks

    DEFF Research Database (Denmark)

    Lerchner, Alexander; Ursta, C.; Hertz, J.

    2006-01-01

    We study the spike statistics of neurons in a network with dynamically balanced excitation and inhibition. Our model, intended to represent a generic cortical column, comprises randomly connected excitatory and inhibitory leaky integrate-and-fire neurons, driven by excitatory input from an external...

  7. Cortical enhancement in chronic subdural hematoma

    International Nuclear Information System (INIS)

    Taguchi, Yoshio; Sato, Jun; Makita, Tadatoshi; Hayashi, Shigetoshi; Nakamura, Norio.

    1981-01-01

    In the CT findings of chronic subdural hematoma, brain enhancement adjacent to a subdural hematoma was seen occasionally after the injection of a contrast material. The authors called this finding ''cortical enhancement'', and 35 cases of chronic subdural hematoma were studied concerning cortical enhancement in relation to age, clinical signs and symptoms, hematoma density, and volume of the hematoma. Eight cases out of the 35 were subjected to measurements of the regional cerebral blood flow preoperatively by the method of the carotid injection of Xe-133. Cortical enhancement was apt to be seen in the cases which revealed intracranial hypertension or disturbance of consciousness, in isodensity or mixed-density hematomas, and in huge subdural hematomas. There was no specific correlation with age distribution. The pathogenesis of cortical enhancement seemed to be the result of cerebral compression with an increase in the contrast material per unit of volume and a prolonged venous outflow from the hemisphere, but no characteristic feature was detected in the average regional cerebral blood flow in our cases. (author)

  8. Spontaneously emerging cortical representations of visual attributes

    Science.gov (United States)

    Kenet, Tal; Bibitchkov, Dmitri; Tsodyks, Misha; Grinvald, Amiram; Arieli, Amos

    2003-10-01

    Spontaneous cortical activity-ongoing activity in the absence of intentional sensory input-has been studied extensively, using methods ranging from EEG (electroencephalography), through voltage sensitive dye imaging, down to recordings from single neurons. Ongoing cortical activity has been shown to play a critical role in development, and must also be essential for processing sensory perception, because it modulates stimulus-evoked activity, and is correlated with behaviour. Yet its role in the processing of external information and its relationship to internal representations of sensory attributes remains unknown. Using voltage sensitive dye imaging, we previously established a close link between ongoing activity in the visual cortex of anaesthetized cats and the spontaneous firing of a single neuron. Here we report that such activity encompasses a set of dynamically switching cortical states, many of which correspond closely to orientation maps. When such an orientation state emerged spontaneously, it spanned several hypercolumns and was often followed by a state corresponding to a proximal orientation. We suggest that dynamically switching cortical states could represent the brain's internal context, and therefore reflect or influence memory, perception and behaviour.

  9. Rehabilitation of cortical blindness secondary to stroke.

    Science.gov (United States)

    Gaber, Tarek A-Z K

    2010-01-01

    Cortical blindness is a rare complication of posterior circulation stroke. However, its complex presentation with sensory, physical, cognitive and behavioural impairments makes it one of the most challenging. Appropriate approach from a rehabilitation standpoint was never reported. Our study aims to discuss the rehabilitation methods and outcomes of a cohort of patients with cortical blindness. The notes of all patients with cortical blindness referred to a local NHS rehabilitation service in the last 6~years were examined. Patients' demographics, presenting symptoms, scan findings, rehabilitation programmes and outcomes were documented. Seven patients presented to our service, six of them were males. The mean age was 63. Patients 1, 2 and 3 had total blindness with severe cognitive and behavioural impairments, wandering and akathisia. All of them failed to respond to any rehabilitation effort and the focus was on damage limitation. Pharmacological interventions had a modest impact on behaviour and sleep pattern. The 3 patients were discharged to a nursing facility. Patients 4, 5, 6 and 7 had partial blindness with variable severity. All of them suffered from significant memory impairment. However, none suffered from any behavioural, physical or other cognitive impairment. Rehabilitation efforts on 3 patients were carried out collaboratively between brain injury occupational therapists and sensory disability officers. All patients experienced significant improvement in handicap and they all maintained community placements. This small cohort of patients suggests that the rehabilitation philosophy and outcomes of these 2 distinct groups of either total or partial cortical blindness differ significantly.

  10. Critical fluctuations in cortical models near instability

    NARCIS (Netherlands)

    Aburn, M.J.; Holmes, C.A.; Roberts, J.A.; Boonstra, T.W.; Breakspear, M.

    2012-01-01

    Computational studies often proceed from the premise that cortical dynamics operate in a linearly stable domain, where fluctuations dissipate quickly and show only short memory. Studies of human electroencephalography (EEG), however, have shown significant autocorrelation at time lags on the scale

  11. Defects in cortical microarchitecture among African-American women with type 2 diabetes.

    Science.gov (United States)

    Yu, E W; Putman, M S; Derrico, N; Abrishamanian-Garcia, G; Finkelstein, J S; Bouxsein, M L

    2015-02-01

    Patients with type 2 diabetes mellitus (DM2) have increased fracture risk. We found that African-American women with DM2 have increased cortical porosity and lower cortical bone density at the radius than non-diabetic controls. These cortical deficits are associated with hyperglycemia and may contribute to skeletal fragility associated with DM2. Fracture risk is increased in patients with type 2 diabetes mellitus (DM2) despite normal areal bone mineral density (aBMD). DM2 is more common in African-Americans than in Caucasians. It is not known whether African-American women with DM2 have deficits in bone microstructure. We measured aBMD at the spine and hip by DXA, and volumetric BMD (vBMD) and microarchitecture at the distal radius and tibia by HR-pQCT in 22 DM2 and 78 non-diabetic African-American women participating in the Study of Women Across the Nation (SWAN). We also measured fasting glucose and HOMA-IR. Age, weight, and aBMD at all sites were similar in both groups. At the radius, cortical porosity was 26% greater, while cortical vBMD and tissue mineral density were lower in women with DM2 than in controls. There were no differences in radius total vBMD or trabecular vBMD between groups. Despite inferior cortical bone properties at the radius, FEA-estimated failure load was similar between groups. Tibia vBMD and microarchitecture were also similar between groups. There were no significant associations between cortical parameters and duration of DM2 or HOMA-IR. However, among women with DM2, higher fasting glucose levels were associated with lower cortical vBMD (r=-0.54, p=0.018). DM2 and higher fasting glucose are associated with unfavorable cortical bone microarchitecture at the distal radius in African-American women. These structural deficits may contribute to the increased fracture risk among women with DM2. Further, our results suggest that hyperglycemia may be involved in mechanisms of skeletal fragility associated with DM2.

  12. Assessment of cortical maturation with prenatal MRI. Part I: normal cortical maturation

    International Nuclear Information System (INIS)

    Fogliarini, Celine; Chaumoitre, Katia; Chapon, Frederique; Levrier, Olivier; Girard, Nadine; Fernandez, Carla; Figarella-Branger, Dominique

    2005-01-01

    Cortical maturation, especially gyral formation, follows a temporospatial schedule and is a good marker of fetal maturation. Although ultrasonography is still the imaging method of choice to evaluate fetal anatomy, MRI has an increasingly important role in the detection of brain abnormalities, especially of cortical development. Knowledge of MRI techniques in utero with the advantages and disadvantages of some sequences is necessary, in order to try to optimize the different magnetic resonance sequences to be able to make an early diagnosis. The different steps of cortical maturation known from histology represent the background necessary for the understanding of maturation in order to be then able to evaluate brain maturation through neuroimaging. Illustrations of the normal cortical maturation are given for each step accessible to MRI for both the cerebral hemispheres and the posterior fossa. (orig.)

  13. Assessment of cortical maturation with prenatal MRI. Part I: normal cortical maturation

    Energy Technology Data Exchange (ETDEWEB)

    Fogliarini, Celine [Faculte Timone, Centre de Resonance Magnetique Biologique et Medicale, Marseille (France); Chaumoitre, Katia [Hopital Nord, Department of Radiology, Marseille (France); Chapon, Frederique; Levrier, Olivier; Girard, Nadine [Hopital Timone, Department of Neuroradiology, Marseille Cedex 5 (France); Fernandez, Carla; Figarella-Branger, Dominique [Hopital Timone, Department of Pathology, Marseille (France)

    2005-08-01

    Cortical maturation, especially gyral formation, follows a temporospatial schedule and is a good marker of fetal maturation. Although ultrasonography is still the imaging method of choice to evaluate fetal anatomy, MRI has an increasingly important role in the detection of brain abnormalities, especially of cortical development. Knowledge of MRI techniques in utero with the advantages and disadvantages of some sequences is necessary, in order to try to optimize the different magnetic resonance sequences to be able to make an early diagnosis. The different steps of cortical maturation known from histology represent the background necessary for the understanding of maturation in order to be then able to evaluate brain maturation through neuroimaging. Illustrations of the normal cortical maturation are given for each step accessible to MRI for both the cerebral hemispheres and the posterior fossa. (orig.)

  14. Model cortical responses for the detection of perceptual onsets and beat tracking in singing

    NARCIS (Netherlands)

    Coath, M.; Denham, S.L.; Smith, L.M.; Honing, H.; Hazan, A.; Holonowicz, P.; Purwins, H.

    2009-01-01

    We describe a biophysically motivated model of auditory salience based on a model of cortical responses and present results that show that the derived measure of salience can be used to identify the position of perceptual onsets in a musical stimulus successfully. The salience measure is also shown

  15. The Reliability of the CVI Range: A Functional Vision Assessment for Children with Cortical Visual Impairment

    Science.gov (United States)

    Newcomb, Sandra

    2010-01-01

    Children who are identified as visually impaired frequently have a functional vision assessment as one way to determine how their visual impairment affects their educational performance. The CVI Range is a functional vision assessment for children with cortical visual impairment. The purpose of the study presented here was to examine the…

  16. Cortical microinfarcts detected in vivo on 3 tesla MRI : Clinical and radiological correlates

    NARCIS (Netherlands)

    Van Dalen, Jan Willem; Scuric, Eva E M; Van Veluw, Susanne J.; Caan, Matthan W A; Nederveen, Aart J.; Biessels, Geert Jan; Van Gool, Willem A.; Richard, Edo

    2015-01-01

    Background and Purpose-Cortical microinfarcts (CMIs) are a common postmortem finding associated with vascular risk factors, cognitive decline, and dementia. Recently, CMIs identified in vivo on 7 Tesla MRI also proved retraceable on 3 Tesla MRI. Methods-We evaluated CMIs on 3 Tesla MRI in a

  17. Cortical microinfarcts detected in vivo on 3 Tesla MRI: clinical and radiological correlates

    NARCIS (Netherlands)

    Dalen, J.W. van; Scuric, E.E.; Veluw, S.J. van; Caan, M.W.; Nederveen, A.J.; Biessels, G.J.; Gool, W.A. van; Richard, E.

    2015-01-01

    BACKGROUND AND PURPOSE: Cortical microinfarcts (CMIs) are a common postmortem finding associated with vascular risk factors, cognitive decline, and dementia. Recently, CMIs identified in vivo on 7 Tesla MRI also proved retraceable on 3 Tesla MRI. METHODS: We evaluated CMIs on 3 Tesla MRI in a

  18. Cortical inactivation by cooling in small animals

    Directory of Open Access Journals (Sweden)

    Ben eCoomber

    2011-06-01

    Full Text Available Reversible inactivation of the cortex by surface cooling is a powerful method for studying the function of a particular area. Implanted cooling cryoloops have been used to study the role of individual cortical areas in auditory processing of awake-behaving cats. Cryoloops have also been used in rodents for reversible inactivation of the cortex, but recently there has been a concern that the cryoloop may also cool non-cortical structures either directly or via the perfusion of blood, cooled as it passed close to the cooling loop. In this study we have confirmed that the loop can inactivate most of the auditory cortex without causing a significant reduction in temperature of the auditory thalamus or other sub-cortical structures. We placed a cryoloop on the surface of the guinea pig cortex, cooled it to 2°C and measured thermal gradients across the neocortical surface. We found that the temperature dropped to 20-24°C among cells within a radius of about 2.5mm away from the loop. This temperature drop was sufficient to reduce activity of most cortical cells and led to the inactivation of almost the entire auditory region. When the temperature of thalamus, midbrain, and middle ear were measured directly during cortical cooling, there was a small drop in temperature (about 4°C but this was not sufficient to directly reduce neural activity. In an effort to visualise the extent of neural inactivation we measured the uptake of thallium ions following an intravenous injection. This confirmed that there was a large reduction of activity across much of the ipsilateral cortex and only a small reduction in subcortical structures.

  19. Cortical thickness, surface area and volume measures in Parkinson's disease, multiple system atrophy and progressive supranuclear palsy.

    Directory of Open Access Journals (Sweden)

    Amanda Worker

    Full Text Available Parkinson's disease (PD, Multiple System Atrophy (MSA and Progressive Supranuclear Palsy (PSP are neurodegenerative diseases that can be difficult to distinguish clinically. The objective of the current study was to use surface-based analysis techniques to assess cortical thickness, surface area and grey matter volume to identify unique morphological patterns of cortical atrophy in PD, MSA and PSP and to relate these patterns of change to disease duration and clinical features.High resolution 3D T1-weighted MRI volumes were acquired from 14 PD patients, 18 MSA, 14 PSP and 19 healthy control participants. Cortical thickness, surface area and volume analyses were carried out using the automated surface-based analysis package FreeSurfer (version 5.1.0. Measures of disease severity and duration were assessed for correlation with cortical morphometric changes in each clinical group.Results show that in PSP, widespread cortical thinning and volume loss occurs within the frontal lobe, particularly the superior frontal gyrus. In addition, PSP patients also displayed increased surface area in the pericalcarine. In comparison, PD and MSA did not display significant changes in cortical morphology.These results demonstrate that patients with clinically established PSP exhibit distinct patterns of cortical atrophy, particularly affecting the frontal lobe. These results could be used in the future to develop a useful clinical application of MRI to distinguish PSP patients from PD and MSA patients.

  20. Automatic Detection of Cortical Bones Haversian Osteonal Boundaries

    Directory of Open Access Journals (Sweden)

    Ilige Hage

    2015-10-01

    Full Text Available This work aims to automatically detect cement lines in decalcified cortical bone sections stained with H&E. Employed is a methodology developed previously by the authors and proven to successfully count and disambiguate the micro-architectural features (namely Haversian canals, canaliculi, and osteocyte lacunae present in the secondary osteons/Haversian system (osteon of cortical bone. This methodology combines methods typically considered separately, namely pulse coupled neural networks (PCNN, particle swarm optimization (PSO, and adaptive threshold (AT. In lieu of human bone, slides (at 20× magnification from bovid cortical bone are used in this study as proxy of human bone. Having been characterized, features with same orientation are used to detect the cement line viewed as the next coaxial layer adjacent to the outermost lamella of the osteon. Employed for this purpose are three attributes for each and every micro-sized feature identified in the osteon lamellar system: (1 orientation, (2 size (ellipse perimeter and (3 Euler number (a topological measure. From a training image, automated parameters for the PCNN network are obtained by forming fitness functions extracted from these attributes. It is found that a 3-way combination of these features attributes yields good representations of the overall osteon boundary (cement line. Near-unity values of classical metrics of quality (precision, sensitivity, specificity, accuracy, and dice suggest that the segments obtained automatically by the optimized artificial intelligent methodology are of high fidelity as compared with manual tracing. For bench marking, cement lines segmented by k-means did not fare as well. An analysis based on the modified Hausdorff distance (MHD of the segmented cement lines also testified to the quality of the detected cement lines vis-a-vis the k-means method.

  1. Cortical and subcortical mechanisms of brain-machine interfaces.

    Science.gov (United States)

    Marchesotti, Silvia; Martuzzi, Roberto; Schurger, Aaron; Blefari, Maria Laura; Del Millán, José R; Bleuler, Hannes; Blanke, Olaf

    2017-06-01

    Technical advances in the field of Brain-Machine Interfaces (BMIs) enable users to control a variety of external devices such as robotic arms, wheelchairs, virtual entities and communication systems through the decoding of brain signals in real time. Most BMI systems sample activity from restricted brain regions, typically the motor and premotor cortex, with limited spatial resolution. Despite the growing number of applications, the cortical and subcortical systems involved in BMI control are currently unknown at the whole-brain level. Here, we provide a comprehensive and detailed report of the areas active during on-line BMI control. We recorded functional magnetic resonance imaging (fMRI) data while participants controlled an EEG-based BMI inside the scanner. We identified the regions activated during BMI control and how they overlap with those involved in motor imagery (without any BMI control). In addition, we investigated which regions reflect the subjective sense of controlling a BMI, the sense of agency for BMI-actions. Our data revealed an extended cortical-subcortical network involved in operating a motor-imagery BMI. This includes not only sensorimotor regions but also the posterior parietal cortex, the insula and the lateral occipital cortex. Interestingly, the basal ganglia and the anterior cingulate cortex were involved in the subjective sense of controlling the BMI. These results inform basic neuroscience by showing that the mechanisms of BMI control extend beyond sensorimotor cortices. This knowledge may be useful for the development of BMIs that offer a more natural and embodied feeling of control for the user. Hum Brain Mapp 38:2971-2989, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  2. Widespread cortical thinning in patients with neuromyelitis optica spectrum disorder.

    Science.gov (United States)

    Kim, S-H; Kwak, K; Hyun, J-W; Jeong, I H; Jo, H-J; Joung, A; Kim, J-H; Lee, S H; Yun, S; Joo, J; Lee, J-M; Kim, H J

    2016-07-01

    Studies on cortical involvement and its relationship with cognitive function in patients with neuromyelitis optica spectrum disorder (NMOSD) remain scarce. The objective of this study was to compare cortical thickness on magnetic resonance imaging (MRI) between patients with NMOSD and multiple sclerosis (MS) and to investigate its relationship with clinical features and cognitive function. This observational clinical imaging study of 91 patients with NMOSD, 52 patients with MS and 44 healthy controls was conducted from 1 December 2013 to 30 April 2015 at the institutional referral center. Three tesla MRI of the brain and neuropsychological tests were performed. Cortical thickness was measured using three-dimensional surface-based analysis. Both sets of patients exhibited cortical thinning throughout the entire brain cortex. Patients with MS showed a significantly greater reduction in cortical thickness over broad regions of the bilateral frontal and parieto-temporal cortices and the left precuneus compared to those with NMOSD. Memory functions in patients with MS were correlated with broad regional cortical thinning, whereas no significant associations were observed between cortical thickness and cognitive function in patients with NMOSD. Widespread cortical thinning was observed in patients with NMOSD and MS, but the extent of cortical thinning was greater in patients with MS. The more severe cortical atrophy may contribute to memory impairment in patients with MS but not in those with NMOSD. These results provide in vivo evidence that the severity and clinical relevance of cortical thinning differ between NMOSD and MS. © 2016 EAN.

  3. Person identification based on multiscale matching of cortical images

    NARCIS (Netherlands)

    Kruizinga, P; Petkov, N; Hertzberger, B; Serazzi, G

    1995-01-01

    A set of so-called cortical images, motivated by the function of simple cells in the primary visual cortex of mammals, is computed from each of two input images and an image pyramid is constructed for each cortical image. The two sets of cortical image pyramids are matched synchronously and an

  4. Cortical gyrification is abnormal in children with prenatal alcohol exposure

    Directory of Open Access Journals (Sweden)

    Timothy J. Hendrickson

    2017-01-01

    Conclusions: Abnormalities in cortical development were seen across the brain in children with PAE compared to controls. Cortical gyrification and IQ were strongly correlated, suggesting that examining mechanisms by which alcohol disrupts cortical formation may yield clinically relevant insights and potential directions for early intervention.

  5. "The mute who can sing": a cortical stimulation study on singing.

    Science.gov (United States)

    Roux, Franck-Emmanuel; Borsa, Stefano; Démonet, Jean-François

    2009-02-01

    In an attempt to identify cortical areas involved in singing in addition to language areas, the authors used a singing task during direct cortical mapping in 5 patients who were amateur singers and had undergone surgery for brain tumors. The organization of the cortical areas involved in language and singing was analyzed in relation with these surgical data. One left-handed and 4 right-handed patients with brain tumors in left (2 cases) and right (3 cases) hemispheres and no significant language or singing deficits underwent surgery with the "awake surgery" technique. All patients had a special interest in singing and were involved in amateur singing activities. They were tested using naming, reading, and singing tasks. Outside primary sensorimotor areas, singing interferences were rare and were exclusively localized in small cortical areas (singing in the Broca region. In the Broca region, no singing interference was found in areas in which interference in naming and reading tasks were detected. Conversely, a specific singing interference was found in nondominant middle frontal gyri in one patient. This interference consisted of abrupt singing arrest without apparent face, mouth, and tongue contraction. Finally, nonspecific singing interferences were found in the right and left precentral gyri in all patients (probably by interference in final articulatory mechanisms of singing). Dissociations between speech and singing found outside primary sensorimotor areas showed that these 2 functions use, in some cortical stages, different cerebral pathways.

  6. Integrated mechanisms of anticipation and rate-of-change computations in cortical circuits.

    Directory of Open Access Journals (Sweden)

    Gabriel D Puccini

    2007-05-01

    Full Text Available Local neocortical circuits are characterized by stereotypical physiological and structural features that subserve generic computational operations. These basic computations of the cortical microcircuit emerge through the interplay of neuronal connectivity, cellular intrinsic properties, and synaptic plasticity dynamics. How these interacting mechanisms generate specific computational operations in the cortical circuit remains largely unknown. Here, we identify the neurophysiological basis of both the rate of change and anticipation computations on synaptic inputs in a cortical circuit. Through biophysically realistic computer simulations and neuronal recordings, we show that the rate-of-change computation is operated robustly in cortical networks through the combination of two ubiquitous brain mechanisms: short-term synaptic depression and spike-frequency adaptation. We then show how this rate-of-change circuit can be embedded in a convergently connected network to anticipate temporally incoming synaptic inputs, in quantitative agreement with experimental findings on anticipatory responses to moving stimuli in the primary visual cortex. Given the robustness of the mechanism and the widespread nature of the physiological machinery involved, we suggest that rate-of-change computation and temporal anticipation are principal, hard-wired functions of neural information processing in the cortical microcircuit.

  7. The participation of cortical amygdala in innate, odor-driven behavior

    Science.gov (United States)

    Root, Cory M.; Denny, Christine A.; Hen, René; Axel, Richard

    2014-01-01

    Innate behaviors are observed in naïve animals without prior learning or experience, suggesting that the neural circuits that mediate these behaviors are genetically determined and stereotyped. The neural circuits that convey olfactory information from the sense organ to the cortical and subcortical olfactory centers have been anatomically defined1-3 but the specific pathways responsible for innate responses to volatile odors have not been identified. We have devised genetic strategies that demonstrate that a stereotyped neural circuit that transmits information from the olfactory bulb to cortical amygdala is necessary for innate aversive and appetitive behaviors. Moreover, we have employed the promoter of the activity-dependent gene, arc, to express the photosensitive ion channel, channelrhodopsin, in neurons of the cortical amygdala activated by odors that elicit innate behaviors. Optical activation of these neurons leads to appropriate behaviors that recapitulate the responses to innate odors. These data indicate that the cortical amygdala plays a critical role in the generation of innate odor-driven behaviors but do not preclude the participation of cortical amygdala in learned olfactory behaviors. PMID:25383519

  8. Pronounced prefronto-temporal cortical thinning in schizophrenia: Neuroanatomical correlate of suicidal behavior?

    Science.gov (United States)

    Besteher, Bianca; Wagner, Gerd; Koch, Kathrin; Schachtzabel, Claudia; Reichenbach, Jürgen R; Schlösser, Ralf; Sauer, Heinrich; Schultz, C Christoph

    2016-10-01

    Schizophrenia is characterized by increased mortality for which suicidality is the decisive factor. An analysis of cortical thickness and folding to further elucidate neuroanatomical correlates of suicidality in schizophrenia has not yet been performed. We searched for relevant brain regions with such differences between patients with suicide-attempts, patients without any suicidal thoughts and healthy controls. 37 schizophrenia patients (14 suicide-attempters and 23 non-suicidal) and 50 age- and gender-matched healthy controls were included. Suicidality was documented through clinical interview and chart review. All participants underwent T1-weighted MRI scans. Whole brain node-by-node cortical thickness and folding were estimated (FreeSurfer Software) and compared. Additionally a three group comparison for prefrontal regions-of-interest was performed in SPSS using a multifactorial GLM. Compared with the healthy controls patients showed a typical pattern of cortical thinning in prefronto-temporal regions and altered cortical folding in the right medial temporal cortex. Patients with suicidal behavior compared with non-suicidal patients demonstrated pronounced (psuicidal patients with non-suicidal patients significant (psuicidal behaviour in schizophrenia. We identified cortical thinning in a network strongly involved in regulation of impulsivity, emotions and planning of behaviour in suicide attempters, which might lead to neuronal dysregulation in this network and consequently to a higher risk of suicidal behavior. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. [Patterns of action potential firing in cortical neurons of neonatal mice and their electrophysiological property].

    Science.gov (United States)

    Furong, Liu; Shengtian, L I

    2016-05-25

    To investigate patterns of action potential firing in cortical heurons of neonatal mice and their electrophysiological properties. The passive and active membrane properties of cortical neurons from 3-d neonatal mice were observed by whole-cell patch clamp with different voltage and current mode. Three patterns of action potential firing were identified in response to depolarized current injection. The effects of action potential firing patterns on voltage-dependent inward and outward current were found. Neurons with three different firing patterns had different thresholds of depolarized current. In the morphology analysis of action potential, the three type neurons were different in rise time, duration, amplitude and threshold of the first action potential evoked by 80 pA current injection. The passive properties were similar in three patterns of action potential firing. These results indicate that newborn cortical neurons exhibit different patterns of action potential firing with different action potential parameters such as shape and threshold.

  10. Spectral fingerprints of large-scale cortical dynamics during ambiguous motion perception.

    Science.gov (United States)

    Helfrich, Randolph F; Knepper, Hannah; Nolte, Guido; Sengelmann, Malte; König, Peter; Schneider, Till R; Engel, Andreas K

    2016-11-01

    Ambiguous stimuli have been widely used to study the neuronal correlates of consciousness. Recently, it has been suggested that conscious perception might arise from the dynamic interplay of functionally specialized but widely distributed cortical areas. While previous research mainly focused on phase coupling as a correlate of cortical communication, more recent findings indicated that additional coupling modes might coexist and possibly subserve distinct cortical functions. Here, we studied two coupling modes, namely phase and envelope coupling, which might differ in their origins, putative functions and dynamics. Therefore, we recorded 128-channel EEG while participants performed a bistable motion task and utilized state-of-the-art source-space connectivity analysis techniques to study the functional relevance of different coupling modes for cortical communication. Our results indicate that gamma-band phase coupling in extrastriate visual cortex might mediate the integration of visual tokens into a moving stimulus during ambiguous visual stimulation. Furthermore, our results suggest that long-range fronto-occipital gamma-band envelope coupling sustains the horizontal percept during ambiguous motion perception. Additionally, our results support the idea that local parieto-occipital alpha-band phase coupling controls the inter-hemispheric information transfer. These findings provide correlative evidence for the notion that synchronized oscillatory brain activity reflects the processing of sensory input as well as the information integration across several spatiotemporal scales. The results indicate that distinct coupling modes are involved in different cortical computations and that the rich spatiotemporal correlation structure of the brain might constitute the functional architecture for cortical processing and specific multi-site communication. Hum Brain Mapp 37:4099-4111, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Identifying Functional Neighborhoods within the Cell Nucleus: Proximity Analysis of Early S-Phase Replicating Chromatin Domains to Sites of Transcription, RNA Polymerase II, HP1γ, Matrin 3 and SAF-A

    Science.gov (United States)

    Malyavantham, Kishore S; Bhattacharya, Sambit; Barbeitos, Marcos; Mukherjee, Lopamudra; Xu, Jinhui; Fackelmayer, Frank O; Berezney, Ronald

    2009-01-01

    Higher order chromatin organization in concert with epigenetic regulation is a key process that determines gene expression at the global level. The organization of dynamic chromatin domains and their associated protein factors is intertwined with nuclear function to create higher levels of functional zones within the cell nucleus. As a step towards elucidating the organization and dynamics of these functional zones, we have investigated the spatial proximities among a constellation of functionally related sites that are found within euchromatic regions of the cell nucleus including: HP1γ, nascent transcript sites (TS), active DNA replicating sites in early S phase (PCNA) and RNA polymerase II sites. We report close associations among these different sites with proximity values specific for each combination. Analysis of matrin 3 and SAF-A sites demonstrates that these nuclear matrix proteins are highly proximal with the functionally related sites as well as to each other and display closely aligned and overlapping regions following application of the minimal spanning tree (MST) algorithm to visualize higher order network-like patterns. Our findings suggest that multiple factors within the nuclear microenvironment collectively form higher order combinatorial arrays of function. We propose a model for the organization of these functional neighborhoods which takes into account the proximity values of the individual sites and their spatial organization within the nuclear architecture. PMID:18618731

  12. Degraded attentional modulation of cortical neural populations in strabismic amblyopia.

    Science.gov (United States)

    Hou, Chuan; Kim, Yee-Joon; Lai, Xin Jie; Verghese, Preeti

    2016-01-01

    Behavioral studies have reported reduced spatial attention in amblyopia, a developmental disorder of spatial vision. However, the neural populations in the visual cortex linked with these behavioral spatial attention deficits have not been identified. Here, we use functional MRI-informed electroencephalography source imaging to measure the effect of attention on neural population activity in the visual cortex of human adult strabismic amblyopes who were stereoblind. We show that compared with controls, the modulatory effects of selective visual attention on the input from the amblyopic eye are substantially reduced in the primary visual cortex (V1) as well as in extrastriate visual areas hV4 and hMT+. Degraded attentional modulation is also found in the normal-acuity fellow eye in areas hV4 and hMT+ but not in V1. These results provide electrophysiological evidence that abnormal binocular input during a developmental critical period may impact cortical connections between the visual cortex and higher level cortices beyond the known amblyopic losses in V1 and V2, suggesting that a deficit of attentional modulation in the visual cortex is an important component of the functional impairment in amblyopia. Furthermore, we find that degraded attentional modulation in V1 is correlated with the magnitude of interocular suppression and the depth of amblyopia. These results support the view that the visual suppression often seen in strabismic amblyopia might be a form of attentional neglect of the visual input to the amblyopic eye.

  13. Abnormalities in Structural Covariance of Cortical Gyrification in Parkinson's Disease.

    Science.gov (United States)

    Xu, Jinping; Zhang, Jiuquan; Zhang, Jinlei; Wang, Yue; Zhang, Yanling; Wang, Jian; Li, Guanglin; Hu, Qingmao; Zhang, Yuanchao

    2017-01-01

    Although abnormal cortical morphology and connectivity between brain regions (structural covariance) have been reported in Parkinson's disease (PD), the topological organizations of large-scale structural brain networks are still poorly understood. In this study, we investigated large-scale structural brain networks in a sample of 37 PD patients and 34 healthy controls (HC) by assessing the structural covariance of cortical gyrification with local gyrification index (lGI). We demonstrated prominent small-world properties of the structural brain networks for both groups. Compared with the HC group, PD patients showed significantly increased integrated characteristic path length and integrated clustering coefficient, as well as decreased integrated global efficiency in structural brain networks. Distinct distributions of hub regions were identified between the two groups, showing more hub regions in the frontal cortex in PD patients. Moreover, the modular analyses revealed significantly decreased integrated regional efficiency in lateral Fronto-Insula-Temporal module, and increased integrated regional efficiency in Parieto-Temporal module in the PD group as compared to the HC group. In summary, our study demonstrated altered topological properties of structural networks at a global, regional and modular level in PD patients. These findings suggests that the structural networks of PD patients have a suboptimal topological organization, resulting in less effective integration of information between brain regions.

  14. Superfund and Toxic Release Inventory Sites - MDC_ContaminatedSite

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — A point feature class of open DERM Contaminated sites - see phase code for status of site. Contaminated sites identifies properties where environmental contamination...

  15. Muscarinic contribution to the acute cortical effects of vagus nerve stimulation

    Science.gov (United States)

    Nichols, Justin A.

    2011-12-01

    Electrical stimulation of the vagus nerve (VNS) has been used to treat more than 60,000 patients with drug-resistant epilepsy and is under investigation as a treatment for several other neurological disorders and conditions. Among these, VNS increases memory performance and enhances recovery of motor and cognitive function in animal models of traumatic brain injury. Recent research indicates that pairing brief VNS with tones multiple-times a day for several weeks induces long-term, input specific cortical plasticity, which can be used to re-normalize the pathological cortical reorganization and eliminate a behavioral correlate of chronic tinnitus in noise exposed rats. Despite the therapeutic potential, the mechanisms of action of VNS remain speculative. In chapter 2 of this dissertation, the acute effects of VNS on cortical synchrony, excitability, and temporal processing are examined. In anesthetized rats implanted with multi-electrode arrays, VNS increased and decorrelated spontaneous multi-unit activity, and suppressed entrainment to repetitive noise burst stimulation at 6 to 8 Hz, but not after systemic administration of the muscarinic antagonist scopolamine. Chapter 3 focuses on VNS-tone pairing induced cortical plasticity. Pairing VNS with a tone one hundred times in anesthetized rats resulted in frequency specific plasticity in 31% of the auditory cortex sites. Half of these sites exhibited a frequency specific increase in firing rate and half exhibited a frequency specific decrease. Muscarinic receptor blockade with scopolamine almost entirely prevented the frequency specific increases, but not decreases. Collectively, these experiments demonstrate the capacity for VNS to not only acutely influence cortical synchrony, and excitability, but to also influence temporal and spectral tuning via muscarinic receptor activation. These results strengthen the hypothesis that acetylcholine and muscarinic receptors are involved in the mechanisms of action of VNS and

  16. Flash fluorescence with indocyanine green videoangiography to identify the recipient artery for bypass with distal middle cerebral artery aneurysms: operative technique.

    Science.gov (United States)

    Rodríguez-Hernández, Ana; Lawton, Michael T

    2012-06-01

    Distal middle cerebral artery (MCA) aneurysms frequently have nonsaccular morphology that necessitates trapping and bypass. Bypasses can be difficult because efferent arteries lie deep in the opercular cleft and may not be easily identifiable. We introduce the "flash fluorescence" technique, which uses videoangiography with indocyanine green (ICG) dye to identify an appropriate recipient artery on the cortical surface for the bypass, enabling a more superficial and easier anastomosis. Flash fluorescence requires 3 steps: (1) temporary clip occlusion of the involved afferent artery; (2) videoangiography demonstrating fluorescence in uninvolved arteries on the cortical surface; and (3) removal of the temporary clip with flash fluorescence in the involved efferent arteries on the cortical surface, thereby identifying a recipient. Alternatively, temporary clips can occlude uninvolved arteries, and videoangiography will demonstrate initial fluorescence in efferent arteries during temporary occlusion and flash fluorescence in uninvolved arteries during reperfusion. From a consecutive series of 604 MCA aneurysms treated microsurgically, 22 (3.6%) were distal aneurysms and 11 required a bypass. The flash fluorescence technique was used in 3 patients to select the recipient artery for 2 superficial temporal artery-to-MCA bypasses and 1 MCA-MCA bypass. The correct recipient was selected in all cases. The flash fluorescence technique provides quick, reliable localization of an appropriate recipient artery for bypass when revascularization is needed for a distal MCA aneurysm. This technique eliminates the need for extensive dissection of the efferent artery and enables a superficial recipient site that makes the anastomosis safer, faster, and less demanding.

  17. Functional cortical mapping of scale illusion

    International Nuclear Information System (INIS)

    Wang, Li-qun; Kuriki, Shinya

    2011-01-01

    We have studied cortical activation using 1.5 T fMRI during 'Scale Illusion', a kind of auditory illusion, in which subjects perceive smooth melodies while listening to dichotic irregular pitch sequences consisting of scale tones, in repeated phrases composed of eight tones. Four male and four female subjects listened to different stimuli, that including illusion-inducing tone sequence, monaural tone sequence and perceived pitch sequence with a control of white noises delivered to the right and left ears in random order. 32 scans with a repetition time (TR) 3 s Between 3 s interval for each type of the four stimuli were performed. In BOLD signals, activation was observed in the prefrontal and temporal cortices, parietal lobule and occipital areas by first-level group analysis. However, there existed large intersubject variability such that systematic tendency of the activation was not clear. The study will be continued to obtain larger number of subjects for group analysis. (author)

  18. Massive cortical reorganization in sighted Braille readers.

    Science.gov (United States)

    Siuda-Krzywicka, Katarzyna; Bola, Łukasz; Paplińska, Małgorzata; Sumera, Ewa; Jednoróg, Katarzyna; Marchewka, Artur; Śliwińska, Magdalena W; Amedi, Amir; Szwed, Marcin

    2016-03-15

    The brain is capable of large-scale reorganization in blindness or after massive injury. Such reorganization crosses the division into separate sensory cortices (visual, somatosensory...). As its result, the visual cortex of the blind becomes active during tactile Braille reading. Although the possibility of such reorganization in the normal, adult brain has been raised, definitive evidence has been lacking. Here, we demonstrate such extensive reorganization in normal, sighted adults who learned Braille while their brain activity was investigated with fMRI and transcranial magnetic stimulation (TMS). Subjects showed enhanced activity for tactile reading in the visual cortex, including the visual word form area (VWFA) that was modulated by their Braille reading speed and strengthened resting-state connectivity between visual and somatosensory cortices. Moreover, TMS disruption of VWFA activity decreased their tactile reading accuracy. Our results indicate that large-scale reorganization is a viable mechanism recruited when learning complex skills.

  19. Permanent Cortical Blindness After Bronchial Artery Embolization

    Energy Technology Data Exchange (ETDEWEB)

    Doorn, Colette S. van, E-mail: cvandoorn@gmail.com; De Boo, Diederick W., E-mail: d.w.deboo@amc.uva.nl [Academic Medical Centre, Department of Radiology (Netherlands); Weersink, Els J. M., E-mail: e.j.m.weersink@amc.uva.nl [Academic Medical Centre, Department of Pulmonology (Netherlands); Delden, Otto M. van, E-mail: o.m.vandelden@amc.uva.nl; Reekers, Jim A., E-mail: j.a.reekers@amc.uva.nl; Lienden, Krijn P. van, E-mail: k.p.vanlienden@amc.uva.nl [Academic Medical Centre, Department of Radiology (Netherlands)

    2013-12-15

    A 35-year-old female with a known medical history of cystic fibrosis was admitted to our institution for massive hemoptysis. CTA depicted a hypertrophied bronchial artery to the right upper lobe and showed signs of recent bleeding at that location. Bronchial artery embolization (BAE) was performed with gelfoam slurry, because pronounced shunting to the pulmonary artery was present. Immediately after BAE, the patient developed bilateral cortical blindness. Control angiography showed an initially not opacified anastomosis between the embolized bronchial artery and the right subclavian artery, near to the origin of the right vertebral artery. Cessation of outflow in the bronchial circulation reversed the flow through the anastomosis and allowed for spill of embolization material into the posterior circulation. Unfortunately the cortical blindness presented was permanent.

  20. Visual Dysfunction in Posterior Cortical Atrophy

    Science.gov (United States)

    Maia da Silva, Mari N.; Millington, Rebecca S.; Bridge, Holly; James-Galton, Merle; Plant, Gordon T.

    2017-01-01

    Posterior cortical atrophy (PCA) is a syndromic diagnosis. It is characterized by progressive impairment of higher (cortical) visual function with imaging evidence of degeneration affecting the occipital, parietal, and posterior temporal lobes bilaterally. Most cases will prove to have Alzheimer pathology. The aim of this review is to summarize the development of the concept of this disorder since it was first introduced. A critical discussion of the evolving diagnostic criteria is presented and the differential diagnosis with regard to the underlying pathology is reviewed. Emphasis is given to the visual dysfunction that defines the disorder, and the classical deficits, such as simultanagnosia and visual agnosia, as well as the more recently recognized visual field defects, are reviewed, along with the evidence on their neural correlates. The latest developments on the imaging of PCA are summarized, with special attention to its role on the differential diagnosis with related conditions. PMID:28861031

  1. Perceptual incongruence influences bistability and cortical activation.

    Directory of Open Access Journals (Sweden)

    Gijs Joost Brouwer

    Full Text Available We employed a parametric psychophysical design in combination with functional imaging to examine the influence of metric changes in perceptual incongruence on perceptual alternation rates and cortical responses. Subjects viewed a bistable stimulus defined by incongruent depth cues; bistability resulted from incongruence between binocular disparity and monocular perspective cues that specify different slants (slant rivalry. Psychophysical results revealed that perceptual alternation rates were positively correlated with the degree of perceived incongruence. Functional imaging revealed systematic increases in activity that paralleled the psychophysical results within anterior intraparietal sulcus, prior to the onset of perceptual alternations. We suggest that this cortical activity predicts the frequency of subsequent alternations, implying a putative causal role for these areas in initiating bistable perception. In contrast, areas implicated in form and depth processing (LOC and V3A were sensitive to the degree of slant, but failed to show increases in activity when these cues were in conflict.

  2. Plasticity of cortical excitatory-inhibitory balance.

    Science.gov (United States)

    Froemke, Robert C

    2015-07-08

    Synapses are highly plastic and are modified by changes in patterns of neural activity or sensory experience. Plasticity of cortical excitatory synapses is thought to be important for learning and memory, leading to alterations in sensory representations and cognitive maps. However, these changes must be coordinated across other synapses within local circuits to preserve neural coding schemes and the organization of excitatory and inhibitory inputs, i.e., excitatory-inhibitory balance. Recent studies indicate that inhibitory synapses are also plastic and are controlled directly by a large number of neuromodulators, particularly during episodes of learning. Many modulators transiently alter excitatory-inhibitory balance by decreasing inhibition, and thus disinhibition has emerged as a major mechanism by which neuromodulation might enable long-term synaptic modifications naturally. This review examines the relationships between neuromodulation and synaptic plasticity, focusing on the induction of long-term changes that collectively enhance cortical excitatory-inhibitory balance for improving perception and behavior.

  3. Shining a light on posterior cortical atrophy.

    Science.gov (United States)

    Crutch, Sebastian J; Schott, Jonathan M; Rabinovici, Gil D; Boeve, Bradley F; Cappa, Stefano F; Dickerson, Bradford C; Dubois, Bruno; Graff-Radford, Neill R; Krolak-Salmon, Pierre; Lehmann, Manja; Mendez, Mario F; Pijnenburg, Yolande; Ryan, Natalie S; Scheltens, Philip; Shakespeare, Tim; Tang-Wai, David F; van der Flier, Wiesje M; Bain, Lisa; Carrillo, Maria C; Fox, Nick C

    2013-07-01

    Posterior cortical atrophy (PCA) is a clinicoradiologic syndrome characterized by progressive decline in visual processing skills, relatively intact memory and language in the early stages, and atrophy of posterior brain regions. Misdiagnosis of PCA is common, owing not only to its relative rarity and unusual and variable presentation, but also because patients frequently first seek the opinion of an ophthalmologist, who may note normal eye examinations by their usual tests but may not appreciate cortical brain dysfunction. Seeking to raise awareness of the disease, stimulate research, and promote collaboration, a multidisciplinary group of PCA research clinicians formed an international working party, which had its first face-to-face meeting on July 13, 2012 in Vancouver, Canada, prior to the Alzheimer's Association International Conference. Copyright © 2013 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  4. Slow cortical evoked potentials after noise exposure

    Energy Technology Data Exchange (ETDEWEB)

    von Wedel, H; Opitz, H J

    1979-07-01

    Human cortical evoked potentials under conditions of stimuation are registrated in the post-stimulatory phase of a five minutes lasting equally masking white noise (90 dB HL). Changes of the evoked potentials during adaptation, possible analogy with high tone losses after noise representation and the origin of tinnitus are examined. Stimulation was started 3 sec after the off-effect of the noise. For five minutes periodically tone bursts were represented. Each train of stimulation consists of tone bursts of three frequencies: 2 kcs, 4 kcs, 8 kcs. The 0.5 sec lasting tones were separated by pauses of 2 sec. During the experiment stimulation and analysis were controlled by a computer. Changes in latency and amplitudes of the cortical evoked potentials were registered. Changes of the adaptation patterns as a function of the poststimulatory time are discussed.

  5. Visual Dysfunction in Posterior Cortical Atrophy

    Directory of Open Access Journals (Sweden)

    Mari N. Maia da Silva

    2017-08-01

    Full Text Available Posterior cortical atrophy (PCA is a syndromic diagnosis. It is characterized by progressive impairment of higher (cortical visual function with imaging evidence of degeneration affecting the occipital, parietal, and posterior temporal lobes bilaterally. Most cases will prove to have Alzheimer pathology. The aim of this review is to summarize the development of the concept of this disorder since it was first introduced. A critical discussion of the evolving diagnostic criteria is presented and the differential diagnosis with regard to the underlying pathology is reviewed. Emphasis is given to the visual dysfunction that defines the disorder, and the classical deficits, such as simultanagnosia and visual agnosia, as well as the more recently recognized visual field defects, are reviewed, along with the evidence on their neural correlates. The latest developments on the imaging of PCA are summarized, with special attention to its role on the differential diagnosis with related conditions.

  6. Thickened cortical bones in congenital neutropenia

    International Nuclear Information System (INIS)

    Boechat, M.I.; Gormley, L.S.; O'Laughlin, B.J.

    1987-01-01

    Congenital neutropenia is an uncommon entity which may be familial and has a wide spectrum of clinical expression. Three sisters with the severe form of the disease, that suffered from recurrent infections which lead to their demise are described. Review of their radiographs revealed the presence of cortical thickening of the bones. Although several syndroms with different bone abnormalities have been reported associated with neutropenia, the radiographic finding of thickened cortex in children with congenital neutropenia has not been previously described. (orig.)

  7. Thickened cortical bones in congenital neutropenia

    Energy Technology Data Exchange (ETDEWEB)

    Boechat, M.I.; Gormley, L.S.; O' Laughlin, B.J.

    1987-02-01

    Congenital neutropenia is an uncommon entity which may be familial and has a wide spectrum of clinical expression. Three sisters with the severe form of the disease, that suffered from recurrent infections which lead to their demise are described. Review of their radiographs revealed the presence of cortical thickening of the bones. Although several syndroms with different bone abnormalities have been reported associated with neutropenia, the radiographic finding of thickened cortex in children with congenital neutropenia has not been previously described.

  8. Motor cortical plasticity in Parkinson's disease.

    Science.gov (United States)

    Udupa, Kaviraja; Chen, Robert

    2013-09-04

    In Parkinson's disease (PD), there are alterations of the basal ganglia (BG) thalamocortical networks, primarily due to degeneration of nigrostriatal dopaminergic neurons. These changes in subcortical networks lead to plastic changes in primary motor cortex (M1), which mediates cortical motor output and is a potential target for treatment of PD. Studies investigating the motor cortical plasticity using non-invasive transcranial magnetic stimulation (TMS) have found altered plasticity in PD, but there are inconsistencies among these studies. This is likely because plasticity depends on many factors such as the extent of dopaminergic loss and disease severity, response to dopaminergic replacement therapies, development of l-DOPA-induced dyskinesias (LID), the plasticity protocol used, medication, and stimulation status in patients treated with deep brain stimulation (DBS). The influences of LID and DBS on BG and M1 plasticity have been explored in animal models and in PD patients. In addition, many other factors such age, genetic factors (e.g., brain derived neurotropic factor and other neurotransmitters or receptors polymorphism), emotional state, time of the day, physical fitness have been documented to play role in the extent of plasticity induced by TMS in human studies. In this review, we summarize the studies that investigated M1 plasticity in PD and demonstrate how these afore-mentioned factors affect motor cortical plasticity in PD. We conclude that it is important to consider the clinical, demographic, and technical factors that influence various plasticity protocols while developing these protocols as diagnostic or prognostic tools in PD. We also discuss how the modulation of cortical excitability and the plasticity with these non-invasive brain stimulation techniques facilitate the understanding of the pathophysiology of PD and help design potential therapeutic possibilities in this disorder.

  9. Computational modeling of epidural cortical stimulation

    Science.gov (United States)

    Wongsarnpigoon, Amorn; Grill, Warren M.

    2008-12-01

    Epidural cortical stimulation (ECS) is a developing therapy to treat neurological disorders. However, it is not clear how the cortical anatomy or the polarity and position of the electrode affects current flow and neural activation in the cortex. We developed a 3D computational model simulating ECS over the precentral gyrus. With the electrode placed directly above the gyrus, about half of the stimulus current flowed through the crown of the gyrus while current density was low along the banks deep in the sulci. Beneath the electrode, neurons oriented perpendicular to the cortical surface were depolarized by anodic stimulation, and neurons oriented parallel to the boundary were depolarized by cathodic stimulation. Activation was localized to the crown of the gyrus, and neurons on the banks deep in the sulci were not polarized. During regulated voltage stimulation, the magnitude of the activating function was inversely proportional to the thickness of the CSF and dura. During regulated current stimulation, the activating function was not sensitive to the thickness of the dura but was slightly more sensitive than during regulated voltage stimulation to the thickness of the CSF. Varying the width of the gyrus and the position of the electrode altered the distribution of the activating function due to changes in the orientation of the neurons beneath the electrode. Bipolar stimulation, although often used in clinical practice, reduced spatial selectivity as well as selectivity for neuron orientation.

  10. SPECT in patients with cortical visual loss.

    Science.gov (United States)

    Silverman, I E; Galetta, S L; Gray, L G; Moster, M; Atlas, S W; Maurer, A H; Alavi, A

    1993-09-01

    Single-photon emission computed tomography (SPECT) with 99mTc-hexamethylpropyleneamine oxime (HMPAO) was used to investigate changes in cerebral blood flow in seven patients with cortical visual impairment. Traumatic brain injury (TBI) was the cause of cortical damage in two patients, cerebral ischemia in two patients and carbon monoxide (CO) poisoning, status epilepticus and Alzheimer's Disease (AD) each in three separate patients. The SPECT scans of the seven patients were compared to T2-weighted magnetic resonance image (MRI) scans of the brain to determine the correlation between functional and anatomical findings. In six of the seven patients, the qualitative interpretation of the SPECT studies supported the clinical findings (i.e., the visual field defect) by revealing altered regional cerebral blood flow (rCBF) in the appropriate regions of the visual pathway. MR scans in all of the patients, on the other hand, were either normal or disclosed smaller lesions than those detected by SPECT. We conclude that SPECT may reveal altered rCBF in patients with cortical visual impairment of various etiologies, even when MRI studies are normal or nondiagnostic.

  11. Rab3A, a possible marker of cortical granules, participates in cortical granule exocytosis in mouse eggs

    Energy Technology Data Exchange (ETDEWEB)

    Bello, Oscar Daniel; Cappa, Andrea Isabel; Paola, Matilde de; Zanetti, María Natalia [Instituto de Histología y Embriología, CONICET – Universidad Nacional de Cuyo, Av. Libertador 80, 5500 Mendoza (Argentina); Fukuda, Mitsunori [Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578 (Japan); Fissore, Rafael A. [Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, 661 North Pleasant Street, Amherst, MA 01003 (United States); Mayorga, Luis S. [Instituto de Histología y Embriología, CONICET – Universidad Nacional de Cuyo, Av. Libertador 80, 5500 Mendoza (Argentina); Michaut, Marcela A., E-mail: mmichaut@gmail.com [Instituto de Histología y Embriología, CONICET – Universidad Nacional de Cuyo, Av. Libertador 80, 5500 Mendoza (Argentina); Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo (Argentina)

    2016-09-10

    Fusion of cortical granules with the oocyte plasma membrane is the most significant event to prevent polyspermy. This particular exocytosis, also known as cortical reaction, is regulated by calcium and its molecular mechanism is still not known. Rab3A, a member of the small GTP-binding protein superfamily, has been implicated in calcium-dependent exocytosis and is not yet clear whether Rab3A participates in cortical granules exocytosis. Here, we examine the involvement of Rab3A in the physiology of cortical granules, particularly, in their distribution during oocyte maturation and activation, and their participation in membrane fusion during cortical granule exocytosis. Immunofluorescence and Western blot analysis showed that Rab3A and cortical granules have a similar migration pattern during oocyte maturation, and that Rab3A is no longer detected after cortical granule exocytosis. These results suggested that Rab3A might be a marker of cortical granules. Overexpression of EGFP-Rab3A colocalized with cortical granules with a Pearson correlation coefficient of +0.967, indicating that Rab3A and cortical granules have almost a perfect colocalization in the egg cortical region. Using a functional assay, we demonstrated that microinjection of recombinant, prenylated and active GST-Rab3A triggered cortical granule exocytosis, indicating that Rab3A has an active role in this secretory pathway. To confirm this active role, we inhibited the function of endogenous Rab3A by microinjecting a polyclonal antibody raised against Rab3A prior to parthenogenetic activation. Our results showed that Rab3A antibody microinjection abolished cortical granule exocytosis in parthenogenetically activated oocytes. Altogether, our findings confirm that Rab3A might function as a marker of cortical granules and participates in cortical granule exocytosis in mouse eggs. - Highlights: • Rab3A has a similar migration pattern to cortical granules in mouse oocytes. • Rab3A can be a marker of

  12. Effect of age at onset on cortical thickness and cognition in posterior cortical atrophy.

    Science.gov (United States)

    Suárez-González, Aida; Lehmann, Manja; Shakespeare, Timothy J; Yong, Keir X X; Paterson, Ross W; Slattery, Catherine F; Foulkes, Alexander J M; Rabinovici, Gil D; Gil-Néciga, Eulogio; Roldán-Lora, Florinda; Schott, Jonathan M; Fox, Nick C; Crutch, Sebastian J

    2016-08-01

    Age at onset (AAO) has been shown to influence the phenotype of Alzheimer's disease (AD), but how it affects atypical presentations of AD remains unknown. Posterior cortical atrophy (PCA) is the most common form of atypical AD. In this study, we aimed to investigate the effect of AAO on cortical thickness and cognitive function in 98 PCA patients. We used Freesurfer (v5.3.0) to compare cortical thickness with AAO both as a continuous variable, and by dichotomizing the groups based on median age (58 years). In both the continuous and dichotomized analyses, we found a pattern suggestive of thinner cortex in precuneus and parietal areas in earlier-onset PCA, and lower cortical thickness in anterior cingulate and prefrontal cortex in later-onset PCA. These cortical thickness differences between PCA subgroups were consistent with earlier-onset PCA patients performing worse on cognitive tests involving parietal functions. Our results provide a suggestion that AAO may not only affect the clinico-anatomical characteristics in AD but may also affect atrophy patterns and cognition within atypical AD phenotypes. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Effect of age at onset on cortical thickness and cognition in posterior cortical atrophy

    Science.gov (United States)

    Suárez-González, Aida; Lehmann, Manja; Shakespeare, Timothy J.; Yong, Keir X.X.; Paterson, Ross W.; Slattery, Catherine F.; Foulkes, Alexander J.M.; Rabinovici, Gil D.; Gil-Néciga, Eulogio; Roldán-Lora, Florinda; Schott, Jonathan M.; Fox, Nick C.; Crutch, Sebastian J.

    2016-01-01

    Age at onset (AAO) has been shown to influence the phenotype of Alzheimer’s disease (AD), but how it affects atypical presentations of AD remains unknown. Posterior cortical atrophy (PCA) is the most common form of atypical AD. In this study, we aimed to investigate the effect of AAO on cortical thickness and cognitive function in 98 PCA patients. We used Freesurfer (v5.3.0) to compare cortical thickness with AAO both as a continuous variable, and by dichotomizing the groups based on median age (58 years). In both the continuous and dichotomized analyses, we found a pattern suggestive of thinner cortex in precuneus and parietal areas in earlier-onset PCA, and lower cortical thickness in anterior cingulate and prefrontal cortex in later-onset PCA. These cortical thickness differences between PCA subgroups were consistent with earlier-onset PCA patients performing worse on cognitive tests involving parietal functions. Our results provide a suggestion that AAO may not only affect the clinico-anatomical characteristics in AD but may also affect atrophy patterns and cognition within atypical AD phenotypes. PMID:27318138

  14. Identifying the transition to the maturation zone in three ecotypes of Arabidopsis thaliana roots.

    Science.gov (United States)

    Cajero Sánchez, Wendy; García-Ponce, Berenice; Sánchez, María de la Paz; Álvarez-Buylla, Elena R; Garay-Arroyo, Adriana

    2018-01-01

    The Arabidopsis thaliana (hereafter Arabidopsis) root has become a useful model for studying how organ morphogenesis emerge from the coordination and balance of cell proliferation and differentiation, as both processes may be observed and quantified in the root at different stages of development. Hence, being able to objectively identify and delimit the different stages of root development has been very important. Up to now, three different zones along the longitudinal axis of the primary root of Arabidopsis, have been identified: the root apical meristematic zone (RAM) with two domains [the proliferative (PD) and the transition domain (TD)], the elongation zone (EZ) and the maturation zone (MZ). We previously reported a method to quantify the length of the cells of the meristematic and the elongation zone, as well as the boundaries or transitions between the root domains along the growing part of the Arabidopsis root. In this study, we provide a more accurate criterion to identify the MZ. Traditionally, the transition between the EZ to the MZ has been established by the emergence of the first root-hair bulge in the epidermis, because this emergence coincides with cell maturation in this cell type. But we have found here that after the emergence of the first root-hair bulge some cells continue to elongate and we have confirmed this in three different Arabidopsis ecotypes. We established the limit between the EZ and the MZ by looking for the closest cortical cell with a longer length than the average cell length of 10 cells after the cortical cell closest to the epidermal cell with the first root-hair bulge in these three ecotypes. In Col-0 and Ws this cell is four cells above the one with the root hair bulge and, in the Ler ecotype, this cell is five cells above. To unambiguously identifying the site at which cells stop elongating and attain their final length and fate at the MZ, we propose to calculate the length of completely elongated cortical cells counting 10

  15. Normal kidney size and renal cortical thickness of the Korean adults

    International Nuclear Information System (INIS)

    Chung, Hee Kyung; Hahm, Chang Kok

    1974-01-01

    1. The kidney size and cortical thickness were measured from intravenous pyelograms of healthy Korean adults of 250 males and 250 females. 2. The measured size and cortical thickness of kidney were following figure (mm). 3. The size of kidney of male is a little larger than female both in vertical length and horizontal width. 4. The renal cortical thickness were not significant in differences between male and female, right and left, in each poles. 5. In the study of distribution of length differences between pairs of kidneys in our series, the length of right kidney is larger in 18.6%, and width in 27.2%. 6. Comparative study is carried out measuring the length of first lumbar vertebral bodies including 4 intervertebral spaces. 7. The site of kidney is larger in the group of greater length of vertebral height. 8. The renal cortical thickness have no significant differences in according to the differences of length of vertebral height, in each poles. 9. Comparing with the western authors, the kidney size of the Korean adult is not smaller than western

  16. High-spatial-resolution mapping of the oxygen concentration in cortical tissue (Conference Presentation)

    Science.gov (United States)

    Jaswal, Rajeshwer S.; Yaseen, Mohammad A.; Fu, Buyin; Boas, David A.; Sakadžic, Sava

    2016-03-01

    Due to a lack of imaging tools for high-resolution imaging of cortical tissue oxygenation, the detailed maps of the oxygen partial pressure (PO2) around arterioles, venules, and capillaries remain largely unknown. Therefore, we have limited knowledge about the mechanisms that secure sufficient oxygen delivery in microvascular domains during brain activation, and provide some metabolic reserve capacity in diseases that affect either microvascular networks or the regulation of cerebral blood flow (CBF). To address this challenge, we applied a Two-Photon PO2 Microscopy to map PO2 at different depths in mice cortices. Measurements were performed through the cranial window in the anesthetized healthy mice as well as in the mouse models of microvascular dysfunctions. In addition, microvascular morphology was recorded by the two-photon microscopy at the end of each experiment and subsequently segmented. Co-registration of the PO2 measurements and exact microvascular morphology enabled quantification of the tissue PO2 dependence on distance from the arterioles, capillaries, and venules at various depths. Our measurements reveal significant spatial heterogeneity of the cortical tissue PO2 distribution that is dominated by the high oxygenation in periarteriolar spaces. In cases of impaired oxygen delivery due to microvascular dysfunction, significant reduction in tissue oxygenation away from the arterioles was observed. These tissue domains may be the initial sites of cortical injury that can further exacerbate the progression of the disease.

  17. Accounting for beta-particle energy loss to cortical bone via paired-image radiation transport (PIRT)

    International Nuclear Information System (INIS)

    Shah, Amish P.; Rajon, Didier A.; Patton, Phillip W.; Jokisch, Derek W.; Bolch, Wesley E.

    2005-01-01

    Current methods of skeletal dose assessment in both medical physics (radionuclide therapy) and health physics (dose reconstruction and risk assessment) rely heavily on a single set of bone and marrow cavity chord-length distributions in which particle energy deposition is tracked within an infinite extent of trabecular spongiosa, with no allowance for particle escape to cortical bone. In the present study, we introduce a paired-image radiation transport (PIRT) model which provides a more realistic three-dimensional (3D) geometry for particle transport in the skeletal site at both microscopic and macroscopic levels of its histology. Ex vivo CT scans were acquired of the pelvis, cranial cap, and individual ribs excised from a 66-year male cadaver (BMI of 22.7 kg m -2 ). For the three skeletal sites, regions of trabecular spongiosa and cortical bone were identified and segmented. Physical sections of interior spongiosa were taken and subjected to microCT imaging. Voxels within the resulting microCT images were then segmented and labeled as regions of bone trabeculae, endosteum, active marrow, and inactive marrow through application of image processing algorithms. The PIRT methodology was then implemented within the EGSNRC radiation transport code whereby electrons of various initial energies are simultaneously tracked within both the ex vivo CT macroimage and the CT microimage of the skeletal site. At initial electron energies greater than 50-200 keV, a divergence in absorbed fractions to active marrow are noted between PIRT model simulations and those estimated under existing techniques of infinite spongiosa transport. Calculations of radionuclide S values under both methodologies imply that current chord-based models may overestimate the absorbed dose to active bone marrow in these skeletal sites by 0% to 27% for low-energy beta emitters ( 33 P, 169 Er, and 177 Lu), by ∼4% to 49% for intermediate-energy beta emitters ( 153 Sm, 186 Re, and 89 Sr), and by ∼14% to

  18. Patterns of Neuropsychological Profile and Cortical Thinning in Parkinson's Disease with Punding.

    Directory of Open Access Journals (Sweden)

    Han Soo Yoo

    Full Text Available Punding, one of dopamine replacement treatment related complications, refers to aimless and stereotyped behaviors. To identify possible neural correlates of punding behavior in patients with Parkinson's disease (PD, we investigated the patterns of cognitive profiles and cortical thinning.Of the 186 subjects with PD screened during the study period, we prospectively enrolled 10 PD patients with punding and 43 without punding on the basis of a structured interview. We performed comprehensive neuropsychological tests and voxel-based and regions-of-interest (ROIs-based cortical thickness analysis between PD patients with and without punding.The prevalence of punding in patients with PD was 5.4%. Punding behaviors were closely related to previous occupations or hobbies and showed a temporal relationship to changes of levodopa-equivalent dose (LED. Significant predisposing factors were a long duration of PD and intake of medications of PD, high total daily LED, dyskinesia, and impulse control disorder. Punding severity was correlated with LED (p = 0.029. The neurocognitive assessment revealed that PD patients with punding showed more severe cognitive deficits in the color Stroop task than did those without punding (p = 0.022. Voxel-based analysis showed that PD-punders had significant cortical thinning in the dorsolateral prefrontal area relative to controls. Additionally, ROI-based analysis revealed that cortical thinning in PD-punders relative to PD-nonpunders was localized in the prefrontal cortices, extending into orbitofrontal area.We demonstrated that PD patients with punding performed poorly on cognitive tasks in frontal executive functions and showed severe cortical thinning in the dorsolateral prefrontal and orbitofrontal areas. These findings suggest that prefrontal modulation may be an essential component in the development of punding behavior in patients with PD.

  19. Meningeal defects alter the tangential migration of cortical interneurons in Foxc1hith/hith mice

    Directory of Open Access Journals (Sweden)

    Zarbalis Konstantinos

    2012-01-01

    Full Text Available Abstract Background Tangential migration presents the primary mode of migration of cortical interneurons translocating into the cerebral cortex from subpallial domains. This migration takes place in multiple streams with the most superficial one located in the cortical marginal zone. While a number of forebrain-expressed molecules regulating this process have emerged, it remains unclear to what extent structures outside the brain, like the forebrain meninges, are involved. Results We studied a unique Foxc1 hypomorph mouse model (Foxc1hith/hith with meningeal defects and impaired tangential migration of cortical interneurons. We identified a territorial correlation between meningeal defects and disruption of interneuron migration along the adjacent marginal zone in these animals, suggesting that impaired meningeal integrity might be the primary cause for the observed migration defects. Moreover, we postulate that the meningeal factor regulating tangential migration that is affected in homozygote mutants is the chemokine Cxcl12. In addition, by using chromatin immunoprecipitation analysis, we provide evidence that the Cxcl12 gene is a direct transcriptional target of Foxc1 in the meninges. Further, we observe migration defects of a lesser degree in Cajal-Retzius cells migrating within the cortical marginal zone, indicating a less important role for Cxcl12 in their migration. Finally, the developmental migration defects observed in Foxc1hith/hith mutants do not lead to obvious differences in interneuron distribution in the adult if compared to control animals. Conclusions Our results suggest a critical role for the forebrain meninges to promote during development the tangential migration of cortical interneurons along the cortical marginal zone and Cxcl12 as the factor responsible for this property.

  20. Mean cortical curvature reflects cytoarchitecture restructuring in mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Jace B. King

    2016-01-01

    Full Text Available In the United States alone, the number of persons living with the enduring consequences of traumatic brain injuries is estimated to be between 3.2 and 5 million. This number does not include individuals serving in the United States military or seeking care at Veterans Affairs hospitals. The importance of understanding the neurobiological consequences of mild traumatic brain injury (mTBI has increased with the return of veterans from conflicts overseas, many of who have suffered this type of brain injury. However, identifying the neuroanatomical regions most affected by mTBI continues to prove challenging. The aim of this study was to assess the use of mean cortical curvature as a potential indicator of progressive tissue loss in a cross-sectional sample of 54 veterans with mTBI compared to 31 controls evaluated with MRI. It was hypothesized that mean cortical curvature would be increased in veterans with mTBI, relative to controls, due in part to cortical restructuring related to tissue volume loss. Mean cortical curvature was assessed in 60 bilateral regions (31 sulcal, 29 gyral. Of the 120 regions investigated, nearly 50% demonstrated significantly increased mean cortical curvature in mTBI relative to controls with 25% remaining significant following multiple comparison correction (all, pFDR < .05. These differences were most prominent in deep gray matter regions of the cortex. Additionally, significant relationships were found between mean cortical curvature and gray and white matter volumes (all, p < .05. These findings suggest potentially unique patterns of atrophy by region and indicate that changes in brain microstructure due to mTBI are sensitive to measures of mean curvature.

  1. Critical Roles of the Direct GABAergic Pallido-cortical Pathway in Controlling Absence Seizures

    Science.gov (United States)

    Li, Min; Ma, Tao; Wu, Shengdun; Ma, Jingling; Cui, Yan; Xia, Yang; Xu, Peng; Yao, Dezhong

    2015-01-01

    The basal ganglia (BG), serving as an intermediate bridge between the cerebral cortex and thalamus, are believed to play crucial roles in controlling absence seizure activities generated by the pathological corticothalamic system. Inspired by recent experiments, here we systematically investigate the contribution of a novel identified GABAergic pallido-cortical pathway, projecting from the globus pallidus externa (GPe) in the BG to the cerebral cortex, to the control of absence seizures. By computational modelling, we find that both increasing the activation of GPe neurons and enhancing the coupling strength of the inhibitory pallido-cortical pathway can suppress the bilaterally synchronous 2–4 Hz spike and wave discharges (SWDs) during absence seizures. Appropriate tuning of several GPe-related pathways may also trigger the SWD suppression, through modulating the activation level of GPe neurons. Furthermore, we show that the previously discovered bidirectional control of absence seizures due to the competition between other two BG output pathways also exists in our established model. Importantly, such bidirectional control is shaped by the coupling strength of this direct GABAergic pallido-cortical pathway. Our work suggests that the novel identified pallido-cortical pathway has a functional role in controlling absence seizures and the presented results might provide testable hypotheses for future experimental studies. PMID:26496656

  2. Functional networks in parallel with cortical development associate with executive functions in children.

    Science.gov (United States)

    Zhong, Jidan; Rifkin-Graboi, Anne; Ta, Anh Tuan; Yap, Kar Lai; Chuang, Kai-Hsiang; Meaney, Michael J; Qiu, Anqi

    2014-07-01

    Children begin performing similarly to adults on tasks requiring executive functions in late childhood, a transition that is probably due to neuroanatomical fine-tuning processes, including myelination and synaptic pruning. In parallel to such structural changes in neuroanatomical organization, development of functional organization may also be associated with cognitive behaviors in children. We examined 6- to 10-year-old children's cortical thickness, functional organization, and cognitive performance. We used structural magnetic resonance imaging (MRI) to identify areas with cortical thinning, resting-state fMRI to identify functional organization in parallel to cortical development, and working memory/response inhibition tasks to assess executive functioning. We found that neuroanatomical changes in the form of cortical thinning spread over bilateral frontal, parietal, and occipital regions. These regions were engaged in 3 functional networks: sensorimotor and auditory, executive control, and default mode network. Furthermore, we found that working memory and response inhibition only associated with regional functional connectivity, but not topological organization (i.e., local and global efficiency of information transfer) of these functional networks. Interestingly, functional connections associated with "bottom-up" as opposed to "top-down" processing were more clearly related to children's performance on working memory and response inhibition, implying an important role for brain systems involved in late childhood. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Anti-correlated cortical networks of intrinsic connectivity in the rat brain.

    Science.gov (United States)

    Schwarz, Adam J; Gass, Natalia; Sartorius, Alexander; Risterucci, Celine; Spedding, Michael; Schenker, Esther; Meyer-Lindenberg, Andreas; Weber-Fahr, Wolfgang

    2013-01-01

    In humans, resting-state blood oxygen level-dependent (BOLD) signals in the default mode network (DMN) are temporally anti-correlated with those from a lateral cortical network involving the frontal eye fields, secondary somatosensory and posterior insular cortices. Here, we demonstrate the existence of an analogous lateral cortical network in the rat brain, extending laterally from anterior secondary sensorimotor regions to the insular cortex and exhibiting low-frequency BOLD fluctuations that are temporally anti-correlated with a midline "DMN-like" network comprising posterior/anterior cingulate and prefrontal cortices. The primary nexus for this anti-correlation relationship was the anterior secondary motor cortex, close to regions that have been identified with frontal eye fields in the rat brain. The anti-correlation relationship was corroborated after global signal removal, underscoring this finding as a robust property of the functional connectivity signature in the rat brain. These anti-correlated networks demonstrate strong anatomical homology to networks identified in human and monkey connectivity studies, extend the known preserved functional connectivity relationships between rodent and primates, and support the use of resting-state functional magnetic resonance imaging as a translational imaging method between rat models and humans.

  4. Age Effects on Cortical Thickness in Cognitively Normal Elderly Individuals

    Directory of Open Access Journals (Sweden)

    Sona Hurtz

    2014-07-01

    Full Text Available Background/Aims: Atrophy in both grey and white matter is found in normal aging. The prefrontal cortex and the frontal lobe white matter are thought to be the most affected regions. Our aim was to examine the effects of normal aging on cortical grey matter using a 3D quantitative cortical mapping method. Methods: We analyzed 1.5-tesla brain magnetic resonance imaging data from 44 cognitively normal elderly subjects using cortical pattern matching and cortical thickness analyses. Linear regression analysis was used to study the effect of age on cortical thickness. 3D map-wide correction for multiple comparisons was conducted with permutation analyses using a threshold of p Results: We found a significant negative association between age and cortical thickness in the right hemisphere (pcorrected = 0.009 and a trend level association in the left hemisphere (pcorrected = 0.081. Age-related changes were greatest in the sensorimotor, bilateral dorsal anterior cingulate and supplementary motor cortices, and the right posterior middle and inferior frontal gyri. Age effects greater in the medial than lateral visual association cortices were also seen bilaterally. Conclusion: Our novel method further validates that normal aging results in diffuse cortical thinning that is most pronounced in the frontal and visual association cortices.

  5. Cortical thickness abnormalities in late adolescence with online gaming addiction.

    Science.gov (United States)

    Yuan, Kai; Cheng, Ping; Dong, Tao; Bi, Yanzhi; Xing, Lihong; Yu, Dahua; Zhao, Limei; Dong, Minghao; von Deneen, Karen M; Liu, Yijun; Qin, Wei; Tian, Jie

    2013-01-01

    Online gaming addiction, as the most popular subtype of Internet addiction, had gained more and more attention from the whole world. However, the structural differences in cortical thickness of the brain between adolescents with online gaming addiction and healthy controls are not well unknown; neither was its association with the impaired cognitive control ability. High-resolution magnetic resonance imaging scans from late adolescence with online gaming addiction (n = 18) and age-, education- and gender-matched controls (n = 18) were acquired. The cortical thickness measurement method was employed to investigate alterations of cortical thickness in individuals with online gaming addiction. The color-word Stroop task was employed to investigate the functional implications of the cortical thickness abnormalities. Imaging data revealed increased cortical thickness in the left precentral cortex, precuneus, middle frontal cortex, inferior temporal and middle temporal cortices in late adolescence with online gaming addiction; meanwhile, the cortical thicknesses of the left lateral orbitofrontal cortex (OFC), insula, lingual gyrus, the right postcentral gyrus, entorhinal cortex and inferior parietal cortex were decreased. Correlation analysis demonstrated that the cortical thicknesses of the left precentral cortex, precuneus and lingual gyrus correlated with duration of online gaming addiction and the cortical thickness of the OFC correlated with the impaired task performance during the color-word Stroop task in adolescents with online gaming addiction. The findings in the current study suggested that the cortical thickness abnormalities of these regions may be implicated in the underlying pathophysiology of online gaming addiction.

  6. State-dependent intrinsic predictability of cortical network dynamics.

    Directory of Open Access Journals (Sweden)

    Leila Fakhraei

    Full Text Available The information encoded in cortical circuit dynamics is fleeting, changing from moment to moment as new input arrives and ongoing intracortical interactions progress. A combination of deterministic and stochastic biophysical mechanisms governs how cortical dynamics at one moment evolve from cortical dynamics in recently preceding moments. Such temporal continuity of cortical dynamics is fundamental to many aspects of cortex function but is not well understood. Here we study temporal continuity by attempting to predict cortical population dynamics (multisite local field potential based on its own recent history in somatosensory cortex of anesthetized rats and in a computational network-level model. We found that the intrinsic predictability of cortical dynamics was dependent on multiple factors including cortical state, synaptic inhibition, and how far into the future the prediction extends. By pharmacologically tuning synaptic inhibition, we obtained a continuum of cortical states with asynchronous population activity at one extreme and stronger, spatially extended synchrony at the other extreme. Intermediate between these extremes we observed evidence for a special regime of population dynamics called criticality. Predictability of the near future (10-100 ms increased as the cortical state was tuned from asynchronous to synchronous. Predictability of the more distant future (>1 s was generally poor, but, surprisingly, was higher for asynchronous states compared to synchronous states. These experimental results were confirmed in a computational network model of spiking excitatory and inhibitory neurons. Our findings demonstrate that determinism and predictability of network dynamics depend on cortical state and the time-scale of the dynamics.

  7. Cortical thickness abnormalities in late adolescence with online gaming addiction.

    Directory of Open Access Journals (Sweden)

    Kai Yuan

    Full Text Available Online gaming addiction, as the most popular subtype of Internet addiction, had gained more and more attention from the whole world. However, the structural differences in cortical thickness of the brain between adolescents with online gaming addiction and healthy controls are not well unknown; neither was its association with the impaired cognitive control ability. High-resolution magnetic resonance imaging scans from late adolescence with online gaming addiction (n = 18 and age-, education- and gender-matched controls (n = 18 were acquired. The cortical thickness measurement method was employed to investigate alterations of cortical thickness in individuals with online gaming addiction. The color-word Stroop task was employed to investigate the functional implications of the cortical thickness abnormalities. Imaging data revealed increased cortical thickness in the left precentral cortex, precuneus, middle frontal cortex, inferior temporal and middle temporal cortices in late adolescence with online gaming addiction; meanwhile, the cortical thicknesses of the left lateral orbitofrontal cortex (OFC, insula, lingual gyrus, the right postcentral gyrus, entorhinal cortex and inferior parietal cortex were decreased. Correlation analysis demonstrated that the cortical thicknesses of the left precentral cortex, precuneus and lingual gyrus correlated with duration of online gaming addiction and the cortical thickness of the OFC correlated with the impaired task performance during the color-word Stroop task in adolescents with online gaming addiction. The findings in the current study suggested that the cortical thickness abnormalities of these regions may be implicated in the underlying pathophysiology of online gaming addiction.

  8. Autosomal dominant arteriopathy with sub cortical infarcts and leucoencephalopathy (CADASIL)

    International Nuclear Information System (INIS)

    Ojeda, Adriana; Tiezzi, Gerardo; Uriarte, Ana M.; Eguren, Leonor

    2002-01-01

    Cerebral autosomal dominant arteriopathy with sub cortical infarcts and leucoencephalopathy (CASADIL) is a systemic hereditary, vascular disease that involves small arteries. Recurrent ischemia, pseudo bulbar paralysis and dementia are characteristic. Other manifestations include migraine and depression. We report an Argentine family with VI generations with evidence of disease in IV. MR examinations were performed on 21 family members (both symptomatic and asymptomatic). The main findings on MR on symptomatic and asymptomatic patients were small lesions with high signal on T2 localised in periventricular white matter, brain stem, basal ganglia and thalamus, and confluent patches on white matter although with high signal on T2 images, usually symmetric. In conclusion we can assess that diffuse myelin loss and small infarcts occurring in cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy well demonstrated with MR. In addition, some of the abnormalities in pre symptomatic patients can be identified on MR images. (author)

  9. Age of language acquisition and cortical language organization in multilingual patients undergoing awake brain mapping.

    Science.gov (United States)

    Fernández-Coello, Alejandro; Havas, Viktória; Juncadella, Montserrat; Sierpowska, Joanna; Rodríguez-Fornells, Antoni; Gabarrós, Andreu

    2017-06-01

    OBJECTIVE Most knowledge regarding the anatomical organization of multilingualism is based on aphasiology and functional imaging studies. However, the results have still to be validated by the gold standard approach, namely electrical stimulation mapping (ESM) during awake neurosurgical procedures. In this ESM study the authors describe language representation in a highly specific group of 13 multilingual individuals, focusing on how age of acquisition may influence the cortical organization of language. METHODS Thirteen patients who had a high degree of proficiency in multiple languages and were harboring lesions within the dominant, left hemisphere underwent ESM while being operated on under awake conditions. Demographic and language data were recorded in relation to age of language acquisition (for native languages and early- and late-acquired languages), neuropsychological pre- and postoperative language testing, the number and location of language sites, and overlapping distribution in terms of language acquisition time. Lesion growth patterns and histopathological characteristics, location, and size were also recorded. The distribution of language sites was analyzed with respect to age of acquisition and overlap. RESULTS The functional language-related sites were distributed in the frontal (55%), temporal (29%), and parietal lobes (16%). The total number of native language sites was 47. Early-acquired languages (including native languages) were represented in 97 sites (55 overlapped) and late-acquired languages in 70 sites (45 overlapped). The overlapping distribution was 20% for early-early, 71% for early-late, and 9% for late-late. The average lesion size (maximum diameter) was 3.3 cm. There were 5 fast-growing and 7 slow-growing lesions. CONCLUSIONS Cortical language distribution in multilingual patients is not homogeneous, and it is influenced by age of acquisition. Early-acquired languages have a greater cortical representation than languages acquired

  10. Censoring distances based on labeled cortical distance maps in cortical morphometry.

    Science.gov (United States)

    Ceyhan, Elvan; Nishino, Tomoyuki; Alexopolous, Dimitrios; Todd, Richard D; Botteron, Kelly N; Miller, Michael I; Ratnanather, J Tilak

    2013-01-01

    It has been demonstrated that shape differences in cortical structures may be manifested in neuropsychiatric disorders. Such morphometric differences can be measured by labeled cortical distance mapping (LCDM) which characterizes the morphometry of the laminar cortical mantle of cortical structures. LCDM data consist of signed/labeled distances of gray matter (GM) voxels with respect to GM/white matter (WM) surface. Volumes and other summary measures for each subject and the pooled distances can help determine the morphometric differences between diagnostic groups, however they do not reveal all the morphometric information contained in LCDM distances. To extract more information from LCDM data, censoring of the pooled distances is introduced for each diagnostic group where the range of LCDM distances is partitioned at a fixed increment size; and at each censoring step, the distances not exceeding the censoring distance are kept. Censored LCDM distances inherit the advantages of the pooled distances but also provide information about the location of morphometric differences which cannot be obtained from the pooled distances. However, at each step, the censored distances aggregate, which might confound the results. The influence of data aggregation is investigated with an extensive Monte Carlo simulation analysis and it is demonstrated that this influence is negligible. As an illustrative example, GM of ventral medial prefrontal cortices (VMPFCs) of subjects with major depressive disorder (MDD), subjects at high risk (HR) of MDD, and healthy control (Ctrl) subjects are used. A significant reduction in laminar thickness of the VMPFC in MDD and HR subjects is observed compared to Ctrl subjects. Moreover, the GM LCDM distances (i.e., locations with respect to the GM/WM surface) for which these differences start to occur are determined. The methodology is also applicable to LCDM-based morphometric measures of other cortical structures affected by disease.

  11. Censoring Distances Based on Labeled Cortical Distance Maps in Cortical Morphometry

    Directory of Open Access Journals (Sweden)

    Elvan eCeyhan

    2013-10-01

    Full Text Available It has been demonstrated that shape differences are manifested in cortical structures due to neuropsychiatric disorders. Such morphometric differences can be measured by labeled cortical distance mapping (LCDM which characterizes the morphometry of the laminar cortical mantle of cortical structures. LCDM data consist of signed/labeled distances of gray matter (GM voxels with respect to GM/white matter (WM surface. Volumes and other summary measures for each subject and the pooled distances can help determine the morphometric differences between diagnostic groups, however they do not reveal all the morphometric information con-tained in LCDM distances. To extract more information from LCDM data, censoring of the pooled distances is introduced for each diagnostic group where the range of LCDM distances is partitioned at a fixed increment size; and at each censoring step, the distances not exceeding the censoring distance are kept. Censored LCDM distances inherit the advantages of the pooled distances but also provide information about the location of morphometric differences which cannot be obtained from the pooled distances. However, at each step, the censored distances aggregate, which might confound the results. The influence of data aggregation is investigated with an extensive Monte Carlo simulation analysis and it is demonstrated that this influence is negligible. As an illustrative example, GM of ventral medial prefrontal cortices (VMPFCs of subjects with major depressive disorder (MDD, subjects at high risk (HR of MDD, and healthy control (Ctrl subjects are used. A significant reduction in laminar thickness of the VMPFC in MDD and HR subjects is observed compared to Ctrl subjects. Moreover, the GM LCDM distances (i.e., locations with respect to the GM/WM surface for which these differences start to occur are determined. The methodology is also applicable to LCDM-based morphometric measures of other cortical structures affected by disease.

  12. Bone heat generated using conventional implant drills versus piezosurgery unit during apical cortical plate perforation.

    Science.gov (United States)

    Lajolo, Carlo; Valente, Nicola Alberto; Romandini, William Giuseppe; Petruzzi, Massimo; Verdugo, Fernando; D'Addona, Antonio

    2018-03-09

    The apical portion of the implant osteotomy receives less irrigation and cooling during surgical preparation. High bone temperatures, above the critical 10°C threshold, may impair osseointegration, particularly, around dense cortical bone. The aim of this study is to evaluate the apical cortical plate temperature increase with two different devices and pressure loads in a porcine rib ex-vivo model. Twenty-four implant sites were prepared on porcine ribs divided into 4 groups of 6 samples each according to the device used (conventional drill system or piezosurgery) and pressure load applied (1000 g or 1500 g). A rubber dam was used to isolate the apical cortical plate from the cooling effect of irrigation. Temperature variation measurements were taken using an infrared thermometer. The piezosurgery unit was 2 times more likely to increase the osteotomy temperature by 10.0°C (OR = 2; 95% CI = 1.136-3.522; p piezosurgery-1000 g) and 8.17°C (SD = 6.12) for group 4 (piezosurgery-1,500 g). The piezosurgery site preparation caused significantly higher temperature increase than conventional drills (p piezosurgery unit is a potential risk during implant site preparation. The piezosurgical device reached significantly higher temperatures than conventional drilling at the apical cortical portion of the osteotomy. The temperature increase is often higher than the critical 10°C threshold. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  13. Pitch-Responsive Cortical Regions in Congenital Amusia.

    Science.gov (United States)

    Norman-Haignere, Sam V; Albouy, Philippe; Caclin, Anne; McDermott, Josh H; Kanwisher, Nancy G; Tillmann, Barbara

    2016-03-09

    Congenital amusia is a lifelong deficit in music perception thought to reflect an underlying impairment in the perception and memory of pitch. The neural basis of amusic impairments is actively debated. Some prior studies have suggested that amusia stems from impaired connectivity between auditory and frontal cortex. However, it remains possible that impairments in pitch coding within auditory cortex also contribute to the disorder, in part because prior studies have not measured responses from the cortical regions most implicated in pitch perception in normal individuals. We addressed this question by measuring fMRI responses in 11 subjects with amusia and 11 age- and education-matched controls to a stimulus contrast that reliably identifies pitch-responsive regions in normal individuals: harmonic tones versus frequency-matched noise. Our findings demonstrate that amusic individuals with a substantial pitch perception deficit exhibit clusters of pitch-responsive voxels that are comparable in extent, selectivity, and anatomical location to those of control participants. We discuss possible explanations for why amusics might be impaired at perceiving pitch relations despite exhibiting normal fMRI responses to pitch in their auditory cortex: (1) individual neurons within the pitch-responsive region might exhibit abnormal tuning or temporal coding not detectable with fMRI, (2) anatomical tracts that link pitch-responsive regions to other brain areas (e.g., frontal cortex) might be altered, and (3) cortical regions outside of pitch-responsive cortex might be abnormal. The ability to identify pitch-responsive regions in individual amusic subjects will make it possible to ask more precise questions about their role in amusia in future work. Copyright © 2016 the authors 0270-6474/16/362986-09$15.00/0.

  14. EEG-guided transcranial magnetic stimulation reveals rapid shifts in motor cortical excitability during the human sleep slow oscillation

    DEFF Research Database (Denmark)

    Bergmann, Til O; Mölle, Matthias; Schmidt, Marlit A

    2012-01-01

    Evoked cortical responses do not follow a rigid input–output function but are dynamically shaped by intrinsic neural properties at the time of stimulation. Recent research has emphasized the role of oscillatory activity in determining cortical excitability. Here we employed EEG-guided transcranial......, closely resembling a spontaneous SO. However, both MEPs and TEPs were consistently larger when evoked during SO up-states than during down-states, and ampliudes within each SO state depended on the actual EEG potential at the time and site of stimulation. These results provide first-time evidence...... magnetic stimulation (TMS) during non-rapid eye movement sleep to examine whether the spontaneous

  15. Subthalamic stimulation modulates cortical motor network activity and synchronization in Parkinson’s disease

    Science.gov (United States)

    Klotz, Rosa; Govindan, Rathinaswamy B.; Scholten, Marlieke; Naros, Georgios; Ramos-Murguialday, Ander; Bunjes, Friedemann; Meisner, Christoph; Plewnia, Christian; Krüger, Rejko

    2015-01-01

    Dynamic modulations of large-scale network activity and synchronization are inherent to a broad spectrum of cognitive processes and are disturbed in neuropsychiatric conditions including Parkinson’s disease. Here, we set out to address the motor network activity and synchronization in Parkinson’s disease and its modulation with subthalamic stimulation. To this end, 20 patients with idiopathic Parkinson’s disease with subthalamic nucleus stimulation were analysed on externally cued right hand finger movements with 1.5-s interstimulus interval. Simultaneous recordings were obtained from electromyography on antagonistic muscles (right flexor digitorum and extensor digitorum) together with 64-channel electroencephalography. Time-frequency event-related spectral perturbations were assessed to determine cortical and muscular activity. Next, cross-spectra in the time-frequency domain were analysed to explore the cortico-cortical synchronization. The time-frequency modulations enabled us to select a time-frequency range relevant for motor processing. On these time-frequency windows, we developed an extension of the phase synchronization index to quantify the global cortico-cortical synchronization and to obtain topographic differentiations of distinct electrode sites with respect to their contributions to the global phase synchronization index. The spectral measures were used to predict clinical and reaction time outcome using regression analysis. We found that movement-related desynchronization of cortical activity in the upper alpha and beta range was significantly facilitated with ‘stimulation on’ compared to ‘stimulation off’ on electrodes over the bilateral parietal, sensorimotor, premotor, supplementary-motor, and prefrontal areas, including the bilateral inferior prefrontal areas. These spectral modulations enabled us to predict both clinical and reaction time improvement from subthalamic stimulation. With ‘stimulation on’, interhemispheric cortico-cortical

  16. Aberrant cortical associative plasticity associated with severe adult Tourette syndrome.

    Science.gov (United States)

    Martín-Rodríguez, Juan Francisco; Ruiz-Rodríguez, María Adilia; Palomar, Francisco J; Cáceres-Redondo, María Teresa; Vargas, Laura; Porcacchia, Paolo; Gómez-Crespo, Mercedes; Huertas-Fernández, Ismael; Carrillo, Fátima; Madruga-Garrido, Marcos; Mir, Pablo

    2015-03-01

    Recent studies have shown altered cortical plasticity in adult patients with Tourette syndrome. However, the clinical significance of this finding remains elusive. Motor cortical plasticity was evaluated in 15 adult patients with severe Tourette syndrome and 16 healthy controls using the paired associative stimulation protocol by transcranial magnetic stimulation. Associations between paired associative stimulation-induced plasticity and relevant clinical variables, including cortical excitability, psychiatric comorbidities, drug treatment and tic severity, were assessed. Motor cortical plasticity was abnormally increased in patients with Tourette syndrome compared with healthy subjects. This abnormal plasticity was independently associated with tic severity. Patients with severe Tourette syndrome display abnormally increased cortical associative plasticity. This aberrant cortical plasticity was associated with tic severity, suggesting an underlying mechanism for tic pathophysiology. © 2015 International Parkinson and Movement Disorder Society.

  17. Critical fluctuations in cortical models near instability

    Directory of Open Access Journals (Sweden)

    Matthew J. Aburn

    2012-08-01

    Full Text Available Computational studies often proceed from the premise that cortical dynamics operate in a linearly stable domain, where fluctuations dissipate quickly and show only short memory. Studies of human EEG, however, have shown significant autocorrelation at time lags on the scale of minutes, indicating the need to consider regimes where nonlinearities influence the dynamics. Statistical properties such as increased autocorrelation length, increased variance, power-law scaling and bistable switching have been suggested as generic indicators of the approach to bifurcation in nonlinear dynamical systems. We study temporal fluctuations in a widely-employed computational model (the Jansen-Rit model of cortical activity, examining the statistical signatures that accompany bifurcations. Approaching supercritical Hopf bifurcations through tuning of the background excitatory input, we find a dramatic increase in the autocorrelation length that depends sensitively on the direction in phase space of the input fluctuations and hence on which neuronal subpopulation is stochastically perturbed. Similar dependence on the input direction is found in the distribution of fluctuation size and duration, which show power law scaling that extends over four orders of magnitude at the Hopf bifurcation. We conjecture that the alignment in phase space between the input noise vector and the center manifold of the Hopf bifurcation is directly linked to these changes. These results are consistent with the possibility of statistical indicators of linear instability being detectable in real EEG time series. However, even in a simple cortical model, we find that these indicators may not necessarily be visible even when bifurcations are present because their expression can depend sensitively on the neuronal pathway of incoming fluctuations.

  18. Sex Differences in the Relationship Between Conduct Disorder and Cortical Structure in Adolescents.

    Science.gov (United States)

    Smaragdi, Areti; Cornwell, Harriet; Toschi, Nicola; Riccelli, Roberta; Gonzalez-Madruga, Karen; Wells, Amy; Clanton, Roberta; Baker, Rosalind; Rogers, Jack; Martin-Key, Nayra; Puzzo, Ignazio; Batchelor, Molly; Sidlauskaite, Justina; Bernhard, Anka; Martinelli, Anne; Kohls, Gregor; Konrad, Kerstin; Baumann, Sarah; Raschle, Nora; Stadler, Christina; Freitag, Christine; Sonuga-Barke, Edmund J S; De Brito, Stephane; Fairchild, Graeme

    2017-08-01

    Previous studies have reported reduced cortical thickness and surface area and altered gyrification in frontal and temporal regions in adolescents with conduct disorder (CD). Although there is evidence that the clinical phenotype of CD differs between males and females, no studies have examined whether such sex differences extend to cortical and subcortical structure. As part of a European multisite study (FemNAT-CD), structural magnetic resonance imaging (MRI) data were collected from 48 female and 48 male participants with CD and from 104 sex-, age-, and pubertal-status-matched controls (14-18 years of age). Data were analyzed using surface-based morphometry, testing for effects of sex, diagnosis, and sex-by-diagnosis interactions, while controlling for age, IQ, scan site, and total gray matter volume. CD was associated with cortical thinning and higher gyrification in ventromedial prefrontal cortex in both sexes. Males with CD showed lower, and females with CD showed higher, supramarginal gyrus cortical thickness compared with controls. Relative to controls, males with CD showed higher gyrification and surface area in superior frontal gyrus, whereas the opposite pattern was seen in females. There were no effects of diagnosis or sex-by-diagnosis interactions on subcortical volumes. Results are discussed with regard to attention-deficit/hyperactivity disorder, depression, and substance abuse comorbidity, medication use, handedness, and CD age of onset. We found both similarities and differences between males and females in CD-cortical structure associations. This initial evidence that the pathophysiological basis of CD may be partly sex-specific highlights the need to consider sex in future neuroimaging studies and suggests that males and females may require different treatments. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  19. Evidence of functional connectivity between auditory cortical areas revealed by amplitude modulation sound processing.

    Science.gov (United States)

    Guéguin, Marie; Le Bouquin-Jeannès, Régine; Faucon, Gérard; Chauvel, Patrick; Liégeois-Chauvel, Catherine

    2007-02-01

    The human auditory cortex includes several interconnected areas. A better understanding of the mechanisms involved in auditory cortical functions requires a detailed knowledge of neuronal connectivity between functional cortical regions. In human, it is difficult to track in vivo neuronal connectivity. We investigated the interarea connection in vivo in the auditory cortex using a method of directed coherence (DCOH) applied to depth auditory evoked potentials (AEPs). This paper presents simultaneous AEPs recordings from insular gyrus (IG), primary and secondary cortices (Heschl's gyrus and planum temporale), and associative areas (Brodmann area [BA] 22) with multilead intracerebral electrodes in response to sinusoidal modulated white noises in 4 epileptic patients who underwent invasive monitoring with depth electrodes for epilepsy surgery. DCOH allowed estimation of the causality between 2 signals recorded from different cortical sites. The results showed 1) a predominant auditory stream within the primary auditory cortex from the most medial region to the most lateral one whatever the modulation frequency, 2) unidirectional functional connection from the primary to secondary auditory cortex, 3) a major auditory propagation from the posterior areas to the anterior ones, particularly at 8, 16, and 32 Hz, and 4) a particular role of Heschl's sulcus dispatching information to the different auditory areas. These findings suggest that cortical processing of auditory information is performed in serial and parallel streams. Our data showed that the auditory propagation could not be associated to a unidirectional traveling wave but to a constant interaction between these areas that could reflect the large adaptive and plastic capacities of auditory cortex. The role of the IG is discussed.

  20. Atypical calcific tendinitis with cortical erosions

    International Nuclear Information System (INIS)

    Kraemer, E.J.; El-Khoury, G.Y.

    2000-01-01

    Objective. To present and discuss six cases of calcific tendinitis in atypical locations (one at the insertion of the pectoralis major and five at the insertion of the gluteus maximus).Patients and results. All cases were associated with cortical erosions, and five had soft tissue calcifications. The initial presentation was confusing and the patients were suspected of having infection or neoplastic disease.Conclusion. Calcific tendinitis is a self-limiting condition. It is important to recognize the imaging features of this condition to avoid unnecessary investigation and surgery. (orig.)

  1. Mean field methods for cortical network dynamics

    DEFF Research Database (Denmark)

    Hertz, J.; Lerchner, Alexander; Ahmadi, M.

    2004-01-01

    We review the use of mean field theory for describing the dynamics of dense, randomly connected cortical circuits. For a simple network of excitatory and inhibitory leaky integrate- and-fire neurons, we can show how the firing irregularity, as measured by the Fano factor, increases...... with the strength of the synapses in the network and with the value to which the membrane potential is reset after a spike. Generalizing the model to include conductance-based synapses gives insight into the connection between the firing statistics and the high- conductance state observed experimentally in visual...

  2. Cisternography contribution in the cortical atrophy diagnosis

    International Nuclear Information System (INIS)

    Calegaro, J.U.M.; Balallai, N.; Suzuki, K.

    1975-01-01

    A 37 years-old woman suffered a car accident. On admission to hospital she presented: torpor, the right pupil greater than the left, both reacting to light, and left hemiparesis with homologous Babinski reflex. She was submitted to carotid arteriogram an air-contrast study without significant findings. Eletroencephalographic examination showed diffuse parenquimatous involvement of left cerebral hemisphery. Scinticisternography demonstrated delayed reabsorption of the radioactive tracer in both frontal areas. A subsequent trepanation made the diagnosis of cortical atrophy in the areas mentioned above. This case shows aditional information concerning anatomic detail provided by isotope cisternography, that eventually can't be detected by air-contrast study [pt

  3. Cerebral cortices of East african early hominids.

    Science.gov (United States)

    Falk, D

    1983-09-09

    An endocast of the frontal lobe of a reconstructed skull, which is approximately 2 million years old, from the Koobi Fora region of Kenya appears to represent the oldest human-like cortical sulcal pattern in the fossil record, while the endocast from another skull from the same region produces an endocast that appears apelike in its frontal lobe and similar to endocasts from earlier South African australopithecines. New analysis of paleoanatomical evidence thus indicates that at least two taxa of early hominids coexisted in East Africa.

  4. Hiperactivacion cortical y deterioro cognitivo en esquizofrenia

    OpenAIRE

    Suazo Bonnelly, Vanessa Johanna

    2014-01-01

    [ES] En este trabajo se estudió la actividad cerebral desorganizada y el deterioro cognitivo adjudicado a pacientes con esquizofrenia. Para estudiar la actividad cerebral se empleó una medida electroencefalográfica de ruido cortical (actividad promediada de fondo no ligada a la tarea) durante el desarrollo de una tarea sencilla (P300) en dos de las bandas oscilatorias (gamma y theta) más asociadas a la organización de la actividad cerebral según la literatura. Se utilizó una medida estructura...

  5. Regional vulnerability of longitudinal cortical association connectivity

    Directory of Open Access Journals (Sweden)

    Rafael Ceschin

    2015-01-01

    Full Text Available Preterm born children with spastic diplegia type of cerebral palsy and white matter injury or periventricular leukomalacia (PVL, are known to have motor, visual and cognitive impairments. Most diffusion tensor imaging (DTI studies performed in this group have demonstrated widespread abnormalities using averaged deterministic tractography and voxel-based DTI measurements. Little is known about structural network correlates of white matter topography and reorganization in preterm cerebral palsy, despite the availability of new therapies and the need for brain imaging biomarkers. Here, we combined novel post-processing methodology of probabilistic tractography data in this preterm cohort to improve spatial and regional delineation of longitudinal cortical association tract abnormalities using an along-tract approach, and compared these data to structural DTI cortical network topology analysis. DTI images were acquired on 16 preterm children with cerebral palsy (mean age 5.6 ± 4 and 75 healthy controls (mean age 5.7 ± 3.4. Despite mean tract analysis, Tract-Based Spatial Statistics (TBSS and voxel-based morphometry (VBM demonstrating diffusely reduced fractional anisotropy (FA reduction in all white matter tracts, the along-tract analysis improved the detection of regional tract vulnerability. The along-tract map-structural network topology correlates revealed two associations: (1 reduced regional posterior–anterior gradient in FA of the longitudinal visual cortical association tracts (inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, optic radiation, posterior thalamic radiation correlated with reduced posterior–anterior gradient of intra-regional (nodal efficiency metrics with relative sparing of frontal and temporal regions; and (2 reduced regional FA within frontal–thalamic–striatal white matter pathways (anterior limb/anterior thalamic radiation, superior longitudinal fasciculus and cortical spinal tract

  6. Cisternography contribution in the cortical atrophy diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Calegaro, J U.M. [Centro de Analises Clinicas e Medicina Nuclear, Londrina (Brazil); Balallai, N; Suzuki, K [Instituto de Neurologia e Neurocirurgia, Londrina (Brazil)

    1975-01-01

    A 37 years-old woman suffered a car accident. On admission to hospital she presented: torpor, the right pupil greater than the left, both reacting to light, and left hemiparesis with homologous Babinski reflex. She was submitted to carotid arteriogram an air-contrast study without significant findings. Eletroencephalographic examination showed diffuse parenquimatous involvement of left cerebral hemisphery. Scinticisternography demonstrated delayed reabsorption of the radioactive tracer in both frontal areas. A subsequent trepanation made the diagnosis of cortical atrophy in the areas mentioned above. This case shows aditional information concerning anatomic detail provided by isotope cisternography, that eventually can't be detected by air-contrast study.

  7. Localization of cortical areas activated by thinking.

    Science.gov (United States)

    Roland, P E; Friberg, L

    1985-05-01

    These experiments were undertaken to demonstrate that pure mental activity, thinking, increases the cerebral blood flow and that different types of thinking increase the regional cerebral blood flow (rCBF) in different cortical areas. As a first approach, thinking was defined as brain work in the form of operations on internal information, done by an awake subject. The rCBF was measured in 254 cortical regions in 11 subjects with the intracarotid 133Xe injection technique. In normal man, changes in the regional cortical metabolic rate of O2 leads to proportional changes in rCBF. One control study was taken with the subjects at rest. Then the rCBF was measured during three different simple algorithm tasks, each consisting of retrieval of a specific memory followed by a simple operation on the retrieved information. Once started, the information processing went on in the brain without any communication with the outside world. In 50-3 thinking, the subjects started with 50 and then, in their minds only, continuously subtracted 3 from the result. In jingle thinking the subjects internally jumped every second word in a nine-word circular jingle. In route-finding thinking the subjects imagined that they started at their front door and then walked alternatively to the left or the right each time they reached a corner. The rCBF increased only in homotypical cortical areas during thinking. The areas in the superior prefrontal cortex increased their rCBF equivalently during the three types of thinking. In the remaining parts of the prefrontal cortex there were multifocal increases of rCBF. The localizations and intensities of these rCBF increases depended on the type of internal operation occurring. The rCBF increased bilaterally in the angular cortex during 50-3 thinking. The rCBF increased in the right midtemporal cortex exclusively during jingle thinking. The intermediate and remote visual association areas, the superior occipital, posterior inferior temporal, and

  8. Outline of a novel architecture for cortical computation

    OpenAIRE

    Majumdar, Kaushik

    2007-01-01

    In this paper a novel architecture for cortical computation has been proposed. This architecture is composed of computing paths consisting of neurons and synapses only. These paths have been decomposed into lateral, longitudinal and vertical components. Cortical computation has then been decomposed into lateral computation (LaC), longitudinal computation (LoC) and vertical computation (VeC). It has been shown that various loop structures in the cortical circuit play important roles in cortica...

  9. Cortical splitting of the mandible after irradiation. Special reference to osteoradionecrosis

    International Nuclear Information System (INIS)

    Katsura, Kouji; Ito, Jusuke; Hayashi, Takafumi; Taira, Shuhzou; Nakajima, Syunichi

    2001-01-01

    The purpose of this study was to discuss the relationship between radiation bone injuries and a splitting of the cortical bone in the radiation field. Between January 1993 and September 1998, 53 patients with head and neck cancer received radiotherapy. The study cohort consisted of 23 patients who were followed with computed tomographic scans more than one year after radiotherapy. We evaluated clinical and computed tomographic features. Computed tomographic scanning was performed with a section thickness of 3 or 4 mm. Bone images were obtained with identical window width (4000 Haunsfield units) and window level (1000 Haunsfield units). Splitting of the cortical bone was defined as disappearance of bone density in the cortical bone, showing a linear shape running parallel to the surface of the cortex. Splitting appeared in 9 sites in 8 patients. All patients fulfilled UICC criteria for classifying oral cancer. Most of the patients received external irradiation with a total radiation dose of 50 or 60 Gy. In all cases, splitting was found in the mandibular cortex at the site of muscle attachment, that was included in the radiation field. Appearance of bone changes in chronological order were periosteal reaction, splitting and bone necrosis. We speculate that splitting results from injuries to bone structure cells caused by blood flow disturbance after surgery and radiotherapy. It is suggested that such splitting can be a predictor of osteoradionecrosis. (author)

  10. Frontal cortical control of posterior sensory and association cortices through the claustrum.

    Science.gov (United States)

    White, Michael G; Mathur, Brian N

    2018-04-06

    The claustrum is a telencephalic gray matter nucleus that is richly interconnected with the neocortex. This structure subserves top-down executive functions that require frontal cortical control of posterior cortical regions. However, functional anatomical support for the claustrum allowing for long-range intercortical communication is lacking. To test this, we performed a channelrhodopsin-assisted long-circuit mapping strategy in mouse brain slices. We find that anterior cingulate cortex input to the claustrum is transiently amplified by claustrum neurons that, in turn, project to parietal association cortex or to primary and secondary visual cortices. Additionally, we observe that claustrum drive of cortical neurons in parietal association cortex is layer-specific, eliciting action potential generation briefly in layers II/III, IV, and VI but not V. These data are the first to provide a functional anatomical substrate through claustrum that may underlie top-down functions, such as executive attention or working memory, providing critical insight to this most interconnected and enigmatic nucleus.

  11. Overweight is not associated with cortical thickness alterations in children

    Directory of Open Access Journals (Sweden)

    Rachel Jane Sharkey

    2015-02-01

    Full Text Available IntroductionSeveral studies report an association between body mass index (BMI and cortical thickness in adults. Some studies demonstrate diffuse cortical thinning in obesity, while others report effects in areas that are associated with self-regulation, such as lateral prefrontal cortex. MethodsThis study used multilevel modelling of data from the NIH Pediatric MRI Data Repository, a mixed longitudinal and cross-sectional database, to examine the relationship between cortical thickness and body weight in children. Cortical thickness was computed at 81,942 vertices of 716 MRI scans from 378 children aged between 4 and 18 years. Body mass index Z score for age was computed for each participant. We preformed vertex-wise statistical analysis of the relationship between cortical thickness and BMI, accounting for age and gender. In addition, cortical thickness was extracted from regions of interest in prefrontal cortex and insula.ResultsNo significant association between cortical thickness and BMI was found, either by statistical parametric mapping or by region of interest analysis. Results remained negative when the analysis was restricted to children aged 12-18.ConclusionsThe correlation between BMI and cortical thickness was not found in this large pediatric sample. The association between BMI and cortical thinning develops after adolescence. This has implications for the nature of the relationship between brain anatomy and weight gain.

  12. Interaction between LRP5 and periostin gene polymorphisms on serum periostin levels and cortical bone microstructure.

    Science.gov (United States)

    Pepe, J; Bonnet, N; Herrmann, F R; Biver, E; Rizzoli, R; Chevalley, T; Ferrari, S L

    2018-02-01

    We investigated the interaction between periostin SNPs and the SNPs of the genes assumed to modulate serum periostin levels and bone microstructure in a cohort of postmenopausal women. We identified an interaction between LRP5 SNP rs648438 and periostin SNP rs9547970 on serum periostin levels and on radial cortical porosity. The purpose of this study is to investigate the interaction between periostin gene polymorphisms (SNPs) and other genes potentially responsible for modulating serum periostin levels and bone microstructure in a cohort of postmenopausal women. In 648 postmenopausal women from the Geneva Retirees Cohort, we analyzed 6 periostin SNPs and another 149 SNPs in 14 genes, namely BMP2, CTNNB1, ESR1, ESR2, LRP5, LRP6, PTH, SPTBN1, SOST, TGFb1, TNFRSF11A, TNFSF11, TNFRSF11B and WNT16. Volumetric BMD and bone microstructure were measured by high-resolution peripheral quantitative computed tomography at the distal radius and tibia. Serum periostin levels were associated with radial cortical porosity, including after adjustment for age, BMI, and years since menopause (p = 0.036). Sixteen SNPs in the ESR1, LRP5, TNFRSF11A, SOST, SPTBN1, TNFRSF11B and TNFSF11 genes were associated with serum periostin levels (p range 0.03-0.001) whereas 26 SNPs in 9 genes were associated with cortical porosity at the radius and/or at the tibia. WNT 16 was the gene with the highest number of SNPs associated with both trabecular and cortical microstructure. The periostin SNP rs9547970 was also associated with cortical porosity (p = 0.04). In particular, SNPs in LRP5, ESR1 and near the TNFRSF11A gene were associated with both cortical porosity and serum periostin levels. Eventually, we identified an interaction between LRP5 SNP rs648438 and periostin SNP rs9547970 on serum periostin levels (interaction p = 0.01) and on radial cortical porosity (interaction p = 0.005). These results suggest that periostin expression is genetically modulated, particularly by polymorphisms

  13. Technical principles of direct bipolar electrostimulation for cortical and subcortical mapping in awake craniotomy.

    Science.gov (United States)

    Pallud, J; Mandonnet, E; Corns, R; Dezamis, E; Parraga, E; Zanello, M; Spena, G

    2017-06-01

    Intraoperative application of electrical current to the brain is a standard technique during brain surgery for inferring the function of the underlying brain. The purpose of intraoperative functional mapping is to reliably identify cortical areas and subcortical pathways involved in eloquent functions, especially motor, sensory, language and cognitive functions. The aim of this article is to review the rationale and the electrophysiological principles of the use of direct bipolar electrostimulation for cortical and subcortical mapping under awake conditions. Direct electrical stimulation is a window into the whole functional network that sustains a particular function. It is an accurate (spatial resolution of about 5mm) and a reproducible technique particularly adapted to clinical practice for brain resection in eloquent areas. If the procedure is rigorously applied, the sensitivity of direct electrical stimulation for the detection of cortical and subcortical eloquent areas is nearly 100%. The main disadvantage of this technique is its suboptimal specificity. Another limitation is the identification of eloquent areas during surgery, which, however, could have been functionally compensated postoperatively if removed surgically. Direct electrical stimulation is an easy, accurate, reliable and safe invasive technique for the intraoperative detection of both cortical and subcortical functional brain connectivity for clinical purpose. In our opinion, it is the optimal technique for minimizing the risk of neurological sequelae when resecting in eloquent brain areas. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Novel Histopathological Patterns in Cortical Tubers of Epilepsy Surgery Patients with Tuberous Sclerosis Complex.

    Directory of Open Access Journals (Sweden)

    Angelika Mühlebner

    Full Text Available Tuberous Sclerosis Complex (TSC is a genetic hamartoma syndrome frequently associated with severe intractable epilepsy. In some TSC patients epilepsy surgery is a promising treatment option provided that the epileptogenic zone can be precisely delineated. TSC brain lesions (cortical tubers contain dysmorphic neurons, brightly eosinophilic giant cells and white matter alterations in various proportions. However, a histological classification system has not been established for tubers. Therefore, the aim of this study was to define distinct histological patterns within tubers based on semi-automated histological quantification and to find clinically significant correlations. In total, we studied 28 cortical tubers and seven samples of perituberal cortex from 28 TSC patients who had undergone epilepsy surgery. We assessed mammalian target of rapamycin complex 1 (mTORC1 activation, the numbers of giant cells, dysmorphic neurons, neurons, and oligodendrocytes, and calcification, gliosis, angiogenesis, inflammation, and myelin content. Three distinct histological profiles emerged based on the proportion of calcifications, dysmorphic neurons and giant cells designated types A, B, and C. In the latter two types we were able to subsequently associate them with specific features on presurgical MRI. Therefore, these histopathological patterns provide consistent criteria for improved definition of the clinico-pathological features of cortical tubers identified by MRI and provide a basis for further exploration of the functional and molecular features of cortical tubers in TSC.

  15. Novel Histopathological Patterns in Cortical Tubers of Epilepsy Surgery Patients with Tuberous Sclerosis Complex.

    Science.gov (United States)

    Mühlebner, Angelika; van Scheppingen, Jackelien; Hulshof, Hanna M; Scholl, Theresa; Iyer, Anand M; Anink, Jasper J; van den Ouweland, Ans M W; Nellist, Mark D; Jansen, Floor E; Spliet, Wim G M; Krsek, Pavel; Benova, Barbora; Zamecnik, Josef; Crino, Peter B; Prayer, Daniela; Czech, Thomas; Wöhrer, Adelheid; Rahimi, Jasmin; Höftberger, Romana; Hainfellner, Johannes A; Feucht, Martha; Aronica, Eleonora

    2016-01-01

    Tuberous Sclerosis Complex (TSC) is a genetic hamartoma syndrome frequently associated with severe intractable epilepsy. In some TSC patients epilepsy surgery is a promising treatment option provided that the epileptogenic zone can be precisely delineated. TSC brain lesions (cortical tubers) contain dysmorphic neurons, brightly eosinophilic giant cells and white matter alterations in various proportions. However, a histological classification system has not been established for tubers. Therefore, the aim of this study was to define distinct histological patterns within tubers based on semi-automated histological quantification and to find clinically significant correlations. In total, we studied 28 cortical tubers and seven samples of perituberal cortex from 28 TSC patients who had undergone epilepsy surgery. We assessed mammalian target of rapamycin complex 1 (mTORC1) activation, the numbers of giant cells, dysmorphic neurons, neurons, and oligodendrocytes, and calcification, gliosis, angiogenesis, inflammation, and myelin content. Three distinct histological profiles emerged based on the proportion of calcifications, dysmorphic neurons and giant cells designated types A, B, and C. In the latter two types we were able to subsequently associate them with specific features on presurgical MRI. Therefore, these histopathological patterns provide consistent criteria for improved definition of the clinico-pathological features of cortical tubers identified by MRI and provide a basis for further exploration of the functional and molecular features of cortical tubers in TSC.

  16. Intrinsic Connections of the Core Auditory Cortical Regions and Rostral Supratemporal Plane in the Macaque Monkey.

    Science.gov (United States)

    Scott, Brian H; Leccese, Paul A; Saleem, Kadharbatcha S; Kikuchi, Yukiko; Mullarkey, Matthew P; Fukushima, Makoto; Mishkin, Mortimer; Saunders, Richard C

    2017-01-01

    In the ventral stream of the primate auditory cortex, cortico-cortical projections emanate from the primary auditory cortex (AI) along 2 principal axes: one mediolateral, the other caudorostral. Connections in the mediolateral direction from core, to belt, to parabelt, have been well described, but less is known about the flow of information along the supratemporal plane (STP) in the caudorostral dimension. Neuroanatomical tracers were injected throughout the caudorostral extent of the auditory core and rostral STP by direct visualization of the cortical surface. Auditory cortical areas were distinguished by SMI-32 immunostaining for neurofilament, in addition to established cytoarchitectonic criteria. The results describe a pathway comprising step-wise projections from AI through the rostral and rostrotemporal fields of the core (R and RT), continuing to the recently identified rostrotemporal polar field (RTp) and the dorsal temporal pole. Each area was strongly and reciprocally connected with the areas immediately caudal and rostral to it, though deviations from strictly serial connectivity were observed. In RTp, inputs converged from core, belt, parabelt, and the auditory thalamus, as well as higher order cortical regions. The results support a rostrally directed flow of auditory information with complex and recurrent connections, similar to the ventral stream of macaque visual cortex. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  17. Estimation of cortical silent period following transcranial magnetic stimulation using a computerised cumulative sum method.

    Science.gov (United States)

    King, Nicolas K K; Kuppuswamy, Annapoorna; Strutton, Paul H; Davey, Nick J

    2006-01-15

    The cortical silent period (CSP) following transcranial magnetic stimulation (TMS) of the motor cortex can be used to measure intra-cortical inhibition and changes in a number of important pathologies affecting the central nervous system. The main drawback of this technique has been the difficulty in accurately identifying the onset and offset of the cortical silent period leading to inter-observer variability. We developed an automated method based on the cumulative sum (Cusum) technique to improve the determination of the duration and area of the cortical silent period. This was compared with experienced raters and two other automated methods. We showed that the automated Cusum method reliably correlated with the experienced raters for both duration and area of CSP. Compared with the automated methods, the Cusum also showed the strongest correlation with the experienced raters. Our results show the Cusum method to be a simple, graphical and powerful method of detecting low-intensity CSP that can be easily automated using standard software.

  18. Distinct molecular components for thalamic- and cortical-dependent plasticity in the lateral amygdala.

    Science.gov (United States)

    Mirante, Osvaldo; Brandalise, Federico; Bohacek, Johannes; Mansuy, Isabelle M

    2014-01-01

    N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD) in the lateral nucleus of the amygdala (LA) is a form of synaptic plasticity thought to be a cellular substrate for the extinction of fear memory. The LA receives converging inputs from the sensory thalamus and neocortex that are weakened following fear extinction. Combining field and patch-clamp electrophysiological recordings in mice, we show that paired-pulse low-frequency stimulation can induce a robust LTD at thalamic and cortical inputs to LA, and we identify different underlying molecular components at these pathways. We show that while LTD depends on NMDARs and activation of the protein phosphatases PP2B and PP1 at both pathways, it requires NR2B-containing NMDARs at the thalamic pathway, but NR2C/D-containing NMDARs at the cortical pathway. LTD appears to be induced post-synaptically at the thalamic input but presynaptically at the cortical input, since post-synaptic calcium chelation and NMDAR blockade prevent thalamic but not cortical LTD. These results highlight distinct molecular features of LTD in LA that may be relevant for traumatic memory and its erasure, and for pathologies such as post-traumatic stress disorder (PTSD).

  19. Distinct molecular components for thalamic- and cortical-dependent plasticity in the lateral amygdala

    Directory of Open Access Journals (Sweden)

    Osvaldo eMirante

    2014-07-01

    Full Text Available N-methyl-D-aspartate receptor (NMDAR-dependent long-term depression (LTD in the lateral nucleus of the amygdala (LA is a form of synaptic plasticity thought to be a cellular substrate for the extinction of fear memory. The LA receives converging inputs from the sensory thalamus and neocortex that are weakened following fear extinction. Combining field and patch-clamp electrophysiological recordings in mice, we show that a paired-pulse low-frequency stimulation can induce a robust LTD at thalamic and cortical inputs to LA, and we identify different underlying molecular components at these pathways. We show that while LTD depends on NMDARs and activation of the protein phosphatases PP2B and PP1 at both pathways, it requires NR2B-containing NMDARs at the thalamic pathway, but NR2C/D-containing NMDARs at the cortical pathway. LTD appears to be induced postsynaptically at the thalamic input but presynaptically at the cortical input, since postsynaptic calcium chelation and NMDAR blockade prevent thalamic but not cortical LTD. These results highlight distinct molecular features of LTD in LA that may be relevant for traumatic memory and its erasure, and for pathologies such as post-traumatic stress disorder (PTSD.

  20. Online Learning for Classification of Alzheimer Disease based on Cortical Thickness and Hippocampal Shape Analysis.

    Science.gov (United States)

    Lee, Ga-Young; Kim, Jeonghun; Kim, Ju Han; Kim, Kiwoong; Seong, Joon-Kyung

    2014-01-01

    Mobile healthcare applications are becoming a growing trend. Also, the prevalence of dementia in modern society is showing a steady growing trend. Among degenerative brain diseases that cause dementia, Alzheimer disease (AD) is the most common. The purpose of this study was to identify AD patients using magnetic resonance imaging in the mobile environment. We propose an incremental classification for mobile healthcare systems. Our classification method is based on incremental learning for AD diagnosis and AD prediction using the cortical thickness data and hippocampus shape. We constructed a classifier based on principal component analysis and linear discriminant analysis. We performed initial learning and mobile subject classification. Initial learning is the group learning part in our server. Our smartphone agent implements the mobile classification and shows various results. With use of cortical thickness data analysis alone, the discrimination accuracy was 87.33% (sensitivity 96.49% and specificity 64.33%). When cortical thickness data and hippocampal shape were analyzed together, the achieved accuracy was 87.52% (sensitivity 96.79% and specificity 63.24%). In this paper, we presented a classification method based on online learning for AD diagnosis by employing both cortical thickness data and hippocampal shape analysis data. Our method was implemented on smartphone devices and discriminated AD patients for normal group.

  1. Role of secondary sensory cortices in emotional memory storage and retrieval in rats.

    Science.gov (United States)

    Sacco, Tiziana; Sacchetti, Benedetto

    2010-08-06

    Visual, acoustic, and olfactory stimuli associated with a highly charged emotional situation take on the affective qualities of that situation. Where the emotional meaning of a given sensory experience is stored is a matter of debate. We found that excitotoxic lesions of auditory, visual, or olfactory secondary sensory cortices impaired remote, but not recent, fear memories in rats. Amnesia was modality-specific and not due to an interference with sensory or emotional processes. In these sites, memory persistence was dependent on ongoing protein kinase Mzeta activity and was associated with an increased activity of layers II-IV, thus suggesting a synaptic strengthening of corticocortical connections. Lesions of the same areas left intact the memory of sensory stimuli not associated with any emotional charge. We propose that secondary sensory cortices support memory storage and retrieval of sensory stimuli that have acquired a behavioral salience with the experience.

  2. Cortical bone mineral content in primary hyperparathyroidism

    International Nuclear Information System (INIS)

    Mautalen, C.; Reyes, H.R.; Ghiringhelli, G.; Fromm, G.

    1986-01-01

    The bone mineral content (BMC) of 35 patients with primary hyperparathyroidism (PHPT) was measured at the mid radius (95% cortical bone) by photon absorptiometry of a 241 Am source. The majority of the patients had an overt disease of moderate to severe degree. Average serum calcium of the group was 12.3 mg/100 ml (range 10.6 to 18.0 mg/100 ml). The percentage of normality of the BMC was (Av +- 1 SD) 75.1 +- 13.0% for the whole group. The average increment of BMC in 14 patients 9 to 26 months after parathyroidectomy was 9.9%, with a wide dispersion. However, a highly significant negative correlation (r: 0.83; P < 0.01) was found between the initial bone mass and the percentage increment per month after surgery. No furhter gain was observed 2 years after parathyroidectomy except in one patient with an extremely severe bone loss. In spite of the gain obtained after surgery the bone mass remained markedly diminished in most patients showing that the cortical bone loss caused by PHPT is mainly irreversible. (author)

  3. Cortical Thickness Changes Associated with Photoparoxysmal Response

    DEFF Research Database (Denmark)

    Hanganu, Alexandru; Groppa, Stanislav A; Deuschl, Günther

    2014-01-01

    Photoparoxysmal response (PPR) is an EEG trait of spike and spike-wave discharges in response to photic stimulation that is closely linked to idiopathic generalized epilepsy (IGE). In our previous studies we showed that PPR is associated with functional alterations in the occipital and frontal co...... in the occipital lobe, frontoparietal regions and temporal lobe, which also show functional changes associated with PPR. Patients with epilepsy present changes in the temporal lobe and supplementary motor area.......-positive-subjects presented a significant decrease of cortical thickness in the temporal cortex in the same group contrast. IGE patients exhibited lower cortical thickness in the temporal lobe bilaterally and in the right paracentral region in comparison to PPR-positive-subjects. Our study demonstrates structural changes......Photoparoxysmal response (PPR) is an EEG trait of spike and spike-wave discharges in response to photic stimulation that is closely linked to idiopathic generalized epilepsy (IGE). In our previous studies we showed that PPR is associated with functional alterations in the occipital and frontal...

  4. Cortical activation in patients with functional hemispherectomy.

    Science.gov (United States)

    Leonhardt, G; Bingel, U; Spiekermann, G; Kurthen, M; Müller, S; Hufnagel, A

    2001-10-01

    Functional hemispherectomy, a safe and effective therapeutical procedure in medically intractable epilepsy, offers the chance to investigate a strictly unilateral cortical activation in ipsilateral limb movement. We assessed the pattern of cortical activation in a group of patients following functional hemispherectomy. We measured regional cerebral blood flow (rCBF) in 6 patients postoperatively and 6 normal subjects with positron emission tomography using 15[O]H2O as a tracer. Brain activation was achieved by passive elbow movements of the affected arm. Analysis of group results and between-group comparisons were performed with statistical parametric mapping, (SPM96). In normal subjects brain activation was found contralaterally in the cranial sensorimotor cortex and the supplementary motor area and ipsilaterally in the inferior parietal cortex. In patients significant rCBF increases were found in the inferior parietal cortex, caudal sensorimotor cortex and the supplementary motor area ipsilaterally. The activation was weaker than in normal subjects. Compared with normal subjects patients showed additional activation in the premotor cortex, caudal sensorimotor cortex and the inferior parietal cortex of the remaining hemisphere. Less activation compared with normal subjects was found in the cranial sensorimotor cortex and the supplementary motor area. A functional network connecting the inferior parietal cortex, premotor cortex and the supplementary motor area as well as the existence of ipsilateral projections originating from these regions may explain why these areas are predominantly involved in reorganization confined to a single hemisphere.

  5. Bayesian automated cortical segmentation for neonatal MRI

    Science.gov (United States)

    Chou, Zane; Paquette, Natacha; Ganesh, Bhavana; Wang, Yalin; Ceschin, Rafael; Nelson, Marvin D.; Macyszyn, Luke; Gaonkar, Bilwaj; Panigrahy, Ashok; Lepore, Natasha

    2017-11-01

    Several attempts have been made in the past few years to develop and implement an automated segmentation of neonatal brain structural MRI. However, accurate automated MRI segmentation remains challenging in this population because of the low signal-to-noise ratio, large partial volume effects and inter-individual anatomical variability of the neonatal brain. In this paper, we propose a learning method for segmenting the whole brain cortical grey matter on neonatal T2-weighted images. We trained our algorithm using a neonatal dataset composed of 3 fullterm and 4 preterm infants scanned at term equivalent age. Our segmentation pipeline combines the FAST algorithm from the FSL library software and a Bayesian segmentation approach to create a threshold matrix that minimizes the error of mislabeling brain tissue types. Our method shows promising results with our pilot training set. In both preterm and full-term neonates, automated Bayesian segmentation generates a smoother and more consistent parcellation compared to FAST, while successfully removing the subcortical structure and cleaning the edges of the cortical grey matter. This method show promising refinement of the FAST segmentation by considerably reducing manual input and editing required from the user, and further improving reliability and processing time of neonatal MR images. Further improvement will include a larger dataset of training images acquired from different manufacturers.

  6. Cortical dynamics of visual change detection based on sensory memory.

    Science.gov (United States)

    Urakawa, Tomokazu; Inui, Koji; Yamashiro, Koya; Tanaka, Emi; Kakigi, Ryusuke

    2010-08-01

    Detecting a visual change was suggested to relate closely to the visual sensory memory formed by visual stimuli before the occurrence of the change, because change detection involves identifying a difference between ongoing and preceding sensory conditions. Previous neuroimaging studies showed that an abrupt visual change activates the middle occipital gyrus (MOG). However, it still remains to be elucidated whether the MOG is related to visual change detection based on sensory memory. Here we tried to settle this issue using a new method of stimulation with blue and red LEDs to emphasize a memory-based change detection process. There were two stimuli, a standard trial stimulus and a deviant trial stimulus. The former was a red light lasting 500 ms, and the latter was a red light lasting 250 ms immediately followed by a blue light lasting 250 ms. Effects of the trial-trial interval, 250 approximately 2000 ms, were investigated to know how cortical responses to the abrupt change (from red to blue) were affected by preceding conditions. The brain response to the deviant trial stimulus was recorded by magnetoencephalography. Results of a multi-dipole analysis showed that the activity in the MOG, peaking at around 150 ms after the change onset, decreased in amplitude as the interval increased, but the earlier activity in BA 17/18 was not affected by the interval. These results suggested that the MOG is an important cortical area relating to the sensory memory-based visual change-detecting system. Copyright 2010 Elsevier Inc. All rights reserved.

  7. Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9 to 13 Years.

    Science.gov (United States)

    Kindler, Joseph M; Pollock, Norman K; Laing, Emma M; Oshri, Assaf; Jenkins, Nathan T; Isales, Carlos M; Hamrick, Mark W; Ding, Ke-Hong; Hausman, Dorothy B; McCabe, George P; Martin, Berdine R; Hill Gallant, Kathleen M; Warden, Stuart J; Weaver, Connie M; Peacock, Munro; Lewis, Richard D

    2017-07-01

    IGF-I is a pivotal hormone in pediatric musculoskeletal development. Although recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9 to 13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA-IR). Cortical bone at the tibia diaphysis (66% site) and total body fat-free soft tissue mass (FFST) were measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA), respectively. IGF-I, insulin, and glucose were measured in fasting sera and HOMA-IR was calculated. Children with high HOMA-IR had greater unadjusted IGF-I (p insulin resistance as a potential suppressor of IGF-I-dependent cortical bone development, though prospective studies are needed. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

  8. Method for determining the schematic presentation for the cortical sulci and venous system

    International Nuclear Information System (INIS)

    Tatemichi, Nobuhiro; Nakano, Hirotake; Inoue, Yoshiharu.

    1994-01-01

    To realize the corticogram of major sulci and venous system, two different image modalities must be superposed with a minimum error : MRI, MRA and X-Ray angiography. The precise schema of cortical sulci have to become possible with the aid of the IR method of MRI that could clearly identify the sulcal system of the outer and internal surface of the hemisphere. The correspondence of the major venous system of MRI with that of angiography was carried out using several skin markers, bone structures and a deep major venous system. This corticogram was used by the neurosurgeons of the hospital for the electrode placement, the topographical identification of the cortical paroxysms and epilepsy surgery. The best argument for the accuracy of sulcal and venous schema could be offered by somato-sensory evoked potential identifying the central sulcus on the corticogram. (author)

  9. Early and phasic cortical metabolic changes in vestibular neuritis onset.

    Directory of Open Access Journals (Sweden)

    Marco Alessandrini

    Full Text Available Functional brain activation studies described the presence of separate cortical areas responsible for central processing of peripheral vestibular information and reported their activation and interactions with other sensory modalities and the changes of this network associated to strategic peripheral or central vestibular lesions. It is already known that cortical changes induced by acute unilateral vestibular failure (UVF are various and undergo variations over time, revealing different cortical involved areas at the onset and recovery from symptoms. The present study aimed at reporting the earliest change in cortical metabolic activity during a paradigmatic form of UVF such as vestibular neuritis (VN, that is, a purely peripheral lesion of the vestibular system, that offers the opportunity to study the cortical response to altered vestibular processing. This research reports [(18F]fluorodeoxyglucose positron emission tomography brain scan data concerning the early cortical metabolic activity associated to symptoms onset in a group of eight patients suffering from VN. VN patients' cortical metabolic activity during the first two days from symptoms onset was compared to that recorded one month later and to a control healthy group. Beside the known cortical response in the sensorimotor network associated to vestibular deafferentation, we show for the first time the involvement of Entorhinal (BAs 28, 34 and Temporal (BA 38 cortices in early phases of symptomatology onset. We interpret these findings as the cortical counterparts of the attempt to reorient oneself in space counteracting the vertigo symptom (Bas 28, 34 and of the emotional response to the new pathologic condition (BA 38 respectively. These interpretations were further supported by changes in patients' subjective ratings in balance, anxiety, and depersonalization/derealization scores when tested at illness onset and one month later. The present findings contribute in expanding

  10. SKA2 Methylation is associated with Decreased Prefrontal Cortical Thickness and Greater PTSD Severity among Trauma-Exposed Veterans

    Science.gov (United States)

    Sadeh, Naomi; Spielberg, Jeffrey M.; Logue, Mark W.; Wolf, Erika J.; Smith, Alicia K.; Lusk, Joanna; Hayes, Jasmeet P.; Sperbeck, Emily; Milberg, William P.; McGlinchey, Regina E.; Salat, David H.; Carter, Weleetka C.; Stone, Annjanette; Schichman, Steven A.; Humphries, Donald E.; Miller, Mark W.

    2015-01-01

    Methylation of the SKA2 gene has recently been identified as a promising biomarker of suicide risk. Based on this finding, we examined associations between SKA2 methylation, cortical thickness, and psychiatric phenotypes linked to suicide in trauma-exposed veterans. 200 trauma-exposed white non-Hispanic veterans of the recent conflicts in Iraq and Afghanistan (91% male) underwent clinical assessment and had blood drawn for genotyping and methylation analysis. 145 participants also had neuroimaging data available. Based on previous research, we examined DNA methylation at the CpG locus cg13989295 as well as DNA methylation adjusted for genotype at the methylation-associated SNP (rs7208505) in relationship to whole-brain cortical thickness, posttraumatic stress disorder symptoms (PTSD), and depression symptoms. Whole-brain vertex-wise analyses identified three clusters in prefrontal cortex that were associated with genotype-adjusted SKA2 DNA methylation (methylationadj). Specifically, DNA methylationadj was associated with bilateral reductions of cortical thickness in frontal pole and superior frontal gyrus, and similar effects were found in the right orbitofrontal cortex and right inferior frontal gyrus. PTSD symptom severity was positively correlated with SKA2 DNA methylationadj and negatively correlated with cortical thickness in these regions. Mediation analyses showed a significant indirect effect of PTSD on cortical thickness via SKA2 methylation status. Results suggest that DNA methylationadj of SKA2 in blood indexes stress-related psychiatric phenotypes and neurobiology, pointing to its potential value as a biomarker of stress exposure and susceptibility. PMID:26324104

  11. Raman spectral markers of collagen denaturation and hydration in human cortical bone tissue are affected by radiation sterilization and high cycle fatigue damage.

    Science.gov (United States)

    Flanagan, Christopher D; Unal, Mustafa; Akkus, Ozan; Rimnac, Clare M

    2017-11-01

    Thermal denaturation and monotonic mechanical damage alter the organic and water-related compartments of cortical bone. These changes can be detected using Raman spectroscopy. However, less is known regarding Raman sensitivity to detect the effects of cyclic fatigue damage and allograft sterilization doses of gamma radiation. To determine if Raman spectroscopic biomarkers of collagen denaturation and hydration are sensitive to the effects of (a) high cycle fatigue damage and (b) 25kGy irradiation. Unirradiated and gamma-radiation sterilized human cortical bone specimens previously tested in vitro under high-cycle (> 100,000 cycles) fatigue conditions at 15MPa, 25MPa, 35MPa, 45MPa, and 55MPa cyclic stress levels were studied. Cortical bone Raman spectral profiles from wavenumber ranges of 800-1750cm -1 and 2700-3800cm -1 were obtained and compared from: a) non-fatigue vs fatigue fracture sites and b) radiated vs. unirradiated states. Raman biomarker ratios 1670/1640 and 3220/2949, which reflect collagen denaturation and organic matrix (mainly collagen)-bound water, respectively, were assessed. One- and two-way ANOVA analyses were utilized to identify differences between groups along with interaction effects between cyclic fatigue and radiation-induced damage. Cyclic fatigue damage resulted in increases in collagen denaturation (1670/1640: 1.517 ± 0.043 vs 1.579 ± 0.021, p Raman spectroscopy can detect the effects of cyclic fatigue damage and 25kGy irradiation via increases in organic matrix (mainly collagen)-bound water. A Raman measure of collagen denaturation was sensitive to cyclic fatigue damage but not 25kGy irradiation. Collagen denaturation was correlated with organic matrix-bound water, suggesting that denaturation of collagen to gelatinous form may expose more binding sites to water by unwinding the triple alpha chains. This research may eventually be useful to help identify allograft quality and more appropriately match donors to recipients. Copyright

  12. Dance Experience and Associations with Cortical Gray Matter Thickness in the Aging Population

    OpenAIRE

    Porat, Shai; Goukasian, Naira; Hwang, Kristy S.; Zanto, Theodore; Do, Triet; Pierce, Jonathan; Joshi, Shantanu; Woo, Ellen; Apostolova, Liana G.

    2016-01-01

    Introduction: We investigated the effect dance experience may have on cortical gray matter thickness and cognitive performance in elderly participants with and without mild cognitive impairment (MCI). Methods: 39 cognitively normal and 48 MCI elderly participants completed a questionnaire regarding their lifetime experience with music, dance, and song. Participants identified themselves as either dancers or nondancers. All participants received structural 1.5-tesla MRI scans and detailed clin...

  13. The participation of cortical amygdala in innate, odor-driven behavior

    OpenAIRE

    Root, Cory M.; Denny, Christine A.; Hen, Ren?; Axel, Richard

    2014-01-01

    Innate behaviors are observed in na?ve animals without prior learning or experience, suggesting that the neural circuits that mediate these behaviors are genetically determined and stereotyped. The neural circuits that convey olfactory information from the sense organ to the cortical and subcortical olfactory centers have been anatomically defined 1-3 but the specific pathways responsible for innate responses to volatile odors have not been identified. We have devised genetic strategies that ...

  14. Impaired response inhibition and excess cortical thickness as candidate endophenotypes for trichotillomania

    DEFF Research Database (Denmark)

    Odlaug, Brian Lawrence; Chamberlain, Samuel R; Derbyshire, Katie L

    2014-01-01

    occupying an intermediate position. Permutation cluster analysis revealed significant excesses of cortical thickness in patients and their relatives compared to controls, in right inferior/middle frontal gyri (Brodmann Area, BA 47 & 11), right lingual gyrus (BA 18), left superior temporal cortex (BA 21......Trichotillomania is characterized by repetitive pulling out of one's own hair. Impaired response inhibition has been identified in patients with trichotillomania, along with gray matter density changes in distributed neural regions including frontal cortex. The objective of this study...

  15. Evoked potentials in large-scale cortical networks elicited by TMS of the visual cortex

    Science.gov (United States)

    Grossman, Emily D.; Srinivasan, Ramesh

    2011-01-01

    Single pulses of transcranial magnetic stimulation (TMS) result in distal and long-lasting oscillations, a finding directly challenging the virtual lesion hypothesis. Previous research supporting this finding has primarily come from stimulation of the motor cortex. We have used single-pulse TMS with simultaneous EEG to target seven brain regions, six of which belong to the visual system [left and right primary visual area V1, motion-sensitive human middle temporal cortex, and a ventral temporal region], as determined with functional MRI-guided neuronavigation, and a vertex “control” site to measure the network effects of the TMS pulse. We found the TMS-evoked potential (TMS-EP) over visual cortex consists mostly of site-dependent theta- and alphaband oscillations. These site-dependent oscillations extended beyond the stimulation site to functionally connected cortical regions and correspond to time windows where the EEG responses maximally diverge (40, 200, and 385 ms). Correlations revealed two site-independent oscillations ∼350 ms after the TMS pulse: a theta-band oscillation carried by the frontal cortex, and an alpha-band oscillation over parietal and frontal cortical regions. A manipulation of stimulation intensity at one stimulation site (right hemisphere V1-V3) revealed sensitivity to the stimulation intensity at different regions of cortex, evidence of intensity tuning in regions distal to the site of stimulation. Together these results suggest that a TMS pulse applied to the visual cortex has a complex effect on brain function, engaging multiple brain networks functionally connected to the visual system with both invariant and site-specific spatiotemporal dynamics. With this characterization of TMS, we propose an alternative to the virtual lesion hypothesis. Rather than a technique that simulates lesions, we propose TMS generates natural brain signals and engages functional networks. PMID:21715670

  16. Non-traumatic cortical subarachnoid haemorrhage: diagnostic work-up and aetiological background

    Energy Technology Data Exchange (ETDEWEB)

    Spitzer, C.; Kosinski, C.M. [University Hospital of RWTH Aachen, Department of Neurology, Aachen (Germany); Mull, M. [University Hospital of RWTH Aachen, Department of Neuroradiology, Aachen (Germany); Rohde, V. [University Hospital of RWTH Aachen, Department of Neurosurgery, Aachen (Germany)

    2005-07-01

    Only 15% of all subarachnoid haemorrhages (SAHs) are not of aneurysmal origin. Among those, circumscribed SAHs along the cortical convexity are rare and have only been described in singular case reports so far. Here, we present a collection of 12 cases of SAH along the convexity, of non-traumatic origin. Over a period of 10 years, 12 cases of circumscribed SAH along the convexity were identified at our clinic. The clinical presentations, neuroradiological SAH characteristics, further diagnostic work-up to identify the underlying aetiologies, the therapy and clinical outcome were analysed. The patients' chief complaints were unspecific cephalgia, focal or generalised seizures and focal neurological deficits. Typical signs of basal SAH, such as nuchal rigidity, thunderclap-headache or alteration of consciousness, were rare. Magnetic resonance imaging (MRI) and digital subtraction angiography (DSA) revealed different aetiologies, namely postpartal posterior encephalopathy (three), cerebral vasculitis (two), dural sinus thrombosis (two), cortical venous thrombosis (one), intracerebral abscesses (one) and cerebral cavernoma (one). Two cases remained unresolved. Treatment of the underlying disease and symptomatic medication led to good clinical outcome in almost all cases. On the basis of these findings, we demonstrate that the clinical presentation, localisation and aetiology of cortical SAH differ clearly from other SAHs. A diagnostic work-up with MRI and eventually DSA is essential. Mostly, the causative disease can be identified, and specific treatment allows a favourable outcome. (orig.)

  17. Cerebellar cortical infarct cavities and vertebral artery disease

    Energy Technology Data Exchange (ETDEWEB)

    Cocker, Laurens J.L. de [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Kliniek Sint-Jan Radiologie, Brussels (Belgium); Compter, A.; Kappelle, L.J.; Worp, H.B. van der [University Medical Center Utrecht, Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, Utrecht (Netherlands); Luijten, P.R.; Hendrikse, J. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands)

    2016-09-15

    Cerebellar cortical infarct cavities are a newly recognised entity associated with atherothromboembolic cerebrovascular disease and worse physical functioning. We aimed to investigate the relationship of cerebellar cortical infarct cavities with symptomatic vertebrobasilar ischaemia and with vascular risk factors. We evaluated the MR images of 46 patients with a recent vertebrobasilar TIA or stroke and a symptomatic vertebral artery stenosis ≥50 % from the Vertebral Artery Stenting Trial (VAST) for the presence of cerebellar cortical infarct cavities ≤1.5 cm. At inclusion in VAST, data were obtained on age, sex, history of vertebrobasilar TIA or stroke, and vascular risk factors. Adjusted risk ratios were calculated with Poisson regression analyses for the relation between cerebellar cortical infarct cavities and vascular risk factors. Sixteen out of 46 (35 %) patients showed cerebellar cortical infarct cavities on the initial MRI, and only one of these 16 patients was known with a previous vertebrobasilar TIA or stroke. In patients with symptomatic vertebrobasilar ischaemia, risk factor profiles of patients with cerebellar cortical infarct cavities were not different from patients without these cavities. Cerebellar cortical infarct cavities are seen on MRI in as much as one third of patients with recently symptomatic vertebral artery stenosis. Since patients usually have no prior history of vertebrobasilar TIA or stroke, cerebellar cortical infarct cavities should be added to the spectrum of common incidental brain infarcts visible on routine MRI. (orig.)

  18. Amygdala activation for eye contact despite complete cortical blindness

    NARCIS (Netherlands)

    Burra, N.; Hervais-Adelman, A.; Kerzel, D.; Tamietto, M.; de Gelder, B.; Pegna, A.J.

    2013-01-01

    Cortical blindness refers to the loss of vision that occurs after destruction of the primary visual cortex. Although there is no sensory cortex and hence no conscious vision, some cortically blind patients show amygdala activation in response to facial or bodily expressions of emotion. Here we

  19. Coherence analysis differentiates between cortical myoclonic tremor and essential tremor

    NARCIS (Netherlands)

    van Rootselaar, AF; Maurits, NM; Koelman, JHTM; van der Hoeven, JH; Bour, LJ; Leenders, KL; Brown, P; Tijssen, MAJ

    Familial cortical myoclonic tremor with epilepsy (FCMTE) is characterized by a distal kinetic tremor, infrequent epileptic attacks, and autosomal dominant inheritance. The tremor is thought to originate from the motor cortex. In our patient group, a premovement cortical spike Could not be

  20. Increased Cortical Thickness in Professional On-Line Gamers

    Science.gov (United States)

    Hyun, Gi Jung; Shin, Yong Wook; Kim, Bung-Nyun; Cheong, Jae Hoon; Jin, Seong Nam

    2013-01-01

    Objective The bulk of recent studies have tested whether video games change the brain in terms of activity and cortical volume. However, such studies are limited by several factors including cross-sectional comparisons, co-morbidity, and short-term follow-up periods. In the present study, we hypothesized that cognitive flexibility and the volume of brain cortex would be correlated with the career length of on-line pro-gamers. Methods High-resolution magnetic resonance scans were acquired in twenty-three pro-gamers recruited from StarCraft pro-game teams. We measured cortical thickness in each individual using FreeSurfer and the cortical thickness was correlated with the career length and the performance of the pro-gamers. Results Career length was positively correlated with cortical thickness in three brain regions: right superior frontal gyrus, right superior parietal gyrus, and right precentral gyrus. Additionally, increased cortical thickness in the prefrontal cortex was correlated with winning rates of the pro-game league. Increased cortical thickness in the prefrontal and parietal cortices was also associated with higher performance of Wisconsin Card Sorting Test. Conclusion Our results suggest that in individuals without pathologic conditions, regular, long-term playing of on-line games is associated with volume changes in the prefrontal and parietal cortices, which are associated with cognitive flexibility. PMID:24474988

  1. Comparative cortical bone thickness between the long bones of humans and five common non-human mammal taxa.

    Science.gov (United States)

    Croker, Sarah L; Reed, Warren; Donlon, Denise

    2016-03-01

    The task of identifying fragments of long bone shafts as human or non-human is difficult but necessary, for both forensic and archaeological cases, and a fast simple method is particularly useful. Previous literature suggests there may be differences in the thickness of the cortical bone between these two groups, but this has not been tested thoroughly. The aim of this study was not only to test this suggestion, but also to provide data that could be of practical assistance for future comparisons. The major limb bones (humerus, radius, femur and tibia) of 50 Caucasoid adult skeletons of known age and sex were radiographed, along with corresponding skeletal elements from sheep, pigs, cattle, large dogs and kangaroos. Measurements were taken from the radiographs at five points along the bone shaft, of shaft diameter, cortical bone thickness, and a cortical thickness index (sum of cortices divided by shaft diameter) in both anteroposterior and mediolateral orientations. Each variable for actual cortical bone thickness as well as cortical thickness indices were compared between the human group (split by sex) and each of the non-human groups in turn, using Student's t-tests. Results showed that while significant differences did exist between the human groups and many of the non-human groups, these were not all in the same direction. That is, some variables in the human groups were significantly greater than, and others were significantly less than, the corresponding variable in the non-human groups, depending on the particular non-human group, sex of the human group, or variable under comparison. This was the case for measurements of both actual cortical bone thickness and cortical thickness index. Therefore, for bone shaft fragments for which the skeletal element is unknown, the overlap in cortical bone thickness between different areas of different bones is too great to allow identification using this method alone. However, by providing extensive cortical bone

  2. Electronic bypass of spinal lesions: activation of lower motor neurons directly driven by cortical neural signals.

    Science.gov (United States)

    Li, Yan; Alam, Monzurul; Guo, Shanshan; Ting, K H; He, Jufang

    2014-07-03

    Lower motor neurons in the spinal cord lose supraspinal inputs after complete spinal cord injury, leading to a loss of volitional control below the injury site. Extensive locomotor training with spinal cord stimulation can restore locomotion function after spinal cord injury in humans and animals. However, this locomotion is non-voluntary, meaning that subjects cannot control stimulation via their natural "intent". A recent study demonstrated an advanced system that triggers a stimulator using forelimb stepping electromyographic patterns to restore quadrupedal walking in rats with spinal cord transection. However, this indirect source of "intent" may mean that other non-stepping forelimb activities may false-trigger the spinal stimulator and thus produce unwanted hindlimb movements. We hypothesized that there are distinguishable neural activities in the primary motor cortex during treadmill walking, even after low-thoracic spinal transection in adult guinea pigs. We developed an electronic spinal bridge, called "Motolink", which detects these neural patterns and triggers a "spinal" stimulator for hindlimb movement. This hardware can be head-mounted or carried in a backpack. Neural data were processed in real-time and transmitted to a computer for analysis by an embedded processor. Off-line neural spike analysis was conducted to calculate and preset the spike threshold for "Motolink" hardware. We identified correlated activities of primary motor cortex neurons during treadmill walking of guinea pigs with spinal cord transection. These neural activities were used to predict the kinematic states of the animals. The appropriate selection of spike threshold value enabled the "Motolink" system to detect the neural "intent" of walking, which triggered electrical stimulation of the spinal cord and induced stepping-like hindlimb movements. We present a direct cortical "intent"-driven electronic spinal bridge to restore hindlimb locomotion after complete spinal cord injury.

  3. Cortical neurogenesis in the absence of centrioles.

    Science.gov (United States)

    Insolera, Ryan; Bazzi, Hisham; Shao, Wei; Anderson, Kathryn V; Shi, Song-Hai

    2014-11-01

    Neuronal production in the mammalian cortex depends on extensive mitoses of radial glial progenitors (RGPs) residing in the ventricular zone (VZ). We examined the function of centrioles in RGPs during cortical neurogenesis in mice by conditional removal of SAS-4, a protein that is required for centriole biogenesis. SAS-4 deletion led to a progressive loss of centrioles, accompanied by RGP detachment from the VZ. Delocalized RGPs did not become outer subventricular zone RGPs (oRGs). Although they remained proliferative, ectopic RGPs, as well as those in the VZ, with a centrosomal deficit exhibited prolonged mitosis, p53 upregulation and apoptosis, resulting in neuronal loss and microcephaly. Simultaneous removal of p53 fully rescued RGP death and microcephaly, but not RGP delocalization and randomized mitotic spindle orientation. Our findings define the functions of centrioles in anchoring RGPs in the VZ and ensuring their efficient mitoses, and reveal the robust adaptability of RGPs in the developing cortex.

  4. Magnetoencephalography from signals to dynamic cortical networks

    CERN Document Server

    Aine, Cheryl

    2014-01-01

    "Magnetoencephalography (MEG) provides a time-accurate view into human brain function. The concerted action of neurons generates minute magnetic fields that can be detected---totally noninvasively---by sensitive multichannel magnetometers. The obtained millisecond accuracycomplements information obtained by other modern brain-imaging tools. Accurate timing is quintessential in normal brain function, often distorted in brain disorders. The noninvasiveness and time-sensitivityof MEG are great assets to developmental studies, as well. This multiauthored book covers an ambitiously wide range of MEG research from introductory to advanced level, from sensors to signals, and from focal sources to the dynamics of cortical networks. Written by active practioners of this multidisciplinary field, the book contains tutorials for newcomers and chapters of new challenging methods and emerging technologies to advanced MEG users. The reader will obtain a firm grasp of the possibilities of MEG in the study of audition, vision...

  5. Localization of cortical areas activated by thinking

    DEFF Research Database (Denmark)

    Roland, P E; Friberg, L

    1985-01-01

    midtemporal cortex exclusively during jingle thinking. The intermediate and remote visual association areas, the superior occipital, posterior inferior temporal, and posterior superior parietal cortex, increased their rCBF exclusively during route-finding thinking. We observed no decreases in rCBF. All r......These experiments were undertaken to demonstrate that pure mental activity, thinking, increases the cerebral blood flow and that different types of thinking increase the regional cerebral blood flow (rCBF) in different cortical areas. As a first approach, thinking was defined as brain work...... communication with the outside world. In 50-3 thinking, the subjects started with 50 and then, in their minds only, continuously subtracted 3 from the result. In jingle thinking the subjects internally jumped every second word in a nine-word circular jingle. In route-finding thinking the subjects imagined...

  6. Premotor and Motor Cortices Encode Reward.

    Directory of Open Access Journals (Sweden)

    Pavan Ramkumar

    Full Text Available Rewards associated with actions are critical for motivation and learning about the consequences of one's actions on the world. The motor cortices are involved in planning and executing movements, but it is unclear whether they encode reward over and above limb kinematics and dynamics. Here, we report a categorical reward signal in dorsal premotor (PMd and primary motor (M1 neurons that corresponds to an increase in firing rates when a trial was not rewarded regardless of whether or not a reward was expected. We show that this signal is unrelated to error magnitude, reward prediction error, or other task confounds such as reward consumption, return reach plan, or kinematic differences across rewarded and unrewarded trials. The availability of reward information in motor cortex is crucial for theories of reward-based learning and motivational influences on actions.

  7. Are the Symptoms of Parkinsonism Cortical in Origin?

    Directory of Open Access Journals (Sweden)

    Gordon W. Arbuthnott

    Full Text Available We present three reasons to suspect that the major deleterious consequence of dopamine loss from the striatum is a cortical malfunction. We suggest that it is cortex, rather than striatum, that should be considered as the source of the debilitating symptoms of Parkinson's disease (PD since: 1. Cortical synapses onto striatal dendritic spines are lost in PD. 2. All known treatments of the symptoms of PD disrupt beta oscillations. Oscillations that are also disrupted following antidromic activation of cortical neurons. 3. The final output of basal ganglia directly modulates thalamic connections to layer I of frontal cortical areas, regions intimately associated with motor behaviour.These three reasons combined with evidence that the current summary diagram of the basal ganglia involvement in PD is imprecise at best, suggest that a re-orientation of the treatment strategies towards cortical, rather than striatal malfunction, is overdue. Keywords: Parkinson's disease, Deep brain stimulation, Layer I, Motor cortex

  8. Jealousy increased by induced relative left frontal cortical activity.

    Science.gov (United States)

    Kelley, Nicholas J; Eastwick, Paul W; Harmon-Jones, Eddie; Schmeichel, Brandon J

    2015-10-01

    Asymmetric frontal cortical activity may be one key to the process linking social exclusion to jealous feelings. The current research examined the causal role of asymmetric frontal brain activity in modulating jealousy in response to social exclusion. Transcranial direct-current stimulation (tDCS) over the frontal cortex to manipulate asymmetric frontal cortical activity was combined with a modified version of the Cyberball paradigm designed to induce jealousy. After receiving 15 min of tDCS, participants were excluded by a desired partner and reported how jealous they felt. Among individuals who were excluded, tDCS to increase relative left frontal cortical activity caused greater levels of self-reported jealousy compared to tDCS to increase relative right frontal cortical activity or sham stimulation. Limitations concerning the specificity of this effect and implications for the role of the asymmetric prefrontal cortical activity in motivated behaviors are discussed. (c) 2015 APA, all rights reserved).

  9. Contextual control of audiovisual integration in low-level sensory cortices

    NARCIS (Netherlands)

    Van Atteveldt, N.; Peterson, Bradley S; Schroeder, Charles E

    Potential sources of multisensory influences on low-level sensory cortices include direct projections from sensory cortices of different modalities, as well as more indirect feedback inputs from higher order multisensory cortical regions. These multiple architectures may be functionally

  10. Cortical hubs form a module for multisensory integration on top of the hierarchy of cortical networks

    Directory of Open Access Journals (Sweden)

    Gorka Zamora-López

    2010-03-01

    Full Text Available Sensory stimuli entering the nervous system follow particular paths of processing, typically separated (segregated from the paths of other modal information. However, sensory perception, awareness and cognition emerge from the combination of information (integration. The corticocortical networks of cats and macaque monkeys display three prominent characteristics: (i modular organisation (facilitating the segregation, (ii abundant alternative processing paths and (iii the presence of highly connected hubs. Here, we study in detail the organisation and potential function of the cortical hubs by graph analysis and information theoretical methods. We find that the cortical hubs form a spatially delocalised, but topologically central module with the capacity to integrate multisensory information in a collaborative manner. With this, we resolve the underlying anatomical substrate that supports the simultaneous capacity of the cortex to segregate and to integrate multisensory information.

  11. Cortical influences drive amyotrophic lateral sclerosis.

    Science.gov (United States)

    Eisen, Andrew; Braak, Heiko; Del Tredici, Kelly; Lemon, Roger; Ludolph, Albert C; Kiernan, Matthew C

    2017-11-01

    The early motor manifestations of sporadic amyotrophic lateral sclerosis (ALS), while rarely documented, reflect failure of adaptive complex motor skills. The development of these skills correlates with progressive evolution of a direct corticomotoneuronal system that is unique to primates and markedly enhanced in humans. The failure of this system in ALS may translate into the split hand presentation, gait disturbance, split leg syndrome and bulbar symptomatology related to vocalisation and breathing, and possibly diffuse fasciculation, characteristic of ALS. Clinical neurophysiology of the brain employing transcranial magnetic stimulation has convincingly demonstrated a presymptomatic reduction or absence of short interval intracortical inhibition, accompanied by increased intracortical facilitation, indicating cortical hyperexcitability. The hallmark of the TDP-43 pathological signature of sporadic ALS is restricted to cortical areas as well as to subcortical nuclei that are under the direct control of corticofugal projections. This provides anatomical support that the origins of the TDP-43 pathology reside in the cerebral cortex itself, secondarily in corticofugal fibres and the subcortical targets with which they make monosynaptic connections. The latter feature explains the multisystem degeneration that characterises ALS. Consideration of ALS as a primary neurodegenerative disorder of the human brain may incorporate concepts of prion-like spread at synaptic terminals of corticofugal axons. Further, such a concept could explain the recognised widespread imaging abnormalities of the ALS neocortex and the accepted relationship between ALS and frontotemporal dementia. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. Age-Related Changes in Trabecular and Cortical Bone Microstructure

    Directory of Open Access Journals (Sweden)

    Huayue Chen

    2013-01-01

    Full Text Available The elderly population has substantially increased worldwide. Aging is a complex process, and the effects of aging are myriad and insidious, leading to progressive deterioration of various organs, including the skeleton. Age-related bone loss and resultant osteoporosis in the elderly population increase the risk for fractures and morbidity. Osteoporosis is one of the most common conditions associated with aging, and age is an independent risk factor for osteoporotic fractures. With the development of noninvasive imaging techniques such as computed tomography (CT, micro-CT, and high resolution peripheral quantitative CT (HR-pQCT, imaging of the bone architecture provides important information about age-related changes in bone microstructure and estimates of bone strength. In the past two decades, studies of human specimens using imaging techniques have revealed decreased bone strength in older adults compared with younger adults. The present paper addresses recently studied age-related changes in trabecular and cortical bone microstructure based primarily on HR-pQCT and micro-CT. We specifically focus on the three-dimensional microstructure of the vertebrae, femoral neck, and distal radius, which are common osteoporotic fracture sites.

  13. Age-related changes in trabecular and cortical bone microstructure.

    Science.gov (United States)

    Chen, Huayue; Zhou, Xiangrong; Fujita, Hiroshi; Onozuka, Minoru; Kubo, Kin-Ya

    2013-01-01

    The elderly population has substantially increased worldwide. Aging is a complex process, and the effects of aging are myriad and insidious, leading to progressive deterioration of various organs, including the skeleton. Age-related bone loss and resultant osteoporosis in the elderly population increase the risk for fractures and morbidity. Osteoporosis is one of the most common conditions associated with aging, and age is an independent risk factor for osteoporotic fractures. With the development of noninvasive imaging techniques such as computed tomography (CT), micro-CT, and high resolution peripheral quantitative CT (HR-pQCT), imaging of the bone architecture provides important information about age-related changes in bone microstructure and estimates of bone strength. In the past two decades, studies of human specimens using imaging techniques have revealed decreased bone strength in older adults compared with younger adults. The present paper addresses recently studied age-related changes in trabecular and cortical bone microstructure based primarily on HR-pQCT and micro-CT. We specifically focus on the three-dimensional microstructure of the vertebrae, femoral neck, and distal radius, which are common osteoporotic fracture sites.

  14. Early magnetic resonance detection of cortical necrosis and acute network injury associated with neonatal and infantile cerebral infarction

    Energy Technology Data Exchange (ETDEWEB)

    Okabe, Tetsuhiko; Aida, Noriko; Nozawa, Kumiko [Kanagawa Children' s Medical Center, Department of Radiology, Yokohama (Japan); Niwa, Tetsu [Kanagawa Children' s Medical Center, Department of Radiology, Yokohama (Japan); Tokai University School of Medicine, Department of Radiology, Isehara (Japan); Shibasaki, Jun [Kanagawa Children' s Medical Center, Department of Neonatology, Yokohama (Japan); Osaka, Hitoshi [Kanagawa Children' s Medical Center, Department of Neurology, Yokohama (Japan)

    2014-05-15

    Knowledge of MRI findings in pediatric cerebral infarction is limited. To determine whether cortical necrosis and network injury appear in the acute phase in post-stroke children and to identify anatomical location of acute network injury and the ages at which these phenomena are seen. Images from 12 children (age range: 0-9 years; neonates [<1 month], n=5; infants [1 month-12 months], n=3; others [≥1 year], n=4) with acute middle cerebral artery (MCA) cortical infarction were retrospectively analyzed. Cortical necrosis was defined as hyperintense cortical lesions on T1-weighted imaging that lacked evidence of hemorrhage. Acute network injury was defined as hyperintense lesions on diffusion-weighted imaging that were not in the MCA territory and had fiber connections with the affected cerebral cortex. MRI was performed within the first week after disease onset. Cortical necrosis was only found in three neonates. Acute network injury was seen in the corticospinal tract (CST), thalamus and corpus callosum. Acute network injury along the CST was found in five neonates and one 7-month-old infant. Acute network injury was evident in the thalamus of four neonates and two infants (ages 4 and 7 months) and in the corpus callosum of five neonates and two infants (ages 4 and 7 months). The entire thalamus was involved in three children when infarction of MCA was complete. In acute MCA cortical infarction, MRI findings indicating cortical necrosis or acute network injury was frequently found in neonates and early infants. Response to injury in a developing brain may be faster than that in a mature one. (orig.)

  15. Negative correlation of cortical thickness with the severity and duration of abdominal pain in Asian women with irritable bowel syndrome.

    Science.gov (United States)

    Chua, Chian Sem; Bai, Chyi-Huey; Shiao, Chen-Yu; Hsu, Chien-Yeh; Cheng, Chiao-Wen; Yang, Kuo-Ching; Chiu, Hung-Wen; Hsu, Jung-Lung

    2017-01-01

    Irritable bowel syndrome (IBS) manifests as chronic abdominal pain. One pathophysiological theory states that the brain-gut axis is responsible for pain control in the intestine. Although several studies have discussed the structural changes in the brain of IBS patients, most of these studies have been conducted in Western populations. Different cultures and sexes experience different pain sensations and have different pain responses. Accordingly, we aimed to identify the specific changes in the cortical thickness of Asian women with IBS and to compare these data to those of non-Asian women with IBS. Thirty Asian female IBS patients (IBS group) and 39 healthy individuals (control group) were included in this study. Brain structural magnetic resonance imaging was performed. We used FreeSurfer to analyze the differences in the cortical thickness and their correlations with patient characteristics. The left cuneus, left rostral middle frontal cortex, left supramarginal cortex, right caudal anterior cingulate cortex, and bilateral insula exhibited cortical thinning in the IBS group compared with those in the controls. Furthermore, the brain cortical thickness correlated negatively the severity as well as duration of abdominal pain. Some of our findings differ from those of Western studies. In our study, all of the significant brain regions in the IBS group exhibited cortical thinning compared with those in the controls. The differences in cortical thickness between the IBS patients and controls may provide useful information to facilitate regulating abdominal pain in IBS patients. These findings offer insights into the association of different cultures and sexes with differences in cortical thinning in patients with IBS.

  16. Early magnetic resonance detection of cortical necrosis and acute network injury associated with neonatal and infantile cerebral infarction

    International Nuclear Information System (INIS)

    Okabe, Tetsuhiko; Aida, Noriko; Nozawa, Kumiko; Niwa, Tetsu; Shibasaki, Jun; Osaka, Hitoshi

    2014-01-01

    Knowledge of MRI findings in pediatric cerebral infarction is limited. To determine whether cortical necrosis and network injury appear in the acute phase in post-stroke children and to identify anatomical location of acute network injury and the ages at which these phenomena are seen. Images from 12 children (age range: 0-9 years; neonates [<1 month], n=5; infants [1 month-12 months], n=3; others [≥1 year], n=4) with acute middle cerebral artery (MCA) cortical infarction were retrospectively analyzed. Cortical necrosis was defined as hyperintense cortical lesions on T1-weighted imaging that lacked evidence of hemorrhage. Acute network injury was defined as hyperintense lesions on diffusion-weighted imaging that were not in the MCA territory and had fiber connections with the affected cerebral cortex. MRI was performed within the first week after disease onset. Cortical necrosis was only found in three neonates. Acute network injury was seen in the corticospinal tract (CST), thalamus and corpus callosum. Acute network injury along the CST was found in five neonates and one 7-month-old infant. Acute network injury was evident in the thalamus of four neonates and two infants (ages 4 and 7 months) and in the corpus callosum of five neonates and two infants (ages 4 and 7 months). The entire thalamus was involved in three children when infarction of MCA was complete. In acute MCA cortical infarction, MRI findings indicating cortical necrosis or acute network injury was frequently found in neonates and early infants. Response to injury in a developing brain may be faster than that in a mature one. (orig.)

  17. Early magnetic resonance detection of cortical necrosis and acute network injury associated with neonatal and infantile cerebral infarction.

    Science.gov (United States)

    Okabe, Tetsuhiko; Aida, Noriko; Niwa, Tetsu; Nozawa, Kumiko; Shibasaki, Jun; Osaka, Hitoshi

    2014-05-01

    Knowledge of MRI findings in pediatric cerebral infarction is limited. To determine whether cortical necrosis and network injury appear in the acute phase in post-stroke children and to identify anatomical location of acute network injury and the ages at which these phenomena are seen. Images from 12 children (age range: 0-9 years; neonates [acute middle cerebral artery (MCA) cortical infarction were retrospectively analyzed. Cortical necrosis was defined as hyperintense cortical lesions on T1-weighted imaging that lacked evidence of hemorrhage. Acute network injury was defined as hyperintense lesions on diffusion-weighted imaging that were not in the MCA territory and had fiber connections with the affected cerebral cortex. MRI was performed within the first week after disease onset. Cortical necrosis was only found in three neonates. Acute network injury was seen in the corticospinal tract (CST), thalamus and corpus callosum. Acute network injury along the CST was found in five neonates and one 7-month-old infant. Acute network injury was evident in the thalamus of four neonates and two infants (ages 4 and 7 months) and in the corpus callosum of five neonates and two infants (ages 4 and 7 months). The entire thalamus was involved in three children when infarction of MCA was complete. In acute MCA cortical infarction, MRI findings indicating cortical necrosis or acute network injury was frequently found in neonates and early infants. Response to injury in a developing brain may be faster than that in a mature one.

  18. A Mechanistic Link from GABA to Cortical Architecture and Perception.

    Science.gov (United States)

    Kolasinski, James; Logan, John P; Hinson, Emily L; Manners, Daniel; Divanbeighi Zand, Amir P; Makin, Tamar R; Emir, Uzay E; Stagg, Charlotte J

    2017-06-05

    Understanding both the organization of the human cortex and its relation to the performance of distinct functions is fundamental in neuroscience. The primary sensory cortices display topographic organization, whereby receptive fields follow a characteristic pattern, from tonotopy to retinotopy to somatotopy [1]. GABAergic signaling is vital to the maintenance of cortical receptive fields [2]; however, it is unclear how this fine-grain inhibition relates to measurable patterns of perception [3, 4]. Based on perceptual changes following perturbation of the GABAergic system, it is conceivable that the resting level of cortical GABAergic tone directly relates to the spatial specificity of activation in response to a given input [5-7]. The specificity of cortical activation can be considered in terms of cortical tuning: greater cortical tuning yields more localized recruitment of cortical territory in response to a given input. We applied a combination of fMRI, MR spectroscopy, and psychophysics to substantiate the link between the cortical neurochemical milieu, the tuning of cortical activity, and variability in perceptual acuity, using human somatosensory cortex as a model. We provide data that explain human perceptual acuity in terms of both the underlying cellular and metabolic processes. Specifically, higher concentrations of sensorimotor GABA are associated with more selective cortical tuning, which in turn is associated with enhanced perception. These results show anatomical and neurochemical specificity and are replicated in an independent cohort. The mechanistic link from neurochemistry to perception provides a vital step in understanding population variability in sensory behavior, informing metabolic therapeutic interventions to restore perceptual abilities clinically. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  19. The biology and dynamics of mammalian cortical granules

    Directory of Open Access Journals (Sweden)

    Liu Min

    2011-11-01

    Full Text Available Abstract Cortical granules are membrane bound organelles located in the cortex of unfertilized oocytes. Following fertilization, cortical granules undergo exocytosis to release their contents into the perivitelline space. This secretory process, which is calcium dependent and SNARE protein-mediated pathway, is known as the cortical reaction. After exocytosis, the released cortical granule proteins are responsible for blocking polyspermy by modifying the oocytes' extracellular matrices, such as the zona pellucida in mammals. Mammalian cortical granules range in size from 0.2 um to 0.6 um in diameter and different from most other regulatory secretory organelles in that they are not renewed once released. These granules are only synthesized in female germ cells and transform an egg upon sperm entry; therefore, this unique cellular structure has inherent interest for our understanding of the biology of fertilization. Cortical granules are long thought to be static and awaiting in the cortex of unfertilized oocytes to be stimulated undergoing exocytosis upon gamete fusion. Not till recently, the dynamic nature of cortical granules is appreciated and understood. The latest studies of mammalian cortical granules document that this organelle is not only biochemically heterogeneous, but also displays complex distribution during oocyte development. Interestingly, some cortical granules undergo exocytosis prior to fertilization; and a number of granule components function beyond the time of fertilization in regulating embryonic cleavage and preimplantation development, demonstrating their functional significance in fertilization as well as early embryonic development. The following review will present studies that investigate the biology of cortical granules and will also discuss new findings that uncover the dynamic aspect of this organelle in mammals.

  20. Monoclonal antibody identification of subpopulations of cerebral cortical neurons affected in Alzheimer's disease

    International Nuclear Information System (INIS)

    Miller, C.A.; Rudnicka, M.; Hinton, D.R.; Blanks, J.C.; Kozlowski, M.

    1987-01-01

    Neuronal degeneration is one of the hallmarks of Alzheimer's disease (AD). Given the paucity of molecular markers available for the identification of neuronal subtypes, the specificity of neuronal loss within the cerebral cortex has been difficult to evaluate. With a panel of four monoclonal antibodies (mAbs) applied to central nervous system tissues from AD patients, the authors have immunocytochemically identified a population of vulnerable cortical neurons; a subpopulation of pyramidal neurons is recognized by mAbs 3F12 and 44.1 in the hippocampus and neocortex, and clusters of multipolar neurons in the entorhinal cortex reactive with mAb 44.1 show selective degeneration. Closely adjacent stellate-like neurons in these regions, identified by mAb 6A2, show striking preservation in AD. The neurons recognized by mAbs 3F12 and 44.1 do not comprise a single known neurotransmitter system. mAb 3A4 identifies a phosphorylated antigen that is undetectable in normal brain but accumulates early in the course of AD in somas of vulnerable neurons. Antigen 3A4 is distinct from material reactive with thioflavin S or antibody generated against paired helical filaments. Initially, antigen 3A4 is localized to neurons in the entorhinal cortex and subiculum, later in the association neocortex, and, ultimately in cases of long duration, in primary sensory cortical regions. mAb 3F12 recognizes multiple bands of immunoblots of homogenates of normal and AD cortical tissues, whereas mAb 3A4 does not bind to immunoblots containing neurofilament proteins or brain homogenates from AD patients. Ultrastructurally, antigen 3A4 is localized to paired-helical filaments. Using these mAbs, further molecular characterization of the affected cortical neurons is now possible

  1. Deficits in Beam-Walking After Neonatal Motor Cortical Lesions are not Spared by Fetal Cortical Transplants in Rats

    OpenAIRE

    Swenson, R. S.; Danielsen, E. H.; Klausen, B. S.; Erlich, E.; Zimmer, J.; Castro, A. J.

    1989-01-01

    Adult rats that sustained unilateral motor cortical lesions at birth demonstrated deficits in traversing an elevated narrow beam. These deficits, manifested by hindlimb slips off the edge of the beam, were not spared in animals that received fetal cortical transplants into the lesion cavity immediately after lesion placement.

  2. Functional specialisation within the cortical language network: effects of cortical dysfunction.

    Science.gov (United States)

    Vandenberghe, R

    2007-01-01

    In the 1990's neuroanatomical models of language and semantic memory have been mainly based on functional neuroimaging studies of brain activity in healthy volunteers and correlational studies between structural lesions in patients and behavioral deficits. In this paper we present a novel approach where we test models that have been developed in healthy volunteers by means of functional imaging in patients in combination with behavioral studies. Study populations consist of patients with focal cortical stroke (n = 2), amnestic mild cognitive impairment (n = 14) and primary progressive aphasia (n = 18). The experiments provide converging evidence that 1. the integrity of the right mid- and anterior fusiform gyrus is required for full and detailed retrieval of knowledge of visual attributes of concrete entities 2. the left posterior superior temporal sulcus is critically involved in lexical-semantic retrieval 3. the anterior temporal pole to the left functions as an associative structure that links the representations of meaning that are distribured over the cortical brain surface. Our experiments also provide us with new insight into the degradation and re-organisation of the language system in cortical neurodegenerative disease.

  3. Shortened cortical silent period in adductor spasmodic dysphonia: evidence for widespread cortical excitability.

    Science.gov (United States)

    Samargia, Sharyl; Schmidt, Rebekah; Kimberley, Teresa Jacobson

    2014-02-07

    The purpose of this study was to compare cortical inhibition in the hand region of the primary motor cortex between subjects with focal hand dystonia (FHD), adductor spasmodic dysphonia (AdSD), and healthy controls. Data from 28 subjects were analyzed (FHD n=11, 53.25 ± 8.74 y; AdSD: n=8, 56.38 ± 7.5 y; and healthy controls: n=941.67 ± 10.85 y). All subjects received single pulse TMS to the left motor cortex to measure cortical silent period (CSP) in the right first dorsal interosseus (FDI) muscle. Duration of the CSP was measured and compared across groups. A one-way ANCOVA with age as a covariate revealed a significant group effect (p<0.001). Post hoc analysis revealed significantly longer CSP duration in the healthy group vs. AdSD group (p<0.001) and FHD group (p<0.001). These results suggest impaired intracortical inhibition is a neurophysiologic characteristic of FHD and AdSD. In addition, the shortened CSP in AdSD provides evidence to support a widespread decrease in cortical inhibition in areas of the motor cortex that represent an asymptomatic region of the body. These findings may inform future investigations of differential diagnosis as well as alternative treatments for focal dystonias. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. Characteristics of high affinity and low affinity adenosine binding sites in human cerebral cortex

    International Nuclear Information System (INIS)

    John, D.; Fox, I.V.

    1986-01-01

    The binding characteristics of human brain cortical membrane fractions were evaluated to test the hypothesis that there are A 1 and A 2 adenosine binding sites. The ligands used were 2-chloro(8- 3 H) adenosine and N 6 -(adenine-2, 8- 3 H) cyclohexayladenosine. Binding of chloroadenosine to human brain cortical membranes was time dependent, reversible and concentration dependent. The kinetic constant determinations from binding studies of the adenosine receptor are presented. Utilizing tritium-cyclohexyladenosine as ligand the authors observed evidence for a high affinity binding site in human brain cortical membranes with a kd of 5 nM

  5. Hanford Site Infrastructure Plan

    International Nuclear Information System (INIS)

    1990-01-01

    The Hanford Site Infrastructure Plan (HIP) has been prepared as an overview of the facilities, utilities, systems, and services that support all activities on the Hanford Site. Its purpose is three-fold: to examine in detail the existing condition of the Hanford Site's aging utility systems, transportation systems, Site services and general-purpose facilities; to evaluate the ability of these systems to meet present and forecasted Site missions; to identify maintenance and upgrade projects necessary to ensure continued safe and cost-effective support to Hanford Site programs well into the twenty-first century. The HIP is intended to be a dynamic document that will be updated accordingly as Site activities, conditions, and requirements change. 35 figs., 25 tabs

  6. Abnormalities of fixation, saccade and pursuit in posterior cortical atrophy.

    Science.gov (United States)

    Shakespeare, Timothy J; Kaski, Diego; Yong, Keir X X; Paterson, Ross W; Slattery, Catherine F; Ryan, Natalie S; Schott, Jonathan M; Crutch, Sebastian J

    2015-07-01

    The clinico-neuroradiological syndrome posterior cortical atrophy is the cardinal 'visual dementia' and most common atypical Alzheimer's disease phenotype, offering insights into mechanisms underlying clinical heterogeneity, pathological propagation and basic visual phenomena (e.g. visual crowding). Given the extensive attention paid to patients' (higher order) perceptual function, it is surprising that there have been no systematic analyses of basic oculomotor function in this population. Here 20 patients with posterior cortical atrophy, 17 patients with typical Alzheimer's disease and 22 healthy controls completed tests of fixation, saccade (including fixation/target gap and overlap conditions) and smooth pursuit eye movements using an infrared pupil-tracking system. Participants underwent detailed neuropsychological and neurological examinations, with a proportion also undertaking brain imaging and analysis of molecular pathology. In contrast to informal clinical evaluations of oculomotor dysfunction frequency (previous studies: 38%, current clinical examination: 33%), detailed eyetracking investigations revealed eye movement abnormalities in 80% of patients with posterior cortical atrophy (compared to 17% typical Alzheimer's disease, 5% controls). The greatest differences between posterior cortical atrophy and typical Alzheimer's disease were seen in saccadic performance. Patients with posterior cortical atrophy made significantly shorter saccades especially for distant targets. They also exhibited a significant exacerbation of the normal gap/overlap effect, consistent with 'sticky fixation'. Time to reach saccadic targets was significantly associated with parietal and occipital cortical thickness measures. On fixation stability tasks, patients with typical Alzheimer's disease showed more square wave jerks whose frequency was associated with lower cerebellar grey matter volume, while patients with posterior cortical atrophy showed large saccadic intrusions

  7. Directed cortical information flow during human object recognition: analyzing induced EEG gamma-band responses in brain's source space.

    Directory of Open Access Journals (Sweden)

    Gernot G Supp

    Full Text Available The increase of induced gamma-band responses (iGBRs; oscillations >30 Hz elicited by familiar (meaningful objects is well established in electroencephalogram (EEG research. This frequency-specific change at distinct locations is thought to indicate the dynamic formation of local neuronal assemblies during the activation of cortical object representations. As analytically power increase is just a property of a single location, phase-synchrony was introduced to investigate the formation of large-scale networks between spatially distant brain sites. However, classical phase-synchrony reveals symmetric, pair-wise correlations and is not suited to uncover the directionality of interactions. Here, we investigated the neural mechanism of visual object processing by means of directional coupling analysis going beyond recording sites, but rather assessing the directionality of oscillatory interactions between brain areas directly. This study is the first to identify the directionality of oscillatory brain interactions in source space during human object recognition and suggests that familiar, but not unfamiliar, objects engage widespread reciprocal information flow. Directionality of cortical information-flow was calculated based upon an established Granger-Causality coupling-measure (partial-directed coherence; PDC using autoregressive modeling. To enable comparison with previous coupling studies lacking directional information, phase-locking analysis was applied, using wavelet-based signal decompositions. Both, autoregressive modeling and wavelet analysis, revealed an augmentation of iGBRs during the presentation of familiar objects relative to unfamiliar controls, which was localized to inferior-temporal, superior-parietal and frontal brain areas by means of distributed source reconstruction. The multivariate analysis of PDC evaluated each possible direction of brain interaction and revealed widespread reciprocal information-transfer during familiar

  8. Subcortical cerebral blood flow and metabolic changes elicited by cortical spreading depression in rat

    Energy Technology Data Exchange (ETDEWEB)

    Mraovitch, S.; Calando, Y.; Goadsby, P.J.; Seylaz, J. (Laboratoire de Recherches Cerebrovasculaire, Paris (France))

    1992-06-01

    Changes in cerebral cortical perfusion (CBF{sub LDF}), local cerebral blood flow (lCBF) and local cerebral glucose utilization (lCGU) elicited by unilateral cortical spreading depression (SD) were monitored and measured in separate groups of rats anesthetized with {alpha}-chloralose. CBF{sub LDF} was recorded with laser Doppler flowmetry, while lCBF and lCGU were measured by the quantitative autoradiographic ({sup 14}C)iodoantipyrine and ({sup 14}C)-2-deoxyglucose methods, respectively. SD elicited a wave of hyperemia after a latency of 2 to 3 min followed by an oligemic phase. Ninety minutes following the onset of SD cortical lCBF and lCGU were essentially the same as on the contralateral side and in sham-treated rats. However, alteration in the lCBF and lCGU in upper and lower brainstem persisted. The present results demonstrate that long-lasting cerebrovascular and metabolic alterations take place within the subcortical regions following SD. These regions provide an attractive site to integrate observations in man concerning spreading depression and the aura of migraine with the other features of the syndrome. 19 refs., 2 figs., 1 tab.

  9. Intraosseous migration of tendinous calcifications: cortical erosions, subcortical migration and extensive intramedullary diffusion, a SIMS series

    Energy Technology Data Exchange (ETDEWEB)

    Malghem, Jacques; Omoumi, Patrick; Lecouvet, Frederic; Berg, Bruno vande [Universite Catholique de Louvain, Departement de radiologie et d' imagerie medicale, Bruxelles (Belgium)

    2015-10-15

    Calcium hydroxyapatite crystal deposition is a common disorder, which sometimes causes acute pain as calcifications dissolve and migrate into adjacent soft tissue. Intraosseous calcium penetration has also been described. We illustrate the appearance of these lesions using a series of 35 cases compiled by members of the French Society of Musculoskeletal Imaging (Societe d'Imagerie Musculo-Squelettique, SIMS). The first group in our series (7 cases) involved calcification-related cortical erosions of the humeral and femoral diaphyses, in particular at the pectoralis major and gluteus maximus insertions. A second group (28 cases) involved the presence of calcium material in subcortical areas. The most common site was the greater tubercle of the humerus, accompanying a calcifying tendinopathy of the supraspinatus. In addition, an extensive intramedullary diffusion of calcium deposits was observed in four of these cases, associated with cortical erosion in one case and subcortical lesions in three cases. Cortical erosions and intraosseous migration of calcifications associated with calcific tendinitis may be confused with neoplasm or infection. It is important to recognize atypical presentations of hydroxyapatite deposition to avoid unnecessary investigation or surgery. (orig.)

  10. Site Features

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset consists of various site features from multiple Superfund sites in U.S. EPA Region 8. These data were acquired from multiple sources at different times...

  11. Metabolism of [14C]indole-3-acetic acid by the cortical and stelar tissues of Zea mays L. roots

    International Nuclear Information System (INIS)

    Nonhebel, H.M.; Hillman, J.R.; Crozier, A.; Wilkins, M.B.

    1985-01-01

    Reverse-phase high-performance liquid chromatography was used to analyse 14 C-labelled metabolites of idole-3-acetic acid (IAA) formed in the cortical and stelar tissues of Zea mays roots. After a 2-h incubation in [ 14 C]IAA, stelar segments had metabolised between 1-6% of the methanol-extractable radioactivity compared with 91-92% by the cortical segments. The pattern of metabolites produced by cortical segments was similar to that produced by intact segments bathed in aqueous solutions of [ 14 C]IAA. In contrast, when IAA was supplied in agar blocks to stelar tissue protruding from the basal ends of segments, negligible metabolism was evident. On the basis of its retention characteristics both before and after methylation, the major metabolite of [ 14 C]IAA in Zea mays root segments was tentatively identified by high-performance liquid chromatography as oxindole-3-acetic acid. (orig.)

  12. Dual Pathology in Rasmussen's Encephalitis: A Report of Coexistent Focal Cortical Dysplasia and Review of the Literature.

    Science.gov (United States)

    Prayson, Richard A

    2012-01-01

    Rasmussen's encephalitis is a well-established, albeit rare cause of medically intractable epilepsy. In a small number of Rasmussen's cases, a second pathology is identified, which independently can cause medically intractable seizures (dual pathology). This paper documents a case of a 13-year-old male who presented with medically intractable epilepsy. The patient underwent a series of surgical resections, early on resulting in a diagnosis of focal cortical dysplasia and later yielding a diagnosis of coexistent Rasmussen's encephalitis, marked by chronic inflammation, microglial nodules, and focal cortical atrophy, combined with focal cortical dysplasia (Palmini et al. type IIA, ILAE type IIA). The literature on dual pathology in the setting of Rasmussen's encephalitis is reviewed.

  13. Dual Pathology in Rasmussen’s Encephalitis: A Report of Coexistent Focal Cortical Dysplasia and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Richard A. Prayson

    2012-01-01

    Full Text Available Rasmussen’s encephalitis is a well-established, albeit rare cause of medically intractable epilepsy. In a small number of Rasmussen's cases, a second pathology is identified, which independently can cause medically intractable seizures (dual pathology. This paper documents a case of a 13-year-old male who presented with medically intractable epilepsy. The patient underwent a series of surgical resections, early on resulting in a diagnosis of focal cortical dysplasia and later yielding a diagnosis of coexistent Rasmussen’s encephalitis, marked by chronic inflammation, microglial nodules, and focal cortical atrophy, combined with focal cortical dysplasia (Palmini et al. type IIA, ILAE type IIA. The literature on dual pathology in the setting of Rasmussen’s encephalitis is reviewed.

  14. Lower layers in the motor cortex are more effective targets for penetrating microelectrodes in cortical prostheses

    Science.gov (United States)

    Parikh, Hirak; Marzullo, Timothy C.; Kipke, Daryl R.

    2009-04-01

    Improving cortical prostheses requires the development of recording neural interfaces that are efficient in terms of providing maximal control information with minimal interface complexity. While the typical approaches have targeted neurons in the motor cortex with multiple penetrating shanks, an alternative approach is to determine an efficient distribution of electrode sites within the layers of the cortex with fewer penetrating shanks. The objective of this study was to compare unit activity in the upper and lower layers of the cortex with respect to movement and direction in order to inform the design of penetrating microelectrodes. Four rats were implanted bilaterally with multi-site single-shank silicon microelectrode arrays in the neck/shoulder region of the motor cortex. We simultaneously recorded unit activity across all layers of the motor cortex while the animal was engaged in a movement direction task. Localization of the electrode array within the different layers of the cortex was determined by histology. We denoted units from layers 2 and 3 and units as upper layer units, and units from layers 5 and 6 as lower layer units. Analysis of unit spiking activity demonstrated that both the upper and lower layers encode movement and direction information. Unit responses in either cortical layer of the cortex were not preferentially associated with contralateral or ipsilateral movement. Aggregate analysis (633 neurons) and best session analysis (75 neurons) indicated that units in the lower layers (layers 5, 6) are more likely to encode direction information when compared to units in the upper layers (layers 2, 3) (p< 0.05). These results suggest that electrode sites clustered in the lower layers provide access to more salient control information for cortical neuroprostheses.

  15. Reconfiguration of Cortical Networks in MDD Uncovered by Multiscale Community Detection with fMRI.

    Science.gov (United States)

    He, Ye; Lim, Sol; Fortunato, Santo; Sporns, Olaf; Zhang, Lei; Qiu, Jiang; Xie, Peng; Zuo, Xi-Nian

    2018-04-01

    Major depressive disorder (MDD) is known to be associated with altered interactions between distributed brain regions. How these regional changes relate to the reorganization of cortical functional systems, and their modulation by antidepressant medication, is relatively unexplored. To identify changes in the community structure of cortical functional networks in MDD, we performed a multiscale community detection algorithm on resting-state functional connectivity networks of unmedicated MDD (uMDD) patients (n = 46), medicated MDD (mMDD) patients (n = 38), and healthy controls (n = 50), which yielded a spectrum of multiscale community partitions. we selected an optimal resolution level by identifying the most stable community partition for each group. uMDD and mMDD groups exhibited a similar reconfiguration of the community structure of the visual association and the default mode systems but showed different reconfiguration profiles in the frontoparietal control (FPC) subsystems. Furthermore, the central system (somatomotor/salience) and 3 frontoparietal subsystems showed strengthened connectivity with other communities in uMDD but, with the exception of 1 frontoparietal subsystem, returned to control levels in mMDD. These findings provide evidence for reconfiguration of specific cortical functional systems associated with MDD, as well as potential effects of medication in restoring disease-related network alterations, especially those of the FPC system.

  16. Selection of independent components based on cortical mapping of electromagnetic activity

    Science.gov (United States)

    Chan, Hui-Ling; Chen, Yong-Sheng; Chen, Li-Fen

    2012-10-01

    Independent component analysis (ICA) has been widely used to attenuate interference caused by noise components from the electromagnetic recordings of brain activity. However, the scalp topographies and associated temporal waveforms provided by ICA may be insufficient to distinguish functional components from artifactual ones. In this work, we proposed two component selection methods, both of which first estimate the cortical distribution of the brain activity for each component, and then determine the functional components based on the parcellation of brain activity mapped onto the cortical surface. Among all independent components, the first method can identify the dominant components, which have strong activity in the selected dominant brain regions, whereas the second method can identify those inter-regional associating components, which have similar component spectra between a pair of regions. For a targeted region, its component spectrum enumerates the amplitudes of its parceled brain activity across all components. The selected functional components can be remixed to reconstruct the focused electromagnetic signals for further analysis, such as source estimation. Moreover, the inter-regional associating components can be used to estimate the functional brain network. The accuracy of the cortical activation estimation was evaluated on the data from simulation studies, whereas the usefulness and feasibility of the component selection methods were demonstrated on the magnetoencephalography data recorded from a gender discrimination study.

  17. Correlation between the thickness of the crestal and buccolingual cortical bone at varying depths and implant stability quotients.

    Directory of Open Access Journals (Sweden)

    Kanthanat Chatvaratthana

    Full Text Available Resonance frequency analysis (RFA is clinically used in dentistry to access the stiffness of dental implants in surrounding bone. However, the clear advantages and disadvantages of this method are still inconclusive. The aim of this study was to investigate and compare implant stability quotient (ISQ values obtained from RFA with parameters obtained from a cone beam computed tomography (CBCT scan of the same region.Nineteen implants (Conelog were inserted in the posterior maxillary and mandibular partially edentulous regions of 16 patients. At the time of implant placement, the ISQ values were obtained using RFA (Osstell. CBCT was used to measure the thickness of the crestal, cortical, buccolingual cortical, and cancellous bone at 3, 6, and 9 mm below the crestal bone level, as indicated by radiographic markers. The ratio of the thickness of the cortical to cancellous bone at varying depths was also calculated and classified into 4 groups (Group 1-4.There was a strong correlation between the crestal cortical bone thickness and ISQ values (P<0.001. The thickness of the buccolingual cortical bone and ratio of the cortical to cancellous bone thickness at 3 mm were significantly related to the ISQ (P = 0.018 and P = 0.034, respectively. Furthermore, the ISQs in Group 1 were the highest compared with those in Group 2 and Group 3, whereas the CBCT parameters at 6 and 9 mm did not have any specific correlation with the ISQ values.This study showed that the ISQ values obtained from RFA highly correlated with the quantity and quality of bone 3 mm below the crestal bone level. The correlation between the ISQ and bone surrounding the implant site was dependent on the depth of measurement. Therefore, RFA can help to predict the marginal bone level, as confirmed in this study.

  18. Epigenetic profiling reveals a developmental decrease in promoter accessibility during cortical maturation in vivo.

    Science.gov (United States)

    Venkatesh, Ishwariya; Simpson, Matthew T; Coley, Denise M; Blackmore, Murray G

    2016-12-01

    Axon regeneration in adult central nervous system (CNS) is limited in part by a developmental decline in the ability of injured neurons to re-express needed regeneration associated genes (RAGs). Adult CNS neurons may lack appropriate pro-regenerative transcription factors, or may display chromatin structure that restricts transcriptional access to RAGs. Here we performed epigenetic profiling around the promoter regions of key RAGs, and found progressive restriction across a time course of cortical maturation. These data identify a potential intrinsic constraint to axon growth in adult CNS neurons. Neurite outgrowth from cultured postnatal cortical neurons, however, proved insensitive to treatments that improve axon growth in other cell types, including combinatorial overexpression of AP1 factors, overexpression of histone acetyltransferases, and pharmacological inhibitors of histone deacetylases. This insensitivity could be due to intermediate chromatin closure at the time of culture, and highlights important differences in cell culture models used to test potential pro-regenerative interventions.

  19. Dominant hemisphere lateralization of cortical parasympathetic control as revealed by frontotemporal dementia

    Science.gov (United States)

    Guo, Christine C.; Sturm, Virginia E.; Zhou, Juan; Gennatas, Efstathios D.; Trujillo, Andrew J.; Hua, Alice Y.; Crawford, Richard; Stables, Lara; Kramer, Joel H.; Rankin, Katherine; Levenson, Robert W.; Rosen, Howard J.; Miller, Bruce L.; Seeley, William W.

    2016-01-01

    The brain continuously influences and perceives the physiological condition of the body. Related cortical representations have been proposed to shape emotional experience and guide behavior. Although previous studies have identified brain regions recruited during autonomic processing, neurological lesion studies have yet to delineate the regions critical for maintaining autonomic outflow. Even greater controversy surrounds hemispheric lateralization along the parasympathetic–sympathetic axis. The behavioral variant of frontotemporal dementia (bvFTD), featuring progressive and often asymmetric degeneration that includes the frontoinsular and cingulate cortices, provides a unique lesion model for elucidating brain structures that control autonomic tone. Here, we show that bvFTD is associated with reduced baseline cardiac vagal tone and that this reduction correlates with left-lateralized functional and structural frontoinsular and cingulate cortex deficits and with reduced agreeableness. Our results suggest that networked brain regions in the dominant hemisphere are critical for maintaining an adaptive level of baseline parasympathetic outflow. PMID:27071080

  20. Dynamics of Ionic Shifts in Cortical Spreading Depression.

    Science.gov (United States)

    Enger, Rune; Tang, Wannan; Vindedal, Gry Fluge; Jensen, Vidar; Johannes Helm, P; Sprengel, Rolf; Looger, Loren L; Nagelhus, Erlend A

    2015-11-01

    Cortical spreading depression is a slowly propagating wave of near-complete depolarization of brain cells followed by temporary suppression of neuronal activity. Accumulating evidence indicates that cortical spreading depression underlies the migraine aura and that similar waves promote tissue damage in stroke, trauma, and hemorrhage. Cortical spreading depression is characterized by neuronal swelling, profound elevation of extracellular potassium and glutamate, multiphasic blood flow changes, and drop in tissue oxygen tension. The slow speed of the cortical spreading depression wave implies that it is mediated by diffusion of a chemical substance, yet the identity of this substance and the pathway it follows are unknown. Intercellular spread between gap junction-coupled neurons or glial cells and interstitial diffusion of K(+) or glutamate have been proposed. Here we use extracellular direct current potential recordings, K(+)-sensitive microelectrodes, and 2-photon imaging with ultrasensitive Ca(2+) and glutamate fluorescent probes to elucidate the spatiotemporal dynamics of ionic shifts associated with the propagation of cortical spreading depression in the visual cortex of adult living mice. Our data argue against intercellular spread of Ca(2+) carrying the cortical spreading depression wavefront and are in favor of interstitial K(+) diffusion, rather than glutamate diffusion, as the leading event in cortical spreading depression. © The Author 2015. Published by Oxford University Press.

  1. Basal Forebrain Gating by Somatostatin Neurons Drives Prefrontal Cortical Activity.

    Science.gov (United States)

    Espinosa, Nelson; Alonso, Alejandra; Morales, Cristian; Espinosa, Pedro; Chávez, Andrés E; Fuentealba, Pablo

    2017-11-17

    The basal forebrain provides modulatory input to the cortex regulating brain states and cognitive processing. Somatostatin-expressing neurons constitute a heterogeneous GABAergic population known to functionally inhibit basal forebrain cortically projecting cells thus favoring sleep and cortical synchronization. However, it remains unclear if somatostatin cells can regulate population activity patterns in the basal forebrain and modulate cortical dynamics. Here, we demonstrate that somatostatin neurons regulate the corticopetal synaptic output of the basal forebrain impinging on cortical activity and behavior. Optogenetic inactivation of somatostatin neurons in vivo rapidly modified neural activity in the basal forebrain, with the consequent enhancement and desynchronization of activity in the prefrontal cortex, reflected in both neuronal spiking and network oscillations. Cortical activation was partially dependent on cholinergic transmission, suppressing slow waves and potentiating gamma oscillations. In addition, recruitment dynamics was cell type-specific, with interneurons showing similar temporal profiles, but stronger responses than pyramidal cells. Finally, optogenetic stimulation of quiescent animals during resting periods prompted locomotor activity, suggesting generalized cortical activation and increased arousal. Altogether, we provide physiological and behavioral evidence indicating that somatostatin neurons are pivotal in gating the synaptic output of the basal forebrain, thus indirectly controlling cortical operations via both cholinergic and non-cholinergic mechanisms. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Influences of brain development and ageing on cortical interactive networks.

    Science.gov (United States)

    Zhu, Chengyu; Guo, Xiaoli; Jin, Zheng; Sun, Junfeng; Qiu, Yihong; Zhu, Yisheng; Tong, Shanbao

    2011-02-01

    To study the effect of brain development and ageing on the pattern of cortical interactive networks. By causality analysis of multichannel electroencephalograph (EEG) with partial directed coherence (PDC), we investigated the different neural networks involved in the whole cortex as well as the anterior and posterior areas in three age groups, i.e., children (0-10 years), mid-aged adults (26-38 years) and the elderly (56-80 years). By comparing the cortical interactive networks in different age groups, the following findings were concluded: (1) the cortical interactive network in the right hemisphere develops earlier than its left counterpart in the development stage; (2) the cortical interactive network of anterior cortex, especially at C3 and F3, is demonstrated to undergo far more extensive changes, compared with the posterior area during brain development and ageing; (3) the asymmetry of the cortical interactive networks declines during ageing with more loss of connectivity in the left frontal and central areas. The age-related variation of cortical interactive networks from resting EEG provides new insights into brain development and ageing. Our findings demonstrated that the PDC analysis of EEG is a powerful approach for characterizing the cortical functional connectivity during brain development and ageing. Copyright © 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  3. Early development of synchrony in cortical activations in the human.

    Science.gov (United States)

    Koolen, N; Dereymaeker, A; Räsänen, O; Jansen, K; Vervisch, J; Matic, V; Naulaers, G; De Vos, M; Van Huffel, S; Vanhatalo, S

    2016-05-13

    Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44 weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. The cortical signature of impaired gesturing: Findings from schizophrenia

    Directory of Open Access Journals (Sweden)

    Petra Verena Viher

    2018-01-01

    Full Text Available Schizophrenia is characterized by deficits in gesturing that is important for nonverbal communication. Research in healthy participants and brain-damaged patients revealed a left-lateralized fronto-parieto-temporal network underlying gesture performance. First evidence from structural imaging studies in schizophrenia corroborates these results. However, as of yet, it is unclear if cortical thickness abnormalities contribute to impairments in gesture performance. We hypothesized that patients with deficits in gesture production show cortical thinning in 12 regions of interest (ROIs of a gesture network relevant for gesture performance and recognition. Forty patients with schizophrenia and 41 healthy controls performed hand and finger gestures as either imitation or pantomime. Group differences in cortical thickness between patients with deficits, patients without deficits, and controls were explored using a multivariate analysis of covariance. In addition, the relationship between gesture recognition and cortical thickness was investigated. Patients with deficits in gesture production had reduced cortical thickness in eight ROIs, including the pars opercularis of the inferior frontal gyrus, the superior and inferior parietal lobes, and the superior and middle temporal gyri. Gesture recognition correlated with cortical thickness in fewer, but mainly the same, ROIs within the patient sample. In conclusion, our results show that impaired gesture production and recognition in schizophrenia is associated with cortical thinning in distinct areas of the gesture network.

  5. Resolving the detailed structure of cortical and thalamic neurons in the adult rat brain with refined biotinylated dextran amine labeling.

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    Ling, Changying; Hendrickson, Michael L; Kalil, Ronald E

    2012-01-01

    Biotinylated dextran amine (BDA) has been used frequently for both anterograde and retrograde pathway tracing in the central nervous system. Typically, BDA labels axons and cell somas in sufficient detail to identify their topographical location accurately. However, BDA labeling often has proved to be inadequate to resolve the fine structural details of axon arbors or the dendrites of neurons at a distance from the site of BDA injection. To overcome this limitation, we varied several experimental parameters associated with the BDA labeling of neurons in the adult rat brain in order to improve the sensitivity of the method. Specifically, we compared the effect on labeling sensitivity of: (a) using 3,000 or 10,000 MW BDA; (b) injecting different volumes of BDA; (c) co-injecting BDA with NMDA; and (d) employing various post-injection survival times. Following the extracellular injection of BDA into the visual cortex, labeled cells and axons were observed in both cortical and thalamic areas of all animals studied. However, the detailed morphology of axon arbors and distal dendrites was evident only under optimal conditions for BDA labeling that take into account the: molecular weight of the BDA used, concentration and volume of BDA injected, post-injection survival time, and toning of the resolved BDA with gold and silver. In these instances, anterogradely labeled axons and retrogradely labeled dendrites were resolved in fine detail, approximating that which can be achieved with intracellularly injected compounds such as biocytin or fluorescent dyes.

  6. Ataxic Hemiparesis Associated with Cortical Infarct Localized in the Postcentral Gyrus.

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    Kinjo, Yoshino; Suda, Satoshi; Sakamoto, Yuki; Okubo, Seiji; Kimura, Kazumi

    2017-09-15

    Ataxic hemiparesis (AH) is a classic lacunar syndrome associated with localized damage to the pons, internal capsule, thalamus, or corona radiata. A depression of metabolic activity known as crossed cerebellar diaschisis (CCD) is frequently observed in the cerebellar hemisphere contralateral to the site of the lesion in patients with AH. Though small cortical or subcortical lesions may result in AH, such occurrences are rare. The current report details the case of a patient with AH resulting from acute infarction associated with localized lesions of the postcentral gyrus who presented without CCD.

  7. The changing roles of neurons in the cortical subplate

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    Michael J Friedlander

    2009-08-01

    Full Text Available Neurons may serve different functions over the course of an organism’s life. Recent evidence suggests that cortical subplate neurons including those that reside in the white matter may perform longitudinal multi-tasking at different stages of development. These cells play a key role in early cortical development in coordinating thalamocortical reciprocal innervation. At later stages of development, they become integrated within the cortical microcircuitry. This type of longitudinal multi-tasking can enhance the capacity for information processing by populations of cells serving different functions over the lifespan. Subplate cells are initially derived when cells from the ventricular zone underlying the cortex migrate to the cortical preplate that is subsequently split by the differentiating neurons of the cortical plate with some neurons locating in the marginal zone and others settling below in the subplate (SP. While the cortical plate neurons form most of the cortical layers (layers 2-6, the marginal zone neurons form layer 1 and the SP neurons become interstitial cells of the white matter as well as forming a compact sublayer along the bottom of layer 6. After serving as transient innervation targets for thalamocortical axons, most of these cells die and layer 4 neurons become innervated by thalamic axons. However, 10-20% survives, remaining into adulthood along the bottom of layer 6 and as a scattered population of interstitial neurons in the white matter. Surviving subplate cells’ axons project throughout the overlying laminae, reaching layer 1 and issuing axon collaterals within white matter and in lower layer