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Sample records for brain reveals unexpected

  1. Unexpected brain finding in pre-autopsy postmortem CT.

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    Chatzaraki, Vasiliki; Bolliger, Stephan A; Thali, Michael J; Eggert, Sebastian; Ruder, Thomas D

    2017-09-01

    A case is presented in which pre-autopsy postmortem computed tomography (PMCT) revealed an unexpected brain abscess with a related frontal sinusitis and an erosion of the posterior wall of the frontal sinus. PMCT findings enabled the forensic pathologists to adapt protective measures during autopsy and protect their health from infection. Pre-autopsy PMCT has been also useful in the early differential diagnosis procedure. The complementary use of postmortem imaging and autopsy can improve the quality of forensic death investigations.

  2. Effects of unexpected chords and of performer's expression on brain responses and electrodermal activity.

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    Stefan Koelsch

    Full Text Available BACKGROUND: There is lack of neuroscientific studies investigating music processing with naturalistic stimuli, and brain responses to real music are, thus, largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: This study investigates event-related brain potentials (ERPs, skin conductance responses (SCRs and heart rate (HR elicited by unexpected chords of piano sonatas as they were originally arranged by composers, and as they were played by professional pianists. From the musical excerpts played by the pianists (with emotional expression, we also created versions without variations in tempo and loudness (without musical expression to investigate effects of musical expression on ERPs and SCRs. Compared to expected chords, unexpected chords elicited an early right anterior negativity (ERAN, reflecting music-syntactic processing and an N5 (reflecting processing of meaning information in the ERPs, as well as clear changes in the SCRs (reflecting that unexpected chords also elicited emotional responses. The ERAN was not influenced by emotional expression, whereas N5 potentials elicited by chords in general (regardless of their chord function differed between the expressive and the non-expressive condition. CONCLUSIONS/SIGNIFICANCE: These results show that the neural mechanisms of music-syntactic processing operate independently of the emotional qualities of a stimulus, justifying the use of stimuli without emotional expression to investigate the cognitive processing of musical structure. Moreover, the data indicate that musical expression affects the neural mechanisms underlying the processing of musical meaning. Our data are the first to reveal influences of musical performance on ERPs and SCRs, and to show physiological responses to unexpected chords in naturalistic music.

  3. Molecular Analyses Reveal Unexpected Genetic Structure in Iberian Ibex Populations.

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    Angelone-Alasaad, Samer; Biebach, Iris; Pérez, Jesús M; Soriguer, Ramón C; Granados, José E

    2017-01-01

    Genetic differentiation in historically connected populations could be the result of genetic drift or adaptation, two processes that imply a need for differing strategies in population management. The aim of our study was to use neutral genetic markers to characterize C. pyrenaica populations genetically and examine results in terms of (i) demographic history, (ii) subspecific classification and (iii) the implications for the management of Iberian ibex. We used 30 neutral microsatellite markers from 333 Iberian ibex to explore genetic diversity in the three main Iberian ibex populations in Spain corresponding to the two persisting subspecies (victoria and hispanica). Our molecular analyses detected recent genetic bottlenecks in all the studied populations, a finding that coincides with the documented demographic decline in C. pyrenaica in recent decades. Genetic divergence between the two C. pyrenaica subspecies (hispanica and victoriae) was substantial (FST between 0.39 and 0.47). Unexpectedly, we found similarly high genetic differentiation between two populations (Sierra Nevada and Maestrazgo) belonging to the subspecies hispanica. The genetic pattern identified in our study could be the result of strong genetic drift due to the severe genetic bottlenecks in the studied populations, caused in turn by the progressive destruction of natural habitat, disease epidemics and/or uncontrolled hunting. Previous Capra pyrenaica conservation decision-making was based on the clear distinction between the two subspecies (victoriae and hispanica); yet our paper raises questions about the usefulness for conservation plans of the distinction between these subspecies.

  4. Magnetoencephalography Reveals Mismatch Field Enhancement from Unexpected Syntactic Category Errors in English Sentences.

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    Kubota, Mikio; Ono, Yumie; Ishiyama, Atsushi; Zouridakis, George; Papanicolaou, Andrew C

    2018-01-01

    The type of syntactic operations that increase neuronal activation in humans as a result of syntactically erroneous, unexpected lexical items in hearing sentences has remained unclear. In the present study, we used recordings of magnetoencephalographic (MEG) activity to compare bare infinitive and full infinitive constructions in English. This research aims to identify the type of syntactic deviance that may trigger an early syntax-related mismatch field (MMF) component when unexpected words appear in sentences. Six speakers of English as a first language were presented with auditory stimuli of sentences or words in a passive odd-ball paradigm while watching a silent movie. The experimental protocol included four sessions, specifically investigating the sentential (structural) versions of full (with the 'to' infinitival particle) and bare infinitival structures (without the particle) and the lexical (non-structure) versions of the verb either with or without the particle to determine whether the structure processing of sentences was a more crucial factor in the detection of the MMF than the simple processing of lexical items in verb-only conditions. The amplitude analysis of the resulting evoked fields showed that the presence of the syntactic category error of bare infinitival structures against syntactic predictions evoked a significantly larger MMF activation with a peak latency of approximately 200ms in the anterior superior temporal sulci in the left hemisphere, compared with the lexical items that did not have any syntactic status. These results clearly demonstrate that syntactically unexpected, illegal input in the bare infinitival structure is likely to be noticed more robustly in the brain while processing the structural information of the entire sentence than the corresponding verb-only items. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. The Crystal Structures of EAP Domains from Staphylococcus aureus Reveal an Unexpected Homology to Bacterial Superantigens

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    Geisbrecht, B V; Hamaoka, B Y; Perman, B; Zemla, A; Leahy, D J

    2005-10-14

    The Eap (extracellular adherence protein) of Staphylococcus aureus functions as a secreted virulence factor by mediating interactions between the bacterial cell surface and several extracellular host proteins. Eap proteins from different Staphylococcal strains consist of four to six tandem repeats of a structurally uncharacterized domain (EAP domain). We have determined the three-dimensional structures of three different EAP domains to 1.8, 2.2, and 1.35 {angstrom} resolution, respectively. These structures reveal a core fold that is comprised of an {alpha}-helix lying diagonally across a five-stranded, mixed {beta}-sheet. Comparison of EAP domains with known structures reveals an unexpected homology with the C-terminal domain of bacterial superantigens. Examination of the structure of the superantigen SEC2 bound to the {beta}-chain of a T-cell receptor suggests a possible ligand-binding site within the EAP domain (Fields, B. A., Malchiodi, E. L., Li, H., Ysern, X., Stauffacher, C. V., Schlievert, P. M., Karjalainen, K., and Mariuzza, R. (1996) Nature 384, 188-192). These results provide the first structural characterization of EAP domains, relate EAP domains to a large class of bacterial toxins, and will guide the design of future experiments to analyze EAP domain structure/function relationships.

  6. Kinase Inhibitor Profiling Reveals Unexpected Opportunities to Inhibit Disease-Associated Mutant Kinases

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    Krisna C. Duong-Ly

    2016-02-01

    Full Text Available Small-molecule kinase inhibitors have typically been designed to inhibit wild-type kinases rather than the mutant forms that frequently arise in diseases such as cancer. Mutations can have serious clinical implications by increasing kinase catalytic activity or conferring therapeutic resistance. To identify opportunities to repurpose inhibitors against disease-associated mutant kinases, we conducted a large-scale functional screen of 183 known kinase inhibitors against 76 recombinant mutant kinases. The results revealed lead compounds with activity against clinically important mutant kinases, including ALK, LRRK2, RET, and EGFR, as well as unexpected opportunities for repurposing FDA-approved kinase inhibitors as leads for additional indications. Furthermore, using T674I PDGFRα as an example, we show how single-dose screening data can provide predictive structure-activity data to guide subsequent inhibitor optimization. This study provides a resource for the development of inhibitors against numerous disease-associated mutant kinases and illustrates the potential of unbiased profiling as an approach to compound-centric inhibitor development.

  7. Phylogenomic analysis of Copepoda (Arthropoda, Crustacea) reveals unexpected similarities with earlier proposed morphological phylogenies.

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    Eyun, Seong-Il

    2017-01-19

    Copepods play a critical role in marine ecosystems but have been poorly investigated in phylogenetic studies. Morphological evidence supports the monophyly of copepods, whereas interordinal relationships continue to be debated. In particular, the phylogenetic position of the order Harpacticoida is still ambiguous and inconsistent among studies. Until now, a small number of molecular studies have been done using only a limited number or even partial genes and thus there is so far no consensus at the order-level. This study attempted to resolve phylogenetic relationships among and within four major copepod orders including Harpacticoida and the phylogenetic position of Copepoda among five other crustacean groups (Anostraca, Cladocera, Sessilia, Amphipoda, and Decapoda) using 24 nuclear protein-coding genes. Phylogenomics has confirmed the monophyly of Copepoda and Podoplea. However, this study reveals surprising differences with the majority of the copepod phylogenies and unexpected similarities with postembryonic characters and earlier proposed morphological phylogenies; More precisely, Cyclopoida is more closely related to Siphonostomatoida than to Harpacticoida which is likely the most basally-branching group of Podoplea. Divergence time estimation suggests that the origin of Harpacticoida can be traced back to the Devonian, corresponding well with recently discovered fossil evidence. Copepoda has a close affinity to the clade of Malacostraca and Thecostraca but not to Branchiopoda. This result supports the hypothesis of the newly proposed clades, Communostraca, Multicrustacea, and Allotriocarida but further challenges the validity of Hexanauplia and Vericrustacea. The first phylogenomic study of Copepoda provides new insights into taxonomic relationships and represents a valuable resource that improves our understanding of copepod evolution and their wide range of ecological adaptations.

  8. VNTR analysis reveals unexpected genetic diversity within Mycoplasma agalactiae, the main causative agent of contagious agalactia

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    Ayling Roger D

    2008-11-01

    Full Text Available Abstract Background Mycoplasma agalactiae is the main cause of contagious agalactia, a serious disease of sheep and goats, which has major clinical and economic impacts. Previous studies of M. agalactiae have shown it to be unusually homogeneous and there are currently no available epidemiological techniques which enable a high degree of strain differentiation. Results We have developed variable number tandem repeat (VNTR analysis using the sequenced genome of the M. agalactiae type strain PG2. The PG2 genome was found to be replete with tandem repeat sequences and 4 were chosen for further analysis. VNTR 5 was located within the hypothetical protein MAG6170 a predicted lipoprotein. VNTR 14 was intergenic between the hypothetical protein MAG3350 and the hypothetical protein MAG3340. VNTR 17 was intergenic between the hypothetical protein MAG4060 and the hypothetical protein MAG4070 and VNTR 19 spanned the 5' end of the pseudogene for a lipoprotein MAG4310 and the 3' end of the hypothetical lipoprotein MAG4320. We have investigated the genetic diversity of 88 M. agalactiae isolates of wide geographic origin using VNTR analysis and compared it with pulsed field gel electrophoresis (PFGE and random amplified polymorphic DNA (RAPD analysis. Simpson's index of diversity was calculated to be 0.324 for PFGE and 0.574 for VNTR analysis. VNTR analysis revealed unexpected diversity within M. agalactiae with 9 different VNTR types discovered. Some correlation was found between geographical origin and the VNTR type of the isolates. Conclusion VNTR analysis represents a useful, rapid first-line test for use in molecular epidemiological analysis of M. agalactiae for outbreak tracing and control.

  9. Proteomic and bioinformatic analysis of epithelial tight junction reveals an unexpected cluster of synaptic molecules

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    Tang Vivian W

    2006-12-01

    double membranes, satellite Golgi apparatus and associated vesicular structures. A working model of the tight junction consisting of multiple functions and sub-domains has been generated using the proteomics and structural data. Conclusion This study provides an unbiased proteomics and bioinformatics approach to elucidate novel functions of the tight junction. The approach has revealed an unexpected cluster associating with synaptic function. This surprising finding suggests that the tight junction may be a novel epithelial synapse for cell-cell communication. Reviewers This article was reviewed by Gáspár Jékely, Etienne Joly and Neil Smalheiser.

  10. Brain response to unexpected novel noises in children with low and high trait anxiety.

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    Hogan, Alexandra M; Butterfield, Elinor L; Phillips, Luke; Hadwin, Julie A

    2007-01-01

    The behavioral inhibition system [Gray, J. A. The neuropsychology of anxiety: An enquiry into the functions of the septo-hippocampal system. Oxford: Oxford University Press, 1982] proposes that anxiety is associated with the processing of novel stimuli. We aimed to explore this relationship by recording auditory event-related potentials associated with unexpected novel noises in typically developing children. Children aged 10-14 years with low (n = 12) and high (n = 11) self-report trait anxiety were assessed using a novelty oddball task. The N1 associated with novel stimuli, specifically the "N1c" component maximal at temporal lobe sites, was of significantly longer latency (p = .014) and greater amplitude (p = .004) in the high compared with the low anxious group. This group difference was supported by linear correlations between N1c amplitude and trait anxiety scores. There was no effect of anxiety on the later novelty P3. These data suggest a subtle moderating role of trait anxiety on brain response to novelty, and further research with clinically anxious children is indicated.

  11. Genomic Admixture Analysis in European Populus spp. Reveals Unexpected Patterns of Reproductive Isolation and Mating

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    Lexer, Christian; Joseph, Jeffrey A.; van Loo, Marcela; Barbará, Thelma; Heinze, Berthold; Bartha, Denes; Castiglione, Stefano; Fay, Michael F.; Buerkle, C. Alex

    2010-01-01

    Admixture between genetically divergent populations facilitates genomic studies of the mechanisms involved in adaptation, reproductive isolation, and speciation, including mapping of the loci involved in these phenomena. Little is known about how pre- and postzygotic barriers will affect the prospects of “admixture mapping” in wild species. We have studied 93 mapped genetic markers (microsatellites, indels, and sequence polymorphisms, ∼60,000 data points) to address this topic in hybrid zones of Populus alba and P. tremula, two widespread, ecologically important forest trees. Using genotype and linkage information and recently developed analytical tools we show that (1) reproductive isolation between these species is much stronger than previously assumed but this cannot prevent the introgression of neutral or advantageous alleles, (2) unexpected genotypic gaps exist between recombinant hybrids and their parental taxa, (3) these conspicuous genotypic patterns are due to assortative mating and strong postzygotic barriers, rather than recent population history. We discuss possible evolutionary trajectories of hybrid lineages between these species and outline strategies for admixture mapping in hybrid zones between highly divergent populations. Datasets such as this one are still rare in studies of natural hybrid zones but should soon become more common as high throughput genotyping and resequencing become feasible in nonmodel species. PMID:20679517

  12. Citizen science reveals unexpected continental-scale evolutionary change in a model organism.

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    Jonathan Silvertown

    Full Text Available Organisms provide some of the most sensitive indicators of climate change and evolutionary responses are becoming apparent in species with short generation times. Large datasets on genetic polymorphism that can provide an historical benchmark against which to test for recent evolutionary responses are very rare, but an exception is found in the brown-lipped banded snail (Cepaea nemoralis. This species is sensitive to its thermal environment and exhibits several polymorphisms of shell colour and banding pattern affecting shell albedo in the majority of populations within its native range in Europe. We tested for evolutionary changes in shell albedo that might have been driven by the warming of the climate in Europe over the last half century by compiling an historical dataset for 6,515 native populations of C. nemoralis and comparing this with new data on nearly 3,000 populations. The new data were sampled mainly in 2009 through the Evolution MegaLab, a citizen science project that engaged thousands of volunteers in 15 countries throughout Europe in the biggest such exercise ever undertaken. A known geographic cline in the frequency of the colour phenotype with the highest albedo (yellow was shown to have persisted and a difference in colour frequency between woodland and more open habitats was confirmed, but there was no general increase in the frequency of yellow shells. This may have been because snails adapted to a warming climate through behavioural thermoregulation. By contrast, we detected an unexpected decrease in the frequency of Unbanded shells and an increase in the Mid-banded morph. Neither of these evolutionary changes appears to be a direct response to climate change, indicating that the influence of other selective agents, possibly related to changing predation pressure and habitat change with effects on micro-climate.

  13. Citizen Science Reveals Unexpected Continental-Scale Evolutionary Change in a Model Organism

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    Silvertown, Jonathan; Cook, Laurence; Cameron, Robert; Dodd, Mike; McConway, Kevin; Worthington, Jenny; Skelton, Peter; Anton, Christian; Bossdorf, Oliver; Baur, Bruno; Schilthuizen, Menno; Fontaine, Benoît; Sattmann, Helmut; Bertorelle, Giorgio; Correia, Maria; Oliveira, Cristina; Pokryszko, Beata; Ożgo, Małgorzata; Stalažs, Arturs; Gill, Eoin; Rammul, Üllar; Sólymos, Péter; Féher, Zoltan; Juan, Xavier

    2011-01-01

    Organisms provide some of the most sensitive indicators of climate change and evolutionary responses are becoming apparent in species with short generation times. Large datasets on genetic polymorphism that can provide an historical benchmark against which to test for recent evolutionary responses are very rare, but an exception is found in the brown-lipped banded snail (Cepaea nemoralis). This species is sensitive to its thermal environment and exhibits several polymorphisms of shell colour and banding pattern affecting shell albedo in the majority of populations within its native range in Europe. We tested for evolutionary changes in shell albedo that might have been driven by the warming of the climate in Europe over the last half century by compiling an historical dataset for 6,515 native populations of C. nemoralis and comparing this with new data on nearly 3,000 populations. The new data were sampled mainly in 2009 through the Evolution MegaLab, a citizen science project that engaged thousands of volunteers in 15 countries throughout Europe in the biggest such exercise ever undertaken. A known geographic cline in the frequency of the colour phenotype with the highest albedo (yellow) was shown to have persisted and a difference in colour frequency between woodland and more open habitats was confirmed, but there was no general increase in the frequency of yellow shells. This may have been because snails adapted to a warming climate through behavioural thermoregulation. By contrast, we detected an unexpected decrease in the frequency of Unbanded shells and an increase in the Mid-banded morph. Neither of these evolutionary changes appears to be a direct response to climate change, indicating that the influence of other selective agents, possibly related to changing predation pressure and habitat change with effects on micro-climate. PMID:21556137

  14. A new GFP-tagged line reveals unexpected Otx2 protein localization in retinal photoreceptors

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    Godement Pierre

    2007-11-01

    Full Text Available Abstract Background Dynamic monitoring of protein expression and localization is fundamental to the understanding of biological processes. The paired-class homeodomain-containing transcription factor Otx2 is essential for normal head and brain development in vertebrates. Recent conditional knockout studies have pointed to multiple roles of this protein during late development and post-natal life. Yet, later expression and functions remain poorly characterized as specific reagents to detect the protein at any stage of development are still missing. Results We generated a new mouse line harbouring an insertion of the GFP gene within the Otx2 coding sequence to monitor the gene activity while preserving most of its functions. Our results demonstrate that this line represents a convenient tool to capture the dynamics of Otx2 gene expression from early embryonic stages to adulthood. In addition, we could visualize the intracellular location of Otx2 protein. In the retina, we reinterpret the former view of protein distribution and show a further level of regulation of intranuclear protein localization, which depends on the cell type. Conclusion The GFP-tagged Otx2 mouse line fully recapitulates previously known expression patterns and brings additional accuracy and easiness of detection of Otx2 gene activity. This opens up the way to live imaging of a highly dynamic actor of brain development and can be adapted to any mutant background to probe for genetic interaction between Otx2 and the mutated gene.

  15. Hydra meiosis reveals unexpected conservation of structural synaptonemal complex proteins across metazoans

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    Fraune, Johanna; Alsheimer, Manfred; Volff, Jean-Nicolas; Busch, Karoline; Fraune, Sebastian; Bosch, Thomas C. G.; Benavente, Ricardo

    2012-01-01

    The synaptonemal complex (SC) is a key structure of meiosis, mediating the stable pairing (synapsis) of homologous chromosomes during prophase I. Its remarkable tripartite structure is evolutionarily well conserved and can be found in almost all sexually reproducing organisms. However, comparison of the different SC protein components in the common meiosis model organisms Saccharomyces cerevisiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus revealed no sequence homology. This discrepancy challenged the hypothesis that the SC arose only once in evolution. To pursue this matter we focused on the evolution of SYCP1 and SYCP3, the two major structural SC proteins of mammals. Remarkably, our comparative bioinformatic and expression studies revealed that SYCP1 and SYCP3 are also components of the SC in the basal metazoan Hydra. In contrast to previous assumptions, we therefore conclude that SYCP1 and SYCP3 form monophyletic groups of orthologous proteins across metazoans. PMID:23012415

  16. Fast detection of unexpected sound intensity decrements as revealed by human evoked potentials.

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    Heike Althen

    Full Text Available The detection of deviant sounds is a crucial function of the auditory system and is reflected by the automatically elicited mismatch negativity (MMN, an auditory evoked potential at 100 to 250 ms from stimulus onset. It has recently been shown that rarely occurring frequency and location deviants in an oddball paradigm trigger a more negative response than standard sounds at very early latencies in the middle latency response of the human auditory evoked potential. This fast and early ability of the auditory system is corroborated by the finding of neurons in the animal auditory cortex and subcortical structures, which restore their adapted responsiveness to standard sounds, when a rare change in a sound feature occurs. In this study, we investigated whether the detection of intensity deviants is also reflected at shorter latencies than those of the MMN. Auditory evoked potentials in response to click sounds were analyzed regarding the auditory brain stem response, the middle latency response (MLR and the MMN. Rare stimuli with a lower intensity level than standard stimuli elicited (in addition to an MMN a more negative potential in the MLR at the transition from the Na to the Pa component at circa 24 ms from stimulus onset. This finding, together with the studies about frequency and location changes, suggests that the early automatic detection of deviant sounds in an oddball paradigm is a general property of the auditory system.

  17. Unexpected Regularity in Swimming Behavior of Clausocalanus furcatus Revealed by a Telecentric 3D Computer Vision System.

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    Giuseppe Bianco

    Full Text Available Planktonic copepods display a large repertoire of motion behaviors in a three-dimensional environment. Two-dimensional video observations demonstrated that the small copepod Clausocalanus furcatus, one the most widely distributed calanoids at low to medium latitudes, presented a unique swimming behavior that was continuous and fast and followed notably convoluted trajectories. Furthermore, previous observations indicated that the motion of C. furcatus resembled a random process. We characterized the swimming behavior of this species in three-dimensional space using a video system equipped with telecentric lenses, which allow tracking of zooplankton without the distortion errors inherent in common lenses. Our observations revealed unexpected regularities in the behavior of C. furcatus that appear primarily in the horizontal plane and could not have been identified in previous observations based on lateral views. Our results indicate that the swimming behavior of C. furcatus is based on a limited repertoire of basic kinematic modules but exhibits greater plasticity than previously thought.

  18. Comparative analyses of developmental transcription factor repertoires in sponges reveal unexpected complexity of the earliest animals.

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    Fortunato, Sofia A V; Adamski, Marcin; Adamska, Maja

    2015-12-01

    Developmental transcription factors (DTFs) control development of animals by affecting expression of target genes, some of which are transcription factors themselves. In bilaterians and cnidarians, conserved DTFs are involved in homologous processes such as gastrulation or specification of neurons. The genome of Amphimedon queenslandica, the first sponge to be sequenced, revealed that only a fraction of these conserved DTF families are present in demosponges. This finding was in line with the view that morphological complexity in the animal lineage correlates with developmental toolkit complexity. However, as the phylum Porifera is very diverse, Amphimedon's genome may not be representative of all sponges. The recently sequenced genomes of calcareous sponges Sycon ciliatum and Leucosolenia complicata allowed investigations of DTFs in a sponge lineage evolutionarily distant from demosponges. Surprisingly, the phylogenetic analyses of identified DTFs revealed striking differences between the calcareous sponges and Amphimedon. As these differences appear to be a result of independent gene loss events in the two sponge lineages, the last common ancestor of sponges had to possess a much more diverse repertoire of DTFs than extant sponges. Developmental expression of sponge homologs of genes involved in specification of the Bilaterian endomesoderm and the neurosensory cells suggests that roles of many DTFs date back to the last common ancestor of all animals. Strikingly, even DTFs displaying apparent pan-metazoan conservation of sequence and function are not immune to being lost from individual species genomes. The quest for a comprehensive picture of the developmental toolkit in the last common metazoan ancestor is thus greatly benefitting from the increasing accessibility of sequencing, allowing comparisons of multiple genomes within each phylum. Copyright © 2015. Published by Elsevier B.V.

  19. Uranus' Southern Circulation Revealed by Voyager-2 Images: Asymmetric, Unique, Unexpected

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    Karkoschka, Erich

    2014-11-01

    The southern half of Uranus' southern hemisphere of Uranus has been exceptionally bland. Only a single discrete feature was detected in Voyager-2 images, and none has been seen in thousands of HST and ground-based images since. All other observed regions on Uranus and jovian planets have many features that defined circulation patterns of the jovian planets, but the circulation of Uranus south of -45 deg latitude has been unknown.We performed a reanalysis of Voyager images of Uranus that revealed dozens of discrete features instead of the single feature known before. We improved flatfielding, pad-pixel treatment, and nonlinearity correction. We greatly decreased noise by averaging up to 1600 images. The result is a rotational profile without major gaps.Uranus' high southern latitudes are exceptional in several aspects: 1) The rotational profile has sharp kinks while it is smooth elsewhere on the ice giants. This puts current ideas of a simple Hadley cell on each hemisphere into question. 2) The rotational profile has a large north-south asymmetry, an order of magnitude larger than elsewhere on the jovian planets. 3) Between -68 and -59 deg latitude, the rotational shear is some 30 times lower than at other latitudes. Here, winds speeds around 200 m/s are regular to the 0.1 m/s level. 4) The South Pole had a spot off center rotating 5 h faster than the interior, which has not been observed elsewhere on jovian planets. 5) Uranus revealed spirals winding around the whole planet more than once that indicate very regular meridional motions, to the 2 cm/s level. 6) The latitude at -84 deg was featureless even at a signal-to-noise ratio of 55,000, one of the blandest zones in nature.Some features show significant evolution within the 5-week observing period providing constraints on dynamics. Features also show distinct spectral characteristics in the 8-filter data set providing constraints on the physical nature of features and their altitude. We have the data to

  20. Single molecule atomic force microscopy of aerolysin pore complexes reveals unexpected star-shaped topography.

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    He, Jianfeng; Wang, Jiabin; Hu, Jun; Sun, Jielin; Czajkowsky, Daniel Mark; Shao, Zhifeng

    2016-04-01

    Aerolysin is the paradigmatic member of a large family of toxins that convert from a water-soluble monomer/dimer into a membrane-spanning oligomeric pore. While there is x-ray crystallographic data of its water-soluble conformation, the most recent structural model of the membrane-inserted pore is based primarily on data of water-soluble tetradecamers of mutant protein, together with computational modeling ultimately performed in vacuum. Here we examine this pore model with atomic force microscopy (AFM) of membrane-associated wild-type complexes and all-atom molecular dynamics (MD) simulations in water. In striking contrast to a disc-shaped cap region predicted by the present model, the AFM images reveal a star-shaped complex, with a central ring surrounded by seven radial projections. Further, the MD simulations suggest that the locations of the receptor-binding (D1) domains in the present model are not correct. However, a modified model in which the D1 domains, rather than localized at fixed positions, adopt a wide range of configurations through fluctuations of an intervening linker is compatible with existing data. Thus our work not only demonstrates the importance of directly resolving such complexes in their native environment but also points to a dynamic receptor binding region, which may be critical for toxin assembly on the cell surface. Copyright © 2015 John Wiley & Sons, Ltd.

  1. Polysomnography reveals unexpectedly high rates of organic sleep disorders in patients with prediagnosed primary insomnia.

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    Crönlein, Tatjana; Geisler, Peter; Langguth, Berthold; Eichhammer, Peter; Jara, Cecilia; Pieh, Christoph; Zulley, Jürgen; Hajak, Göran

    2012-12-01

    It is a matter of debate whether patients with primary insomnia require a polysomnographic examination in order to exclude specific sleep disorders such as sleep apnea syndrome (SAS) or periodic limb movements (PLM). Using a prospective design, we investigated the prevalence of organic sleep disorders by means of polysomnography (PSG) in a series of patients who were previously diagnosed with primary insomnia. This diagnosis was based on a clinical exam and an ambulatory monitoring device or previous PSG. Seventy-seven women and 16 men (mean age 55.12 ± 13.21 years) who were admitted for cognitive behavioral therapy for insomnia were evaluated by PSG including cardiorespiratory parameters and tibialis EMG. Among them, 50 patients had undergone a clinical exam by a sleep specialist; in 18 patients, actigraphy or portable monitoring had been performed to exclude SAS or PLM; 25 patients had undergone PSG in another sleep lab previously. In 32 patients (34% of the sample), a PSG revealed a specific sleep disorder (SAS 16; PLMD 11; both 5), resulting in therapeutic consequences for 21 patients (SAS 10; PLMD 9; both 2). SAS and PLM patients were older and SAS patients had a higher body mass index than insomnia patients without additional findings. Indications for a PSG should be handled less restrictively in the diagnostic workup of older insomnia patients since they have a higher risk of comorbid sleep disorders even in the absence of the clinical signs of SAS or PLM.

  2. Integrated analyses resolve conflicts over squamate reptile phylogeny and reveal unexpected placements for fossil taxa.

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    Reeder, Tod W; Townsend, Ted M; Mulcahy, Daniel G; Noonan, Brice P; Wood, Perry L; Sites, Jack W; Wiens, John J

    2015-01-01

    Squamate reptiles (lizards and snakes) are a pivotal group whose relationships have become increasingly controversial. Squamates include >9000 species, making them the second largest group of terrestrial vertebrates. They are important medicinally and as model systems for ecological and evolutionary research. However, studies of squamate biology are hindered by uncertainty over their relationships, and some consider squamate phylogeny unresolved, given recent conflicts between molecular and morphological results. To resolve these conflicts, we expand existing morphological and molecular datasets for squamates (691 morphological characters and 46 genes, for 161 living and 49 fossil taxa, including a new set of 81 morphological characters and adding two genes from published studies) and perform integrated analyses. Our results resolve higher-level relationships as indicated by molecular analyses, and reveal hidden morphological support for the molecular hypothesis (but not vice-versa). Furthermore, we find that integrating molecular, morphological, and paleontological data leads to surprising placements for two major fossil clades (Mosasauria and Polyglyphanodontia). These results further demonstrate the importance of combining fossil and molecular information, and the potential problems of estimating the placement of fossil taxa from morphological data alone. Thus, our results caution against estimating fossil relationships without considering relevant molecular data, and against placing fossils into molecular trees (e.g. for dating analyses) without considering the possible impact of molecular data on their placement.

  3. Ultrastructural analysis of salivary glands in a phytophagous stink bug revealed the presence of unexpected muscles.

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    Castellanos, Nathaly; Martínez, Luis C; Silva, Eder H; Teodoro, Adenir V; Serrão, José Eduardo; Oliveira, Eugênio E

    2017-01-01

    The exceptional abilities of stink bugs (Hemiptera: Pentatomidae) to colonize a diverse group of plants have been attributed to the feeding behaviors and the functions of the salivary complex of these insects. Here, we describe the ultrastructure of the salivary glands of the Neotropical brown stink bug, Euschistus heros, which is a major component of the pentatomid pest complex on soybeans, Glycine max, in the neotropics. Our results revealed a salivary gland complex consisting of two lobes (i.e., anterior and posterior), with a constriction between them (i.e., the hilum), in which the salivary and accessory gland ducts are inserted. The principal gland epithelium has a single layer of cells lining an enlarged lumen filled with saliva, and these cells are cuboidal, rich in rough endoplasmic reticulum and secretory vesicles, with well-developed nuclei, all of which are typical features of protein-secreting cells. We report, for the first time in insects, the presence of a layer of muscle cells surrounding the columnar hilum epithelium. The accessory salivary gland cells are cuboidal with nuclei containing condensed chromatin and cytoplasm rich in vacuoles and rough endoplasmic reticulum, indicating the potential involvement of these glands in water transport/secretion. The lumen content of each lobe of the principal gland suggests that the lobes produce different compounds. Thus, our results suggest that the E. heros salivary complex might have unconventional mechanisms to mix/release saliva, which might help explain the polyphagous abilities of these insects.

  4. Integrated analyses resolve conflicts over squamate reptile phylogeny and reveal unexpected placements for fossil taxa.

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    Tod W Reeder

    Full Text Available Squamate reptiles (lizards and snakes are a pivotal group whose relationships have become increasingly controversial. Squamates include >9000 species, making them the second largest group of terrestrial vertebrates. They are important medicinally and as model systems for ecological and evolutionary research. However, studies of squamate biology are hindered by uncertainty over their relationships, and some consider squamate phylogeny unresolved, given recent conflicts between molecular and morphological results. To resolve these conflicts, we expand existing morphological and molecular datasets for squamates (691 morphological characters and 46 genes, for 161 living and 49 fossil taxa, including a new set of 81 morphological characters and adding two genes from published studies and perform integrated analyses. Our results resolve higher-level relationships as indicated by molecular analyses, and reveal hidden morphological support for the molecular hypothesis (but not vice-versa. Furthermore, we find that integrating molecular, morphological, and paleontological data leads to surprising placements for two major fossil clades (Mosasauria and Polyglyphanodontia. These results further demonstrate the importance of combining fossil and molecular information, and the potential problems of estimating the placement of fossil taxa from morphological data alone. Thus, our results caution against estimating fossil relationships without considering relevant molecular data, and against placing fossils into molecular trees (e.g. for dating analyses without considering the possible impact of molecular data on their placement.

  5. Common and unexpected findings in mummies from ancient Egypt and South America as revealed by CT.

    Science.gov (United States)

    Jackowski, Christian; Bolliger, Stephan; Thali, Michael J

    2008-01-01

    Computed tomography (CT) has proved to be a valuable investigative tool for mummy research and is the method of choice for examining mummies. It allows for noninvasive insight, especially with virtual endoscopy, which reveals detailed information about the mummy's sex, age, constitution, injuries, health, and mummification techniques used. CT also supplies three-dimensional information about the scanned object. Mummification processes can be summarized as "artificial," when the procedure was performed on a body with the aim of preservation, or as "natural," when the body's natural environment resulted in preservation. The purpose of artificial mummification was to preserve that person's morphologic features by delaying or arresting the decay of the body. The ancient Egyptians are most famous for this. Their use of evisceration followed by desiccation with natron (a compound of sodium salts) to halt putrefaction and prevent rehydration was so effective that their embalmed bodies have survived for nearly 4500 years. First, the body was cleaned with a natron solution; then internal organs were removed through the cribriform plate and abdomen. The most important, and probably the most lengthy, phase was desiccation. After the body was dehydrated, the body cavities were rinsed and packed to restore the body's former shape. Finally, the body was wrapped. Animals were also mummified to provide food for the deceased, to accompany the deceased as pets, because they were seen as corporal manifestations of deities, and as votive offerings. Artificial mummification was performed on every continent, especially in South and Central America. (c) RSNA, 2008.

  6. Brain rhythms reveal a hierarchical network organization.

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    G Karl Steinke

    2011-10-01

    Full Text Available Recordings of ongoing neural activity with EEG and MEG exhibit oscillations of specific frequencies over a non-oscillatory background. The oscillations appear in the power spectrum as a collection of frequency bands that are evenly spaced on a logarithmic scale, thereby preventing mutual entrainment and cross-talk. Over the last few years, experimental, computational and theoretical studies have made substantial progress on our understanding of the biophysical mechanisms underlying the generation of network oscillations and their interactions, with emphasis on the role of neuronal synchronization. In this paper we ask a very different question. Rather than investigating how brain rhythms emerge, or whether they are necessary for neural function, we focus on what they tell us about functional brain connectivity. We hypothesized that if we were able to construct abstract networks, or "virtual brains", whose dynamics were similar to EEG/MEG recordings, those networks would share structural features among themselves, and also with real brains. Applying mathematical techniques for inverse problems, we have reverse-engineered network architectures that generate characteristic dynamics of actual brains, including spindles and sharp waves, which appear in the power spectrum as frequency bands superimposed on a non-oscillatory background dominated by low frequencies. We show that all reconstructed networks display similar topological features (e.g. structural motifs and dynamics. We have also reverse-engineered putative diseased brains (epileptic and schizophrenic, in which the oscillatory activity is altered in different ways, as reported in clinical studies. These reconstructed networks show consistent alterations of functional connectivity and dynamics. In particular, we show that the complexity of the network, quantified as proposed by Tononi, Sporns and Edelman, is a good indicator of brain fitness, since virtual brains modeling diseased states

  7. Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions.

    Science.gov (United States)

    Cory, Seth A; Van Vranken, Jonathan G; Brignole, Edward J; Patra, Shachin; Winge, Dennis R; Drennan, Catherine L; Rutter, Jared; Barondeau, David P

    2017-07-03

    In eukaryotes, sulfur is mobilized for incorporation into multiple biosynthetic pathways by a cysteine desulfurase complex that consists of a catalytic subunit (NFS1), LYR protein (ISD11), and acyl carrier protein (ACP). This NFS1-ISD11-ACP (SDA) complex forms the core of the iron-sulfur (Fe-S) assembly complex and associates with assembly proteins ISCU2, frataxin (FXN), and ferredoxin to synthesize Fe-S clusters. Here we present crystallographic and electron microscopic structures of the SDA complex coupled to enzyme kinetic and cell-based studies to provide structure-function properties of a mitochondrial cysteine desulfurase. Unlike prokaryotic cysteine desulfurases, the SDA structure adopts an unexpected architecture in which a pair of ISD11 subunits form the dimeric core of the SDA complex, which clarifies the critical role of ISD11 in eukaryotic assemblies. The different quaternary structure results in an incompletely formed substrate channel and solvent-exposed pyridoxal 5'-phosphate cofactor and provides a rationale for the allosteric activator function of FXN in eukaryotic systems. The structure also reveals the 4'-phosphopantetheine-conjugated acyl-group of ACP occupies the hydrophobic core of ISD11, explaining the basis of ACP stabilization. The unexpected architecture for the SDA complex provides a framework for understanding interactions with acceptor proteins for sulfur-containing biosynthetic pathways, elucidating mechanistic details of eukaryotic Fe-S cluster biosynthesis, and clarifying how defects in Fe-S cluster assembly lead to diseases such as Friedreich's ataxia. Moreover, our results support a lock-and-key model in which LYR proteins associate with acyl-ACP as a mechanism for fatty acid biosynthesis to coordinate the expression, Fe-S cofactor maturation, and activity of the respiratory complexes.

  8. Post-genomic analyses of fungal lignocellulosic biomass degradation reveal the unexpected potential of the plant pathogen Ustilago maydis

    Directory of Open Access Journals (Sweden)

    Couturier Marie

    2012-02-01

    Full Text Available Abstract Background Filamentous fungi are potent biomass degraders due to their ability to thrive in ligno(hemicellulose-rich environments. During the last decade, fungal genome sequencing initiatives have yielded abundant information on the genes that are putatively involved in lignocellulose degradation. At present, additional experimental studies are essential to provide insights into the fungal secreted enzymatic pools involved in lignocellulose degradation. Results In this study, we performed a wide analysis of 20 filamentous fungi for which genomic data are available to investigate their biomass-hydrolysis potential. A comparison of fungal genomes and secretomes using enzyme activity profiling revealed discrepancies in carbohydrate active enzymes (CAZymes sets dedicated to plant cell wall. Investigation of the contribution made by each secretome to the saccharification of wheat straw demonstrated that most of them individually supplemented the industrial Trichoderma reesei CL847 enzymatic cocktail. Unexpectedly, the most striking effect was obtained with the phytopathogen Ustilago maydis that improved the release of total sugars by 57% and of glucose by 22%. Proteomic analyses of the best-performing secretomes indicated a specific enzymatic mechanism of U. maydis that is likely to involve oxido-reductases and hemicellulases. Conclusion This study provides insight into the lignocellulose-degradation mechanisms by filamentous fungi and allows for the identification of a number of enzymes that are potentially useful to further improve the industrial lignocellulose bioconversion process.

  9. Metatranscriptomic analysis of a high-sulfide aquatic spring reveals insights into sulfur cycling and unexpected aerobic metabolism

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    Anne M. Spain

    2015-09-01

    Full Text Available Zodletone spring is a sulfide-rich spring in southwestern Oklahoma characterized by shallow, microoxic, light-exposed spring water overlaying anoxic sediments. Previously, culture-independent 16S rRNA gene based diversity surveys have revealed that Zodletone spring source sediments harbor a highly diverse microbial community, with multiple lineages putatively involved in various sulfur-cycling processes. Here, we conducted a metatranscriptomic survey of microbial populations in Zodletone spring source sediments to characterize the relative prevalence and importance of putative phototrophic, chemolithotrophic, and heterotrophic microorganisms in the sulfur cycle, the identity of lineages actively involved in various sulfur cycling processes, and the interaction between sulfur cycling and other geochemical processes at the spring source. Sediment samples at the spring’s source were taken at three different times within a 24-h period for geochemical analyses and RNA sequencing. In depth mining of datasets for sulfur cycling transcripts revealed major sulfur cycling pathways and taxa involved, including an unexpected potential role of Actinobacteria in sulfide oxidation and thiosulfate transformation. Surprisingly, transcripts coding for the cyanobacterial Photosystem II D1 protein, methane monooxygenase, and terminal cytochrome oxidases were encountered, indicating that genes for oxygen production and aerobic modes of metabolism are actively being transcribed, despite below-detectable levels (<1 µM of oxygen in source sediment. Results highlight transcripts involved in sulfur, methane, and oxygen cycles, propose that oxygenic photosynthesis could support aerobic methane and sulfide oxidation in anoxic sediments exposed to sunlight, and provide a viewpoint of microbial metabolic lifestyles under conditions similar to those seen during late Archaean and Proterozoic eons.

  10. Novel and Unexpected Microbial Diversity in Acid Mine Drainage in Svalbard (78° N, Revealed by Culture-Independent Approaches

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    Antonio García-Moyano

    2015-10-01

    Full Text Available Svalbard, situated in the high Arctic, is an important past and present coal mining area. Dozens of abandoned waste rock piles can be found in the proximity of Longyearbyen. This environment offers a unique opportunity for studying the biological control over the weathering of sulphide rocks at low temperatures. Although the extension and impact of acid mine drainage (AMD in this area is known, the native microbial communities involved in this process are still scarcely studied and uncharacterized. Several abandoned mining areas were explored in the search for active AMD and a culture-independent approach was applied with samples from two different runoffs for the identification and quantification of the native microbial communities. The results obtained revealed two distinct microbial communities. One of the runoffs was more extreme with regards to pH and higher concentration of soluble iron and heavy metals. These conditions favored the development of algal-dominated microbial mats. Typical AMD microorganisms related to known iron-oxidizing bacteria (Acidithiobacillus ferrivorans, Acidobacteria and Actinobacteria dominated the bacterial community although some unexpected populations related to Chloroflexi were also significant. No microbial mats were found in the second area. The geochemistry here showed less extreme drainage, most likely in direct contact with the ore under the waste pile. Large deposits of secondary minerals were found and the presence of iron stalks was revealed by microscopy analysis. Although typical AMD microorganisms were also detected here, the microbial community was dominated by other populations, some of them new to this type of system (Saccharibacteria, Gallionellaceae. These were absent or lowered in numbers the farther from the spring source and they could represent native populations involved in the oxidation of sulphide rocks within the waste rock pile. This environment appears thus as a highly interesting

  11. Health, Happiness and Human Enhancement-Dealing with Unexpected Effects of Deep Brain Stimulation.

    Science.gov (United States)

    Schermer, Maartje

    2013-01-01

    Deep Brain Stimulation (DBS) is a treatment involving the implantation of electrodes into the brain. Presently, it is used for neurological disorders like Parkinson's disease, but indications are expanding to psychiatric disorders such as depression, addiction and Obsessive Compulsive Disorder (OCD). Theoretically, it may be possible to use DBS for the enhancement of various mental functions. This article discusses a case of an OCD patient who felt very happy with the DBS treatment, even though her symptoms were not reduced. First, it is explored if the argument that 'doctors are not in the business of trading happiness', as used by her psychiatrist to justify his discontinuation of the DBS treatment, holds. The relationship between enhancement and the goals of medicine is discussed and it is concluded that even though the goals of medicine do not set strict limits and may even include certain types of enhancement, there are some good reasons for limiting the kind of things doctors are required or allowed to do. Next, the case is discussed from the perspective of beneficence and autonomy. It is argued that making people feel good is not the same as enhancing their well-being and that it is unlikely-though not absolutely impossible-that the well-being of the happy OCD patient is really improved. Finally, some concerns regarding the autonomy of a request made under the influence of DBS treatment are considered.

  12. Interaction proteomics reveals brain region-specific AMPA receptor complexes

    NARCIS (Netherlands)

    Chen, N.; Pandya, N.J.; Koopmans, F.T.W.; Castelo-Szekelv, V.; van der Schors, R.C.; Smit, A.B.; Li, K.W.

    2014-01-01

    Fast excitatory synaptic transmission in the brain is mediated by glutamate acting on postsynaptic AMPA receptors. Recent studies have revealed a substantial number of AMPA receptor auxiliary proteins, which potentially contribute to the regulation of AMPA receptor trafficking, subcellular receptor

  13. Transcriptome analyses of adult mouse brain reveal enrichment of lncRNAs in specific brain regions and neuronal populations

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    Beena Mary Kadakkuzha

    2015-03-01

    Full Text Available Despite the importance of the long noncoding RNAs (lncRNAs in regulating biological functions, the expression profiles of lncRNAs in the sub-regions of the mammalian brain and neuronal populations remain largely uncharacterized. By analyzing RNASeq datasets, we demonstrate region specific enrichment of populations of lncRNAs and mRNAs in the mouse hippocampus and prefrontal cortex (PFC, the two major regions of the brain involved in memory storage and neuropsychiatric disorders. We identified 2,759 lncRNAs and 17,859 mRNAs in the hippocampus and 2561 lncRNAs and 17,464 mRNAs expressed in the PFC. The lncRNAs identified correspond to ~14% of the transcriptome of the hippocampus and PFC and ~70% of the lncRNAs annotated in the mouse genome (NCBIM37 and are localized along the chromosomes as varying numbers of clusters. Importantly, we also found that few of the tested lncRNA-mRNA pairs that share a genomic locus display specific co-expression in a region-specific manner. Furthermore, we find that sub-regions of the brain and specific neuronal populations have characteristic lncRNA expression signatures. These results reveal an unexpected complexity of the lncRNA expression in the mouse brain.

  14. Negative brain potentials elicited by an unexpected color patch or word.

    Science.gov (United States)

    Katayama, J; Yagi, A

    1992-10-01

    The purpose of this study was to examine whether a physical stimulus that deviates from a semantic context can elicit the N400 component of event-related brain potentials (ERPs). ERPs were recorded while 12 students judged the veracity of a simple statement (e.g., red/is not/blue) presented with the order of subject (S), object (O), and verb (V), which is normal in Japanese grammar. In one condition, S was a color patch and O was a word representing the color, while in the other condition, S was a color name and O was a patch. In both conditions, a late additional negative potential was elicited by the O stimulus when it was mismatched with S. In addition, the negativities elicited by the incongruous color patch and word had the same morphology and scalp distribution. The results indicate that not only a word but a physical stimulus which deviates from a semantic context can elicit the N400 component.

  15. A Novel Brain Decoding Method: a Correlation Network Framework for Revealing Brain Connections

    OpenAIRE

    Yu, Siyu; Zheng, Nanning; Ma, Yongqiang; Wu, Hao; Chen, Badong

    2017-01-01

    Brain decoding is a hot spot in cognitive science, which focuses on reconstructing perceptual images from brain activities. Analyzing the correlations of collected data from human brain activities and representing activity patterns are two problems in brain decoding based on functional magnetic resonance imaging (fMRI) signals. However, existing correlation analysis methods mainly focus on the strength information of voxel, which reveals functional connectivity in the cerebral cortex. They te...

  16. Diffusion Tensor Tractography Reveals Disrupted Structural Connectivity during Brain Aging

    Science.gov (United States)

    Lin, Lan; Tian, Miao; Wang, Qi; Wu, Shuicai

    2017-10-01

    Brain aging is one of the most crucial biological processes that entail many physical, biological, chemical, and psychological changes, and also a major risk factor for most common neurodegenerative diseases. To improve the quality of life for the elderly, it is important to understand how the brain is changed during the normal aging process. We compared diffusion tensor imaging (DTI)-based brain networks in a cohort of 75 healthy old subjects by using graph theory metrics to describe the anatomical networks and connectivity patterns, and network-based statistic (NBS) analysis was used to identify pairs of regions with altered structural connectivity. The NBS analysis revealed a significant network comprising nine distinct fiber bundles linking 10 different brain regions showed altered white matter structures in young-old group compare with middle-aged group (p < .05, family-wise error-corrected). Our results might guide future studies and help to gain a better understanding of brain aging.

  17. Identification of four functional NR3B isoforms in developing white matter reveals unexpected diversity among glutamate receptors.

    Science.gov (United States)

    Domingues, António M de Jesus; Neugebauer, Karla M; Fern, Robert

    2011-05-01

    Functional neurotransmitter receptors are expressed in central white matter, where they mediate ischemic damage to glia and may be involved in cell-cell signalling. In this study, we analysed NMDA receptor NR1, NR2B-C and NR3A-B subunit expression in the brain and optic nerve by molecular cloning. In addition to the canonical forms of NR1 and NR2, four previously unknown NR3B variants, generated by alternative splicing, were identified. The variants encoded for isoforms with deletions of 8/15 amino acids in the N-terminal domain or 200/375 amino acids removing one or three transmembrane domains and part of the C-terminal domain, as compared with the previously characterized NR3B isoform. Co-expression of NR3B isoforms with NR1/NR2A-C modulated the amplitude and Mg(2+)-sensitivity of glutamate responses in a NR2 subunit-dependent fashion, with significant variations in the effects produced by different isoforms. These effects were not the result of reduced surface expression of the receptor complex since all NR3B isoforms reduced surface expression by a similar degree. These data reveal previously uncharacterized regulation of NMDA receptor function by alternative splicing of the NR3B subunit. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  18. Resting-state brain organization revealed by functional covariance networks.

    Directory of Open Access Journals (Sweden)

    Zhiqiang Zhang

    Full Text Available BACKGROUND: Brain network studies using techniques of intrinsic connectivity network based on fMRI time series (TS-ICN and structural covariance network (SCN have mapped out functional and structural organization of human brain at respective time scales. However, there lacks a meso-time-scale network to bridge the ICN and SCN and get insights of brain functional organization. METHODOLOGY AND PRINCIPAL FINDINGS: We proposed a functional covariance network (FCN method by measuring the covariance of amplitude of low-frequency fluctuations (ALFF in BOLD signals across subjects, and compared the patterns of ALFF-FCNs with the TS-ICNs and SCNs by mapping the brain networks of default network, task-positive network and sensory networks. We demonstrated large overlap among FCNs, ICNs and SCNs and modular nature in FCNs and ICNs by using conjunctional analysis. Most interestingly, FCN analysis showed a network dichotomy consisting of anti-correlated high-level cognitive system and low-level perceptive system, which is a novel finding different from the ICN dichotomy consisting of the default-mode network and the task-positive network. CONCLUSION: The current study proposed an ALFF-FCN approach to measure the interregional correlation of brain activity responding to short periods of state, and revealed novel organization patterns of resting-state brain activity from an intermediate time scale.

  19. A new fossil from the mid-Paleocene of New Zealand reveals an unexpected diversity of world's oldest penguins

    Science.gov (United States)

    Mayr, Gerald; De Pietri, Vanesa L.; Paul Scofield, R.

    2017-04-01

    We describe leg bones of a giant penguin from the mid-Paleocene Waipara Greensand of New Zealand. The specimens were found at the type locality of Waimanu manneringi and together with this species they constitute the oldest penguin fossils known to date. Tarsometatarsus dimensions indicate a species that reached the size of Anthropornis nordenskjoeldi, one of the largest known penguin species. Stem group penguins therefore attained a giant size very early in their evolution, with this gigantism existing for more than 30 million years. The new fossils are from a species that is phylogenetically more derived than Waimanu, and the unexpected coexistence of Waimanu with more derived stem group Sphenisciformes documents a previously unknown diversity amongst the world's oldest penguins. The characteristic tarsometatarsus shape of penguins evolved early on, and the significant morphological disparity between Waimanu and the new fossil conflicts with recent Paleocene divergence estimates for penguins, suggesting an older, Late Cretaceous, origin.

  20. A new fossil from the mid-Paleocene of New Zealand reveals an unexpected diversity of world's oldest penguins.

    Science.gov (United States)

    Mayr, Gerald; De Pietri, Vanesa L; Paul Scofield, R

    2017-04-01

    We describe leg bones of a giant penguin from the mid-Paleocene Waipara Greensand of New Zealand. The specimens were found at the type locality of Waimanu manneringi and together with this species they constitute the oldest penguin fossils known to date. Tarsometatarsus dimensions indicate a species that reached the size of Anthropornis nordenskjoeldi, one of the largest known penguin species. Stem group penguins therefore attained a giant size very early in their evolution, with this gigantism existing for more than 30 million years. The new fossils are from a species that is phylogenetically more derived than Waimanu, and the unexpected coexistence of Waimanu with more derived stem group Sphenisciformes documents a previously unknown diversity amongst the world's oldest penguins. The characteristic tarsometatarsus shape of penguins evolved early on, and the significant morphological disparity between Waimanu and the new fossil conflicts with recent Paleocene divergence estimates for penguins, suggesting an older, Late Cretaceous, origin.

  1. Digital tissue and what it may reveal about the brain.

    Science.gov (United States)

    Morgan, Josh L; Lichtman, Jeff W

    2017-10-30

    Imaging as a means of scientific data storage has evolved rapidly over the past century from hand drawings, to photography, to digital images. Only recently can sufficiently large datasets be acquired, stored, and processed such that tissue digitization can actually reveal more than direct observation of tissue. One field where this transformation is occurring is connectomics: the mapping of neural connections in large volumes of digitized brain tissue.

  2. NMR spectroscopy reveals unexpected structural variation at the protein-protein interface in MHC class I molecules

    Energy Technology Data Exchange (ETDEWEB)

    Beerbaum, Monika; Ballaschk, Martin; Erdmann, Natalja [Leibniz-Institut fuer Molekulare Pharmakologie (FMP) (Germany); Schnick, Christina [Freie Universitaet Berlin, Institut fuer Immungenetik, Charite-Universitaetsmedizin Berlin (Germany); Diehl, Anne [Leibniz-Institut fuer Molekulare Pharmakologie (FMP) (Germany); Uchanska-Ziegler, Barbara; Ziegler, Andreas [Freie Universitaet Berlin, Institut fuer Immungenetik, Charite-Universitaetsmedizin Berlin (Germany); Schmieder, Peter, E-mail: schmieder@fmp-berlin.de [Leibniz-Institut fuer Molekulare Pharmakologie (FMP) (Germany)

    2013-10-15

    {beta}{sub 2}-Microglobulin ({beta}{sub 2}m) is a small, monomorphic protein non-covalently bound to the heavy chain (HC) in polymorphic major histocompatibility complex (MHC) class I molecules. Given the high evolutionary conservation of structural features of {beta}{sub 2}m in various MHC molecules as shown by X-ray crystallography, {beta}{sub 2}m is often considered as a mere scaffolding protein. Using nuclear magnetic resonance (NMR) spectroscopy, we investigate here whether {beta}{sub 2}m residues at the interface to the HC exhibit changes depending on HC polymorphisms and the peptides bound to the complex in solution. First we show that human {beta}{sub 2}m can effectively be produced in deuterated form using high-cell-density-fermentation and we employ the NMR resonance assignments obtained for triple-labeled {beta}{sub 2}m bound to the HLA-B*27:09 HC to examine the {beta}{sub 2}m-HC interface. We then proceed to compare the resonances of {beta}{sub 2}m in two minimally distinct subtypes, HLA-B*27:09 and HLA-B*27:05, that are differentially associated with the spondyloarthropathy Ankylosing Spondylitis. Each of these subtypes is complexed with four distinct peptides for which structural information is already available. We find that only the resonances at the {beta}{sub 2}m-HC interface show a variation of their chemical shifts between the different complexes. This indicates the existence of an unexpected plasticity that enables {beta}{sub 2}m to accommodate changes that depend on HC polymorphism as well as on the bound peptide through subtle structural variations of the protein-protein interface.

  3. Symbolic joint entropy reveals the coupling of various brain regions

    Science.gov (United States)

    Ma, Xiaofei; Huang, Xiaolin; Du, Sidan; Liu, Hongxing; Ning, Xinbao

    2018-01-01

    The convergence and divergence of oscillatory behavior of different brain regions are very important for the procedure of information processing. Measurements of coupling or correlation are very useful to study the difference of brain activities. In this study, EEG signals were collected from ten subjects under two conditions, i.e. eyes closed state and idle with eyes open. We propose a nonlinear algorithm, symbolic joint entropy, to compare the coupling strength among the frontal, temporal, parietal and occipital lobes and between two different states. Instead of decomposing the EEG into different frequency bands (theta, alpha, beta, gamma etc.), the novel algorithm is to investigate the coupling from the entire spectrum of brain wave activities above 4Hz. The coupling coefficients in two states with different time delay steps are compared and the group statistics are presented as well. We find that the coupling coefficient of eyes open state with delay consistently lower than that of eyes close state across the group except for one subject, whereas the results without delay are not consistent. The differences between two brain states with non-zero delay can reveal the intrinsic inter-region coupling better. We also use the well-known Hénon map data to validate the algorithm proposed in this paper. The result shows that the method is robust and has a great potential for other physiologic time series.

  4. Culture-independent genome sequencing of clinical samples reveals an unexpected heterogeneity of infections by Chlamydia pecorum.

    Science.gov (United States)

    Bachmann, Nathan L; Sullivan, Mitchell J; Jelocnik, Martina; Myers, Garry S A; Timms, Peter; Polkinghorne, Adam

    2015-05-01

    Chlamydia pecorum is an important global pathogen of livestock, and it is also a significant threat to the long-term survival of Australia's koala populations. This study employed a culture-independent DNA capture approach to sequence C. pecorum genomes directly from clinical swab samples collected from koalas with chlamydial disease as well as from sheep with arthritis and conjunctivitis. Investigations into single-nucleotide polymorphisms within each of the swab samples revealed that a portion of the reads in each sample belonged to separate C. pecorum strains, suggesting that all of the clinical samples analyzed contained mixed populations of genetically distinct C. pecorum isolates. This observation was independent of the anatomical site sampled and the host species. Using the genomes of strains identified in each of these samples, whole-genome phylogenetic analysis revealed that a clade containing a bovine and a koala isolate is distinct from other clades comprised of livestock or koala C. pecorum strains. Providing additional evidence to support exposure of koalas to Australian livestock strains, two minor strains assembled from the koala swab samples clustered with livestock strains rather than koala strains. Culture-independent probe-based genome capture and sequencing of clinical samples provides the strongest evidence yet to suggest that naturally occurring chlamydial infections are comprised of multiple genetically distinct strains. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  5. Expression profiling reveals an unexpected growth-stimulating effect of surplus iron on the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Du, Yang; Cheng, Wang; Li, Wei-Fang

    2012-08-01

    Iron homeostasis plays a crucial role in growth and division of cells in all kingdoms of life. Although yeast iron metabolism has been extensively studied, little is known about the molecular mechanism of response to surplus iron. In this study, expression profiling of Saccharomyces cerevisiae in the presence of surplus iron revealed a dual effect at 1 and 4 h. A cluster of stress-responsive genes was upregulated via activation of the stress-resistance transcription factor Msn4, which indicated the stress effect of surplus iron on yeast metabolism. Genes involved in aerobic metabolism and several anabolic pathways are also upregulated in iron-surplus conditions, which could significantly accelerate yeast growth. This dual effect suggested that surplus iron might participate in a more complex metabolic network, in addition to serving as a stress inducer. These findings contribute to our understanding of the global response of yeast to the fluctuating availability of iron in the environment.

  6. Fine-scale acoustic telemetry reveals unexpected lake trout, Salvelinus namaycush, spawning habitats in northern Lake Huron, North America

    Science.gov (United States)

    Binder, Thomas; Farha, Steve A.; Thompson, Henry T.; Holbrook, Christopher; Bergstedt, Roger A.; Riley, Stephen; Bronte, Charles R.; He, Ji; Krueger, Charles C.

    2017-01-01

    Previous studies of lake trout, Salvelinus namaycush, spawning habitat in the Laurentian Great Lakes have used time- and labour-intensive survey methods and have focused on areas with historic observations of spawning aggregations and on habitats prejudged by researchers to be suitable for spawning. As an alternative, we used fine-scale acoustic telemetry to locate, describe and compare lake trout spawning habitats. Adult lake trout were implanted with acoustic transmitters and tracked during five consecutive spawning seasons in a 19–27 km2 region of the Drummond Island Refuge, Lake Huron, using the VEMCO Positioning System. Acoustic telemetry revealed discrete areas of aggregation on at least five reefs in the study area, subsequently confirmed by divers to contain deposited eggs. Notably, several identified spawning sites would likely not have been discovered using traditional methods because either they were too small and obscure to stand out on a bathymetric map or because they did not conform to the conceptual model of spawning habitat held by many biologists. Our most unique observation was egg deposition in gravel and rubble substrates located at the base of and beneath overhanging edges of large boulders. Spawning sites typically comprised acoustic transmitters offers potential to expand current conceptual models of critical spawning habitat.

  7. Morphology informed by phylogeny reveals unexpected patterns of species differentiation in the aquatic moss Rhynchostegium riparioides s.l.

    Science.gov (United States)

    Hutsemékers, Virginie; Vieira, Cristiana C; Ros, Rosa María; Huttunen, Sanna; Vanderpoorten, Alain

    2012-02-01

    Bryophyte floras typically exhibit extremely low levels of endemism. The interpretation, that this might reflect taxonomic shortcomings, is tested here for the Macaronesian flora, using the moss species complex of Rhynchostegium riparioides as a model. The deep polyphyly of R. riparioides across its distribution range reveals active differentiation that better corresponds to geographic than morphological differences. Morphometric analyses are, in fact, blurred by a size gradient that accounts for 80% of the variation observed among gametophytic traits. The lack of endemic diversification observed in R. riparioides in Macaronesia weakens the idea that the low rates of endemism observed in the Macaronesian bryophyte flora might solely be explained by taxonomic shortcomings. To the reverse, the striking polyphyly of North American and European lineages of R. riparioides suggests that the similarity between the floras of these continents has been over-emphasized. Discriminant analyses point to the existence of morphological discontinuities among the lineages resolved by the molecular phylogeny. The global rate of error associated to species identification based on morphology (0.23) indicates, however, that intergradation of shape and size characters among species in the group challenges their identification. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Micro-CT scan reveals an unexpected high-volume and interconnected pore network in a Cretaceous Sanagasta dinosaur eggshell.

    Science.gov (United States)

    Hechenleitner, E Martín; Grellet-Tinner, Gerald; Foley, Matthew; Fiorelli, Lucas E; Thompson, Michael B

    2016-03-01

    The Cretaceous Sanagasta neosauropod nesting site (La Rioja, Argentina) was the first confirmed instance of extinct dinosaurs using geothermal-generated heat to incubate their eggs. The nesting strategy and hydrothermal activities at this site led to the conclusion that the surprisingly 7 mm thick-shelled eggs were adapted to harsh hydrothermal microenvironments. We used micro-CT scans in this study to obtain the first three-dimensional microcharacterization of these eggshells. Micro-CT-based analyses provide a robust assessment of gas conductance in fossil dinosaur eggshells with complex pore canal systems, allowing calculation, for the first time, of the shell conductance through its thickness. This novel approach suggests that the shell conductance could have risen during incubation to seven times more than previously estimated as the eggshell erodes. In addition, micro-CT observations reveal that the constant widening and branching of pore canals form a complex funnel-like pore canal system. Furthermore, the high density of pore canals and the presence of a lateral canal network in the shell reduce the risks of pore obstruction during the extended incubation of these eggs in a relatively highly humid and muddy nesting environment. © 2016 The Author(s).

  9. Micro-CT scan reveals an unexpected high-volume and interconnected pore network in a Cretaceous Sanagasta dinosaur eggshell

    Science.gov (United States)

    Grellet-Tinner, Gerald; Foley, Matthew; Thompson, Michael B.

    2016-01-01

    The Cretaceous Sanagasta neosauropod nesting site (La Rioja, Argentina) was the first confirmed instance of extinct dinosaurs using geothermal-generated heat to incubate their eggs. The nesting strategy and hydrothermal activities at this site led to the conclusion that the surprisingly 7 mm thick-shelled eggs were adapted to harsh hydrothermal microenvironments. We used micro-CT scans in this study to obtain the first three-dimensional microcharacterization of these eggshells. Micro-CT-based analyses provide a robust assessment of gas conductance in fossil dinosaur eggshells with complex pore canal systems, allowing calculation, for the first time, of the shell conductance through its thickness. This novel approach suggests that the shell conductance could have risen during incubation to seven times more than previously estimated as the eggshell erodes. In addition, micro-CT observations reveal that the constant widening and branching of pore canals form a complex funnel-like pore canal system. Furthermore, the high density of pore canals and the presence of a lateral canal network in the shell reduce the risks of pore obstruction during the extended incubation of these eggs in a relatively highly humid and muddy nesting environment. PMID:27009182

  10. Covert waking brain activity reveals instantaneous sleep depth.

    Directory of Open Access Journals (Sweden)

    Scott M McKinney

    Full Text Available The neural correlates of the wake-sleep continuum remain incompletely understood, limiting the development of adaptive drug delivery systems for promoting sleep maintenance. The most useful measure for resolving early positions along this continuum is the alpha oscillation, an 8-13 Hz electroencephalographic rhythm prominent over posterior scalp locations. The brain activation signature of wakefulness, alpha expression discloses immediate levels of alertness and dissipates in concert with fading awareness as sleep begins. This brain activity pattern, however, is largely ignored once sleep begins. Here we show that the intensity of spectral power in the alpha band actually continues to disclose instantaneous responsiveness to noise--a measure of sleep depth--throughout a night of sleep. By systematically challenging sleep with realistic and varied acoustic disruption, we found that sleepers exhibited markedly greater sensitivity to sounds during moments of elevated alpha expression. This result demonstrates that alpha power is not a binary marker of the transition between sleep and wakefulness, but carries rich information about immediate sleep stability. Further, it shows that an empirical and ecologically relevant form of sleep depth is revealed in real-time by EEG spectral content in the alpha band, a measure that affords prediction on the order of minutes. This signal, which transcends the boundaries of classical sleep stages, could potentially be used for real-time feedback to novel, adaptive drug delivery systems for inducing sleep.

  11. In-Depth Glyco-Peptidomics Approach Reveals Unexpected Diversity of Glycosylated Peptides and Atypical Post-Translational Modifications in Dendroaspis angusticeps Snake Venom

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    Michel Degueldre

    2017-11-01

    Full Text Available Animal venoms represent a valuable source of bioactive peptides that can be derived into useful pharmacological tools, or even innovative drugs. In this way, the venom of Dendroaspis angusticeps (DA, the Eastern Green Mamba, has been intensively studied during recent years. It mainly contains hundreds of large toxins from 6 to 9 kDa, each displaying several disulfide bridges. These toxins are the main target of venom-based studies due to their valuable activities obtained by selectively targeting membrane receptors, such as ion channels or G-protein coupled receptors. This study aims to demonstrate that the knowledge of venom composition is still limited and that animal venoms contain unexpected diversity and surprises. A previous study has shown that Dendroaspis angusticeps venom contains not only a cocktail of classical toxins, but also small glycosylated peptides. Following this work, a deep exploration of DA glycopeptidome by a dual nano liquid chromatography coupled to electrospray ionization mass spectrometry (nanoLC-ESI-MS and Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS analyses was initiated. This study reveals unsuspected structural diversity of compounds such as 221 glycopeptides, displaying different glycan structures. Sequence alignments underline structural similarities with natriuretic peptides already characterized in Elapidae venoms. Finally, the presence of an S-cysteinylation and hydroxylation of proline on four glycopeptides, never described to date in snake venoms, is also revealed by proteomics and affined by nuclear magnetic resonance (NMR experiments.

  12. A study on the biosynthesis of hygrophorone B(12) in the mushroom Hygrophorus abieticola reveals an unexpected labelling pattern in the cyclopentenone moiety.

    Science.gov (United States)

    Otto, Alexander; Porzel, Andrea; Schmidt, Jürgen; Wessjohann, Ludger; Arnold, Norbert

    2015-10-01

    The hitherto unknown natural formation of hygrophorones, antibacterial and antifungal cyclopentenone derivatives from mushrooms, was investigated for hygrophorone B(12) in Hygrophorus abieticola Krieglst. ex Gröger & Bresinsky by feeding experiments in the field using (13)C labelled samples of D-glucose and sodium acetate. The incorporation of (13)C isotopes was extensively studied using 1D and 2D NMR spectroscopy as well as ESI-HRMS analyses. In the experiment with [U-(13)C6]-glucose, six different (13)C2 labelled isotopomers were observed in the 2D INADEQUATE spectrum due to incorporation of [1,2-(13)C2]-acetyl-CoA. This labelling pattern demonstrated that hygrophorone B(12) is derived from a fatty acid-polyketide route instead of a 1,4-α-D-glucan derived anhydrofructose pathway. The experiment with [2-(13)C]-acetate revealed an unexpected incorporation pattern in the cyclopentenone functionality of hygrophorone B(12). Four single-labelled isotopomers, in particular [1-(13)C]-, [2-(13)C]-, [3-(13)C]-, and [4-(13)C]-hygrophorone B(12), were detected that showed only half enrichment in comparison to the respective labelled alkyl side chain carbons. This labelling pattern indicates the formation of a symmetrical intermediate during hygrophorone B(12) biosynthesis. Based on these observations, a biogenetic route via a 4-oxo fatty acid and a chrysotrione B homologue is discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Unexpected effects of peripherally administered kynurenic acid on cortical spreading depression and related blood–brain barrier permeability

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    Oláh G

    2013-09-01

    Full Text Available Gáspár Oláh,1 Judit Herédi,1 Ákos Menyhárt,1 Zsolt Czinege,2 Dávid Nagy,1 János Fuzik,1 Kitti Kocsis,1 Levente Knapp,1 Erika Krucsó,1 Levente Gellért,1 Zsolt Kis,1 Tamás Farkas,1 Ferenc Fülöp,3 Árpád Párdutz,4 János Tajti,4 László Vécsei,4 József Toldi1 1Department of Physiology, Anatomy and Neuroscience, 2Department of Software Engineering, 3Institute of Pharmaceutical Chemistry and MTA-SZTE Research Group for Stereochemistry, 4Department of Neurology and MTA-SZTE Neuroscience Research Group, University of Szeged, Szeged, Hungary Abstract: Cortical spreading depression (CSD involves a slowly-propagating depolarization wave in the cortex, which can appear in numerous pathophysiological conditions, such as migraine with aura, stroke, and traumatic brain injury. Neurons and glial cells are also depolarized transiently during the phenomena. CSD is followed by a massive increase in glutamate release and by changes in the brain microcirculation. The aim of this study was to investigate the effects of two N-methyl-D-aspartate receptor antagonists, endogenous kynurenic acid (KYNA and dizocilpine, on CSD and the related blood–brain barrier (BBB permeability in rats. In intact animals, KYNA hardly crosses the BBB but has some positive features as compared with its precursor L-Kynurenine, which is frequently used in animal studies (KYNA cannot be metabolized to excitotoxic agents such as 3-hydroxy-L-kynurenine and quinolinic acid. We therefore investigated the possible effects of peripherally administered KYNA. Repetitive CSD waves were elicited by the application of 1 M KCl solution to the cortex. Direct current-electrocorticograms were measured for 1 hour. Four parameters of the waves were compared. Evans blue dye and fluorescent microscopy were used to study the possible changes in the permeability of the BBB. The results demonstrated that N-methyl-D-aspartate receptor antagonists can reduce the number of CSD waves and decrease

  14. MRI reveals brain abnormalities in drug-naive Parkinson's disease.

    Science.gov (United States)

    Planetta, Peggy J; McFarland, Nikolaus R; Okun, Michael S; Vaillancourt, David E

    2014-01-01

    Most brain studies of Parkinson's disease (PD) focus on patients who are already taking antiparkinsonian medication. This makes it difficult to isolate the effects of disease from those of treatment. We review magnetic resonance imaging evidence supporting the hypothesis that early-stage untreated PD patients have structural and functional abnormalities in the brain, some of which are related to motor symptoms.

  15. 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.

  16. Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders

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    Qingying Meng

    2016-05-01

    Full Text Available Nutrition plays a significant role in the increasing prevalence of metabolic and brain disorders. Here we employ systems nutrigenomics to scrutinize the genomic bases of nutrient–host interaction underlying disease predisposition or therapeutic potential. We conducted transcriptome and epigenome sequencing of hypothalamus (metabolic control and hippocampus (cognitive processing from a rodent model of fructose consumption, and identified significant reprogramming of DNA methylation, transcript abundance, alternative splicing, and gene networks governing cell metabolism, cell communication, inflammation, and neuronal signaling. These signals converged with genetic causal risks of metabolic, neurological, and psychiatric disorders revealed in humans. Gene network modeling uncovered the extracellular matrix genes Bgn and Fmod as main orchestrators of the effects of fructose, as validated using two knockout mouse models. We further demonstrate that an omega-3 fatty acid, DHA, reverses the genomic and network perturbations elicited by fructose, providing molecular support for nutritional interventions to counteract diet-induced metabolic and brain disorders. Our integrative approach complementing rodent and human studies supports the applicability of nutrigenomics principles to predict disease susceptibility and to guide personalized medicine.

  17. Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders.

    Science.gov (United States)

    Meng, Qingying; Ying, Zhe; Noble, Emily; Zhao, Yuqi; Agrawal, Rahul; Mikhail, Andrew; Zhuang, Yumei; Tyagi, Ethika; Zhang, Qing; Lee, Jae-Hyung; Morselli, Marco; Orozco, Luz; Guo, Weilong; Kilts, Tina M; Zhu, Jun; Zhang, Bin; Pellegrini, Matteo; Xiao, Xinshu; Young, Marian F; Gomez-Pinilla, Fernando; Yang, Xia

    2016-05-01

    Nutrition plays a significant role in the increasing prevalence of metabolic and brain disorders. Here we employ systems nutrigenomics to scrutinize the genomic bases of nutrient-host interaction underlying disease predisposition or therapeutic potential. We conducted transcriptome and epigenome sequencing of hypothalamus (metabolic control) and hippocampus (cognitive processing) from a rodent model of fructose consumption, and identified significant reprogramming of DNA methylation, transcript abundance, alternative splicing, and gene networks governing cell metabolism, cell communication, inflammation, and neuronal signaling. These signals converged with genetic causal risks of metabolic, neurological, and psychiatric disorders revealed in humans. Gene network modeling uncovered the extracellular matrix genes Bgn and Fmod as main orchestrators of the effects of fructose, as validated using two knockout mouse models. We further demonstrate that an omega-3 fatty acid, DHA, reverses the genomic and network perturbations elicited by fructose, providing molecular support for nutritional interventions to counteract diet-induced metabolic and brain disorders. Our integrative approach complementing rodent and human studies supports the applicability of nutrigenomics principles to predict disease susceptibility and to guide personalized medicine. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Occurrence of specific environmental risk factors in brain tissues of sudden infant death and sudden intrauterine unexpected death victims assessed with gas chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Termopoli, Veronica; Famiglini, Giorgio; Palma, Pierangela; Magrini, Laura; Cappiello, Achille

    2015-03-01

    Sudden infant death syndrome (SIDS) and sudden intrauterine unexpected death syndrome (SIUDS) are an unresolved teaser in the social-medical and health setting of modern medicine and are the result of multifactorial interactions. Recently, prenatal exposure to environmental contaminants has been associated with negative pregnancy outcomes, and verification of their presence in fetal and newborn tissues is of crucial importance. A gas chromatography-tandem mass spectrometry (MS/MS) method, using a triple quadrupole analyzer, is proposed to assess the presence of 20 organochlorine pesticides, two organophosphate pesticides, one carbamate (boscalid), and a phenol (bisphenol A) in human brain tissues. Samples were collected during autopsies of infants and fetuses that died suddenly without any evident cause. The method involves a liquid-solid extraction using n-hexane as the extraction solvent. The extracts were purified with Florisil cartridges prior to the final determination. Recovery experiments using lamb brain spiked at three different concentrations in the range of 1-50 ng g(-1) were performed, with recoveries ranging from 79 to 106%. Intraday and interday repeatability were evaluated, and relative standard deviations lower than 10% and 18%, respectively, were obtained. The selectivity and sensitivity achieved in multiple reaction monitoring mode allowed us to achieve quantification and confirmation in a real matrix at levels as low as 0.2-0.6 ng g(-1). Two MS/MS transitions were acquired for each analyte, using the Q/q ratio as the confirmatory parameter. This method was applied to the analysis of 14 cerebral cortex samples (ten SIUDS and four SIDS cases), and confirmed the presence of several selected compounds.

  19. Transcriptomic analysis of autistic brain reveals convergent molecular pathology.

    Science.gov (United States)

    Voineagu, Irina; Wang, Xinchen; Johnston, Patrick; Lowe, Jennifer K; Tian, Yuan; Horvath, Steve; Mill, Jonathan; Cantor, Rita M; Blencowe, Benjamin J; Geschwind, Daniel H

    2011-05-25

    Autism spectrum disorder (ASD) is a common, highly heritable neurodevelopmental condition characterized by marked genetic heterogeneity. Thus, a fundamental question is whether autism represents an aetiologically heterogeneous disorder in which the myriad genetic or environmental risk factors perturb common underlying molecular pathways in the brain. Here, we demonstrate consistent differences in transcriptome organization between autistic and normal brain by gene co-expression network analysis. Remarkably, regional patterns of gene expression that typically distinguish frontal and temporal cortex are significantly attenuated in the ASD brain, suggesting abnormalities in cortical patterning. We further identify discrete modules of co-expressed genes associated with autism: a neuronal module enriched for known autism susceptibility genes, including the neuronal specific splicing factor A2BP1 (also known as FOX1), and a module enriched for immune genes and glial markers. Using high-throughput RNA sequencing we demonstrate dysregulated splicing of A2BP1-dependent alternative exons in the ASD brain. Moreover, using a published autism genome-wide association study (GWAS) data set, we show that the neuronal module is enriched for genetically associated variants, providing independent support for the causal involvement of these genes in autism. In contrast, the immune-glial module showed no enrichment for autism GWAS signals, indicating a non-genetic aetiology for this process. Collectively, our results provide strong evidence for convergent molecular abnormalities in ASD, and implicate transcriptional and splicing dysregulation as underlying mechanisms of neuronal dysfunction in this disorder.

  20. Study Reveals Brain Biology behind Self-Control

    Science.gov (United States)

    Sparks, Sarah D.

    2011-01-01

    A new neuroscience twist on a classic psychology study offers some clues to what makes one student able to buckle down for hours of homework before a test while his classmates party. The study published in the September 2011 edition of "Proceedings of the National Academy of Science," suggests environmental cues may "hijack" the brain's mechanisms…

  1. PET imaging reveals brain functional changes in internet gaming disorder.

    Science.gov (United States)

    Tian, Mei; Chen, Qiaozhen; Zhang, Ying; Du, Fenglei; Hou, Haifeng; Chao, Fangfang; Zhang, Hong

    2014-07-01

    Internet gaming disorder is an increasing problem worldwide, resulting in critical academic, social, and occupational impairment. However, the neurobiological mechanism of internet gaming disorder remains unknown. The aim of this study is to assess brain dopamine D2 (D2)/Serotonin 2A (5-HT2A) receptor function and glucose metabolism in the same subjects by positron emission tomography (PET) imaging approach, and investigate whether the correlation exists between D2 receptor and glucose metabolism. Twelve drug-naive adult males who met criteria for internet gaming disorder and 14 matched controls were studied with PET and (11)C-N-methylspiperone ((11)C-NMSP) to assess the availability of D2/5-HT2A receptors and with (18)F-fluoro-D-glucose ((18)F-FDG) to assess regional brain glucose metabolism, a marker of brain function. (11)C-NMSP and (18)F-FDG PET imaging data were acquired in the same individuals under both resting and internet gaming task states. In internet gaming disorder subjects, a significant decrease in glucose metabolism was observed in the prefrontal, temporal, and limbic systems. Dysregulation of D2 receptors was observed in the striatum, and was correlated to years of overuse. A low level of D2 receptors in the striatum was significantly associated with decreased glucose metabolism in the orbitofrontal cortex. For the first time, we report the evidence that D2 receptor level is significantly associated with glucose metabolism in the same individuals with internet gaming disorder, which indicates that D2/5-HT2A receptor-mediated dysregulation of the orbitofrontal cortex could underlie a mechanism for loss of control and compulsive behavior in internet gaming disorder subjects.

  2. PET imaging reveals brain functional changes in internet gaming disorder

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Mei; Zhang, Ying; Du, Fenglei; Hou, Haifeng; Chao, Fangfang; Zhang, Hong [The Second Hospital of Zhejiang University School of Medicine, Department of Nuclear Medicine, Hangzhou, Zhejiang (China); Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou (China); Chen, Qiaozhen [The Second Hospital of Zhejiang University School of Medicine, Department of Nuclear Medicine, Hangzhou, Zhejiang (China); The Second Affiliated Hospital of Zhejiang University School of Medicine, Department of Psychiatry, Hangzhou (China)

    2014-07-15

    Internet gaming disorder is an increasing problem worldwide, resulting in critical academic, social, and occupational impairment. However, the neurobiological mechanism of internet gaming disorder remains unknown. The aim of this study is to assess brain dopamine D{sub 2} (D{sub 2})/Serotonin 2A (5-HT{sub 2A}) receptor function and glucose metabolism in the same subjects by positron emission tomography (PET) imaging approach, and investigate whether the correlation exists between D{sub 2} receptor and glucose metabolism. Twelve drug-naive adult males who met criteria for internet gaming disorder and 14 matched controls were studied with PET and {sup 11}C-N-methylspiperone ({sup 11}C-NMSP) to assess the availability of D{sub 2}/5-HT{sub 2A} receptors and with {sup 18}F-fluoro-D-glucose ({sup 18}F-FDG) to assess regional brain glucose metabolism, a marker of brain function. {sup 11}C-NMSP and {sup 18}F-FDG PET imaging data were acquired in the same individuals under both resting and internet gaming task states. In internet gaming disorder subjects, a significant decrease in glucose metabolism was observed in the prefrontal, temporal, and limbic systems. Dysregulation of D{sub 2} receptors was observed in the striatum, and was correlated to years of overuse. A low level of D{sub 2} receptors in the striatum was significantly associated with decreased glucose metabolism in the orbitofrontal cortex. For the first time, we report the evidence that D{sub 2} receptor level is significantly associated with glucose metabolism in the same individuals with internet gaming disorder, which indicates that D{sub 2}/5-HT{sub 2A} receptor-mediated dysregulation of the orbitofrontal cortex could underlie a mechanism for loss of control and compulsive behavior in internet gaming disorder subjects. (orig.)

  3. The brain's functional network architecture reveals human motives.

    Science.gov (United States)

    Hein, Grit; Morishima, Yosuke; Leiberg, Susanne; Sul, Sunhae; Fehr, Ernst

    2016-03-04

    Goal-directed human behaviors are driven by motives. Motives are, however, purely mental constructs that are not directly observable. Here, we show that the brain's functional network architecture captures information that predicts different motives behind the same altruistic act with high accuracy. In contrast, mere activity in these regions contains no information about motives. Empathy-based altruism is primarily characterized by a positive connectivity from the anterior cingulate cortex (ACC) to the anterior insula (AI), whereas reciprocity-based altruism additionally invokes strong positive connectivity from the AI to the ACC and even stronger positive connectivity from the AI to the ventral striatum. Moreover, predominantly selfish individuals show distinct functional architectures compared to altruists, and they only increase altruistic behavior in response to empathy inductions, but not reciprocity inductions. Copyright © 2016, American Association for the Advancement of Science.

  4. Sleep Deprivation Reveals Altered Brain Perfusion Patterns in Somnambulism.

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    Thien Thanh Dang-Vu

    Full Text Available Despite its high prevalence, relatively little is known about the pathophysiology of somnambulism. Increasing evidence indicates that somnambulism is associated with functional abnormalities during wakefulness and that sleep deprivation constitutes an important drive that facilitates sleepwalking in predisposed patients. Here, we studied the neural mechanisms associated with somnambulism using Single Photon Emission Computed Tomography (SPECT with 99mTc-Ethylene Cysteinate Dimer (ECD, during wakefulness and after sleep deprivation.Ten adult sleepwalkers and twelve controls with normal sleep were scanned using 99mTc-ECD SPECT in morning wakefulness after a full night of sleep. Eight of the sleepwalkers and nine of the controls were also scanned during wakefulness after a night of total sleep deprivation. Between-group comparisons of regional cerebral blood flow (rCBF were performed to characterize brain activity patterns during wakefulness in sleepwalkers.During wakefulness following a night of total sleep deprivation, rCBF was decreased bilaterally in the inferior temporal gyrus in sleepwalkers compared to controls.Functional neural abnormalities can be observed during wakefulness in somnambulism, particularly after sleep deprivation and in the inferior temporal cortex. Sleep deprivation thus not only facilitates the occurrence of sleepwalking episodes, but also uncovers patterns of neural dysfunction that characterize sleepwalkers during wakefulness.

  5. Sleep Deprivation Reveals Altered Brain Perfusion Patterns in Somnambulism.

    Science.gov (United States)

    Dang-Vu, Thien Thanh; Zadra, Antonio; Labelle, Marc-Antoine; Petit, Dominique; Soucy, Jean-Paul; Montplaisir, Jacques

    2015-01-01

    Despite its high prevalence, relatively little is known about the pathophysiology of somnambulism. Increasing evidence indicates that somnambulism is associated with functional abnormalities during wakefulness and that sleep deprivation constitutes an important drive that facilitates sleepwalking in predisposed patients. Here, we studied the neural mechanisms associated with somnambulism using Single Photon Emission Computed Tomography (SPECT) with 99mTc-Ethylene Cysteinate Dimer (ECD), during wakefulness and after sleep deprivation. Ten adult sleepwalkers and twelve controls with normal sleep were scanned using 99mTc-ECD SPECT in morning wakefulness after a full night of sleep. Eight of the sleepwalkers and nine of the controls were also scanned during wakefulness after a night of total sleep deprivation. Between-group comparisons of regional cerebral blood flow (rCBF) were performed to characterize brain activity patterns during wakefulness in sleepwalkers. During wakefulness following a night of total sleep deprivation, rCBF was decreased bilaterally in the inferior temporal gyrus in sleepwalkers compared to controls. Functional neural abnormalities can be observed during wakefulness in somnambulism, particularly after sleep deprivation and in the inferior temporal cortex. Sleep deprivation thus not only facilitates the occurrence of sleepwalking episodes, but also uncovers patterns of neural dysfunction that characterize sleepwalkers during wakefulness.

  6. X-ray structures of two proteins belonging to Pfam DUF178 revealed unexpected structural similarity to the DUF191 Pfam family

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    Burley Stephen K

    2007-10-01

    Full Text Available Abstract Background Pfam is a comprehensive collection of protein domains and families, with a range of well-established information including genome annotation. Pfam has two large series of functionally uncharacterized families, known as Domains of Unknown Function (DUFs and Uncharacterized Protein Families (UPFs. Results Crystal structures of two proteins from Deinococcus radiodurans and Streptomyces coelicolor belonging to Pfam protein family DUF178 (ID: PF02621 have been determined using Selenium-Single-wavelength Anomalous Dispersion (Se-SAD. Based on the structure, we have identified the putative function for this family of protein. Conclusion Unexpectedly, we found that DUF178 Pfam is remarkably similar to Pfam family DUF191 suggesting that the sequence-based classification alone may not be sufficient to classify proteins into Pfam families.

  7. Algebraic Topology of Multi-Brain Connectivity Networks Reveals Dissimilarity in Functional Patterns during Spoken Communications.

    Science.gov (United States)

    Tadić, Bosiljka; Andjelković, Miroslav; Boshkoska, Biljana Mileva; Levnajić, Zoran

    2016-01-01

    Human behaviour in various circumstances mirrors the corresponding brain connectivity patterns, which are suitably represented by functional brain networks. While the objective analysis of these networks by graph theory tools deepened our understanding of brain functions, the multi-brain structures and connections underlying human social behaviour remain largely unexplored. In this study, we analyse the aggregate graph that maps coordination of EEG signals previously recorded during spoken communications in two groups of six listeners and two speakers. Applying an innovative approach based on the algebraic topology of graphs, we analyse higher-order topological complexes consisting of mutually interwoven cliques of a high order to which the identified functional connections organise. Our results reveal that the topological quantifiers provide new suitable measures for differences in the brain activity patterns and inter-brain synchronisation between speakers and listeners. Moreover, the higher topological complexity correlates with the listener's concentration to the story, confirmed by self-rating, and closeness to the speaker's brain activity pattern, which is measured by network-to-network distance. The connectivity structures of the frontal and parietal lobe consistently constitute distinct clusters, which extend across the listener's group. Formally, the topology quantifiers of the multi-brain communities exceed the sum of those of the participating individuals and also reflect the listener's rated attributes of the speaker and the narrated subject. In the broader context, the presented study exposes the relevance of higher topological structures (besides standard graph measures) for characterising functional brain networks under different stimuli.

  8. Algebraic Topology of Multi-Brain Connectivity Networks Reveals Dissimilarity in Functional Patterns during Spoken Communications.

    Directory of Open Access Journals (Sweden)

    Bosiljka Tadić

    Full Text Available Human behaviour in various circumstances mirrors the corresponding brain connectivity patterns, which are suitably represented by functional brain networks. While the objective analysis of these networks by graph theory tools deepened our understanding of brain functions, the multi-brain structures and connections underlying human social behaviour remain largely unexplored. In this study, we analyse the aggregate graph that maps coordination of EEG signals previously recorded during spoken communications in two groups of six listeners and two speakers. Applying an innovative approach based on the algebraic topology of graphs, we analyse higher-order topological complexes consisting of mutually interwoven cliques of a high order to which the identified functional connections organise. Our results reveal that the topological quantifiers provide new suitable measures for differences in the brain activity patterns and inter-brain synchronisation between speakers and listeners. Moreover, the higher topological complexity correlates with the listener's concentration to the story, confirmed by self-rating, and closeness to the speaker's brain activity pattern, which is measured by network-to-network distance. The connectivity structures of the frontal and parietal lobe consistently constitute distinct clusters, which extend across the listener's group. Formally, the topology quantifiers of the multi-brain communities exceed the sum of those of the participating individuals and also reflect the listener's rated attributes of the speaker and the narrated subject. In the broader context, the presented study exposes the relevance of higher topological structures (besides standard graph measures for characterising functional brain networks under different stimuli.

  9. Educational games for brain health: revealing their unexplored potential through a neurocognitive approach.

    Science.gov (United States)

    Fissler, Patrick; Kolassa, Iris-Tatjana; Schrader, Claudia

    2015-01-01

    Educational games link the motivational nature of games with learning of knowledge and skills. Here, we go beyond effects on these learning outcomes. We review two lines of evidence which indicate the currently unexplored potential of educational games to promote brain health: First, gaming with specific neurocognitive demands (e.g., executive control), and second, educational learning experiences (e.g., studying foreign languages) improve brain health markers. These markers include cognitive ability, brain function, and brain structure. As educational games allow the combination of specific neurocognitive demands with educational learning experiences, they seem to be optimally suited for promoting brain health. We propose a neurocognitive approach to reveal this unexplored potential of educational games in future research.

  10. Educational games for brain health: revealing their unexplored potential through a neurocognitive approach

    Directory of Open Access Journals (Sweden)

    Patrick eFissler

    2015-07-01

    Full Text Available Educational games link the motivational nature of games with learning of knowledge and skills. Here, we go beyond effects on these learning outcomes. We review two lines of evidence which indicate the currently unexplored potential of educational games to promote brain health: First, gaming with specific neurocognitive demands (e.g., executive control, and second, educational learning experiences (e.g., studying foreign languages improve brain health markers. These markers include cognitive ability, brain function, and brain structure. As educational games allow the combination of specific neurocognitive demands with educational learning experiences, they seem to be optimally suited for promoting brain health. We propose a neurocognitive approach to reveal this unexplored potential of educational games in future research.

  11. Overlapping communities reveal rich structure in large-scale brain networks during rest and task conditions.

    Science.gov (United States)

    Najafi, Mahshid; McMenamin, Brenton W; Simon, Jonathan Z; Pessoa, Luiz

    2016-07-15

    Large-scale analysis of functional MRI data has revealed that brain regions can be grouped into stable "networks" or communities. In many instances, the communities are characterized as relatively disjoint. Although recent work indicates that brain regions may participate in multiple communities (for example, hub regions), the extent of community overlap is poorly understood. To address these issues, here we investigated large-scale brain networks based on "rest" and task human functional MRI data by employing a mixed-membership Bayesian model that allows each brain region to belong to all communities simultaneously with varying membership strengths. The approach allowed us to 1) compare the structure of disjoint and overlapping communities; 2) determine the relationship between functional diversity (how diverse is a region's functional activation repertoire) and membership diversity (how diverse is a region's affiliation to communities); 3) characterize overlapping community structure; 4) characterize the degree of non-modularity in brain networks; 5) study the distribution of "bridges", including bottleneck and hub bridges. Our findings revealed the existence of dense community overlap that was not limited to "special" hubs. Furthermore, the findings revealed important differences between community organization during rest and during specific task states. Overall, we suggest that dense overlapping communities are well suited to capture the flexible and task dependent mapping between brain regions and their functions. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Altered brain anatomical networks and disturbed connection density in brain tumor patients revealed by diffusion tensor tractography.

    Science.gov (United States)

    Yu, Zhou; Tao, Ling; Qian, Zhiyu; Wu, Jiangfen; Liu, Hongyi; Yu, Yun; Song, Jiantai; Wang, Shaobo; Sun, Jinyang

    2016-11-01

    Brain tumor patients are usually accompanied by impairments in cognitive functions, and these dysfunctions arise from the altered diffusion tensor of water molecules and disrupted neuronal conduction in white matter. Diffusion tensor imaging (DTI) is a powerful noninvasive imaging technique that can reflect diffusion anisotropy of water and brain white matter neural connectivity in vivo. This study was aimed to analyze the topological properties and connection densities of the brain anatomical networks in brain tumor patients based on DTI and provide new insights into the investigation of the structural plasticity and compensatory mechanism of tumor patient's brain. In this study, the brain anatomical networks of tumor patients and healthy controls were constructed using the tracking of white matter fiber bundles based on DTI and the topological properties of these networks were described quantitatively. The statistical comparisons were performed between two groups with six DTI parameters: degree, regional efficiency, local efficiency, clustering coefficient, vulnerability, and betweenness centrality. In order to localize changes in structural connectivity to specific brain regions, a network-based statistic approach was utilized. By comparing the edge connection density of brain network between two groups, the edges with greater difference in connection density were associated with three functional systems. Compared with controls, tumor patients show a significant increase in small-world feature of cerebral structural network. Two-sample two-tailed t test indicates that the regional properties are altered in 17 regions ([Formula: see text]). Study reveals that the positive and negative changes in vulnerability take place in the 14 brain areas. In addition, tumor patients lose 3 hub regions and add 2 new hubs when compared to normal controls. Eleven edges show much significantly greater connection density in the patients than in the controls. Most of the edges with

  13. Altered brain structural networks in attention deficit/hyperactivity disorder children revealed by cortical thickness.

    Science.gov (United States)

    Liu, Tian; Chen, Yanni; Li, Chenxi; Li, Youjun; Wang, Jue

    2017-07-04

    This study investigated the cortical thickness and topological features of human brain anatomical networks related to attention deficit/hyperactivity disorder. Data were collected from 40 attention deficit/hyperactivity disorder children and 40 normal control children. Interregional correlation matrices were established by calculating the correlations of cortical thickness between all pairs of cortical regions (68 regions) of the whole brain. Further thresholds were applied to create binary matrices to construct a series of undirected and unweighted graphs, and global, local, and nodal efficiencies were computed as a function of the network cost. These experimental results revealed abnormal cortical thickness and correlations in attention deficit/hyperactivity disorder, and showed that the brain structural networks of attention deficit/hyperactivity disorder subjects had inefficient small-world topological features. Furthermore, their topological properties were altered abnormally. In particular, decreased global efficiency combined with increased local efficiency in attention deficit/hyperactivity disorder children led to a disorder-related shift of the network topological structure toward regular networks. In addition, nodal efficiency, cortical thickness, and correlation analyses revealed that several brain regions were altered in attention deficit/hyperactivity disorder patients. These findings are in accordance with a hypothesis of dysfunctional integration and segregation of the brain in patients with attention deficit/hyperactivity disorder and provide further evidence of brain dysfunction in attention deficit/hyperactivity disorder patients by observing cortical thickness on magnetic resonance imaging.

  14. Lifespan Development of the Human Brain Revealed by Large-Scale Network Eigen-Entropy

    Directory of Open Access Journals (Sweden)

    Yiming Fan

    2017-09-01

    Full Text Available Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying functional connectivity patterns of the developing and aging brain. Normal brain development is characterized by continuous and significant network evolution through infancy, childhood, and adolescence, following specific maturational patterns. Normal aging is related to some resting state brain networks disruption, which are associated with certain cognitive decline. It is a big challenge to design an integral metric to track connectome evolution patterns across the lifespan, which is to understand the principles of network organization in the human brain. In this study, we first defined a brain network eigen-entropy (NEE based on the energy probability (EP of each brain node. Next, we used the NEE to characterize the lifespan orderness trajectory of the whole-brain functional connectivity of 173 healthy individuals ranging in age from 7 to 85 years. The results revealed that during the lifespan, the whole-brain NEE exhibited a significant non-linear decrease and that the EP distribution shifted from concentration to wide dispersion, implying orderness enhancement of functional connectome over age. Furthermore, brain regions with significant EP changes from the flourishing (7–20 years to the youth period (23–38 years were mainly located in the right prefrontal cortex and basal ganglia, and were involved in emotion regulation and executive function in coordination with the action of the sensory system, implying that self-awareness and voluntary control performance significantly changed during neurodevelopment. However, the changes from the youth period to middle age (40–59 years were located in the mesial temporal lobe and caudate, which are associated with long-term memory, implying that the memory of the human brain begins to decline with age during this period. Overall, the findings suggested that the human connectome

  15. miR-31 mutants reveal continuous glial homeostasis in the adult Drosophila brain.

    Science.gov (United States)

    Foo, Lynette Caizhen; Song, Shilin; Cohen, Stephen Michael

    2017-05-02

    The study of adult neural cell production has concentrated on neurogenesis. The mechanisms controlling adult gliogenesis are still poorly understood. Here, we provide evidence for a homeostatic process that maintains the population of glial cells in the Drosophila adult brain. Flies lacking microRNA miR-31a start adult life with a normal complement of glia, but transiently lose glia due to apoptosis. miR-31a expression identifies a subset of predominantly gliogenic adult neural progenitor cells. Failure to limit expression of the predicted E3 ubiquitin ligase, Rchy1, in these cells results in glial loss. After an initial decline in young adults, glial numbers recovered due to compensatory overproduction of new glia by adult progenitor cells, indicating an unexpected plasticity of the Drosophila nervous system. Experimentally induced ablation of glia was also followed by recovery of glia over time. These studies provide evidence for a homeostatic mechanism that maintains the number of glia in the adult fly brain. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  16. Analysis of spatial-temporal gene expression patterns reveals dynamics and regionalization in developing mouse brain.

    Science.gov (United States)

    Chou, Shen-Ju; Wang, Chindi; Sintupisut, Nardnisa; Niou, Zhen-Xian; Lin, Chih-Hsu; Li, Ker-Chau; Yeang, Chen-Hsiang

    2016-01-20

    Allen Brain Atlas (ABA) provides a valuable resource of spatial/temporal gene expressions in mammalian brains. Despite rich information extracted from this database, current analyses suffer from several limitations. First, most studies are either gene-centric or region-centric, thus are inadequate to capture the superposition of multiple spatial-temporal patterns. Second, standard tools of expression analysis such as matrix factorization can capture those patterns but do not explicitly incorporate spatial dependency. To overcome those limitations, we proposed a computational method to detect recurrent patterns in the spatial-temporal gene expression data of developing mouse brains. We demonstrated that regional distinction in brain development could be revealed by localized gene expression patterns. The patterns expressed in the forebrain, medullary and pontomedullary, and basal ganglia are enriched with genes involved in forebrain development, locomotory behavior, and dopamine metabolism respectively. In addition, the timing of global gene expression patterns reflects the general trends of molecular events in mouse brain development. Furthermore, we validated functional implications of the inferred patterns by showing genes sharing similar spatial-temporal expression patterns with Lhx2 exhibited differential expression in the embryonic forebrains of Lhx2 mutant mice. These analysis outcomes confirm the utility of recurrent expression patterns in studying brain development.

  17. Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain.

    Science.gov (United States)

    Lake, Blue B; Ai, Rizi; Kaeser, Gwendolyn E; Salathia, Neeraj S; Yung, Yun C; Liu, Rui; Wildberg, Andre; Gao, Derek; Fung, Ho-Lim; Chen, Song; Vijayaraghavan, Raakhee; Wong, Julian; Chen, Allison; Sheng, Xiaoyan; Kaper, Fiona; Shen, Richard; Ronaghi, Mostafa; Fan, Jian-Bing; Wang, Wei; Chun, Jerold; Zhang, Kun

    2016-06-24

    The human brain has enormously complex cellular diversity and connectivities fundamental to our neural functions, yet difficulties in interrogating individual neurons has impeded understanding of the underlying transcriptional landscape. We developed a scalable approach to sequence and quantify RNA molecules in isolated neuronal nuclei from a postmortem brain, generating 3227 sets of single-neuron data from six distinct regions of the cerebral cortex. Using an iterative clustering and classification approach, we identified 16 neuronal subtypes that were further annotated on the basis of known markers and cortical cytoarchitecture. These data demonstrate a robust and scalable method for identifying and categorizing single nuclear transcriptomes, revealing shared genes sufficient to distinguish previously unknown and orthologous neuronal subtypes as well as regional identity and transcriptomic heterogeneity within the human brain. Copyright © 2016, American Association for the Advancement of Science.

  18. Developmentally-Dynamic Murine Brain Proteomes and Phosphoproteomes Revealed by Quantitative Proteomics

    Directory of Open Access Journals (Sweden)

    Peter F. Doubleday

    2014-04-01

    Full Text Available Developmental processes are governed by a diverse suite of signaling pathways employing reversible phosphorylation. Recent advances in large-scale phosphoproteomic methodologies have made possible the identification and quantification of hundreds to thousands of phosphorylation sites from primary tissues. Towards a global characterization of proteomic changes across brain development, we present the results of a large-scale quantitative mass spectrometry study comparing embryonic, newborn and adult murine brain. Using anti-phosphotyrosine immuno-affinity chromatography and strong cation exchange (SCX chromatography, coupled to immobilized metal affinity chromatography (IMAC, we identified and quantified over 1,750 phosphorylation sites and over 1,300 proteins between three developmental states. Bioinformatic analyses highlight functions associated with the identified proteins and phosphoproteins and their enrichment at distinct developmental stages. These results serve as a primary reference resource and reveal dynamic developmental profiles of proteins and phosphoproteins from the developing murine brain.

  19. Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain.

    Directory of Open Access Journals (Sweden)

    Erwin van Vliet

    Full Text Available BACKGROUND: Intrauterine Growth Restriction (IUGR due to placental insufficiency occurs in 5-10% of pregnancies and is a major risk factor for abnormal neurodevelopment. The perinatal diagnosis of IUGR related abnormal neurodevelopment represents a major challenge in fetal medicine. The development of clinical biomarkers is considered a promising approach, but requires the identification of biochemical/molecular alterations by IUGR in the fetal brain. This targeted metabolomics study in a rabbit IUGR model aimed to obtain mechanistic insight into the effects of IUGR on the fetal brain and identify metabolite candidates for biomarker development. METHODOLOGY/PRINCIPAL FINDINGS: At gestation day 25, IUGR was induced in two New Zealand rabbits by 40-50% uteroplacental vessel ligation in one horn and the contralateral horn was used as control. At day 30, fetuses were delivered by Cesarian section, weighed and brains collected for metabolomics analysis. Results showed that IUGR fetuses had a significantly lower birth and brain weight compared to controls. Metabolomics analysis using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS and database matching identified 78 metabolites. Comparison of metabolite intensities using a t-test demonstrated that 18 metabolites were significantly different between control and IUGR brain tissue, including neurotransmitters/peptides, amino acids, fatty acids, energy metabolism intermediates and oxidative stress metabolites. Principle component and hierarchical cluster analysis showed cluster formations that clearly separated control from IUGR brain tissue samples, revealing the potential to develop predictive biomarkers. Moreover birth weight and metabolite intensity correlations indicated that the extent of alterations was dependent on the severity of IUGR. CONCLUSIONS: IUGR leads to metabolic alterations in the fetal rabbit brain, involving neuronal viability, energy metabolism, amino

  20. Metabolomics Reveals Metabolic Alterations by Intrauterine Growth Restriction in the Fetal Rabbit Brain

    Science.gov (United States)

    van Vliet, Erwin; Eixarch, Elisenda; Illa, Miriam; Arbat-Plana, Ariadna; González-Tendero, Anna; Hogberg, Helena T.; Zhao, Liang; Hartung, Thomas; Gratacos, Eduard

    2013-01-01

    Background Intrauterine Growth Restriction (IUGR) due to placental insufficiency occurs in 5–10% of pregnancies and is a major risk factor for abnormal neurodevelopment. The perinatal diagnosis of IUGR related abnormal neurodevelopment represents a major challenge in fetal medicine. The development of clinical biomarkers is considered a promising approach, but requires the identification of biochemical/molecular alterations by IUGR in the fetal brain. This targeted metabolomics study in a rabbit IUGR model aimed to obtain mechanistic insight into the effects of IUGR on the fetal brain and identify metabolite candidates for biomarker development. Methodology/Principal Findings At gestation day 25, IUGR was induced in two New Zealand rabbits by 40–50% uteroplacental vessel ligation in one horn and the contralateral horn was used as control. At day 30, fetuses were delivered by Cesarian section, weighed and brains collected for metabolomics analysis. Results showed that IUGR fetuses had a significantly lower birth and brain weight compared to controls. Metabolomics analysis using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) and database matching identified 78 metabolites. Comparison of metabolite intensities using a t-test demonstrated that 18 metabolites were significantly different between control and IUGR brain tissue, including neurotransmitters/peptides, amino acids, fatty acids, energy metabolism intermediates and oxidative stress metabolites. Principle component and hierarchical cluster analysis showed cluster formations that clearly separated control from IUGR brain tissue samples, revealing the potential to develop predictive biomarkers. Moreover birth weight and metabolite intensity correlations indicated that the extent of alterations was dependent on the severity of IUGR. Conclusions IUGR leads to metabolic alterations in the fetal rabbit brain, involving neuronal viability, energy metabolism, amino acid levels, fatty

  1. Analysis of the effects of polyphenols on human spermatozoa reveals unexpected impacts on mitochondrial membrane potential, oxidative stress and DNA integrity; implications for assisted reproductive technology.

    Science.gov (United States)

    Aitken, R J; Muscio, L; Whiting, S; Connaughton, H S; Fraser, B A; Nixon, B; Smith, N D; De Iuliis, G N

    2016-12-01

    The need to protect human spermatozoa from oxidative stress during assisted reproductive technology, has prompted a detailed analysis of the impacts of phenolic compounds on the functional integrity of these cells. Investigation of 16 individual compounds revealed a surprising variety of negative effects including: (i) a loss of mitochondrial membrane potential (Δψm) via mechanisms that were not related to opening of the permeability transition pore but associated with a reduction in thiol expression, (ii) a decline in intracellular reduced glutathione, (iii) the stimulation of pro-oxidant activity including the induction of ROS generation from mitochondrial and non-mitochondrial sources, (iv) stimulation of lipid peroxidation, (v) the generation of oxidative DNA damage, and (vi) impaired sperm motility. For most of the polyphenolic compounds examined, the loss of motility was gradual and highly correlated with the induction of lipid peroxidation (r=0.889). The exception was gossypol, which induced a rapid loss of motility due to its inherent alkylating activity; one consequence of which was a marked reduction in carboxymethyl lysine expression on the sperm tail; a post-translational modification that is known to play a key role in the regulation of sperm movement. The only polyphenols that did not appear to have adverse effects on spermatozoa were resveratrol, genistein and THP at doses below 100μM. These compounds could, therefore, have some therapeutic potential in a clinical setting. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Single-cell profiling of lineage determining transcription factors in antigen-specific CD4+T cells reveals unexpected complexity in recall responses during immune reconstitution.

    Science.gov (United States)

    Phetsouphanh, Chansavath; Xu, Yin; Munier, Mee Ling; Zaunders, John J; Kelleher, Anthony D

    2017-08-01

    Recent studies of protein and gene expression at the single-cell level have revealed that the memory T-cell compartment is more heterogeneous than previously acknowledged. Identifying different T helper subsets involved in memory responses at the single-cell level is thus necessary to understand the level of heterogeneity within this population. Antigen-specific CD4 + T cells were measured using the CD25/OX40 assay together with a qualitative multiplex single-cell RT-PCR assay. Transcription profiles and subset proportions within the antigen-specific CD4 + T-cell population were dissected. Cytomegalovirus (CMV)-specific CD4 + T-cell responses skewed toward a Th1 response, whereas Tetanus toxoid responses skewed toward a Th2 type response. Fluctuations in CD4 + T-cell subsets were observed within the HIV-Gag-specific response during ongoing antiretroviral therapy. Strong effector responses (Th1) were observed in early treatment, however with ongoing therapy this effector response significantly decreased in combination with an increase in Tregs and circulating Tfh-like BCL-6 + memory cells. The apparent increase in Tcm in peripheral blood after a several weeks of antiretroviral therapy may be due to Tfh-like cell egress from germinal centers into the periphery.

  3. Evans blue staining reveals vascular leakage associated with focal areas of host-parasite interaction in brains of pigs infected with Taenia solium.

    Science.gov (United States)

    Marzal, Miguel; Guerra-Giraldez, Cristina; Paredes, Adriana; Cangalaya, Carla; Rivera, Andrea; Gonzalez, Armando E; Mahanty, Siddhartha; Garcia, Hector H; Nash, Theodore E

    2014-01-01

    Cysticidal drug treatment of viable Taenia solium brain parenchymal cysts leads to an acute pericystic host inflammatory response and blood brain barrier breakdown (BBB), commonly resulting in seizures. Naturally infected pigs, untreated or treated one time with praziquantel were sacrificed at 48 hr and 120 hr following the injection of Evans blue (EB) to assess the effect of treatment on larval parasites and surrounding tissue. Examination of harvested non encapsulated muscle cysts unexpectedly revealed one or more small, focal round region(s) of Evans blue dye infiltration (REBI) on the surface of otherwise non dye-stained muscle cysts. Histopathological analysis of REBI revealed focal areas of eosinophil-rich inflammatory infiltrates that migrated from the capsule into the tegument and internal structures of the parasite. In addition some encapsulated brain cysts, in which the presence of REBI could not be directly assessed, showed histopathology identical to that of the REBI. Muscle cysts with REBI were more frequent in pigs that had received praziquantel (6.6% of 3736 cysts; n = 6 pigs) than in those that were untreated (0.2% of 3172 cysts; n = 2 pigs). Similar results were found in the brain, where 20.7% of 29 cysts showed histopathology identical to muscle REBI cysts in praziquantel-treated pigs compared to the 4.3% of 47 cysts in untreated pigs. Closer examination of REBI infiltrates showed that EB was taken up only by eosinophils, a major component of the cellular infiltrates, which likely explains persistence of EB in the REBI. REBI likely represent early damaging host responses to T. solium cysts and highlight the focal nature of this initial host response and the importance of eosinophils at sites of host-parasite interaction. These findings suggest new avenues for immunomodulation to reduce inflammatory side effects of anthelmintic therapy.

  4. The structure of monoacylglycerol lipase from Bacillus sp. H257 reveals unexpected conservation of the cap architecture between bacterial and human enzymes.

    Science.gov (United States)

    Rengachari, Srinivasan; Bezerra, Gustavo A; Riegler-Berket, Lina; Gruber, Christian C; Sturm, Christian; Taschler, Ulrike; Boeszoermenyi, Andras; Dreveny, Ingrid; Zimmermann, Robert; Gruber, Karl; Oberer, Monika

    2012-07-01

    Monoacylglycerol lipases (MGLs) catalyse the hydrolysis of monoacylglycerol into free fatty acid and glycerol. MGLs have been identified throughout all genera of life and have adopted different substrate specificities depending on their physiological role. In humans, MGL plays an integral part in lipid metabolism affecting energy homeostasis, signalling processes and cancer cell progression. In bacteria, MGLs degrade short-chain monoacylglycerols which are otherwise toxic to the organism. We report the crystal structures of MGL from the bacterium Bacillus sp. H257 (bMGL) in its free form at 1.2Å and in complex with phenylmethylsulfonyl fluoride at 1.8Å resolution. In both structures, bMGL adopts an α/β hydrolase fold with a cap in an open conformation. Access to the active site residues, which were unambiguously identified from the protein structure, is facilitated by two different channels. The larger channel constitutes the highly hydrophobic substrate binding pocket with enough room to accommodate monoacylglycerol. The other channel is rather small and resembles the proposed glycerol exit hole in human MGL. Molecular dynamics simulation of bMGL yielded open and closed states of the entrance channel and the glycerol exit hole. Despite differences in the number of residues, secondary structure elements, and low sequence identity in the cap region, this first structure of a bacterial MGL reveals striking structural conservation of the overall cap architecture in comparison with human MGL. Thus it provides insight into the structural conservation of the cap amongst MGLs throughout evolution and provides a framework for rationalising substrate specificities in each organism. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Revealing time-unlocked brain activity from MEG measurements by common waveform estimation.

    Directory of Open Access Journals (Sweden)

    Yusuke Takeda

    Full Text Available Brain activities related to cognitive functions, such as attention, occur with unknown and variable delays after stimulus onsets. Recently, we proposed a method (Common Waveform Estimation, CWE that could extract such brain activities from magnetoencephalography (MEG or electroencephalography (EEG measurements. CWE estimates spatiotemporal MEG/EEG patterns occurring with unknown and variable delays, referred to here as unlocked waveforms, without hypotheses about their shapes. The purpose of this study is to demonstrate the usefulness of CWE for cognitive neuroscience. For this purpose, we show procedures to estimate unlocked waveforms using CWE and to examine their role. We applied CWE to the MEG epochs during Go trials of a visual Go/NoGo task. This revealed unlocked waveforms with interesting properties, specifically large alpha oscillations around the temporal areas. To examine the role of the unlocked waveform, we attempted to estimate the strength of the brain activity of the unlocked waveform in various conditions. We made a spatial filter to extract the component reflecting the brain activity of the unlocked waveform, applied this spatial filter to MEG data under different conditions (a passive viewing, a simple reaction time, and Go/NoGo tasks, and calculated the powers of the extracted components. Comparing the powers across these conditions suggests that the unlocked waveforms may reflect the inhibition of the task-irrelevant activities in the temporal regions while the subject attends to the visual stimulus. Our results demonstrate that CWE is a potential tool for revealing new findings of cognitive brain functions without any hypothesis in advance.

  6. Revealing pathologies in the liquid crystalline structures of the brain by polarimetric studies (Presentation Recording)

    Science.gov (United States)

    Bakhshetyan, Karen; Melkonyan, Gurgen G.; Galstian, Tigran V.; Saghatelyan, Armen

    2015-10-01

    Natural or "self" alignment of molecular complexes in living tissue represents many similarities with liquid crystals (LC), which are anisotropic liquids. The orientational characteristics of those complexes may be related to many important functional parameters and their study may reveal important pathologies. The know-how, accumulated thanks to the study of LC materials, may thus be used to this end. One of the traditionally used methods, to characterize those materials, is the polarized light imaging (PLI) that allows for label-free analysis of anisotropic structures in the brain tissue and can be used, for example, for the analysis of myelinated fiber bundles. In the current work, we first attempted to apply the PLI on the mouse histological brain sections to create a map of anisotropic structures using cross-polarizer transmission light. Then we implemented the PLI for comparative study of histological sections of human postmortem brain samples under normal and pathological conditions, such as Parkinson's disease (PD). Imaging the coronal, sagittal and horizontal sections of mouse brain allowed us to create a false color-coded fiber orientation map under polarized light. In human brain datasets for both control and PD groups we measured the pixel intensities in myelin-rich subregions of internal capsule and normalized these to non-myelinated background signal from putamen and caudate nucleus. Quantification of intensities revealed a statistically significant reduction of fiber intensity of PD compared to control subjects (2.801 +/- 0.303 and 3.724 +/- 0.07 respectively; *p < 0.05). Our study confirms the validity of PLI method for visualizing myelinated axonal fibers. This relatively simple technique can become a promising tool for study of neurodegenerative diseases where labeling-free imaging is an important benefit.

  7. Multifrequency magnetic resonance elastography of the brain reveals tissue degeneration in neuromyelitis optica spectrum disorder

    Energy Technology Data Exchange (ETDEWEB)

    Streitberger, Kaspar-Josche [Charite - Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany); Charite - Universitaetsmedizin Berlin, Department of Neurology with Experimental Neurology, Berlin (Germany); Fehlner, Andreas; Sack, Ingolf [Charite - Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany); Pache, Florence [Charite - Universitaetsmedizin Berlin, Department of Neurology with Experimental Neurology, Berlin (Germany); Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Lacheta, Anna; Papazoglou, Sebastian; Brandt, Alexander [Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Bellmann-Strobl, Judith [Max Delbrueck Center for Molecular Medicine and Charite - Universitaetsmedizin Berlin, Experimental and Clinical Research Center, Berlin (Germany); Ruprecht, Klemens [Charite - Universitaetsmedizin Berlin, Department of Neurology with Experimental Neurology, Berlin (Germany); Braun, Juergen [Charite - Universitaetsmedizin Berlin, Institute of Medical Informatics, Berlin (Germany); Paul, Friedemann [Charite - Universitaetsmedizin Berlin, Department of Neurology with Experimental Neurology, Berlin (Germany); Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Max Delbrueck Center for Molecular Medicine and Charite - Universitaetsmedizin Berlin, Experimental and Clinical Research Center, Berlin (Germany); Wuerfel, Jens [Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Max Delbrueck Center for Molecular Medicine and Charite - Universitaetsmedizin Berlin, Experimental and Clinical Research Center, Berlin (Germany); Medical Image Analysis Center (MIAC AG), Basel (Switzerland)

    2017-05-15

    Application of multifrequency magnetic resonance elastography (MMRE) of the brain parenchyma in patients with neuromyelitis optica spectrum disorder (NMOSD) compared to age matched healthy controls (HC). 15 NMOSD patients and 17 age- and gender-matched HC were examined using MMRE. Two three-dimensional viscoelastic parameter maps, the magnitude G* and phase angle φ of the complex shear modulus were reconstructed by simultaneous inversion of full wave-field data in 1.9-mm isotropic resolution at 7 harmonic drive frequencies from 30 to 60 Hz. In NMOSD patients, a significant reduction of G* was observed within the white matter fraction (p = 0.017), predominantly within the thalamic regions (p = 0.003), compared to HC. These parameters exceeded the reduction in brain volume measured in patients versus HC (p = 0.02 whole-brain volume reduction). Volumetric differences in white matter fraction and the thalami were not detectable between patients and HC. However, phase angle φ was decreased in patients within the white matter (p = 0.03) and both thalamic regions (p = 0.044). MMRE reveals global tissue degeneration with accelerated softening of the brain parenchyma in patients with NMOSD. The predominant reduction of stiffness is found within the thalamic region and related white matter tracts, presumably reflecting Wallerian degeneration. (orig.)

  8. Insights into the metabolic response to traumatic brain injury as revealed by 13C NMR spectroscopy.

    Directory of Open Access Journals (Sweden)

    Brenda eBartnik-Olson

    2013-10-01

    Full Text Available The present review highlights critical issues related to cerebral metabolism following traumatic brain injury (TBI and the use of 13C labeled substrates and nuclear magnetic resonance (NMR spectroscopy to study these changes. First we address some pathophysiologic factors contributing to metabolic dysfunction following TBI. We then examine how 13C NMR spectroscopy strategies have been used to investigate energy metabolism, neurotransmission, the intracellular redox state, and neuroglial compartmentation following injury. 13C NMR spectroscopy studies of brain extracts from animal models of TBI have revealed enhanced glycolytic production of lactate, evidence of pentose phosphate pathway (PPP activation, and alterations in neuronal and astrocyte oxidative metabolism that are dependent on injury severity. Differential incorporation of label into glutamate and glutamine from 13C labeled glucose or acetate also suggest TBI-induced adaptations to the glutamate-glutamine cycle.

  9. Arctic driftwood reveals unexpectedly rich fungal diversity

    Czech Academy of Sciences Publication Activity Database

    Blanchette, R.A.; Held, B.W.; Hellmann, L.; Millman, L.; Büntgen, Ulf

    2016-01-01

    Roč. 23, OCT (2016), s. 58-65 ISSN 1754-5048 R&D Projects: GA MŠk(CZ) EE2.3.20.0248 Institutional support: RVO:67179843 Keywords : Ascomycota * Basidiomycota * Biodegradation * Community ecology * Greenland * Iceland * its * Russia * Soft rot * Taxonomy * Wood decay Subject RIV: EH - Ecology, Behaviour Impact factor: 3.219, year: 2016

  10. Unexpected high plasma cobalamin

    DEFF Research Database (Denmark)

    Arendt, Johan F B; Nexo, Ebba

    2013-01-01

    It is well-established that more than 8% of patients examined for vitamin B12 deficiency unexpectedly have increased plasma levels of the vitamin, but so far there are no guidelines for the clinical interpretation of such findings. In this review, we summarise known associations between high plasma...... cobalamin binding proteins, transcobalamin and haptocorrin. Based on current knowledge, we suggest a strategy for the clinical interpretation of unexpected high plasma cobalamin. Since a number of the associated diseases are critical and life-threatening, the strategy promotes the concept of 'think...

  11. Neural correlates of apathy revealed by lesion mapping in participants with traumatic brain injuries.

    Science.gov (United States)

    Knutson, Kristine M; Monte, Olga Dal; Raymont, Vanessa; Wassermann, Eric M; Krueger, Frank; Grafman, Jordan

    2014-03-01

    Apathy, common in neurological disorders, is defined as disinterest and loss of motivation, with a reduction in self-initiated activity. Research in diseased populations has shown that apathy is associated with variations in the volume of brain regions such as the anterior cingulate and the frontal lobes. The goal of this study was to determine the neural signatures of apathy in people with penetrating traumatic brain injuries (pTBIs), as to our knowledge, these have not been studied in this sample. We studied 176 male Vietnam War veterans with pTBIs using voxel-based lesion-symptom mapping (VLSM) and apathy scores from the UCLA Neuropsychiatric Inventory (NPI), a structured inventory of symptoms completed by a caregiver. Our results revealed that increased apathy symptoms were associated with brain damage in limbic and cortical areas of the left hemisphere including the anterior cingulate, inferior, middle, and superior frontal regions, insula, and supplementary motor area. Our results are consistent with the literature, and extend them to people with focal pTBI. Apathy is a significant symptom since it can reduce participation of the patient in family and other social interactions, and diminish affective decision-making. Copyright © 2013 Wiley Periodicals, Inc.

  12. Gene set based integrated data analysis reveals phenotypic differences in a brain cancer model.

    Directory of Open Access Journals (Sweden)

    Kjell Petersen

    Full Text Available A key challenge in the data analysis of biological high-throughput experiments is to handle the often low number of samples in the experiments compared to the number of biomolecules that are simultaneously measured. Combining experimental data using independent technologies to illuminate the same biological trends, as well as complementing each other in a larger perspective, is one natural way to overcome this challenge. In this work we investigated if integrating proteomics and transcriptomics data from a brain cancer animal model using gene set based analysis methodology, could enhance the biological interpretation of the data relative to more traditional analysis of the two datasets individually. The brain cancer model used is based on serial passaging of transplanted human brain tumor material (glioblastoma--GBM through several generations in rats. These serial transplantations lead over time to genotypic and phenotypic changes in the tumors and represent a medically relevant model with a rare access to samples and where consequent analyses of individual datasets have revealed relatively few significant findings on their own. We found that the integrated analysis both performed better in terms of significance measure of its findings compared to individual analyses, as well as providing independent verification of the individual results. Thus a better context for overall biological interpretation of the data can be achieved.

  13. Statistics of weighted brain networks reveal hierarchical organization and Gaussian degree distribution.

    Science.gov (United States)

    Ivković, Miloš; Kuceyeski, Amy; Raj, Ashish

    2012-01-01

    Whole brain weighted connectivity networks were extracted from high resolution diffusion MRI data of 14 healthy volunteers. A statistically robust technique was proposed for the removal of questionable connections. Unlike most previous studies our methods are completely adapted for networks with arbitrary weights. Conventional statistics of these weighted networks were computed and found to be comparable to existing reports. After a robust fitting procedure using multiple parametric distributions it was found that the weighted node degree of our networks is best described by the normal distribution, in contrast to previous reports which have proposed heavy tailed distributions. We show that post-processing of the connectivity weights, such as thresholding, can influence the weighted degree asymptotics. The clustering coefficients were found to be distributed either as gamma or power-law distribution, depending on the formula used. We proposed a new hierarchical graph clustering approach, which revealed that the brain network is divided into a regular base-2 hierarchical tree. Connections within and across this hierarchy were found to be uncommonly ordered. The combined weight of our results supports a hierarchically ordered view of the brain, whose connections have heavy tails, but whose weighted node degrees are comparable.

  14. Single-nanotube tracking reveals the nanoscale organization of the extracellular space in the live brain

    Science.gov (United States)

    Godin, Antoine G.; Varela, Juan A.; Gao, Zhenghong; Danné, Noémie; Dupuis, Julien P.; Lounis, Brahim; Groc, Laurent; Cognet, Laurent

    2017-03-01

    The brain is a dynamic structure with the extracellular space (ECS) taking up almost a quarter of its volume. Signalling molecules, neurotransmitters and nutrients transit via the ECS, which constitutes a key microenvironment for cellular communication and the clearance of toxic metabolites. The spatial organization of the ECS varies during sleep, development and aging and is probably altered in neuropsychiatric and degenerative diseases, as inferred from electron microscopy and macroscopic biophysical investigations. Here we show an approach to directly observe the local ECS structures and rheology in brain tissue using super-resolution imaging. We inject single-walled carbon nanotubes into rat cerebroventricles and follow the near-infrared emission of individual nanotubes as they diffuse inside the ECS for tens of minutes in acute slices. Because of the interplay between the nanotube geometry and the ECS local environment, we can extract information about the dimensions and local viscosity of the ECS. We find a striking diversity of ECS dimensions down to 40 nm, and as well as of local viscosity values. Moreover, by chemically altering the extracellular matrix of the brains of live animals before nanotube injection, we reveal that the rheological properties of the ECS are affected, but these alterations are local and inhomogeneous at the nanoscale.

  15. A functional genomics screen in planarians reveals regulators of whole-brain regeneration

    Science.gov (United States)

    Roberts-Galbraith, Rachel H; Brubacher, John L; Newmark, Phillip A

    2016-01-01

    Planarians regenerate all body parts after injury, including the central nervous system (CNS). We capitalized on this distinctive trait and completed a gene expression-guided functional screen to identify factors that regulate diverse aspects of neural regeneration in Schmidtea mediterranea. Our screen revealed molecules that influence neural cell fates, support the formation of a major connective hub, and promote reestablishment of chemosensory behavior. We also identified genes that encode signaling molecules with roles in head regeneration, including some that are produced in a previously uncharacterized parenchymal population of cells. Finally, we explored genes downregulated during planarian regeneration and characterized, for the first time, glial cells in the planarian CNS that respond to injury by repressing several transcripts. Collectively, our studies revealed diverse molecules and cell types that underlie an animal’s ability to regenerate its brain. DOI: http://dx.doi.org/10.7554/eLife.17002.001 PMID:27612384

  16. Magnetic resonance volumetry reveals focal brain atrophy in transient epileptic amnesia.

    Science.gov (United States)

    Butler, Christopher; van Erp, Willemijn; Bhaduri, Amit; Hammers, Alexander; Heckemann, Rolf; Zeman, Adam

    2013-09-01

    Transient epileptic amnesia (TEA) is a recently described epilepsy syndrome characterized by recurrent episodes of isolated memory loss. It is associated with two unusual forms of interictal memory impairment: accelerated long-term forgetting (ALF) and autobiographical amnesia. We investigated the neural basis of TEA using manual volumetry and automated multi-atlas-based segmentation of whole-brain magnetic resonance imaging data from 40 patients with TEA and 20 healthy controls. Both methods confirmed the presence of subtle, bilateral hippocampal atrophy. Additional atrophy was revealed in perirhinal and orbitofrontal cortices. The volumes of these regions correlated with anterograde memory performance. No structural correlates were found for ALF or autobiographical amnesia. The results support the hypothesis that TEA is a focal medial temporal lobe epilepsy syndrome but reveal additional pathology in connected brain regions. The unusual interictal memory deficits of TEA remain unexplained by structural pathology and may reflect physiological disruption of memory networks by subclinical epileptiform activity. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Dependency Network Analysis (DEPNA) Reveals Context Related Influence of Brain Network Nodes.

    Science.gov (United States)

    Jacob, Yael; Winetraub, Yonatan; Raz, Gal; Ben-Simon, Eti; Okon-Singer, Hadas; Rosenberg-Katz, Keren; Hendler, Talma; Ben-Jacob, Eshel

    2016-06-07

    Communication between and within brain regions is essential for information processing within functional networks. The current methods to determine the influence of one region on another are either based on temporal resolution, or require a predefined model for the connectivity direction. However these requirements are not always achieved, especially in fMRI studies, which have poor temporal resolution. We thus propose a new graph theory approach that focuses on the correlation influence between selected brain regions, entitled Dependency Network Analysis (DEPNA). Partial correlations are used to quantify the level of influence of each node during task performance. As a proof of concept, we conducted the DEPNA on simulated datasets and on two empirical motor and working memory fMRI tasks. The simulations revealed that the DEPNA correctly captures the network's hierarchy of influence. Applying DEPNA to the functional tasks reveals the dynamics between specific nodes as would be expected from prior knowledge. To conclude, we demonstrate that DEPNA can capture the most influencing nodes in the network, as they emerge during specific cognitive processes. This ability opens a new horizon for example in delineating critical nodes for specific clinical interventions.

  18. Revealing the cerebral regions and networks mediating vulnerability to depression: oxidative metabolism mapping of rat brain.

    Science.gov (United States)

    Harro, Jaanus; Kanarik, Margus; Kaart, Tanel; Matrov, Denis; Kõiv, Kadri; Mällo, Tanel; Del Río, Joaquin; Tordera, Rosa M; Ramirez, Maria J

    2014-07-01

    The large variety of available animal models has revealed much on the neurobiology of depression, but each model appears as specific to a significant extent, and distinction between stress response, pathogenesis of depression and underlying vulnerability is difficult to make. Evidence from epidemiological studies suggests that depression occurs in biologically predisposed subjects under impact of adverse life events. We applied the diathesis-stress concept to reveal brain regions and functional networks that mediate vulnerability to depression and response to chronic stress by collapsing data on cerebral long term neuronal activity as measured by cytochrome c oxidase histochemistry in distinct animal models. Rats were rendered vulnerable to depression either by partial serotonergic lesion or by maternal deprivation, or selected for a vulnerable phenotype (low positive affect, low novelty-related activity or high hedonic response). Environmental adversity was brought about by applying chronic variable stress or chronic social defeat. Several brain regions, most significantly median raphe, habenula, retrosplenial cortex and reticular thalamus, were universally implicated in long-term metabolic stress response, vulnerability to depression, or both. Vulnerability was associated with higher oxidative metabolism levels as compared to resilience to chronic stress. Chronic stress, in contrast, had three distinct patterns of effect on oxidative metabolism in vulnerable vs. resilient animals. In general, associations between regional activities in several brain circuits were strongest in vulnerable animals, and chronic stress disrupted this interrelatedness. These findings highlight networks that underlie resilience to stress, and the distinct response to stress that occurs in vulnerable subjects. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Theory of mind for processing unexpected events across contexts.

    Science.gov (United States)

    Dungan, James A; Stepanovic, Michael; Young, Liane

    2016-08-01

    Theory of mind, or mental state reasoning, may be particularly useful for making sense of unexpected events. Here, we investigated unexpected behavior across both social and non-social contexts in order to characterize the precise role of theory of mind in processing unexpected events. We used functional magnetic resonance imaging to examine how people respond to unexpected outcomes when initial expectations were based on (i) an object's prior behavior, (ii) an agent's prior behavior and (iii) an agent's mental states. Consistent with prior work, brain regions for theory of mind were preferentially recruited when people first formed expectations about social agents vs non-social objects. Critically, unexpected vs expected outcomes elicited greater activity in dorsomedial prefrontal cortex, which also discriminated in its spatial pattern of activity between unexpected and expected outcomes for social events. In contrast, social vs non-social events elicited greater activity in precuneus across both expected and unexpected outcomes. Finally, given prior information about an agent's behavior, unexpected vs expected outcomes elicited an especially robust response in right temporoparietal junction, and the magnitude of this difference across participants correlated negatively with autistic-like traits. Together, these findings illuminate the distinct contributions of brain regions for theory of mind for processing unexpected events across contexts. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  20. Artificial selection on relative brain size reveals a positive genetic correlation between brain size and proactive personality in the guppy.

    Science.gov (United States)

    Kotrschal, Alexander; Lievens, Eva J P; Dahlbom, Josefin; Bundsen, Andreas; Semenova, Svetlana; Sundvik, Maria; Maklakov, Alexei A; Winberg, Svante; Panula, Pertti; Kolm, Niclas

    2014-04-01

    Animal personalities range from individuals that are shy, cautious, and easily stressed (a "reactive" personality type) to individuals that are bold, innovative, and quick to learn novel tasks, but also prone to routine formation (a "proactive" personality type). Although personality differences should have important consequences for fitness, their underlying mechanisms remain poorly understood. Here, we investigated how genetic variation in brain size affects personality. We put selection lines of large- and small-brained guppies (Poecilia reticulata), with known differences in cognitive ability, through three standard personality assays. First, we found that large-brained animals were faster to habituate to, and more exploratory in, open field tests. Large-brained females were also bolder. Second, large-brained animals excreted less cortisol in a stressful situation (confinement). Third, large-brained animals were slower to feed from a novel food source, which we interpret as being caused by reduced behavioral flexibility rather than lack of innovation in the large-brained lines. Overall, the results point toward a more proactive personality type in large-brained animals. Thus, this study provides the first experimental evidence linking brain size and personality, an interaction that may affect important fitness-related aspects of ecology such as dispersal and niche exploration. © 2013 The Authors. Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

  1. ARTIFICIAL SELECTION ON RELATIVE BRAIN SIZE REVEALS A POSITIVE GENETIC CORRELATION BETWEEN BRAIN SIZE AND PROACTIVE PERSONALITY IN THE GUPPY

    Science.gov (United States)

    Kotrschal, Alexander; Lievens, Eva JP; Dahlbom, Josefin; Bundsen, Andreas; Semenova, Svetlana; Sundvik, Maria; Maklakov, Alexei A; Winberg, Svante; Panula, Pertti; Kolm, Niclas; Morrow, E

    2014-01-01

    Animal personalities range from individuals that are shy, cautious, and easily stressed (a “reactive” personality type) to individuals that are bold, innovative, and quick to learn novel tasks, but also prone to routine formation (a “proactive” personality type). Although personality differences should have important consequences for fitness, their underlying mechanisms remain poorly understood. Here, we investigated how genetic variation in brain size affects personality. We put selection lines of large- and small-brained guppies (Poecilia reticulata), with known differences in cognitive ability, through three standard personality assays. First, we found that large-brained animals were faster to habituate to, and more exploratory in, open field tests. Large-brained females were also bolder. Second, large-brained animals excreted less cortisol in a stressful situation (confinement). Third, large-brained animals were slower to feed from a novel food source, which we interpret as being caused by reduced behavioral flexibility rather than lack of innovation in the large-brained lines. Overall, the results point toward a more proactive personality type in large-brained animals. Thus, this study provides the first experimental evidence linking brain size and personality, an interaction that may affect important fitness-related aspects of ecology such as dispersal and niche exploration. PMID:24359469

  2. Lost for emotion words: What motor and limbic brain activity reveals about autism and semantic theory

    Science.gov (United States)

    Moseley, Rachel L.; Shtyrov, Yury; Mohr, Bettina; Lombardo, Michael V.; Baron-Cohen, Simon; Pulvermüller, Friedemann

    2015-01-01

    Autism spectrum conditions (ASC) are characterised by deficits in understanding and expressing emotions and are frequently accompanied by alexithymia, a difficulty in understanding and expressing emotion words. Words are differentially represented in the brain according to their semantic category and these difficulties in ASC predict reduced activation to emotion-related words in limbic structures crucial for affective processing. Semantic theories view ‘emotion actions’ as critical for learning the semantic relationship between a word and the emotion it describes, such that emotion words typically activate the cortical motor systems involved in expressing emotion actions such as facial expressions. As ASC are also characterised by motor deficits and atypical brain structure and function in these regions, motor structures would also be expected to show reduced activation during emotion-semantic processing. Here we used event-related fMRI to compare passive processing of emotion words in comparison to abstract verbs and animal names in typically-developing controls and individuals with ASC. Relatively reduced brain activation in ASC for emotion words, but not matched control words, was found in motor areas and cingulate cortex specifically. The degree of activation evoked by emotion words in the motor system was also associated with the extent of autistic traits as revealed by the Autism Spectrum Quotient. We suggest that hypoactivation of motor and limbic regions for emotion word processing may underlie difficulties in processing emotional language in ASC. The role that sensorimotor systems and their connections might play in the affective and social-communication difficulties in ASC is discussed. PMID:25278250

  3. Electrical brain responses in language-impaired children reveal grammar-specific deficits.

    Directory of Open Access Journals (Sweden)

    Elisabeth Fonteneau

    2008-03-01

    Full Text Available Scientific and public fascination with human language have included intensive scrutiny of language disorders as a new window onto the biological foundations of language and its evolutionary origins. Specific language impairment (SLI, which affects over 7% of children, is one such disorder. SLI has received robust scientific attention, in part because of its recent linkage to a specific gene and loci on chromosomes and in part because of the prevailing question regarding the scope of its language impairment: Does the disorder impact the general ability to segment and process language or a specific ability to compute grammar? Here we provide novel electrophysiological data showing a domain-specific deficit within the grammar of language that has been hitherto undetectable through behavioural data alone.We presented participants with Grammatical(G-SLI, age-matched controls, and younger child and adult controls, with questions containing syntactic violations and sentences containing semantic violations. Electrophysiological brain responses revealed a selective impairment to only neural circuitry that is specific to grammatical processing in G-SLI. Furthermore, the participants with G-SLI appeared to be partially compensating for their syntactic deficit by using neural circuitry associated with semantic processing and all non-grammar-specific and low-level auditory neural responses were normal.The findings indicate that grammatical neural circuitry underlying language is a developmentally unique system in the functional architecture of the brain, and this complex higher cognitive system can be selectively impaired. The findings advance fundamental understanding about how cognitive systems develop and all human language is represented and processed in the brain.

  4. Whole brain white matter changes revealed by multiple diffusion metrics in multiple sclerosis: A TBSS study

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yaou, E-mail: asiaeurope80@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Duan, Yunyun, E-mail: xiaoyun81.love@163.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); He, Yong, E-mail: yong.h.he@gmail.com [State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875 (China); Yu, Chunshui, E-mail: csyuster@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Wang, Jun, E-mail: jun_wang@bnu.edu.cn [State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875 (China); Huang, Jing, E-mail: sainthj@126.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Ye, Jing, E-mail: jingye.2007@yahoo.com.cn [Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Parizel, Paul M., E-mail: paul.parizel@ua.ac.be [Department of Radiology, Antwerp University Hospital and University of Antwerp, Wilrijkstraat 10, 2650 Edegem, 8 Belgium (Belgium); Li, Kuncheng, E-mail: kunchengli55@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Shu, Ni, E-mail: nshu55@gmail.com [State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875 (China)

    2012-10-15

    Objective: To investigate whole brain white matter changes in multiple sclerosis (MS) by multiple diffusion indices, we examined patients with diffusion tensor imaging and utilized tract-based spatial statistics (TBSS) method to analyze the data. Methods: Forty-one relapsing-remitting multiple sclerosis (RRMS) patients and 41 age- and gender-matched normal controls were included in this study. Diffusion weighted images were acquired by employing a single-shot echo planar imaging sequence on a 1.5 T MR scanner. Voxel-wise analyses of multiple diffusion metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were performed with TBSS. Results: The MS patients had significantly decreased FA (9.11%), increased MD (8.26%), AD (3.48%) and RD (13.17%) in their white matter skeletons compared with the controls. Through TBSS analyses, we found abnormal diffusion changes in widespread white matter regions in MS patients. Specifically, decreased FA, increased MD and increased RD were involved in whole-brain white matter, while several regions exhibited increased AD. Furthermore, white matter regions with significant correlations between the diffusion metrics and the clinical variables (the EDSS scores, disease durations and white matter lesion loads) in MS patients were identified. Conclusion: Widespread white matter abnormalities were observed in MS patients revealed by multiple diffusion metrics. The diffusion changes and correlations with clinical variables were mainly attributed to increased RD, implying the predominant role of RD in reflecting the subtle pathological changes in MS.

  5. Water diffusion closely reveals neural activity status in rat brain loci affected by anesthesia.

    Directory of Open Access Journals (Sweden)

    Yoshifumi Abe

    2017-04-01

    Full Text Available Diffusion functional MRI (DfMRI reveals neuronal activation even when neurovascular coupling is abolished, contrary to blood oxygenation level-dependent (BOLD functional MRI (fMRI. Here, we show that the water apparent diffusion coefficient (ADC derived from DfMRI increased in specific rat brain regions under anesthetic conditions, reflecting the decreased neuronal activity observed with local field potentials (LFPs, especially in regions involved in wakefulness. In contrast, BOLD signals showed nonspecific changes, reflecting systemic effects of the anesthesia on overall brain hemodynamics status. Electrical stimulation of the central medial thalamus nucleus (CM exhibiting this anesthesia-induced ADC increase led the animals to transiently wake up. Infusion in the CM of furosemide, a specific neuronal swelling blocker, led the ADC to increase further locally, although LFP activity remained unchanged, and increased the current threshold awakening the animals under CM electrical stimulation. Oppositely, induction of cell swelling in the CM through infusion of a hypotonic solution (-80 milliosmole [mOsm] artificial cerebrospinal fluid [aCSF] led to a local ADC decrease and a lower current threshold to wake up the animals. Strikingly, the local ADC changes produced by blocking or enhancing cell swelling in the CM were also mirrored remotely in areas functionally connected to the CM, such as the cingulate and somatosensory cortex. Together, those results strongly suggest that neuronal swelling is a significant mechanism underlying DfMRI.

  6. Cardiac angiosarcoma: an unexpected diagnosis

    Directory of Open Access Journals (Sweden)

    Milton Roberto Furst Crenitte

    2014-09-01

    Full Text Available Cardiac angiosarcoma is a rare entity. The incidence through autopsy findings ranges between 0.001% and 0.03%. The disease usually presents with non-specific symptoms, although asymptomatic cases are frequent; therefore, diagnosis is unexpected and consequently delayed. The authors report the case of a middle-aged man with a recent onset cough and dyspnea. He sought medical care several times without receiving a definite diagnosis until a plain chest radiography was taken showing a mediastinal enlargement, which was the reason why he was hospitalized for clinical investigation. During the diagnostic workup, an echodopplercardiogram and a thoracic computed tomography were performed, showing a heterogeneous soft-tissue mass infiltrating the pericardium and the anterior atrial wall. Multiple and scattered pulmonary nodules were also present. A pulmonary nodule was biopsied, which revealed an angiosarcoma. The clinical features added to the radiological and histological findings permitted the diagnosis of right atrial angiosarcoma. The authors highlight the unexpected pattern in the presentation of cardiac tumors.

  7. Deep brain stimulation reveals emotional impact processing in ventromedial prefrontal cortex

    DEFF Research Database (Denmark)

    Gjedde, Albert; Geday, Jacob

    2009-01-01

    We tested the hypothesis that modulation of monoaminergic tone with deep-brain stimulation (DBS) of subthalamic nucleus would reveal a site of reactivity in the ventromedial prefrontal cortex that we previously identified by modulating serotonergic and noradrenergic mechanisms by blocking serotonin...... and the change of blood flow associated with the DBS. In subjects with a low emotional impact, activity measured as blood flow rose when the electrode was turned on, while in subjects of high impact, the activity at this site in the ventromedial prefrontal cortex declined when the electrode was turned on. We...... conclude that changes of neurotransmission in the ventromedial prefrontal cortex had an effect on the tissue that depends on changes of monoamine concentration interacting with specific combinations of inhibitory and excitatory monoamine receptors....

  8. Unexpected ruptured aneurysm during posterior fossa surgery.

    Science.gov (United States)

    Chenin, L; Capel, C; N'Da, H; Lefranc, M; Peltier, J

    2014-10-01

    Surgery is the recommended treatment for unique significant cerebellar metastasis, particularly in cases of hydrocephalus. Complications of posterior fossa surgery are associated with high risk of morbidity and mortality. We present a unique case of unexpected peroperative rupture of a cerebellar superior artery aneurysm during posterior fossa surgery. During posterior cranial fossa surgery, severe arterial bleeding occurred in front of the medulla oblongata. Immediate postoperative computed tomographic (CT) angiography revealed a fusiform aneurysm from a distal branch of the left superior cerebellar artery. To our knowledge, this is the first reported operative case of unexpected infratentorial ruptured aneurysm during posterior fossa surgery. Copyright © 2014. Published by Elsevier Masson SAS.

  9. USE OF DIFFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING FOR REVEALING HYPOXIC-ISCHEMIC BRAIN LESIONS IN NEONATES

    OpenAIRE

    E. V. Shimchenko; E. I. Kleshchenko; K. F. Goloseyev

    2014-01-01

    The article presents advantages of use of diffusion-weighted magnetic resonance imaging (DW MRI) for revealing hypoxic-ischemic brain lesions in neonates. The trial included 97 neonates with perinatal brain lesion who had been undergoing treatment at a resuscitation department or neonatal pathology department in the first month of life. The article shows high information value of diffusion-weighted images (DWI) for diagnostics of hypoxic-ischemic lesions in comparison with regular standard mo...

  10. Direct visualization of alpha-synuclein oligomers reveals previously undetected pathology in Parkinson's disease brain.

    Science.gov (United States)

    Roberts, Rosalind F; Wade-Martins, Richard; Alegre-Abarrategui, Javier

    2015-06-01

    Oligomeric forms of alpha-synuclein are emerging as key mediators of pathogenesis in Parkinson's disease. Our understanding of the exact contribution of alpha-synuclein oligomers to disease is limited by the lack of a technique for their specific detection. We describe a novel method, the alpha-synuclein proximity ligation assay, which specifically recognizes alpha-synuclein oligomers. In a blinded study with post-mortem brain tissue from patients with Parkinson's disease (n = 8, age range 73-92 years, four males and four females) and age- and sex-matched controls (n = 8), we show that the alpha-synuclein proximity ligation assay reveals previously unrecognized pathology in the form of extensive diffuse deposition of alpha-synuclein oligomers. These oligomers are often localized, in the absence of Lewy bodies, to neuroanatomical regions mildly affected in Parkinson's disease. Diffuse alpha-synuclein proximity ligation assay signal is significantly more abundant in patients compared to controls in regions including the cingulate cortex (1.6-fold increase) and the reticular formation of the medulla (6.5-fold increase). In addition, the alpha-synuclein proximity ligation assay labels very early perikaryal aggregates in morphologically intact neurons that may precede the development of classical Parkinson's disease lesions, such as pale bodies or Lewy bodies. Furthermore, the alpha-synuclein proximity ligation assay preferentially detects early-stage, loosely compacted lesions such as pale bodies in patient tissue, whereas Lewy bodies, considered heavily compacted late lesions are only very exceptionally stained. The alpha-synuclein proximity ligation assay preferentially labels alpha-synuclein oligomers produced in vitro compared to monomers and fibrils, while stained oligomers in human brain display a distinct intermediate proteinase K resistance, suggesting the detection of a conformer that is different from both physiological, presynaptic alpha

  11. SNTF immunostaining reveals previously undetected axonal pathology in traumatic brain injury.

    Science.gov (United States)

    Johnson, Victoria E; Stewart, William; Weber, Maura T; Cullen, D Kacy; Siman, Robert; Smith, Douglas H

    2016-01-01

    Diffuse axonal injury (DAI) is a common feature of severe traumatic brain injury (TBI) and may also be a predominant pathology in mild TBI or "concussion". The rapid deformation of white matter at the instant of trauma can lead to mechanical failure and calcium-dependent proteolysis of the axonal cytoskeleton in association with axonal transport interruption. Recently, a proteolytic fragment of alpha-II spectrin, "SNTF", was detected in serum acutely following mild TBI in patients and was prognostic for poor clinical outcome. However, direct evidence that this fragment is a marker of DAI has yet to be demonstrated in either humans following TBI or in models of mild TBI. Here, we used immunohistochemistry (IHC) to examine for SNTF in brain tissue following both severe and mild TBI. Human severe TBI cases (survival brains from an established model of mild TBI at 6, 48 and 72 h post-injury versus shams. IHC specific for SNTF was compared to that of amyloid precursor protein (APP), the current standard for DAI diagnosis, and other known markers of axonal pathology including non-phosphorylated neurofilament-H (SMI-32), neurofilament-68 (NF-68) and compacted neurofilament-medium (RMO-14) using double and triple immunofluorescent labeling. Supporting its use as a biomarker of DAI, SNTF immunoreactive axons were observed at all time points following both human severe TBI and in the model of mild TBI. Interestingly, SNTF revealed a subpopulation of degenerating axons, undetected by the gold-standard marker of transport interruption, APP. While there was greater axonal co-localization between SNTF and APP after severe TBI in humans, a subset of SNTF positive axons displayed no APP accumulation. Notably, some co-localization was observed between SNTF and the less abundant neurofilament subtype markers. Other SNTF positive axons, however, did not co-localize with any other markers. Similarly, RMO-14 and NF-68 positive axonal pathology existed independent of SNTF and APP

  12. Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

    NARCIS (Netherlands)

    Guadalupe, Tulio; Mathias, Samuel R.; Vanerp, Theo G. M.; Whelan, Christopher D.; Zwiers, Marcel P.; Abe, Yoshinari; Abramovic, Lucija; Agartz, Ingrid; Andreassen, Ole A.; Arias-Vasquez, Alejandro; Aribisala, Benjamin S.; Armstrong, Nicola J.; Arolt, Volker; Artiges, Eric; Ayesa-Arriola, Rosa; Baboyan, Vatche G.; Banaschewski, Tobias; Barker, Gareth; Bastin, Mark E.; Baune, Bernhard T.; Blangero, John; Bokde, Arun L. . W.; Boedhoe, Premika S. . W.; Bose, Anushree; Brem, Silvia; Brodaty, Henry; Bromberg, Uli; Brooks, Samantha; Buechel, Christian; Buitelaar, Jan; Calhoun, Vince D.; Cannon, Dara M.; Cattrell, Anna; Cheng, Yuqi; Conrod, Patricia J.; Conzelmann, Annette; Corvin, Aiden; Crespo-Facorro, Benedicto; Crivello, Fabrice; Dannlowski, Udo; De Zubicaray, Greig I.; De Zwarte, Sonja M. C.; Deary, Ian J.; Desrivieres, Sylvane; Doan, Nhat Trung; Donohoe, Gary; Dorum, Erlend S.; Ehrlich, Stefan; Espeseth, Thomas; Fernandez, Guillen; Flor, Herta; Fouche, Jean-Paul; Frouin, Vincent; Fukunaga, Masaki; Gallinat, Jurgen; Garavan, Hugh; Gill, Michael; Suarez, Andrea Gonzalez; Gowland, Penny; Grabe, Hans J.; Grotegerd, Dominik; Gruber, Oliver; Hagenaars, Saskia; Hashimoto, Ryota; Hauser, Tobias U.; Heinz, Andreas; Hibar, Derrek P.; Hoekstra, Pieter J.; Hoogman, Martine; Howells, Fleur M.; Hu, Hao; Pol, Hilleke E. Hulshoff; Huyser, Chaim; Ittermann, Bernd; Jahanshad, Neda; Jonsson, Erik G.; Jurk, Sarah; Kahn, Rene S.; Kelly, Sinead; Kraemer, Bernd; Kugel, Harald; Kwon, Jun Soo; Lemaitre, Herve; Lesch, Klaus-Peter; Lochner, Christine; Luciano, Michelle; Marquand, Andre F.; Martin, Nicholas G.; Martinez-Zalacain, Ignacio; Martinot, Jean-Luc; Mataix-Cols, David; Mather, Karen; McDonald, Colm; McMahon, Katie L.; Medland, Sarah E.; Menchon, Jose M.; Morris, Derek W.; Mothersill, Omar; Maniega, Susana Munoz; Mwangi, Benson; Nakamae, Takashi; Nakao, Tomohiro; Narayanaswaamy, Janardhanan C.; Nees, Frauke; Nordvik, Jan E.; Onnink, A. Marten H.; Opel, Nils; Ophoff, Roel; Martinot, Marie-Laure Paillere; Orfanos, Dimitri Papadopoulos; Pauli, Paul; Paus, Tomas; Poustka, Luise; Reddy, Janardhan Y. C.; Renteria, Miguel E.; Roiz-Santianez, Roberto; Roos, Annerine; Royle, Natalie A.; Sachdev, Perminder; Sanchez-Juan, Pascual; Schmaal, Lianne; Schumann, Gunter; Shumskaya, Elena; Smolka, Michael N.; Soares, Jair C.; Soriano-Mas, Carles; Stein, Dan J.; Strike, Lachlan T.; Toro, Roberto; Turner, Jessica A.; Tzourio-Mazoyer, Nathalie; Uhlmann, Anne; Hernandez, Maria Valdes; Van den Heuvel, Odile A.; Van der Meer, Dennis; Van Haren, Neeltje E. M.; Veltman, Dick J.; Venkatasubramanian, Ganesan; Vetter, Nora C.; Vuletic, Daniella; Walitza, Susanne; Walter, Henrik; Walton, Esther; Wang, Zhen; Wardlaw, Joanna; Wen, Wei; Westlye, Lars T.; Whelan, Robert; Wittfeld, Katharina; Wolfers, Thomas; Wright, Margaret J.; Xu, Jian; Xu, Xiufeng; Yun, Je-Yeon; Zhao, JingJing; Franke, Barbara; Thompson, Paul M.; Glahn, David C.; Mazoyer, Bernard; Fisher, Simon E.; Francks, Clyde

    2017-01-01

    The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain

  13. A 24-hour temporal profile of in vivo brain and heart pet imaging reveals a nocturnal peak in brain 18F-fluorodeoxyglucose uptake.

    Directory of Open Access Journals (Sweden)

    Daan R van der Veen

    Full Text Available Using positron emission tomography, we measured in vivo uptake of (18F-fluorodeoxyglucose (FDG in the brain and heart of C57Bl/6 mice at intervals across a 24-hour light-dark cycle. Our data describe a significant, high amplitude rhythm in FDG uptake throughout the whole brain, peaking at the mid-dark phase of the light-dark cycle, which is the active phase for nocturnal mice. Under these conditions, heart FDG uptake did not vary with time of day, but did show biological variation throughout the 24-hour period for measurements within the same mice. FDG uptake was scanned at different times of day within an individual mouse, and also compared to different times of day between individuals, showing both biological and technical reproducibility of the 24-hour pattern in FDG uptake. Regional analysis of brain FDG uptake revealed especially high amplitude rhythms in the olfactory bulb and cortex, while low amplitude rhythms were observed in the amygdala, brain stem and hypothalamus. Low amplitude 24-hour rhythms in regional FDG uptake may be due to multiple rhythms with different phases in a single brain structure, quenching some of the amplitude. Our data show that the whole brain exhibits significant, high amplitude daily variation in glucose uptake in living mice. Reports applying the 2-deoxy-D[(14C]-glucose method for the quantitative determination of the rates of local cerebral glucose utilization indicate only a small number of brain regions exhibiting a day versus night variation in glucose utilization. In contrast, our data show 24-hour patterns in glucose uptake in most of the brain regions examined, including several regions that do not show a difference in glucose utilization. Our data also emphasizes a methodological requirement of controlling for the time of day of scanning FDG uptake in the brain in both clinical and pre-clinical settings, and suggests waveform normalization of FDG measurements at different times of the day.

  14. Disrupted Brain Functional Organization in Epilepsy Revealed by Graph Theory Analysis.

    Science.gov (United States)

    Song, Jie; Nair, Veena A; Gaggl, Wolfgang; Prabhakaran, Vivek

    2015-06-01

    The human brain is a complex and dynamic system that can be modeled as a large-scale brain network to better understand the reorganizational changes secondary to epilepsy. In this study, we developed a brain functional network model using graph theory methods applied to resting-state fMRI data acquired from a group of epilepsy patients and age- and gender-matched healthy controls. A brain functional network model was constructed based on resting-state functional connectivity. A minimum spanning tree combined with proportional thresholding approach was used to obtain sparse connectivity matrices for each subject, which formed the basis of brain networks. We examined the brain reorganizational changes in epilepsy thoroughly at the level of the whole brain, the functional network, and individual brain regions. At the whole-brain level, local efficiency was significantly decreased in epilepsy patients compared with the healthy controls. However, global efficiency was significantly increased in epilepsy due to increased number of functional connections between networks (although weakly connected). At the functional network level, there were significant proportions of newly formed connections between the default mode network and other networks and between the subcortical network and other networks. There was a significant proportion of decreasing connections between the cingulo-opercular task control network and other networks. Individual brain regions from different functional networks, however, showed a distinct pattern of reorganizational changes in epilepsy. These findings suggest that epilepsy alters brain efficiency in a consistent pattern at the whole-brain level, yet alters brain functional networks and individual brain regions differently.

  15. Sudden unexpected death in a mouse model of Dravet syndrome

    Science.gov (United States)

    Kalume, Franck; Westenbroek, Ruth E.; Cheah, Christine S.; Yu, Frank H.; Oakley, John C.; Scheuer, Todd; Catterall, William A.

    2013-01-01

    Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death in intractable epilepsies, but physiological mechanisms that lead to SUDEP are unknown. Dravet syndrome (DS) is an infantile-onset intractable epilepsy caused by heterozygous loss-of-function mutations in the SCN1A gene, which encodes brain type-I voltage-gated sodium channel NaV1.1. We studied the mechanism of premature death in Scn1a heterozygous KO mice and conditional brain- and cardiac-specific KOs. Video monitoring demonstrated that SUDEP occurred immediately following generalized tonic-clonic seizures. A history of multiple seizures was a strong risk factor for SUDEP. Combined video-electroencephalography-electrocardiography revealed suppressed interictal resting heart-rate variability and episodes of ictal bradycardia associated with the tonic phases of generalized tonic-clonic seizures. Prolonged atropine-sensitive ictal bradycardia preceded SUDEP. Similar studies in conditional KO mice demonstrated that brain, but not cardiac, KO of Scn1a produced cardiac and SUDEP phenotypes similar to those found in DS mice. Atropine or N-methyl scopolamine treatment reduced the incidence of ictal bradycardia and SUDEP in DS mice. These findings suggest that SUDEP is caused by apparent parasympathetic hyperactivity immediately following tonic-clonic seizures in DS mice, which leads to lethal bradycardia and electrical dysfunction of the ventricle. These results have important implications for prevention of SUDEP in DS patients. PMID:23524966

  16. USE OF DIFFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING FOR REVEALING HYPOXIC-ISCHEMIC BRAIN LESIONS IN NEONATES

    Directory of Open Access Journals (Sweden)

    E. V. Shimchenko

    2014-01-01

    Full Text Available The article presents advantages of use of diffusion-weighted magnetic resonance imaging (DW MRI for revealing hypoxic-ischemic brain lesions in neonates. The trial included 97 neonates with perinatal brain lesion who had been undergoing treatment at a resuscitation department or neonatal pathology department in the first month of life. The article shows high information value of diffusion-weighted images (DWI for diagnostics of hypoxic-ischemic lesions in comparison with regular standard modes. In the event of no structural brain lesions of neonates, pronounced increase in signal characteristics revealed by DWI indicated considerable pathophysiological alterations. Subsequently, children developed structural alterations in the form of cystic encephalomalacia with expansion of cerebrospinal fluid spaces manifested with pronounced neurological deficit. DW MRI has been offered as a method of prognosticating further neurological development of children on early stages. 

  17. PCNA immunoreactivity revealing normal proliferative activity in the brain of an adult Elasmobranch, Torpedo marmorata.

    Science.gov (United States)

    Margotta, Vito

    2007-01-01

    The brain of adult heterothermic vertebrates can be already provided of quiescent cells, scattered ("matrix cells") and/or clustered ("matrix areas"). These typical cells, in some regions located at or near ventricular surfaces and at peri-ependymal layers, in other territories populating their framework, maintain some embryonic properties and are responsible of normal or variously experimentally induced proliferative activities. On these topics there are a great number of reports concerning Teleostean Osteichthyes, Urodele and Anuran Amphibians, Lacertilian Reptiles. At the contrary, only few are the contributions regarding the Petromyzontidae. Involving an immunocytochemical marker, the Proliferating Cell Nuclear Antigen (PCNA), revealing proliferative events, in the last years we have undertaken a reappraisal focused on these encephalic performances in normal adult poikilothermal vertebrates. To provide a valid comparison between our results and the literature data, our choice of the specimens was based on the desire to employ organisms belonging to the same or phylogenetically close species used by previous Authors in similar studies. In our immunocytochemical panorama there is a substantial agreement between our contributions and bibliographic references concerning natural encephalic proliferative phenomena in these vertebrates. At this point of our study, the last missing piece was represented by the Chondrichthyes about which the literature data are lacking. In order to fill this gap, the aim of the present research is to investigate, involving the same PCNA test, whether proliferative events also persist in the brain of adult cartilaginous fishes. The immunostaining images obtained in the Elasmo branch Torpedo marmorata, well-known for the emission of high electrical discharges, exhibit undifferentiated cells in relationship with the ependymal epithelium lining the cavities of all cerebral districts; some other neuroblasts are scattered in the mesencephalic

  18. Comparison of Dolphins' Body and Brain Measurements with Four Other Groups of Cetaceans Reveals Great Diversity.

    Science.gov (United States)

    Ridgway, Sam H; Carlin, Kevin P; Van Alstyne, Kaitlin R; Hanson, Alicia C; Tarpley, Raymond J

    2016-01-01

    We compared mature dolphins with 4 other groupings of mature cetaceans. With a large data set, we found great brain diversity among 5 different taxonomic groupings. The dolphins in our data set ranged in body mass from about 40 to 6,750 kg and in brain mass from 0.4 to 9.3 kg. Dolphin body length ranged from 1.3 to 7.6 m. In our combined data set from the 4 other groups of cetaceans, body mass ranged from about 20 to 120,000 kg and brain mass from about 0.2 to 9.2 kg, while body length varied from 1.21 to 26.8 m. Not all cetaceans have large brains relative to their body size. A few dolphins near human body size have human-sized brains. On the other hand, the absolute brain mass of some other cetaceans is only one-sixth as large. We found that brain volume relative to body mass decreases from Delphinidae to a group of Phocoenidae and Monodontidae, to a group of other odontocetes, to Balaenopteroidea, and finally to Balaenidae. We also found the same general trend when we compared brain volume relative to body length, except that the Delphinidae and Phocoenidae-Monodontidae groups do not differ significantly. The Balaenidae have the smallest relative brain mass and the lowest cerebral cortex surface area. Brain parts also vary. Relative to body mass and to body length, dolphins also have the largest cerebellums. Cortex surface area is isometric with brain size when we exclude the Balaenidae. Our data show that the brains of Balaenidae are less convoluted than those of the other cetaceans measured. Large vascular networks inside the cranial vault may help to maintain brain temperature, and these nonbrain tissues increase in volume with body mass and with body length ranging from 8 to 65% of the endocranial volume. Because endocranial vascular networks and other adnexa, such as the tentorium cerebelli, vary so much in different species, brain size measures from endocasts of some extinct cetaceans may be overestimates. Our regression of body length on endocranial

  19. Using the virtual brain to reveal the role of oscillations and plasticity in shaping brain's dynamical landscape.

    Science.gov (United States)

    Roy, Dipanjan; Sigala, Rodrigo; Breakspear, Michael; McIntosh, Anthony Randal; Jirsa, Viktor K; Deco, Gustavo; Ritter, Petra

    2014-12-01

    Spontaneous brain activity, that is, activity in the absence of controlled stimulus input or an explicit active task, is topologically organized in multiple functional networks (FNs) maintaining a high degree of coherence. These "resting state networks" are constrained by the underlying anatomical connectivity between brain areas. They are also influenced by the history of task-related activation. The precise rules that link plastic changes and ongoing dynamics of resting-state functional connectivity (rs-FC) remain unclear. Using the framework of the open source neuroinformatics platform "The Virtual Brain," we identify potential computational mechanisms that alter the dynamical landscape, leading to reconfigurations of FNs. Using a spiking neuron model, we first demonstrate that network activity in the absence of plasticity is characterized by irregular oscillations between low-amplitude asynchronous states and high-amplitude synchronous states. We then demonstrate the capability of spike-timing-dependent plasticity (STDP) combined with intrinsic alpha (8-12 Hz) oscillations to efficiently influence learning. Further, we show how alpha-state-dependent STDP alters the local area dynamics from an irregular to a highly periodic alpha-like state. This is an important finding, as the cortical input from the thalamus is at the rate of alpha. We demonstrate how resulting rhythmic cortical output in this frequency range acts as a neuronal tuner and, hence, leads to synchronization or de-synchronization between brain areas. Finally, we demonstrate that locally restricted structural connectivity changes influence local as well as global dynamics and lead to altered rs-FC.

  20. Water diffusion reveals networks that modulate multiregional morphological plasticity after repetitive brain stimulation.

    Science.gov (United States)

    Abe, Mitsunari; Fukuyama, Hidenao; Mima, Tatsuya

    2014-03-25

    Repetitive brain stimulation protocols induce plasticity in the stimulated site in brain slice models. Recent evidence from network models has indicated that additional plasticity-related changes occur in nonstimulated remote regions. Despite increasing use of brain stimulation protocols in experimental and clinical settings, the neural substrates underlying the additional effects in remote regions are unknown. Diffusion-weighted MRI (DWI) probes water diffusion and can be used to estimate morphological changes in cortical tissue that occur with the induction of plasticity. Using DWI techniques, we estimated morphological changes induced by application of repetitive transcranial magnetic stimulation (rTMS) over the left primary motor cortex (M1). We found that rTMS altered water diffusion in multiple regions including the left M1. Notably, the change in water diffusion was retained longest in the left M1 and remote regions that had a correlation of baseline fluctuations in water diffusion before rTMS. We conclude that synchronization of water diffusion at rest between stimulated and remote regions ensures retention of rTMS-induced changes in water diffusion in remote regions. Synchronized fluctuations in the morphology of cortical microstructures between stimulated and remote regions might identify networks that allow retention of plasticity-related morphological changes in multiple regions after brain stimulation protocols. These results increase our understanding of the effects of brain stimulation-induced plasticity on multiregional brain networks. DWI techniques could provide a tool to evaluate treatment effects of brain stimulation protocols in patients with brain disorders.

  1. Sparse coding reveals greater functional connectivity in female brains during naturalistic emotional experience.

    Directory of Open Access Journals (Sweden)

    Yudan Ren

    Full Text Available Functional neuroimaging is widely used to examine changes in brain function associated with age, gender or neuropsychiatric conditions. FMRI (functional magnetic resonance imaging studies employ either laboratory-designed tasks that engage the brain with abstracted and repeated stimuli, or resting state paradigms with little behavioral constraint. Recently, novel neuroimaging paradigms using naturalistic stimuli are gaining increasing attraction, as they offer an ecologically-valid condition to approximate brain function in real life. Wider application of naturalistic paradigms in exploring individual differences in brain function, however, awaits further advances in statistical methods for modeling dynamic and complex dataset. Here, we developed a novel data-driven strategy that employs group sparse representation to assess gender differences in brain responses during naturalistic emotional experience. Comparing to independent component analysis (ICA, sparse coding algorithm considers the intrinsic sparsity of neural coding and thus could be more suitable in modeling dynamic whole-brain fMRI signals. An online dictionary learning and sparse coding algorithm was applied to the aggregated fMRI signals from both groups, which was subsequently factorized into a common time series signal dictionary matrix and the associated weight coefficient matrix. Our results demonstrate that group sparse representation can effectively identify gender differences in functional brain network during natural viewing, with improved sensitivity and reliability over ICA-based method. Group sparse representation hence offers a superior data-driven strategy for examining brain function during naturalistic conditions, with great potential for clinical application in neuropsychiatric disorders.

  2. Aberrant spontaneous brain activity in chronic tinnitus patients revealed by resting-state functional MRI

    Directory of Open Access Journals (Sweden)

    Yu-Chen Chen

    2014-01-01

    Conclusions: The present study confirms that chronic tinnitus patients have aberrant ALFF in many brain regions, which is associated with specific clinical tinnitus characteristics. ALFF disturbance in specific brain regions might be used to identify the neuro-pathophysiological mechanisms in chronic tinnitus patients.

  3. MRI reveals brain abnormalities in drug-naïve Parkinson’s disease

    OpenAIRE

    Planetta, Peggy J.; McFarland, Nikolaus R.; Okun, Michael S.; Vaillancourt, David E.

    2014-01-01

    Most brain studies of Parkinson’s disease (PD) focus on patients who are already taking anti-parkinsonian medication. This makes it difficult to isolate the effects of disease from those of treatment. We review MRI evidence supporting the hypothesis that early-stage, untreated PD patients have structural and functional abnormalities in the brain, some of which are related to motor symptoms.

  4. Molecular anatomy of the gut-brain axis revealed with transgenic technologies: implications in metabolic research

    Science.gov (United States)

    Udit, Swalpa; Gautron, Laurent

    2013-01-01

    Neurons residing in the gut-brain axis remain understudied despite their important role in coordinating metabolic functions. This lack of knowledge is observed, in part, because labeling gut-brain axis neurons and their connections using conventional neuroanatomical methods is inherently challenging. This article summarizes genetic approaches that enable the labeling of distinct populations of gut-brain axis neurons in living laboratory rodents. In particular, we review the respective strengths and limitations of currently available genetic and viral approaches that permit the marking of gut-brain axis neurons without the need for antibodies or conventional neurotropic tracers. Finally, we discuss how these methodological advances are progressively transforming the study of the healthy and diseased gut-brain axis in the context of its role in chronic metabolic diseases, including diabetes and obesity. PMID:23914153

  5. Brain classification reveals the right cerebellum as the best biomarker of dyslexia

    Directory of Open Access Journals (Sweden)

    Demonet Jean

    2009-06-01

    Full Text Available Abstract Background Developmental dyslexia is a specific cognitive disorder in reading acquisition that has genetic and neurological origins. Despite histological evidence for brain differences in dyslexia, we recently demonstrated that in large cohort of subjects, no differences between control and dyslexic readers can be found at the macroscopic level (MRI voxel, because of large variances in brain local volumes. In the present study, we aimed at finding brain areas that most discriminate dyslexic from control normal readers despite the large variance across subjects. After segmenting brain grey matter, normalizing brain size and shape and modulating the voxels' content, normal readers' brains were used to build a 'typical' brain via bootstrapped confidence intervals. Each dyslexic reader's brain was then classified independently at each voxel as being within or outside the normal range. We used this simple strategy to build a brain map showing regional percentages of differences between groups. The significance of this map was then assessed using a randomization technique. Results The right cerebellar declive and the right lentiform nucleus were the two areas that significantly differed the most between groups with 100% of the dyslexic subjects (N = 38 falling outside of the control group (N = 39 95% confidence interval boundaries. The clinical relevance of this result was assessed by inquiring cognitive brain-based differences among dyslexic brain subgroups in comparison to normal readers' performances. The strongest difference between dyslexic subgroups was observed between subjects with lower cerebellar declive (LCD grey matter volumes than controls and subjects with higher cerebellar declive (HCD grey matter volumes than controls. Dyslexic subjects with LCD volumes performed worse than subjects with HCD volumes in phonologically and lexicon related tasks. Furthermore, cerebellar and lentiform grey matter volumes interacted in dyslexic

  6. Brain classification reveals the right cerebellum as the best biomarker of dyslexia

    Science.gov (United States)

    Pernet, Cyril R; Poline, Jean Baptiste; Demonet, Jean François; Rousselet, Guillaume A

    2009-01-01

    Background Developmental dyslexia is a specific cognitive disorder in reading acquisition that has genetic and neurological origins. Despite histological evidence for brain differences in dyslexia, we recently demonstrated that in large cohort of subjects, no differences between control and dyslexic readers can be found at the macroscopic level (MRI voxel), because of large variances in brain local volumes. In the present study, we aimed at finding brain areas that most discriminate dyslexic from control normal readers despite the large variance across subjects. After segmenting brain grey matter, normalizing brain size and shape and modulating the voxels' content, normal readers' brains were used to build a 'typical' brain via bootstrapped confidence intervals. Each dyslexic reader's brain was then classified independently at each voxel as being within or outside the normal range. We used this simple strategy to build a brain map showing regional percentages of differences between groups. The significance of this map was then assessed using a randomization technique. Results The right cerebellar declive and the right lentiform nucleus were the two areas that significantly differed the most between groups with 100% of the dyslexic subjects (N = 38) falling outside of the control group (N = 39) 95% confidence interval boundaries. The clinical relevance of this result was assessed by inquiring cognitive brain-based differences among dyslexic brain subgroups in comparison to normal readers' performances. The strongest difference between dyslexic subgroups was observed between subjects with lower cerebellar declive (LCD) grey matter volumes than controls and subjects with higher cerebellar declive (HCD) grey matter volumes than controls. Dyslexic subjects with LCD volumes performed worse than subjects with HCD volumes in phonologically and lexicon related tasks. Furthermore, cerebellar and lentiform grey matter volumes interacted in dyslexic subjects, so that lower and

  7. Graph Theoretical Analysis Reveals: Women's Brains Are Better Connected than Men's.

    Directory of Open Access Journals (Sweden)

    Balázs Szalkai

    Full Text Available Deep graph-theoretic ideas in the context with the graph of the World Wide Web led to the definition of Google's PageRank and the subsequent rise of the most popular search engine to date. Brain graphs, or connectomes, are being widely explored today. We believe that non-trivial graph theoretic concepts, similarly as it happened in the case of the World Wide Web, will lead to discoveries enlightening the structural and also the functional details of the animal and human brains. When scientists examine large networks of tens or hundreds of millions of vertices, only fast algorithms can be applied because of the size constraints. In the case of diffusion MRI-based structural human brain imaging, the effective vertex number of the connectomes, or brain graphs derived from the data is on the scale of several hundred today. That size facilitates applying strict mathematical graph algorithms even for some hard-to-compute (or NP-hard quantities like vertex cover or balanced minimum cut. In the present work we have examined brain graphs, computed from the data of the Human Connectome Project, recorded from male and female subjects between ages 22 and 35. Significant differences were found between the male and female structural brain graphs: we show that the average female connectome has more edges, is a better expander graph, has larger minimal bisection width, and has more spanning trees than the average male connectome. Since the average female brain weighs less than the brain of males, these properties show that the female brain has better graph theoretical properties, in a sense, than the brain of males. It is known that the female brain has a smaller gray matter/white matter ratio than males, that is, a larger white matter/gray matter ratio than the brain of males; this observation is in line with our findings concerning the number of edges, since the white matter consists of myelinated axons, which, in turn, roughly correspond to the connections

  8. Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain.

    Science.gov (United States)

    Lieblein-Boff, Jacqueline C; Johnson, Elizabeth J; Kennedy, Adam D; Lai, Chron-Si; Kuchan, Matthew J

    2015-01-01

    Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula, and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and postmortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem metabolomic analyses were performed on human infant brain tissues in three regions important for learning and memory: the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510) were excluded. In addition, moderate correlations with xenobiotic relationships (2) or those driven by single outliers (3) were excluded from further study. Lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region-specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development.

  9. Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain.

    Directory of Open Access Journals (Sweden)

    Jacqueline C Lieblein-Boff

    Full Text Available Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula, and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and postmortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem metabolomic analyses were performed on human infant brain tissues in three regions important for learning and memory: the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510 were excluded. In addition, moderate correlations with xenobiotic relationships (2 or those driven by single outliers (3 were excluded from further study. Lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region-specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development.

  10. Analysis of spatial-temporal gene expression patterns reveals dynamics and regionalization in developing mouse brain

    OpenAIRE

    Shen-Ju Chou; Chindi Wang; Nardnisa Sintupisut; Zhen-Xian Niou; Chih-Hsu Lin; Ker-Chau Li; Chen-Hsiang Yeang

    2016-01-01

    Allen Brain Atlas (ABA) provides a valuable resource of spatial/temporal gene expressions in mammalian brains. Despite rich information extracted from this database, current analyses suffer from several limitations. First, most studies are either gene-centric or region-centric, thus are inadequate to capture the superposition of multiple spatial-temporal patterns. Second, standard tools of expression analysis such as matrix factorization can capture those patterns but do not explicitly incorp...

  11. Invasion and Evasion: Investigations on Early Glioblastoma Growth Reveal Two Novel Mechanisms of Brain Tumor Progression

    OpenAIRE

    Baker, Gregory Joseph

    2014-01-01

    As glioma cells infiltrate the brain they associate with various microanatomic structures such as blood vessels and myelinated white matter tracts. How distinct invasion patterns coordinate tumor growth and influence clinical outcomes remains poorly understood. We have investigated how perivascular invasion affects glioma growth patterning and response to anti-angiogenic therapy within the highly vascularized brain. Orthotopically implanted rodent and human glioma cells are shown to common...

  12. Positron Emission Tomography Reveals Abnormal Topological Organization in Functional Brain Network in Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Qiu eXiangzhe

    2016-05-01

    Full Text Available Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM. However, the DM-related changes in the topological properties in functional brain networks are almost unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs, followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized shortest path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing the functional evidence for the abnormalities of brain networks in DM.

  13. Brain damages in ketamine addicts as revealed by magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Chunmei eWang

    2013-07-01

    Full Text Available Ketamine, a known antagonist of N-methyl-D-aspartic (NMDA glutamate receptors, had been used as an anesthetic particularly for pediatric or for cardiac patients. Unfortunately, ketamine has become an abusive drug in many parts of the world while chronic and prolonged usage led to damages of many organs including the brain. However, no studies on possible damages in the brains induced by chronic ketamine abuse have been documented in the human via neuroimaging. This paper described for the first time via employing magnetic resonance imaging (MRI the changes in ketamine addicts of 0.5 to 12 years and illustrated the possible brain regions susceptible to ketamine abuse. Twenty-one ketamine addicts were recruited and the results showed that the lesions in the brains of ketamine addicts were located in many regions which appeared 2-4 years after ketamine addiction. Cortical atrophy was usually evident in the frontal, parietal or occipital cortices of addicts. Such study confirmed that many brain regions in the human were susceptible to chronic ketamine injury and presented a diffuse effect of ketamine on the brain which might differ from other central nervous system (CNS drugs, such as cocaine, heroin and methamphetamine.

  14. Do salt cravings in children with autistic disorders reveal low blood sodium depleting brain taurine and glutamine?

    Science.gov (United States)

    Good, Peter

    2011-12-01

    Because boys are four times more likely than girls to develop autism, the role of male hormones (androgens) has received considerable scrutiny. Some researchers implicate arginine vasopressin, an androgen-dependent hormone from the pituitary gland that elicits male behavior. Elevated vasopressin is also the most common cause of low blood sodium (hyponatremia)--most serious in the brains of children. Hyponatremia causes astrocytes to swell, then release the amino acids taurine and glutamine and their water to compensate. Taurin--the brain osmolyte/inhibitory neurotransmitter that suppresses vasopressin--was the amino acid most wasted or depleted in urine of autistic children. Glutamine is a critical metabolic fuel in brain neurons, astrocytes, endothelial cells, and the intestines, especially during hypoglycemia. Because glutamine is not thought to cross the blood-brain barrier significantly, the implications of low blood glutamine in these children are not recognized. Yet children with high brain glutamine from urea cycle disorders are rarely diagnosed with autistic disorders. Other common events in autistic children that release vasopressin are gastrointestinal inflammation, hypoglycemia, and stress. Signs of hyponatremia in these children are salt cravings reported online and anecdotally, deep yellow urine revealing concentration, and relief of autistic behavior by fluid/salt diets. Several interventions offer promise: (a) taurine to suppress vasopressin and replenish astrocytes; (b) glutamine as fuel for intestines and brain; (c) arginine to spare glutamine, detoxify ammonia, and increase brain blood flow; and (d) oral rehydration salts to compensate dilutional hyponatremia. This hypothesis appears eminently testable: Does your child crave salt? Is his urine deep yellow? Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Effects of anesthetic agents on brain blood oxygenation level revealed with ultra-high field MRI.

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    Luisa Ciobanu

    Full Text Available During general anesthesia it is crucial to control systemic hemodynamics and oxygenation levels. However, anesthetic agents can affect cerebral hemodynamics and metabolism in a drug-dependent manner, while systemic hemodynamics is stable. Brain-wide monitoring of this effect remains highly challenging. Because T(2*-weighted imaging at ultra-high magnetic field strengths benefits from a dramatic increase in contrast to noise ratio, we hypothesized that it could monitor anesthesia effects on brain blood oxygenation. We scanned rat brains at 7T and 17.2T under general anesthesia using different anesthetics (isoflurane, ketamine-xylazine, medetomidine. We showed that the brain/vessels contrast in T(2*-weighted images at 17.2T varied directly according to the applied pharmacological anesthetic agent, a phenomenon that was visible, but to a much smaller extent at 7T. This variation is in agreement with the mechanism of action of these agents. These data demonstrate that preclinical ultra-high field MRI can monitor the effects of a given drug on brain blood oxygenation level in the absence of systemic blood oxygenation changes and of any neural stimulation.

  16. Tensor-based morphometry and stereology reveal brain pathology in the complexin1 knockout mouse.

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    Catherine Kielar

    Full Text Available Complexins (Cplxs are small, soluble, regulatory proteins that bind reversibly to the SNARE complex and modulate synaptic vesicle release. Cplx1 knockout mice (Cplx1(-/- have the earliest known onset of ataxia seen in a mouse model, although hitherto no histopathology has been described in these mice. Nevertheless, the profound neurological phenotype displayed by Cplx1(-/- mutants suggests that significant functional abnormalities must be present in these animals. In this study, MRI was used to automatically detect regions where structural differences were not obvious when using a traditional histological approach. Tensor-based morphometry of Cplx1(-/- mouse brains showed selective volume loss from the thalamus and cerebellum. Stereological analysis of Cplx1(-/- and Cplx1(+/+ mice brain slices confirmed the volume loss in the thalamus as well as loss in some lobules of the cerebellum. Finally, stereology was used to show that there was loss of cerebellar granule cells in Cplx1(-/- mice when compared to Cplx1(+/+ animals. Our study is the first to describe pathological changes in Cplx1(-/- mouse brain. We suggest that the ataxia in Cplx1(-/- mice is likely to be due to pathological changes in both cerebellum and thalamus. Reduced levels of Cplx proteins have been reported in brains of patients with neurodegenerative diseases. Therefore, understanding the effects of Cplx depletion in brains from Cplx1(-/- mice may also shed light on the mechanisms underlying pathophysiology in disorders in which loss of Cplx1 occurs.

  17. scMRI reveals large-scale brain network abnormalities in autism.

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    Brandon A Zielinski

    Full Text Available Autism is a complex neurological condition characterized by childhood onset of dysfunction in multiple cognitive domains including socio-emotional function, speech and language, and processing of internally versus externally directed stimuli. Although gross brain anatomic differences in autism are well established, recent studies investigating regional differences in brain structure and function have yielded divergent and seemingly contradictory results. How regional abnormalities relate to the autistic phenotype remains unclear. We hypothesized that autism exhibits distinct perturbations in network-level brain architecture, and that cognitive dysfunction may be reflected by abnormal network structure. Network-level anatomic abnormalities in autism have not been previously described. We used structural covariance MRI to investigate network-level differences in gray matter structure within two large-scale networks strongly implicated in autism, the salience network and the default mode network, in autistic subjects and age-, gender-, and IQ-matched controls. We report specific perturbations in brain network architecture in the salience and default-mode networks consistent with clinical manifestations of autism. Extent and distribution of the salience network, involved in social-emotional regulation of environmental stimuli, is restricted in autism. In contrast, posterior elements of the default mode network have increased spatial distribution, suggesting a 'posteriorization' of this network. These findings are consistent with a network-based model of autism, and suggest a unifying interpretation of previous work. Moreover, we provide evidence of specific abnormalities in brain network architecture underlying autism that are quantifiable using standard clinical MRI.

  18. Clinical study on eating disorders. Brain atrophy revealed by cranial computed tomography scans

    Energy Technology Data Exchange (ETDEWEB)

    Nishiwaki, Shinichi

    1988-06-01

    Cranial computed tomography (CT) scans were reviewed in 34 patients with anorexia nervosa (Group I) and 22 with bulimia (Group II) to elucidate the cause and pathological significance of morphological brain alterations. The findings were compared with those from 47 normal women. The incidence of brain atrophy was significantly higher in Group I (17/34, 50%) and Group II (11/22, 50%) than the control group (3/47, 6%). In Group I, there was a significant increase in the left septum-caudate distance, the maximum width of interhemispheric fissure, the width of the both-side Sylvian fissures adjacent to the skull, and the maximum width of the third ventricle. A significant increase in the maximum width of interhemispheric fissure and the width of the left-side Sylvian fissure adjacent to the skull were noted as well in Group II. Ventricular brain ratios were significantly higher in Groups I and II than the control group (6.76 and 7.29 vs 4.55). Brain atrophy did not correlate with age, body weight, malnutrition, eating behavior, depression, thyroid function, EEG findings, or intelligence scale. In Group I, serum cortisol levels after the administration of dexamethasone were correlated with ventricular brain ratio. (Namekawa, K) 51 refs.

  19. Cytogenomic profiling of breast cancer brain metastases reveals potential for repurposing targeted therapeutics.

    Science.gov (United States)

    Bollig-Fischer, Aliccia; Michelhaugh, Sharon K; Wijesinghe, Priyanga; Dyson, Greg; Kruger, Adele; Palanisamy, Nallasivam; Choi, Lydia; Alosh, Baraa; Ali-Fehmi, Rouba; Mittal, Sandeep

    2015-06-10

    Breast cancer brain metastases remain a significant clinical problem. Chemotherapy is ineffective and a lack of treatment options result in poor patient outcomes. Targeted therapeutics have proven to be highly effective in primary breast cancer, but lack of molecular genomic characterization of metastatic brain tumors is hindering the development of new treatment regimens. Here we contribute to fill this void by reporting on gene copy number variation (CNV) in 10 breast cancer metastatic brain tumors, assayed by array comparative genomic hybridization (aCGH). Results were compared to a list of cancer genes verified by others to influence cancer. Cancer gene aberrations were identified in all specimens and pathway-level analysis was applied to aggregate data, which identified stem cell pluripotency pathway enrichment and highlighted recurring, significant amplification of SOX2, PIK3CA, NTRK1, GNAS, CTNNB1, and FGFR1. For a subset of the metastatic brain tumor samples (n = 4) we compared patient-matched primary breast cancer specimens. The results of our CGH analysis and validation by alternative methods indicate that oncogenic signals driving growth of metastatic tumors exist in the original cancer. This report contributes support for more rapid development of new treatments of metastatic brain tumors, the use of genomic-based diagnostic tools and repurposed drug treatments.

  20. Dying Is Unexpectedly Positive.

    Science.gov (United States)

    Goranson, Amelia; Ritter, Ryan S; Waytz, Adam; Norton, Michael I; Gray, Kurt

    2017-07-01

    In people's imagination, dying seems dreadful; however, these perceptions may not reflect reality. In two studies, we compared the affective experience of people facing imminent death with that of people imagining imminent death. Study 1 revealed that blog posts of near-death patients with cancer and amyotrophic lateral sclerosis were more positive and less negative than the simulated blog posts of nonpatients-and also that the patients' blog posts became more positive as death neared. Study 2 revealed that the last words of death-row inmates were more positive and less negative than the simulated last words of noninmates-and also that these last words were less negative than poetry written by death-row inmates. Together, these results suggest that the experience of dying-even because of terminal illness or execution-may be more pleasant than one imagines.

  1. Revealing a brain network endophenotype in families with idiopathic generalised epilepsy.

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    Fahmida A Chowdhury

    Full Text Available Idiopathic generalised epilepsy (IGE has a genetic basis. The mechanism of seizure expression is not fully known, but is assumed to involve large-scale brain networks. We hypothesised that abnormal brain network properties would be detected using EEG in patients with IGE, and would be manifest as a familial endophenotype in their unaffected first-degree relatives. We studied 117 participants: 35 patients with IGE, 42 unaffected first-degree relatives, and 40 normal controls, using scalp EEG. Graph theory was used to describe brain network topology in five frequency bands for each subject. Frequency bands were chosen based on a published Spectral Factor Analysis study which demonstrated these bands to be optimally robust and independent. Groups were compared, using Bonferroni correction to account for nonindependent measures and multiple groups. Degree distribution variance was greater in patients and relatives than controls in the 6-9 Hz band (p = 0.0005, p = 0.0009 respectively. Mean degree was greater in patients than healthy controls in the 6-9 Hz band (p = 0.0064. Clustering coefficient was higher in patients and relatives than controls in the 6-9 Hz band (p = 0.0025, p = 0.0013. Characteristic path length did not differ between groups. No differences were found between patients and unaffected relatives. These findings suggest brain network topology differs between patients with IGE and normal controls, and that some of these network measures show similar deviations in patients and in unaffected relatives who do not have epilepsy. This suggests brain network topology may be an inherited endophenotype of IGE, present in unaffected relatives who do not have epilepsy, as well as in affected patients. We propose that abnormal brain network topology may be an endophenotype of IGE, though not in itself sufficient to cause epilepsy.

  2. Clinical standardized fMRI reveals altered language lateralization in patients with brain tumor.

    Science.gov (United States)

    Partovi, S; Jacobi, B; Rapps, N; Zipp, L; Karimi, S; Rengier, F; Lyo, J K; Stippich, C

    2012-12-01

    Brain tumors affecting language-relevant areas may influence language lateralization. The purpose of this study was to systematically investigate language lateralization in brain tumor patients using clinical language fMRI, comparing the results with a group of healthy volunteers. Fifty-seven strictly right-handed patients with left-hemispheric-space intracranial masses (mainly neoplastic) affecting either the Broca area (n = 19) or Wernicke area (n = 38) were prospectively enrolled in this study. Fourteen healthy volunteers served as a control group. Standardized clinical language fMRI, using visually triggered sentence- and word-generation paradigms, was performed on a 1.5T MR scanner. Semiautomated analyses of all functional data were conducted on an individual basis using BrainVoyager. A regional lateralization index was calculated for Broca and Wernicke areas separately versus their corresponding right-hemisphere homologs. In masses affecting the Broca area, a significant decrease in the lateralization index was found when performing word generation (P = .0017), whereas when applying sentence generation, the decrease did not reach statistical significance (P = .851). Masses affecting the Wernicke area induced a significant decrease of the lateralization index when performing sentence generation (P = .0007), whereas when applying word generation, the decrease was not statistically significant (P = .310). Clinical language fMRI was feasible for patients with brain tumors and provided relevant presurgical information by localizing essential language areas and determining language dominance. A significant effect of the brain masses on language lateralization was observed, with a shift toward the contralesional, nondominant hemisphere. This may reflect compensatory mechanisms of the brain to maintain communicative abilities.

  3. Atypical Brain Responses to Reward Cues in Autism as Revealed by Event-Related Potentials

    Science.gov (United States)

    Kohls, Gregor; Peltzer, Judith; Schulte-Ruther, Martin; Kamp-Becker, Inge; Remschmidt, Helmut; Herpertz-Dahlmann, Beate; Konrad, Kerstin

    2011-01-01

    Social motivation deficit theories suggest that children with autism do not properly anticipate and appreciate the pleasure of social stimuli. In this study, we investigated event-related brain potentials evoked by cues that triggered social versus monetary reward anticipation in children with autism. Children with autism showed attenuated P3…

  4. Three-dimensional textural analysis of brain images reveals distributed grey-matter abnormalities in schizophrenia

    Energy Technology Data Exchange (ETDEWEB)

    Ganeshan, Balaji [University of Sussex, Falmer, Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Brighton (United Kingdom); University of Sussex, Falmer, Department of Engineering and Design, Brighton (United Kingdom); Miles, Kenneth A.; Critchley, Hugo D. [University of Sussex, Falmer, Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Brighton (United Kingdom); Young, Rupert C.D.; Chatwin, Christopher R. [University of Sussex, Falmer, Department of Engineering and Design, Brighton (United Kingdom); Gurling, Hugh M.D. [University College London, Department of Mental Health Sciences, London (United Kingdom)

    2010-04-15

    Three-dimensional (3-D) selective- and relative-scale texture analysis (TA) was applied to structural magnetic resonance (MR) brain images to quantify the presence of grey-matter (GM) and white-matter (WM) textural abnormalities associated with schizophrenia. Brain TA comprised volume filtration using the Laplacian of Gaussian filter to highlight fine, medium and coarse textures within GM and WM, followed by texture quantification. Relative TA (e.g. ratio of fine to medium) was also computed. T1-weighted MR whole-brain images from 32 participants with diagnosis of schizophrenia (n = 10) and healthy controls (n = 22) were examined. Five patients possessed marker alleles (SZ8) associated with schizophrenia on chromosome 8 in the pericentriolar material 1 gene while the remaining five had not inherited any of the alleles (SZ0). Filtered fine GM texture (mean grey-level intensity; MGI) most significantly differentiated schizophrenic patients from controls (P = 0.0058; area under the receiver-operating characteristic curve = 0.809, sensitivity = 90%, specificity = 70%). WM measurements did not distinguish the two groups. Filtered GM and WM textures (MGI) correlated with total GM and WM volume respectively. Medium-to-coarse GM entropy distinguished SZ0 from controls (P = 0.0069) while measures from SZ8 were intermediate between the two. 3-D TA of brain MR enables detection of subtle distributed morphological features associated with schizophrenia, determined partly by susceptibility genes. (orig.)

  5. Perceptual Shift in Bilingualism: Brain Potentials Reveal Plasticity in Pre-Attentive Colour Perception

    Science.gov (United States)

    Athanasopoulos, Panos; Dering, Benjamin; Wiggett, Alison; Kuipers, Jan-Rouke; Thierry, Guillaume

    2010-01-01

    The validity of the linguistic relativity principle continues to stimulate vigorous debate and research. The debate has recently shifted from the behavioural investigation arena to a more biologically grounded field, in which tangible physiological evidence for language effects on perception can be obtained. Using brain potentials in a colour…

  6. Brain imaging reveals neuronal circuitry underlying the crow’s perception of human faces

    Science.gov (United States)

    Marzluff, John M.; Miyaoka, Robert; Minoshima, Satoshi; Cross, Donna J.

    2012-01-01

    Crows pay close attention to people and can remember specific faces for several years after a single encounter. In mammals, including humans, faces are evaluated by an integrated neural system involving the sensory cortex, limbic system, and striatum. Here we test the hypothesis that birds use a similar system by providing an imaging analysis of an awake, wild animal’s brain as it performs an adaptive, complex cognitive task. We show that in vivo imaging of crow brain activity during exposure to familiar human faces previously associated with either capture (threatening) or caretaking (caring) activated several brain regions that allow birds to discriminate, associate, and remember visual stimuli, including the rostral hyperpallium, nidopallium, mesopallium, and lateral striatum. Perception of threatening faces activated circuitry including amygdalar, thalamic, and brainstem regions, known in humans and other vertebrates to be related to emotion, motivation, and conditioned fear learning. In contrast, perception of caring faces activated motivation and striatal regions. In our experiments and in nature, when perceiving a threatening face, crows froze and fixed their gaze (decreased blink rate), which was associated with activation of brain regions known in birds to regulate perception, attention, fear, and escape behavior. These findings indicate that, similar to humans, crows use sophisticated visual sensory systems to recognize faces and modulate behavioral responses by integrating visual information with expectation and emotion. Our approach has wide applicability and potential to improve our understanding of the neural basis for animal behavior. PMID:22984177

  7. Magnetic resonance spectroscopy reveals an impaired brain metabolic profile in mice resistant to cerebral malaria infected with Plasmodium berghei ANKA.

    Science.gov (United States)

    Penet, Marie-France; Kober, Frank; Confort-Gouny, Sylviane; Le Fur, Yann; Dalmasso, Christiane; Coltel, Nicolas; Liprandi, Agnès; Gulian, Jean-Marc; Grau, Georges E; Cozzone, Patrick J; Viola, Angèle

    2007-05-11

    Malaria is a major cause of morbidity and mortality with an annual death toll exceeding one million. Severe malaria is a complex multisystem disorder, including one or more of the following complications: cerebral malaria, anemia, acidosis, jaundice, respiratory distress, renal insufficiency, coagulation anomalies, and hyperparasitemia. Using a combined in vivo/in vitro metabolic-based approach, we investigated the putative pathogenic effects of Plasmodium berghei ANKA on brain, in a mouse strain developing malaria but resistant to cerebral malaria. The purpose was to determine whether the infection could cause a brain dysfunction distinct from the classic cerebral syndrome. Mice resistant to cerebral malaria were infected with P. berghei ANKA and explored during both the symptomless and the severe stage of the disease by using in vivo brain magnetic resonance imaging and spectroscopy. The infected mice did not present the lesional and metabolic hallmarks of cerebral malaria. However, brain dysfunction caused by anemia, parasite burden, and hepatic damage was evidenced. We report an increase in cerebral blood flow, a process allowing temporary maintenance of oxygen supply to brain despite anemia. Besides, we document metabolic anomalies affecting choline-derived compounds, myo-inositol, glutamine, glycine, and alanine. The choline decrease appears related to parasite proliferation. Glutamine, myo-inositol, glycine, and alanine variations together indicate a hepatic encephalopathy, a finding in agreement with the liver damage detected in mice, which is also a feature of the human disease. These results reveal the vulnerability of brain to malaria infection at the severe stage of the disease even in the absence of cerebral malaria.

  8. Multi-study integration of brain cancer transcriptomes reveals organ-level molecular signatures.

    Directory of Open Access Journals (Sweden)

    Jaeyun Sung

    Full Text Available We utilized abundant transcriptomic data for the primary classes of brain cancers to study the feasibility of separating all of these diseases simultaneously based on molecular data alone. These signatures were based on a new method reported herein--Identification of Structured Signatures and Classifiers (ISSAC--that resulted in a brain cancer marker panel of 44 unique genes. Many of these genes have established relevance to the brain cancers examined herein, with others having known roles in cancer biology. Analyses on large-scale data from multiple sources must deal with significant challenges associated with heterogeneity between different published studies, for it was observed that the variation among individual studies often had a larger effect on the transcriptome than did phenotype differences, as is typical. For this reason, we restricted ourselves to studying only cases where we had at least two independent studies performed for each phenotype, and also reprocessed all the raw data from the studies using a unified pre-processing pipeline. We found that learning signatures across multiple datasets greatly enhanced reproducibility and accuracy in predictive performance on truly independent validation sets, even when keeping the size of the training set the same. This was most likely due to the meta-signature encompassing more of the heterogeneity across different sources and conditions, while amplifying signal from the repeated global characteristics of the phenotype. When molecular signatures of brain cancers were constructed from all currently available microarray data, 90% phenotype prediction accuracy, or the accuracy of identifying a particular brain cancer from the background of all phenotypes, was found. Looking forward, we discuss our approach in the context of the eventual development of organ-specific molecular signatures from peripheral fluids such as the blood.

  9. Expecting the unexpected

    DEFF Research Database (Denmark)

    Mcneill, Ilona M.; Dunlop, Patrick D.; Heath, Jonathan B.

    2013-01-01

    People who live in wildfire-prone communities tend to form their own hazard-related expectations, which may influence their willingness to prepare for a fire. Past research has already identified two important expectancy-based factors associated with people's intentions to prepare for a natural......) and measured actual rather than intended preparedness. In addition, we tested the relation between preparedness and two additional threat-related expectations: the expectation that one can rely on an official warning and the expectation of encountering obstacles (e.g., the loss of utilities) during a fire....... A survey completed by 1,003 residents of wildfire-prone areas in Perth, Australia, revealed that perceived risk (especially risk severity) and perceived protection responsibility were both positively associated with all types of preparedness, but the latter did not significantly predict preparedness after...

  10. Water diffusion reveals networks that modulate multiregional morphological plasticity after repetitive brain stimulation

    OpenAIRE

    Abe, Mitsunari; Fukuyama, Hidenao; Mima, Tatsuya

    2014-01-01

    Repetitive brain stimulation is an established experimental protocol that induces plasticity in the stimulated site. Recent evidence indicates additional plasticity-related changes in remote nonstimulated regions. However, the neural substrates underlying the remote effects are unknown. Diffusion-weighted MRI (DWI) probes water diffusion and can be used to estimate morphological changes in cortical tissue that occur with the induction of plasticity. We used DWI to evaluate morphological chang...

  11. Exercise challenge in Gulf War Illness reveals two subgroups with altered brain structure and function.

    Directory of Open Access Journals (Sweden)

    Rakib U Rayhan

    Full Text Available Nearly 30% of the approximately 700,000 military personnel who served in Operation Desert Storm (1990-1991 have developed Gulf War Illness, a condition that presents with symptoms such as cognitive impairment, autonomic dysfunction, debilitating fatigue and chronic widespread pain that implicate the central nervous system. A hallmark complaint of subjects with Gulf War Illness is post-exertional malaise; defined as an exacerbation of symptoms following physical and/or mental effort. To study the causal relationship between exercise, the brain, and changes in symptoms, 28 Gulf War veterans and 10 controls completed an fMRI scan before and after two exercise stress tests to investigate serial changes in pain, autonomic function, and working memory. Exercise induced two clinical Gulf War Illness subgroups. One subgroup presented with orthostatic tachycardia (n = 10. This phenotype correlated with brainstem atrophy, baseline working memory compensation in the cerebellar vermis, and subsequent loss of compensation after exercise. The other subgroup developed exercise induced hyperalgesia (n = 18 that was associated with cortical atrophy and baseline working memory compensation in the basal ganglia. Alterations in cognition, brain structure, and symptoms were absent in controls. Our novel findings may provide an understanding of the relationship between the brain and post-exertional malaise in Gulf War Illness.

  12. Fluorescent nanodiamond tracking reveals intraneuronal transport abnormalities induced by brain-disease-related genetic risk factors

    Science.gov (United States)

    Haziza, Simon; Mohan, Nitin; Loe-Mie, Yann; Lepagnol-Bestel, Aude-Marie; Massou, Sophie; Adam, Marie-Pierre; Le, Xuan Loc; Viard, Julia; Plancon, Christine; Daudin, Rachel; Koebel, Pascale; Dorard, Emilie; Rose, Christiane; Hsieh, Feng-Jen; Wu, Chih-Che; Potier, Brigitte; Herault, Yann; Sala, Carlo; Corvin, Aiden; Allinquant, Bernadette; Chang, Huan-Cheng; Treussart, François; Simonneau, Michel

    2017-05-01

    Brain diseases such as autism and Alzheimer's disease (each inflicting >1% of the world population) involve a large network of genes displaying subtle changes in their expression. Abnormalities in intraneuronal transport have been linked to genetic risk factors found in patients, suggesting the relevance of measuring this key biological process. However, current techniques are not sensitive enough to detect minor abnormalities. Here we report a sensitive method to measure the changes in intraneuronal transport induced by brain-disease-related genetic risk factors using fluorescent nanodiamonds (FNDs). We show that the high brightness, photostability and absence of cytotoxicity allow FNDs to be tracked inside the branches of dissociated neurons with a spatial resolution of 12 nm and a temporal resolution of 50 ms. As proof of principle, we applied the FND tracking assay on two transgenic mouse lines that mimic the slight changes in protein concentration (∼30%) found in the brains of patients. In both cases, we show that the FND assay is sufficiently sensitive to detect these changes.

  13. Brain connectivity in late-life depression and aging revealed by network analysis.

    Science.gov (United States)

    Charlton, Rebecca A; Leow, Alex; GadElkarim, Johnson; Zhang, Aifeng; Ajilore, Olusola; Yang, Shaolin; Lamar, Melissa; Kumar, Anand

    2015-06-01

    To use novel methods to examine age associations across an integrated brain network in healthy older adults (HOA) and individuals with late-life depression (LLD). Graph theory metrics describe the organizational configuration of both the global network and specified brain regions. Cross-sectional data were acquired. Graph theory was used to explore diffusion tensor imaging-derived white matter networks. Forty-eight HOA and 28 adults with LLD were recruited from the community. Global and local metrics in prefrontal, cingulate, and temporal regions were calculated. Group differences and associations with age were explored. Group differences were noted in local metrics of the right prefrontal and temporal regions, but no significant differences were observed on global metrics. Local (not global) metrics were associated with age differently across groups. For HOA, local metrics across all regions correlated with age, whereas in adults with LLD, correlations were only observed within temporal regions. In keeping with hypothesized regions impacted by LLD, stronger hubs in right temporal regions were observed among HOA, whereas LLD individuals were characterized by robust hubs in frontal regions. We demonstrate widespread age-related changes in local network properties among HOA with different and more restricted local changes in LLD. Although a preliminary analysis, different patterns of correlations in local networks coupled with equivalent global metrics may reflect altered local structural brain networks in patients with LLD. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  14. Genetic depletion of brain 5HT reveals a common molecular pathway mediating compulsivity and impulsivity.

    Science.gov (United States)

    Angoa-Pérez, Mariana; Kane, Michael J; Briggs, Denise I; Sykes, Catherine E; Shah, Mrudang M; Francescutti, Dina M; Rosenberg, David R; Thomas, David M; Kuhn, Donald M

    2012-06-01

    Neuropsychiatric disorders characterized by behavioral disinhibition, including disorders of compulsivity (e.g. obsessive-compulsive disorder; OCD) and impulse-control (e.g. impulsive aggression), are severe, highly prevalent and chronically disabling. Treatment options for these diseases are extremely limited. The pathophysiological bases of disorders of behavioral disinhibition are poorly understood but it has been suggested that serotonin dysfunction may play a role. Mice lacking the gene encoding brain tryptophan hydroxylase 2 (Tph2-/-), the initial and rate-limiting enzyme in the synthesis of serotonin, were tested in numerous behavioral assays that are well known for their utility in modeling human neuropsychiatric diseases. Mice lacking Tph2 (and brain 5HT) show intense compulsive and impulsive behaviors to include extreme aggression. The impulsivity is motor in form and not cognitive because Tph2-/- mice show normal acquisition and reversal learning on a spatial learning task. Restoration of 5HT levels by treatment of Tph2-/- mice with its immediate precursor 5-hydroxytryptophan attenuated compulsive and impulsive-aggressive behaviors. Surprisingly, in Tph2-/- mice, the lack of 5HT was not associated with anxiety-like behaviors. The results indicate that 5HT mediates behavioral disinhibition in the mammalian brain independent of anxiogenesis. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

  15. Expression weighted cell type enrichments reveal genetic and cellular nature of major brain disorders

    Directory of Open Access Journals (Sweden)

    Nathan Gerald Skene

    2016-01-01

    Full Text Available The cell types that trigger the primary pathology in many brain diseases remain largely unknown. One route to understanding the primary pathological cell type for a particular disease is to identify the cells expressing susceptibility genes. Although this is straightforward for monogenic conditions where the causative mutation may alter expression of a cell type specific marker, methods are required for the common polygenic disorders. We developed the Expression Weighted Cell Type Enrichment (EWCE method that uses single cell transcriptomes to generate the probability distribution associated with a gene list having an average level of expression within a cell type. Following validation, we applied EWCE to human genetic data from cases of epilepsy, Schizophrenia, Autism, Intellectual Disability, Alzheimer’s disease, Multiple Sclerosis and anxiety disorders. Genetic susceptibility primarily affected microglia in Alzheimer’s and Multiple Sclerosis; was shared between interneurons and pyramidal neurons in Autism and Schizophrenia; while intellectual disabilities and epilepsy were attributable to a range of cell-types, with the strongest enrichment in interneurons. We hypothesised that the primary cell type pathology could trigger secondary changes in other cell types and these could be detected by applying EWCE to transcriptome data from diseased tissue. In Autism, Schizophrenia and Alzheimer’s disease we find evidence of pathological changes in all of the major brain cell types. These findings give novel insight into the cellular origins and progression in common brain disorders. The methods can be applied to any tissue and disorder and have applications in validating mouse models.

  16. Small RNA sequencing-microarray analyses in Parkinson leukocytes reveal deep brain stimulation-induced and splicing changes that classify brain region transcriptomes

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    Lilach eSoreq

    2013-05-01

    Full Text Available MicroRNAs (miRNAs are key post transcriptional regulators of their multiple target genes. However, the detailed profile of miRNA expression in Parkinson's disease, the second most common neurodegenerative disease worldwide and the first motor disorder has not been charted yet. Here, we report comprehensive miRNA profiling by next-generation small-RNA sequencing, combined with targets inspection by splice-junction and exon arrays interrogating leukocyte RNA in Parkinson’s disease patients before and after deep brain stimulation (DBS treatment and of matched healthy control volunteers (HC. RNA-Seq analysis identified 254 miRNAs and 79 passenger strand forms as expressed in blood leukocytes, 16 of which were modified in patients pre treatment as compared to HC. 11 miRNAs were modified following brain stimulation, 5 of which were changed inversely to the disease induced changes. Stimulation cessation further induced changes in 11 miRNAs. Transcript isoform abundance analysis yielded 332 changed isoforms in patients compared to HC, which classified brain transcriptomes of 47 PD and control independent microarrays. Functional enrichment analysis highlighted mitochondrion organization. DBS induced 155 splice changes, enriched in ubiquitin homeostasis. Cellular composition analysis revealed immune cell activity pre and post treatment. Overall, 217 disease and 74 treatment alternative isoforms were predictably targeted by modified miRNAs within both 3’ and 5’ untranslated ends and coding sequence sites. The stimulation-induced network sustained 4 miRNAs and 7 transcripts of the disease network. We believe that the presented dynamic networks provide a novel avenue for identifying disease and treatment-related therapeutic targets. Furthermore, the identification of these networks is a major step forward in the road for understanding the molecular basis for neurological and neurodegenerative diseases and assessment of the impact of brain stimulation

  17. Small RNA sequencing-microarray analyses in Parkinson leukocytes reveal deep brain stimulation-induced splicing changes that classify brain region transcriptomes

    Science.gov (United States)

    Soreq, Lilach; Salomonis, Nathan; Bronstein, Michal; Greenberg, David S.; Israel, Zvi; Bergman, Hagai; Soreq, Hermona

    2013-01-01

    MicroRNAs (miRNAs) are key post transcriptional regulators of their multiple target genes. However, the detailed profile of miRNA expression in Parkinson's disease, the second most common neurodegenerative disease worldwide and the first motor disorder has not been charted yet. Here, we report comprehensive miRNA profiling by next-generation small-RNA sequencing, combined with targets inspection by splice-junction and exon arrays interrogating leukocyte RNA in Parkinson's disease patients before and after deep brain stimulation (DBS) treatment and of matched healthy control volunteers (HC). RNA-Seq analysis identified 254 miRNAs and 79 passenger strand forms as expressed in blood leukocytes, 16 of which were modified in patients pre-treatment as compared to HC. 11 miRNAs were modified following brain stimulation 5 of which were changed inversely to the disease induced changes. Stimulation cessation further induced changes in 11 miRNAs. Transcript isoform abundance analysis yielded 332 changed isoforms in patients compared to HC, which classified brain transcriptomes of 47 PD and control independent microarrays. Functional enrichment analysis highlighted mitochondrion organization. DBS induced 155 splice changes, enriched in ubiquitin homeostasis. Cellular composition analysis revealed immune cell activity pre and post treatment. Overall, 217 disease and 74 treatment alternative isoforms were predictably targeted by modified miRNAs within both 3′ and 5′ untranslated ends and coding sequence sites. The stimulation-induced network sustained 4 miRNAs and 7 transcripts of the disease network. We believe that the presented dynamic networks provide a novel avenue for identifying disease and treatment-related therapeutic targets. Furthermore, the identification of these networks is a major step forward in the road for understanding the molecular basis for neurological and neurodegenerative diseases and assessment of the impact of brain stimulation on human diseases

  18. The Small Molecule 2-Azido-2-deoxy-glucose Is a Metabolic Chemical Reporter of O-GlcNAc Modifications in Mammalian Cells, Revealing an Unexpected Promiscuity of O-GlcNAc Transferase.

    Science.gov (United States)

    Zaro, Balyn W; Batt, Anna R; Chuh, Kelly N; Navarro, Marisol X; Pratt, Matthew R

    2017-03-17

    Glycans can be directly labeled using unnatural monosaccharide analogs, termed metabolic chemical reporters (MCRs). These compounds enable the secondary visualization and identification of glycoproteins by taking advantage of bioorthogonal reactions. Most widely used MCRs have azides or alkynes at the 2-N-acetyl position but are not selective for one class of glycoprotein over others. To address this limitation, we are exploring additional MCRs that have bioorthogonal functionality at other positions. Here, we report the characterization of 2-azido-2-deoxy-glucose (2AzGlc). We find that 2AzGlc selectively labels intracellular O-GlcNAc modifications, which further supports a somewhat unexpected, structural flexibility in this pathway. In contrast to the endogenous modification N-acetyl-glucosamine (GlcNAc), we find that 2AzGlc is not dynamically removed from protein substrates and that treatment with higher concentrations of per-acetylated 2AzGlc is toxic to cells. Finally, we demonstrate that this toxicity is an inherent property of the small-molecule, as removal of the 6-acetyl-group renders the corresponding reporter nontoxic but still results in protein labeling.

  19. Brain-specific rescue of Clock reveals system-driven transcriptional rhythms in peripheral tissue.

    Science.gov (United States)

    Hughes, Michael E; Hong, Hee-Kyung; Chong, Jason L; Indacochea, Alejandra A; Lee, Samuel S; Han, Michael; Takahashi, Joseph S; Hogenesch, John B

    2012-01-01

    The circadian regulatory network is organized in a hierarchical fashion, with a central oscillator in the suprachiasmatic nuclei (SCN) orchestrating circadian oscillations in peripheral tissues. The nature of the relationship between central and peripheral oscillators, however, is poorly understood. We used the tetOFF expression system to specifically restore Clock function in the brains of Clock(Δ19) mice, which have compromised circadian clocks. Rescued mice showed normal locomotor rhythms in constant darkness, with activity period lengths approximating wildtype controls. We used microarray analysis to assess whether brain-specific rescue of circadian rhythmicity was sufficient to restore circadian transcriptional output in the liver. Compared to Clock mutants, Clock-rescue mice showed significantly larger numbers of cycling transcripts with appropriate phase and period lengths, including many components of the core circadian oscillator. This indicates that the SCN oscillator overcomes local circadian defects and signals directly to the molecular clock. Interestingly, the vast majority of core clock genes in liver were responsive to Clock expression in the SCN, suggesting that core clock genes in peripheral tissues are intrinsically sensitive to SCN cues. Nevertheless, most circadian output in the liver was absent or severely low-amplitude in Clock-rescue animals, demonstrating that the majority of peripheral transcriptional rhythms depend on a fully functional local circadian oscillator. We identified several new system-driven rhythmic genes in the liver, including Alas1 and Mfsd2. Finally, we show that 12-hour transcriptional rhythms (i.e., circadian "harmonics") are disrupted by Clock loss-of-function. Brain-specific rescue of Clock converted 12-hour rhythms into 24-hour rhythms, suggesting that signaling via the central circadian oscillator is required to generate one of the two daily peaks of expression. Based on these data, we conclude that 12-hour rhythms

  20. Brain-specific rescue of Clock reveals system-driven transcriptional rhythms in peripheral tissue.

    Directory of Open Access Journals (Sweden)

    Michael E Hughes

    Full Text Available The circadian regulatory network is organized in a hierarchical fashion, with a central oscillator in the suprachiasmatic nuclei (SCN orchestrating circadian oscillations in peripheral tissues. The nature of the relationship between central and peripheral oscillators, however, is poorly understood. We used the tetOFF expression system to specifically restore Clock function in the brains of Clock(Δ19 mice, which have compromised circadian clocks. Rescued mice showed normal locomotor rhythms in constant darkness, with activity period lengths approximating wildtype controls. We used microarray analysis to assess whether brain-specific rescue of circadian rhythmicity was sufficient to restore circadian transcriptional output in the liver. Compared to Clock mutants, Clock-rescue mice showed significantly larger numbers of cycling transcripts with appropriate phase and period lengths, including many components of the core circadian oscillator. This indicates that the SCN oscillator overcomes local circadian defects and signals directly to the molecular clock. Interestingly, the vast majority of core clock genes in liver were responsive to Clock expression in the SCN, suggesting that core clock genes in peripheral tissues are intrinsically sensitive to SCN cues. Nevertheless, most circadian output in the liver was absent or severely low-amplitude in Clock-rescue animals, demonstrating that the majority of peripheral transcriptional rhythms depend on a fully functional local circadian oscillator. We identified several new system-driven rhythmic genes in the liver, including Alas1 and Mfsd2. Finally, we show that 12-hour transcriptional rhythms (i.e., circadian "harmonics" are disrupted by Clock loss-of-function. Brain-specific rescue of Clock converted 12-hour rhythms into 24-hour rhythms, suggesting that signaling via the central circadian oscillator is required to generate one of the two daily peaks of expression. Based on these data, we conclude

  1. Diurnal microstructural variations in healthy adult brain revealed by diffusion tensor imaging.

    Directory of Open Access Journals (Sweden)

    Chunxiang Jiang

    Full Text Available Biorhythm is a fundamental property of human physiology. Changes in the extracellular space induced by cell swelling in response to the neural activity enable the in vivo characterization of cerebral microstructure by measuring the water diffusivity using diffusion tensor imaging (DTI. To study the diurnal microstructural alterations of human brain, fifteen right-handed healthy adult subjects were recruited for DTI studies in two repeated sessions (8∶30 AM and 8∶30 PM within a 24-hour interval. Fractional anisotropy (FA, apparent diffusion coefficient (ADC, axial (λ// and radial diffusivity (λ⊥ were compared pixel by pixel between the sessions for each subject. Significant increased morning measurements in FA, ADC, λ// and λ⊥ were seen in a wide range of brain areas involving frontal, parietal, temporal and occipital lobes. Prominent evening dominant λ⊥ (18.58% was detected in the right inferior temporal and ventral fusiform gyri. AM-PM variation of λ⊥ was substantially left side hemisphere dominant (p<0.05, while no hemispheric preference was observed for the same analysis for ADC (p = 0.77, λ// (p = 0.08 or FA (p = 0.25. The percentage change of ADC, λ//, λ⊥, and FA were 1.59%, 2.15%, 1.20% and 2.84%, respectively, for brain areas without diurnal diffusivity contrast. Microstructural variations may function as the substrates of the phasic neural activities in correspondence to the environment adaptation in a light-dark cycle. This research provided a baseline for researches in neuroscience, sleep medicine, psychological and psychiatric disorders, and necessitates that diurnal effect should be taken into account in following up studies using diffusion tensor quantities.

  2. Physics of brain dynamics: Fokker-Planck analysis reveals changes in EEG {delta}-{theta} interactions in anaesthesia

    Energy Technology Data Exchange (ETDEWEB)

    Bahraminasab, A; Stefanovska, A; McClintock, P V E [Department of Physics, Lancaster University, Lancaster LA1 4YB (United Kingdom); Ghasemi, F; Friedrich, R [Institute of Theoretical Physics, Westfaelische Wilhelms-Universitaet Wilhelm-Klemm-Strasse 9, 48149 Muenster (Germany)], E-mail: aneta@lancaster.ac.uk

    2009-10-15

    We use drift and diffusion coefficients to reveal interactions between different oscillatory processes underlying a complex signal and apply the method to EEG {delta} and {theta} frequencies in the brain. By analysis of data recorded from rats during anaesthesia, we consider the stability and basins of attraction of fixed points in the phase portrait of the deterministic part of the retrieved stochastic process. We show that different classes of dynamics are associated with deep and light anaesthesia, and we demonstrate that the predominant directionality of the interaction is such that {theta} drives {delta}.

  3. Ex-vivo diffusion MRI reveals microstructural alterations in stress-sensitive brain regions: A chronic mild stress recovery study

    DEFF Research Database (Denmark)

    Khan, Ahmad Raza; Hansen, Brian; Wiborg, Ove

    Depression is a leading cause of disability worldwide and causes significant microstructural alterations in stress-sensitive brain regions. However, the potential recovery of these microstructural alterations has not previously been investigated, which we, therefore, set out to do using diffusion...... MRI (d-MRI) in the chronic mild stress (CMS) rat model of depression. This study reveals significant microstructural alterations after 8 weeks of recovery, in the opposite direction to change induced by stress in the acute phase of the experiment. Such findings may be useful in the prognosis...

  4. Whole-brain analytic measures of network communication reveal increased structure-function correlation in right temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    Jonathan Wirsich

    2016-01-01

    In rTLE patients, we found a widespread hypercorrelated functional network. Network communication analysis revealed greater unspecific branching of the shortest path (search information in the structural connectome and a higher global correlation between the structural and functional connectivity for the patient group. We also found evidence for a preserved structural rich-club in the patient group. In sum, global augmentation of structure-function correlation might be linked to a smaller functional repertoire in rTLE patients, while sparing the central core of the brain which may represent a pathway that facilitates the spread of seizures.

  5. Near-infrared spectroscopy can reveal increases in brain activity related to animal-assisted therapy.

    Science.gov (United States)

    Morita, Yuka; Ebara, Fumio; Morita, Yoshimitsu; Horikawa, Etsuo

    2017-08-01

    [Purpose] Previous studies have indicated that animal-assisted therapy can promote recovery of psychological, social, and physiological function in mental disorders. This study was designed as a pilot evaluation of the use of near-infrared spectroscopy to objectively identify changes in brain activity that could mediate the effect of animal-assisted therapy. [Subjects and Methods] The participants were 20 healthy students (10 males and 10 females; age 19-21 years) of the Faculty of Agriculture, Saga University. Participants were shown a picture of a Tokara goat or shack (control) while prefrontal cortical oxygenated haemoglobin levels (representing neural activity) were measured by near-infrared spectroscopy. [Results] The prefrontal cortical near-infrared spectroscopy signal was significantly higher during viewing of the animal picture than during a rest condition or during viewing of the control picture. [Conclusion] Our results suggest that near-infrared spectroscopy can be used to objectively identify brain activity changes during human mentation regarding animals; furthermore, these preliminary results suggest the efficacy of animal-assisted therapy could be related to increased activation of the prefrontal cortex.

  6. Multiple brain networks underpinning word learning from fluent speech revealed by independent component analysis.

    Science.gov (United States)

    López-Barroso, Diana; Ripollés, Pablo; Marco-Pallarés, Josep; Mohammadi, Bahram; Münte, Thomas F; Bachoud-Lévi, Anne-Catherine; Rodriguez-Fornells, Antoni; de Diego-Balaguer, Ruth

    2015-04-15

    Although neuroimaging studies using standard subtraction-based analysis from functional magnetic resonance imaging (fMRI) have suggested that frontal and temporal regions are involved in word learning from fluent speech, the possible contribution of different brain networks during this type of learning is still largely unknown. Indeed, univariate fMRI analyses cannot identify the full extent of distributed networks that are engaged by a complex task such as word learning. Here we used Independent Component Analysis (ICA) to characterize the different brain networks subserving word learning from an artificial language speech stream. Results were replicated in a second cohort of participants with a different linguistic background. Four spatially independent networks were associated with the task in both cohorts: (i) a dorsal Auditory-Premotor network; (ii) a dorsal Sensory-Motor network; (iii) a dorsal Fronto-Parietal network; and (iv) a ventral Fronto-Temporal network. The level of engagement of these networks varied through the learning period with only the dorsal Auditory-Premotor network being engaged across all blocks. In addition, the connectivity strength of this network in the second block of the learning phase correlated with the individual variability in word learning performance. These findings suggest that: (i) word learning relies on segregated connectivity patterns involving dorsal and ventral networks; and (ii) specifically, the dorsal auditory-premotor network connectivity strength is directly correlated with word learning performance. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Quantitative Susceptibility Mapping Reveals an Association between Brain Iron Load and Depression Severity

    Directory of Open Access Journals (Sweden)

    Shun Yao

    2017-08-01

    Full Text Available Previous studies have detected abnormal serum ferritin levels in patients with depression; however, the results have been inconsistent. This study used quantitative susceptibility mapping (QSM for the first time to examine brain iron concentration in depressed patients and evaluated whether it is related to severity. We included three groups of age- and gender-matched participants: 30 patients with mild-moderate depression (MD, 14 patients with major depression disorder (MDD and 20 control subjects. All participants underwent MR scans with a 3D gradient-echo sequence reconstructing for QSM and performed the 17-item Hamilton Depression Rating Scale (HDRS test. In MDD, the susceptibility value in the bilateral putamen was significantly increased compared with MD or control subjects. In addition, a significant difference was also observed in the left thalamus in MDD patients compared with controls. However, the susceptibility values did not differ between MD patients and controls. The susceptibility values positively correlated with the severity of depression as indicated by the HDRS scores. Our results provide evidence that brain iron deposition may be associated with depression and may even be a biomarker for investigating the pathophysiological mechanism of depression.

  8. Partitioning heritability analysis reveals a shared genetic basis of brain anatomy and schizophrenia.

    Science.gov (United States)

    Lee, P H; Baker, J T; Holmes, A J; Jahanshad, N; Ge, T; Jung, J-Y; Cruz, Y; Manoach, D S; Hibar, D P; Faskowitz, J; McMahon, K L; de Zubicaray, G I; Martin, N H; Wright, M J; Öngür, D; Buckner, R; Roffman, J; Thompson, P M; Smoller, J W

    2016-12-01

    Schizophrenia is a devastating neurodevelopmental disorder with a complex genetic etiology. Widespread cortical gray matter loss has been observed in patients and prodromal samples. However, it remains unresolved whether schizophrenia-associated cortical structure variations arise due to disease etiology or secondary to the illness. Here we address this question using a partitioning-based heritability analysis of genome-wide single-nucleotide polymorphism (SNP) and neuroimaging data from 1750 healthy individuals. We find that schizophrenia-associated genetic variants explain a significantly enriched proportion of trait heritability in eight brain phenotypes (false discovery rate=10%). In particular, intracranial volume and left superior frontal gyrus thickness exhibit significant and robust associations with schizophrenia genetic risk under varying SNP selection conditions. Cross-disorder comparison suggests that the neurogenetic architecture of schizophrenia-associated brain regions is, at least in part, shared with other psychiatric disorders. Our study highlights key neuroanatomical correlates of schizophrenia genetic risk in the general population. These may provide fundamental insights into the complex pathophysiology of the illness, and a potential link to neurocognitive deficits shaping the disorder.

  9. Bilingualism at the core of the brain. Structural differences between bilinguals and monolinguals revealed by subcortical shape analysis.

    Science.gov (United States)

    Burgaleta, Miguel; Sanjuán, Ana; Ventura-Campos, Noelia; Sebastian-Galles, Núria; Ávila, César

    2016-01-15

    Naturally acquiring a language shapes the human brain through a long-lasting learning and practice process. This is supported by previous studies showing that managing more than one language from early childhood has an impact on brain structure and function. However, to what extent bilingual individuals present neuroanatomical peculiarities at the subcortical level with respect to monolinguals is yet not well understood, despite the key role of subcortical gray matter for a number of language functions, including monitoring of speech production and language control - two processes especially solicited by bilinguals. Here we addressed this issue by performing a subcortical surface-based analysis in a sample of monolinguals and simultaneous bilinguals (N=88) that only differed in their language experience from birth. This analysis allowed us to study with great anatomical precision the potential differences in morphology of key subcortical structures, namely, the caudate, accumbens, putamen, globus pallidus and thalamus. Vertexwise analyses revealed significantly expanded subcortical structures for bilinguals compared to monolinguals, localized in bilateral putamen and thalamus, as well as in the left globus pallidus and right caudate nucleus. A topographical interpretation of our results suggests that a more complex phonological system in bilinguals may lead to a greater development of a subcortical brain network involved in monitoring articulatory processes. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Repeated diffusion MRI reveals earliest time point for stratification of radiotherapy response in brain metastases

    Science.gov (United States)

    Mahmood, Faisal; Johannesen, Helle H.; Geertsen, Poul; Hansen, Rasmus H.

    2017-04-01

    An imaging biomarker for early prediction of treatment response potentially provides a non-invasive tool for better prognostics and individualized management of the disease. Radiotherapy (RT) response is generally related to changes in gross tumor volume manifesting months later. In this prospective study we investigated the apparent diffusion coefficient (ADC), perfusion fraction and pseudo diffusion coefficient derived from diffusion weighted MRI as potential early biomarkers for radiotherapy response of brain metastases. It was a particular aim to assess the optimal time point for acquiring the DW-MRI scan during the course of treatment, since to our knowledge this important question has not been addressed directly in previous studies. Twenty-nine metastases (N  =  29) from twenty-one patients, treated with whole-brain fractionated external beam RT were analyzed. Patients were scanned with a 1 T MRI system to acquire DW-, T2*W-, T2W- and T1W scans, before start of RT, at each fraction and at follow up two to three months after RT. The DW-MRI parameters were derived using regions of interest based on high b-value images (b  =  800 s mm-2). Both volumetric and RECIST criteria were applied for response evaluation. It was found that in non-responding metastases the mean ADC decreased and in responding metastases it increased. The volume based response proved to be far more consistently predictable by the ADC change found at fraction number 7 and later, compared to the linear response (RECIST). The perfusion fraction and pseudo diffusion coefficient did not show sufficient prognostic value with either response assessment criteria. In conclusion this study shows that the ADC derived using high b-values may be a reliable biomarker for early assessment of radiotherapy response for brain metastases patients. The earliest response stratification can be achieved using two DW-MRI scans, one pre-treatment and one at treatment day 7-9 (equivalent to 21 Gy).

  11. Immunogold labeling reveals subcellular localisation of silica nanoparticles in a human blood-brain barrier model

    Science.gov (United States)

    Ye, Dong; Anguissola, Sergio; O'Neill, Tiina; Dawson, Kenneth A.

    2015-05-01

    Subcellular location of nanoparticles has been widely investigated with fluorescence microscopy, via fluorescently labeled antibodies to visualise target antigens in cells. However, fluorescence microscopy, such as confocal or live cell imaging, has generally limited 3D spatial resolution. Conventional electron microscopy can be useful in bridging resolution gap, but still not ideal in resolving subcellular organelle identities. Using the pre-embedding immunogold electron microscopic imaging, we performed accurate examination of the intracellular trafficking and gathered further evidence of transport mechanisms of silica nanoparticles across a human in vitro blood-brain barrier model. Our approach can effectively immunolocalise a variety of intracellular compartments and provide new insights into the uptake and subcellular transport of nanoparticles.Subcellular location of nanoparticles has been widely investigated with fluorescence microscopy, via fluorescently labeled antibodies to visualise target antigens in cells. However, fluorescence microscopy, such as confocal or live cell imaging, has generally limited 3D spatial resolution. Conventional electron microscopy can be useful in bridging resolution gap, but still not ideal in resolving subcellular organelle identities. Using the pre-embedding immunogold electron microscopic imaging, we performed accurate examination of the intracellular trafficking and gathered further evidence of transport mechanisms of silica nanoparticles across a human in vitro blood-brain barrier model. Our approach can effectively immunolocalise a variety of intracellular compartments and provide new insights into the uptake and subcellular transport of nanoparticles. Electronic supplementary information (ESI) available: Nanoparticle characterisation data, preservation of cellular structures, staining controls, optimisation of size amplification via the silver enhancement, and more imaging results from anti-clathrin and anti-caveolin 1

  12. Graph coarse-graining reveals differences in the module-level structure of functional brain networks.

    Science.gov (United States)

    Kujala, Rainer; Glerean, Enrico; Pan, Raj Kumar; Jääskeläinen, Iiro P; Sams, Mikko; Saramäki, Jari

    2016-11-01

    Networks have become a standard tool for analyzing functional magnetic resonance imaging (fMRI) data. In this approach, brain areas and their functional connections are mapped to the nodes and links of a network. Even though this mapping reduces the complexity of the underlying data, it remains challenging to understand the structure of the resulting networks due to the large number of nodes and links. One solution is to partition networks into modules and then investigate the modules' composition and relationship with brain functioning. While this approach works well for single networks, understanding differences between two networks by comparing their partitions is difficult and alternative approaches are thus necessary. To this end, we present a coarse-graining framework that uses a single set of data-driven modules as a frame of reference, enabling one to zoom out from the node- and link-level details. As a result, differences in the module-level connectivity can be understood in a transparent, statistically verifiable manner. We demonstrate the feasibility of the method by applying it to networks constructed from fMRI data recorded from 13 healthy subjects during rest and movie viewing. While independently partitioning the rest and movie networks is shown to yield little insight, the coarse-graining framework enables one to pinpoint differences in the module-level structure, such as the increased number of intra-module links within the visual cortex during movie viewing. In addition to quantifying differences due to external stimuli, the approach could also be applied in clinical settings, such as comparing patients with healthy controls. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  13. A Social Network Approach Reveals Associations between Mouse Social Dominance and Brain Gene Expression

    Science.gov (United States)

    So, Nina; Franks, Becca; Lim, Sean; Curley, James P.

    2015-01-01

    Modelling complex social behavior in the laboratory is challenging and requires analyses of dyadic interactions occurring over time in a physically and socially complex environment. In the current study, we approached the analyses of complex social interactions in group-housed male CD1 mice living in a large vivarium. Intensive observations of social interactions during a 3-week period indicated that male mice form a highly linear and steep dominance hierarchy that is maintained by fighting and chasing behaviors. Individual animals were classified as dominant, sub-dominant or subordinate according to their David’s Scores and I& SI ranking. Using a novel dynamic temporal Glicko rating method, we ascertained that the dominance hierarchy was stable across time. Using social network analyses, we characterized the behavior of individuals within 66 unique relationships in the social group. We identified two individual network metrics, Kleinberg’s Hub Centrality and Bonacich’s Power Centrality, as accurate predictors of individual dominance and power. Comparing across behaviors, we establish that agonistic, grooming and sniffing social networks possess their own distinctive characteristics in terms of density, average path length, reciprocity out-degree centralization and out-closeness centralization. Though grooming ties between individuals were largely independent of other social networks, sniffing relationships were highly predictive of the directionality of agonistic relationships. Individual variation in dominance status was associated with brain gene expression, with more dominant individuals having higher levels of corticotropin releasing factor mRNA in the medial and central nuclei of the amygdala and the medial preoptic area of the hypothalamus, as well as higher levels of hippocampal glucocorticoid receptor and brain-derived neurotrophic factor mRNA. This study demonstrates the potential and significance of combining complex social housing and intensive

  14. A Social Network Approach Reveals Associations between Mouse Social Dominance and Brain Gene Expression.

    Science.gov (United States)

    So, Nina; Franks, Becca; Lim, Sean; Curley, James P

    2015-01-01

    Modelling complex social behavior in the laboratory is challenging and requires analyses of dyadic interactions occurring over time in a physically and socially complex environment. In the current study, we approached the analyses of complex social interactions in group-housed male CD1 mice living in a large vivarium. Intensive observations of social interactions during a 3-week period indicated that male mice form a highly linear and steep dominance hierarchy that is maintained by fighting and chasing behaviors. Individual animals were classified as dominant, sub-dominant or subordinate according to their David's Scores and I& SI ranking. Using a novel dynamic temporal Glicko rating method, we ascertained that the dominance hierarchy was stable across time. Using social network analyses, we characterized the behavior of individuals within 66 unique relationships in the social group. We identified two individual network metrics, Kleinberg's Hub Centrality and Bonacich's Power Centrality, as accurate predictors of individual dominance and power. Comparing across behaviors, we establish that agonistic, grooming and sniffing social networks possess their own distinctive characteristics in terms of density, average path length, reciprocity out-degree centralization and out-closeness centralization. Though grooming ties between individuals were largely independent of other social networks, sniffing relationships were highly predictive of the directionality of agonistic relationships. Individual variation in dominance status was associated with brain gene expression, with more dominant individuals having higher levels of corticotropin releasing factor mRNA in the medial and central nuclei of the amygdala and the medial preoptic area of the hypothalamus, as well as higher levels of hippocampal glucocorticoid receptor and brain-derived neurotrophic factor mRNA. This study demonstrates the potential and significance of combining complex social housing and intensive

  15. A Social Network Approach Reveals Associations between Mouse Social Dominance and Brain Gene Expression.

    Directory of Open Access Journals (Sweden)

    Nina So

    Full Text Available Modelling complex social behavior in the laboratory is challenging and requires analyses of dyadic interactions occurring over time in a physically and socially complex environment. In the current study, we approached the analyses of complex social interactions in group-housed male CD1 mice living in a large vivarium. Intensive observations of social interactions during a 3-week period indicated that male mice form a highly linear and steep dominance hierarchy that is maintained by fighting and chasing behaviors. Individual animals were classified as dominant, sub-dominant or subordinate according to their David's Scores and I& SI ranking. Using a novel dynamic temporal Glicko rating method, we ascertained that the dominance hierarchy was stable across time. Using social network analyses, we characterized the behavior of individuals within 66 unique relationships in the social group. We identified two individual network metrics, Kleinberg's Hub Centrality and Bonacich's Power Centrality, as accurate predictors of individual dominance and power. Comparing across behaviors, we establish that agonistic, grooming and sniffing social networks possess their own distinctive characteristics in terms of density, average path length, reciprocity out-degree centralization and out-closeness centralization. Though grooming ties between individuals were largely independent of other social networks, sniffing relationships were highly predictive of the directionality of agonistic relationships. Individual variation in dominance status was associated with brain gene expression, with more dominant individuals having higher levels of corticotropin releasing factor mRNA in the medial and central nuclei of the amygdala and the medial preoptic area of the hypothalamus, as well as higher levels of hippocampal glucocorticoid receptor and brain-derived neurotrophic factor mRNA. This study demonstrates the potential and significance of combining complex social housing

  16. Exploring Deep Space - Uncovering the Anatomy of Periventricular Structures to Reveal the Lateral Ventricles of the Human Brain.

    Science.gov (United States)

    Colibaba, Alexandru S; Calma, Aicee Dawn B; Webb, Alexandra L; Valter, Krisztina

    2017-10-22

    Anatomy students are typically provided with two-dimensional (2D) sections and images when studying cerebral ventricular anatomy and students find this challenging. Because the ventricles are negative spaces located deep within the brain, the only way to understand their anatomy is by appreciating their boundaries formed by related structures. Looking at a 2D representation of these spaces, in any of the cardinal planes, will not enable visualisation of all of the structures that form the boundaries of the ventricles. Thus, using 2D sections alone requires students to compute their own mental image of the 3D ventricular spaces. The aim of this study was to develop a reproducible method for dissecting the human brain to create an educational resource to enhance student understanding of the intricate relationships between the ventricles and periventricular structures. To achieve this, we created a video resource that features a step-by-step guide using a fiber dissection method to reveal the lateral and third ventricles together with the closely related limbic system and basal ganglia structures. One of the advantages of this method is that it enables delineation of the white matter tracts that are difficult to distinguish using other dissection techniques. This video is accompanied by a written protocol that provides a systematic description of the process to aid in the reproduction of the brain dissection. This package offers a valuable anatomy teaching resource for educators and students alike. By following these instructions educators can create teaching resources and students can be guided to produce their own brain dissection as a hands-on practical activity. We recommend that this video guide be incorporated into neuroanatomy teaching to enhance student understanding of the morphology and clinical relevance of the ventricles.

  17. Generalized spike and waves: effect of discharge duration on brain networks as revealed by BOLD fMRI.

    Science.gov (United States)

    Pugnaghi, Matteo; Carmichael, David W; Vaudano, Anna E; Chaudhary, Umair J; Benuzzi, Francesca; Di Bonaventura, Carlo; Giallonardo, Anna T; Rodionov, Roman; Walker, Matthew C; Duncan, John S; Meletti, Stefano; Lemieux, Louis

    2014-01-01

    In the past decade, the possibility of combining recordings of EEG and functional MRI (EEG-fMRI), has brought a new insight into the brain network underlying generalized spike wave discharges (GSWD). Nevertheless, how GSWD duration influences this network is not fully understood. In this study we aim to investigate whether GSWD duration had a threshold (non-linear) and/or a linear effect on the amplitude of the associated BOLD changes in any brain regions. This could help in elucidating if there is an hemodynamic background supporting the differentiation between interictal and ictal events. We studied a population of 42 patients with idiopathic generalized epilepsies (IGE) who underwent resting-state EEG-fMRI recordings in three centres (London, UK; Modena, Italy; Rome, Italy), applying a parametric analysis of the GSWD duration. Patients were classified as having Childhood Absence epilepsy, Juvenile Absence Epilepsy, or Juvenile Myoclonic Epilepsy. At the population level linear GSWD duration-related BOLD signal changes were found in a network of brain regions: mainly BOLD increase in thalami and cerebral ventricles, and BOLD decrease in posterior cingulate, precuneus and bilateral parietal regions. No region of significant BOLD change was found in the group analysis for the non-linear effect of GSWD duration. To explore the possible effect of both the different IGE sub-syndromes and the different protocols and scanning equipment used in the study, a full-factorial ANOVA design was performed revealing no significant differences. These findings support the idea that the amplitude of the BOLD changes is linearly related to the GSWD duration with no universal threshold effect of spike and wave duration on the brain network supporting this activity.

  18. Global deprivation of brain-derived neurotrophic factor in the CNS reveals an area-specific requirement for dendritic growth.

    Science.gov (United States)

    Rauskolb, Stefanie; Zagrebelsky, Marta; Dreznjak, Anita; Deogracias, Rubén; Matsumoto, Tomoya; Wiese, Stefan; Erne, Beat; Sendtner, Michael; Schaeren-Wiemers, Nicole; Korte, Martin; Barde, Yves-Alain

    2010-02-03

    Although brain-derived neurotrophic factor (BDNF) is linked with an increasing number of conditions causing brain dysfunction, its role in the postnatal CNS has remained difficult to assess. This is because the bdnf-null mutation causes the death of the animals before BDNF levels have reached adult levels. In addition, the anterograde axonal transport of BDNF complicates the interpretation of area-specific gene deletion. The present study describes the generation of a new conditional mouse mutant essentially lacking BDNF throughout the CNS. It shows that BDNF is not essential for prolonged postnatal survival, but that the behavior of such mutant animals is markedly altered. It also reveals that BDNF is not a major survival factor for most CNS neurons and for myelination of their axons. However, it is required for the postnatal growth of the striatum, and single-cell analyses revealed a marked decreased in dendritic complexity and spine density. In contrast, BDNF is dispensable for the growth of the hippocampus and only minimal changes were observed in the dendrites of CA1 pyramidal neurons in mutant animals. Spine density remained unchanged, whereas the proportion of the mushroom-type spine was moderately decreased. In line with these in vivo observations, we found that BDNF markedly promotes the growth of cultured striatal neurons and of their dendrites, but not of those of hippocampal neurons, suggesting that the differential responsiveness to BDNF is part of a neuron-intrinsic program.

  19. Dissecting the social brain: Introducing the EmpaToM to reveal distinct neural networks and brain-behavior relations for empathy and Theory of Mind.

    Science.gov (United States)

    Kanske, Philipp; Böckler, Anne; Trautwein, Fynn-Mathis; Singer, Tania

    2015-11-15

    Successful social interactions require both affect sharing (empathy) and understanding others' mental states (Theory of Mind, ToM). As these two functions have mostly been investigated in isolation, the specificity of the underlying neural networks and the relation of these networks to the respective behavioral indices could not be tested. Here, we present a novel fMRI paradigm (EmpaToM) that independently manipulates both empathy and ToM. Experiments 1a/b (N=90) validated the task with established empathy and ToM paradigms on a behavioral and neural level. Experiment 2 (N=178) employed the EmpaToM and revealed clearly separable neural networks including anterior insula for empathy and ventral temporoparietal junction for ToM. These distinct networks could be replicated in task-free resting state functional connectivity. Importantly, brain activity in these two networks specifically predicted the respective behavioral indices, that is, inter-individual differences in ToM related brain activity predicted inter-individual differences in ToM performance, but not empathic responding, and vice versa. Taken together, the validated EmpaToM allows separation of affective and cognitive routes to understanding others. It may thus benefit future clinical, developmental, and intervention studies on identifying selective impairments and improvement in specific components of social cognition. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Ablation of TNF-RI/RII expression in Alzheimer's disease mice leads to an unexpected enhancement of pathology: implications for chronic pan-TNF-α suppressive therapeutic strategies in the brain.

    Science.gov (United States)

    Montgomery, Sara L; Mastrangelo, Michael A; Habib, Diala; Narrow, Wade C; Knowlden, Sara A; Wright, Terry W; Bowers, William J

    2011-10-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by severe memory loss and cognitive impairment. Neuroinflammation, including the extensive production of pro-inflammatory molecules and the activation of microglia, has been implicated in the disease process. Tumor necrosis factor (TNF)-α, a prototypic pro-inflammatory cytokine, is elevated in AD, is neurotoxic, and colocalizes with amyloid plaques in AD animal models and human brains. We previously demonstrated that the expression of TNF-α is increased in AD mice at ages preceding the development of hallmark amyloid and tau pathological features and that long-term expression of this cytokine in these mice leads to marked neuronal death. Such observations suggest that TNF-α signaling promotes AD pathogenesis and that therapeutics suppressing this cytokine's activity may be beneficial. To dissect TNF-α receptor signaling requirements in AD, we generated triple-transgenic AD mice (3xTg-AD) lacking both TNF-α receptor 1 (TNF-RI) and 2 (TNF-RII), 3xTg-ADxTNF-RI/RII knock out, the cognate receptors of TNF-α. These mice exhibit enhanced amyloid and tau-related pathological features by the age of 15 months, in stark contrast to age-matched 3xTg-AD counterparts. Moreover, 3xTg-ADxTNF-RI/RII knock out-derived primary microglia reveal reduced amyloid-β phagocytic marker expression and phagocytosis activity, indicating that intact TNF-α receptor signaling is critical for microglial-mediated uptake of extracellular amyloid-β peptide pools. Overall, our results demonstrate that globally ablated TNF receptor signaling exacerbates pathogenesis and argues against long-term use of pan-anti-TNF-α inhibitors for the treatment of AD. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  1. A network analysis of ¹⁵O-H₂O PET reveals deep brain stimulation effects on brain network of Parkinson's disease.

    Science.gov (United States)

    Park, Hae-Jeong; Park, Bumhee; Kim, Hae Yu; Oh, Maeng-Keun; Kim, Joong Il; Yoon, Misun; Lee, Jong Doo; Chang, Jin Woo

    2015-05-01

    As Parkinson's disease (PD) can be considered a network abnormality, the effects of deep brain stimulation (DBS) need to be investigated in the aspect of networks. This study aimed to examine how DBS of the bilateral subthalamic nucleus (STN) affects the motor networks of patients with idiopathic PD during motor performance and to show the feasibility of the network analysis using cross-sectional positron emission tomography (PET) images in DBS studies. We obtained [¹⁵O]H₂O PET images from ten patients with PD during a sequential finger-to-thumb opposition task and during the resting state, with DBS-On and DBS-Off at STN. To identify the alteration of motor networks in PD and their changes due to STN-DBS, we applied independent component analysis (ICA) to all the cross-sectional PET images. We analysed the strength of each component according to DBS effects, task effects and interaction effects. ICA blindly decomposed components of functionally associated distributed clusters, which were comparable to the results of univariate statistical parametric mapping. ICA further revealed that STN-DBS modifies usage-strengths of components corresponding to the basal ganglia-thalamo-cortical circuits in PD patients by increasing the hypoactive basal ganglia and by suppressing the hyperactive cortical motor areas, ventrolateral thalamus and cerebellum. Our results suggest that STN-DBS may affect not only the abnormal local activity, but also alter brain networks in patients with PD. This study also demonstrated the usefulness of ICA for cross-sectional PET data to reveal network modifications due to DBS, which was not observable using the subtraction method.

  2. Microarray analysis of a salamander hopeful monster reveals transcriptional signatures of paedomorphic brain development

    Directory of Open Access Journals (Sweden)

    Putta Srikrishna

    2010-06-01

    Full Text Available Abstract Background The Mexican axolotl (Ambystoma mexicanum is considered a hopeful monster because it exhibits an adaptive and derived mode of development - paedomorphosis - that has evolved rapidly and independently among tiger salamanders. Unlike related tiger salamanders that undergo metamorphosis, axolotls retain larval morphological traits into adulthood and thus present an adult body plan that differs dramatically from the ancestral (metamorphic form. The basis of paedomorphic development was investigated by comparing temporal patterns of gene transcription between axolotl and tiger salamander larvae (Ambystoma tigrinum tigrinum that typically undergo a metamorphosis. Results Transcript abundances from whole brain and pituitary were estimated via microarray analysis on four different days post hatching (42, 56, 70, 84 dph and regression modeling was used to independently identify genes that were differentially expressed as a function of time in both species. Collectively, more differentially expressed genes (DEGs were identified as unique to the axolotl (n = 76 and tiger salamander (n = 292 than were identified as shared (n = 108. All but two of the shared DEGs exhibited the same temporal pattern of expression and the unique genes tended to show greater changes later in the larval period when tiger salamander larvae were undergoing anatomical metamorphosis. A second, complementary analysis that directly compared the expression of 1320 genes between the species identified 409 genes that differed as a function of species or the interaction between time and species. Of these 409 DEGs, 84% exhibited higher abundances in tiger salamander larvae at all sampling times. Conclusions Many of the unique tiger salamander transcriptional responses are probably associated with metamorphic biological processes. However, the axolotl also showed unique patterns of transcription early in development. In particular, the axolotl showed a genome

  3. Down Syndrome Developmental Brain Transcriptome Reveals Defective Oligodendrocyte Differentiation and Myelination.

    Science.gov (United States)

    Olmos-Serrano, Jose Luis; Kang, Hyo Jung; Tyler, William A; Silbereis, John C; Cheng, Feng; Zhu, Ying; Pletikos, Mihovil; Jankovic-Rapan, Lucija; Cramer, Nathan P; Galdzicki, Zygmunt; Goodliffe, Joseph; Peters, Alan; Sethares, Claire; Delalle, Ivana; Golden, Jeffrey A; Haydar, Tarik F; Sestan, Nenad

    2016-03-16

    Trisomy 21, or Down syndrome (DS), is the most common genetic cause of developmental delay and intellectual disability. To gain insight into the underlying molecular and cellular pathogenesis, we conducted a multi-region transcriptome analysis of DS and euploid control brains spanning from mid-fetal development to adulthood. We found genome-wide alterations in the expression of a large number of genes, many of which exhibited temporal and spatial specificity and were associated with distinct biological processes. In particular, we uncovered co-dysregulation of genes associated with oligodendrocyte differentiation and myelination that were validated via cross-species comparison to Ts65Dn trisomy mice. Furthermore, we show that hypomyelination present in Ts65Dn mice is in part due to cell-autonomous effects of trisomy on oligodendrocyte differentiation and results in slower neocortical action potential transmission. Together, these results identify defects in white matter development and function in DS, and they provide a transcriptional framework for further investigating DS neuropathogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Repeated diffusion MRI reveals earliest time point for stratification of radiotherapy response in brain metastases

    DEFF Research Database (Denmark)

    Mahmood, Faisal; Johannesen, Helle H; Geertsen, Poul

    2017-01-01

    An imaging biomarker for early prediction of treatment response potentially provides a non-invasive tool for better prognostics and individualized management of the disease. Radiotherapy (RT) response is generally related to changes in gross tumor volume manifesting months later. In this prospect......An imaging biomarker for early prediction of treatment response potentially provides a non-invasive tool for better prognostics and individualized management of the disease. Radiotherapy (RT) response is generally related to changes in gross tumor volume manifesting months later....... In this prospective study we investigated the apparent diffusion coefficient (ADC), perfusion fraction and pseudo diffusion coefficient derived from diffusion weighted MRI as potential early biomarkers for radiotherapy response of brain metastases. It was a particular aim to assess the optimal time point...... response (RECIST). The perfusion fraction and pseudo diffusion coefficient did not show sufficient prognostic value with either response assessment criteria. In conclusion this study shows that the ADC derived using high b-values may be a reliable biomarker for early assessment of radiotherapy response...

  5. Differences in brain circuitry for appetitive and reactive aggression as revealed by realistic auditory scripts

    Directory of Open Access Journals (Sweden)

    James Kenneth Moran

    2014-12-01

    Full Text Available Aggressive behavior is thought to divide into two motivational elements: The first being a self-defensively motivated aggression against threat and a second, hedonically motivated ‘appetitive’ aggression. Appetitive aggression is the less understood of the two, often only researched within abnormal psychology. Our approach is to understand it as a universal and adaptive response, and examine the functional neural activity of ordinary men (N=50 presented with an imaginative listening task involving a murderer describing a kill. We manipulated motivational context in a between-subjects design to evoke appetitive or reactive aggression, against a neutral control, measuring activity with Magnetoencephalography (MEG. Results show differences in left frontal regions in delta (2-5 Hz and alpha band (8-12 Hz for aggressive conditions and right parietal delta activity differentiating appetitive and reactive aggression. These results validate the distinction of reward-driven appetitive aggression from reactive aggression in ordinary populations at the level of functional neural brain circuitry.

  6. Error-related negativity in the skilled brain of pianists reveals motor simulation.

    Science.gov (United States)

    Proverbio, Alice Mado; Cozzi, Matteo; Orlandi, Andrea; Carminati, Manuel

    2017-03-27

    Evidences have been provided of a crucial role of multimodal audio-visuomotor processing in subserving the musical ability. In this paper we investigated whether musical audiovisual stimulation might trigger the activation of motor information in the brain of professional pianists, due to the presence of permanent gestures/sound associations. At this aim EEG was recorded in 24 pianists and naive participants engaged in the detection of rare targets while watching hundreds of video clips showing a pair of hands in the act of playing, along with a compatible or incompatible piano soundtrack. Hands size and apparent distance allowed self-ownership and agency illusions, and therefore motor simulation. Event-related potentials (ERPs) and relative source reconstruction showed the presence of an Error-related negativity (ERN) to incongruent trials at anterior frontal scalp sites, only in pianists, with no difference in naïve participants. ERN was mostly explained by an anterior cingulate cortex (ACC) source. Other sources included "hands" IT regions, the superior temporal gyrus (STG) involved in conjoined auditory and visuomotor processing, SMA and cerebellum (representing and controlling motor subroutines), and regions involved in body parts representation (somatosensory cortex, uncus, cuneus and precuneus). The findings demonstrate that instrument-specific audiovisual stimulation is able to trigger error shooting and correction neural responses via motor resonance and mirroring, being a possible aid in learning and rehabilitation. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. TMS interference with primacy and recency mechanisms reveals bimodal episodic encoding in the human brain.

    Science.gov (United States)

    Innocenti, Iglis; Cappa, Stefano F; Feurra, Matteo; Giovannelli, Fabio; Santarnecchi, Emiliano; Bianco, Giovanni; Cincotta, Massimo; Rossi, Simone

    2013-01-01

    A classic finding of the psychology of memory is the "serial position effect." Immediate free recall of a word list is more efficient for items presented early (primacy effect) or late (recency effect), with respect to those in the middle. In an event-related, randomized block design, we interfered with the encoding of unrelated words lists with brief trains of repetitive TMS (rTMS), applied coincidently with the acoustic presentation of each word to the left dorsolateral pFC, the left intraparietal lobe, and a control site (vertex). Interference of rTMS with encoding produced a clear-cut double dissociation on accuracy during immediate free recall. The primacy effect was selectively worsened by rTMS of the dorsolateral pFC, whereas recency was selectively worsened by rTMS of the intraparietal lobe. These results are in agreement with the double dissociation between short-term and long-term memory observed in neuropsychological patients and provide direct evidence of distinct cortical mechanisms of encoding in the human brain.

  8. Colored motifs reveal computational building blocks in the C. elegans brain.

    Directory of Open Access Journals (Sweden)

    Jifeng Qian

    Full Text Available BACKGROUND: Complex networks can often be decomposed into less complex sub-networks whose structures can give hints about the functional organization of the network as a whole. However, these structural motifs can only tell one part of the functional story because in this analysis each node and edge is treated on an equal footing. In real networks, two motifs that are topologically identical but whose nodes perform very different functions will play very different roles in the network. METHODOLOGY/PRINCIPAL FINDINGS: Here, we combine structural information derived from the topology of the neuronal network of the nematode C. elegans with information about the biological function of these nodes, thus coloring nodes by function. We discover that particular colorations of motifs are significantly more abundant in the worm brain than expected by chance, and have particular computational functions that emphasize the feed-forward structure of information processing in the network, while evading feedback loops. Interneurons are strongly over-represented among the common motifs, supporting the notion that these motifs process and transduce the information from the sensor neurons towards the muscles. Some of the most common motifs identified in the search for significant colored motifs play a crucial role in the system of neurons controlling the worm's locomotion. CONCLUSIONS/SIGNIFICANCE: The analysis of complex networks in terms of colored motifs combines two independent data sets to generate insight about these networks that cannot be obtained with either data set alone. The method is general and should allow a decomposition of any complex networks into its functional (rather than topological motifs as long as both wiring and functional information is available.

  9. NMR-Based Metabolic Profiling Reveals Neurochemical Alterations in the Brain of Rats Treated with Sorafenib.

    Science.gov (United States)

    Du, Changman; Shao, Xue; Zhu, Ruiming; Li, Yan; Zhao, Qian; Fu, Dengqi; Gu, Hui; Kong, Jueying; Luo, Li; Long, Hailei; Deng, Pengchi; Wang, Huijuan; Hu, Chunyan; Zhao, Yinglan; Cen, Xiaobo

    2015-11-01

    Sorafenib, an active multi-kinase inhibitor, has been widely used as a chemotherapy drug to treat advanced clear-cell renal cell carcinoma patients. In spite of the relative safety, sorafenib has been shown to exert a negative impact on cognitive functioning in cancer patients, specifically on learning and memory; however, the underlying mechanism remains unclear. In this study, an NMR-based metabolomics approach was applied to investigate the neurochemical effects of sorafenib in rats. Male rats were once daily administrated with 120 mg/kg sorafenib by gavage for 3, 7, and 28 days, respectively. NMR-based metabolomics coupled with histopathology examinations for hippocampus, prefrontal cortex (PFC), and striatum were performed. The (1)H NMR spectra data were analyzed by using multivariate pattern recognition techniques to show the time-dependent biochemical variations induced by sorafenib. Excellent separation was obtained and distinguishing metabolites were observed between sorafenib-treated and control rats. A total of 36 differential metabolites in hippocampus of rats treated with sorafenib were identified, some of which were significantly changed. Furthermore, these modified metabolites mainly reflected the disturbances in neurotransmitters, energy metabolism, membrane, and amino acids. However, only a few metabolites in PFC and striatum were altered by sorafenib. Additionally, no apparent histological changes in these three brain regions were observed in sorafenib-treated rats. Together, our findings demonstrate the disturbed metabonomics pathways, especially, in hippocampus, which may underlie the sorafenib-induced cognitive deficits in patients. This work also shows the advantage of NMR-based metabolomics over traditional approach on the study of biochemical effects of drugs.

  10. Pathway analysis reveals common pro-survival mechanisms of metyrapone and carbenoxolone after traumatic brain injury.

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    Helen L Hellmich

    Full Text Available Developing new pharmacotherapies for traumatic brain injury (TBI requires elucidation of the neuroprotective mechanisms of many structurally and functionally diverse compounds. To test our hypothesis that diverse neuroprotective drugs similarly affect common gene targets after TBI, we compared the effects of two drugs, metyrapone (MT and carbenoxolone (CB, which, though used clinically for noncognitive conditions, improved learning and memory in rats and humans. Although structurally different, both MT and CB inhibit a common molecular target, 11β hydroxysteroid dehydrogenase type 1, which converts inactive cortisone to cortisol, thereby effectively reducing glucocorticoid levels. We examined injury-induced signaling pathways to determine how the effects of these two compounds correlate with pro-survival effects in surviving neurons of the injured rat hippocampus. We found that treatment of TBI rats with MT or CB acutely induced in hippocampal neurons transcriptional profiles that were remarkably similar (i.e., a coordinated attenuation of gene expression across multiple injury-induced cell signaling networks. We also found, to a lesser extent, a coordinated increase in cell survival signals. Analysis of injury-induced gene expression altered by MT and CB provided additional insight into the protective effects of each. Both drugs attenuated expression of genes in the apoptosis, death receptor and stress signaling pathways, as well as multiple genes in the oxidative phosphorylation pathway such as subunits of NADH dehydrogenase (Complex1, cytochrome c oxidase (Complex IV and ATP synthase (Complex V. This suggests an overall inhibition of mitochondrial function. Complex 1 is the primary source of reactive oxygen species in the mitochondrial oxidative phosphorylation pathway, thus linking the protective effects of these drugs to a reduction in oxidative stress. The net effect of the drug-induced transcriptional changes observed here indicates that

  11. Non-parametric permutation thresholding for adaptive nonlinear beamformer analysis on MEG revealed oscillatory neuronal dynamics in human brain.

    Science.gov (United States)

    Ishii, Ryouhei; Canuet, Leonides; Aoki, Yasunori; Ikeda, Shunichiro; Hata, Masahiro; Iwase, Masao; Takeda, Masatoshi

    2013-01-01

    Adaptive nonlinear beamformer technique for analyzing magnetoencephalography (MEG) data has been proved to be powerful tool for both brain research and clinical applications. A general method of analyzing multiple subject data with a formal statistical treatment for the group data has been developed and applied for various types of MEG data. Our latest application of this method was frontal midline theta rhythm (Fmθ), which indicates focused attention and appears widely distributed over medial prefrontal areas in EEG recordings. To localize cortical generators of the magnetic counterpart of Fmθ precisely and identify cortical sources and underlying neural activity associated with mental calculation processing (i.e., arithmetic subtraction), we applied adaptive nonlinear beamformer and permutation analysis on MEG data. As a result, it was indicated that Fmθ is generated in the dorsal anterior cingulate and adjacent medial prefrontal cortex. Gamma event-related synchronization is as an index of activation in right parietal regions subserving mental subtraction associated with basic numerical processing and number-based spatial attention. Gamma desynchronization appeared in the right lateral prefrontal cortex, likely representing a mechanism to interrupt neural activity that can interfere with the ongoing cognitive task. We suggest that the combination of adaptive nonlinear beamformer and permutation analysis on MEG data is quite powerful tool to reveal the oscillatory neuronal dynamics in human brain.

  12. Functional imaging of brain responses to different outcomes of hypothesis testing: revealed in a category induction task.

    Science.gov (United States)

    Li, Fuhong; Cao, Bihua; Luo, Yuejia; Lei, Yi; Li, Hong

    2013-02-01

    Functional magnetic resonance imaging (fMRI) was used to examine differences in brain activation that occur when a person receives the different outcomes of hypothesis testing (HT). Participants were provided with a series of images of batteries and were asked to learn a rule governing what kinds of batteries were charged. Within each trial, the first two charged batteries were sequentially displayed, and participants would generate a preliminary hypothesis based on the perceptual comparison. Next, a third battery that served to strengthen, reject, or was irrelevant to the preliminary hypothesis was displayed. The fMRI results revealed that (1) no significant differences in brain activation were found between the 2 hypothesis-maintain conditions (i.e., strengthen and irrelevant conditions); and (2) compared with the hypothesis-maintain conditions, the hypothesis-reject condition activated the left medial frontal cortex, bilateral putamen, left parietal cortex, and right cerebellum. These findings are discussed in terms of the neural correlates of the subcomponents of HT and working memory manipulation. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Multiplex Brain Proteomic Analysis Revealed the Molecular Therapeutic Effects of Buyang Huanwu Decoction on Cerebral Ischemic Stroke Mice.

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    Hong-Jhang Chen

    Full Text Available Stroke is the second-leading cause of death worldwide, and tissue plasminogen activator (TPA is the only drug used for a limited group of stroke patients in the acute phase. Buyang Huanwu Decoction (BHD, a traditional Chinese medicine prescription, has long been used for improving neurological functional recovery in stroke. In this study, we characterized the therapeutic effect of TPA and BHD in a cerebral ischemia/reperfusion (CIR injury mouse model using multiplex proteomics approach. After the iTRAQ-based proteomics analysis, 1310 proteins were identified from the mouse brain with <1% false discovery rate. Among them, 877 quantitative proteins, 10.26% (90/877, 1.71% (15/877, and 2.62% (23/877 of the proteins was significantly changed in the CIR, BHD treatment, and TPA treatment, respectively. Functional categorization analysis showed that BHD treatment preserved the integrity of the blood-brain barrier (BBB (Alb, Fga, and Trf, suppressed excitotoxicity (Grm5, Gnai, and Gdi, and enhanced energy metabolism (Bdh, thereby revealing its multiple effects on ischemic stroke mice. Moreover, the neurogenesis marker doublecortin was upregulated, and the activity of glycogen synthase kinase 3 (GSK-3 and Tau was inhibited, which represented the neuroprotective effects. However, TPA treatment deteriorated BBB breakdown. This study highlights the potential of BHD in clinical applications for ischemic stroke.

  14. Brain quantitative proteomic responses reveal new insight of benzotriazole neurotoxicity in female Chinese rare minnow (Gobiocypris rarus).

    Science.gov (United States)

    Liang, Xuefang; Martyniuk, Christopher J; Zha, Jinmiao; Wang, Zijian

    2016-12-01

    Benzotriazole (BT) is a high-production volume chemical which has been ubiquitously detected in aquatic environments. Although adverse effects from acute and chronic exposure to BT have been reported, the neurotoxic effect of BT and the mechanisms of toxicity are not well documented. In this study, adult female Chinese rare minnow (Gobiocypris rarus) were exposed to 0.05, 0.5, and 5mg/L BT for 28days. The brain proteome showed that BT exposure mainly involved in metabolic process, signal transduction, stress response, cytoskeleton, and transport. Pathway analysis revealed that cellular processes affected by BT included cellular respiration, G-protein signal cascades, Ca(2+)-dependent signaling, cell cycle and apoptosis. Moreover, data on relative mRNA levels demonstrated that genes related to these toxic pathways were also significantly affected by BT. Furthermore, proteins affected by BT such as CKBB, GS, HPCA, VDAC1, and FLOT1A are associated with neurological disorders. Therefore, our finding suggested that BT induced molecular responses in the brain and could provide new insight into BT neurotoxicity in Chinese rare minnow. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Asymmetry of Hemispheric Network Topology Reveals Dissociable Processes between Functional and Structural Brain Connectome in Community-Living Elders

    OpenAIRE

    Yu Sun; Junhua Li; John Suckling; Lei Feng

    2017-01-01

    Human brain is structurally and functionally asymmetrical and the asymmetries of brain phenotypes have been shown to change in normal aging. Recent advances in graph theoretical analysis have showed topological lateralization between hemispheric networks in the human brain throughout the lifespan. Nevertheless, apparent discrepancies of hemispheric asymmetry were reported between the structural and functional brain networks, indicating the potentially complex asymmetry patterns between struct...

  16. Sudden Unexpected Death in Epilepsy (SUDEP)

    Science.gov (United States)

    ... this? Submit What's this? Submit Button Sudden Unexpected Death in Epilepsy (SUDEP) Recommend on Facebook Tweet Share ... living with epilepsy, the risk of Sudden Unexpected Death in Epilepsy (SUDEP) is an important concern. SUDEP ...

  17. Gender differences of brain glucose metabolic networks revealed by FDG-PET: evidence from a large cohort of 400 young adults.

    Directory of Open Access Journals (Sweden)

    Yuxiao Hu

    Full Text Available BACKGROUND: Gender differences of the human brain are an important issue in neuroscience research. In recent years, an increasing amount of evidence has been gathered from noninvasive neuroimaging studies supporting a sexual dimorphism of the human brain. However, there is a lack of imaging studies on gender differences of brain metabolic networks based on a large population sample. MATERIALS AND METHODS: FDG PET data of 400 right-handed, healthy subjects, including 200 females (age: 25:45 years, mean age ± SD: 40.9 ± 3.9 years and 200 age-matched males were obtained and analyzed in the present study. We first investigated the regional differences of brain glucose metabolism between genders using a voxel-based two-sample t-test analysis. Subsequently, we investigated the gender differences of the metabolic networks. Sixteen metabolic covariance networks using seed-based correlation were analyzed. Seven regions showing significant regional metabolic differences between genders, and nine regions conventionally used in the resting-state network studies were selected as regions-of-interest. Permutation tests were used for comparing within- and between-network connectivity between genders. RESULTS: Compared with the males, females showed higher metabolism in the posterior part and lower metabolism in the anterior part of the brain. Moreover, there were widely distributed patterns of the metabolic networks in the human brain. In addition, significant gender differences within and between brain glucose metabolic networks were revealed in the present study. CONCLUSION: This study provides solid data that reveal gender differences in regional brain glucose metabolism and brain glucose metabolic networks. These observations might contribute to the better understanding of the gender differences in human brain functions, and suggest that gender should be included as a covariate when designing experiments and explaining results of brain glucose metabolic

  18. Transsynaptic Tracing from Taste Receptor Cells Reveals Local Taste Receptor Gene Expression in Gustatory Ganglia and Brain.

    Science.gov (United States)

    Voigt, Anja; Bojahr, Juliane; Narukawa, Masataka; Hübner, Sandra; Boehm, Ulrich; Meyerhof, Wolfgang

    2015-07-01

    Taste perception begins in the oral cavity by interactions of taste stimuli with specific receptors. Specific subsets of taste receptor cells (TRCs) are activated upon tastant stimulation and transmit taste signals to afferent nerve fibers and ultimately to the brain. How specific TRCs impinge on the innervating nerves and how the activation of a subset of TRCs leads to the discrimination of tastants of different qualities and intensities is incompletely understood. To investigate the organization of taste circuits, we used gene targeting to express the transsynaptic tracer barley lectin (BL) in the gustatory system of mice. Because TRCs are not synaptically connected with the afferent nerve fibers, we first analyzed tracer production and transfer within the taste buds (TBs). Surprisingly, we found that BL is laterally transferred across all cell types in TBs of mice expressing the tracer under control of the endogenous Tas1r1 and Tas2r131 promotor, respectively. Furthermore, although we detected the BL tracer in both ganglia and brain, we also found local low-level Tas1r1 and Tas2r131 gene, and thus tracer expression in these tissues. Finally, we identified the Tas1r1 and Tas2r131-expressing cells in the peripheral and CNS using a binary genetic approach. Together, our data demonstrate that genetic transsynaptic tracing from bitter and umami receptor cells does not selectively label taste-specific neuronal circuits and reveal local taste receptor gene expression in the gustatory ganglia and the brain. Previous papers described the organization of taste pathways in mice expressing a transsynaptic tracer from transgenes in bitter or sweet/umami-sensing taste receptor cells. However, reported results differ dramatically regarding the numbers of synapses crossed and the reduction of signal intensity after each transfer step. Nevertheless, all groups claimed this approach appropriate for quality-specific visualization of taste pathways. In the present study, we

  19. Hydrogen magnetic resonance spectroscopy follow-up after radiation therapy of human brain cancer: Unexpected inverse correlation between the changes in tumor choline level and post-gadolinium magnetic resonance imaging contrast

    NARCIS (Netherlands)

    P.E. Sijens (Paul); C.J. Vecht (Charles); P.C. Levendag (Peter); P. van Dijk (Pieter); M. Oudkerk (Matthijs)

    1995-01-01

    textabstractRATIONALE AND OBJECTIVES The anatomic and metabolic changes in human brain tumors treated by radiation therapy were compared using gadolinium–enhanced magnetic resonance imaging and hydrogen (1H) magnetic resonance spectroscopy. The study was intended to assess the potential

  20. Genome-wide identification of Bcl11b gene targets reveals role in brain-derived neurotrophic factor signaling.

    Directory of Open Access Journals (Sweden)

    Bin Tang

    Full Text Available B-cell leukemia/lymphoma 11B (Bcl11b is a transcription factor showing predominant expression in the striatum. To date, there are no known gene targets of Bcl11b in the nervous system. Here, we define targets for Bcl11b in striatal cells by performing chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq in combination with genome-wide expression profiling. Transcriptome-wide analysis revealed that 694 genes were significantly altered in striatal cells over-expressing Bcl11b, including genes showing striatal-enriched expression similar to Bcl11b. ChIP-seq analysis demonstrated that Bcl11b bound a mixture of coding and non-coding sequences that were within 10 kb of the transcription start site of an annotated gene. Integrating all ChIP-seq hits with the microarray expression data, 248 direct targets of Bcl11b were identified. Functional analysis on the integrated gene target list identified several zinc-finger encoding genes as Bcl11b targets, and further revealed a significant association of Bcl11b to brain-derived neurotrophic factor/neurotrophin signaling. Analysis of ChIP-seq binding regions revealed significant consensus DNA binding motifs for Bcl11b. These data implicate Bcl11b as a novel regulator of the BDNF signaling pathway, which is disrupted in many neurological disorders. Specific targeting of the Bcl11b-DNA interaction could represent a novel therapeutic approach to lowering BDNF signaling specifically in striatal cells.

  1. PrP-C1 fragment in cattle brains reveals features of the transmissible spongiform encephalopathy associated PrPsc.

    Science.gov (United States)

    Serra, Fabienne; Müller, Joachim; Gray, John; Lüthi, Ramona; Dudas, Sandor; Czub, Stefanie; Seuberlich, Torsten

    2017-03-15

    Three different types of bovine spongiform encephalopathy (BSE) are known and supposedly caused by distinct prion strains: the classical (C-) BSE type that was typically found during the BSE epidemic, and two relatively rare atypical BSE types, termed H-BSE and L-BSE. The three BSE types differ in the molecular phenotype of the disease associated prion protein, namely the N-terminally truncated proteinase K (PK) resistant prion protein fragment (PrP res ). In this study, we report and analyze yet another PrP res type (PrP res-2011 ), which was found in severely autolytic brain samples of two cows in the framework of disease surveillance in Switzerland in 2011. Analysis of brain tissues from these animals by PK titration and PK inhibitor assays ruled out the process of autolysis as the cause for the aberrant PrP res profile. Immunochemical characterization of the PrP fragments present in the 2011 cases by epitope mapping indicated that PrP res-2011 corresponds in its primary sequence to the physiologically occurring PrP-C1 fragment. However, high speed centrifugation, sucrose gradient assay and NaPTA precipitation revealed biochemical similarities between PrP res-2011 and the disease-associated prion protein found in BSE affected cattle in terms of detergent insolubility, PK resistance and PrP aggregation. Although it remains to be established whether PrP res-2011 is associated with a transmissible disease, our results point out the need of further research on the role the PrP-C1 aggregation and misfolding in health and disease. Copyright © 2017. Published by Elsevier B.V.

  2. Voxel-based morphometry analysis reveals frontal brain differences in participants with ADHD and their unaffected siblings

    NARCIS (Netherlands)

    Bralten, Janita; Greven, Corina U.; Franke, Barbara; Mennes, Maarten; Zwiers, Marcel P.; Rommelse, Nanda N. J.; Hartman, Catharina; van der Meer, Dennis; O'Dwyer, Laurence; Oosterlaan, Jaap; Hoekstra, Pieter J.; Heslenfeld, Dirk; Arias-Vasquez, Alejandro; Buitelaar, Jan K.

    Background: Data on structural brain alterations in patients with attention-deficit/hyperactivity disorder (ADHD) have been inconsistent. Both ADHD and brain volumes have a strong genetic loading, but whether brain alterations in patients with ADHD are familial has been underexplored. We aimed to

  3. Voxel-based morphometry analysis reveals frontal brain differences in participants with ADHD and their unaffected siblings

    NARCIS (Netherlands)

    Bralten, J.; Greven, C.U.; Franke, B.; Mennes, M.; Zwiers, M.P.; Rommelse, N.N.J.; Hartman, C.A.; Meer, D. van der; O'Dwyer, L.; Oosterlaan, J.; Hoekstra, P.J.; Heslenfeld, D.; Arias-Vasquez, A.; Buitelaar, J.K.

    2016-01-01

    BACKGROUND: Data on structural brain alterations in patients with attention-deficit/hyperactivity disorder (ADHD) have been inconsistent. Both ADHD and brain volumes have a strong genetic loading, but whether brain alterations in patients with ADHD are familial has been underexplored. We aimed to

  4. Revealing the brain's adaptability and the transcranial direct current stimulation facilitating effect in inhibitory control by multiscale entropy.

    Science.gov (United States)

    Liang, Wei-Kuang; Lo, Men-Tzung; Yang, Albert C; Peng, Chung-Kang; Cheng, Shih-Kuen; Tseng, Philip; Juan, Chi-Hung

    2014-04-15

    The abilities to inhibit impulses and withdraw certain responses are critical for human's survival in a fast-changing environment. These processes happen fast, in a complex manner, and sometimes are difficult to capture with fMRI or mean electrophysiological brain signal alone. Therefore, an alternative measure that can reveal the efficiency of the neural mechanism across multiple timescales is needed for the investigation of these brain functions. The present study employs a new approach to analyzing electroencephalography (EEG) signal: the multiscale entropy (MSE), which groups data points with different timescales to reveal any occurrence of repeated patterns, in order to theoretically quantify the complexity (indicating adaptability and efficiency) of neural systems during the process of inhibitory control. From this MSE perspective, EEG signals of successful stop trials are more complex and information rich than that of unsuccessful stop trials. We further applied transcranial direct current stimulation (tDCS), with anodal electrode over presupplementary motor area (preSMA), to test the relationship between behavioral modification with the complexity of EEG signals. We found that tDCS can further increase the EEG complexity of the frontal lobe. Furthermore, the MSE pattern was found to be different between high and low performers (divided by their stop-signal reaction time), where the high-performing group had higher complexity in smaller scales and less complexity in larger scales in comparison to the low-performing group. In addition, this between-group MSE difference was found to interact with the anodal tDCS, where the increase of MSE in low performers benefitted more from the anodal tDCS. Together, the current study demonstrates that participants who suffer from poor inhibitory control can efficiently improve their performance with 10min of electrical stimulation, and such cognitive improvement can be effectively traced back to the complexity within the

  5. Diminished social reward anticipation in the broad autism phenotype as revealed by event-related brain potentials.

    Science.gov (United States)

    Cox, Anthony; Kohls, Gregor; Naples, Adam J; Mukerji, Cora E; Coffman, Marika C; Rutherford, Helena J V; Mayes, Linda C; McPartland, James C

    2015-10-01

    Diminished responsivity to reward incentives is a key contributor to the social-communication problems seen in autism spectrum disorders (ASDs). Social motivation theories suggest that individuals with ASD do not experience social interactions as rewarding, leading to negative consequences for the development of brain circuitry subserving social information. In this study, we examined neural responses to social and non-social reward anticipation in 35 typically developing young adults, examining modulation of reward sensitivity by level of autistic traits. Using an Event-related potential incentive-delay task incorporating novel, more ecologically valid forms of reward, higher expression of autistic traits was associated with an attenuated P3 response to the anticipation of social (simulated real-time video feedback from an observer), but not non-social (candy), rewards. Exploratory analyses revealed that this was unrelated to mentalizing ability. The P3 component reflects motivated attention to reward signals, suggesting attenuated motivation allocation specific to social incentives. The study extends prior findings of atypical reward anticipation in ASD, demonstrating that attenuated social reward responsiveness extends to autistic traits in the range of typical functioning. Results support the development of innovative paradigms for investigating social and non-social reward responsiveness. Insight into vulnerabilities in reward processing is critical for understanding social function in ASD. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  6. Event-related brain potentials reveal correlates of the transformation of stimulus functions through derived relations in healthy humans.

    Science.gov (United States)

    O'Regan, L M; Farina, F R; Hussey, I; Roche, R A P

    2015-03-02

    This research aimed to explore the neural correlates of relational learning by recording high-density EEG during a behavioural task involving derivation levels of varying complexity. A total of 15 participants (5 male; age range 18-23 years; mean age=20.0 years) completed contextual cue training, relational learning, function training and a derivation task while 128-channel event-related potentials (ERPs) were recorded from the scalp (Background). Differences in response latencies were observed between the two derived (symmetry and equivalence) and directly trained relations, with longest latencies found for equivalence and shortest for the directly trained relations. This pattern failed to reach statistical significance. Importantly, ERPs revealed an early P3a positivity (from 230 to 350ms) over right posterior scalp sites. Significantly larger mean amplitudes were found at three channels (P6, E115 and E121) for the equivalence relations compared to the two other types (Results). We believe this may constitute a first demonstration of differences in brain electrophysiology in the transformation of stimulus functions through derived relations of hierarchical levels of complexity (Conclusions). Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Tactile Object Familiarity in the Blind Brain Reveals the Supramodal Perceptual-Mnemonic Nature of the Perirhinal Cortex

    Science.gov (United States)

    Cacciamani, Laura; Likova, Lora T.

    2016-01-01

    This study is the first to investigate the neural underpinnings of tactile object familiarity in the blind during both perception and memory. In the sighted, the perirhinal cortex (PRC) has been implicated in the assessment of visual object familiarity—a crucial everyday task—as evidenced by reduced activation when an object becomes familiar. Here, to examine the PRC’s role in tactile object familiarity in the absence of vision, we trained blind participants on a unique memory-guided drawing technique and measured brain activity while they perceptually explored raised-line drawings, drew them from tactile memory, and scribbled (control). Functional magnetic resonance imaging (fMRI) before and after a week of training revealed a significant decrease in PRC activation from pre- to post-training (i.e., from unfamiliar to familiar) during perceptual exploration as well as memory-guided drawing, but not scribbling. This familiarity-based reduction is the first evidence that the PRC represents tactile object familiarity in the blind. Furthermore, the finding of this effect during both tactile perception and tactile memory provides the critical link in establishing the PRC as a structure whose representations are supramodal for both perception and memory. PMID:27148002

  8. Tactile object familiarity in the blind brain reveals the supramodal perceptual-mnemonic nature of the perirhinal cortex

    Directory of Open Access Journals (Sweden)

    Laura eCacciamani

    2016-04-01

    Full Text Available This study is the first to investigate the neural underpinnings of tactile object familiarity in the blind during both perception and memory. In the sighted, the perirhinal cortex (PRC has been implicated in the assessment of visual object familiarity—a crucial everyday task—as evidenced by reduced activation when an object becomes familiar. Here, to examine the PRC’s role in tactile object familiarity in the absence of vision, we trained blind subjects on a unique memory-guided drawing technique and measured brain activity while they perceptually explored raised-line drawings, drew them from tactile memory, and scribbled (control. FMRI before and after a week of training revealed a significant decrease in PRC activation from pre- to post-training (i.e., from unfamiliar to familiar during perceptual exploration as well as memory-guided drawing, but not scribbling. This familiarity-based reduction is the first evidence that the PRC represents tactile object familiarity in the blind. Furthermore, the finding of this effect during both tactile perception and tactile memory provides the critical link in establishing the PRC as a structure whose representations are supramodal for both perception and memory.

  9. Phonological abilities in literacy-impaired children: Brain potentials reveal deficient phoneme discrimination, but intact prosodic processing

    Directory of Open Access Journals (Sweden)

    Claudia Männel

    2017-02-01

    Full Text Available Intact phonological processing is crucial for successful literacy acquisition. While individuals with difficulties in reading and spelling (i.e., developmental dyslexia are known to experience deficient phoneme discrimination (i.e., segmental phonology, findings concerning their prosodic processing (i.e., suprasegmental phonology are controversial. Because there are no behavior-independent studies on the underlying neural correlates of prosodic processing in dyslexia, these controversial findings might be explained by different task demands. To provide an objective behavior-independent picture of segmental and suprasegmental phonological processing in impaired literacy acquisition, we investigated event-related brain potentials during passive listening in typically and poor-spelling German school children. For segmental phonology, we analyzed the Mismatch Negativity (MMN during vowel length discrimination, capturing automatic auditory deviancy detection in repetitive contexts. For suprasegmental phonology, we analyzed the Closure Positive Shift (CPS that automatically occurs in response to prosodic boundaries. Our results revealed spelling group differences for the MMN, but not for the CPS, indicating deficient segmental, but intact suprasegmental phonological processing in poor spellers. The present findings point towards a differential role of segmental and suprasegmental phonology in literacy disorders and call for interventions that invigorate impaired literacy by utilizing intact prosody in addition to training deficient phonemic awareness.

  10. Sudden, unexpected death due to glioblastoma: report of three fatal cases and review of the literature

    OpenAIRE

    Riezzo, Irene; Zamparese, Rosanna; Neri, Margherita; de Stefano, Francesco; Parente, Ruggero; Pomara, Cristoforo; Turillazzi, Emanuela; Ventura, Francesco; Fineschi, Vittorio

    2013-01-01

    Abstract Sudden death from an undiagnosed primary intracranial neoplasm is an exceptionally rare event, with reported frequencies in the range of 0.02% to 2.1% in medico-legal autopsy series and only 12% of all cases of sudden, unexpected death due to primary intracranial tumors are due to glioblastomas. We present three cases of sudden, unexpected death due to glioblastoma, with different brain localization and expression. A complete methodological forensic approach by means of autopsy, hist...

  11. Chamomile reveals to be a potent galactogogue: the unexpected effect.

    Science.gov (United States)

    Silva, Fernando V; Dias, Francisca; Costa, Gustavo; Campos, Maria da Graça

    2018-01-01

    Good habits of breastfeeding have been associated with many long-term health benefits. Nowadays, improvement is seen in the health of children and mothers who practice exclusive breastfeeding for the first six months of life. The search of new potent stimulants for milk production is important to promote lactation, mainly in cases where breastfeeding is a difficult task. This report presents a case of a woman who accidentally realized an abundant amount of milk and had high breast tension, a few hours after consuming chamomile. Although usual consumption of chamomile during pregnancy and lactation are documented for several purposes, the galactogogue effect was never reported. In this case report, we document for the first time the influence of chamomile in a lactating woman by increasing lactogenesis. This article also highlights the need of more research in this field to assure the safety of the intake, by women, of herbal product without the risk for them or the newborns.

  12. Phylogenetic relationships within Aglaopheniidae (Cnidaria, Hydrozoa) reveal unexpected generic diversity

    OpenAIRE

    Postaire, Bautisse; Magalon, Hélène; Bourmaud, Chloé A.-F.,; Gravier-Bonnet, Nicole; Bruggemann, Henrich J.

    2015-01-01

    International audience; Morphology can be misleading in the representation of phylogenetic relationships, especially in simple organisms like cnidarians and particularly in hydrozoans. These suspension feeders are widely distributed in many marine ecosystems, and the family Aglaopheniidae Marktanner-Turneretscher, 1890 is among the most diverse and visible, especially on tropical coral reefs. The taxonomy of this family is based on morphological characters with emphasis on reproductive struct...

  13. Single muscle fiber proteomics reveals unexpected mitochondrial specialization

    DEFF Research Database (Denmark)

    Murgia, Marta; Nagaraj, Nagarjuna; Deshmukh, Atul S

    2015-01-01

    Mammalian skeletal muscles are composed of multinucleated cells termed slow or fast fibers according to their contractile and metabolic properties. Here, we developed a high-sensitivity workflow to characterize the proteome of single fibers. Analysis of segments of the same fiber by traditional...... and unbiased proteomics methods yielded the same subtype assignment. We discovered novel subtype-specific features, most prominently mitochondrial specialization of fiber types in substrate utilization. The fiber type-resolved proteomes can be applied to a variety of physiological and pathological conditions...... and illustrate the utility of single cell type analysis for dissecting proteomic heterogeneity....

  14. Correlation profiling of brain sub-cellular proteomes reveals co-assembly of synaptic proteins and subcellular distribution

    NARCIS (Netherlands)

    Pandya, N.J. (Nikhil J.); Koopmans, F. (Frank); J.A. Slotman (Johan A.); Paliukhovich, I. (Iryna); A.B. Houtsmuller (Adriaan); A.B. Smit (August); Li, K.W. (Ka Wan)

    2017-01-01

    textabstractProtein correlation profiling might assist in defining co-assembled proteins and subcellular distribution. Here, we quantified the proteomes of five biochemically isolated mouse brain cellular sub-fractions, with emphasis on synaptic compartments, from three brain regions, hippocampus,

  15. Proton Magnetic Resonance Spectroscopy and MRI Reveal No Evidence for Brain Mitochondrial Dysfunction in Children with Autism Spectrum Disorder

    Science.gov (United States)

    Corrigan, Neva M.; Shaw, Dennis. W. W.; Richards, Todd L.; Estes, Annette M.; Friedman, Seth D.; Petropoulos, Helen; Artru, Alan A.; Dager, Stephen R.

    2012-01-01

    Brain mitochondrial dysfunction has been proposed as an etiologic factor in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopic imaging ([superscript 1]HMRS) and MRI were used to assess for evidence of brain mitochondrial dysfunction in longitudinal samples of children with ASD or developmental delay (DD), and cross-sectionally…

  16. Masked priming of conceptual features reveals differential brain activation during unconscious access to conceptual action and sound information.

    Directory of Open Access Journals (Sweden)

    Natalie M Trumpp

    Full Text Available Previous neuroimaging studies suggested an involvement of sensory-motor brain systems during conceptual processing in support of grounded cognition theories of conceptual memory. However, in these studies with visible stimuli, contributions of strategic imagery or semantic elaboration processes to observed sensory-motor activity cannot be entirely excluded. In the present study, we therefore investigated the electrophysiological correlates of unconscious feature-specific priming of action- and sound-related concepts within a novel feature-priming paradigm to specifically probe automatic processing of conceptual features without the contribution of possibly confounding factors such as orthographic similarity or response congruency. Participants were presented with a masked subliminal prime word and a subsequent visible target word. In the feature-priming conditions primes as well as targets belonged to the same conceptual feature dimension (action or sound, e.g., typewriter or radio whereas in the two non-priming conditions, either the primes or the targets consisted of matched control words with low feature relevance (e.g., butterfly or candle. Event-related potential analyses revealed unconscious feature-specific priming effects at fronto-central electrodes within 100 to 180 ms after target stimulus onset that differed with regard to topography and underlying neural generators. In congruency with previous findings under visible stimulation conditions, these differential subliminal ERP feature-priming effects demonstrate an unconscious automatic access to action versus sound features of concepts. The present results therefore support grounded cognition theory suggesting that activity in sensory and motor areas during conceptual processing can also occur unconsciously and is not mandatorily accompanied by a vivid conscious experience of the conceptual content such as in imagery.

  17. Masked Priming of Conceptual Features Reveals Differential Brain Activation during Unconscious Access to Conceptual Action and Sound Information

    Science.gov (United States)

    Trumpp, Natalie M.; Traub, Felix; Kiefer, Markus

    2013-01-01

    Previous neuroimaging studies suggested an involvement of sensory-motor brain systems during conceptual processing in support of grounded cognition theories of conceptual memory. However, in these studies with visible stimuli, contributions of strategic imagery or semantic elaboration processes to observed sensory-motor activity cannot be entirely excluded. In the present study, we therefore investigated the electrophysiological correlates of unconscious feature-specific priming of action- and sound-related concepts within a novel feature-priming paradigm to specifically probe automatic processing of conceptual features without the contribution of possibly confounding factors such as orthographic similarity or response congruency. Participants were presented with a masked subliminal prime word and a subsequent visible target word. In the feature-priming conditions primes as well as targets belonged to the same conceptual feature dimension (action or sound, e.g., typewriter or radio) whereas in the two non-priming conditions, either the primes or the targets consisted of matched control words with low feature relevance (e.g., butterfly or candle). Event-related potential analyses revealed unconscious feature-specific priming effects at fronto-central electrodes within 100 to 180 ms after target stimulus onset that differed with regard to topography and underlying neural generators. In congruency with previous findings under visible stimulation conditions, these differential subliminal ERP feature-priming effects demonstrate an unconscious automatic access to action versus sound features of concepts. The present results therefore support grounded cognition theory suggesting that activity in sensory and motor areas during conceptual processing can also occur unconsciously and is not mandatorily accompanied by a vivid conscious experience of the conceptual content such as in imagery. PMID:23741518

  18. Coagulation and fibrinolytic parameters as predictors for small-vessel disease revealed by magnetic resonance imaging of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Kohriyama, Tatsuo; Yamaguchi, Shinya; Tanaka, Eiji; Yamamura, Yasuhiro; Nakamura, Shigenobu [Hiroshima Univ. (Japan). School of Medicine

    1996-05-01

    We correlated coagulation and fibrinolytic parameters with small-vessel disease revealed by magnetic resonance imaging (MRI) of the brain. One hundred and eleven patients with asymptomatic or symptomatic cerebral infarction were randomly selected for the study; 57 males and 54 females with an average age of 66.6{+-}9.6, age range 40 to 85, years old. Among them, 76 patients had a history of symptomatic cerebral infarction; 38 patients hypertension; and 24 patients diabetes mellitus. Patients with large cortical infarction, cerebral hemorrhage, demyelinating disease or mass lesions were excluded from the present study. The MRI scans were reviewed for areas with increased signal intensity on T2-weighted images. The small infarction was defined as a lesion less than 10 mm in diameter. The activity of von Willebrand factor (vWF) correlated significantly with the grade of caps at the anterior and posterior horns of the lateral ventricle, and the number of small infarctions in the subcortical white matter and basal ganglia, suggesting vWF could be a predictor for these small-vessel disease. The grade of caps at posterior horn of the lateral ventricle and the number of small infarctions in the subcortical white matter were associated significantly with the concentration of plasma fibrinogen and reversely with the activity of antithrombin III, an inhibitory factor in coagulation system. These results indicate that hypercoagulable state may causatively relate with small-vessel disease in the territory of medullary artery branching from cortical artery. On the contrary, these coagulation parameters did not correlate significantly with small ischemic lesions in the territory of perforating artery. No correlation was observed between the level of marker proteins for platelet activation and the degree of small-vessel disease, indicating the activation of platelet could not associate with the etiology of small-vessel disease. (author)

  19. Group-Level Progressive Alterations in Brain Connectivity Patterns Revealed by Diffusion-Tensor Brain Networks across Severity Stages in Alzheimer's Disease.

    Science.gov (United States)

    Rasero, Javier; Alonso-Montes, Carmen; Diez, Ibai; Olabarrieta-Landa, Laiene; Remaki, Lakhdar; Escudero, Iñaki; Mateos, Beatriz; Bonifazi, Paolo; Fernandez, Manuel; Arango-Lasprilla, Juan Carlos; Stramaglia, Sebastiano; Cortes, Jesus M

    2017-01-01

    Alzheimer's disease (AD) is a chronically progressive neurodegenerative disease highly correlated to aging. Whether AD originates by targeting a localized brain area and propagates to the rest of the brain across disease-severity progression is a question with an unknown answer. Here, we aim to provide an answer to this question at the group-level by looking at differences in diffusion-tensor brain networks. In particular, making use of data from Alzheimer's Disease Neuroimaging Initiative (ADNI), four different groups were defined (all of them matched by age, sex and education level): G1 (N1 = 36, healthy control subjects, Control), G2 (N2 = 36, early mild cognitive impairment, EMCI), G3 (N3 = 36, late mild cognitive impairment, LMCI) and G4 (N4 = 36, AD). Diffusion-tensor brain networks were compared across three disease stages: stage I (Control vs. EMCI), stage II (Control vs. LMCI) and stage III (Control vs. AD). The group comparison was performed using the multivariate distance matrix regression analysis, a technique that was born in genomics and was recently proposed to handle brain functional networks, but here applied to diffusion-tensor data. The results were threefold: First, no significant differences were found in stage I. Second, significant differences were found in stage II in the connectivity pattern of a subnetwork strongly associated to memory function (including part of the hippocampus, amygdala, entorhinal cortex, fusiform gyrus, inferior and middle temporal gyrus, parahippocampal gyrus and temporal pole). Third, a widespread disconnection across the entire AD brain was found in stage III, affecting more strongly the same memory subnetwork appearing in stage II, plus the other new subnetworks, including the default mode network, medial visual network, frontoparietal regions and striatum. Our results are consistent with a scenario where progressive alterations of connectivity arise as the disease severity increases and provide the brain areas

  20. Altered spontaneous brain activity in patients with acute spinal cord injury revealed by resting-state functional MRI.

    Directory of Open Access Journals (Sweden)

    Ling Zhu

    Full Text Available Previous neuroimaging studies have provided evidence of structural and functional reorganization of brain in patients with chronic spinal cord injury (SCI. However, it remains unknown whether the spontaneous brain activity changes in acute SCI. In this study, we investigated intrinsic brain activity in acute SCI patients using a regional homogeneity (ReHo analysis based on resting-state functional magnetic resonance imaging.A total of 15 patients with acute SCI and 16 healthy controls participated in the study. The ReHo value was used to evaluate spontaneous brain activity, and voxel-wise comparisons of ReHo were performed to identify brain regions with altered spontaneous brain activity between groups. We also assessed the associations between ReHo and the clinical scores in brain regions showing changed spontaneous brain activity.Compared with the controls, the acute SCI patients showed decreased ReHo in the bilateral primary motor cortex/primary somatosensory cortex, bilateral supplementary motor area/dorsal lateral prefrontal cortex, right inferior frontal gyrus, bilateral dorsal anterior cingulate cortex and bilateral caudate; and increased ReHo in bilateral precuneus, the left inferior parietal lobe, the left brainstem/hippocampus, the left cingulate motor area, bilateral insula, bilateral thalamus and bilateral cerebellum. The average ReHo values of the left thalamus and right insula were negatively correlated with the international standards for the neurological classification of spinal cord injury motor scores.Our findings indicate that acute distant neuronal damage has an immediate impact on spontaneous brain activity. In acute SCI patients, the ReHo was prominently altered in brain regions involved in motor execution and cognitive control, default mode network, and which are associated with sensorimotor compensatory reorganization. Abnormal ReHo values in the left thalamus and right insula could serve as potential biomarkers for

  1. RNA Sequencing Analysis Reveals Interactions between Breast Cancer or Melanoma Cells and the Tissue Microenvironment during Brain Metastasis.

    Science.gov (United States)

    Sato, Ryo; Nakano, Teppei; Hosonaga, Mari; Sampetrean, Oltea; Harigai, Ritsuko; Sasaki, Takashi; Koya, Ikuko; Okano, Hideyuki; Kudoh, Jun; Saya, Hideyuki; Arima, Yoshimi

    2017-01-01

    Metastasis is the main cause of treatment failure and death in cancer patients. Metastasis of tumor cells to the brain occurs frequently in individuals with breast cancer, non-small cell lung cancer, or melanoma. Despite recent advances in our understanding of the causes and in the treatment of primary tumors, the biological and molecular mechanisms underlying the metastasis of cancer cells to the brain have remained unclear. Metastasizing cancer cells interact with their microenvironment in the brain to establish metastases. We have now developed mouse models of brain metastasis based on intracardiac injection of human breast cancer or melanoma cell lines, and we have performed RNA sequencing analysis to identify genes in mouse brain tissue and the human cancer cells whose expression is associated specifically with metastasis. We found that the expressions of the mouse genes Tph2, Sspo, Ptprq, and Pole as well as those of the human genes CXCR4, PLLP, TNFSF4, VCAM1, SLC8A2, and SLC7A11 were upregulated in brain tissue harboring metastases. Further characterization of such genes that contribute to the establishment of brain metastases may provide a basis for the development of new therapeutic strategies and consequent improvement in the prognosis of cancer patients.

  2. RNA Sequencing Analysis Reveals Interactions between Breast Cancer or Melanoma Cells and the Tissue Microenvironment during Brain Metastasis

    Directory of Open Access Journals (Sweden)

    Ryo Sato

    2017-01-01

    Full Text Available Metastasis is the main cause of treatment failure and death in cancer patients. Metastasis of tumor cells to the brain occurs frequently in individuals with breast cancer, non–small cell lung cancer, or melanoma. Despite recent advances in our understanding of the causes and in the treatment of primary tumors, the biological and molecular mechanisms underlying the metastasis of cancer cells to the brain have remained unclear. Metastasizing cancer cells interact with their microenvironment in the brain to establish metastases. We have now developed mouse models of brain metastasis based on intracardiac injection of human breast cancer or melanoma cell lines, and we have performed RNA sequencing analysis to identify genes in mouse brain tissue and the human cancer cells whose expression is associated specifically with metastasis. We found that the expressions of the mouse genes Tph2, Sspo, Ptprq, and Pole as well as those of the human genes CXCR4, PLLP, TNFSF4, VCAM1, SLC8A2, and SLC7A11 were upregulated in brain tissue harboring metastases. Further characterization of such genes that contribute to the establishment of brain metastases may provide a basis for the development of new therapeutic strategies and consequent improvement in the prognosis of cancer patients.

  3. Asymmetry of Hemispheric Network Topology Reveals Dissociable Processes between Functional and Structural Brain Connectome in Community-Living Elders

    Directory of Open Access Journals (Sweden)

    Yu Sun

    2017-11-01

    Full Text Available Human brain is structurally and functionally asymmetrical and the asymmetries of brain phenotypes have been shown to change in normal aging. Recent advances in graph theoretical analysis have showed topological lateralization between hemispheric networks in the human brain throughout the lifespan. Nevertheless, apparent discrepancies of hemispheric asymmetry were reported between the structural and functional brain networks, indicating the potentially complex asymmetry patterns between structural and functional networks in aging population. In this study, using multimodal neuroimaging (resting-state fMRI and structural diffusion tensor imaging, we investigated the characteristics of hemispheric network topology in 76 (male/female = 15/61, age = 70.08 ± 5.30 years community-dwelling older adults. Hemispheric functional and structural brain networks were obtained for each participant. Graph theoretical approaches were then employed to estimate the hemispheric topological properties. We found that the optimal small-world properties were preserved in both structural and functional hemispheric networks in older adults. Moreover, a leftward asymmetry in both global and local levels were observed in structural brain networks in comparison with a symmetric pattern in functional brain network, suggesting a dissociable process of hemispheric asymmetry between structural and functional connectome in healthy older adults. Finally, the scores of hemispheric asymmetry in both structural and functional networks were associated with behavioral performance in various cognitive domains. Taken together, these findings provide new insights into the lateralized nature of multimodal brain connectivity, highlight the potentially complex relationship between structural and functional brain network alterations, and augment our understanding of asymmetric structural and functional specializations in normal aging.

  4. Prohibitin: an unexpected role in sex dimorphic functions

    OpenAIRE

    Nguyen, K. Hoa; Ande, Sudharsana R.; Mishra, Suresh

    2016-01-01

    Sex differences are known to exist in adipose and immune functions in the body, and sex steroid hormones are known to be involved in sexually dimorphic biological and pathological processes related to adipose-immune interaction. However, our knowledge of proteins that mediate such differences is poor. Two novel obese mice models, Mito-Ob and m-Mito-Ob, that have been reported recently have revealed an unexpected role of a pleiotropic protein, prohibitin (PHB), in sex differences in adipose an...

  5. Gender differences in the structural connectome of the teenage brain revealed by generalized q-sampling MRI

    Directory of Open Access Journals (Sweden)

    Yeu-Sheng Tyan

    2017-01-01

    Full Text Available The question of whether there are biological differences between male and female brains is a fraught one, and political positions and prior expectations seem to have a strong influence on the interpretation of scientific data in this field. This question is relevant to issues of gender differences in the prevalence of psychiatric conditions, including autism, attention deficit hyperactivity disorder (ADHD, Tourette's syndrome, schizophrenia, dyslexia, depression, and eating disorders. Understanding how gender influences vulnerability to these conditions is significant. Diffusion magnetic resonance imaging (dMRI provides a non-invasive method to investigate brain microstructure and the integrity of anatomical connectivity. Generalized q-sampling imaging (GQI has been proposed to characterize complicated fiber patterns and distinguish fiber orientations, providing an opportunity for more accurate, higher-order descriptions through the water diffusion process. Therefore, we aimed to investigate differences in the brain's structural network between teenage males and females using GQI. This study included 59 (i.e., 33 males and 26 females age- and education-matched subjects (age range: 13 to 14 years. The structural connectome was obtained by graph theoretical and network-based statistical (NBS analyses. Our findings show that teenage male brains exhibit better intrahemispheric communication, and teenage female brains exhibit better interhemispheric communication. Our results also suggest that the network organization of teenage male brains is more local, more segregated, and more similar to small-world networks than teenage female brains. We conclude that the use of an MRI study with a GQI-based structural connectomic approach like ours presents novel insights into network-based systems of the brain and provides a new piece of the puzzle regarding gender differences.

  6. Magnetic Resonance Imaging of Cerebral Malaria Patients Reveals Distinct Pathogenetic Processes in Different Parts of the Brain

    OpenAIRE

    Sanjib Mohanty; Benjamin, Laura A; Megharay Majhi; Premanand Panda; Sam Kampondeni; Sahu, Praveen K.; Akshaya Mohanty; Mahanta, Kishore C.; Rajyabardhan Pattnaik; Rashmi R. Mohanty; Sonia Joshi; Anita Mohanty; Ian W. Turnbull; Dondorp, Arjen M.; Taylor, Terrie E.

    2017-01-01

    ABSTRACT The mechanisms underlying the rapidly reversible brain swelling described in patients with cerebral malaria (CM) are unknown. Using a 1.5-Tesla (T) magnetic resonance imaging (MRI) scanner, we undertook an observational study in Rourkela, India, of 11 Indian patients hospitalized with CM and increased brain volume. Among the 11 cases, there were 5 adults and 6 children. All patients had reduced consciousness and various degrees of cortical swelling at baseline. The latter was predomi...

  7. Our Faces in the Dog's Brain: Functional Imaging Reveals Temporal Cortex Activation during Perception of Human Faces.

    Science.gov (United States)

    Cuaya, Laura V; Hernández-Pérez, Raúl; Concha, Luis

    2016-01-01

    Dogs have a rich social relationship with humans. One fundamental aspect of it is how dogs pay close attention to human faces in order to guide their behavior, for example, by recognizing their owner and his/her emotional state using visual cues. It is well known that humans have specific brain regions for the processing of other human faces, yet it is unclear how dogs' brains process human faces. For this reason, our study focuses on describing the brain correlates of perception of human faces in dogs using functional magnetic resonance imaging (fMRI). We trained seven domestic dogs to remain awake, still and unrestrained inside an MRI scanner. We used a visual stimulation paradigm with block design to compare activity elicited by human faces against everyday objects. Brain activity related to the perception of faces changed significantly in several brain regions, but mainly in the bilateral temporal cortex. The opposite contrast (i.e., everyday objects against human faces) showed no significant brain activity change. The temporal cortex is part of the ventral visual pathway, and our results are consistent with reports in other species like primates and sheep, that suggest a high degree of evolutionary conservation of this pathway for face processing. This study introduces the temporal cortex as candidate to process human faces, a pillar of social cognition in dogs.

  8. Connectivity in Language Areas of the Brain in Cochlear Implant Users as Revealed by fNIRS.

    Science.gov (United States)

    McKay, Colette M; Shah, Adnan; Seghouane, Abd-Krim; Zhou, Xin; Cross, William; Litovsky, Ruth

    2016-01-01

    Many studies, using a variety of imaging techniques, have shown that deafness induces functional plasticity in the brain of adults with late-onset deafness, and in children changes the way the auditory brain develops. Cross modal plasticity refers to evidence that stimuli of one modality (e.g. vision) activate neural regions devoted to a different modality (e.g. hearing) that are not normally activated by those stimuli. Other studies have shown that multimodal brain networks (such as those involved in language comprehension, and the default mode network) are altered by deafness, as evidenced by changes in patterns of activation or connectivity within the networks. In this paper, we summarise what is already known about brain plasticity due to deafness and propose that functional near-infra-red spectroscopy (fNIRS) is an imaging method that has potential to provide prognostic and diagnostic information for cochlear implant users. Currently, patient history factors account for only 10 % of the variation in post-implantation speech understanding, and very few post-implantation behavioural measures of hearing ability correlate with speech understanding. As a non-invasive, inexpensive and user-friendly imaging method, fNIRS provides an opportunity to study both pre- and post-implantation brain function. Here, we explain the principle of fNIRS measurements and illustrate its use in studying brain network connectivity and function with example data.

  9. Connectivity profiles reveal the relationship between brain areas for social cognition in human and monkey temporoparietal cortex.

    Science.gov (United States)

    Mars, Rogier B; Sallet, Jérôme; Neubert, Franz-Xaver; Rushworth, Matthew F S

    2013-06-25

    The human ability to infer the thoughts and beliefs of others, often referred to as "theory of mind," as well as the predisposition to even consider others, are associated with activity in the temporoparietal junction (TPJ) area. Unlike the case of most human brain areas, we have little sense of whether or how TPJ is related to brain areas in other nonhuman primates. It is not possible to address this question by looking for similar task-related activations in nonhuman primates because there is no evidence that nonhuman primates engage in theory-of-mind tasks in the same manner as humans. Here, instead, we explore the relationship by searching for areas in the macaque brain that interact with other macaque brain regions in the same manner as human TPJ interacts with other human brain regions. In other words, we look for brain regions with similar positions within a distributed neural circuit in the two species. We exploited the fact that human TPJ has a unique functional connectivity profile with cortical areas with known homologs in the macaque. For each voxel in the macaque temporal and parietal cortex we evaluated the similarity of its functional connectivity profile to that of human TPJ. We found that areas in the middle part of the superior temporal cortex, often associated with the processing of faces and other social stimuli, have the most similar connectivity profile. These results suggest that macaque face processing areas and human mentalizing areas might have a similar precursor.

  10. Our Faces in the Dog's Brain: Functional Imaging Reveals Temporal Cortex Activation during Perception of Human Faces.

    Directory of Open Access Journals (Sweden)

    Laura V Cuaya

    Full Text Available Dogs have a rich social relationship with humans. One fundamental aspect of it is how dogs pay close attention to human faces in order to guide their behavior, for example, by recognizing their owner and his/her emotional state using visual cues. It is well known that humans have specific brain regions for the processing of other human faces, yet it is unclear how dogs' brains process human faces. For this reason, our study focuses on describing the brain correlates of perception of human faces in dogs using functional magnetic resonance imaging (fMRI. We trained seven domestic dogs to remain awake, still and unrestrained inside an MRI scanner. We used a visual stimulation paradigm with block design to compare activity elicited by human faces against everyday objects. Brain activity related to the perception of faces changed significantly in several brain regions, but mainly in the bilateral temporal cortex. The opposite contrast (i.e., everyday objects against human faces showed no significant brain activity change. The temporal cortex is part of the ventral visual pathway, and our results are consistent with reports in other species like primates and sheep, that suggest a high degree of evolutionary conservation of this pathway for face processing. This study introduces the temporal cortex as candidate to process human faces, a pillar of social cognition in dogs.

  11. Analysis of tumor- and stroma-supplied proteolytic networks reveals a brain metastasis-promoting role for cathepsin S

    Science.gov (United States)

    Sevenich, Lisa; Bowman, Robert L.; Mason, Steven D.; Quail, Daniela F.; Rapaport, Franck; Elie, Benelita T.; Brogi, Edi; Brastianos, Priscilla K.; Hahn, William C.; Holsinger, Leslie J.; Massagué, Joan; Leslie, Christina S.; Joyce, Johanna A.

    2014-01-01

    Metastasis remains the most common cause of death in most cancers, with limited therapies for combating disseminated disease. While the primary tumor microenvironment is an important regulator of cancer progression, it is less well understood how different tissue environments influence metastasis. We analyzed tumor-stroma interactions that modulate organ tropism of brain, bone and lung metastasis in xenograft models. We identified a number of potential modulators of site-specific metastasis, including cathepsin S as a regulator of breast-to-brain metastasis. High cathepsin S expression at the primary site correlated with decreased brain metastasis-free survival in breast cancer patients. Both macrophages and tumor cells produce cathepsin S, and only the combined depletion significantly reduced brain metastasis in vivo. Cathepsin S specifically mediates blood-brain barrier transmigration via proteolytic processing of the junctional adhesion molecule (JAM)-B. Pharmacological inhibition of cathepsin S significantly reduced experimental brain metastasis, supporting its consideration as a therapeutic target for this disease. PMID:25086747

  12. Group-Level Progressive Alterations in Brain Connectivity Patterns Revealed by Diffusion-Tensor Brain Networks across Severity Stages in Alzheimer’s Disease

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    Javier Rasero

    2017-07-01

    Full Text Available Alzheimer’s disease (AD is a chronically progressive neurodegenerative disease highly correlated to aging. Whether AD originates by targeting a localized brain area and propagates to the rest of the brain across disease-severity progression is a question with an unknown answer. Here, we aim to provide an answer to this question at the group-level by looking at differences in diffusion-tensor brain networks. In particular, making use of data from Alzheimer’s Disease Neuroimaging Initiative (ADNI, four different groups were defined (all of them matched by age, sex and education level: G1 (N1 = 36, healthy control subjects, Control, G2 (N2 = 36, early mild cognitive impairment, EMCI, G3 (N3 = 36, late mild cognitive impairment, LMCI and G4 (N4 = 36, AD. Diffusion-tensor brain networks were compared across three disease stages: stage I (Control vs. EMCI, stage II (Control vs. LMCI and stage III (Control vs. AD. The group comparison was performed using the multivariate distance matrix regression analysis, a technique that was born in genomics and was recently proposed to handle brain functional networks, but here applied to diffusion-tensor data. The results were threefold: First, no significant differences were found in stage I. Second, significant differences were found in stage II in the connectivity pattern of a subnetwork strongly associated to memory function (including part of the hippocampus, amygdala, entorhinal cortex, fusiform gyrus, inferior and middle temporal gyrus, parahippocampal gyrus and temporal pole. Third, a widespread disconnection across the entire AD brain was found in stage III, affecting more strongly the same memory subnetwork appearing in stage II, plus the other new subnetworks, including the default mode network, medial visual network, frontoparietal regions and striatum. Our results are consistent with a scenario where progressive alterations of connectivity arise as the disease severity increases and provide the

  13. Why don't you like me? Midfrontal theta power in response to unexpected peer rejection feedback.

    Science.gov (United States)

    van der Molen, M J W; Dekkers, L M S; Westenberg, P M; van der Veen, F M; van der Molen, M W

    2017-02-01

    Social connectedness theory posits that the brain processes social rejection as a threat to survival. Recent electrophysiological evidence suggests that midfrontal theta (4-8Hz) oscillations in the EEG provide a window on the processing of social rejection. Here we examined midfrontal theta dynamics (power and inter-trial phase synchrony) during the processing of social evaluative feedback. We employed the Social Judgment paradigm in which 56 undergraduate women (mean age=19.67 years) were asked to communicate their expectancies about being liked vs. disliked by unknown peers. Expectancies were followed by feedback indicating social acceptance vs. rejection. Results revealed a significant increase in EEG theta power to unexpected social rejection feedback. This EEG theta response could be source-localized to brain regions typically reported during activation of the saliency network (i.e., dorsal anterior cingulate cortex, insula, inferior frontal gyrus, frontal pole, and the supplementary motor area). Theta phase dynamics mimicked the behavior of the time-domain averaged feedback-related negativity (FRN) by showing stronger phase synchrony for feedback that was unexpected vs. expected. Theta phase, however, differed from the FRN by also displaying stronger phase synchrony in response to rejection vs. acceptance feedback. Together, this study highlights distinct roles for midfrontal theta power and phase synchrony in response to social evaluative feedback. Our findings contribute to the literature by showing that midfrontal theta oscillatory power is sensitive to social rejection but only when peer rejection is unexpected, and this theta response is governed by a widely distributed neural network implicated in saliency detection and conflict monitoring. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Complex interplay between brain function and structure during cerebral amyloidosis in APP transgenic mouse strains revealed by multi-parametric MRI comparison.

    OpenAIRE

    Grandjean J.; Derungs R.; Kulic L.; Welt T.; Henkerlmann M.; Nitsch R.M.; Rudin M.

    2016-01-01

    Alzheimer's disease is a fatal neurodegenerative disorder affecting the aging population. Neuroimaging methods in particular magnetic resonance imaging (MRI) have helped reveal alterations in the brain structure metabolism and function of patients and in groups at risk of developing AD yet the nature of these alterations is poorly understood. Neuroimaging in mice is attractive for investigating mechanisms underlying functional and structural changes associated with AD pathology. Several precl...

  15. What can volumes reveal about human brain evolution? A framework for bridging behavioral, histometric and volumetric perspectives

    Directory of Open Access Journals (Sweden)

    Alexandra A de Sousa

    2014-06-01

    Full Text Available An overall relationship between brain size and cognitive ability exists across primates. Can more specific information about neural function be gleaned from cortical area volumes? Numerous studies have found significant relationships between brain structures and behaviors. However, few studies have speculated about brain structure-function relationships from the microanatomical to the macroanatomical level. Here we address this problem in comparative neuroanatomy, where the functional relevance of overall brain size and the sizes of cortical regions have been poorly understood, by considering comparative psychology, with measures of visual acuity and the perception of visual illusions. We outline a model where the macroscopic size (volume or surface area of a cortical region (such as the primary visual cortex, V1 is related to the microstructure of discrete brain regions. The hypothesis developed here is that a larger absolute V1 can process more information with greater fidelity due to having more neurons to represent a field of space. This is the first time that the necessary comparative neuroanatomical research at the microstructural level has been brought to bear on the issue. The evidence suggests that as the size of V1 increases: the number of neurons increases, the neuron density decreases, and the density of neuronal connections increases. Thus, we describe how information about gross neuromorphology, using V1 as a model for the study of other cortical areas, may permit interpretations of cortical function.

  16. Magnetic Resonance Imaging of Cerebral Malaria Patients Reveals Distinct Pathogenetic Processes in Different Parts of the Brain.

    Science.gov (United States)

    Mohanty, Sanjib; Benjamin, Laura A; Majhi, Megharay; Panda, Premanand; Kampondeni, Sam; Sahu, Praveen K; Mohanty, Akshaya; Mahanta, Kishore C; Pattnaik, Rajyabardhan; Mohanty, Rashmi R; Joshi, Sonia; Mohanty, Anita; Turnbull, Ian W; Dondorp, Arjen M; Taylor, Terrie E; Wassmer, Samuel C

    2017-01-01

    The mechanisms underlying the rapidly reversible brain swelling described in patients with cerebral malaria (CM) are unknown. Using a 1.5-Tesla (T) magnetic resonance imaging (MRI) scanner, we undertook an observational study in Rourkela, India, of 11 Indian patients hospitalized with CM and increased brain volume. Among the 11 cases, there were 5 adults and 6 children. All patients had reduced consciousness and various degrees of cortical swelling at baseline. The latter was predominately posterior in distribution. The findings on diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps were consistent with vasogenic edema in all cases. Reversibility after 48 to 72 h was observed in >90% of cases. DWI/ADC mismatch suggested the additional presence of cytotoxic edema in the basal nuclei of 5 patients; all of these had perfusion parameters consistent with vascular engorgement and not with ischemic infarcts. Our results suggest that an impairment of the blood-brain barrier is responsible for the brain swelling in CM. In 5 cases, vasogenic edema occurred in conjunction with changes in the basal nuclei consistent with venous congestion, likely to be caused by the sequestration of Plasmodium falciparum-infected erythrocytes. While both mechanisms have been individually postulated to play an important role in the development of CM, this is the first demonstration of their concurrent involvement in different parts of the brain. The clinical and radiological characteristics observed in the majority of our patients are consistent with posterior reversible encephalopathy syndrome (PRES), and we show for the first time a high frequency of PRES in the context of CM. IMPORTANCE The pathophysiology and molecular mechanisms underlying cerebral malaria (CM) are still poorly understood. Recent neuroimaging studies demonstrated that brain swelling is a common feature in CM and a major contributor to death in pediatric patients. Consequently, determining the

  17. Coping with Unexpected Events: Depression and Trauma

    Science.gov (United States)

    ... Announcements Partnering with DBSA Coping With Unexpected Events: Depression and Trauma Responding to Traumatic Events When we ... immediately. back to top How to Cope with Depression After Trauma The healing process after a traumatic ...

  18. Exploratory metabolomic analyses reveal compounds correlated with lutein concentration in frontal cortex, hippocampus, and occipital cortex of human infant brain

    Science.gov (United States)

    Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with...

  19. Glucose metabolism during resting state reveals abnormal brain networks organization in the Alzheimer's disease and mild cognitive impairment.

    Directory of Open Access Journals (Sweden)

    Gretel Sanabria-Diaz

    Full Text Available This paper aims to study the abnormal patterns of brain glucose metabolism co-variations in Alzheimer disease (AD and Mild Cognitive Impairment (MCI patients compared to Normal healthy controls (NC using the Alzheimer Disease Neuroimaging Initiative (ADNI database. The local cerebral metabolic rate for glucose (CMRgl in a set of 90 structures belonging to the AAL atlas was obtained from Fluro-Deoxyglucose Positron Emission Tomography data in resting state. It is assumed that brain regions whose CMRgl values are significantly correlated are functionally associated; therefore, when metabolism is altered in a single region, the alteration will affect the metabolism of other brain areas with which it interrelates. The glucose metabolism network (represented by the matrix of the CMRgl co-variations among all pairs of structures was studied using the graph theory framework. The highest concurrent fluctuations in CMRgl were basically identified between homologous cortical regions in all groups. Significant differences in CMRgl co-variations in AD and MCI groups as compared to NC were found. The AD and MCI patients showed aberrant patterns in comparison to NC subjects, as detected by global and local network properties (global and local efficiency, clustering index, and others. MCI network's attributes showed an intermediate position between NC and AD, corroborating it as a transitional stage from normal aging to Alzheimer disease. Our study is an attempt at exploring the complex association between glucose metabolism, CMRgl covariations and the attributes of the brain network organization in AD and MCI.

  20. In vivo proton magnetic resonance spectroscopy reveals region specific metabolic responses to SIV infection in the macaque brain

    Directory of Open Access Journals (Sweden)

    Joo Chan-Gyu

    2009-06-01

    Full Text Available Abstract Background In vivo proton magnetic resonance spectroscopy (1H-MRS studies of HIV-infected humans have demonstrated significant metabolic abnormalities that vary by brain region, but the causes are poorly understood. Metabolic changes in the frontal cortex, basal ganglia and white matter in 18 SIV-infected macaques were investigated using MRS during the first month of infection. Results Changes in the N-acetylaspartate (NAA, choline (Cho, myo-inositol (MI, creatine (Cr and glutamine/glutamate (Glx resonances were quantified both in absolute terms and relative to the creatine resonance. Most abnormalities were observed at the time of peak viremia, 2 weeks post infection (wpi. At that time point, significant decreases in NAA and NAA/Cr, reflecting neuronal injury, were observed only in the frontal cortex. Cr was significantly elevated only in the white matter. Changes in Cho and Cho/Cr were similar across the brain regions, increasing at 2 wpi, and falling below baseline levels at 4 wpi. MI and MI/Cr levels were increased across all brain regions. Conclusion These data best support the hypothesis that different brain regions have variable intrinsic vulnerabilities to neuronal injury caused by the AIDS virus.

  1. Quantitative Analysis of Kynurenine Aminotransferase II in the Adult Rat Brain Reveals High Expression in Proliferative Zones and Corpus Callosum.

    Science.gov (United States)

    Song, Chang; Clark, Sarah M; Vaughn, Chloe N; Nicholson, James D; Murphy, Kelley J; Mou, Ta-Chung M; Schwarcz, Robert; Hoffman, Gloria E; Tonelli, Leonardo H

    2018-01-15

    Kynurenic acid, a metabolite of the kynurenine pathway of tryptophan degradation, acts as an endogenous antagonist of alpha7 nicotinic and NMDA receptors and is implicated in a number of neurophysiological and neuropathological processes including cognition and neurodegenerative events. Therefore, kynurenine aminotransferase II (KAT II/AADAT), the enzyme responsible for the formation of the majority of neuroactive kynurenic acid in the brain, has prompted significant interest. Using immunohistochemistry, this enzyme was localized primarily in astrocytes throughout the adult rat brain, but detailed neuroanatomical studies are lacking. Here, we employed quantitative in situ hybridization to analyze the relative expression of KAT II mRNA in the brain of rats under normal conditions and 6 h after the administration of lipopolysaccharides (LPSs). Specific hybridization signals for KAT II were detected, with the highest expression in the subventricular zone (SVZ), the rostral migratory stream and the floor of the third ventricle followed by the corpus callosum and the hippocampus. This pattern of mRNA expression was paralleled by differential protein expression, determined by serial dilutions of antibodies (up to 1:1 million), and was confirmed to be primarily astrocytic in nature. The mRNA signal in the SVZ and the hippocampus was substantially increased by the LPS treatment without detectable changes elsewhere. These results demonstrate that KAT II is expressed in the rat brain in a region-specific manner and that gene expression is sensitive to inflammatory processes. This suggests an unrecognized role for kynurenic acid in the brain's germinal zones. Published by Elsevier Ltd.

  2. Brain networks engaged in audiovisual integration during speech perception revealed by persistent homology-based network filtration.

    Science.gov (United States)

    Kim, Heejung; Hahm, Jarang; Lee, Hyekyoung; Kang, Eunjoo; Kang, Hyejin; Lee, Dong Soo

    2015-05-01

    The human brain naturally integrates audiovisual information to improve speech perception. However, in noisy environments, understanding speech is difficult and may require much effort. Although the brain network is supposed to be engaged in speech perception, it is unclear how speech-related brain regions are connected during natural bimodal audiovisual or unimodal speech perception with counterpart irrelevant noise. To investigate the topological changes of speech-related brain networks at all possible thresholds, we used a persistent homological framework through hierarchical clustering, such as single linkage distance, to analyze the connected component of the functional network during speech perception using functional magnetic resonance imaging. For speech perception, bimodal (audio-visual speech cue) or unimodal speech cues with counterpart irrelevant noise (auditory white-noise or visual gum-chewing) were delivered to 15 subjects. In terms of positive relationship, similar connected components were observed in bimodal and unimodal speech conditions during filtration. However, during speech perception by congruent audiovisual stimuli, the tighter couplings of left anterior temporal gyrus-anterior insula component and right premotor-visual components were observed than auditory or visual speech cue conditions, respectively. Interestingly, visual speech is perceived under white noise by tight negative coupling in the left inferior frontal region-right anterior cingulate, left anterior insula, and bilateral visual regions, including right middle temporal gyrus, right fusiform components. In conclusion, the speech brain network is tightly positively or negatively connected, and can reflect efficient or effortful processes during natural audiovisual integration or lip-reading, respectively, in speech perception.

  3. Violence-related content in video game may lead to functional connectivity changes in brain networks as revealed by fMRI-ICA in young men.

    Science.gov (United States)

    Zvyagintsev, M; Klasen, M; Weber, R; Sarkheil, P; Esposito, F; Mathiak, K A; Schwenzer, M; Mathiak, K

    2016-04-21

    In violent video games, players engage in virtual aggressive behaviors. Exposure to virtual aggressive behavior induces short-term changes in players' behavior. In a previous study, a violence-related version of the racing game "Carmageddon TDR2000" increased aggressive affects, cognitions, and behaviors compared to its non-violence-related version. This study investigates the differences in neural network activity during the playing of both versions of the video game. Functional magnetic resonance imaging (fMRI) recorded ongoing brain activity of 18 young men playing the violence-related and the non-violence-related version of the video game Carmageddon. Image time series were decomposed into functional connectivity (FC) patterns using independent component analysis (ICA) and template-matching yielded a mapping to established functional brain networks. The FC patterns revealed a decrease in connectivity within 6 brain networks during the violence-related compared to the non-violence-related condition: three sensory-motor networks, the reward network, the default mode network (DMN), and the right-lateralized frontoparietal network. Playing violent racing games may change functional brain connectivity, in particular and even after controlling for event frequency, in the reward network and the DMN. These changes may underlie the short-term increase of aggressive affects, cognitions, and behaviors as observed after playing violent video games. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  4. Brain Membrane Proteome and Phosphoproteome Reveal Molecular Basis Associating with Nursing and Foraging Behaviors of Honeybee Workers.

    Science.gov (United States)

    Han, Bin; Fang, Yu; Feng, Mao; Hu, Han; Hao, Yue; Ma, Chuan; Huo, Xinmei; Meng, Lifeng; Zhang, Xufeng; Wu, Fan; Li, Jianke

    2017-10-06

    The brain is a vital organ in regulating complex social behaviors of honeybees including learning and memory. Knowledge of how brain membrane proteins and their phosphorylation underlie the age-related behavioral polyethism is still lacking. A hitherto age-resolved brain membrane proteome and phosphoproteome were reported in adult worker bees from two strains of honeybee (Apis mellifera ligustica): Italian bee (ITB) and Royal Jelly bee (RJB), a line selected from ITB for increased RJ outputs over four decades. There were 1079 membrane protein groups identified, and 417 unique phosphosites were located in 179 membrane protein groups mainly phosphorylated by kinase families of MAPKs, CDKs, and CK2. Age-resolved dynamics of brain membrane proteome and phosphoproteome are indicative of their correlation with the neurobiological requirements during the adult life of honeybee workers. To stimulate immature brain cell development in newly emerged bees (NEBs), the enriched functional classes associated with metabolism of carbohydrates, nucleosides, and lipids by the up-regulated proteins suggest their enhanced role in driving cell maturity of the brain. In nurse bees (NBs) and forager bees (FBs), a higher number of membrane proteins and phosphoproteins were expressed as compared with in the young stages, and the enriched signal-transduction-related pathways by the up-regulated proteins suggest their significances in sustaining the intensive information processing during nursing and foraging activities. Notably, RJB has shaped unique membrane proteome and phosphoproteome settings to consolidate nursing and foraging behaviors in response to decades of selection underpinning the elevated RJ yields. In RJB NBs, the enriched pathways of phosphatidylinositol signaling and arachidonic acid metabolism indicate a stronger olfaction sensation in response to larval pheromone stimulation. In RJB FBs, the enriched pathways related to signal processing such as SNARE interactions in

  5. Effects of Hormone Therapy on Brain Volumes Changes of Postmenopausal Women Revealed by Optimally-Discriminative Voxel-Based Morphometry.

    Directory of Open Access Journals (Sweden)

    Tianhao Zhang

    Full Text Available The Women's Health Initiative Memory Study Magnetic Resonance Imaging (WHIMS-MRI provides an opportunity to evaluate how menopausal hormone therapy (HT affects the structure of older women's brains. Our earlier work based on region of interest (ROI analysis demonstrated potential structural changes underlying adverse effects of HT on cognition. However, the ROI-based analysis is limited in statistical power and precision, and cannot provide fine-grained mapping of whole-brain changes.We aimed to identify local structural differences between HT and placebo groups from WHIMS-MRI in a whole-brain refined level, by using a novel method, named Optimally-Discriminative Voxel-Based Analysis (ODVBA. ODVBA is a recently proposed imaging pattern analysis approach for group comparisons utilizing a spatially adaptive analysis scheme to accurately locate areas of group differences, thereby providing superior sensitivity and specificity to detect the structural brain changes over conventional methods.Women assigned to HT treatments had significant Gray Matter (GM losses compared to the placebo groups in the anterior cingulate and the adjacent medial frontal gyrus, and the orbitofrontal cortex, which persisted after multiple comparison corrections. There were no regions where HT was significantly associated with larger volumes compared to placebo, although a trend of marginal significance was found in the posterior cingulate cortical area. The CEE-Alone and CEE+MPA groups, although compared with different placebo controls, demonstrated similar effects according to the spatial patterns of structural changes.HT had adverse effects on GM volumes and risk for cognitive impairment and dementia in older women. These findings advanced our understanding of the neurobiological underpinnings of HT effects.

  6. A Voxel-Based Morphometry Study Reveals Local Brain Structural Alterations associated With Ambient Fine Particles in older women

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    Ramon Casanova

    2016-10-01

    Full Text Available Objective: Exposure to ambient fine particulate matter (PM2.5: PM with aerodynamic diameters <2.5µm has been linked with cognitive deficits in older adults. Using fine-grained voxel-wise analyses, we examined whether PM2.5 exposure also affects brain structure.Methods: Brain MRI data were obtained from 1,365 women (aged 71-89 in the Women’s Health Initiative Memory Study and local brain volumes were estimated using RAVENS (regional analysis of volumes in normalized space. Based on geocoded residential locations and air monitoring data from the U.S. Environmental Protection Agency, we employed a spatiotemporal model to estimate long-term (3-year average exposure to ambient PM2.5 preceding MRI scans. Voxel-wise linear regression models were fit separately to gray matter (GM and white matter (WM maps to analyze associations between brain structure and PM2.5 exposure, with adjustment for potential confounders. Results: Increased PM2.5 exposure was associated with smaller volumes in both cortical GM and subcortical WM areas. For GM, associations were clustered in the bilateral superior, middle, and medial frontal gyri. For WM, the largest clusters were in the frontal lobe, with smaller clusters in the temporal, parietal, and occipital lobes. No statistically significant associations were observed between PM2.5 exposure and hippocampal volumes. Conclusions: Long-term PM2.5 exposures may accelerate loss of both GM and WM in older women. While our previous work linked WM decreased volumes to PM2.5 air pollution, this is the first neuroimaging study reporting associations between air pollution exposure and smaller volumes of cortical GM. Our data support the hypothesized synaptic neurotoxicity of airborne particles.

  7. Novel biochemical manipulation of brain serotonin reveals a role of serotonin in the circadian rhythm of sleep-wake cycles.

    Science.gov (United States)

    Nakamaru-Ogiso, Eiko; Miyamoto, Hiroyuki; Hamada, Kozo; Tsukada, Koji; Takai, Katsuji

    2012-06-01

    Serotonin (5-HT) neurons have been implicated in the modulation of many physiological functions, including mood regulation, feeding, and sleep. Impaired or altered 5-HT neurotransmission appears to be involved in depression and anxiety symptoms, as well as in sleep disorders. To investigate brain 5-HT functions in sleep, we induced 5-HT deficiency through acute tryptophan depletion in rats by intraperitoneally injecting a tryptophan-degrading enzyme called tryptophan side chain oxidase I (TSOI). After the administration of TSOI (20 units), plasma tryptophan levels selectively decreased to 1-2% of those of controls within 2 h, remained under 1% for 12-24 h, and then recovered between 72 and 96 h. Following plasma tryptophan levels, brain 5-HT levels decreased to ∼30% of the control level after 6 h, remained at this low level for 20-30 h, and returned to normal after 72 h. In contrast, brain norepinephreine and dopamine levels remained unchanged. After TSOI injection, the circadian rhythms of the sleep-wake cycle and locomotive activity were lost and broken into minute(s) ultradian alternations. The hourly slow-wave sleep (SWS) time significantly increased at night, but decreased during the day, whereas rapid eye movement sleep was significantly reduced during the day. However, daily total (cumulative) SWS time was retained at the normal level. As brain 5-HT levels gradually recovered 48 h after TSOI injection, the circadian rhythms of sleep-wake cycles and locomotive activity returned to normal. Our results suggest that 5-HT with a rapid turnover rate plays an important role in the circadian rhythm of sleep-wake cycles. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  8. Ganglioside Profiling of the Human Retina: Comparison with Other Ocular Structures, Brain and Plasma Reveals Tissue Specificities.

    Science.gov (United States)

    Sibille, Estelle; Berdeaux, Olivier; Martine, Lucy; Bron, Alain M; Creuzot-Garcher, Catherine P; He, Zhiguo; Thuret, Gilles; Bretillon, Lionel; Masson, Elodie A Y

    2016-01-01

    Gangliosides make a wide family of glycosphingolipids, highly heterogeneous in both the ceramide moiety and the oligosaccharide chain. While ubiquitously expressed in mammalian tissues, they are particularly abundant in the brain and the peripheral nervous system. Gangliosides are known to play a crucial role in the development, maintenance and functional integrity of the nervous system. However, the expression and roles of gangliosides in the retina, although often considered as a window on the brain, has been far less studied. We performed an in-depth analysis of gangliosides of the human retina, especially using powerful LC/MS methods. We compared the pattern of ganglioside classes and ceramide molecular species of this tissue with other ocular structures and with brain and plasma in elderly human individuals. About a hundred of ganglioside molecular species among 15 distinct classes were detected illustrating the huge structural diversity of these compounds. The retina exhibited a very diverse ganglioside profile and shared several common features with the brain (prominence of tetraosylgangliosides, abundance of d20:1 long chain base and 18:0 fatty acid…). However, the retina stood out with the specific expression of GD3, GT3 and AcGT3, which further presented a peculiar molecular species distribution. The unique ganglioside pattern we observed in the human retina suggests that these ganglioside species play a specific role in the structure and function of this tissue. This lipidomic study, by highlighting retina specific ganglioside species, opens up novel research directions for a better understanding of the biological role of gangliosides in the retina.

  9. Simultaneous Brain-Cervical Cord fMRI Reveals Intrinsic Spinal Cord Plasticity during Motor Sequence Learning.

    Science.gov (United States)

    Vahdat, Shahabeddin; Lungu, Ovidiu; Cohen-Adad, Julien; Marchand-Pauvert, Veronique; Benali, Habib; Doyon, Julien

    2015-06-01

    The spinal cord participates in the execution of skilled movements by translating high-level cerebral motor representations into musculotopic commands. Yet, the extent to which motor skill acquisition relies on intrinsic spinal cord processes remains unknown. To date, attempts to address this question were limited by difficulties in separating spinal local effects from supraspinal influences through traditional electrophysiological and neuroimaging methods. Here, for the first time, we provide evidence for local learning-induced plasticity in intact human spinal cord through simultaneous functional magnetic resonance imaging of the brain and spinal cord during motor sequence learning. Specifically, we show learning-related modulation of activity in the C6-C8 spinal region, which is independent from that of related supraspinal sensorimotor structures. Moreover, a brain-spinal cord functional connectivity analysis demonstrates that the initial linear relationship between the spinal cord and sensorimotor cortex gradually fades away over the course of motor sequence learning, while the connectivity between spinal activity and cerebellum gains strength. These data suggest that the spinal cord not only constitutes an active functional component of the human motor learning network but also contributes distinctively from the brain to the learning process. The present findings open new avenues for rehabilitation of patients with spinal cord injuries, as they demonstrate that this part of the central nervous system is much more plastic than assumed before. Yet, the neurophysiological mechanisms underlying this intrinsic functional plasticity in the spinal cord warrant further investigations.

  10. Proteomic Analysis of Brain and Cerebrospinal Fluid from the Three Major Forms of Neuronal Ceroid Lipofuscinosis Reveals Potential Biomarkers.

    Science.gov (United States)

    Sleat, David E; Tannous, Abla; Sohar, Istvan; Wiseman, Jennifer A; Zheng, Haiyan; Qian, Meiqian; Zhao, Caifeng; Xin, Winnie; Barone, Rosemary; Sims, Katherine B; Moore, Dirk F; Lobel, Peter

    2017-10-06

    Clinical trials have been conducted for the neuronal ceroid lipofuscinoses (NCLs), a group of neurodegenerative lysosomal diseases that primarily affect children. Whereas clinical rating systems will evaluate long-term efficacy, biomarkers to measure short-term response to treatment would be extremely valuable. To identify candidate biomarkers, we analyzed autopsy brain and matching CSF samples from controls and three genetically distinct NCLs due to deficiencies in palmitoyl protein thioesterase 1 (CLN1 disease), tripeptidyl peptidase 1 (CLN2 disease), and CLN3 protein (CLN3 disease). Proteomic and biochemical methods were used to analyze lysosomal proteins, and, in general, we find that changes in protein expression compared with control were most similar between CLN2 disease and CLN3 disease. This is consistent with previous observations of biochemical similarities between these diseases. We also conducted unbiased proteomic analyses of CSF and brain using isobaric labeling/quantitative mass spectrometry. Significant alterations in protein expression were identified in each NCL, including reduced STXBP1 in CLN1 disease brain. Given the confounding variable of post-mortem changes, additional validation is required, but this study provides a useful starting set of candidate NCL biomarkers for further evaluation.

  11. Graph theoretical analysis reveals the reorganization of the brain network pattern in primary open angle glaucoma patients

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jieqiong [Chinese Academy of Sciences, State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Beijing (China); Li, Ting; Xian, Junfang [Capital Medical University, Department of Radiology, Beijing Tongren Hospital, Beijing (China); Wang, Ningli [Capital Medical University, Department of Ophthalmology, Beijing Tongren Hospital, Beijing (China); He, Huiguang [Chinese Academy of Sciences, State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Beijing (China); Chinese Academy of Sciences, Research Center for Brain-Inspired Intelligence, Institute of Automation, Beijing (China)

    2016-11-15

    Most previous glaucoma studies with resting-state fMRI have focused on the neuronal activity in the individual structure of the brain, yet ignored the functional communication of anatomically separated structures. The purpose of this study is to investigate the efficiency of the functional communication change or not in glaucoma patients. We applied the resting-state fMRI data to construct the connectivity network of 25 normal controls and 25 age-gender-matched primary open angle glaucoma patients. Graph theoretical analysis was performed to assess brain network pattern differences between the two groups. No significant differences of the global network measures were found between the two groups. However, the local measures were radically reorganized in glaucoma patients. Comparing with the hub regions in normal controls' network, we found that six hub regions disappeared and nine hub regions appeared in the network of patients. In addition, the betweenness centralities of two altered hub regions, right fusiform gyrus and right lingual gyrus, were significantly correlated with the visual field mean deviation. Although the efficiency of functional communication is preserved in the brain network of the glaucoma at the global level, the efficiency of functional communication is altered in some specialized regions of the glaucoma. (orig.)

  12. Brain abscess with an unexpected finding: Actinomyces meyeri CNS infection

    DEFF Research Database (Denmark)

    Eiset, Andreas Halgreen; Thomsen, Marianne Kragh; Wejse, Christian

    Background: CNS infection caused by Actinomyces spp. is rare and the subtype Actinomyces meyeri even rarer. Risk factors include periodontal disease and alcohol overuse. We present a case report of a 54-year-old female with dental and lung foci. Case history: A female was hospitalised with tonic......-up. The source of infection was most likely periodontitis with spread to the lungs from aspiration or oropharyngeal secretion into the respiratory tract, alternatively from haematogenous spread. Conclusions: We report of the successful treatment of a cerebral abscess caused by A. meyeri with narrow spectrum...

  13. Investigating Initial Disclosures and Reactions to Unexpected, Positive HPV Diagnosis

    Science.gov (United States)

    Smith, Rachel A.; Hernandez, Rachael; Catona, Danielle

    2013-01-01

    Initial disclosures of health conditions are critical communication moments. Existing research focuses on disclosers; integrating confidants into studies of initial disclosures is needed. Guided by the disclosure decision-making model (DD-MM; Greene, 2009), this study examined what diagnosed persons and confidants may say when faced with unexpected test results and unexpected disclosures, respectively. Participants (N = 151) recorded an audio-visual message for another person, after imagining that they or the other person had just received unexpected, positive HPV test results. The qualitative analysis revealed four themes: (1) impression management and social distance, (2) invisible symptoms and advice regarding future disclosures, (3) expressing and acknowledging emotional reactions, and (4) misunderstandings and lacking knowledge about HPV. These findings suggested that DD-MM may be a relevant framework for understanding not only when disclosers share, but what disclosers and confidants say in early conversations about new diagnoses. While disclosers’ and confidants’ messages showed marked similarities, important differences appeared. For example, confidants focused on assuaging disclosers’ fear about the consequences, whereas disclosers expressed distress related to their uncertainty about the prognosis of an HPV infection and how to prepare for next steps. The discussion highlighted implications for the DD-MM, HPV disclosures, and future interventions. PMID:25642121

  14. Changes in Male Rat Sexual Behavior and Brain Activity Revealed by Functional Magnetic Resonance Imaging in Response to Chronic Mild Stress.

    Science.gov (United States)

    Chen, Guotao; Yang, Baibing; Chen, Jianhuai; Zhu, Leilei; Jiang, Hesong; Yu, Wen; Zang, Fengchao; Chen, Yun; Dai, Yutian

    2017-12-21

    G, Yang B, Chen J, et al. Changes in Male Rat Sexual Behavior and Brain Activity Revealed by Functional Magnetic Resonance Imaging in Response to Chronic Mild Stress. J Sex Med 2017;XX:XXX-XXX. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  15. FTIR Imaging of Brain Tissue Reveals Crystalline Creatine Deposits Are an ex Vivo Marker of Localized Ischemia during Murine Cerebral Malaria: General Implications for Disease Neurochemistry

    Science.gov (United States)

    2012-01-01

    Phosphocreatine is a major cellular source of high energy phosphates, which is crucial to maintain cell viability under conditions of impaired metabolic states, such as decreased oxygen and energy availability (i.e., ischemia). Many methods exist for the bulk analysis of phosphocreatine and its dephosphorylated product creatine; however, no method exists to image the distribution of creatine or phosphocreatine at the cellular level. In this study, Fourier transform infrared (FTIR) spectroscopic imaging has revealed the ex vivo development of creatine microdeposits in situ in the brain region most affected by the disease, the cerebellum of cerebral malaria (CM) diseased mice; however, such deposits were also observed at significantly lower levels in the brains of control mice and mice with severe malaria. In addition, the number of deposits was observed to increase in a time-dependent manner during dehydration post tissue cutting. This challenges the hypotheses in recent reports of FTIR spectroscopic imaging where creatine microdeposits found in situ within thin sections from epileptic, Alzheimer’s (AD), and amlyoid lateral sclerosis (ALS) diseased brains were proposed to be disease specific markers and/or postulated to contribute to the brain pathogenesis. As such, a detailed investigation was undertaken, which has established that the creatine microdeposits exist as the highly soluble HCl salt or zwitterion and are an ex-vivo tissue processing artifact and, hence, have no effect on disease pathogenesis. They occur as a result of creatine crystallization during dehydration (i.e., air-drying) of thin sections of brain tissue. As ischemia and decreased aerobic (oxidative metabolism) are common to many brain disorders, regions of elevated creatine-to-phosphocreatine ratio are likely to promote crystal formation during tissue dehydration (due to the lower water solubility of creatine relative to phosphocreatine). The results of this study have demonstrated that

  16. A comparative antibody analysis of Pannexin1 expression in four rat brain regions reveals varying subcellular localizations

    Directory of Open Access Journals (Sweden)

    Angela C Cone

    2013-02-01

    Full Text Available Pannexin1 (Panx1 channels release cytosolic ATP in response to signaling pathways. Panx1 is highly expressed in the central nervous system. We used four antibodies with different Panx1 anti-peptide epitopes to analyze four regions of rat brain. These antibodies labeled the same bands in Western blots and had highly similar patterns of immunofluorescence in tissue culture cells expressing Panx1, but Western blots of brain lysates from Panx1 knockout and control mice showed different banding patterns. Localizations of Panx1 in brain slices were generated using automated wide-field mosaic confocal microscopy for imaging large regions of interest while retaining maximum resolution for examining cell populations and compartments. We compared Panx1 expression over the cerebellum, hippocampus with adjacent cortex, thalamus and olfactory bulb. While Panx1 localizes to the same neuronal cell types, subcellular localizations differ. Two antibodies with epitopes against the intracellular loop and one against the carboxy terminus preferentially labeled cell bodies, while an antibody raised against an N-terminal peptide highlighted neuronal processes more than cell bodies. These labeling patterns may be a reflection of different cellular and subcellular localizations of full-length and/or modified Panx1 channels where each antibody is highlighting unique or differentially accessible Panx1 populations. However, we cannot rule out that one or more of these antibodies have specificity issues. All data associated with experiments from these four antibodies are presented in a manner that allows them to be compared and our claims thoroughly evaluated, rather than eliminating results that were questionable. Each antibody is given a unique identifier through the NIF Antibody Registry that can be used to track usage of individual antibodies across papers and all image and metadata are made available in the public repository, the Cell Centered Database, for on

  17. Proteomic analysis of the mitochondria from embryonic and postnatal rat brains reveals response to developmental changes in energy demands.

    Science.gov (United States)

    Villeneuve, Lance M; Stauch, Kelly L; Fox, Howard S

    2014-09-23

    Many biological processes converge on the mitochondria. In such systems, where many pathways converge, manipulation of the components can produce varied and far-reaching effects. Due to the centrality of the mitochondria in many cellular pathways, we decided to investigate the brain mitochondrial proteome during early development. Using a SWATH mass spectrometry-based technique, we were able to identify vast proteomic alterations between whole brain mitochondria from rats at embryonic day 18 compared to postnatal day 7. These findings include statistically significant alterations in proteins involved in glycolysis and mitochondrial trafficking/dynamics. Additionally, bioinformatic analysis enabled the identification of HIF1A and XBP1 as upstream transcriptional regulators of many of the differentially expressed proteins. These data suggest that the cell is rearranging the mitochondria to accommodate special energy demands and that cytosolic proteins exert mitochondrial effects through dynamic interactions with the mitochondria. Although mitochondria play critical roles in many cellular pathways, our understanding of how these organelles change over time is limited. The changes occurring in the mitochondria at early time points are especially important as many mitochondrial disorders produce neurological dysfunction early in life. Herein, we utilize a SWATH mass spectrometry approach to quantify proteomic alterations of rat brain mitochondria between embryonic and postnatal stages. We found this method to be highly reproducible, enabling the identification of alterations in many biochemical pathways and mitochondrial properties. This insight into the distinct changes in these biological pathways to maintain homeostasis under divergent conditions will help elucidate the pathological changes occurring in disease states. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Integration of miRNA and protein profiling reveals coordinated neuroadaptations in the alcohol-dependent mouse brain.

    Directory of Open Access Journals (Sweden)

    Giorgio Gorini

    Full Text Available The molecular mechanisms underlying alcohol dependence involve different neurochemical systems and are brain region-dependent. Chronic Intermittent Ethanol (CIE procedure, combined with a Two-Bottle Choice voluntary drinking paradigm, represents one of the best available animal models for alcohol dependence and relapse drinking. MicroRNAs, master regulators of the cellular transcriptome and proteome, can regulate their targets in a cooperative, combinatorial fashion, ensuring fine tuning and control over a large number of cellular functions. We analyzed cortex and midbrain microRNA expression levels using an integrative approach to combine and relate data to previous protein profiling from the same CIE-subjected samples, and examined the significance of the data in terms of relative contribution to alcohol consumption and dependence. MicroRNA levels were significantly altered in CIE-exposed dependent mice compared with their non-dependent controls. More importantly, our integrative analysis identified modules of coexpressed microRNAs that were highly correlated with CIE effects and predicted target genes encoding differentially expressed proteins. Coexpressed CIE-relevant proteins, in turn, were often negatively correlated with specific microRNA modules. Our results provide evidence that microRNA-orchestrated translational imbalances are driving the behavioral transition from alcohol consumption to dependence. This study represents the first attempt to combine ex vivo microRNA and protein expression on a global scale from the same mammalian brain samples. The integrative systems approach used here will improve our understanding of brain adaptive changes in response to drug abuse and suggests the potential therapeutic use of microRNAs as tools to prevent or compensate multiple neuroadaptations underlying addictive behavior.

  19. Baseline brain activity changes in patients with clinically isolated syndrome revealed by resting-state functional MRI

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yaou; Duan, Yunyun; Liang, Peipeng; Jia, Xiuqin; Yu, Chunshui [Dept. of Radiology, Xuanwu Hospital, Capital Medical Univ., Beijing (China); Ye, Jing [Dept. of Neurology, Xuanwu Hospital, Capital Medical Univ., Beijing (China); Butzkueven, Helmut [Dept. of Medicine, Univ. of Melbourne, Melbourne (Australia); Dong, Huiqing [Dept. of Neurology, Xuanwu Hospital, Capital Medical Univ., Beijing (China); Li, Kuncheng [Dept. of Radiology, Xuanwu Hospital, Capital Medical Univ., Beijing (China); Beijing Key Laboratory of MRI and Brain Informatics, Beijing (China)], E-mail: likuncheng1955@yahoo.com.cn

    2012-11-15

    Background A clinically isolated syndrome (CIS) is the first manifestation of multiple sclerosis (MS). Previous task-related functional MRI studies demonstrate functional reorganization in patients with CIS. Purpose To assess baseline brain activity changes in patients with CIS by using the technique of regional amplitude of low frequency fluctuation (ALFF) as an index in resting-state fMRI. Material and Methods Resting-state fMRIs data acquired from 37 patients with CIS and 37 age- and sex-matched normal controls were compared to investigate ALFF differences. The relationships between ALFF in regions with significant group differences and the EDSS (Expanded Disability Status Scale), disease duration, and T2 lesion volume (T2LV) were further explored. Results Patients with CIS had significantly decreased ALFF in the right anterior cingulate cortex, right caudate, right lingual gyrus, and right cuneus (P < 0.05 corrected for multiple comparisons using Monte Carlo simulation) compared to normal controls, while no significantly increased ALFF were observed in CIS. No significant correlation was found between the EDSS, disease duration, T2LV, and ALFF in regions with significant group differences. Conclusion In patients with CIS, resting-state fMRI demonstrates decreased activity in several brain regions. These results are in contrast to patients with established MS, in whom ALFF demonstrates several regions of increased activity. It is possible that this shift from decreased activity in CIS to increased activity in MS could reflect the dynamics of cortical reorganization.

  20. Double-wave-vector diffusion-weighted imaging reveals microscopic diffusion anisotropy in the living human brain.

    Science.gov (United States)

    Lawrenz, Marco; Finsterbusch, Jürgen

    2013-04-01

    Diffusion-tensor imaging is widely used to characterize diffusion in biological tissue, however, the derived anisotropy information, e.g., the fractional anisotropy, is ambiguous. For instance, low values of the diffusion anisotropy in brain white matter voxels may reflect a reduced axon density, i.e., a loss of fibers, or a lower fiber coherence within the voxel, e.g., more crossing fibers. This ambiguity can be avoided with experiments involving two diffusion-weighting periods applied successively in a single acquisition, so-called double-wave-vector or double-pulsed-field-gradient experiments. For a long mixing time between the two periods such experiments are sensitive to the cells' eccentricity, i.e., the diffusion anisotropy present on a microscopic scale. In this study, it is shown that this microscopic diffusion anisotropy can be detected in white matter in the living human brain, even in a macroscopically isotropic region-of-interest (fractional anisotropy = 0). The underlying signal difference between parallel and orthogonal wave vector orientations does not show up in standard diffusion-weighting experiments but is specific to the double-wave-vector experiment. Furthermore, the modulation amplitude observed is very similar for regions-of-interest with different fractional anisotrpy values. Thus, double-wave-vector experiments may provide a direct and reliable access to white matter integrity independent of the actual fiber orientation distribution within the voxel. Copyright © 2012 Wiley Periodicals, Inc.

  1. Next-Generation Sequencing Techniques Reveal that Genomic Imprinting Is Absent in Day-Old Gallus gallus domesticus Brains.

    Science.gov (United States)

    Wang, Qiong; Li, Kaiyang; Zhang, Daixi; Li, Junying; Xu, Guiyun; Zheng, Jiangxia; Yang, Ning; Qu, Lujiang

    2015-01-01

    Genomic imprinting is a phenomenon characterized by parent-of-origin-specific gene expression. While widely documented in viviparous mammals and plants, imprinting in oviparous birds remains controversial. Because genomic imprinting is temporal- and tissue-specific, we investigated this phenomenon only in the brain tissues of 1-day-old chickens (Gallus gallus). We used next-generation sequencing technology to compare four transcriptomes pooled from 11 chickens, generated from reciprocally crossed families, to the DNA sequences of their parents. Candidate imprinted genes were then selected from these sequence alignments and subjected to verification experiments that excluded all but one SNP. Subsequent experiments performed with two new sets of reciprocally crossed families resulted in the exclusion of that candidate SNP as well. Attempts to find evidence of genomic imprinting from long non-coding RNAs yielded negative results. We therefore conclude that genomic imprinting is absent in the brains of 1-day-old chickens. However, due to the temporal and tissue specificity of imprinting, our results cannot be extended to all growth stages and tissue types.

  2. Similarities and differences between the brain networks underlying allocentric and egocentric spatial learning in rat revealed by cytochrome oxidase histochemistry.

    Science.gov (United States)

    Rubio, S; Begega, A; Méndez, M; Méndez-López, M; Arias, J L

    2012-10-25

    The involvement of different brain regions in place- and response-learning was examined using a water cross-maze. Rats were trained to find the goal from the initial arm by turning left at the choice point (egocentric strategy) or by using environmental cues (allocentric strategy). Although different strategies were required, the same maze and learning conditions were used. Using cytochrome oxidase histochemistry as a marker of cellular activity, the function of the 13 diverse cortical and subcortical regions was assessed in rats performing these two tasks. Our results show that allocentric learning depends on the recruitment of a large functional network, which includes the hippocampal CA3, dentate gyrus, medial mammillary nucleus and supramammillary nucleus. Along with the striatum, these last three structures are also related to egocentric spatial learning. The present study provides evidence for the contribution of these regions to spatial navigation and supports a possible functional interaction between the two memory systems, as their structural convergence may facilitate functional cooperation in the behaviours guided by more than one strategy. In summary, it can be argued that spatial learning is based on dynamic functional systems in which the interaction of brain regions is modulated by task requirements. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Consciousness and arousal effects on emotional face processing as revealed by brain oscillations. A gamma band analysis.

    Science.gov (United States)

    Balconi, Michela; Lucchiari, Claudio

    2008-01-01

    It remains an open question whether it is possible to assign a single brain operation or psychological function for facial emotion decoding to a certain type of oscillatory activity. Gamma band activity (GBA) offers an adequate tool for studying cortical activation patterns during emotional face information processing. In the present study brain oscillations were analyzed in response to facial expression of emotions. Specifically, GBA modulation was measured when twenty subjects looked at emotional (angry, fearful, happy, and sad faces) or neutral faces in two different conditions: supraliminal (10 ms) vs subliminal (150 ms) stimulation (100 target-mask pairs for each condition). The results showed that both consciousness and significance of the stimulus in terms of arousal can modulate the power synchronization (ERD decrease) during 150-350 time range: an early oscillatory event showed its peak at about 200 ms post-stimulus. GBA was enhanced by supraliminal more than subliminal elaboration, as well as more by high arousal (anger and fear) than low arousal (happiness and sadness) emotions. Finally a left-posterior dominance for conscious elaboration was found, whereas right hemisphere was discriminant in emotional processing of face in comparison with neutral face.

  4. Body representations in the human brain revealed by kinesthetic illusions and their essential contributions to motor control and corporeal awareness.

    Science.gov (United States)

    Naito, Eiichi; Morita, Tomoyo; Amemiya, Kaoru

    2016-03-01

    The human brain can generate a continuously changing postural model of our body. Somatic (proprioceptive) signals from skeletal muscles and joints contribute to the formation of the body representation. Recent neuroimaging studies of proprioceptive bodily illusions have elucidated the importance of three brain systems (motor network, specialized parietal systems, right inferior fronto-parietal network) in the formation of the human body representation. The motor network, especially the primary motor cortex, processes afferent input from skeletal muscles. Such information may contribute to the formation of kinematic/dynamic postural models of limbs, thereby enabling fast online feedback control. Distinct parietal regions appear to play specialized roles in the transformation/integration of information across different coordinate systems, which may subserve the adaptability and flexibility of the body representation. Finally, the right inferior fronto-parietal network, connected by the inferior branch of the superior longitudinal fasciculus, is consistently recruited when an individual experiences various types of bodily illusions and its possible roles relate to corporeal awareness, which is likely elicited through a series of neuronal processes of monitoring and accumulating bodily information and updating the body representation. Because this network is also recruited when identifying one's own features, the network activity could be a neuronal basis for self-consciousness. Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  5. Royal jelly-like protein localization reveals differences in hypopharyngeal glands buildup and conserved expression pattern in brains of bumblebees and honeybees

    Directory of Open Access Journals (Sweden)

    Štefan Albert

    2014-03-01

    Full Text Available Royal jelly proteins (MRJPs of the honeybee bear several open questions. One of them is their expression in tissues other than the hypopharyngeal glands (HGs, the site of royal jelly production. The sole MRJP-like gene of the bumblebee, Bombus terrestris (BtRJPL, represents a pre-diversification stage of the MRJP gene evolution in bees. Here we investigate the expression of BtRJPL in the HGs and the brain of bumblebees. Comparison of the HGs of bumblebees and honeybees revealed striking differences in their morphology with respect to sex- and caste-specific appearance, number of cells per acinus, and filamentous actin (F-actin rings. At the cellular level, we found a temporary F-actin-covered meshwork in the secretory cells, which suggests a role for actin in the biogenesis of the end apparatus in HGs. Using immunohistochemical localization, we show that BtRJPL is expressed in the bumblebee brain, predominantly in the Kenyon cells of the mushroom bodies, the site of sensory integration in insects, and in the optic lobes. Our data suggest that a dual gland-brain function preceded the multiplication of MRJPs in the honeybee lineage. In the course of the honeybee evolution, HGs dramatically changed their morphology in order to serve a food-producing function.

  6. Genomics analysis of potassium channel genes in songbirds reveals molecular specializations of brain circuits for the maintenance and production of learned vocalizations

    Science.gov (United States)

    2013-01-01

    Background A fundamental question in molecular neurobiology is how genes that determine basic neuronal properties shape the functional organization of brain circuits underlying complex learned behaviors. Given the growing availability of complete vertebrate genomes, comparative genomics represents a promising approach to address this question. Here we used genomics and molecular approaches to study how ion channel genes influence the properties of the brain circuitry that regulates birdsong, a learned vocal behavior with important similarities to human speech acquisition. We focused on potassium (K-)Channels, which are major determinants of neuronal cell excitability. Starting with the human gene set of K-Channels, we used cross-species mRNA/protein alignments, and syntenic analysis to define the full complement of orthologs, paralogs, allelic variants, as well as novel loci not previously predicted in the genome of zebra finch (Taeniopygia guttata). We also compared protein coding domains in chicken and zebra finch orthologs to identify genes under positive selective pressure, and those that contained lineage-specific insertions/deletions in functional domains. Finally, we conducted comprehensive in situ hybridizations to determine the extent of brain expression, and identify K-Channel gene enrichments in nuclei of the avian song system. Results We identified 107 K-Channel finch genes, including 6 novel genes common to non-mammalian vertebrate lineages. Twenty human genes are absent in songbirds, birds, or sauropsids, or unique to mammals, suggesting K-Channel properties may be lineage-specific. We also identified specific family members with insertions/deletions and/or high dN/dS ratios compared to chicken, a non-vocal learner. In situ hybridization revealed that while most K-Channel genes are broadly expressed in the brain, a subset is selectively expressed in song nuclei, representing molecular specializations of the vocal circuitry. Conclusions Together

  7. Extensive Direct Subcortical Cerebellum-Basal Ganglia Connections in Human Brain as Revealed by Constrained Spherical Deconvolution Tractography.

    Science.gov (United States)

    Milardi, Demetrio; Arrigo, Alessandro; Anastasi, Giuseppe; Cacciola, Alberto; Marino, Silvia; Mormina, Enricomaria; Calamuneri, Alessandro; Bruschetta, Daniele; Cutroneo, Giuseppina; Trimarchi, Fabio; Quartarone, Angelo

    2016-01-01

    The connections between the cerebellum and basal ganglia were assumed to occur at the level of neocortex. However evidences from animal data have challenged this old perspective showing extensive subcortical pathways linking the cerebellum with the basal ganglia. Here we tested the hypothesis if these connections also exist between the cerebellum and basal ganglia in the human brain by using diffusion magnetic resonance imaging and tractography. Fifteen healthy subjects were analyzed by using constrained spherical deconvolution technique obtained with a 3T magnetic resonance imaging scanner. We found extensive connections running between the subthalamic nucleus and cerebellar cortex and, as novel result, we demonstrated a direct route linking the dentate nucleus to the internal globus pallidus as well as to the substantia nigra. These findings may open a new scenario on the interpretation of basal ganglia disorders.

  8. Brain Basics

    Medline Plus

    Full Text Available ... These circuits control specific body functions such as sleep and speech. The brain continues maturing well into a person's early 20s. ... that regulates many functions, including mood, appetite, and sleep. synapse —The tiny gap between neurons, where nerve impulses are sent from one neuron to ... of Deep Brain Stimulation Brain’s Alertness Circuitry Revealed New BRAIN Grants ...

  9. Naturalistic fMRI Mapping Reveals Superior Temporal Sulcus as the Hub for the Distributed Brain Network for Social Perception

    Science.gov (United States)

    Lahnakoski, Juha M.; Glerean, Enrico; Salmi, Juha; Jääskeläinen, Iiro P.; Sams, Mikko; Hari, Riitta; Nummenmaa, Lauri

    2012-01-01

    Despite the abundant data on brain networks processing static social signals, such as pictures of faces, the neural systems supporting social perception in naturalistic conditions are still poorly understood. Here we delineated brain networks subserving social perception under naturalistic conditions in 19 healthy humans who watched, during 3-T functional magnetic resonance imaging (fMRI), a set of 137 short (approximately 16 s each, total 27 min) audiovisual movie clips depicting pre-selected social signals. Two independent raters estimated how well each clip represented eight social features (faces, human bodies, biological motion, goal-oriented actions, emotion, social interaction, pain, and speech) and six filler features (places, objects, rigid motion, people not in social interaction, non-goal-oriented action, and non-human sounds) lacking social content. These ratings were used as predictors in the fMRI analysis. The posterior superior temporal sulcus (STS) responded to all social features but not to any non-social features, and the anterior STS responded to all social features except bodies and biological motion. We also found four partially segregated, extended networks for processing of specific social signals: (1) a fronto-temporal network responding to multiple social categories, (2) a fronto-parietal network preferentially activated to bodies, motion, and pain, (3) a temporo-amygdalar network responding to faces, social interaction, and speech, and (4) a fronto-insular network responding to pain, emotions, social interactions, and speech. Our results highlight the role of the pSTS in processing multiple aspects of social information, as well as the feasibility and efficiency of fMRI mapping under conditions that resemble the complexity of real life. PMID:22905026

  10. Naturalistic fMRI mapping reveals superior temporal sulcus as the hub for the distributed brain network for social perception

    Directory of Open Access Journals (Sweden)

    Juha Marko Lahnakoski

    2012-08-01

    Full Text Available Despite the abundant data on brain networks processing static social signals, such as pictures of faces, the neural systems supporting social perception in naturalistic conditions are still poorly understood. Here we delineated brain networks subserving social perception under naturalistic conditions in 19 healthy humans who watched, during 3-tesla functional magnetic imaging (fMRI, a set of 137 short (~16 s each, total 27 min audiovisual movie clips depicting pre-selected social signals. Two independent raters estimated how well each clip represented eight social features (faces, human bodies, biological motion, goal-oriented actions, emotion, social interaction, pain, and speech and six filler features (places, objects, rigid motion, people not in social interaction, non-goal-oriented action and non-human sounds lacking social content. These ratings were used as predictors in the fMRI analysis. The posterior superior temporal sulcus (STS responded to all social features but not to any non-social features, and the anterior STS responded to all social features except bodies and biological motion. We also found four partially segregated, extended networks for processing of specific social signals: 1 a fronto-temporal network responding to multiple social categories, 2 a fronto-parietal network preferentially activated to bodies, motion and pain, 3 a temporo-amygdalar network responding to faces, social interaction and speech, and 4 a fronto-insular network responding to pain, emotions, social interactions, and speech. Our results highlight the role of the posterior STS in processing multiple aspects of social information, as well as the feasibility and efficiency of fMRI mapping under conditions that resemble the complexity of real life.

  11. Naturalistic FMRI mapping reveals superior temporal sulcus as the hub for the distributed brain network for social perception.

    Science.gov (United States)

    Lahnakoski, Juha M; Glerean, Enrico; Salmi, Juha; Jääskeläinen, Iiro P; Sams, Mikko; Hari, Riitta; Nummenmaa, Lauri

    2012-01-01

    Despite the abundant data on brain networks processing static social signals, such as pictures of faces, the neural systems supporting social perception in naturalistic conditions are still poorly understood. Here we delineated brain networks subserving social perception under naturalistic conditions in 19 healthy humans who watched, during 3-T functional magnetic resonance imaging (fMRI), a set of 137 short (approximately 16 s each, total 27 min) audiovisual movie clips depicting pre-selected social signals. Two independent raters estimated how well each clip represented eight social features (faces, human bodies, biological motion, goal-oriented actions, emotion, social interaction, pain, and speech) and six filler features (places, objects, rigid motion, people not in social interaction, non-goal-oriented action, and non-human sounds) lacking social content. These ratings were used as predictors in the fMRI analysis. The posterior superior temporal sulcus (STS) responded to all social features but not to any non-social features, and the anterior STS responded to all social features except bodies and biological motion. We also found four partially segregated, extended networks for processing of specific social signals: (1) a fronto-temporal network responding to multiple social categories, (2) a fronto-parietal network preferentially activated to bodies, motion, and pain, (3) a temporo-amygdalar network responding to faces, social interaction, and speech, and (4) a fronto-insular network responding to pain, emotions, social interactions, and speech. Our results highlight the role of the pSTS in processing multiple aspects of social information, as well as the feasibility and efficiency of fMRI mapping under conditions that resemble the complexity of real life.

  12. Task-Related Edge Density (TED-A New Method for Revealing Dynamic Network Formation in fMRI Data of the Human Brain.

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    Gabriele Lohmann

    Full Text Available The formation of transient networks in response to external stimuli or as a reflection of internal cognitive processes is a hallmark of human brain function. However, its identification in fMRI data of the human brain is notoriously difficult. Here we propose a new method of fMRI data analysis that tackles this problem by considering large-scale, task-related synchronisation networks. Networks consist of nodes and edges connecting them, where nodes correspond to voxels in fMRI data, and the weight of an edge is determined via task-related changes in dynamic synchronisation between their respective times series. Based on these definitions, we developed a new data analysis algorithm that identifies edges that show differing levels of synchrony between two distinct task conditions and that occur in dense packs with similar characteristics. Hence, we call this approach "Task-related Edge Density" (TED. TED proved to be a very strong marker for dynamic network formation that easily lends itself to statistical analysis using large scale statistical inference. A major advantage of TED compared to other methods is that it does not depend on any specific hemodynamic response model, and it also does not require a presegmentation of the data for dimensionality reduction as it can handle large networks consisting of tens of thousands of voxels. We applied TED to fMRI data of a fingertapping and an emotion processing task provided by the Human Connectome Project. TED revealed network-based involvement of a large number of brain areas that evaded detection using traditional GLM-based analysis. We show that our proposed method provides an entirely new window into the immense complexity of human brain function.

  13. Task-Related Edge Density (TED)-A New Method for Revealing Dynamic Network Formation in fMRI Data of the Human Brain.

    Science.gov (United States)

    Lohmann, Gabriele; Stelzer, Johannes; Zuber, Verena; Buschmann, Tilo; Margulies, Daniel; Bartels, Andreas; Scheffler, Klaus

    2016-01-01

    The formation of transient networks in response to external stimuli or as a reflection of internal cognitive processes is a hallmark of human brain function. However, its identification in fMRI data of the human brain is notoriously difficult. Here we propose a new method of fMRI data analysis that tackles this problem by considering large-scale, task-related synchronisation networks. Networks consist of nodes and edges connecting them, where nodes correspond to voxels in fMRI data, and the weight of an edge is determined via task-related changes in dynamic synchronisation between their respective times series. Based on these definitions, we developed a new data analysis algorithm that identifies edges that show differing levels of synchrony between two distinct task conditions and that occur in dense packs with similar characteristics. Hence, we call this approach "Task-related Edge Density" (TED). TED proved to be a very strong marker for dynamic network formation that easily lends itself to statistical analysis using large scale statistical inference. A major advantage of TED compared to other methods is that it does not depend on any specific hemodynamic response model, and it also does not require a presegmentation of the data for dimensionality reduction as it can handle large networks consisting of tens of thousands of voxels. We applied TED to fMRI data of a fingertapping and an emotion processing task provided by the Human Connectome Project. TED revealed network-based involvement of a large number of brain areas that evaded detection using traditional GLM-based analysis. We show that our proposed method provides an entirely new window into the immense complexity of human brain function.

  14. Unexpected complications of bonded mandibular lingual retainers.

    NARCIS (Netherlands)

    Katsaros, C.; Livas, C.; Renkema, A.M.

    2007-01-01

    INTRODUCTION: The flexible spiral wire (FSW) retainer is the most frequently used type of fixed retainer bonded on all 6 anterior teeth. Our aim in this article was to demonstrate unexpected posttreatment changes in the labiolingual position of the mandibular anterior teeth associated with the use

  15. Brain structural abnormalities in behavior therapy-resistant obsessive-compulsive disorder revealed by voxel-based morphometry

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    Hashimoto N

    2014-10-01

    Full Text Available Nobuhiko Hashimoto,1 Shutaro Nakaaki,2 Akiko Kawaguchi,1 Junko Sato,1 Harumasa Kasai,3 Takashi Nakamae,4 Jin Narumoto,4 Jun Miyata,5 Toshi A Furukawa,6,7 Masaru Mimura2 1Department of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; 2Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; 3Department of Central Radiology, Nagoya City University Hospital, Nagoya, Japan; 4Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; 5Department of Psychiatry, Graduate School of Medicine, Kyoto University, Kyoto, Japan; 6Department of Health Promotion and Human Behavior, 7Department of Clinical Epidemiology, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan Background: Although several functional imaging studies have demonstrated that behavior therapy (BT modifies the neural circuits involved in the pathogenesis of obsessive-compulsive disorder (OCD, the structural abnormalities underlying BT-resistant OCD remain unknown. Methods: In this study, we examined the existence of regional structural abnormalities in both the gray matter and the white matter of patients with OCD at baseline using voxel-based morphometry in responders (n=24 and nonresponders (n=15 to subsequent BT. Three-dimensional T1-weighted magnetic resonance imaging was performed before the completion of 12 weeks of BT. Results: Relative to the responders, the nonresponders exhibited significantly smaller gray matter volumes in the right ventromedial prefrontal cortex, the right orbitofrontal cortex, the right precentral gyrus, and the left anterior cingulate cortex. In addition, relative to the responders, the nonresponders exhibited significantly smaller white matter volumes in the left cingulate bundle and the left superior frontal white matter. Conclusion: These results suggest that the brain

  16. A low-affinity antagonist reveals saturation and desensitization in mature synapses in the auditory brain stem.

    Science.gov (United States)

    Chanda, Soham; Xu-Friedman, Matthew A

    2010-04-01

    Postsynaptic receptor desensitization has been observed to contribute to depression in immature synapses. However, it is not clear whether desensitization persists and causes depression in mature synapses. We investigate this issue at the endbulb of Held, the synapse made by auditory nerve (AN) fibers onto bushy cells (BCs) of the anteroventral cochlear nucleus, where depression could influence the processing of sound information. Experiments using cyclothiazide (CTZ) have implicated desensitization in endbulbs from postnatal day 16 (P16) to P21 mice, but application of γ-D-glutamylglycine (DGG) did not reveal desensitization in endbulbs >P22. To reconcile these findings, we have studied the effects of both CTZ and DGG on endbulbs from P5 to P40 CBA/CaJ mice. In paired-pulse protocols, both CTZ and DGG reduced depression in all ages at intervals 20 ms, consistent with DGG's use to prevent saturation. DGG application revealed receptor saturation even under conditions of very low release probability. Preventing desensitization by CTZ occluded the effects of DGG on desensitization and revealed the effects of saturation at short intervals. We developed an approach to separate DGG's effect on saturation from its effect on desensitization, which showed that desensitization has an impact during bursts of auditory nerve activity. Dynamic-clamp experiments indicated that desensitization can reduce BC spike probability and increase latency and jitter. Thus desensitization may affect sound processing in the mature auditory system.

  17. Brain potentials to native phoneme discrimination reveal the origin of individual differences in learning the sounds of a second language.

    Science.gov (United States)

    Díaz, Begoña; Baus, Cristina; Escera, Carles; Costa, Albert; Sebastián-Gallés, Núria

    2008-10-21

    Human beings differ in their ability to master the sounds of their second language (L2). Phonetic training studies have proposed that differences in phonetic learning stem from differences in psychoacoustic abilities rather than speech-specific capabilities. We aimed at finding the origin of individual differences in L2 phonetic acquisition in natural learning contexts. We consider two alternative explanations: a general psychoacoustic origin vs. a speech-specific one. For this purpose, event-related potentials (ERPs) were recorded from two groups of early, proficient Spanish-Catalan bilinguals who differed in their mastery of the Catalan (L2) phonetic contrast /e-epsilon/. Brain activity in response to acoustic change detection was recorded in three different conditions involving tones of different length (duration condition), frequency (frequency condition), and presentation order (pattern condition). In addition, neural correlates of speech change detection were also assessed for both native (/o/-/e/) and nonnative (/o/-/ö/) phonetic contrasts (speech condition). Participants' discrimination accuracy, reflected electrically as a mismatch negativity (MMN), was similar between the two groups of participants in the three acoustic conditions. Conversely, the MMN was reduced in poor perceivers (PP) when they were presented with speech sounds. Therefore, our results support a speech-specific origin of individual variability in L2 phonetic mastery.

  18. First- and second-order contrast sensitivity functions reveal disrupted visual processing following mild traumatic brain injury.

    Science.gov (United States)

    Spiegel, Daniel P; Reynaud, Alexandre; Ruiz, Tatiana; Laguë-Beauvais, Maude; Hess, Robert; Farivar, Reza

    2016-05-01

    Vision is disrupted by traumatic brain injury (TBI), with vision-related complaints being amongst the most common in this population. Based on the neural responses of early visual cortical areas, injury to the visual cortex would be predicted to affect both 1(st) order and 2(nd) order contrast sensitivity functions (CSFs)-the height and/or the cut-off of the CSF are expected to be affected by TBI. Previous studies have reported disruptions only in 2(nd) order contrast sensitivity, but using a narrow range of parameters and divergent methodologies-no study has characterized the effect of TBI on the full CSF for both 1(st) and 2(nd) order stimuli. Such information is needed to properly understand the effect of TBI on contrast perception, which underlies all visual processing. Using a unified framework based on the quick contrast sensitivity function, we measured full CSFs for static and dynamic 1(st) and 2(nd) order stimuli. Our results provide a unique dataset showing alterations in sensitivity for both 1(st) and 2(nd) order visual stimuli. In particular, we show that TBI patients have increased sensitivity for 1(st) order motion stimuli and decreased sensitivity to orientation-defined and contrast-defined 2(nd) order stimuli. In addition, our data suggest that TBI patients' sensitivity for both 1(st) order stimuli and 2(nd) order contrast-defined stimuli is shifted towards higher spatial frequencies. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. NIRS-Based Hyperscanning Reveals Inter-brain Neural Synchronization during Cooperative Jenga Game with Face-to-Face Communication.

    Science.gov (United States)

    Liu, Ning; Mok, Charis; Witt, Emily E; Pradhan, Anjali H; Chen, Jingyuan E; Reiss, Allan L

    2016-01-01

    Functional near-infrared spectroscopy (fNIRS) is an increasingly popular technology for studying social cognition. In particular, fNIRS permits simultaneous measurement of hemodynamic activity in two or more individuals interacting in a naturalistic setting. Here, we used fNIRS hyperscanning to study social cognition and communication in human dyads engaged in cooperative and obstructive interaction while they played the game of Jenga™. Novel methods were developed to identify synchronized channels for each dyad and a structural node-based spatial registration approach was utilized for inter-dyad analyses. Strong inter-brain neural synchrony (INS) was observed in the posterior region of the right middle and superior frontal gyrus, in particular Brodmann area 8 (BA8), during cooperative and obstructive interaction. This synchrony was not observed during the parallel game play condition and the dialog section, suggesting that BA8 was involved in goal-oriented social interaction such as complex interactive movements and social decision-making. INS was also observed in the dorsomedial prefrontal cortex (dmPFC), in particular Brodmann 9, during cooperative interaction only. These additional findings suggest that BA9 may be particularly engaged when theory-of-mind (ToM) is required for cooperative social interaction. The new methods described here have the potential to significantly extend fNIRS applications to social cognitive research.

  20. NIRS-based hyperscanning reveals inter-brain neural synchronization during cooperative Jenga game with face-to-face communication

    Directory of Open Access Journals (Sweden)

    Ning eLiu

    2016-03-01

    Full Text Available Functional near-infrared spectroscopy (fNIRS is an increasingly popular technology for studying social cognition. In particular, fNIRS permits simultaneous measurement of hemodynamic activity in two or more individuals interacting in a naturalistic setting. Here, we used fNIRS hyperscanning to study social cognition and communication in human dyads engaged in cooperative and non-cooperative interaction while they played the game of Jenga™. Novel methods were developed to identify synchronized channels for each dyad and a structural node-based spatial registration approach was utilized for inter-dyad analyses. Strong inter-brain neural synchrony (INS was observed in the posterior region of the right middle and superior frontal gyrus, in particular Brodmann area 8, during cooperative and obstructive interaction. This synchrony was not observed during the parallel game play condition and the dialogue section, suggesting that BA8 was involved in goal-oriented social interaction such as complex interactive movements and social decision-making. INS was also observed in the dorsomedial prefrontal region (dmPFC, in particular Brodmann 9, during cooperative interaction only. These additional findings suggest that BA9 may be particularly engaged when theory-of-mind is required for cooperative social interaction. The new methods described here have the potential to significantly extend fNIRS applications to social cognitive research.

  1. Relational and procedural memory systems in the goldfish brain revealed by trace and delay eyeblink-like conditioning.

    Science.gov (United States)

    Gómez, A; Rodríguez-Expósito, B; Durán, E; Martín-Monzón, I; Broglio, C; Salas, C; Rodríguez, F

    2016-12-01

    The presence of multiple memory systems supported by different neural substrata has been demonstrated in animal and human studies. In mammals, two variants of eyeblink classical conditioning, differing only in the temporal relationships between the conditioned stimulus (CS) and the unconditioned stimulus (US), have been widely used to study the neural substrata of these different memory systems. Delay conditioning, in which both stimuli coincide in time, depends on a non-relational memory system supported by the cerebellum and associated brainstem circuits. In contrast, trace conditioning, in which a stimulus-free time gap separates the CS and the US, requires a declarative or relational memory system, thus depending on forebrain structures in addition to the cerebellum. The distinction between the explicit or relational and the implicit or procedural memory systems that support trace and delay classical conditioning has been extensively studied in mammals, but studies in other vertebrate groups are relatively scarce. In the present experiment we analyzed the differential involvement of the cerebellum and the telencephalon in delay and trace eyeblink-like classical conditioning in goldfish. The results show that whereas the cerebellum lesion prevented the eyeblink-like conditioning in both procedures, the telencephalon ablation impaired exclusively the acquisition of the trace conditioning. These data showing that comparable neural systems support delay and trace eyeblink conditioning in teleost fish and mammals suggest that these separate memory systems and their neural bases could be a shared ancestral brain feature of the vertebrate lineage. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Modelling a ciliopathy: Ahi1 knockdown in model systems reveals an essential role in brain, retinal, and renal development.

    Science.gov (United States)

    Simms, Roslyn J; Hynes, Ann Marie; Eley, Lorraine; Inglis, David; Chaudhry, Bill; Dawe, Helen R; Sayer, John A

    2012-03-01

    Joubert syndrome and related diseases (JSRD) are cerebello-oculo-renal syndromes with phenotypes including cerebellar hypoplasia, retinal dystrophy, and nephronophthisis (a cystic kidney disease). Mutations in AHI1 are the most common genetic cause of JSRD, with developmental hindbrain anomalies and retinal degeneration being prominent features. We demonstrate that Ahi1, a WD40 domain-containing protein, is highly conserved throughout evolution and its expression associates with ciliated organisms. In zebrafish ahi1 morphants, the phenotypic spectrum of JSRD is modeled, with embryos showing brain, eye, and ear abnormalities, together with renal cysts and cloacal dilatation. Following ahi1 knockdown in zebrafish, we demonstrate loss of cilia at Kupffer's vesicle and subsequently defects in cardiac left-right asymmetry. Finally, using siRNA in renal epithelial cells we demonstrate a role for Ahi1 in both ciliogenesis and cell-cell junction formation. These data support a role for Ahi1 in epithelial cell organization and ciliary formation and explain the ciliopathy phenotype of AHI1 mutations in man.

  3. Suppression subtraction hybridization (SSH) and macroarray techniques reveal differential gene expression profiles in brain of sea bream infected with nodavirus.

    Science.gov (United States)

    Dios, S; Poisa-Beiro, L; Figueras, A; Novoa, B

    2007-03-01

    Despite of the impact that viruses have on aquatic organisms, relatively little is known on how fish fight against these infections. In this work, the brain gene expression pattern of sea bream (Sparus aurata) in response to nodavirus infection was investigated. We used the suppression subtractive hybridization (SSH) method to generate a subtracted cDNA library enriched with gene transcripts differentially expressed after 1 day post-infection. Some of the ESTs from the infected tissues fell in gene categories related to stress and immune responses. For the reverse library (ESTs expressed in controls compared with infected tissues) the most abundant transcripts were of ribosomal and mitochondrial nature. Several ESTs potentially induced by virus exposure were selected for in vivo expression studies. We observed a clear difference in expression between infected and control samples for two candidate genes, ubiquitin conjugating enzyme 7 interacting protein, which seems to play an important role in apoptosis and the interferon induced protein with helicase C domain 1 (mda-5) that contributes to apoptosis and regulates the type I IFN production, a key molecule of the antiviral innate response in most organisms.

  4. Event-related brain potentials reveal the time-course of language change detection in early bilinguals.

    Science.gov (United States)

    Kuipers, Jan-Rouke; Thierry, Guillaume

    2010-05-01

    Using event-related brain potentials, we investigated the temporal course of language change detection in proficient bilinguals as compared to matched controls. Welsh-English bilingual participants and English controls were presented with a variant of the oddball paradigm involving picture-word pairs. The language of the spoken word was manipulated such that English was the frequent stimulus (75%) and Welsh the infrequent stimulus (25%). We also manipulated semantic relatedness between pictures and words, such that only half of the pictures were followed by a word that corresponded with the identity of the picture. The P2 wave was significantly modulated by language in the bilingual group only, suggesting that this group detected a language change as early as 200 ms after word onset. Monolinguals also reliably detected the language change, but at a later stage of semantic integration (N400 range), since Welsh words were perceived as meaningless. The early detection of a language change in bilinguals triggered stimulus re-evaluation mechanisms reflected by a significant P600 modulation by Welsh words. Furthermore, compared to English unrelated words, English words matching the picture identity elicited significantly greater P2 amplitudes in the bilingual group only, suggesting that proficient bilinguals validate an incoming word against their expectation based on the context. Overall, highly proficient bilinguals appear to detect language changes very early on during speech perception and to consciously monitor language changes when they occur. 2010 Elsevier Inc. All rights reserved.

  5. Asynchronous presentation of global and local information reveals effects of attention on brain electrical activity specific to each level

    Directory of Open Access Journals (Sweden)

    Jorge eIglesias-Fuster

    2015-01-01

    Full Text Available The neural basis of selective attention within hierarchically organized Navon figures has been extensively studied with event related potentials (ERPs, by contrasting responses obtained when attending the global and the local echelons. The findings are inherently ambiguous because both levels are always presented together. Thus only a mixture of the brain responses to two levels can be observed. Here, we use a method that allows unveiling of global and local letters at distinct times, enabling estimation of separate ERPs related to each level. Two interspersed oddball streams were presented, each using letters from one level and comprised of frequent distracters and rare targets. Previous work and our Experiment 1 show that it is difficult to divide attention between two such streams of stimuli. ERP recording in Experiment 2 evinced an early selection negativity (SN, with latencies to the 50% area of about 266 ms for global distracters and 276 ms for local distracters that was larger for attended relative to unattended distracters. The SN was larger over right posterior occipito-temporal derivations for global stimuli and over left posterior occipito-temporal derivations for local stimuli (although the latter was less strongly lateralized. A discrimination negativity (DN, accompanied by a P3b was larger for attended targets relative to attended distracters, with latencies to the 50% area of about 316 ms for global stimuli and 301 ms for local stimuli, which presented a similar distribution for both levels over left temporo-parietal electrodes. The two negativities apparently index successive stages in the processing of a selected level within a compound figure. By resolving the ambiguity of traditional designs, our method allowed us to observe the effects of attention for each hierarchical level on its own.

  6. Brain plasticity and cortical correlates of osseoperception revealed by punctate mechanical stimulation of osseointegrated oral implants during fMRI.

    Science.gov (United States)

    Habre-Hallage, Pascale; Dricot, Laurence; Jacobs, Reinhilde; van Steenberghe, Daniel; Reychler, Hervé; Grandin, Cecile B

    2012-01-01

    Our aim was to unveil the cortical neural correlates of osseoperception, i.e. the tactile sensation perceived when loading a bone-anchored implant, by taking oral implants as a model. This was performed in a cross-sectional observational study with 9 volunteering patients and 10 age-matched controls. For each patient, functional magnetic resonance imaging (fRMI) recordings were made during punctate mechanical stimulation of either teeth or osseointegrated implants in the maxillary incisor area. During fMRI recordings, 1 Hz punctate tactile stimuli were applied either on a maxillary left central incisor, canine tooth or central incisor implant. A block design paradigm was used to stimulate, in 9 patients, maxillary left central incisor implants (I21-p) and maxillary left canines (T23-p). In 10 control subjects, maxillary left central incisors and canines (T21-c, T23-c) were stimulated. Random effect group analyses were performed for each stimulated site, and differences in cortical activity elicited when loading teeth or implants were examined using ANOVA. As a group, patients activated somatosensory area S2 bilaterally for both I21 and T23, while controls activated S1 and S2 bilaterally for T21 and T23. At an individual level, S1 was activated by 4/9 implants, mainly on the ipsilateral side. The stimulated implants activated a larger bilateral cortical network outside the somatosensory areas: in parietal, frontal and insular lobes, the main clusters being located in the inferior frontal gyri. Stimulation of T23 in patients resulted in an activation pattern intermediate between that of the implants and that of natural teeth. This study demonstrates that punctate mechanical stimulation of oral implants activates both primary and secondary cortical somatosensory areas. It also suggests that brain plasticity occurs when extracted teeth are replaced by endosseous implants. This cortical activation may represent the underlying mechanism of osseoperception.

  7. Pattern of attack of a galling insect reveals an unexpected preference-performance linkage on medium-sized resources Padrão de ataque de um inseto galhador revela uma inesperada ligação entre preferência e performance sobre recursos de tamanho médio

    Directory of Open Access Journals (Sweden)

    Jean C. Santos

    2010-03-01

    Full Text Available Pattern of attack of a galling insect reveals an unexpected preference-performance linkage on medium-sized resources. The Plant Vigor Hypothesis (PVH predicts oviposition preference and higher offspring performance on longer and fast-growing shoots, and although several studies have tested its predictions, long-term studies concerning the patterns of host selection by galling species are still lacking. The PVH was tested in this study using Bauhinia brevipes (Fabaceae as the host of a leaf gall midge, Asphondylia microcapillata (Diptera, Cecidomyiidae during three consecutive years. Shoots were collected from the same 80 plants between 2001 and 2003 and shoot length, number of healthy and galled leaves, gall number, and mortality factors were recorded. Nearly 600 galls were found on the 5,800 shoots collected. Medium-sized shoots supported from 46 to 70% of all galls, with greater gall survival rate in 2002 and 2003. A decrease in parasitism rate coupled with an increase in gall predation lead to a constant similar gall survivorship rate in all years (x = 22.7%. Although gall abundance varied among years (122 in 2001, 114 in 2002 and 359 in 2003 preference for longer shoots was not observed because the percentage of galled shoots and galled leaves were higher on medium shoot length classes in all years. The observed distribution of gall abundance and galled shoots were always greater than the expected distribution on medium shoot length classes. These findings do not support the PVH, and show that A. microcapillata can maximize the female preference and larval performance on medium-sized shoots of B. brevipes.A Hipótese do Vigor de Plantas (HVP prevê uma oviposição preferencial e alta performance da prole em ramos longos e de crescimento rápido da planta hospedeira. Embora diversos estudos tenham testado suas predições, estudos de longa duração focados no padrão de seleção de planta hospedeira por insetos galhadores ainda s

  8. The human brain and face: mechanisms of cranial, neurological and facial development revealed through malformations of holoprosencephaly, cyclopia and aberrations in chromosome 18.

    Science.gov (United States)

    Gondré-Lewis, Marjorie C; Gboluaje, Temitayo; Reid, Shaina N; Lin, Stephen; Wang, Paul; Green, William; Diogo, Rui; Fidélia-Lambert, Marie N; Herman, Mary M

    2015-09-01

    The study of inborn genetic errors can lend insight into mechanisms of normal human development and congenital malformations. Here, we present the first detailed comparison of cranial and neuro pathology in two exceedingly rare human individuals with cyclopia and alobar holoprosencephaly (HPE) in the presence and absence of aberrant chromosome 18 (aCh18). The aCh18 fetus contained one normal Ch18 and one with a pseudo-isodicentric duplication of chromosome 18q and partial deletion of 18p from 18p11.31 where the HPE gene, TGIF, resides, to the p terminus. In addition to synophthalmia, the aCh18 cyclopic malformations included a failure of induction of most of the telencephalon - closely approximating anencephaly, unchecked development of brain stem structures, near absence of the sphenoid bone and a malformed neurocranium and viscerocranium that constitute the median face. Although there was complete erasure of the olfactory and superior nasal structures, rudiments of nasal structures derived from the maxillary bone were evident, but with absent pharyngeal structures. The second non-aCh18 cyclopic fetus was initially classified as a true Cyclops, as it appeared to have a proboscis and one median eye with a single iris, but further analysis revealed two eye globes as expected for synophthalmic cyclopia. Furthermore, the proboscis was associated with the medial ethmoid ridge, consistent with an incomplete induction of these nasal structures, even as the nasal septum and paranasal sinuses were apparently developed. An important conclusion of this study is that it is the brain that predicts the overall configuration of the face, due to its influence on the development of surrounding skeletal structures. The present data using a combination of macroscopic, computed tomography (CT) and magnetic resonance imaging (MRI) techniques provide an unparalleled analysis on the extent of the effects of median defects, and insight into normal development and patterning of the brain

  9. Multivariate imaging-genetics study of MRI gray matter volume and SNPs reveals biological pathways correlated with brain structural differences in Attention Deficit Hyperactivity Disorder

    Directory of Open Access Journals (Sweden)

    Sabin Khadka

    2016-07-01

    Full Text Available Background: Attention Deficit Hyperactivity Disorder (ADHD is a prevalent neurodevelopmental disorder affecting children, adolescents, and adults. Its etiology is not well-understood, but it is increasingly believed to result from diverse pathophysiologies that affect the structure and function of specific brain circuits. Although one of the best-studied neurobiological abnormalities in ADHD is reduced fronto-striatal-cerebellar gray matter volume, its specific genetic correlates are largely unknown. Methods: In this study, T1-weighted MR images of brain structure were collected from 198 adolescents (63 ADHD-diagnosed. A multivariate parallel independent component analysis technique (Para-ICA identified imaging-genetic relationships between regional gray matter volume and single nucleotide polymorphism data. Results: Para-ICA analyses extracted 14 components from genetic data and 9 from MR data. An iterative cross-validation using randomly-chosen sub-samples indicated acceptable stability of these ICA solutions. A series of partial correlation analyses controlling for age, sex, and ethnicity revealed two genotype-phenotype component pairs significantly differed between ADHD and non-ADHD groups, after a Bonferroni correction for multiple comparisons. The brain phenotype component not only included structures frequently found to have abnormally low volume in previous ADHD studies, but was also significantly associated with ADHD differences in symptom severity and performance on cognitive tests frequently found to be impaired in patients diagnosed with the disorder. Pathway analysis of the genotype component identified several different biological pathways linked to these structural abnormalities in ADHD. Conclusions: Some of these pathways implicate well-known dopaminergic neurotransmission and neurodevelopment hypothesized to be abnormal in ADHD. Other more recently implicated pathways included glutamatergic and GABA-eric physiological systems

  10. Regulatory RNAs discovered in unexpected places.

    Science.gov (United States)

    Pek, Jun Wei; Okamura, Katsutomo

    2015-01-01

    Recent studies have discovered both small and long noncoding RNAs (ncRNAs) encoded in unexpected places. These ncRNA genes were surprises at the time of their discovery, but many quickly became well-accepted families of functional regulatory RNA species. Even after years of extensive gene annotation studies using high-throughput sequencing technologies, new types of ncRNA genes continue to be discovered in unexpected places. We highlight ncRNAs that have atypical structures and that are encoded in what are generally considered 'junk' sequences, such as spacers and introns. We also discuss current bottlenecks in the approaches for identifying novel ncRNAs and the possibility that many remain to be discovered. © 2015 Wiley Periodicals, Inc.

  11. Lemierre syndrome and unexpected death in childhood.

    Science.gov (United States)

    Gilbert, John D; Warner, Morgyn S; Byard, Roger W

    2009-11-01

    Lemierre syndrome refers to necrotizing infections of the head due to Fusobacterium necrophorum and has been called the 'forgotten disease' due to its rarity in the antibiotic era. Recently, however, more cases have been documented in the literature suggesting that there has been an increase in incidence. A 10-year-old boy is reported who had a five-day history of ear infection, with the development of fever, drowsiness and ipsilateral neck swelling. Unexpected cardiac arrest occurred soon after medical assessment. At autopsy, right otitis media was demonstrated with extension of suppurative infection into subcutaneous tissues behind the ear and also into the extradural space at the lateral end of the petrous temporal bone. There was also septic thrombophlebitis of the adjacent sigmoid sinus, but no evidence of meningitis. This case demonstrates yet another infectious condition that may be associated with rapid deterioration and unexpected death in childhood. An autopsy approach to suspected sepsis in childhood is outlined.

  12. Delayed defibrillation caused by unexpected ECG artifact.

    Science.gov (United States)

    Stewart, John A

    2008-11-01

    Incorrect lead selection and unexpected ECG artifact during an attempted resuscitation after inhospital cardiac arrest resulted in undetected lack of cardiac monitoring for approximately 13 minutes. The patient was finally countershocked and regained a spontaneous pulse but was determined to have experienced profound neurologic damage and died shortly after being extubated. This type of failure may be common, particularly with older monitor/defibrillators. Caregivers, health care organizations, and device manufacturers should be aware of this potential problem and institute preventive measures.

  13. Comparative transcriptome analysis in induced neural stem cells reveals defined neural cell identities in vitro and after transplantation into the adult rodent brain

    Directory of Open Access Journals (Sweden)

    Anna-Lena Hallmann

    2016-05-01

    Full Text Available Reprogramming technology enables the production of neural progenitor cells (NPCs from somatic cells by direct transdifferentiation. However, little is known on how neural programs in these induced neural stem cells (iNSCs differ from those of alternative stem cell populations in vitro and in vivo. Here, we performed transcriptome analyses on murine iNSCs in comparison to brain-derived neural stem cells (NSCs and pluripotent stem cell-derived NPCs, which revealed distinct global, neural, metabolic and cell cycle-associated marks in these populations. iNSCs carried a hindbrain/posterior cell identity, which could be shifted towards caudal, partially to rostral but not towards ventral fates in vitro. iNSCs survived after transplantation into the rodent brain and exhibited in vivo-characteristics, neural and metabolic programs similar to transplanted NSCs. However, iNSCs vastly retained caudal identities demonstrating cell-autonomy of regional programs in vivo. These data could have significant implications for a variety of in vitro- and in vivo-applications using iNSCs.

  14. Expression of progerin in aging mouse brains reveals structural nuclear abnormalities without detectible significant alterations in gene expression, hippocampal stem cells or behavior

    DEFF Research Database (Denmark)

    Baek, Jean-Ha; Schmidt, Eva; Viceconte, Nikenza

    2015-01-01

    Hutchinson–Gilford progeria syndrome (HGPS) is a segmental progeroid syndrome with multiple features suggestive of premature accelerated aging. Accumulation of progerin is thought to underlie the pathophysiology of HGPS. However, despite ubiquitous expression of lamin A in all differentiated cells...... also been found in several tissues from normal individuals, but it is not clear if low levels of progerin contribute to the aging of the brain. In an attempt to clarify the origin of this phenomenon, we have developed an inducible transgenic mouse model with expression of the most common HGPS mutation...... of hippocampal neurons of HGPS animals, there were only negligible changes in gene expression after 63 weeks of transgenic expression. Behavioral analysis and neurogenesis assays, following long-term expression of the HGPS mutation, did not reveal significant pathology. Our results suggest that certain tissues...

  15. Studying the MicroRNA role as a survival predictor and revealing its part in malignancy level determination in patients with supratentorial gliomas of brain

    Science.gov (United States)

    Stupak, E. V.; Veryaskina, Yu. A.; Titov, S. E.; Achmerova, L. G.; Stupak, V. V.; Dolzhenko, D. A.; Rabinovich, S. S.; Narodov, A. A.; Ivanov, M. K.; Zhimulev, I. F.; Kolesnikov, N. N.

    2017-09-01

    The numerous data show, that microRNA (miRNA) are direct participants of carcinogenesis. Also miRNA plays the role of a diagnostic and prognostic marker for different types of cancer, including gliomas. The aim of this research is to make the comparative analysis of 10 micro RNA (miR-124, -125b, -16, -181b, -191, -21, -221, -223, -31 and -451) expression profiles. The analysis was made for gliomas with different malignancy degree, then compared with the samples of the adjacent not changed tissues (n = 90). During the study the specific profiles of miRNA expression for various histotypes of tumors were revealed. It was determined, that miRNA acts as a predictor of patient survival in the cases with malignant supratentorial brain tumors. The diagnostic approaches based on miRNA expression profile were designed. It will help to determine the malignancy level and to predict the course of the disease.

  16. Brain microstructural abnormalities revealed by diffusion tensor images in patients with treatment-resistant depression compared with major depressive disorder before treatment

    Energy Technology Data Exchange (ETDEWEB)

    Zhou Yan, E-mail: clare1475@hotmail.com [Department of Radiology, Ren-Ji Hospital, Jiao Tong University Medical School, Shanghai 200127 (China); Qin Lingdi, E-mail: flyfool318@hotmail.com [Department of Radiology, Ren-Ji Hospital, Jiao Tong University Medical School, Shanghai 200127 (China); Chen Jun, E-mail: doctor_cj@msn.com [Shanghai Mental Health Center, Jiao Tong University Medical School, Shanghai, 200030 (China); Qian Lijun, E-mail: dearqlj@hotmail.com [Department of Radiology, Ren-Ji Hospital, Jiao Tong University Medical School, Shanghai 200127 (China); Tao Jing, E-mail: jing318@hotmail.com [Department of Radiology, Ren-Ji Hospital, Jiao Tong University Medical School, Shanghai 200127 (China); Fang Yiru, E-mail: fangyr@sina.com [Shanghai Mental Health Center, Jiao Tong University Medical School, Shanghai, 200030 (China); Xu Jianrong, E-mail: xujianr@hotmail.com [Department of Radiology, Ren-Ji Hospital, Jiao Tong University Medical School, Shanghai 200127 (China)

    2011-11-15

    Treatment-resistant depression (TRD) is a therapeutic challenge for clinicians. Despite a growing interest in this area, an understanding of the pathophysiology of depression, particularly TRD, remains lacking. This study aims to detect the white matter abnormalities of whole brain fractional anisotropy (FA) in patients with TRD compared with major depressive disorder (MDD) before treatment by voxel-based analysis using diffusion tensor imaging. A total of 100 patients first diagnosed with untreated MDD underwent diffusion tensor imaging scans. 8 weeks after the first treatment, 54 patients showed response to the medication, whereas 46 did not. Finally, 20 patients were diagnosed with TRD after undergoing another treatment. A total of 20 patients with TRD and another 20 with MDD before treatment matched in gender, age, and education was enrolled in the research. For every subject, an FA map was generated and analyzed using SPM5. Subsequently, t-test was conducted to compare the FA values voxel to voxel between the two groups (p < 0.001 [FDR corrected], t > 7.57, voxel size > 30). Voxel-based morphometric (VBM) analysis was performed using T1W images. Significant reductions in FA were found in the white matter located in the bilateral of the hippocampus (left hippocampus: t = 7.63, voxel size = 50; right hippocampus: t = 7.82, voxel size = 48). VBM analysis revealed no morphological abnormalities between the two groups. Investigation of brain anisotropy revealed significantly decreased FA in both sides of the hippocampus. Although preliminary, our findings suggest that microstructural abnormalities in the hippocampus indicate vulnerability to treatment resistance.

  17. Tracking the Emergence of Host-Specific Simian Immunodeficiency Virus env and nef Populations Reveals nef Early Adaptation and Convergent Evolution in Brain of Naturally Progressing Rhesus Macaques.

    Science.gov (United States)

    Lamers, Susanna L; Nolan, David J; Rife, Brittany D; Fogel, Gary B; McGrath, Michael S; Burdo, Tricia H; Autissier, Patrick; Williams, Kenneth C; Goodenow, Maureen M; Salemi, Marco

    2015-08-01

    evolutionary patterns in the gp120 and nef genes leading to the emergence of host-specific viral populations and potentially linked to disease progression. Although each macaque exhibited unique immune profiles, macaque-specific nef sequences evolving under selection were consistently detected in plasma samples at 3 months postinfection, significantly earlier than in gp120 macaque-specific sequences. On the other hand, nef sequences in brain tissues, collected at necropsy of two animals with detectable infection in the central nervous system (CNS), revealed convergent evolution. The results not only indicate that early adaptation of nef in the new host may be essential for successful infection, but also suggest that specific nef variants may be required for SIV to efficiently invade CNS macrophages and/or enhance macrophage migration, resulting in HIV neuropathology. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  18. Stretched peer-review on unexpected results (GMOs).

    Science.gov (United States)

    Myhr, A I

    2005-01-01

    Science is the basis for governance of risk from genetically modified organisms (GMO), and it is also a primary source of legitimacy for policy decision. However, recently the publication of unexpected results has caused controversies and challenged the way in which science should be performed, be published in scientific journals, and how preliminary results should be communicated. These studies have subsequently, after being accepted for publication within the peer-review process of leading scientific journals, been thoroughly re-examined by many actors active within the GMO debate and thereby drawn extensive media coverage. The publicized charges that the research involved does not constitute significant evidence or represent bad science have in fact deflected attention away from the important questions related to ecological and health risks raised by the research. In this paper, I will argue that unexpected findings may represent "early warnings." Although early warnings may not represent reality, such reports are necessary to inform other scientists and regulators, and should be followed up by further research to reveal the validity of the warnings. Furthermore, science that embraces robust, participatory and transparent approaches will be imperative in the future to reduce the present controversy surrounding GMO use and release.

  19. Blood-brain barrier specific permeability assay reveals N-methylated tyramine derivatives in standardised leaf extracts and herbal products of Ginkgo biloba.

    Science.gov (United States)

    Könczöl, Árpád; Rendes, Kata; Dékány, Miklós; Müller, Judit; Riethmüller, Eszter; Balogh, György Tibor

    2016-11-30

    The linkage between the central nervous system availability and neuropharmacological activity of the constituents of Ginkgo biloba L. extracts (GBE) is still incomplete. In this study, the in vitro blood-brain barrier (BBB) permeability profile of the standardised GBE was investigated by the parallel artificial membrane permeability assay (PAMPA). Biomarkers, such as terpene trilactones, flavonoid aglycones and ginkgotoxin exerted moderate or good BBB-permeability potential (BBB+), while glycosides and biflavones were predicted as unable to pass the BBB. N-methyltyramine (NMT) and N,N-dimethyltyramine or hordenine (Hor) were identified among BBB+ compounds, while subsequent direct HRMS analysis revealed tyramine (Tyr) and N,N,N-trimethyltyramine or candicine (Can) in GBE as trace constituents. Distribution of Tyr, NMT, Hor and Can was determined by a validated ion-exchange mechanism-based liquid chromatography-electrospray ionisation-mass spectrometry (LC-ESI-MS) method in G. biloba samples, such as herbal drugs and dietary supplements. The total content of the four tyramine derivatives in various GBEs ranged from 7.3 up to 6357μg/g dry extract with NMT and Hor as most abundant ones. Considering the pharmacological activities and the revealed fluctuation in the concentration of the analysed adrenergic protoalkaloids, the presented rapid LC-ESI-MS method is proposed for monitoring of the levels of Tyr, NMT, Hor and Can in G. biloba products. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Analysis of Post-Traumatic Brain Injury Gene Expression Signature Reveals Tubulins, Nfe2l2, Nfkb, Cd44, and S100a4 as Treatment Targets.

    Science.gov (United States)

    Lipponen, Anssi; Paananen, Jussi; Puhakka, Noora; Pitkänen, Asla

    2016-08-17

    We aimed to define the chronically altered gene expression signature of traumatic brain injury (TBI-sig) to discover novel treatments to reverse pathologic gene expression or reinforce the expression of recovery-related genes. Genome-wide RNA-sequencing was performed at 3 months post-TBI induced by lateral fluid-percussion injury in rats. We found 4964 regulated genes in the perilesional cortex and 1966 in the thalamus (FDR sig was used for a LINCS analysis which identified 11 compounds that showed a strong connectivity with the TBI-sig in neuronal cell lines. Of these, celecoxib and sirolimus were recently reported to have a disease-modifying effect in in vivo animal models of epilepsy. Other compounds revealed by the analysis were BRD-K91844626, BRD-A11009626, NO-ASA, BRD-K55260239, SDZ-NKT-343, STK-661558, BRD-K75971499, ionomycin, and desmethylclomipramine. Network analysis of overlapping genes revealed the effects on tubulins (Tubb2a, Tubb3, Tubb4b), Nfe2l2, S100a4, Cd44, and Nfkb2, all of which are linked to TBI-relevant outcomes, including epileptogenesis and tissue repair. Desmethylclomipramine modulated most of the gene targets considered favorable for TBI outcome. Our data demonstrate long-lasting transcriptomics changes after TBI. LINCS analysis predicted that these changes could be modulated by various compounds, some of which are already in clinical use but never tested in TBI.

  1. Circadian variation in unexpected postoperative death

    DEFF Research Database (Denmark)

    Rosenberg, J; Pedersen, M H; Ramsing, T

    1992-01-01

    . This study examined the circadian variation of sudden unexpected death following abdominal surgery between 1985 and 1989 inclusive. Deaths were divided into those occurring during the day (08.00-16.00 hours), evening (16.00-24.00 hours) and night (24.00-08.00 hours). Twenty-three deaths were considered...... deaths occurred at night-time. These results suggest a need for further studies of sleep- and respiration-related effects on postoperative nocturnal cardiac function. The efficacy of monitoring during this apparent high-risk period should be evaluated....

  2. A translational murine model of sub-lethal intoxication with Shiga toxin 2 reveals novel ultrastructural findings in the brain striatum.

    Directory of Open Access Journals (Sweden)

    Carla Tironi-Farinati

    Full Text Available Infection by Shiga toxin-producing Escherichia coli causes hemorrhagic colitis, hemolytic uremic syndrome (HUS, acute renal failure, and also central nervous system complications in around 30% of the children affected. Besides, neurological deficits are one of the most unrepairable and untreatable outcomes of HUS. Study of the striatum is relevant because basal ganglia are one of the brain areas most commonly affected in patients that have suffered from HUS and since the deleterious effects of a sub-lethal dose of Shiga toxin have never been studied in the striatum, the purpose of this study was to attempt to simulate an infection by Shiga toxin-producing E. coli in a murine model. To this end, intravenous administration of a sub-lethal dose of Shiga toxin 2 (0.5 ηg per mouse was used and the correlation between neurological manifestations and ultrastructural changes in striatal brain cells was studied in detail. Neurological manifestations included significant motor behavior abnormalities in spontaneous motor activity, gait, pelvic elevation and hind limb activity eight days after administration of the toxin. Transmission electron microscopy revealed that the toxin caused early perivascular edema two days after administration, as well as significant damage in astrocytes four days after administration and significant damage in neurons and oligodendrocytes eight days after administration. Interrupted synapses and mast cell extravasation were also found eight days after administration of the toxin. We thus conclude that the chronological order of events observed in the striatum could explain the neurological disorders found eight days after administration of the toxin.

  3. Language learning and brain reorganization in a 3.5-year-old child with left perinatal stroke revealed using structural and functional connectivity.

    Science.gov (United States)

    François, Clément; Ripollés, Pablo; Bosch, Laura; Garcia-Alix, Alfredo; Muchart, Jordi; Sierpowska, Joanna; Fons, Carme; Solé, Jorgina; Rebollo, Monica; Gaitán, Helena; Rodriguez-Fornells, Antoni

    2016-04-01

    Brain imaging methods have contributed to shed light on the possible mechanisms of recovery and cortical reorganization after early brain insult. The idea that a functional left hemisphere is crucial for achieving a normalized pattern of language development after left perinatal stroke is still under debate. We report the case of a 3.5-year-old boy born at term with a perinatal ischemic stroke of the left middle cerebral artery, affecting mainly the supramarginal gyrus, superior parietal and insular cortex extending to the precentral and postcentral gyri. Neurocognitive development was assessed at 25 and 42 months of age. Language outcomes were more extensively evaluated at the latter age with measures on receptive vocabulary, phonological whole-word production and linguistic complexity in spontaneous speech. Word learning abilities were assessed using a fast-mapping task to assess immediate and delayed recall of newly mapped words. Functional and structural imaging data as well as a measure of intrinsic connectivity were also acquired. While cognitive, motor and language levels from the Bayley Scales fell within the average range at 25 months, language scores were below at 42 months. Receptive vocabulary fell within normal limits but whole word production was delayed and the child had limited spontaneous speech. Critically, the child showed clear difficulties in both the immediate and delayed recall of the novel words, significantly differing from an age-matched control group. Neuroimaging data revealed spared classical cortical language areas but an affected left dorsal white-matter pathway together with right lateralized functional activations. In the framework of the model for Social Communication and Language Development, these data confirm the important role of the left arcuate fasciculus in understanding and producing morpho-syntactic elements in sentences beyond two word combinations and, most importantly, in learning novel word-referent associations, a

  4. Complex interplay between brain function and structure during cerebral amyloidosis in APP transgenic mouse strains revealed by multi-parametric MRI comparison.

    Science.gov (United States)

    Grandjean, Joanes; Derungs, Rebecca; Kulic, Luka; Welt, Tobias; Henkelman, Mark; Nitsch, Roger M; Rudin, Markus

    2016-07-01

    Alzheimer's disease is a fatal neurodegenerative disorder affecting the aging population. Neuroimaging methods, in particular magnetic resonance imaging (MRI), have helped reveal alterations in the brain structure, metabolism, and function of patients and in groups at risk of developing AD, yet the nature of these alterations is poorly understood. Neuroimaging in mice is attractive for investigating mechanisms underlying functional and structural changes associated with AD pathology. Several preclinical murine models of AD have been generated based on transgenic insertion of human mutated APP genes. Depending on the specific mutations, mouse strains express different aspects of amyloid pathology, e.g. intracellular amyloid-β (Aβ) aggregates, parenchymal plaques, or cerebral amyloid angiopathy. We have applied multi-parametric MRI in three transgenic mouse lines to compare changes in brain function with resting-state fMRI and structure with diffusion tensor imaging and high resolution anatomical imaging. E22ΔAβ developing intracellular Aβ aggregates did not present functional or structural alterations compared to their wild-type littermates. PSAPP mice displaying parenchymal amyloid plaques displayed mild functional changes within the supplementary and barrel field cortices, and increased isocortical volume relative to controls. Extensive reduction in functional connectivity in the sensory-motor cortices and within the default mode network, as well as local volume increase in the midbrain relative to wild-type have been observed in ArcAβ mice bearing intracellular Aβ aggregates as well as parenchymal and vascular amyloid deposits. Patterns of functional and structural changes appear to be strain-specific and not directly related to amyloid deposition. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. A brain-wide association study of DISC1 genetic variants reveals a relationship with the structure and functional connectivity of the precuneus in schizophrenia.

    Science.gov (United States)

    Gong, Xiaohong; Lu, Wenlian; Kendrick, Keith M; Pu, Weidan; Wang, Chu; Jin, Li; Lu, Guangmin; Liu, Zhening; Liu, Haihong; Feng, Jianfeng

    2014-11-01

    The Disrupted in Schizophrenia Gene 1 (DISC1) plays a role in both neural signaling and development and is associated with schizophrenia, although its links to altered brain structure and function in this disorder are not fully established. Here we have used structural and functional MRI to investigate links with six DISC1 single nucleotide polymorphisms (SNPs). We employed a brain-wide association analysis (BWAS) together with a Jacknife internal validation approach in 46 schizophrenia patients and 24 matched healthy control subjects. Results from structural MRI showed significant associations between all six DISC1 variants and gray matter volume in the precuneus, post-central gyrus and middle cingulate gyrus. Associations with specific SNPs were found for rs2738880 in the left precuneus and right post-central gyrus, and rs1535530 in the right precuneus and middle cingulate gyrus. Using regions showing structural associations as seeds a resting-state functional connectivity analysis revealed significant associations between all 6 SNPS and connectivity between the right precuneus and inferior frontal gyrus. The connection between the right precuneus and inferior frontal gyrus was also specifically associated with rs821617. Importantly schizophrenia patients showed positive correlations between the six DISC-1 SNPs associated gray matter volume in the left precuneus and right post-central gyrus and negative symptom severity. No correlations with illness duration were found. Our results provide the first evidence suggesting a key role for structural and functional connectivity associations between DISC1 polymorphisms and the precuneus in schizophrenia. Copyright © 2014 Wiley Periodicals, Inc.

  6. Distinct BOLD fMRI Responses of Capsaicin-Induced Thermal Sensation Reveal Pain-Related Brain Activation in Nonhuman Primates.

    Science.gov (United States)

    Asad, Abu Bakar Ali; Seah, Stephanie; Baumgartner, Richard; Feng, Dai; Jensen, Andres; Manigbas, Elaine; Henry, Brian; Houghton, Andrea; Evelhoch, Jeffrey L; Derbyshire, Stuart W G; Chin, Chih-Liang

    2016-01-01

    Approximately 20% of the adult population suffer from chronic pain that is not adequately treated by current therapies, highlighting a great need for improved treatment options. To develop effective analgesics, experimental human and animal models of pain are critical. Topically/intra-dermally applied capsaicin induces hyperalgesia and allodynia to thermal and tactile stimuli that mimics chronic pain and is a useful translation from preclinical research to clinical investigation. Many behavioral and self-report studies of pain have exploited the use of the capsaicin pain model, but objective biomarker correlates of the capsaicin augmented nociceptive response in nonhuman primates remains to be explored. Here we establish an aversive capsaicin-induced fMRI model using non-noxious heat stimuli in Cynomolgus monkeys (n = 8). BOLD fMRI data were collected during thermal challenge (ON:20 s/42°C; OFF:40 s/35°C, 4-cycle) at baseline and 30 min post-capsaicin (0.1 mg, topical, forearm) application. Tail withdrawal behavioral studies were also conducted in the same animals using 42°C or 48°C water bath pre- and post- capsaicin application (0.1 mg, subcutaneous, tail). Group comparisons between pre- and post-capsaicin application revealed significant BOLD signal increases in brain regions associated with the 'pain matrix', including somatosensory, frontal, and cingulate cortices, as well as the cerebellum (paired t-test, pinduced reduction of latency at both temperatures. These findings provide insights into the specific brain regions involved with aversive, 'pain-like', responses in a nonhuman primate model. Future studies may employ both behavioral and fMRI measures as translational biomarkers to gain deeper understanding of pain processing and evaluate the preclinical efficacy of novel analgesics.

  7. Brain Basics

    Medline Plus

    Full Text Available ... are sent from one neuron to another. Share Science News NIMH Launches Director Twitter Account Ethics of Deep Brain Stimulation Brain’s Alertness Circuitry Revealed More General Health Information from NIH MEDLINEPlus : Authoritative information from government ...

  8. Brain Basics

    Medline Plus

    Full Text Available ... all. She was happily married and successful in business. Then, after a serious setback at work, she ... from one neuron to another. Share Science News Ethics of Deep Brain Stimulation Brain’s Alertness Circuitry Revealed ...

  9. Dynamic genome wide expression profiling of Drosophila head development reveals a novel role of Hunchback in retinal glia cell development and blood-brain barrier integrity.

    Directory of Open Access Journals (Sweden)

    Montserrat Torres-Oliva

    2018-01-01

    Full Text Available Drosophila melanogaster head development represents a valuable process to study the developmental control of various organs, such as the antennae, the dorsal ocelli and the compound eyes from a common precursor, the eye-antennal imaginal disc. While the gene regulatory network underlying compound eye development has been extensively studied, the key transcription factors regulating the formation of other head structures from the same imaginal disc are largely unknown. We obtained the developmental transcriptome of the eye-antennal discs covering late patterning processes at the late 2nd larval instar stage to the onset and progression of differentiation at the end of larval development. We revealed the expression profiles of all genes expressed during eye-antennal disc development and we determined temporally co-expressed genes by hierarchical clustering. Since co-expressed genes may be regulated by common transcriptional regulators, we combined our transcriptome dataset with publicly available ChIP-seq data to identify central transcription factors that co-regulate genes during head development. Besides the identification of already known and well-described transcription factors, we show that the transcription factor Hunchback (Hb regulates a significant number of genes that are expressed during late differentiation stages. We confirm that hb is expressed in two polyploid subperineurial glia cells (carpet cells and a thorough functional analysis shows that loss of Hb function results in a loss of carpet cells in the eye-antennal disc. Additionally, we provide for the first time functional data indicating that carpet cells are an integral part of the blood-brain barrier. Eventually, we combined our expression data with a de novo Hb motif search to reveal stage specific putative target genes of which we find a significant number indeed expressed in carpet cells.

  10. Genetic silencing of Nox2 and Nox4 reveals differential roles of these NADPH oxidase homologues in the vasopressor and dipsogenic effects of brain angiotensin II.

    Science.gov (United States)

    Peterson, Jeffrey R; Burmeister, Melissa A; Tian, Xin; Zhou, Yi; Guruju, Mallikarjuna R; Stupinski, John A; Sharma, Ram V; Davisson, Robin L

    2009-11-01

    The renin-angiotensin system exerts a tremendous influence over fluid balance and arterial pressure. Angiotensin II (Ang-II), the effector peptide of the renin-angiotensin system, acts in the central nervous system to regulate neurohumoral outflow and thirst. Dysregulation of Ang-II signaling in the central nervous system is implicated in cardiovascular diseases; however, the mechanisms remain poorly understood. Recently we established that NADPH oxidase (Nox)-derived superoxide acting in the forebrain subfornical organ is critical in the physiological responses to central Ang-II. In addition, we have found that Nox2 and Nox4 are the most abundantly expressed Nox homologues within Ang-II-sensitive sites in the forebrain. To dissect out the functional importance and unique roles of these Nox enzymes in the pressor and dipsogenic effects of central Ang-II, we developed adenoviral vectors expressing small interfering RNA to selectively silence Nox2 or Nox4 expression in the subfornical organ. Our results demonstrate that both Nox2 and Nox4 are required for the full vasopressor effects of brain Ang-II but that only Nox2 is coupled to the Ang-II-induced water intake response. These studies establish the importance of both Nox2- and Nox4-containing NADPH oxidases in the actions of Ang-II in the central nervous system and are the first to reveal differential involvement of these Nox enzymes in the various physiological effects of central Ang-II.

  11. Genetic silencing of Nox2 and Nox4 reveals differential roles of these NADPH oxidase homologues in the vasopressor and dipsogenic effects of brain angiotensin-II

    Science.gov (United States)

    Peterson, Jeffrey R.; Burmeister, Melissa A.; Tian, Xin; Zhou, Yi; Guruju, Mallikarjuna R.; Stupinski, John A.; Sharma, Ram V.; Davisson, Robin L.

    2009-01-01

    The renin angiotensin system (RAS) exerts a tremendous influence over fluid balance and arterial pressure. Angiotensin II (Ang-II), the effector peptide of the RAS, acts in the CNS to regulate neurohumoral outflow and thirst. Dysregulation of Ang-II signaling in the CNS is implicated in cardiovascular diseases, however the mechanisms remain poorly understood. Recently we established that NADPH oxidase (Nox)-derived superoxide acting in the forebrain subfornical organ (SFO) is critical in the physiologic responses to central Ang-II. In addition, we have found that Nox2 and Nox4 are the most abundantly expressed Nox homologues within Ang-II-sensitive sites in the forebrain. To dissect out the functional importance and unique roles of these Nox enzymes in the pressor and dipsogenic effects of central Ang-II, we developed adenoviral vectors expressing siRNA to selectively silence Nox2 or Nox4 expression in the SFO. Our results demonstrate that both Nox2 and Nox4 are required for the full vasopressor effects of brain Ang-II, but that only Nox2 is coupled to the Ang-II-induced water intake response. These studies establish the importance of both Nox2- and Nox4-containing NADPH oxidases in the actions of Ang-II in the CNS, and are the first to reveal differential involvement of these Nox enzymes in the various physiologic effects of central Ang-II. PMID:19805637

  12. Assigning cause for sudden unexpected infant death.

    Science.gov (United States)

    Hunt, Carl E; Darnall, Robert A; McEntire, Betty L; Hyma, Bruce A

    2015-06-01

    We have reached a conundrum in assigning cause of death for sudden unexpected infant deaths. We summarize the discordant perspectives and approaches and how they have occurred, and recommend a pathway toward improved consistency. This lack of consistency affects pediatricians and other health care professionals, scientific investigators, medical examiners and coroners, law enforcement agencies, families, and support or advocacy groups. We recommend that an interdisciplinary international committee be organized to review current approaches for assigning cause of death, and to identify a consensus strategy for improving consistency. This effort will need to encompass intrinsic risk factors or infant vulnerability in addition to known environmental risk factors including unsafe sleep settings, and must be sufficiently flexible to accommodate a progressively expanding knowledge base.

  13. Sudden unexpected death in infancy in Denmark

    DEFF Research Database (Denmark)

    Winkel, Bo Gregers; Holst, Anders Gaarsdal; Theilade, Juliane

    2011-01-01

    Abstract Background. Incidence of sudden unexpected death in infancy (SUDI) and sudden infant death syndrome (SIDS) differs among studies and non-autopsied cases are difficult to assess. Objectives. To investigate causes of sudden death in infancy in a nationwide setting. Validate the use...... of the ICD-10 code for SIDS (R95) in the Danish Cause of Death registry. Design. A retrospective analysis of all infant deaths (death certificates and autopsy reports were read. Results. We identified 192 SUDI cases (10% of total deaths, 0.42 per 1000 births......) with autopsy performed in 87% of cases. In total, 49% of autopsied SUDI cases were defined as SIDS (5% of all deaths, 0.22 per 1000 births); Cardiac cause of death was denoted in 24% of cases. The Danish Cause of Death Registry misclassified 30% of SIDS cases. Conclusions. A large proportion of infant deaths...

  14. Focal adhesion kinase signaling in unexpected places.

    Science.gov (United States)

    Kleinschmidt, Elizabeth G; Schlaepfer, David D

    2017-04-01

    Focal adhesion kinase (FAK) is a cytoplasmic protein-tyrosine kinase first identified at extracellular matrix and integrin receptor cell adhesion sites and is a key regulator of cell movement. FAK is activated by a variety of stimuli. Herein, we discuss advances in conformational-associated FAK activation and dimerization mechanisms. Additionally, new roles have emerged for FAK signaling at cell adhesions, adherens junctions, endosomes, and the nucleus. In light of these new findings, we review how FAK activation at these sites is connected to the regulation of integrin recycling-activation, vascular permeability, cell survival, and transcriptional regulation, respectively. Studies uncovering FAK signaling connections in unexpected places within cells have yielded important new regulatory insights in cell biology. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Unexpected Translations in Urban Policy Mobility

    DEFF Research Database (Denmark)

    Zapata, Patrik; Zapata Campos, Maria José

    2015-01-01

    Implementation gaps between policy goals and outcomes are of increasing concern in practice and research. We explore the translation chains through which urban policies become mobile and are translated into practice. Informed by the city management and policy mobility literature, we conduct a case...... study of La Chureca, the rubbish dump and slum of Managua, Nicaragua, and its renewal programme. The Acahualinca Programme was implemented via translation chains enacted by many policy translators. It was translated into residents' and waste collectors' interests, its language packaged in artefacts...... such as prototypes in order to travel. It was made mobile via relational sites or situations providing safe and accessible connections with Chureca residents. Paradoxically, these places also allowed extraordinary connections between actors located in different scales and spaces, facilitating unexpected local...

  16. Unexpected flood loss correlations across Europe

    Science.gov (United States)

    Booth, Naomi; Boyd, Jessica

    2017-04-01

    Floods don't observe country borders, as highlighted by major events across Europe that resulted in heavy economic and insured losses in 1999, 2002, 2009 and 2013. Flood loss correlations between some countries occur along multi-country river systems or between neighbouring nations affected by the same weather systems. However, correlations are not so obvious and whilst flooding in multiple locations across Europe may appear independent, for a re/insurer providing cover across the continent, these unexpected correlations can lead to high loss accumulations. A consistent, continental-scale method that allows quantification and comparison of losses, and identifies correlations in loss between European countries is therefore essential. A probabilistic model for European river flooding was developed that allows estimation of potential losses to pan-European property portfolios. By combining flood hazard and exposure information in a catastrophe modelling platform, we can consider correlations between river basins across Europe rather than being restricted to country boundaries. A key feature of the model is its statistical event set based on extreme value theory. Using historical river flow data, the event set captures spatial and temporal patterns of flooding across Europe and simulates thousands of events representing a full range of possible scenarios. Some known correlations were identified, such as between neighbouring Belgium and Luxembourg where 28% of events that affect either country produce a loss in both. However, our model identified some unexpected correlations including between Austria and Poland, and Poland and France, which are geographically distant. These correlations in flood loss may be missed by traditional methods and are key for re/insurers with risks in multiple countries. The model also identified that 46% of European river flood events affect more than one country. For more extreme events with a return period higher than 200 years, all events

  17. Unexpected MRI findings in clinically suspected Legg-Calve-Perthes disease

    Energy Technology Data Exchange (ETDEWEB)

    Lobert, Philip F.; Dillman, Jonathan R.; Strouse, Peter J.; Hernandez, Ramiro J. [University of Michigan Health System, Department of Radiology, Section of Pediatric Radiology, C.S. Mott Children' s Hospital/F3503, Ann Arbor, MI (United States)

    2011-03-15

    In the setting of clinically suspected Legg-Calve-Perthes (LCP) disease and negative/equivocal radiographs, contrast-enhanced MRI can be performed to confirm the diagnosis. To determine the frequency of unexpected causes of hip pain as identified by MRI in children with clinically suspected LCP disease and negative/equivocal radiographs. All pediatric contrast-enhanced MRI examinations of the pelvis and hips performed between January 2000 and February 2009 to evaluate for possible LCP disease in the setting of negative/equivocal radiographs were identified. MRI examinations performed to evaluate for secondary avascular necrosis were excluded. Imaging reports were retrospectively reviewed for unexpected clinically important causes of hip pain. Thirty-six pediatric patients underwent contrast-enhanced MRI examinations for clinically suspected LCP disease in the setting of negative/equivocal radiographs. Twenty-two (61%) imaging studies were normal, while four (11%) imaging studies demonstrated findings consistent with LCP disease. Ten (28%) imaging studies revealed unexpected clinically important causes of hip pain, including nonspecific unilateral joint effusion and synovitis (n = 7, juvenile chronic arthritis was eventually diagnosed in 3 patients), sacral fracture (n = 1), apophyseal injury (n = 1), and femoral head subluxation (n = 1). MRI frequently reveals unexpected clinically important causes of hip pain in children with suspected LCP disease and negative/equivocal radiographs. (orig.)

  18. Voxel-based morphometry and fMRI revealed differences in brain gray matter in breastfed and milk formula–fed children

    Science.gov (United States)

    Background and Purpose: Infant diets may have significant impact on brain development in children. The aim of this study was to evaluate brain grey matter structure and function in 8-year-old children who were predominantly breastfed (BF) or fed cow’s milk formula (MF) as infants. Materials and Me...

  19. Gene expression profiling in the stress control brain region hypothalamic paraventricular nucleus reveals a novel gene network including Amyloid beta Precursor Protein

    Directory of Open Access Journals (Sweden)

    Deussing Jan M

    2010-10-01

    Full Text Available Abstract Background The pivotal role of stress in the precipitation of psychiatric diseases such as depression is generally accepted. This study aims at the identification of genes that are directly or indirectly responding to stress. Inbred mouse strains that had been evidenced to differ in their stress response as well as in their response to antidepressant treatment were chosen for RNA profiling after stress exposure. Gene expression and regulation was determined by microarray analyses and further evaluated by bioinformatics tools including pathway and cluster analyses. Results Forced swimming as acute stressor was applied to C57BL/6J and DBA/2J mice and resulted in sets of regulated genes in the paraventricular nucleus of the hypothalamus (PVN, 4 h or 8 h after stress. Although the expression changes between the mouse strains were quite different, they unfolded in phases over time in both strains. Our search for connections between the regulated genes resulted in potential novel signalling pathways in stress. In particular, Guanine nucleotide binding protein, alpha inhibiting 2 (GNAi2 and Amyloid β (A4 precursor protein (APP were detected as stress-regulated genes, and together with other genes, seem to be integrated into stress-responsive pathways and gene networks in the PVN. Conclusions This search for stress-regulated genes in the PVN revealed its impact on interesting genes (GNAi2 and APP and a novel gene network. In particular the expression of APP in the PVN that is governing stress hormone balance, is of great interest. The reported neuroprotective role of this molecule in the CNS supports the idea that a short acute stress can elicit positive adaptational effects in the brain.

  20. Categories of preventable unexpected infant deaths.

    Science.gov (United States)

    Taylor, E M; Emery, J L

    1990-01-01

    The conclusions of confidential inquiries into 115 registered unexpected infant deaths over a period of nine years were reviewed. Deaths were classified based on the total information available into group A: poor prognosis (n = 7), group B: treatable disease (n = 45), group C: minor disease (n = 32), group D: no disease (n = 19), group E: probably accidental (n = 4), and group F: probably filicide (n = 8). Less than 20% of deaths corresponded to the classic definition of sudden infant death syndrome (SIDS). Babies who died during the course of potentially treatable disease had more adverse family and social factors: the parents were less likely to be owner occupiers, or own a car or telephone, their mothers were more likely to be young, to smoke, and to present late in pregnancy. Babies who died of minor disease tended to come from similar backgrounds, their families had greater levels of stress and the deaths appeared to be due to more than one factor. Babies who died with no terminal disease were younger, and more likely to be boys. Their families appeared to be demographically similar to those of a control group and to the general population. PMID:2357095

  1. Infants preferentially approach and explore the unexpected.

    Science.gov (United States)

    Sim, Zi L; Xu, Fei

    2017-11-01

    Looking time experiments based on the violation-of-expectation (VOE) method have consistently demonstrated that infants look longer when their expectations are violated. However, it remains an open question whether similar effects will be observed in infants' approach behaviours. Specifically, do infants selectively approach and explore sources that violate their expectations? In this study, we address this question by examining how infants' looking times are related to their approach and exploration behaviours. Using a traditional VOE method and a crawling paradigm, we demonstrate a strong correspondence between looking time and approach behaviours, which indicates that 13-month-old infants preferentially explore sources of unexpected events. Such spontaneous exploration may provide learning opportunities and allow infants to play an active role in driving their own development. Statement of contribution What is already known on this subject? Infants look longer when their expectations are violated. There is some evidence that infants also preferentially explore objects that violate their 'core' physical expectations. What the present study adds? There is a clear correspondence between infants' looking behaviour and their approach behaviour. Expectancy violations involving non-core knowledge can similarly influence infants' exploration. © 2017 The British Psychological Society.

  2. Ombud's Corner: unexpected turn in the conversation?

    CERN Multimedia

    Sudeshna Datta-Cockerill

    2014-01-01

    Regular informal conversations with colleagues play a very important part in weaving the fabric of team spirit. They allow us to build the working relationships that are vital to the success of our projects and to create an environment of good will that is instrumental in averting potential conflict or crises. However, sometimes they can come with unexpected surprises…   Eric and his colleagues always meet on Monday mornings to have coffee together, before starting the working week. This is a very privileged moment for the team when there are no formal barriers or professional concerns: Mary may talk about a film that she saw at the weekend, Eric often goes hiking in the Jura with his friend Stefan, Hans has always got a story about his son’s prowess on the school football team and occasionally there is a bit of special news such as Louisa’s recent marriage, Pierre’s baby’s christening or Claude’s daughter’s graduation&...

  3. A novel brain tumour model in zebrafish reveals the role of YAP activation in MAPK- and PI3K-induced malignant growth

    Directory of Open Access Journals (Sweden)

    Marie Mayrhofer

    2017-01-01

    Full Text Available Somatic mutations activating MAPK and PI3K signalling play a pivotal role in both tumours and brain developmental disorders. We developed a zebrafish model of brain tumours based on somatic expression of oncogenes that activate MAPK and PI3K signalling in neural progenitor cells and found that HRASV12 was the most effective in inducing both heterotopia and invasive tumours. Tumours, but not heterotopias, require persistent activation of phospho (p-ERK and express a gene signature similar to the mesenchymal glioblastoma subtype, with a strong YAP component. Application of an eight-gene signature to human brain tumours establishes that YAP activation distinguishes between mesenchymal glioblastoma and low grade glioma in a wide The Cancer Genome Atlas (TCGA sample set including gliomas and glioblastomas (GBMs. This suggests that the activation of YAP might be an important event in brain tumour development, promoting malignant versus benign brain lesions. Indeed, co-expression of dominant-active YAP (YAPS5A and HRASV12 abolishes the development of heterotopias and leads to the sole development of aggressive tumours. Thus, we have developed a model proving that neurodevelopmental disorders and brain tumours might originate from the same activation of oncogenes through somatic mutations, and established that YAP activation is a hallmark of malignant brain tumours.

  4. 42 CFR 493.861 - Standard; Unexpected antibody detection.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Standard; Unexpected antibody detection. 493.861 Section 493.861 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN..., Or Any Combination of These Tests § 493.861 Standard; Unexpected antibody detection. (a) Failure to...

  5. Orthographic Processing and Visual Sequential Memory in Unexpectedly Poor Spellers

    Science.gov (United States)

    Holmes, Virginia M.; Malone, Aisling M.; Redenbach, Holly

    2008-01-01

    Does unexpectedly poor spelling in adults result from inferior visual sequential memory? In one experiment, unexpectedly poor spellers performed significantly worse than better spellers in the immediate reproduction of sequences of visual symbols, but in a second experiment, the effect was not replicated. Poor spellers were also no worse at the…

  6. A brain-wide association study of DISC1 genetic variants reveals a relationship with the structure and functional connectivity of the precuneus in schizophrenia

    OpenAIRE

    Gong, Xiaohong; Lu, Wenlian; Kendrick, Keith M.; Pu, Weidan; Wang, Chu; Jin, Li; Lu, Guangmin; Liu, Zhening; LIU Haihong(The United Graduate School of Education, Tokyo Gakugei University); Feng, Jianfeng

    2014-01-01

    The Disrupted in Schizophrenia Gene 1 (DISC1) plays a role in both neural signalling and development and is associated with schizophrenia, although its links to altered brain structure and function in this disorder are not fully established. Here we have used structural and functional MRI to investigate links with six DISC1 single nucleotide polymorphisms (SNPs). We employed a brain-wide association analysis (BWAS) together with a Jacknife internal validation approach in 46 schizophrenia pati...

  7. Resting-state functional MRI reveals altered brain connectivity and its correlation with motor dysfunction in a mouse model of Huntington's disease.

    Science.gov (United States)

    Li, Qiang; Li, Gang; Wu, Dan; Lu, Hanbing; Hou, Zhipeng; Ross, Christopher A; Yang, Yihong; Zhang, Jiangyang; Duan, Wenzhen

    2017-12-01

    Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder, and no cure is available currently. Treatment of HD is likely to be most beneficial in the early, possibly pre-manifestation stage. The challenge is to determine the best time for intervention and evaluate putative efficacy in the absence of clinical symptoms. Resting-state functional MRI may represent a promising tool to develop biomarker reflecting early neuronal dysfunction in HD brain, because it can examine multiple brain networks without confounding effects of cognitive ability, which makes the resting-state fMRI promising as a translational bridge between preclinical study in animal models and clinical findings in HD patients. In this study, we examined brain regional connectivity and its correlation to brain atrophy, as well as motor function in the 18-week-old N171-82Q HD mice. HD mice exhibited significantly altered functional connectivity in multiple networks. Particularly, the weaker intra-striatum connectivity was positively correlated with striatal atrophy, while striatum-retrosplenial cortex connectivity is negatively correlated with striatal atrophy. The resting-state brain regional connectivity had no significant correlation with motor deficits in HD mice. Our results suggest that altered brain connectivity detected by resting-state fMRI might serve as an early disease biomarker in HD.

  8. A Neonate with Susceptibility to Long QT Syndrome Type 6 who Presented with Ventricular Fibrillation and Sudden Unexpected Infant Death.

    Science.gov (United States)

    Sauer, Charles W; Marc-Aurele, Krishelle L

    2016-07-28

    BACKGROUND This is a case of a neonate with susceptibility to long QT syndrome (LQTS) who presented with a sudden unexpected infant death. Experts continue to debate whether universal electrocardiogram (ECG) screening of all newborns is feasible, practical, and cost-effective. CASE REPORT A 19-day-old neonate was found unresponsive by her mother. ECG showed ventricular fibrillation and a combination of a lidocaine drip plus multiple defibrillations converted the rhythm to normal sinus. Unfortunately, MRI brain imaging showed multiple infarcts and EEG showed burst suppression pattern with frequent seizures; life supportive treatment was stopped and the infant died. Genetic testing revealed two mutations in the KCNE2 gene consistent with susceptibility to LQTS type 6. CONCLUSIONS We believe this case is the first to demonstrate both a precipitating electrocardiographic and genetic cause of death for an infant with LQTS, showing a cause-and-effect relationship between LQTS mutation, ventricular arrhythmia, and death. We wonder whether universal ECG newborn screening to prevent LQTS death could have saved this baby.

  9. Single Nucleotide Polymorphism (SNP) Arrays and Unexpected Consanguinity: Considerations for Clinicians When Returning Results to Families

    Science.gov (United States)

    Delgado, Fernanda; Tabor, Holly K.; Chow, Penny M.; Conta, Jessie H.; Feldman, Kenneth W.; Tsuchiya, Karen D.; Beck, Anita E.

    2014-01-01

    Purpose The broad use of SNP microarrays has increased identification of unexpected consanguinity. Therefore, guidelines to address reporting of consanguinity have been published for clinical laboratories. Because no such guidelines exist for clinicians, we describe a case and present recommendations for clinicians to disclose unexpected consanguinity to families. Methods In a boy with multiple endocrine abnormalities and structural birth defects, SNP array analysis revealed ~23% autosomal homozygosity suggestive of a 1st-degree parental relationship. We assembled an interdisciplinary healthcare team, planned the most appropriate way to discuss results of the SNP array with the adult mother including the possibility of multiple autosomal recessive disorders in her child, and finally met with her as a team. Results From these discussions, we developed four major considerations for clinicians returning results of unexpected consanguinity, all guided by the child’s best interests: 1) ethical and legal obligations for reporting possible abuse, 2) preservation of the clinical relationship, 3) attention to justice and psychosocial challenges, and 4) utilization of the SNP array results to guide further testing. Conclusion As SNP arrays become a common clinical diagnostic tool, clinicians can use this framework to return results of unexpected consanguinity to families in a supportive and productive manner. PMID:25232848

  10. Single-nucleotide polymorphism arrays and unexpected consanguinity: considerations for clinicians when returning results to families.

    Science.gov (United States)

    Delgado, Fernanda; Tabor, Holly K; Chow, Penny M; Conta, Jessie H; Feldman, Kenneth W; Tsuchiya, Karen D; Beck, Anita E

    2015-05-01

    The broad use of single-nucleotide polymorphism microarrays has increased identification of unexpected consanguinity. Therefore, guidelines to address reporting of consanguinity have been published for clinical laboratories. Because no such guidelines for clinicians exist, we describe a case and present recommendations for clinicians to disclose unexpected consanguinity to families. In a boy with multiple endocrine abnormalities and structural birth defects, single-nucleotide polymorphism array analysis revealed ~23% autosomal homozygosity suggestive of a first-degree parental relationship. We assembled an interdisciplinary health-care team, planned the most appropriate way to discuss results of the single-nucleotide polymorphism array with the adult mother, including the possibility of multiple autosomal recessive disorders in her child, and finally met with her as a team. From these discussions, we developed four major considerations for clinicians returning results of unexpected consanguinity, all guided by the child's best interests: (i) ethical and legal obligations for reporting possible abuse, (ii) preservation of the clinical relationship, (iii) attention to justice and psychosocial challenges, and (iv) utilization of the single-nucleotide polymorphism array results to guide further testing. As single-nucleotide polymorphism arrays become a common clinical diagnostic tool, clinicians can use this framework to return results of unexpected consanguinity to families in a supportive and productive manner.

  11. Autistic Traits Affect P300 Response to Unexpected Events, regardless of Mental State Inferences

    Directory of Open Access Journals (Sweden)

    Mitsuhiko Ishikawa

    2017-01-01

    Full Text Available Limited use of contextual information has been suggested as a way of understanding cognition in people with autism spectrum disorder (ASD. However, it has also been argued that individuals with ASD may have difficulties inferring others’ mental states. Here, we examined how individuals with different levels of autistic traits respond to contextual deviations by measuring event-related potentials that reflect context usage. The Autism Spectrum Quotient (AQ was used to quantify autistic-like traits in 28 university students, and 19 participants were defined as Low or High AQ groups. To additionally examine inferences about mental state, two belief conditions (with or without false belief were included. Participants read short stories in which the final sentence included either an expected or an unexpected word and rated the word’s degree of deviation from expectation. P300 waveform analysis revealed that unexpected words were associated with larger P300 waveforms for the Low AQ group, but smaller P300 responses in the High AQ group. Additionally, AQ social skill subscores were positively correlated with evaluation times in the Unexpected condition, whether a character’s belief was false or not. This suggests that autistic traits can affect responses to unexpected events, possibly because of decreased availability of context information.

  12. Unexpected distribution of KRIT1 inside the nucleus: new insight in a complex molecular pathway

    Directory of Open Access Journals (Sweden)

    S. Marzo

    2014-03-01

    Full Text Available KRIT1 is an 84kDa protein that lacks any relevant catalytic domains, associated with the cerebral cavernous malformation disease. We have investigated by means of ultrastructural immunocytochemistry the nuclear distribution of KRIT1 in different cell lines, revealing its unexpected localization on actively transcribing nuclear domains such as the perichromatin fibrils and the nucleolar dense fibrillar component. These preliminary data indicate a still undescribed and unknown role for KRIT1 inside the nucleus.

  13. Comprehensive Identification of Long Non-coding RNAs in Purified Cell Types from the Brain Reveals Functional LncRNA in OPC Fate Determination.

    Directory of Open Access Journals (Sweden)

    Xiaomin Dong

    2015-12-01

    Full Text Available Long non-coding RNAs (lncRNAs (> 200 bp play crucial roles in transcriptional regulation during numerous biological processes. However, it is challenging to comprehensively identify lncRNAs, because they are often expressed at low levels and with more cell-type specificity than are protein-coding genes. In the present study, we performed ab initio transcriptome reconstruction using eight purified cell populations from mouse cortex and detected more than 5000 lncRNAs. Predicting the functions of lncRNAs using cell-type specific data revealed their potential functional roles in Central Nervous System (CNS development. We performed motif searches in ENCODE DNase I digital footprint data and Mouse ENCODE promoters to infer transcription factor (TF occupancy. By integrating TF binding and cell-type specific transcriptomic data, we constructed a novel framework that is useful for systematically identifying lncRNAs that are potentially essential for brain cell fate determination. Based on this integrative analysis, we identified lncRNAs that are regulated during Oligodendrocyte Precursor Cell (OPC differentiation from Neural Stem Cells (NSCs and that are likely to be involved in oligodendrogenesis. The top candidate, lnc-OPC, shows highly specific expression in OPCs and remarkable sequence conservation among placental mammals. Interestingly, lnc-OPC is significantly up-regulated in glial progenitors from experimental autoimmune encephalomyelitis (EAE mouse models compared to wild-type mice. OLIG2-binding sites in the upstream regulatory region of lnc-OPC were identified by ChIP (chromatin immunoprecipitation-Sequencing and validated by luciferase assays. Loss-of-function experiments confirmed that lnc-OPC plays a functional role in OPC genesis. Overall, our results substantiated the role of lncRNA in OPC fate determination and provided an unprecedented data source for future functional investigations in CNS cell types. We present our datasets and

  14. The unexpected response of kelp to wave motion

    Science.gov (United States)

    Mullarney, J. C.; Pilditch, C. A.

    2014-12-01

    Kelp ecosystems offer many ecosystem services such as providing critical habitat for numerous species, trapping contaminants and nutrients and influencing coastal morphology. However, the extent to which kelp 'goes with the flow' as opposed to dissipating wave and current energy is unclear. We present innovative measurements of the wave-forced motion of the giant kelp Macrocystis pyrifera at different heights along the length of the stipe using a series of accelerometers attached at fixed intervals. Observations were taken at the Aramoana breakwater ("the Mole"), located at the entrance to Otago Harbor, New Zealand. This field site encompassed a wave-exposed region open to Pacific swells and a sheltered (harbor) region. Analysis of wave gauge measurements revealed that forcing was dominated by the swell frequency (0.11 Hz). However, the spectra also indicated periods of substantial energy at lower, infragravity wave frequencies (0.011 Hz). Preliminary analysis of the accelerometer data shows significant differences in displacement over the stem length, with large motions apparent at both the top and bottom of the kelp (consistent with visual observations from divers). Initial observations also revealed an unexpected result; different sections of the kelp responded most strongly to different forcing frequencies. In particular, the lowest sensor showed peaks in energy close to both swell and infragravity periods, whereas the higher sensor revealed the surprising result of a strong response at the infragravity frequencies but little movement at the swell frequencies. We discuss how these results may allow us to determine the extent to which aquatic plants are adapted to minimize stresses imposed by fluid flow and potential consequences for present and future plant community distributions.

  15. Multidimensional frequency domain analysis of full-volume fMRI reveals significant effects of age, gender and mental illness on the spatiotemporal organization of resting-state brain activity

    Directory of Open Access Journals (Sweden)

    Robyn L. Miller

    2015-06-01

    Full Text Available Clinical research employing functional magnetic resonance imaging (fMRI is often conducted within the connectionist paradigm, focusing on patterns of connectivity between voxels, regions of interest (ROIs or spatially distributed functional networks. Connectivity-based analyses are concerned with pairwise correlations of the temporal activation associated with restrictions of the whole-brain hemodynamic signal to locations of a priori interest. There is a more abstract question however that such spatially granular correlation-based approaches do not elucidate: Are the broad spatiotemporal organizing principles of brains in certain populations distinguishable from those of others? Global patterns (in space and time of hemodynamic activation are rarely scrutinized for features that might characterize complex psychiatric conditions, aging effects or gender – among other variables of potential interest to researchers. We introduce a canonical, transparent technique for characterizing the role in overall brain activation of spatially scaled periodic patterns with given temporal recurrence rates. A core feature of our technique is the spatiotemporal spectral profile (STSP, a readily interpretable 2D reduction of the native four-dimensional brain × time frequency domain that is still big enough to capture important group differences in globally patterned brain activation. Its power to distinguish populations of interest is demonstrated on a large balanced multi-site resting fMRI dataset with nearly equal numbers of schizophrenia patients and healthy controls. Our analysis reveals striking differences in the spatiotemporal organization of brain activity that correlate with the presence of diagnosed schizophrenia, as well as with gender and age. To the best of our knowledge, this is the first demonstration that a 4D frequency domain analysis of full volume fMRI data exposes clinically or demographically relevant differences in resting-state brain

  16. A genome-wide in situ hybridization map of RNA-binding proteins reveals anatomically restricted expression in the developing mouse brain

    Directory of Open Access Journals (Sweden)

    Stern Charlene

    2005-07-01

    Full Text Available Abstract Background In eukaryotic cells, RNA-binding proteins (RBPs contribute to gene expression by regulating the form, abundance, and stability of both coding and non-coding RNA. In the vertebrate brain, RBPs account for many distinctive features of RNA processing such as activity-dependent transcript localization and localized protein synthesis. Several RBPs with activities that are important for the proper function of adult brain have been identified, but how many RBPs exist and where these genes are expressed in the developing brain is uncharacterized. Results Here we describe a comprehensive catalogue of the unique RBPs encoded in the mouse genome and provide an online database of RBP expression in developing brain. We identified 380 putative RBPs in the mouse genome. Using in situ hybridization, we visualized the expression of 323 of these RBP genes in the brains of developing mice at embryonic day 13.5, when critical fate choice decisions are made and at P0, when major structural components of the adult brain are apparent. We demonstrate i that 16 of the 323 RBPs examined show neural-specific expression at the stages we examined, and ii that a far larger subset (221 shows regionally restricted expression in the brain. Of the regionally restricted RBPs, we describe one group that is preferentially expressed in the E13.5 ventricular areas and a second group that shows spatially restricted expression in post-mitotic regions of the embryonic brain. Additionally, we find a subset of RBPs that share the same complex pattern of expression, in proliferating regions of the embryonic and postnatal NS and peripheral tissues. Conclusion Our data show that, in contrast to their proposed ubiquitous involvement in gene regulation, most RBPs are not uniformly expressed. Here we demonstrate the region-specific expression of RBPs in proliferating vs. post-mitotic brain regions as well as cell-type-specific RBP expression. We identify uncharacterized RBPs

  17. Unexpected patterns of plastic energy allocation in stochastic environments.

    Science.gov (United States)

    Fischer, Barbara; Taborsky, Barbara; Dieckmann, Ulf

    2009-03-01

    When environmental conditions vary stochastically, individuals accrue fitness benefits by exhibiting phenotypic plasticity. Here we analyze a general dynamic-programming model describing an individual's optimal energy allocation in a stochastic environment. After maturation, individuals repeatedly decide how to allocate incoming energy between reproduction and maintenance. We analyze the optimal fraction of energy invested in reproduction and the resultant degree of plasticity in dependence on environmental variability and predictability. Our analyses reveal unexpected patterns of optimal energy allocation. When energy availability is low, all energy is allocated to reproduction, although this implies that individuals will not survive after reproduction. Above a certain threshold of energy availability, the optimal reproductive investment decreases to a minimum and even vanishes entirely in highly variable environments. With further improving energy availability, optimal reproductive investment gradually increases again. Costs of plasticity affect this allocation pattern only quantitatively. Our results show that optimal reproductive investment does not increase monotonically with growing energy availability and that small changes in energy availability can lead to major variations in optimal energy allocation. Our results help to unify two apparently opposing predictions from life-history theory, that organisms should increase reproductive investment both with improved environmental conditions and when conditions deteriorate ("terminal investment").

  18. Bah humbug: Unexpected Christmas cards and the reciprocity norm.

    Science.gov (United States)

    Meier, Brian P

    2016-01-01

    The reciprocity norm refers to the expectation that people will help those who helped them. A well-known study revealed that the norm is strong with Christmas cards, with 20% of people reciprocating a Christmas card received from a stranger. I attempted to conceptually replicate and extend this effect. In Study 1, 755 participants received a Christmas card supposedly from a more- versus less-similar stranger. The reciprocation rate was unexpectedly low (2%), which did not allow for a test of a similarity effect. Two potential reasons for this low rate were examined in Study 2 in which 494 participants reported their likelihood of reciprocating a Christmas card from a stranger as well as their felt suspicions/threat about the card and their frequency of e-mail use. Reciprocation likelihood was negatively correlated with perceived threat/suspicion and e-mail use. It appears that reciprocating a gift from a stranger in offline settings may be less likely than expected.

  19. What happens to your brain on the way to Mars.

    Science.gov (United States)

    Parihar, Vipan K; Allen, Barrett; Tran, Katherine K; Macaraeg, Trisha G; Chu, Esther M; Kwok, Stephanie F; Chmielewski, Nicole N; Craver, Brianna M; Baulch, Janet E; Acharya, Munjal M; Cucinotta, Francis A; Limoli, Charles L

    2015-05-01

    As NASA prepares for the first manned spaceflight to Mars, questions have surfaced concerning the potential for increased risks associated with exposure to the spectrum of highly energetic nuclei that comprise galactic cosmic rays. Animal models have revealed an unexpected sensitivity of mature neurons in the brain to charged particles found in space. Astronaut autonomy during long-term space travel is particularly critical as is the need to properly manage planned and unanticipated events, activities that could be compromised by accumulating particle traversals through the brain. Using mice subjected to space-relevant fluences of charged particles, we show significant cortical- and hippocampal-based performance decrements 6 weeks after acute exposure. Animals manifesting cognitive decrements exhibited marked and persistent radiation-induced reductions in dendritic complexity and spine density along medial prefrontal cortical neurons known to mediate neurotransmission specifically interrogated by our behavioral tasks. Significant increases in postsynaptic density protein 95 (PSD-95) revealed major radiation-induced alterations in synaptic integrity. Impaired behavioral performance of individual animals correlated significantly with reduced spine density and trended with increased synaptic puncta, thereby providing quantitative measures of risk for developing cognitive decrements. Our data indicate an unexpected and unique susceptibility of the central nervous system to space radiation exposure, and argue that the underlying radiation sensitivity of delicate neuronal structure may well predispose astronauts to unintended mission-critical performance decrements and/or longer-term neurocognitive sequelae.

  20. Unexpected relationships of substructured populations in Chinese Locusta migratoria

    Directory of Open Access Journals (Sweden)

    Ji Ya-Jie

    2009-06-01

    Uvarov in 1930s needs to be revised. The three groups of locusts probably have separate evolutionary histories that were most likely linked to Quaternary glaciations events, and derived from different ancestral refugial populations following postglacial expansions. Conclusion The migratory locust populations in China have differentiated into three genetically distinct groups despite high dispersal capability. While this clarified long-standing suspicions on the subspecific diversification of this species in China, it also revealed that the locusts in the vast area of East China are not the oriental subspecies but the Asiatic subspecies, an unexpected substructuring pattern. The distribution pattern of the three locust groups in China may be primarily defined by adaptive differentiation coupled to Quaternary glaciations events. Our results are of general significance both for locust research and for phylogeographical study of flora and fauna in China, illustrating the potential importance of phylogeographical history in shaping the divergence and distribution patterns of widespread species with strong dispersal ability.

  1. Network-based analysis reveals stronger local diffusion-based connectivity and different correlations with oral language skills in brains of children with high functioning autism spectrum disorders.

    Science.gov (United States)

    Li, Hai; Xue, Zhong; Ellmore, Timothy M; Frye, Richard E; Wong, Stephen T C

    2014-02-01

    Neuroimaging has uncovered both long-range and short-range connectivity abnormalities in the brains of individuals with autism spectrum disorders (ASD). However, the precise connectivity abnormalities and the relationship between these abnormalities and cognition and ASD symptoms have been inconsistent across studies. Indeed, studies find both increases and decreases in connectivity, suggesting that connectivity changes in the ASD brain are not merely due to abnormalities in specific connections, but rather, due to changes in the structure of the network in which the brain areas interact (i.e., network topology). In this study, we examined the differences in the network topology between high-functioning ASD patients and age and gender matched typically developing (TD) controls. After quantitatively characterizing the whole-brain connectivity network using diffusion tensor imaging (DTI) data, we searched for brain regions with different connectivity between ASD and TD. A measure of oral language ability was then correlated with the connectivity changes to determine the functional significance of such changes. Whole-brain connectivity measures demonstrated greater local connectivity and shorter path length in ASD as compared to TD. Stronger local connectivity was found in ASD, especially in regions such as the left superior parietal lobule, the precuneus and angular gyrus, and the right supramarginal gyrus. The relationship between oral language ability and local connectivity within these regions was significantly different between ASD and TD. Stronger local connectivity was associated with better performance in ASD and poorer performance in TD. This study supports the notion that increased local connectivity is compensatory for supporting cognitive function in ASD. Copyright © 2012 Wiley Periodicals, Inc.

  2. Recording of brain activity across spatial scales

    NARCIS (Netherlands)

    Lewis, C.M.; Bosman, C.A.; Fries, P.

    2015-01-01

    Brain activity reveals exquisite coordination across spatial scales, from local microcircuits to brain-wide networks. Understanding how the brain represents, transforms and communicates information requires simultaneous recordings from distributed nodes of whole brain networks with single-cell

  3. Metabolomic Analyses of Brain Tissue in Sepsis Induced by Cecal Ligation Reveal Specific Redox Alterations-Protective Effects of the Oxygen Radical Scavenger Edaravone

    DEFF Research Database (Denmark)

    Hara, Naomi; Chijiiwa, Miyuki; Yara, Miki

    2015-01-01

    at analyzing the preventive effect of the free radical scavenger edaravone on sepsis-induced brain alterations. Sepsis was induced by cecal ligation and puncture (CLP) and the mice were divided into three groups-CLP vehicle (CLPV), CLP and edaravone (MCI-186, 3-methyl-1-phenyl-2-pyrazolin-5-one) (CLPE...

  4. Recombinant Adeno-Associated Virus-Mediated microRNA Delivery into the Postnatal Mouse Brain Reveals a Role for miR-134 in Dendritogenesis in Vivo

    DEFF Research Database (Denmark)

    Christensen, Mette; Larsen, Lars A; Kauppinen, Sakari

    2010-01-01

    delivery of microRNAs in vivo by use of recombinant adeno-associated virus (rAAV). rAAV-mediated overexpression of miR-134 in neurons of the postnatal mouse brain provided evidence for a negative role of miR-134 in dendritic arborization of cortical layer V pyramidal neurons in vivo, thereby confirming...

  5. Resting-state fMRI revealed different brain activities responding to valproic acid and levetiracetam in benign epilepsy with central-temporal spikes

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qirui; Zhang, Zhiqiang; Xu, Qiang; Wu, Han; Li, Zhipeng; Lu, Guangming [Nanjing University School of Medicine, Department of Medical Imaging, Jinling Hospital, Nanjing (China); Yang, Fang; Li, Qian [Nanjing University School of Medicine, Department of Neurology, Jinling Hospital, Nanjing (China); Hu, Zheng [Nanjing Children' s Hospital, Department of Neurology, Nanjing (China); Dante, Mantini [Faculty of Kinesiology and Rehabilitation Sciences, KU Leuven (Belgium); Li, Kai [Suzhou University, Laboratory of Molecular Medicine, Suzhou (China)

    2017-05-15

    Our aim was to investigate regional difference in brain activities in response to antiepileptic drug (AED) medications in benign epilepsy with central-temporal spikes (BECTS) using resting-state functional magnetic resonance imaging (fMRI). Fifty-seven patients with BECTS underwent resting-state fMRI scans after receiving either valproic acid (VPA) (n = 15), levetiracetam (LEV) (n = 21), or no medication (n = 21). fMRI regional homogeneity (ReHo) parameter among the three groups of patients were compared and were correlated with total doses of AED in the two medicated groups. Compared with patients on no-medication, patients receiving either VPA or LEV showed decreased ReHo in the central-temporal region, frontal cortex, and thalamus. In particular, the VPA group showed greater ReHo decrease in the thalamus and milder in cortices and caudate heads compared with the LEV group. In addition, the VPA group demonstrated a negative correlation between ReHo values in the central-temporal region and medication dose. Both VPA and LEV inhibit resting-state neural activity in the central-temporal region, which is the main epileptogenic focus of BECTS. VPA reduced brain activity in the cortical epileptogenic regions and thalamus evenly, whereas LEV reduced brain activity predominantly in the cortices. Interestingly, VPA showed a cumulative effect on inhibiting brain activity in the epileptogenic regions in BECTS. (orig.)

  6. An optimized method for measuring hypocretin-1 peptide in the mouse brain reveals differential circadian regulation of hypocretin-1 levels rostral and caudal to the hypothalamus

    DEFF Research Database (Denmark)

    Justinussen, Jessica; Holm, A; Kornum, B R

    2015-01-01

    as does prepro-hypocretin mRNA in the hypothalamus. However, in midbrain and brainstem tissue caudal to the hypothalamus, there was less circadian fluctuation and a tendency for higher levels during the light phase. These data suggest that regulation of the hypocretin system differs between brain areas....

  7. Staged Venture Capital Investment considering Unexpected Major Events

    Directory of Open Access Journals (Sweden)

    Yindong Zhang

    2017-01-01

    Full Text Available This paper presents a dynamic model of capital financing, taking into consideration unexpected major events occurring within continuous time model. We are considering a special jump-diffusion model first described by Samuelson (1973 while using traditional geometric Brownian motion. This paper seeks to accurately show the innovative project valuation when unexpected major events occur and get the analytical results of the project option value. Furthermore, we analyzed the impact of multistaged financing; results indicated that both sources of uncertainty positively impact the project option value; particularly, the option price when considering unexpected major events occurrence is larger than the option price without unexpected major events. Based on a comparative-static analysis, new propositions for optimal amount of investment and optimal level of project are derived from simulations.

  8. Unexpected hypotension in catecholamine reversal: a case report

    OpenAIRE

    Okada, Yohei; Ishi, Wataru; Narumiya, Hiromichi; Liduka, Ryoji

    2017-01-01

    Background Catecholamine agents are commonly used to support circulation; however, they may cause unexpected hypotension in a special situation. Here we describe the first unexpected case of hypotension in response to catecholamine agents. Case presentation A 29-year-old Japanese man with schizophrenia was transferred to our emergency department. He was in shock and in coma. After fluid resuscitation, we induced catecholamine agents; however, his blood pressure decreased to 59/40 mmHg in resp...

  9. Genome-wide analysis of brain and gonad transcripts reveals changes of key sex reversal-related genes expression and signaling pathways in three stages of Monopterus albus.

    Directory of Open Access Journals (Sweden)

    Wei Chi

    Full Text Available The natural sex reversal severely affects the sex ratio and thus decreases the productivity of the rice field eel (Monopterus albus. How to understand and manipulate this process is one of the major issues for the rice field eel stocking. So far the genomics and transcriptomics data available for this species are still scarce. Here we provide a comprehensive study of transcriptomes of brain and gonad tissue in three sex stages (female, intersex and male from the rice field eel to investigate changes in transcriptional level during the sex reversal process.Approximately 195 thousand unigenes were generated and over 44.4 thousand were functionally annotated. Comparative study between stages provided multiple differentially expressed genes in brain and gonad tissue. Overall 4668 genes were found to be of unequal abundance between gonad tissues, far more than that of the brain tissues (59 genes. These genes were enriched in several different signaling pathways. A number of 231 genes were found with different levels in gonad in each stage, with several reproduction-related genes included. A total of 19 candidate genes that could be most related to sex reversal were screened out, part of these genes' expression patterns were validated by RT-qPCR. The expression of spef2, maats1, spag6 and dmc1 were abundant in testis, but was barely detected in females, while the 17β-hsd12, zpsbp3, gal3 and foxn5 were only expressed in ovary.This study investigated the complexity of brain and gonad transcriptomes in three sex stages of the rice field eel. Integrated analysis of different gene expression and changes in signaling pathways, such as PI3K-Akt pathway, provided crucial data for further study of sex transformation mechanisms.

  10. Genome-wide analysis of brain and gonad transcripts reveals changes of key sex reversal-related genes expression and signaling pathways in three stages of Monopterus albus.

    Science.gov (United States)

    Chi, Wei; Gao, Yu; Hu, Qing; Guo, Wei; Li, Dapeng

    2017-01-01

    The natural sex reversal severely affects the sex ratio and thus decreases the productivity of the rice field eel (Monopterus albus). How to understand and manipulate this process is one of the major issues for the rice field eel stocking. So far the genomics and transcriptomics data available for this species are still scarce. Here we provide a comprehensive study of transcriptomes of brain and gonad tissue in three sex stages (female, intersex and male) from the rice field eel to investigate changes in transcriptional level during the sex reversal process. Approximately 195 thousand unigenes were generated and over 44.4 thousand were functionally annotated. Comparative study between stages provided multiple differentially expressed genes in brain and gonad tissue. Overall 4668 genes were found to be of unequal abundance between gonad tissues, far more than that of the brain tissues (59 genes). These genes were enriched in several different signaling pathways. A number of 231 genes were found with different levels in gonad in each stage, with several reproduction-related genes included. A total of 19 candidate genes that could be most related to sex reversal were screened out, part of these genes' expression patterns were validated by RT-qPCR. The expression of spef2, maats1, spag6 and dmc1 were abundant in testis, but was barely detected in females, while the 17β-hsd12, zpsbp3, gal3 and foxn5 were only expressed in ovary. This study investigated the complexity of brain and gonad transcriptomes in three sex stages of the rice field eel. Integrated analysis of different gene expression and changes in signaling pathways, such as PI3K-Akt pathway, provided crucial data for further study of sex transformation mechanisms.

  11. A systematic integrated analysis of brain expression profiles reveals YAP1 and other prioritized hub genes as important upstream regulators in Alzheimer's disease.

    Science.gov (United States)

    Xu, Min; Zhang, Deng-Feng; Luo, Rongcan; Wu, Yong; Zhou, Hejiang; Kong, Li-Li; Bi, Rui; Yao, Yong-Gang

    2018-02-01

    Profiling the spatial-temporal expression pattern and characterizing the regulatory networks of brain tissues are vital for understanding the pathophysiology of Alzheimer's disease (AD). We performed a systematic integrated analysis of expression profiles of AD-affected brain tissues (684 AD and 562 controls). A network-based convergent functional genomic approach was used to prioritize possible regulator genes during AD development, followed by functional characterization. We generated a complete list of differentially expressed genes and hub genes of the transcriptomic network in AD brain and constructed a Web server (www.alzdata.org) for public access. Seventeen hub genes active at the early stages, especially YAP1, were recognized as upstream regulators of the AD network. Cellular assays proved that early alteration of YAP1 could promote AD by influencing the whole transcriptional network. Early expression disturbance of hub genes is an important feature of AD development, and interfering with this process may reverse the disease progression. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  12. Bilinguals at the "cocktail party": dissociable neural activity in auditory-linguistic brain regions reveals neurobiological basis for nonnative listeners' speech-in-noise recognition deficits.

    Science.gov (United States)

    Bidelman, Gavin M; Dexter, Lauren

    2015-04-01

    We examined a consistent deficit observed in bilinguals: poorer speech-in-noise (SIN) comprehension for their nonnative language. We recorded neuroelectric mismatch potentials in mono- and bi-lingual listeners in response to contrastive speech sounds in noise. Behaviorally, late bilinguals required ∼10dB more favorable signal-to-noise ratios to match monolinguals' SIN abilities. Source analysis of cortical activity demonstrated monotonic increase in response latency with noise in superior temporal gyrus (STG) for both groups, suggesting parallel degradation of speech representations in auditory cortex. Contrastively, we found differential speech encoding between groups within inferior frontal gyrus (IFG)-adjacent to Broca's area-where noise delays observed in nonnative listeners were offset in monolinguals. Notably, brain-behavior correspondences double dissociated between language groups: STG activation predicted bilinguals' SIN, whereas IFG activation predicted monolinguals' performance. We infer higher-order brain areas act compensatorily to enhance impoverished sensory representations but only when degraded speech recruits linguistic brain mechanisms downstream from initial auditory-sensory inputs. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Multi-modal analysis of functional connectivity and cerebral blood flow reveals shared and unique effects of propofol in large-scale brain networks.

    Science.gov (United States)

    Qiu, Maolin; Scheinost, Dustin; Ramani, Ramachandran; Constable, R Todd

    2017-03-01

    Anesthesia-induced changes in functional connectivity and cerebral blow flow (CBF) in large-scale brain networks have emerged as key markers of reduced consciousness. However, studies of functional connectivity disagree on which large-scale networks are altered or preserved during anesthesia, making it difficult to find a consensus amount studies. Additionally, pharmacological alterations in CBF could amplify or occlude changes in connectivity due to the shared variance between CBF and connectivity. Here, we used data-driven connectivity methods and multi-modal imaging to investigate shared and unique neural correlates of reduced consciousness for connectivity in large-scale brain networks. Rs-fMRI and CBF data were collected from the same subjects during an awake and deep sedation condition induced by propofol. We measured whole-brain connectivity using the intrinsic connectivity distribution (ICD), a method not reliant on pre-defined seed regions, networks of interest, or connectivity thresholds. The shared and unique variance between connectivity and CBF were investigated. Finally, to account for shared variance, we present a novel extension to ICD that incorporates cerebral blood flow (CBF) as a scaling factor in the calculation of global connectivity, labeled CBF-adjusted ICD). We observed altered connectivity in multiple large-scale brain networks including the default mode (DMN), salience, visual, and motor networks and reduced CBF in the DMN, frontoparietal network, and thalamus. Regional connectivity and CBF were significantly correlated during both the awake and propofol condition. Nevertheless changes in connectivity and CBF between the awake and deep sedation condition were only significantly correlated in a subsystem of the DMN, suggesting that, while there is significant shared variance between the modalities, changes due to propofol are relatively unique. Similar, but less significant, results were observed in the CBF-adjusted ICD analysis, providing

  14. Brain Basics

    Medline Plus

    Full Text Available ... are sent from one neuron to another. Share Science News Brain’s Alertness Circuitry Revealed New BRAIN Grants ... human volunteers PubMed Central: An archive of life sciences journals NIH Research Fact Sheets NIH Office of ...

  15. The Unexpected Past of a Dwarf Galaxy

    Science.gov (United States)

    1996-08-01

    New Light on Cannibalism in the Local Group of Galaxies The Local Group of Galaxies consists of a few large spiral galaxies - for instance the Milky Way galaxy in which we live, and the Andromeda galaxy that is visible to the unaided eye in the northern constellation of the same name - as well as two dozen much smaller galaxies of mostly irregular shape. Whereas the larger galaxies have extended halos of very old stars, no such halos have ever been seen around the smaller ones. Now, however, Dante Minniti and Albert Zijlstra [1], working at the ESO 3.5-metre New Technology Telescope (NTT), have found a large halo of old and metal-poor stars around one of the dwarf galaxies in the Local Group. This finding is quite unexpected. It revises our understanding of star formation in these galaxies and provides important information about the past evolution of galaxies [2]. Galaxy halos The Milky Way galaxy is surrounded by a large, roughly spherical halo of old stars. The diameter is about 100,000 light years and the stars therein, known as Population II stars, are among the oldest known, with ages of 10 billion years or even more. They also differ from the younger stars nearer to the main plane of the Milky Way (in which our 4.7 billion year old Sun is located) by being very metal-poor. Many of the halo stars consist almost solely of hydrogen and helium, reflecting the composition of matter in the young Universe. This halo is important for our understanding of the processes that led to the formation of the Milky Way galaxy. It is believed that many of the halo stars and those of the same type found in globular clusters existed already before the Milky Way had fully formed. Galaxy cannibalism Many astronomers suspect that galaxies evolve and gradually grow larger and heavier by practising cannibalism on their own kind. In this picture, when two galaxies collide in space, the stars and nebulae in the smaller one will disperse and soon be taken over by the larger one, which

  16. Unexpectedly high burden of rotavirus gastroenteritis in very young infants

    Directory of Open Access Journals (Sweden)

    Reilly Megan

    2010-06-01

    Full Text Available Abstract Background The highest incidence of rotavirus gastroenteritis has generally been reported in children 6-24 months of age. Young infants are thought to be partially protected by maternal antibodies acquired transplacentally or via breast milk. The purpose of our study was to assess the age distribution of children with confirmed community-acquired rotavirus gastroenteritis presenting to an urban referral hospital. Methods Children presenting to The Children's Hospital of Philadelphia with acute gastroenteritis have been monitored for the presence of rotavirus antigen in the stool by ELISA (followed by genotyping if ELISA-positive since the 1994-95 epidemic season. Results Over the last 12 rotavirus seasons prior to the introduction of the pentavalent rotavirus vaccine in 2006, stool specimens from 1646 patients tested positive for community-acquired rotavirus infection. Gender or age was not recorded in 6 and 5 cases, respectively. Overall, 58% of the cases occurred in boys. G1 was the predominant VP7 serotype, accounting for 72% of cases. The median (IQR age was 11 (5-21 months. A total of 790 (48% cases occurred in children outside the commonly quoted peak age range, with 27% in infants 24 months of age. A total of 220 (13% cases occurred during the first 3 months of life, and the highest number of episodes per month of age [97 (6%] was observed during the second month of life. Conclusions The incidence of community-acquired rotavirus gastroenteritis monitored over 12 seasons in the prevaccine era at a major university hospital was nearly constant for each month of age during the first year of life, revealing an unexpectedly high incidence of symptomatic rotavirus disease in infants

  17. Unexpected Control Structure Interaction on International Space Station

    Science.gov (United States)

    Gomez, Susan F.; Platonov, Valery; Medina, Elizabeth A.; Borisenko, Alexander; Bogachev, Alexey

    2017-01-01

    On June 23, 2011, the International Space Station (ISS) was performing a routine 180 degree yaw maneuver in support of a Russian vehicle docking when the on board Russian Segment (RS) software unexpectedly declared two attitude thrusters failed and switched thruster configurations in response to unanticipated ISS dynamic motion. Flight data analysis after the maneuver indicated that higher than predicted structural loads had been induced at various locations on the United States (U.S.) segment of the ISS. Further analysis revealed that the attitude control system was firing thrusters in response to both structural flex and rigid body rates, which resonated the structure and caused high loads and fatigue cycles. It was later determined that the thruster themselves were healthy. The RS software logic, which was intended to react to thruster failures, had instead been heavily influenced by interaction between the control system and structural flex. This paper will discuss the technical aspects of the control structure interaction problem that led to the RS control system firing thrusters in response to structural flex, the factors that led to insufficient preflight analysis of the thruster firings, and the ramifications the event had on the ISS. An immediate consequence included limiting which thrusters could be used for attitude control. This complicated the planning of on-orbit thruster events and necessitated the use of suboptimal thruster configurations that increased propellant usage and caused thruster lifetime usage concerns. In addition to the technical aspects of the problem, the team dynamics and communication shortcomings that led to such an event happening in an environment where extensive analysis is performed in support of human space flight will also be examined. Finally, the technical solution will be presented, which required a multidisciplinary effort between the U.S. and Russian control system engineers and loads and dynamics structural engineers to

  18. Cross-sectional analysis of data from the U.S. clinical trials database reveals poor translational clinical trial effort for traumatic brain injury, compared with stroke.

    Directory of Open Access Journals (Sweden)

    Lucia M Li

    Full Text Available Traumatic brain injury (TBI is an important public health problem, comparable to stroke in incidence and prevalence. Few interventions have proven efficacy in TBI, and clinical trials are, therefore, necessary to advance management in TBI. We describe the current clinical trial landscape in traumatic brain injury and compare it with the trial efforts for stroke. For this, we analysed all stroke and TBI studies registered on the US Clinical Trials (www.clinicaltrials.gov database over a 10-year period (01/01/2000 to 01/31/2013. This methodology has been previously used to analyse clinical trial efforts in other specialties. We describe the research profile in each area: total number of studies, total number of participants and change in number of research studies over time. We also analysed key study characteristics, such as enrolment number and scope of recruitment. We found a mismatch between relative public health burden and relative research effort in each disease. Despite TBI having comparable prevalence and higher incidence than stroke, it has around one fifth of the number of clinical trials and participant recruitment. Both stroke and TBI have experienced an increase in the number of studies over the examined time period, but the rate of growth for TBI is one third that for stroke. Small-scale (<1000 participants per trial and single centre studies form the majority of clinical trials in both stroke and TBI, with TBI having significantly fewer studies with international recruitment. We discuss the consequences of these findings and how the situation might be improved. A sustained research effort, entailing increased international collaboration and rethinking the methodology of running clinical trials, is required in order to improve outcomes after traumatic brain injury.

  19. Assessment of the structural brain network reveals altered connectivity in children with unilateral cerebral palsy due to periventricular white matter lesions.

    Science.gov (United States)

    Pannek, Kerstin; Boyd, Roslyn N; Fiori, Simona; Guzzetta, Andrea; Rose, Stephen E

    2014-01-01

    Cerebral palsy (CP) is a term to describe the spectrum of disorders of impaired motor and sensory function caused by a brain lesion occurring early during development. Diffusion MRI and tractography have been shown to be useful in the study of white matter (WM) microstructure in tracts likely to be impacted by the static brain lesion. The purpose of this study was to identify WM pathways with altered connectivity in children with unilateral CP caused by periventricular white matter lesions using a whole-brain connectivity approach. Data of 50 children with unilateral CP caused by periventricular white matter lesions (5-17 years; manual ability classification system [MACS] I = 25/II = 25) and 17 children with typical development (CTD; 7-16 years) were analysed. Structural and High Angular Resolution Diffusion weighted Images (HARDI; 64 directions, b = 3000 s/mm(2)) were acquired at 3 T. Connectomes were calculated using whole-brain probabilistic tractography in combination with structural parcellation of the cortex and subcortical structures. Connections with altered fractional anisotropy (FA) in children with unilateral CP compared to CTD were identified using network-based statistics (NBS). The relationship between FA and performance of the impaired hand in bimanual tasks (Assisting Hand Assessment-AHA) was assessed in connections that showed significant differences in FA compared to CTD. FA was reduced in children with unilateral CP compared to CTD. Seven pathways, including the corticospinal, thalamocortical, and fronto-parietal association pathways were identified simultaneously in children with left and right unilateral CP. There was a positive relationship between performance of the impaired hand in bimanual tasks and FA within the cortico-spinal and thalamo-cortical pathways (r(2) = 0.16-0.44; p < 0.05). This study shows that network-based analysis of structural connectivity can identify alterations in FA in unilateral CP, and that these

  20. The effect of unexpected bereavement on mortality in older couples.

    Science.gov (United States)

    Shah, Sunil M; Carey, Iain M; Harris, Tess; Dewilde, Stephen; Victor, Christina R; Cook, Derek G

    2013-06-01

    We sought to determine whether unexpected bereavement has a greater impact on mortality in the surviving partner than death of a partner with preexisting chronic disease or disability. In a UK primary care database (The Health Improvement Network), we identified 171,720 couples aged 60 years and older. We compared the rise in mortality in the first year after bereavement in those whose partner died without recorded chronic disease (unexpected bereavement) to those whose deceased partner had a diagnosis of chronic disease (known morbidity). For unexpected bereavement (13.4% of all bereavements), the adjusted hazard ratio for death in the first year after bereavement was 1.61 (95% confidence interval [CI] = 1.39, 1.86) compared with 1.21 (95% CI = 1.14, 1.30) where the partner had known morbidity. Differences between bereaved groups were significant (P = .001) and present for both men and women. Unexpected bereavement has a greater relative mortality impact than bereavement preceded by chronic disease. Our findings highlight the potential value of preparing individuals for the death of a spouse with known morbidity and providing extra support after bereavement for those experiencing sudden unexpected bereavement.

  1. Unexpected photoluminescence of fluorinated naphthalene diimides.

    Science.gov (United States)

    Maniam, Subashani; Cox, Rosalind P; Langford, Steven J; Bell, Toby D M

    2015-03-02

    Two new amino core-substituted naphthalene diimides (cNDIs) bearing fluorinated side chains have been synthesised. Steady-state and time-resolved fluorescence spectroscopy reveals unprecedented optical properties for the cNDIs with high quantum yields of ∼0.8 and fluorescence lifetimes of ∼13 ns in a range of solvents. These properties are apparent at the level of single molecules, where the compounds also show exceptional photostability under pulsed-laser excitation. Photon emission is remarkably consistent with very few long timescale (millisecond or longer) interruptions with molecules regularly undergoing >10(7) cycles of excitation and emission. Intermittencies owing to triplet-state formation occur on a sub-millisecond timescale with a low yield of 1-2%, indicating that the presence of the fluorine atoms does not lead to a significant triplet yield through the heavy-atom effect. These properties make the compounds excellent candidates for single-molecule labelling applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Disrupted small-world brain functional network topology in male patients with severe obstructive sleep apnea revealed by resting-state fMRI.

    Science.gov (United States)

    Chen, Li-Ting; Fan, Xiao-Le; Li, Hai-Jun; Nie, Si; Gong, Hong-Han; Zhang, Wei; Zeng, Xian-Jun; Long, Ping; Peng, De-Chang

    2017-01-01

    Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder that can damage cognitive function. However, the functional network organization remains poorly understood. The aim of this study was to investigate the topological properties of OSA patients using a graph theoretical analysis. A total of 30 male patients with untreated severe OSA and 25 male education- and age-matched good sleepers (GSs) underwent functional magnetic resonance imaging (MRI) examinations. Clinical and cognitive evaluations were conducted by an experienced psychologist. GRETNA (a toolbox for topological analysis of imaging connectomics) was used to construct the brain functional network and calculate the small-world properties (γ, λ, σ, Eglob, and Eloc). Relationships between these small-world properties and clinical and neuropsychological assessments were investigated in OSA patients. The networks of both OSA patients and GSs exhibited efficient small-world topology over the sparsity range of 0.05-0.40. Compared with GSs, the OSA group had significantly decreased γ, but significantly increased λ and σ. The OSA group's brain network showed significantly decreased Eglob (Pworld properties may be the mechanism of cognitive impairment in OSA patients. In addition, σ, γ, and λ could be used as a quantitative physiological index for auxiliary clinical diagnoses.

  3. Unexpected Bone Metastases from Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Sandra Gibiezaite

    2015-01-01

    Full Text Available Objective. To present a complicated case of differentiated thyroid carcinoma (DTC with metastases to the skull that was evident on I-131 whole body scan (WBS but negative on other imaging modalities in a low risk patient. Methods. We will discuss clinical course, imaging, pathological findings, and treatment of the patient with skull metastasis from DTC. Pertinent literature on imaging and pathology findings as well as radioactive iodine (RAI treatment impact on quality of life and survival in patients with bone metastases from DTC will be reviewed. Results. The patient is a 37-year-old woman with a diagnosis of DTC who had focal areas of increased uptake in the head on WBS with no correlative findings on CT and MRI. Initially, false positive findings were suspected since patient had a low risk for developing metastases. However, the persistent findings on post-RAI treatment WBS, following two courses of treatment, were highly concerning for metastatic bone disease. WBC performed 6 months following the second RAI treatment revealed resolution of the findings. Conclusions. False positive findings in WBS are frequent and may be due to contamination, perspiration, or folliculitis of the scalp as well as benign lesions such as meningioma, hematoma, cavernous angioma, and metallic sutures. However, metastatic disease should always be considered even if the patient has low risk of distant metastatic disease and correlative images do not support the diagnosis. RAI therapy appears to improve the survival rates and quality of life of thyroid cancer patients with bone metastases based on retrospective studies.

  4. An unexpected twist in viral capsid maturation

    Energy Technology Data Exchange (ETDEWEB)

    Gertsman, Ilya; Gan, Lu; Guttman, Miklos; Lee, Kelly; Speir, Jeffrey A.; Duda, Robert L.; Hendrix, Roger W.; Komives, Elizabeth A.; Johnson, John E.; (Pitt); (Scripps); (UCSD)

    2009-04-14

    Lambda-like double-stranded (ds) DNA bacteriophage undergo massive conformational changes in their capsid shell during the packaging of their viral genomes. Capsid shells are complex organizations of hundreds of protein subunits that assemble into intricate quaternary complexes that ultimately are able to withstand over 50 atm of pressure during genome packaging. The extensive integration between subunits in capsids requires the formation of an intermediate complex, termed a procapsid, from which individual subunits can undergo the necessary refolding and structural rearrangements needed to transition to the more stable capsid. Although various mature capsids have been characterized at atomic resolution, no such procapsid structure is available for a dsDNA virus or bacteriophage. Here we present a procapsid X-ray structure at 3.65 {angstrom} resolution, termed prohead II, of the lambda-like bacteriophage HK97, the mature capsid structure of which was previously solved to 3.44 {angstrom}. A comparison of the two largely different capsid forms has unveiled an unprecedented expansion mechanism that describes the transition. Crystallographic and hydrogen/deuterium exchange data presented here demonstrate that the subunit tertiary structures are significantly different between the two states, with twisting and bending motions occurring in both helical and -sheet regions. We also identified subunit interactions at each three-fold axis of the capsid that are maintained throughout maturation. The interactions sustain capsid integrity during subunit refolding and provide a fixed hinge from which subunits undergo rotational and translational motions during maturation. Previously published calorimetric data of a closely related bacteriophage, P22, showed that capsid maturation was an exothermic process that resulted in a release of 90 kJ mol{sup -1} of energy. We propose that the major tertiary changes presented in this study reveal a structural basis for an exothermic

  5. An Unexpected Twist in Viral Capsid Maturation

    Science.gov (United States)

    Gertsman, Ilya; Gan, Lu; Guttman, Miklos; Lee, Kelly; Speir, Jeffrey A.; Duda, Robert L.; Hendrix, Roger W.; Komives, Elizabeth A.; Johnson, John E.

    2009-01-01

    Lambda-like dsDNA bacteriophage undergo massive conformational changes in their capsid shell during the packaging of their viral genomes. Capsid shells are complex organizations of hundreds of protein subunits that assemble into intricate quaternary complexes that ultimately are able to withstand over 50 atm. of pressure during genome packaging1. The extensive integration between subunits in capsids is unlikely to form in a single assembly step, therefore requiring formation of an intermediate complex, termed a procapsid, from which individual subunits can undergo the necessary refolding and structural rearrangements needed to transition to the more stable capsid. Though various mature capsids have been characterized at atomic resolution, no such procapsid structure is available for a dsDNA virus or bacteriophage that undergoes large scale conformational changes. We present a procapsid x-ray structure at 3.65Å resolution, termed Prohead II, of the lambda like bacteriophage HK97, whose mature capsid structure was previously solved to 3.44 Å2. A comparison of the two largely different capsid forms has unveiled an unprecedented expansion mechanism that describes the transition. Crystallographic and Hydrogen/Deuterium exchange data presented here demonstrates that the subunit tertiary structures are significantly different between the two states, with twisting and bending motions occurring in both helical and β-sheet regions. We have also discovered conserved subunit interactions at each 3-fold of the virus capsid, from which capsid subunits maintain their integrity during refolding, facilitating the rotational and translational motions of maturation. Calormetric data of a closely related bacteriophage, P22, showed that capsid maturation was an exothermic process that resulted in a release of 90KJ/mol of energy3. We propose the major tertiary changes presented in this study reveal a structural basis for an exothermic maturation process likely present in many ds

  6. Brain Basics

    Medline Plus

    Full Text Available ... About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain Brain ... called the hypothalamic-pituitary-adrenal (HPA) axis. Brain Basics in Real Life Brain Basics in Real Life— ...

  7. Unexpected marked seizure improvement in paediatric epilepsy surgery candidates

    DEFF Research Database (Denmark)

    Hoei-Hansen, Christina E; Mathiasen, René; Uldall, Peter

    2016-01-01

    PURPOSE: Epilepsy surgery is performed based on the assumption that medical refractory epilepsy will continue. Rarely seizure freedom occurs before surgery is performed, while the patient is being evaluated as an epilepsy surgery candidate. The aim of this study was to describe the number...... of children withdrawn from an epilepsy surgery programme due to unexpected seizure improvement. METHODS: We retrospectively studied 173 children under 18 years with medical refractory epilepsy referred for epilepsy surgery between 1996 and 2010. Medical records were reviewed in 2012 and 2015. RESULTS......: At the first evaluation point in 2012, 13 patients were withdrawn from the epilepsy surgery programme due to unexpected marked improvement. In 2015, 6 of them were still seizure free. They had unexpected seizure freedom due to change in AED treatment (n=3) or after a febrile episode (n=3). The mean number...

  8. Evaluating impacts of unexpected earning on precision of profit estimation

    Directory of Open Access Journals (Sweden)

    Hossein Kazemi

    2013-03-01

    Full Text Available Precision in earning report has always been a concern among investors, and when there are some negative adjustments on earning, investor may find it challenging to decide whether they should hold or sell their shares. This paper studies the impact of earning precision and unexpected earning adjustments on firms whose share are listed on Tehran Stock Exchange. The proposed study of this paper considers three hypotheses including whether earning precision has negative relationship with unexpected profit, whether it has a negative with unexpected decline in profit and finally, whether, in prediction on negative news compared with positive news, there is a negative relationship between stronger earnings forecast and precision of earning forecast. The study gathers the necessary data from official news released for some firms whose shares were active over the period 2003-2012. The study uses two regression models and the results of regression analysis have confirmed all hypotheses of this survey.

  9. Gene expression profiling in brain of mice exposed to the marine neurotoxin ciguatoxin reveals an acute anti-inflammatory, neuroprotective response

    Directory of Open Access Journals (Sweden)

    Ryan James C

    2010-08-01

    Full Text Available Abstract Background Ciguatoxins (CTXs are polyether marine neurotoxins and potent activators of voltage-gated sodium channels. This toxin is carried by multiple reef-fish species and human consumption of ciguatoxins can result in an explosive gastrointestinal/neurologic illness. This study characterizes the global transcriptional response in mouse brain to a symptomatic dose of the highly toxic Pacific ciguatoxin P-CTX-1 and additionally compares this data to transcriptional profiles from liver and whole blood examined previously. Adult male C57/BL6 mice were injected with 0.26 ng/g P-CTX-1 while controls received only vehicle. Animals were sacrificed at 1, 4 and 24 hrs and transcriptional profiling was performed on brain RNA with Agilent whole genome microarrays. RT-PCR was used to independently validate gene expression and the web tool DAVID was used to analyze gene ontology (GO and molecular pathway enrichment of the gene expression data. Results A pronounced 4°C hypothermic response was recorded in these mice, reaching a minimum at 1 hr and lasting for 8 hrs post toxin exposure. Ratio expression data were filtered by intensity, fold change and p-value, with the resulting data used for time course analysis, K-means clustering, ontology classification and KEGG pathway enrichment. Top GO hits for this gene set included acute phase response and mono-oxygenase activity. Molecular pathway analysis showed enrichment for complement/coagulation cascades and metabolism of xenobiotics. Many immediate early genes such as Fos, Jun and Early Growth Response isoforms were down-regulated although others associated with stress such as glucocorticoid responsive genes were up-regulated. Real time PCR confirmation was performed on 22 differentially expressed genes with a correlation of 0.9 (Spearman's Rho, p Conclusions Many of the genes differentially expressed in this study, in parallel with the hypothermia, figure prominently in protection against

  10. In vivo functional brain mapping in a conditional mouse model of human tauopathy (tauP301L) reveals reduced neural activity in memory formation structures.

    Science.gov (United States)

    Perez, Pablo D; Hall, Gabrielle; Kimura, Tetsuya; Ren, Yan; Bailey, Rachel M; Lewis, Jada; Febo, Marcelo; Sahara, Naruhiko

    2013-02-04

    Tauopathies are characterized by intracellular deposition of the microtubule-associated protein tau as filamentous aggregates. The rTg4510 mouse conditionally expresses mutant human tau protein in various forebrain areas under the Tet-off expression system. Mice develop neurofibrillary tangles, with significant neuronal loss and cognitive deficits by 6 months of age. Previous behavioral and biochemical work has linked the expression and aggregates of mutant tau to functional impairments. The present work used manganese-enhanced magnetic resonance imaging (MEMRI) to investigate basal levels of brain activity in the rTg4510 and control mice. Our results show an unmistakable curtailment of neural activity in the amygdala and hippocampus, two regions known for their role in memory formation, but not the cortex, cerebellum, striatum and hypothalamus in tau expressing mice. Behavioral impairments associated with changes in activity in these areas may correspond to age progressive mutant tau(P301L)-induced neurodegeneration.

  11. An Expectorated "Stent": An Unexpected Complication of EBUS-TBNA.

    Science.gov (United States)

    Zamora, Felix D; Moughrabieh, Anas; Gibson, Heidi; Podgaetz, Eitan; Dincer, H Erhan

    2017-07-01

    Endobronchial ultrasound-guided transbronchial needle aspiration has a low complication rate and is a cost-effective procedure for mediastinal staging and diagnosis when compared with the more invasive mediastinoscopy. There are increasing case reports of unexpected complications including equipment failures with and without significant medical consequences. Knowledge of complications, including those that are rare, is essential for the physician performing this minimally invasive procedure. We report a case of a retained foreign body from the unexpected separation of a distal spring/coil mechanism from the Olympus ViziShot Aspiration needle following early needle deployment within the working channel of the bronchoscope.

  12. Unexpected Coexisting Myocardial Infarction Detected by Delayed Enhancement MRI

    Directory of Open Access Journals (Sweden)

    Edouard Gerbaud

    2009-01-01

    Full Text Available We report a case of an unexpected coexisting anterior myocardial infarction detected by delayed enhancement MRI in a 41-year-old man following a presentation with a first episode of chest pain during inferior acute myocardial infarction. This second necrotic area was not initially suspected because there were no ECG changes in the anterior leads and the left descending coronary artery did not present any significant stenoses on emergency coronary angiography. Unrecognised myocardial infarction may carry important prognostic implications. CMR is currently the best imaging technique to detect unexpected infarcts.

  13. Newborn brain event-related potentials revealing atypical processing of sound frequency and the subsequent association with later literacy skills in children with familial dyslexia.

    Science.gov (United States)

    Leppänen, Paavo H T; Hämäläinen, Jarmo A; Salminen, Hanne K; Eklund, Kenneth M; Guttorm, Tomi K; Lohvansuu, Kaisa; Puolakanaho, Anne; Lyytinen, Heikki

    2010-01-01

    The role played by an auditory-processing deficit in dyslexia has been debated for several decades. In a longitudinal study using brain event-related potentials (ERPs) we investigated 1) whether dyslexic children with familial risk background would show atypical pitch processing from birth and 2) how these newborn ERPs later relate to these same children's pre-reading cognitive skills and literacy outcomes. Auditory ERPs were measured at birth for tones varying in pitch and presented in an oddball paradigm (1100 Hz, 12%, and 1000 Hz, 88%). The brain responses of the typically reading control group children (TRC group, N=25) showed clear differentiation between the frequencies, while those of the group of reading disability with familial risk (RDFR, 8 children) and the group of typical readers with familial risk (TRFR, 14 children) did not differentiate between the tones. The ERPs of the latter two groups differed from those of the TRC group. However, the two risk groups also showed a differential hemispheric ERP pattern. Furthermore, newborn ERPs reflecting passive change detection were associated with phonological skills and letter knowledge prior to school age and with phoneme duration perception, reading speed (RS) and spelling accuracy in the 2nd grade of school. The early obligatory response was associated with more general pre-school language skills, as well as with RS and reading accuracy (RA). Results suggest that a proportion of dyslexic readers with familial risk background are affected by atypical auditory processing. This is already present at birth and also relates to pre-reading phonological processing and speech perception. These early differences in auditory processing could later affect phonological representations and reading development. However, atypical auditory processing is unlikely to suffice as a sole explanation for dyslexia but rather as one risk factor, dependent on the genetic profile of the child. Copyright © 2010 Elsevier Srl. All

  14. Transcriptome-Wide Mega-Analyses Reveal Joint Dysregulation of Immunologic Genes and Transcription Regulators in Brain and Blood in Schizophrenia

    Science.gov (United States)

    Hess, Jonathan L.; Tylee, Daniel S.; Barve, Rahul; de Jong, Simone; Ophoff, Roel A.; Kumarasinghe, Nishantha; Tooney, Paul; Schall, Ulrich; Gardiner, Erin; Beveridge, Natalie Jane; Scott, Rodney J.; Yasawardene, Surangi; Perera, Antionette; Mendis, Jayan; Carr, Vaughan; Kelly, Brian; Cairns, Murray; Tsuang, Ming T.; Glatt, Stephen J.

    2016-01-01

    The application of microarray technology in schizophrenia research was heralded as paradigm-shifting, as it allowed for high-throughput assessment of cell and tissue function. This technology was widely adopted, initially in studies of postmortem brain tissue, and later in studies of peripheral blood. The collective body of schizophrenia microarray literature contains apparent inconsistencies between studies, with failures to replicate top hits, in part due to small sample sizes, cohort-specific effects, differences in array types, and other confounders. In an attempt to summarize existing studies of schizophrenia cases and non-related comparison subjects, we performed two mega-analyses of a combined set of microarray data from postmortem prefrontal cortices (n = 315) and from ex-vivo blood tissues (n = 578). We adjusted regression models per gene to remove non-significant covariates, providing best-estimates of transcripts dysregulated in schizophrenia. We also examined dysregulation of functionally related gene sets and gene co-expression modules, and assessed enrichment of cell types and genetic risk factors. The identities of the most significantly dysregulated genes were largely distinct for each tissue, but the findings indicated common emergent biological functions (e.g. immunity) and regulatory factors (e.g., predicted targets of transcription factors and miRNA species across tissues). Our network-based analyses converged upon similar patterns of heightened innate immune gene expression in both brain and blood in schizophrenia. We also constructed generalizable machine-learning classifiers using the blood-based microarray data. Our study provides an informative atlas for future pathophysiologic and biomarker studies of schizophrenia. PMID:27450777

  15. Involvement of the middle frontal gyrus in language switching as revealed by electrical stimulation mapping and functional magnetic resonance imaging in bilingual brain tumor patients.

    Science.gov (United States)

    Sierpowska, Joanna; Fernandez-Coello, Alejandro; Gomez-Andres, Alba; Camins, Àngels; Castañer, Sara; Juncadella, Montserrat; Gabarrós, Andreu; Rodríguez-Fornells, Antoni

    2018-02-01

    Neural basis of language switching and the cognitive models of bilingualism remain controversial. We explored the functional neuroanatomy of language switching implementing a new multimodal protocol assessing neuropsychological, functional magnetic resonance and intraoperative electrical stimulation mapping results. A prospective series of 9 Spanish-Catalan bilingual candidates for awake brain surgery underwent a specific language switching paradigm implemented both before and after surgery, throughout the electrical stimulation procedure and during functional magnetic resonance both pre- and postoperatively. All patients were harboring left-hemispheric intrinsic brain lesions and were presenting functional language-related activations within the affected hemisphere. Language functional maps were reconstructed on the basis of the intraoperative electrical stimulation results and compared to the functional magnetic resonance findings. Single language-naming sites (Spanish and Catalan), as well as language switching naming sites were detected by electrical stimulation mapping in 8 patients (in one patient only Spanish related sites were detected). Single naming points outnumbered the switching points and did not overlap with each other. Within the frontal lobe, the single language naming sites were found significantly more frequently within the inferior frontal gyrus as compared to the middle frontal gyrus [X 2 (1) = 20.3, p language switching and their neuropsychological scores did not differ significantly from the pre-surgical examinations. Our results suggest a functional division of the frontal cortex between naming and language switching functions, supporting that non-language specific cognitive control prefrontal regions (middle frontal gyrus) are essential to maintain an effective communication together with the classical language-related sites (inferior frontal gyrus). Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Integrative taxonomy reveals an unexpected diversity in Geastrum section Geastrum (Geastrales, Basidiomycota)

    NARCIS (Netherlands)

    Zamora, J.C.; Calonge, F.D.; Martín, M.P.

    2015-01-01

    A revision of the classification of Geastrum sect. Geastrum is presented on the basis of an integrative taxonomic approach, which involves the study of morphological, molecular, ecological, and chorological data. Four DNA regions are analysed: the ITS and LSU nrDNA, rpb1, and atp6. Phylogenetic

  17. Revealing unexpected effects of rescue robots’ team-membership in a virtual environment

    NARCIS (Netherlands)

    Horsch, C.H.G.; Smets, N.J.J.M.; Neerincx, M.A.; Cuijpers, R.A.

    2013-01-01

    In urban search and rescue (USAR) situations resources are limited and workload is high. Robots that act as team players instead of tools could help in these situations. A Virtual Reality (VR) experiment was set up to test if team performance of a human-robot team increases when the robot act as

  18. The transcriptome of Euglena gracilis reveals unexpected metabolic capabilities for carbohydrate and natural product biochemistry.

    Science.gov (United States)

    O'Neill, Ellis C; Trick, Martin; Hill, Lionel; Rejzek, Martin; Dusi, Renata G; Hamilton, Chris J; Zimba, Paul V; Henrissat, Bernard; Field, Robert A

    2015-10-01

    Euglena gracilis is a highly complex alga belonging to the green plant line that shows characteristics of both plants and animals, while in evolutionary terms it is most closely related to the protozoan parasites Trypanosoma and Leishmania. This well-studied organism has long been known as a rich source of vitamins A, C and E, as well as amino acids that are essential for the human diet. Here we present de novo transcriptome sequencing and preliminary analysis, providing a basis for the molecular and functional genomics studies that will be required to direct metabolic engineering efforts aimed at enhancing the quality and quantity of high value products from E. gracilis. The transcriptome contains over 30,000 protein-encoding genes, supporting metabolic pathways for lipids, amino acids, carbohydrates and vitamins, along with capabilities for polyketide and non-ribosomal peptide biosynthesis. The metabolic and environmental robustness of Euglena is supported by a substantial capacity for responding to biotic and abiotic stress: it has the capacity to deploy three separate pathways for vitamin C (ascorbate) production, as well as producing vitamin E (α-tocopherol) and, in addition to glutathione, the redox-active thiols nor-trypanothione and ovothiol.

  19. Structural Characterization of Whirlin Reveals an Unexpected and Dynamic Supramodule Conformation of Its PDZ Tandem.

    Science.gov (United States)

    Delhommel, Florent; Cordier, Florence; Bardiaux, Benjamin; Bouvier, Guillaume; Colcombet-Cazenave, Baptiste; Brier, Sébastien; Raynal, Bertrand; Nouaille, Sylvie; Bahloul, Amel; Chamot-Rooke, Julia; Nilges, Michael; Petit, Christine; Wolff, Nicolas

    2017-11-07

    Hearing relies on the transduction of sound-evoked vibrations into electric signals, occurring in the stereocilia bundle of hair cells. The bundle is organized in a staircase pattern formed by rows of packed stereocilia. This architecture is pivotal to transduction and involves a network of scaffolding proteins with hitherto uncharacterized features. Key interactions in this network are mediated by PDZ domains. Here, we describe the architecture of the first two PDZ domains of whirlin, a protein involved in these assemblies and associated with congenital deaf-blindness. C-terminal hairpin extensions of the PDZ domains mediate the transient supramodular assembly, which improves the binding capacity of the first domain. We determined a detailed structural model of the closed conformation of the PDZ tandem and characterized its equilibrium with an ensemble of open conformations. The structural and dynamic behavior of this PDZ tandem provides key insights into the regulatory mechanisms involved in the hearing machinery. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. The structure of the scaffold nucleoporin Nup120 reveals a new and unexpected domain architecture.

    Science.gov (United States)

    Leksa, Nina C; Brohawn, Stephen G; Schwartz, Thomas U

    2009-08-12

    Nucleocytoplasmic transport is mediated by nuclear pore complexes (NPCs), enormous protein assemblies residing in circular openings in the nuclear envelope. The NPC is modular, with transient and stable components. The stable core is essentially built from two multiprotein complexes, the Y-shaped heptameric Nup84 complex and the Nic96 complex, arranged around an eightfold axis. We present the crystal structure of Nup120(1-757), one of the two short arms of the Y-shaped Nup84 complex. The protein adopts a compact oval shape built around a novel bipartite alpha-helical domain intimately integrated with a beta-propeller domain. The domain arrangement is substantially different from the Nup85*Seh1 complex, which forms the other short arm of the Y. With the data presented here, we establish that all three branches of the Y-shaped Nup84 complex are tightly connected by helical interactions and that the beta-propellers likely form interaction site(s) to neighboring complexes.

  1. Ultrastructural analysis of salivary glands in a phytophagous stink bug revealed the presence of unexpected muscles

    National Research Council Canada - National Science Library

    Nathaly Castellanos; Luis C Martínez; Eder H Silva; Adenir V Teodoro; José Eduardo Serrão; Eugênio E Oliveira

    2017-01-01

    The exceptional abilities of stink bugs (Hemiptera: Pentatomidae) to colonize a diverse group of plants have been attributed to the feeding behaviors and the functions of the salivary complex of these insects...

  2. Proteome-wide search reveals unexpected RNA-binding proteins in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Nikoleta G Tsvetanova

    2010-09-01

    Full Text Available The vast landscape of RNA-protein interactions at the heart of post-transcriptional regulation remains largely unexplored. Indeed it is likely that, even in yeast, a substantial fraction of the regulatory RNA-binding proteins (RBPs remain to be discovered. Systematic experimental methods can play a key role in discovering these RBPs--most of the known yeast RBPs lack RNA-binding domains that might enable this activity to be predicted. We describe here a proteome-wide approach to identify RNA-protein interactions based on in vitro binding of RNA samples to yeast protein microarrays that represent over 80% of the yeast proteome. We used this procedure to screen for novel RBPs and RNA-protein interactions. A complementary mass spectrometry technique also identified proteins that associate with yeast mRNAs. Both the protein microarray and mass spectrometry methods successfully identify previously annotated RBPs, suggesting that other proteins identified in these assays might be novel RBPs. Of 35 putative novel RBPs identified by either or both of these methods, 12, including 75% of the eight most highly-ranked candidates, reproducibly associated with specific cellular RNAs. Surprisingly, most of the 12 newly discovered RBPs were enzymes. Functional characteristics of the RNA targets of some of the novel RBPs suggest coordinated post-transcriptional regulation of subunits of protein complexes and a possible link between mRNA trafficking and vesicle transport. Our results suggest that many more RBPs still remain to be identified and provide a set of candidates for further investigation.

  3. Pegasoferae, an unexpected mammalian clade revealed by tracking ancient retroposon insertions.

    Science.gov (United States)

    Nishihara, Hidenori; Hasegawa, Masami; Okada, Norihiro

    2006-06-27

    Despite the recent large-scale efforts dedicated to comprehensive phylogenetic analyses using mitochondrial and nuclear DNA sequences, several relationships among mammalian orders remain controversial. Here, we present an extensive application of retroposon (L1) insertion analysis to the phylogenetic relationships among almost all mammalian orders. In addition to demonstrating the validity of Glires, Euarchontoglires, Laurasiatheria, and Boreoeutheria, we demonstrate an interordinal clade that links Chiroptera, Carnivora, and Perissodactyla within Laurasiatheria. Re-examination of a large DNA sequence data set yielded results consistent with our conclusion. We propose a superordinal name "Pegasoferae" for this clade of Chiroptera + Perissodactyla + Carnivora + Pholidota. The presence of a single incongruent L1 locus generates a tree in which the group of Carnivora + Perissodactyla associates with Cetartiodactyla but not with Chiroptera. This result suggests that incomplete lineage sorting of an ancestral dimorphism occurred with regard to the presence or absence of retroposon alleles in a common ancestor of Scrotifera (Pegasoferae + Cetartiodactyla), which was followed by rapid divergence into the extant orders over an evolutionarily short period. Accordingly, Euungulata (Cetartiodactyla + Perissodactyla) and Fereuungulata (Carnivora + Pholidota + Perissodactyla + Cetartiodactyla) cannot be validated as natural groups. The interordinal mammalian relationships presented here provide a cornerstone for future studies in the reconstruction of mammalian classifications, including extinct species, on evolution of large genomic sequences and structure, and in developmental analysis of morphological diversification.

  4. AKATSUKI-IR2 reveals unexpected opacity disruption affecting Venus's lower clouds every 9 days

    Science.gov (United States)

    Peralta, J.; Satoh, T.; Horinouchi, T.; Ogohara, K.; Kouyama, T.; Murakami, S.; Imamura, T.; McGouldrick, K.; Sato, T. M.; Limaye, S.; García-Melendo, E.; Sánchez-Lavega, A.; Hueso, R.

    2017-09-01

    The images of AKATSUKI acquired with the camera IR2 at 1.74-2.3 µm report the discovery of an equatorial disruption or "bow" between 30ºN‒30ºS of the Venus's lower clouds at 50 km. This feature appears on the night every 9 terrestrial days during more than 8 months, and introduces a dramatic and abrupt increase of the cloud opacity and reducing the thermal radiance in a factor of about 1:2 from its brightest to the darkest side.

  5. Vigilance task-related change in brain functional connectivity as revealed by wavelet phase coherence analysis of near-infrared spectroscopy signals

    Directory of Open Access Journals (Sweden)

    Wang Wei

    2016-08-01

    Full Text Available This study aims to assess the vigilance task-related change in connectivity in healthy adults using wavelet phase coherence (WPCO analysis of near-infrared spectroscopy signals (NIRS. NIRS is a non-invasive neuroimaging technique for assessing brain activity. Continuous recordings of the NIRS signals were obtained from the prefrontal cortex (PFC and sensorimotor cortical areas of 20 young healthy adults (24.9±3.3 years during a 10-min resting state and a 20-min vigilance task state. The vigilance task was used to simulate driving mental load by judging three random numbers (i.e., whether odd numbers. The task was divided into two sessions: the first 10 minutes (Task t1 and the second 10 minutes (Task t2. The WPCO of six channel pairs were calculated in five frequency intervals: 0.6–2 Hz (I, 0.145–0.6 Hz (II, 0.052–0.145 Hz (III, 0.021–0.052 Hz (IV, and 0.0095–0.021 Hz (V. The significant WPCO formed global connectivity (GC maps in intervals I and II and functional connectivity (FC maps in intervals III to V. Results show that the GC levels in interval I and FC levels in interval III were significantly lower in the Task t2 than in the resting state (p < 0.05, particularly between the left PFC and bilateral sensorimotor regions. Also, the reaction time shows an increase in Task t2 compared with that in Task t1. However, no significant difference in WPCO was found between Task t1 and resting state. The results showed that the change in FC at the range of 0.6-2 Hz was not attributed to the vigilance task pe se, but the interaction effect of vigilance task and time factors. The findings suggest that the decreased attention level might be partly attributed to the reduced GC levels between the left prefrontal region and sensorimotor area. The present results provide a new insight into the vigilance task-related brain activity.

  6. Unexpected Maternal Convulsion: An Idiopathic Case of Posterior Reversible Encephalopathy Syndrome after Delivery

    Directory of Open Access Journals (Sweden)

    Jila Agah

    2016-01-01

    Full Text Available Posterior reversible encephalopathy syndrome (PRES is associated with various clinical manifestations such as headache, blurred vision, confusion and tonic-clonic convulsion. Some of the predisposing factors for PRES include hypertensive encephalopathy, preeclampsia and eclampsia, lupus erythematosus, thrombotic thrombocytopenic purpura and long-term use of immunosuppressive drugs. This condition rarely occurs after normotensive and uneventful pregnancies. Several theories have been proposed on the etiology of PRES. For instance, endothelial injury and brain edema have been reported as possible causes of PRES. Although PRES is a temporary condition, proper and timely management of the disorder in the acute phase is critical for the prevention of permanent neurological complications. During pregnancy, PRES is normally accompanied with hypertension. In this paper, we present a rare case of PRES in a normotensive pregnancy in a 25-year-old parturient woman (Gravida 2, Ab 1. The patient unexpectedly manifested symptoms of tonic-clonic convulsion one hour after an uneventful vaginal delivery, which were successfully managed. According to our observations, PRES has various clinical manifestations with unexpected occurrence in some cases. Therefore, it is recommended that maternity centers be well-equipped with resuscitation tools, emergency drugs and expert staff so as to manage unforeseen PRES efficiently and prevent permanent maternal neurological complications and mortality.

  7. Sudden Unexpected Infant Deaths May Be Underestimated: Study

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_166269.html Sudden Unexpected Infant Deaths May Be Underestimated: Study Lack of standardized death ... U.S. Institute of Child Health and Human Development. Sudden Infant Death Syndrome (SIDS) is deemed a distinct form of ...

  8. A properly conducted trial of a ventouse can prevent unexpected ...

    African Journals Online (AJOL)

    1991-05-04

    May 4, 1991 ... should be replaced by primary caesarean section. Unexpected failures of instrumental deliveries are associated with a high incidence of neonatal asphyxia and neurological sequelae. I-3. Trial of instrumentation, as introduced by Douglass and. Kaltreider4 in 1953, is well established in the management of.

  9. Mathematics Placement Test: Typical Results with Unexpected Outcomes

    Science.gov (United States)

    Ingalls, Victoria

    2011-01-01

    Based on the results of a prior case-study analysis of mathematics placement at one university, the mathematics department developed and piloted a mathematics placement test. This article describes the implementation process for a mathematics placement test and further analyzes the test results for the pilot group. As an unexpected result, the…

  10. The prevalence of HIV in the sudden, unexplained and unexpected ...

    African Journals Online (AJOL)

    Purpose: To determine the prevalence of HIV in the sudden, unexplained and unexpected (SUU) death population admitted to the Pretoria Medico-Legal Laboratory. Methods: This study was conducted at the Pretoria Medico-Legal Laboratory. Blood samples were obtained from decedents who died suddenly and/or ...

  11. Thallium-201 accumulation in cerebral candidiasis: Unexpected finding on SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Tonami, N.; Matsuda, H.; Ooba, H.; Yokoyama, K.; Hisada, K.; Ikeda, K.; Yamashita, J. (Kanazawa Univ. (Japan))

    1990-06-01

    The authors present an unexpected finding of Tl-201 uptake in the intracerebral lesions due to candidiasis. SPECT demonstrated the extent of the lesions and a high target-to-background ratio. The regions where abnormal Tl-201 accumulation was seen were nearly consistent with CT scans of those enhanced by a contrast agent. After treatment, most of the abnormal Tl-201 accumulation disappeared.

  12. An unexpected death during oxygen-ozone therapy.

    Science.gov (United States)

    Marchetti, D; La Monaca, G

    2000-06-01

    An unexpected death is described that was caused by gas embolism that occurred during oxygen-ozone (O2/O3) therapy administered by autohemotransfusion for psoriasis. This unusual complication suggests the necessity of investigating benefits and adverse effects of medical ozone application.

  13. Unexpected regiospecific formation and DNA binding of new 3 ...

    Indian Academy of Sciences (India)

    New 3-(acridin-9-yl)methyl-2-substituted imino-1,3-thiazolidin-4-ones were regiospecifically synthesized from unstable (acridin-9-yl)methyl thioureas and methyl bromoacetate (MBA) or bromoacetyl bromide (BAB). Unexpected formation of only one thiazolidinone regioisomer with both the reagents was due to a new ...

  14. Unexpected pathological findings in skills training and assessing skills

    NARCIS (Netherlands)

    Boendermaker, PM; Pols, J; Scherpbier, AJJA

    1999-01-01

    This article draws attention to unexpected pathological findings encountered by students and teachers when examining one another and/or simulated patients in skips training and assessment sessions. Although no literature on the subject was found it appears to be not uncommon far students and

  15. Unexpected diversity during community succession in the apple flower microbiome.

    Science.gov (United States)

    Shade, Ashley; McManus, Patricia S; Handelsman, Jo

    2013-02-26

    Despite its importance to the host, the flower microbiome is poorly understood. We report a culture-independent, community-level assessment of apple flower microbial diversity and dynamics. We collected flowers from six apple trees at five time points, starting before flowers opened and ending at petal fall. We applied streptomycin to half of the trees when flowers opened. Assessment of microbial diversity using tag pyrosequencing of 16S rRNA genes revealed that the apple flower communities were rich and diverse and dominated by members of TM7 and Deinococcus-Thermus, phyla about which relatively little is known. From thousands of taxa, we identified six successional groups with coherent dynamics whose abundances peaked at different times before and after bud opening. We designated the groups Pioneer, Early, Mid, Late, Climax, and Generalist communities. The successional pattern was attributed to a set of prevalent taxa that were persistent and gradually changing in abundance. These taxa had significant associations with other community members, as demonstrated with a cooccurrence network based on local similarity analysis. We also detected a set of less-abundant, transient taxa that contributed to general tree-to-tree variability but not to the successional pattern. Communities on trees sprayed with streptomycin had slightly lower phylogenetic diversity than those on unsprayed trees but did not differ in structure or succession. Our results suggest that changes in apple flower microbial community structure are predictable over the life of the flower, providing a basis for ecological understanding and disease management. Flowering plants (angiosperms) represent a diverse group of an estimated 400,000 species, and their successful cultivation is essential to agriculture. Yet fundamental knowledge of flower-associated microbiotas remains largely unknown. Even less well understood are the changes that flower microbial communities experience through time. Flowers are

  16. In vivo functional brain mapping in a conditional mouse model of human tauopathy (taup301l reveals reduced neural activity in memory formation structures

    Directory of Open Access Journals (Sweden)

    Perez Pablo D

    2013-02-01

    Full Text Available Abstract Background Tauopathies are characterized by intracellular deposition of the microtubule-associated protein tau as filamentous aggregates. The rTg4510 mouse conditionally expresses mutant human tau protein in various forebrain areas under the Tet-off expression system. Mice develop neurofibrillary tangles, with significant neuronal loss and cognitive deficits by 6 months of age. Previous behavioral and biochemical work has linked the expression and aggregates of mutant tau to functional impairments. The present work used manganese-enhanced magnetic resonance imaging (MEMRI to investigate basal levels of brain activity in the rTg4510 and control mice. Results Our results show an unmistakable curtailment of neural activity in the amygdala and hippocampus, two regions known for their role in memory formation, but not the cortex, cerebellum, striatum and hypothalamus in tau expressing mice. Conclusion Behavioral impairments associated with changes in activity in these areas may correspond to age progressive mutant tauP301L-induced neurodegeneration.

  17. Early brain changes associated with psychotherapy in major depressive disorder revealed by resting-state fMRI: evidence for the top-down regulation theory.

    Science.gov (United States)

    Huang, Xiaolan; Huang, Peiyu; Li, Dan; Zhang, Yong; Wang, Tao; Mu, Jun; Li, Qi; Xie, Peng

    2014-12-01

    Major depressive disorder (MDD) is associated with dysfunction of the emotional circuitry in the brain. Psychotherapy and antidepressant treatment both aid in modulating this dysfunction, albeit probably through different mechanisms. A plausible "top-down" emotional regulation mechanism for psychotherapy has been described in previous studies, but the underlying findings are still contradictory. A total of 23 MDD patients and 20 healthy controls were enrolled. The early neural effects within 5 weeks of guided imagery-a psychotherapeutic method for treating depression-were assessed through resting-state functional magnetic resonance imaging using the regional homogeneity analytical method. At baseline, regional homogeneity was reduced in cortical regions and increased in limbic areas in the pre-treatment scans of MDD patients as compared to controls. After 5 weeks of guided imagery therapy, regional homogeneity in the ventromedial prefrontal cortex and the anterior cingulate gyrus both increased. Higher pre-treatment regional homogeneity in the dorsal anterior cingulate gyrus was positively correlated with an improved response to guided imagery therapy. The changes in regional homogeneity induced by guided imagery therapy demonstrate that this method of psychotherapy takes effect through a "top-down" mechanism. Future studies comparing various psychotherapeutic methodologies across multiple time points in the treatment course should yield more valuable insights on this topic. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Genetic Labeling Reveals Novel Cellular Targets of Schizophrenia Susceptibility Gene: Distribution of GABA and Non-GABA ErbB4-Positive Cells in Adult Mouse Brain

    Science.gov (United States)

    Bean, Jonathan C.; Lin, Thiri W.; Sathyamurthy, Anupama; Liu, Fang; Yin, Dong-Min; Xiong, Wen-Cheng

    2014-01-01

    Neuregulin 1 (NRG1) and its receptor ErbB4 are schizophrenia risk genes. NRG1-ErbB4 signaling plays a critical role in neural development and regulates neurotransmission and synaptic plasticity. Nevertheless, its cellular targets remain controversial. ErbB4 was thought to express in excitatory neurons, although recent studies disputed this view. Using mice that express a fluorescent protein under the promoter of the ErbB4 gene, we determined in what cells ErbB4 is expressed and their identity. ErbB4 was widely expressed in the mouse brain, being highest in amygdala and cortex. Almost all ErbB4-positive cells were GABAergic in cortex, hippocampus, basal ganglia, and most of amygdala in neonatal and adult mice, suggesting GABAergic transmission as a major target of NRG1-ErbB4 signaling in these regions. Non-GABAergic, ErbB4-positive cells were present in thalamus, hypothalamus, midbrain, and hindbrain. In particular, ErbB4 is expressed in serotoninergic neurons of raphe nuclei but not in norepinephrinergic neurons of the locus ceruleus. In hypothalamus, ErbB4 is present in neurons that express oxytocin. Finally, ErbB4 is expressed in a group of cells in the subcortical areas that are positive for S100 calcium binding protein β. These results identify novel cellular targets of NRG1-ErbB4 signaling. PMID:25274830

  19. Next generation sequencing revealed DNA ligase IV deficiency in a "developmentally normal" patient with massive brain Epstein-Barr virus-positive diffuse large B-cell lymphoma.

    Science.gov (United States)

    Sharapova, Svetlana O; Chang, Elizabeth Yenhui; Guryanova, Irina E; Proleskovskaya, Inna V; Fedorova, Alina S; Rutskaya, Elena A; Aleinikova, Olga V

    2016-02-01

    Here we present an unusual case of DNA ligase IV deficiency syndrome without dysmorphic facial findings and microcephaly complicated with Epstein-Barr virus-associated large B-cell lymphoma with the right lung involvement and a massive brain tumor lesion in a two-year-old female. PID panel was used for sequencing 55 genes. Most genes have >98% exon coverage including splicing sites. LIG4 gene has 100% exon and splicing site coverage. This was used in Ion Torrent PGM system, the library kit was made by Agilent with Haloplex technology. The sequence analysis software was Alamut, direct sequencing of LIG4 gene was performed after NGS results. We identified three heterozygous mutations in LIG4 gene c.2736+3delC and c.8 C>T (p.A3V) inherited from mother and c.26C>T (p.T9I) - from father after PID panel sequencing and some additional polymorphisms in ATM, NOD2 and NLRP3 genes. This case broadens the clinical spectrum of DNA ligase IV deficiency. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Heart – Brain Signaling in PFO Related Stroke: Differential Plasma Proteomic Expression Patterns Revealed with a Two-Pass LC-MS/MS Discovery Workflow

    Science.gov (United States)

    Lopez, Mary F; Sarracino, David A; Vogelsang, Maryann; Sutton, Jennifer N; Athanas, Michael; Krastins, Bryan; Garces, Alejandra; Prakash, Amol; Peterman, Scott; Demirjian, Zareh; Ignacio, Inglessis-Azuaje I; Feeney, Kathleen; Elia, Mikaela; McMullin, David; William Dec, G; Palacios, Igor; Lo, Eng H; Buonanno, Ferdinand; Ning, MingMing

    2013-01-01

    Patent foramen ovale (PFO) is highly prevalent and associated with more than 150,000 strokes per year. Traditionally, it is thought that PFOs facilitate strokes by allowing venous clots to travel directly to the brain. However, only a small portion of PFO stroke patients have a known tendency to form blood clots, and the best treatment for this multi-organ disease is unclear. Therefore, mapping the changes in systemic circulation of PFO-related stroke is crucial in understanding the pathophysiology in order to individualize the best clinical treatment for each patient. We initiated a study using a novel quantitative, Two-Pass discovery workflow using high-resolution LC-MS/MS coupled with label-free analysis to track protein expression in PFO patients before and after endovascular closure of the PFO. Using this approach, we were able to demonstrate quantitative differences in protein expression between both PFO-related and non PFO-related ischemic stroke groups as well as before and after PFO closure. As an initial step in understanding the molecular landscape of PFO-related physiology, our methods have yielded biologically relevant information on the synergistic and functional redundancy of various cell-signaling molecules with respect to PFO circulatory physiology. The resulting protein expression patterns were related to canonical pathways including prothrombin activation, atherosclerosis signaling, acute phase response, LXR/RXR activation and coagulation system. In particular, post PFO closure, numerous proteins demonstrated reduced expression in stroke-related canonical pathways such as acute inflammatory response and coagulation signaling. These findings demonstrate the feasibility and robustness of using a proteomic approach for biomarker discovery to help gauge therapeutic efficacy in stroke. PMID:23147404

  1. Brain Basics

    Medline Plus

    Full Text Available ... Brain Research Glossary Brain Basics (PDF, 10 pages) Introduction Watch the Brain Basics video Welcome. Brain Basics provides information on how the brain works, how mental illnesses ...

  2. Brain Basics

    Science.gov (United States)

    ... Events About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  3. Brain Basics

    Medline Plus

    Full Text Available ... Events About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  4. Brain Basics

    Medline Plus

    Full Text Available ... Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, ... learning more about how the brain grows and works in healthy people, and how normal brain development ...

  5. 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.

  6. Icariin reverses corticosterone-induced depression-like behavior, decrease in hippocampal brain-derived neurotrophic factor (BDNF) and metabolic network disturbances revealed by NMR-based metabonomics in rats.

    Science.gov (United States)

    Gong, Meng-Juan; Han, Bin; Wang, Shu-mei; Liang, Sheng-wang; Zou, Zhong-jie

    2016-05-10

    Previously published reports have revealed the antidepressant-like effects of icariin in a chronic mild stress model of depression and in a social defeat stress model in mice. However, the therapeutic effect of icariin in an animal model of glucocorticoid-induced depression remains unclear. This study aimed to investigate antidepressant-like effect and the possible mechanisms of icariin in a rat model of corticosterone (CORT)-induced depression by using a combination of behavioral and biochemical assessments and NMR-based metabonomics. The depression model was established by subcutaneous injections of CORT for 21 consecutive days in rats, as evidenced by reduced sucrose intake and hippocampal brain-derived neurotrophic factor (BDNF) levels, together with an increase in immobility time in a forced swim test (FST). Icariin significantly increased sucrose intake and hippocampal BDNF level and decreased the immobility time in FST in CORT-induced depressive rats, suggesting its potent antidepressant activity. Moreover, metabonomic analysis identified eight, five and three potential biomarkers associated with depression in serum, urine and brain tissue extract, respectively. These biomarkers are primarily involved in energy metabolism, lipid metabolism, amino acid metabolism and gut microbe metabolism. Icariin reversed the pathological process of CORT-induced depression, partially via regulation of the disturbed metabolic pathways. These results provide important mechanistic insights into the protective effects of icariin against CORT-induced depression and metabolic dysfunction. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Unexpected behaviour of cross sections of high energy protons

    Directory of Open Access Journals (Sweden)

    Dremin I.M.

    2017-01-01

    Full Text Available Nobody expected that protons will try to keep their entity in their collisions at higher and higher energies. However, the comparison of experimental results on proton-proton interactions from ISR to LHC energies clearly shows this tendency with a definitely increasing share of the elasic scattering cross section. This unexpected behaviour immediately leads to the unexpected corollary about the shape of the spatial interaction region of the two protons. The unquestionable principle of unitarity combined with available experimental data on elastic scattering is used to get new conclusions about this shape. Its evolution at present energies from the ISR to the LHC and predictions about its behaviour at ever higher energies are considered. The shape can transform rather drastically if the share of elastic processes keeps rising. The possible origin of the effect and its interrelation to the strong interaction dynamics are speculated. Cosmic ray studies can help in clarifying this behaviour.

  8. Fuzzy Concepts in the Detection of Unexpected Situations

    Directory of Open Access Journals (Sweden)

    J. Bíla

    2007-01-01

    Full Text Available This paper establishes three essential classes of unexpected situations (UX1, UX2, UX3, and concentrates attention on UX3 detection. Theconcepts of a special Model of System of Situations (MSS and a Model of a System of Faults (MSF are introduced. An original method isproposed for detecting unexpected situations indicating a violation of a proper invariant of MSS (MSF. The presented approach offers apromising application for starting and ending phases of complex processes, for knowledge discoveries on data and knowledge basesdeveloped with incomplete experience, and for modeling communication processes with unknown (disguised communication subjects. Thepaper also presents a way to utilize ill-separable situations for UX3 detection. The paper deals with the conceptual background for detectingUX3 situations, recapitulates recent results in this field and opens the ways for further research.

  9. Brains and the Dynamics of "Wants" and "Cans" in Learning

    NARCIS (Netherlands)

    Van Geert, P. L. C.; Steenbeek, H.

    Immordino-Yang's description of the unexpected recovery of 2 boys with severe brain trauma is an example of the interplay between the plasticity of the brain and the plasticity of the context. It highlights the dynamics of "wants and cans" and the specific role of motivation in this dynamic. As an

  10. Instructing with advanced collaboration technology: lessons learned and unexpected transformations

    OpenAIRE

    Nosek, John T.

    2006-01-01

    This paper provides lessons learned and some unexpected transformations in the learning process when advanced collaboration technology was used to overcome limitations of a popular, existing collaboration technology. The activities pursued in these advanced undergraduate and graduate computer and information sciences courses replicate many of the activities in collaborative knowledge work in organizations. Therefore, the lessons learned should be applicable to transforming other kinds of join...

  11. Unexpected marked seizure improvement in paediatric epilepsy surgery candidates.

    Science.gov (United States)

    Hoei-Hansen, Christina E; Mathiasen, René; Uldall, Peter

    2017-02-01

    Epilepsy surgery is performed based on the assumption that medical refractory epilepsy will continue. Rarely seizure freedom occurs before surgery is performed, while the patient is being evaluated as an epilepsy surgery candidate. The aim of this study was to describe the number of children withdrawn from an epilepsy surgery programme due to unexpected seizure improvement. We retrospectively studied 173 children under 18 years with medical refractory epilepsy referred for epilepsy surgery between 1996 and 2010. Medical records were reviewed in 2012 and 2015. At the first evaluation point in 2012, 13 patients were withdrawn from the epilepsy surgery programme due to unexpected marked improvement. In 2015, 6 of them were still seizure free. They had unexpected seizure freedom due to change in AED treatment (n=3) or after a febrile episode (n=3). The mean number of years they had had seizures was 3.4 years (range 0.6-6.2 years) and the number of seizures at inclusion was 209 per month (range 6-750 per month). The duration of follow-up was 6.6 years after inclusion into the epilepsy surgery programme (range 4.0-13.0 years). The aetiology of the epilepsy for these patients was heterotopia (n=1), focal cortical dysplasia (n=3), infarction (n=1) and unknown, with normal MRI (n=1). They all had an IQ in the normal range. Two of the remaining 7 children were operated later. Unexpected seizure control may occur during epilepsy surgery evaluation. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  12. Unexpected regiospecific formation and DNA binding of new 3 ...

    Indian Academy of Sciences (India)

    DOI 10.1007/s12039-015-1023-7. Unexpected regiospecific formation and DNA binding of new. 3-(acridin-9-yl)methyl-2-iminothiazolidin-4-ones. JÁN IMRICHa∗, DANICA SABOLOVÁb, MÁRIA VILKOVÁa and JÚLIA KUDLÁ ˇCOVÁb. aDepartment of Organic Chemistry bDepartment of Biochemistry, Institute of Chemistry,.

  13. The Triangle of Death in Alzheimer's Disease Brain: The Aberrant Cross-Talk Among Energy Metabolism, Mammalian Target of Rapamycin Signaling, and Protein Homeostasis Revealed by Redox Proteomics.

    Science.gov (United States)

    Di Domenico, Fabio; Barone, Eugenio; Perluigi, Marzia; Butterfield, D Allan

    2017-03-10

    Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder and represents one of the most disabling conditions. AD shares many features in common with systemic insulin resistance diseases, suggesting that it can be considered as a metabolic disease, characterized by reduced insulin-stimulated growth and survival signaling, increased oxidative stress (OS), proinflammatory cytokine activation, mitochondrial dysfunction, impaired energy metabolism, and altered protein homeostasis. Recent Advances: Reduced glucose utilization and energy metabolism in AD have been associated with the buildup of amyloid-β peptide and hyperphosphorylated tau, increased OS, and the accumulation of unfolded/misfolded proteins. Mammalian target of rapamycin (mTOR), which is aberrantly activated in AD since early stages, plays a key role during AD neurodegeneration by, on one side, inhibiting insulin signaling as a negative feedback mechanism and, on the other side, regulating protein homeostasis (synthesis/clearance). It is likely that the concomitant and mutual alterations of energy metabolism-mTOR signaling-protein homeostasis might represent a self-sustaining triangle of harmful events that trigger the degeneration and death of neurons and the development and progression of AD. Intriguingly, the altered cross-talk between the components of such a triangle of death, beyond altering the redox homeostasis of the neuron, is further exacerbated by increased levels of OS that target and impair key components of the pathways involved. Redox proteomic studies in human samples and animal models of AD-like dementia led to identification of oxidatively modified components of the pathways composing the triangle of death, therefore revealing the crucial role of OS in fueling this aberrant vicious cycle. The identification of compounds able to restore the function of the pathways targeted by oxidative damage might represent a valuable therapeutic approach to slow or delay AD. Antioxid

  14. Encountering unexpected difficult airway: relationship with the intubation difficulty scale.

    Science.gov (United States)

    Koh, Wonuk; Kim, Hajung; Kim, Kyongsun; Ro, Young-Jin; Yang, Hong-Seuk

    2016-06-01

    An unexpected difficult intubation can be very challenging and if it is not managed properly, it may expose the encountered patient to significant risks. The intubation difficulty scale (IDS) has been used as a validated method to evaluate a global degree of intubation difficulty. The aims of this study were to evaluate the prevalence and characteristics of unexpected difficult intubation using the IDS. We retrospectively reviewed 951 patients undergoing elective surgery in a single medical center. Patients expected to have a difficult intubation or who had history of difficult intubation were excluded. Each patient was assessed by the IDS scoring system with seven variables. Total prevalence of difficult intubation and the contributing individual factors were further analyzed. For the 951 patients, the difficult intubation cases presenting IDS > 5 was 5.8% of total cases (n = 55). The prevalence of Cormack-Lehane Grade 3 or 4 was 16.2% (n = 154). Most of the difficult intubation cases were managed by simple additional maneuvers and techniques such as stylet application, additional lifting force and laryngeal pressure. Unexpected difficult airway was present in 5.8% of patients and most was managed effectively. Among the components of IDS, the Cormack-Lehane grade was most sensitive for predicting difficult intubation.

  15. Neural stem cells sustain natural killer cells that dictate recovery from brain inflammation

    Science.gov (United States)

    Liu, Qiang; Sanai, Nader; Jin, Wei-Na; La Cava, Antonio; Van Kaer, Luc; Shi, Fu-Dong

    2017-01-01

    Recovery from organ-specific autoimmune diseases largely relies on the mobilization of endogenous repair mechanisms and local factors that control them. Natural killer (NK) cells are swiftly mobilized to organs targeted by autoimmunity and typically undergo numerical contraction when inflammation wanes. We report the unexpected finding that NK cells are retained in the brain subventricular zone (SVZ) during the chronic phase of multiple sclerosis in humans and its animal model in mice. These NK cells were found preferentially in close proximity to SVZ neural stem cells (NSCs) that produce interleukin-15 and sustain functionally competent NK cells. Moreover, NK cells limited the reparative capacity of NSCs following brain inflammation. These findings reveal that reciprocal interactions between NSCs and NK cells regulate neurorepair. PMID:26752157

  16. Brain herniation

    Science.gov (United States)

    ... herniation; Uncal herniation; Subfalcine herniation; Tonsillar herniation; Herniation - brain ... Brain herniation occurs when something inside the skull produces pressure that moves brain tissues. This is most ...

  17. Rural families' interpretations of experiencing unexpected transition in the wake of a natural disaster

    Directory of Open Access Journals (Sweden)

    Gisele Cristina Manfrini Fernandes

    Full Text Available Abstract: Natural disasters affect populations in various parts of the world. The impacts of disasters can cause many problems to the health of people and disruption to family life, potentially leading to an unexpected transition. The objective of this paper is to present the unexpected transitional experiences of rural families following a natural disaster. A multiple case study of six families was conducted with children and adolescents in a rural area affected by a 2008 disaster in southern Brazil. For data collection, we used participant observation, narrative interviews, genograms, ecomaps and an instrument called calendar routine. The analysis of the data resulted in different family interpretations about the changes resulting from the storm and compared life before and after the disaster. The loss of homes and loved ones, migration, unemployment, and losses from the farm were the main changes associated with new development tasks. The experiences of family transition after the disaster revealed that losses influenced social lives, daily routines and the preservation of cultural values.

  18. Unexpected findings at imaging: Predicting frequency in various types of studies

    Energy Technology Data Exchange (ETDEWEB)

    Lumbreras, Blanca [Public Health Department, Miguel Hernandez University (Spain); CIBER en Epidemiologia y Salud Publica (Spain)], E-mail: blumbreras@umh.es; Gonzalez-Alvarez, Isabel [Radiodiagnostic Department, San Juan Hospital, 03550 Alicante (Spain)], E-mail: gonzalez_isa@gva.es; Lorente, Ma Fernanda [Radiodiagnostic Department, San Juan Hospital, 03550 Alicante (Spain)], E-mail: MARFERLORENTE@telefonica.net; Calbo, Jorge [Radiodiagnostic Department, San Juan Hospital, 03550 Alicante (Spain)], E-mail: jocalma@hotmail.com; Aranaz, Jesus [Preventive Medicine Department, San Juan Hospital, 03550 Alicante (Spain)], E-mail: aranaz_jes@gva.es; Hernandez-Aguado, Ildefonso [Public Health Department, Miguel Hernandez University (Spain); CIBER en Epidemiologia y Salud Publica (Spain)], E-mail: ihernandez@umh.es

    2010-04-15

    Objective: The objective was to evaluate the prevalence and associated variables of unsuspected findings from imaging tests in clinical practice. Material and Methods: Cross-sectional study of patients referred for an imaging test in 2006. Two independent radiologists classified the imaging tests according to the presence or absence of an unexpected finding in relation with the causes that prompted the test (kappa = 0.95). A thorough chart review of these patients was carried out as a quality control. Results: Out of 3259 patients in the study, 488 revealed unsuspected findings (15.0%). The prevalence of abnormal findings varied according to age: from 20.4% (150/734) in the over 74-group to 9.0% (76/847) in the under 43-group. The largest prevalence was in the category of infectious diseases (14/49, 28.6%) and in CT (260/901, 28.9%) and ultrasound (138/668, 20.7%). Studies showing moderate clinical information on the referral form were less likely to show unexpected findings than those with null or minor information (OR 0.51; 95% CI 0.36-0.73). Conclusion: Clinicians should expect the frequency of diseases detectable by imaging to increase in the future. Further research with follow-up of these findings is needed to estimate the effect of imaging technologies on final health outcomes.

  19. Risk, Unexpected Uncertainty, and Estimation Uncertainty: Bayesian Learning in Unstable Settings

    Science.gov (United States)

    Payzan-LeNestour, Elise; Bossaerts, Peter

    2011-01-01

    Recently, evidence has emerged that humans approach learning using Bayesian updating rather than (model-free) reinforcement algorithms in a six-arm restless bandit problem. Here, we investigate what this implies for human appreciation of uncertainty. In our task, a Bayesian learner distinguishes three equally salient levels of uncertainty. First, the Bayesian perceives irreducible uncertainty or risk: even knowing the payoff probabilities of a given arm, the outcome remains uncertain. Second, there is (parameter) estimation uncertainty or ambiguity: payoff probabilities are unknown and need to be estimated. Third, the outcome probabilities of the arms change: the sudden jumps are referred to as unexpected uncertainty. We document how the three levels of uncertainty evolved during the course of our experiment and how it affected the learning rate. We then zoom in on estimation uncertainty, which has been suggested to be a driving force in exploration, in spite of evidence of widespread aversion to ambiguity. Our data corroborate the latter. We discuss neural evidence that foreshadowed the ability of humans to distinguish between the three levels of uncertainty. Finally, we investigate the boundaries of human capacity to implement Bayesian learning. We repeat the experiment with different instructions, reflecting varying levels of structural uncertainty. Under this fourth notion of uncertainty, choices were no better explained by Bayesian updating than by (model-free) reinforcement learning. Exit questionnaires revealed that participants remained unaware of the presence of unexpected uncertainty and failed to acquire the right model with which to implement Bayesian updating. PMID:21283774

  20. Risk, unexpected uncertainty, and estimation uncertainty: Bayesian learning in unstable settings.

    Directory of Open Access Journals (Sweden)

    Elise Payzan-LeNestour

    Full Text Available Recently, evidence has emerged that humans approach learning using Bayesian updating rather than (model-free reinforcement algorithms in a six-arm restless bandit problem. Here, we investigate what this implies for human appreciation of uncertainty. In our task, a Bayesian learner distinguishes three equally salient levels of uncertainty. First, the Bayesian perceives irreducible uncertainty or risk: even knowing the payoff probabilities of a given arm, the outcome remains uncertain. Second, there is (parameter estimation uncertainty or ambiguity: payoff probabilities are unknown and need to be estimated. Third, the outcome probabilities of the arms change: the sudden jumps are referred to as unexpected uncertainty. We document how the three levels of uncertainty evolved during the course of our experiment and how it affected the learning rate. We then zoom in on estimation uncertainty, which has been suggested to be a driving force in exploration, in spite of evidence of widespread aversion to ambiguity. Our data corroborate the latter. We discuss neural evidence that foreshadowed the ability of humans to distinguish between the three levels of uncertainty. Finally, we investigate the boundaries of human capacity to implement Bayesian learning. We repeat the experiment with different instructions, reflecting varying levels of structural uncertainty. Under this fourth notion of uncertainty, choices were no better explained by Bayesian updating than by (model-free reinforcement learning. Exit questionnaires revealed that participants remained unaware of the presence of unexpected uncertainty and failed to acquire the right model with which to implement Bayesian updating.

  1. Rural families' interpretations of experiencing unexpected transition in the wake of a natural disaster.

    Science.gov (United States)

    Fernandes, Gisele Cristina Manfrini; Boehs, Astrid Eggert; Denham, Sharon A; Nitschke, Rosane Gonçalves; Martini, Jussara Gue

    2017-02-13

    Natural disasters affect populations in various parts of the world. The impacts of disasters can cause many problems to the health of people and disruption to family life, potentially leading to an unexpected transition. The objective of this paper is to present the unexpected transitional experiences of rural families following a natural disaster. A multiple case study of six families was conducted with children and adolescents in a rural area affected by a 2008 disaster in southern Brazil. For data collection, we used participant observation, narrative interviews, genograms, ecomaps and an instrument called calendar routine. The analysis of the data resulted in different family interpretations about the changes resulting from the storm and compared life before and after the disaster. The loss of homes and loved ones, migration, unemployment, and losses from the farm were the main changes associated with new development tasks. The experiences of family transition after the disaster revealed that losses influenced social lives, daily routines and the preservation of cultural values.

  2. The heartbrake of social rejection: heart rate deceleration in response to unexpected peer rejection.

    Science.gov (United States)

    Gunther Moor, Bregtje; Crone, Eveline A; van der Molen, Maurits W

    2010-09-01

    Social relationships are vitally important in human life. Social rejection in particular has been conceptualized as a potent social cue resulting in feelings of hurt. Our study investigated the psychophysiological manifestation of hurt feelings by examining the beat-by-beat heart rate response associated with the processing of social rejection. Study participants were presented with a series of unfamiliar faces and were asked to predict whether they would be liked by the other person. Following each judgment, participants were provided with feedback indicating that the person they had viewed had either accepted or rejected them. Feedback was associated with transient heart rate slowing and a return to baseline that was considerably delayed in response to unexpected social rejection. Our results reveal that the processing of unexpected social rejection is associated with a sizable response of the parasympathetic nervous system. These findings are interpreted in terms of a cardiovagal manifestation of a neural mechanism implicated in the central control of autonomic function during cognitive processes and affective regulation.

  3. Genetic architecture supports mosaic brain evolution and independent brain-body size regulation

    National Research Council Canada - National Science Library

    Hager, Reinmar; Lu, Lu; Rosen, Glenn D; Williams, Robert W

    2012-01-01

    ... to selection and evolve independent of other parts or overall brain size. However, comparisons among mammals with matched brain weights often reveal greater differences in brain part size, arguing against strong developmental constraints...

  4. Brain Basics

    Medline Plus

    Full Text Available ... PDF, 10 pages) Introduction Watch the Brain Basics video Welcome. Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, and ongoing research that helps ...

  5. Brain Basics

    Medline Plus

    Full Text Available ... Brain Research Glossary Brain Basics (PDF, 10 pages) Introduction Watch the Brain Basics video Welcome. Brain Basics ... depression experience when starting treatment. Gene Studies ... medication. This information may someday make it possible to predict who ...

  6. Brain Basics

    Medline Plus

    Full Text Available ... Brain Research Glossary Brain Basics (PDF, 10 pages) Introduction Watch the Brain Basics video Welcome. Brain Basics ... fear hub," which activates our natural "fight-or-flight" response to confront or escape from a dangerous ...

  7. Brain Lesions

    Science.gov (United States)

    Symptoms Brain lesions By Mayo Clinic Staff A brain lesion is an abnormality seen on a brain-imaging test, such as ... tomography (CT). On CT or MRI scans, brain lesions appear as dark or light spots that don' ...

  8. Brain Basics

    Medline Plus

    Full Text Available ... Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a middle- ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses ...

  9. Revealing latent value of clinically acquired CTs of traumatic brain injury through multi-atlas segmentation in a retrospective study of 1,003 with external cross-validation

    Science.gov (United States)

    Plassard, Andrew J.; Kelly, Patrick D.; Asman, Andrew J.; Kang, Hakmook; Patel, Mayur B.; Landman, Bennett A.

    2015-03-01

    Medical imaging plays a key role in guiding treatment of traumatic brain injury (TBI) and for diagnosing intracranial hemorrhage; most commonly rapid computed tomography (CT) imaging is performed. Outcomes for patients with TBI are variable and difficult to predict upon hospital admission. Quantitative outcome scales (e.g., the Marshall classification) have been proposed to grade TBI severity on CT, but such measures have had relatively low value in staging patients by prognosis. Herein, we examine a cohort of 1,003 subjects admitted for TBI and imaged clinically to identify potential prognostic metrics using a "big data" paradigm. For all patients, a brain scan was segmented with multi-atlas labeling, and intensity/volume/texture features were computed in a localized manner. In a 10-fold crossvalidation approach, the explanatory value of the image-derived features is assessed for length of hospital stay (days), discharge disposition (five point scale from death to return home), and the Rancho Los Amigos functional outcome score (Rancho Score). Image-derived features increased the predictive R2 to 0.38 (from 0.18) for length of stay, to 0.51 (from 0.4) for discharge disposition, and to 0.31 (from 0.16) for Rancho Score (over models consisting only of non-imaging admission metrics, but including positive/negative radiological CT findings). This study demonstrates that high volume retrospective analysis of clinical imaging data can reveal imaging signatures with prognostic value. These targets are suited for follow-up validation and represent targets for future feature selection efforts. Moreover, the increase in prognostic value would improve staging for intervention assessment and provide more reliable guidance for patients.

  10. [Unexpected outings of Alzheimer patients living in retirement homes: Therapeutic perspectives].

    Science.gov (United States)

    Brossard, F; Caron, R

    2016-10-01

    Various behavior disorders can occur during Alzheimer's disease, in particular unexpected outings. This article aims at understanding the diverse mechanisms present during a "runaway" episode, which can manifest in an acute way. The authors bring to light through clinical examples what is at work from a psychological perspective in order to create new accompaniment methods. First, the authors reviewed the literature on runaway episodes in order to point out necessary themes for reflection. Then, from a Freudian theoretical model, they brought to light four fundamental mechanisms: hallucinations, false recognition, non-recognition, and recognition. These are mainly, although not exhaustively, understood from perceptions, memory-traces, indications of quality, and memories. This theory was questioned by means of presented clinical cases. Various post-Freudian models allowed the authors to emphasize the pathological experience in the role of perceptions and the functions, which come into play in the psychic economy. By going back and forth between theory and clinical cases, the authors underline the importance of perception in the phenomenon of unexpected outings. Finally, the Lacanian psychoanalytical theories provide a framework to question clinical cases but also provide answers to the criticisms found in the diverse reserved models. Through this study the authors hypothesize that the runaway episodes are not senseless but result from the interaction between the effects of the brain damage and the anxiety, which they arouse in the subjectivity of the person suffering from Alzheimer's. Leaning on false-recognitions, hallucinations, and non-recognitions such as were described in "Project for a scientific psychology", the authors put forward the hypothesis that these mechanisms express themselves in an imaginary relation, as in psychosis. The question of whether the runaway episodes of Alzheimer's sufferers can be classified as psychotic breakouts with a loss of touch

  11. Fenofibrate unexpectedly induces cardiac hypertrophy in mice lacking MuRF1.

    Science.gov (United States)

    Parry, Traci L; Desai, Gopal; Schisler, Jonathan C; Li, Luge; Quintana, Megan T; Stanley, Natalie; Lockyer, Pamela; Patterson, Cam; Willis, Monte S

    2016-01-01

    The muscle-specific ubiquitin ligase muscle ring finger-1 (MuRF1) is critical in regulating both pathological and physiological cardiac hypertrophy in vivo. Previous work from our group has identified MuRF1's ability to inhibit serum response factor and insulin-like growth factor-1 signaling pathways (via targeted inhibition of cJun as underlying mechanisms). More recently, we have identified that MuRF1 inhibits fatty acid metabolism by targeting peroxisome proliferator-activated receptor alpha (PPARα) for nuclear export via mono-ubiquitination. Since MuRF1-/- mice have an estimated fivefold increase in PPARα activity, we sought to determine how challenge with the PPARα agonist fenofibrate, a PPARα ligand, would affect the heart physiologically. In as little as 3 weeks, feeding with fenofibrate/chow (0.05% wt/wt) induced unexpected pathological cardiac hypertrophy not present in age-matched sibling wild-type (MuRF1+/+) mice, identified by echocardiography, cardiomyocyte cross-sectional area, and increased beta-myosin heavy chain, brain natriuretic peptide, and skeletal muscle α-actin mRNA. In addition to pathological hypertrophy, MuRF1-/- mice had an unexpected differential expression in genes associated with the pleiotropic effects of fenofibrate involved in the extracellular matrix, protease inhibition, hemostasis, and the sarcomere. At both 3 and 8 weeks of fenofibrate treatment, the differentially expressed MuRF1-/- genes most commonly had SREBP-1 and E2F1/E2F promoter regions by TRANSFAC analysis (54 and 50 genes, respectively, of the 111 of the genes >4 and cardiac hypertrophy, and hemostasis. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Brain Basics

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    Full Text Available ... Mental Illnesses Clinical Trials Outreach Research Priorities Funding Labs at NIMH News & Events About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain Brain Basics in Real Life Brain Research Glossary Brain Basics (PDF, 10 pages) ...

  13. Observing virtual arms that you imagine are yours increases the galvanic skin response to an unexpected threat.

    Directory of Open Access Journals (Sweden)

    Karin Hägni

    Full Text Available Multi-modal visuo-tactile stimulation of the type performed in the rubber hand illusion can induce the brain to temporarily incorporate external objects into the body image. In this study we show that audio-visual stimulation combined with mental imagery more rapidly elicits an elevated physiological response (skin conductance after an unexpected threat to a virtual limb, compared to audio-visual stimulation alone. Two groups of subjects seated in front of a monitor watched a first-person perspective view of slow movements of two virtual arms intercepting virtual balls rolling towards the viewer. One group was instructed to simply observe the movements of the two virtual arms, while the other group was instructed to observe the virtual arms and imagine that the arms were their own. After 84 seconds the right virtual arm was unexpectedly "stabbed" by a knife and began "bleeding". This aversive stimulus caused both groups to show a significant increase in skin conductance. In addition, the observation-with-imagery group showed a significantly higher skin conductance (p<0.05 than the observation-only group over a 2-second period shortly after the aversive stimulus onset. No corresponding change was found in subjects' heart rates. Our results suggest that simple visual input combined with mental imagery may induce the brain to measurably temporarily incorporate external objects into its body image.

  14. Alopecia associated with unexpected leakage from electron cone

    Energy Technology Data Exchange (ETDEWEB)

    Wen, B.C.; Pennington, E.C.; Hussey, D.H.; Jani, S.K.

    1989-06-01

    Excessive irradiation due to unexpected leakage was found on a patient receiving electron beam therapy. The cause of this leakage was analyzed and the amount of leakage was measured for different electron beam energies. The highest leakage occurred with a 6 x 6 cm cone using a 12 MeV electron beam. The leakage dose measured along the side of the cone could be as great as 40%. Until the cones are modified or redesigned, it is advised that all patient setups be carefully reviewed to assure that no significant patient areas are in the side scatter region.

  15. Unexpected death holograms: Animitas urban appeal in Chile

    Directory of Open Access Journals (Sweden)

    Lautaro Ojeda Ledesma

    2011-01-01

    Full Text Available This paper aims at performing an integral analysis of the relation between popular religiousness and urban space in Chilean animitas [little shrines] practices. In order to do this, we propose a multipurpose analysis scheme, holding the concept of "unexpected death hologram". This scheme puts forward three supplementary classifications: animita as a holographic subject, as a holographic object and as a holographic place. Finally, these three classifications supplemented by interviews and topologic analyses show almost all the sociospatial factors present in this practice, accounting for the urban importance that this type of popular practice has

  16. Unexpected rules using a conceptual distance based on fuzzy ontology

    Directory of Open Access Journals (Sweden)

    Mohamed Said Hamani

    2014-01-01

    Full Text Available One of the major drawbacks of data mining methods is that they generate a notably large number of rules that are often obvious or useless or, occasionally, out of the user’s interest. To address such drawbacks, we propose in this paper an approach that detects a set of unexpected rules in a discovered association rule set. Generally speaking, the proposed approach investigates the discovered association rules using the user’s domain knowledge, which is represented by a fuzzy domain ontology. Next, we rank the discovered rules according to the conceptual distances of the rules.

  17. Unexpected death in patients suffering from eating disorders. A medico-legal study.

    Science.gov (United States)

    Rajs, J; Rajs, E; Lundman, T

    1986-12-01

    Medico-legal investigation into causes of unexpected death of five persons who suffered from eating disorders did not give distinct pathoanatomical explanations. The analysis disclosed a number of risk factors whose interplay may have resulted in a circulatory catastrophy. These factors were of organisational and ideological character: simultaneous treatment at different departments, lack of contact with psychiatrists, or unclear criteria for admission to hospital; or somatic: circulatory and electrocardiographic S-T and T wave abnormalities, hypopotassemia and hypoglycemia, as well as anergy of the emaciated patient which may have led to symptoms of bronchopneumonia being overlooked. Morphological investigation revealed heart atrophy as well as recent lesions such as haemorrhages, fragmentation and contraction bands of the myofibres. In two extremely emaciated patients there was a disproportion between the size of the mitral valves and the atrophic ventricular wall, an appearance similar to "floppy valves". In one instance an erroneously inserted gastric tube contributed to vomiting, hypopotassemia and sudden death.

  18. Comprehensive study of unexpected microscope condensers formed in sample arrangements commonly used in optical microscopy.

    Science.gov (United States)

    Desai, Darshan B; Aldawsari, Mabkhoot Mudith S; Alharbi, Bandar Mohammed H; Sen, Sanchari; Grave de Peralta, Luis

    2015-09-01

    We show that various setups for optical microscopy which are commonly used in biomedical laboratories behave like efficient microscope condensers that are responsible for observed subwavelength resolution. We present a series of experiments and simulations that reveal how inclined illumination from such unexpected condensers occurs when the sample is perpendicularly illuminated by a microscope's built-in white-light source. In addition, we demonstrate an inexpensive add-on optical module that serves as an efficient and lightweight microscope condenser. Using such add-on optical module in combination with a low-numerical-aperture objective lens and Fourier plane imaging microscopy technique, we demonstrate detection of photonic crystals with a period nearly eight times smaller than the Rayleigh resolution limit.

  19. Sudden Unexpected Infant Deaths: Sleep Environment and Circumstances

    Science.gov (United States)

    Schnitzer, Patricia G.; Covington, Theresa M.; Dykstra, Heather K.

    2012-01-01

    Objectives. We sought to describe the characteristics and sleep circumstances of infants who die suddenly and unexpectedly and to examine similarities and differences in risk factors among infants whose deaths are classified as resulting from sudden infant death syndrome (SIDS), suffocation, or undetermined causes. Methods. We used 2005 to 2008 data from 9 US states to assess 3136 sleep-related sudden unexpected infant deaths (SUIDs). Results. Only 25% of infants were sleeping in a crib or on their back when found; 70% were on a surface not intended for infant sleep (e.g., adult bed). Importantly, 64% of infants were sharing a sleep surface, and almost half of these infants were sleeping with an adult. Infants whose deaths were classified as suffocation or undetermined cause were significantly more likely than were infants whose deaths were classified as SIDS to be found on a surface not intended for infant sleep and to be sharing that sleep surface. Conclusions. We identified modifiable sleep environment risk factors in a large proportion of the SUIDs assessed in this study. Our results make an important contribution to the mounting evidence that sleep environment hazards contribute to SUIDs. PMID:22515860

  20. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  1. Brain Basics

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    Full Text Available ... Brain Research Glossary Brain Basics (PDF, 10 pages) Introduction Watch the Brain Basics video Welcome. Brain Basics ... basic, working unit of the brain and nervous system, which processes and transmits information. neurotransmitter —A chemical produced by neurons that carries ...

  2. Brain Basics

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    Full Text Available ... learning more about how the brain grows and works in healthy people, and how normal brain development and function can go awry, leading to mental illnesses. Brain Basics will introduce you to some of this science, such as: ... of the brain communicate and work with each other How changes in the brain ...

  3. Cambrian stalked echinoderms show unexpected plasticity of arm construction.

    Science.gov (United States)

    Zamora, S; Smith, A B

    2012-01-22

    Feeding arms carrying coelomic extensions of the theca are thought to be unique to crinoids among stemmed echinoderms. However, a new two-armed echinoderm from the earliest Middle Cambrian of Spain displays a highly unexpected morphology. X-ray microtomographic analysis of its arms shows they are polyplated in their proximal part with a dorsal series of uniserial elements enclosing a large coelomic lumen. Distally, the arm transforms into the more standard biserial structure of a blastozoan brachiole. Phylogenetic analysis demonstrates that this taxon lies basal to rhombiferans as sister-group to pleurocystitid and glyptocystitid blastozoans, drawing those clades deep into the Cambrian. We demonstrate that Cambrian echinoderms show surprising variability in the way their appendages are constructed, and that the appendages of at least some blastozoans arose as direct outgrowths of the body in much the same way as the arms of crinoids.

  4. Affects of the unexpected: when inconsistency feels good (or bad).

    Science.gov (United States)

    Noordewier, Marret K; Stapel, Diederik A

    2010-05-01

    Affective responses to disconfirmation of expectancies have paradoxical features: Incongruency is uncomfortable and elicits negative affect, but how do people feel when the incongruent outcome is positive? This article shows that affective responses to disconfirmed expectancies depend on whether people value consistency and thus focus on the expectancy-congruency of the outcome or on its valence. People with high need for structure, a prevention focus, or for whom mortality is salient, assign more value to consistency and are more congruency focused: They feel more positive after congruent outcomes than after incongruent outcomes (independent of valence). People with low need for structure, a promotion focus, or for whom mortality is not salient, value consistency less and are more outcome focused: They feel more positive after positive outcomes than after negative outcomes (independent of congruency). This article furthermore shows how responses to the unexpected unfold and that a congruency focus requires less cognitive resources than an outcome focus.

  5. Unexpected fold in the circumsporozoite protein target of malaria vaccines

    Energy Technology Data Exchange (ETDEWEB)

    Doud, Michael B.; Koksal, Adem C.; Mi, Li-Zhi; Song, Gaojie; Lu, Chafen; Springer, Timothy A. (Harvard-Med)

    2012-10-09

    Circumsporozoite (CS) protein is the major surface component of Plasmodium falciparum sporozoites and is essential for host cell invasion. A vaccine containing tandem repeats, region III, and thrombospondin type-I repeat (TSR) of CS is efficacious in phase III trials but gives only a 35% reduction in severe malaria in the first year postimmunization. We solved crystal structures showing that region III and TSR fold into a single unit, an '{alpha}TSR' domain. The {alpha}TSR domain possesses a hydrophobic pocket and core, missing in TSR domains. CS binds heparin, but {alpha}TSR does not. Interestingly, polymorphic T-cell epitopes map to specialized {alpha}TSR regions. The N and C termini are unexpectedly close, providing clues for sporozoite sheath organization. Elucidation of a unique structure of a domain within CS enables rational design of next-generation subunit vaccines and functional and medicinal chemical investigation of the conserved hydrophobic pocket.

  6. Unexpected response of high Alpine Lake waters to climate warming.

    Science.gov (United States)

    Thies, Hansjörg; Nickus, Ulrike; Mair, Volkmar; Tessadri, Richard; Tait, Danilo; Thaler, Bertha; Psenner, Roland

    2007-11-01

    Over the past two decades, we have observed a substantial rise in solute concentration at two remote high mountain lakes in catchments of metamorphic rocks in the European Alps. At Rasass See, the electrical conductivity increased 18-fold. Unexpectedly high nickel concentrations at Rasass See, which exceeded the limit in drinking water by more than 1 order of magnitude, cannot be related to catchment geology. We attribute these changes in lake water quality to solute release from the ice of an active rock glacier in the catchment as a response to climate warming. Similar processes occurred at the higher elevation lake Schwarzsee ob Sölden, where electrical conductivity has risen 3-fold during the past two decades.

  7. Unexpected pulmonary hypertensive crisis after surgery for ocular malignant melanoma.

    Science.gov (United States)

    Sato, Kaori; Saji, Tsutomu; Kaneko, Taku; Takahashi, Kei; Sugi, Kaoru

    2014-11-24

    To report a case of unexpected pulmonary hypertensive crisis caused by endothelin release from melanoma cells after surgery for choroidal melanoma. A 56-year-old man suddenly developed dyspnea after resection of choroidal melanoma. Worsening hypoxia required intensive treatment, including percutaneous cardiopulmonary support, after which a series of tests were immediately performed. The tentative diagnosis was idiopathic pulmonary arterial hypertension. Previous studies noted a significant association between melanoma and endothelin (ET)-1. We hypothesized that a substantial amount of ET-1 had been released from malignant melanoma cells during resection, thus triggering the pulmonary hypertensive crisis in our patient. The patient fully recovered after intensive treatment and administration of the endothelin receptor antagonist bosentan. The success of bosentan treatment, along with the extremely high level of ET-1 on pathologic analysis, confirmed our hypothesis regarding the increase in plasma ET-1 level. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Unexpected Perinatal Loss versus Sids-a Common Neuropathologic Entity

    Science.gov (United States)

    Matturri, Luigi; Mauri, Maria; Elena Ferrero, Maria; Lavezzi, Anna Maria

    2008-01-01

    Objective: To evaluate the involvement of alterations of the central autonomic nervous system, particularly of the brainstem and cerebellum, in a wide set of victims of sudden and unexplained perinatal and infant death. Material and Methods: The study population consisted of 63 stillbirths, 28 neonatal deaths and 140 suspected SIDS. The victims were subjected to in-depth anatomopathological examination following appropriate guidelines. The protocol included, in particular, the histological evaluation on serial sections of the cardiorespiratory autonomic nervous system. Results: A diagnosis of “unexplained death” was established for 217 of the 231 victims (59 stillbirths, 28 newborns and 130 SIDS). In a very high percentage of these deaths (84%) we observed one or more anomalies of the nuclei and/or structures of the brainstem and cerebellum related to vital functions. Conclusion: Unexpected perinatal loss should not be regarded as a separate entity from SIDS, given the common neuropathological substrates. PMID:19018308

  9. Brain dynamics of distractibility: interaction between top-down and bottom-up mechanisms of auditory attention.

    Science.gov (United States)

    Bidet-Caulet, Aurélie; Bottemanne, Laure; Fonteneau, Clara; Giard, Marie-Hélène; Bertrand, Olivier

    2015-05-01

    Attention improves the processing of specific information while other stimuli are disregarded. A good balance between bottom-up (attentional capture by unexpected salient stimuli) and top-down (selection of relevant information) mechanisms is crucial to be both task-efficient and aware of our environment. Only few studies have explored how an isolated unexpected task-irrelevant stimulus outside the attention focus can disturb the top-down attention mechanisms necessary to the good performance of the ongoing task, and how these top-down mechanisms can modulate the bottom-up mechanisms of attentional capture triggered by an unexpected event. We recorded scalp electroencephalography in 18 young adults performing a new paradigm measuring distractibility and assessing both bottom-up and top-down attention mechanisms, at the same time. Increasing task load in top-down attention was found to reduce early processing of the distracting sound, but not bottom-up attentional capture mechanisms nor the behavioral distraction cost in reaction time. Moreover, the impact of bottom-up attentional capture by distracting sounds on target processing was revealed as a delayed latency of the N100 sensory response to target sounds mirroring increased reaction times. These results provide crucial information into how bottom-up and top-down mechanisms dynamically interact and compete in the human brain, i.e. on the precarious balance between voluntary attention and distraction.

  10. Sudden unexpected infant deaths associated with car seats.

    Science.gov (United States)

    Bamber, Andrew R; Pryce, Jeremy; Ashworth, Michael T; Sebire, Neil J

    2014-06-01

    The purpose of this study was to investigate the frequency, circumstances, demographics, and causes of death of infants dying while seated in car safety seats. A retrospective review of a pediatric autopsy database at a specialist center over a 16-year period was undertaken to identify any infant deaths (aged car safety seat. Fourteen car seat-associated deaths were identified from a total of 1,465 coronial infant autopsies (0.96 %). Four involved infants were being appropriately transported in the car seat, all of whom had a medical underlying cause of death (one infection and three congenital heart disease). The majority (10 cases; 70 %) occurred while car seats were being inappropriately used, outside of the car, including as an alternative to a cot or high-chair. Five of these infants died of explained causes, but four deaths remained unexplained after autopsy, and in one no cause of death was available. There were no cases of previously healthy infants dying unexpectedly in a car seat when it was being used appropriately, and in this series there were no cases of traumatic death associated with car seats, either during road traffic accidents, or from falling or being suspended from a car seat. Infant deaths in car seats are rare. These data support the recommendation that car seats be used only for transport and not as alternatives for cots or high-chairs. More research is required to investigate the effect of travel in car seats on infants with underlying conditions. There appears to be no increased risk of unexpected deaths of healthy infants transported appropriately in car seats.

  11. Unexpectedly strong anion-π interactions on the graphene flakes.

    Science.gov (United States)

    Shi, Guosheng; Ding, Yihong; Fang, Haiping

    2012-05-30

    Interactions of anions with simple aromatic compounds have received growing attention due to their relevancy in various fields. Yet, the anion-π interactions are generally very weak, for example, there is no favorable anion-π interaction for the halide anion F(-) on the simplest benzene surface unless the H-atoms are substituted by the highly negatively charged F. In this article, we report a type of particularly strong anion-π interactions by investigating the adsorptions of three halide anions, that is, F(-), Cl(-), and Br(-), on the hydrogenated-graphene flake using the density functional theory. The anion-π interactions on the graphene flake are shown to be unexpectedly strong compared to those on simple aromatic compounds, for example, the F(-)-adsorption energy is as large as 17.5 kcal/mol on a graphene flake (C(84) H(24)) and 23.5 kcal/mol in the periodic boundary condition model calculations on a graphene flake C(113) (the supercell containing a F(-) ion and 113 carbon atoms). The unexpectedly large adsorption energies of the halide anions on the graphene flake are ascribed to the effective donor-acceptor interactions between the halide anions and the graphene flake. These findings on the presence of very strong anion-π interactions between halide ions and the graphene flake, which are disclosed for the first time, are hoped to strengthen scientific understanding of the chemical and physical characteristics of the graphene in an electrolyte solution. These favorable interactions of anions with electron-deficient graphene flakes may be applicable to the design of a new family of neutral anion receptors and detectors. Copyright © 2012 Wiley Periodicals, Inc.

  12. Brain Malformations

    Science.gov (United States)

    Most brain malformations begin long before a baby is born. Something damages the developing nervous system or causes it ... medicines, infections, or radiation during pregnancy interferes with brain development. Parts of the brain may be missing, ...

  13. Brain surgery

    Science.gov (United States)

    Craniotomy; Surgery - brain; Neurosurgery; Craniectomy; Stereotactic craniotomy; Stereotactic brain biopsy; Endoscopic craniotomy ... cut depends on where the problem in the brain is located. The surgeon creates a hole in ...

  14. Brain Basics

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    Full Text Available ... Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a ... brain. DNA —The "recipe of life," containing inherited genetic information that helps to define physical and some ...

  15. Brain Basics

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    Full Text Available ... brain's structure, studies show that brain growth in children with autism appears to peak early. And as ... grow there are differences in brain development in children who develop bipolar disorder than children who do ...

  16. Brain Basics

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    Full Text Available ... brain's structure, studies show that brain growth in children with autism appears to peak early. And as they grow there are differences in brain development in children who develop bipolar disorder than children ...

  17. Brain Basics

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    Full Text Available ... imaging (MRI), which uses magnetic fields to take pictures of the brain's structure, studies show that brain ... imaging technique that uses magnetic fields to take pictures of the brain's structure. mutation —A change in ...

  18. Brain Basics

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    Full Text Available ... as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are the basic working unit of the brain ... specialized for the function of conducting messages. A neuron has three basic parts: Cell body which includes ...

  19. Brain Basics

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    Full Text Available ... of the brain's structure, studies show that brain growth in children with autism appears to peak early. And as they grow there are differences in brain development in children who develop bipolar disorder than children ...

  20. Brain Basics

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    Full Text Available ... science, such as: How the brain develops How genes and the environment affect the brain The basic ... that with brain development in people mental disorders. Genes and environmental cues both help to direct this ...

  1. Brain Basics

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    Full Text Available ... the Brain Meet Sarah Sarah is a middle-aged woman who seemed to have it all. She ... brain's structure, studies show that brain growth in children with autism appears to peak early. And as ...

  2. Brain Basics

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    Full Text Available ... about how the brain grows and works in healthy people, and how normal brain development and function ... chart how the brain develops over time in healthy people and are working to compare that with ...

  3. Brain Basics

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    Full Text Available ... Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a middle- ... unit of the brain and nervous system, which processes and transmits information. neurotransmitter —A chemical produced by ...

  4. Brain Basics

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    Full Text Available ... Mental Illnesses Clinical Trials Outreach Outreach Home Stakeholder Engagement Outreach Partnership Program Alliance for Research Progress Coalition ... Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, ...

  5. Brain Basics

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    Full Text Available ... in Real Life Brain Research Glossary Brain Basics (PDF, 10 pages) Introduction Watch the Brain Basics video ... and epigenetic changes can be passed on to future generations. Further understanding of genes and epigenetics may ...

  6. Brain Basics

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    Full Text Available ... can lead to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits ... tailored treatments, and possibly prevention of such illnesses. The Working Brain Neurotransmitters Everything we do relies on ...

  7. Scalp spindles are associated with widespread intracranial activity with unexpectedly low synchrony

    Science.gov (United States)

    Frauscher, Birgit; von Ellenrieder, Nicolás; Dubeau, François; Gotman, Jean

    2015-01-01

    In humans, the knowledge of intracranial correlates of spindles is mainly gathered from noninvasive neurophysiologic and functional imaging studies which provide an indirect estimate of neuronal intracranial activity. This potential limitation can be overcome by intracranial electroencephalography used in presurgical epilepsy evaluation. We investigated the intracranial correlates of scalp spindles using combined scalp and intracerebral depth electrodes covering the frontal, parietal and temporal neocortex, and the scalp and intracranial correlates of hippocampal and insula spindles in 35 pre-surgical epilepsy patients. Spindles in the scalp were accompanied by widespread cortical increases in sigma band energy (10–16 Hz): the highest percentages were observed in the frontoparietal lateral and mesial cortex, whereas in temporal lateral and mesial structures only a low or no simultaneous increase was present. This intracranial involvement during scalp spindles showed no consistent pattern, and exhibited unexpectedly low synchrony across brain regions. Hippocampal spindles were shorter and spatially restricted with a low synchrony even within the temporal lobe. Similar results were found for the insula. We suggest that the generation of spindles is under a high local cortical influence contributing to the concept of sleep as a local phenomenon and challenging the notion of spindles as widespread synchronous oscillations. PMID:25450108

  8. Comprehensive regional and temporal gene expression profiling of the rat brain during the first 24 h after experimental stroke identifies dynamic ischemia-induced gene expression patterns, and reveals a biphasic activation of genes in surviving tissue

    DEFF Research Database (Denmark)

    Rickhag, Karl Mattias; Wieloch, Tadeusz; Gidö, Gunilla

    2006-01-01

    -dehydrogenase1, and Choline kinase) or cell death-regulating genes such as mitochondrial CLIC. We conclude that a biphasic transcriptional up-regulation of the brain-derived neurotrophic factor (BDNF)-G-protein coupled receptor (GPCR)-mitogen-activated protein (MAP) kinase signaling pathways occurs in surviving...... tissue, concomitant with a progressive and persistent activation of cell proliferation signifying tissue regeneration, which provide the means for cell survival and postischemic brain plasticity.......In order to identify biological processes relevant for cell death and survival in the brain following stroke, the postischemic brain transcriptome was studied by a large-scale cDNA array analysis of three peri-infarct brain regions at eight time points during the first 24 h of reperfusion following...

  9. The Consequential Problems of Unexpected Events for Human Element and Construction Organizations

    OpenAIRE

    Amir Khosravi; Abdul Hakim Bin Mohammed

    2013-01-01

    Unexpected events are unpredictable or beyond the control of human. The aim of this study was to identify the consequential problems of unexpected events faced by construction managers and project managers. In undertaking this investigation, we used an exploratory semi-structured interview and a questionnaire survey method. The results of this research showed that the consequential problems of unexpected events were frequently wicked, wicked messes and messes types of problems. These wicked, ...

  10. Inducible knockout of Mef2a, -c, and -d from nestin-expressing stem/progenitor cells and their progeny unexpectedly uncouples neurogenesis and dendritogenesis in vivo

    Science.gov (United States)

    Latchney, Sarah E.; Jiang, Yindi; Petrik, David P.; Eisch, Amelia J.; Hsieh, Jenny

    2015-01-01

    Myocyte enhancer factor (Mef)-2 transcription factors are implicated in activity-dependent neuronal processes during development, but the role of MEF2 in neural stem/progenitor cells (NSPCs) in the adult brain is unknown. We used a transgenic mouse in which Mef2a, -c, and -d were inducibly deleted in adult nestin-expressing NSPCs and their progeny. Recombined cells in the hippocampal granule cell layer were visualized and quantified by yellow fluorescent protein (YFP) expression. In control mice, postmitotic neurons expressed Mef2a, -c, and -d, whereas type 1 stem cells and proliferating progenitors did not. Based on this expression, we hypothesized that Mef2a, -c, and -d deletion in adult nestin-expressing NSPCs and their progeny would result in fewer mature neurons. Control mice revealed an increase in YFP+ neurons and dendrite formation over time. Contrary to our hypothesis, inducible Mef2 KO mice also displayed an increase in YFP+ neurons over time—but with significantly stunted dendrites—suggesting an uncoupling of neuron survival and dendritogenesis. We also found non–cell-autonomous effects after Mef2a, -c, and -d deletion. These in vivo findings indicate a surprising functional role for Mef2a, -c, and -d in cell- and non–cell-autonomous control of adult hippocampal neurogenesis that is distinct from its role during development.—Latchney, S. E., Jiang, Y., Petrik, D. P., Eisch, A. J., Hsieh, J. Inducible knockout of Mef2a, -c, and -d from nestin-expressing stem/progenitor cells and their progeny unexpectedly uncouples neurogenesis and dendritogenesis in vivo. PMID:26286136

  11. Synthesis and characterization of regioselectively substituted curdlan hetero esters via an unexpected acyl migration.

    Science.gov (United States)

    Chien, Chih-Ying; Enomoto-Rogers, Yukiko; Takemura, Akio; Iwata, Tadahisa

    2017-01-02

    Regioselectively substituted curdlan esters were synthesized by protecting the C6 primary hydroxyl group with a triphenylmethyl group followed by the acylation of the secondary hydroxyl groups at C2 and C4. The subsequent detritylation of C6 trityl group under acidic conditions revealed an unexpected acyl migration from C4 to C6. This unique acyl migration in curdlan was first observed, which haven't been reported in other polysaccharides such as cellulose. The rate of this migration was found to be dependent on the length of the acyl group, leading to the proposal of a new mechanism for this transformation. Based on these results, we synthesized 2,6-di-O-acetyl-4-O-propionyl-curdlan, which was fully characterized by (1)H NMR, (13)C NMR, COSY, HSQC and HMBC analyses. Thermogravimetric analysis and differential scanning calorimetry measurements revealed that the regioselective esterification to curdlan promoted its crystallization compared with randomly mixed ester derivatives. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Unexpected Convergent Evolution of Nasal Domes between Pleistocene Bovids and Cretaceous Hadrosaur Dinosaurs.

    Science.gov (United States)

    O'Brien, Haley D; Faith, J Tyler; Jenkins, Kirsten E; Peppe, Daniel J; Plummer, Thomas W; Jacobs, Zenobia L; Li, Bo; Joannes-Boyau, Renaud; Price, Gilbert; Feng, Yue-Xing; Tryon, Christian A

    2016-02-22

    The fossil record provides tangible, historical evidence for the mode and operation of evolution across deep time. Striking patterns of convergence are some of the strongest examples of these operations, whereby, over time, similar environmental and/or behavioral pressures precipitate similarity in form and function between disparately related taxa. Here we present fossil evidence for an unexpected convergence between gregarious plant-eating mammals and dinosaurs. Recent excavations of Late Pleistocene deposits on Rusinga Island, Kenya, have uncovered a catastrophic assemblage of the wildebeest-like bovid Rusingoryx atopocranion. Previously known from fragmentary material, these new specimens reveal large, hollow, osseous nasal crests: a craniofacial novelty for mammals that is remarkably comparable to the nasal crests of lambeosaurine hadrosaur dinosaurs. Using adult and juvenile material from this assemblage, as well as computed tomographic imaging, we investigate this convergence from morphological, developmental, functional, and paleoenvironmental perspectives. Our detailed analyses reveal broad parallels between R. atopocranion and basal Lambeosaurinae, suggesting that osseous nasal crests may require a highly specific combination of ontogeny, evolution, and environmental pressures in order to develop. Copyright © 2016 E