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Sample records for cortical cells imaged

  1. 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

  2. Functional topography of single cortical cells: an intracellular approach combined with optical imaging.

    Science.gov (United States)

    Buzás, P; Eysel, U T; Kisvárday, Z F

    1998-11-01

    Pyramidal cells mediating long-range corticocortical connections have been assumed to play an important role in visual perceptual mechanisms [C.D. Gilbert, Horizontal integration and cortical dynamics, Neuron 9 (1992) 1-13]. However, no information is available as yet on the specificity of individual pyramidal cells with respect to functional maps, e.g., orientation map. Here, we show a combination of techniques with which the functional topography of single pyramidal neurons can be explored in utmost detail. To this end, we used optical imaging of intrinsic signals followed by intracellular recording and staining with biocytin in vivo. The axonal and dendritic trees of the labelled neurons were reconstructed in three dimensions and aligned with corresponding functional orientation maps. The results indicate that, contrary to the sharp orientation tuning of neurons shown by the recorded spike activity, the efferent connections (axon terminal distribution) of the same pyramidal cells were found to terminate at a much broader range of orientations. Copyright 1998 Elsevier Science B.V.

  3. Quantitative Live Imaging of Human Embryonic Stem Cell Derived Neural Rosettes Reveals Structure-Function Dynamics Coupled to Cortical Development.

    Science.gov (United States)

    Ziv, Omer; Zaritsky, Assaf; Yaffe, Yakey; Mutukula, Naresh; Edri, Reuven; Elkabetz, Yechiel

    2015-10-01

    Neural stem cells (NSCs) are progenitor cells for brain development, where cellular spatial composition (cytoarchitecture) and dynamics are hypothesized to be linked to critical NSC capabilities. However, understanding cytoarchitectural dynamics of this process has been limited by the difficulty to quantitatively image brain development in vivo. Here, we study NSC dynamics within Neural Rosettes--highly organized multicellular structures derived from human pluripotent stem cells. Neural rosettes contain NSCs with strong epithelial polarity and are expected to perform apical-basal interkinetic nuclear migration (INM)--a hallmark of cortical radial glial cell development. We developed a quantitative live imaging framework to characterize INM dynamics within rosettes. We first show that the tendency of cells to follow the INM orientation--a phenomenon we referred to as radial organization, is associated with rosette size, presumably via mechanical constraints of the confining structure. Second, early forming rosettes, which are abundant with founder NSCs and correspond to the early proliferative developing cortex, show fast motions and enhanced radial organization. In contrast, later derived rosettes, which are characterized by reduced NSC capacity and elevated numbers of differentiated neurons, and thus correspond to neurogenesis mode in the developing cortex, exhibit slower motions and decreased radial organization. Third, later derived rosettes are characterized by temporal instability in INM measures, in agreement with progressive loss in rosette integrity at later developmental stages. Finally, molecular perturbations of INM by inhibition of actin or non-muscle myosin-II (NMII) reduced INM measures. Our framework enables quantification of cytoarchitecture NSC dynamics and may have implications in functional molecular studies, drug screening, and iPS cell-based platforms for disease modeling.

  4. Quantitative Live Imaging of Human Embryonic Stem Cell Derived Neural Rosettes Reveals Structure-Function Dynamics Coupled to Cortical Development.

    Directory of Open Access Journals (Sweden)

    Omer Ziv

    2015-10-01

    Full Text Available Neural stem cells (NSCs are progenitor cells for brain development, where cellular spatial composition (cytoarchitecture and dynamics are hypothesized to be linked to critical NSC capabilities. However, understanding cytoarchitectural dynamics of this process has been limited by the difficulty to quantitatively image brain development in vivo. Here, we study NSC dynamics within Neural Rosettes--highly organized multicellular structures derived from human pluripotent stem cells. Neural rosettes contain NSCs with strong epithelial polarity and are expected to perform apical-basal interkinetic nuclear migration (INM--a hallmark of cortical radial glial cell development. We developed a quantitative live imaging framework to characterize INM dynamics within rosettes. We first show that the tendency of cells to follow the INM orientation--a phenomenon we referred to as radial organization, is associated with rosette size, presumably via mechanical constraints of the confining structure. Second, early forming rosettes, which are abundant with founder NSCs and correspond to the early proliferative developing cortex, show fast motions and enhanced radial organization. In contrast, later derived rosettes, which are characterized by reduced NSC capacity and elevated numbers of differentiated neurons, and thus correspond to neurogenesis mode in the developing cortex, exhibit slower motions and decreased radial organization. Third, later derived rosettes are characterized by temporal instability in INM measures, in agreement with progressive loss in rosette integrity at later developmental stages. Finally, molecular perturbations of INM by inhibition of actin or non-muscle myosin-II (NMII reduced INM measures. Our framework enables quantification of cytoarchitecture NSC dynamics and may have implications in functional molecular studies, drug screening, and iPS cell-based platforms for disease modeling.

  5. Cortical Actin Flow in T Cells Quantified by Spatio-temporal Image Correlation Spectroscopy of Structured Illumination Microscopy Data.

    Science.gov (United States)

    Ashdown, George; Pandžić, Elvis; Cope, Andrew; Wiseman, Paul; Owen, Dylan

    2015-12-17

    Filamentous-actin plays a crucial role in a majority of cell processes including motility and, in immune cells, the formation of a key cell-cell interaction known as the immunological synapse. F-actin is also speculated to play a role in regulating molecular distributions at the membrane of cells including sub-membranous vesicle dynamics and protein clustering. While standard light microscope techniques allow generalized and diffraction-limited observations to be made, many cellular and molecular events including clustering and molecular flow occur in populations at length-scales far below the resolving power of standard light microscopy. By combining total internal reflection fluorescence with the super resolution imaging method structured illumination microscopy, the two-dimensional molecular flow of F-actin at the immune synapse of T cells was recorded. Spatio-temporal image correlation spectroscopy (STICS) was then applied, which generates quantifiable results in the form of velocity histograms and vector maps representing flow directionality and magnitude. This protocol describes the combination of super-resolution imaging and STICS techniques to generate flow vectors at sub-diffraction levels of detail. This technique was used to confirm an actin flow that is symmetrically retrograde and centripetal throughout the periphery of T cells upon synapse formation.

  6. Relationship between higher cortical dysfunction and the findings of magnetic resonance imaging in systemic lupus erythematosus

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    Maeshima, Etsuko; Maeshima, Shinichiro; Yamada, Yoichi; Yukawa, Susumu [Wakayama Medical Coll. (Japan)

    1996-04-01

    The relationship between systemic lupus erythematosus (SLE) and organic lesions was investigated by magnetic resonance imaging (MRI) to clarify the etiology of higher cortical dysfunction in SLE. The subjects were 10 patients with SLE, and higher cortical dysfunction was observed in 8 (80%) of the 10 patients. Five (82.5%) of the 8 patients showed abnormal MRI findings. The findings of higher cortical dysfunction were consistent with the MRI findings in 1 of the 5 patients, but not in the remaining four. MRI revealed no lesion despite the presence of higher cortical dysfunction in three patients. These results suggest that the association of organic changes and functional changes in cerebral nerve cells is important for etiology of higher cortical dysfunction in SLE. (author).

  7. Relationship between higher cortical dysfunction and the findings of magnetic resonance imaging in systemic lupus erythematosus

    International Nuclear Information System (INIS)

    Maeshima, Etsuko; Maeshima, Shinichiro; Yamada, Yoichi; Yukawa, Susumu

    1996-01-01

    The relationship between systemic lupus erythematosus (SLE) and organic lesions was investigated by magnetic resonance imaging (MRI) to clarify the etiology of higher cortical dysfunction in SLE. The subjects were 10 patients with SLE, and higher cortical dysfunction was observed in 8 (80%) of the 10 patients. Five (82.5%) of the 8 patients showed abnormal MRI findings. The findings of higher cortical dysfunction were consistent with the MRI findings in 1 of the 5 patients, but not in the remaining four. MRI revealed no lesion despite the presence of higher cortical dysfunction in three patients. These results suggest that the association of organic changes and functional changes in cerebral nerve cells is important for etiology of higher cortical dysfunction in SLE. (author)

  8. Subcortical orientation biases explain orientation selectivity of visual cortical cells.

    Science.gov (United States)

    Vidyasagar, Trichur R; Jayakumar, Jaikishan; Lloyd, Errol; Levichkina, Ekaterina V

    2015-04-01

    The primary visual cortex of carnivores and primates shows an orderly progression of domains of neurons that are selective to a particular orientation of visual stimuli such as bars and gratings. We recorded from single-thalamic afferent fibers that terminate in these domains to address the issue whether the orientation sensitivity of these fibers could form the basis of the remarkable orientation selectivity exhibited by most cortical cells. We first performed optical imaging of intrinsic signals to obtain a map of orientation domains on the dorsal aspect of the anaesthetized cat's area 17. After confirming using electrophysiological recordings the orientation preferences of single neurons within one or two domains in each animal, we pharmacologically silenced the cortex to leave only the afferent terminals active. The inactivation of cortical neurons was achieved by the superfusion of either kainic acid or muscimol. Responses of single geniculate afferents were then recorded by the use of high impedance electrodes. We found that the orientation preferences of the afferents matched closely with those of the cells in the orientation domains that they terminated in (Pearson's r = 0.633, n = 22, P = 0.002). This suggests a possible subcortical origin for cortical orientation selectivity. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  9. MR imaging and positron emission tomography of cortical heterotopia

    Energy Technology Data Exchange (ETDEWEB)

    Bairamian, D.; Di Chiro, G.; Theodore, W.H.; Holmes, M.D.; Dorwart, R.H.; Larson, S.M.

    1985-11-01

    Heterotopia of the gray matter is a developmental malformation in which ectopic cortex is found in the white matter of the brain. A case of a 33-year-old man with cortical heterotopia who had a lifelong history of seizures and psychomotor retardation is reported, including the results of cerebral CT, magnetic resonance imaging, and positron emission tomography using YF-2-deoxyglucose.

  10. MR imaging and positron emission tomography of cortical heterotopia

    International Nuclear Information System (INIS)

    Bairamian, D.; Di Chiro, G.; Theodore, W.H.; Holmes, M.D.; Dorwart, R.H.; Larson, S.M.

    1985-01-01

    Heterotopia of the gray matter is a developmental malformation in which ectopic cortex is found in the white matter of the brain. A case of a 33-year-old man with cortical heterotopia who had a lifelong history of seizures and psychomotor retardation is reported, including the results of cerebral CT, magnetic resonance imaging, and positron emission tomography using 18 F-2-deoxyglucose

  11. Restriction Spectrum Imaging As a Potential Measure of Cortical Neurite Density in Autism

    OpenAIRE

    Carper, Ruth A.; Treiber, Jeffrey M.; White, Nathan S.; Kohli, Jiwandeep S.; M?ller, Ralph-Axel

    2017-01-01

    Autism postmortem studies have shown various cytoarchitectural anomalies in cortical and limbic areas including increased cell packing density, laminar disorganization, and narrowed minicolumns. However, there is little evidence on dendritic and axonal organization in ASD. Recent imaging techniques have the potential for non-invasive, in vivo studies of small-scale structure in the human brain, including gray matter. Here, Restriction Spectrum Imaging (RSI), a multi-shell diffusion-weighted i...

  12. Magnetic Resonance Perfusion Imaging in Malformations of Cortical Development

    Energy Technology Data Exchange (ETDEWEB)

    Widjaja, ED.; Wilkinson, I.D.; Griffiths, P.D. [Academic Section of Radiolog y, Univ. of Sheffield, Sheffield (United Kingdom)

    2007-10-15

    Background: Malformations of cortical development vary in neuronal maturity and level of functioning. Purpose: To characterize regional relative cerebral blood volume (rCBV) and difference in first moment transit time (TTfm) in polymicrogyria and cortical tubers using magnetic resonance (MR) perfusion imaging. Material and Methods: MR imaging and dynamic T2*-weighted MR perfusion imaging were performed in 13 patients with tuberous sclerosis complex, 10 with polymicrogyria, and 18 controls with developmental delay but no macroscopic brain abnormality. Regions of interest were placed in cortical tubers or polymicrogyric cortex and in the contralateral normal-appearing side in patients with malformations. In 'control' subjects, regions of interest were placed in the frontal and parietal lobes in both hemispheres. The rCBV and TTfm of the tuber/contralateral side (rCBVRTSC and TTFMTSC) as well as those of the polymicrogyria/contralateral side (rCBVRPMG and TTFMPMG) were assessed. The right-to-left asymmetry of rCBV and TTfm in the control group was also assessed (rCBVRControls and TTFMControls). Results: There was no significant asymmetry between right and left rCBV or TTfm (P>0.05) in controls. There was significant reduction in rCBVRTSC compared to rCBVRControls (P<0.05), but no significant difference in TTFMTSC compared to TTFMControls (P>0.05). There were no significant differences between rCBVRPMG and rCBVRControls (P>0.05) or TTFMPMG and TTFMControls (P>0.05). Conclusion: Our findings imply that cerebral blood volume of polymicrogyria is similar to normal cortex, but there is reduced cerebral blood volume in cortical tubers. The lower rCBV ratio of cortical tubers may be related to known differences in pathogenetic timing of the underlying abnormalities during brain development or the presence of gliosis.

  13. Magnetic Resonance Perfusion Imaging in Malformations of Cortical Development

    International Nuclear Information System (INIS)

    Widjaja, ED.; Wilkinson, I.D.; Griffiths, P.D.

    2007-01-01

    Background: Malformations of cortical development vary in neuronal maturity and level of functioning. Purpose: To characterize regional relative cerebral blood volume (rCBV) and difference in first moment transit time (TTfm) in polymicrogyria and cortical tubers using magnetic resonance (MR) perfusion imaging. Material and Methods: MR imaging and dynamic T2*-weighted MR perfusion imaging were performed in 13 patients with tuberous sclerosis complex, 10 with polymicrogyria, and 18 controls with developmental delay but no macroscopic brain abnormality. Regions of interest were placed in cortical tubers or polymicrogyric cortex and in the contralateral normal-appearing side in patients with malformations. In 'control' subjects, regions of interest were placed in the frontal and parietal lobes in both hemispheres. The rCBV and TTfm of the tuber/contralateral side (rCBVRTSC and TTFMTSC) as well as those of the polymicrogyria/contralateral side (rCBVRPMG and TTFMPMG) were assessed. The right-to-left asymmetry of rCBV and TTfm in the control group was also assessed (rCBVRControls and TTFMControls). Results: There was no significant asymmetry between right and left rCBV or TTfm (P>0.05) in controls. There was significant reduction in rCBVRTSC compared to rCBVRControls (P 0.05). There were no significant differences between rCBVRPMG and rCBVRControls (P>0.05) or TTFMPMG and TTFMControls (P>0.05). Conclusion: Our findings imply that cerebral blood volume of polymicrogyria is similar to normal cortex, but there is reduced cerebral blood volume in cortical tubers. The lower rCBV ratio of cortical tubers may be related to known differences in pathogenetic timing of the underlying abnormalities during brain development or the presence of gliosis

  14. Noncontact ultrasound imaging applied to cortical bone phantoms

    OpenAIRE

    Bulman, J. B.; Ganezer, K. S.; Halcrow, P. W.; Neeson, Ian

    2012-01-01

    Purpose: The purpose of this paper was to take the first steps toward applying noncontact ultrasound (NCU) to the tasks of monitoring osteoporosis and quantitative ultrasound imaging (QUS) of cortical bone. The authors also focused on the advantages of NCU, such as its lack of reliance on a technologist to apply transducers and a layer of acoustical coupling gel, the ability of the transducers to operate autonomously as specified by preprogrammed software, and the likely reduction in statisti...

  15. Difference in trafficking of brain-derived neurotrophic factor between axons and dendrites of cortical neurons, revealed by live-cell imaging

    Directory of Open Access Journals (Sweden)

    Kohara Keigo

    2005-06-01

    Full Text Available Abstract Background Brain-derived neurotrophic factor (BDNF, which is sorted into a regulated secretory pathway of neurons, is supposed to act retrogradely through dendrites on presynaptic neurons or anterogradely through axons on postsynaptic neurons. Depending on which is the case, the pattern and direction of trafficking of BDNF in dendrites and axons are expected to be different. To address this issue, we analyzed movements of green fluorescent protein (GFP-tagged BDNF in axons and dendrites of living cortical neurons by time-lapse imaging. In part of the experiments, the expression of BDNF tagged with cyan fluorescent protein (CFP was compared with that of nerve growth factor (NGF tagged with yellow fluorescent protein (YFP, to see whether fluorescent protein-tagged BDNF is expressed in a manner specific to this neurotrophin. Results We found that BDNF tagged with GFP or CFP was expressed in a punctated manner in dendrites and axons in about two-thirds of neurons into which plasmid cDNAs had been injected, while NGF tagged with GFP or YFP was diffusely expressed even in dendrites in about 70% of the plasmid-injected neurons. In neurons in which BDNF-GFP was expressed as vesicular puncta in axons, 59 and 23% of the puncta were moving rapidly in the anterograde and retrograde directions, respectively. On the other hand, 64% of BDNF-GFP puncta in dendrites did not move at all or fluttered back and forth within a short distance. The rest of the puncta in dendrites were moving relatively smoothly in either direction, but their mean velocity of transport, 0.47 ± 0.23 (SD μm/s, was slower than that of the moving puncta in axons (0.73 ± 0.26 μm/s. Conclusion The present results show that the pattern and velocity of the trafficking of fluorescence protein-tagged BDNF are different between axons and dendrites, and suggest that the anterograde transport in axons may be the dominant stream of BDNF to release sites.

  16. 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

  17. Motor features in posterior cortical atrophy and their imaging correlates.

    Science.gov (United States)

    Ryan, Natalie S; Shakespeare, Timothy J; Lehmann, Manja; Keihaninejad, Shiva; Nicholas, Jennifer M; Leung, Kelvin K; Fox, Nick C; Crutch, Sebastian J

    2014-12-01

    Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by impaired higher visual processing skills; however, motor features more commonly associated with corticobasal syndrome may also occur. We investigated the frequency and clinical characteristics of motor features in 44 PCA patients and, with 30 controls, conducted voxel-based morphometry, cortical thickness, and subcortical volumetric analyses of their magnetic resonance imaging. Prominent limb rigidity was used to define a PCA-motor subgroup. A total of 30% (13) had PCA-motor; all demonstrating asymmetrical left upper limb rigidity. Limb apraxia was more frequent and asymmetrical in PCA-motor, as was myoclonus. Tremor and alien limb phenomena only occurred in this subgroup. The subgroups did not differ in neuropsychological test performance or apolipoprotein E4 allele frequency. Greater asymmetry of atrophy occurred in PCA-motor, particularly involving right frontoparietal and peri-rolandic cortices, putamen, and thalamus. The 9 patients (including 4 PCA-motor) with pathology or cerebrospinal fluid all showed evidence of Alzheimer's disease. Our data suggest that PCA patients with motor features have greater atrophy of contralateral sensorimotor areas but are still likely to have underlying Alzheimer's disease. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Motor features in posterior cortical atrophy and their imaging correlates☆

    Science.gov (United States)

    Ryan, Natalie S.; Shakespeare, Timothy J.; Lehmann, Manja; Keihaninejad, Shiva; Nicholas, Jennifer M.; Leung, Kelvin K.; Fox, Nick C.; Crutch, Sebastian J.

    2014-01-01

    Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by impaired higher visual processing skills; however, motor features more commonly associated with corticobasal syndrome may also occur. We investigated the frequency and clinical characteristics of motor features in 44 PCA patients and, with 30 controls, conducted voxel-based morphometry, cortical thickness, and subcortical volumetric analyses of their magnetic resonance imaging. Prominent limb rigidity was used to define a PCA-motor subgroup. A total of 30% (13) had PCA-motor; all demonstrating asymmetrical left upper limb rigidity. Limb apraxia was more frequent and asymmetrical in PCA-motor, as was myoclonus. Tremor and alien limb phenomena only occurred in this subgroup. The subgroups did not differ in neuropsychological test performance or apolipoprotein E4 allele frequency. Greater asymmetry of atrophy occurred in PCA-motor, particularly involving right frontoparietal and peri-rolandic cortices, putamen, and thalamus. The 9 patients (including 4 PCA-motor) with pathology or cerebrospinal fluid all showed evidence of Alzheimer's disease. Our data suggest that PCA patients with motor features have greater atrophy of contralateral sensorimotor areas but are still likely to have underlying Alzheimer's disease. PMID:25086839

  19. APLP2 regulates neuronal stem cell differentiation during cortical development.

    Science.gov (United States)

    Shariati, S Ali M; Lau, Pierre; Hassan, Bassem A; Müller, Ulrike; Dotti, Carlos G; De Strooper, Bart; Gärtner, Annette

    2013-03-01

    Expression of amyloid precursor protein (APP) and its two paralogues, APLP1 and APLP2 during brain development coincides with key cellular events such as neuronal differentiation and migration. However, genetic knockout and shRNA studies have led to contradictory conclusions about their role during embryonic brain development. To address this issue, we analysed in depth the role of APLP2 during neurogenesis by silencing APLP2 in vivo in an APP/APLP1 double knockout mouse background. We find that under these conditions cortical progenitors remain in their undifferentiated state much longer, displaying a higher number of mitotic cells. In addition, we show that neuron-specific APLP2 downregulation does not impact the speed or position of migrating excitatory cortical neurons. In summary, our data reveal that APLP2 is specifically required for proper cell cycle exit of neuronal progenitors, and thus has a distinct role in priming cortical progenitors for neuronal differentiation.

  20. Curved planar reconstruction of MR images in focal cortical dysplasia of the brain

    International Nuclear Information System (INIS)

    Chung, Gyung Ho; Lee, Sang Yong; Kim, Chong So; Kim, Young Kon; Lee, Young Hwan; Jeong, Su Hyun

    2002-01-01

    To describe curved planar reconstruction imaging (CPR) and determine its usefulness in the evaluation of focal cortical dysplasia of the brain. In 17 cases of focal cortical dysplasia (cortical dysplasia (n=9), schizencephaly (n=5), and heterotopia (n=3), CPR images were created using a multiplanar reconstruction program and imaging data obtained during T1 magnetization prepared rapid acquisition gradient-echo MR imaging. We assessed the precise configuration of abnormalities and their relation to adjacent gyri and sulci. CPRI showed the brain cortex as a 2D panoramic image, demonstrating the precise configurations and locations of dysplasia-associated abnormalities and their relation to adjacent gyri and sulci, and the precise shape of the gray-white matter interface. CPRI can provide important radiological information about the extension and configuration of focal cortical dysplasia, and its relation to neighboring cortical structures. We believe that CPRI should form an essential part of the routine investigation os suspected cases of focal cortical dysplasia

  1. Nanoscaffold's stiffness affects primary cortical cell network formation

    NARCIS (Netherlands)

    Xie, Sijia; Schurink, Bart; Wolbers, F.; Lüttge, Regina; Hassink, Gerrit Cornelis

    2014-01-01

    Networks of neurons cultured on-chip can provide insights into both normal and disease-state brain function. The ability to guide neuronal growth in specific, artificially designed patterns allows us to study how brain function follows form. Primary cortical cells cultured on nanograting scaffolds,

  2. Noncontact ultrasound imaging applied to cortical bone phantoms.

    Science.gov (United States)

    Bulman, J B; Ganezer, K S; Halcrow, P W; Neeson, Ian

    2012-06-01

    The purpose of this paper was to take the first steps toward applying noncontact ultrasound (NCU) to the tasks of monitoring osteoporosis and quantitative ultrasound imaging (QUS) of cortical bone. The authors also focused on the advantages of NCU, such as its lack of reliance on a technologist to apply transducers and a layer of acoustical coupling gel, the ability of the transducers to operate autonomously as specified by preprogrammed software, and the likely reduction in statistical and systematic errors associated with the variability in the pressure applied by the clinician to the transmitting transducer that NCU might provide. The authors also undertook this study in order to find additional applications of NCU beyond its past limited usage in assessing the severity of third degree burns. A noncontact ultrasound imaging system using a pair of specially designed broadband, 1.5 MHz noncontact piezoelectric transducers and cortical bone phantoms, were used to determine bone mineral density (BMD), speed of sound (SOS), integrated response (IR), and ultrasonic transmittance. Air gaps of greater than 3 cm, two transmission and two reflection paths, and a digital signal processor were also used in the collection of data from phantoms of nominal mass densities that varied from 1.17 to 2.25 g/cm(3) and in bone mineral density from 0 to 1.7 g/cm(3). Good correlations between known BMD and measured SOS, IR, and transmittance were obtained for all 17 phantoms, and methods for quantifying and minimizing sources of systematic errors were outlined. The BMD of the phantom sets extended through most of the in vivo range found in cortical bone. A total of 16-20 repeated measurements of the SOS, thickness, and IR for the phantom set that were conducted over a period of several months showed a small variation in the range of measurements of ±1%-2%. These NCU data were shown to be in agreement with similar results using contact ultrasound to be within 1%-2%. Transmittance

  3. Human cerebral cortices: signal variation on diffusion-weighted MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Asao, Chiaki [Kumamoto Regional Medical Center, Department of Radiology, Kumamoto (Japan); National Hospital Organization Kumamoto Medical Center, Department of Radiology, Kumamoto (Japan); Hirai, Toshinori; Yamashita, Yasuyuki [Kumamoto University Graduate School of Medical Sciences, Department of Diagnostic Radiology, Kumamoto (Japan); Yoshimatsu, Shunji [National Hospital Organization Kumamoto Medical Center, Department of Radiology, Kumamoto (Japan); Matsukawa, Tetsuya; Imuta, Masanori [Kumamoto Regional Medical Center, Department of Radiology, Kumamoto (Japan); Sagara, Katsuro [Kumamoto Regional Medical Center, Department of Internal Medicine, Kumamoto (Japan)

    2008-03-15

    We have often encountered high signal intensity (SI) of the cingulate gyrus and insula during diffusion-weighted magnetic resonance imaging (DW-MRI) on neurologically healthy adults. To date, cortical signal heterogeneity on DW images has not been investigated systematically. The purpose of our study was to determine whether there is regional signal variation in the brain cortices of neurologically healthy adults on DW-MR images. The SI of the cerebral cortices on DW-MR images at 1.5 T was evaluated in 50 neurologically healthy subjects (34 men, 16 women; age range 33-84 years; mean age 57.6 years). The cortical SI in the cingulate gyrus, insula, and temporal, occipital, and parietal lobes was graded relative to the SI of the frontal lobe. Contrast-to-noise ratios (CNRs) on DW-MR images were compared for each cortical area. Diffusion changes were analyzed by visually assessment of the differences in appearance among the cortices on apparent diffusion coefficient (ADC) maps. Increased SI was frequently seen in the cingulate gyrus and insula regardless of patient age. There were no significant gender- or laterality-related differences. The CNR was significantly higher in the cingulate gyrus and insula than in the other cortices (p <.01), and significant differences existed among the cortical regions (p <.001). There were no apparent ADC differences among the cortices on ADC maps. Regional signal variation of the brain cortices was observed on DW-MR images of healthy subjects, and the cingulate gyrus and insula frequently manifested high SI. These findings may help in the recognition of cortical signal abnormalities as visualized on DW-MR images. (orig.)

  4. Human cerebral cortices: signal variation on diffusion-weighted MR imaging

    International Nuclear Information System (INIS)

    Asao, Chiaki; Hirai, Toshinori; Yamashita, Yasuyuki; Yoshimatsu, Shunji; Matsukawa, Tetsuya; Imuta, Masanori; Sagara, Katsuro

    2008-01-01

    We have often encountered high signal intensity (SI) of the cingulate gyrus and insula during diffusion-weighted magnetic resonance imaging (DW-MRI) on neurologically healthy adults. To date, cortical signal heterogeneity on DW images has not been investigated systematically. The purpose of our study was to determine whether there is regional signal variation in the brain cortices of neurologically healthy adults on DW-MR images. The SI of the cerebral cortices on DW-MR images at 1.5 T was evaluated in 50 neurologically healthy subjects (34 men, 16 women; age range 33-84 years; mean age 57.6 years). The cortical SI in the cingulate gyrus, insula, and temporal, occipital, and parietal lobes was graded relative to the SI of the frontal lobe. Contrast-to-noise ratios (CNRs) on DW-MR images were compared for each cortical area. Diffusion changes were analyzed by visually assessment of the differences in appearance among the cortices on apparent diffusion coefficient (ADC) maps. Increased SI was frequently seen in the cingulate gyrus and insula regardless of patient age. There were no significant gender- or laterality-related differences. The CNR was significantly higher in the cingulate gyrus and insula than in the other cortices (p <.01), and significant differences existed among the cortical regions (p <.001). There were no apparent ADC differences among the cortices on ADC maps. Regional signal variation of the brain cortices was observed on DW-MR images of healthy subjects, and the cingulate gyrus and insula frequently manifested high SI. These findings may help in the recognition of cortical signal abnormalities as visualized on DW-MR images. (orig.)

  5. 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.

  6. Regional quantitative analysis of cortical surface maps of FDG PET images

    CERN Document Server

    Protas, H D; Hayashi, K M; Chin Lung, Yu; Bergsneider, M; Sung Cheng, Huang

    2006-01-01

    Cortical surface maps are advantageous for visualizing the 3D profile of cortical gray matter development and atrophy, and for integrating structural and functional images. In addition, cortical surface maps for PET data, when analyzed in conjunction with structural MRI data allow us to investigate, and correct for, partial volume effects. Here we compared quantitative regional PET values based on a 3D cortical surface modeling approach with values obtained directly from the 3D FDG PET images in various atlas-defined regions of interest (ROIs; temporal, parietal, frontal, and occipital lobes). FDG PET and 3D MR (SPGR) images were obtained and aligned to ICBM space for 15 normal subjects. Each image was further elastically warped in 2D parameter space of the cortical surface, to align major cortical sulci. For each point within a 15 mm distance of the cortex, the value of the PET intensity was averaged to give a cortical surface map of FDG uptake. The average PET values on the cortical surface map were calcula...

  7. The concept of transcortical cell assemblies: a key to the understanding of cortical lateralization and interhemispheric interaction.

    Science.gov (United States)

    Pulvermüller, F; Mohr, B

    1996-01-01

    According to Hebb, elements of higher cognitive processes, such as concepts, words and mental images, are realized in the brain as cortical cell assemblies, i.e. large and strongly connected neuron populations that form functional units. Neurons belonging to such assemblies may be scattered over wide cortical areas, and some cell assemblies may even comprise neurons of both hemispheres (transcortical assemblies). If full activation (ignition) of an assembly leads to fast circulation of neuronal activity in the assembly, this process should be visible in high-frequency cortical responses. Some evidence will be reviewed that cell assembly ignition indeed leads to changes in high-frequency cortical responses which can be recorded in the EEG and MEG. Within the cell assembly-framework, the question of cortical laterality translates into the question of how neurons of transcortical assemblies are balanced between the hemispheres. This approach allows for different degrees of laterality. Recent evidence is summarized that the degree of laterality indeed differs between language units. For example, the cortical representation of certain words appears to be strongly lateralized to the left hemisphere while those of others are less lateralized. If neurons of both hemispheres are part of one assembly bihemispheric processing should lead to a processing advantage compared to processing in the dominant hemisphere alone. The latter appears to be the case for lexical processing, as revealed by recent behavioral studies. In conclusion, the cell assembly-framework suggests a more fine-grained description of the issue of cortical laterality; it is not appropriate to ask whether "modules" supporting higher cortical functions are located either in the left or right hemisphere. Rather, it appears fruitful to ask how the neurons of transcortical cell assemblies are balanced between the hemispheres.

  8. Local pulsatile contractions are an intrinsic property of the myosin 2A motor in the cortical cytoskeleton of adherent cells.

    Science.gov (United States)

    Baird, Michelle A; Billington, Neil; Wang, Aibing; Adelstein, Robert S; Sellers, James R; Fischer, Robert S; Waterman, Clare M

    2017-01-15

    The role of nonmuscle myosin 2 (NM2) pulsatile dynamics in generating contractile forces required for developmental morphogenesis has been characterized, but whether these pulsatile contractions are an intrinsic property of all actomyosin networks is not known. Here we used live-cell fluorescence imaging to show that transient, local assembly of NM2A "pulses" occurs in the cortical cytoskeleton of single adherent cells of mesenchymal, epithelial, and sarcoma origin, independent of developmental signaling cues and cell-cell or cell-ECM interactions. We show that pulses in the cortical cytoskeleton require Rho-associated kinase- or myosin light chain kinase (MLCK) activity, increases in cytosolic calcium, and NM2 ATPase activity. Surprisingly, we find that cortical cytoskeleton pulses specifically require the head domain of NM2A, as they do not occur with either NM2B or a 2B-head-2A-tail chimera. Our results thus suggest that pulsatile contractions in the cortical cytoskeleton are an intrinsic property of the NM2A motor that may mediate its role in homeostatic maintenance of tension in the cortical cytoskeleton of adherent cells. © 2017 Baird et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  9. Global gray matter changes in posterior cortical atrophy: A serial imaging study

    NARCIS (Netherlands)

    Lehmann, M.; Barnes, J.; Ridgway, G.R.; Ryan, N.S.; Warrington, E.K.; Crutch, S.J.; Fox, N.C.

    2012-01-01

    Background: Posterior cortical atrophy (PCA) is a neurodegenerative condition predominantly associated with Alzheimer's disease (AD) pathology. Cross-sectional imaging studies have shown different atrophy patterns in PCA patients compared with typical amnestic Alzheimer's disease (tAD) patients,

  10. Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images

    NARCIS (Netherlands)

    Guo, Shengwen; Lai, Chunren; Wu, Congling; Cen, Guiyin; Hariharan, A.; Vijayakumari, Anupa A.; Aarabi, Mohammad Hadi; Aballi, John; Nour, Abd Elazeim Abd Alla Mohamed; Abdelaziz, Mohammed; Abdolalizadeh, AmirHussein; Abdollahi, Mahsa; Abdul Aziz, Siti Aishah; Salam, Amritha Abdul; Abdulaziz, Nidhal; Abdulkadir, Ahmed; Abdullah, Sachal; Abdullah, Osama; Abrigo, Jill; Adachi, Noriaki; Adamson, Christopher; Adduru, Viraj; Adel, Tameem; Aderghal, Karim; Ades-Aron, Benjamin; Adeyosoye, Michael; Adlard, Paul; Srinivasa, Ag; Aganj, Iman; Agarwal, Ayush; Agarwal, Anupam; Agarwal, Anchit; Aguero, Cinthya; Aguiar, Pablo; Ahdidan, Jamila; Ahmad, Fayyaz; Ahmad, Rziwan; Ahmadi, Hessam; Ahmed, Nisar; Sid, Farid Ahmed; Ai, Edward; Ai, Qing; Aicha, Benyahia; Aitharaju, Sai; Aiyer, Aditya; Akkus, Zeynettin; Akodad, Sanae; Akramifard, Hamid; Aksman, Leon; Aktas, Said; Al-Janabi, Omar; Al-Nuaimi, Ali; AlAila, BahaaEddin; Alakwaa, Fadhl; Alam, Saruar; Alam, Fakhre; Alam Zaidi, Syed Farhan; Alan, Wiener; Alansari, Mukhtar; Alareqi, Ebrahim; Alberdi, Ane; Albsoul, Mohammad; Alderson, Thomas; Aleem, Hassan; Alex, Aishwarya; Alexander, Jacob; Alexopoulos, Panagiotis; Alfoldi, Jessica; Ali, Ayesha; Ali, Imdad; Alimoradian, Shirin; Aljabar, Paul; Aljabbouli, Hasan; Aljovic, Almir; Allen, Genevera; Alliende, Luz Maria; Almaguel, Frankis; Almgren, Hannes; Montes, Carmen Alonso; Alowaisheq, Tasneem; Alryalat, Saif Aldeen; Alsado, Majd; Alsaedi, Abdalrahman; Alshehri, Haifa; Altaf, Tooba; Altendahl, Marie; Altmann, Andre; Alvand, Ashkan; Filho, Manoel Alves; Alzubi, Raid; Amaral, Robert; Ambatipudi, Mythri; Amernath, Remya; Amlien, Inge; Amoroso, Nicola; Amri, Hakima; Anastasiou, Athanasios; Anbarasi, Jani; Anbarjafari, Gholamreza; Anderson, Wes; Anderson, Jeff; Anderson, Valerie; Anderson, Loretta; Andonov, Jovan; Andova, Vesna; Andreopoulou, Irene; Andrews, K. Abigail; Andrews, Cameron; Angeles, Michel; Anne-Laure, Aziz; Ansari, Ghulam Jillani; Ansari, Sharaf; Anstey, Kaarin; Antunes, Augusto; Aoshuang, Zhang; Aouf, Mazin; Aow Yong, Li Yew; Aporntewan, Chatchawit; Apostolova, Liana; Appiah, Frank; Apsvalka, Dace; Arab, Abazar; Araque Caballero, Miguel Ángel; Arbabyazd, Mohammad; Arbelaez, Pablo; Archer, Kellie; Ardekani, Babak; Aretouli, Eleni; Arfanakis, Konstantinos; Arisi, Ivan; Armentrout, Steven; Arnold, Matthias; Arnold, Steven; Arslan, Salim; Artacho-Perula, Emilio; Arthofer, Christoph; Aruchamy, Srinivasan; Arya, Zobair; Pizarro, Carlos Asensio; Ashford, Wes; Ashraf, Azhaar; Askland, Kathleen; Aslaksen, Per; Aslakson, Eric; Aso, Toshihiko; Astphan, Michele; Ataloglou, Dimitrios; Atay, Meltem; Athanas, Argus; Atri, Roozbeh; Au, April; Aurich, Maike; Avants, Brian; Awasthi, Niharika; Awate, Suyash; Ayaz, Aymen; Son, Yesim Aydin; Aydogan, Dogu Baran; Ayhan, Murat; Ayton, Scott; Aziz, Adel; Azmi, Mohd Hafrizal; Ba, Maowen; Bach, Kevin; Badea, Alexandra; Bag, Asim; Bagewadi, Shweta; Bai, Xiangqi; Bai, Zilong; Bai, Haoli; Baird, Geoffrey; Baiwen, Zhang; Baker, Elizabeth; Baker, John; Bakker, Arnold; Ball, Erika; Ballén Galindo, Miguel Ángel; Banaei, Amin; Bandyopadhyay, Dipankar; Bang, Ki Hun; Bangen, Katherine; Banks, Sarah; Banning, Leonie; Bao, Wan Yun; Barakat, Rita; Barbará, Eduardo; Barber, Philip; Barber, Robert; de Araujo, Flavia Roberta Barbosa; Barnes, Josephine; Barredo, Jennifer; Barret, Olivier; Barrett, Matthew; Barsamian, Barsam; Barsky, Andrey; Bartel, Fabian; Bartoszewicz, Jakub; Bartram-Shaw, David; Barwood, Caroline; Basavaraj, Suryakanth; Basavaraj, Arshitha; Basiouny, Ahmed; Baskaran, Bhuvaneshwari; Basu, Arindam; Baths, Veeky; Bathula, Deepti; Batmanghelich, Nematollah Kayhan; Bauer, Roman; Bauer, Corinna; Bawa, Vanshika; Bayley, Peter; Bayram, Ali; Bazi, Yakoub; Beach, Thomas; Beaudoin, Kristin; Beaulieu, Christian; Becker, Cassiano; Beckett, Laurel; Bedding, Alun; Beer, Simone; Beer, Joanne; Beg, Mirza Faisal; Behfar, Qumars; Behjat, Hamed; Behjat, Hamid; Behseta, Sam; Bekris, Lynn; Suresh, Mahanand Belathur; Belichenko, Nadia; Bellio, Maura; Belyaev, Mikhail; Bemiller, Shane; Ahmed, Olfa Ben; Ben Bouallègue, Fayçal; Benedikt, Michael; Benge, Jared; Benitez, Andreana; Benlloch, Jose María; Benn, Marianne; Benyoussef, El Mehdi; Bergeron, David; Bermudez, Elaine; Bessadok, Alaa; Betzel, Richard; Bezuidenhoudt, Mauritz; Bhagwat, Nikhil; Bhalerao, Shailesh; Bhandari, Anindya; Bhasin, Harsh; Bhati, Radhika; Bhatkoti, Pushkar; Bhatt, Priya; Bhattacharjee, Debotosh; Bhattacharyya, Sudeepa; Bi, Rui; Bi, Jinbo; Bi, Harvy; Biancardi, Alberto; Bidart, Rene; Bilgel, Murat; Billiet, Thibo; Binczyk, Franciszek; Bingsheng, Huang; Bird, Christopher; Bischof, Gérard; Bishnoi, Ram; Biswas, Shameek; Bjelke, David; Black, Sandra; Blackwood, Jennifer; Blaese, Elise; Blair, James; Blanchard, Gilles; Bloom, Toby; Blujus, Jenna; Blusztajn, Jan Krzysztof; Bo, Wu; Bo, Jun; Boda, Ravi; Boellaard, Ronald; Bogorodzki, Piotr; Bokde, Arun; Bolhasani, Ehsan; Bonakdarpour, Borna; Bonazzoli, Matthew; Bône, Alexandre; Borkowsky, Jennifer; Borrajo, Danielle; Bos, Isabelle; Bosco, Paolo; Bott, Nicholas; Rodrigues, Renato Botter Maio Lopes; Boughanmi, Amani; Bougias, Haralabos; Boulier, Thomas; Bourgeat, Pierrick; Bouyagoub, Samira; Bowes, Mike; Boyes, Richard; Bozoki, Andrea; Bradshaw, Tyler; Pereira, Joana Braga; Brahami, Yoann; Brambati, Simona Maria; Bras, Jose; Braskie, Meredith; Brecheisen, Ralph; Bregman, Noa; Brewer, James; Briassouli, Alexia; Brickman, Adam; Bridges, Robert; Brihmat, Nabila; Brinkmann, Benjamin; Britschgi, Markus; Broers, Thomas; Bron, Esther; Brown, Jesse; Brown, Matthew; Brown, Abel; Brown, Maria; Brunberg, James; Bu, Tao; Bubbico, Giovanna; Bubenik, Peter; Bubu, Omonigho; Buchanan, Daniel; Buchholz, Hans-Georg; Buchsbaum, Bradley; Buck, Katharina; Buckley, Rachel; Budgeon, Charley; Buhl, Derek; Sánchez, Manuel Buitrago; Bundela, Saurabh; Burciu, Irina; Burgos, Ninon; Burke, Shanna; Burn, Katherine; Burns, Jeffrey; Burns, Gully; Burzykowski, Tomasz; Bush, Sammie; Buss, Stephanie; Butcher, Bradley; Butt, Victoria; Buxbaum, Joseph; Sandeep, C. S.; Cabrera, Cristóbal; Cahyaningrum, Winda; Cai, Zhen-Nao; Cai, Siqi; Cai, Erik; Cajka, Tomas; Calamia, Matthew; Caligiuri, Maria Eugenia; Calixte, Christopher; Calon, Frederic; Cameron, Briana; Campbell, Roy; Lopez, Jose Antonio Campos; Cao, Hongliu; Cao, Jiguo; Cao, Guanqun; Cao, Bo; Capizzano, Aristides; Capon, Daniel; Carmasin, Jeremy; Carmichael, Owen; Carr, Sarah; Carrier, Jason; Carter, Greg; Carvalho, Luis; Carvalho, Janessa; Carvalho, Carolina; Casamitjana, Adrià; Casanova, Ramon; Casas, Josep R.; Cash, David; Castelluccio, Pete; Castiglioni, Isabella; Caswell, Carrie; Cattell, Liam; Cauda, Franco; Cepeda, Ileana; Çevik, Alper; Cha, Jungho; Chakrabarti, Shreya; Chakraborty, Shouvik; Chammam, Takwa; Chan, Christina; Chand, Ganesh; Chang, Catie; Chang, Yu-Ming; Chang, Rui; Chang, Hyunggi; Chang, Yu-Chuan; Chang, Ki Jung; Chang, Che-Wei; Chantrel, Steeve; Chao, Justin; Chao, Linda; Chapleau, Marianne; Charil, Arnaud; Chatterjee, Pratishtha; Chatterjee, Sambit; Chaudhry, Zainab; Chauhan, Harmanpreet; Chehade, Abdallah; Chekuri, Omkar; Cheloshkina, Kseniia; Chen, Jianhong; Chen, Gang; Chen, Geng; Chen, Ting-Huei; Chen, Yin Jie; Chen, Xi; Chen, Tzu-Chieh; Chen, Guojun; Chen, Shuzhong; Chen, Jerome; Chen, Fang; Chen, Kaifeng; Chen, Gennan; Chen, Jason; Chen, Guanhua; Chen, Ying-Hsiang; Chen, Ming-Hui; Chen, Chenbingyao; Chen, S. Y.; Chen, Hsu-Hsin; Chen, Xing; Chen, Kewei; Chen, Yuhan; Chen, Hugo; Chen, Rong; Chen, Ing-jou; Chen, Jun; Chen, Jean; Chen, Bo; Cheng, Danni; Cheng, Hewei; Cheng, Yong; Cheng, Yang; Cheng, Zhang; Cheng, Wai Ho; Chenhall, Tanya; Chepkoech, Joy-Loi; Cherukuri, Venkateswararao; Chhibber, Aparna; Chi, Haoyuan; Chi, Chih-Lin; Chiang, Gloria; Chiesa, Patrizia; Childress, Daniel Micah; Chilukuri, Yogitha; Fatt, Cherise Chin; Chincarini, Andrea; Ching, Christopher; Chiotis, Konstantinos; Cho, Soo Hyun; Cho, Yongrae; Cho, Sooyun; Choi, Jun-Sik; Choi, Hongyoon; Choi, Yeoreum; Choi, Sophia; Choi, Jaesik; Choi, Euna; Choo, I. L. Han; Chopra, Vishal; Chougrad, Hiba; Chouraki, Vincent; Christini, Amanda; Chu, Yufang; Chuang, Tzu-Chao; Chuanji, Luo; Chuanjian, Yu; Chun, Marvin; Chun, Sung; Chung, Ai; Chung, Yu-Min; Chung, Jung-Che; Chung, Ai Wern; Chung, Jaeeun; Chyzhyk, Darya; Ciarleglio, Adam; Cioli, Claudia; Cittanti, Corrado; Cives, Ana; Clark, Marissa; Clayton, David; Clement, Mark; Clifft, Daniel; Climer, Sharlee; Clouston, Sean; Clunie, David; Cohen, Phoebe; Cohen, Taco; Cole, Michael; Cole, James; Colletti, Patrick; Collingwood, Joanna; Comley, Robert; Conklin, Bryan; Conner, Lindsay; Conover, Joanne; Contardo-Berning, Ivona; Conway, Ronan; Copani, Agata; Coppola, Giovanni; Corbett, Syl; Corlier, Fabian; Correia, Rui; Cosman, Joshua; Costantino, Sebastian; Coubard, Olivier; Coulson, Elizabeth; Couser, Elizabeth; Cox, Kris; Coyle, Patrick; Cozzi, Brian; Craddock, Cameron; Crawford, Karen; Creese, Byron; Cribben, Ivor; Crisostomo-Wynne, Theodore; Crossley, Nicolas; Croteau, Etienne; Cruchaga, Carlos; Cuajungco, Math; Cui, Jing; Cui, Sue; Cullen, Nicholas; Cuneo, Daniel; Cutanda, Vicente; Cynader, Max; Binu, D.; D'Avossa, Giovanni; Dai, Tian; Dai, Peng; Dai, Hui; Davied Hong, Daivied Hong; Dakovic, Marko; Dalca, Adrian; Damiani, Stefano; Dammak, Mouna; Damoiseaux, Jessica; Dan, Zou; Dang, Xuan Hong; Dang, Shilpa; Daniel, Zinkert; Danjou, Fabrice; Darby, Eveleen; Darby, Ryan; Dardzinska, Agnieszka; Darst, Burcu; Darvesh, Sultan; Das, Kalyan; Das, Devsmita; Das, Sandhitsu; Das, Dulumani; Datta, Shounak; Dauvillier, Jérôme; Davatzikos, Christos; Davidson, Ian; de Boer, Renske; de Bruijne, Marleen; de Buhan, Maya; de Jager, Philip; de La Concha Vega, Nuño; de Lange, Siemon; de Luis Garcia, Rodrigo; de Marco, Matteo; de Sitter, Alexandra; Dean, Scott; Decarli, Charles; Decker, Summer; del Gaizo, John; Demir, Zeynep; Denby, Charles; Deng, Yanjia; Deng, Wanyu; Denisova, Kristina; Denney, William; Depue, Brendan; DeRamus, Thomas; Desikan, Rahul; Desplats, Paula; Desrosiers, Christian; Devadas, Vivek; Devanarayan, Viswanath; Devarajan, Sridharan; Devenyi, Gabriel; Dezhina, Zalina; Dhami, Devendra; Dharsee, Moyez; Dhillon, Permesh; Di, Xin; Di Mauro, Nicola; Diah, Kimberly; Diamond, Sara; Diaz-Asper, Catherine; Diciotti, Stefano; Dickerson, Bradford; Dickie, David Alexander; Dickinson, Philip; Dicks, Ellen; Diedrich, Karl; Dieumegarde, Louis; Dill, Vanderson; Dilliott, Allison; Ding, Zhaohua; Ding, Shanshan; Ding, Yanhui; Ding, Xiuhua; Ding, Xuemei; Dinov, Ivo; Dinu, Valentin; Diouf, Ibrahima; Dmitriev, Phillip; Dobromyslin, Vitaly; Dodge, Hiroko; Dolui, Sudipto; Dona, Olga; Dondelinger, Frank; Dong, Wen; Dong, Hao-Ming; Kehoe, Patricio Donnelly; Donohue, Michael; Dore, Vincent; Dougherty, Chase; Doughty, Mitchell; Dowling, N. Maritza; Doyle, Senan; Doyle, Andrew; Dragan, Matthew; Draganski, Bogdan; Draghici, Sorin; Dragomir, Andrei; Drake, Derek; Drake, Erin; Drd, Shilpa; Dronkers, Nina; Drozdowski, Madelyn; Du, Changde; Du, Yuhui; Du, Lei; Du, Guangwei; Du, Xingqi; Duan, Fang; Duan, Yuzhuo; Duan, Kuaikuai; Duchesne, Simon; Duggento, Andrea; Dukart, Juergen; Dumont, Matthieu; Dunn, Ruth; Duong, Vu; Duraisamy, Baskar; Duran, Tugce; Durrleman, Stanley; Dutta, Joyita; Dyrba, Martin; Dyvorne, Hadrien; R, Amulya E.; Eads, Jennifer; Eastman, Jennifer; Eaton, Susan; Edlund, Christopher; Edmonds, Emily; Edmondson, Mackenzie; Ehsan, Fatima; El-Gabalawy, Fady; Elander, Annie; Elango, Vidhya E.; Eldeeb, Ghaidaa; Elgamal, Fatmaelzahraa; Rodrigues, Yuri Elias; Elman, Jeremy; Elrakaiby, Nada; Emahazion, Tesfai; Emami, Behnaz; Embrechts, Jurriën; Emran Khan Emon, Mohammad Asif; Emrani, Saba; Emrani, Asieh; Emri, Miklós; Engelhardt, Barbara; Engle, Bob; Epstein, Noam; Er, Fusun; Erhardt, Erik; Eriksson, Oscar; Omay, Zeynep Erson; Escudero, Javier; Eshleman, Jason; Eskildsen, Simon; Espinosa, Luis; Essex, Ryan; Esteban, Oscar; Estrada, Karol; Ethell, Douglas; Ethridge, Kimberly; Ettehadi, Seyedrohollah; Eva, Bouguen; Evenden, Dave; Evtikheeve, Rina; Ewert, Siobhan; Fague, Scot; Fahmi, Rachid; Faizal, Sherin; Falahati, Farshad; Fan, Li; Fan, Zhen; Fan, Yong; Fan, Maohua; Fan, Yonghui; Fan, Sili; Fan, Ruzong; Fang, Chen; Fang, Xiaoling; Fanjul-Vélez, Félix; Fanti, Alessandro; Far, Bab; Farah, Martha; Farahani, Naemeh; Farahibozorg, Seyedehrezvan; Farahnak, Farhood; Farajpour, Maryam; Fardo, David; Farkhani, Sadaf; Farnsworth, Bryn; Farooq, Hamza; Farooq, Ammarah; Farouk, Yasmeen; Farrar, Danielle; Farrer, Lindsay; Fatemehh, Fatemeh; Fatemizadeh, Emad; Fatfat, Kim; Fatima, Shizza; Faux, Noel; Favan-Niven, Anne; Favary, Clélia; Fazlollahi, Amir; Fei, Gao; Feingold, Franklin; Feizi, Soheil; Félix, Eloy; Femminella, Grazia Daniela; Feng, Zijun; Feng, Ao; Feng, Brad; Feng, Xinyang; Feragen, Aasa; Fereidouni, Marzieh; Fernandes, Miguel; Fernández, Víctor; Ferrari, Ricardo; Ferraris, Sebastiano; Ferreira, Francisco; Ferreira, Luiz Kobuti; Ferreira, Hugo; Fiecas, Mark; Fieremans, Els; Fiford, Cassidy; Figurski, Michal; Filippi, Massimo; Filshtein, Teresa; Findley, Caleigh; Finger, Elizabeth; Firth, Nicholas; Fischer, Christopher; Fischer, Florian; Fitall, Simon; Fleet, Blair; Fleishman, Greg; Flokas, Lambros; Flores, Alberto; Focke, Niels; Fok, Wai Yan; Foldi, Nancy; Fôlego, Guilherme; Forero, Aura; Fornage, Myriam; Fos Guarinos, Belén; Founshtein, Gregory; Franc, Benjamin; Francois, Clement; Franke, Katja; Fraser, Mark; Frasier, Mark; Frederick, Blaise; Freitas, Fernandho; Escalin, Frency Jj; Freudenberg-Hua, Yun; Friedman, Brad; Friedmann, Theodore; Friedrich, Christoph M.; Frings, Lars; Frisoni, Giovanni; Fritzsche, Klaus; Frolov, Alexander; Frost, Robert; Fu, Ling; Fu, Zening; Fudao, Ke; Fuentes, Emmanuel; Fujishima, Motonobu; Fujiwara, Ken; Fukami, Tadanori; Funk, Cory; Furcila, Diana; Fuselier, Jessica; Nagarjuna Reddy, G.; Gaasterland, Terry; Gabelle, Audrey; Gahm, Jin; Gaiteri, Chris; Gajawelli, Niharika; Galantino, Alexis; Galarza Hernández, Javier; Galasko, Douglas; Galea, Liisa; Galisot, Gaetan; Sánchez, Antonio Javier Gallego; Gallins, Paul; Gamberger, Dragan; Gan, Hong Seng; Gan, Gavin; Ganapathi, Subha; Gancayco, Christina; Gangishetti, Umesh; Ganzetti, Marco; Gao, Fei; Gao, Jingjing; Gao, Linlin; Gao, Tianxiang; Gao, Yuanyuan; Gao, Xiaohong; Garani, Ranjini; Garbarino, Sara; Garcia, Ivan; Garcia, Xiadnai; Garcia, Jorge; Garcia, Tanya; Garcia Arias, Hernan Felipe; de La Garza, Angel Garcia; Gaig, Mireia Garcia; Novoa, Jorge Garcia; Valero, Mar Garcia; Garcia-Ojalvo, Jord; García-Polo, Pablo; Garg, Rahul; Garg, Gaurav; Garg, Divya; Garibotto, Valentina; Garvey, Matthew; Garza-Villarreal, Eduardo; Gaubert, Malo; Gauthier, Serge; Gavett, Brandon; Gavidia, Giovana; Gavtash, Barzin; Gawryluk, Jodie; Gbah, Messon; Ge, Tian; Geerts, Hugo; Geisser, Niklaus; Geng, Junxian; Gentili, Claudio; Gess, Felix; Ghaderi, Halleh; Ghahari, Shabnam; Ghanbari, Yaghoob; Ghazi-Saidi, Ladan; Ghodrati, Mojgan; Ghorbani, Behnaz; Ghoreishiamiri, Reyhaneh; Ghosal, Sayan; Ghosh, Sukanta; Ghosh, Saheb; Ghosh, Sreya; Ghoshal, Ankur; Giannicola, Galetta; Gibert, Karina; Gibson, Gary; Gieschke, Ronald; Gil Valencia, Jorge Mario; Gillen, Daniel; Giordani, Alessandro; Giraldo, Diana; Gispert, Juan D.; Gitelman, Darren; Giuffrida, Mario Valerio; Madhu, G. K.; Glass, Jesse; Glazier, Brad; Gleason, Carey; Glerean, Enrico; Glozman, Tanya; Godbey, Michael; Goettlich, Martin; Gogoi, Minakshi; Gola, Kelly; Golbabaei, Soroosh; Golden, Daniel; Goldstein, Felicia; Gomes, Carlos; de Olivera, Ramon Gomes Durães; Gomez, Isabel; Gomez Gonzalez, Juan Pablo; Gomez-Verdejo, Vanessa; Gong, Weikang; Gong, Enhao; Gong, Kuang; Gonneaud, Julie; Gonzalez, Clio; Gonzalez, Evelio; Gonzalez, Gerardo; Moreira, Eduardo Gonzalez; Goodman, James; Gopinath, Srinath; Gopu, Anusharani; Gordon, Brian; Gordon, David; Gordon, Mark; Gorriz, Juan Manuel; Gors, Dorothy; Göttler, Jens; Gounari, Xanthippi; Goyal, Devendra; Graf, John; Graff, Ariel; Graham, Leah; Graham, Jinko; Grajski, Kamil; Grami, Maziyar; Grand'Maison, Marilyn; Grant, Kiran; Grassi, Elena; Gray, Katherine; Grecchi, Elisabetta; Green, Robert; Green, Elaine; Greenberg, Jonathan; Greening, Steven; Greenwood, Bryson; Gregori, Johannes; Gregory, Michael; Greicius, Michael; Greve, Douglas; Griffin, Jason; Grill, Joshua; Grodner, Kelsey; Grolmusz, Vince; Groot, Perry; Groothuis, Irme; Gross, Alden; Grundstad, Arne; Grundy, Edward; Grzegorczyk, Tomasz; Nandith, G. S.; Gu, David; Gu, Jiena; Gu, Yun; Gu, Ginam; Guan, Sheng; Guan, Yuanfang; Guennel, Tobias; Guerin, Laurent; Guerrero, Ricardo; Guerrier, Laura; Guevara, Pamela; Guggari, Shankru; Roy, Abhijit Guha; Guidotti, Roberto; Guillon, Jérémy; Gulcher, Jeff; Gulia, Sarita; Gumedze, Freedom; Gunawardena, Nishan; Gunn, Roger; Guo, Michael; Guo, Xiao; Guo, Xingzhi; Guo, Yi; Kai, Zhang Guo; Zhao, Ma Guo; Gupta, Navin; Gupta, Anubha; Gupta, Ishaan; Guren, Onan; Gurnani, Ashita; Gurol, Mahmut Edip; Guzman, Gloria; Gyy, Gyy; Rajanna, Vanamala H.; Ha, Seongwook; Haacke, Ewart; Haaksma, Miriam; Habadi, Maryam; Habeck, Christian; Habes, Mohamad; Hackspiel Zarate, Maria Mercedes; Hadimani, Ravi; Hahn, William; Hahn, Tim; Haight, Thaddeus; Hair, Nicole; Haixing, Wang; Hajarolasvadi, Noushin; Hajjar, Ihab; Hajjo, Rima; Halchenko, Yaroslav; Hall, Anette; Hallock, Kevin; Hamdi, Shah Muhammad; Hameed, Farhan; Hamidian, Hajar; Han, Dong; Han, Yang; Han, Hio-Been; Han, Qingchang; Han, Beomsoo; Han, Duke; Han, Shizhong; Han, Xiaoxia; Han, Peipei; Han, Joo Yoon; Han, Dong-Sig; Handsaker, Robert; Hanna-Pladdy, Brenda; Hanseeuw, Bernard; Hansson, Björn; Hao, Yang; Hao, Jhon; Happ, Clara; Harischandra, Dilshan; Haritaoglu, Esin; Harris, Richard; Harris, Breanna; Hart, Brian; Hartzell, James; Harvey, Danielle; Hashimoto, Tsuyoshi; Hasooni, Hossein; Hassan, Moaied; Hassan, Mehdi; Hassanzadeh, Hamid Reza; Hassanzadeh, Oktie; Hatton, Sean; Hawchar, Jinan; Hayashi, Toshihiro; Hayashi, Norio; Hayes, Jasmeet; Hayete, Boris; Haynor, David; He, Linchen; He, Yan; He, Yao; He, Huiguang; Heegaard, Niels; Hefny, Mohamed; Heil, Julius; Heindel, William; Henderson, Samuel; Henf, Judith; Henriquez, Claudio; Herholz, Karl; Hermessi, Haithem; Hernandez, Monica; Herrera, Luis; Hibar, Derrek; Hidane, Moncef; Higuchi, Satomi; Hind, Jade; Hives, Florent; Hoang, Mimi; Hobel, Zachary; Hoffman, John; Hofmeister, Jeremy; Hohman, Timothy; Holder, Daniel; Holguin, Jess; Holmes, Robin; Hong, John; Hongliang, Zou; Hongyu, Guo; Hopkins, Paul; Hor, Soheil; Hornbeck, Russ; Horng, Andy; Horton, Wesley; Hosny, Khalid; Hosseini, Eghbal; Hosseini, Hadi; Hosseini, Zahra; Asl, Ehsan Hosseini; Hou, Beibei; Houghton, Richard; Houghton, Katherine; Householder, Erin; Howlett, James; Hsiao, John; Hsiao, Ing-Tsung; Hsu, Chih-Chin; Hu, Xixi; Hu, Lingjing; Hu, Nan; Hu, Kun; Hu, Tao; Hu, Li; Hu, Xiaolan; Hua, Fei; Huang, Marissa; Huang, Qi; Huang, Michelle; Huang, Chao; Huang, JunMing; Huang, Xingyuan; Huang, Yuhan; Huang, Sing-Hang; Huang, Shuai; Huang, Peiyu; Huang, Chun-Chao; Huang, Zhiyue; Huang, Meiyan; Huang, Zhiwen; Hubrich, Markus; Huestis, Michael; Huey, Edward; Hufton, Andrew; Huijbers, Willem; Huisman, Sjoerd; Hung, Joe; Hunsaker, Naomi; Hunt, Fostor; Huppertz, Hans-Jürgen; Huser, Vojtech; Hussain, Lal; Hutchison, R. Matthew; Hutton, Alexandre; Huyck, Els; Hwang, Jihye; Hyun, JungMoon; Iakovakis, Dimitris; Ibañez, Victoria; Ide, Kayoko; Igarashi, Takuma; Iglesias, Juan Eugenio; Muñoz, Laura Igual; Iidaka, Tetsuya; Ikeuchi, Takeshi; Ikhena, John; Ikuta, Toshikazu; Im, Hyung-Jun; Insausti, Ana; Insel, Philip; Invernizzi, Azzurra; Iosif, Ana-Maria; Ip, Nancy; Irizarry, Sierra; Irmak, Emrah; Irwin, David; Isaza, Mariano; Ishii, Makoto; Ishii, Kenji; Islam, Jyoti; Israel, Ariel; Isufi, Elvin; Ito, Kaori; Ito, Masato; Izquierdo, Walter; Alphin, J.; Akhila, J. A.; Jaberzadeh, Amir; Jackowiak, Edward; Jackson, Eric; Jackson, Chris; Jackson, Jonathan; Jacob, Samson; Jacobsen, Nina; Jacobsen, Jörn; Jacquemont, Thomas; Jacques, Nerline; Jaeger, Ralf; Jafari, Tahere; Jafari-Khouzani, Kourosh; Jagadish, Akshay Kumar; Jagtap, Priti; Jagust, William; Jahr, Joseph; Jain, Shubhankar; Jain, Shubham; Jaiswal, Ayush; Jaiswal, Akshay; Jait, Amine; Jakkoju, Chetan; Jakobsson, Andreas; James, Olga; James, Oliver; Jamlai, Maedeh; Jammeh, Emmanuel; Janardhana, Lajavanthi; Jang, Jinseong; Jang, Jae-Won; Jang, Jinhee; Jang, Hyesue; Janghel, Rekh Ram; Jawahar, Shasvat; Jean, Kharne; Jean-Baptiste, Schiratti; Jedynak, Bruno; Jefferson, Angela; Jennings, Danna; Jennings, Dominique; Jeon, Seun; Jeong, Yong; Jester, Charles; Jethwa, Ketan; Jha, Debesh; Ji, Gong-Jun; Ji, Chong; Ji, Jin; Jia, Bowen; Jiacheng, Lee; Jiajia, Guo; Jian, Weijian; Jiang, Shan; Jiang, Chunxiang; Jianhua, Gao; Jiao, Zhuqing; Jiao, Zeyu; Jiao, Du; Jimenez Alaniz, Juan Ramon; Gomez, Carolina Jimenez; Jiménez-Huete, Adolfo; Jimura, Koji; Jin, Yan; Jin, Zhu; Jogia, Jigar; Johansson, Per; John, Kimberley; Johnsen, Stian; Johnson, Leonard; Johnson, Sterling; Johnson, Kent; Johnston, Jane; Johnston, Stephen; Jomeiri, Alireza; Jonas, Katherine; Jones, Richard; Jones-Davis, Dorothy; Jönsson, Linus; Joseph, Jane; Joshi, Himanshu; Joshi, Shantanu; Joshi, Abhinay; Joyce, Katherine; Juengling, Freimut; Jung, Youngjin; Junker, Viv; Junwei, Ding; Jyothi, Singaraju; Jyotiyana, Monika; Sarthaj, K.; Kachouane, Mouloud; Kadian, Amit; Kaewaramsri, Yothin; Kaicheng, Li; Kaiser, Marcus; Kakinami, Lisa; Kalra, Sanjay; Kam, Hye Jin; Kamarudin, Nur Shazwani; Kaminker, Josh; Kandel, Benjamin; Kandiah, Nagaendran; Kaneko, Tomoki; Kang, Yun Seok; Kang, Ju Hee; Kang, Hakmook; Kang, Jian; Kansal, Anuraag; Kaouache, Mohammed; Kaplan, Adam; Kottaram, Akhil Karazhma; Karim, Faizan; Karimi-Mostowfi, Nicki; Karjoo, Mahboobe; Karlin, Daniel; Karp, Juliana; Karray, Chiheb; Kartsonis, Nick; Karu, Naama; Kasa, Jaya; Kasiri, Keyvan; Katako, Audrey; Kato, Ryo; Katsonis, Panagiotis; Katti, Hkkatti; Kaur, Prabhjot; Kauwe, John; Kawaguchi, Atsushi; Kazemi, Samaneh; Kazemi, Yosra; Rijan, K. C.; Kechin, Andrey; Kelkhoff, Douglas; Kelleher, Thomas; Kellner-Weldon, Frauke; Kennion, Oliver; Kerr, Daniel; Kesler, Shelli; Kesselman, Carl; Kessler, Daniel; Keuken, Max; Keyvanfard, Farzaneh; Khademi, April; Khajehnejad, Moein; Khan, Wasim; Khan, Tabrej; Khan, Hikmat; Khan, Anzalee; Khan, Samreen; Khanmohammadi, Sina; Khasanova, Tatiana; Khazaee, Ali; Khazan, Lenny; Kherif, Ferath; Khl, Aym; KHlif, Mohamed Salah; Khondoker, Mizanur; Khoo, Sok Kean; Khosrowabadi, Reza; Khurshid, Kiran; Kianfard, Reihaneh; Kida, Satoshi; Kiddle, Steven; Kikuchi, Masashi; Killiany, Ron; Kim, Jeongchul; Kim, Jong Hun; Kim, Hyunwoo; Kim, Jongin; Kim, Yeo Jin; Kim, Jung-Jae; Kim, Hang-Rai; Kim, Jaeyeol; Kim, Ki Hwan; Kim, Joseph; Kim, Younghoon; Kim, Mijung; Kim, Jeongsik; Kim, Bohyun; Kim, Taehyun; Kim, Heeyoung; Kim, Seonjik; Kim, Nakyoung; Kim, Byeongnam; Kim, ChanMi; Kim, Jeonghun; Kim, Seong Yoon; Kim, Sunhee; Kingery, Lisle; Kinnunen, Kirsi; Kinomes, Marie; Kirchner, Jan Hendrik; Caldwell, Jessica Kirkland; Kirwan, Brock; Kitamura, Chiemi; Kitty, Kitty; Kiviat, David; Kiyasova, Vera; Klein, Richard; Klein, Alison; Klein, Gregory; Klein, Jan; Kleinman, Aaron; Kling, Mitchel; Klinger, Joern; Klinger, Rebecca; Klink, Katharina; Kocaturk, Mustafa; Koch, Philipp Johannes; Kochova, Elena; Koenig, Loren; Koh, Natalie; Köhler, Jens Erik; Koikkalainen, Juha; Koini, Marisa; Kolachalama, Vijaya; Koncz, Rebecca; Kong, Xiang-Zhen; Kong, Vincent; Kong, Xiangzhen; Kong, Dehan; Kong, Linglong; Konukoglu, Ender; Kopeinigg, Daniel; Kopera, Krzysztof; Koppers, Simon; Korb, Matheus; Korfiatis, Panagiotis; Korolev, Igor; Korolev, Sergey; Korostyshevskiy, Valeriy; Koshiya, Heena; Kost, James; Kotari, Vikas; Koutra, Danai; Koychev, Ivan; Kruthika, K. R.; Krahnke, Tillmann; Krause, Matthew; Kraybill, Matt; Kriebel, Martin; Hari Krishna, M.; Krohn, Stephan; Kruggel, Frithjof; Kuceyeski, Amy; Kuhl, Donald; Kulshreshtha, Devang; Kumar, Santosh; Kumar, Sambath; Kumar, Kuldeep; Kumar, Anil; Kumar, Abhishek; Kumar, A.; Kumar, Saurabh; Kumar, Ashwani; Kumar, Ambar; Kumar, Dinesh; Kumar, Rishab; Kumarasinghe, Janaka; Kundu, Suprateek; Kung, Te-Han; Kuo, Li-Wei; Kuo, Phillip; Channappa, Usha Kuppe; Kuriakose, Elmy; Kurian, P.; Kwan, Kenneth; Kwasigroch, Arkadiusz; Kwon, Young Hye; Kyeong, Sunghyon; Fleur, Claire La; Wungo, Supriyadi La; Labbe, Tomas; Lacombe, Daniel; Lad, Meher; Lahoti, Geet; Lai, Ying Liang; Lai, Catherine; Lai, Dongbing; Laird, Dillon; Lakatos, Anita; Lam, Alice; Lama, Ramesh; Lambert, Christian; Landau, Susan; Landman, Bennett; Landre, Victor; Lane, Elizabeth; Lange, Catharina; Langenieux, Alexandre; Lareau, Caleb; Larson, Katelyn; Latif, Ghazanfar; Lauber, Ross; Lawliet, Z. H.; Lawrence, Emma; Lazar, Anca; Le, Ngan; Le, Thi Khuyen; Le, Matthieu; Guen, Yann Le; Scouiller, Stephanie Le; Leandrou, Stephanos; Leatherday, Christopher; Leavitt, Mackenzie; Ledbetter, Christina; Lee, Hyekyoung; Lee, Wook; Lee, Annie; Lee, Jaehong; Lee, Dongyoung; Lee, Joel; Lee, Song-Ting; Lee, Kuo-Jung; Lee, Subin; Lee, Jaeho; Lee, Catherine; Lee, Gyungtae; Lee, Suzee; Lee, Erik; Lee, Yunseong; Lee, Sang-Gil; Lee, Seonjoo; Lee, Peng Jung; Lee, Hyunna; Lee, Cheng-Hsien; Lee, Hengtong; Lee, Mi Ri; Lee, Ilgu; Lee, Qixiang; Lefterov, Iliya; Leger, Charlie; Lehallier, Benoit; Lei, B.; Lei, Shi; Lei, Hongxing; Lei, Haoyun; Leong, Tze Yun; Leong, Sharlene; Leoutsakos, Jeannie-Marie; Lepore, Natasha; Lerch, Ondrej; Leung, Yip Sang; Leung, Yuk Yee; Leung, Shuyu; Leung, Hoi-Chung; Leung, Ming-Ying; Levakov, Gidon; Levine, Abraham; Li, Chawn; Li, Miranda; Li, Huijie; Li, Junning; Li, Xiaofeng; Li, Yi; Li, Jinchao; Li, Tianhong; Li, Yongming; Li, Xiangrui; Li, Tieqiang; Li, Yan; Li, Fuhai; Li, Feijiang; Li, Shuyang; Li, Zhi; Li, Xing; Li, Rongjian; Li, Rui; Li, Y. U.; Li, Kang; Li, Zhenzhen; Li, Qingqin; Li, Wenjun; Li, Yang; Li, Jialu; Li, Guangyu; Li, Michelle; Li, Yibai; Li, Yupeng; Li, Tao; Li, Zhujun; Li, Yafen; Li, Muwei; Li, Xuan; Li, Yi-Ju; Li, Cen Sing; Li, X. W.; Li, Yingjie; Li, Lin; Li, Yihan Jessie; Li, Yaqing; Li, Xiantao; Li, Xingfeng; Li, Chenxi; Li, Chao; Li, Jicong; Li, Jiewei; Li, Tengfei; Li, Wei; Li, Xinzhong; Li, Nannan; Li, Chunfei; Li, Yeshu; Liang, Chen; Liang, Nanying; Liang, Jingjing; Liang, Shengxiang; Liang, Xiaoyun; Liang, Xia; Liang, Ying; Liberman, Sofia; Libon, David; Liébana, Sergio; Liedes, Hilkka; Lim, Wee Keong; Lim, Yen Ying; Lin, Yenching; Lin, Katherine; Lin, Ming; Lin, Ai-Ling; Lin, Ching-Heng; Lin, Bing; Lin, Lin; Lin, Jyh-Miin; Lin, W. M.; Lin, Chien-Tong; Lin, Liyan; Lin, Jing; Lindberg, Olof; Linesch, Paul; Linn, Kristin; Lippert, Christoph; Litovka, Nikita; Little, Graham; Liu, Man-Yun; Liu, Jin; Liu, Chin-Fu; Liu, Zhaowen; Liu, Eulanca; Liu, Weixiang; Liu, K. E.; Liu, Hao Chen; Liu, Jia; Liu, Richann; Liu, Dongbo; Liu, Victor; Liu, Wenjie; Liu, Tao; Liu, Xiaoli; Liu, Yong; Liu, Lin; Liu, Dan; Liu, Xiuwen; Liu, Mengmeng; Liu, Chia-Shang; Liu, Ying; Liu, Yan; Liu, Xueqing; Liu, Han; Liu, Chien-Liang; Liu, Sidong; Liu, Jundong; Liu, Yang; Liu, Tianming; Liu, Tingshan; Liu, Ning; Liu, Lan; Liuyu, Liuyu; Lizarraga, Gabriel; Llido, Jerome; Lobach, Iryna; Lockhart, Samuel; Loft, Henrik; Lohr, Kelly; Lon, Hoi Kei; Lone, Kashif Javed; Long, Ziyi; Long, Xiaojing; Longo, Frank; Alves, Isadora Lopes; Lopez, Guadalupe; Lorenzi, Marco; Lotan, Eyal; Louie, Gregory; Louis, Maxime; Loukas, Andreas; Love, Seth; Lowe, Deborah; Lu, Bin; Lu, Chia-Feng; Lu, Zixiang; Lu, Lijun; Lu, Pascal; Lu, Shen; Lu, Qing; Lu, Zheshen; Lu, Chuan; Lu, Patty; Lu, Hangquan; Lu, Bo; Luktuke, Yadnyesh; Luo, Wei; Luo, Suhuai; Luo, Sheng; Luo, Shaojun; Luo, Peggy; Luo, Shan; Luo, Weidong; Luo, Liao; Luo, Xiao; Lupton, Michelle; Lutz, Michael; Lv, Eric; Lyu, Juan; Angshul, M.; Radha, M. R.; Dinesh, M. S.; Ma, Xiangyu; Ma, Chao; Ma, Li; Ma, Yu; Ma, Qianli; MacArthur, Daniel; Macey, Paul; Mach, Eric; MacPhee, Imola; Madadi, Mahboubeh; Madan, Christopher; Madan, Bharat; Madero, Giovanny; Madhavan, Radhika; Madhyastha, Tara; Maeno, Nobuhisa; Magsood, Hamzah; Mah, Linda; Mahdavi, Shirin; Mahdavi, Asef; Mahmoud, Abeer; Mahmoud, Hentati; Mahmoud, Kariman; Mahmoudi, Ahmad; Dehkordi, Siamak Mahmoudian; Mahor, Monika; Mahseredjian, Taleen; Mai, Cha; Maia, Rui; Maiti, Taps; Maj, Carlo; Maji, Pradipta; Majidpour, Jafar; Makhlouf, Laouchedi; Makino, Satoshi; Makrievski, Stefan; Makse, Hernan; Malagi, Archana; Malakhova, Katerina; Malamon, John; Malashenkova, Irina; Malchano, Zach; Maleki-Balajoo, Somayeh; Malik, Sadia; Malik, Tamoor; Mallik, Abhirup; Malm, Tarja; Malpas, Charles; Malpica, Norberto; Malviya, Meenakshi; Mamandi, A.; Manandhar, Abinash; Mandal, Pravat; Mandali, Alekhya; Mane, Prajakta; Manning, Emily; Manoufali, Mohamed; Manser, Paul; Mantini, Dante; Mantri, Ninad; Manyakov, Nikolay; Manzak, Dİlek; Mao, Shuai; Maoyu, Tian; Maple Grødem, Jodi; Maravilla, Kenneth; Marco, Simonetti; Marcus, Daniel; Margetis, John; Margolin, Richard; Mariano, Laura; Marinescu, Razvan Valentin; Markett, Sebastian; Markiewicz, Pawel; Marnane, Michael; Maroof, Asif; Marple, Laura; Marques, Cristiane; Marrakchi, Linda; Marshall, Gad; Märtens, Kaspar; Mårtensson, Gustav; Marti, Cristian; Martin, Harold; Martinaud, Olivier; Martinez, Victor; Martinez, Oliver; Martinez, Jesus; Martinez, Carlos; Abadías, Neus Martinez; Torteya, Antonio Martinez; Martini, Jean-Baptiste; Martins, Samuel; Masciotra, Viviane; Masmoudi, Ahmed; Masny, Aliaksandr; Shah, Pir Masoom; Massaro, Tyler; Masumoto, Jun; Matan, Cristy; Mate, Karen; Mateus, Pedro; Mather, Mara; Mather, Karen; Mathew, Jesia; Mathias, Samuel; Mathiyalagan, Tamilalaghan; Matloff, Will; Matsubara, Keisuke; Matsubara, Takashi; Matsuda, Yukihisa; Matthews, Dawn; Mattis, Paul; May, Patrick; Mayburd, Anatoly; Mayo, Chantel; Mayordomo, Elvira; Mbuyi, Gaylord; McCallum, Colleen; McCann, Bryony; McCollough, Todd; McCormick, Shannon; McCurdy, Sean; McDonald, Carrie; McEligot, Archana; McEvoy, Linda; McGeown, William; McGinnis, Scott; McHugh, Thomas; McIntosh, Elissa; McIntosh, Randy; McKenzie, Andrew; McLaren, Donald; McMillan, Corey; McMillan, Alan; McPherson, Brent; McRae-McKee, Kevin; Zaini, Muhammad Hafiz Md; Meadowcroft, Mark; Mecca, Adam; Meda, Shashwath; Medikonda, Venkata Srinu; Meeker, Karin; Megherbi, Thinhinane; Mehmood, Anum; Mehrtash, Alireza; Meiberth, Dix; Meier, Dominik; Meijerman, Antoine; Mejia, Jose; Mekkayil, Lasitha; Meles, Sanne; Melie-Garcia, Lester; Melo, Hans; Melrose, Rebecca; Melzer, Corina; Mendes, Aline; Leon, Ricardo Antonio Mendoza; Gonzalez, Manuel Menendez; Meng, Dewen; Meng, Xianglai; Meng, Guilin; Mengel, David; Menon, Ramesh; Menon, Ravi; Mercado, Flavio; Messick, Viviana; Meyer, Pierre-Francois; Meyer, Carsten; Mezher, Adam; Mi, Liang; Miao, Hongyu; Michailovich, Oleg; Michels, Lars; Mickael, Guedj; Mikhail, Mark; Mikhno, Arthur; Milana, Diletta; Miller, Rachel; Miller, Brendan; Millikin, Colleen; Min, Byung Wook; Minadakis, George; Minghui, Hu; Chinh, Truong Minh; Minkova, Lora; Miranda, Michelle; Misevic, Dusan; Mishra, Amit; Mishra, Chetan; Mishra, Shiwangi; Mishra, Ashutosh; Mishra, Krishna; Misquitta, Karen; Mitchell, Brian; Mithawala, Keyur; Mitnitski, Arnold; Mitra, Sinjini; Mittal, Gaurav; Mittner, Matthias; Miyapuram, Krishna Prasad; Mlalazi, Rebaone; Mo, Daojun; Moghekar, Abhay; Moguilner, Sebastian; Moh, Heba; Mohabir, Mark; Mohajer, Bahram; Mohamed, Moataz; Mohammadi, Sadeq; Mohammadi-Nejad, Ali-Reza; Mohammady, Saed; Taqi, Arwa Mohammed; Mohan, Kishore Kumar; Mohy-Ud-Din, Hassan; Moitra, Dipanjan; Mojaradi, Mehdi; Mojtabavi, Alireza; Molina, Helena; Mollon, Jennifer; Molteni, Erika; Montajabi, Mohaddeseh; Montal, Victor; Montazami, Aram; Monté-Rubio, Gemma; Montembeault, Maxime; Montero-Odasso, Manuel; Montillo, Albert; Moon, Byung-Seung; Moon, Chan; Moon, Chooza; Moore, Archer; Morabito, Francesco C.; Moradi, Masoud; Moraes, Renato; Ballesteros, Orlando Morales; Morales-Henriquez, Daniela; Moratal, David; Moreno, Herman; Morihara, Ryuta; Mormino, Elizabeth; Morris, Jeffrey; Mortamet, Bénédicte; Morton, John; Moscato, Pablo; Rial, Alexis Moscoso; Mossa, Abdela Ahmed; Mottaghi, Setare; Mouelhi, Aymen; Moussavi, Arezou; Moustafa, Ahmed; Mowrey, Wenzhu; Mtetwa, Lungile; Muehlboeck, Sebastian; Mueller, Susanne; Mueller-Sarnowski, Felix; Mufidah, Ratna; Mukherjee, Rik; Mukherjee, Shubhabrata; Müller, Christian; Müller, Hans-Peter; Mullins, Paul; Mullins, Roger; Muncy, Nathan; Munir, Akhtar; Munirathinam, Ramesh; Munoz, David; Munro, Catherine; Muranevici, Gabriela; Rendon, Santiago Murillo; Murilo, Robson; Murphy, Sonya; Muscio, Cristina; Musso, Gabriel; Mustafa, Yasser; Myall, Daniel; Gayathri, N.; Nabavi, Shahab; Nabeel, Eman; Nagele, Robert; Naghshbandi, Hane; Naik, Shruti; Najmitabrizi, Neda; Nakawah, Mohammad Obadah; Nalls, Mike; Namboori, Krishnan; Nancy, Annie; Napolitano, Giulio; Narayan, Manjari; Narkhede, Atul; Naseri, Mahsa; Nasrallah, Ilya; Nasrallah, Fatima; Nassif, Rana; Nath, Sruthi R.; Nathoo, Farouk; Nation, Daniel; Naughton, Brian; Nault, Larry; Nautiyal, Deeksha; Nayak, Deepak Ranjan; Naz, Mufassra; Nazemian, Shayan; Nazeri, Arash; Neckoska, Emilija; Neelamegam, Malinee; Nehary, Ebrahim; Nelson, Peter; Nelson, Linda; Nematzadeh, Hosein; Nerur, Shubha; Nesteruk, Thomas; Neu, Scott; Ng, Yen-Bee; Nguyen, Tin; Nguyen, Thanh; Nguyen, Harrison; Nguyen, Nghi; Trung, Hieu Nguyen; Ni, Lucy; Nian, Yongjian; Nichols, Thomas; Nicodemus, Kristin; Nie, Yunlong; Nielsen, Casper; Nikolov, Robert; Nila, Jessica; Nishioka, Christopher; Njeh, Ines; Njie, Emalick; Nobakht, Samaneh; Noble, Andrew; Noda, Art; Noroozi, Ali; Norton, Derek; Nosarti, Chiara; Nosheny, Rachel; Notsu, Akifumi; Novak, Gerald; Nozadi, Seyed Hossein; Nu, Fen; Nudelman, Kelly; Nunes, Adonay; Nunes, Ana; Núñez, Christian; Nuno, Michelle; Nuriel, Tal; Nygaard, Haakon; Nyquist, Paul; O'Bott, Jacob; O'Charoen, Sirimon; O'Neill, William; O'Rawe, Jonathan; Obrzut, Grzegorz; Och, Ganzorig; Odaibo, David; Odry, Benjamin; Oehmichen, Axel; Ofori, Edward; Ogunsanmi, Abdulfatai; Oguz, Kaya; Oh, Jungsu; Oh, Minyoung; Oh, Hwamee; Ohigashi, Hironori; Oishi, Kenichi; Oishi, Naoya; Okhravi, Hamid; Okonkwo, Ozioma; Okyay, Savaş; Oliveira, Cyrill; Oliveira, João; Oliveira, Francisco; Oliver, Ruth; Olmos, Salvador; Olszowy, Wiktor; Oltra-Cucarella, Javier; Önen, Zehra; Ong, Rowena; Onoda, Keiichi; Onyike, Chiadi; Operto, Grégory; Oppedal, Ketil; Orejuela, Juan; Orhon, Atila; Orozco, Max; Ortuño, Juan; Osadebey, Michael; Osborn, Joseph; Osoba, Osonde; Ostadrahimi, Hamid; Ostovari, Parisa; Otis, Sarah; Overgaard, Shauna; Owen, Catrin Elin; Oxtoby, Neil; Öziç, Muhammet Üsame; Ozkaya, Gorkem; Okur, Ozlem Ozmen; Ozsolak, Fatih; Ozyildirim, Melis; Pa, Judy; Pacheco, Joe; Pack, Gary; Padilla, Daniel; Cerezo, Berizohar Padilla; Padovese, Bruno; Pae, Chongwon; Pagano, Gennaro; Pahuja, Gunjan; Pai, Shraddha; Pajavand, Shahryar; Pajula, Juha; Pak, Kyoungjune; Pakzad, Ashkan; Palaniappan, Mathiyalagan; Palanisamy, Sindhu; Palmqvist, Sebastian; Palsson, Frosti; Pan, Dan; Pan, Tiffany; Pan, Yuqing; Pan, Wei; Pan, Sun; Pan, Hongliang; Pan, Xiaoxi; Pandey, Lokesh; Pang, Qiaoyu; Pangilinan, Erin; Pannetier, Nicolas; Panpan, Xu; Panyavaraporn, Jantana; Pardini, Matteo; Paredes, José; Parikh, Jignesh; Park, Seongbeom; Park, Young Ho; Park, Min Tae; Park, Hyunjin; Park, Sejin; Park, JongSeong; Park, DooHyun; Park, Ji Eun; Park, Yuhyun; Park, Jiyong; Parker, Jason; Parker, Richard; Parodi, Alice; Bautista, Yohn Jairo Parra; Parrish, Marcus; Parthiban, Preethy; Pascariello, Guido; Pascual, Belen; Paskov, Hristo; Pasquini, Lorenzo; Tantaleán, Julio Sergio Eduardo Pastor; Pastur, Lucas; Patel, Raihaan; Patel, Sejal; Paterson, Ross; Paton, Bryan; Patriarche, Julia; Patriat, Rémi; Pattichis, Constantinos; Paul, Debashis; Pawar, Kuldeep; Pawlak, Mikolaj; Paz, Rotem; Pedroto, Maria; Pelekanos, Matthew; Péléraux, Annick; Peng, Dan; Peng, Jing; Pengfei, Tian; Perani, Daniela; Peraza, Luis; Pereira, Fabricio; Pereira, Francisco; Perkins, Diana; Perneczky, Robert; Persad, Umesh; Peter, Jessica; Peters, Mette; Peters, Ruth; Pether, Mark; Petrella, Jeffrey; Petrenko, Roman; Petrone, Paula; Petrov, Dmitry; Pezzatini, Daniele; Pfenning, Andreas; Pham, Chi-Tuan; Philipson, Pete; Phillips, Jeffrey; Phillips, Nicole; Phophalia, Ashish; Phuah, Chia-Ling; Pichai, Shanthi; Pichardo, Cesar; Binette, Alexa Pichet; Pietras, Olga; Pietrzyk, Mariusz; Pike, Kerryn; Pillai, Jagan; Piludu, Francesca; Pineda, Joanna; Ping, He; Pirraglia, Elizabeth; Pither, Richard; Piyush, Ranjan; Pizzi, Nick; Gonzalez, Luis Fernando Planella; Plassard, Andrew; Platero, Carlos; Plocharski, Maciej; Podhorski, Adam; Poggiali, Davide; Poghosyan, Mher; Pohl, Kilian; Poirier, Judes; Polakow, Jean Jacques; Politis, Marios; Poljak, Anne; Poloni, Katia Maria; Poole, Victoria; Poppenk, Jordan; Porsteinsson, Anton; Portelius, Erik; Posta, Filippo; Posthuma, Danielle; Potashman, Michele; Poulin, Stephane; Pourmennati, Bahar; Prahlad, Tejas; Pranav, Lee; Prasanth, Isaac; Prashar, Ajay; Prescott, Jeff; Prevedello, Luciano; Previtali, Fabio; Pricer, James; Prichard, James; Prince, Jerry; Prins, Samantha; Pritchard, Christopher; Priya, Priya; Priya, Anandh; Priyanka, Ahana; Properzi, Michael; Prosser, Angus; Proust-Lima, Cécile; Pruessner, Jens; Pu, Jian; Punjabi, Arjun; Punugu, Venkatapavani Pallavi; Puri, Dilip; Renjini, Anurenjan Purushothaman; Pyeon, DoYeong; Qader, Abu; Qi, Zeyao; Qi, Baihong; Qian, Xiaoning; Qian, Long; Qiao, Ju; Qiao, Jocelin; Qiaoli, Zhang; Qin, Hongsen; Qin, Wang; Qin, Tian; Qin, Yuanyuan; Qin, Qinxiaotie; Qin, Qiao; Qing, Zhao; Qiongling, Li; Qiu, Yu; Qiu, Wendy; Qiu, Deqiang; Qiu, Yingwei; Quadrelli, Scott; Qualls, Jake; Quan, Li; Quarg, Peter; Qureshi, Adnan; Anand, R.; Chitra, R.; Balaji, R.; Madhusudhan, R. N.; Raamana, Pradeep Reddy; Rabbia, Michael; Rabin, Laura; Radke, David; Pc, Muhammed Raees; Rafeiean, Mahsa; Raha, Oindrila; Rahimi, Amir; Arashloo, Shervin Rahimzadeh; Rai, Vipin; Rajamanickam, Karunanithi; Rajan, Surya; Rajapakse, Jagath; Rajaram, Sampath; Rajendran, Rajeswari; Rakovski, Cyril; Ramalhosa, Ivo; Raman, Fabio; Ramasamy, Ellankavi; Ramasangu, Hariharan; Ramirez, Alfredo; Ramos Pérez, Ana Victoria; Rana, Rahul; Rane, Swati; Rao, Anil; Rao, Vikram; Rashidi, Arash; Rasoanaivo, Oly; Rassem, Taha; Rastgoo, Hossein; Rath, Daniel; Ratnarajah, Nagulan; Ravikirthi, Prabhasa; Ravipati, Kaushik; RaviPrakash, Harish; Rawdha, Bousseta; Ray, Meredith; Ray, Debashree; Ray, Nilanjan; Ray, Dipankar; Ray, Soumi; Rebbah, Sana; Redding, Morgan; Regnerus, Bouke; Rehn, Patrick; Rehouma, Rokaya; Reid, Robert; Reimer, Alyssa; Reiss, Philip; Reitz, Christiane; Rekabi, Maryam; Rekik, Islem; Ren, Xuhua; Ren, Fujia; Ren, Xiaowei; Ren, Weijie; Renehan, William; Rennert, Lior; Rey, Samuel; Reyes, Pablo; Reza, Rifat; Rezaee, Khosro; Rhinn, Herve; Lorenzo, Pablo Ribalta; Ribeiro, Adèle Helena; Richards, John; Richards, Burt; Richards, Todd; Richardson, Hamish; Richiardi, Jonas; Richter, Nils; Ridge, Perry; Ridgway, Gerard; Ridha, Basil; Ried, Janina; Riedel, Brandalyn; Riphagen, Joost; Ritter, Kerstin; Rivaz, Hassan; Rivers-Auty, Jack; Allah, Mina Rizk; Rizzi, Massimo; Roalf, David; Robb, Catherine; Roberson, Erik; Robieson, Weining; Rocca-Serra, Philippe; Rodrigues, Marcos Antonio; Rodriguez, Alain; Aguiar, Güise Lorenzo Rodríguez; Rodriguez-Sanchez, Antonio; Rodriguez-Vieitez, Elena; Roes, Meighen; Rogalski, Emily; Rogers, James; Rogers, Baxter; Rohani, Hosna; Rollins, Carin; Rollo, Jenny; Romanillos, Adrian; Romero, Marcelo; Romero, Klaus; Rominger, Axel; Rondina, Jane; Ronquillo, Jeremiah; Roohparvar, Sanaz; Rosand, Jonathan; Rose, Gregory; Roshchupkin, Gennady; Rosoce, Jeremy; Ross, David; Ross, Joel; Ross, Owen; Rossi, Stephanie; Roussarie, Jean-Pierre; Roy, Arkaprava; Roy, Snehashis; Ruble, Cara; Rubright, Jonathan; Rudovic, Ognjen; Ruggiero, Denise; Rui, Qiao; Ruiz, Pablo; Rullmann, Michael; Rusmevichientong, Pimbucha; Russell, Rolf; Rutten, Julie; Saadatmand-Tarzjan, Mahdi; Saba, Valiallah; Sabuncu, Mert; Sacuiu, Simona; Sampathkumar, Srihari Sadhu; Sadikhov, Shamil; Saeedi, Sarah; Saf, Naz; Safapur, Alireza; Safi, Asad; Saint-Aubert, Laure; Saito, Noboru; Saito, Naomi; Sakata, Muneyuki; Frigerio, Carlo Sala; Sala-Llonch, Roser; Salah, Zainab; Salamanca, Luis; Salat, David; Salehzade, Mahdi; Salter, Hugh; Samatova, Nagiza; Sampat, Mehul; Gonzalez, Jorge Samper; Samtani, Mahesh; Samuel, Pearl; Bohorquez, Sandra Sanabria; Sanbao, Cheng; Sanchez, Iñigo; Sánchez, Irina; Sandella, Nick; Sanderlin, Ashley Hannah; Sanders, Elizabeth; Sankar, Tejas; Sanroma, Gerard; Sanson, Horacio; Santamaria, Mar; de Lourdes, Daniella; de Andrade, Luna Santana; Santhanam, Prasanna; Ribeiro, Andre Santos; Sardi, Pablo; Sardina, Davide; Saremi, Arvin; Sarica, Alessia; Sarnowski, Chloé; Sarraf, Saman; Saslow, Adam; Sato, Takayuki; Sato, Joao; Sattler, Sophia; Savic, Milos; Saxon, Jillian; Saya, Boson; Saykin, Andrew; Sbeiti, Elia; Scarapicchia, Vanessa; Scelsi, Marzia Antonella; Schaerer, Joel; Scharre, Douglas; Scherr, Martin; Schevenels, Klara; Schibler, Tony; Schiller, Florian; Schirmer, Markus; Schmansky, Nick; Schmidt, Marco; Schmidt, Paul; Schmitz, Taylor; Schmuker, Michael; Schneider, Anja; Schneider, Reinhard; Schoemaker, Dorothee; Schöll, Michael; Schouten, Tijn; Schramm, Hauke; Schreiber, Frank; Schultz, Timothy; Schultz, Aaron; Schürmann, Heike; Schwab, Patrick; Schwartz, Pamela; Schwarz, Adam; Schwarz, Christopher; Schwarzbauer, Christian; Scott, Julia; Scott, F. Jeffrey; Scott, David; Scussel, Artur; Seale, William; Seamons, John; Seemiller, Joseph; Sekine, Tetsuro; Selnes, Per; Sembritzki, Klaus; Senanayake, Vijitha; Seneca, Nicholas; Senjem, Matthew; Filho, Antonio Carlos Senra; Sensi, Stefano; Seo, Eun Hyun; Seo, Kangwon; Seong, Sibaek; Sepeta, Leigh; Seraji-Bozorgzad, Navid; Serra-Cayuela, Arnau; Seshadri, Sudha; Sgouros, Nicholas; Sha, Miao; Shackman, Alexander; Shafee, Rebecca; Shah, Rupali; Shah, Hitul; Shahid, Mohammad; Shahparian, Nastaran; Shakeri, Mahsa; Shams, Sara; Shams, Ali; Baboli, Aref Shams; Shamul, Naomi; Shan, Guogen; Shang, Yuan; Shao, Rui; Shao, Hanyu; Shao, Xiaozhe; Shaoxun, Yuan; Noghabi, Hossein Sharifi; Sharlene, Newman; Sharma, Avinash; Sharma, Ankita; Sharma, Aman; Shaw, Leslie; Shaw, Saurabh; Shcherbinin, Sergey; Sheline, Yvette; Shen, Li; Shen, Yanhe; Shen, Qian; Sherriff, Ian; Shi, Xin; Shi, Lei; Shi, Yonggang; Shi, Yue; Shi, Yupan; Shi, Jie; Shi, Feng; Shiban, Nisreen; Shields, Trevor; Shiiba, Takuro; Shiino, Akihiko; Shin, Peter; Shin, Hoo Chang; Shin, Daniel; Shine, James; Shinohara, Russell; Shirakashi, Yoshitomo; Shirali, Ramin; Shirer, William; Shiva, Karthik; Shmuel, Amir; Shojaei, Zahra; Shojaei, Samane; Shokouhi, Sepideh; Short, Jennifer; Shu, Qing; Shu, Ziyu; Shu, Hao; Shu, Xinghui; Shukla, Rahul; Sibilia, Francesca; Sikka, Apoorva; Rincón, Santiago Smith Silva; Silveira, Margarida; Simon, Howard; Simonneau, Michel; Simonovsky, Martin; Singanamalli, Asha; Singh, TirathaRaj; Singh, Ambuj; Singh, Satya; Singlelob, John; Sinha, Sampada; Sipko, Maciej; Sistla, Kamala; Sivera, Raphael; Skillbäck, Tobias; Skocik, Michael; Slade, Emily; Smisek, Miroslav; Smith, Louise; Smith, Emily; Smith, Elliot; Smith, Lidia; de Lima, John Wesley Soares; Soemedi, Rachel; Sohail, Aamir; Soheili-Nezhad, Sourena; Sokolow, Sophie; Sokurenko, Maria; Soldan, Anja; Soman, Salil; Sone, Je Yeong; Song, Joonyoung; Song, Xiaowei; Soni, Ameet; Soni, Priyank; Sonkar, Gaurav; Sonmez, Ege; Sonpatki, Pranali; Sorooshyari, Siamak; Diaz, Roberto Carlos Sotero; Sotolongo-Grau, Oscar; Sou, Ka Lon; Soursou, Georgia; Spampinato, Maria Vittoria; Spedding, Alexander; Spenger, Christian; Spiegel, Jonathan; Spiegel, RenÃ; Spies, Lothar; Spiro, Oliver; Spooner, Annette; Springate, Beth; Spronk, Marjolein; Squillario, Margherita; Sreenivasan, Karthik; Srikanth, Velandai; Srinivasan, Sneha; Srivastava, Mashrin; Srivastava, Anant; Srivatsa, Shantanu; Stage, Eddie; Stanley-Olson, Alexis; Steenland, Nelson; Steffener, Jason; Steyvers, Mark; Stickel, Ariana; Stone, David; Storkey, Amos; Storrs, Judd; Straminsky, Axel; Strittmatter, Stephen; Su, Yi; Sudmann-Day, Matthew; Sudre, Carole; Sudsanguan, Salintip; Sugishita, Morihiro; Suh, Devin; Suk, Heung-Il; Sulimov, Pavel; Sullivan, Margot; Sullivan, Kenneth; Sullivan, Jenna; Sumbaly, Ronak; Sun, Liyan; Sun, Xinwei; Sun, Haoran; Sun, Chung-Kai; Sun, Yongcong; Sun, Yu; Sun, Mingjie; Sun, Qian; Sun, Zeyu; Sun, Liang; Sun, Xiaoyan; Sun, Wei; Sundaramoorthy, Karthik Prakash; Sundaresan, Mali; Sunderland, John; Sundermann, Erin; Sunkishala, Raja; Surampudi, Govinda; Surampudi Venkata, Suresh Kumar; Surendran, Neha; Suresh, Adarsh; Suryavanshi, Priya; Susi, Gianluca; Suthaharan, Praveen; Sutphen, Courtney; Swati, Zar Nawab Khan; Sweet, Robert; Swinford, Cecily; Syaifullah, Ali Haidar; Szoeke, Cassandra; Sørensen, Lauge; Cuenco, Karen T.; Jafari, Hossein Tabatabaei; Tadayon, Ehsan; Taebi, Yasaman; Tahaei, Marzieh S.; Tahmasebi, Amir; Tai, Leon; Takahashi, Ryoji; Takahashi, Ryuichi; Takahashi, Hideyuki; Takao, Hidemasa; Takeuchi, Tomoko; Talib, Sophie; Taljan, Kyle; Tam, Angela; Tam, Roger; Tamang, Kishan; Tan, Chin Hong; Tan, Luqiao; Tan, Lin; Tan, Tian Swee; Tancredi, Daniel; Tanenbaum, Aaron; Tang, Yucong; Tang, Xiaoying; Tang, Chuangao; Tang, Cheng; Tang, Lingkai; Tang, Min; Tang, Hao; Tanigaki, Kenji; Tanoori, Betsabeh; Tansey, Wesley; Tantiwetchayanon, Khajonsak; Tanveer, M.; Tao, Qiushan; Tao, Chong; Tarawneh, Rawan; Tarnow, Eugen; Tartaglia, Maria Carmela; Tasaki, Shinya; Taswell, Koby; Taswell, Carl; Tatsuoka, Curtis; Taylan, Pakize; Taylor, Jonathan; Taylor, Brad; Tayubi, Iftikhar; Tchistiakova, Ekaterina; tee, Yee Kai; Teipel, Stefan; Temizer, Leyla; Kate, Mara Ten; Tenbergen, Carlijn; Tenenbaum, Jessica; Teng, Zi; Teng, Yuan-Ching; Teng, Edmond; Termenon, Maite; Terry, Eloise; Thaker, Ashesh; Theobald, Chuck; Thiel, Taylor; Thiele, Ines; Thiele, Frank; Thierry, Jean Pierre; Thirunavu, Vineeth; Thomas, Chris; Thomas, Kelsey; Thomas, Anoop Jacob; Thomas, Benjamin; Thomas, Ronald; Thomas, Adam; Thomopoulos, Sophia; Thompson, Gerard; Thompson, Jeff; Thompson, Will; Thompson, Paul; Thung, Kimhan; Tian, Sijia; Tierney, Mary; Tilquin, Florian; Tingay, Karen; Tirrell, Lee; Tirumalai, Sindhuja; Tobis, Jonathan; Todkari, Suhasini; Tohka, Jussi; Tokuda, Takahiko; Toledo, Juan B.; Toledo, Jon; Tolonen, Antti; Tombari, Federico; Tomiyama, Tetsuro; Tomola, Lauren; Tong, Yunjie; Tong, Liz; Tong, Li; Tong, Xiaoran; Torgerson, Carinna; Toro, Roberto; Torok, Levente; Toschi, Nicola; Tosto, Giuseppe; Tosun, Duygu; Tourandaz, Morteza; Toussaint, Paule; Towhidi, Sasan Maximilian; Towler, Stephen; Toyama, Teruhide; Tractenberg, Rochelle E.; Tran, Thao; Tran, Daniel; Trapani, Benjamin; Tremolizzo, Lucio; Tripathi, Shashi; Trittschuh, Emily; Trivedi, Ashish; Trojacanec, Katarina; Truong, Dennis; Tsanas, Athanasios; Tse, Kai-Hei; Tsoy, Elena; Tu, Yanshuai; Tubeleviciute-Aydin, Agne; Tubi, Meral; Tucholka, Alan; Tufail, Ahsan; Tumati, Shankar; Tuo, Shouheng; Tuovinen, Timo; Tustison, Nicholas; Tutunji, Rayyan; Tward, Daniel; Tyagi, Gaurav; Tzioras, Nikolaos; Raghavendra, U.; Uberti, Daniela; Uchiyama, Yoshikazu; Ueki, Masao; Ulug, Aziz; Umek, Robert; University, Northwestern; de Almeida, Sofia Urioste Y. Nunes; Urrutia, Leandro; Usama, Ahmed; Ustun, Ali Alp; Uus, Alena; Uyar, Muharrem Umit; Visalatchi, V.; Rajinikanth, V.; Vafaei, Amin; Vairre, Darlene; Vaishnavi, Sanjeev; Vaithinathan, Krishnakumar; Vakorin, Vasily; Hernández, Maria Valdés; van Bokhoven, Pieter; Deerlin, Vivianna Van; van der Brug, Marcel; Dijk, Koene Van; van Duijn, Cornelia; van Erp, Theo; van Hooren, Roy; Leemput, Koen Van; van Loenhoud, Anita; Schependom, Jeroen Van; van Velden, Floris; van Westen, Danielle; Vandekar, Simon; Vandijck, Manu; Vanhoutte, Matthieu; Vannini, Patrizia; Vansteenkiste, Elias; Varatharajah, Yogatheesan; Vardarajan, Badri; Varey, Stephen; Vargas, Hernan; Varkey, Julia; Varma, Susheel; Varma, Vijay; Varma, Sudhr; Vasanthakumar, Aparna; Vashi, Tejal; Vasilchuk, Kseniia; Vassileva, Albena; Vatsalan, Dinusha; Vb, Nastaran; Veeramacheneni, Teja; Veeranah, Darvesh; Vejdani, Kaveh; Veldsman, Michele; Velgos, Stefanie; Veloso, Adriano; Vemuri, Prashanthi; Venero, Cesar; Venkataraman, Ashwin; Venkatasubramanian, Palamadai; Venkatraghavan, Vikram; Venugopal, Vinisha; Venugopalan, Janani; Verbeeck, Rudi; Verbel, David; Verbist, Bie; Verdoliva, Luisa; Verma, Ajay Kumar; Verma, Tarun; Verma, Ishan; Veronese, Mattia; Grabovetsky, Alejandro Vicente; Victor, Jonathan; Vieira, Domingos; Vijayaraj, Vinesh Raja; Vikas, Vinutha; Vilaplana, Veronica; Vilaplana, Eduard; Villar, José Ramón; Vincent, Fabrice; Vinkler, Mojmir; Viswanath, Satish; Viswanathan, Srikrishnan; Vitek, Michael; Viti, Mario; Vladutu, Liviu; Vlock, Daniel; Voineskos, Aristotle; Vora, Anvi; Vos, Stephanie; Voyle, Nicola; Vrenken, Hugo; Vu, Tien Duong; Vucetic, Zivjena; Vuksanovic, Vesna; Wachinger, Christian; Wada, Masataka; Wade, Sara; Wagstyl, Konrad; Wahba, Grace; Waldorf, Johannes; Walker, Douglas; Moore, Kim Poki Walker; Walsh, Dominic; Wan, Lin; Wang, Di; Wang, Jane-Ling; Wang, Yongmao; Wang, Huaming; Wang, Miao; Wang, Zi-Rui; Wang, Zheyu; Wang, Z. E.; Wang, Lucy; Wang, Bin; Wang, Lei; Wang, Jason; Wang, Cathy; Wang, Jing; Wang, Xiuyuan; Wang, Dai; Wang, Lingyu; Wang, Jianjia; Wang, Yuan; Wang, Yujiang; Wang, Ming-Liang; Wang, De; Wang, Ling; Wang, Liangliang; Wang, Jianxin; Wang, Zhanyu; Wang, William Shi-Yuan; Wang, HuiFu; Wang, Weixin; Wang, Zhenxun; Wang, Wei; Wang, Junwen; Wang, Yipei; Wang, Shanshan; Wang, Yinying; Wang, Chengjia; Wang, Yuanjia; Wang, Kerry; Wang, Li-San; Wang, Kangcheng; Wang, Rui; Wang, Kai; Wang, Qian; Wang, Xinying; Wang, Xinglong; Wang, Jeff; Wang, Tianyi; Wang, Honglang; Wang, Xuekuan; Wang, Yongxiang; Wang, Hong; Wang, Silun; Waring, Stephen; Warren, David; Wasule, Vijay; Watanabe, Yoshiyuki; Wearn, Alfie; Wee, Chong-Yaw; Wegmayr, Viktor; Wehenkel, Marie; Wei, Rizhen; Wei, Zheng; Wei, Penghu; Wei, Yongbin; Wei, Guohui; Wei, Changshuai; Weichart, Emily; Weiler, Marina; Weise, Christopher; Weisong, Zhong; Weisshuhn, Philip; Weizheng, Yan; Wen, Canhong; Wen, Junhao; Wen, Wei; Wen, Zhenfu; Wen, Hao; Wenzel, Fabian; Werhane, Madeleine; Westaway, Shawn; Westlye, Lars T.; Westman, Eric; Whardana, Adithya; Whitcher, Brandon; Whittington, Alexander; Wicks, Stephen; Wiens, Jenna; Wildsmith, Kristin; Wilhelmsen, Kirk; Wilkinson, Andrea; Willette, Auriel; Williams, Kristin; Williams, Robert; Williams, Rebecca; Wilman, Alan; Wilmot, Beth; Wilson, Lorraine; Win, Juliet; Windpass, F. C.; Wink, Alle Meije; Winter, Nils; Winzeck, Stefan; Wirth, Miranka; Wishart, Heather; Wisniewski, Gary; Wiste, Heather; Wolpe, Noham; Wolz, Robin; Wong, Stephen; Wong, Swee Seong; Wong, Tak-Lam; Woo, Jongwook; Woo, Taekang; Woo, Young; Wood, Levi; Worth, Andrew; Wrenn, Jesse; Wright, Paul; Wu, Guorong; Wu, Lynn; Wu, Shawn; Wu, Menglin; Wu, Ruige; Wu, Shaoju; Wu, Chong; Wu, Juhao; Wu, Liyun; Wu, Yu-Te; Wu, Yuankai; Wu, Helen; Xia, Weiming; Xiang, Xu; Xiangmao, Kong; Xiao, Yiming; Xiao, Jie; Xiao, Y. U.; Xiaoxi, Ji; Xiaoya, Zhu; Xiaoying, Qi; Xie, Yuchen; Xie, Zhiyong; Xie, Lei; Xie, Xiancheng; Xin, Huang; Xingyi, Huang; Xiong, Yuanpeng; Xiong, Momiao; Xu, Yongchao; Xu, XiaoYing; Xu, Qiqi; Xu, Lijun; Xu, Hewen; Xu, Yunlong; Xu, Zhilei; Xu, Ziliang; Xu, Jiayuan; Xu, Yadong; Xu, Lu; Xu, Shuoyu; Xue, Fei; Xuesong, Yang; Xz, Zarric; Yadav, Rishi; Yaish, Aviv; Yakushev, Igor; Yamada, Shigeki; Yamamoto, Utako; Yamashita, Alexandre; Yamashita, Fumio; Yan, Li; Yan, Yu; Yan, Jianhua; Yan, Shiju; Yan, Chao-Gan; Yan, Qingyu; Yan, Jingwen; Yan, Chen; Yan, Meng; Yang, Meng; Yang, Bin; Yang, Jiarui; Yang, Zhi; Yang, Xianfeng; Yang, Sli; Yang, Liang; Yang, Robert; Yang, Aleex; Yang, Hyungjeong; Yang, ChengHao; Yang, Haiwei; Yang, Jhih-Ying; Yang, Xu; Yangyang, Xia; Yao, Xufeng; Yaping, Wang; Yaqiong, Bi; Yared, Surafael; Yashin, Anatoliy; Yassine, Hussein; Yau, Tat; Yavorsky, Christian; Ye, Chang; Ye, Byoung Seok; Ye, Joy; Ye, Yongkai; Ye, Yuting; Ye, Wu; Yelampalli, Praveen Kumar Reddy; Thomas Yeo, B. T.; Yi, Zhao; Yi, Wang; Yi, Yuan; Yijing, Ruan; Yilmaz, Zeynep; Yin, Baocai; Yin, Tang-Kai; Ying, Li; Yingjiang, Wu; Yiyun, Yu; Yoichiro, Sato; Yokoyama, Jennifer; Yong, Zhang; Yonghong, Shi; Yonghu, Guo; Yongqi, Huang; Yoo, Inwan; Yoon, So Hoon; Yoon, Jee Seok; Yoon, Seung-Yong; Yoshida, Hisako; Yoshio, Kiyofumi; You, Jia; You, You; You, Xiaozhen; Young, Alexandra; Yu, Peng; Yu, Jaemin; Yu, Lin; Yu, Sui; Yu, Philip S.; Yu, Guan; Yu, Fengli; Yu, Jiaxin; Yu, Shaode; Yu, Suizhi; Yu, Donghyeon; Yuan, Yue; Yuan, Shaofeng; Yuan, Shuai; Yuanyuan, Chen; Yue, Ye; Yue, Cynthia; Yunaiyama, Daisuke; YushaoChen, YushaoChen; Yushkevich, Paul; Yx, W.; Zafeiris, Dimitrios; Zagorchev, Lyubomir; Zalocusky, Kelly; Zamorano, Francisco; Zandifar, Azar; Zanella, Laura; Zang, Yufeng; Zanke, Brent; Zaranek, Alexander Wait; Zawaideh, Mazen; Zawawi, Nour; Zee, Jarcy; Zeighami, Yashar; Zeitzer, Jamie; Zemla, Jeffrey; Zeng, Qi; Zeng, Fan; Zeng, Donglin; Zeng, Wei; Zeng, Yingying; Ženko, Bernard; Zereshki, Ehsan; Zeskind, Benjamin; Zhan, Justin; Zhang, Chenghui; Zhang, Yixuan; Zhang, Xiong; Zhang, Li; Zhang, Zhi; Zhang, Jianlun; Zhang, Jing; Zhang, Jianwei; Zhang, Yufei; Zhang, Sai; Zhang, Shan; Zhang, Xiaoling; Zhang, Changle; Zhang, Qingtian; Zhang, Fan; Zhang, Xiangliang; Zhang, Linda; Zhang, Yingteng; Zhang, Jianhua; Zhang, Xiaoqun; Zhang, Ziwei; Zhang, Ping; Zhang, Tuo; Zhang, Bin; Zhang, Hong; Zhang, Yuping; Zhang, Zhan; Zhang, Yu; Zhang, Jie; Zhang, Lijun; Zhang, ChengZhi; Zhang, Jian; Zhang, Peng; Zhang, Zhengjun; Zhang, Wen; Zhang, Guishan; Zhang, Xixue; Zhang, Tianhao; Zhangyi, Zhangyi; Zhao, Wenting; Zhao, Xuewu; Zhao, Peng; Zhao, Yifei; Zhao, Xing-Ming; Zhao, Di; Zhao, Qian; Zhao, Yang; Zhao, Lu; Zheng, Lijuan; Zheng, Kaiping; Zheng, Weihao; Zheng, Du; Zheng, Muhua; Zheng, Qiang; Zheng, Bichen; Zheng, Lihong; Zhong, Wenxuan; Zhong, Yujia; Zhou, Tian; Zhou, Jiayin; Zhou, Zhen; Zhou, Yongxia; Zhou, Lixin; Zhou, Bowei; Zhou, Juan; Zhou, Qixin; Zhou, Levi; Zhou, Fengfeng; Zhou, Jiayu; Zhou, Luping; Zhou, Yun; Zhou, Yingjie; Zhou, Ying; Zhou, Frankie; Zhu, Zonghai; Zhu, Xiaoya; Zhu, Xiaolu; Zhu, Shanfeng; Zhu, David; Zhu, Hongxiao; Zhu, Lida; Zhu, Xiaofeng; Zhuxin, Jin; Zigon, Robert; Zille, Pascal; Zimmer, Eduardo; Zimmer, Jennifer; Zimmerman, Earl; Zimmerman, Karl; Zimmermann, Joelle; Zipperer, Erin; Zito, Giancarlo; Zou, Yang; Zuo, Maria; Zywiec, Andrew

    2017-01-01

    Neuroimaging measurements derived from magnetic resonance imaging provide important information required for detecting changes related to the progression of mild cognitive impairment (MCI). Cortical features and changes play a crucial role in revealing unique anatomical patterns of brain regions,

  11. Imprint lithography provides topographical nanocues to guide cell growth in primary cortical cell culture

    NARCIS (Netherlands)

    Xie, S.; Luttge, R.

    2014-01-01

    In this paper, we describe a technology platform to study the effect of nanocues on the cell growth direction in primary cortical cell culture. Topographical cues to cells are provided using nanoscale features created by Jet and Flash Imprint Lithography, coated with polyethylenimine. We

  12. RADIONUCLIDE IMAGING IN THE ASSESSMENT OF THE RESIDUAL CORTICAL FUNCTION OF OBSTRUCTIVE NEPHROPATHIES

    OpenAIRE

    川村, 寿一; 伊藤, 坦; 王, 本欽; 吉田, 修; 藤田, 透

    1980-01-01

    The diagnostic value of 99m-Tc-DMSA renal scintigraphy was assessed in 156 kidneys of 107 patients with a variety of obstructive nephropathies. DMSA renal cortical imaging well demonstrated morphological changes in the renal parenchyma around the dilated pelvocalyceal system. DMSA renal uptake, as a marker of cortical functioning mass, paralleled the grading of the hydronephrotic changes on IVP. DMSA renal scintigram well visualizes the residual functioning area in the renal parenchyma and DM...

  13. The dynamic interplay of plasma membrane domains and cortical microtubules in secondary cell wall patterning

    Directory of Open Access Journals (Sweden)

    Yoshihisa eOda

    2013-12-01

    Full Text Available Patterning of the cellulosic cell wall underlies the shape and function of plant cells. The cortical microtubule array plays a central role in the regulation of cell wall patterns. However, the regulatory mechanisms by which secondary cell wall patterns are established through cortical microtubules remain to be fully determined. Our recent study in xylem vessel cells revealed that a mutual inhibitory interaction between cortical microtubules and distinct plasma membrane domains leads to distinctive patterning in secondary cell walls. Our research revealed that the recycling of active and inactive ROP proteins by a specific GAP and GEF pair establishes distinct de novo plasma membrane domains. Active ROP recruits a plant-specific microtubule-associated protein, MIDD1, which mediates the mutual interaction between cortical microtubules and plasma membrane domains. In this mini review, we summarize recent research regarding secondary wall patterning, with a focus on the emerging interplay between plasma membrane domains and cortical microtubules through MIDD1 and ROP.

  14. Diffusion tensor imaging of the cortical plate and subplate in very-low-birth-weight infants

    Energy Technology Data Exchange (ETDEWEB)

    Dudink, Jeroen; Govaert, Paul; Zwol, Arjen L. van; Conneman, Nikk; Goudoever, Johannes B. van [Erasmus MC-Sophia Children' s Hospital, Division of Neonatology, Department of Paediatrics, Rotterdam (Netherlands); Buijs, Jan [Maxima Medical Center, Division of Neonatology, Department of Paediatrics, Veldhoven (Netherlands); Lequin, Maarten [Erasmus MC-Sophia Children' s Hospital, Division of Paediatrics, Department of Radiology, Rotterdam, Zuid-holland (Netherlands)

    2010-08-15

    Many intervention studies in preterm infants aim to improve neurodevelopmental outcome, but short-term proxy outcome measurements are lacking. Cortical plate and subplate development could be such a marker. Our aim was to provide normal DTI reference values for the cortical plate and subplate of preterm infants. As part of an ongoing study we analysed diffusion tensor imaging (DTI) images of 19 preterm infants without evidence of injury on conventional MRI, with normal outcome (Bayley-II assessed at age 2), and scanned in the first 4 days of life. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values in the frontal and temporal subplate and cortical plate were measured in single and multiple voxel regions of interest (ROI) placed on predefined regions. Using single-voxel ROIs, statistically significant inverse correlation was found between gestational age (GA) and FA of the frontal (r = -0.5938, P = 0.0058) and temporal (r = -0.4912, P = 0.0327) cortical plate. ADC values had a significant positive correlation with GA in the frontal (r = 0.5427, P = 0.0164) and temporal (r = 0.5540, P = 0.0138) subplate. Diffusion tensor imaging allows in vivo exploration of the evolving cortical plate and subplate. We provide FA and ADC values of the subplate and cortical plate in very-low-birth-weight (VLBW) infants with normal developmental outcome that can be used as reference values. (orig.)

  15. Diffusion tensor imaging of the cortical plate and subplate in very-low-birth-weight infants

    International Nuclear Information System (INIS)

    Dudink, Jeroen; Govaert, Paul; Zwol, Arjen L. van; Conneman, Nikk; Goudoever, Johannes B. van; Buijs, Jan; Lequin, Maarten

    2010-01-01

    Many intervention studies in preterm infants aim to improve neurodevelopmental outcome, but short-term proxy outcome measurements are lacking. Cortical plate and subplate development could be such a marker. Our aim was to provide normal DTI reference values for the cortical plate and subplate of preterm infants. As part of an ongoing study we analysed diffusion tensor imaging (DTI) images of 19 preterm infants without evidence of injury on conventional MRI, with normal outcome (Bayley-II assessed at age 2), and scanned in the first 4 days of life. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values in the frontal and temporal subplate and cortical plate were measured in single and multiple voxel regions of interest (ROI) placed on predefined regions. Using single-voxel ROIs, statistically significant inverse correlation was found between gestational age (GA) and FA of the frontal (r = -0.5938, P = 0.0058) and temporal (r = -0.4912, P = 0.0327) cortical plate. ADC values had a significant positive correlation with GA in the frontal (r = 0.5427, P = 0.0164) and temporal (r = 0.5540, P = 0.0138) subplate. Diffusion tensor imaging allows in vivo exploration of the evolving cortical plate and subplate. We provide FA and ADC values of the subplate and cortical plate in very-low-birth-weight (VLBW) infants with normal developmental outcome that can be used as reference values. (orig.)

  16. Cortical cell and neuron density estimates in one chimpanzee hemisphere.

    Science.gov (United States)

    Collins, Christine E; Turner, Emily C; Sawyer, Eva Kille; Reed, Jamie L; Young, Nicole A; Flaherty, David K; Kaas, Jon H

    2016-01-19

    The density of cells and neurons in the neocortex of many mammals varies across cortical areas and regions. This variability is, perhaps, most pronounced in primates. Nonuniformity in the composition of cortex suggests regions of the cortex have different specializations. Specifically, regions with densely packed neurons contain smaller neurons that are activated by relatively few inputs, thereby preserving information, whereas regions that are less densely packed have larger neurons that have more integrative functions. Here we present the numbers of cells and neurons for 742 discrete locations across the neocortex in a chimpanzee. Using isotropic fractionation and flow fractionation methods for cell and neuron counts, we estimate that neocortex of one hemisphere contains 9.5 billion cells and 3.7 billion neurons. Primary visual cortex occupies 35 cm(2) of surface, 10% of the total, and contains 737 million densely packed neurons, 20% of the total neurons contained within the hemisphere. Other areas of high neuron packing include secondary visual areas, somatosensory cortex, and prefrontal granular cortex. Areas of low levels of neuron packing density include motor and premotor cortex. These values reflect those obtained from more limited samples of cortex in humans and other primates.

  17. 4D segmentation of brain MR images with constrained cortical thickness variation.

    Directory of Open Access Journals (Sweden)

    Li Wang

    Full Text Available Segmentation of brain MR images plays an important role in longitudinal investigation of developmental, aging, disease progression changes in the cerebral cortex. However, most existing brain segmentation methods consider multiple time-point images individually and thus cannot achieve longitudinal consistency. For example, cortical thickness measured from the segmented image will contain unnecessary temporal variations, which will affect the time related change pattern and eventually reduce the statistical power of analysis. In this paper, we propose a 4D segmentation framework for the adult brain MR images with the constraint of cortical thickness variations. Specifically, we utilize local intensity information to address the intensity inhomogeneity, spatial cortical thickness constraint to maintain the cortical thickness being within a reasonable range, and temporal cortical thickness variation constraint in neighboring time-points to suppress the artificial variations. The proposed method has been tested on BLSA dataset and ADNI dataset with promising results. Both qualitative and quantitative experimental results demonstrate the advantage of the proposed method, in comparison to other state-of-the-art 4D segmentation methods.

  18. A computational framework for cortical microtubule dynamics in realistically shaped plant cells.

    Directory of Open Access Journals (Sweden)

    Bandan Chakrabortty

    2018-02-01

    Full Text Available Plant morphogenesis is strongly dependent on the directional growth and the subsequent oriented division of individual cells. It has been shown that the plant cortical microtubule array plays a key role in controlling both these processes. This ordered structure emerges as the collective result of stochastic interactions between large numbers of dynamic microtubules. To elucidate this complex self-organization process a number of analytical and computational approaches to study the dynamics of cortical microtubules have been proposed. To date, however, these models have been restricted to two dimensional planes or geometrically simple surfaces in three dimensions, which strongly limits their applicability as plant cells display a wide variety of shapes. This limitation is even more acute, as both local as well as global geometrical features of cells are expected to influence the overall organization of the array. Here we describe a framework for efficiently simulating microtubule dynamics on triangulated approximations of arbitrary three dimensional surfaces. This allows the study of microtubule array organization on realistic cell surfaces obtained by segmentation of microscopic images. We validate the framework against expected or known results for the spherical and cubical geometry. We then use it to systematically study the individual contributions of global geometry, cell-edge induced catastrophes and cell-face induced stability to array organization in a cuboidal geometry. Finally, we apply our framework to analyze the highly non-trivial geometry of leaf pavement cells of Arabidopsis thaliana, Nicotiana benthamiana and Hedera helix. We show that our simulations can predict multiple features of the microtubule array structure in these cells, revealing, among others, strong constraints on the orientation of division planes.

  19. A computational framework for cortical microtubule dynamics in realistically shaped plant cells

    KAUST Repository

    Chakrabortty, Bandan; Blilou, Ikram; Scheres, Ben; Mulder, Bela M.

    2018-01-01

    Plant morphogenesis is strongly dependent on the directional growth and the subsequent oriented division of individual cells. It has been shown that the plant cortical microtubule array plays a key role in controlling both these processes. This ordered structure emerges as the collective result of stochastic interactions between large numbers of dynamic microtubules. To elucidate this complex self-organization process a number of analytical and computational approaches to study the dynamics of cortical microtubules have been proposed. To date, however, these models have been restricted to two dimensional planes or geometrically simple surfaces in three dimensions, which strongly limits their applicability as plant cells display a wide variety of shapes. This limitation is even more acute, as both local as well as global geometrical features of cells are expected to influence the overall organization of the array. Here we describe a framework for efficiently simulating microtubule dynamics on triangulated approximations of arbitrary three dimensional surfaces. This allows the study of microtubule array organization on realistic cell surfaces obtained by segmentation of microscopic images. We validate the framework against expected or known results for the spherical and cubical geometry. We then use it to systematically study the individual contributions of global geometry, cell-edge induced catastrophes and cell-face induced stability to array organization in a cuboidal geometry. Finally, we apply our framework to analyze the highly non-trivial geometry of leaf pavement cells of Arabidopsis thaliana, Nicotiana benthamiana and Hedera helix. We show that our simulations can predict multiple features of the microtubule array structure in these cells, revealing, among others, strong constraints on the orientation of division planes.

  20. A computational framework for cortical microtubule dynamics in realistically shaped plant cells

    KAUST Repository

    Chakrabortty, Bandan

    2018-02-02

    Plant morphogenesis is strongly dependent on the directional growth and the subsequent oriented division of individual cells. It has been shown that the plant cortical microtubule array plays a key role in controlling both these processes. This ordered structure emerges as the collective result of stochastic interactions between large numbers of dynamic microtubules. To elucidate this complex self-organization process a number of analytical and computational approaches to study the dynamics of cortical microtubules have been proposed. To date, however, these models have been restricted to two dimensional planes or geometrically simple surfaces in three dimensions, which strongly limits their applicability as plant cells display a wide variety of shapes. This limitation is even more acute, as both local as well as global geometrical features of cells are expected to influence the overall organization of the array. Here we describe a framework for efficiently simulating microtubule dynamics on triangulated approximations of arbitrary three dimensional surfaces. This allows the study of microtubule array organization on realistic cell surfaces obtained by segmentation of microscopic images. We validate the framework against expected or known results for the spherical and cubical geometry. We then use it to systematically study the individual contributions of global geometry, cell-edge induced catastrophes and cell-face induced stability to array organization in a cuboidal geometry. Finally, we apply our framework to analyze the highly non-trivial geometry of leaf pavement cells of Arabidopsis thaliana, Nicotiana benthamiana and Hedera helix. We show that our simulations can predict multiple features of the microtubule array structure in these cells, revealing, among others, strong constraints on the orientation of division planes.

  1. Restoration of Thickness, Density, and Volume for Highly Blurred Thin Cortical Bones in Clinical CT Images.

    Science.gov (United States)

    Pakdel, Amirreza; Hardisty, Michael; Fialkov, Jeffrey; Whyne, Cari

    2016-11-01

    In clinical CT images containing thin osseous structures, accurate definition of the geometry and density is limited by the scanner's resolution and radiation dose. This study presents and validates a practical methodology for restoring information about thin bone structure by volumetric deblurring of images. The methodology involves 2 steps: a phantom-free, post-reconstruction estimation of the 3D point spread function (PSF) from CT data sets, followed by iterative deconvolution using the PSF estimate. Performance of 5 iterative deconvolution algorithms, blind, Richardson-Lucy (standard, plus Total Variation versions), modified residual norm steepest descent (MRNSD), and Conjugate Gradient Least-Squares were evaluated using CT scans of synthetic cortical bone phantoms. The MRNSD algorithm resulted in the highest relative deblurring performance as assessed by a cortical bone thickness error (0.18 mm) and intensity error (150 HU), and was subsequently applied on a CT image of a cadaveric skull. Performance was compared against micro-CT images of the excised thin cortical bone samples from the skull (average thickness 1.08 ± 0.77 mm). Error in quantitative measurements made from the deblurred images was reduced 82% (p < 0.01) for cortical thickness and 55% (p < 0.01) for bone mineral mass. These results demonstrate a significant restoration of geometrical and radiological density information derived for thin osseous features.

  2. Cortical region of interest definition on SPECT brain images using X-ray CT registration

    Energy Technology Data Exchange (ETDEWEB)

    Tzourio, N.; Sutton, D. (Commissariat a l' Energie Atomique, Orsay (France). Service Hospitalier Frederic Joliot); Joliot, M. (Commissariat a l' Energie Atomique, Orsay (France). Service Hospitalier Frederic Joliot INSERM, Orsay (France)); Mazoyer, B.M. (Commissariat a l' Energie Atomique, Orsay (France). Service Hospitalier Frederic Joliot Antenne d' Information Medicale, C.H.U. Bichat, Paris (France)); Charlot, V. (Hopital Louis Mourier, Colombes (France). Service de Psychiatrie); Salamon, G. (CHU La Timone, Marseille (France). Service de Neuroradiologie)

    1992-11-01

    We present a method for brain single photon emission computed tomography (SPECT) analysis based on individual registration of anatomical (CT) and functional ([sup 133]Xe regional cerebral blood flow) images and on the definition of three-dimensional functional regions of interest. Registration of CT and SPECT is performed through adjustment of CT-defined cortex limits to the SPECT image. Regions are defined by sectioning a cortical ribbon on the CT images, copied over the SPECT images and pooled through slices to give 3D cortical regions of interest. The proposed method shows good intra- and interobserver reproducibility (regional intraclass correlation coefficient [approx equal]0.98), and good accuracy in terms of repositioning ([approx equal]3.5 mm) as compared to the SPECT image resolution (14 mm). The method should be particularly useful for analysing SPECT studies when variations in brain anatomy (normal or abnormal) must be accounted for. (orig.).

  3. Identification and characterization of insulin receptors on foetal-mouse brain-cortical cells.

    OpenAIRE

    Van Schravendijk, C F; Hooghe-Peters, E L; De Meyts, P; Pipeleers, D G

    1984-01-01

    The occurrence of insulin receptors was investigated in freshly dissociated brain-cortical cells from mouse embryos. By analogy with classical insulin-binding cell types, binding of 125I-insulin to foetal brain-cortical cells was time- and pH-dependent, only partially reversible, and competed for by unlabelled insulin and closely related peptides. Desalanine-desasparagine-insulin, pig proinsulin, hagfish insulin and turkey insulin were respectively 2%, 4%, 2% and 200% as potent as bovine insu...

  4. Two-photon NADH imaging exposes boundaries of oxygen diffusion in cortical vascular supply regions.

    Science.gov (United States)

    Kasischke, Karl A; Lambert, Elton M; Panepento, Ben; Sun, Anita; Gelbard, Harris A; Burgess, Robert W; Foster, Thomas H; Nedergaard, Maiken

    2011-01-01

    Oxygen transport imposes a possible constraint on the brain's ability to sustain variable metabolic demands, but oxygen diffusion in the cerebral cortex has not yet been observed directly. We show that concurrent two-photon fluorescence imaging of endogenous nicotinamide adenine dinucleotide (NADH) and the cortical microcirculation exposes well-defined boundaries of tissue oxygen diffusion in the mouse cortex. The NADH fluorescence increases rapidly over a narrow, very low pO(2) range with a p(50) of 3.4 ± 0.6 mm Hg, thereby establishing a nearly binary reporter of significant, metabolically limiting hypoxia. The transient cortical tissue boundaries of NADH fluorescence exhibit remarkably delineated geometrical patterns, which define the limits of tissue oxygen diffusion from the cortical microcirculation and bear a striking resemblance to the ideal Krogh tissue cylinder. The visualization of microvessels and their regional contribution to oxygen delivery establishes penetrating arterioles as major oxygen sources in addition to the capillary network and confirms the existence of cortical oxygen fields with steep microregional oxygen gradients. Thus, two-photon NADH imaging can be applied to expose vascular supply regions and to localize functionally relevant microregional cortical hypoxia with micrometer spatial resolution.

  5. Imaging and radiological-pathological correlation in histologically proven cases of focal cortical dysplasia and other glial and neuronoglial malformative lesions in adults

    International Nuclear Information System (INIS)

    Gomez-Anson, B.; Thom, M.; Moran, N.; Stevens, J.; Scaravilli, F.

    2000-01-01

    Focal cortical dysplasia (FCD) is a pathological entity first described in 1971. Other more subtle cortical malformations found in patients with epilepsy include microdysgenesis (MD), and glioneuronal hamartias. Although these glial and neuronoglial malformations have distinct histological features, there is terminological confusion in the radiological literature. Few cases have been reported in adults with both imaging and histology. We address these issues, giving a radiological-pathological correlation of histologically proven cortical malformations in adults. We describe clinical, radiological and histological features of 12 cases (five FCD, five MD with glioneuronal hamartias, and two hamartomas), unassociated with other conditions, and discuss them in the light of the literature. FCD is usually seen on MRI as cortical thickening, with or without signal change, which may extend into the adjacent white matter. On histology, abnormal neurons and/or glial cells, blurring of the grey-white matter interface, myelin pallor, demyelination, and gliosis may be found. Glioneuronal hamartias and hamartomas usually appear as complex masses on MRI. FCD and hamartias may be associated, and a combination of imaging findings may be seen on MRI. Atrophy of the ipsilateral hippocampus may be present on MRI in patients with hamartias, and minor cell loss on histology, but not definitive hippocampal sclerosis. Although the imaging findings of cortical malformations are protean, some characteristic MRI features, with histological correlates, may be found. The relevance of most of these observations remains unclear. (orig.)

  6. Evaluation of trabecular bone patterns on dental radiographic images: influence of cortical bone

    Science.gov (United States)

    Amouriq, Yves; Evenou, Pierre; Arlicot, Aurore; Normand, Nicolas; Layrolle, Pierre; Weiss, Pierre; Guédon, Jean-Pierre

    2010-03-01

    For some authors trabecular bone is highly visible in intraoral radiographs. For other authors, the observed intrabony trabecular pattern is a representation of only the endosteal surface of cortical bone, not of intermedullary striae. The purpose of this preliminary study was to investigate the true anatomical structures that are visible in routine dental radiographs and classically denoted trabecular bone. This is a major point for bone texture analysis on radiographs. Computed radiography (CR) images of dog mandible section in molar region were compared with simulations calculated from high-resolution micro-CT volumes. Calculated simulations were obtained using the Mojette Transform. By digitally editing the CT volume, the simulations were separated into trabecular and cortical components into a region of interest. Different images were compared and correlated, some bone micro-architecture parameters calculated. A high correlation was found between computed radiographs and calculated simulations from micro-CT. The Mojette transform was successful to obtain high quality images. Cortical bone did not contribute to change in a major way simulated images. These first results imply that intrabony trabecular pattern observed on radiographs can not only be a representation of the cortical bone endosteal surface and that trabecular bone is highly visible in intraoral radiographs.

  7. 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.

  8. Rehabilitation-triggered cortical plasticity after stroke: in vivo imaging at multiple scales (Conference Presentation)

    Science.gov (United States)

    Allegra Mascaro, Anna Letizia; Conti, Emilia; Lai, Stefano; Spalletti, Cristina; Di Giovanna, Antonino Paolo; Alia, Claudia; Panarese, Alessandro; Sacconi, Leonardo; Micera, Silvestro; Caleo, Matteo; Pavone, Francesco S.

    2017-02-01

    Neurorehabilitation protocols based on the use of robotic devices provide a highly repeatable therapy and have recently shown promising clinical results. Little is known about how rehabilitation molds the brain to promote motor recovery of the affected limb. We used a custom-made robotic platform that provides quantitative assessment of forelimb function in a retraction test. Complementary imaging techniques allowed us to access to the multiple facets of robotic rehabilitation-induced cortical plasticity after unilateral photothrombotic stroke in mice Primary Motor Cortex (Caudal Forelimb Area - CFA). First, we analyzed structural features of vasculature and dendritic reshaping in the peri-infarct area with two-photon fluorescence microscopy. Longitudinal analysis of dendritic branches and spines of pyramidal neurons suggests that robotic rehabilitation promotes the stabilization of peri-infarct cortical excitatory circuits, which is not accompanied by consistent vascular reorganization towards pre-stroke conditions. To investigate if this structural stabilization was linked to functional remapping, we performed mesoscale wide-field imaging on GCaMP6 mice while performing the motor task on the robotic platform. We revealed temporal and spatial features of the motor-triggered cortical activation, shining new light on rehabilitation-induced functional remapping of the ipsilesional cortex. Finally, by using an all-optical approach that combines optogenetic activation of the contralesional hemisphere and wide-field functional imaging of peri-infarct area, we dissected the effect of robotic rehabilitation on inter-hemispheric cortico-cortical connectivity.

  9. Live-cell imaging.

    Science.gov (United States)

    Cole, Richard

    2014-01-01

    It would be hard to argue that live-cell imaging has not changed our view of biology. The past 10 years have seen an explosion of interest in imaging cellular processes, down to the molecular level. There are now many advanced techniques being applied to live cell imaging. However, cellular health is often under appreciated. For many researchers, if the cell at the end of the experiment has not gone into apoptosis or is blebbed beyond recognition, than all is well. This is simply incorrect. There are many factors that need to be considered when performing live-cell imaging in order to maintain cellular health such as: imaging modality, media, temperature, humidity, PH, osmolality, and photon dose. The wavelength of illuminating light, and the total photon dose that the cells are exposed to, comprise two of the most important and controllable parameters of live-cell imaging. The lowest photon dose that achieves a measureable metric for the experimental question should be used, not the dose that produces cover photo quality images. This is paramount to ensure that the cellular processes being investigated are in their in vitro state and not shifted to an alternate pathway due to environmental stress. The timing of the mitosis is an ideal canary in the gold mine, in that any stress induced from the imaging will result in the increased length of mitosis, thus providing a control model for the current imagining conditions.

  10. 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.

  11. Visualization of migration of human cortical neurons generated from induced pluripotent stem cells.

    Science.gov (United States)

    Bamba, Yohei; Kanemura, Yonehiro; Okano, Hideyuki; Yamasaki, Mami

    2017-09-01

    Neuronal migration is considered a key process in human brain development. However, direct observation of migrating human cortical neurons in the fetal brain is accompanied by ethical concerns and is a major obstacle in investigating human cortical neuronal migration. We established a novel system that enables direct visualization of migrating cortical neurons generated from human induced pluripotent stem cells (hiPSCs). We observed the migration of cortical neurons generated from hiPSCs derived from a control and from a patient with lissencephaly. Our system needs no viable brain tissue, which is usually used in slice culture. Migratory behavior of human cortical neuron can be observed more easily and more vividly by its fluorescence and glial scaffold than that by earlier methods. Our in vitro experimental system provides a new platform for investigating development of the human central nervous system and brain malformation. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Spiking cortical model-based nonlocal means method for speckle reduction in optical coherence tomography images

    Science.gov (United States)

    Zhang, Xuming; Li, Liu; Zhu, Fei; Hou, Wenguang; Chen, Xinjian

    2014-06-01

    Optical coherence tomography (OCT) images are usually degraded by significant speckle noise, which will strongly hamper their quantitative analysis. However, speckle noise reduction in OCT images is particularly challenging because of the difficulty in differentiating between noise and the information components of the speckle pattern. To address this problem, the spiking cortical model (SCM)-based nonlocal means method is presented. The proposed method explores self-similarities of OCT images based on rotation-invariant features of image patches extracted by SCM and then restores the speckled images by averaging the similar patches. This method can provide sufficient speckle reduction while preserving image details very well due to its effectiveness in finding reliable similar patches under high speckle noise contamination. When applied to the retinal OCT image, this method provides signal-to-noise ratio improvements of >16 dB with a small 5.4% loss of similarity.

  13. Cortical magnetic resonance imaging findings in familial pediatric bipolar disorder.

    Science.gov (United States)

    Chang, Kiki; Barnea-Goraly, Naama; Karchemskiy, Asya; Simeonova, Diana Iorgova; Barnes, Patrick; Ketter, Terence; Reiss, Allan L

    2005-08-01

    Morphometric magnetic resonance imaging (MRI) studies of pediatric bipolar disorder (BD) have not reported on gray matter volumes but have reported increased lateral ventricular size and presence of white matter hyperintensities (WMH). We studied gray matter volume, ventricular-to-brain ratios (VBR), and number of WMH in patients with familial, pediatric BD compared with control subjects. Twenty subjects with BD (aged 14.6 +/- 2.8 years; 4 female) according to the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia, each with a parent with BD, and 20 age-, gender-, and intelligence quotient-matched healthy control subjects (aged 14.1 +/- 2.8 years; 4 female) were scanned at 3 T. Most subjects were taking psychotropic medications. A high-resolution T1-weighted spoiled gradient echo three-dimensional MRI sequence was analyzed by BrainImage for volumetric measurements, and T2-weighted images were read by a neuroradiologist to determine presence of WMH. After covarying for age and total brain volume, there were no significant differences between subjects with BD and control subjects in volume of cerebral (p = .09) or prefrontal gray matter (p = .34). Subjects with BD did not have elevated numbers of WMH or greater VBR when compared with control subjects. Children and adolescents with familial BD do not seem to have decreased cerebral grey matter or increased numbers of WMH, dissimilar to findings in adults with BD. Gray matter decreases and development of WMH might be later sequelae of BD or unique to adult-onset BD.

  14. Audiovisual functional magnetic resonance imaging adaptation reveals multisensory integration effects in object-related sensory cortices.

    Science.gov (United States)

    Doehrmann, Oliver; Weigelt, Sarah; Altmann, Christian F; Kaiser, Jochen; Naumer, Marcus J

    2010-03-03

    Information integration across different sensory modalities contributes to object recognition, the generation of associations and long-term memory representations. Here, we used functional magnetic resonance imaging adaptation to investigate the presence of sensory integrative effects at cortical levels as early as nonprimary auditory and extrastriate visual cortices, which are implicated in intermediate stages of object processing. Stimulation consisted of an adapting audiovisual stimulus S(1) and a subsequent stimulus S(2) from the same basic-level category (e.g., cat). The stimuli were carefully balanced with respect to stimulus complexity and semantic congruency and presented in four experimental conditions: (1) the same image and vocalization for S(1) and S(2), (2) the same image and a different vocalization, (3) different images and the same vocalization, or (4) different images and vocalizations. This two-by-two factorial design allowed us to assess the contributions of auditory and visual stimulus repetitions and changes in a statistically orthogonal manner. Responses in visual regions of right fusiform gyrus and right lateral occipital cortex were reduced for repeated visual stimuli (repetition suppression). Surprisingly, left lateral occipital cortex showed stronger responses to repeated auditory stimuli (repetition enhancement). Similarly, auditory regions of interest of the right middle superior temporal gyrus and sulcus exhibited repetition suppression to auditory repetitions and repetition enhancement to visual repetitions. Our findings of crossmodal repetition-related effects in cortices of the respective other sensory modality add to the emerging view that in human subjects sensory integrative mechanisms operate on earlier cortical processing levels than previously assumed.

  15. 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.

  16. TONNEAU2/FASS Regulates the Geometry of Microtubule Nucleation and Cortical Array Organization in Interphase Arabidopsis Cells[C][W

    Science.gov (United States)

    Kirik, Angela; Ehrhardt, David W.; Kirik, Viktor

    2012-01-01

    Organization of microtubules into ordered arrays involves spatial and temporal regulation of microtubule nucleation. Here, we show that acentrosomal microtubule nucleation in plant cells involves a previously unknown regulatory step that determines the geometry of microtubule nucleation. Dynamic imaging of interphase cortical microtubules revealed that the ratio of branching to in-bundle microtubule nucleation on cortical microtubules is regulated by the Arabidopsis thaliana B′′ subunit of protein phosphatase 2A, which is encoded by the TONNEAU2/FASS (TON2) gene. The probability of nucleation from γ-tubulin complexes localized at the cell cortex was not affected by a loss of TON2 function, suggesting a specific role of TON2 in regulating the nucleation geometry. Both loss of TON2 function and ectopic targeting of TON2 to the plasma membrane resulted in defects in cell shape, suggesting the importance of TON2-mediated regulation of the microtubule cytoskeleton in cell morphogenesis. Loss of TON2 function also resulted in an inability for cortical arrays to reorient in response to light stimulus, suggesting an essential role for TON2 and microtubule branching nucleation in reorganization of microtubule arrays. Our data establish TON2 as a regulator of interphase microtubule nucleation and provide experimental evidence for a novel regulatory step in the process of microtubule-dependent nucleation. PMID:22395485

  17. Detection of cortical activities on eye movement using functional magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Masaki; Kawai, Kazushige; Kitahara, Kenji [Jikei Univ., Tokyo (Japan). School of Medicine; Soulie, D.; Cordoliani, Y.S.; Iba-Zizen, M.T.; Cabanis, E.A.

    1997-11-01

    Cortical activity during eye movement was examined with functional magnetic resonance imaging. Horizontal saccadic eye movements and smooth pursuit eye movements were elicited in normal subjects. Activity in the frontal eye field was found during both saccadic and smooth pursuit eye movements at the posterior margin of the middle frontal gyrus and in parts of the precentral sulcus and precentral gyrus bordering the middle frontal gyrus (Brodmann`s areas 8, 6, and 9). In addition, activity in the parietal eye field was found in the deep, upper margin of the angular gyrus and of the supramarginal gyrus (Brodmann`s areas 39 and 40) during saccadic eye movement. Activity of V5 was found at the intersection of the ascending limb of the inferior temporal sulcus and the lateral occipital sulcus during smooth pursuit eye movement. Our results suggest that functional magnetic resonance imaging is useful for detecting cortical activity during eye movement. (author)

  18. Detection of cortical activities on eye movement using functional magnetic resonance imaging

    International Nuclear Information System (INIS)

    Yoshida, Masaki; Kawai, Kazushige; Kitahara, Kenji; Soulie, D.; Cordoliani, Y.S.; Iba-Zizen, M.T.; Cabanis, E.A.

    1997-01-01

    Cortical activity during eye movement was examined with functional magnetic resonance imaging. Horizontal saccadic eye movements and smooth pursuit eye movements were elicited in normal subjects. Activity in the frontal eye field was found during both saccadic and smooth pursuit eye movements at the posterior margin of the middle frontal gyrus and in parts of the precentral sulcus and precentral gyrus bordering the middle frontal gyrus (Brodmann's areas 8, 6, and 9). In addition, activity in the parietal eye field was found in the deep, upper margin of the angular gyrus and of the supramarginal gyrus (Brodmann's areas 39 and 40) during saccadic eye movement. Activity of V5 was found at the intersection of the ascending limb of the inferior temporal sulcus and the lateral occipital sulcus during smooth pursuit eye movement. Our results suggest that functional magnetic resonance imaging is useful for detecting cortical activity during eye movement. (author)

  19. Two-photon NADH imaging exposes boundaries of oxygen diffusion in cortical vascular supply regions

    OpenAIRE

    Kasischke, Karl A; Lambert, Elton M; Panepento, Ben; Sun, Anita; Gelbard, Harris A; Burgess, Robert W; Foster, Thomas H; Nedergaard, Maiken

    2010-01-01

    Oxygen transport imposes a possible constraint on the brain's ability to sustain variable metabolic demands, but oxygen diffusion in the cerebral cortex has not yet been observed directly. We show that concurrent two-photon fluorescence imaging of endogenous nicotinamide adenine dinucleotide (NADH) and the cortical microcirculation exposes well-defined boundaries of tissue oxygen diffusion in the mouse cortex. The NADH fluorescence increases rapidly over a narrow, very low pO2 range with a p ...

  20. Whole brain diffeomorphic metric mapping via integration of sulcal and gyral curves, cortical surfaces, and images

    Science.gov (United States)

    Du, Jia; Younes, Laurent; Qiu, Anqi

    2011-01-01

    This paper introduces a novel large deformation diffeomorphic metric mapping algorithm for whole brain registration where sulcal and gyral curves, cortical surfaces, and intensity images are simultaneously carried from one subject to another through a flow of diffeomorphisms. To the best of our knowledge, this is the first time that the diffeomorphic metric from one brain to another is derived in a shape space of intensity images and point sets (such as curves and surfaces) in a unified manner. We describe the Euler–Lagrange equation associated with this algorithm with respect to momentum, a linear transformation of the velocity vector field of the diffeomorphic flow. The numerical implementation for solving this variational problem, which involves large-scale kernel convolution in an irregular grid, is made feasible by introducing a class of computationally friendly kernels. We apply this algorithm to align magnetic resonance brain data. Our whole brain mapping results show that our algorithm outperforms the image-based LDDMM algorithm in terms of the mapping accuracy of gyral/sulcal curves, sulcal regions, and cortical and subcortical segmentation. Moreover, our algorithm provides better whole brain alignment than combined volumetric and surface registration (Postelnicu et al., 2009) and hierarchical attribute matching mechanism for elastic registration (HAMMER) (Shen and Davatzikos, 2002) in terms of cortical and subcortical volume segmentation. PMID:21281722

  1. Microbial Cell Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Doktycz, Mitchel John [ORNL; Sullivan, Claretta [Eastern Virginia Medical School; Mortensen, Ninell P [ORNL; Allison, David P [ORNL

    2011-01-01

    Atomic force microscopy (AFM) is finding increasing application in a variety of fields including microbiology. Until the emergence of AFM, techniques for ivnestigating processes in single microbes were limited. From a biologist's perspective, the fact that AFM can be used to generate high-resolution images in buffers or media is its most appealing feature as live-cell imaging can be pursued. Imaging living cells by AFM allows dynamic biological events to be studied, at the nanoscale, in real time. Few areas of biological research have as much to gain as microbiology from the application of AFM. Whereas the scale of microbes places them near the limit of resolution for light microscopy. AFM is well suited for the study of structures on the order of a micron or less. Although electron microscopy techniques have been the standard for high-resolution imaging of microbes, AFM is quickly gaining favor for several reasons. First, fixatives that impair biological activity are not required. Second, AFM is capable of detecting forces in the pN range, and precise control of the force applied to the cantilever can be maintained. This combination facilitates the evaluation of physical characteristics of microbes. Third, rather than yielding the composite, statistical average of cell populations, as is the case with many biochemical assays, the behavior of single cells can be monitored. Despite the potential of AFM in microbiology, there are several limitations that must be considered. For example, the time required to record an image allows for the study of gross events such as cell division or membrane degradation from an antibiotic but precludes the evaluation of biological reactions and events that happen in just fractions of a second. Additionally, the AFM is a topographical tool and is restricted to imaging surfaces. Therefore, it cannot be used to look inside cells as with opticla and transmission electron microscopes. other practical considerations are the

  2. Cortical interneurons from human pluripotent stem cells: prospects for neurological and psychiatric disease

    Directory of Open Access Journals (Sweden)

    Charles Edward Arber

    2013-03-01

    Full Text Available Cortical interneurons represent 20% of the cells in the cortex. These cells are local inhibitory neurons whose function is to modulate the firing activities of the excitatory projection neurons. Cortical interneuron dysfunction is believed to lead to runaway excitation underlying (or implicated in seizure-based diseases, such as epilepsy, autism and schizophrenia. The complex development of this cell type and the intricacies involved in defining the relative subtypes are being increasingly well defined. This has led to exciting experimental cell therapy in model organisms, whereby fetal-derived interneuron precursors can reverse seizure severity and reduce mortality in adult epileptic rodents. These proof-of-principle studies raise hope for potential interneuron-based transplantation therapies for treating epilepsy. On the other hand, cortical neurons generated from patient iPSCs serve as a valuable tool to explore genetic influences of interneuron development and function. This is a fundamental step in enhancing our understanding of the molecular basis of neuropsychiatric illnesses and the development of targeted treatments. Protocols are currently being developed for inducing cortical interneuron subtypes from mouse and human pluripotent stem cells. This review sets out to summarize the progress made in cortical interneuron development, fetal tissue transplantation and the recent advance in stem cell differentiation towards interneurons.

  3. Combined small-molecule inhibition accelerates the derivation of functional, early-born, cortical neurons from human pluripotent stem cells

    Science.gov (United States)

    Qi, Yuchen; Zhang, Xin-Jun; Renier, Nicolas; Wu, Zhuhao; Atkin, Talia; Sun, Ziyi; Ozair, M. Zeeshan; Tchieu, Jason; Zimmer, Bastian; Fattahi, Faranak; Ganat, Yosif; Azevedo, Ricardo; Zeltner, Nadja; Brivanlou, Ali H.; Karayiorgou, Maria; Gogos, Joseph; Tomishima, Mark; Tessier-Lavigne, Marc; Shi, Song-Hai; Studer, Lorenz

    2017-01-01

    Considerable progress has been made in converting human pluripotent stem cells (hPSCs) into functional neurons. However, the protracted timing of human neuron specification and functional maturation remains a key challenge that hampers the routine application of hPSC-derived lineages in disease modeling and regenerative medicine. Using a combinatorial small-molecule screen, we previously identified conditions for the rapid differentiation of hPSCs into peripheral sensory neurons. Here we generalize the approach to central nervous system (CNS) fates by developing a small-molecule approach for accelerated induction of early-born cortical neurons. Combinatorial application of 6 pathway inhibitors induces post-mitotic cortical neurons with functional electrophysiological properties by day 16 of differentiation, in the absence of glial cell co-culture. The resulting neurons, transplanted at 8 days of differentiation into the postnatal mouse cortex, are functional and establish long-distance projections, as shown using iDISCO whole brain imaging. Accelerated differentiation into cortical neuron fates should facilitate hPSC-based strategies for disease modeling and cell therapy in CNS disorders. PMID:28112759

  4. Displacement of the mitotic apparatuses by centrifugation reveals cortical actin organization during cytokinesis in cultured tobacco BY-2 cells.

    Science.gov (United States)

    Arima, Kengo; Tamaoki, Daisuke; Mineyuki, Yoshinobu; Yasuhara, Hiroki; Nakai, Tomonori; Shimmen, Teruo; Yoshihisa, Tohru; Sonobe, Seiji

    2018-06-19

    In plant cytokinesis, actin is thought to be crucial in cell plate guidance to the cortical division zone (CDZ), but its organization and function are not fully understood. To elucidate actin organization during cytokinesis, we employed an experimental system, in which the mitotic apparatus is displaced and separated from the CDZ by centrifugation and observed using a global-local live imaging microscope that enabled us to record behavior of actin filaments in the CDZ and the whole cell division process in parallel. In this system, returning movement of the cytokinetic apparatus in cultured-tobacco BY-2 cells occurs, and there is an advantage to observe actin organization clearly during the cytokinetic phase because more space was available between the CDZ and the distantly formed phragmoplast. Actin cables were clearly observed between the CDZ and the phragmoplast in BY-2 cells expressing GFP-fimbrin after centrifugation. Both the CDZ and the edge of the expanding phragmoplast had actin bulges. Using live-cell imaging including the global-local live imaging microscopy, we found actin filaments started to accumulate at the actin-depleted zone when cell plate expansion started even in the cell whose cell plate failed to reach the CDZ. These results suggest that specific accumulation of actin filaments at the CDZ and the appearance of actin cables between the CDZ and the phragmoplast during cell plate formation play important roles in the guidance of cell plate edges to the CDZ.

  5. Cytokines effects on radio-induced apoptosis in cortical and hippocampal rat cells in culture

    International Nuclear Information System (INIS)

    Coffigny, H.; Briot, D.; Le Nin, I.

    2000-01-01

    In the central nervous system in development the radio-induced cell death occurs mainly by apoptosis. The effects of modulating factors like cytokines were studied on this kind of death. To handle more easily parameters implicated in nerve cell apoptosis, we studied the effects of radiation with a in vitro system. Cells were isolated from rat foetal cortex and hippocampus, two of the major structures implicated in human mental retardation observed after exposition in utero at Hiroshima and Nagasaki. Cortical or hippocampal cells were isolated from 17 day-old rat foetuses by enzymatic and mechanical treatments and irradiated with 0.50 or 1 Gy. The cells from both structures were cultured 1 or 3 days in serum free medium. Cytokines like βNGF, NT3, EGF, βTGF, α and βFGF, IGF I and II, interleukines like Il 1β, Il 2 and IL 6 were added to the medium. In 3 days cortical cell culture, only βFGF increased cell survival with as little as 10 ng/ml. This effect was dose dependent. In hippocampal cell culture, no significant increase of cell survival occurred with 10 ng/ml of any cytokines. In the same system culture with 1 Gy irradiation, the positive or negative effect of the association of βFGF with another cytokine was tested on cell survival. Only the association with EGF induced higher cell survival in cortical cell culture. In hippocampal cell culture where βFGF alone had no effect, the cell survival was not modified by the association. In the same system, the triple association of βFGF-EGF with another cytokine was tested on hippocampal and cortical cell cultures. No significant effect was observed in both cultures but cell survival trented to decrease with βTGF. In order to avoid the mitotic effect of cytokines in the 3 day-old culture, experiments were carried out on 20 hours cell culture, before the end of the first round of the cell cycle, with the selected cytokines (βFGF or βFGF-EGF). Without irradiation, the percentage of cortical cell survival

  6. Automatic cortical surface reconstruction of high-resolution T1 echo planar imaging data.

    Science.gov (United States)

    Renvall, Ville; Witzel, Thomas; Wald, Lawrence L; Polimeni, Jonathan R

    2016-07-01

    Echo planar imaging (EPI) is the method of choice for the majority of functional magnetic resonance imaging (fMRI), yet EPI is prone to geometric distortions and thus misaligns with conventional anatomical reference data. The poor geometric correspondence between functional and anatomical data can lead to severe misplacements and corruption of detected activation patterns. However, recent advances in imaging technology have provided EPI data with increasing quality and resolution. Here we present a framework for deriving cortical surface reconstructions directly from high-resolution EPI-based reference images that provide anatomical models exactly geometric distortion-matched to the functional data. Anatomical EPI data with 1mm isotropic voxel size were acquired using a fast multiple inversion recovery time EPI sequence (MI-EPI) at 7T, from which quantitative T1 maps were calculated. Using these T1 maps, volumetric data mimicking the tissue contrast of standard anatomical data were synthesized using the Bloch equations, and these T1-weighted data were automatically processed using FreeSurfer. The spatial alignment between T2(⁎)-weighted EPI data and the synthetic T1-weighted anatomical MI-EPI-based images was improved compared to the conventional anatomical reference. In particular, the alignment near the regions vulnerable to distortion due to magnetic susceptibility differences was improved, and sampling of the adjacent tissue classes outside of the cortex was reduced when using cortical surface reconstructions derived directly from the MI-EPI reference. The MI-EPI method therefore produces high-quality anatomical data that can be automatically segmented with standard software, providing cortical surface reconstructions that are geometrically matched to the BOLD fMRI data. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Quantification of renal cortical blood flow using factor analysis of O-15 water dynamic PET images

    International Nuclear Information System (INIS)

    Seo, Kang Jun; Ahn, Ji Young; Lee, Jae Sung; Paeng, Jin Chul; Cheon, Gi Jeong; Lee, Dong Soo; Noh, Tae Won; Chung, June Key; Lee, Myung Chul

    2000-01-01

    To obtain spatial distribution of renal factor images, input function, and regional tissue time-activity curve (TAC) from O-15 water dynamic PET images non-invasively, factor analysis (FA) was used. O-15 water dynamic PET scans were performed on 3 normal dogs (22 ∼ 29 kg) with the bolus injection of O-15 water (555 ∼ 740 Mbq). We performed FA on the masked dynamic images and obtained the pure TACs and the corresponding factor images. Microsphere experiment also was performed. 37MBq of microsphere labeled with Sc-46 was injected into the left ventricle. Arterial input functions derived from the PET images using FA were compared with the invasively derived arterial blood samples. The renal cortical blood flow using the TACs by FA was within the normal range of 1.23 ∼ 2.46 ml/min/g. In microsphere study, the renal cortical blood flow of left kidney by FA was 2.49±0.47 ml/min/g (1.81∼2.90 ml/min/g) and by microsphere was 2.52 ±0.19 ml/min/g (2.34 ∼2.68 ml/min/g). In right kidney, flow by FA was 2.02 ±0.32 ml/min/g (1.82∼2.49 ml/min/g) and by microsphere was 2.49 ±0.27 ml/min/g (2.02∼2.7). FA is a useful and robust method to extract input functions and tissue TACs from O-15 dynamic renal PET. Renal cortical blood flow can be estimated non-invasively using FA and it will be helpful for the assessment of renal functional disease

  8. Influence of basis images and skull position on evaluation of cortical bone thickness in cone beam computed tomography.

    Science.gov (United States)

    Nascimento, Monikelly do Carmo Chagas; Boscolo, Solange Maria de Almeida; Haiter-Neto, Francisco; Santos, Emanuela Carla Dos; Lambrichts, Ivo; Pauwels, Ruben; Jacobs, Reinhilde

    2017-06-01

    The aim of this study was to assess the influence of the number of basis images and the orientation of the skull on the evaluation of cortical alveolar bone in cone beam computed tomography (CBCT). Eleven skulls with a total of 59 anterior teeth were selected. CBCT images were acquired by using 4 protocols, by varying the rotation of the tube-detector arm and the orientation of the skull (protocol 1: 360°/0°; protocol 2: 180°/0°; protocol 3: 180°/90°; protocol 4: 180°/180°). Observers evaluated cortical bone as absent, thin, or thick. Direct observation of the skulls was used as the gold standard. Intra- and interobserver agreement, as well as agreement of scoring between the 3 bone thickness classifications, were calculated by using the κ statistic. The Wilcoxon signed-rank test was used to compare the 4 protocols. For lingual cortical bone, protocol 1 showed no statistical difference from the gold standard. Higher reliability was found in protocol 3 for absent (κ = 0.80) and thin (κ = 0.47) cortices, whereas for thick cortical bone, protocol 2 was more consistent (κ = 0.60). In buccal cortical bone, protocol 1 obtained the highest agreement for absent cortices (κ = 0.61), whereas protocol 4 was better for thin cortical plates (κ = 0.38) and protocol 2 for thick cortical plates (κ = 0.40). No consistent effect of the number of basis images or head orientation for visual detection of alveolar bone was detected, except for lingual cortical bone, for which full rotation scanning showed improved visualization. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Mouse embryonic stem cell culture for generation of three-dimensional retinal and cortical tissues.

    Science.gov (United States)

    Eiraku, Mototsugu; Sasai, Yoshiki

    2011-12-15

    Generation of compound tissues with complex structures is a major challenge in cell biology. In this article, we describe a protocol for mouse embryonic stem cell (ESC) culture for in vitro generation of three-dimensional retinal tissue, comparing it with the culture protocol for cortical tissue generation. Dissociated ESCs are reaggregated in a 96-well plate with reduced cell-plate adhesion and cultured as floating aggregates. Retinal epithelium is efficiently generated when ESC aggregates are cultured in serum-free medium containing extracellular matrix proteins, spontaneously forming hemispherical vesicles and then progressively transforming into a shape reminiscent of the embryonic optic cup in 9-10 d. In long-term culture, the ESC-derived optic cup generates a fully stratified retinal tissue consisting of all major neural retinal components. In contrast, the cortical differentiation culture can be started without exogenous extracellular matrix proteins, and it generates stratified cortical epithelia consisting of four distinct layers in 13 d.

  10. Preservation of visual cortical function following retinal pigment epithelium transplantation in the RCS rat using optical imaging techniques.

    Science.gov (United States)

    Gias, Carlos; Jones, Myles; Keegan, David; Adamson, Peter; Greenwood, John; Lund, Ray; Martindale, John; Johnston, David; Berwick, Jason; Mayhew, John; Coffey, Peter

    2007-04-01

    The aim of this study was to determine the extent of cortical functional preservation following retinal pigment epithelium (RPE) transplantation in the Royal College of Surgeons (RCS) rat using single-wavelength optical imaging and spectroscopy. The cortical responses to visual stimulation in transplanted rats at 6 months post-transplantation were compared with those from age-matched untreated dystrophic and non-dystrophic rats. Our results show that cortical responses were evoked in non-dystrophic rats to both luminance changes and pattern stimulation, whereas no response was found in untreated dystrophic animals to any of the visual stimuli tested. In contrast, a cortical response was elicited in most of the transplanted rats to luminance changes and in many of those a response was also evoked to pattern stimulation. Although the transplanted rats did not respond to high spatial frequency information we found evidence of preservation in the cortical processing of luminance changes and low spatial frequency stimulation. Anatomical sections of transplanted rat retinas confirmed the capacity of RPE transplantation to rescue photoreceptors. Good correlation was found between photoreceptor survival and the extent of cortical function preservation determined with optical imaging techniques. This study determined the efficacy of RPE transplantation to preserve visual cortical processing and established optical imaging as a powerful technique for its assessment.

  11. Clinical and imaging characteristics of localized megalencephaly: a retrospective comparison of diffuse hemimegalencephaly and multilobar cortical dysplasia

    Energy Technology Data Exchange (ETDEWEB)

    Nakahashi, Masumi; Tsushima, Yoshito; Amanuma, Makoto; Endo, Keigo [Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Sato, Noriko; Ota, Miho [National Center Hospital of Neurology and Psychiatry, Department of Radiology, Kodaira, Tokyo (Japan); Yagishita, Akira [Tokyo Metropolitan Neurological Hospital, Department of Neuroradiology, Kokubunji, Tokyo (Japan); Saito, Yoshiaki; Sugai, Kenji; Sasaki, Masayuki [National Center Hospital of Neurology and Psychiatry, Department of Child Neurology, Kodaira, Tokyo (Japan); Natsume, Jun [Nagoya University Graduate School of Medicine, Department of Pediatrics, Nagoya, Aichi (Japan)

    2009-12-15

    Hemimegalencephaly is a well-known congenital malformation. However, localized megalencephaly, which may be one of the subtypes of hemimegalencephaly, has not been separately investigated. In the present study, we attempted to characterize the clinical and magnetic resonance (MR) imaging features of localized megalencephaly in comparison with ordinary diffuse hemimegalencephaly and multilobar cortical dysplasia. MR findings for 43 patients with hemimegalencephaly and ten with multilobar cortical dysplasia, which is the differential diagnosis of localized megalencephaly, were retrospectively reviewed. Clinical findings such as the onset and severity of seizures and imaging findings including the affected area of the brain, structures outside of the hemisphere, and interval morphological changes were examined. Of the 43 patients, 11 showed signs of localized megalencephaly (25.6%). Localized megalencephaly was predominantly seen on the left side (72.7%) and had a tendency toward severe-grade seizures compared to multilobar cortical dysplasia. The frequencies of the extracerebral abnormalities in the diffuse hemimegalencephaly, localized megalencephaly, and multilobar cortical dysplasia groups were 84.4%, 36.4%, and 0.0%, respectively. There were three localized megalencephaly patients whose affected areas shrank and whose images were similar to those of multilobar cortical dysplasia. Localized megalencephaly accounts for one quarter of all hemimegalencephaly cases in this study. The incidence of extracerebral abnormalities in patients with localized hemimegalencephaly was almost half that of patients with diffuse hemimegalencephaly. Extracerebral abnormalities were absent in patients with multilobar cortical dysplasia. Associated extracerebral abnormalities may be a clue to differentiating localized megalencephaly from multilobar cortical dysplasia. (orig.)

  12. Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images

    Directory of Open Access Journals (Sweden)

    Shengwen Guo

    2017-05-01

    Full Text Available Neuroimaging measurements derived from magnetic resonance imaging provide important information required for detecting changes related to the progression of mild cognitive impairment (MCI. Cortical features and changes play a crucial role in revealing unique anatomical patterns of brain regions, and further differentiate MCI patients from normal states. Four cortical features, namely, gray matter volume, cortical thickness, surface area, and mean curvature, were explored for discriminative analysis among three groups including the stable MCI (sMCI, the converted MCI (cMCI, and the normal control (NC groups. In this study, 158 subjects (72 NC, 46 sMCI, and 40 cMCI were selected from the Alzheimer's Disease Neuroimaging Initiative. A sparse-constrained regression model based on the l2-1-norm was introduced to reduce the feature dimensionality and retrieve essential features for the discrimination of the three groups by using a support vector machine (SVM. An optimized strategy of feature addition based on the weight of each feature was adopted for the SVM classifier in order to achieve the best classification performance. The baseline cortical features combined with the longitudinal measurements for 2 years of follow-up data yielded prominent classification results. In particular, the cortical thickness produced a classification with 98.84% accuracy, 97.5% sensitivity, and 100% specificity for the sMCI–cMCI comparison; 92.37% accuracy, 84.78% sensitivity, and 97.22% specificity for the cMCI–NC comparison; and 93.75% accuracy, 92.5% sensitivity, and 94.44% specificity for the sMCI–NC comparison. The best performances obtained by the SVM classifier using the essential features were 5–40% more than those using all of the retained features. The feasibility of the cortical features for the recognition of anatomical patterns was certified; thus, the proposed method has the potential to improve the clinical diagnosis of sub-types of MCI and

  13. Sensorimotor cortical activity in patients with complete spinal cord injury: a functional magnetic resonance imaging study.

    Science.gov (United States)

    Sabbah, P; de, Schonen S; Leveque, C; Gay, S; Pfefer, F; Nioche, C; Sarrazin, J L; Barouti, H; Tadie, M; Cordoliani, Y S

    2002-01-01

    Residual activation of the cortex was investigated in nine patients with complete spinal cord injury between T6 and L1 by functional magnetic resonance imaging (fMRI). Brain activations were recorded under four conditions: (1) a patient attempting to move his toes with flexion-extension, (2) a patient imagining the same movement, (3) passive proprio-somesthesic stimulation of the big toes without visual control, and (4) passive proprio-somesthesic stimulation of the big toes with visual control by the patient. Passive proprio-somesthesic stimulation of the toes generated activation posterior to the central sulcus in the three patients who also showed a somesthesic evoked potential response to somesthesic stimulation. When performed under visual control, activations were observed in two more patients. In all patients, activations were found in the cortical areas involved in motor control (i.e., primary sensorimotor cortex, premotor regions and supplementary motor area [SMA]) during attempts to move or mental imagery of these tasks. It is concluded that even several years after injury with some local cortical reorganization, activation of lower limb cortical networks can be generated either by the attempt to move, the mental evocation of the action, or the visual feedback of a passive proprio-somesthesic stimulation.

  14. Accuracy limits for the determination of cortical width and density: the influence of object size and CT imaging parameters

    International Nuclear Information System (INIS)

    Prevrhal, S.; Engelke, K.; Kalender, W.A.

    1999-01-01

    In this study we analysed the accuracy of computed tomography (CT) measurements in assessing cortical bone. We determined the dependency of thickness and density measurements on the true width and density of the cortex and on the spatial resolution in the CT images using two optimized segmentation methods. As a secondary goal, we assessed the ability of CT to reflect small changes in cortical thickness. Two different bone-mimicking phantoms with varying cortical thickness were scanned with single-slice CT on a Somatom Plus 4 scanner. Images were reconstructed with both a standard and a high-resolution convolution kernel. Two special operator-independent segmentation methods were used to automatically detect the edges of the cortical shell. We measured cortical thickness and density and compared the phantom measurements with theoretical computations by simulating a cross-sectional shape of the cortical shell. Based on the simulations, we calculated CT's power to detect small changes in cortical thickness. Simulations and phantom measurements were in very good agreement. Cortical thickness could be measured with an error of less than 10% if the true thickness was larger than 0.9 (0.7) mm for the standard (high-resolution) kernel which is close to the full width at half maximum (FWHM) of the point spread functions for these kernels and our scanner. Density measurements yielded errors of less than 10% for true cortical thickness values above two to three times the FWHM corresponding to 2.5 (2) mm in our case. The simulations showed that a 10% change in cortical width would not be detected with satisfying probability in bones with a cortical shell thinner than 1.2 mm. An accurate determination of the cortical thickness is limited to bones with a thickness higher than the FWHM of the scanner's point spread function. Therefore, the use of a high-resolution reconstruction kernel is crucial. Cortical bone mineral density can only be measured accurately in bones two to three

  15. Time-sequential observation of spindle and phragmoplast orientation in BY-2 cells with altered cortical actin microfilament patterning.

    Science.gov (United States)

    Kojo, Kei H; Yasuhara, Hiroki; Hasezawa, Seiichiro

    2014-01-01

    Precise division plane determination is essential for plant development. At metaphase, a dense actin microfilament meshwork appears on both sides of the cell center, forming a characteristic cortical actin microfilament twin peak pattern in BY-2 cells. We previously reported a strong correlation between altered cortical actin microfilament patterning and an oblique mitotic spindle orientation, implying that these actin microfilament twin peaks play a role in the regulation of mitotic spindle orientation. In the present study, time-sequential observation was used to reveal the progression from oblique phragmoplast to oblique cell plate orientation in cells with altered cortical actin microfilament patterning. In contrast to cells with normal actin microfilament twin peaks, oblique phragmoplast reorientation was rarely observed in cells with altered cortical actin microfilament patterning. These results support the important roles of cortical actin microfilament patterning in division plane orientation.

  16. Localizing ECoG electrodes on the cortical anatomy without post-implantation imaging

    Science.gov (United States)

    Gupta, Disha; Hill, N. Jeremy; Adamo, Matthew A.; Ritaccio, Anthony; Schalk, Gerwin

    2014-01-01

    Introduction Electrocorticographic (ECoG) grids are placed subdurally on the cortex in people undergoing cortical resection to delineate eloquent cortex. ECoG signals have high spatial and temporal resolution and thus can be valuable for neuroscientific research. The value of these data is highest when they can be related to the cortical anatomy. Existing methods that establish this relationship rely either on post-implantation imaging using computed tomography (CT), magnetic resonance imaging (MRI) or X-Rays, or on intra-operative photographs. For research purposes, it is desirable to localize ECoG electrodes on the brain anatomy even when post-operative imaging is not available or when intra-operative photographs do not readily identify anatomical landmarks. Methods We developed a method to co-register ECoG electrodes to the underlying cortical anatomy using only a pre-operative MRI, a clinical neuronavigation device (such as BrainLab VectorVision), and fiducial markers. To validate our technique, we compared our results to data collected from six subjects who also had post-grid implantation imaging available. We compared the electrode coordinates obtained by our fiducial-based method to those obtained using existing methods, which are based on co-registering pre- and post-grid implantation images. Results Our fiducial-based method agreed with the MRI–CT method to within an average of 8.24 mm (mean, median = 7.10 mm) across 6 subjects in 3 dimensions. It showed an average discrepancy of 2.7 mm when compared to the results of the intra-operative photograph method in a 2D coordinate system. As this method does not require post-operative imaging such as CTs, our technique should prove useful for research in intra-operative single-stage surgery scenarios. To demonstrate the use of our method, we applied our method during real-time mapping of eloquent cortex during a single-stage surgery. The results demonstrated that our method can be applied intra

  17. Plant cortical microtubule dynamics and cell division plane orientation

    NARCIS (Netherlands)

    Chakrabortty, Bandan

    2017-01-01

    This thesis work aimed at a better understanding of the molecular basis of oriented cell division in plant cell. As, the efficiency of plant morphogenesis depends on oriented cell division, this work should contribute towards a fundamental understanding of the molecular basis of efficient plant

  18. Generation of induced pluripotent stem cells with high efficiency from human embryonic renal cortical cells.

    Science.gov (United States)

    Yao, Ling; Chen, Ruifang; Wang, Pu; Zhang, Qi; Tang, Hailiang; Sun, Huaping

    2016-01-01

    Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) emerges as a prospective therapeutic angle in regenerative medicine and a tool for drug screening. Although increasing numbers of iPSCs from different sources have been generated, there has been limited progress in yield of iPSC. Here, we show that four Yamanaka factors Oct4, Sox2, Klf4 and c-Myc can convert human embryonic renal cortical cells (hERCCs) to pluripotent stem cells with a roughly 40-fold higher reprogramming efficiency compared with that of adult human dermal fibroblasts. These iPSCs show pluripotency in vitro and in vivo, as evidenced by expression of pluripotency associated genes, differentiation into three embryonic germ layers by teratoma tests, as well as neuronal fate specification by embryoid body formation. Moreover, the four exogenous genes are effectively silenced in these iPSCs. This study highlights the use of hERCCs to generate highly functional human iPSCs which may aid the study of genetic kidney diseases and accelerate the development of cell-based regenerative therapy.

  19. 101 labeled brain images and a consistent human cortical labeling protocol

    Directory of Open Access Journals (Sweden)

    Arno eKlein

    2012-12-01

    Full Text Available We introduce the Mindboggle-101 dataset, the largest and most complete set of free, publicly accessible, manually labeled human brain images. To manually label the macroscopic anatomy in magnetic resonance images of 101 healthy participants, we created a new cortical labeling protocol that relies on robust anatomical landmarks and minimal manual edits after initialization with automated labels. The Desikan-Killiany-Tourville (DKT protocol is intended to improve the ease, consistency, and accuracy of labeling human cortical areas. Given how difficult it is to label brains, the Mindboggle-101 dataset is intended to serve as brain atlases for use in labeling other brains, as a normative dataset to establish morphometric variation in a healthy population for comparison against clinical populations, and contribute to the development, training, testing, and evaluation of automated registration and labeling algorithms. To this end, we also introduce benchmarks for the evaluation of such algorithms by comparing our manual labels with labels automatically generated by probabilistic and multi-atlas registration-based approaches. All data and related software and updated information are available on the http://www.mindboggle.info/data/ website.

  20. 101 Labeled Brain Images and a Consistent Human Cortical Labeling Protocol

    Science.gov (United States)

    Klein, Arno; Tourville, Jason

    2012-01-01

    We introduce the Mindboggle-101 dataset, the largest and most complete set of free, publicly accessible, manually labeled human brain images. To manually label the macroscopic anatomy in magnetic resonance images of 101 healthy participants, we created a new cortical labeling protocol that relies on robust anatomical landmarks and minimal manual edits after initialization with automated labels. The “Desikan–Killiany–Tourville” (DKT) protocol is intended to improve the ease, consistency, and accuracy of labeling human cortical areas. Given how difficult it is to label brains, the Mindboggle-101 dataset is intended to serve as brain atlases for use in labeling other brains, as a normative dataset to establish morphometric variation in a healthy population for comparison against clinical populations, and contribute to the development, training, testing, and evaluation of automated registration and labeling algorithms. To this end, we also introduce benchmarks for the evaluation of such algorithms by comparing our manual labels with labels automatically generated by probabilistic and multi-atlas registration-based approaches. All data and related software and updated information are available on the http://mindboggle.info/data website. PMID:23227001

  1. The effects of caffeine ingestion on cortical areas: functional imaging study.

    Science.gov (United States)

    Park, Chan-A; Kang, Chang-Ki; Son, Young-Don; Choi, Eun-Jung; Kim, Sang-Hoon; Oh, Seung-Taek; Kim, Young-Bo; Park, Chan-Woong; Cho, Zang-Hee

    2014-05-01

    The effect of caffeine as a cognitive enhancer is well known; however, caffeine-induced changes in the cortical regions are still not very clear. Therefore, in this study, we conducted an investigation of the activation and deactivation with blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) and of metabolic activity change with positron emission tomography (PET) in the human brain. Fourteen healthy subjects performed a visuomotor task inducing attention with 3T MRI, and PET imaging was also carried out in seven subjects to determine the cerebral glucose metabolic changes of caffeine at rest. The result by fMRI showed increased BOLD activation in the left cerebellum, putamen, insula, thalamus and the right primary motor cortex, and decreased BOLD deactivation in the posterior medial and the left posterior lateral cortex. Also, the resting state PET data showed reduced metabolic activity in the putamen, caudate nucleus, insula, pallidum and posterior medial cortex. The common cortical regions between fMRI and PET, such as putamen, insula and posterior medial cortex, where significant changes occurred after caffeine ingestion, are well known to play an important role in cognitive function like attention. This result suggests that the effect of caffeine as a cognitive enhancer is derived by modulating the attentional areas. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Increased cortical-limbic anatomical network connectivity in major depression revealed by diffusion tensor imaging.

    Directory of Open Access Journals (Sweden)

    Peng Fang

    Full Text Available Magnetic resonance imaging studies have reported significant functional and structural differences between depressed patients and controls. Little attention has been given, however, to the abnormalities in anatomical connectivity in depressed patients. In the present study, we aim to investigate the alterations in connectivity of whole-brain anatomical networks in those suffering from major depression by using machine learning approaches. Brain anatomical networks were extracted from diffusion magnetic resonance images obtained from both 22 first-episode, treatment-naive adults with major depressive disorder and 26 matched healthy controls. Using machine learning approaches, we differentiated depressed patients from healthy controls based on their whole-brain anatomical connectivity patterns and identified the most discriminating features that represent between-group differences. Classification results showed that 91.7% (patients=86.4%, controls=96.2%; permutation test, p<0.0001 of subjects were correctly classified via leave-one-out cross-validation. Moreover, the strengths of all the most discriminating connections were increased in depressed patients relative to the controls, and these connections were primarily located within the cortical-limbic network, especially the frontal-limbic network. These results not only provide initial steps toward the development of neurobiological diagnostic markers for major depressive disorder, but also suggest that abnormal cortical-limbic anatomical networks may contribute to the anatomical basis of emotional dysregulation and cognitive impairments associated with this disease.

  3. Cortical phase changes in Alzheimer's disease at 7T MRI: a novel imaging marker.

    Science.gov (United States)

    van Rooden, Sanneke; Versluis, Maarten J; Liem, Michael K; Milles, Julien; Maier, Andrea B; Oleksik, Ania M; Webb, Andrew G; van Buchem, Mark A; van der Grond, Jeroen

    2014-01-01

    Postmortem studies have indicated the potential of high-field magnetic resonance imaging (MRI) to visualize amyloid depositions in the cerebral cortex. The aim of this study is to test this hypothesis in patients with Alzheimer's disease (AD). T2*-weighted MRI was performed in 16 AD patients and 15 control subjects. All magnetic resonance images were scored qualitatively by visual assessment, and quantitatively by measuring phase shifts in the cortical gray matter and hippocampus. Statistical analysis was performed to assess differences between groups. Patients with AD demonstrated an increased phase shift in the cortex in the temporoparietal, frontal, and parietal regions (P < .005), and this was associated with individual Mini-Mental State Examination scores (r = -0.54, P < .05). Increased cortical phase shift in AD patients demonstrated on 7-tesla T2*-weighted MRI is a potential new biomarker for AD, which may reflect amyloid pathology in the early stages. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  4. Neuroanatomical correlates of tinnitus revealed by cortical thickness analysis and diffusion tensor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Aldhafeeri, Faten M [The University of Liverpool, Department of Medical Imaging, School of Health Sciences, Liverpool (United Kingdom); King Khalid General Hospital, Ministry of Health, Radiology Department, Hafral-batin (Saudi Arabia); Mackenzie, Ian; Kay, Tony [Aintree University Hospitals NHS Foundation Trust, Liverpool (United Kingdom); Alghamdi, Jamaan [The University of Liverpool, Department of Medical Imaging, School of Health Sciences, Liverpool (United Kingdom); King Abdul Aziz University, Physics Department, Faculty of Sciences, Jeddah (Saudi Arabia); Sluming, Vanessa [The University of Liverpool, Department of Medical Imaging, School of Health Sciences, Liverpool (United Kingdom); Magnetic Resonance and Image Analysis Research Centre, Liverpool (United Kingdom)

    2012-08-15

    Tinnitus is a poorly understood auditory perception of sound in the absence of external stimuli. Convergent evidence proposes that tinnitus perception involves brain structural alterations as part of its pathophysiology. The aim of this study is to investigate the structural brain changes that might be associated with tinnitus-related stress and negative emotions. Using high-resolution magnetic resonance imaging and diffusion tensor imaging, we investigated grey matter and white matter (WM) alterations by estimating cortical thickness measures, fractional anisotropy and mean diffusivity in 14 tinnitus subjects and 14 age- and sex-matched non-tinnitus subjects. Significant cortical thickness reductions were found in the prefrontal cortex (PFC), temporal lobe and limbic system in tinnitus subjects compared to non-tinnitus subjects. Tinnitus sufferers were found to have disrupted WM integrity in tracts involving connectivity of the PFC, temporal lobe, thalamus and limbic system. Our results suggest that such neural changes may represent neural origins for tinnitus or consequences of tinnitus and its associations. (orig.)

  5. Neuroanatomical correlates of tinnitus revealed by cortical thickness analysis and diffusion tensor imaging

    International Nuclear Information System (INIS)

    Aldhafeeri, Faten M.; Mackenzie, Ian; Kay, Tony; Alghamdi, Jamaan; Sluming, Vanessa

    2012-01-01

    Tinnitus is a poorly understood auditory perception of sound in the absence of external stimuli. Convergent evidence proposes that tinnitus perception involves brain structural alterations as part of its pathophysiology. The aim of this study is to investigate the structural brain changes that might be associated with tinnitus-related stress and negative emotions. Using high-resolution magnetic resonance imaging and diffusion tensor imaging, we investigated grey matter and white matter (WM) alterations by estimating cortical thickness measures, fractional anisotropy and mean diffusivity in 14 tinnitus subjects and 14 age- and sex-matched non-tinnitus subjects. Significant cortical thickness reductions were found in the prefrontal cortex (PFC), temporal lobe and limbic system in tinnitus subjects compared to non-tinnitus subjects. Tinnitus sufferers were found to have disrupted WM integrity in tracts involving connectivity of the PFC, temporal lobe, thalamus and limbic system. Our results suggest that such neural changes may represent neural origins for tinnitus or consequences of tinnitus and its associations. (orig.)

  6. Imaging and reconstruction of cell cortex structures near the cell surface

    Science.gov (United States)

    Jin, Luhong; Zhou, Xiaoxu; Xiu, Peng; Luo, Wei; Huang, Yujia; Yu, Feng; Kuang, Cuifang; Sun, Yonghong; Liu, Xu; Xu, Yingke

    2017-11-01

    Total internal reflection fluorescence microscopy (TIRFM) provides high optical sectioning capability and superb signal-to-noise ratio for imaging of cell cortex structures. The development of multi-angle (MA)-TIRFM permits high axial resolution imaging and reconstruction of cellular structures near the cell surface. Cytoskeleton is composed of a network of filaments, which are important for maintenance of cell function. The high-resolution imaging and quantitative analysis of filament organization would contribute to our understanding of cytoskeleton regulation in cell. Here, we used a custom-developed MA-TIRFM setup, together with stochastic photobleaching and single molecule localization method, to enhance the lateral resolution of TIRFM imaging to about 100 nm. In addition, we proposed novel methods to perform filament segmentation and 3D reconstruction from MA-TIRFM images. Furthermore, we applied these methods to study the 3D localization of cortical actin and microtubule structures in U373 cancer cells. Our results showed that cortical actins localize ∼ 27 nm closer to the plasma membrane when compared with microtubules. We found that treatment of cells with chemotherapy drugs nocodazole and cytochalasin B disassembles cytoskeletal network and induces the reorganization of filaments towards the cell periphery. In summary, this study provides feasible approaches for 3D imaging and analyzing cell surface distribution of cytoskeletal network. Our established microscopy platform and image analysis toolkits would facilitate the study of cytoskeletal network in cells.

  7. Effects of deuterium oxide and galvanic vestibular stimulation on visual cortical cell function

    International Nuclear Information System (INIS)

    Reinis, S.; Landolt, J.P.; Weiss, D.S.; Money, K.E.

    1984-01-01

    The spontaneous and evoked unit activities of complex visual cortical cells were recorded from Brodmann's area 18 in immobilized, unanesthetized cats before, during, and after stimulation of the vestibular system. The vestibular system was stimulated by intravenous injection of deuterium oxide (D2O)--a noted nystagmogenic agent--or by direct galvanic stimulation of the labyrinth. Measures of the receptive-field areas, poststimulus time histograms, directional preferences, and the optimal speed of the light bar stimulating the cell were obtained before and after the application of D2O. Directional preferences were determined in a novel manner, using a method derived from a hierarchical clustering technique. Data were collected and analyzed from a) visual cortical cells in cats with intact labyrinths, b) visual cortical cells in cats following bilateral labrinthectomies, and c) nonvisual cortical cells in cats with intact labyrinths. The other cellular characteristics were also altered by the D2O. Galvanic stimulation of the labyrinth resembles, in its effects, the injection of D2O. In labyrinth-intact cats, the time course of area 18 spontaneous activity dramatically increased 30 min or more after D2O was administered. It peaked 2-3 h later and still had not returned to preinjection levels even 7 h after the D2O administration. In bilaterally labyrinthectomized cats, the spontaneous activity of the visual cells did not change following D2O administration. In nonvisual cells from labyrinth-intact cats, the spontaneous activity demonstrated a slight but significant decrease over time after D2O injection. In pilot studies, the cats were injected with D2O. Within 8-10 min afterward, signs of positional nystagmus commenced; and within 30 min, problems in maintaining balance were noted. This continued for 7-8 h before disappearing. In the labyrinthectomized animals, such effects were not observed

  8. Effects of deuterium oxide and galvanic vestibular stimulation on visual cortical cell function

    Energy Technology Data Exchange (ETDEWEB)

    Reinis, S.; Landolt, J.P.; Weiss, D.S.; Money, K.E.

    1984-03-01

    The spontaneous and evoked unit activities of complex visual cortical cells were recorded from Brodmann's area 18 in immobilized, unanesthetized cats before, during, and after stimulation of the vestibular system. The vestibular system was stimulated by intravenous injection of deuterium oxide (D2O)--a noted nystagmogenic agent--or by direct galvanic stimulation of the labyrinth. Measures of the receptive-field areas, poststimulus time histograms, directional preferences, and the optimal speed of the light bar stimulating the cell were obtained before and after the application of D2O. Directional preferences were determined in a novel manner, using a method derived from a hierarchical clustering technique. Data were collected and analyzed from a) visual cortical cells in cats with intact labyrinths, b) visual cortical cells in cats following bilateral labrinthectomies, and c) nonvisual cortical cells in cats with intact labyrinths. The other cellular characteristics were also altered by the D2O. Galvanic stimulation of the labyrinth resembles, in its effects, the injection of D2O. In labyrinth-intact cats, the time course of area 18 spontaneous activity dramatically increased 30 min or more after D2O was administered. It peaked 2-3 h later and still had not returned to preinjection levels even 7 h after the D2O administration. In bilaterally labyrinthectomized cats, the spontaneous activity of the visual cells did not change following D2O administration. In nonvisual cells from labyrinth-intact cats, the spontaneous activity demonstrated a slight but significant decrease over time after D2O injection. In pilot studies, the cats were injected with D2O. Within 8-10 min afterward, signs of positional nystagmus commenced; and within 30 min, problems in maintaining balance were noted. This continued for 7-8 h before disappearing. In the labyrinthectomized animals, such effects were not observed.

  9. Magnetoencephalographic Imaging of Auditory and Somatosensory Cortical Responses in Children with Autism and Sensory Processing Dysfunction

    Directory of Open Access Journals (Sweden)

    Carly Demopoulos

    2017-05-01

    Full Text Available This study compared magnetoencephalographic (MEG imaging-derived indices of auditory and somatosensory cortical processing in children aged 8–12 years with autism spectrum disorder (ASD; N = 18, those with sensory processing dysfunction (SPD; N = 13 who do not meet ASD criteria, and typically developing control (TDC; N = 19 participants. The magnitude of responses to both auditory and tactile stimulation was comparable across all three groups; however, the M200 latency response from the left auditory cortex was significantly delayed in the ASD group relative to both the TDC and SPD groups, whereas the somatosensory response of the ASD group was only delayed relative to TDC participants. The SPD group did not significantly differ from either group in terms of somatosensory latency, suggesting that participants with SPD may have an intermediate phenotype between ASD and TDC with regard to somatosensory processing. For the ASD group, correlation analyses indicated that the left M200 latency delay was significantly associated with performance on the WISC-IV Verbal Comprehension Index as well as the DSTP Acoustic-Linguistic index. Further, these cortical auditory response delays were not associated with somatosensory cortical response delays or cognitive processing speed in the ASD group, suggesting that auditory delays in ASD are domain specific rather than associated with generalized processing delays. The specificity of these auditory delays to the ASD group, in addition to their correlation with verbal abilities, suggests that auditory sensory dysfunction may be implicated in communication symptoms in ASD, motivating further research aimed at understanding the impact of sensory dysfunction on the developing brain.

  10. Intravital imaging of a massive lymphocyte response in the cortical dura of mice after peripheral infection by trypanosomes.

    Directory of Open Access Journals (Sweden)

    Jonathan A Coles

    2015-04-01

    Full Text Available Peripheral infection by Trypanosoma brucei, the protozoan responsible for sleeping sickness, activates lymphocytes, and, at later stages, causes meningoencephalitis. We have videoed the cortical meninges and superficial parenchyma of C56BL/6 reporter mice infected with T.b.brucei. By use of a two-photon microscope to image through the thinned skull, the integrity of the tissues was maintained. We observed a 47-fold increase in CD2+ T cells in the meninges by 12 days post infection (dpi. CD11c+ dendritic cells also increased, and extravascular trypanosomes, made visible either by expression of a fluorescent protein, or by intravenous injection of furamidine, appeared. The likelihood that invasion will spread from the meninges to the parenchyma will depend strongly on whether the trypanosomes are below the arachnoid membrane, or above it, in the dura. Making use of optical signals from the skull bone, blood vessels and dural cells, we conclude that up to 40 dpi, the extravascular trypanosomes were essentially confined to the dura, as were the great majority of the T cells. Inhibition of T cell activation by intraperitoneal injection of abatacept reduced the numbers of meningeal T cells at 12 dpi and their mean speed fell from 11.64 ± 0.34 μm/min (mean ± SEM to 5.2 ± 1.2 μm/min (p = 0.007. The T cells occasionally made contact lasting tens of minutes with dendritic cells, indicative of antigen presentation. The population and motility of the trypanosomes tended to decline after about 30 dpi. We suggest that the lymphocyte infiltration of the meninges may later contribute to encephalitis, but have no evidence that the dural trypanosomes invade the parenchyma.

  11. ImaEdge - a platform for quantitative analysis of the spatiotemporal dynamics of cortical proteins during cell polarization.

    Science.gov (United States)

    Zhang, Zhen; Lim, Yen Wei; Zhao, Peng; Kanchanawong, Pakorn; Motegi, Fumio

    2017-12-15

    Cell polarity involves the compartmentalization of the cell cortex. The establishment of cortical compartments arises from the spatial bias in the activity and concentration of cortical proteins. The mechanistic dissection of cell polarity requires the accurate detection of dynamic changes in cortical proteins, but the fluctuations of cell shape and the inhomogeneous distributions of cortical proteins greatly complicate the quantitative extraction of their global and local changes during cell polarization. To address these problems, we introduce an open-source software package, ImaEdge, which automates the segmentation of the cortex from time-lapse movies, and enables quantitative extraction of cortical protein intensities. We demonstrate that ImaEdge enables efficient and rigorous analysis of the dynamic evolution of cortical PAR proteins during Caenorhabditis elegans embryogenesis. It is also capable of accurate tracking of varying levels of transgene expression and discontinuous signals of the actomyosin cytoskeleton during multiple rounds of cell division. ImaEdge provides a unique resource for quantitative studies of cortical polarization, with the potential for application to many types of polarized cells.This article has an associated First Person interview with the first authors of the paper. © 2017. Published by The Company of Biologists Ltd.

  12. A new methodology of second messenger imaging for higher cortical functions by positron emission tomography

    International Nuclear Information System (INIS)

    Imahori, Yoshio; Ueda, Satoshi

    1992-01-01

    Neuronal manifestations are driven by second messenger systems in central nervous system through the neuronal transmission process. Receptor-mediated phosphatidylinositol (PI) response images may reflect neuronal activation in higher cortical function with a high sensitivity based on the common amplifying mechanism of the second messenger. Many bioactive compounds related to PI turnover have simple carbohydrate structures without amines and [ 11 C]ethylketene acylation has been found as the most effective labeling method of these compounds for positron emission tomography. [ 11 C]ethylketene was produced by the pyrolytic decomposition of [1- 11 C]butyric acid. This new method was made possible by the reaction under the no-carrier-added condition. To visualize the response in vivo, we synthesized sn-1,2-[ 11 C]diacylglycerols (DAGs) as a specific tracer for the PI response and [ 11 C]phorbol esters as a ligand for protein kinase C. In autoradiographic studies it was demonstrated that sn-1,2-[ 11 C]DAGs incorporation sites were discretely localized especially in the neocortex, which were concomitant with columnar structures. These results suggested that sn-1,2-[ 11 C]DAG can serve as an extrinsic substrate for the PI turnover by the phosphorylation mechanism and intensive neuronal processing, as a higher cortical function, occurs in these areas on the basis of receptor-mediated PI response. (author)

  13. Phenotype Analysis and Quantification of Proliferating Cells in the Cortical Gray Matter of the Adult Rat

    International Nuclear Information System (INIS)

    Mori, Tetsuji; Wakabayashi, Taketoshi; Takamori, Yasuharu; Kitaya, Kotaro; Yamada, Hisao

    2009-01-01

    In intact adult mammalian brains, there are two neurogenic regions: the subependymal zone and the subgranular layer of the hippocampus. Even outside these regions, small numbers of proliferating precursors do exist. Many studies suggest that the majority of these are oligodendrocyte precursors that express NG2, a chondroitin sulfate proteoglycan, and most of the residual proliferating cells seem to be endothelial cells. However, it is still unclear whether NG2-immunonegative proliferating precursors are present, because previous studies have neglected their possible existence. In this study, we systematically analyzed the phenotypes of the proliferating cells in the intact adult rat cortical gray matter. We improved our techniques and carefully characterized the proliferating cells, because there were several problems with identifying and quantifying the proliferating cells: the detection of NG2-expressing cells was dependent on the fixation condition; there were residual proliferating leukocytes in the blood vessels; and two anti-NG2 antibodies gave rise to different staining patterns. Moreover, we used two methods, BrdU and Ki67 immunostaining, to quantify the proliferating cells. Our results strongly suggest that in the intact adult cerebral cortical gray matter, there were only two types of proliferating cells: the majority were NG2-expressing cells, including pericytes, and the rest were endothelial cells

  14. Imaging separation of neuronal from vascular effects of cocaine on rat cortical brain in vivo

    International Nuclear Information System (INIS)

    Yuan, Z.; Du, C.; Luo, Z.; Volkow, N.D.; Pan, Y.

    2011-01-01

    MRI techniques to study brain function assume coupling between neuronal activity, metabolism and flow. However, recent evidence of physiological uncoupling between neuronal and cerebrovascular events highlights the need for methods to simultaneously measure these three properties. We report a multimodality optical approach that integrates dual-wavelength laser speckle imaging (measures changes in blood flow, blood volume and hemoglobin oxygenation), digital-frequency-ramping optical coherence tomography (images quantitative 3D vascular network) and Rhod2 fluorescence (images intracellular calcium for measure of neuronal activity) at high spatiotemporal resolutions (30 (micro)m, 10 Hz) and over a large field of view (3 x 5 mm 2 ). We apply it to assess cocaine's effects in rat cortical brain and show an immediate decrease 3.5 ± 0.9 min, phase (1) in the oxygen content of hemoglobin and the cerebral blood flow followed by an overshoot 7.1 ± 0.2 min, phase (2) lasting over 20 min whereas Ca 2+ increased immediately (peaked at t = 4.1 ± 0.4 min) and remained elevated. This enabled us to identify a delay (2.9 ± 0.5 min) between peak neuronal and vascular responses in phase 2. The ability of this multimodality optical approach for simultaneous imaging at high spatiotemporal resolutions permits us to distinguish the vascular versus cellular changes of the brain, thus complimenting other neuroimaging modalities for brain functional studies (e. g., PET, fMRI).

  15. Imaging separation of neuronal from vascular effects of cocaine on rat cortical brain in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Z.; Du, C.; Yuan, Z.; Luo, Z.; Volkow, N.D.; Pan, Y.; Du, C.

    2010-09-08

    MRI techniques to study brain function assume coupling between neuronal activity, metabolism and flow. However, recent evidence of physiological uncoupling between neuronal and cerebrovascular events highlights the need for methods to simultaneously measure these three properties. We report a multimodality optical approach that integrates dual-wavelength laser speckle imaging (measures changes in blood flow, blood volume and hemoglobin oxygenation), digital-frequency-ramping optical coherence tomography (images quantitative 3D vascular network) and Rhod2 fluorescence (images intracellular calcium for measure of neuronal activity) at high spatiotemporal resolutions (30 {micro}m, 10 Hz) and over a large field of view (3 x 5 mm{sup 2}). We apply it to assess cocaine's effects in rat cortical brain and show an immediate decrease 3.5 {+-} 0.9 min, phase (1) in the oxygen content of hemoglobin and the cerebral blood flow followed by an overshoot 7.1 {+-} 0.2 min, phase (2) lasting over 20 min whereas Ca{sup 2+} increased immediately (peaked at t = 4.1 {+-} 0.4 min) and remained elevated. This enabled us to identify a delay (2.9 {+-} 0.5 min) between peak neuronal and vascular responses in phase 2. The ability of this multimodality optical approach for simultaneous imaging at high spatiotemporal resolutions permits us to distinguish the vascular versus cellular changes of the brain, thus complimenting other neuroimaging modalities for brain functional studies (e. g., PET, fMRI).

  16. Astrocyte morphology after cortical stab wound revealed by single-cell confocal 3D morphometry

    Czech Academy of Sciences Publication Activity Database

    Chvátal, Alexandr; Anděrová, Miroslava; Petřík, David; Syková, Eva

    č. 2 (2003), s. 63 ISSN 0894-1491. [European Meeting on Glia l Cell Function in Health and Disease /6./. Berlín, 03.09.2003-06.09.2003] R&D Projects: GA ČR GA305/02/1528; GA MŠk LN00A065 Institutional research plan: CEZ:AV0Z5039906; CEZ:MSM 111300004 Keywords : cortical stab wound * morphometry Subject RIV: FH - Neurology Impact factor: 4.677, year: 2003

  17. Contribution of constitutively proliferating precursor cell subtypes to dentate neurogenesis after cortical infarcts

    Directory of Open Access Journals (Sweden)

    Oberland Julia

    2010-11-01

    Full Text Available Abstract Background It is well known that focal ischemia increases neurogenesis in the adult dentate gyrus of the hippocampal formation but the cellular mechanisms underlying this proliferative response are only poorly understood. We here investigated whether precursor cells which constitutively proliferate before the ischemic infarct contribute to post-ischemic neurogenesis. To this purpose, transgenic mice expressing green fluorescent protein (GFP under the control of the nestin promoter received repetitive injections of the proliferation marker bromodeoxyuridine (BrdU prior to induction of cortical infarcts. We then immunocytochemically analyzed the fate of these BrdU-positive precursor cell subtypes from day 4 to day 28 after the lesion. Results Quantification of BrdU-expressing precursor cell populations revealed no alteration in number of radial glia-like type 1 cells but a sequential increase of later precursor cell subtypes in lesioned animals (type 2a cells at day 7, type 3 cells/immature neurons at day 14. These alterations result in an enhanced survival of mature neurons 4 weeks postinfarct. Conclusions Focal cortical infarcts recruit dentate precursor cells generated already before the infarct and significantly contribute to an enhanced neurogenesis. Our findings thereby increase our understanding of the complex cellular mechanisms of postlesional neurogenesis.

  18. Generation of human cortical neurons from a new immortal fetal neural stem cell line

    International Nuclear Information System (INIS)

    Cacci, E.; Villa, A.; Parmar, M.; Cavallaro, M.; Mandahl, N.; Lindvall, O.; Martinez-Serrano, A.; Kokaia, Z.

    2007-01-01

    Isolation and expansion of neural stem cells (NSCs) of human origin are crucial for successful development of cell therapy approaches in neurodegenerative diseases. Different epigenetic and genetic immortalization strategies have been established for long-term maintenance and expansion of these cells in vitro. Here we report the generation of a new, clonal NSC (hc-NSC) line, derived from human fetal cortical tissue, based on v-myc immortalization. Using immunocytochemistry, we show that these cells retain the characteristics of NSCs after more than 50 passages. Under proliferation conditions, when supplemented with epidermal and basic fibroblast growth factors, the hc-NSCs expressed neural stem/progenitor cell markers like nestin, vimentin and Sox2. When growth factors were withdrawn, proliferation and expression of v-myc and telomerase were dramatically reduced, and the hc-NSCs differentiated into glia and neurons (mostly glutamatergic and GABAergic, as well as tyrosine hydroxylase-positive, presumably dopaminergic neurons). RT-PCR analysis showed that the hc-NSCs retained expression of Pax6, Emx2 and Neurogenin2, which are genes associated with regionalization and cell commitment in cortical precursors during brain development. Our data indicate that this hc-NSC line could be useful for exploring the potential of human NSCs to replace dead or damaged cortical cells in animal models of acute and chronic neurodegenerative diseases. Taking advantage of its clonality and homogeneity, this cell line will also be a valuable experimental tool to study the regulatory role of intrinsic and extrinsic factors in human NSC biology

  19. Mesenchymal stem cells can modulate longitudinal changes in cortical thickness and its related cognitive decline in patients with multiple system atrophy

    Directory of Open Access Journals (Sweden)

    Mun Kyung eSunwoo

    2014-06-01

    Full Text Available Multiple system atrophy (MSA is an adult-onset sporadic neurodegenerative disease. Because the prognosis of MSA is fatal, neuroprotective or regenerative strategies may be invaluable in MSA treatment. Previously, we obtained clinical and imaging evidence that mesenchymal stem cell (MSC treatment could have a neuroprotective role in MSA patients. In the present study, we evaluated the effects of MSC therapy on longitudinal changes in subcortical deep grey matter volumes and cortical thickness and their association with cognitive performance. Clinical and imaging data were obtained from our previous randomized trial of autologous MSC in MSA patients. During 1-year follow-up, we assessed longitudinal differences in subcortical deep grey matter volumes and cortical thickness between placebo (n=15 and MSC groups (n=11. Next, we performed correlation analysis between the changes in cortical thickness and changes in the Korean version of the Montreal Cognitive Assessment (MoCA scores and detailed cognitive performance. There were no significant differences in age, gender ratio, disease duration, clinical severity, MoCA score, or education level between the groups. The subcortical volumetric analysis revealed that the changes in deep grey matter volumes of the caudate, putamen, and thalamus did not differ significantly between the groups. The areas of cortical thinning over time in the placebo group were more extensive, including the frontal, temporal, and parietal areas, whereas these areas in the MSC group were less extensive. Correlation analysis indicated that declines in MoCA scores and phonemic fluency were significantly correlated with cortical thinning of the frontal and posterior temporal areas and anterior temporal areas in MSA patients, respectively. These results suggest that MSC treatment in patients with MSA may modulate cortical thinning over time and related cognitive performance, inferring a future therapeutic candidate for cognitive

  20. Cell-specific gain modulation by synaptically released zinc in cortical circuits of audition.

    Science.gov (United States)

    Anderson, Charles T; Kumar, Manoj; Xiong, Shanshan; Tzounopoulos, Thanos

    2017-09-09

    In many excitatory synapses, mobile zinc is found within glutamatergic vesicles and is coreleased with glutamate. Ex vivo studies established that synaptically released (synaptic) zinc inhibits excitatory neurotransmission at lower frequencies of synaptic activity but enhances steady state synaptic responses during higher frequencies of activity. However, it remains unknown how synaptic zinc affects neuronal processing in vivo. Here, we imaged the sound-evoked neuronal activity of the primary auditory cortex in awake mice. We discovered that synaptic zinc enhanced the gain of sound-evoked responses in CaMKII-expressing principal neurons, but it reduced the gain of parvalbumin- and somatostatin-expressing interneurons. This modulation was sound intensity-dependent and, in part, NMDA receptor-independent. By establishing a previously unknown link between synaptic zinc and gain control of auditory cortical processing, our findings advance understanding about cortical synaptic mechanisms and create a new framework for approaching and interpreting the role of the auditory cortex in sound processing.

  1. Simultaneous imaging of cerebral partial pressure of oxygen and blood flow during functional activation and cortical spreading depression

    Science.gov (United States)

    Sakadžić, Sava; Yuan, Shuai; Dilekoz, Ergin; Ruvinskaya, Svetlana; Vinogradov, Sergei A.; Ayata, Cenk; Boas, David A.

    2009-01-01

    We developed a novel imaging technique that provides real-time two-dimensional maps of the absolute partial pressure of oxygen and relative cerebral blood flow in rats by combining phosphorescence lifetime imaging with laser speckle contrast imaging. Direct measurement of blood oxygenation based on phosphorescence lifetime is not significantly affected by changes in the optical parameters of the tissue during the experiment. The potential of the system as a novel tool for quantitative analysis of the dynamic delivery of oxygen to support brain metabolism was demonstrated in rats by imaging cortical responses to forepaw stimulation and the propagation of cortical spreading depression waves. This new instrument will enable further study of neurovascular coupling in normal and diseased brain. PMID:19340106

  2. Effects of aging and sensory loss on glial cells in mouse visual and auditory cortices

    Science.gov (United States)

    Tremblay, Marie-Ève; Zettel, Martha L.; Ison, James R.; Allen, Paul D.; Majewska, Ania K.

    2011-01-01

    Normal aging is often accompanied by a progressive loss of receptor sensitivity in hearing and vision, whose consequences on cellular function in cortical sensory areas have remained largely unknown. By examining the primary auditory (A1) and visual (V1) cortices in two inbred strains of mice undergoing either age-related loss of audition (C57BL/6J) or vision (CBA/CaJ), we were able to describe cellular and subcellular changes that were associated with normal aging (occurring in A1 and V1 of both strains) or specifically with age-related sensory loss (only in A1 of C57BL/6J or V1 of CBA/CaJ), using immunocytochemical electron microscopy and light microscopy. While the changes were subtle in neurons, glial cells and especially microglia were transformed in aged animals. Microglia became more numerous and irregularly distributed, displayed more variable cell body and process morphologies, occupied smaller territories, and accumulated phagocytic inclusions that often displayed ultrastructural features of synaptic elements. Additionally, evidence of myelination defects were observed, and aged oligodendrocytes became more numerous and were more often encountered in contiguous pairs. Most of these effects were profoundly exacerbated by age-related sensory loss. Together, our results suggest that the age-related alteration of glial cells in sensory cortical areas can be accelerated by activity-driven central mechanisms that result from an age-related loss of peripheral sensitivity. In light of our observations, these age-related changes in sensory function should be considered when investigating cellular, cortical and behavioral functions throughout the lifespan in these commonly used C57BL/6J and CBA/CaJ mouse models. PMID:22223464

  3. Apoptosis after irradiation of the rat cortical and hippocampal cells in culture

    International Nuclear Information System (INIS)

    Coffigny, H.; Lane, M.C.

    1997-01-01

    During the development of the central nervous system many neurons are generated but over 50% die by natural apoptosis; this phenomenon occurred in neurons without or with wrong connections with their target cells. Children exposed in utero to Hiroshima or Nagasaki bombing presented microcephaly due to cell deaths and mental retardation. In animals, the number of apoptotic cells in the developing central nervous system increased as a function of the dose received. In vitro, we have shown that 1 Gy irradiation induced 50 % decrease of cortical and hippocampal cell survival. Nervous cells when seeded in a plate were round without processes. Neuritis outgrowth increased with culture time and physical contacts were established between cells. Our purpose is to test the importance of these contacts in the radio-induced apoptosis. (authors)

  4. Imaging mass spectrometry (IMS) of cortical lipids from preclinical to severe stages of Alzheimer's disease.

    Science.gov (United States)

    Gónzalez de San Román, E; Manuel, I; Giralt, M T; Ferrer, I; Rodríguez-Puertas, R

    2017-09-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disease affecting millions of patients worldwide. Previous studies have demonstrated alterations in the lipid composition of lipid extracts from plasma and brain samples of AD patients. However, there is no consensus regarding the qualitative and quantitative changes of lipids in brains from AD patients. In addition, the recent developments in imaging mass spectrometry methods are leading to a new stage in the in situ analysis of lipid species in brain tissue slices from human postmortem samples. The present study uses the matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS), permitting the direct anatomical analysis of lipids in postmortem brain sections from AD patients, which are compared with the intensity of the lipid signal in samples from matched subjects with no neurological diseases. The frontal cortex samples from AD patients were classified in three groups based on Braak's histochemical criteria, ranging from non-cognitively impaired patients to those severely affected. The main results indicate a depletion of different sulfatide lipid species from the earliest stages of the disease in both white and gray matter areas of the frontal cortex. Therefore, the decrease in sulfatides in cortical areas could be considered as a marker of the disease, but may also indicate neurochemical modifications related to the pathogenesis of the disease. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Decrease in the cortical intensity on T2-weighted magnetic resonance imaging with aging in normal subjects

    International Nuclear Information System (INIS)

    Imon, Yukari; Murata, Yoshio; Kajima, Toshio; Nakamura, Shigenobu; Yamaguchi, Shinya

    1997-01-01

    We reported previously that Low T 2 intensity areas (LIAs) are more common in patients with central nervous system (CNS) diseases than in those with no such diseases, and that the occurrence of LIAs increases with aging. To determine a relationship between the intensity changes and aging, we investigated the intensity of the cerebral cortex in 26 normal Japanese individuals. Measurements of brain MRIs were performed with a Signa Advantage apparatus at 1.5 tesla. T 2 -weighted images were obtained using the spin-echo pulse sequences. On our laboratory console, we measured signal intensities in the regions of interest in the prefrontal, motor, sensory, parietal, temporal, or occipital cortex, and in the frontal white matter. To remove the effect of the system gain settings on signal intensity, that of cerebrospinal fluid was used as reference according to the method of Pujol et al. The average intensity in the temporal and prefrontal cortices was the highest, followed in order by the parietal, sensory, motor, and occipital cortices. The intensity in the temporal and parietal cortices decreased significantly with aging, and that in the motor and sensory cortices had a tendency to decrease with aging. The intensity in the motor and sensory cortices of the elderly subjects and that in the occipital cortex throughout all ages were lower than that in the prefrontal white matter, which would result in the appearance of LIAs. The average intensity of each cerebral cortex was inversely related to the non-heme iron content previously reported. It is likely that the difference in intensity among the cortices reflects variations of the non-heme iron content, and that the change in intensity with aging could be due to the increase in such cortical senile changes as that of microglia, astroglia, and senile plaques, which contain iron or iron-related proteins. The temporal cortex is most susceptible to senile changes. (K.H.)

  6. Improving prediction of Alzheimer’s disease using patterns of cortical thinning and homogenizing images according to disease stage

    DEFF Research Database (Denmark)

    Eskildsen, Simon Fristed; Coupé, Pierrick; García-Lorenzo, Daniel

    Predicting Alzheimer’s disease (AD) in individuals with some symptoms of cognitive decline may have great influence on treatment choice and guide subject selection in trials on disease modifying drugs. Structural MRI has the potential of revealing early signs of neurodegeneration in the human brain...... and may thus aid in predicting and diagnosing AD. Surface-based cortical thickness measurements from T1-weighted MRI have demonstrated high sensitivity to cortical gray matter changes. In this study, we investigated the possibility of using patterns of cortical thickness measurements for predicting AD...... of conversion from MCI to AD can be improved by learning the atrophy patterns that are specific to the different stages of disease progression. This has the potential to guide the further development of imaging biomarkers in AD....

  7. A cortical attractor network with Martinotti cells driven by facilitating synapses.

    Directory of Open Access Journals (Sweden)

    Pradeep Krishnamurthy

    Full Text Available The population of pyramidal cells significantly outnumbers the inhibitory interneurons in the neocortex, while at the same time the diversity of interneuron types is much more pronounced. One acknowledged key role of inhibition is to control the rate and patterning of pyramidal cell firing via negative feedback, but most likely the diversity of inhibitory pathways is matched by a corresponding diversity of functional roles. An important distinguishing feature of cortical interneurons is the variability of the short-term plasticity properties of synapses received from pyramidal cells. The Martinotti cell type has recently come under scrutiny due to the distinctly facilitating nature of the synapses they receive from pyramidal cells. This distinguishes these neurons from basket cells and other inhibitory interneurons typically targeted by depressing synapses. A key aspect of the work reported here has been to pinpoint the role of this variability. We first set out to reproduce quantitatively based on in vitro data the di-synaptic inhibitory microcircuit connecting two pyramidal cells via one or a few Martinotti cells. In a second step, we embedded this microcircuit in a previously developed attractor memory network model of neocortical layers 2/3. This model network demonstrated that basket cells with their characteristic depressing synapses are the first to discharge when the network enters an attractor state and that Martinotti cells respond with a delay, thereby shifting the excitation-inhibition balance and acting to terminate the attractor state. A parameter sensitivity analysis suggested that Martinotti cells might, in fact, play a dominant role in setting the attractor dwell time and thus cortical speed of processing, with cellular adaptation and synaptic depression having a less prominent role than previously thought.

  8. 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.

  9. Squamous cell cancer (image)

    Science.gov (United States)

    Squamous cell cancer involves cancerous changes to the cells of the middle portion of the epidermal skin layer. It is ... malignant tumor, and is more aggressive than basal cell cancer, but still may be relatively slow-growing. It ...

  10. Characteristics of lesional and extra-lesional cortical grey matter in relapsing-remitting and secondary progressive multiple sclerosis: A magnetisation transfer and diffusion tensor imaging study.

    Science.gov (United States)

    Yaldizli, Özgür; Pardini, Matteo; Sethi, Varun; Muhlert, Nils; Liu, Zheng; Tozer, Daniel J; Samson, Rebecca S; Wheeler-Kingshott, Claudia Am; Yousry, Tarek A; Miller, David H; Chard, Declan T

    2016-02-01

    In multiple sclerosis (MS), diffusion tensor and magnetisation transfer imaging are both abnormal in lesional and extra-lesional cortical grey matter, but differences between clinical subtypes and associations with clinical outcomes have only been partly assessed. To compare mean diffusivity, fractional anisotropy and magnetisation transfer ratio (MTR) in cortical grey matter lesions (detected using phase-sensitive inversion recovery (PSIR) imaging) and extra-lesional cortical grey matter, and assess associations with disability in relapse-onset MS. Seventy-two people with MS (46 relapsing-remitting (RR), 26 secondary progressive (SP)) and 36 healthy controls were included in this study. MTR, mean diffusivity and fractional anisotropy were measured in lesional and extra-lesional cortical grey matter. Mean fractional anisotropy was higher and MTR lower in lesional compared with extra-lesional cortical grey matter. In extra-lesional cortical grey matter mean fractional anisotropy and MTR were lower, and mean diffusivity was higher in the MS group compared with controls. Mean MTR was lower and mean diffusivity was higher in lesional and extra-lesional cortical grey matter in SPMS when compared with RRMS. These differences were independent of disease duration. In multivariate analyses, MTR in extra-lesional more so than lesional cortical grey matter was associated with disability. Magnetic resonance abnormalities in lesional and extra-lesional cortical grey matter are greater in SPMS than RRMS. Changes in extra-lesional compared with lesional cortical grey matter are more consistently associated with disability. © The Author(s), 2015.

  11. 3D osteocyte lacunar morphometric properties and distributions in human femoral cortical bone using synchrotron radiation micro-CT images.

    Science.gov (United States)

    Dong, Pei; Haupert, Sylvain; Hesse, Bernhard; Langer, Max; Gouttenoire, Pierre-Jean; Bousson, Valérie; Peyrin, Françoise

    2014-03-01

    Osteocytes, the most numerous bone cells, are thought to be actively involved in the bone modeling and remodeling processes. The morphology of osteocyte is hypothesized to adapt according to the physiological mechanical loading. Three-dimensional micro-CT has recently been used to study osteocyte lacunae. In this work, we proposed a computationally efficient and validated automated image analysis method to quantify the 3D shape descriptors of osteocyte lacunae and their distribution in human femurs. Thirteen samples were imaged using Synchrotron Radiation (SR) micro-CT at ID19 of the ESRF with 1.4μm isotropic voxel resolution. With a field of view of about 2.9×2.9×1.4mm(3), the 3D images include several tens of thousands of osteocyte lacunae. We designed an automated quantification method to segment and extract 3D cell descriptors from osteocyte lacunae. An image moment-based approach was used to calculate the volume, length, width, height and anisotropy of each osteocyte lacuna. We employed a fast algorithm to further efficiently calculate the surface area, the Euler number and the structure model index (SMI) of each lacuna. We also introduced the 3D lacunar density map to directly visualize the lacunar density variation over a large field of view. We reported the lacunar morphometric properties and distributions as well as cortical bone histomorphometric indices on the 13 bone samples. The mean volume and surface were found to be 409.5±149.7μm(3) and 336.2±94.5μm(2). The average dimensions were of 18.9±4.9μm in length, 9.2±2.1μm in width and 4.8±1.1μm in depth. We found lacunar number density and six osteocyte lacunar descriptors, three axis lengths, two anisotropy ratios and SMI, that are significantly correlated to bone porosity at a same local region. The proposed method allowed an automatic and efficient direct 3D analysis of a large population of bone cells and is expected to provide reliable biological information for better understanding the

  12. Persistent expression of BMP-4 in embryonic chick adrenal cortical cells and its role in chromaffin cell development

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    Halbach Oliver

    2008-10-01

    Full Text Available Abstract Background Adrenal chromaffin cells and sympathetic neurons both originate from the neural crest, yet signals that trigger chromaffin development remain elusive. Bone morphogenetic proteins (BMPs emanating from the dorsal aorta are important signals for the induction of a sympathoadrenal catecholaminergic cell fate. Results We report here that BMP-4 is also expressed by adrenal cortical cells throughout chick embryonic development, suggesting a putative role in chromaffin cell development. Moreover, bone morphogenetic protein receptor IA is expressed by both cortical and chromaffin cells. Inhibiting BMP-4 with noggin prevents the increase in the number of tyrosine hydroxylase positive cells in adrenal explants without affecting cell proliferation. Hence, adrenal BMP-4 is likely to induce tyrosine hydroxylase in sympathoadrenal progenitors. To investigate whether persistent BMP-4 exposure is able to induce chromaffin traits in sympathetic ganglia, we locally grafted BMP-4 overexpressing cells next to sympathetic ganglia. Embryonic day 8 chick sympathetic ganglia, in addition to principal neurons, contain about 25% chromaffin-like cells. Ectopic BMP-4 did not increase this proportion, yet numbers and sizes of 'chromaffin' granules were significantly increased. Conclusion BMP-4 may serve to promote specific chromaffin traits, but is not sufficient to convert sympathetic neurons into a chromaffin phenotype.

  13. Cortical imaging on a head template: a simulation study using a resistor mesh model (RMM).

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    Chauveau, Nicolas; Franceries, Xavier; Aubry, Florent; Celsis, Pierre; Rigaud, Bernard

    2008-09-01

    The T1 head template model used in Statistical Parametric Mapping Version 2000 (SPM2), was segmented into five layers (scalp, skull, CSF, grey and white matter) and implemented in 2 mm voxels. We designed a resistor mesh model (RMM), based on the finite volume method (FVM) to simulate the electrical properties of this head model along the three axes for each voxel. Then, we introduced four dipoles of high eccentricity (about 0.8) in this RMM, separately and simultaneously, to compute the potentials for two sets of conductivities. We used the direct cortical imaging technique (CIT) to recover the simulated dipoles, using 60 or 107 electrodes and with or without addition of Gaussian white noise (GWN). The use of realistic conductivities gave better CIT results than standard conductivities, lowering the blurring effect on scalp potentials and displaying more accurate position areas when CIT was applied to single dipoles. Simultaneous dipoles were less accurately localized, but good qualitative and stable quantitative results were obtained up to 5% noise level for 107 electrodes and up to 10% noise level for 60 electrodes, showing that a compromise must be found to optimize both the number of electrodes and the noise level. With the RMM defined in 2 mm voxels, the standard 128-electrode cap and 5% noise appears to be the upper limit providing reliable source positions when direct CIT is used. The admittance matrix defining the RMM is easy to modify so as to adapt to different conductivities. The next step will be the adaptation of individual real head T2 images to the RMM template and the introduction of anisotropy using diffusion imaging (DI).

  14. Leptomeningeal collateralization in acute ischemic stroke: Impact on prominent cortical veins in susceptibility-weighted imaging

    International Nuclear Information System (INIS)

    Verma, Rajeev K.; Hsieh, Kety; Gratz, Pascal P.; Schankath, Adrian C.; Mordasini, Pasquale; Zubler, Christoph; Kellner-Weldon, Frauke; Jung, Simon; Schroth, Gerhard; Gralla, Jan; El-Koussy, Marwan

    2014-01-01

    Background: The extent of hypoperfusion is an important prognostic factor in acute ischemic stroke. Previous studies have postulated that the extent of prominent cortical veins (PCV) on susceptibility-weighted imaging (SWI) reflects the extent of hypoperfusion. Our aim was to investigate, whether there is an association between PCV and the grade of leptomeningeal arterial collateralization in acute ischemic stroke. In addition, we analyzed the correlation between SWI and perfusion-MRI findings. Methods: 33 patients with acute ischemic stroke due to a thromboembolic M1-segment occlusion underwent MRI followed by digital subtraction angiography (DSA) and were subdivided into two groups with very good to good and moderate to no leptomeningeal collaterals according to the DSA. The extent of PCV on SWI, diffusion restriction (DR) on diffusion-weighted imaging (DWI) and prolonged mean transit time (MTT) on perfusion-imaging were graded according to the Alberta Stroke Program Early CT Score (ASPECTS). The National Institutes of Health Stroke Scale (NIHSS) scores at admission and the time between symptom onset and MRI were documented. Results: 20 patients showed very good to good and 13 patients poor to no collateralization. PCV-ASPECTS was significantly higher for cases with good leptomeningeal collaterals versus those with poor leptomeningeal collaterals (mean 4.1 versus 2.69; p = 0.039). MTT-ASPECTS was significantly lower than PCV-ASPECTS in all 33 patients (mean 1.0 versus 3.5; p < 0.00). Conclusions: In our small study the grade of leptomeningeal collateralization correlates with the extent of PCV in SWI in acute ischemic stroke, due to the deoxyhemoglobin to oxyhemoglobin ratio. Consequently, extensive PCV correlate with poor leptomeningeal collateralization while less pronounced PCV correlate with good leptomeningeal collateralization. Further SWI is a very helpful tool in detecting tissue at risk but cannot replace PWI since MTT detects significantly more ill

  15. Markers of Pluripotency in Human Amniotic Epithelial Cells and Their Differentiation to Progenitor of Cortical Neurons

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    García-Castro, Irma Lydia; García-López, Guadalupe; Ávila-González, Daniela; Flores-Herrera, Héctor; Molina-Hernández, Anayansi; Portillo, Wendy; Ramón-Gallegos, Eva; Díaz, Néstor Fabián

    2015-01-01

    Human pluripotent stem cells (hPSC) have promise for regenerative medicine due to their auto-renovation and differentiation capacities. Nevertheless, there are several ethical and methodological issues about these cells that have not been resolved. Human amniotic epithelial cells (hAEC) have been proposed as source of pluripotent stem cells. Several groups have studied hAEC but have reported inconsistencies about their pluripotency properties. The aim of the present study was the in vitro characterization of hAEC collected from a Mexican population in order to identify transcription factors involved in the pluripotency circuitry and to determine their epigenetic state. Finally, we evaluated if these cells differentiate to cortical progenitors. We analyzed qualitatively and quantitatively the expression of the transcription factors of pluripotency (OCT4, SOX2, NANOG, KLF4 and REX1) by RT-PCR and RT-qPCR in hAEC. Also, we determined the presence of OCT4, SOX2, NANOG, SSEA3, SSEA4, TRA-1-60, E-cadherin, KLF4, TFE3 as well as the proliferation and epigenetic state by immunocytochemistry of the cells. Finally, hAEC were differentiated towards cortical progenitors using a protocol of two stages. Here we show that hAEC, obtained from a Mexican population and cultured in vitro (P0-P3), maintained the expression of several markers strongly involved in pluripotency maintenance (OCT4, SOX2, NANOG, TFE3, KLF4, SSEA3, SSEA4, TRA-1-60 and E-cadherin). Finally, when hAEC were treated with growth factors and small molecules, they expressed markers characteristic of cortical progenitors (TBR2, OTX2, NeuN and β-III-tubulin). Our results demonstrated that hAEC express naïve pluripotent markers (KLF4, REX1 and TFE3) as well as the cortical neuron phenotype after differentiation. This highlights the need for further investigation of hAEC as a possible source of hPSC. PMID:26720151

  16. Cytotoxic and biological effects of bulk fill composites on rat cortical neuron cells.

    Science.gov (United States)

    Kamalak, Hakan; Kamalak, Aliye; Taghizadehghalehjoughi, Ali; Hacımüftüoğlu, Ahmet; Nalcı, Kemal Alp

    2018-03-28

    The aim of this study was to investigate potential cellular responses and biological effects of new generation dental composites on cortical neuron cells in two different exposure times. The study group included five different bulk-fill flow able composites; Surefil SDR Flow, X-tra Base Flow, Venus Bulk Flow, Filtek Bulk Flow and Tetric-Evo Flow. They were filled in Teflon molds (Height: 4 mm, Width: 6 mm) and irradiated for 20 s. Cortical neuron cells were inoculated into 24-well plates. After 80% of the wells were coated, the 3 µm membrane was inserted and dental filling materials were added. The experiment was continued for 24 and 72 h. Cell viability measured by MTT assay test, total antioxidant and total oxidant status were examined using real assay diagnostic kits. The patterns of cell death (apoptosis) were analyzed using annexin V-FITC staining with flow cytometry. Β-defensins were quantitatively assessed by RT-PCR. IL-6, IL-8 and IL-10 cytokines were measured from the supernatants. All composites significantly affected analyses parameters during the exposure durations. Our data provide evidence that all dental materials tested are cytotoxic in acute phase and these effects are induced cellular death after different exposure periods. Significant cytotoxicity was detected in TE, XB, SS, FBF and VBF groups at 24 and 72 h, respectively.

  17. Active learning of cortical connectivity from two-photon imaging data

    Science.gov (United States)

    Wang, Ye; Dunson, David; Sapiro, Guillermo; Ringach, Dario

    2018-01-01

    Understanding how groups of neurons interact within a network is a fundamental question in system neuroscience. Instead of passively observing the ongoing activity of a network, we can typically perturb its activity, either by external sensory stimulation or directly via techniques such as two-photon optogenetics. A natural question is how to use such perturbations to identify the connectivity of the network efficiently. Here we introduce a method to infer sparse connectivity graphs from in-vivo, two-photon imaging of population activity in response to external stimuli. A novel aspect of the work is the introduction of a recommended distribution, incrementally learned from the data, to optimally refine the inferred network. Unlike existing system identification techniques, this “active learning” method automatically focuses its attention on key undiscovered areas of the network, instead of targeting global uncertainty indicators like parameter variance. We show how active learning leads to faster inference while, at the same time, provides confidence intervals for the network parameters. We present simulations on artificial small-world networks to validate the methods and apply the method to real data. Analysis of frequency of motifs recovered show that cortical networks are consistent with a small-world topology model. PMID:29718955

  18. Active learning of cortical connectivity from two-photon imaging data.

    Directory of Open Access Journals (Sweden)

    Martín A Bertrán

    Full Text Available Understanding how groups of neurons interact within a network is a fundamental question in system neuroscience. Instead of passively observing the ongoing activity of a network, we can typically perturb its activity, either by external sensory stimulation or directly via techniques such as two-photon optogenetics. A natural question is how to use such perturbations to identify the connectivity of the network efficiently. Here we introduce a method to infer sparse connectivity graphs from in-vivo, two-photon imaging of population activity in response to external stimuli. A novel aspect of the work is the introduction of a recommended distribution, incrementally learned from the data, to optimally refine the inferred network. Unlike existing system identification techniques, this "active learning" method automatically focuses its attention on key undiscovered areas of the network, instead of targeting global uncertainty indicators like parameter variance. We show how active learning leads to faster inference while, at the same time, provides confidence intervals for the network parameters. We present simulations on artificial small-world networks to validate the methods and apply the method to real data. Analysis of frequency of motifs recovered show that cortical networks are consistent with a small-world topology model.

  19. 3D printed phantoms mimicking cortical bone for the assessment of ultrashort echo time magnetic resonance imaging.

    Science.gov (United States)

    Rai, Robba; Manton, David; Jameson, Michael G; Josan, Sonal; Barton, Michael B; Holloway, Lois C; Liney, Gary P

    2018-02-01

    Human cortical bone has a rapid T2∗ decay, and it can be visualized using ultrashort echo time (UTE) techniques in magnetic resonance imaging (MRI). These sequences operate at the limits of gradient and transmit-receive signal performance. Development of multicompartment anthropomorphic phantoms that can mimic human cortical bone can assist with quality assurance and optimization of UTE sequences. The aims of this study were to (a) characterize the MRI signal properties of a photopolymer resin that can be 3D printed, (b) develop multicompartment phantoms based on the resin, and (c) demonstrate the feasibility of using these phantoms to mimic human anatomy in the assessment of UTE sequences. A photopolymer resin (Prismlab China Ltd, Shanghai, China) was imaged on a 3 Tesla MRI system (Siemens Skyra) to characterize its MRI properties with emphasis on T2∗ signal and longevity. Two anthropomorphic phantoms, using the 3D printed resin to simulate skeletal anatomy, were developed and imaged using UTE sequences. A skull phantom was developed and used to assess the feasibility of using the resin to develop a complex model with realistic morphological human characteristics. A tibia model was also developed to assess the suitability of the resin at mimicking a simple multicompartment anatomical model and imaged using a three-dimensional UTE sequence (PETRA). Image quality measurements of signal-to-noise ratio (SNR) and contrast factor were calculated and these were compared to in vivo values. The T2∗ and T 1 (mean ± standard deviation) of the photopolymer resin was found to be 411 ± 19 μs and 74.39 ± 13.88 ms, respectively, and demonstrated no statistically significant change during 4 months of monitoring. The resin had a similar T2∗ decay to human cortical bone; however, had lower T 1 properties. The bone water concentration of the resin was 59% relative to an external water reference phantom, and this was higher than in vivo values reported for human cortical

  20. 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)

  1. Cell-Specific Loss of SNAP25 from Cortical Projection Neurons Allows Normal Development but Causes Subsequent Neurodegeneration.

    Science.gov (United States)

    Hoerder-Suabedissen, Anna; Korrell, Kim V; Hayashi, Shuichi; Jeans, Alexander; Ramirez, Denise M O; Grant, Eleanor; Christian, Helen C; Kavalali, Ege T; Wilson, Michael C; Molnár, Zoltán

    2018-05-30

    Synaptosomal associated protein 25 kDa (SNAP25) is an essential component of the SNARE complex regulating synaptic vesicle fusion. SNAP25 deficiency has been implicated in a variety of cognitive disorders. We ablated SNAP25 from selected neuronal populations by generating a transgenic mouse (B6-Snap25tm3mcw (Snap25-flox)) with LoxP sites flanking exon5a/5b. In the presence of Cre-recombinase, Snap25-flox is recombined to a truncated transcript. Evoked synaptic vesicle release is severely reduced in Snap25 conditional knockout (cKO) neurons as shown by live cell imaging of synaptic vesicle fusion and whole cell patch clamp recordings in cultured hippocampal neurons. We studied Snap25 cKO in subsets of cortical projection neurons in vivo (L5-Rbp4-Cre; L6-Ntsr1-Cre; L6b-Drd1a-Cre). cKO neurons develop normal axonal projections, but axons are not maintained appropriately, showing signs of swelling, fragmentation and eventually complete absence. Onset and progression of degeneration are dependent on the neuron type, with L5 cells showing the earliest and most severe axonal loss. Ultrastructural examination revealed that cKO neurites contain autophagosome/lysosome-like structures. Markers of inflammation such as Iba1 and lipofuscin are increased only in adult cKO cortex. Snap25 cKO can provide a model to study genetic interactions with environmental influences in several disorders.

  2. Imaging the impact of cortical microcirculation on synaptic structure and sensory-evoked hemodynamic responses in vivo.

    Directory of Open Access Journals (Sweden)

    Shengxiang Zhang

    2007-05-01

    Full Text Available In vivo two-photon microscopy was used to image in real time dendrites and their spines in a mouse photothrombotic stroke model that reduced somatosensory cortex blood flow in discrete regions of cortical functional maps. This approach allowed us to define relationships between blood flow, cortical structure, and function on scales not previously achieved with macroscopic imaging techniques. Acute ischemic damage to dendrites was triggered within 30 min when blood flow over >0.2 mm(2 of cortical surface was blocked. Rapid damage was not attributed to a subset of clotted or even leaking vessels (extravasation alone. Assessment of stroke borders revealed a remarkably sharp transition between intact and damaged synaptic circuitry that occurred over tens of mum and was defined by a transition between flowing and blocked vessels. Although dendritic spines were normally ~13 microm from small flowing vessels, we show that intact dendritic structure can be maintained (in areas without flowing vessels by blood flow from vessels that are on average 80 microm away. Functional imaging of intrinsic optical signals associated with activity-evoked hemodynamic responses in somatosensory cortex indicated that sensory-induced changes in signal were blocked in areas with damaged dendrites, but were present ~400 microm away from the border of dendritic damage. These results define the range of influence that blood flow can have on local cortical fine structure and function, as well as to demonstrate that peri-infarct tissues can be functional within the first few hours after stroke and well positioned to aid in poststroke recovery.

  3. Segmentation of nanotomographic cortical bone images for quantitative characterization of the osteoctyte lacuno-canalicular network

    Energy Technology Data Exchange (ETDEWEB)

    Ciani, A.; Kewish, C. M. [Synchrotron Soleil, L’Orme des Merisiers, 91192 Saint-Aubin (France); Guizar-Sicairos, M.; Diaz, A.; Holler, M. [Paul Scherrer Institut, 5232 Villigen PSI (Switzerland); Pallu, S.; Achiou, Z.; Jennane, R.; Toumi, H.; Lespessailles, E. [Univ Orléans, I3MTO, Ea 4708, 45000 Orléans (France)

    2016-01-28

    A newly developed data processing method able to characterize the osteocytes lacuno-canalicular network (LCN) is presented. Osteocytes are the most abundant cells in the bone, living in spaces called lacunae embedded inside the bone matrix and connected to each other with an extensive network of canals that allows for the exchange of nutrients and for mechanotransduction functions. The geometrical three-dimensional (3D) architecture is increasingly thought to be related to the macroscopic strength or failure of the bone and it is becoming the focus for investigating widely spread diseases such as osteoporosis. To obtain 3D LCN images non-destructively has been out of reach until recently, since tens-of-nanometers scale resolution is required. Ptychographic tomography was validated for bone imaging in [1], showing clearly the LCN. The method presented here was applied to 3D ptychographic tomographic images in order to extract morphological and geometrical parameters of the lacuno-canalicular structures.

  4. Combined structural and functional imaging reveals cortical deactivations in grapheme-colour synaesthesia

    Directory of Open Access Journals (Sweden)

    Erik eO'Hanlon

    2013-10-01

    Full Text Available Synaesthesia is a heritable condition in which particular stimuli generate specific and consistent sensory percepts or associations in another modality or processing stream. Functional neuroimaging studies have identified potential correlates of these experiences, including, in some but not all cases, the hyperactivation of visuotemporal areas and of parietal areas thought to be involved in perceptual binding. Structural studies have identified a similarly variable spectrum of differences between synaesthetes and controls. However, it remains unclear the extent to which these neural correlates reflect the synaesthetic experience itself or additional phenotypes associated with the condition. Here, we acquired both structural and functional neuroimaging data comparing thirteen grapheme-colour synaesthetes with eleven non-synaesthetes. Using voxel-based morphometry and diffusion tensor imaging, we identify a number of clusters of increased volume of grey matter, of white matter or of increased fractional anisotropy in synaesthetes versus controls. To assess the possible involvement of these areas in the synaesthetic experience, we used nine areas of increased grey matter volume as regions of interest in an fMRI experiment that characterised the contrast in response to stimuli which induced synaesthesia (i.e. letters versus those which did not (non-meaningful symbols. Two of these areas, in left lateral occipital cortex and in postcentral gyrus, showed sensitivity to this contrast in synaesthetes but not controls. Unexpectedly, in both regions, the letter stimuli produced a strong negative BOLD signal in synaesthetes. An additional whole-brain fMRI analysis identified fourteen areas, three of which were driven mainly by a negative BOLD response to letters in synaesthetes. Our findings suggest that cortical deactivations may be involved in the conscious experience of internally generated synaesthetic percepts

  5. Epileptic Networks in Focal Cortical Dysplasia Revealed Using Electroencephalography–Functional Magnetic Resonance Imaging

    Science.gov (United States)

    Thornton, Rachel; Vulliemoz, Serge; Rodionov, Roman; Carmichael, David W; Chaudhary, Umair J; Diehl, Beate; Laufs, Helmut; Vollmar, Christian; McEvoy, Andrew W; Walker, Matthew C; Bartolomei, Fabrice; Guye, Maxime; Chauvel, Patrick; Duncan, John S; Lemieux, Louis

    2011-01-01

    Objective Surgical treatment of focal epilepsy in patients with focal cortical dysplasia (FCD) is most successful if all epileptogenic tissue is resected. This may not be evident on structural magnetic resonance imaging (MRI), so intracranial electroencephalography (icEEG) is needed to delineate the seizure onset zone (SOZ). EEG-functional MRI (fMRI) can reveal interictal discharge (IED)-related hemodynamic changes in the irritative zone (IZ). We assessed the value of EEG-fMRI in patients with FCD-associated focal epilepsy by examining the relationship between IED-related hemodynamic changes, icEEG findings, and postoperative outcome. Methods Twenty-three patients with FCD-associated focal epilepsy undergoing presurgical evaluation including icEEG underwent simultaneous EEG-fMRI at 3T. IED-related hemodynamic changes were modeled, and results were overlaid on coregistered T1-weighted MRI scans fused with computed tomography scans showing the intracranial electrodes. IED-related hemodynamic changes were compared with the SOZ on icEEG and postoperative outcome at 1 year. Results Twelve of 23 patients had IEDs during recording, and 11 of 12 had significant IED-related hemodynamic changes. The fMRI results were concordant with the SOZ in 5 of 11 patients, all of whom had a solitary SOZ on icEEG. Four of 5 had >50% reduction in seizure frequency following resective surgery. The remaining 6 of 11 patients had widespread or discordant regions of IED-related fMRI signal change. Five of 6 had either a poor surgical outcome (<50% reduction in seizure frequency) or widespread SOZ precluding surgery. Interpretation Comparison of EEG-fMRI with icEEG suggests that EEG-fMRI may provide useful additional information about the SOZ in FCD. Widely distributed discordant regions of IED-related hemodynamic change appear to be associated with a widespread SOZ and poor postsurgical outcome. ANN NEUROL 2011 PMID:22162063

  6. Human Mesenchymal Stem Cell Treatment Normalizes Cortical Gene Expression after Traumatic Brain Injury.

    Science.gov (United States)

    Darkazalli, Ali; Vied, Cynthia; Badger, Crystal-Dawn; Levenson, Cathy W

    2017-01-01

    Traumatic brain injury (TBI) results in a progressive disease state with many adverse and long-term neurological consequences. Mesenchymal stem cells (MSCs) have emerged as a promising cytotherapy and have been previously shown to reduce secondary apoptosis and cognitive deficits associated with TBI. Consistent with the established literature, we observed that systemically administered human MSCs (hMSCs) accumulate with high specificity at the TBI lesion boundary zone known as the penumbra. Substantial work has been done to illuminate the mechanisms by which MSCs, and the bioactive molecules they secrete, exert their therapeutic effect. However, no such work has been published to examine the effect of MSC treatment on gene expression in the brain post-TBI. In the present study, we use high-throughput RNA sequencing (RNAseq) of cortical tissue from the TBI penumbra to assess the molecular effects of both TBI and subsequent treatment with intravenously delivered hMSCs. RNAseq revealed that expression of almost 7000 cortical genes in the penumbra were differentially regulated by TBI. Pathway analysis using the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway database revealed that TBI regulated a large number of genes belonging to pathways involved in metabolism, receptor-mediated cell signaling, neuronal plasticity, immune cell recruitment and infiltration, and neurodegenerative disease. Remarkably, hMSC treatment was found to normalize 49% of all genes disrupted by TBI, with notably robust normalization of specific pathways within the categories mentioned above, including neuroactive receptor-ligand interactions (57%), glycolysis and gluconeogenesis (81%), and Parkinson's disease (100%). These data provide evidence in support of the multi-mechanistic nature of stem cell therapy and suggest that hMSC treatment is capable of simultaneously normalizing a wide variety of important molecular pathways that are disrupted by brain injury.

  7. CT and MR imaging of non-cavernous cranial dural arteriovenous fistulas: Findings associated with cortical venous reflux

    Energy Technology Data Exchange (ETDEWEB)

    Letourneau-Guillon, Laurent; Cruz, Juan Pablo; Krings, Timo, E-mail: Timo.Krings@uhn.ca

    2015-08-15

    Highlights: • The conventional neuroimaging manifestations of dural arteriovenous fistulas are highly variable. • Identification of cortical venous reflux is important to prevent complications. • Tortuous and dilated vessels without a nidus are associated with cortical venous reflux. • Digital subtraction angiography remains the gold standard for DAVF diagnosis. - Abstract: Purpose: To compare the conventional CT and MR findings of DAVFs in relation to the venous drainage pattern on digital subtraction angiography (DSA). Materials and Methods: Cross-sectional imaging findings (CT and/or MR) in 92 patients were compared to the presence of cortical venous reflux (CVR) on DSA. Results: Imaging features significantly more prevalent in patients with CVR included: abnormally dilated and tortuous leptomeningeal vessels (92% vs. 4%, p < 0.001) or medullary vessels (69% vs. 0%, p < 0.001), venous ectasias (45% vs. 0%, p < 0.001) and focal vasogenic edema (38% vs. 0%, p < 0.001). The following findings trended towards association but did not reach the p value established following Bonferroni correction: dilated external carotid artery branches (71% vs. 38%, p = 0.005), cluster of vessels surrounding dural venous sinus (50% vs. 19%, p = 0.009), presence of hemorrhage (33 vs. 12%, p = 0.040), and parenchymal enhancement (21% vs. 0%, p = 0.030). Conclusion: In the appropriate clinical setting, recognition of ancillary signs presumably related to venous arterialization and congestion as well as arterial feeder hypertrophy should prompt DSA confirmation to identify DAVFs associated with CVR.

  8. Effects of high-fat diet and losartan on renal cortical blood flow using contrast ultrasound imaging.

    Science.gov (United States)

    Declèves, Anne-Emilie; Rychak, Joshua J; Smith, Dan J; Sharma, Kumar

    2013-11-01

    Obesity-related kidney disease occurs as a result of complex interactions between metabolic and hemodynamic effects. Changes in microvascular perfusion may play a major role in kidney disease; however, these changes are difficult to assess in vivo. Here, we used perfusion ultrasound imaging to evaluate cortical blood flow in a mouse model of high-fat diet-induced kidney disease. C57BL/6J mice were randomized to a standard diet (STD) or a high-fat diet (HFD) for 30 wk and then treated either with losartan or a placebo for an additional 6 wk. Noninvasive ultrasound perfusion imaging of the kidney was performed during infusion of a microbubble contrast agent. Blood flow within the microvasculature of the renal cortex and medulla was derived from imaging data. An increase in the time required to achieve full cortical perfusion was observed for HFD mice relative to STD. This was reversed following treatment with losartan. These data were concurrent with an increased glomerular filtration rate in HFD mice compared with STD- or HFD-losartan-treated mice. Losartan treatment also abrogated fibro-inflammatory disease, assessed by markers at the protein and messenger level. Finally, a reduction in capillary density was found in HFD mice, and this was reversed upon losartan treatment. This suggests that alterations in vascular density may be responsible for the elevated perfusion time observed by imaging. These data demonstrate that ultrasound contrast imaging is a robust and sensitive method for evaluating changes in renal microvascular perfusion and that cortical perfusion time may be a useful parameter for evaluating obesity-related renal disease.

  9. Aging increases microglial proliferation, delays cell migration, and decreases cortical neurogenesis after focal cerebral ischemia.

    Science.gov (United States)

    Moraga, Ana; Pradillo, Jesús M; García-Culebras, Alicia; Palma-Tortosa, Sara; Ballesteros, Ivan; Hernández-Jiménez, Macarena; Moro, María A; Lizasoain, Ignacio

    2015-05-10

    Aging is not just a risk factor of stroke, but it has also been associated with poor recovery. It is known that stroke-induced neurogenesis is reduced but maintained in the aged brain. However, there is no consensus on how neurogenesis is affected after stroke in aged animals. Our objective is to determine the role of aging on the process of neurogenesis after stroke. We have studied neurogenesis by analyzing proliferation, migration, and formation of new neurons, as well as inflammatory parameters, in a model of cerebral ischemia induced by permanent occlusion of the middle cerebral artery in young- (2 to 3 months) and middle-aged mice (13 to 14 months). Aging increased both microglial proliferation, as shown by a higher number of BrdU(+) cells and BrdU/Iba1(+) cells in the ischemic boundary and neutrophil infiltration. Interestingly, aging increased the number of M1 monocytes and N1 neutrophils, consistent with pro-inflammatory phenotypes when compared with the alternative M2 and N2 phenotypes. Aging also inhibited (subventricular zone) SVZ cell proliferation by decreasing both the number of astrocyte-like type-B (prominin-1(+)/epidermal growth factor receptor (EGFR)(+)/nestin(+)/glial fibrillary acidic protein (GFAP)(+) cells) and type-C cells (prominin-1(+)/EGFR(+)/nestin(-)/Mash1(+) cells), and not affecting apoptosis, 1 day after stroke. Aging also inhibited migration of neuroblasts (DCX(+) cells), as indicated by an accumulation of neuroblasts at migratory zones 14 days after injury; consistently, aged mice presented a smaller number of differentiated interneurons (NeuN(+)/BrdU(+) and GAD67(+) cells) in the peri-infarct cortical area 14 days after stroke. Our data confirm that stroke-induced neurogenesis is maintained but reduced in aged animals. Importantly, we now demonstrate that aging not only inhibits proliferation of specific SVZ cell subtypes but also blocks migration of neuroblasts to the damaged area and decreases the number of new interneurons in

  10. Small-molecule aggregation inhibitors reduce excess amyloid in a trisomy 16 mouse cortical cell line

    Directory of Open Access Journals (Sweden)

    ANDRÉA C PAULA LIMA

    2008-01-01

    Full Text Available We have previously characterized a number of small molecule organic compounds that prevent the aggregation of the β-amyloid peptide and its neurotoxicity in hippocampal neuronal cultures. We have now evaluated the effects of such compounds on amyloid precursor protein (APP accumulation in the CTb immortalized cell line derived from the cerebral cortex of a trisomy 16 mouse, an animal model of Down's syndrome. Compared to a non-trisomic cortical cell line (CNh, CTb cells overexpress APP and exhibit slightly elevated resting intracellular Ca2+ levéis ([Ca2+]¡. Here, we show that the compounds 2,4-dinitrophenol, 3-nitrophenol and 4-anisidine decreased intracellular accumulation of APP in CTb cells. Those compounds were non-toxic to the cells, and slightly increased the basal [Ca2+]¡. Results indícate that the compounds tested can be leads for the development of drugs to decrease intracellular vesicular accumulation of APP in trisomic cells.

  11. CELSR2, encoding a planar cell polarity protein, is a putative gene in Joubert syndrome with cortical heterotopia, microophthalmia, and growth hormone deficiency.

    Science.gov (United States)

    Vilboux, Thierry; Malicdan, May Christine V; Roney, Joseph C; Cullinane, Andrew R; Stephen, Joshi; Yildirimli, Deniz; Bryant, Joy; Fischer, Roxanne; Vemulapalli, Meghana; Mullikin, James C; Steinbach, Peter J; Gahl, William A; Gunay-Aygun, Meral

    2017-03-01

    Joubert syndrome is a ciliopathy characterized by a specific constellation of central nervous system malformations that result in the pathognomonic "molar tooth sign" on imaging. More than 27 genes are associated with Joubert syndrome, but some patients do not have mutations in any of these genes. Celsr1, Celsr2, and Celsr3 are the mammalian orthologues of the drosophila planar cell polarity protein, flamingo; they play important roles in neural development, including axon guidance, neuronal migration, and cilium polarity. Here, we report bi-allelic mutations in CELSR2 in a Joubert patient with cortical heterotopia, microophthalmia, and growth hormone deficiency. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. Imaging cortical activity following affective stimulation with a high temporal and spatial resolution

    Directory of Open Access Journals (Sweden)

    Catani Claudia

    2009-07-01

    Full Text Available Abstract Background The affective and motivational relevance of a stimulus has a distinct impact on cortical processing, particularly in sensory areas. However, the spatial and temporal dynamics of this affective modulation of brain activities remains unclear. The purpose of the present study was the development of a paradigm to investigate the affective modulation of cortical networks with a high temporal and spatial resolution. We assessed cortical activity with MEG using a visual steady-state paradigm with affective pictures. A combination of a complex demodulation procedure with a minimum norm estimation was applied to assess the temporal variation of the topography of cortical activity. Results Statistical permutation analyses of the results of the complex demodulation procedure revealed increased steady-state visual evoked field amplitudes over occipital areas following presentation of affective pictures compared to neutral pictures. This differentiation shifted in the time course from occipital regions to parietal and temporal regions. Conclusion It can be shown that stimulation with affective pictures leads to an enhanced activity in occipital region as compared to neutral pictures. However, the focus of differentiation is not stable over time but shifts into temporal and parietal regions within four seconds of stimulation. Thus, it can be crucial to carefully choose regions of interests and time intervals when analyzing the affective modulation of cortical activity.

  13. Human endothelial progenitor cells rescue cortical neurons from oxygen-glucose deprivation induced death.

    Science.gov (United States)

    Bacigaluppi, Susanna; Donzelli, Elisabetta; De Cristofaro, Valentina; Bragazzi, Nicola Luigi; D'Amico, Giovanna; Scuteri, Arianna; Tredici, Giovanni

    2016-09-19

    Cerebral ischemia is characterized by both acute and delayed neuronal injuries. Neuro-protection is a major issue that should be properly addressed from a pharmacological point of view, and cell-based treatment approaches are of interest due to their potential pleiotropic effects. Endothelial progenitor cells have the advantage of being mobilized from the bone marrow into the circulation, but have been less studied than other stem cells, such as mesenchymal stem cells. Therefore, the comparison between human endothelial progenitor cells (hEPC) and human mesenchymal progenitor cells (hMSC) in terms of efficacy in rescuing neurons from cell death after transitory ischemia is the aim of the current study, in the effort to address further directions. In vitro model of oxygen-glucose deprivation (OGD) on a primary culture of rodent cortical neurons was set up with different durations of exposure: 1, 2 and 3hrs with assessment of neuron survival. The 2hrs OGD was chosen for the subsequent experiments. After 2hrs OGD neurons were either placed in indirect co-culture with hMSC or hEPC or cultured in hMSC or hEPC conditioned medium and cell viability was evaluated by MTT assay. At day 2 after 2hrs OGD exposure, mean neuronal survival was 47.9±24.2%. In contrast, after treatment with hEPC and hMSC indirect co-culture was 74.1±27.3%; and 69.4±18.8%, respectively. In contrast, treatment with conditioned medium did not provide any advantage in terms of survival to OGD neurons The study shows the efficacy of hEPC in indirect co-culture to rescue neurons from cell death after OGD, comparable to that of hMSC. hEPC deserve further studies given their potential interest for ischemia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Mesenchymal stem cells can modulate longitudinal changes in cortical thickness and its related cognitive decline in patients with multiple system atrophy

    Science.gov (United States)

    Sunwoo, Mun Kyung; Yun, Hyuk Jin; Song, Sook K.; Ham, Ji Hyun; Hong, Jin Yong; Lee, Ji E.; Lee, Hye S.; Sohn, Young H.; Lee, Jong-Min; Lee, Phil Hyu

    2014-01-01

    Multiple system atrophy (MSA) is an adult-onset, sporadic neurodegenerative disease. Because the prognosis of MSA is fatal, neuroprotective or regenerative strategies may be invaluable in MSA treatment. Previously, we obtained clinical and imaging evidence that mesenchymal stem cell (MSC) treatment could have a neuroprotective role in MSA patients. In the present study, we evaluated the effects of MSC therapy on longitudinal changes in subcortical deep gray matter volumes and cortical thickness and their association with cognitive performance. Clinical and imaging data were obtained from our previous randomized trial of autologous MSC in MSA patients. During 1-year follow-up, we assessed longitudinal differences in automatic segmentation-based subcortical deep gray matter volumes and vertex-wise cortical thickness between placebo (n = 15) and MSC groups (n = 11). Next, we performed correlation analysis between the changes in cortical thickness and changes in the Korean version of the Montreal Cognitive Assessment (MoCA) scores and cognitive performance of each cognitive subdomain using a multiple, comparison correction. There were no significant differences in age at baseline, age at disease onset, gender ratio, disease duration, clinical severity, MoCA score, or education level between the groups. The automated subcortical volumetric analysis revealed that the changes in subcortical deep gray matter volumes of the caudate, putamen, and thalamus did not differ significantly between the groups. The areas of cortical thinning over time in the placebo group were more extensive, including the frontal, temporal, and parietal areas, whereas these areas in the MSC group were less extensive. Correlation analysis indicated that declines in MoCA scores and phonemic fluency during the follow-up period were significantly correlated with cortical thinning of the frontal and posterior temporal areas and anterior temporal areas in MSA patients, respectively. In contrast, no

  15. Modification of response functions of cat visual cortical cells by spatially congruent perturbing stimuli.

    Science.gov (United States)

    Kabara, J F; Bonds, A B

    2001-12-01

    Responses of cat striate cortical cells to a drifting sinusoidal grating were modified by the superimposition of a second, perturbing grating (PG) that did not excite the cell when presented alone. One consequence of the presence of a PG was a shift in the tuning curves. The orientation tuning of all 41 cells exposed to a PG and the spatial frequency tuning of 83% of the 23 cells exposed to a PG showed statistically significant dislocations of both the response function peak and center of mass from their single grating values. As found in earlier reports, the presence of PGs suppressed responsiveness. However, reductions measured at the single grating optimum orientation or spatial frequency were on average 1.3 times greater than the suppression found at the peak of the response function modified by the presence of the PG. Much of the loss in response seen at the single grating optimum is thus a result of a shift in the tuning function rather than outright suppression. On average orientation shifts were repulsive and proportional (approximately 0.10 deg/deg) to the angle between the perturbing stimulus and the optimum single grating orientation. Shifts in the spatial frequency response function were both attractive and repulsive, resulting in an overall average of zero. For both simple and complex cells, PGs generally broadened orientation response function bandwidths. Similarly, complex cell spatial frequency response function bandwidths broadened. Simple cell spatial frequency response functions usually did not change, and those that did broadened only 4% on average. These data support the hypothesis that additional sinusoidal components in compound stimuli retune cells' response functions for orientation and spatial frequency.

  16. Locally formed dopamine inhibits Na+-K+-ATPase activity in rat renal cortical tubule cells

    International Nuclear Information System (INIS)

    Seri, I.; Kone, B.C.; Gullans, S.R.; Aperia, A.; Brenner, B.M.; Ballermann, B.J.

    1988-01-01

    Dopamine, generated locally from L-dopa, inhibits Na + -K + -ATPase in permeabilized rat proximal tubules under maximum transport rate conditions for sodium. To determine whether locally formed dopamine inhibits Na + -K + -ATPase activity in intact cortical tubule cells we studied the effect of L-dopa on ouabain-sensitive oxygen consumption rate (Qo 2 ) and 86 Rb uptake in renal cortical tubule cell suspensions. L-Dopa did not affect ouabain-insensitive Qo 2 or mitochondrial respiration. However, L-dopa inhibited ouabain-sensitive Qo 2 in a concentration-dependent manner, with half-maximal inhibition (K 0.5 ) of 5 x 10 -7 M and a maximal inhibition of 14.1 ± 1.5% at 10 -4 M. L-Dopa also blunted the nystatin-stimulated Qo 2 in a concentration-dependent manner, indicating the L-dopa directly inhibits Na + -K + -ATPase activity and not sodium entry. Ouabain-sensitive 86 Rb uptake was also inhibited by L-dopa. Carbidopa, an inhibitor of the conversion of L-dopa to dopamine, eliminated the effect of L-dopa on ouabain-sensitive Qo 2 and 86 Rb uptake, indicating that dopamine rather than L-dopa was the active agent. The finding that the L-dopa concentration-response curve was shifted to the left by one order of magnitude in the presence of nystatin suggests that the inhibitory effect is enhanced when the intracellular sodium concentration is increased. By studying the effect of L-dopa on ouabain-sensitive Qo 2 at increasing extracellular sodium concentrations in the presence of nystatin, the authors demonstrated that the inhibitory effect of locally formed dopamine on the Na + -K + -ATPase is indeed dependent on the sodium available for the enzyme and occurs in an uncompetitive manner

  17. MDMA (Ecstasy) Decreases the Number of Neurons and Stem Cells in Embryonic Cortical Cultures

    DEFF Research Database (Denmark)

    Kindlundh-Högberg, Anna M S; Pickering, Chris; Wicher, Grzegorz

    2010-01-01

    Ecstasy, 3,4-methylenedioxymetamphetamine (MDMA), is a recreational drug used among adolescents, including young pregnant women. MDMA passes the placental barrier and may therefore influence fetal development. The aim was to investigate the direct effect of MDMA on cortical cells using dissociated...... CNS cortex of rat embryos, E17. The primary culture was exposed to a single dose of MDMA and collected 5 days later. MDMA caused a dramatic, dose-dependent (100 and 400 muM) decrease in nestin-positive stem cell density, as well as a significant reduction (400 muM) in NeuN-positive cells. By q......PCR, MDMA (200 muM) caused a significant decrease in mRNA expression of the 5HT3 receptor, dopamine D(1) receptor, and glutamate transporter EAAT2-1, as well as an increase in mRNA levels of the NMDA NR1 receptor subunit and the 5HT(1A) receptor. In conclusion, MDMA caused a marked reduction in stem cells...

  18. Homocysteine Aggravates Cortical Neural Cell Injury through Neuronal Autophagy Overactivation following Rat Cerebral Ischemia-Reperfusion

    Directory of Open Access Journals (Sweden)

    Yaqian Zhao

    2016-07-01

    Full Text Available Elevated homocysteine (Hcy levels have been reported to be involved in neurotoxicity after ischemic stroke. However, the underlying mechanisms remain incompletely understood to date. In the current study, we hypothesized that neuronal autophagy activation may be involved in the toxic effect of Hcy on cortical neurons following cerebral ischemia. Brain cell injury was determined by hematoxylin-eosin (HE staining and TdT-mediated dUTP Nick-End Labeling (TUNEL staining. The level and localization of autophagy were detected by transmission electron microscopy, western blot and immunofluorescence double labeling. The oxidative DNA damage was revealed by immunofluorescence of 8-Hydroxy-2′-deoxyguanosine (8-OHdG. Hcy treatment aggravated neuronal cell death, significantly increased the formation of autophagosomes and the expression of LC3B and Beclin-1 in the brain cortex after middle cerebral artery occlusion-reperfusion (MCAO. Immunofluorescence analysis of LC3B and Beclin-1 distribution indicated that their expression occurred mainly in neurons (NeuN-positive and hardly in astrocytes (GFAP-positive. 8-OHdG expression was also increased in the ischemic cortex of Hcy-treated animals. Conversely, LC3B and Beclin-1 overexpression and autophagosome accumulation caused by Hcy were partially blocked by the autophagy inhibitor 3-methyladenine (3-MA. Hcy administration enhanced neuronal autophagy, which contributes to cell death following cerebral ischemia. The oxidative damage-mediated autophagy may be a molecular mechanism underlying neuronal cell toxicity of elevated Hcy level.

  19. Synaptic integration of transplanted interneuron progenitor cells into native cortical networks.

    Science.gov (United States)

    Howard, MacKenzie A; Baraban, Scott C

    2016-08-01

    Interneuron-based cell transplantation is a powerful method to modify network function in a variety of neurological disorders, including epilepsy. Whether new interneurons integrate into native neural networks in a subtype-specific manner is not well understood, and the therapeutic mechanisms underlying interneuron-based cell therapy, including the role of synaptic inhibition, are debated. In this study, we tested subtype-specific integration of transplanted interneurons using acute cortical brain slices and visualized patch-clamp recordings to measure excitatory synaptic inputs, intrinsic properties, and inhibitory synaptic outputs. Fluorescently labeled progenitor cells from the embryonic medial ganglionic eminence (MGE) were used for transplantation. At 5 wk after transplantation, MGE-derived parvalbumin-positive (PV+) interneurons received excitatory synaptic inputs, exhibited mature interneuron firing properties, and made functional synaptic inhibitory connections to native pyramidal cells that were comparable to those of native PV+ interneurons. These findings demonstrate that MGE-derived PV+ interneurons functionally integrate into subtype-appropriate physiological niches within host networks following transplantation. Copyright © 2016 the American Physiological Society.

  20. Normalization of cortical thickness measurements across different T1 magnetic resonance imaging protocols by novel W-Score standardization.

    Science.gov (United States)

    Chung, Jinyong; Yoo, Kwangsun; Lee, Peter; Kim, Chan Mi; Roh, Jee Hoon; Park, Ji Eun; Kim, Sang Joon; Seo, Sang Won; Shin, Jeong-Hyeon; Seong, Joon-Kyung; Jeong, Yong

    2017-10-01

    The use of different 3D T1-weighted magnetic resonance (T1 MR) imaging protocols induces image incompatibility across multicenter studies, negating the many advantages of multicenter studies. A few methods have been developed to address this problem, but significant image incompatibility still remains. Thus, we developed a novel and convenient method to improve image compatibility. W-score standardization creates quality reference values by using a healthy group to obtain normalized disease values. We developed a protocol-specific w-score standardization to control the protocol effect, which is applied to each protocol separately. We used three data sets. In dataset 1, brain T1 MR images of normal controls (NC) and patients with Alzheimer's disease (AD) from two centers, acquired with different T1 MR protocols, were used (Protocol 1 and 2, n = 45/group). In dataset 2, data from six subjects, who underwent MRI with two different protocols (Protocol 1 and 2), were used with different repetition times, echo times, and slice thicknesses. In dataset 3, T1 MR images from a large number of healthy normal controls (Protocol 1: n = 148, Protocol 2: n = 343) were collected for w-score standardization. The protocol effect and disease effect on subjects' cortical thickness were analyzed before and after the application of protocol-specific w-score standardization. As expected, different protocols resulted in differing cortical thickness measurements in both NC and AD subjects. Different measurements were obtained for the same subject when imaged with different protocols. Multivariate pattern difference between measurements was observed between the protocols. Classification accuracy between two protocols was nearly 90%. After applying protocol-specific w-score standardization, the differences between the protocols substantially decreased. Most importantly, protocol-specific w-score standardization reduced both univariate and multivariate differences in the images while

  1. Applications of brain blood flow imaging in behavioral neurophysiology: cortical field activation hypothesis

    International Nuclear Information System (INIS)

    Roland, P.E.

    1985-01-01

    The 133 xenon intracarotid method for rCBF measurements has been a very useful method for functional mapping and functional dissection of the cerebral cortex in humans. With this method it has been shown that different types of cortical information treatment activate different cortical areas and furthermore that sensory and motor functions of the cerebral cortex could be dissected into anatomical and informational subcomponents by behavioral manipulations. The brain organizes its own activity. One of the principles of organization was that the brain could recruit in advance cortical fields that were expected to participate in a certain type of information operation. During brain work in awake human beings the cerebral cortex was activated in fields that, projected on the cerebral surface, most often had a size greater than 3 CM 2 . Such activated fields appeared no matter which type of information processing was going on in the brain: during planning and execution of voluntary movements, during preparation for sensory information processing, and during sensory information processing, as well as during cognitive brain work and retrieval of specific memories. Therefore, it was hypothesized that cortical field activation was the physiological manifestation of normal brain work in awake humans

  2. Development of cortical morphology evaluated with longitudinal MR brain images of preterm infants

    NARCIS (Netherlands)

    Moeskops, P.; Benders, M.J.N.L.; Kersbergen, K.J.; Groenendaal, F.; de Vries, L.S.; Viergever, M.A.; Išgum, I.

    2015-01-01

    INTRODUCTION: The cerebral cortex develops rapidly in the last trimester of pregnancy. In preterm infants, brain development is very vulnerable because of their often complicated extra-uterine conditions. The aim of this study was to quantitatively describe cortical development in a cohort of 85

  3. Applications of brain blood flow imaging in behavioral neurophysiology: cortical field activation hypothesis

    Energy Technology Data Exchange (ETDEWEB)

    Roland, P.E.

    1985-01-01

    The /sup 133/xenon intracarotid method for rCBF measurements has been a very useful method for functional mapping and functional dissection of the cerebral cortex in humans. With this method it has been shown that different types of cortical information treatment activate different cortical areas and furthermore that sensory and motor functions of the cerebral cortex could be dissected into anatomical and informational subcomponents by behavioral manipulations. The brain organizes its own activity. One of the principles of organization was that the brain could recruit in advance cortical fields that were expected to participate in a certain type of information operation. During brain work in awake human beings the cerebral cortex was activated in fields that, projected on the cerebral surface, most often had a size greater than 3 CM/sup 2/. Such activated fields appeared no matter which type of information processing was going on in the brain: during planning and execution of voluntary movements, during preparation for sensory information processing, and during sensory information processing, as well as during cognitive brain work and retrieval of specific memories. Therefore, it was hypothesized that cortical field activation was the physiological manifestation of normal brain work in awake humans.

  4. Medicago truncatula and Glomus intraradices gene expression in cortical cells harboring arbuscules in the arbuscular mycorrhizal symbiosis

    Directory of Open Access Journals (Sweden)

    Tang Yuhong

    2009-01-01

    Full Text Available Abstract Background Most vascular flowering plants have the capacity to form symbiotic associations with arbuscular mycorrhizal (AM fungi. The symbiosis develops in the roots where AM fungi colonize the root cortex and form arbuscules within the cortical cells. Arbuscules are enveloped in a novel plant membrane and their establishment requires the coordinated cellular activities of both symbiotic partners. The arbuscule-cortical cell interface is the primary functional interface of the symbiosis and is of central importance in nutrient exchange. To determine the molecular events the underlie arbuscule development and function, it is first necessary to identify genes that may play a role in this process. Toward this goal we used the Affymetrix GeneChip® Medicago Genome Array to document the M. truncatula transcript profiles associated with AM symbiosis, and then developed laser microdissection (LM of M. truncatula root cortical cells to enable analyses of gene expression in individual cell types by RT-PCR. Results This approach led to the identification of novel M. truncatula and G. intraradices genes expressed in colonized cortical cells and in arbuscules. Within the arbuscule, expression of genes associated with the urea cycle, amino acid biosynthesis and cellular autophagy was detected. Analysis of gene expression in the colonized cortical cell revealed up-regulation of a lysine motif (LysM-receptor like kinase, members of the GRAS transcription factor family and a symbiosis-specific ammonium transporter that is a likely candidate for mediating ammonium transport in the AM symbiosis. Conclusion Transcript profiling using the Affymetrix GeneChip® Medicago Genome Array provided new insights into gene expression in M. truncatula roots during AM symbiosis and revealed the existence of several G. intraradices genes on the M. truncatula GeneChip®. A laser microdissection protocol that incorporates low-melting temperature Steedman's wax, was

  5. Imaging the 3D structure of secondary osteons in human cortical bone using phase-retrieval tomography

    Energy Technology Data Exchange (ETDEWEB)

    Arhatari, B D; Peele, A G [Department of Physics, La Trobe University, Victoria 3086 (Australia); Cooper, D M L [Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon (Canada); Thomas, C D L; Clement, J G [Melbourne Dental School, University of Melbourne, Victoria 3010 (Australia)

    2011-08-21

    By applying a phase-retrieval step before carrying out standard filtered back-projection reconstructions in tomographic imaging, we were able to resolve structures with small differences in density within a densely absorbing sample. This phase-retrieval tomography is particularly suited for the three-dimensional segmentation of secondary osteons (roughly cylindrical structures) which are superimposed upon an existing cortical bone structure through the process of turnover known as remodelling. The resulting images make possible the analysis of the secondary osteon structure and the relationship between an osteon and the surrounding tissue. Our observations have revealed many different and complex 3D structures of osteons that could not be studied using previous methods. This work was carried out using a laboratory-based x-ray source, which makes obtaining these sorts of images readily accessible.

  6. Populations of Radial Glial Cells Respond Differently to Reelin and Neuregulin1 in a Ferret Model of Cortical Dysplasia

    Science.gov (United States)

    2010-10-28

    postnatally [11,12,13,14,15]. Ferrets are also the smallest mammals with a convoluted cortex [16]. Proliferation of intermediate progenitor cells in ferrets...24th day of development (E24) disrupts early cortical development, resulting in a thin and poorly laminated cortex, where neurons migrating radially and

  7. Renal Medullary and Cortical Correlates in Fibrosis, Epithelial Mass, Microvascularity, and Microanatomy Using Whole Slide Image Analysis Morphometry.

    Directory of Open Access Journals (Sweden)

    Alton B Farris

    Full Text Available Renal tubulointerstitial injury often leads to interstitial fibrosis and tubular atrophy (IF/TA. IF/TA is typically assessed in the renal cortex and can be objectively quantitated with computerized image analysis (IA. However, the human medulla accounts for a substantial proportion of the nephron; therefore, medullary scarring will have important cortical consequences and may parallel overall chronic renal injury. Trichrome, periodic acid-Schiff (PAS, and collagen III immunohistochemistry (IHC were visually examined and quantitated on scanned whole slide images (WSIs (N = 67 cases. When tuned to measure fibrosis, IA of trichrome and Trichrome-PAS (T-P WSIs correlated for all anatomic compartments (among cortex, medulla, and entire tissue, r = 0.84 to 0.89, P all <0.0001; and collagen III deposition correlated between compartments (r = 0.69 to 0.89, P <0.0001 to 0.0002; however, trichrome and T-P measures did not correlate with collagen deposition, suggesting heterogeneous contributions to extracellular matrix deposition. Epithelial cell mass (EPCM correlated between cortex and medulla when measured with cytokeratin IHC and with the trichrome red portion (r = 0.85 and 0.66, respectively, all P < 0.0001. Visual assessment also correlated between compartments for fibrosis and EPCM. Correlations were found between increasing medullary inner stripe (IS width and fibrosis in all of the tissue and the medulla by trichrome morphometry (r = 0.56, P < 0.0001, and r = 0.48, P = 0.00008, respectively. Weak correlations were found between increasing IS width and decreasing visual assessment of all tissue EPCM. Microvessel density (MVD and microvessel area (MVA measured using a MVD algorithm applied to CD34 IHC correlated significantly between all compartments (r = 0.76 to 0.87 for MVD and 0.71 to 0.87 for MVA, P all < 0.0001. Overall, these findings demonstrate the interrelatedness of the cortex and medulla and the importance of considering the renal

  8. Nifedipine-activated Ca(2+) permeability in newborn rat cortical collecting duct cells in primary culture.

    Science.gov (United States)

    Valencia, L; Bidet, M; Martial, S; Sanchez, E; Melendez, E; Tauc, M; Poujeol, C; Martin, D; Namorado, M D; Reyes, J L; Poujeol, P

    2001-05-01

    To characterize Ca(2+) transport in newborn rat cortical collecting duct (CCD) cells, we used nifedipine, which in adult rat distal tubules inhibits the intracellular Ca(2+) concentration ([Ca(2+)](i)) increase in response to hormonal activation. We found that the dihydropyridine (DHP) nifedipine (20 microM) produced an increase in [Ca(2+)](i) from 87.6 +/- 3.3 nM to 389.9 +/- 29.0 nM in 65% of the cells. Similar effects of other DHP (BAY K 8644, isradipine) were also observed. Conversely, DHPs did not induce any increase in [Ca(2+)](i) in cells obtained from proximal convoluted tubule. In CCD cells, neither verapamil nor diltiazem induced any rise in [Ca(2+)](i). Experiments in the presence of EGTA showed that external Ca(2+) was required for the nifedipine effect, while lanthanum (20 microM), gadolinium (100 microM), and diltiazem (20 microM) inhibited the effect. Experiments done in the presence of valinomycin resulted in the same nifedipine effect, showing that K(+) channels were not involved in the nifedipine-induced [Ca(2+)](i) rise. H(2)O(2) also triggered [Ca(2+)](i) rise. However, nifedipine-induced [Ca(2+)](i) increase was not affected by protamine. In conclusion, the present results indicate that 1) primary cultures of cells from terminal nephron of newborn rats are a useful tool for investigating Ca(2+) transport mechanisms during growth, and 2) newborn rat CCD cells in primary culture exhibit a new apical nifedipine-activated Ca(2+) channel of capacitive type (either transient receptor potential or leak channel).

  9. Brain-wide Maps Reveal Stereotyped Cell-Type-Based Cortical Architecture and Subcortical Sexual Dimorphism.

    Science.gov (United States)

    Kim, Yongsoo; Yang, Guangyu Robert; Pradhan, Kith; Venkataraju, Kannan Umadevi; Bota, Mihail; García Del Molino, Luis Carlos; Fitzgerald, Greg; Ram, Keerthi; He, Miao; Levine, Jesse Maurica; Mitra, Partha; Huang, Z Josh; Wang, Xiao-Jing; Osten, Pavel

    2017-10-05

    The stereotyped features of neuronal circuits are those most likely to explain the remarkable capacity of the brain to process information and govern behaviors, yet it has not been possible to comprehensively quantify neuronal distributions across animals or genders due to the size and complexity of the mammalian brain. Here we apply our quantitative brain-wide (qBrain) mapping platform to document the stereotyped distributions of mainly inhibitory cell types. We discover an unexpected cortical organizing principle: sensory-motor areas are dominated by output-modulating parvalbumin-positive interneurons, whereas association, including frontal, areas are dominated by input-modulating somatostatin-positive interneurons. Furthermore, we identify local cell type distributions with more cells in the female brain in 10 out of 11 sexually dimorphic subcortical areas, in contrast to the overall larger brains in males. The qBrain resource can be further mined to link stereotyped aspects of neuronal distributions to known and unknown functions of diverse brain regions. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Cortical Double-Opponent Cells in Color Perception: Perceptual Scaling and Chromatic Visual Evoked Potentials.

    Science.gov (United States)

    Nunez, Valerie; Shapley, Robert M; Gordon, James

    2018-01-01

    In the early visual cortex V1, there are currently only two known neural substrates for color perception: single-opponent and double-opponent cells. Our aim was to explore the relative contributions of these neurons to color perception. We measured the perceptual scaling of color saturation for equiluminant color checkerboard patterns (designed to stimulate double-opponent neurons preferentially) and uniformly colored squares (designed to stimulate only single-opponent neurons) at several cone contrasts. The spatially integrative responses of single-opponent neurons would produce the same response magnitude for checkerboards as for uniform squares of the same space-averaged cone contrast. However, perceived saturation of color checkerboards was higher than for the corresponding squares. The perceptual results therefore imply that double-opponent cells are involved in color perception of patterns. We also measured the chromatic visual evoked potential (cVEP) produced by the same stimuli; checkerboard cVEPs were much larger than those for corresponding squares, implying that double-opponent cells also contribute to the cVEP response. The total Fourier power of the cVEP grew sublinearly with cone contrast. However, the 6-Hz Fourier component's power grew linearly with contrast-like saturation perception. This may also indicate that cortical coding of color depends on response dynamics.

  11. Stimulus-dependent modulation of spike burst length in cat striate cortical cells.

    Science.gov (United States)

    DeBusk, B C; DeBruyn, E J; Snider, R K; Kabara, J F; Bonds, A B

    1997-07-01

    Burst activity, defined by groups of two or more spikes with intervals of cats. Bursting varied broadly across a population of 507 simple and complex cells. Half of this population had > or = 42% of their spikes contained in bursts. The fraction of spikes in bursts did not vary as a function of average firing rate and was stationary over time. Peaks in the interspike interval histograms were found at both 3-5 ms and 10-30 ms. In many cells the locations of these peaks were independent of firing rate, indicating a quantized control of firing behavior at two different time scales. The activity at the shorter time scale most likely results from intrinsic properties of the cell membrane, and that at the longer scale from recurrent network excitation. Burst frequency (bursts per s) and burst length (spikes per burst) both depended on firing rate. Burst frequency was essentially linear with firing rate, whereas burst length was a nonlinear function of firing rate and was also governed by stimulus orientation. At a given firing rate, burst length was greater for optimal orientations than for nonoptimal orientations. No organized orientation dependence was seen in bursts from lateral geniculate nucleus cells. Activation of cortical contrast gain control at low response amplitudes resulted in no burst length modulation, but burst shortening at optimal orientations was found in responses characterized by supersaturation. At a given firing rate, cortical burst length was shortened by microinjection of gamma-aminobutyric acid (GABA), and bursts became longer in the presence of N-methyl-bicuculline, a GABA(A) receptor blocker. These results are consistent with a model in which responses are reduced at nonoptimal orientations, at least in part, by burst shortening that is mediated by GABA. A similar mechanism contributes to response supersaturation at high contrasts via recruitment of inhibitory responses that are tuned to adjacent orientations. Burst length modulation can serve

  12. Cell wall matrix polysaccharide distribution and cortical microtubule organization: two factors controlling mesophyll cell morphogenesis in land plants.

    Science.gov (United States)

    Sotiriou, P; Giannoutsou, E; Panteris, E; Apostolakos, P; Galatis, B

    2016-03-01

    This work investigates the involvement of local differentiation of cell wall matrix polysaccharides and the role of microtubules in the morphogenesis of mesophyll cells (MCs) of three types (lobed, branched and palisade) in the dicotyledon Vigna sinensis and the fern Asplenium nidus. Homogalacturonan (HGA) epitopes recognized by the 2F4, JIM5 and JIM7 antibodies and callose were immunolocalized in hand-made leaf sections. Callose was also stained with aniline blue. We studied microtubule organization by tubulin immunofluorescence and transmission electron microscopy. In both plants, the matrix cell wall polysaccharide distribution underwent definite changes during MC differentiation. Callose constantly defined the sites of MC contacts. The 2F4 HGA epitope in V. sinensis first appeared in MC contacts but gradually moved towards the cell wall regions facing the intercellular spaces, while in A. nidus it was initially localized at the cell walls delimiting the intercellular spaces, but finally shifted to MC contacts. In V. sinensis, the JIM5 and JIM7 HGA epitopes initially marked the cell walls delimiting the intercellular spaces and gradually shifted in MC contacts, while in A. nidus they constantly enriched MC contacts. In all MC types examined, the cortical microtubules played a crucial role in their morphogenesis. In particular, in palisade MCs, cortical microtubule helices, by controlling cellulose microfibril orientation, forced these MCs to acquire a truncated cone-like shape. Unexpectedly in V. sinensis, the differentiation of colchicine-affected MCs deviated completely, since they developed a cell wall ingrowth labyrinth, becoming transfer-like cells. The results of this work and previous studies on Zea mays (Giannoutsou et al., Annals of Botany 2013; 112: : 1067-1081) revealed highly controlled local cell wall matrix differentiation in MCs of species belonging to different plant groups. This, in coordination with microtubule-dependent cellulose microfibril

  13. Thalamo–cortical network underlying deep brain stimulation of centromedian thalamic nuclei in intractable epilepsy: a multimodal imaging analysis

    Directory of Open Access Journals (Sweden)

    Kim SH

    2017-10-01

    Full Text Available Seong Hoon Kim,1 Sung Chul Lim,1 Dong Won Yang,1 Jeong Hee Cho,1 Byung-Chul Son,2 Jiyeon Kim,3 Seung Bong Hong,4 Young-Min Shon4 1Department of Neurology, 2Department of Neurosurgery, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seoul, 3Department of Neurology, Korea University Ansan Hospital, College of Medicine, Korea University, Ansan, 4Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Objective: Deep brain stimulation (DBS of the centromedian thalamic nucleus (CM can be an alternative treatment option for intractable epilepsy patients. Since CM may be involved in widespread cortico-subcortical networks, identification of the cortical sub-networks specific to the target stimuli may provide further understanding on the underlying mechanisms of CM DBS. Several brain structures have distinguishing brain connections that may be related to the pivotal propagation and subsequent clinical effect of DBS.Methods: To explore core structures and their connections relevant to CM DBS, we applied electroencephalogram (EEG and diffusion tensor imaging (DTI to 10 medically intractable patients – three generalized epilepsy (GE and seven multifocal epilepsy (MFE patients unsuitable for resective surgery. Spatiotemporal activation pattern was mapped from scalp EEG by delivering low-frequency stimuli (5 Hz. Structural connections between the CM and the cortical activation spots were assessed using DTI.Results: We confirmed an average 72% seizure reduction after CM DBS and its clinical efficiency remained consistent during the observation period (mean 21 months. EEG data revealed sequential source propagation from the anterior cingulate, followed by the frontotemporal regions bilaterally. In addition, maximal activation was found in the left cingulate gyrus and the right medial frontal cortex during the right and left CM stimulation, respectively

  14. Association of Cortical Lesion Burden on 7-T Magnetic Resonance Imaging With Cognition and Disability in Multiple Sclerosis.

    Science.gov (United States)

    Harrison, Daniel M; Roy, Snehashis; Oh, Jiwon; Izbudak, Izlem; Pham, Dzung; Courtney, Susan; Caffo, Brian; Jones, Craig K; van Zijl, Peter; Calabresi, Peter A

    2015-09-01

    Cortical lesions (CLs) contribute to physical and cognitive disability in multiple sclerosis (MS). Accurate methods for visualization of CLs are necessary for future clinical studies and therapeutic trials in MS. To evaluate the clinical relevance of measures of CL burden derived from high-field magnetic resonance imaging (MRI) in MS. An observational clinical imaging study was conducted at an academic MS center. Participants included 36 individuals with MS (30 relapsing-remitting, 6 secondary or primary progressive) and 15 healthy individuals serving as controls. The study was conducted from March 10, 2010, to November 23, 2012, and analysis was performed from June 1, 2011, to September 30, 2014. Seven-Tesla MRI of the brain was performed with 0.5-mm isotropic resolution magnetization-prepared rapid acquisition gradient echo (MPRAGE) and whole-brain, 3-dimensional, 1.0-mm isotropic resolution magnetization-prepared, fluid-attenuated inversion recovery (MPFLAIR). Cortical lesions, seen as hypointensities on MPRAGE, were manually segmented. Lesions were classified as leukocortical, intracortical, or subpial. Images were segmented using the Lesion-TOADS (Topology-Preserving Anatomical Segmentation) algorithm, and brain structure volumes and white matter (WM) lesion volume were reported. Volumes were normalized to intracranial volume. Physical disability was measured by the Expanded Disability Status Scale (EDSS). Cognitive disability was measured with the Minimal Assessment of Cognitive Function in MS battery. Cortical lesions were noted in 35 of 36 participants (97%), with a median of 16 lesions per participant (range, 0-99). Leukocortical lesion volume correlated with WM lesion volume (ρ = 0.50; P = .003) but not with cortical volume; subpial lesion volume inversely correlated with cortical volume (ρ = -0.36; P = .04) but not with WM lesion volume. Total CL count and volume, measured as median (range), were significantly increased in participants

  15. Protection of cortical cells by equine estrogens against glutamate-induced excitotoxicity is mediated through a calcium independent mechanism

    Directory of Open Access Journals (Sweden)

    Perrella Joel

    2005-05-01

    Full Text Available Abstract Background High concentrations of glutamate can accumulate in the brain and may be involved in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease. This form of neurotoxicity involves changes in the regulation of cellular calcium (Ca2+ and generation of free radicals such as peroxynitrite (ONOO-. Estrogen may protect against glutamate-induced cell death by reducing the excitotoxic Ca2+ influx associated with glutamate excitotoxicity. In this study, the inhibition of N-methyl-D-aspartate (NMDA receptor and nitric oxide synthase (NOS along with the effect of 17β-estradiol (17β-E2 and a more potent antioxidant Δ8, 17β-estradiol (Δ8, 17β-E2 on cell viability and intracellular Ca2+ ([Ca2+]i, following treatment of rat cortical cells with glutamate, was investigated. Results Primary rat cortical cells were cultured for 7–12 days in Neurobasal medium containing B27 supplements. Addition of glutamate (200 μM decreased cell viability to 51.3 ± 0.7% compared to control. Treatment with the noncompetitive NMDAR antagonist, MK-801, and the NOS inhibitor, L-NAME, completely prevented cell death. Pretreatment (24 hrs with 17β-E2 and Δ8, 17β-E2 (0.01 to 10 μM significantly reduced cell death. 17β-E2 was more potent than Δ8, 17β-E2. Glutamate caused a rapid 2.5 fold increase in [Ca2+]i. Treatment with 0.001 to 10 μM MK-801 reduced the initial Ca2+ influx by 14–41% and increased cell viability significantly. Pretreatment with 17β-E2 and Δ8, 17β-E2 had no effect on Ca2+ influx but protected the cortical cells against glutamate-induced cell death. Conclusion Glutamate-induced cell death in cortical cultures can occur through NMDAR and NOS-linked mechanisms by increasing nitric oxide and ONOO-. Equine estrogens: 17β-E2 and Δ8, 17β-E2, significantly protected cortical cells against glutamate-induced excitotoxicity by a mechanism that appears to be independent of Ca2+ influx. To our knowledge, this is a first

  16. Association of In Vivo [18F]AV-1451 Tau PET Imaging Results With Cortical Atrophy and Symptoms in Typical and Atypical Alzheimer Disease.

    Science.gov (United States)

    Xia, Chenjie; Makaretz, Sara J; Caso, Christina; McGinnis, Scott; Gomperts, Stephen N; Sepulcre, Jorge; Gomez-Isla, Teresa; Hyman, Bradley T; Schultz, Aaron; Vasdev, Neil; Johnson, Keith A; Dickerson, Bradford C

    2017-04-01

    Previous postmortem studies have long demonstrated that neurofibrillary tangles made of hyperphosphorylated tau proteins are closely associated with Alzheimer disease clinical phenotype and neurodegeneration pattern. Validating these associations in vivo will lead to new diagnostic tools for Alzheimer disease and better understanding of its neurobiology. To examine whether topographical distribution and severity of hyperphosphorylated tau pathologic findings measured by fluorine 18-labeled AV-1451 ([18F]AV-1451) positron emission tomographic (PET) imaging are linked with clinical phenotype and cortical atrophy in patients with Alzheimer disease. This observational case series, conducted from July 1, 2012, to July 30, 2015, in an outpatient referral center for patients with neurodegenerative diseases, included 6 patients: 3 with typical amnesic Alzheimer disease and 3 with atypical variants (posterior cortical atrophy, logopenic variant primary progressive aphasia, and corticobasal syndrome). Patients underwent [18F]AV-1451 PET imaging to measure tau burden, carbon 11-labeled Pittsburgh Compound B ([11C]PiB) PET imaging to measure amyloid burden, and structural magnetic resonance imaging to measure cortical thickness. Seventy-seven age-matched controls with normal cognitive function also underwent structural magnetic resonance imaging but not tau or amyloid PET imaging. Tau burden, amyloid burden, and cortical thickness. In all 6 patients (3 women and 3 men; mean age 61.8 years), the underlying clinical phenotype was associated with the regional distribution of the [18F]AV-1451 signal. Furthermore, within 68 cortical regions of interest measured from each patient, the magnitude of cortical atrophy was strongly correlated with the magnitude of [18F]AV-1451 binding (3 patients with amnesic Alzheimer disease, r = -0.82; P localizing and quantifying hyperphosphorylated tau in vivo, results of tau PET imaging will likely serve as a key biomarker that links a

  17. Cortical Bone Stem Cell Therapy Preserves Cardiac Structure and Function After Myocardial Infarction.

    Science.gov (United States)

    Sharp, Thomas E; Schena, Giana J; Hobby, Alexander R; Starosta, Timothy; Berretta, Remus M; Wallner, Markus; Borghetti, Giulia; Gross, Polina; Yu, Daohai; Johnson, Jaslyn; Feldsott, Eric; Trappanese, Danielle M; Toib, Amir; Rabinowitz, Joseph E; George, Jon C; Kubo, Hajime; Mohsin, Sadia; Houser, Steven R

    2017-11-10

    Cortical bone stem cells (CBSCs) have been shown to reduce ventricular remodeling and improve cardiac function in a murine myocardial infarction (MI) model. These effects were superior to other stem cell types that have been used in recent early-stage clinical trials. However, CBSC efficacy has not been tested in a preclinical large animal model using approaches that could be applied to patients. To determine whether post-MI transendocardial injection of allogeneic CBSCs reduces pathological structural and functional remodeling and prevents the development of heart failure in a swine MI model. Female Göttingen swine underwent left anterior descending coronary artery occlusion, followed by reperfusion (ischemia-reperfusion MI). Animals received, in a randomized, blinded manner, 1:1 ratio, CBSCs (n=9; 2×10 7 cells total) or placebo (vehicle; n=9) through NOGA-guided transendocardial injections. 5-ethynyl-2'deoxyuridine (EdU)-a thymidine analog-containing minipumps were inserted at the time of MI induction. At 72 hours (n=8), initial injury and cell retention were assessed. At 3 months post-MI, cardiac structure and function were evaluated by serial echocardiography and terminal invasive hemodynamics. CBSCs were present in the MI border zone and proliferating at 72 hours post-MI but had no effect on initial cardiac injury or structure. At 3 months, CBSC-treated hearts had significantly reduced scar size, smaller myocytes, and increased myocyte nuclear density. Noninvasive echocardiographic measurements showed that left ventricular volumes and ejection fraction were significantly more preserved in CBSC-treated hearts, and invasive hemodynamic measurements documented improved cardiac structure and functional reserve. The number of EdU + cardiac myocytes was increased in CBSC- versus vehicle- treated animals. CBSC administration into the MI border zone reduces pathological cardiac structural and functional remodeling and improves left ventricular functional reserve

  18. Restoration of Progranulin Expression Rescues Cortical Neuron Generation in an Induced Pluripotent Stem Cell Model of Frontotemporal Dementia

    Directory of Open Access Journals (Sweden)

    Susanna Raitano

    2015-01-01

    Full Text Available To understand how haploinsufficiency of progranulin (PGRN causes frontotemporal dementia (FTD, we created induced pluripotent stem cells (iPSCs from patients carrying the GRNIVS1+5G > C mutation (FTD-iPSCs. FTD-iPSCs were fated to cortical neurons, the cells most affected in FTD. Although generation of neuroprogenitors was unaffected, their further differentiation into CTIP2-, FOXP2-, or TBR1-TUJ1 double-positive cortical neurons, but not motorneurons, was significantly decreased in FTD-neural progeny. Zinc finger nuclease-mediated introduction of GRN cDNA into the AAVS1 locus corrected defects in cortical neurogenesis, demonstrating that PGRN haploinsufficiency causes inefficient cortical neuron generation. RNA sequencing analysis confirmed reversal of the altered gene expression profile following genetic correction. We identified the Wnt signaling pathway as one of the top defective pathways in FTD-iPSC-derived neurons, which was reversed following genetic correction. Differentiation of FTD-iPSCs in the presence of a WNT inhibitor mitigated defective corticogenesis. Therefore, we demonstrate that PGRN haploinsufficiency hampers corticogenesis in vitro.

  19. Locally formed dopamine inhibits Na sup + -K sup + -ATPase activity in rat renal cortical tubule cells

    Energy Technology Data Exchange (ETDEWEB)

    Seri, I.; Kone, B.C.; Gullans, S.R.; Aperia, A.; Brenner, B.M.; Ballermann, B.J. (Harvard Medical School, Boston, MA (USA) Karolinska Institute, Stockholm (Sweden))

    1988-10-01

    Dopamine, generated locally from L-dopa, inhibits Na{sup +}-K{sup +}-ATPase in permeabilized rat proximal tubules under maximum transport rate conditions for sodium. To determine whether locally formed dopamine inhibits Na{sup +}-K{sup +}-ATPase activity in intact cortical tubule cells we studied the effect of L-dopa on ouabain-sensitive oxygen consumption rate ({dot Q}o{sub 2}) and {sup 86}Rb uptake in renal cortical tubule cell suspensions. L-Dopa did not affect ouabain-insensitive {dot Q}o{sub 2} or mitochondrial respiration. However, L-dopa inhibited ouabain-sensitive {dot Q}o{sub 2} in a concentration-dependent manner, with half-maximal inhibition (K{sub 0.5}) of 5 {times} 10{sup {minus}7} M and a maximal inhibition of 14.1 {plus minus} 1.5% at 10{sup {minus}4}M. L-Dopa also blunted the nystatin-stimulated {dot Q}o{sub 2} in a concentration-dependent manner, indicating the L-dopa directly inhibits Na{sup +}-K{sup +}-ATPase activity and not sodium entry. Ouabain-sensitive {sup 86}Rb uptake was also inhibited by L-dopa. Carbidopa, an inhibitor of the conversion of L-dopa to dopamine, eliminated the effect of L-dopa on ouabain-sensitive {dot Q}o{sub 2} and {sup 86}Rb uptake, indicating that dopamine rather than L-dopa was the active agent. The finding that the L-dopa concentration-response curve was shifted to the left by one order of magnitude in the presence of nystatin suggests that the inhibitory effect is enhanced when the intracellular sodium concentration is increased. By studying the effect of L-dopa on ouabain-sensitive {dot Q}o{sub 2} at increasing extracellular sodium concentrations in the presence of nystatin, the authors demonstrated that the inhibitory effect of locally formed dopamine on the Na{sup +}-K{sup +}-ATPase is indeed dependent on the sodium available for the enzyme and occurs in an uncompetitive manner.

  20. Where are we? The anatomy of the murine cortical meninges revisited for intravital imaging, immunology, and clearance of waste from the brain.

    Science.gov (United States)

    Coles, Jonathan A; Myburgh, Elmarie; Brewer, James M; McMenamin, Paul G

    2017-09-01

    Rapid progress is being made in understanding the roles of the cerebral meninges in the maintenance of normal brain function, in immune surveillance, and as a site of disease. Most basic research on the meninges and the neural brain is now done on mice, major attractions being the availability of reporter mice with fluorescent cells, and of a huge range of antibodies useful for immunocytochemistry and the characterization of isolated cells. In addition, two-photon microscopy through the unperforated calvaria allows intravital imaging of the undisturbed meninges with sub-micron resolution. The anatomy of the dorsal meninges of the mouse (and, indeed, of all mammals) differs considerably from that shown in many published diagrams: over cortical convexities, the outer layer, the dura, is usually thicker than the inner layer, the leptomeninx, and both layers are richly vascularized and innervated, and communicate with the lymphatic system. A membrane barrier separates them and, in disease, inflammation can be localized to one layer or the other, so experimentalists must be able to identify the compartment they are studying. Here, we present current knowledge of the functional anatomy of the meninges, particularly as it appears in intravital imaging, and review their role as a gateway between the brain, blood, and lymphatics, drawing on information that is scattered among works on different pathologies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Regulation of cyclic AMP metabolism by prostaglandins in rabbit cortical collecting tubule cells

    International Nuclear Information System (INIS)

    Sonnenburg, W.K.

    1987-01-01

    In the rabbit cortical collecting tubule (RCCT), prostaglandin E 1 (PGE 1 ) and prostaglandin E 2 (PGE 2 ) at 1 nM inhibit arginine-vasopressin (AVP)-induced water reabsorption, while 100 nM PGE 1 and PGE 2 alone stimulate water reabsorption. Reported here are studies designed to investigate the molecular basis for the biphasic physiological action of PGE 1 and PGE 2 in the collecting duct. In freshly isolated RCCT cells, PGE 1 , PGE 2 , and 16,16-dimethyl-PGE 2 (DM-PGE 2 ) stimulated cAMP synthesis at concentrations ranging from 0.1 to 10 M. Other prostaglandins including the synthetic PGE 2 analogue, sulprostone, failed to stimulate cAMP synthesis. Moreover, sulprostone did not antagonize PGE 2 -stimulated cAMP formation. In contrast, PGE 2 and sulprostone at concentrations ranging from 1 to 100 nM, inhibited AVP-induced cAMP accumulation in freshly isolated RCCT cells. PGE 2 , PGE 1 , DM-PGE 2 and sulprostone at 100 nM were equally effective in inhibiting AVP-induced cAMP formation. Moreover sulprostone inhibited AVP-stimulated adenylate cyclase activity. These results suggest that PGE derivatives mediate either inhibition or activation of adenylate cyclase by stimulating different PGE receptors. To further test this concept, PGE 2 binding to freshly isolated RCCT cell membranes was characterized. Two different classes of PGE 2 binding were detected. / 3 H/PGE 2 binding to the high affinity class of sites was increased by the GTP-analogue, GTP S, while pertussis toxin pretreatment blocked the stimulatory action. In contrast, / 3 H/ PGE 2 binding to the low affinity class of sites was decreased by GTP S; this inhibitory effect was not blocked by pertussis toxin pretreatment

  2. Magnetic resonance imaging of trabecular and cortical bone in mice: comparison of high resolution in vivo and ex vivo MR images with corresponding histology

    International Nuclear Information System (INIS)

    Weber, Michael H.; Sharp, Jonathan C.; Latta, Peter; Sramek, Milos; Hassard, H. Thomas; Orr, F. William

    2005-01-01

    Measurements of bone morphometry and remodeling have been shown to reflect bone strength and can be used to diagnose degenerative bone disease. In this study, in vivo and ex vivo magnetic resonance imaging (MRI) techniques to assess trabecular and cortical bone properties have been compared to each other and to histology as a novel means for the quantification of bone. Femurs of C57Bl/6 mice were examined both in vivo and ex vivo on an 11.7 T MRI scanner, followed by histologic processing and morphometry. A thresholding analysis technique was applied to the MRI images to generate contour lines and to delineate the boundaries between bone and marrow. Using MRI, an optimal correlation with histology was obtained with an in vivo longitudinal sectioned short echo time gradient-echo versus an in vivo long echo time spin-echo sequence or an ex vivo pulse sequence. Gradient-echo images were acquired with a maximum in-plane resolution of 35 μm. Our results demonstrated that in both the in vivo and ex vivo data sets, the percent area of marrow increases and percent area of trabecular bone and cortical bone thickness decreases moving from the epiphyseal growth plate to the diaphysis. These changes, observed with MRI, correlate with the histological data. Investigations using in vivo MRI gradient-echo sequences consistently gave the best correlation with histology. Our quantitative evaluation using both ex vivo and in vivo MRI was found to be an effective means to visualize non-invasively the normal variation in trabecular and cortical bone as compared to a histological 'gold standard' The experiments validated in vivo MRI as a potential high resolution technique for investigating both soft tissue, such as marrow, and bone without radiation exposure

  3. Induction of superficial cortical layer neurons from mouse embryonic stem cells by valproic acid.

    Science.gov (United States)

    Juliandi, Berry; Abematsu, Masahiko; Sanosaka, Tsukasa; Tsujimura, Keita; Smith, Austin; Nakashima, Kinichi

    2012-01-01

    Within the developing mammalian cortex, neural progenitors first generate deep-layer neurons and subsequently more superficial-layer neurons, in an inside-out manner. It has been reported recently that mouse embryonic stem cells (mESCs) can, to some extent, recapitulate cortical development in vitro, with the sequential appearance of neurogenesis markers resembling that in the developing cortex. However, mESCs can only recapitulate early corticogenesis; superficial-layer neurons, which are normally produced in later developmental periods in vivo, are under-represented. This failure of mESCs to reproduce later corticogenesis in vitro implies the existence of crucial factor(s) that are absent or uninduced in existing culture systems. Here we show that mESCs can give rise to superficial-layer neurons efficiently when treated with valproic acid (VPA), a histone deacetylase inhibitor. VPA treatment increased the production of Cux1-positive superficial-layer neurons, and decreased that of Ctip2-positive deep-layer neurons. These results shed new light on the mechanisms of later corticogenesis. Copyright © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  4. Protein phosphatase 2ACα gene knock-out results in cortical atrophy through activating hippo cascade in neuronal progenitor cells.

    Science.gov (United States)

    Liu, Bo; Sun, Li-Hua; Huang, Yan-Fei; Guo, Li-Jun; Luo, Li-Shu

    2018-02-01

    Protein phosphatase 2ACα (PP2ACα), a vital member of the protein phosphatase family, has been studied primarily as a regulator for the development, growth and protein synthesis of a lot of cell types. Dysfunction of PP2ACα protein results in neurodegenerative disease; however, this finding has not been directly confirmed in the mouse model with PP2ACα gene knock-out. Therefore, in this study presented here, we generated the PP2ACα gene knock-out mouse model by the Cre-loxP targeting gene system, with the purpose to directly observe the regulatory role of PP2ACα gene in the development of mouse's cerebral cortex. We observe that knocking-out PP2ACα gene in the central nervous system (CNS) results in cortical neuronal shrinkage, synaptic plasticity impairments, and learning/memory deficits. Further study reveals that PP2ACα gene knock-out initiates Hippo cascade in cortical neuroprogenitor cells (NPCs), which blocks YAP translocation into the nuclei of NPCs. Notably, p73, directly targeted by Hippo cascade, can bind to the promoter of glutaminase2 (GLS2) that plays a dominant role in the enzymatic regulation of glutamate/glutamine cycle. Finally, we find that PP2ACα gene knock-out inhibits the glutamine synthesis through up-regulating the activity of phosphorylated-p73 in cortical NPCs. Taken together, it concludes that PP2ACα critically supports cortical neuronal growth and cognitive function via regulating the signaling transduction of Hippo-p73 cascade. And PP2ACα indirectly modulates the glutamine synthesis of cortical NPCs through targeting p73 that plays a direct transcriptional regulatory role in the gene expression of GLS2. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Deafferentation-Induced Plasticity of Visual Callosal Connections: Predicting Critical Periods and Analyzing Cortical Abnormalities Using Diffusion Tensor Imaging

    Directory of Open Access Journals (Sweden)

    Jaime F. Olavarria

    2012-01-01

    Full Text Available Callosal connections form elaborate patterns that bear close association with striate and extrastriate visual areas. Although it is known that retinal input is required for normal callosal development, there is little information regarding the period during which the retina is critically needed and whether this period correlates with the same developmental stage across species. Here we review the timing of this critical period, identified in rodents and ferrets by the effects that timed enucleations have on mature callosal connections, and compare it to other developmental milestones in these species. Subsequently, we compare these events to diffusion tensor imaging (DTI measurements of water diffusion anisotropy within developing cerebral cortex. We observed that the relationship between the timing of the critical period and the DTI-characterized developmental trajectory is strikingly similar in rodents and ferrets, which opens the possibility of using cortical DTI trajectories for predicting the critical period in species, such as humans, in which this period likely occurs prenatally. Last, we discuss the potential of utilizing DTI to distinguish normal from abnormal cerebral cortical development, both within the context of aberrant connectivity induced by early retinal deafferentation, and more generally as a potential tool for detecting abnormalities associated with neurodevelopmental disorders.

  6. An automated tool for cortical feature analysis: Application to differences on 7 Tesla T2* -weighted images between young and older healthy subjects.

    Science.gov (United States)

    Doan, Nhat Trung; van Rooden, Sanneke; Versluis, Maarten J; Buijs, Mathijs; Webb, Andrew G; van der Grond, Jeroen; van Buchem, Mark A; Reiber, Johan H C; Milles, Julien

    2015-07-01

    High field T 2 * -weighted MR images of the cerebral cortex are increasingly used to study tissue susceptibility changes related to aging or pathologies. This paper presents a novel automated method for the computation of quantitative cortical measures and group-wise comparison using 7 Tesla T 2 * -weighted magnitude and phase images. The cerebral cortex was segmented using a combination of T 2 * -weighted magnitude and phase information and subsequently was parcellated based on an anatomical atlas. Local gray matter (GM)/white matter (WM) contrast and cortical profiles, which depict the magnitude or phase variation across the cortex, were computed from the magnitude and phase images in each parcellated region and further used for group-wise comparison. Differences in local GM/WM contrast were assessed using linear regression analysis. Regional cortical profiles were compared both globally and locally using permutation testing. The method was applied to compare a group of 10 young volunteers with a group of 15 older subjects. Using local GM/WM contrast, significant differences were revealed in at least 13 of 17 studied regions. Highly significant differences between cortical profiles were shown in all regions. The proposed method can be a useful tool for studying cortical changes in normal aging and potentially in neurodegenerative diseases. Magn Reson Med 74:240-248, 2015. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

  7. Imaging of sickle cell disease

    International Nuclear Information System (INIS)

    Crowley, J.J.; Sarnaik, S.

    1999-01-01

    Sickle cell disease is an important health care issue in the United States and in certain areas in Africa, the Middle East and India. Although a great deal of progress has been made in understanding the disease at the molecular and pathophysiologic level, specific treatment which is safe and accessible for most patients is still elusive. Going into the next millennium, the management of this disease is still largely dependent on early diagnosis and the treatment of complications with supportive care. Thus, diagnosis and evaluation of the complications of the disease are crucial in directing clinical care at the bedside. Modern imaging modalities have greatly improved, and their application in the patient with the sickling disorders has enhanced the decision - making process. The purpose of this article is to review the clinical aspects of common complications of the disease and to discuss imaging approaches which are useful in their evaluation. (orig.)

  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. Comparative proteomic analysis of kidney distal convoluted tubule and cortical collecting duct cells following long-term hormonal stimulation

    DEFF Research Database (Denmark)

    Wu, Qi; Moller, Hanne; Rosenbaek, Lena Lindtoft

    2017-01-01

    The distal convoluted tubule (DCT) and the cortical collecting ducts (CCD) are portions of renal tubule that are partly responsible for maintaining the systemic concentrations of potassium, sodium, calcium and magnesium. Despite being structurally similar, DCT and CCD cells have different transpo...... FDR threshold in one cell type plus the unique proteins in this cell type. These 1025 mpkDCT specific proteins and 1211 mpkCCD specific proteins under the three conditions were subjected to further bioinformatics analyses including Panther and DAVID gene ontology analyses, E3 ligase...

  10. Imaging derived cortical thickness reduction in high-functioning autism: key regions and temporal slope.

    Science.gov (United States)

    Scheel, Christian; Rotarska-Jagiela, Anna; Schilbach, Leonhard; Lehnhardt, Fritz G; Krug, Barbara; Vogeley, Kai; Tepest, Ralf

    2011-09-15

    Cortical thickness (CT) changes possibly contribute to the complex symptomatology of autism. The aberrant developmental trajectories underlying such differences in certain brain regions and their continuation in adulthood are a matter of intense debate. We studied 28 adults with high-functioning autism (HFA) and 28 control subjects matched for age, gender, IQ and handedness. A surface-based whole brain analysis utilizing FreeSurfer was employed to detect CT differences between the two diagnostic groups and to investigate the time course of age-related changes. Direct comparison with control subjects revealed thinner cortex in HFA in the posterior superior temporal sulcus (pSTS) of the left hemisphere. Considering the time course of CT development we found clusters around the pSTS and cuneus in the left and the paracentral lobule in the right hemisphere to be thinner in HFA with comparable age-related slopes in patients and controls. Conversely, we found clusters around the supramarginal gyrus and inferior parietal lobule (IPL) in the left and the precentral and postcentral gyrus in the right hemisphere to be thinner in HFA, but with different age-related slopes in patients and controls. In the latter regions CT showed a steady decrease in controls but no analogous thinning in HFA. CT analyses contribute in characterizing neuroanatomical correlates of HFA. Reduced CT is present in brain regions involved in social cognition. Furthermore, our results demonstrate that aberrant brain development leading to such differences is proceeding throughout adulthood. Discrepancies in prior morphometric studies may be induced by the complex time course of cortical changes. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Automatic cortical surface reconstruction of high-resolution T1 echo planar imaging data

    OpenAIRE

    Renvall, Ville; Witzel, Thomas; Wald, Lawrence L.; Polimeni, Jonathan R.

    2016-01-01

    Echo planar imaging (EPI) is the method of choice for the majority of functional magnetic resonance imaging (fMRI), yet EPI is prone to geometric distortions and thus misaligns with conventional anatomical reference data. The poor geometric correspondence between functional and anatomical data can lead to severe misplacements and corruption of detected activation patterns. However, recent advances in imaging technology have provided EPI data with increasing quality and resolution. Here we pre...

  12. Mevalonosomes: specific vacuoles containing the mevalonate pathway in Plocamium brasiliense cortical cells (Rhodophyta).

    Science.gov (United States)

    Paradas, Wladimir Costa; Crespo, Thalita Mendes; Salgado, Leonardo Tavares; de Andrade, Leonardo Rodrigues; Soares, Angélica Ribeiro; Hellio, Claire; Paranhos, Ricardo Rogers; Hill, Lilian Jorge; de Souza, Geysa Marinho; Kelecom, Alphonse Germaine Albert Charles; Da Gama, Bernardo Antônio Perez; Pereira, Renato Crespo; Amado-Filho, Gilberto Menezes

    2015-04-01

    This paper has identified, for the first time in a member of the Rhodophyta, a vacuolar organelle containing enzymes that are involved in the mevalonate pathway-an important step in red algal isoprenoid biosynthesis. These organelles were named mevalonosomes (Mev) and were found in the cortical cells (CC) of Plocamium brasiliense, a marine macroalgae that synthesizes several halogenated monoterpenes. P. brasiliense specimens were submitted to a cytochemical analysis of the activity of the 3-hydroxy-3-methylglutaryl-CoA synthase (HMGS). Using transmission electron microscopy (TEM), we confirmed the presence of HMGS activity within the Mev. Because HMGS is necessary for the biosynthesis of halogenated monoterpenes, we isolated a hexanic fraction (HF) rich in halogenated monoterpenes from P. brasiliense that contained a pentachlorinated monoterpene as a major metabolite. Because terpenes are often related to chemical defense, the antifouling (AF) activity of pentachlorinated monoterpene was tested. We found that the settlement of the mussel Perna perna was reduced by HF treatment (2.25 times less than control; 40% and 90% of fouled surface, respectively; P = 0.001; F9,9 = 1.13). The HF (at 10 μg · mL(-1) ) also inhibited three species of fouling microalgae (Chlorarachnion reptans, Cylindrotheca cloisterium, and Exanthemachrysis gayraliae), while at a higher concentration (50 μg · mL(-1) ), it inhibited the bacteria Halomonas marina, Polaribacter irgensii, Pseudoalteromonas elyakovii, Shewanella putrefaciens, and Vibrio aestuarianus. The AF activity of P. brasiliense halogenated monoterpenes and the localization of HMGS activity inside Mev suggest that this cellular structure found in CC may play a role in thallus protection against biofouling. © 2015 Phycological Society of America.

  13. 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

  14. Microtubule heterogeneity of Ornithogalum umbellatum ovary epidermal cells: non-stable cortical microtubules and stable lipotubuloid microtubules.

    Science.gov (United States)

    Kwiatkowska, Maria; Stępiński, Dariusz; Polit, Justyna T; Popłońska, Katarzyna; Wojtczak, Agnieszka

    2011-01-01

    Lipotubuloids, structures containing lipid bodies and microtubules, are described in ovary epidermal cells of Ornithogalum umbellatum. Microtubules of lipotubuloids can be fixed in electron microscope fixative containing only buffered OsO(4) or in glutaraldehyde with OsO(4) post-fixation, or in a mixture of OsO(4) and glutaraldehyde. None of these substances fixes cortical microtubules of ovary epidermis of this plant which is characterized by dynamic longitudinal growth. However, cortical microtubules can be fixed with cold methanol according immunocytological methods with the use of β-tubulin antibodies and fluorescein. The existence of cortical microtubules has also been evidenced by EM observations solely after the use of taxol, microtubule stabilizer, and fixation in a glutaraldehyde/OsO(4) mixture. These microtubules mostly lie transversely, sometimes obliquely, and rarely parallel to the cell axis. Staining, using Ruthenium Red and silver hexamine, has revealed that lipotubuloid microtubules surface is covered with polysaccharides. The presumption has been made that the presence of a polysaccharide layer enhances the stability of lipotubuloid microtubules.

  15. Drosophila sosie functions with βH-Spectrin and actin organizers in cell migration, epithelial morphogenesis and cortical stability

    Science.gov (United States)

    Urwyler, Olivier; Cortinas-Elizondo, Fabiola; Suter, Beat

    2012-01-01

    Summary Morphogenesis in multicellular organisms requires the careful coordination of cytoskeletal elements, dynamic regulation of cell adhesion and extensive cell migration. sosie (sie) is a novel gene required in various morphogenesis processes in Drosophila oogenesis. Lack of sie interferes with normal egg chamber packaging, maintenance of epithelial integrity and control of follicle cell migration, indicating that sie is involved in controlling epithelial integrity and cell migration. For these functions sie is required both in the germ line and in the soma. Consistent with this, Sosie localizes to plasma membranes in the germ line and in the somatic follicle cells and is predicted to present an EGF-like domain on the extracellular side. Two positively charged residues, C-terminal to the predicted transmembrane domain (on the cytoplasmic side), are required for normal plasma membrane localization of Sosie. Because sie also contributes to normal cortical localization of βH-Spectrin, it appears that cortical βH-Spectrin mediates some of the functions of sosie. sie also interacts with the genes coding for the actin organizers Filamin and Profilin and, in the absence of sie function, F-actin is less well organized and nurse cells frequently fuse. PMID:23213377

  16. Drosophila sosie functions with β(H)-Spectrin and actin organizers in cell migration, epithelial morphogenesis and cortical stability.

    Science.gov (United States)

    Urwyler, Olivier; Cortinas-Elizondo, Fabiola; Suter, Beat

    2012-10-15

    Morphogenesis in multicellular organisms requires the careful coordination of cytoskeletal elements, dynamic regulation of cell adhesion and extensive cell migration. sosie (sie) is a novel gene required in various morphogenesis processes in Drosophila oogenesis. Lack of sie interferes with normal egg chamber packaging, maintenance of epithelial integrity and control of follicle cell migration, indicating that sie is involved in controlling epithelial integrity and cell migration. For these functions sie is required both in the germ line and in the soma. Consistent with this, Sosie localizes to plasma membranes in the germ line and in the somatic follicle cells and is predicted to present an EGF-like domain on the extracellular side. Two positively charged residues, C-terminal to the predicted transmembrane domain (on the cytoplasmic side), are required for normal plasma membrane localization of Sosie. Because sie also contributes to normal cortical localization of β(H)-Spectrin, it appears that cortical β(H)-Spectrin mediates some of the functions of sosie. sie also interacts with the genes coding for the actin organizers Filamin and Profilin and, in the absence of sie function, F-actin is less well organized and nurse cells frequently fuse.

  17. Cortical mapping by functional magnetic resonance imaging in patients with brain tumors

    International Nuclear Information System (INIS)

    Majos, Agata; Stefanczyk, Ludomir; Goraj, Bozena; Tybor, Krzysztof

    2005-01-01

    The aim of our study was to establish the effectiveness of the functional MRI (fMRI) technique in comparison with intraoperative cortical stimulation (ICS) in planning cortex-saving neurosurgical interventions. The combination of sensory and motor stimulation during fMRI experiments was used to improve the exactness of central sulcus localization. The study subjects were 30 volunteers and 33 patients with brain tumors in the rolandic area. Detailed topographical relations of activated areas in fMRI and intraoperative techniques were compared. The agreement in the location defined by the two methods for motor centers was found to be 84%; for sensory centers it was 83%. When both kinds of activation are taken into account this agreement increases to 98%. A significant relation was found between fMRI and ICS for the agreement of the distance both for motor and sensory centers (p=0.0021-0.0024). Also a strong dependence was found between the agreement of the location and the agreement of the distance for both kinds of stimulation. The spatial correlation between fMRI and ICS methods for the sensorimotor cortex is very high. fMRI combining functional and structural information is very helpful for preoperative neurosurgical planning. The sensitivity of the fMRI technique in brain mapping increases when using both motor and sensory paradigms in the same patient. (orig.)

  18. k-space sampling optimization for ultrashort TE imaging of cortical bone: Applications in radiation therapy planning and MR-based PET attenuation correction

    International Nuclear Information System (INIS)

    Hu, Lingzhi; Traughber, Melanie; Su, Kuan-Hao; Pereira, Gisele C.; Grover, Anu; Traughber, Bryan; Muzic, Raymond F. Jr.

    2014-01-01

    Purpose: The ultrashort echo-time (UTE) sequence is a promising MR pulse sequence for imaging cortical bone which is otherwise difficult to image using conventional MR sequences and also poses strong attenuation for photons in radiation therapy and PET imaging. The authors report here a systematic characterization of cortical bone signal decay and a scanning time optimization strategy for the UTE sequence through k-space undersampling, which can result in up to a 75% reduction in acquisition time. Using the undersampled UTE imaging sequence, the authors also attempted to quantitatively investigate the MR properties of cortical bone in healthy volunteers, thus demonstrating the feasibility of using such a technique for generating bone-enhanced images which can be used for radiation therapy planning and attenuation correction with PET/MR. Methods: An angularly undersampled, radially encoded UTE sequence was used for scanning the brains of healthy volunteers. Quantitative MR characterization of tissue properties, including water fraction and R2 ∗ = 1/T2 ∗ , was performed by analyzing the UTE images acquired at multiple echo times. The impact of different sampling rates was evaluated through systematic comparison of the MR image quality, bone-enhanced image quality, image noise, water fraction, and R2 ∗ of cortical bone. Results: A reduced angular sampling rate of the UTE trajectory achieves acquisition durations in proportion to the sampling rate and in as short as 25% of the time required for full sampling using a standard Cartesian acquisition, while preserving unique MR contrast within the skull at the cost of a minimal increase in noise level. The R2 ∗ of human skull was measured as 0.2–0.3 ms −1 depending on the specific region, which is more than ten times greater than the R2 ∗ of soft tissue. The water fraction in human skull was measured to be 60%–80%, which is significantly less than the >90% water fraction in brain. High-quality, bone

  19. Associations of unilateral whisker and olfactory signals induce synapse formation and memory cell recruitment in bilateral barrel cortices: cellular mechanism for unilateral training toward bilateral memory

    Directory of Open Access Journals (Sweden)

    Zilong Gao

    2016-12-01

    Full Text Available Somatosensory signals and operative skills learned by unilateral limbs can be retrieved bilaterally. In terms of cellular mechanism underlying this unilateral learning toward bilateral memory, we hypothesized that associative memory cells in bilateral cortices and synapse innervations between them were produced. In the examination of this hypothesis, we have observed that paired unilateral whisker and odor stimulations led to odorant-induced whisker motions in bilateral sides, which were attenuated by inhibiting the activity of barrel cortices. In the mice that showed bilateral cross-modal responses, the neurons in both sides of barrel cortices became to encode this new odor signal alongside the innate whisker signal. Axon projections and synapse formations from the barrel cortex, which was co-activated with the piriform cortex, toward its contralateral barrel cortex were upregulated. Glutamatergic synaptic transmission in bilateral barrel cortices was upregulated and GABAergic synaptic transmission was downregulated. The associative activations of the sensory cortices facilitate new axon projection, glutamatergic synapse formation and GABAergic synapse downregulation, which drive the neurons to be recruited as associative memory cells in the bilateral cortices. Our data reveals the productions of associative memory cells and synapse innervations in bilateral sensory cortices for unilateral training toward bilateral memory.

  20. A multichip aVLSI system emulating orientation selectivity of primary visual cortical cells.

    Science.gov (United States)

    Shimonomura, Kazuhiro; Yagi, Tetsuya

    2005-07-01

    In this paper, we designed and fabricated a multichip neuromorphic analog very large scale integrated (aVLSI) system, which emulates the orientation selective response of the simple cell in the primary visual cortex. The system consists of a silicon retina and an orientation chip. An image, which is filtered by a concentric center-surround (CS) antagonistic receptive field of the silicon retina, is transferred to the orientation chip. The image transfer from the silicon retina to the orientation chip is carried out with analog signals. The orientation chip selectively aggregates multiple pixels of the silicon retina, mimicking the feedforward model proposed by Hubel and Wiesel. The chip provides the orientation-selective (OS) outputs which are tuned to 0 degrees, 60 degrees, and 120 degrees. The feed-forward aggregation reduces the fixed pattern noise that is due to the mismatch of the transistors in the orientation chip. The spatial properties of the orientation selective response were examined in terms of the adjustable parameters of the chip, i.e., the number of aggregated pixels and size of the receptive field of the silicon retina. The multichip aVLSI architecture used in the present study can be applied to implement higher order cells such as the complex cell of the primary visual cortex.

  1. Mesenchymal stem cells from cortical bone demonstrate increased clonal incidence, potency, and developmental capacity compared to their bone marrow–derived counterparts

    Directory of Open Access Journals (Sweden)

    Daniel Blashki

    2016-08-01

    Full Text Available In this study, we show that matrix dense cortical bone is the more potent compartment of bone than bone marrow as a stromal source for mesenchymal stem cells as isolated from adult rats. Lineage-depleted cortical bone-mesenchymal stem cells demonstrated >150-fold enrichment of colony forming unit–fibroblasts per cell incidence. compared to lineage-depleted bone marrow-mesenchymal stem cells, corresponding to a 70-fold increase in absolute recovered colony forming unit–fibroblasts. The composite phenotype Lin−/CD45−/CD31−/VLA-1+/Thy-1+ enriched for clonogenic mesenchymal stem cells solely from cortical bone–derived cells from which 70% of clones spontaneously differentiated into all lineages of bone, cartilage, and adipose. Both populations generated vascularized bone tissue within subcutaneous implanted collagen scaffolds; however, cortical bone–derived cells formed significantly more osteoid than bone marrow counterparts, quantified by histology. The data demonstrate that our isolation protocol identifies and validates mesenchymal stem cells with superior clonal, proliferative, and developmental potential from cortical bone compared to the bone marrow niche although marrow persists as the typical source for mesenchymal stem cells both in the literature and current pre-clinical therapies.

  2. Biophysical network modeling of the dLGN circuit: Effects of cortical feedback on spatial response properties of relay cells.

    Directory of Open Access Journals (Sweden)

    Pablo Martínez-Cañada

    2018-01-01

    Full Text Available Despite half-a-century of research since the seminal work of Hubel and Wiesel, the role of the dorsal lateral geniculate nucleus (dLGN in shaping the visual signals is not properly understood. Placed on route from retina to primary visual cortex in the early visual pathway, a striking feature of the dLGN circuit is that both the relay cells (RCs and interneurons (INs not only receive feedforward input from retinal ganglion cells, but also a prominent feedback from cells in layer 6 of visual cortex. This feedback has been proposed to affect synchronicity and other temporal properties of the RC firing. It has also been seen to affect spatial properties such as the center-surround antagonism of thalamic receptive fields, i.e., the suppression of the response to very large stimuli compared to smaller, more optimal stimuli. Here we explore the spatial effects of cortical feedback on the RC response by means of a a comprehensive network model with biophysically detailed, single-compartment and multicompartment neuron models of RCs, INs and a population of orientation-selective layer 6 simple cells, consisting of pyramidal cells (PY. We have considered two different arrangements of synaptic feedback from the ON and OFF zones in the visual cortex to the dLGN: phase-reversed ('push-pull' and phase-matched ('push-push', as well as different spatial extents of the corticothalamic projection pattern. Our simulation results support that a phase-reversed arrangement provides a more effective way for cortical feedback to provide the increased center-surround antagonism seen in experiments both for flashing spots and, even more prominently, for patch gratings. This implies that ON-center RCs receive direct excitation from OFF-dominated cortical cells and indirect inhibitory feedback from ON-dominated cortical cells. The increased center-surround antagonism in the model is accompanied by spatial focusing, i.e., the maximum RC response occurs for smaller stimuli

  3. Biophysical network modeling of the dLGN circuit: Effects of cortical feedback on spatial response properties of relay cells

    Science.gov (United States)

    Martínez-Cañada, Pablo; Halnes, Geir; Fyhn, Marianne

    2018-01-01

    Despite half-a-century of research since the seminal work of Hubel and Wiesel, the role of the dorsal lateral geniculate nucleus (dLGN) in shaping the visual signals is not properly understood. Placed on route from retina to primary visual cortex in the early visual pathway, a striking feature of the dLGN circuit is that both the relay cells (RCs) and interneurons (INs) not only receive feedforward input from retinal ganglion cells, but also a prominent feedback from cells in layer 6 of visual cortex. This feedback has been proposed to affect synchronicity and other temporal properties of the RC firing. It has also been seen to affect spatial properties such as the center-surround antagonism of thalamic receptive fields, i.e., the suppression of the response to very large stimuli compared to smaller, more optimal stimuli. Here we explore the spatial effects of cortical feedback on the RC response by means of a a comprehensive network model with biophysically detailed, single-compartment and multicompartment neuron models of RCs, INs and a population of orientation-selective layer 6 simple cells, consisting of pyramidal cells (PY). We have considered two different arrangements of synaptic feedback from the ON and OFF zones in the visual cortex to the dLGN: phase-reversed (‘push-pull’) and phase-matched (‘push-push’), as well as different spatial extents of the corticothalamic projection pattern. Our simulation results support that a phase-reversed arrangement provides a more effective way for cortical feedback to provide the increased center-surround antagonism seen in experiments both for flashing spots and, even more prominently, for patch gratings. This implies that ON-center RCs receive direct excitation from OFF-dominated cortical cells and indirect inhibitory feedback from ON-dominated cortical cells. The increased center-surround antagonism in the model is accompanied by spatial focusing, i.e., the maximum RC response occurs for smaller stimuli when

  4. Optical cell sorting with multiple imaging modalities

    DEFF Research Database (Denmark)

    Banas, Andrew; Carrissemoux, Caro; Palima, Darwin

    2017-01-01

    healthy cells. With the richness of visual information, a lot of microscopy techniques have been developed and have been crucial in biological studies. To utilize their complementary advantages we adopt both fluorescence and brightfield imaging in our optical cell sorter. Brightfield imaging has...... the advantage of being non-invasive, thus maintaining cell viability. Fluorescence imaging, on the other hand, takes advantages of the chemical specificity of fluorescence markers and can validate machine vision results from brightfield images. Visually identified cells are sorted using optical manipulation...

  5. Hyperintensity on diffusion weighted image along ipsilateral cortical spinal tract after cerebral ischemic stroke: A diffusion tensor analysis

    International Nuclear Information System (INIS)

    Liu Xiang; Tian Wei; Li Lilin; Kolar, Balasubramanya; Qiu Xing; Chen, Feng; Dogra, Vikram S.

    2012-01-01

    Purpose: Hyperintensity along the ipsilateral cortical spinal tract (CST) on a diffusion weighted imaging (DWI) has been reported to may be associated with motor disability after brain infarction and can be misdiagnosed as a new infarction. However, the underlying patho-physiology related to this finding is not clear. The goal of our study was to analyze the diffusion tensor imaging (DTI) changes in patients with this hyperintensity. Materials and methods: Eight patients (50 ± 10 years) who exhibited hyperintensity on DWI along ipsilateral CST from 3 to 21 days after stroke onset were reviewed as positive group, including 5 patients with serial DTI examinations. Twelve patients without hyperintensity during the matched examination time were classified as reference group. The apparent diffusion coefficient (ADC), fractional anisotropy (FA), and eigenvalues and their ratios (ipsilateral/contralateral value) in cerebral peduncle were measured, their correlation with motor function scale at eight months after stroke onset were evaluated. Results: The serial examinations showed that hyperintensity could eventually disappear. Both the ipsilateral ADC and FA values were significantly decreased (p < 0.05) compared to the contralateral side. The ipsilateral FA significantly correlated with motor function scale in both groups (r = 0.875, 0.738; p = 0.004, 0.006 respectively). Conclusions: The hyperintensity on DWI is a transient pathological process of Wallerian degeneration after ischemic stroke, its diffusion characteristics include concurrent significant decrease of ipsilateral ADC and FA. The ipsilateral FA value has the potential to predict neurological motor function outcome in such patients.

  6. The Touch and Zap Method for In Vivo Whole-Cell Patch Recording of Intrinsic and Visual Responses of Cortical Neurons and Glial Cells

    Science.gov (United States)

    Schramm, Adrien E.; Marinazzo, Daniele; Gener, Thomas; Graham, Lyle J.

    2014-01-01

    Whole-cell patch recording is an essential tool for quantitatively establishing the biophysics of brain function, particularly in vivo. This method is of particular interest for studying the functional roles of cortical glial cells in the intact brain, which cannot be assessed with extracellular recordings. Nevertheless, a reasonable success rate remains a challenge because of stability, recording duration and electrical quality constraints, particularly for voltage clamp, dynamic clamp or conductance measurements. To address this, we describe “Touch and Zap”, an alternative method for whole-cell patch clamp recordings, with the goal of being simpler, quicker and more gentle to brain tissue than previous approaches. Under current clamp mode with a continuous train of hyperpolarizing current pulses, seal formation is initiated immediately upon cell contact, thus the “Touch”. By maintaining the current injection, whole-cell access is spontaneously achieved within seconds from the cell-attached configuration by a self-limited membrane electroporation, or “Zap”, as seal resistance increases. We present examples of intrinsic and visual responses of neurons and putative glial cells obtained with the revised method from cat and rat cortices in vivo. Recording parameters and biophysical properties obtained with the Touch and Zap method compare favourably with those obtained with the traditional blind patch approach, demonstrating that the revised approach does not compromise the recorded cell. We find that the method is particularly well-suited for whole-cell patch recordings of cortical glial cells in vivo, targeting a wider population of this cell type than the standard method, with better access resistance. Overall, the gentler Touch and Zap method is promising for studying quantitative functional properties in the intact brain with minimal perturbation of the cell's intrinsic properties and local network. Because the Touch and Zap method is performed semi

  7. The Touch and Zap method for in vivo whole-cell patch recording of intrinsic and visual responses of cortical neurons and glial cells.

    Science.gov (United States)

    Schramm, Adrien E; Marinazzo, Daniele; Gener, Thomas; Graham, Lyle J

    2014-01-01

    Whole-cell patch recording is an essential tool for quantitatively establishing the biophysics of brain function, particularly in vivo. This method is of particular interest for studying the functional roles of cortical glial cells in the intact brain, which cannot be assessed with extracellular recordings. Nevertheless, a reasonable success rate remains a challenge because of stability, recording duration and electrical quality constraints, particularly for voltage clamp, dynamic clamp or conductance measurements. To address this, we describe "Touch and Zap", an alternative method for whole-cell patch clamp recordings, with the goal of being simpler, quicker and more gentle to brain tissue than previous approaches. Under current clamp mode with a continuous train of hyperpolarizing current pulses, seal formation is initiated immediately upon cell contact, thus the "Touch". By maintaining the current injection, whole-cell access is spontaneously achieved within seconds from the cell-attached configuration by a self-limited membrane electroporation, or "Zap", as seal resistance increases. We present examples of intrinsic and visual responses of neurons and putative glial cells obtained with the revised method from cat and rat cortices in vivo. Recording parameters and biophysical properties obtained with the Touch and Zap method compare favourably with those obtained with the traditional blind patch approach, demonstrating that the revised approach does not compromise the recorded cell. We find that the method is particularly well-suited for whole-cell patch recordings of cortical glial cells in vivo, targeting a wider population of this cell type than the standard method, with better access resistance. Overall, the gentler Touch and Zap method is promising for studying quantitative functional properties in the intact brain with minimal perturbation of the cell's intrinsic properties and local network. Because the Touch and Zap method is performed semi

  8. In Vivo Imaging of Cortical Inflammation and Subpial Pathology in Multiple Sclerosis by Combined PET and MRI

    Science.gov (United States)

    2015-09-01

    microglia to assess whether more severe structural cortical pathology in MS is related to the presence of neuroinflammation. Our initial findings...potential biomarkers of MS progression. Since cortical lesions appeared topographically related to focal meningeal inflammation in some pathological ...mm3, p=0.004 adjusting for age and total intracranial volume). In MS, cortical thinning was related with diffuse inflammation in cortex, thalamus and

  9. Cortical phase changes in Alzheimer's disease at 7T MRI: a novel imaging marker

    NARCIS (Netherlands)

    van Rooden, S.; Versluis, M.J.; Liem, M.K.; Milles, J.; Maier, A.B.; Oleksik, A.M.; Webb, A.G.; van Buchem, M.A.; van der Grond, J.

    2014-01-01

    Background: Postmortem studies have indicated the potential of high-field magnetic resonance imaging (MRI) to visualize amyloid depositions in the cerebral cortex. The aim of this study is to test this hypothesis in patients with Alzheimer's disease (AD). Methods: T2*-weighted MRI was performed in

  10. Non-linear Membrane Properties in Entorhinal Cortical Stellate Cells Reduce Modulation of Input-Output Responses by Voltage Fluctuations

    Science.gov (United States)

    Fernandez, Fernando R.; Malerba, Paola; White, John A.

    2015-01-01

    The presence of voltage fluctuations arising from synaptic activity is a critical component in models of gain control, neuronal output gating, and spike rate coding. The degree to which individual neuronal input-output functions are modulated by voltage fluctuations, however, is not well established across different cortical areas. Additionally, the extent and mechanisms of input-output modulation through fluctuations have been explored largely in simplified models of spike generation, and with limited consideration for the role of non-linear and voltage-dependent membrane properties. To address these issues, we studied fluctuation-based modulation of input-output responses in medial entorhinal cortical (MEC) stellate cells of rats, which express strong sub-threshold non-linear membrane properties. Using in vitro recordings, dynamic clamp and modeling, we show that the modulation of input-output responses by random voltage fluctuations in stellate cells is significantly limited. In stellate cells, a voltage-dependent increase in membrane resistance at sub-threshold voltages mediated by Na+ conductance activation limits the ability of fluctuations to elicit spikes. Similarly, in exponential leaky integrate-and-fire models using a shallow voltage-dependence for the exponential term that matches stellate cell membrane properties, a low degree of fluctuation-based modulation of input-output responses can be attained. These results demonstrate that fluctuation-based modulation of input-output responses is not a universal feature of neurons and can be significantly limited by subthreshold voltage-gated conductances. PMID:25909971

  11. Chronic intraventricular administration of lysergic acid diethylamide (LSD) affects the sensitivity of cortical cells to monocular deprivation.

    Science.gov (United States)

    McCall, M A; Tieman, D G; Hirsch, H V

    1982-11-04

    In kittens, but not in adult cats, depriving one eye of pattern vision by suturing the lids shut (monocular deprivation or MD) for one week reduces the proportion of binocular units in the visual cortex. A sensitivity of cortical units in adult cats to MD can be produced by infusing exogenous monoamines into the visual cortex. Since LSD interacts with monoamines, we have examined the effects of chronic administration of LSD on the sensitivity to MD for cortical cells in adult cats. Cats were assigned randomly to one of four conditions: MD/LSD, MD/No-LSD, No-MD/LSD, No-MD/No-LSD. An osmotic minipump delivered either LSD or the vehicle solution alone during a one-week period of MD. The animals showed no obvious anomalies during the administration of the drug. After one week the response properties of single units in area 17 of the visual cortex were studied without knowledge of the contents of the individual minipumps. With the exception of ocular dominance, the response properties of units recorded in all animals did not differ from normal. In the control animals (MD/No-LSD, No-MD/LSD, No-MD/No-LSD) the average proportion of binocular cells was 78%; similar to that observed for normal adult cats. However, in the experimental animals, which received LSD during the period of MD, only 52% of the cells were binocular. Our results suggest that chronic intraventricular administration of LSD affects either directly or indirectly the sensitivity of cortical neurons to MD.

  12. Fast automatic quantitative cell replication with fluorescent live cell imaging

    Directory of Open Access Journals (Sweden)

    Wang Ching-Wei

    2012-01-01

    Full Text Available Abstract Background live cell imaging is a useful tool to monitor cellular activities in living systems. It is often necessary in cancer research or experimental research to quantify the dividing capabilities of cells or the cell proliferation level when investigating manipulations of the cells or their environment. Manual quantification of fluorescence microscopic image is difficult because human is neither sensitive to fine differences in color intensity nor effective to count and average fluorescence level among cells. However, auto-quantification is not a straightforward problem to solve. As the sampling location of the microscopy changes, the amount of cells in individual microscopic images varies, which makes simple measurement methods such as the sum of stain intensity values or the total number of positive stain within each image inapplicable. Thus, automated quantification with robust cell segmentation techniques is required. Results An automated quantification system with robust cell segmentation technique are presented. The experimental results in application to monitor cellular replication activities show that the quantitative score is promising to represent the cell replication level, and scores for images from different cell replication groups are demonstrated to be statistically significantly different using ANOVA, LSD and Tukey HSD tests (p-value Conclusion A robust automated quantification method of live cell imaging is built to measure the cell replication level, providing a robust quantitative analysis system in fluorescent live cell imaging. In addition, the presented unsupervised entropy based cell segmentation for live cell images is demonstrated to be also applicable for nuclear segmentation of IHC tissue images.

  13. In vivo cell tracking with bioluminescence imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Eun; Kalimuthu, Senthilkumar; Ahn, Byeong Cheol [Dept. of Nuclear Medicine, Kyungpook National University School of Medicine and Hospital, Daegu (Korea, Republic of)

    2015-03-15

    Molecular imaging is a fast growing biomedical research that allows the visual representation, characterization and quantification of biological processes at the cellular and subcellular levels within intact living organisms. In vivo tracking of cells is an indispensable technology for development and optimization of cell therapy for replacement or renewal of damaged or diseased tissue using transplanted cells, often autologous cells. With outstanding advantages of bioluminescence imaging, the imaging approach is most commonly applied for in vivo monitoring of transplanted stem cells or immune cells in order to assess viability of administered cells with therapeutic efficacy in preclinical small animal models. In this review, a general overview of bioluminescence is provided and recent updates of in vivo cell tracking using the bioluminescence signal are discussed.

  14. Congenital malformations of the supratentorial brain. Pt. 1. Disorders of cortical development

    International Nuclear Information System (INIS)

    Ertl-Wagner, B.; Rummeny, C.; Reiser, M.F.

    2003-01-01

    Disorders of supratentorial cortical development are usually divided into disorders of neuronal proliferation, neuronal migration and cortical organization. Based upon molecular biologic discoveries, a modified classification has recently been proposed. The category of malformations of abnormal neuronal and glial proliferation and apoptosis now includes microlissencephalies, megalencephalies, hemimegalencephalies and cortical dysplasias with balloon cells. Malformations due to abnormal neuronal migration now subsume the lissencephaly spectrum including the subcortical band heterotopias, the cobblestone complex and the group of heterotopias. Malformations due to abnormal cortical organization include the spectrum of polymicrogyria and schizencephaly as well as cortical dysplasias without balloon cells. High-resolution magnetic resonance imaging (MRI) has led to an increasing awareness of these malformations. This article aims to illustrate the classification, MRI presentation and relevant clinical features of the most commonly encountered disorders of cortical development. (orig.) [de

  15. 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.

  16. Synchrotron nanoscopy imaging study of scalp hair in breast cancer patients and healthy individuals: Difference in medulla loss and cortical membrane enhancements.

    Science.gov (United States)

    Han, Sung-Mi; Chikawa, Jun-Ichi; Jeon, Jae-Kun; Hwang, Min-Young; Lim, Jun; Jeong, Young-Ju; Park, Sung-Hwan; Kim, Hong-Tae; Jheon, Sanghoon; Kim, Jong-Ki

    2016-01-01

    Nanoscopic synchrotron X-ray imaging was performed on scalp hair samples of patients with breast cancer and healthy individuals to investigate any structural differences as diagnostic tool. Hair strands were divided into 2-3 segments along the strands from root to tip, followed by imaging either in projection or in CT scanning with a monochromatic 6.78-keV X-ray using zone-plate optics with a resolving power of 60 nm. All the examined cancer hairs exhibited medulla loss with cancer stage-dependent pattern; complete loss, discontinuous or trace along the strands. In contrast, medullas were well retained without complete loss in the healthy hair. In the CT-scanned axial images, the cortical spindle compartments had no contrast in the healthy hair, but appeared hypointense in contrast to the surrounding hyperintense cortical membrane complex in the cancer hair. In conclusion, observation of medulla loss and cortical membrane enhancements in the hair strands of breast cancer patients demonstrated structural variations in the cancer hair, providing a new platform for further synchrotron X-ray imaging study of screening breast cancer patients. © 2015 Wiley Periodicals, Inc.

  17. Opposite reactivity of meningeal versus cortical microvessels to the nitric oxide donor glyceryl trinitrate evaluated in vivo with two-photon imaging.

    Directory of Open Access Journals (Sweden)

    Evgeny Pryazhnikov

    Full Text Available Vascular changes underlying headache in migraine patients induced by Glyceryl trinitrate (GTN were previously studied with various imaging techniques. Despite the long history of medical and experimental use of GTN, its effects on the brain vasculature are still poorly understood presumably due to low spatial resolution of the imaging modalities used so far. We took advantage of the micrometer-scale vertical resolution of two-photon microscopy to differentiate between the vasodynamic effects of GTN on meningeal versus cortical vessels imaged simultaneously in anesthetized rats through either thinned skull or glass-sealed cranial window. Intermediate and small calibre vessels were visualized in vivo by imaging intravascular fluorescent dextran, and detection of blood flow direction allowed identification of individual arterioles and venules. We found that i.p.-injected GTN induced a transient constriction of meningeal arterioles, while their cortical counterparts were, in contrast, dilated. These opposing effects of GTN were restricted to arterioles, whereas the effects on venules were insignificant. Interestingly, the NO synthase inhibitor L-NAME did not affect the diameter of meningeal vessels but induced a constriction of cortical vessels. The different cellular environment in cortex versus meninges as well as distinct vessel wall anatomical features probably play crucial role in the observed phenomena. These findings highlight differential region- and vessel-type-specific effects of GTN on cranial vessels, and may implicate new vascular mechanisms of NO-mediated primary headaches.

  18. 7T T₂*-weighted magnetic resonance imaging reveals cortical phase differences between early- and late-onset Alzheimer's disease.

    Science.gov (United States)

    van Rooden, Sanneke; Doan, Nhat Trung; Versluis, Maarten J; Goos, Jeroen D C; Webb, Andrew G; Oleksik, Ania M; van der Flier, Wiesje M; Scheltens, Philip; Barkhof, Frederik; Weverling-Rynsburger, Annelies W E; Blauw, Gerard Jan; Reiber, Johan H C; van Buchem, Mark A; Milles, Julien; van der Grond, Jeroen

    2015-01-01

    The aim of this study is to explore regional iron-related differences in the cerebral cortex, indicative of Alzheimer's disease pathology, between early- and late-onset Alzheimer's disease (EOAD, LOAD, respectively) patients using 7T magnetic resonance phase images. High-resolution T2(∗)-weighted scans were acquired in 12 EOAD patients and 17 LOAD patients with mild to moderate disease and 27 healthy elderly control subjects. Lobar peak-to-peak phase shifts and regional mean phase contrasts were computed. An increased peak-to-peak phase shift was found for all lobar regions in EOAD patients compared with LOAD patients (p < 0.05). Regional mean phase contrast in EOAD patients was higher than in LOAD patients in the superior medial and middle frontal gyrus, anterior and middle cingulate gyrus, postcentral gyrus, superior and inferior parietal gyrus, and precuneus (p ≤ 0.042). These data suggest that EOAD patients have an increased iron accumulation, possibly related to an increased amyloid deposition, in specific cortical regions as compared with LOAD patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. NK cells and T cells: mirror images?

    NARCIS (Netherlands)

    Versteeg, R.

    1992-01-01

    The expression of MHC class I molecules protects cells against lysis by natural killer (NK) cells. It is possible that NK cells are 'educated' to recognize self MHC class I molecules and that the combination of self peptide and MHC class I molecule blocks NK-mediated lysis. Here, Rogier Versteeg

  20. 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.

  1. Meeting report--Imaging the Cell.

    Science.gov (United States)

    Moreau, Violaine; Cordelières, Fabrice P; Poujol, Christel; Sagot, Isabelle; Saltel, Frédéric

    2015-11-01

    Every two years, the French Society for Cell Biology (SBCF) organises an international meeting called 'Imaging the Cell'. This year, the 8th edition was held on 24-26 June 2015 at University of Bordeaux Campus Victoire in the city of Bordeaux, France, a UNESCO World Heritage site. Over the course of three days, the meeting provided a forum for experts in different areas of cell imaging. Its unique approach was to combine conventional oral presentations during morning sessions with practical workshops at hosting institutes and the Bordeaux Imaging Center during the afternoons. The meeting, co-organised by Violaine Moreau and Frédéric Saltel (both INSERM U1053, Bordeaux, France), Christel Poujol and Fabrice Cordelières (both Bordeaux Imaging Center, Bordeaux, France) and Isabelle Sagot (Institut de Biochimie et Génétique Cellulaires, Bordeaux, France), brought together about 120 scientists including 16 outstanding speakers to discuss the latest advances in cell imaging. Thanks to recent progress in imaging technologies, cell biologists are now able to visualise, follow and manipulate cellular processes with unprecedented accuracy. The meeting sessions and workshops highlighted some of the most exciting developments in the field, with sessions dedicated to optogenetics, high-content screening, in vivo and live-cell imaging, correlative light and electron microscopy, as well as super-resolution imaging. © 2015. Published by The Company of Biologists Ltd.

  2. Normal distribution and medullary-to-cortical shift of Nestin-expressing cells in acute renal ischemia.

    Science.gov (United States)

    Patschan, D; Michurina, T; Shi, H K; Dolff, S; Brodsky, S V; Vasilieva, T; Cohen-Gould, L; Winaver, J; Chander, P N; Enikolopov, G; Goligorsky, M S

    2007-04-01

    Nestin, a marker of multi-lineage stem and progenitor cells, is a member of intermediate filament family, which is expressed in neuroepithelial stem cells, several embryonic cell types, including mesonephric mesenchyme, endothelial cells of developing blood vessels, and in the adult kidney. We used Nestin-green fluorescent protein (GFP) transgenic mice to characterize its expression in normal and post-ischemic kidneys. Nestin-GFP-expressing cells were detected in large clusters within the papilla, along the vasa rectae, and, less prominently, in the glomeruli and juxta-glomerular arterioles. In mice subjected to 30 min bilateral renal ischemia, glomerular, endothelial, and perivascular cells showed increased Nestin expression. In the post-ischemic period, there was an increase in fluorescence intensity with no significant changes in the total number of Nestin-GFP-expressing cells. Time-lapse fluorescence microscopy performed before and after ischemia ruled out the possibility of engraftment by the circulating Nestin-expressing cells, at least within the first 3 h post-ischemia. Incubation of non-perfused kidney sections resulted in a medullary-to-cortical migration of Nestin-GFP-positive cells with the rate of expansion of their front averaging 40 microm/30 min during the first 3 h and was detectable already after 30 min of incubation. Explant matrigel cultures of the kidney and aorta exhibited sprouting angiogenesis with cells co-expressing Nestin and endothelial marker, Tie-2. In conclusion, several lines of circumstantial evidence identify a sub-population of Nestin-expressing cells with the mural cells, which are recruited in the post-ischemic period to migrate from the medulla toward the renal cortex. These migrating Nestin-positive cells may be involved in the process of post-ischemic tissue regeneration.

  3. Characterization of focal cortical dysplasia with balloon cells by layer-specific markers: Evidence for differential vulnerability of interneurons.

    Science.gov (United States)

    Nakagawa, Julia M; Donkels, Catharina; Fauser, Susanne; Schulze-Bonhage, Andreas; Prinz, Marco; Zentner, Josef; Haas, Carola A

    2017-04-01

    Focal cortical dysplasia (FCD) is a major cause of pharmacoresistant focal epilepsy. Little is known about the pathomechanisms underlying the characteristic cytoarchitectural abnormalities associated with FCD. In the present study, a broad panel of markers identifying layer-specific neuron subpopulations was applied to characterize dyslamination and structural alterations in FCD with balloon cells (FCD 2b). Pan-neuronal neuronal nuclei (NeuN) and layer-specific protein expression (Reelin, Calbindin, Calretinin, SMI32 (nonphosphorylated neurofilament H), Parvalbumin, transducin-like enhancer protein 4 (TLE4), and Vimentin) was studied by immunohistochemistry on paraffin sections of FCD2b cases (n = 22) and was compared to two control groups with (n = 7) or without epilepsy (n = 4 postmortem cases). Total and layer-specific neuron densities were systematically quantified by cell counting considering age at surgery and brain region. We show that in FCD2b total neuron densities across all six cortical layers were not significantly different from controls. In addition, we present evidence that a basic laminar arrangement of layer-specific neuron subtypes was preserved despite the severe disturbance of cortical structure. SMI32-positive pyramidal neurons showed no significant difference in total numbers, but a reduction in layers III and V. The densities of supragranular Calbindin- and Calretinin-positive interneurons in layers II and III were not different from controls, whereas Parvalbumin-expressing interneurons, primarily located in layer IV, were significantly reduced in numbers when compared to control cases without epilepsy. In layer VI, the density of TLE4-positive projection neurons was significantly increased. Altogether, these data show that changes in cellular composition mainly affect deep cortical layers in FCD2b. The application of a broad panel of markers defining layer-specific neuronal subpopulations revealed that in FCD2b neuronal diversity and a basic

  4. A chondroblastoma versus a giant cell tumor: emphasis on the MR imaging features

    Energy Technology Data Exchange (ETDEWEB)

    Chai, Jee Won; Hong, Sung Hwan; Choi, Ja Young; Kim, Na Ra; Choi, Jung Ah; Kang, Heung Sik [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2007-10-15

    To assess the MR imaging features in differentiating a chondroblastoma (CB) from a giant cell tumor (GCT), with an emphasis on the accompanying peritumoral bone marrow edema. MR imaging findings in 20 patients with CB were compared with the imaging features of 22 patients with GCT. The location of the lesion, signal intensity, adjacent cortical change, degree of accompanying bone marrow edema, synovitis in the adjacent joint and cystic change were analyzed. The findings of CB and GCT were examined statistically with use of Fisher's exact test. The incidence ratios of MR imaging findings were as follows (CB:GCT). Metaphyseal dominant involvement (2:21), partial cortical disruption (2:14), extensive bone marrow edema surrounding the tumor (14:0) and synovitis in the adjacent joint (11:2) were statistically different in incidence between CB and GCT ({rho} < 0.01). The inhomogeneous signal intensity (17:17) and cystic change (10:15) were not different in incidence between a CB and GCT. The presence of metaphyseal dominant involvement and cortical disruption favors a diagnosis of a GCT rather than a CB. In contrast, extensive bone marrow edema surrounding the tumor and synovitis in the adjacent joint are highly indicative of a CB.

  5. A chondroblastoma versus a giant cell tumor: emphasis on the MR imaging features

    International Nuclear Information System (INIS)

    Chai, Jee Won; Hong, Sung Hwan; Choi, Ja Young; Kim, Na Ra; Choi, Jung Ah; Kang, Heung Sik

    2007-01-01

    To assess the MR imaging features in differentiating a chondroblastoma (CB) from a giant cell tumor (GCT), with an emphasis on the accompanying peritumoral bone marrow edema. MR imaging findings in 20 patients with CB were compared with the imaging features of 22 patients with GCT. The location of the lesion, signal intensity, adjacent cortical change, degree of accompanying bone marrow edema, synovitis in the adjacent joint and cystic change were analyzed. The findings of CB and GCT were examined statistically with use of Fisher's exact test. The incidence ratios of MR imaging findings were as follows (CB:GCT). Metaphyseal dominant involvement (2:21), partial cortical disruption (2:14), extensive bone marrow edema surrounding the tumor (14:0) and synovitis in the adjacent joint (11:2) were statistically different in incidence between CB and GCT (ρ < 0.01). The inhomogeneous signal intensity (17:17) and cystic change (10:15) were not different in incidence between a CB and GCT. The presence of metaphyseal dominant involvement and cortical disruption favors a diagnosis of a GCT rather than a CB. In contrast, extensive bone marrow edema surrounding the tumor and synovitis in the adjacent joint are highly indicative of a CB

  6. Persistence of Functional Sensory Maps in the Absence of Cortical Layers in the Somsatosensory Cortex of Reeler Mice

    OpenAIRE

    Guy, Julien; Wagener, Robin J.; M?ck, Martin; Staiger, Jochen F.

    2014-01-01

    In rodents, layer IV of the primary somatosensory cortex contains the barrel field, where individual, large facial whiskers are represented as a dense cluster of cells. In the reeler mouse, a model of disturbed cortical development characterized by a loss of cortical lamination, the barrel field exists in a distorted manner. Little is known about the consequences of such a highly disturbed lamination on cortical function in this model. We used in vivo intrinsic signal optical imaging together...

  7. Ethanol induces cell-cycle activity and reduces stem cell diversity to alter both regenerative capacity and differentiation potential of cerebral cortical neuroepithelial precursors

    Directory of Open Access Journals (Sweden)

    Tingling Joseph D

    2005-09-01

    Full Text Available Abstract Background The fetal cortical neuroepithelium is a mosaic of distinct progenitor populations that elaborate diverse cellular fates. Ethanol induces apoptosis and interferes with the survival of differentiating neurons. However, we know little about ethanol's effects on neuronal progenitors. We therefore exposed neurosphere cultures from fetal rat cerebral cortex, to varying ethanol concentrations, to examine the impact of ethanol on stem cell fate. Results Ethanol promoted cell cycle progression, increased neurosphere number and increased diversity in neurosphere size, without inducing apoptosis. Unlike controls, dissociated cortical progenitors exposed to ethanol exhibited morphological evidence for asymmetric cell division, and cells derived from ethanol pre-treated neurospheres exhibited decreased proliferation capacity. Ethanol significantly reduced the numbers of cells expressing the stem cell markers CD117, CD133, Sca-1 and ABCG2, without decreasing nestin expression. Furthermore, ethanol-induced neurosphere proliferation was not accompanied by a commensurate increase in telomerase activity. Finally, cells derived from ethanol-pretreated neurospheres exhibited decreased differentiation in response to retinoic acid. Conclusion The reduction in stem cell number along with a transient ethanol-driven increase in cell proliferation, suggests that ethanol promotes stem to blast cell maturation, ultimately depleting the reserve proliferation capacity of neuroepithelial cells. However, the lack of a concomitant change in telomerase activity suggests that neuroepithelial maturation is accompanied by an increased potential for genomic instability. Finally, the cellular phenotype that emerges from ethanol pre-treated, stem cell depleted neurospheres is refractory to additional differentiation stimuli, suggesting that ethanol exposure ablates or delays subsequent neuronal differentiation.

  8. Squamous cell carcinoma - invasive (image)

    Science.gov (United States)

    This irregular red nodule is an invasive squamous cell carcinoma (a form of skin cancer). Initial appearance, shown here, may be very similar to a noncancerous growth called a keratoacanthoma. Squamous cell cancers ...

  9. 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.

  10. Effect of synthetic cell-binding peptide on the healing of cortical segmental bone defects

    International Nuclear Information System (INIS)

    Cakmak, G.; Bolukbasi, S.; Simsek, A.; Senkoylu, A.; Erdem, O.; Yilmaz, G.

    2006-01-01

    To determine the effect of inorganic bone matric/Pepgen P-15 (ABM/P-15) on the healing of a critical sized segmental defect in a rat radius using a radiological and histological grading system. We carried out this study at the Research Laboratories, Gazi University School of Medicine in 2004. Critical sized segmental defects were created in the radius of 36 Wistar rats. Thirteen defects were filled with ABM/P-15 Flow (gel form), 12 defects were filled with ABM/P-15, and 11 defects were used as a control group. The rats were sacrified at the tenth week, and healing of the defects was evaluated radiographically and histologically. The usage of ABM/P-15 and ABM/P-15 Flow were demonstrated to improve healing of segmental bone defects compared with the control group. Statistical evaluation showed that there were significant differences between control sites, and the sites treated with P-15 and P-15 Flow (p=0.011). The highest radiological and histological grades were achieved by P-15. Segmental cortical bone defects may be treated with ABM/P-15 instead of bone allografts, and autografts. According to the radiological and histological parameters measured in this study, the implantation of ABM/P-15 resulted in optimum healing of the segmental cortical bone defects. Pepgen P-15 has a positive effect on bone healing, without any immunogenic features and disease transmission risk. Therefore, ABM/P-15 can also be used for orthopedic surgery. (author)

  11. Imaging rapid redistribution of sensory-evoked depolarization through existing cortical pathways after targeted stroke in mice.

    Science.gov (United States)

    Sigler, Albrecht; Mohajerani, Majid H; Murphy, Timothy H

    2009-07-14

    Evidence suggests that recovery from stroke damage results from the production of new synaptic pathways within surviving brain regions over weeks. To address whether brain function might redistribute more rapidly through preexisting pathways, we examined patterns of sensory-evoked depolarization in mouse somatosensory cortex within hours after targeted stroke to a subset of the forelimb sensory map. Brain activity was mapped with voltage-sensitive dye imaging allowing millisecond time resolution over 9 mm(2) of brain. Before targeted stroke, we report rapid activation of the forelimb area within 10 ms of contralateral forelimb stimulation and more delayed activation of related areas of cortex such as the hindlimb sensory and motor cortices. After stroke to a subset of the forelimb somatosensory cortex map, function was lost in ischemic areas within the forelimb map center, but maintained in regions 200-500 microm blood flow deficits indicating the size of a perfused, but nonfunctional, penumbra. In many cases, stroke led to only partial loss of the forelimb map, indicating that a subset of a somatosensory domain can function on its own. Within the forelimb map spared by stroke, forelimb-stimulated responses became delayed in kinetics, and their center of activity shifted into adjacent hindlimb and posterior-lateral sensory areas. We conclude that the focus of forelimb-specific somatosensory cortex activity can be rapidly redistributed after ischemic damage. Given that redistribution occurs within an hour, the effect is likely to involve surviving accessory pathways and could potentially contribute to rapid behavioral compensation or direct future circuit rewiring.

  12. DYRK1A-mediated Cyclin D1 Degradation in Neural Stem Cells Contributes to the Neurogenic Cortical Defects in Down Syndrome

    Directory of Open Access Journals (Sweden)

    Sònia Najas

    2015-02-01

    Full Text Available Alterations in cerebral cortex connectivity lead to intellectual disability and in Down syndrome, this is associated with a deficit in cortical neurons that arises during prenatal development. However, the pathogenic mechanisms that cause this deficit have not yet been defined. Here we show that the human DYRK1A kinase on chromosome 21 tightly regulates the nuclear levels of Cyclin D1 in embryonic cortical stem (radial glia cells, and that a modest increase in DYRK1A protein in transgenic embryos lengthens the G1 phase in these progenitors. These alterations promote asymmetric proliferative divisions at the expense of neurogenic divisions, producing a deficit in cortical projection neurons that persists in postnatal stages. Moreover, radial glial progenitors in the Ts65Dn mouse model of Down syndrome have less Cyclin D1, and Dyrk1a is the triplicated gene that causes both early cortical neurogenic defects and decreased nuclear Cyclin D1 levels in this model. These data provide insights into the mechanisms that couple cell cycle regulation and neuron production in cortical neural stem cells, emphasizing that the deleterious effect of DYRK1A triplication in the formation of the cerebral cortex begins at the onset of neurogenesis, which is relevant to the search for early therapeutic interventions in Down syndrome.

  13. Imaging cell competition in Drosophila imaginal discs.

    Science.gov (United States)

    Ohsawa, Shizue; Sugimura, Kaoru; Takino, Kyoko; Igaki, Tatsushi

    2012-01-01

    Cell competition is a process in which cells with higher fitness ("winners") survive and proliferate at the expense of less fit neighbors ("losers"). It has been suggested that cell competition is involved in a variety of biological processes such as organ size control, tissue homeostasis, cancer progression, and the maintenance of stem cell population. By advent of a genetic mosaic technique, which enables to generate fluorescently marked somatic clones in Drosophila imaginal discs, recent studies have presented some aspects of molecular mechanisms underlying cell competition. Now, with a live-imaging technique using ex vivo-cultured imaginal discs, we can dissect the spatiotemporal nature of competitive cell behaviors within multicellular communities. Here, we describe procedures and tips for live imaging of cell competition in Drosophila imaginal discs. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Virus-mediated swapping of zolpidem-insensitive with zolpidem-sensitive GABA(A) receptors in cortical pyramidal cells.

    Science.gov (United States)

    Sumegi, Mate; Fukazawa, Yugo; Matsui, Ko; Lorincz, Andrea; Eyre, Mark D; Nusser, Zoltan; Shigemoto, Ryuichi

    2012-04-01

    Recently developed pharmacogenetic and optogenetic approaches, with their own advantages and disadvantages, have become indispensable tools in modern neuroscience. Here, we employed a previously described knock-in mouse line (GABA(A)Rγ2(77I)lox) in which the γ2 subunit of the GABA(A) receptor (GABA(A)R) was mutated to become zolpidem insensitive (γ2(77I)) and used viral vectors to swap γ2(77I) with wild-type, zolpidem-sensitive γ2 subunits (γ2(77F)). The verification of unaltered density and subcellular distribution of the virally introduced γ2 subunits requires their selective labelling. For this we generated six N- and six C-terminal-tagged γ2 subunits, with which cortical cultures of GABA(A)Rγ2(−/−) mice were transduced using lentiviruses. We found that the N-terminal AU1 tag resulted in excellent immunodetection and unimpaired synaptic localization. Unaltered kinetic properties of the AU1-tagged γ2 ((AU1)γ2(77F)) channels were demonstrated with whole-cell patch-clamp recordings of spontaneous IPSCs from cultured cells. Next, we carried out stereotaxic injections of lenti- and adeno-associated viruses containing Cre-recombinase and the (AU1)γ2(77F) subunit (Cre-2A-(AU1)γ2(77F)) into the neocortex of GABA(A)Rγ2(77I)lox mice. Light microscopic immunofluorescence and electron microscopic freeze-fracture replica immunogold labelling demonstrated the efficient immunodetection of the AU1 tag and the normal enrichment of the (AU1)γ2(77F) subunits in perisomatic GABAergic synapses. In line with this,miniature and action potential-evoked IPSCs whole-cell recorded from transduced cells had unaltered amplitudes, kinetics and restored zolpidem sensitivity. Our results obtained with a wide range of structural and functional verification methods reveal unaltered subcellular distributions and functional properties of γ2(77I) and (AU1)γ2(77F) GABA(A)Rs in cortical pyramidal cells. This transgenic–viral pharmacogenetic approach has the advantage that it

  15. Skeletal MR imaging in sickle cell disease

    International Nuclear Information System (INIS)

    Effmann, E.L.; Kinney, T.R.; Utz, J.A.; Merten, D.F.; Herfkens, R.J.

    1986-01-01

    The authors evaluated eight patients with sickle cell disease (mean age, 15.75 years; range 5-19 years) using MR imaging performed 24-72 hours after hospital admission for crisis. Coronal images of the lower extremities were obtained with a General Electric 1.5-T system and pulse sequences of TR/TE = 500/25 msec and 2,000/40, 80 msec. In three patients a mild decrease in signal intensity was seen on both T1- and T2-weighted images, probably secondary to marrow hyperplasia. In two patients a marked decrease in signal intensity was seen on both T1- and T2-weighted images, probably secondary to the diamagnetic effects of marrow iron. Six patients had bone infarct(s) which appeared as well-defined areas with prolonged T2 relaxation times. MR imaging appears promising for the evaluation of bone marrow in sickle cell anemia

  16. PET imaging of adoptive progenitor cell therapies

    International Nuclear Information System (INIS)

    Gelovani, Juri G.

    2008-01-01

    The overall objective of this application is to develop novel technologies for non-invasive imaging of adoptive stem cell-based therapies with positron emission tomography (PET) that would be applicable to human patients. To achieve this objective, stem cells will be genetically labeled with a PET-reporter gene and repetitively imaged to assess their distribution, migration, differentiation, and persistence using a radiolabeled reporter probe. This new imaging technology will be tested in adoptive progenitor cell-based therapy models in animals, including: delivery pro-apoptotic genes to tumors, and T-cell reconstitution for immunostimulatory therapy during allogeneic bone marrow progenitor cell transplantation. Technical and Scientific Merits. Non-invasive whole body imaging would significantly aid in the development and clinical implementation of various adoptive progenitor cell-based therapies by providing the means for non-invasive monitoring of the fate of injected progenitor cells over a long period of observation. The proposed imaging approaches could help to address several questions related to stem cell migration and homing, their long-term viability, and their subsequent differentiation. The ability to image these processes non-invasively in 3D and repetitively over a long period of time is very important and will help the development and clinical application of various strategies to control and direct stem cell migration and differentiation. Approach to accomplish the work. Stem cells will be genetically with a reporter gene which will allow for repetitive non-invasive 'tracking' of the migration and localization of genetically labeled stem cells and their progeny. This is a radically new approach that is being developed for future human applications and should allow for a long term (many years) repetitive imaging of the fate of tissues that develop from the transplanted stem cells. Why the approach is appropriate. The novel approach to stem cell imaging

  17. PET imaging of adoptive progenitor cell therapies.

    Energy Technology Data Exchange (ETDEWEB)

    Gelovani, Juri G.

    2008-05-13

    Objectives. The overall objective of this application is to develop novel technologies for non-invasive imaging of adoptive stem cell-based therapies with positron emission tomography (PET) that would be applicable to human patients. To achieve this objective, stem cells will be genetically labeled with a PET-reporter gene and repetitively imaged to assess their distribution, migration, differentiation, and persistence using a radiolabeled reporter probe. This new imaging technology will be tested in adoptive progenitor cell-based therapy models in animals, including: delivery pro-apoptotic genes to tumors, and T-cell reconstitution for immunostimulatory therapy during allogeneic bone marrow progenitor cell transplantation. Technical and Scientific Merits. Non-invasive whole body imaging would significantly aid in the development and clinical implementation of various adoptive progenitor cell-based therapies by providing the means for non-invasive monitoring of the fate of injected progenitor cells over a long period of observation. The proposed imaging approaches could help to address several questions related to stem cell migration and homing, their long-term viability, and their subsequent differentiation. The ability to image these processes non-invasively in 3D and repetitively over a long period of time is very important and will help the development and clinical application of various strategies to control and direct stem cell migration and differentiation. Approach to accomplish the work. Stem cells will be genetically with a reporter gene which will allow for repetitive non-invasive “tracking” of the migration and localization of genetically labeled stem cells and their progeny. This is a radically new approach that is being developed for future human applications and should allow for a long term (many years) repetitive imaging of the fate of tissues that develop from the transplanted stem cells. Why the approach is appropriate. The novel approach to

  18. Lipid domains in intact fiber-cell plasma membranes isolated from cortical and nuclear regions of human eye lenses of donors from different age groups.

    Science.gov (United States)

    Raguz, Marija; Mainali, Laxman; O'Brien, William J; Subczynski, Witold K

    2015-03-01

    The results reported here clearly document changes in the properties and the organization of fiber-cell membrane lipids that occur with age, based on electron paramagnetic resonance (EPR) analysis of lens membranes of clear lenses from donors of age groups from 0 to 20, 21 to 40, and 61 to 80 years. The physical properties, including profiles of the alkyl chain order, fluidity, hydrophobicity, and oxygen transport parameter, were investigated using EPR spin-labeling methods, which also provide an opportunity to discriminate coexisting lipid domains and to evaluate the relative amounts of lipids in these domains. Fiber-cell membranes were found to contain three distinct lipid environments: bulk lipid domain, which appears minimally affected by membrane proteins, and two domains that appear due to the presence of membrane proteins, namely boundary and trapped lipid domains. In nuclear membranes the amount of boundary and trapped phospholipids as well as the amount of cholesterol in trapped lipid domains increased with the donors' age and was greater than that in cortical membranes. The difference between the amounts of lipids in domains uniquely formed due to the presence of membrane proteins in nuclear and cortical membranes increased with the donors' age. It was also shown that cholesterol was to a large degree excluded from trapped lipid domains in cortical membranes. It is evident that the rigidity of nuclear membranes was greater than that of cortical membranes for all age groups. The amount of lipids in domains of low oxygen permeability, mainly in trapped lipid domains, were greater in nuclear than cortical membranes and increased with the age of donors. These results indicate that the nuclear fiber cell plasma membranes were less permeable to oxygen than cortical membranes and become less permeable to oxygen with age. In clear lenses, age-related changes in the lens lipid and protein composition and organization appear to occur in ways that increase fiber

  19. Cell phones as imaging sensors

    Science.gov (United States)

    Bhatti, Nina; Baker, Harlyn; Marguier, Joanna; Berclaz, Jérôme; Süsstrunk, Sabine

    2010-04-01

    Camera phones are ubiquitous, and consumers have been adopting them faster than any other technology in modern history. When connected to a network, though, they are capable of more than just picture taking: Suddenly, they gain access to the power of the cloud. We exploit this capability by providing a series of image-based personal advisory services. These are designed to work with any handset over any cellular carrier using commonly available Multimedia Messaging Service (MMS) and Short Message Service (SMS) features. Targeted at the unsophisticated consumer, these applications must be quick and easy to use, not requiring download capabilities or preplanning. Thus, all application processing occurs in the back-end system (i.e., as a cloud service) and not on the handset itself. Presenting an image to an advisory service in the cloud, a user receives information that can be acted upon immediately. Two of our examples involve color assessment - selecting cosmetics and home décor paint palettes; the third provides the ability to extract text from a scene. In the case of the color imaging applications, we have shown that our service rivals the advice quality of experts. The result of this capability is a new paradigm for mobile interactions - image-based information services exploiting the ubiquity of camera phones.

  20. Role of three-dimensional fluid-attenuated inversion recovery (3D FLAIR) and proton density magnetic resonance imaging for the detection and evaluation of lesion extent of focal cortical dysplasia in patients with refractory epilepsy

    International Nuclear Information System (INIS)

    Saini, Jitender; Kesavadas, Chandrasekharan; Thomas, Bejoy; Singh, Atampreet; Rathore, Chathurbhuj; Radhakrishnan, Ashalatha; Radhakrishnan, Kurupath; Bahuleyan, Biji

    2010-01-01

    Background: Focal cortical dysplasia (FCD) is often associated with epilepsy. Identification of FCD can be difficult due to subtle magnetic resonance imaging (MRI) changes. Though fluid-attenuated inversion recovery (FLAIR) sequence detects the majority of these lesions, smaller lesions may go unnoticed while larger lesions may be poorly delineated. Purpose: To determine the ability of a specialized epilepsy protocol in visualizing and delineating the extent of FCD. Material and Methods: We compared the imaging findings in nine patients with cortical malformation who underwent routine epilepsy MR imaging as well as a specialized epilepsy protocol. All imaging was done on a 1.5T MR unit. The specialized epilepsy protocol included 3D FLAIR in the sagittal plane as well as proton density (PD) and high-resolution T2-weighted (T2W) images in the transverse plane. Results: In all nine patients, the specialized protocol identified lesion anatomy better. In three patients in whom routine MRI was normal, the specialized epilepsy protocol including 3D FLAIR helped in identifying the lesions. One of these patients underwent surgery, and histo-pathology revealed a cortical dysplasia. In one patient, lesion characterization was improved, while in the remaining patients the extent of the FCD was more clearly demonstrated in the 3D FLAIR and PD images. Statistical analysis of images for cortical thickness, cortical signal intensity, adjacent white matter abnormalities, and gray-white matter junction showed significant statistical difference in the ability of 3D FLAIR to assess these aspects over conventional images. PD images were also found superior to the routine epilepsy protocol in assessment of cortical signal, adjacent white matter, and gray-white matter junction. Conclusion: Specialized MRI sequences and techniques should be performed whenever there is a high suspicion of cortical dysplasia, especially when they remain occult on conventional MR protocols. These techniques

  1. Statolith sedimentation kinetics and force transduction to the cortical endoplasmic reticulum in gravity-sensing Arabidopsis columella cells.

    Science.gov (United States)

    Leitz, Guenther; Kang, Byung-Ho; Schoenwaelder, Monica E A; Staehelin, L Andrew

    2009-03-01

    The starch statolith hypothesis of gravity sensing in plants postulates that the sedimentation of statoliths in specialized statocytes (columella cells) provides the means for converting the gravitational potential energy into a biochemical signal. We have analyzed the sedimentation kinetics of statoliths in the central S2 columella cells of Arabidopsis thaliana. The statoliths can form compact aggregates with gap sizes between statoliths approaching sedimentation phase, the statoliths tend to move at a distance to the cortical endoplasmic reticulum (ER) boundary and interact only transiently with the ER. Statoliths moved by laser tweezers against the ER boundary experience an elastic lift force upon release from the optical trap. High-resolution electron tomography analysis of statolith-to-ER contact sites indicate that the weight of statoliths is sufficient to locally deform the ER membranes that can potentially activate mechanosensitive ion channels. We suggest that in root columella cells, the transduction of the kinetic energy of sedimenting statoliths into a biochemical signal involves a combination of statolith-driven motion of the cytosol, statolith-induced deformation of the ER membranes, and a rapid release of kinetic energy from the ER during reorientation to activate mechanosensitive sites within the central columella cells.

  2. L-Ascorbate Protects Against Methamphetamine-Induced Neurotoxicity of Cortical Cells via Inhibiting Oxidative Stress, Autophagy, and Apoptosis.

    Science.gov (United States)

    Huang, Ya-Ni; Yang, Ling-Yu; Wang, Jing-Ya; Lai, Chien-Cheng; Chiu, Chien-Tsai; Wang, Jia-Yi

    2017-01-01

    Methamphetamine (METH)-induced cell death contributes to the pathogenesis of neurotoxicity; however, the relative roles of oxidative stress, apoptosis, and autophagy remain unclear. L-Ascorbate, also called vitamin (Vit.) C, confers partial protection against METH neurotoxicity via induction of heme oxygenase-1. We further investigated the role of Vit. C in METH-induced oxidative stress, apoptosis, and autophagy in cortical cells. Exposure to lower concentrations (0.1, 0.5, 1 mM) of METH had insignificant effects on ROS production, whereas cells exposed to 5 mM METH exhibited ROS production in a time-dependent manner. We confirmed METH-induced apoptosis (by nuclear morphology revealed by Hoechst 33258 staining and Western blot showing the protein levels of pro-caspase 3 and cleaved caspase 3) and autophagy (by Western blot showing the protein levels of Belin-1 and conversion of microtubule-associated light chain (LC)3-I to LC3-II and autophagosome staining by monodansylcadaverine). The apoptosis as revealed by cleaved caspase-3 expression marked an increase at 18 h after METH exposure while both autophagic markers, Beclin 1 and LC3-II, marked an increase in cells exposed to METH for 6 and 24 h, respectively. Treating cells with Vit. C 30 min before METH exposure time-dependently attenuated the production of ROS. Vitamin C also attenuated METH-induced Beclin 1 and LC3-II expression and METH toxicity. Treatment of cells with Vit. C before METH exposure attenuated the expression of cleaved caspase-3 and reduced the number of METH-induced apoptotic cells. We suggest that the protective effect of Vit. C against METH toxicity might be through attenuation of ROS production, autophagy, and apoptosis.

  3. 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

  4. Quantitative Renal Cortical Perfusion in Human Subjects with Magnetic Resonance Imaging Using Iron-Oxide Nanoparticles: Influence of T1 Shortening

    Energy Technology Data Exchange (ETDEWEB)

    Morell, A.; Ahlstrom, H.; Schoenberg, S.O.; Abildgaard, A.; Bock, M.; Bjoernerud, A. (Dept. of Diagnostic Radiology, Uppsala Univ. Hospital, Uppsala (Sweden))

    2008-10-15

    Background: Using conventional contrast agents, the technique of quantitative perfusion by observing the transport of a bolus with magnetic resonance imaging (MRI) is limited to the brain due to extravascular leakage. Purpose: To perform quantitative perfusion measurements in humans with an intravascular contrast agent, and to estimate the influence of the T1 relaxivity of the contrast agent on the first-pass response. Material and Methods: Renal cortical perfusion was measured quantitatively in six patients with unilateral renal artery stenosis using a rapid gradient double-echo sequence in combination with an intravenous bolus injection of NC100150 Injection, an intravascular contrast agent based on iron-oxide nanoparticles. The influence of T1 relaxivity was measured by comparing perfusion results based on single- and double-echo data. Results: The mean values of cortical blood flow, cortical blood volume, and mean transit time in the normal kidneys were measured to 339+-60 ml/min/100 g, 41+-8 ml/100 g, and 7.3+-1.0 s, respectively, based on double-echo data. The corresponding results based on single-echo data, which are not compensated for the T1 relaxivity, were 254+-47 ml/min/100 g, 27+-3 ml/100 g, and 6+-1.2 s, respectively. Conclusion: The use of a double-echo sequence enabled elimination of confounding T1 effects and consequent systematic underestimation of the perfusion.

  5. 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...

  6. Prefrontal cortical parvalbumin and somatostatin expression and cell density increase during adolescence and are modified by BDNF and sex.

    Science.gov (United States)

    Du, X; Serena, K; Hwang, W; Grech, A M; Wu, Y W C; Schroeder, A; Hill, R A

    2018-04-01

    Brain-derived neurotrophic factor (BDNF) is known to play a critical role early in the development of cortical GABAergic interneurons. Recently our laboratory and others have shown protracted development of specific subpopulations of GABAergic interneurons extending into adolescence. BDNF expression also changes significantly across adolescent development. However the role of BDNF in regulating GABAergic changes across adolescence remains unclear. Here, we performed a week-by-week analysis of the protein expression and cell density of three major GABAergic interneurons, parvalbumin (PV), somatostatin (SST) and calretinin (Cal) in the medial prefrontal cortex from prepubescence (week 3) to adulthood (week 12). In order to assess how BDNF and sex might influence the adolescent trajectory of GABAergic interneurons we compared WT as well as BDNF heterozygous (+/-) male and female mice. In both males and females PV expression increases during adolescent development in the mPFC. Compared to wild-types, PV expression was reduced in male but not female BDNF+/- mice throughout adolescent development. This reduction in protein expression corresponded with reduced cell density, specifically within the infralimbic prefrontal cortex. SST expression increased in early adolescent WT females and this upregulation was delayed in BDNF+/-. SST cell density also increased in early adolescent mPFC of WT female mice, with BDNF+/- again showing a reduced pattern of expression. Cal protein expression was also sex-dependently altered across adolescence with WT males showing a steady decline but that of BDNF+/- remaining unaltered. Reduced cell density in on the other hand was observed particularly in male BDNF+/- mice. In females, Cal protein expression and cell density remained largely stable. Our results show that PV, SST and calretinin interneurons are indeed still developing into early adolescence in the mPFC and that BDNF plays a critical, sex-specific role in mediating expression and

  7. Multichannel Image Mosaicing of Stem Cells

    OpenAIRE

    Alessandro Bevilacqua; Alessandro Gherardi; Filippo Piccinini

    2010-01-01

    Image mosaicing techniques are usually employed to offer researchers a wider field of view of microscopic image of biological samples. a mosaic is commonly achieved using automated microscopes and often with one “color" channel, whether it refers to natural or fluorescent analysis. In this work we present a method to achieve three subsequent mosaics of the same part of a stem cell culture analyzed in phase contrast and in fluorescence, with a common non-automated inverted microscope. The mosa...

  8. Increase in cortical pyramidal cell excitability accompanies depression-like behavior in mice: a transcranial magnetic stimulation study.

    Science.gov (United States)

    Sun, Peng; Wang, Furong; Wang, Li; Zhang, Yu; Yamamoto, Ryo; Sugai, Tokio; Zhang, Qing; Wang, Zhengda; Kato, Nobuo

    2011-11-09

    Clinical evidence suggests that cortical excitability is increased in depressives. We investigated its cellular basis in a mouse model of depression. In a modified version of forced swimming (FS), mice were initially forced to swim for 5 consecutive days and then were treated daily with repetitive transcranial magnetic stimulation (rTMS) or sham treatment for the following 4 weeks without swimming. On day 2 through day 5, the mice manifested depression-like behaviors. The next and last FS was performed 4 weeks later, which revealed a 4 week maintenance of depression-like behavior in the sham mice. In slices from the sham controls, excitability in cingulate cortex pyramidal cells was elevated in terms of membrane potential and frequencies of spikes evoked by current injection. Depolarized resting potential was shown to depend on suppression of large conductance calcium-activated potassium (BK) channels. This BK channel suppression was confirmed by measuring spike width, which depends on BK channels. Chronic rTMS treatment during the 4 week period significantly reduced the depression-like behavior. In slices obtained from the rTMS mice, normal excitability and BK channel activity were recovered. Expression of a scaffold protein Homer1a was reduced by the FS and reversed by rTMS in the cingulate cortex. Similar recovery in the same behavioral, electrophysiological, and biochemical features was observed after chronic imipramine treatment. The present study demonstrated that manifestation and disappearance of depression-like behavior are in parallel with increase and decrease in cortical neuronal excitability in mice and suggested that regulation of BK channels by Homer1a is involved in this parallelism.

  9. Does the presence of tumor-induced cortical bone destruction at CT have any prognostic value in newly diagnosed diffuse large B-cell lymphoma?

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Hugo J.A.; Nievelstein, Rutger A.J.; Kwee, Thomas C. [University Medical Center Utrecht, Department of Radiology and Nuclear Medicine, Utrecht (Netherlands); Klerk, John M.H. de [Meander Medical Center, Department of Nuclear Medicine, Amersfoort (Netherlands); Fijnheer, Rob [Meander Medical Center, Department of Hematology, Amersfoort (Netherlands); Heggelman, Ben G.F. [Meander Medical Center, Department of Radiology, Amersfoort (Netherlands); Dubois, Stefan V. [Meander Medical Center, Department of Pathology, Amersfoort (Netherlands)

    2015-05-01

    To determine the prognostic value of tumor-induced cortical bone destruction at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). This retrospective study included 105 patients with newly diagnosed DLBCL who had undergone CT and bone marrow biopsy (BMB) before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisolone) chemo-immunotherapy. Cox regression analyses were used to determine the associations of cortical bone status at CT (absence vs. presence of tumor-induced cortical bone destruction), BMB findings (negative vs. positive for lymphomatous involvement), and dichotomized National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) strata (low risk vs. high risk) with progression-free survival (PFS) and overall survival (OS). Univariate Cox regression analysis indicated that cortical bone status at CT was no significant predictor of either PFS or OS (p = 0.358 and p = 0.560, respectively), whereas BMB findings (p = 0.002 and p = 0.013, respectively) and dichotomized NCCN-IPI risk strata (p = 0.002 and p = 0.003, respectively) were significant predictors of both PFS and OS. In the multivariate Cox proportional hazards model, only the dichotomized NCCN-IPI score was an independent predictive factor of PFS and OS (p = 0.004 and p = 0.003, respectively). The presence of tumor-induced cortical bone destruction at CT was not found to have any prognostic implications in newly diagnosed DLBCL. (orig.)

  10. Comparative study of muscarinic acetylcholine receptors of human and rat cortical glial cells

    International Nuclear Information System (INIS)

    Demushkin, V.P.; Burbaeva, G.S.; Dzhaliashvili, T.A.; Plyashkevich, Y.G.

    1985-01-01

    The aim of the present investigation was a comparative studyof muscarinic acetylcholine receptors in human and rat glial cells. ( 3 H)Quinuclidinyl-benzylate (( 3 H)-QB), atropine, platiphylline, decamethonium, carbamylcholine, tubocurarine, and nicotine were used. The glial cell fraction was obtained from the cerebral cortex of rats weighing 130-140 g and from the frontal pole of the postmortem brain from men aged 60-70 years. The use of the method of radioimmune binding of ( 3 H)-QB with human and rat glial cell membranes demonstrated the presence of a muscarinic acetylcholine receptor in the glial cells

  11. Analysis of Neural Stem Cells from Human Cortical Brain Structures In Vitro.

    Science.gov (United States)

    Aleksandrova, M A; Poltavtseva, R A; Marei, M V; Sukhikh, G T

    2016-05-01

    Comparative immunohistochemical analysis of the neocortex from human fetuses showed that neural stem and progenitor cells are present in the brain throughout the gestation period, at least from week 8 through 26. At the same time, neural stem cells from the first and second trimester fetuses differed by the distribution, morphology, growth, and quantity. Immunocytochemical analysis of neural stem cells derived from fetuses at different gestation terms and cultured under different conditions showed their differentiation capacity. Detailed analysis of neural stem cell populations derived from fetuses on gestation weeks 8-9, 18-20, and 26 expressing Lex/SSEA1 was performed.

  12. DHM (Digital Holography Microscope) for imaging cells

    International Nuclear Information System (INIS)

    Emery, Yves; Cuche, Etienne; Colomb, Tristan; Depeursinge, Christian; Rappaz, Benjamin; Marquet, Pierre; Magistretti, Pierre

    2007-01-01

    Light interaction with a sample modifies both intensity and phase of the illuminating wave. Any available supports for image recording are only sensitive to intensity, but Denis Gabor [P. Marquet, B. Rappaz, P. Magistretti, et. al. Digital Holography for quantitative phase-contrast imaging, Optics Letters, 30, 5, pp 291-93 (2005)] invented in 1948 a way to encode the phase as an intensity variation: the h ologram . Digital Holographic Microscopy (DHM) [D. Gabor, A new microscopic principle, Nature, 1948] implements digitally this powerful hologram. Characterization of various pollen grains and of morphology changes of neurones associated with hypotonic shock demonstrates the potential of DHM for imaging cells

  13. Expression of Rac1 alternative 3' UTRs is a cell specific mechanism with a function in dendrite outgrowth in cortical neurons.

    Science.gov (United States)

    Braz, Sandra Oliveira; Cruz, Andrea; Lobo, Andrea; Bravo, Joana; Moreira-Ribeiro, Joana; Pereira-Castro, Isabel; Freitas, Jaime; Relvas, Joao B; Summavielle, Teresa; Moreira, Alexandra

    2017-06-01

    The differential expression of mRNAs containing tandem alternative 3' UTRs, achieved by mechanisms of alternative polyadenylation and post-transcriptional regulation, has been correlated with a variety of cellular states. In differentiated cells and brain tissues there is a general use of distal polyadenylation signals, originating mRNAs with longer 3' UTRs, in contrast with proliferating cells and other tissues such as testis, where most mRNAs contain shorter 3' UTRs. Although cell type and state are relevant in many biological processes, how these mechanisms occur in specific brain cell types is still poorly understood. Rac1 is a member of the Rho family of small GTPases with essential roles in multiple cellular processes, including cell differentiation and axonal growth. Here we used different brain cell types and tissues, including oligodendrocytes, microglia, astrocytes, cortical and hippocampal neurons, and optical nerve, to show that classical Rho GTPases express mRNAs with alternative 3' UTRs differently, by gene- and cell- specific mechanisms. In particular, we show that Rac1 originate mRNA isoforms with longer 3' UTRs specifically during neurite growth of cortical, but not hippocampal neurons. Furthermore, we demonstrate that the longest Rac1 3' UTR is necessary for driving the mRNA to the neurites, and also for neurite outgrowth in cortical neurons. Our results indicate that the expression of Rac1 longer 3' UTR is a gene and cell-type specific mechanism in the brain, with a new physiological function in cortical neuron differentiation. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Improving the Post-Stroke Therapeutic Potency of Mesenchymal Multipotent Stromal Cells by Cocultivation With Cortical Neurons: The Role of Crosstalk Between Cells.

    Science.gov (United States)

    Babenko, Valentina A; Silachev, Denis N; Zorova, Ljubava D; Pevzner, Irina B; Khutornenko, Anastasia A; Plotnikov, Egor Y; Sukhikh, Gennady T; Zorov, Dmitry B

    2015-09-01

    The goal of the present study was to maximally alleviate the negative impact of stroke by increasing the therapeutic potency of injected mesenchymal multipotent stromal cells (MMSCs). To pursue this goal, the intercellular communications of MMSCs and neuronal cells were studied in vitro. As a result of cocultivation of MMSCs and rat cortical neurons, we proved the existence of intercellular contacts providing transfer of cellular contents from one cell to another. We present evidence of intercellular exchange with fluorescent probes specifically occupied by cytosol with preferential transfer from neurons toward MMSCs. In contrast, we observed a reversed transfer of mitochondria (from MMSCs to neural cells). Intravenous injection of MMSCs in a postischemic period alleviated the pathological indexes of a stroke, expressed as a lower infarct volume in the brain and partial restoration of neurological status. Also, MMSCs after cocultivation with neurons demonstrated more profound neuroprotective effects than did unprimed MMSCs. The production of the brain-derived neurotrophic factor was slightly increased in MMSCs, and the factor itself was redistributed in these cells after cocultivation. The level of Miro1 responsible for intercellular traffic of mitochondria was increased in MMSCs after cocultivation. We conclude that the exchange by cellular compartments between neural and stem cells improves MMSCs' protective abilities for better rehabilitation after stroke. This could be used as an approach to enhance the therapeutic benefits of stem cell therapy to the damaged brain. The idea of priming stem cells before practical use for clinical purposes was applied. Thus, cells were preconditioned by coculturing them with the targeted cells (i.e., neurons for the treatment of brain pathological features) before the transfusion of stem cells to the organism. Such priming improved the capacity of stem cells to treat stroke. Some additional minimal study will be required to

  15. Recent advances in live cell imaging of hepatoma cells

    Science.gov (United States)

    2014-01-01

    Live cell imaging enables the study of dynamic processes of living cells in real time by use of suitable reporter proteins and the staining of specific cellular structures and/or organelles. With the availability of advanced optical devices and improved cell culture protocols it has become a rapidly growing research methodology. The success of this technique relies mainly on the selection of suitable reporter proteins, construction of recombinant plasmids possessing cell type specific promoters as well as reliable methods of gene transfer. This review aims to provide an overview of the recent developments in the field of marker proteins (bioluminescence and fluorescent) and methodologies (fluorescent resonance energy transfer, fluorescent recovery after photobleaching and proximity ligation assay) employed as to achieve an improved imaging of biological processes in hepatoma cells. Moreover, different expression systems of marker proteins and the modes of gene transfer are discussed with emphasis on the study of lipid droplet formation in hepatocytes as an example. PMID:25005127

  16. Voxel-based statistical analysis of cerebral glucose metabolism in the rat cortical deafness model by 3D reconstruction of brain from autoradiographic images

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Sung; Park, Kwang Suk [Seoul National University College of Medicine, Department of Nuclear Medicine, 28 Yungun-Dong, Chongno-Ku, Seoul (Korea); Seoul National University College of Medicine, Department of Biomedical Engineering, Seoul (Korea); Ahn, Soon-Hyun; Oh, Seung Ha; Kim, Chong Sun; Chung, June-Key; Lee, Myung Chul [Seoul National University College of Medicine, Department of Otolaryngology, Head and Neck Surgery, Seoul (Korea); Lee, Dong Soo; Jeong, Jae Min [Seoul National University College of Medicine, Department of Nuclear Medicine, 28 Yungun-Dong, Chongno-Ku, Seoul (Korea)

    2005-06-01

    Animal models of cortical deafness are essential for investigation of the cerebral glucose metabolism in congenital or prelingual deafness. Autoradiographic imaging is mainly used to assess the cerebral glucose metabolism in rodents. In this study, procedures for the 3D voxel-based statistical analysis of autoradiographic data were established to enable investigations of the within-modal and cross-modal plasticity through entire areas of the brain of sensory-deprived animals without lumping together heterogeneous subregions within each brain structure into a large region of interest. Thirteen 2-[1-{sup 14}C]-deoxy-D-glucose autoradiographic images were acquired from six deaf and seven age-matched normal rats (age 6-10 weeks). The deafness was induced by surgical ablation. For the 3D voxel-based statistical analysis, brain slices were extracted semiautomatically from the autoradiographic images, which contained the coronal sections of the brain, and were stacked into 3D volume data. Using principal axes matching and mutual information maximization algorithms, the adjacent coronal sections were co-registered using a rigid body transformation, and all sections were realigned to the first section. A study-specific template was composed and the realigned images were spatially normalized onto the template. Following count normalization, voxel-wise t tests were performed to reveal the areas with significant differences in cerebral glucose metabolism between the deaf and the control rats. Continuous and clear edges were detected in each image after registration between the coronal sections, and the internal and external landmarks extracted from the spatially normalized images were well matched, demonstrating the reliability of the spatial processing procedures. Voxel-wise t tests showed that the glucose metabolism in the bilateral auditory cortices of the deaf rats was significantly (P<0.001) lower than that in the controls. There was no significantly reduced metabolism in

  17. Voxel-based statistical analysis of cerebral glucose metabolism in the rat cortical deafness model by 3D reconstruction of brain from autoradiographic images

    International Nuclear Information System (INIS)

    Lee, Jae Sung; Park, Kwang Suk; Ahn, Soon-Hyun; Oh, Seung Ha; Kim, Chong Sun; Chung, June-Key; Lee, Myung Chul; Lee, Dong Soo; Jeong, Jae Min

    2005-01-01

    Animal models of cortical deafness are essential for investigation of the cerebral glucose metabolism in congenital or prelingual deafness. Autoradiographic imaging is mainly used to assess the cerebral glucose metabolism in rodents. In this study, procedures for the 3D voxel-based statistical analysis of autoradiographic data were established to enable investigations of the within-modal and cross-modal plasticity through entire areas of the brain of sensory-deprived animals without lumping together heterogeneous subregions within each brain structure into a large region of interest. Thirteen 2-[1- 14 C]-deoxy-D-glucose autoradiographic images were acquired from six deaf and seven age-matched normal rats (age 6-10 weeks). The deafness was induced by surgical ablation. For the 3D voxel-based statistical analysis, brain slices were extracted semiautomatically from the autoradiographic images, which contained the coronal sections of the brain, and were stacked into 3D volume data. Using principal axes matching and mutual information maximization algorithms, the adjacent coronal sections were co-registered using a rigid body transformation, and all sections were realigned to the first section. A study-specific template was composed and the realigned images were spatially normalized onto the template. Following count normalization, voxel-wise t tests were performed to reveal the areas with significant differences in cerebral glucose metabolism between the deaf and the control rats. Continuous and clear edges were detected in each image after registration between the coronal sections, and the internal and external landmarks extracted from the spatially normalized images were well matched, demonstrating the reliability of the spatial processing procedures. Voxel-wise t tests showed that the glucose metabolism in the bilateral auditory cortices of the deaf rats was significantly (P<0.001) lower than that in the controls. There was no significantly reduced metabolism in any

  18. [3D FSPGR (fast spoiled gradient echo) magnetic resonance imaging in the diagnosis of focal cortical dysplasia in children].

    Science.gov (United States)

    Alikhanov, A A; Sinitsyn, V E; Perepelova, E M; Mukhin, K Iu; Demushkina, A A; Omarova, M O; Piliia, S V

    2001-01-01

    Small dysplastic lesions of the cerebral cortex are often missed by conventional MRI methods. The identification of subtle structural abnormalities by traditional multiplanar rectilinear slices is often limited by the complex convolutional pattern of the brain. We used a method of FSPGR (fast spoiled gradient-echo) of three-dimensional MRI data that improves the anatomical display of the sulcal structure of the hemispheric convexities. It also reduces the asymmetric sampling of gray-white matter that may lead to false-positive results. We present 5 from 12 patients with dysplastic cortical lesions in whom conventional two-dimensional and three-dimensional MRI with multiplanar reformatting was initially considered normal. Subsequent studies using 3D FSPGR identified various types of focal cortical dysplasia in all. These results indicate that an increase in the detection of subtle focal dysplastic lesions may be accomplished when one improves the anatomical display of the brain sulcal structure by performing 3D FSPGR.

  19. Phospho-Rb mediating cell cycle reentry induces early apoptosis following oxygen-glucose deprivation in rat cortical neurons.

    Science.gov (United States)

    Yu, Ying; Ren, Qing-Guo; Zhang, Zhao-Hui; Zhou, Ke; Yu, Zhi-Yuan; Luo, Xiang; Wang, Wei

    2012-03-01

    The aim of this study was to investigate the relationship between cell cycle reentry and apoptosis in cultured cortical neurons following oxygen-glucose deprivation (OGD). We found that the percentage of neurons with BrdU uptake, TUNEL staining, and colocalized BrdU uptake and TUNEL staining was increased relative to control 6, 12 and 24 h after 1 h of OGD. The number of neurons with colocalized BrdU and TUNEL staining was decreased relative to the number of TUNEL-positive neurons at 24 h. The expression of phosphorylated retinoblastoma protein (phospho-Rb) was significantly increased 6, 12 and 24 h after OGD, parallel with the changes in BrdU uptake. Phospho-Rb and TUNEL staining were colocalized in neurons 6 and 12 h after OGD. This colocalization was strikingly decreased 24 h after OGD. Treatment with the cyclin-dependent kinase inhibitor roscovitine (100 μM) decreased the expression of phospho-Rb and reduced neuronal apoptosis in vitro. These results demonstrated that attempted cell cycle reentry with phosphorylation of Rb induce early apoptosis in neurons after OGD and there must be other mechanisms involved in the later stages of neuronal apoptosis besides cell cycle reentry. Phosphoralated Rb may be an important factor which closely associates aberrant cell cycle reentry with the early stages of neuronal apoptosis following ischemia/hypoxia in vitro, and pharmacological interventions for neuroprotection may be useful directed at this keypoint.

  20. Plasma membrane--cortical cytoskeleton interactions: a cell biology approach with biophysical considerations.

    Science.gov (United States)

    Kapus, András; Janmey, Paul

    2013-07-01

    From a biophysical standpoint, the interface between the cell membrane and the cytoskeleton is an intriguing site where a "two-dimensional fluid" interacts with an exceedingly complex three-dimensional protein meshwork. The membrane is a key regulator of the cytoskeleton, which not only provides docking sites for cytoskeletal elements through transmembrane proteins, lipid binding-based, and electrostatic interactions, but also serves as the source of the signaling events and molecules that control cytoskeletal organization and remolding. Conversely, the cytoskeleton is a key determinant of the biophysical and biochemical properties of the membrane, including its shape, tension, movement, composition, as well as the mobility, partitioning, and recycling of its constituents. From a cell biological standpoint, the membrane-cytoskeleton interplay underlies--as a central executor and/or regulator--a multitude of complex processes including chemical and mechanical signal transduction, motility/migration, endo-/exo-/phagocytosis, and other forms of membrane traffic, cell-cell, and cell-matrix adhesion. The aim of this article is to provide an overview of the tight structural and functional coupling between the membrane and the cytoskeleton. As biophysical approaches, both theoretical and experimental, proved to be instrumental for our understanding of the membrane/cytoskeleton interplay, this review will "oscillate" between the cell biological phenomena and the corresponding biophysical principles and considerations. After describing the types of connections between the membrane and the cytoskeleton, we will focus on a few key physical parameters and processes (force generation, curvature, tension, and surface charge) and will discuss how these contribute to a variety of fundamental cell biological functions. © 2013 American Physiological Society.

  1. Pulsed DC Electric Field-Induced Differentiation of Cortical Neural Precursor Cells.

    Directory of Open Access Journals (Sweden)

    Hui-Fang Chang

    Full Text Available We report the differentiation of neural stem and progenitor cells solely induced by direct current (DC pulses stimulation. Neural stem and progenitor cells in the adult mammalian brain are promising candidates for the development of therapeutic neuroregeneration strategies. The differentiation of neural stem and progenitor cells depends on various in vivo environmental factors, such as nerve growth factor and endogenous EF. In this study, we demonstrated that the morphologic and phenotypic changes of mouse neural stem and progenitor cells (mNPCs could be induced solely by exposure to square-wave DC pulses (magnitude 300 mV/mm at frequency of 100-Hz. The DC pulse stimulation was conducted for 48 h, and the morphologic changes of mNPCs were monitored continuously. The length of primary processes and the amount of branching significantly increased after stimulation by DC pulses for 48 h. After DC pulse treatment, the mNPCs differentiated into neurons, astrocytes, and oligodendrocytes simultaneously in stem cell maintenance medium. Our results suggest that simple DC pulse treatment could control the fate of NPCs. With further studies, DC pulses may be applied to manipulate NPC differentiation and may be used for the development of therapeutic strategies that employ NPCs to treat nervous system disorders.

  2. Pulsed DC Electric Field-Induced Differentiation of Cortical Neural Precursor Cells.

    Science.gov (United States)

    Chang, Hui-Fang; Lee, Ying-Shan; Tang, Tang K; Cheng, Ji-Yen

    2016-01-01

    We report the differentiation of neural stem and progenitor cells solely induced by direct current (DC) pulses stimulation. Neural stem and progenitor cells in the adult mammalian brain are promising candidates for the development of therapeutic neuroregeneration strategies. The differentiation of neural stem and progenitor cells depends on various in vivo environmental factors, such as nerve growth factor and endogenous EF. In this study, we demonstrated that the morphologic and phenotypic changes of mouse neural stem and progenitor cells (mNPCs) could be induced solely by exposure to square-wave DC pulses (magnitude 300 mV/mm at frequency of 100-Hz). The DC pulse stimulation was conducted for 48 h, and the morphologic changes of mNPCs were monitored continuously. The length of primary processes and the amount of branching significantly increased after stimulation by DC pulses for 48 h. After DC pulse treatment, the mNPCs differentiated into neurons, astrocytes, and oligodendrocytes simultaneously in stem cell maintenance medium. Our results suggest that simple DC pulse treatment could control the fate of NPCs. With further studies, DC pulses may be applied to manipulate NPC differentiation and may be used for the development of therapeutic strategies that employ NPCs to treat nervous system disorders.

  3. Monitoring stem cells in phase contrast imaging

    Science.gov (United States)

    Lam, K. P.; Dempsey, K. P.; Collins, D. J.; Richardson, J. B.

    2016-04-01

    Understanding the mechanisms behind the proliferation of Mesenchymal Stem cells (MSCs) can offer a greater insight into the behaviour of these cells throughout their life cycles. Traditional methods of determining the rate of MSC differentiation rely on population based studies over an extended time period. However, such methods can be inadequate as they are unable to track cells as they interact; for example, in autologous cell therapies for osteoarthritis, the development of biological assays that could predict in vivo functional activity and biological action are particularly challenging. Here further research is required to determine non-histochemical biomarkers which provide correlations between cell survival and predictive functional outcome. This paper proposes using a (previously developed) advanced texture-based analysis algorithm to facilitate in vitro cells tracking using time-lapsed microscopy. The technique was adopted to monitor stem cells in the context of unlabelled, phase contrast imaging, with the goal of examining the cell to cell interactions in both monoculture and co-culture systems. The results obtained are analysed using established exploratory procedures developed for time series data and compared with the typical fluorescent-based approach of cell labelling. A review of the progress and the lessons learned are also presented.

  4. Pre- and postmortem imaging of transplanted cells

    Directory of Open Access Journals (Sweden)

    Andrzejewska A

    2015-09-01

    Full Text Available Anna Andrzejewska,1 Adam Nowakowski,1 Miroslaw Janowski,1–4 Jeff WM Bulte,3–7 Assaf A Gilad,3,4 Piotr Walczak,3,4,8 Barbara Lukomska11NeuroRepair Department, 2Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland; 3Russell H Morgan Department of Radiology and Radiological Science, Division of MR Research, 4Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, 5Department of Biomedical Engineering, 6Department of Chemical & Biomolecular Engineering, 7Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; 8Department of Radiology, Faculty of Medical Sciences, University of Warmia and Mazury, Olsztyn, PolandAbstract: Therapeutic interventions based on the transplantation of stem and progenitor cells have garnered increasing interest. This interest is fueled by successful preclinical studies for indications in many diseases, including the cardiovascular, central nervous, and musculoskeletal system. Further progress in this field is contingent upon access to techniques that facilitate an unambiguous identification and characterization of grafted cells. Such methods are invaluable for optimization of cell delivery, improvement of cell survival, and assessment of the functional integration of grafted cells. Following is a focused overview of the currently available cell detection and tracking methodologies that covers the entire spectrum from pre- to postmortem cell identification.Keywords: stem cells, transplantation, SPECT, MRI, bioluminescence, cell labeling

  5. Protein kinase D stabilizes aldosterone-induced ERK1/2 MAP kinase activation in M1 renal cortical collecting duct cells to promote cell proliferation.

    LENUS (Irish Health Repository)

    McEneaney, Victoria

    2010-01-01

    Aldosterone elicits transcriptional responses in target tissues and also rapidly stimulates the activation of protein kinase signalling cascades independently of de novo protein synthesis. Here we investigated aldosterone-induced cell proliferation and extra-cellular regulated kinase 1 and 2 (ERK1\\/2) mitogen activated protein (MAP) kinase signalling in the M1 cortical collecting duct cell line (M1-CCD). Aldosterone promoted the proliferative growth of M1-CCD cells, an effect that was protein kinase D1 (PKD1), PKCdelta and ERK1\\/2-dependent. Aldosterone induced the rapid activation of ERK1\\/2 with peaks of activation at 2 and 10 to 30 min after hormone treatment followed by sustained activation lasting beyond 120 min. M1-CCD cells suppressed in PKD1 expression exhibited only the early, transient peaks in ERK1\\/2 activation without the sustained phase. Aldosterone stimulated the physical association of PKD1 with ERK1\\/2 within 2 min of treatment. The mineralocorticoid receptor (MR) antagonist RU28318 inhibited the early and late phases of aldosterone-induced ERK1\\/2 activation, and also aldosterone-induced proliferative cell growth. Aldosterone induced the sub-cellular redistribution of ERK1\\/2 to the nuclei at 2 min and to cytoplasmic sites, proximal to the nuclei after 30 min. This sub-cellular distribution of ERK1\\/2 was inhibited in cells suppressed in the expression of PKD1.

  6. Longitudinal Magnetic Resonance Imaging (MRI) Analysis of the Developmental Changes of Tourette Syndrome Reveal Reduced Diffusion in the Cortico-Striato-Thalamo-Cortical Pathways

    DEFF Research Database (Denmark)

    Debes, Nanette; Jeppesen, Signe; Raghava, Jayachandra Mitta

    2015-01-01

    There is evidence that cortico-striato-thalamo-cortical pathways are involved in Tourette syndrome. We performed a longitudinal imaging study in 22 patients and 21 healthy controls in order to examine the development of tics and its correlation with magnetic resonance imaging (MRI) findings....... Patients were divided in a group with persisting and a group with remission of tics. We found a decrease in volume of left putamen in controls, but not in patients. We found changes in mean diffusivity between patients and controls in right caudate nucleus, thalamus, and frontal lobe. In contrast...... to controls, parallel and perpendicular diffusivity decreased in patients and were most pronounced in the patients with persisting tics compared to those with remission. The findings suggest that the development of the brain in patients with remission resembles the normal development more than in patients...

  7. Creutzfeldt-Jakob Disease with a prion protein gene codon 180 mutation presenting asymmetric cortical high-intensity on magnetic resonance imaging.

    Science.gov (United States)

    Amano, Yuko; Kimura, Noriyuki; Hanaoka, Takuya; Aso, Yasuhiro; Hirano, Teruyuki; Murai, Hiroyuki; Satoh, Katsuya; Matsubara, Etsuro

    2015-01-01

    Here we report a genetically confirmed case of Creutzfeldt-Jakob disease with a prion protein gene codon 180 mutation presenting atypical magnetic resonance imaging findings. The present case exhibited an acute onset and lateralized neurologic signs, and progressive cognitive impairment. No myoclonus or periodic synchronous discharges on electroencephalography were observed. Diffusion-weighted images revealed areas of high signal intensity in the right frontal and temporal cortices at onset that extended to the whole cortex and basal ganglia of the right cerebral hemisphere at 3 months. Although the cerebrospinal fluid (CSF) was initially negative for neuron specific enolase, tau protein, 14-3-3 protein, and abnormal prion protein, the CSF was positive for these brain-derived proteins at 3 months after onset.

  8. 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

  9. Imaging in haematopoietic stem cell transplantation

    International Nuclear Information System (INIS)

    Evans, A.; Steward, C.G.; Lyburn, I.D.; Grier, D.J.

    2003-01-01

    Haematopoietic stem cell transplantation (SCT) is used to treat a wide range of malignant and non-malignant haematological conditions, solid malignancies, and metabolic and autoimmune diseases. Although imaging has a limited role before SCT, it is important after transplantation when it may support the clinical diagnosis of a variety of complications. It may also be used to monitor the effect of therapy and to detect recurrence of the underlying disease if the transplant is unsuccessful. We present a pictorial review of the imaging of patients who have undergone SCT, based upon 15 years experience in a large unit performing both adult and paediatric transplants

  10. STEM CELL IMAGING: FROM BENCH TO BEDSIDE

    Science.gov (United States)

    Nguyen, Patricia K.; Riegler, Johannes; Wu, Joseph C.

    2014-01-01

    Although cellular therapies hold great promise for the treatment of human disease, results from several initial clinical trials have not shown a level of efficacy required for their use as a first line therapy. Here we discuss how in vivo molecular imaging has helped identify barriers to clinical translation and potential strategies that may contribute to successful transplantation and improved outcomes, with a focus on cardiovascular and neurological diseases. We conclude with a perspective on the future role of molecular imaging in defining safety and efficacy for stem cell clinical implementation. PMID:24702995

  11. Imaging in haematopoietic stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Evans, A.; Steward, C.G.; Lyburn, I.D.; Grier, D.J

    2003-03-01

    Haematopoietic stem cell transplantation (SCT) is used to treat a wide range of malignant and non-malignant haematological conditions, solid malignancies, and metabolic and autoimmune diseases. Although imaging has a limited role before SCT, it is important after transplantation when it may support the clinical diagnosis of a variety of complications. It may also be used to monitor the effect of therapy and to detect recurrence of the underlying disease if the transplant is unsuccessful. We present a pictorial review of the imaging of patients who have undergone SCT, based upon 15 years experience in a large unit performing both adult and paediatric transplants.

  12. Positron Emission Tomography Imaging Reveals Auditory and Frontal Cortical Regions Involved with Speech Perception and Loudness Adaptation.

    Directory of Open Access Journals (Sweden)

    Georg Berding

    Full Text Available Considerable progress has been made in the treatment of hearing loss with auditory implants. However, there are still many implanted patients that experience hearing deficiencies, such as limited speech understanding or vanishing perception with continuous stimulation (i.e., abnormal loudness adaptation. The present study aims to identify specific patterns of cerebral cortex activity involved with such deficiencies. We performed O-15-water positron emission tomography (PET in patients implanted with electrodes within the cochlea, brainstem, or midbrain to investigate the pattern of cortical activation in response to speech or continuous multi-tone stimuli directly inputted into the implant processor that then delivered electrical patterns through those electrodes. Statistical parametric mapping was performed on a single subject basis. Better speech understanding was correlated with a larger extent of bilateral auditory cortex activation. In contrast to speech, the continuous multi-tone stimulus elicited mainly unilateral auditory cortical activity in which greater loudness adaptation corresponded to weaker activation and even deactivation. Interestingly, greater loudness adaptation was correlated with stronger activity within the ventral prefrontal cortex, which could be up-regulated to suppress the irrelevant or aberrant signals into the auditory cortex. The ability to detect these specific cortical patterns and differences across patients and stimuli demonstrates the potential for using PET to diagnose auditory function or dysfunction in implant patients, which in turn could guide the development of appropriate stimulation strategies for improving hearing rehabilitation. Beyond hearing restoration, our study also reveals a potential role of the frontal cortex in suppressing irrelevant or aberrant activity within the auditory cortex, and thus may be relevant for understanding and treating tinnitus.

  13. Positron Emission Tomography Imaging Reveals Auditory and Frontal Cortical Regions Involved with Speech Perception and Loudness Adaptation.

    Science.gov (United States)

    Berding, Georg; Wilke, Florian; Rode, Thilo; Haense, Cathleen; Joseph, Gert; Meyer, Geerd J; Mamach, Martin; Lenarz, Minoo; Geworski, Lilli; Bengel, Frank M; Lenarz, Thomas; Lim, Hubert H

    2015-01-01

    Considerable progress has been made in the treatment of hearing loss with auditory implants. However, there are still many implanted patients that experience hearing deficiencies, such as limited speech understanding or vanishing perception with continuous stimulation (i.e., abnormal loudness adaptation). The present study aims to identify specific patterns of cerebral cortex activity involved with such deficiencies. We performed O-15-water positron emission tomography (PET) in patients implanted with electrodes within the cochlea, brainstem, or midbrain to investigate the pattern of cortical activation in response to speech or continuous multi-tone stimuli directly inputted into the implant processor that then delivered electrical patterns through those electrodes. Statistical parametric mapping was performed on a single subject basis. Better speech understanding was correlated with a larger extent of bilateral auditory cortex activation. In contrast to speech, the continuous multi-tone stimulus elicited mainly unilateral auditory cortical activity in which greater loudness adaptation corresponded to weaker activation and even deactivation. Interestingly, greater loudness adaptation was correlated with stronger activity within the ventral prefrontal cortex, which could be up-regulated to suppress the irrelevant or aberrant signals into the auditory cortex. The ability to detect these specific cortical patterns and differences across patients and stimuli demonstrates the potential for using PET to diagnose auditory function or dysfunction in implant patients, which in turn could guide the development of appropriate stimulation strategies for improving hearing rehabilitation. Beyond hearing restoration, our study also reveals a potential role of the frontal cortex in suppressing irrelevant or aberrant activity within the auditory cortex, and thus may be relevant for understanding and treating tinnitus.

  14. Cell-Type Specific Development of the Hyperpolarization-Activated Current, Ih, in Prefrontal Cortical Neurons

    Directory of Open Access Journals (Sweden)

    Sha-Sha Yang

    2018-05-01

    Full Text Available H-current, also known as hyperpolarization-activated current (Ih, is an inward current generated by the hyperpolarization-activated cyclic nucleotide-gated (HCN cation channels. Ih plays an essential role in regulating neuronal properties, synaptic integration and plasticity, and synchronous activity in the brain. As these biological factors change across development, the brain undergoes varying levels of vulnerability to disorders like schizophrenia that disrupt prefrontal cortex (PFC-dependent function. However, developmental changes in Ih in PFC neurons remains untested. Here, we examine Ih in pyramidal neurons vs. gamma-aminobutyric acid (GABAergic parvalbumin-expressing (PV+ interneurons in developing mouse PFC. Our findings show that the amplitudes of Ih in these cell types are identical during the juvenile period but differ at later time points. In pyramidal neurons, Ih amplitude significantly increases from juvenile to adolescence and follows a similar trend into adulthood. In contrast, the amplitude of Ih in PV+ interneurons decreases from juvenile to adolescence, and does not change from adolescence to adulthood. Moreover, the kinetics of HCN channels in pyramidal neurons is significantly slower than in PV+ interneurons, with a gradual decrease in pyramidal neurons and a gradual increase in PV+ cells across development. Our study reveals distinct developmental trajectories of Ih in pyramidal neurons and PV+ interneurons. The cell-type specific alteration of Ih during the critical period from juvenile to adolescence reflects the contribution of Ih to the maturation of the PFC and PFC-dependent function. These findings are essential for a better understanding of normal PFC function, and for elucidating Ih’s crucial role in the pathophysiology of neurodevelopmental disorders.

  15. Nonislet Cell Tumor Hypoglycemia in a Patient with Adrenal Cortical Carcinoma

    Directory of Open Access Journals (Sweden)

    Se Won Kim

    2016-01-01

    Full Text Available Nonislet cell tumor hypoglycemia (NICTH is a rare but serious paraneoplastic syndrome in which a tumor secretes incompletely processed precursors of insulin-like growth factor-II (IGF-II, causing hypoglycemia. Here, we report an exceptional case of NICTH caused by nonfunctioning adrenocortical carcinoma in a 39-year-old male with recurrent hypoglycemia. The patient’s serum IGF-II/IGF-I ratio had increased to 27.8. The serum level of the IGF-II/IGF-I ratio was normalized after removal of the tumor, and the hypoglycemic attacks no longer occurred after the operation.

  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

    2015-09-01

    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.

  17. Imaging of ovarian clear cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, Toshihiko; Sawano, Seishi; Yamada, Keiko [Japanese Foundation for Cancer Research, Tokyo (Japan). Hospital] (and others)

    1999-12-01

    The aim of this study is to examine the appearance of ovarian clear cell adenocarcinoma (OCCA) on MR, CT, US. In 39 cases with OCCA, the imaging characteristics of OCCA were evaluated morphologically and classified into three groups, that was, monomural nodule type, multi-mural nodule type and predominantly solid type. Forty-three percent of the patients had endometriosis. Contrast material-enhanced MRI was the most useful method for diagnosis of OCCA. (author)

  18. Detection of viable cortical neurons using benzodiazepine receptor imaging after reversible focal ischaemia in rats: comparison with regional cerebral blood flow

    International Nuclear Information System (INIS)

    Watanabe, Yoshiyuki; Nakano, Takayuki; Yutani, Kenji; Nishimura, Hiroshi; Nishimura, Tsunehiko; Kusuoka, Hideo; Nakamura, Hironobu

    2000-01-01

    To elucidate the utility of benzodiazepine receptor imaging for the detection of viable cortical neurons, dual-tracer autoradiography using iodine-125 iomazenil (IMZ) and iodine-123 N-isopropyl-4-iodoamphetamine (IMP) was performed in a model of reversible focal ischaemia during the acute and subacute phases. The right middle cerebral artery of anaesthetized rats was occluded for 60 min using an intraluminal filament and reperfused. In the acute phase study, 125 I-IMZ (370 kBq) was injected via the femoral vein at 2 h after reperfusion, and 123 I-IMP (37 MBq) was injected at 50 min post-injection. Rats were sacrificed 10 min after the injection of 123 I-IMP. In the subacute phase study, the same procedure was performed at 5 days after reperfusion. In the acute phase, the IMP uptake was significantly decreased in almost all areas of the lesioned hemisphere, an exception being the cerebellum; however, the IMZ uptake was significantly decreased only in ischaemic cores. The discrepancy between IMZ and IMP uptake was observed in the lateral neocortex and the lateral caudate putamen (CPu), which were most frequently damaged in this ischaemic model. In the subacute phase, the IMZ uptake in lesioned rats was significantly decreased only in the parietal lobe and hippocampus, though the IMP uptake was decreased in many regions of lesioned hemispheres (the frontal, parietal cortex, CPu, hippocampus and thalamus). Histopathological findings indicated that both the IMP and the IMZ uptake was markedly decreased in necrotic areas. Although the IMP uptake was significantly decreased in the ischaemic areas, the IMZ uptake was maintained in these areas. These results suggest that benzodiazepine receptor imaging is superior to regional cerebral blood flow imaging for the detection of viable cortical neurons in both the acute and subacute phases of ischaemia. (orig.)

  19. Detection of viable cortical neurons using benzodiazepine receptor imaging after reversible focal ischaemia in rats: comparison with regional cerebral blood flow

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Yoshiyuki [Dept. of Radiology, Osaka National Hospital (Japan); Nakano, Takayuki; Yutani, Kenji; Nishimura, Hiroshi; Nishimura, Tsunehiko [Div. of Tracer Kinetics, Osaka University Medical School (Japan); Kusuoka, Hideo [Clinical Research Institute, Osaka National Hospital (Japan); Nakamura, Hironobu [Dept. of Radiology, Osaka University Medical School (Japan)

    2000-03-01

    To elucidate the utility of benzodiazepine receptor imaging for the detection of viable cortical neurons, dual-tracer autoradiography using iodine-125 iomazenil (IMZ) and iodine-123 N-isopropyl-4-iodoamphetamine (IMP) was performed in a model of reversible focal ischaemia during the acute and subacute phases. The right middle cerebral artery of anaesthetized rats was occluded for 60 min using an intraluminal filament and reperfused. In the acute phase study, {sup 125}I-IMZ (370 kBq) was injected via the femoral vein at 2 h after reperfusion, and {sup 123}I-IMP (37 MBq) was injected at 50 min post-injection. Rats were sacrificed 10 min after the injection of {sup 123}I-IMP. In the subacute phase study, the same procedure was performed at 5 days after reperfusion. In the acute phase, the IMP uptake was significantly decreased in almost all areas of the lesioned hemisphere, an exception being the cerebellum; however, the IMZ uptake was significantly decreased only in ischaemic cores. The discrepancy between IMZ and IMP uptake was observed in the lateral neocortex and the lateral caudate putamen (CPu), which were most frequently damaged in this ischaemic model. In the subacute phase, the IMZ uptake in lesioned rats was significantly decreased only in the parietal lobe and hippocampus, though the IMP uptake was decreased in many regions of lesioned hemispheres (the frontal, parietal cortex, CPu, hippocampus and thalamus). Histopathological findings indicated that both the IMP and the IMZ uptake was markedly decreased in necrotic areas. Although the IMP uptake was significantly decreased in the ischaemic areas, the IMZ uptake was maintained in these areas. These results suggest that benzodiazepine receptor imaging is superior to regional cerebral blood flow imaging for the detection of viable cortical neurons in both the acute and subacute phases of ischaemia. (orig.)

  20. Decreased cortical activation in response to a motion stimulus in anisometropic amblyopic eyes using functional magnetic resonance imaging.

    Science.gov (United States)

    Bonhomme, Gabrielle R; Liu, Grant T; Miki, Atsushi; Francis, Ellie; Dobre, M-C; Modestino, Edward J; Aleman, David O; Haselgrove, John C

    2006-12-01

    Motion perception abnormalities and extrastriate abnormalities have been suggested in amblyopia. Functional MRI (fMRI) and motion stimuli were used to study whether interocular differences in activation are detectable in motion-sensitive cortical areas in patients with anisometropic amblyopia. We performed fMRI at 1.5 T 4 control subjects (20/20 OU), 1 with monocular suppression (20/25), and 2 with anisometropic amblyopia (20/60, 20/800). Monocular suppression was thought to be form fruste of amblyopia. The experimental stimulus consisted of expanding and contracting concentric rings, whereas the control condition consisted of stationary concentric rings. Activation was determined by contrasting the 2 conditions for each eye. Significant fMRI activation and comparable right and left eye activation was found in V3a and V5 in all control subjects (Average z-values in L vs R contrast 0.42, 0.43) and in the subject with monocular suppression (z = 0.19). The anisometropes exhibited decreased extrastriate activation in their amblyopic eyes compared with the fellow eyes (zs = 2.12, 2.76). Our data suggest motion-sensitive cortical structures may be less active when anisometropic amblyopic eyes are stimulated with moving rings. These results support the hypothesis that extrastriate cortex is affected in anisometropic amblyopia. Although suggestive of a magnocellular defect, the exact mechanism is unclear.

  1. A new level set model for cell image segmentation

    Science.gov (United States)

    Ma, Jing-Feng; Hou, Kai; Bao, Shang-Lian; Chen, Chun

    2011-02-01

    In this paper we first determine three phases of cell images: background, cytoplasm and nucleolus according to the general physical characteristics of cell images, and then develop a variational model, based on these characteristics, to segment nucleolus and cytoplasm from their relatively complicated backgrounds. In the meantime, the preprocessing obtained information of cell images using the OTSU algorithm is used to initialize the level set function in the model, which can speed up the segmentation and present satisfactory results in cell image processing.

  2. Cortical grey matter and subcortical white matter brain microstructural changes in schizophrenia are localised and age independent: a case-control diffusion tensor imaging study.

    Science.gov (United States)

    Chiapponi, Chiara; Piras, Fabrizio; Piras, Federica; Fagioli, Sabrina; Caltagirone, Carlo; Spalletta, Gianfranco

    2013-01-01

    It is still unknown whether the structural brain impairments that characterize schizophrenia (SZ) worsen during the lifetime. Here, we aimed to describe age-related microstructural brain changes in cortical grey matter and subcortical white matter of patients affected by SZ. In this diffusion tensor imaging study, we included 69 patients diagnosed with SZ and 69 healthy control (HC) subjects, age and gender matched. We carried out analyses of covariance, with diagnosis as fixed factor and brain diffusion-related parameters as dependent variables, and controlled for the effect of education. White matter fractional anisotropy decreased in the entire age range spanned (18-65 years) in both SZ and HC and was significantly lower in younger patients with SZ, with no interaction (age by diagnosis) effect in fiber tracts including corpus callosum, corona radiata, thalamic radiations and external capsule. Also, grey matter mean diffusivity increased in the entire age range in both SZ and HC and was significantly higher in younger patients, with no age by diagnosis interaction in the left frontal operculum cortex, left insula and left planum polare and in the right temporal pole and right intracalcarine cortex. In individuals with SZ we found that localized brain cortical and white matter subcortical microstructural impairments appear early in life but do not worsen in the 18-65 year age range.

  3. Test-retest variability of high resolution positron emission tomography (PET) imaging of cortical serotonin (5HT2A) receptors in older, healthy adults

    International Nuclear Information System (INIS)

    Chow, Tiffany W; Mamo, David C; Uchida, Hiroyuki; Graff-Guerrero, Ariel; Houle, Sylvain; Smith, Gwenn S; Pollock, Bruce G; Mulsant, Benoit H

    2009-01-01

    Position emission tomography (PET) imaging using [ 18 F]-setoperone to quantify cortical 5-HT 2A receptors has the potential to inform pharmacological treatments for geriatric depression and dementia. Prior reports indicate a significant normal aging effect on serotonin 5HT 2A receptor (5HT 2A R) binding potential. The purpose of this study was to assess the test-retest variability of [ 18 F]-setoperone PET with a high resolution scanner (HRRT) for measuring 5HT 2A R availability in subjects greater than 60 years old. Methods: Six healthy subjects (age range = 65–78 years) completed two [ 18 F]-setoperone PET scans on two separate occasions 5–16 weeks apart. The average difference in the binding potential (BP ND ) as measured on the two occasions in the frontal and temporal cortical regions ranged between 2 and 12%, with the lowest intraclass correlation coefficient in anterior cingulate regions. We conclude that the test-retest variability of [ 18 F]-setoperone PET in elderly subjects is comparable to that of [ 18 F]-setoperone and other 5HT 2A R radiotracers in younger subject samples

  4. Cortical grey matter and subcortical white matter brain microstructural changes in schizophrenia are localised and age independent: a case-control diffusion tensor imaging study.

    Directory of Open Access Journals (Sweden)

    Chiara Chiapponi

    Full Text Available It is still unknown whether the structural brain impairments that characterize schizophrenia (SZ worsen during the lifetime. Here, we aimed to describe age-related microstructural brain changes in cortical grey matter and subcortical white matter of patients affected by SZ. In this diffusion tensor imaging study, we included 69 patients diagnosed with SZ and 69 healthy control (HC subjects, age and gender matched. We carried out analyses of covariance, with diagnosis as fixed factor and brain diffusion-related parameters as dependent variables, and controlled for the effect of education. White matter fractional anisotropy decreased in the entire age range spanned (18-65 years in both SZ and HC and was significantly lower in younger patients with SZ, with no interaction (age by diagnosis effect in fiber tracts including corpus callosum, corona radiata, thalamic radiations and external capsule. Also, grey matter mean diffusivity increased in the entire age range in both SZ and HC and was significantly higher in younger patients, with no age by diagnosis interaction in the left frontal operculum cortex, left insula and left planum polare and in the right temporal pole and right intracalcarine cortex. In individuals with SZ we found that localized brain cortical and white matter subcortical microstructural impairments appear early in life but do not worsen in the 18-65 year age range.

  5. Coconut oil protects cortical neurons from amyloid beta toxicity by enhancing signaling of cell survival pathways.

    Science.gov (United States)

    Nafar, F; Clarke, J P; Mearow, K M

    2017-05-01

    Alzheimer's disease is a progressive neurodegenerative disease that has links with other conditions that can often be modified by dietary and life-style interventions. In particular, coconut oil has received attention as having potentially having benefits in lessening the cognitive deficits associated with Alzheimer's disease. In a recent report, we showed that neuron survival in cultures co-treated with coconut oil and Aβ was rescued compared to cultures exposed only to Aβ. Here we investigated treatment with Aβ for 1, 6 or 24 h followed by addition of coconut oil for a further 24 h, or treatment with coconut oil for 24 h followed by Aβ exposure for various periods. Neuronal survival and several cellular parameters (cleaved caspase 3, synaptophysin labeling and ROS) were assessed. In addition, the influence of these treatments on relevant signaling pathways was investigated with Western blotting. In terms of the treatment timing, our data indicated that coconut oil rescues cells pre-exposed to Aβ for 1 or 6 h, but is less effective when the pre-exposure has been 24 h. However, pretreatment with coconut oil prior to Aβ exposure showed the best outcomes. Treatment with octanoic or lauric acid also provided protection against Aβ, but was not as effective as the complete oil. The coconut oil treatment reduced the number of cells with cleaved caspase and ROS labeling, as well as rescuing the loss of synaptophysin labeling observed with Aβ treatment. Treatment with coconut oil, as well as octanoic, decanoic and lauric acids, resulted in a modest increase in ketone bodies compared to controls. The biochemical data suggest that Akt and ERK activation may contribute to the survival promoting influence of coconut oil. This was supported by observations that a PI3-Kinase inhibitor blocked the rescue effect of CoOil on Aβ amyloid toxicity. Further studies into the mechanisms of action of coconut oil and its constituent medium chain fatty acids are warranted

  6. Distinct Thalamic Reticular Cell Types Differentially Modulate Normal and Pathological Cortical Rhythms

    Directory of Open Access Journals (Sweden)

    Alexandra Clemente-Perez

    2017-06-01

    Full Text Available Integrative brain functions depend on widely distributed, rhythmically coordinated computations. Through its long-ranging connections with cortex and most senses, the thalamus orchestrates the flow of cognitive and sensory information. Essential in this process, the nucleus reticularis thalami (nRT gates different information streams through its extensive inhibition onto other thalamic nuclei, however, we lack an understanding of how different inhibitory neuron subpopulations in nRT function as gatekeepers. We dissociated the connectivity, physiology, and circuit functions of neurons within rodent nRT, based on parvalbumin (PV and somatostatin (SOM expression, and validated the existence of such populations in human nRT. We found that PV, but not SOM, cells are rhythmogenic, and that PV and SOM neurons are connected to and modulate distinct thalamocortical circuits. Notably, PV, but not SOM, neurons modulate somatosensory behavior and disrupt seizures. These results provide a conceptual framework for how nRT may gate incoming information to modulate brain-wide rhythms.

  7. Alterations in a Unique Class of Cortical Chandelier Cell Axon Cartridges in Schizophrenia.

    Science.gov (United States)

    Rocco, Brad R; DeDionisio, Adam M; Lewis, David A; Fish, Kenneth N

    2017-07-01

    The axons of chandelier cells (ChCs) target the axon initial segment of pyramidal neurons, forming an array of boutons termed a cartridge. In schizophrenia, the density of cartridges detectable by gamma-aminobutyric acid (GABA) membrane transporter 1 immunoreactivity is lower, whereas the density of axon initial segments detectable by immunoreactivity for the α2 subunit of the GABA A receptor is higher in layers 2/superficial 3 of the prefrontal cortex. These findings were interpreted as compensatory responses to lower GABA levels in ChCs. However, we recently found that in schizophrenia, ChC cartridge boutons contain normal levels of the 67 kDa isoform of glutamic acid decarboxylase (GAD67) protein, the enzyme responsible for GABA synthesis in these boutons. To understand these findings we quantified the densities of ChC cartridges immunoreactive for vesicular GABA transporter (vGAT+), which is present in all cartridge boutons, and the subset of cartridges that contain calbindin (CB+). Prefrontal cortex tissue sections from 20 matched pairs of schizophrenia and unaffected comparison subjects were immunolabeled for vGAT, GAD67, and CB. The mean density of vGAT+/CB+ cartridges was 2.7-fold higher, exclusively in layer 2 of schizophrenia subjects, whereas the density of vGAT+/CB- cartridges did not differ between subject groups. Neither vGAT, CB, or GAD67 protein levels per ChC bouton nor the number of boutons per cartridge differed between subject groups. Our findings of a greater density of CB+ ChC cartridges in prefrontal cortex layer 2 from schizophrenia subjects suggests that the normal developmental pruning of these cartridges is blunted in the illness. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  8. Firing-rate based network modeling of the dLGN circuit: Effects of cortical feedback on spatiotemporal response properties of relay cells.

    Science.gov (United States)

    Mobarhan, Milad Hobbi; Halnes, Geir; Martínez-Cañada, Pablo; Hafting, Torkel; Fyhn, Marianne; Einevoll, Gaute T

    2018-05-01

    Visually evoked signals in the retina pass through the dorsal geniculate nucleus (dLGN) on the way to the visual cortex. This is however not a simple feedforward flow of information: there is a significant feedback from cortical cells back to both relay cells and interneurons in the dLGN. Despite four decades of experimental and theoretical studies, the functional role of this feedback is still debated. Here we use a firing-rate model, the extended difference-of-Gaussians (eDOG) model, to explore cortical feedback effects on visual responses of dLGN relay cells. For this model the responses are found by direct evaluation of two- or three-dimensional integrals allowing for fast and comprehensive studies of putative effects of different candidate organizations of the cortical feedback. Our analysis identifies a special mixed configuration of excitatory and inhibitory cortical feedback which seems to best account for available experimental data. This configuration consists of (i) a slow (long-delay) and spatially widespread inhibitory feedback, combined with (ii) a fast (short-delayed) and spatially narrow excitatory feedback, where (iii) the excitatory/inhibitory ON-ON connections are accompanied respectively by inhibitory/excitatory OFF-ON connections, i.e. following a phase-reversed arrangement. The recent development of optogenetic and pharmacogenetic methods has provided new tools for more precise manipulation and investigation of the thalamocortical circuit, in particular for mice. Such data will expectedly allow the eDOG model to be better constrained by data from specific animal model systems than has been possible until now for cat. We have therefore made the Python tool pyLGN which allows for easy adaptation of the eDOG model to new situations.

  9. Functional imaging of microdomains in cell membranes.

    Science.gov (United States)

    Duggan, James; Jamal, Ghadir; Tilley, Mark; Davis, Ben; McKenzie, Graeme; Vere, Kelly; Somekh, Michael G; O'Shea, Paul; Harris, Helen

    2008-10-01

    The presence of microdomains or rafts within cell membranes is a topic of intense study and debate. The role of these structures in cell physiology, however, is also not yet fully understood with many outstanding problems. This problem is partly based on the small size of raft structures that presents significant problems to their in vivo study, i.e., within live cell membranes. But the structure and dynamics as well as the factors that control the assembly and disassembly of rafts are also of major interest. In this review we outline some of the problems that the study of rafts in cell membranes present as well as describing some views of what are considered the generalised functions of membrane rafts. We point to the possibility that there may be several different 'types' of membrane raft in cell membranes and consider the factors that affect raft assembly and disassembly, particularly, as some researchers suggest that the lifetimes of rafts in cell membranes may be sub-second. We attempt to review some of the methods that offer the ability to interrogate rafts directly as well as describing factors that appear to affect their functionality. The former include both near-field and far-field optical approaches as well as scanning probe techniques. Some of the advantages and disadvantages of these techniques are outlined. Finally, we describe our own views of raft functionality and properties, particularly, concerning the membrane dipole potential, and describe briefly some of the imaging strategies we have developed for their study.

  10. A new model of strabismic amblyopia: Loss of spatial acuity due to increased temporal dispersion of geniculate X-cell afferents on to cortical neurons.

    Science.gov (United States)

    Crewther, D P; Crewther, S G

    2015-09-01

    Although the neural locus of strabismic amblyopia has been shown to lie at the first site of binocular integration, first in cat and then in primate, an adequate mechanism is still lacking. Here we hypothesise that increased temporal dispersion of LGN X-cell afferents driven by the deviating eye onto single cortical neurons may provide a neural mechanism for strabismic amblyopia. This idea was investigated via single cell extracellular recordings of 93 X and 50 Y type LGN neurons from strabismic and normal cats. Both X and Y neurons driven by the non-deviating eye showed shorter latencies than those driven by either the strabismic or normal eyes. Also the mean latency difference between X and Y neurons was much greater for the strabismic cells compared with the other two groups. The incidence of lagged X-cells driven by the deviating eye of the strabismic cats was higher than that of LGN X-cells from normal animals. Remarkably, none of the cells recorded from the laminae driven by the non-deviating eye were of the lagged class. A simple computational model was constructed in which a mixture of lagged and non-lagged afferents converge on to single cortical neurons. Model cut-off spatial frequencies to a moving grating stimulus were sensitive to the temporal dispersion of the geniculate afferents. Thus strabismic amblyopia could be viewed as a lack of developmental tuning of geniculate lags for neurons driven by the amblyopic eye. Monocular control of fixation by the non-deviating eye is associated with reduced incidence of lagged neurons, suggesting that in normal vision, lagged neurons might play a role in maintaining binocular connections for cortical neurons. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Regulation of cortical contractility and spindle positioning by the protein phosphatase 6 PPH-6 in one-cell stage C. elegans embryos

    Science.gov (United States)

    Afshar, Katayoun; Werner, Michael E.; Tse, Yu Chung; Glotzer, Michael; Gönczy, Pierre

    2010-01-01

    Modulation of the microtubule and the actin cytoskeleton is crucial for proper cell division. Protein phosphorylation is known to be an important regulatory mechanism modulating these cytoskeletal networks. By contrast, there is a relative paucity of information regarding how protein phosphatases contribute to such modulation. Here, we characterize the requirements for protein phosphatase PPH-6 and its associated subunit SAPS-1 in one-cell stage C. elegans embryos. We establish that the complex of PPH-6 and SAPS-1 (PPH-6/SAPS-1) is required for contractility of the actomyosin network and proper spindle positioning. Our analysis demonstrates that PPH-6/SAPS-1 regulates the organization of cortical non-muscle myosin II (NMY-2). Accordingly, we uncover that PPH-6/SAPS-1 contributes to cytokinesis by stimulating actomyosin contractility. Furthermore, we demonstrate that PPH-6/SAPS-1 is required for the proper generation of pulling forces on spindle poles during anaphase. Our results indicate that this requirement is distinct from the role in organizing the cortical actomyosin network. Instead, we uncover that PPH-6/SAPS-1 contributes to the cortical localization of two positive regulators of pulling forces, GPR-1/2 and LIN-5. Our findings provide the first insights into the role of a member of the PP6 family of phosphatases in metazoan development. PMID:20040490

  12. Imaging in Patients with Merkel Cell Carcinoma

    International Nuclear Information System (INIS)

    Enzenhofer, E.; Ubl, P.; Czerny, C.; Erovic, B. M.

    2013-01-01

    Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine tumor of the skin with a mortality rate of approximately 25% (Peloschek et al., 2010). Accurate assessment of nodal involvement in patients with MCC predicts significantly overall outcome (Smith et al., 2012 and Ortin-Perez et al., 2007). Due to the rarity of this highly aggressive disease, only a few imaging reports on MCC were published, and subsequently still to date no accepted imaging algorithm for MCC is available. For primary staging of MCC, general recommendations have included ultrasonography, chest X-ray CT, and MRI, but recent articles show that the use of sentinel node and FDG-PET/PET-CT is gaining more and more importance

  13. Functional mapping of thalamic nuclei and their integration into cortico-striatal-thalamo-cortical loops via ultra-high resolution imaging- From animal anatomy to in vivo imaging in humans

    Directory of Open Access Journals (Sweden)

    Coraline D. Metzger

    2013-05-01

    Full Text Available The thalamus, a crucial node in the well-described cortico-striatal-thalamo-cortical circuits, has been the focus of functional and structural imaging studies investigating human emotion, cognition and memory. Invasive work in animals and post-mortem investigations have revealed the rich cytoarchitectonics and functional specificity of the thalamus. Given current restrictions in the spatial resolution of non-invasive imaging modalities, there is, however, a translational gap between functional and structural information on these circuits in humans and animals as well as between histological and cellular evidence and their relationship to psychological functioning.With the advance of higher field strengths for MR approaches, better spatial resolution is now available promising to overcome this conceptual problem.We here review these two levels, which exist for both neuroscientific and clinical investigations, and then focus on current attempts to overcome conceptual boundaries of these observations with the help of high-resolution imaging.

  14. Development of Self-Assembled Nanoribbon Bound Peptide-Polyaniline Composite Scaffolds and Their Interactions with Neural Cortical Cells

    Directory of Open Access Journals (Sweden)

    Andrew M. Smith

    2018-01-01

    Full Text Available Degenerative neurological disorders and traumatic brain injuries cause significant damage to quality of life and often impact survival. As a result, novel treatments are necessary that can allow for the regeneration of neural tissue. In this work, a new biomimetic scaffold was designed with potential for applications in neural tissue regeneration. To develop the scaffold, we first prepared a new bolaamphiphile that was capable of undergoing self-assembly into nanoribbons at pH 7. Those nanoribbons were then utilized as templates for conjugation with specific proteins known to play a critical role in neural tissue growth. The template (Ile-TMG-Ile was prepared by conjugating tetramethyleneglutaric acid with isoleucine and the ability of the bolaamphiphile to self-assemble was probed at a pH range of 4 through 9. The nanoribbons formed under neutral conditions were then functionalized step-wise with the basement membrane protein laminin, the neurotropic factor artemin and Type IV collagen. The conductive polymer polyaniline (PANI was then incorporated through electrostatic and π–π stacking interactions to the scaffold to impart electrical properties. Distinct morphology changes were observed upon conjugation with each layer, which was also accompanied by an increase in Young’s Modulus as well as surface roughness. The Young’s Modulus of the dried PANI-bound biocomposite scaffolds was found to be 5.5 GPa, indicating the mechanical strength of the scaffold. Thermal phase changes studied indicated broad endothermic peaks upon incorporation of the proteins which were diminished upon binding with PANI. The scaffolds also exhibited in vitro biodegradable behavior over a period of three weeks. Furthermore, we observed cell proliferation and short neurite outgrowths in the presence of rat neural cortical cells, confirming that the scaffolds may be applicable in neural tissue regeneration. The electrochemical properties of the scaffolds were also

  15. Development of Self-Assembled Nanoribbon Bound Peptide-Polyaniline Composite Scaffolds and Their Interactions with Neural Cortical Cells

    Science.gov (United States)

    Smith, Andrew M.; Pajovich, Harrison T.; Banerjee, Ipsita A.

    2018-01-01

    Degenerative neurological disorders and traumatic brain injuries cause significant damage to quality of life and often impact survival. As a result, novel treatments are necessary that can allow for the regeneration of neural tissue. In this work, a new biomimetic scaffold was designed with potential for applications in neural tissue regeneration. To develop the scaffold, we first prepared a new bolaamphiphile that was capable of undergoing self-assembly into nanoribbons at pH 7. Those nanoribbons were then utilized as templates for conjugation with specific proteins known to play a critical role in neural tissue growth. The template (Ile-TMG-Ile) was prepared by conjugating tetramethyleneglutaric acid with isoleucine and the ability of the bolaamphiphile to self-assemble was probed at a pH range of 4 through 9. The nanoribbons formed under neutral conditions were then functionalized step-wise with the basement membrane protein laminin, the neurotropic factor artemin and Type IV collagen. The conductive polymer polyaniline (PANI) was then incorporated through electrostatic and π–π stacking interactions to the scaffold to impart electrical properties. Distinct morphology changes were observed upon conjugation with each layer, which was also accompanied by an increase in Young’s Modulus as well as surface roughness. The Young’s Modulus of the dried PANI-bound biocomposite scaffolds was found to be 5.5 GPa, indicating the mechanical strength of the scaffold. Thermal phase changes studied indicated broad endothermic peaks upon incorporation of the proteins which were diminished upon binding with PANI. The scaffolds also exhibited in vitro biodegradable behavior over a period of three weeks. Furthermore, we observed cell proliferation and short neurite outgrowths in the presence of rat neural cortical cells, confirming that the scaffolds may be applicable in neural tissue regeneration. The electrochemical properties of the scaffolds were also studied by

  16. Longitudinal in vivo magnetic resonance imaging studies in experimental allergic encephalomyelitis : effect of a neurotrophic treatment on cortical lesion development

    NARCIS (Netherlands)

    Duckers, H.J.; Muller, H J; Verhaagen, J; Nicolay, K; Gispen, Willem Hendrik

    Proton magnetic resonance imaging enables non-invasive monitoring of lesion formation in multiple sclerosis and has an important role in assessing the potential effects of therapy. T2-weighted and short tau inversion recovery magnetic resonance imaging were used to assess the effect of a

  17. Profiling pleural effusion cells by a diffraction imaging method

    Science.gov (United States)

    Al-Qaysi, Safaa; Hong, Heng; Wen, Yuhua; Lu, Jun Q.; Feng, Yuanming; Hu, Xin-Hua

    2018-02-01

    Assay of cells in pleural effusion (PE) is an important means of disease diagnosis. Conventional cytology of effusion samples, however, has low sensitivity and depends heavily on the expertise of cytopathologists. We applied a polarization diffraction imaging flow cytometry method on effusion cells to investigate their features. Diffraction imaging of the PE cell samples has been performed on 6000 to 12000 cells for each effusion cell sample of three patients. After prescreening to remove images by cellular debris and aggregated non-cellular particles, the image textures were extracted with a gray level co-occurrence matrix (GLCM) algorithm. The distribution of the imaged cells in the GLCM parameters space was analyzed by a Gaussian Mixture Model (GMM) to determine the number of clusters among the effusion cells. These results yield insight on textural features of diffraction images and related cellular morphology in effusion samples and can be used toward the development of a label-free method for effusion cells assay.

  18. 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.

  19. Single-cell magnetic imaging using a quantum diamond microscope.

    Science.gov (United States)

    Glenn, D R; Lee, K; Park, H; Weissleder, R; Yacoby, A; Lukin, M D; Lee, H; Walsworth, R L; Connolly, C B

    2015-08-01

    We apply a quantum diamond microscope for detection and imaging of immunomagnetically labeled cells. This instrument uses nitrogen-vacancy (NV) centers in diamond for correlated magnetic and fluorescence imaging. Our device provides single-cell resolution and a field of view (∼1 mm(2)) two orders of magnitude larger than that of previous NV imaging technologies, enabling practical applications. To illustrate, we quantified cancer biomarkers expressed by rare tumor cells in a large population of healthy cells.

  20. Quantitative imaging of epithelial cell scattering identifies specific inhibitors of cell motility and cell-cell dissociation

    NARCIS (Netherlands)

    Loerke, D.; le Duc, Q.; Blonk, I.; Kerstens, A.; Spanjaard, E.; Machacek, M.; Danuser, G.; de Rooij, J.

    2012-01-01

    The scattering of cultured epithelial cells in response to hepatocyte growth factor (HGF) is a model system that recapitulates key features of metastatic cell behavior in vitro, including disruption of cell-cell adhesions and induction of cell migration. We have developed image analysis tools that

  1. Coupled Imaging with [18F]FBB and [18F]FDG in AD Subjects Show a Selective Association Between Amyloid Burden and Cortical Dysfunction in the Brain.

    Science.gov (United States)

    Chiaravalloti, Agostino; Castellano, Anna Elisa; Ricci, Maria; Barbagallo, Gaetano; Sannino, Pasqualina; Ursini, Francesco; Karalis, Georgios; Schillaci, Orazio

    2018-02-05

    The present study was aimed to investigate the relationships between dysfunction of cortical glucose metabolism as detectable by means of 2-deoxy-2-[ 18 F]fluoro -D-glucose ([ 18 F]FDG) positron emission tomography/x-ray computed tomography (PET/CT) and amyloid burden as detectable by means of 4-{(E)-2-[4-(2-{2-[2-[ 18 F]fluoroethoxy]ethoxy}ethoxy)phenyl]vinyl}-N-methylaniline (florbetaben; [ 18 F]FBB) in a group of patients affected by Alzheimer's disease (AD). We examined 38 patients newly diagnosed with AD according to the NINCDS-ADRDA criteria. All the subjects underwent a PET/CT scan using both [ 18 F]FDG and [ 18 F]FBB with an average interval of 1 month. We used statistical parametric mapping (SPM8) implemented in Matlab R2012b and WFU pickatlas for the definition of a region of interest (ROI) mask including the whole cortex. These data were then normalized on the counts of the cerebellum and then used for a regression analysis on [ 18 F]FDG scans in SPM. Furthermore, 58 control subjects were used as control group for [ 18 F]FDG PET/CT scans. SPM analysis in AD patients showed a significant negative correlation between [ 18 F] FBB and [ 18 F] FDG uptake in temporal and parietal lobes bilaterally. Of note, these areas in AD patients displayed a marked glucose hypometabolism compared to control group. Combined imaging with [ 18 F]FBB and [ 18 FFDG shows that amyloid burden in the brain is related to cortical dysfunction of temporal and parietal lobes in AD.

  2. 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.

  3. 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.)

  4. Survival of plant tissue at super-low temperatures v. An electron microscope study of ice in cortical cells cooled rapidly.

    Science.gov (United States)

    Sakai, A; Otsuka, K

    1967-12-01

    Experiments were carried out with cortical cells in twig bark of mulberry trees in winter in order to clarify the mechanism of survival at super-low temperatures with rapid cooling and rewarming. Attention was given to the relation between the existence of intracellular ice crystals and survival.Cortical cells were cooled rapidly by direct immersion into liquid nitrogen or isopentane cooled at various temperatures. After immersion, they were freeze-substituted with absolute ethanol at -78 degrees . They were then embedded, sectioned and examined under the electron microscope for the presence and distribution of cavities left after ice removal.Cells were found to remain alive and contain no ice cavities when immersed rapidly into isopentane baths kept below -60 degrees . Those cells at intermediate temperatures from -20 degrees to -45 degrees , were almost all destroyed. It was also observed that many ice cavities were contained in the cells immersed rapidly into isopentane baths at -30 degrees . The data seem to indicate that no ice crystals were formed when cooled rapidly by direct immersion into isopentane baths below -60 degrees or into liquid nitrogen.The tissue sections immersed in liquid nitrogen were rapidly transferred to isopentane baths at temperatures ranging from -70 degrees to -10 degrees before rapid rewarming. There was little damage when samples were held at temperatures below -50 degrees for 10 minutes or below -60 degrees for 16 hours. No cavities were found in these cells. Above -45 degrees , and especially at -30 degrees , however, all cells were completely destroyed even when exposed only for 1 minute. Many ice cavities were observed throughout these cells. The results obtained may be explained in terms of the growth rate of intracellular ice crystals.

  5. Optimal staining methods for delineation of cortical areas and neuron counts in human brains.

    Science.gov (United States)

    Uylings, H B; Zilles, K; Rajkowska, G

    1999-04-01

    For cytoarchitectonic delineation of cortical areas in human brain, the Gallyas staining for somata with its sharp contrast between cell bodies and neuropil is preferable to the classical Nissl staining, the more so when an image analysis system is used. This Gallyas staining, however, does not appear to be appropriate for counting neuron numbers in pertinent brain areas, due to the lack of distinct cytological features between small neurons and glial cells. For cell counting Nissl is preferable. In an optimal design for cell counting at least both the Gallyas and the Nissl staining must be applied, the former staining for cytoarchitectural delineaton of cortical areas and the latter for counting the number of neurons in the pertinent cortical areas. Copyright 1999 Academic Press.

  6. Laser speckle imaging identification of increases in cortical microcirculatory blood flow induced by motor activity during awake craniotomy ; Clinical article

    NARCIS (Netherlands)

    E. Klijn (Elko); M.E.J.L. Hulscher (Marlies); R.K. Balvers (Rutger); W.P.J. Holland (Wim); J. Bakker (Jan); A.J.P.E. Vincent (Arnoud); C.M.F. Dirven (Clemens); C. Ince (Can)

    2013-01-01

    textabstractObject. The goal of awake neurosurgery is to maximize resection of brain lesions with minimal injury to functional brain areas. Laser speckle imaging (LSI) is a noninvasive macroscopic technique with high spatial and temporal resolution used to monitor changes in capillary perfusion. In

  7. Laser speckle imaging identification of increases in cortical microcirculatory blood flow induced by motor activity during awake craniotomy

    NARCIS (Netherlands)

    Klijn, Eva; Hulscher, Hester C.; Balvers, Rutger K.; Holland, Wim P. J.; Bakker, Jan; Vincent, Arnaud J. P. E.; Dirven, Clemens M. F.; Ince, Can

    2013-01-01

    The goal of awake neurosurgery is to maximize resection of brain lesions with minimal injury to functional brain areas. Laser speckle imaging (LSI) is a noninvasive macroscopic technique with high spatial and temporal resolution used to monitor changes in capillary perfusion. In this study, the

  8. 7T T-2*-weighted magnetic resonance imaging reveals cortical phase differences between early- and late-onset Alzheimer's disease

    NARCIS (Netherlands)

    van Rooden, S.; Doan, N.T.; Versluis, M.J.; Goos, J.D.C.; Webb, A.G.; Oleksik, A.M.; van der Flier, W.M.; Scheltens, P.; Barkhof, F.; Weverlinge-Rynsburger, A.W.E.; Blauw, G. J.; Reiber, J.H.C.; van Buchem, M.A.; Milles, J.; van der Grond, J.

    2015-01-01

    The aim of this study is to explore regional iron-related differences in the cerebral cortex, indicative of Alzheimer's disease pathology, between early- and late-onset Alzheimer's disease (EOAD, LOAD, respectively) patients using 7T magnetic resonance phase images. High-resolution T

  9. ASSESSMENT OF CHEMICAL EFFECTS ON NEURITE OUTGROWTH, NEURONAL POLARIZATION AND SYNAPTOGENESIS IN RAT CORTICAL NEURONS USING HIGH CONTENT IMAGE ANALYSIS

    Science.gov (United States)

    There is a need for efficient, cost-effective methods for screening and prioritization of potential developmental neurotoxicants. One approach uses in vitro cell culture models that can recapitulate the critical processes of nervous system development. In vitro, primary cultures ...

  10. Longitudinal in vivo magnetic resonance imaging studies in experimental allergic encephalomyelitis: effect of a neurotrophic treatment on cortical lesion development

    Energy Technology Data Exchange (ETDEWEB)

    Gispen, W.H. [Rudolf Magnus Institute for Neurosciences, Department of Medical Pharmacology, Medical Faculty, Utrecht University Utrecht (Netherlands); Nicolay, K. [Department of in vivo NMR, Bijvoet Center, Utrecht University Utrecht (Netherlands); Verhaagen, J. [Rudolf Magnus Institute for Neurosciences, Department of Medical Pharmacology, Medical Faculty, Utrecht University Utrecht (Netherlands); Muller, H.J. [Department of in vivo NMR, Bijvoet Center, Utrecht University Utrecht (Netherlands); Duckers, H.J. [Rudolf Magnus Institute for Neurosciences, Department of Medical Pharmacology, Medical Faculty, Utrecht University Utrecht (Netherlands)

    1997-02-14

    Proton magnetic resonance imaging enables non-invasive monitoring of lesion formation in multiple sclerosis and has an important role in assessing the potential effects of therapy. T2-weighted and short {tau} inversion recovery magnetic resonance imaging were used to assess the effect of a neurotrophic adrenocorticotrophic hormone{sub 4-9} analogue [H-Met(O{sub 2})-Glu-His-Phe-d-Lys-Phe-OH] on the volume of lesions in the brains of rats suffering from chronic experimental allergic encephalomyelitis, an animal equivalent of multiple sclerosis. Lesion volume was monitored during a five-month period. Magnetic resonance imaging indicated that treatment with the adrenocorticotrophic hormone{sub 4-9} analogue significantly reduced the lesion volume by 84 and 85% 10 and 20 weeks after lesion induction, respectively. Furthermore, peptide treatment significantly reduced chronic experimental allergic encephalomyelitis-related neurological symptoms during the chronic phase of the disease (week 3 until week 20 after lesion induction). Both functional and morphological recovery were considerably advanced by peptide treatment. Twenty weeks after lesion induction rats with chronic experimental allergic encephalomyelitis were killed for histological analysis, to correlate magnetic resonance imaging findings with morphological changes. The regions of abnormally high signal intensities on T2-weighted magnetic resonance images coincided with areas of demyelination and concomitant widespread inflammatory infiltration, oedema formation and enlarged ventricles.The improved neurological status and the 84% reduction in the lesion volume in the cerebrum of rats chronic experimental allergic encephalomyelitis point to the potential value of trophic peptides in the development of strategies for limiting the damage caused by central demyelinating lesions in syndromes such as multiple sclerosis. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  11. Longitudinal in vivo magnetic resonance imaging studies in experimental allergic encephalomyelitis: effect of a neurotrophic treatment on cortical lesion development

    International Nuclear Information System (INIS)

    Gispen, W.H.; Nicolay, K.; Verhaagen, J.; Muller, H.J.; Duckers, H.J.

    1997-01-01

    Proton magnetic resonance imaging enables non-invasive monitoring of lesion formation in multiple sclerosis and has an important role in assessing the potential effects of therapy. T2-weighted and short τ inversion recovery magnetic resonance imaging were used to assess the effect of a neurotrophic adrenocorticotrophic hormone 4-9 analogue [H-Met(O 2 )-Glu-His-Phe-d-Lys-Phe-OH] on the volume of lesions in the brains of rats suffering from chronic experimental allergic encephalomyelitis, an animal equivalent of multiple sclerosis. Lesion volume was monitored during a five-month period. Magnetic resonance imaging indicated that treatment with the adrenocorticotrophic hormone 4-9 analogue significantly reduced the lesion volume by 84 and 85% 10 and 20 weeks after lesion induction, respectively. Furthermore, peptide treatment significantly reduced chronic experimental allergic encephalomyelitis-related neurological symptoms during the chronic phase of the disease (week 3 until week 20 after lesion induction). Both functional and morphological recovery were considerably advanced by peptide treatment. Twenty weeks after lesion induction rats with chronic experimental allergic encephalomyelitis were killed for histological analysis, to correlate magnetic resonance imaging findings with morphological changes. The regions of abnormally high signal intensities on T2-weighted magnetic resonance images coincided with areas of demyelination and concomitant widespread inflammatory infiltration, oedema formation and enlarged ventricles.The improved neurological status and the 84% reduction in the lesion volume in the cerebrum of rats chronic experimental allergic encephalomyelitis point to the potential value of trophic peptides in the development of strategies for limiting the damage caused by central demyelinating lesions in syndromes such as multiple sclerosis. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  12. Prenatal Exposure to Autism-Specific Maternal Autoantibodies Alters Proliferation of Cortical Neural Precursor Cells, Enlarges Brain, and Increases Neuronal Size in Adult Animals.

    Science.gov (United States)

    Martínez-Cerdeño, Verónica; Camacho, Jasmin; Fox, Elizabeth; Miller, Elaine; Ariza, Jeanelle; Kienzle, Devon; Plank, Kaela; Noctor, Stephen C; Van de Water, Judy

    2016-01-01

    Autism spectrum disorders (ASDs) affect up to 1 in 68 children. Autism-specific autoantibodies directed against fetal brain proteins have been found exclusively in a subpopulation of mothers whose children were diagnosed with ASD or maternal autoantibody-related autism. We tested the impact of autoantibodies on brain development in mice by transferring human antigen-specific IgG directly into the cerebral ventricles of embryonic mice during cortical neurogenesis. We show that autoantibodies recognize radial glial cells during development. We also show that prenatal exposure to autism-specific maternal autoantibodies increased stem cell proliferation in the subventricular zone (SVZ) of the embryonic neocortex, increased adult brain size and weight, and increased the size of adult cortical neurons. We propose that prenatal exposure to autism-specific maternal autoantibodies directly affects radial glial cell development and presents a viable pathologic mechanism for the maternal autoantibody-related prenatal ASD risk factor. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Live-Cell, Label-Free Identification of GABAergic and Non-GABAergic Neurons in Primary Cortical Cultures Using Micropatterned Surface

    Science.gov (United States)

    Kono, Sho; Kushida, Takatoshi; Hirano-Iwata, Ayumi; Niwano, Michio; Tanii, Takashi

    2016-01-01

    Excitatory and inhibitory neurons have distinct roles in cortical dynamics. Here we present a novel method for identifying inhibitory GABAergic neurons from non-GABAergic neurons, which are mostly excitatory glutamatergic neurons, in primary cortical cultures. This was achieved using an asymmetrically designed micropattern that directs an axonal process to the longest pathway. In the current work, we first modified the micropattern geometry to improve cell viability and then studied the axon length from 2 to 7 days in vitro (DIV). The cell types of neurons were evaluated retrospectively based on immunoreactivity against GAD67, a marker for inhibitory GABAergic neurons. We found that axons of non-GABAergic neurons grow significantly longer than those of GABAergic neurons in the early stages of development. The optimal threshold for identifying GABAergic and non-GABAergic neurons was evaluated to be 110 μm at 6 DIV. The method does not require any fluorescence labelling and can be carried out on live cells. The accuracy of identification was 98.2%. We confirmed that the high accuracy was due to the use of a micropattern, which standardized the development of cultured neurons. The method promises to be beneficial both for engineering neuronal networks in vitro and for basic cellular neuroscience research. PMID:27513933

  14. A new level set model for cell image segmentation

    International Nuclear Information System (INIS)

    Ma Jing-Feng; Chen Chun; Hou Kai; Bao Shang-Lian

    2011-01-01

    In this paper we first determine three phases of cell images: background, cytoplasm and nucleolus according to the general physical characteristics of cell images, and then develop a variational model, based on these characteristics, to segment nucleolus and cytoplasm from their relatively complicated backgrounds. In the meantime, the preprocessing obtained information of cell images using the OTSU algorithm is used to initialize the level set function in the model, which can speed up the segmentation and present satisfactory results in cell image processing. (cross-disciplinary physics and related areas of science and technology)

  15. Modeling neurodevelopment and cortical dysfunction in SPG11-linked hereditary spastic paraplegia using human induced pluripotent stem cells

    OpenAIRE

    Mishra, Himanshu Kumar

    2016-01-01

    Hereditary spastic paraplegias (HSPs) are a heterogeneous group of inherited motor neuron diseases characterized by progressive spasticity and weakness of the lower limbs. Mutations in the Spastic Paraplegia Gene11 (SPG11), encoding spatacsin, cause the most frequent form of autosomal recessive HSP. SPG11 patients are clinically distinguishable from most other HSPs, by severe cortical atrophy and presence of a thin corpus callosum (TCC), associated with cognitive deficits. Partly due to l...

  16. Imaging of Human Hepatic Stem Cells In Vivo

    International Nuclear Information System (INIS)

    Hsu, E.W.

    2006-01-01

    Report on progress in MRI and PET of stem cell tracking. Human hepatic stem cell imaging for both MRI and PET have been accomplished within SCID/nod mice, and succeeded in cell specificity labeling with in vitro, ex vivo, and in vivo image tracking. For MRI, stem cell labeling was accomplished by two methods: (1) in vitro labeling the stem cells just prior to in vivo transplantation, and/or (2) transplanting the stem cells into SCID/nod mice and in vivo specificity labeling the cells just prior to MRI. For labeling techniques 1 and 2, multiple image controls were utilized and include: (A) stem cells(-) and contrast label(-), (B) stem cells(+) and contrast label(-), and (C) stem cells(-) and contrast label(+) help to confirm signal noise background interference, which is a result of slight nonspecific cell labeling. Contrast labeled stem cells are directly transplanted into liver tissues, the tissues excised, and immediately MR imaged to determine cell dispersion dynamics. In this method, the contrast labeled cells appear as void foci throughout the organs. The images are imported into Metamorph imaging software and analyzed for foci radii, diameter, and to discern spheroid volumes. Then, cell numbers are extrapolated to understand ''imaged'' cell aggregate requirements using this technique. For this ex vivo method, a cell aggregate of ∼100 stem cells is required to MRI monitor signal activities. For in vivo imaging, contrast labeled human stem cells within SCID/nod mice are also confirmed as small foci voids and are evident within liver tissues. Initially, these short-term studies where accomplished by in vitro labeling stem cells, transplanting the cells, then in vivo imaging the tissues between days 3-15. Next and to avoid imaged time limitations of detaching contrast agents, the proliferative stem cells were labeled after transplantation, and before MR imaging. This was accomplished to confirm the ability to specifically label unique cell subsets after the

  17. Pseudo-reorganization of language cortical function at fMR imaging: a consequence of tumor-induced neurovascular uncoupling.

    Science.gov (United States)

    Ulmer, John L; Krouwer, Hendrikus G; Mueller, Wade M; Ugurel, M Sahin; Kocak, Mehmet; Mark, Leighton P

    2003-02-01

    A left-handed patient with a grade II left frontal lobe astrocytoma had spontaneous seizures causing speech arrest and uncontrolled right upper extremity movements. Word-generation functional MR (fMR) imaging showed activity nearly exclusively in the right inferior frontal gyrus. The clinical history of the speech arrest and the intraoperative mapping proved left-hemisphere language dominance. Tumor involvement of the left inferior frontal gyrus caused uncoupling of the blood oxygenation level-dependent (BOLD) and neuronal response, leading to the erroneous fMR imaging appearance of right-hemisphere language dominance. Discrepancies between BOLD and intraoperative mapping in areas near lesions illustrate the complementary nature of these techniques.

  18. 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. ...

  19. Analysis of live cell images: Methods, tools and opportunities.

    Science.gov (United States)

    Nketia, Thomas A; Sailem, Heba; Rohde, Gustavo; Machiraju, Raghu; Rittscher, Jens

    2017-02-15

    Advances in optical microscopy, biosensors and cell culturing technologies have transformed live cell imaging. Thanks to these advances live cell imaging plays an increasingly important role in basic biology research as well as at all stages of drug development. Image analysis methods are needed to extract quantitative information from these vast and complex data sets. The aim of this review is to provide an overview of available image analysis methods for live cell imaging, in particular required preprocessing image segmentation, cell tracking and data visualisation methods. The potential opportunities recent advances in machine learning, especially deep learning, and computer vision provide are being discussed. This review includes overview of the different available software packages and toolkits. Copyright © 2017. Published by Elsevier Inc.

  20. Advances of reporter gene imaging monitoring stem cell therapy

    International Nuclear Information System (INIS)

    Pei Zhijun; Zhang Yongxue

    2010-01-01

    Stem cell transplantation in the treatment of various tissue damage or degenerative diseases are research hotspots both at home and abroad. However, ignorance of the homing, differentiation and functional expression of the stem cell in vivo influence the further development of stem cell therapy. As an important component of molecular imaging technology, reporter gene imaging dynamically monitors the change of stem cell in vivo via monitoring the expression of transfected reporter gene. This paper briefly describes the latest research progress and the future development trend of the monitoring of reporter gene imaging in stem cell therapy in vivo. (authors)

  1. Spatio-temporal image correlation spectroscopy and super-resolution microscopy to quantify molecular dynamics in T cells.

    Science.gov (United States)

    Ashdown, George W; Owen, Dylan M

    2018-02-02

    Many cellular processes are regulated by the spatio-temporal organisation of signalling complexes, cytoskeletal components and membranes. One such example is at the T cell immunological synapse where the retrograde flow of cortical filamentous (F)-actin from the synapse periphery drives signalling protein microclusters towards the synapse centre. The density of this mesh however, makes visualisation and analysis of individual actin fibres difficult due to the resolution limit of conventional microscopy. Recently, super-resolution methods such as structured illumination microscopy (SIM) have surpassed this resolution limit. Here, we apply SIM to better visualise the dense cortical actin meshwork in T cell synapses formed against activating, antibody-coated surfaces and image under total-internal reflection fluorescence (TIRF) illumination. To analyse the observed molecular flows, and the relationship between them, we apply spatio-temporal image correlation spectroscopy (STICS) and its cross-correlation variant (STICCS). We show that the dynamic cortical actin mesh can be visualised with unprecedented detail and that STICS/STICCS can output accurate, quantitative maps of molecular flow velocity and directionality from such data. We find that the actin flow can be disrupted using small molecule inhibitors of actin polymerisation. This combination of imaging and quantitative analysis may provide an important new tool for researchers to investigate the molecular dynamics at cellular length scales. Here we demonstrate the retrograde flow of F-actin which may be important for the clustering and dynamics of key signalling proteins within the plasma membrane, a phenomenon which is vital to correct T cell activation and therefore the mounting of an effective immune response. Copyright © 2018. Published by Elsevier Inc.

  2. 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

  3. Neuroprotective effects of orientin on oxygen-glucose deprivation/reperfusion-induced cell injury in primary culture of rat cortical neurons.

    Science.gov (United States)

    Tian, Tian; Zeng, Junan; Zhao, Guangyu; Zhao, Wenjing; Gao, Songyi; Liu, Li

    2018-01-01

    Orientin (luteolin-8-C-glucoside) is a phenolic compound found abundantly in millet, juice, and peel of passion fruit and has been shown to have antioxidant properties. In the present study, we explored the effects of orientin on oxygen-glucose deprivation/reperfusion (OGD/RP)-induced cell injury in primary culture of rat cortical neurons using an in vitro model of neonatal ischemic brain injury. The reduced cell viability and elevated lactate dehydrogenase leakage were observed after OGD/RP exposure, which were then reversed by orientin (10, 20, and 30 µM) pretreatment in a dose-dependent manner. Additionally, OGD/RP treatment resulted in significant oxidative stress, accompanied by enhanced intracellular reactive oxygen species (ROS) generation, and obvious depletion in the activities of intracellular Mn-superoxide dismutase, catalase, and glutathione peroxidase antioxidases. However, these effects were dose dependently restored by orientin pretreatment. We also found that orientin pretreatment dose dependently suppressed [Ca 2+ ] i increase and mitochondrial membrane potential dissipation caused by OGD/RP in primary culture of rat cortical neurons. Western blot analysis showed that OGD/RP exposure induced a distinct decrease of Bcl-2 protein and a marked elevation of Bax, caspase-3, and cleaved caspase-3 proteins; whereas these effects were dose dependently reversed by orientin incubation. Both the caspase-3 activity and the apoptosis rate were increased under OGD/RP treatment, but was then dose dependently down-regulated by orientin (10, 20, and 30 µM) incubation. Moreover, orientin pretreatment dose dependently inhibited OGD/RP-induced phosphorylation of JNK and ERK1/2. Notably, JNK inhibitor SP600125 and ERK1/2 inhibitor PD98059 also dramatically attenuated OGD/RP-induced cell viability loss and ROS generation, and further, orientin failed to protect cortical neurons with the interference of JNK activator anisomycin or ERK1/2 activator FGF-2. Taken

  4. Distribution and Network of Basal Temporal Language Areas: A Study of the Combination of Electric Cortical Stimulation and Diffusion Tensor Imaging.

    Science.gov (United States)

    Enatsu, Rei; Kanno, Aya; Ookawa, Satoshi; Ochi, Satoko; Ishiai, Sumio; Nagamine, Takashi; Mikuni, Nobuhiro

    2017-10-01

    The basal temporal language area (BTLA) is considered to have several functions in language processing; however, its brain network is still unknown. This study investigated the distribution and networks of the BTLA using a combination of electric cortical stimulation and diffusion tensor imaging (DTI). 10 patients with intractable focal epilepsy who underwent presurgical evaluation with subdural electrodes were enrolled in this study (language dominant side: 6 patients, language nondominant side: 4 patients). Electric stimulation at 50 Hz was applied to the electrodes during Japanese sentence reading, morphograms (kanji) reading, and syllabograms (kana) reading tasks to identify the BTLA. DTI was used to identify the subcortical fibers originating from the BTLA found by electric stimulation. The BTLA was found in 6 patients who underwent implantation of the subdural electrodes in the dominant hemisphere. The BTLA was located anywhere between 20 mm and 56 mm posterior to the temporal tips. In 3 patients, electric stimulation of some or all areas within the BTLA induced disturbance in reading of kanji words only. DTI detected the inferior longitudinal fasciculus (ILF) in all patients and the uncinate fasciculus (UF) in 1 patient, originating from the BTLA. ILF was detected from both kanji-specific areas and kanji-nonspecific areas. This study indicates that the network of the BTLA is a part of a ventral stream and is mainly composed of the ILF, which acts as a critical structure for lexical retrieval. ILF is also associated with the specific processing of kanji words. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. The neuroprotective effect of rat adipose tissue-derived mesenchymal stem cell-conditioned medium on cortical neurons using an in vitro model of SCI inflammation.

    Science.gov (United States)

    Szekiova, Eva; Slovinska, Lucia; Blasko, Juraj; Plsikova, Jana; Cizkova, Dasa

    2018-04-01

    Objectives In this study, a new approach was used with an in vitro model in which neural cells were exposed to conditioned media from the injured spinal cord (SCI-CM) mimicking a local inflammatory microenvironment . Subsequently, the neuroprotective effect of rat adipose tissue-derived msesenchymal stem cell-conditioned media (ATMSC-CM) was investigated through a cell-free based therapy, which was used to treat cortical neurons and astrocytes under inflammation. Methods Primary cell cultures isolated from postnatal day (P6) Wistar rat brain cortex were exposed to SCI-CM derived from the central lesion, rostral and caudal segments of injured spinal cord. After 48 h incubation, the SCI-CM was replaced and primary cultures were cultivated either in DMEM media alone or in ATMSC-CM for 72 h. The impact of ATMSC-CM on the viability of neurons and astrocytes was assessed using a CyQUANT® Direct Cell Proliferation Assay Kit as well as immunocytochemistry analysis. Results Immunocytochemical analysis revealed significant decrease in the number of MAP2 positive neurons exposed to SCI-CM compared to Control. Protection by ATMSC-CM was associated with increased survival of neurons compared to primary culture cultivated in DMEM media alone. The ATMSC-CM effect on astrocytes was more variable and without any significant impact. Conclusion The results demonstrate that SCI-CM mimicking inflammation can reduce cortical neuron survival, and subsequent exposure to ATMSC-CM can stabilize the neuronal population most likely via released neuroprotective and trophic factors. In addition, astrogliosis was not affected by ATMSC-CM.

  6. Can high-resolution peripheral quantitative computed tomography imaging of subchondral and cortical bone predict condylar fracture in Thoroughbred racehorses?

    Science.gov (United States)

    Trope, G D; Ghasem-Zadeh, A; Anderson, G A; Mackie, E J; Whitton, R C

    2015-07-01

    High-resolution 3D imaging may improve the prediction and/or early identification of condylar fractures of the distal metacarpus/tarsus and reduce the frequency of breakdown injury in racehorses. To test the hypotheses that horses suffering condylar fractures have higher bone volume fraction (BV/TV) of the distal metacarpal epiphysis, greater subchondral bone thickness at the fracture site and higher second moment of inertia in the metacarpal midshaft as identified with high-resolution 3D imaging. Cross-sectional study using cadaver material. Thoroughbreds that died on racetracks were grouped as: 1) horses with third metacarpal (McIII) fractures with a condylar component (cases, n = 13); 2) horses with no limb fracture (controls, n = 8); 3) horses with fractures in other bones or suspensory apparatus disruption (other fatal injuries, n = 16). The palmar condyles of McIII and the midshaft were examined with high resolution peripheral quantitative computed tomography (HR-pQCT). Statistical analysis included logistic regression and Spearman's correlation. There were no significant differences in BV/TV of distal McIII and second moment of inertia of the midshaft between cases and controls. Epiphyseal bone BV/TV was greater in injured limbs of horses with any fatal limb injury (Groups 1 and 3 combined) compared with controls (odds ratio = 1.20, 95% confidence interval 1.01-1.42, P = 0.034). An epiphyseal BV/TV>0.742 resulted in a sensitivity of 82.8% and specificity of 62.5% in identifying horses with fatal limb injury. In horses without condylar fracture, increased subchondral bone thickness was associated with palmar osteochondral disease lesions in the adjacent condyle (rs = 0.65, Phorses at risk of any fatal breakdown injury but not metacarpal condylar fractures. Measurement of parasagittal groove subchondral bone thickness is complicated by adjacent palmar osteochondral disease lesions. Thus, high-resolution imaging of the distal metacarpus appears to have limited

  7. Multimodal quantitative phase and fluorescence imaging of cell apoptosis

    Science.gov (United States)

    Fu, Xinye; Zuo, Chao; Yan, Hao

    2017-06-01

    Fluorescence microscopy, utilizing fluorescence labeling, has the capability to observe intercellular changes which transmitted and reflected light microscopy techniques cannot resolve. However, the parts without fluorescence labeling are not imaged. Hence, the processes simultaneously happen in these parts cannot be revealed. Meanwhile, fluorescence imaging is 2D imaging where information in the depth is missing. Therefore the information in labeling parts is also not complete. On the other hand, quantitative phase imaging is capable to image cells in 3D in real time through phase calculation. However, its resolution is limited by the optical diffraction and cannot observe intercellular changes below 200 nanometers. In this work, fluorescence imaging and quantitative phase imaging are combined to build a multimodal imaging system. Such system has the capability to simultaneously observe the detailed intercellular phenomenon and 3D cell morphology. In this study the proposed multimodal imaging system is used to observe the cell behavior in the cell apoptosis. The aim is to highlight the limitations of fluorescence microscopy and to point out the advantages of multimodal quantitative phase and fluorescence imaging. The proposed multimodal quantitative phase imaging could be further applied in cell related biomedical research, such as tumor.

  8. Higher Vulnerability of Menadione-Exposed Cortical Astrocytes of Glutaryl-CoA Dehydrogenase Deficient Mice to Oxidative Stress, Mitochondrial Dysfunction, and Cell Death: Implications for the Neurodegeneration in Glutaric Aciduria Type I.

    Science.gov (United States)

    Rodrigues, Marília Danyelle Nunes; Seminotti, Bianca; Zanatta, Ângela; de Mello Gonçalves, Aline; Bellaver, Bruna; Amaral, Alexandre Umpierrez; Quincozes-Santos, André; Goodman, Stephen Irwin; Woontner, Michael; Souza, Diogo Onofre; Wajner, Moacir

    2017-08-01

    Patients affected by glutaric aciduria type I (GA-I) show progressive cortical leukoencephalopathy whose pathogenesis is poorly known. In the present work, we exposed cortical astrocytes of wild-type (Gcdh +/+ ) and glutaryl-CoA dehydrogenase knockout (Gcdh -/- ) mice to the oxidative stress inducer menadione and measured mitochondrial bioenergetics, redox homeostasis, and cell viability. Mitochondrial function (MTT and JC1-mitochondrial membrane potential assays), redox homeostasis (DCFH oxidation, nitrate and nitrite production, GSH concentrations and activities of the antioxidant enzymes SOD and GPx), and cell death (propidium iodide incorporation) were evaluated in primary cortical astrocyte cultures of Gcdh +/+ and Gcdh -/- mice unstimulated and stimulated by menadione. We also measured the pro-inflammatory response (TNFα levels, IL1-β and NF-ƙB) in unstimulated astrocytes obtained from these mice. Gcdh -/- mice astrocytes were more vulnerable to menadione-induced oxidative stress (decreased GSH concentrations and altered activities of the antioxidant enzymes), mitochondrial dysfunction (decrease of MTT reduction and JC1 values), and cell death as compared with Gcdh +/+ astrocytes. A higher inflammatory response (TNFα, IL1-β and NF-ƙB) was also observed in Gcdh -/- mice astrocytes. These data indicate a higher susceptibility of Gcdh -/- cortical astrocytes to oxidative stress and mitochondrial dysfunction, probably leading to cell death. It is presumed that these pathomechanisms may contribute to the cortical leukodystrophy observed in GA-I patients.

  9. Mapping the dynamics of cortical neuroplasticity of skilled motor learning using micro X-ray fluorescence and histofluorescence imaging of zinc in the rat

    Science.gov (United States)

    Alaverdashvili, Mariam; Paterson, Phyllis G.

    2017-01-01

    Synchrotron-based X-ray fluorescence imaging (XFI) of zinc (Zn) has been recently implemented to understand the efficiency of various therapeutic interventions targeting post-stroke neuroprotection and neuroplasticity. However, it is uncertain if micro XFI can resolve neuroplasticity-induced changes. Thus, we explored if learning-associated behavioral changes would be accompanied by changes in cortical Zn concentration measured by XFI in healthy adult rats. Proficiency in a skilled reach-to-eat task during early and late stages of motor learning served as a functional measure of neuroplasticity. c-Fos protein and vesicular Zn expression were employed as indirect neuronal measures of brain plasticity. A total Zn map (20 × 20 × 30 μm3 resolution) generated by micro XFI failed to reflect increases in either c-Fos or vesicular Zn in the motor cortex contralateral to the trained forelimb or improved proficiency in the skilled reaching task. Remarkably, vesicular Zn increased in the late stage of motor learning along with a concurrent decrease in the number of c-fos-ip neurons relative to the early stage of motor learning. This inverse dynamics of c-fos and vesicular Zn level as the motor skill advances suggest that a qualitatively different neural population, comprised of fewer active but more efficiently connected neurons, supports a skilled action in the late versus early stage of motor learning. The lack of sensitivity of the XFI-generated Zn map to visualize the plasticity-associated changes in vesicular Zn suggests that the Zn level measured by micro XFI should not be used as a surrogate marker of neuroplasticity in response to the acquisition of skilled motor actions. Nanoscopic XFI could be explored in future as a means of imaging these subtle physiological changes. PMID:27840249

  10. MR imaging features of spindle cell lipoma

    Energy Technology Data Exchange (ETDEWEB)

    Kirwadi, Anand; Abdul-Halim, Rehan; Highland, Adrian; Kotnis, Nikhil [Sheffield Teaching Hospitals NHS Trust, Radiology Department, Sheffield (United Kingdom); Fernando, Malee [Sheffield Teaching Hospitals NHS Trust, Histopathology Department, Sheffield (United Kingdom)

    2014-02-15

    To assess the MR imaging features of spindle cell lipomas (SCL) and to compare these appearances directly with the histopathological findings. A retrospective review of our soft tissue tumor database was performed. This yielded 1,327 histologically proven lipomas, of which 25 were confirmed as being SCLs. Fourteen of the 25 patients had MR examinations available for review and only these patients were included in our study. Lesions were assessed at MR examination for the degree of internal fat signal content with grade 0 representing 0 % fat signal and grade 4 100 % fat signal. The degree of fat suppression and contrast-enhancement pattern were also recorded. The excision specimens were independently reviewed by a consultant histopathologist. The histology specimens were assessed for the amount of internal fat and non-adipose tissue and graded using the same scale applied for the imaging. Where core needle biopsy (CNB) was performed, the CNB specimens were also examined for positive features of SCL. In our study, 93 % (13/14) of our patients were male and the average age was 58 years. 65 % (9/14) of the lesions presented in the upper back, shoulder, or neck. All lesions were subcutaneous. 35 % (5/14) of the SCLs demonstrated grade 3 (>75 %) or grade 4 (100 %) fat signal on MR examination. 35 % (5/14) of the lesions had grade 2 (25-75 %) fat signal and 29 % (4/14) of the lesions demonstrated grade 0 (0 %) or grade 1 (<25 %) fat signal. 43 % (6/14) of lesions demonstrated homogenous fat suppression, 28 % (4/14) showed focal areas of high internal signal, and 28 % (4/14) had diffuse internal high signal on fluid-sensitive fat-saturated sequences. 86 % (6/7) of the cases demonstrated septal/nodular enhancement. The diagnosis was evident on the CNB specimen in 100 % (9/9) cases. The histopathology fat content grade was in agreement with the imaging grade in 86 % (12/14) cases. The internal signal pattern of SCL can range broadly, with low fat content lesions seen almost

  11. The GluN2B subunit represents a major functional determinant of NMDA receptors in human induced pluripotent stem cell-derived cortical neurons

    Directory of Open Access Journals (Sweden)

    Ioana Neagoe

    2018-04-01

    Full Text Available Abnormal signaling pathways mediated by N-methyl-d-aspartate receptors (NMDARs have been implicated in the pathogenesis of various CNS disorders and have been long considered as promising points of therapeutic intervention. However, few efforts have been previously described concerning evaluation of therapeutic modulators of NMDARs and their downstream pathways in human neurons with endogenous expression of NMDARs. In the present study, we assessed expression, functionality, and subunit composition of endogenous NMDARs in human induced pluripotent stem cell (hiPSC-derived cortical neurons (iCell Neurons and iCell GlutaNeurons. We initially confirmed the expected pharmacological response of iCell Neurons and iCell GlutaNeurons to NMDA by patch-clamp recordings. Subsequent pharmacological interrogation using GluN2 subunit-selective antagonists revealed the predominance of GluN2B in both iCell Neurons and iCell GlutaNeurons. This observation was also supported by qRT-PCR and Western blot analyses of GluN2 subunit expression as well as pharmacological experiments using positive allosteric modulators with distinct GluN2 subunit selectivity. We conclude that iCell Neurons and iCell GlutaNeurons express functional GluN2B-containing NMDARs and could serve as a valuable system for development and validation of GluN2B-modulating pharmaceutical agents. Keywords: Human induced pluripotent stem cell-derived neurons, iCell Neurons, iCell GlutaNeurons, NMDA receptors, GluN2B, Positive allosteric modulators

  12. Molecular Imaging in Stem Cell Therapy for Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Fahuan Song

    2014-01-01

    Full Text Available Spinal cord injury (SCI is a serious disease of the center nervous system (CNS. It is a devastating injury with sudden loss of motor, sensory, and autonomic function distal to the level of trauma and produces great personal and societal costs. Currently, there are no remarkable effective therapies for the treatment of SCI. Compared to traditional treatment methods, stem cell transplantation therapy holds potential for repair and functional plasticity after SCI. However, the mechanism of stem cell therapy for SCI remains largely unknown and obscure partly due to the lack of efficient stem cell trafficking methods. Molecular imaging technology including positron emission tomography (PET, magnetic resonance imaging (MRI, optical imaging (i.e., bioluminescence imaging (BLI gives the hope to complete the knowledge concerning basic stem cell biology survival, migration, differentiation, and integration in real time when transplanted into damaged spinal cord. In this paper, we mainly review the molecular imaging technology in stem cell therapy for SCI.

  13. Enhancement of Median Nerve Regeneration by Mesenchymal Stem Cells Engraftment in an Absorbable Conduit: Improvement of Peripheral Nerve Morphology with Enlargement of Somatosensory Cortical Representation.

    Directory of Open Access Journals (Sweden)

    Julia Teixeira Oliveira

    2014-10-01

    Full Text Available We studied the morphology and the cortical representation of the median nerve (MN, 10 weeks after a transection immediately followed by treatment with tubulization using a polycaprolactone (PCL conduit with or without bone marrow-derived mesenchymal stem cell (MSC transplant. In order to characterize the cutaneous representation of MN inputs in primary somatosensory cortex (S1, electrophysiological cortical mapping of the somatosensory representation of the forepaw and adjacent body parts was performed after acute lesion of all brachial plexus nerves, except for the MN. This was performed in ten adult male Wistar rats randomly assigned in 3 groups: MN Intact (n=4, PCL-Only (n=3 and PCL+MSC (n=3. Ten weeks before mapping procedures in animals from PCL-Only and PCL+MSC groups, animal were subjected to MN transection with removal of a 4-mm-long segment, immediately followed by suturing a PCL conduit to the nerve stumps with (PCL+MSC group or without (PCL-Only group injection of MSC into the conduit. After mapping the representation of the MN in S1, animals had a segment of the regenerated nerve processed for light and transmission electron microscopy. For histomorphometric analysis of the nerve segment, sample size was increased to 5 animals per experimental group. The PCL+MSC group presented a higher number of myelinated fibers and a larger cortical representation of MN inputs in S1 (3,383±390 fibers; 2.3 mm2, respectively than the PCL-Only group (2,226±575 fibers; 1.6 mm2. In conclusion, MSC-based therapy associated with PCL conduits can improve MN regeneration. This treatment seems to rescue the nerve representation in S1, thus minimizing the stabilization of new representations of adjacent body parts in regions previously responsive to the MN.

  14. AUTOMATED CELL SEGMENTATION WITH 3D FLUORESCENCE MICROSCOPY IMAGES.

    Science.gov (United States)

    Kong, Jun; Wang, Fusheng; Teodoro, George; Liang, Yanhui; Zhu, Yangyang; Tucker-Burden, Carol; Brat, Daniel J

    2015-04-01

    A large number of cell-oriented cancer investigations require an effective and reliable cell segmentation method on three dimensional (3D) fluorescence microscopic images for quantitative analysis of cell biological properties. In this paper, we present a fully automated cell segmentation method that can detect cells from 3D fluorescence microscopic images. Enlightened by fluorescence imaging techniques, we regulated the image gradient field by gradient vector flow (GVF) with interpolated and smoothed data volume, and grouped voxels based on gradient modes identified by tracking GVF field. Adaptive thresholding was then applied to voxels associated with the same gradient mode where voxel intensities were enhanced by a multiscale cell filter. We applied the method to a large volume of 3D fluorescence imaging data of human brain tumor cells with (1) small cell false detection and missing rates for individual cells; and (2) trivial over and under segmentation incidences for clustered cells. Additionally, the concordance of cell morphometry structure between automated and manual segmentation was encouraging. These results suggest a promising 3D cell segmentation method applicable to cancer studies.

  15. Atrophy and Primary Somatosensory Cortical Reorganization after Unilateral Thoracic Spinal Cord Injury: A Longitudinal Functional Magnetic Resonance Imaging Study

    Directory of Open Access Journals (Sweden)

    Jia-Sheng Rao

    2013-01-01

    Full Text Available The effects of traumatic spinal cord injury (SCI on the changes in the central nervous system (CNS over time may depend on the dynamic interaction between the structural integrity of the spinal cord and the capacity of the brain plasticity. Functional magnetic resonance imaging (fMRI was used in a longitudinal study on five rhesus monkeys to observe cerebral activation during upper limb somatosensory tasks in healthy animals and after unilateral thoracic SCI. The changes in the spinal cord diameters were measured, and the correlations among time after the lesion, structural changes in the spinal cord, and primary somatosensory cortex (S1 reorganization were also determined. After SCI, activation of the upper limb in S1 shifted to the region which generally dominates the lower limb, and the rostral spinal cord transverse diameter adjacent to the lesion exhibited obvious atrophy, which reflects the SCI-induced changes in the CNS. A significant correlation was found among the time after the lesion, the spinal cord atrophy, and the degree of contralateral S1 reorganization. The results indicate the structural changes in the spinal cord and the dynamic reorganization of the cerebral activation following early SCI stage, which may help to further understand the neural plasticity in the CNS.

  16. Cell-based therapies and imaging in cardiology.

    Science.gov (United States)

    Bengel, Frank M; Schachinger, Volker; Dimmeler, Stefanie

    2005-12-01

    Cell therapy for cardiac repair has emerged as one of the most exciting and promising developments in cardiovascular medicine. Evidence from experimental and clinical studies is increasing that this innovative treatment will influence clinical practice in the future. But open questions and controversies with regard to the basic mechanisms of this therapy continue to exist and emphasise the need for specific techniques to visualise the mechanisms and success of therapy in vivo. Several non-invasive imaging approaches which aim at tracking of transplanted cells in the heart have been introduced. Among these are direct labelling of cells with radionuclides or paramagnetic agents, and the use of reporter genes for imaging of cell transplantation and differentiation. Initial studies have suggested that these molecular imaging techniques have great potential. Integration of cell imaging into studies of cardiac cell therapy holds promise to facilitate further growth of the field towards a broadly clinically useful application.

  17. Cell-based therapies and imaging in cardiology

    Energy Technology Data Exchange (ETDEWEB)

    Bengel, Frank M. [Technische Universitaet Muenchen, Nuklearmedizinische Klinik und Poliklinik, Munich (Germany); Schachinger, Volker; Dimmeler, Stefanie [University of Frankfurt, Department of Molecular Cardiology, Frankfurt (Germany)

    2005-12-01

    Cell therapy for cardiac repair has emerged as one of the most exciting and promising developments in cardiovascular medicine. Evidence from experimental and clinical studies is increasing that this innovative treatment will influence clinical practice in the future. But open questions and controversies with regard to the basic mechanisms of this therapy continue to exist and emphasise the need for specific techniques to visualise the mechanisms and success of therapy in vivo. Several non-invasive imaging approaches which aim at tracking of transplanted cells in the heart have been introduced. Among these are direct labelling of cells with radionuclides or paramagnetic agents, and the use of reporter genes for imaging of cell transplantation and differentiation. Initial studies have suggested that these molecular imaging techniques have great potential. Integration of cell imaging into studies of cardiac cell therapy holds promise to facilitate further growth of the field towards a broadly clinically useful application. (orig.)

  18. Autofluorescence imaging of basal cell carcinoma by smartphone RGB camera

    Science.gov (United States)

    Lihachev, Alexey; Derjabo, Alexander; Ferulova, Inesa; Lange, Marta; Lihacova, Ilze; Spigulis, Janis

    2015-12-01

    The feasibility of smartphones for in vivo skin autofluorescence imaging has been investigated. Filtered autofluorescence images from the same tissue area were periodically captured by a smartphone RGB camera with subsequent detection of fluorescence intensity decreasing at each image pixel for further imaging the planar distribution of those values. The proposed methodology was tested clinically with 13 basal cell carcinoma and 1 atypical nevus. Several clinical cases and potential future applications of the smartphone-based technique are discussed.

  19. Investigation progress of imaging techniques monitoring stem cell therapy

    International Nuclear Information System (INIS)

    Wu Jun; An Rui

    2006-01-01

    Recently stem cell therapy has showed potential clinical application in diabetes mellitus, cardiovascular diseases, malignant tumor and trauma. Efficient techniques of non-invasively monitoring stem cell transplants will accelerate the development of stem cell therapies. This paper briefly reviews the clinical practice of stem cell, in addition, makes a review of monitoring methods including magnetic resonance and radionuclide imaging which have been used in stem cell therapy. (authors)

  20. 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 ...

  1. Ethanol-induced transcriptional activation of programmed cell death 4 (Pdcd4 is mediated by GSK-3β signaling in rat cortical neuroblasts.

    Directory of Open Access Journals (Sweden)

    Amanjot Kaur Riar

    Full Text Available Ingestion of ethanol (ETOH during pregnancy induces grave abnormalities in developing fetal brain. We have previously reported that ETOH induces programmed cell death 4 (PDCD4, a critical regulator of cell growth, in cultured fetal cerebral cortical neurons (PCNs and in the cerebral cortex in vivo and affect protein synthesis as observed in Fetal Alcohol Spectrum Disorder (FASD. However, the mechanism which activates PDCD4 in neuronal systems is unclear and understanding this regulation may provide a counteractive strategy to correct the protein synthesis associated developmental changes seen in FASD. The present study investigates the molecular mechanism by which ethanol regulates PDCD4 in cortical neuroblasts, the immediate precursor of neurons. ETOH treatment significantly increased PDCD4 protein and transcript expression in spontaneously immortalized rat brain neuroblasts. Since PDCD4 is regulated at both the post-translational and post-transcriptional level, we assessed ETOH's effect on PDCD4 protein and mRNA stability. Chase experiments demonstrated that ETOH does not significantly impact either PDCD4 protein or mRNA stabilization. PDCD4 promoter-reporter assays confirmed that PDCD4 is transcriptionally regulated by ETOH in neuroblasts. Given a critical role of glycogen synthase kinase 3β (GSK-3β signaling in regulating protein synthesis and neurotoxic mechanisms, we investigated the involvement of GSK-3β and showed that multifunctional GSK-3β was significantly activated in response to ETOH in neuroblasts. In addition, we found that ETOH-induced activation of PDCD4 was inhibited by pharmacologic blockade of GSK-3β using inhibitors, lithium chloride (LiCl and SB-216763 or siRNA mediated silencing of GSK-3β. These results suggest that ethanol transcriptionally upregulates PDCD4 by enhancing GSK-3β signaling in cortical neuroblasts. Further, we demonstrate that canonical Wnt-3a/GSK-3β signaling is involved in regulating PDCD4 protein

  2. 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.

  3. 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

  4. Preparation of Single Cells for Imaging Mass Spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Berman, E S; Fortson, S L; Kulp, K S; Checchi, K D; Wu, L; Felton, J S; Wu, K J

    2007-10-24

    Characterizing chemical changes within single cells is important for determining fundamental mechanisms of biological processes that will lead to new biological insights and improved disease understanding. Imaging biological systems with mass spectrometry (MS) has gained popularity in recent years as a method for creating precise chemical maps of biological samples. In order to obtain high-quality mass spectral images that provide relevant molecular information about individual cells, samples must be prepared so that salts and other cell-culture components are removed from the cell surface and the cell contents are rendered accessible to the desorption beam. We have designed a cellular preparation protocol for imaging MS that preserves the cellular contents for investigation and removes the majority of the interfering species from the extracellular matrix. Using this method, we obtain excellent imaging results and reproducibility in three diverse cell types: MCF7 human breast cancer cells, Madin-Darby canine kidney (MDCK) cells, and NIH/3T3 mouse fibroblasts. This preparation technique allows routine imaging MS analysis of cultured cells, allowing for any number of experiments aimed at furthering scientific understanding of molecular processes within individual cells.

  5. In vivo SPECT reporter gene imaging of regulatory T cells.

    Directory of Open Access Journals (Sweden)

    Ehsan Sharif-Paghaleh

    Full Text Available Regulatory T cells (Tregs were identified several years ago and are key in controlling autoimmune diseases and limiting immune responses to foreign antigens, including alloantigens. In vivo imaging techniques including intravital microscopy as well as whole body imaging using bioluminescence probes have contributed to the understanding of in vivo Treg function, their mechanisms of action and target cells. Imaging of the human sodium/iodide symporter via Single Photon Emission Computed Tomography (SPECT has been used to image various cell types in vivo. It has several advantages over the aforementioned imaging techniques including high sensitivity, it allows non-invasive whole body studies of viable cell migration and localisation of cells over time and lastly it may offer the possibility to be translated to the clinic. This study addresses whether SPECT/CT imaging can be used to visualise the migratory pattern of Tregs in vivo. Treg lines derived from CD4(+CD25(+FoxP3(+ cells were retrovirally transduced with a construct encoding for the human Sodium Iodide Symporter (NIS and the fluorescent protein mCherry and stimulated with autologous DCs. NIS expressing self-specific Tregs were specifically radiolabelled in vitro with Technetium-99m pertechnetate ((99mTcO(4(- and exposure of these cells to radioactivity did not affect cell viability, phenotype or function. In addition adoptively transferred Treg-NIS cells were imaged in vivo in C57BL/6 (BL/6 mice by SPECT/CT using (99mTcO(4(-. After 24 hours NIS expressing Tregs were observed in the spleen and their localisation was further confirmed by organ biodistribution studies and flow cytometry analysis. The data presented here suggests that SPECT/CT imaging can be utilised in preclinical imaging studies of adoptively transferred Tregs without affecting Treg function and viability thereby allowing longitudinal studies within disease models.

  6. 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.

  7. Synergy by secretory phospholipase A2 and glutamate on inducing cell death and sustained arachidonic acid metabolic changes in primary cortical neuronal cultures

    DEFF Research Database (Denmark)

    Kolko, M; DeCoster, M A; de Turco, E B

    1996-01-01

    glutamate and sPLA2 from bee venom. sPLA2, at concentrations eliciting low neurotoxicity (acid into triacylglycerols. Free [3H]arachidonic acid accumulated at higher enzyme concentrations......, from Taipan snake venom. The NMDA receptor antagonist MK-801 blocked glutamate effects and partially inhibited sPLA2 OS2 but not sPLA2 from bee venom-induced arachidonic acid release. Thus, the synergy with glutamate and very low concentrations of exogenously added sPLA2 suggests a potential role......Secretory and cytosolic phospholipases A2 (sPLA2 and cPLA2) may contribute to the release of arachidonic acid and other bioactive lipids, which are modulators of synaptic function. In primary cortical neuron cultures, neurotoxic cell death and [3H]arachidonate metabolism was studied after adding...

  8. Optofluidic fluorescent imaging cytometry on a cell phone.

    Science.gov (United States)

    Zhu, Hongying; Mavandadi, Sam; Coskun, Ahmet F; Yaglidere, Oguzhan; Ozcan, Aydogan

    2011-09-01

    Fluorescent microscopy and flow cytometry are widely used tools in biomedical sciences. Cost-effective translation of these technologies to remote and resource-limited environments could create new opportunities especially for telemedicine applications. Toward this direction, here we demonstrate the integration of imaging cytometry and fluorescent microscopy on a cell phone using a compact, lightweight, and cost-effective optofluidic attachment. In this cell-phone-based optofluidic imaging cytometry platform, fluorescently labeled particles or cells of interest are continuously delivered to our imaging volume through a disposable microfluidic channel that is positioned above the existing camera unit of the cell phone. The same microfluidic device also acts as a multilayered optofluidic waveguide and efficiently guides our excitation light, which is butt-coupled from the side facets of our microfluidic channel using inexpensive light-emitting diodes. Since the excitation of the sample volume occurs through guided waves that propagate perpendicular to the detection path, our cell-phone camera can record fluorescent movies of the specimens as they are flowing through the microchannel. The digital frames of these fluorescent movies are then rapidly processed to quantify the count and the density of the labeled particles/cells within the target solution of interest. We tested the performance of our cell-phone-based imaging cytometer by measuring the density of white blood cells in human blood samples, which provided a decent match to a commercially available hematology analyzer. We further characterized the imaging quality of the same platform to demonstrate a spatial resolution of ~2 μm. This cell-phone-enabled optofluidic imaging flow cytometer could especially be useful for rapid and sensitive imaging of bodily fluids for conducting various cell counts (e.g., toward monitoring of HIV+ patients) or rare cell analysis as well as for screening of water quality in

  9. Red blood cell image enhancement techniques for cells with ...

    African Journals Online (AJOL)

    quality or challenging conditions of the images such as poor illumination of blood smear and most importantly overlapping RBC. The algorithm comprises of two RBC segmentation that can be selected based on the image quality, circle mask technique and grayscale blood smear image processing. Detail explanations ...

  10. Live Cell Imaging of Alphaherpes Virus Anterograde Transport and Spread

    Science.gov (United States)

    Taylor, Matthew P.; Kratchmarov, Radomir; Enquist, Lynn W.

    2013-01-01

    Advances in live cell fluorescence microscopy techniques, as well as the construction of recombinant viral strains that express fluorescent fusion proteins have enabled real-time visualization of transport and spread of alphaherpes virus infection of neurons. The utility of novel fluorescent fusion proteins to viral membrane, tegument, and capsids, in conjunction with live cell imaging, identified viral particle assemblies undergoing transport within axons. Similar tools have been successfully employed for analyses of cell-cell spread of viral particles to quantify the number and diversity of virions transmitted between cells. Importantly, the techniques of live cell imaging of anterograde transport and spread produce a wealth of information including particle transport velocities, distributions of particles, and temporal analyses of protein localization. Alongside classical viral genetic techniques, these methodologies have provided critical insights into important mechanistic questions. In this article we describe in detail the imaging methods that were developed to answer basic questions of alphaherpes virus transport and spread. PMID:23978901

  11. Statolith Sedimentation Kinetics and Force Transduction to the Cortical Endoplasmic Reticulum in Gravity-Sensing Arabidopsis Columella Cells[W][OA

    Science.gov (United States)

    Leitz, Guenther; Kang, Byung-Ho; Schoenwaelder, Monica E.A.; Staehelin, L. Andrew

    2009-01-01

    The starch statolith hypothesis of gravity sensing in plants postulates that the sedimentation of statoliths in specialized statocytes (columella cells) provides the means for converting the gravitational potential energy into a biochemical signal. We have analyzed the sedimentation kinetics of statoliths in the central S2 columella cells of Arabidopsis thaliana. The statoliths can form compact aggregates with gap sizes between statoliths approaching sedimentation phase, the statoliths tend to move at a distance to the cortical endoplasmic reticulum (ER) boundary and interact only transiently with the ER. Statoliths moved by laser tweezers against the ER boundary experience an elastic lift force upon release from the optical trap. High-resolution electron tomography analysis of statolith-to-ER contact sites indicate that the weight of statoliths is sufficient to locally deform the ER membranes that can potentially activate mechanosensitive ion channels. We suggest that in root columella cells, the transduction of the kinetic energy of sedimenting statoliths into a biochemical signal involves a combination of statolith-driven motion of the cytosol, statolith-induced deformation of the ER membranes, and a rapid release of kinetic energy from the ER during reorientation to activate mechanosensitive sites within the central columella cells. PMID:19276442

  12. Similar PDK1-AKT-mTOR pathway activation in balloon cells and dysmorphic neurons of type II focal cortical dysplasia with refractory epilepsy.

    Science.gov (United States)

    Lin, Yuan-xiang; Lin, Kun; Kang, De-zhi; Liu, Xin-xiu; Wang, Xing-fu; Zheng, Shu-fa; Yu, Liang-hong; Lin, Zhang-ya

    2015-05-01

    Dysmorphic neurons and balloon cells constitute the neuropathological hallmarks of type II focal cortical dysplasias (FCDs) with refractory epilepsy. The genesis of these cells may be critical to the histological findings in type II FCD. Recent work has shown enhanced activation of the mTOR cascade in both balloon cells and dysmorphic neurons, suggesting a common pathogenesis for these two neuropathological hallmarks. A direct comparative analysis of balloon cells and dysmorphic neurons might identify a molecular link between balloon cells and dysmorphic neurons. Here, we addressed whether PDK1-AKT-mTOR activation differentiates balloon cells from dysmorphic neurons. We used immunohistochemistry with antibodies against phosphorylated (p)-PDK1 (Ser241), p-AKT (Thr308), p-AKT (Ser473), p-mTOR (Ser2448), p-P70S6K (Thr229), and p-p70S6 kinase (Thr389) in balloon cells compared with dysmorphic neurons. Strong or moderate staining for components of the PDK1-AKT-mTOR signaling pathway was observed in both balloon cells and dysmorphic neurons. However, only a few pyramidal neurons displayed weak staining in control group (perilesional neocortex and histologically normal neocortex). Additionally, p-PDK1 (Ser241) and p-AKT (Thr308) staining in balloon cells were stronger than in dysmorphic neurons, whereas p-P70S6K (Thr229) and p-p70S6 kinase (Thr389) staining in balloon cells was weaker than in dysmorphic neurons. In balloon cells, p-AKT (Ser473) and p-mTOR (Ser2448) staining was comparable with the staining in dysmorphic neurons. Our data support the previously suggested pathogenic relationship between balloon cells and dysmorphic neurons concerning activation of the PDK1-AKT-mTOR, which may play important roles in the pathogenesis of type II FCD. Differential expression of some components of the PDK1-AKT-mTOR pathway between balloon cells and dysmorphic neurons may result from cell-specific gene expression. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Design of microdevices for long-term live cell imaging

    International Nuclear Information System (INIS)

    Chen, Huaying; Nordon, Robert E; Rosengarten, Gary; Li, Musen

    2012-01-01

    Advances in fluorescent live cell imaging provide high-content information that relates a cell's life events to its ancestors. An important requirement to track clonal growth and development is the retention of motile cells derived from an ancestor within the same microscopic field of view for days to weeks, while recording fluorescence images and controlling the mechanical and biochemical microenvironments that regulate cell growth and differentiation. The aim of this study was to design a microwell device for long-term, time-lapse imaging of motile cells with the specific requirements of (a) inoculating devices with an average of one cell per well and (b) retaining progeny of cells within a single microscopic field of view for extended growth periods. A two-layer PDMS microwell culture device consisting of a parallel-plate flow cell bonded on top of a microwell array was developed for cell capture and clonal culture. Cell deposition statistics were related to microwell geometry (plate separation and well depth) and the Reynolds number. Computational fluid dynamics was used to simulate flow in the microdevices as well as cell–fluid interactions. Analysis of the forces acting upon a cell was used to predict cell docking zones, which were confirmed by experimental observations. Cell–fluid dynamic interactions are important considerations for design of microdevices for long-term, live cell imaging. The analysis of force and torque balance provides a reasonable approximation for cell displacement forces. It is computationally less intensive compared to simulation of cell trajectories, and can be applied to a wide range of microdevice geometries to predict the cell docking behavior. (paper)

  14. Self-adhesive microculture system for extended live cell imaging.

    Science.gov (United States)

    Skommer, J; McGuinness, D; Wlodkowic, D

    2011-06-01

    Gas permeable and biocompatible soft polymers are convenient for biological applications. Using the soft polymer poly(dimethylsiloxane) (PDMS), we established a straightforward technique for in-house production of self-adhesive and optical grade microculture devices. A gas permeable PDMS layer effectively protects against medium evaporation, changes in osmolarity, contamination and drug diffusion. These chip-based devices can be used effectively for long term mammalian cell culture and support a range of bioassays used in pharmacological profiling of anti-cancer drugs. Results obtained on a panel of hematopoietic and solid tumor cell lines during screening of investigative anti-cancer agents corresponded well to those obtained in a conventional cell culture on polystyrene plates. The cumulative correlation analysis of multiple cell lines and anti-cancer drugs showed no adverse effects on cell viability or cell growth retardation during microscale static cell culture. PDMS devices also can be custom modified for many bio-analytical purposes and are interfaced easily with both inverted and upright cell imaging platforms. Moreover, PDMS microculture devices are suitable for extended real time cell imaging. Data from the multicolor, real time analysis of apoptosis on human breast cancer MCF-7 cells provided further evidence that elimination of redundant centrifugation/washing achieved during microscale real time analysis facilitates preservation of fragile apoptotic cells and provides dynamic cellular information at high resolution. Because only small reaction volumes are required, such devices offer reduced use of consumables as well as simplified manipulations during all stages of live cell imaging.

  15. MRI of fibrous cortical defect and non-ossifying fibroma

    Energy Technology Data Exchange (ETDEWEB)

    Mishima, Yoshiko; Aoki, Takatoshi; Watanabe, Hideyuki; Nakata, Hajime; Hashimoto, Hiroshi; Nakamura, Toshitaka [Univ. of Occupational and Environmental Health, Kitakyushu, Fukuoka (Japan). School of Medicine

    1999-02-01

    Fibrous cortical defect and non-ossifying fibroma are the benign fibrous lesions of bone commonly involving children. Their diagnosis is usually done with radiography, and MR examinations are rarely performed. We evaluated MRI findings of 11 lesions in 10 cases of fibrous cortical defect and non-ossifying fibroma. Signal intensity of the lesions was varied and large lesions (2 cm<) tended to show heterogeneous signal intensity on both T1-weighted and T2-weighted images corresponding to a mixture of components including fibrous tissue, hemosiderin and foam cells. MRI helps to delineate the extent of the involved bone and to assess the various histological components of the lesions. However, their diagnosis is basically made on the radiographic findings and the role of MRI is limited. (author)

  16. 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

  17. Close the Textbook & Open "The Cell: An Image Library"

    Science.gov (United States)

    Saunders, Cheston; Taylor, Amy

    2014-01-01

    Many students leave the biology classroom with misconceptions centered on cellular structure. This article presents an activity in which students utilize images from an online database called "The Cell: An Image Library" (http://www.cellimagelibrary. org/) to gain a greater understanding of the diversity of cellular structure and the…

  18. Molecular Imaging and Therapy of Merkel Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Beylergil, Volkan, E-mail: beylergv@mskcc.org [Molecular and Imaging Therapy Service, Department of Radiology Box 77, Memorial Sloan-Kettering Cancer Center 1275 York Ave, New York, NY 10065 (United States); Carrasquillo, Jorge A. [Molecular and Imaging Therapy Service, Department of Radiology Box 77, Memorial Sloan-Kettering Cancer Center 1275 York Ave, New York, NY 10065 (United States); Department of Radiology, Weill Cornell Medical Center, New York, NY 10065 (United States)

    2014-04-29

    Several molecular imaging modalities have been evaluated in the management of Merkel cell carcinoma (MCC), a rare and aggressive tumor with a high tendency to metastasize. Continuous progress in the field of molecular imaging might improve management in these patients. The authors review the current modalities and their impact on MCC in this brief review article.

  19. Molecular Imaging and Therapy of Merkel Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Volkan Beylergil

    2014-04-01

    Full Text Available Several molecular imaging modalities have been evaluated in the management of Merkel cell carcinoma (MCC, a rare and aggressive tumor with a high tendency to metastasize. Continuous progress in the field of molecular imaging might improve management in these patients. The authors review the current modalities and their impact on MCC in this brief review article.

  20. Deep Learning Automates the Quantitative Analysis of Individual Cells in Live-Cell Imaging Experiments.

    Science.gov (United States)

    Van Valen, David A; Kudo, Takamasa; Lane, Keara M; Macklin, Derek N; Quach, Nicolas T; DeFelice, Mialy M; Maayan, Inbal; Tanouchi, Yu; Ashley, Euan A; Covert, Markus W

    2016-11-01

    Live-cell imaging has opened an exciting window into the role cellular heterogeneity plays in dynamic, living systems. A major critical challenge for this class of experiments is the problem of image segmentation, or determining which parts of a microscope image correspond to which individual cells. Current approaches require many hours of manual curation and depend on approaches that are difficult to share between labs. They are also unable to robustly segment the cytoplasms of mammalian cells. Here, we show that deep convolutional neural networks, a supervised machine learning method, can solve this challenge for multiple cell types across the domains of life. We demonstrate that this approach can robustly segment fluorescent images of cell nuclei as well as phase images of the cytoplasms of individual bacterial and mammalian cells from phase contrast images without the need for a fluorescent cytoplasmic marker. These networks also enable the simultaneous segmentation and identification of different mammalian cell types grown in co-culture. A quantitative comparison with prior methods demonstrates that convolutional neural networks have improved accuracy and lead to a significant reduction in curation time. We relay our experience in designing and optimizing deep convolutional neural networks for this task and outline several design rules that we found led to robust performance. We conclude that deep convolutional neural networks are an accurate method that require less curation time, are generalizable to a multiplicity of cell types, from bacteria to mammalian cells, and expand live-cell imaging capabilities to include multi-cell type systems.

  1. Segmentation and classification of cell cycle phases in fluorescence imaging.

    Science.gov (United States)

    Ersoy, Ilker; Bunyak, Filiz; Chagin, Vadim; Cardoso, M Christina; Palaniappan, Kannappan

    2009-01-01

    Current chemical biology methods for studying spatiotemporal correlation between biochemical networks and cell cycle phase progression in live-cells typically use fluorescence-based imaging of fusion proteins. Stable cell lines expressing fluorescently tagged protein GFP-PCNA produce rich, dynamically varying sub-cellular foci patterns characterizing the cell cycle phases, including the progress during the S-phase. Variable fluorescence patterns, drastic changes in SNR, shape and position changes and abundance of touching cells require sophisticated algorithms for reliable automatic segmentation and cell cycle classification. We extend the recently proposed graph partitioning active contours (GPAC) for fluorescence-based nucleus segmentation using regional density functions and dramatically improve its efficiency, making it scalable for high content microscopy imaging. We utilize surface shape properties of GFP-PCNA intensity field to obtain descriptors of foci patterns and perform automated cell cycle phase classification, and give quantitative performance by comparing our results to manually labeled data.

  2. Small molecule probes for plant cell wall polysaccharide imaging

    Directory of Open Access Journals (Sweden)

    Ian eWallace

    2012-05-01

    Full Text Available Plant cell walls are composed of interlinked polymer networks consisting of cellulose, hemicelluloses, pectins, proteins, and lignin. The ordered deposition of these components is a dynamic process that critically affects the development and differentiation of plant cells. However, our understanding of cell wall synthesis and remodeling, as well as the diverse cell wall architectures that result from these processes, has been limited by a lack of suitable chemical probes that are compatible with live-cell imaging. In this review, we summarize the currently available molecular toolbox of probes for cell wall polysaccharide imaging in plants, with particular emphasis on recent advances in small molecule-based fluorescent probes. We also discuss the potential for further development of small molecule probes for the analysis of cell wall architecture and dynamics.

  3. Quantitative volumetric Raman imaging of three dimensional cell cultures

    Science.gov (United States)

    Kallepitis, Charalambos; Bergholt, Mads S.; Mazo, Manuel M.; Leonardo, Vincent; Skaalure, Stacey C.; Maynard, Stephanie A.; Stevens, Molly M.

    2017-03-01

    The ability to simultaneously image multiple biomolecules in biologically relevant three-dimensional (3D) cell culture environments would contribute greatly to the understanding of complex cellular mechanisms and cell-material interactions. Here, we present a computational framework for label-free quantitative volumetric Raman imaging (qVRI). We apply qVRI to a selection of biological systems: human pluripotent stem cells with their cardiac derivatives, monocytes and monocyte-derived macrophages in conventional cell culture systems and mesenchymal stem cells inside biomimetic hydrogels that supplied a 3D cell culture environment. We demonstrate visualization and quantification of fine details in cell shape, cytoplasm, nucleus, lipid bodies and cytoskeletal structures in 3D with unprecedented biomolecular specificity for vibrational microspectroscopy.

  4. PET molecular imaging in stem cell therapy for neurological diseases

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jiachuan; Zhang, Hong [Second Affiliated Hospital of Zhejiang University School of Medicine, Department of Nuclear Medicine, Hangzhou, Zhejiang (China); Zhejiang University, Medical PET Center, Hangzhou (China); Institute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou (China); Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou (China); Tian, Mei [University of Texas, M.D. Anderson Cancer Center, Department of Experimental Diagnostic Imaging, Houston, TX (United States)

    2011-10-15

    Human neurological diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal cord injury and multiple sclerosis are caused by loss of different types of neurons and glial cells in the brain and spinal cord. At present, there are no effective therapies against these disorders. Discovery of the therapeutic potential of stem cells offers new strategies for the treatment of neurological diseases. Direct assessment of stem cells' survival, interaction with the host and impact on neuronal functions after transplantation requires advanced in vivo imaging techniques. Positron emission tomography (PET) is a potential molecular imaging modality to evaluate the viability and function of transplanted tissue or stem cells in the nervous system. This review focuses on PET molecular imaging in stem cell therapy for neurological diseases. (orig.)

  5. Dynamic imaging of cell-free and cell-associated viral capture in mature dendritic cells.

    Science.gov (United States)

    Izquierdo-Useros, Nuria; Esteban, Olga; Rodriguez-Plata, Maria T; Erkizia, Itziar; Prado, Julia G; Blanco, Julià; García-Parajo, Maria F; Martinez-Picado, Javier

    2011-12-01

    Dendritic cells (DCs) capture human immunodeficiency virus (HIV) through a non-fusogenic mechanism that enables viral transmission to CD4(+) T cells, contributing to in vivo viral dissemination. Although previous studies have provided important clues to cell-free viral capture by mature DCs (mDCs), dynamic and kinetic insight on this process is still missing. Here, we used three-dimensional video microscopy and single-particle tracking approaches to dynamically dissect both cell-free and cell-associated viral capture by living mDCs. We show that cell-free virus capture by mDCs operates through three sequential phases: virus binding through specific determinants expressed in the viral particle, polarized or directional movements toward concrete regions of the cell membrane and virus accumulation in a sac-like structure where trapped viral particles display a hindered diffusive behavior. Moreover, real-time imaging of cell-associated viral transfer to mDCs showed a similar dynamics to that exhibited by cell-free virus endocytosis leading to viral accumulation in compartments. However, cell-associated HIV type 1 transfer to mDCs was the most effective pathway, boosted throughout enhanced cellular contacts with infected CD4(+) T cells. Our results suggest that in lymphoid tissues, mDC viral uptake could occur either by encountering cell-free or cell-associated virus produced by infected cells generating the perfect scenario to promote HIV pathogenesis and impact disease progression. © 2011 John Wiley & Sons A/S.

  6. Immunomagnetic cell separation, imaging, and analysis using Captivate ferrofluids

    Science.gov (United States)

    Jones, Laurie; Beechem, Joseph M.

    2002-05-01

    We have developed applications of CaptivateTM ferrofluids, paramagnetic particles (approximately 200 nm diameter), for isolating and analyzing cell populations in combination with fluorescence-based techniques. Using a microscope-mounted magnetic yoke and sample insertion chamber, fluorescent images of magnetically captured cells were obtained in culture media, buffer, or whole blood, while non-magnetically labeled cells sedimented to the bottom of the chamber. We combined this immunomagnetic cell separation and imaging technique with fluorescent staining, spectroscopy, and analysis to evaluate cell surface receptor-containing subpopulations, live/dead cell ratios, apoptotic/dead cell ratios, etc. The acquired images were analyzed using multi-color parameters, as produced by nucleic acid staining, esterase activity, or antibody labeling. In addition, the immunomagnetically separated cell fractions were assessed through microplate analysis using the CyQUANT Cell Proliferation Assay. These methods should provide an inexpensive alternative to some flow cytometric measurements. The binding capacities of the streptavidin- labled Captivate ferrofluid (SA-FF) particles were determined to be 8.8 nmol biotin/mg SA-FF, using biotin-4- fluorescein, and > 106 cells/mg SA-FF, using several cell types labeled with biotinylated probes. For goat anti- mouse IgG-labeled ferrofluids (GAM-FF), binding capacities were established to be approximately 0.2 - 7.5 nmol protein/mg GAM-FF using fluorescent conjugates of antibodies, protein G, and protein A.

  7. Characterization of energy and neurotransmitter metabolism in cortical glutamatergic neurons derived from human induced pluripotent stem cells: A novel approach to study metabolism in human neurons.

    Science.gov (United States)

    Aldana, Blanca I; Zhang, Yu; Lihme, Maria Fog; Bak, Lasse K; Nielsen, Jørgen E; Holst, Bjørn; Hyttel, Poul; Freude, Kristine K; Waagepetersen, Helle S

    2017-06-01

    Alterations in the cellular metabolic machinery of the brain are associated with neurodegenerative disorders such as Alzheimer's disease. Novel human cellular disease models are essential in order to study underlying disease mechanisms. In the present study, we characterized major metabolic pathways in neurons derived from human induced pluripotent stem cells (hiPSC). With this aim, cultures of hiPSC-derived neurons were incubated with [U- 13 C]glucose, [U- 13 C]glutamate or [U- 13 C]glutamine. Isotopic labeling in metabolites was determined using gas chromatography coupled to mass spectrometry, and cellular amino acid content was quantified by high-performance liquid chromatography. Additionally, we evaluated mitochondrial function using real-time assessment of oxygen consumption via the Seahorse XF e 96 Analyzer. Moreover, in order to validate the hiPSC-derived neurons as a model system, a metabolic profiling was performed in parallel in primary neuronal cultures of mouse cerebral cortex and cerebellum. These serve as well-established models of GABAergic and glutamatergic neurons, respectively. The hiPSC-derived neurons were previously characterized as being forebrain-specific cortical glutamatergic neurons. However, a comparable preparation of predominantly mouse cortical glutamatergic neurons is not available. We found a higher glycolytic capacity in hiPSC-derived neurons compared to mouse neurons and a substantial oxidative metabolism through the mitochondrial tricarboxylic acid (TCA) cycle. This finding is supported by the extracellular acidification and oxygen consumption rates measured in the cultured human neurons. [U- 13 C]Glutamate and [U- 13 C]glutamine were found to be efficient energy substrates for the neuronal cultures originating from both mice and humans. Interestingly, isotopic labeling in metabolites from [U- 13 C]glutamate was higher than that from [U- 13 C]glutamine. Although the metabolic profile of hiPSC-derived neurons in vitro was

  8. Comparison of four decontamination treatments on porcine renal decellularized extracellular matrix structure, composition, and support of human renal cortical tubular epithelium cells.

    Science.gov (United States)

    Poornejad, Nafiseh; Nielsen, Jeffery J; Morris, Ryan J; Gassman, Jason R; Reynolds, Paul R; Roeder, Beverly L; Cook, Alonzo D

    2016-03-01

    Engineering whole organs from porcine decellularized extracellular matrix and human cells may lead to a plentiful source of implantable organs. Decontaminating the porcine decellularized extracellular matrix scaffolds is an essential step prior to introducing human cells. However, decontamination of whole porcine kidneys is a major challenge because the decontamination agent or irradiation needs to diffuse deep into the structure to eliminate all microbial contamination while minimizing damage to the structure and composition of the decellularized extracellular matrix. In this study, we compared four decontamination treatments that could be applicable to whole porcine kidneys: 70% ethanol, 0.2% peracetic acid in 1 M NaCl, 0.2% peracetic acid in 4% ethanol, and gamma (γ)-irradiation. Porcine kidneys were decellularized by perfusion of 0.5% (w/v) aqueous solution of sodium dodecyl sulfate and the four decontamination treatments were optimized using segments (n = 60) of renal tissue to ensure a consistent comparison. Although all four methods were successful in decontamination, γ-irradiation was very damaging to collagen fibers and glycosaminoglycans, leading to less proliferation of human renal cortical tubular epithelium cells within the porcine decellularized extracellular matrix. The effectiveness of the other three optimized solution treatments were then all confirmed using whole decellularized porcine kidneys (n = 3). An aqueous solution of 0.2% peracetic acid in 1 M NaCl was determined to be the best method for decontamination of porcine decellularized extracellular matrix. © The Author(s) 2015.

  9. Temperature-dependent imaging of living cells by AFM

    International Nuclear Information System (INIS)

    Espenel, Cedric; Giocondi, Marie-Cecile; Seantier, Bastien; Dosset, Patrice; Milhiet, Pierre-Emmanuel; Le Grimellec, Christian

    2008-01-01

    Characterization of lateral organization of plasma membranes is a prerequisite to the understanding of membrane structure-function relationships in living cells. Lipid-lipid and lipid-protein interactions are responsible for the existence of various membrane microdomains involved in cell signalization and in numerous pathologies. Developing approaches for characterizing microdomains associate identification tools like recognition imaging with high-resolution topographical imaging. Membrane properties are markedly dependent on temperature. However, mesoscopic scale topographical information of cell surface in a temperature range covering most of cell biology experimentation is still lacking. In this work we have examined the possibility of imaging the temperature-dependent behavior of eukaryotic cells by atomic force microscopy (AFM). Our results establish that the surface of living CV1 kidney cells can be imaged by AFM, between 5 and 37 deg. C, both in contact and tapping modes. These first temperature-dependent data show that large cell structures appeared essentially stable at a microscopic scale. On the other hand, as shown by contact mode AFM, the surface was highly dynamic at a mesoscopic scale, with marked changes in apparent topography, friction, and deflection signals. When keeping the scanning conditions constant, a progressive loss in the image contrast was however observed, using tapping mode, on decreasing the temperature

  10. Optical Imaging for Stem Cell Differentiation to Neuronal Lineage

    International Nuclear Information System (INIS)

    Hwang, Do Won; Lee, Dong Soo

    2012-01-01

    In regenerative medicine, the prospect of stem cell therapy hold great promise for the recovery of injured tissues and effective treatment of intractable diseases. Tracking stem cell fate provides critical information to understand and evaluate the success of stem cell therapy. The recent emergence of in vivo noninvasive molecular imaging has enabled assessment of the behavior of grafted stem cells in living subjects. In this review, we provide an overview of current optical imaging strategies based on cell or tissue specific reporter gene expression and of in vivo methods to monitor stem cell differentiation into neuronal lineages. These methods use optical reporters either regulated by neuron-specific promoters or containing neuron-specific microRNA binding sites. Both systems revealed dramatic changes in optical reporter imaging signals in cells differentiating a yeast GAL4 amplification system or an engineering-enhanced luciferase reported gene. Furthermore, we propose an advanced imaging system to monitor neuronal differentiation during neurogenesis that uses in vivo multiplexed imaging techniques capable of detecting several targets simultaneously

  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. Information management for high content live cell imaging

    Directory of Open Access Journals (Sweden)

    White Michael RH

    2009-07-01

    Full Text Available Abstract Background High content live cell imaging experiments are able to track the cellular localisation of labelled proteins in multiple live cells over a time course. Experiments using high content live cell imaging will generate multiple large datasets that are often stored in an ad-hoc manner. This hinders identification of previously gathered data that may be relevant to current analyses. Whilst solutions exist for managing image data, they are primarily concerned with storage and retrieval of the images themselves and not the data derived from the images. There is therefore a requirement for an information management solution that facilitates the indexing of experimental metadata and results of high content live cell imaging experiments. Results We have designed and implemented a data model and information management solution for the data gathered through high content live cell imaging experiments. Many of the experiments to be stored measure the translocation of fluorescently labelled proteins from cytoplasm to nucleus in individual cells. The functionality of this database has been enhanced by the addition of an algorithm that automatically annotates results of these experiments with the timings of translocations and periods of any oscillatory translocations as they are uploaded to the repository. Testing has shown the algorithm to perform well with a variety of previously unseen data. Conclusion Our repository is a fully functional example of how high throughput imaging data may be effectively indexed and managed to address the requirements of end users. By implementing the automated analysis of experimental results, we have provided a clear impetus for individuals to ensure that their data forms part of that which is stored in the repository. Although focused on imaging, the solution provided is sufficiently generic to be applied to other functional proteomics and genomics experiments. The software is available from: fhttp://code.google.com/p/livecellim/

  13. Live cell imaging of Arabidopsis root hairs

    NARCIS (Netherlands)

    Ketelaar, T.

    2014-01-01

    Root hairs are tubular extensions from the root surface that expand by tip growth. This highly focused type of cell expansion, combined with position of root hairs on the surface of the root, makes them ideal cells for microscopic observation. This chapter describes the method that is routinely used

  14. 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.)

  15. Live cell imaging of in vitro human trophoblast syncytialization.

    Science.gov (United States)

    Wang, Rui; Dang, Yan-Li; Zheng, Ru; Li, Yue; Li, Weiwei; Lu, Xiaoyin; Wang, Li-Juan; Zhu, Cheng; Lin, Hai-Yan; Wang, Hongmei

    2014-06-01

    Human trophoblast syncytialization, a process of cell-cell fusion, is one of the most important yet least understood events during placental development. Investigating the fusion process in a placenta in vivo is very challenging given the complexity of this process. Application of primary cultured cytotrophoblast cells isolated from term placentas and BeWo cells derived from human choriocarcinoma formulates a biphasic strategy to achieve the mechanism of trophoblast cell fusion, as the former can spontaneously fuse to form the multinucleated syncytium and the latter is capable of fusing under the treatment of forskolin (FSK). Live-cell imaging is a powerful tool that is widely used to investigate many physiological or pathological processes in various animal models or humans; however, to our knowledge, the mechanism of trophoblast cell fusion has not been reported using a live- cell imaging manner. In this study, a live-cell imaging system was used to delineate the fusion process of primary term cytotrophoblast cells and BeWo cells. By using live staining with Hoechst 33342 or cytoplasmic dyes or by stably transfecting enhanced green fluorescent protein (EGFP) and DsRed2-Nuc reporter plasmids, we observed finger-like protrusions on the cell membranes of fusion partners before fusion and the exchange of cytoplasmic contents during fusion. In summary, this study provides the first video recording of the process of trophoblast syncytialization. Furthermore, the various live-cell imaging systems used in this study will help to yield molecular insights into the syncytialization process during placental development. © 2014 by the Society for the Study of Reproduction, Inc.

  16. Comparison of segmentation algorithms for fluorescence microscopy images of cells.

    Science.gov (United States)

    Dima, Alden A; Elliott, John T; Filliben, James J; Halter, Michael; Peskin, Adele; Bernal, Javier; Kociolek, Marcin; Brady, Mary C; Tang, Hai C; Plant, Anne L

    2011-07-01

    The analysis of fluorescence microscopy of cells often requires the determination of cell edges. This is typically done using segmentation techniques that separate the cell objects in an image from the surrounding background. This study compares segmentation results from nine different segmentation techniques applied to two different cell lines and five different sets of imaging conditions. Significant variability in the results of segmentation was observed that was due solely to differences in imaging conditions or applications of different algorithms. We quantified and compared the results with a novel bivariate similarity index metric that evaluates the degree of underestimating or overestimating a cell object. The results show that commonly used threshold-based segmentation techniques are less accurate than k-means clustering with multiple clusters. Segmentation accuracy varies with imaging conditions that determine the sharpness of cell edges and with geometric features of a cell. Based on this observation, we propose a method that quantifies cell edge character to provide an estimate of how accurately an algorithm will perform. The results of this study will assist the development of criteria for evaluating interlaboratory comparability. Published 2011 Wiley-Liss, Inc.

  17. High resolution ultrasound and photoacoustic imaging of single cells

    Directory of Open Access Journals (Sweden)

    Eric M. Strohm

    2016-03-01

    Full Text Available High resolution ultrasound and photoacoustic images of stained neutrophils, lymphocytes and monocytes from a blood smear were acquired using a combined acoustic/photoacoustic microscope. Photoacoustic images were created using a pulsed 532 nm laser that was coupled to a single mode fiber to produce output wavelengths from 532 nm to 620 nm via stimulated Raman scattering. The excitation wavelength was selected using optical filters and focused onto the sample using a 20× objective. A 1000 MHz transducer was co-aligned with the laser spot and used for ultrasound and photoacoustic images, enabling micrometer resolution with both modalities. The different cell types could be easily identified due to variations in contrast within the acoustic and photoacoustic images. This technique provides a new way of probing leukocyte structure with potential applications towards detecting cellular abnormalities and diseased cells at the single cell level.

  18. High resolution imaging of surface patterns of single bacterial cells

    International Nuclear Information System (INIS)

    Greif, Dominik; Wesner, Daniel; Regtmeier, Jan; Anselmetti, Dario

    2010-01-01

    We systematically studied the origin of surface patterns observed on single Sinorhizobium meliloti bacterial cells by comparing the complementary techniques atomic force microscopy (AFM) and scanning electron microscopy (SEM). Conditions ranged from living bacteria in liquid to fixed bacteria in high vacuum. Stepwise, we applied different sample modifications (fixation, drying, metal coating, etc.) and characterized the observed surface patterns. A detailed analysis revealed that the surface structure with wrinkled protrusions in SEM images were not generated de novo but most likely evolved from similar and naturally present structures on the surface of living bacteria. The influence of osmotic stress to the surface structure of living cells was evaluated and also the contribution of exopolysaccharide and lipopolysaccharide (LPS) by imaging two mutant strains of the bacterium under native conditions. AFM images of living bacteria in culture medium exhibited surface structures of the size of single proteins emphasizing the usefulness of AFM for high resolution cell imaging.

  19. Comparative transcriptional survey between laser-microdissected cells from laminar abscission zone and petiolar cortical tissue during ethylene-promoted abscission in citrus leaves

    Directory of Open Access Journals (Sweden)

    Tadeo Francisco R

    2009-10-01

    Full Text Available Abstract Background Abscission is the cell separation process by which plants are able to shed organs. It has a great impact on the yield of most crop plants. At the same time, the process itself also constitutes an excellent model to study cell separation processes, since it occurs in concrete areas known as abscission zones (AZs which are composed of a specific cell type. However, molecular approaches are generally hampered by the limited area and cell number constituting the AZ. Therefore, detailed studies at the resolution of cell type are of great relevance in order to accurately describe the process and to identify potential candidate genes for biotechnological applications. Results Efficient protocols for the isolation of specific citrus cell types, namely laminar abscission zone (LAZ and petiolar cortical (Pet cells based on laser capture microdissection (LCM and for RNA microextraction and amplification have been developed. A comparative transcriptome analysis between LAZ and Pet from citrus leaf explants subjected to an in-vitro 24 h ethylene treatment was performed utilising microarray hybridization and analysis. Our analyses of gene functional classes differentially represented in ethylene-treated LAZ revealed an activation program dominated by the expression of genes associated with protein synthesis, protein fate, cell type differentiation, development and transcription. The extensive repertoire of genes associated with cell wall biosynthesis and metabolism strongly suggests that LAZ layers activate both catabolic and anabolic wall modification pathways during the abscission program. In addition, over-representation of particular members of different transcription factor families suggests important roles for these genes in the differentiation of the effective cell separation layer within the many layers contained in the citrus LAZ. Preferential expression of stress-related and defensive genes in Pet reveals that this tissue is

  20. In vitro evidence for participation of DEC-205 expressed by thymic cortical epithelial cells in clearance of apoptotic thymocytes.

    NARCIS (Netherlands)

    Small, M; Kraal, G.

    2003-01-01

    Binding of apoptotic cells was compared after incubation of thymocytes with two clones of murine thymic stromal cells to which CD4(+)/CD8(+) thymocytes attach. With the BA/10, but not the BA/2, clone, thymocytes with apoptotic morphology were bound irreversibly. These tightly bound thymocytes were

  1. Quantitative volumetric Raman imaging of three dimensional cell cultures

    KAUST Repository

    Kallepitis, Charalambos

    2017-03-22

    The ability to simultaneously image multiple biomolecules in biologically relevant three-dimensional (3D) cell culture environments would contribute greatly to the understanding of complex cellular mechanisms and cell–material interactions. Here, we present a computational framework for label-free quantitative volumetric Raman imaging (qVRI). We apply qVRI to a selection of biological systems: human pluripotent stem cells with their cardiac derivatives, monocytes and monocyte-derived macrophages in conventional cell culture systems and mesenchymal stem cells inside biomimetic hydrogels that supplied a 3D cell culture environment. We demonstrate visualization and quantification of fine details in cell shape, cytoplasm, nucleus, lipid bodies and cytoskeletal structures in 3D with unprecedented biomolecular specificity for vibrational microspectroscopy.

  2. Fast globally optimal segmentation of cells in fluorescence microscopy images.

    Science.gov (United States)

    Bergeest, Jan-Philip; Rohr, Karl

    2011-01-01

    Accurate and efficient segmentation of cells in fluorescence microscopy images is of central importance for the quantification of protein expression in high-throughput screening applications. We propose a new approach for segmenting cell nuclei which is based on active contours and convex energy functionals. Compared to previous work, our approach determines the global solution. Thus, the approach does not suffer from local minima and the segmentation result does not depend on the initialization. We also suggest a numeric approach for efficiently computing the solution. The performance of our approach has been evaluated using fluorescence microscopy images of different cell types. We have also performed a quantitative comparison with previous segmentation approaches.

  3. Live cell imaging reveals at novel view of DNA

    International Nuclear Information System (INIS)

    Moritomi-Yano, Keiko; Yano, Ken-ichi

    2010-01-01

    Non-homologous end-joining (NHEJ) is the major repair pathway for DNA double-strand breaks (DSBs) that are the most severe form of DNA damages. Recently, live cell imaging techniques coupled with laser micro-irradiation were used to analyze the spatio-temporal behavior of the NHEJ core factors upon DSB induction in living cells. Based on the live cell imaging studies, we proposed a novel two-phase model for DSB sensing and protein assembly in the NHEJ pathway. This new model provides a novel view of the dynamic protein behavior on DSBs and broad implications for the molecular mechanism of NHEJ. (author)

  4. Automatic Cell Segmentation in Fluorescence Images of Confluent Cell Monolayers Using Multi-object Geometric Deformable Model

    OpenAIRE

    Yang, Zhen; Bogovic, John A.; Carass, Aaron; Ye, Mao; Searson, Peter C.; Prince, Jerry L.

    2013-01-01

    With the rapid development of microscopy for cell imaging, there is a strong and growing demand for image analysis software to quantitatively study cell morphology. Automatic cell segmentation is an important step in image analysis. Despite substantial progress, there is still a need to improve the accuracy, efficiency, and adaptability to different cell morphologies. In this paper, we propose a fully automatic method for segmenting cells in fluorescence images of confluent cell monolayers. T...

  5. Cross-Sectional Transport Imaging in a Multijunction Solar Cell

    Energy Technology Data Exchange (ETDEWEB)

    Haegel, Nancy M.; Ke, Chi-Wen; Taha, Hesham; Guthrey, Harvey; Fetzer, C. M.; King, Richard

    2015-06-14

    Combining highly localized electron-beam excitation at a point with the spatial resolution capability of optical near-field imaging, we have imaged carrier transport in a cross-sectioned multijunction (GaInP/GaInAs/Ge) solar cell. We image energy transport associated with carrier diffusion throughout the full width of the middle (GaInAs) cell and luminescent coupling from point excitation in the top cell GaInP to the middle cell. Supporting cathodoluminescence and near-field photoluminescence measurements demonstrate excitation-dependent Fermi level splitting effects that influence cross-sectioned spectroscopy results as well as transport limitations on the spatial resolution of cross-sectional measurements.

  6. Multimodal nonlinear imaging of arabidopsis thaliana root cell

    Science.gov (United States)

    Jang, Bumjoon; Lee, Sung-Ho; Woo, Sooah; Park, Jong-Hyun; Lee, Myeong Min; Park, Seung-Han

    2017-07-01

    Nonlinear optical microscopy has enabled the possibility to explore inside the living organisms. It utilizes ultrashort laser pulse with long wavelength (greater than 800nm). Ultrashort pulse produces high peak power to induce nonlinear optical phenomenon such as two-photon excitation fluorescence (TPEF) and harmonic generations in the medium while maintaining relatively low average energy pre area. In plant developmental biology, confocal microscopy is widely used in plant cell imaging after the development of biological fluorescence labels in mid-1990s. However, fluorescence labeling itself affects the sample and the sample deviates from intact condition especially when labelling the entire cell. In this work, we report the dynamic images of Arabidopsis thaliana root cells. This demonstrates the multimodal nonlinear optical microscopy is an effective tool for long-term plant cell imaging.

  7. 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.

  8. Differences in the mechanical properties of the developing cerebral cortical proliferative zone between mice and ferrets at both the tissue and single-cell levels

    Directory of Open Access Journals (Sweden)

    Arata Nagasaka

    2016-11-01

    Full Text Available Cell-producing events in developing tissues are mechanically dynamic throughout the cell cycle. In many epithelial systems, cells are apicobasally tall, with nuclei and somata that adopt different apicobasal positions because nuclei and somata move in a cell cycle–dependent manner. This movement is apical during G2 phase and basal during G1 phase, whereas mitosis occurs at the apical surface. These movements are collectively referred to as interkinetic nuclear migration, and such epithelia are called pseudostratified. The embryonic mammalian cerebral cortical neuroepithelium is a good model for highly pseudostratified epithelia, and we previously found differences between mice and ferrets in both horizontal cellular density (greater in ferrets and nuclear/somal movements (slower during G2 and faster during G1 in ferrets. These differences suggest that neuroepithelial cells alter their nucleokinetic behavior in response to physical factors that they encounter, which may form the basis for evolutionary transitions towards more abundant brain-cell production from mice to ferrets and primates. To address how mouse and ferret neuroepithelia may differ physically in a quantitative manner, we used atomic force microscopy to determine that the vertical stiffness of their apical surface is greater in ferrets (Young’s modulus = 1700 Pa than in mice (1400 Pa. We systematically analyzed factors underlying the apical-surface stiffness through experiments to pharmacologically inhibit actomyosin or microtubules and to examine recoiling behaviors of the apical surface upon laser ablation and also through electron microscopy to observe adherens junction. We found that although both actomyosin and microtubules are partly responsible for the apical-surface stiffness, the mousecells is

  9. Live-cell imaging: new avenues to investigate retinal regeneration

    Directory of Open Access Journals (Sweden)

    Manuela Lahne

    2017-01-01

    Full Text Available Sensing and responding to our environment requires functional neurons that act in concert. Neuronal cell loss resulting from degenerative diseases cannot be replaced in humans, causing a functional impairment to integrate and/or respond to sensory cues. In contrast, zebrafish (Danio rerio possess an endogenous capacity to regenerate lost neurons. Here, we will focus on the processes that lead to neuronal regeneration in the zebrafish retina. Dying retinal neurons release a damage signal, tumor necrosis factor α, which induces the resident radial glia, the Müller glia, to reprogram and re-enter the cell cycle. The Müller glia divide asymmetrically to produce a Müller glia that exits the cell cycle and a neuronal progenitor cell. The arising neuronal progenitor cells undergo several rounds of cell divisions before they migrate to the site of damage to differentiate into the neuronal cell types that were lost. Molecular and immunohistochemical studies have predominantly provided insight into the mechanisms that regulate retinal regeneration. However, many processes during retinal regeneration are dynamic and require live-cell imaging to fully discern the underlying mechanisms. Recently, a multiphoton imaging approach of adult zebrafish retinal cultures was developed. We will discuss the use of live-cell imaging, the currently available tools and those that need to be developed to advance our knowledge on major open questions in the field of retinal regeneration.

  10. Use of Colchicine in Cortical Area 1 of the Hippocampus Impairs Transmission of Non-Motivational Information by the Pyramidal Cells

    Directory of Open Access Journals (Sweden)

    Nosaibeh Riahi Zaniani

    2013-11-01

    Full Text Available Colchicine, a potent neurotoxin derived from plants, has been recently introduced as a degenerative toxin of small pyramidal cells in the cortical area 1 of the hippocampus (CA1. In this study, the effect of the alkaloid in CA1 on the behaviors in the conditioning task was measured. Injections of colchicine (1,5 μg/rat, intra-CA1 was performed in the male Wistar rats, while the animals were settled and cannulated in a stereotaxic apparatus. In the control group solely injection of saline (1 μl/rat, intra-CA1 was used. One week later, all the animals passed the saline conditioning task using a three-day schedule of an unbiased paradigm. They were administered saline (1 ml/kg, s.c. twice a day throughout the conditioning phase. To evaluate the possible effects of cell injury by the toxin on the pyramidal cells, both the motivational signals while in the conditioning box and the non-motivational locomotive signs of the treated and control rats were measured. Based on the present study the alkaloid caused no change in the score of place conditioning, but affected both the sniffing and grooming behaviors in the group that received colchicine. However, the alkaloid did not show the significant effect on the rearing or compartment entering in the rats. According to the findings, the intra-CA1 injection of colchicine may impair the neuronal transmission of non-motivational information by the pyramidal cells in the dorsal hippocampus.

  11. Applying image quality in cell phone cameras: lens distortion

    Science.gov (United States)

    Baxter, Donald; Goma, Sergio R.; Aleksic, Milivoje

    2009-01-01

    This paper describes the framework used in one of the pilot studies run under the I3A CPIQ initiative to quantify overall image quality in cell-phone cameras. The framework is based on a multivariate formalism which tries to predict overall image quality from individual image quality attributes and was validated in a CPIQ pilot program. The pilot study focuses on image quality distortions introduced in the optical path of a cell-phone camera, which may or may not be corrected in the image processing path. The assumption is that the captured image used is JPEG compressed and the cellphone camera is set to 'auto' mode. As the used framework requires that the individual attributes to be relatively perceptually orthogonal, in the pilot study, the attributes used are lens geometric distortion (LGD) and lateral chromatic aberrations (LCA). The goal of this paper is to present the framework of this pilot project starting with the definition of the individual attributes, up to their quantification in JNDs of quality, a requirement of the multivariate formalism, therefore both objective and subjective evaluations were used. A major distinction in the objective part from the 'DSC imaging world' is that the LCA/LGD distortions found in cell-phone cameras, rarely exhibit radial behavior, therefore a radial mapping/modeling cannot be used in this case.

  12. Dual photon excitation microscopy and image threshold segmentation in live cell imaging during compression testing.

    Science.gov (United States)

    Moo, Eng Kuan; Abusara, Ziad; Abu Osman, Noor Azuan; Pingguan-Murphy, Belinda; Herzog, Walter

    2013-08-09

    Morphological studies of live connective tissue cells are imperative to helping understand cellular responses to mechanical stimuli. However, photobleaching is a constant problem to accurate and reliable live cell fluorescent imaging, and various image thresholding methods have been adopted to account for photobleaching effects. Previous studies showed that dual photon excitation (DPE) techniques are superior over conventional one photon excitation (OPE) confocal techniques in minimizing photobleaching. In this study, we investigated the effects of photobleaching resulting from OPE and DPE on morphology of in situ articular cartilage chondrocytes across repeat laser exposures. Additionally, we compared the effectiveness of three commonly-used image thresholding methods in accounting for photobleaching effects, with and without tissue loading through compression. In general, photobleaching leads to an apparent volume reduction for subsequent image scans. Performing seven consecutive scans of chondrocytes in unloaded cartilage, we found that the apparent cell volume loss caused by DPE microscopy is much smaller than that observed using OPE microscopy. Applying scan-specific image thresholds did not prevent the photobleaching-induced volume loss, and volume reductions were non-uniform over the seven repeat scans. During cartilage loading through compression, cell fluorescence increased and, depending on the thresholding method used, led to different volume changes. Therefore, different conclusions on cell volume changes may be drawn during tissue compression, depending on the image thresholding methods used. In conclusion, our findings confirm that photobleaching directly affects cell morphology measurements, and that DPE causes less photobleaching artifacts than OPE for uncompressed cells. When cells are compressed during tissue loading, a complicated interplay between photobleaching effects and compression-induced fluorescence increase may lead to interpretations in

  13. Dynamics of myosin II organization into cortical contractile networks and fibers

    Science.gov (United States)

    Nie, Wei; Wei, Ming-Tzo; Ou-Yang, Daniel; Jedlicka, Sabrina; Vavylonis, Dimitrios

    2014-03-01

    The morphology of adhered cells critically depends on the formation of a contractile meshwork of parallel and cross-linked stress fibers along the contacting surface. The motor activity and mini-filament assembly of non-muscle myosin II is an important component of cell-level cytoskeletal remodeling during mechanosensing. To monitor the dynamics of myosin II, we used confocal microscopy to image cultured HeLa cells that stably express myosin regulatory light chain tagged with GFP (MRLC-GFP). MRLC-GFP was monitored in time-lapse movies at steady state and during the response of cells to varying concentrations of blebbistatin which disrupts actomyosin stress fibers. Using image correlation spectroscopy analysis, we quantified the kinetics of disassembly and reassembly of actomyosin networks and compared them to studies by other groups. This analysis suggested that the following processes contribute to the assembly of cortical actomyosin into fibers: random myosin mini-filament assembly and disassembly along the cortex; myosin mini-filament aligning and contraction; stabilization of cortical myosin upon increasing contractile tension. We developed simple numerical simulations that include those processes. The results of simulations of cells at steady state and in response to blebbistatin capture some of the main features observed in the experiments. This study provides a framework to help interpret how different cortical myosin remodeling kinetics may contribute to different cell shape and rigidity depending on substrate stiffness.

  14. Progress in molecular nuclear medicine imaging of pancreatic beta cells

    International Nuclear Information System (INIS)

    Wu Haifei; Yin Hongyan; Liu Shuai; Zhang Yifan

    2010-01-01

    Diabetes mellitus is a common and frequently occurring disease which seriously threaten the health of human beings. Type 1 and type 2 diabetes respectively results from being destroyed and insufficient beta-cell mass. The associated symptoms appear until 50%-60% decrease of beta-cell mass. Because pancreas is deeply located in the body, with few beta-cell mass, the current methods of clinical diagnosis are invasive and late. So diagnosis of metabolism disease of beta-cell early non-invasively becomes more and more popular, imaging diagnosis of diabetes mellitus becomes the focus of researches, but how to estimate the mass of beta-cell still an important subject in imaging technology. (authors)

  15. 3D/4D multiscale imaging in acute lymphoblastic leukemia cells: visualizing dynamics of cell death

    Science.gov (United States)

    Sarangapani, Sreelatha; Mohan, Rosmin Elsa; Patil, Ajeetkumar; Lang, Matthew J.; Asundi, Anand

    2017-06-01

    Quantitative phase detection is a new methodology that provides quantitative information on cellular morphology to monitor the cell status, drug response and toxicity. In this paper the morphological changes in acute leukemia cells treated with chitosan were detected using d'Bioimager a robust imaging system. Quantitative phase image of the cells was obtained with numerical analysis. Results show that the average area and optical volume of the chitosan treated cells is significantly reduced when compared with the control cells, which reveals the effect of chitosan on the cancer cells. From the results it can be attributed that d'Bioimager can be used as a non-invasive imaging alternative to measure the morphological changes of the living cells in real time.

  16. FogBank: a single cell segmentation across multiple cell lines and image modalities.

    Science.gov (United States)

    Chalfoun, Joe; Majurski, Michael; Dima, Alden; Stuelten, Christina; Peskin, Adele; Brady, Mary

    2014-12-30

    Many cell lines currently used in medical research, such as cancer cells or stem cells, grow in confluent sheets or colonies. The biology of individual cells provide valuable information, thus the separation of touching cells in these microscopy images is critical for counting, identification and measurement of individual cells. Over-segmentation of single cells continues to be a major problem for methods based on morphological watershed due to the high level of noise in microscopy cell images. There is a need for a new segmentation method that is robust over a wide variety of biological images and can accurately separate individual cells even in challenging datasets such as confluent sheets or colonies. We present a new automated segmentation method called FogBank that accurately separates cells when confluent and touching each other. This technique is successfully applied to phase contrast, bright field, fluorescence microscopy and binary images. The method is based on morphological watershed principles with two new features to improve accuracy and minimize over-segmentation. First, FogBank uses histogram binning to quantize pixel intensities which minimizes the image noise that causes over-segmentation. Second, FogBank uses a geodesic distance mask derived from raw images to detect the shapes of individual cells, in contrast to the more linear cell edges that other watershed-like algorithms produce. We evaluated the segmentation accuracy against manually segmented datasets using two metrics. FogBank achieved segmentation accuracy on the order of 0.75 (1 being a perfect match). We compared our method with other available segmentation techniques in term of achieved performance over the reference data sets. FogBank outperformed all related algorithms. The accuracy has also been visually verified on data sets with 14 cell lines across 3 imaging modalities leading to 876 segmentation evaluation images. FogBank produces single cell segmentation from confluent cell

  17. Nano-imaging of single cells using STIM

    Energy Technology Data Exchange (ETDEWEB)

    Ren Minqin [Centre for Ion Beam Applications (CIBA), Department of Physics, National University of Singapore, Singapore 117542 (Singapore); Department of Biochemistry, National University of Singapore (Singapore); Kan, J.A. van [Centre for Ion Beam Applications (CIBA), Department of Physics, National University of Singapore, Singapore 117542 (Singapore); Bettiol, A.A. [Centre for Ion Beam Applications (CIBA), Department of Physics, National University of Singapore, Singapore 117542 (Singapore); Daina, Lim [Department of Anatomy, National University of Singapore (Singapore); Gek, Chan Yee [Department of Anatomy, National University of Singapore (Singapore); Huat, Bay Boon [Department of Anatomy, National University of Singapore (Singapore); Whitlow, H.J. [Department of Physics, University of Jyvaskyla, P.O. Box 35 (YFL), FIN-40014 (Finland); Osipowicz, T. [Centre for Ion Beam Applications (CIBA), Department of Physics, National University of Singapore, Singapore 117542 (Singapore); Watt, F. [Centre for Ion Beam Applications (CIBA), Department of Physics, National University of Singapore, Singapore 117542 (Singapore)]. E-mail: phywattf@nus.edu.sg

    2007-07-15

    Scanning transmission ion microscopy (STIM) is a technique which utilizes the energy loss of high energy (MeV) ions passing through a sample to provide structural images. In this paper, we have successfully demonstrated STIM imaging of single cells at the nano-level using the high resolution capability of the proton beam writing facility at the Centre for Ion Beam Applications, National University of Singapore. MCF-7 breast cancer cells (American Type Culture Collection [ATCC]) were seeded on to silicon nitride windows, backed by a Hamamatsu pin diode acting as a particle detector. A reasonable contrast was obtained using 1 MeV protons and excellent contrast obtained using 1 MeV alpha particles. In a further experiment, nano-STIM was also demonstrated using cells seeded on to the pin diode directly, and high quality nano-STIM images showing the nucleus and multiple nucleoli were extracted before the detector was significantly damaged.

  18. Multilocular cystic renal cell carcinoma: imaging and clinical correlation

    International Nuclear Information System (INIS)

    Xu Yong; Zhang Sheng

    2013-01-01

    Multilocular cystic renal cell carcinoma (MCRCC) is a subtype of clear cell renal cell carcinoma and has mild clinical symptoms and a favorable prognosis. Accordingly, nephron-sparing surgery is recommended as a therapeutic strategy. If histologic subtype of MCRCC can be predicted preoperatively with an acceptable level of accuracy, it may be important in predicting prognosis and make clinical management. Most MCRCCs show characteristic cross-sectional imaging findings and permit accurate diagnosis before the treatment. Cross -sectional imaging of MCRCC reveals a well -defined multilocular cystic mass with irregularly enhanced thickened septa and without enhanced intracystic solid nodule. It is often classified as Bosniak classification Ⅲ , which is significantly different from that of other renal cystic masses. The clinical, pathologic, and radiologic features of MCRCC were discussed and illustrated in this article. The role of the imaging preoperative evaluation for MCRCC, and management implications were emphasized. (authors)

  19. Imaging: Guiding the Clinical Translation of Cardiac Stem Cell Therapy

    Science.gov (United States)

    Nguyen, Patricia K.; Lan, Feng; Wang, Yongming; Wu, Joseph C.

    2011-01-01

    Stem cells have been touted as the holy grail of medical therapy with promises to regenerate cardiac tissue, but it appears the jury is still out on this novel therapy. Using advanced imaging technology, scientists have discovered that these cells do not survive nor engraft long-term. In addition, only marginal benefit has been observed in large animal studies and human trials. However, all is not lost. Further application of advanced imaging technology will help scientists unravel the mysteries of stem cell therapy and address the clinical hurdles facing its routine implementation. In this review, we will discuss how advanced imaging technology will help investigators better define the optimal delivery method, improve survival and engraftment, and evaluate efficacy and safety. Insights gained from this review may direct the development of future preclinical investigations and clinical trials. PMID:21960727

  20. Characterization of energy and neurotransmitter metabolism in cortical glutamatergic neurons derived from human induced pluripotent stem cells

    DEFF Research Database (Denmark)

    Aldana, Blanca I; Zhang, Yu; Lihme, Maria Fog

    2017-01-01

    pathways in neurons derived from human induced pluripotent stem cells (hiPSC). With this aim, cultures of hiPSC-derived neurons were incubated with [U-(13)C]glucose, [U-(13)C]glutamate or [U-(13)C]glutamine. Isotopic labeling in metabolites was determined using gas chromatography coupled to mass...

  1. Red Blood Cell Count Automation Using Microscopic Hyperspectral Imaging Technology.

    Science.gov (United States)

    Li, Qingli; Zhou, Mei; Liu, Hongying; Wang, Yiting; Guo, Fangmin

    2015-12-01

    Red blood cell counts have been proven to be one of the most frequently performed blood tests and are valuable for early diagnosis of some diseases. This paper describes an automated red blood cell counting method based on microscopic hyperspectral imaging technology. Unlike the light microscopy-based red blood count methods, a combined spatial and spectral algorithm is proposed to identify red blood cells by integrating active contour models and automated two-dimensional k-means with spectral angle mapper algorithm. Experimental results show that the proposed algorithm has better performance than spatial based algorithm because the new algorithm can jointly use the spatial and spectral information of blood cells.

  2. Nrdp1 Increases Ischemia Induced Primary Rat Cerebral Cortical Neurons and Pheochromocytoma Cells Apoptosis Via Downregulation of HIF-1α Protein

    Directory of Open Access Journals (Sweden)

    Yuan Zhang

    2017-09-01

    Full Text Available Neuregulin receptor degradation protein-1 (Nrdp1 is an E3 ubiquitin ligase that targets proteins for degradation and regulates cell growth, apoptosis and oxidative stress in various cell types. We have previously shown that Nrdp1 is implicated in ischemic cardiomyocyte death. In this study, we investigated the change of Nrdp1 expression in ischemic neurons and its role in ischemic neuronal injury. Primary rat cerebral cortical neurons and pheochromocytoma (PC12 cells were infected with adenoviral constructs expressing Nrdp1 gene or its siRNA before exposing to oxygen-glucose deprivation (OGD treatment. Our data showed that Nrdp1 was upregulated in ischemic brain tissue 3 h after middle cerebral artery occlusion (MCAO and in OGD-treated neurons. Of note, Nrdp1 overexpression by Ad-Nrdp1 enhanced OGD-induced neuron apoptosis, while knockdown of Nrdp1 with siRNA attenuated this effect, implicating a role of Nrdp1 in ischemic neuron injury. Moreover, Nrdp1 upregulation is accompanied by increased protein ubiquitylation and decreased protein levels of ubiquitin-specific protease 8 (USP8 in OGD-treated neurons, which led to a suppressed interaction between USP8 and HIF-1α and subsequently a reduction in HIF-1α protein accumulation in neurons under OGD conditions. In conclusion, our data support an important role of Nrdp1 upregulation in ischemic neuronal death, and suppressing the interaction between USP8 and HIF-1α and consequently the hypoxic adaptive response of neurons may account for this detrimental effect.

  3. 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.

  4. 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.

  5. Chronological alterations of diagnostic imaging of renal cell carcinoma

    International Nuclear Information System (INIS)

    Arima, Kiminobu; Sugimura, Yoshiki; Yanagawa, Makoto; Tochigi, Hiromi; Kawamura, Juichi

    1994-01-01

    A review of 156 cases of renal cell carcinoma diagnosed during a 20-year period demonstrated the changes of initial signs/symptoms and imaging modalities for detection and definition. According to the imaging modality used for diagnosing renal cell carcinoma, clinical pictures were chronologically examined over 4 periods: 1973 to 1979 (before CT era), 1980 to 1984 (early CT era), 1985 to 1987 (CT era) and 1988 to 1992 (CT/MRI era). With regards to initial signs or symptoms, the proportion of classical trials has gradually decreased, while that of tumors noted incidentally has increased. As for imaging modalities for detection, the proportion of IVP has gradually decreased and that of CT and US has increased over the periods. With regard to imaging modalities for definition, the proportion of angiography has decreased and that of CT has increased. From chronological changes in clinical pictures and imaging modalities, we suggested a decision tree of imaging modalities for detection and definition of renal cell carcinoma. (author)

  6. Magnetic resonance imaging of large chromophobe renal cell carcinomas

    International Nuclear Information System (INIS)

    Sasaguri, Kohei; Irie, Hiroyuki; Kamochi, Noriyuki; Nakazono, Takahiko; Yamaguchi, Ken; Uozumi, Jiro; Kudo, Sho

    2010-01-01

    The objective of this study was to clarify the magnetic resonance imaging (MRI) findings of large chromophobe renal cell carcinomas. Five patients diagnosed pathologically with chromophobe renal cell carcinoma are included. MRI findings were retrospectively evaluated for the tumor contour, uniformity and hypointensity of the rim of the tumor on T2-weighted images, ''micro-scopic fat'', enhancement degree and pattern on dynamic study, and necrosis in the tumor, among other findings. The tumor size ranged from 4.8 to 13.7 cm (mean 7.9 cm). The tumor contour was well defined in four patients. All but one tumor showed a hypointensity rim, and all tumors had a heterogeneous appearance on T2-weighted images. ''Microscopic fat'' was detected in one case. All tumors demonstrated low enhancement compared to that of the renal cortex. All tumors showed heterogeneous enhancement on postcontrast images. Necrosis was seen in four. Hemorrhage and renal vein thrombosis was seen in one. Chromophobe renal cell carcinomas of large size tend to have a heterogeneous appearance on post-contrast and T2-weighted images, a well-defined tumor contour with a hypointensity rim on T2-wighted images, and lower enhancement than that of the renal cortex. Tumor necrosis is easily apparent, and ''microscopic fat'' may be observed. (author)

  7. [Development of a Fluorescence Probe for Live Cell Imaging].

    Science.gov (United States)

    Shibata, Aya

    2017-01-01

     Probes that detect specific biological materials are indispensable tools for deepening our understanding of various cellular phenomena. In live cell imaging, the probe must emit fluorescence only when a specific substance is detected. In this paper, we introduce a new probe we developed for live cell imaging. Glutathione S-transferase (GST) activity is higher in tumor cells than in normal cells and is involved in the development of resistance to various anticancer drugs. We previously reported the development of a general strategy for the synthesis of probes for detection of GST enzymes, including fluorogenic, bioluminogenic, and 19 F-NMR probes. Arylsulfonyl groups were used as caging groups during probe design. The fluorogenic probes were successfully used to quantitate very low levels of GST activity in cell extracts and were also successfully applied to the imaging of microsomal MGST1 activity in living cells. The bioluminogenic and 19 F-NMR probes were able to detect GST activity in Escherichia coli cells. Oligonucleotide-templated reactions are powerful tools for nucleic acid sensing. This strategy exploits the target strand as a template for two functionalized probes and provides a simple molecular mechanism for multiple turnover reactions. We developed a nucleophilic aromatic substitution reaction-triggered fluorescent probe. The probe completed its reaction within 30 s of initiation and amplified the fluorescence signal from 0.5 pM target oligonucleotide by 1500 fold under isothermal conditions. Additionally, we applied the oligonucleotide-templated reaction for molecular releasing and peptide detection.

  8. Impairment of preoperative language mapping by lesion location: a functional magnetic resonance imaging, navigated transcranial magnetic stimulation, and direct cortical stimulation study.

    Science.gov (United States)

    Ille, Sebastian; Sollmann, Nico; Hauck, Theresa; Maurer, Stefanie; Tanigawa, Noriko; Obermueller, Thomas; Negwer, Chiara; Droese, Doris; Boeckh-Behrens, Tobias; Meyer, Bernhard; Ringel, Florian; Krieg, Sandro M

    2015-08-01

    Language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) is increasingly used and has already replaced functional MRI (fMRI) in some institutions for preoperative mapping of neurosurgical patients. Yet some factors affect the concordance of both methods with direct cortical stimulation (DCS), most likely by lesions affecting cortical oxygenation levels. Therefore, the impairment of the accuracy of rTMS and fMRI was analyzed and compared with DCS during awake surgery in patients with intraparenchymal lesions. Language mapping was performed by DCS, rTMS, and fMRI using an object-naming task in 27 patients with left-sided perisylvian lesions, and the induced language errors of each method were assigned to the cortical parcellation system. Subsequently, the receiver operating characteristics were calculated for rTMS and fMRI and compared with DCS as ground truth for regions with (w/) and without (w/o) the lesion in the mapped regions. The w/ subgroup revealed a sensitivity of 100% (w/o 100%), a specificity of 8% (w/o 5%), a positive predictive value of 34% (w/o: 53%), and a negative predictive value (NPV) of 100% (w/o: 100%) for the comparison of rTMS versus DCS. Findings for the comparison of fMRI versus DCS within the w/ subgroup revealed a sensitivity of 32% (w/o: 62%), a specificity of 88% (w/o: 60%), a positive predictive value of 56% (w/o: 62%), and a NPV of 73% (w/o: 60%). Although strengths and weaknesses exist for both rTMS and fMRI, the results show that rTMS is less affected by a brain lesion than fMRI, especially when performing mapping of language-negative cortical regions based on sensitivity and NPV.

  9. 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.

  10. PET imaging of T cells: Target identification and feasibility assessment.

    Science.gov (United States)

    Auberson, Yves P; Briard, Emmanuelle; Rudolph, Bettina; Kaupmann, Klemen; Smith, Paul; Oberhauser, Berndt

    2018-06-01

    Imaging T cells using positron emission tomography (PET) would be highly useful for diagnosis and monitoring in immunology and oncology patients. There are however no obvious targets that can be used to develop imaging agents for this purpose. We evaluated several potential target proteins with selective expression in T cells, and for which lead molecules were available: PKC , Lck, ZAP70 and Itk. Ultimately, we focused on Itk (interleukin-2-inducible T cell kinase) and identified a tool molecule with properties suitable for in vivo imaging of T cells, (5aR)-5,5-difluoro-5a-methyl-N-(1-((S)-3-(methylsulfonyl)-phenyl)(tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazol-4-yl)-1,4,4a,5,5a,6-hexahydro-cyclopropa[f]-indazole-3-carboxamide (23). While not having the optimal profile for clinical use, this molecule indicates that it might be possible to develop Itk-selective PET ligands for imaging the distribution of T cells in patients. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Protein kinase D1 modulates aldosterone-induced ENaC activity in a renal cortical collecting duct cell line.

    LENUS (Irish Health Repository)

    McEneaney, Victoria

    2010-08-30

    Aldosterone treatment of M1-CCD cells stimulated an increase in epithelial Na(+) channel (ENaC) alpha-subunit expression that was mainly localized to the apical membrane. PKD1-suppressed cells constitutively expressed ENaCalpha at low abundance, with no increase after aldosterone treatment. In the PKD1-suppressed cells, ENaCalpha was mainly localized proximal to the basolateral surface of the epithelium both before and after aldosterone treatment. Apical membrane insertion of ENaCbeta in response to aldosterone treatment was also sensitive to PKD1 suppression as was the aldosterone-induced rise in the amiloride-sensitive, trans-epithelial current (I(TE)). The interaction of the mineralocorticoid receptor (MR) with specific elements in the promoters of aldosterone responsive genes is stabilized by ligand interaction and phosphorylation. PKD1 suppression inhibited aldosterone-induced SGK-1 expression. The nuclear localization of MR was also blocked by PKD1 suppression and MEK antagonism implicating both these kinases in MR nuclear stabilization. PKD1 thus modulates aldosterone-induced ENaC activity through the modulation of sub-cellular trafficking and the stabilization of MR nuclear localization.

  12. Multiphoton autofluorescence lifetime imaging of induced pluripotent stem cells

    Science.gov (United States)

    Uchugonova, Aisada

    2017-06-01

    The multiphoton fluorescence lifetime imaging tomograph MPTflex with its flexible 360-deg scan head, articulated arm, and tunable femtosecond laser source was employed to study induced pluripotent stem cell (iPS) cultures. Autofluorescence (AF) lifetime imaging was performed with 250-ps temporal resolution and submicron spatial resolution using time-correlated single-photon counting. The two-photon excited AF was based on the metabolic coenzymes NAD(P)H and flavin adenine dinucleotide/flavoproteins. iPS cells generated from mouse embryonic fibroblasts (MEFs) and cocultured with growth-arrested MEFs as feeder cells have been studied. Significant differences on AF lifetime signatures were identified between iPS and feeder cells as well as between their differentiating counterparts.

  13. Quantitative image analysis for investigating cell-matrix interactions

    Science.gov (United States)

    Burkel, Brian; Notbohm, Jacob

    2017-07-01

    The extracellular matrix provides both chemical and physical cues that control cellular processes such as migration, division, differentiation, and cancer progression. Cells can mechanically alter the matrix by applying forces that result in matrix displacements, which in turn may localize to form dense bands along which cells may migrate. To quantify the displacements, we use confocal microscopy and fluorescent labeling to acquire high-contrast images of the fibrous material. Using a technique for quantitative image analysis called digital volume correlation, we then compute the matrix displacements. Our experimental technology offers a means to quantify matrix mechanics and cell-matrix interactions. We are now using these experimental tools to modulate mechanical properties of the matrix to study cell contraction and migration.

  14. A G protein-coupled receptor (GPCR) in red: live cell imaging of the kappa opioid receptor-tdTomato fusion protein (KOPR-tdT) in neuronal cells

    Science.gov (United States)

    Huang, Peng; Chiu, Yi-Ting; Chen, Chongguang; Wang, Yujun; Liu-Chen, Lee-Yuan

    2013-01-01

    Introduction In contrast to green fluorescent protein and variants (GFPs), red fluorescent proteins (RFPs) have rarely been employed for generation of GPCR fusion proteins, likely because of formation of aggregates and cell toxicity of some RFPs. Among all the RFPs available, tdTomato (tdT), one of the non-aggregating RFP, has the highest brightness score (about 3 times that of eGFP) and unsurpassed photostability. Methods We fused tdT to the KOPR C-terminus. The KOPR-tdT cDNA construct was transfected into Neuro2A mouse neuroblastoma cell line (Neuro2A cells) and rat cortical primary neurons for characterization of pharmacological properties and imaging studies on KOPR trafficking. Results KOPR-tdT retained KOPR properties (cell surface expression, ligand binding, agonist-induced signaling and internalization) when expressed in Neuro2A cells and rat primary cortical neurons. Live cell imaging of KOPR-tdT enables visualization of time course of agonist-induced internalization of KOPR in real time for 60 min, without photobleaching and apparent cell toxicity. U50,488H-induced KOPR internalization occurred as early as 4 min and plateaued at about 30 min. A unique pattern of internalized KOPR in processes of primary neurons was induced by U50,488H. Discussion tdT is an alternative to, or even a better tool than, GFPs for fusing to GPCR for trafficking studies, because tdT has higher brightness and thus better resolution and less photobleaching problems due to reduced laser power used. It also has advantages associated with its longer-wavelength emission including spectral separation from autofluorescence and GFPs, reduced cell toxicity the laser may impose, and greater tissue penetration. These advantages of tdT over GPFs may be critical for live cell imaging studies of GPCRs in vitro and for studying GPCRs in vivo because of their low abundance. PMID:23856011

  15. In vivo imaging of the retinal pigment epithelial cells

    Science.gov (United States)

    Morgan, Jessica Ijams Wolfing

    The retinal pigment epithelial (RPE) cells form an important layer of the retina because they are responsible for providing metabolic support to the photoreceptors. Techniques to image the RPE layer include autofluorescence imaging with a scanning laser ophthalmoscope (SLO). However, previous studies were unable to resolve single RPE cells in vivo. This thesis describes the technique of combining autofluorescence, SLO, adaptive optics (AO), and dual-wavelength simultaneous imaging and registration to visualize the individual cells in the RPE mosaic in human and primate retina for the first time in vivo. After imaging the RPE mosaic non-invasively, the cell layer's structure and regularity were characterized using quantitative metrics of cell density, spacing, and nearest neighbor distances. The RPE mosaic was compared to the cone mosaic, and RPE imaging methods were confirmed using histology. The ability to image the RPE mosaic led to the discovery of a novel retinal change following light exposure; 568 nm exposures caused an immediate reduction in autofluorescence followed by either full recovery or permanent damage in the RPE layer. A safety study was conducted to determine the range of exposure irradiances that caused permanent damage or transient autofluorescence reductions. Additionally, the threshold exposure causing autofluorescence reduction was determined and reciprocity of radiant exposure was confirmed. Light exposures delivered by the AOSLO were not significantly different than those delivered by a uniform source. As all exposures tested were near or below the permissible light levels of safety standards, this thesis provides evidence that the current light safety standards need to be revised. Finally, with the retinal damage and autofluorescence reduction thresholds identified, the methods of RPE imaging were modified to allow successful imaging of the individual cells in the RPE mosaic while still ensuring retinal safety. This thesis has provided a

  16. Post-adolescent developmental changes in cortical complexity

    OpenAIRE

    Sandu, Anca-Larisa; Izard, Edouard; Specht, Karsten; Beneventi, Harald; Lundervold, Arvid; Ystad, Martin

    2014-01-01

    Background: Post-adolescence is known to be a period of general maturation and development in the human brain. In brain imaging, volumetric and morphologic cortical grey-matter changes can easily be assessed, but the analysis of cortical complexity seems to have been broadly neglected for this age interval. Methods: Magnetic resonance imaging (MRI) was used to acquire structural brain images. The study involved 17 adolescents (mean age 14.1 ± 0.27, 11 girls) who were compared with 1...

  17. Contraction of gut smooth muscle cells assessed by fluorescence imaging

    Directory of Open Access Journals (Sweden)

    Yohei Tokita

    2015-03-01

    Full Text Available Here we discuss the development of a novel cell imaging system for the evaluation of smooth muscle cell (SMC contraction. SMCs were isolated from the circular and longitudinal muscular layers of mouse small intestine by enzymatic digestion. SMCs were stimulated by test agents, thereafter fixed in acrolein. Actin in fixed SMCs was stained with phalloidin and cell length was determined by measuring diameter at the large end of phalloidin-stained strings within the cells. The contractile response was taken as the decrease in the average length of a population of stimulated-SMCs. Various mediators and chemically identified compounds of daikenchuto (DKT, pharmaceutical-grade traditional Japanese prokinetics, were examined. Verification of the integrity of SMC morphology by phalloidin and DAPI staining and semi-automatic measurement of cell length using an imaging analyzer was a reliable method by which to quantify the contractile response. Serotonin, substance P, prostaglandin E2 and histamine induced SMC contraction in concentration-dependent manner. Two components of DKT, hydroxy-α-sanshool and hydroxy-β-sanshool, induced contraction of SMCs. We established a novel cell imaging technique to evaluate SMC contractility. This method may facilitate investigation into SMC activity and its role in gastrointestinal motility, and may assist in the discovery of new prokinetic agents.

  18. Imaging of complications from hematopoietic stem cell transplant

    International Nuclear Information System (INIS)

    Pandey, Tarun; Maximin, Suresh; Bhargava, Puneet

    2014-01-01

    Stem cell transplant has been the focus of clinical research for a long time given its potential to treat several incurable diseases like hematological malignancies, diabetes mellitus, and neuro-degenerative disorders like Parkinson disease. Hematopoietic stem cell transplantation (HSCT) is the oldest and most widely used technique of stem cell transplant. HSCT has not only been used to treat hematological disorders including hematological malignancies, but has also been found useful in treamtent of genetic, immunological, and solid tumors like neuroblastoma, lymphoma, and germ cell tumors. In spite of the rapid advances in stem cell technology, success rate with this technique has not been universal and many complications have also been seen with this form of therapy. The key to a successful HSCT therapy lies in early diagnosis and effective management of complications associated with this treatment. Our article aims to review the role of imaging in diagnosis and management of stem cell transplant complications associated with HSCT

  19. Cellular transfer of magnetic nanoparticles via cell microvesicles: impact on cell tracking by magnetic resonance imaging.

    Science.gov (United States)

    Silva, Amanda K Andriola; Wilhelm, Claire; Kolosnjaj-Tabi, Jelena; Luciani, Nathalie; Gazeau, Florence

    2012-05-01

    Cell labeling with magnetic nanoparticles can be used to monitor the fate of transplanted cells in vivo by magnetic resonance imaging. However, nanoparticles initially internalized in administered cells might end up in other cells of the host organism. We investigated a mechanism of intercellular cross-transfer of magnetic nanoparticles to different types of recipient cells via cell microvesicles released under cellular stress. Three cell types (mesenchymal stem cells, endothelial cells and macrophages) were labeled with 8-nm iron oxide nanoparticles. Then cells underwent starvation stress, during which they produced microvesicles that were subsequently transferred to unlabeled recipient cells. The analysis of the magnetophoretic mobility of donor cells indicated that magnetic load was partially lost under cell stress. Microvesicles shed by stressed cells participated in the release of magnetic label. Moreover, such microvesicles were uptaken by naïve cells, resulting in cellular redistribution of nanoparticles. Iron load of recipient cells allowed their detection by MRI. Cell microvesicles released under stress may be disseminated throughout the organism, where they can be uptaken by host cells. The transferred cargo may be sufficient to allow MRI detection of these secondarily labeled cells, leading to misinterpretations of the effectiveness of transplanted cells.

  20. Unraveling cell processes: interference imaging interwoven with data analysis

    DEFF Research Database (Denmark)

    Brazhe, Nadezda; Brazhe, Alexey; Pavlov, A N

    2006-01-01

    The paper presents results on the application of interference microscopy and wavelet-analysis for cell visualization and studies of cell dynamics. We demonstrate that interference imaging of erythrocytes can reveal reorganization of the cytoskeleton and inhomogenity in the distribution of hemoglo......The paper presents results on the application of interference microscopy and wavelet-analysis for cell visualization and studies of cell dynamics. We demonstrate that interference imaging of erythrocytes can reveal reorganization of the cytoskeleton and inhomogenity in the distribution...... properties differ from cell type to cell type and depend on the cellular compartment. Our results suggest that low frequency variations (0.1-0.6 Hz) result from plasma membrane processes and that higher frequency variations (20-26 Hz) are related to the movement of vesicles. Using double-wavelet analysis, we...... study the modulation of the 1 Hz rhythm in neurons and reveal its changes under depolarization and hyperpolarization of the plasma membrane. We conclude that interference microscopy combined with wavelet analysis is a useful technique for non-invasive cell studies, cell visualization, and investigation...

  1. The Role of Biotransformation and Oxidative Stress in 3,5-Dichloroaniline (3,5-DCA) Induced Nephrotoxicity in Isolated Renal Cortical Cells from Male Fischer 344 Rats

    Science.gov (United States)

    Racine, Christopher R.; Ferguson, Travis; Preston, Debbie; Ward, Dakota; Ball, John; Anestis, Dianne; Valentovic, Monica; Rankin, Gary O.

    2016-01-01

    Among the mono- and dichloroanilines, 3,5-Dichloroaniline (3,5-DCA) is the most potent nephrotoxicant in vivo and in vitro. However, the role of renal biotransformation in 3,5-DCA induced nephrotoxicity is unknown. The current study was designed to determine the in vitro nephrotoxic potential of 3,5-DCA in isolated renal cortical cells (IRCC) obtained from male Fischer 344 rats, and the role of renal bioactivation and oxidative stress in 3,5-DCA nephrotoxicity. IRCC (~4 million cells/ml) from male rats were exposed to 3,5-DCA (0-1.0 mM) for up to 120 min. In IRCC, 3,5-DCA was cytotoxic at 1.0 mM by 60 min as evidenced by the increased release of lactate dehydrogenase (LDH), but 120 min was required for 3,5-DCA 0.5 mM to increase LDH release. In subsequent studies, IRCC were exposed to a pretreatment (antioxidant or enzyme inhibitor) prior to exposure to 3,5-DCA (1.0 mM) for 90 min. Cytotoxicity induced by 3,5-DCA was attenuated by pretreatment with inhibitors of flavin-containing monooxygenase (FMO; methimazole, N-octylamine), cytochrome P450 (CYP; piperonyl butoxide, metyrapone), or peroxidase (indomethacin, mercaptosuccinate) enzymes. Use of more selective CYP inhibitors suggested that the CYP 2C family contributed to 3,5-DCA bioactivation. Antioxidants (glutathione, N-acetyl-L-cysteine, α-tocopherol, ascorbate, pyruvate) also attenuated 3,5-DCA nephrotoxicity, but oxidized glutathione levels and the oxidized/reduced glutathione ratios were not increased. These results indicate that 3,5-DCA may be activated via several renal enzyme systems to toxic metabolites, and that free radicals, but not oxidative stress, contribute to 3,5-DCA induced nephrotoxicity in vitro. PMID:26808022

  2. A probabilistic cell model in background corrected image sequences for single cell analysis

    Directory of Open Access Journals (Sweden)

    Fieguth Paul

    2010-10-01

    Full Text Available Abstract Background Methods of manual cell localization and outlining are so onerous that automated tracking methods would seem mandatory for handling huge image sequences, nevertheless manual tracking is, astonishingly, still widely practiced in areas such as cell biology which are outside the influence of most image processing research. The goal of our research is to address this gap by developing automated methods of cell tracking, localization, and segmentation. Since even an optimal frame-to-frame association method cannot compensate and recover from poor detection, it is clear that the quality of cell tracking depends on the quality of cell detection within each frame. Methods Cell detection performs poorly where the background is not uniform and includes temporal illumination variations, spatial non-uniformities, and stationary objects such as well boundaries (which confine the cells under study. To improve cell detection, the signal to noise ratio of the input image can be increased via accurate background estimation. In this paper we investigate background estimation, for the purpose of cell detection. We propose a cell model and a method for background estimation, driven by the proposed cell model, such that well structure can be identified, and explicitly rejected, when estimating the background. Results The resulting background-removed images have fewer artifacts and allow cells to be localized and detected more reliably. The experimental results generated by applying the proposed method to different Hematopoietic Stem Cell (HSC image sequences are quite promising. Conclusion The understanding of cell behavior relies on precise information about the temporal dynamics and spatial distribution of cells. Such information may play a key role in disease research and regenerative medicine, so automated methods for observation and measurement of cells from microscopic images are in high demand. The proposed method in this paper is capable

  3. 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)

  4. In vivo fluorescence imaging of primate retinal ganglion cells and retinal pigment epithelial cells

    Science.gov (United States)

    Gray, Daniel C.; Merigan, William; Wolfing, Jessica I.; Gee, Bernard P.; Porter, Jason; Dubra, Alfredo; Twietmeyer, Ted H.; Ahamd, Kamran; Tumbar, Remy; Reinholz, Fred; Williams, David R.

    2006-08-01

    The ability to resolve single cells noninvasively in the living retina has important applications for the study of normal retina, diseased retina, and the efficacy of therapies for retinal disease. We describe a new instrument for high-resolution, in vivo imaging of the mammalian retina that combines the benefits of confocal detection, adaptive optics, multispectral, and fluorescence imaging. The instrument is capable of imaging single ganglion cells and their axons through retrograde transport in ganglion cells of fluorescent dyes injected into the monkey lateral geniculate nucleus (LGN). In addition, we demonstrate a method involving simultaneous imaging in two spectral bands that allows the integration of very weak signals across many frames despite inter-frame movement of the eye. With this method, we are also able to resolve the smallest retinal capillaries in fluorescein angiography and the mosaic of retinal pigment epithelium (RPE) cells with lipofuscin autofluorescence.

  5. Autofluorescence-Free Live-Cell Imaging Using Terbium Nanoparticles.

    Science.gov (United States)

    Cardoso Dos Santos, M; Goetz, J; Bartenlian, H; Wong, K-L; Charbonnière, L J; Hildebrandt, N

    2018-04-18

    Fluorescent nanoparticles (NPs) have become irreplaceable tools for advanced cellular and subcellular imaging. While very bright NPs require excitation with UV or visible light, which can create strong autofluorescence of biological components, NIR-excitable NPs without autofluorescence issues exhibit much lower brightness. Here, we show the application of a new type of surface-photosensitized terbium NPs (Tb-NPs) for autofluorescence-free intracellular imaging in live HeLa cells. The combination of exceptionally high brightness, high photostability, and long photoluminecence (PL) lifetimes for highly efficient suppression of the short-lived autofluorescence allowed for time-gated PL imaging of intracellular vesicles over 72 h without toxicity and at extremely low Tb-NP concentrations down to 12 pM. Detection of highly resolved long-lifetime (ms) PL decay curves from small (∼10 μm 2 ) areas within single cells within a few seconds emphasized the unprecedented photophysical properties of Tb-NPs for live-cell imaging that extend well beyond currently available nanometric imaging agents.

  6. 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

  7. Quantifying Solar Cell Cracks in Photovoltaic Modules by Electroluminescence Imaging

    DEFF Research Database (Denmark)

    Spataru, Sergiu; Hacke, Peter; Sera, Dezso

    2015-01-01

    This article proposes a method for quantifying the percentage of partially and totally disconnected solar cell cracks by analyzing electroluminescence images of the photovoltaic module taken under high- and low-current forward bias. The method is based on the analysis of the module’s electrolumin...

  8. MR-based imaging of neural stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Politi, Letterio S. [San Raffaele Scientific Institute, Neuroradiology Department, Milano (Italy)

    2007-06-15

    The efficacy of therapies based on neural stem cells (NSC) has been demonstrated in preclinical models of several central nervous system (CNS) diseases. Before any potential human application of such promising therapies can be envisaged, there are some important issues that need to be solved. The most relevant one is the requirement for a noninvasive technique capable of monitoring NSC delivery, homing to target sites and trafficking. Knowledge of the location and temporospatial migration of either transplanted or genetically modified NSC is of the utmost importance in analyzing mechanisms of correction and cell distribution. Further, such a technique may represent a crucial step toward clinical application of NSC-based approaches in humans, for both designing successful protocols and monitoring their outcome. Among the diverse imaging approaches available for noninvasive cell tracking, such as nuclear medicine techniques, fluorescence and bioluminescence, magnetic resonance imaging (MRI) has unique advantages. Its high temporospatial resolution, high sensitivity and specificity render MRI one of the most promising imaging modalities available, since it allows dynamic visualization of migration of transplanted cells in animal models and patients during clinically useful time periods. Different cellular and molecular labeling approaches for MRI depiction of NSC are described and discussed in this review, as well as the most relevant issues to be considered in optimizing molecular imaging techniques for clinical application. (orig.)

  9. In Vivo Imaging of Natural Killer Cell Trafficking in Tumors

    NARCIS (Netherlands)

    Galli, Filippo; Rapisarda, Anna Serafina; Stabile, Helena; Malviya, Gaurav; Manni, Isabella; Bonanno, Elena; Piaggio, Giulia; Gismondi, Angela; Santoni, Angela; Signore, Alberto

    2015-01-01

    Natural killer cells (NKs) are important effectors of the innate immune system, with marked antitumor activity. Imaging NK trafficking in vivo may be relevant to following up the efficacy of new therapeutic approaches aiming at increasing tumor-infiltrating NKs (TINKs). The specific aims of present

  10. MR-based imaging of neural stem cells

    International Nuclear Information System (INIS)

    Politi, Letterio S.

    2007-01-01

    The efficacy of therapies based on neural stem cells (NSC) has been demonstrated in preclinical models of several central nervous system (CNS) diseases. Before any potential human application of such promising therapies can be envisaged, there are some important issues that need to be solved. The most relevant one is the requirement for a noninvasive technique capable of monitoring NSC delivery, homing to target sites and trafficking. Knowledge of the location and temporospatial migration of either transplanted or genetically modified NSC is of the utmost importance in analyzing mechanisms of correction and cell distribution. Further, such a technique may represent a crucial step toward clinical application of NSC-based approaches in humans, for both designing successful protocols and monitoring their outcome. Among the diverse imaging approaches available for noninvasive cell tracking, such as nuclear medicine techniques, fluorescence and bioluminescence, magnetic resonance imaging (MRI) has unique advantages. Its high temporospatial resolution, high sensitivity and specificity render MRI one of the most promising imaging modalities available, since it allows dynamic visualization of migration of transplanted cells in animal models and patients during clinically useful time periods. Different cellular and molecular labeling approaches for MRI depiction of NSC are described and discussed in this review, as well as the most relevant issues to be considered in optimizing molecular imaging techniques for clinical application. (orig.)

  11. Hierarchical imaging: a new concept for targeted imaging of large volumes from cells to tissues.

    Science.gov (United States)

    Wacker, Irene; Spomer, Waldemar; Hofmann, Andreas; Thaler, Marlene; Hillmer, Stefan; Gengenbach, Ulrich; Schröder, Rasmus R

    2016-12-12

    Imaging large volumes such as entire cells or small model organisms at nanoscale resolution seemed an unrealistic, rather tedious task so far. Now, technical advances have lead to several electron microscopy (EM) large volume imaging techniques. One is array tomography, where ribbons of ultrathin serial sections are deposited on solid substrates like silicon wafers or glass coverslips. To ensure reliable retrieval of multiple ribbons from the boat of a diamond knife we introduce a substrate holder with 7 axes of translation or rotation specifically designed for that purpose. With this device we are able to deposit hundreds of sections in an ordered way in an area of 22 × 22 mm, the size of a coverslip. Imaging such arrays in a standard wide field fluorescence microscope produces reconstructions with 200 nm lateral resolution and 100 nm (the section thickness) resolution in z. By hierarchical imaging cascades in the scanning electron microscope (SEM), using a new software platform, we can address volumes from single cells to complete organs. In our first example, a cell population isolated from zebrafish spleen, we characterize different cell types according to their organelle inventory by segmenting 3D reconstructions of complete cells imaged with nanoscale resolution. In addition, by screening large numbers of cells at decreased resolution we can define the percentage at which different cell types are present in our preparation. With the second example, the root tip of cress, we illustrate how combining information from intermediate resolution data with high resolution data from selected regions of interest can drastically reduce the amount of data that has to be recorded. By imaging only the interesting parts of a sample considerably less data need to be stored, handled and eventually analysed. Our custom-designed substrate holder allows reproducible generation of section libraries, which can then be imaged in a hierarchical way. We demonstrate, that EM

  12. Effects of dimeric PSD-95 inhibition on excitotoxic cell death and outcome after controlled cortical impact in rats

    DEFF Research Database (Denmark)

    Sommer, Jens Bak; Bach, Anders; Rytter, Hana Malá

    2017-01-01

    Therapeutic effects of PSD-95 inhibition have been demonstrated in numerous studies of stroke; however only few studies have assessed the effects of PSD-95 inhibitors in traumatic brain injury (TBI). As the pathophysiology of TBI partially overlaps with that of stroke, PSD-95 inhibition may also...... assessed in a water maze at two weeks post-trauma, and at four weeks lesion volumes were estimated. Overall, UCCB01-144 did not protect against NMDA-toxicity in neuronal cultures or experimental TBI in rats. Important factors that should be investigated further in future studies assessing the effects...... be an effective therapeutic strategy in TBI. The objectives of the present study were to assess the effects of a dimeric inhibitor of PSD-95, UCCB01-144, on excitotoxic cell death in vitro and outcome after experimental TBI in rats in vivo. In addition, the pharmacokinetic parameters of UCCB01-144 were...

  13. Low concentrations of the solvent dimethyl sulphoxide alter intrinsic excitability properties of cortical and hippocampal pyramidal cells.

    Directory of Open Access Journals (Sweden)

    Francesco Tamagnini

    Full Text Available Dimethylsulfoxide (DMSO is a widely used solvent in biology. It has many applications perhaps the most common of which is in aiding the preparation of drug solutions from hydrophobic chemical entities. Recent studies have suggested that this molecule may be able to induce apoptosis in neural tissues urging caution regarding its introduction into humans, for example as part of stem cell transplants. Here we have used in vitro electrophysiological methods applied to murine brain slices to examine whether a few hours treatment with 0.05% DMSO (a concentration regarded by many as innocuous alters intrinsic excitability properties of neurones. We investigated pyramidal neurones in two distinct brain regions, namely area CA1 of the hippocampus and layer 2 of perirhinal cortex. In the former there was no effect on resting potential but input resistance was decreased by DMSO pre-treatment. In line with this action potential count for any level of depolarizing current stimulus was reduced by ∼25% following DMSO treatment. Ih-mediated "sag" was also increased in CA1 pyramids and action potential waveform analysis demonstrated that DMSO treatment moved action potential threshold towards resting potential. In perirhinal cortex a decreased action potential output for various depolarizing current stimuli was also seen. In these cells action potential threshold was unaltered by DMSO but a significant increase in action potential width was apparent. These data indicate that pre-treatment with this widely employed solvent can elicit multifaceted neurophysiological changes in mammalian neurones at concentrations below those frequently encountered in the published literature.

  14. Live cell imaging of actin dynamics in dexamethasone-treated porcine trabecular meshwork cells.

    Science.gov (United States)

    Fujimoto, Tomokazu; Inoue, Toshihiro; Inoue-Mochita, Miyuki; Tanihara, Hidenobu

    2016-04-01

    The regulation of the actin cytoskeleton in trabecular meshwork (TM) cells is important for controlling outflow of the aqueous humor. In some reports, dexamethasone (DEX) increased the aqueous humor outflow resistance and induced unusual actin structures, such as cross-linked actin networks (CLAN), in TM cells. However, the functions and dynamics of CLAN in TM cells are not completely known, partly because actin stress fibers have been observed only in fixed cells. We conducted live-cell imaging of the actin dynamics in TM cells with or without DEX treatment. An actin-green fluorescent protein (GFP) fusion construct with a modified insect virus was transfected into porcine TM cells. Time-lapse imaging of live TM cells treated with 25 μM Y-27632 and 100 nM DEX was performed using an inverted fluorescence microscope. Fluorescent images were recorded every 15 s for 30 min after Y-27632 treatment or every 30 min for 72 h after DEX treatment. The GFP-actin was expressed in 22.7 ± 10.9% of the transfected TM cells. In live TM cells, many actin stress fibers were observed before the Y-27632 treatment. Y-27632 changed the cell shape and decreased stress fibers in a time-dependent manner. In fixed cells, CLAN-like structures were seen in 26.5 ± 1.7% of the actin-GFP expressed PTM cells treated with DEX for 72 h. In live imaging, there was 28% CLAN-like structure formation at 72 h after DEX treatment, and the lifetime of CLAN-like structures increased after DEX treatment. The DEX-treated cells with CLAN-like structures showed less migration than DEX-treated cells without CLAN-like structures. Furthermore, the control cells (without DEX treatment) with CLAN-like structures also showed less migration than the control cells without CLAN-like structures. These results suggested that CLAN-like structure formation was correlated with cell migration in TM cells. Live cell imaging of the actin cytoskeleton provides valuable information on the actin dynamics in TM

  15. Insulin and IGF-1 activate Kir4.1/5.1 channels in cortical collecting duct principal cells to control basolateral membrane voltage.

    Science.gov (United States)

    Zaika, Oleg; Palygin, Oleg; Tomilin, Viktor; Mamenko, Mykola; Staruschenko, Alexander; Pochynyuk, Oleh

    2016-02-15

    Potassium Kir4.1/5.1 channels are abundantly expressed at the basolateral membrane of principal cells in the cortical collecting duct (CCD), where they are thought to modulate transport rates by controlling transepithelial voltage. Insulin and insulin-like growth factor-1 (IGF-1) stimulate apically localized epithelial sodium channels (ENaC) to augment sodium reabsorption in the CCD. However, little is known about their actions on potassium channels localized at the basolateral membrane. In this study, we implemented patch-clamp analysis in freshly isolated murine CCD to assess the effect of these hormones on Kir4.1/5.1 at both single channel and cellular levels. We demonstrated that K(+)-selective conductance via Kir4.1/5.1 is the major contributor to the macroscopic current recorded from the basolateral side in principal cells. Acute treatment with 10 μM amiloride (ENaC blocker), 100 nM tertiapin-Q (TPNQ; ROMK inhibitor), and 100 μM ouabain (Na(+)-K(+)-ATPase blocker) failed to produce a measurable effect on the macroscopic current. In contrast, Kir4.1 inhibitor nortriptyline (100 μM), but not fluoxetine (100 μM), virtually abolished whole cell K(+)-selective conductance. Insulin (100 nM) markedly increased the open probability of Kir4.1/5.1 and nortriptyline-sensitive whole cell current, leading to significant hyperpolarization of the basolateral membrane. Inhibition of the phosphatidylinositol 3-kinase cascade with LY294002 (20 μM) abolished action of insulin on Kir4.1/5.1. IGF-1 had similar stimulatory actions on Kir4.1/5.1-mediated conductance only when applied at a higher (500 nM) concentration and was ineffective at 100 nM. We concluded that both insulin and, to a lesser extent, IGF-1 activate Kir4.1/5.1 channel activity and open probability to hyperpolarize the basolateral membrane, thereby facilitating Na(+) reabsorption in the CCD. Copyright © 2016 the American Physiological Society.

  16. Cell Matrix Remodeling Ability Shown by Image Spatial Correlation

    Science.gov (United States)

    Chiu, Chi-Li; Digman, Michelle A.; Gratton, Enrico

    2013-01-01

    Extracellular matrix (ECM) remodeling is a critical step of many biological and pathological processes. However, most of the studies to date lack a quantitative method to measure ECM remodeling at a scale comparable to cell size. Here, we applied image spatial correlation to collagen second harmonic generation (SHG) images to quantitatively evaluate the degree of collagen remodeling by cells. We propose a simple statistical method based on spatial correlation functions to determine the size of high collagen density area around cells. We applied our method to measure collagen remodeling by two breast cancer cell lines (MDA-MB-231 and MCF-7), which display different degrees of invasiveness, and a fibroblast cell line (NIH/3T3). We found distinct collagen compaction levels of these three cell lines by applying the spatial correlation method, indicating different collagen remodeling ability. Furthermore, we quantitatively measured the effect of Latrunculin B and Marimastat on MDA-MB-231 cell line collagen remodeling ability and showed that significant collagen compaction level decreases with these treatments. PMID:23935614

  17. Segmentation of fluorescence microscopy cell images using unsupervised mining.

    Science.gov (United States)

    Du, Xian; Dua, Sumeet

    2010-05-28

    The accurate measurement of cell and nuclei contours are critical for the sensitive and specific detection of changes in normal cells in several medical informatics disciplines. Within microscopy, this task is facilitated using fluorescence cell stains, and segmentation is often the first step in such approaches. Due to the complex nature of cell issues and problems inherent to microscopy, unsupervised mining approaches of clustering can be incorporated in the segmentation of cells. In this study, we have developed and evaluated the performance of multiple unsupervised data mining techniques in cell image segmentation. We adapt four distinctive, yet complementary, methods for unsupervised learning, including those based on k-means clustering, EM, Otsu's threshold, and GMAC. Validation measures are defined, and the performance of the techniques is evaluated both quantitatively and qualitatively using synthetic and recently published real data. Experimental results demonstrate that k-means, Otsu's threshold, and GMAC perform similarly, and have more precise segmentation results than EM. We report that EM has higher recall values and lower precision results from under-segmentation due to its Gaussian model assumption. We also demonstrate that these methods need spatial information to segment complex real cell images with a high degree of efficacy, as expected in many medical informatics applications.

  18. Cell and Tissue Imaging with Molecularly Imprinted Polymers.

    Science.gov (United States)

    Panagiotopoulou, Maria; Kunath, Stephanie; Haupt, Karsten; Tse Sum Bui, Bernadette

    2017-01-01

    Advanced tools for cell imaging are of particular interest as they can detect, localize and quantify molecular targets like abnormal glycosylation sites that are biomarkers of cancer and infection. Targeting these biomarkers is often challenging due to a lack of receptor materials. Molecularly imprinted polymers (MIPs) are promising artificial receptors; they can be tailored to bind targets specifically, be labeled easily, and are physically and chemically stable. Herein, we demonstrate the application of MIPs as artificial antibodies for selective labeling and imaging of cellular targets, on the example of hyaluronan and sialylation moieties on fixated human skin cells and tissues. Thus, fluorescently labeled MIP nanoparticles templated with glucuronic acid (MIPGlcA) and N-acetylneuraminic acid (MIPNANA) are respectively applied. Two different fluorescent probes are used: (1) MIPGlcA particles, ~400 nm in size are labeled with the dye rhodamine that target the extracellular hyaluronan on cells and tissue specimens and (2) MIP-coated InP/ZnS quantum dots (QDs) of two different colors, ~125 nm in size that target the extracellular and intracellular hyaluronan and sialylation sites. Green and red emitting QDs are functionalized with MIPGlcA and MIPNANA respectively, enabling multiplexed cell imaging. This is a general approach that can also be adapted to other target molecules on and in cells.

  19. Super-resolution Microscopy in Plant Cell Imaging.

    Science.gov (United States)

    Komis, George; Šamajová, Olga; Ovečka, Miroslav; Šamaj, Jozef

    2015-12-01

    Although the development of super-resolution microscopy methods dates back to 1994, relevant applications in plant cell imaging only started to emerge in 2010. Since then, the principal super-resolution methods, including structured-illumination microscopy (SIM), photoactivation localization microscopy (PALM), stochastic optical reconstruction microscopy (STORM), and stimulated emission depletion microscopy (STED), have been implemented in plant cell research. However, progress has been limited due to the challenging properties of plant material. Here we summarize the basic principles of existing super-resolution methods and provide examples of applications in plant science. The limitations imposed by