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Sample records for brain reveals unexpected

  1. Saturn's Rings Reveal Unexpected Phenomena

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    李颖

    2004-01-01

    Safely in orbit around Saturn, NASA's Cassini spacecraft sent back its first close-up images of the massive planet's rings on July 1, revealing an unexpectedly varied terrain featuring surprisingly sharp edges, braids and delicate ridges.

  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. Unexpected events induce motor slowing via a brain mechanism for action-stopping with global suppressive effects.

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    Wessel, Jan R; Aron, Adam R

    2013-11-20

    When an unexpected event occurs in everyday life (e.g., a car honking), one experiences a slowing down of ongoing action (e.g., of walking into the street). Motor slowing following unexpected events is a ubiquitous phenomenon, both in laboratory experiments as well as such everyday situations, yet the underlying mechanism is unknown. We hypothesized that unexpected events recruit the same inhibition network in the brain as does complete cancellation of an action (i.e., action-stopping). Using electroencephalography and independent component analysis in humans, we show that a brain signature of successful outright action-stopping also exhibits activity following unexpected events, and more so in blocks with greater motor slowing. Further, using transcranial magnetic stimulation to measure corticospinal excitability, we show that an unexpected event has a global motor suppressive effect, just like outright action-stopping. Thus, unexpected events recruit a common mechanism with outright action-stopping, moreover with global suppressive effects. These findings imply that we can now leverage the considerable extant knowledge of the neural architecture and functional properties of the stopping system to better understand the processing of unexpected events, including perhaps how they induce distraction via global suppression.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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. PMID:26253310

  11. Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect.

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    Fassihi, Hiva; Sethi, Mieran; Fawcett, Heather; Wing, Jonathan; Chandler, Natalie; Mohammed, Shehla; Craythorne, Emma; Morley, Ana M S; Lim, Rongxuan; Turner, Sally; Henshaw, Tanya; Garrood, Isabel; Giunti, Paola; Hedderly, Tammy; Abiona, Adesoji; Naik, Harsha; Harrop, Gemma; McGibbon, David; Jaspers, Nicolaas G J; Botta, Elena; Nardo, Tiziana; Stefanini, Miria; Young, Antony R; Sarkany, Robert P E; Lehmann, Alan R

    2016-03-01

    Xeroderma pigmentosum (XP) is a rare DNA repair disorder characterized by increased susceptibility to UV radiation (UVR)-induced skin pigmentation, skin cancers, ocular surface disease, and, in some patients, sunburn and neurological degeneration. Genetically, it is assigned to eight complementation groups (XP-A to -G and variant). For the last 5 y, the UK national multidisciplinary XP service has provided follow-up for 89 XP patients, representing most of the XP patients in the United Kingdom. Causative mutations, DNA repair levels, and more than 60 clinical variables relating to dermatology, ophthalmology, and neurology have been measured, using scoring systems to categorize disease severity. This deep phenotyping has revealed unanticipated heterogeneity of clinical features, between and within complementation groups. Skin cancer is most common in XP-C, XP-E, and XP-V patients, previously considered to be the milder groups based on cellular analyses. These patients have normal sunburn reactions and are therefore diagnosed later and are less likely to adhere to UVR protection. XP-C patients are specifically hypersensitive to ocular damage, and XP-F and XP-G patients appear to be much less susceptible to skin cancer than other XP groups. Within XP groups, different mutations confer susceptibility or resistance to neurological damage. Our findings on this large cohort of XP patients under long-term follow-up reveal that XP is more heterogeneous than has previously been appreciated. Our data now enable provision of personalized prognostic information and management advice for each XP patient, as well as providing new insights into the functions of the XP proteins. PMID:26884178

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

    Science.gov (United States)

    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.

  13. Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect

    Science.gov (United States)

    Fassihi, Hiva; Sethi, Mieran; Fawcett, Heather; Wing, Jonathan; Chandler, Natalie; Mohammed, Shehla; Craythorne, Emma; Morley, Ana M. S.; Lim, Rongxuan; Turner, Sally; Henshaw, Tanya; Garrood, Isabel; Giunti, Paola; Hedderly, Tammy; Abiona, Adesoji; Naik, Harsha; Harrop, Gemma; McGibbon, David; Jaspers, Nicolaas G. J.; Botta, Elena; Nardo, Tiziana; Stefanini, Miria; Young, Antony R.; Sarkany, Robert P. E.; Lehmann, Alan R.

    2016-01-01

    Xeroderma pigmentosum (XP) is a rare DNA repair disorder characterized by increased susceptibility to UV radiation (UVR)-induced skin pigmentation, skin cancers, ocular surface disease, and, in some patients, sunburn and neurological degeneration. Genetically, it is assigned to eight complementation groups (XP-A to -G and variant). For the last 5 y, the UK national multidisciplinary XP service has provided follow-up for 89 XP patients, representing most of the XP patients in the United Kingdom. Causative mutations, DNA repair levels, and more than 60 clinical variables relating to dermatology, ophthalmology, and neurology have been measured, using scoring systems to categorize disease severity. This deep phenotyping has revealed unanticipated heterogeneity of clinical features, between and within complementation groups. Skin cancer is most common in XP-C, XP-E, and XP-V patients, previously considered to be the milder groups based on cellular analyses. These patients have normal sunburn reactions and are therefore diagnosed later and are less likely to adhere to UVR protection. XP-C patients are specifically hypersensitive to ocular damage, and XP-F and XP-G patients appear to be much less susceptible to skin cancer than other XP groups. Within XP groups, different mutations confer susceptibility or resistance to neurological damage. Our findings on this large cohort of XP patients under long-term follow-up reveal that XP is more heterogeneous than has previously been appreciated. Our data now enable provision of personalized prognostic information and management advice for each XP patient, as well as providing new insights into the functions of the XP proteins. PMID:26884178

  14. Metagenomic investigation of the geologically unique Hellenic Volcanic Arc reveals a distinctive ecosystem with unexpected physiology.

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    Oulas, Anastasis; Polymenakou, Paraskevi N; Seshadri, Rekha; Tripp, H James; Mandalakis, Manolis; Paez-Espino, A David; Pati, Amrita; Chain, Patrick; Nomikou, Paraskevi; Carey, Steven; Kilias, Stephanos; Christakis, Christos; Kotoulas, Georgios; Magoulas, Antonios; Ivanova, Natalia N; Kyrpides, Nikos C

    2016-04-01

    Hydrothermal vents represent a deep, hot, aphotic biosphere where chemosynthetic primary producers, fuelled by chemicals from Earth's subsurface, form the basis of life. In this study, we examined microbial mats from two distinct volcanic sites within the Hellenic Volcanic Arc (HVA). The HVA is geologically and ecologically unique, with reported emissions of CO2 -saturated fluids at temperatures up to 220°C and a notable absence of macrofauna. Metagenomic data reveals highly complex prokaryotic communities composed of chemolithoautotrophs, some methanotrophs, and to our surprise, heterotrophs capable of anaerobic degradation of aromatic hydrocarbons. Our data suggest that aromatic hydrocarbons may indeed be a significant source of carbon in these sites, and instigate additional research into the nature and origin of these compounds in the HVA. Novel physiology was assigned to several uncultured prokaryotic lineages; most notably, a SAR406 representative is attributed with a role in anaerobic hydrocarbon degradation. This dataset, the largest to date from submarine volcanic ecosystems, constitutes a significant resource of novel genes and pathways with potential biotechnological applications. PMID:26487573

  15. Expression of secreted Wnt pathway components reveals unexpected complexity of the planarian amputation response.

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    Gurley, Kyle A; Elliott, Sarah A; Simakov, Oleg; Schmidt, Heiko A; Holstein, Thomas W; Sánchez Alvarado, Alejandro

    2010-11-01

    Regeneration is widespread throughout the animal kingdom, but our molecular understanding of this process in adult animals remains poorly understood. Wnt/β-catenin signaling plays crucial roles throughout animal life from early development to adulthood. In intact and regenerating planarians, the regulation of Wnt/β-catenin signaling functions to maintain and specify anterior/posterior (A/P) identity. Here, we explore the expression kinetics and RNAi phenotypes for secreted members of the Wnt signaling pathway in the planarian Schmidtea mediterranea. Smed-wnt and sFRP expression during regeneration is surprisingly dynamic and reveals fundamental aspects of planarian biology that have been previously unappreciated. We show that after amputation, a wounding response precedes rapid re-organization of the A/P axis. Furthermore, cells throughout the body plan can mount this response and reassess their new A/P location in the complete absence of stem cells. While initial stages of the amputation response are stem cell independent, tissue remodeling and the integration of a new A/P address with anatomy are stem cell dependent. We also show that WNT5 functions in a reciprocal manner with SLIT to pattern the planarian mediolateral axis, while WNT11-2 patterns the posterior midline. Moreover, we perform an extensive phylogenetic analysis on the Smed-wnt genes using a method that combines and integrates both sequence and structural alignments, enabling us to place all nine genes into Wnt subfamilies for the first time. PMID:20707997

  16. Metagenomic investigation of the geologically unique Hellenic Volcanic Arc reveals a distinctive ecosystem with unexpected physiology.

    Science.gov (United States)

    Oulas, Anastasis; Polymenakou, Paraskevi N; Seshadri, Rekha; Tripp, H James; Mandalakis, Manolis; Paez-Espino, A David; Pati, Amrita; Chain, Patrick; Nomikou, Paraskevi; Carey, Steven; Kilias, Stephanos; Christakis, Christos; Kotoulas, Georgios; Magoulas, Antonios; Ivanova, Natalia N; Kyrpides, Nikos C

    2016-04-01

    Hydrothermal vents represent a deep, hot, aphotic biosphere where chemosynthetic primary producers, fuelled by chemicals from Earth's subsurface, form the basis of life. In this study, we examined microbial mats from two distinct volcanic sites within the Hellenic Volcanic Arc (HVA). The HVA is geologically and ecologically unique, with reported emissions of CO2 -saturated fluids at temperatures up to 220°C and a notable absence of macrofauna. Metagenomic data reveals highly complex prokaryotic communities composed of chemolithoautotrophs, some methanotrophs, and to our surprise, heterotrophs capable of anaerobic degradation of aromatic hydrocarbons. Our data suggest that aromatic hydrocarbons may indeed be a significant source of carbon in these sites, and instigate additional research into the nature and origin of these compounds in the HVA. Novel physiology was assigned to several uncultured prokaryotic lineages; most notably, a SAR406 representative is attributed with a role in anaerobic hydrocarbon degradation. This dataset, the largest to date from submarine volcanic ecosystems, constitutes a significant resource of novel genes and pathways with potential biotechnological applications.

  17. Morphology and molecules reveal unexpected cryptic diversity in the enigmatic genus Sinobirma Bryk, 1944 (Lepidoptera: Saturniidae.

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    Rodolphe Rougerie

    Full Text Available The wild silkmoth genus Sinobirma Bryk, 1944 is a poorly known monotypic taxon from the eastern end of the Himalaya Range. It was convincingly proposed to be closely related to some members of an exclusively Afro-tropical group of Saturniidae, but its biogeographical and evolutionary history remains enigmatic. After examining recently collected material from Tibet, northern India, and northeastern Myanmar, we realized that this unique species, S. malaisei Bryk, 1944 only known so far from a few specimens and from a very restricted area near the border between north-eastern Myanmar and the Yunnan province of China, may in fact belong to a group of closely related cryptic species. In this work, we combined morphological comparative study, DNA barcoding, and the sequences of a nuclear marker (D2 expansion segment of the 28S rRNA gene to unequivocally delimit three distinct species in the genus Sinobirma, of which two are described as new to science: S. myanmarensis sp. n. and S. bouyeri sp. n. An informative DNA barcode sequence was obtained from the female holotype of S. malaisei--collected in 1934--ensuring the proper assignation of this name to the newly collected and studied specimens. Our findings represent another example of the potential of coupling traditional taxonomy and DNA barcoding for revealing and solving difficult cases of cryptic diversity. This approach is now being generalized to the world fauna of Saturniidae, with the participation of most of the taxonomists studying these moths.

  18. The Crystal Structure of Cancer Osaka Thyroid Kinase Reveals an Unexpected Kinase Domain Fold*

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    Gutmann, Sascha; Hinniger, Alexandra; Fendrich, Gabriele; Drückes, Peter; Antz, Sylvie; Mattes, Henri; Möbitz, Henrik; Ofner, Silvio; Schmiedeberg, Niko; Stojanovic, Aleksandar; Rieffel, Sebastien; Strauss, André; Troxler, Thomas; Glatthar, Ralf; Sparrer, Helmut

    2015-01-01

    Macrophages are important cellular effectors in innate immune responses and play a major role in autoimmune diseases such as rheumatoid arthritis. Cancer Osaka thyroid (COT) kinase, also known as mitogen-activated protein kinase kinase kinase 8 (MAP3K8) and tumor progression locus 2 (Tpl-2), is a serine-threonine (ST) kinase and is a key regulator in the production of pro-inflammatory cytokines in macrophages. Due to its pivotal role in immune biology, COT kinase has been identified as an attractive target for pharmaceutical research that is directed at the discovery of orally available, selective, and potent inhibitors for the treatment of autoimmune disorders and cancer. The production of monomeric, recombinant COT kinase has proven to be very difficult, and issues with solubility and stability of the enzyme have hampered the discovery and optimization of potent and selective inhibitors. We developed a protocol for the production of recombinant human COT kinase that yields pure and highly active enzyme in sufficient yields for biochemical and structural studies. The quality of the enzyme allowed us to establish a robust in vitro phosphorylation assay for the efficient biochemical characterization of COT kinase inhibitors and to determine the x-ray co-crystal structures of the COT kinase domain in complex with two ATP-binding site inhibitors. The structures presented in this study reveal two distinct ligand binding modes and a unique kinase domain architecture that has not been observed previously. The structurally versatile active site significantly impacts the design of potent, low molecular weight COT kinase inhibitors. PMID:25918157

  19. Genetic analysis reveals an unexpected role of BMP7 in initiation of ureteric bud outgrowth in mouse embryos.

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    Alexandre Gonçalves

    Full Text Available BACKGROUND: Genetic analysis in the mouse revealed that GREMLIN1 (GREM1-mediated antagonism of BMP4 is essential for ureteric epithelial branching as the disruption of ureteric bud outgrowth and renal agenesis in Grem1-deficient embryos is restored by additional inactivation of one Bmp4 allele. Another BMP ligand, BMP7, was shown to control the proliferative expansion of nephrogenic progenitors and its requirement for nephrogenesis can be genetically substituted by Bmp4. Therefore, we investigated whether BMP7 in turn also participates in inhibiting ureteric bud outgrowth during the initiation of metanephric kidney development. METHODOLOGY/PRINCIPAL FINDINGS: Genetic inactivation of one Bmp7 allele in Grem1-deficient mouse embryos does not alleviate the bilateral renal agenesis, while complete inactivation of Bmp7 restores ureteric bud outgrowth and branching. In mouse embryos lacking both Grem1 and Bmp7, GDNF/WNT11 feedback signaling and the expression of the Etv4 target gene, which regulates formation of the invading ureteric bud tip, are restored. In contrast to the restoration of ureteric bud outgrowth and branching, nephrogenesis remains aberrant as revealed by the premature loss of Six2 expressing nephrogenic progenitor cells. Therefore, very few nephrons develop in kidneys lacking both Grem1 and Bmp7 and the resulting dysplastic phenotype is indistinguishable from the one of Bmp7-deficient mouse embryos. CONCLUSIONS/SIGNIFICANCE: Our study reveals an unexpected inhibitory role of BMP7 during the onset of ureteric bud outgrowth. As BMP4, BMP7 and GREM1 are expressed in distinct mesenchymal and epithelial domains, the localized antagonistic interactions of GREM1 with BMPs could restrict and guide ureteric bud outgrowth and branching. The robustness and likely significant redundancy of the underlying signaling system is evidenced by the fact that global reduction of Bmp4 or inactivation of Bmp7 are both able to restore ureteric bud outgrowth

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

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    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. PMID:24273618

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

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    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.

  2. 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

  3. 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.

  4. Unexpected high 35S concentration revealing strong downward transport of stratospheric air during the monsoon transitional period in East Asia

    Science.gov (United States)

    Lin, Mang; Zhang, Zhisheng; Su, Lin; Su, Binbin; Liu, Lanzhong; Tao, Jun; Fung, Jimmy C. H.; Thiemens, Mark H.

    2016-03-01

    October is the monsoon transitional period in East Asia (EA) involving a series of synoptic activities that may enhance the downward transport of stratospheric air to the planetary boundary layer (PBL). Here we use cosmogenic 35S in sulfate aerosols (35SO42-) as a tracer for air masses originating from the stratosphere and transported downward to quantify these mixing processes. From 1 year 35SO42- measurements (March 2014 to February 2015) at a background station in EA we find remarkably enhanced 35SO42- concentration (3150 atoms m-3) in October, the highest value ever reported for natural sulfate aerosols. A four-box 1-D model and meteorological analysis reveal that strong downward transport from the free troposphere is a vital process entraining aged stratospheric air masses to the PBL. The aged stratospheric masses are accumulated in the PBL, accelerating the SO2 transformation to SO42-. Implications for the tropospheric O3 budget and the CO2 biogeochemical cycle are discussed.

  5. Multilocus phylogenetic analyses reveal unexpected abundant diversity and significant disjunct distribution pattern of the Hedgehog Mushrooms (Hydnum L.).

    Science.gov (United States)

    Feng, Bang; Wang, Xiang-Hua; Ratkowsky, David; Gates, Genevieve; Lee, Su See; Grebenc, Tine; Yang, Zhu L

    2016-01-01

    Hydnum is a fungal genus proposed by Linnaeus in the early time of modern taxonomy. It contains several ectomycorrhizal species which are commonly consumed worldwide. However, Hydnum is one of the most understudied fungal genera, especially from a molecular phylogenetic view. In this study, we extensively gathered specimens of Hydnum from Asia, Europe, America and Australasia, and analyzed them by using sequences of four gene fragments (ITS, nrLSU, tef1α and rpb1). Our phylogenetic analyses recognized at least 31 phylogenetic species within Hydnum, 15 of which were reported for the first time. Most Australasian species were recognized as strongly divergent old relics, but recent migration between Australasia and the Northern Hemisphere was also detected. Within the Northern Hemisphere, frequent historical biota exchanges between the Old World and the New World via both the North Atlantic Land Bridge and the Bering Land Bridge could be elucidated. Our study also revealed that most Hydnum species found in subalpine areas of the Hengduan Mountains in southwestern China occur in northeastern/northern China and Europe, indicating that the composition of the mycobiota in the Hengduan Mountains reigion is more complicated than what we have known before. PMID:27151256

  6. Analysis of Two Putative Candida albicans Phosphopantothenoylcysteine Decarboxylase / Protein Phosphatase Z Regulatory Subunits Reveals an Unexpected Distribution of Functional Roles

    Science.gov (United States)

    Petrényi, Katalin; Molero, Cristina; Kónya, Zoltán; Erdődi, Ferenc; Ariño, Joaquin; Dombrádi, Viktor

    2016-01-01

    Protein phosphatase Z (Ppz) is a fungus specific enzyme that regulates cell wall integrity, cation homeostasis and oxidative stress response. Work on Saccharomyces cerevisiae has shown that the enzyme is inhibited by Hal3/Vhs3 moonlighting proteins that together with Cab3 constitute the essential phosphopantothenoylcysteine decarboxylase (PPCDC) enzyme. In Candida albicans CaPpz1 is also involved in the morphological changes and infectiveness of this opportunistic human pathogen. To reveal the CaPpz1 regulatory context we searched the C. albicans database and identified two genes that, based on the structure of their S. cerevisiae counterparts, were termed CaHal3 and CaCab3. By pull down analysis and phosphatase assays we demonstrated that both of the bacterially expressed recombinant proteins were able to bind and inhibit CaPpz1 as well as its C-terminal catalytic domain (CaPpz1-Cter) with comparable efficiency. The binding and inhibition were always more pronounced with CaPpz1-Cter, indicating a protective effect against inhibition by the N-terminal domain in the full length protein. The functions of the C. albicans proteins were tested by their overexpression in S. cerevisiae. Contrary to expectations we found that only CaCab3 and not CaHal3 rescued the phenotypic traits that are related to phosphatase inhibition by ScHal3, such as tolerance to LiCl or hygromycin B, requirement for external K+ concentrations, or growth in a MAP kinase deficient slt2 background. On the other hand, both of the Candida proteins turned out to be essential PPCDC components and behaved as their S. cerevisiae counterparts: expression of CaCab3 and CaHal3 rescued the cab3 and hal3 vhs3 S. cerevisiae mutations, respectively. Thus, both CaHal3 and CaCab3 retained the PPCDC related functions and have the potential for CaPpz1 inhibition in vitro. The fact that only CaCab3 exhibits its phosphatase regulatory potential in vivo suggests that in C. albicans CaCab3, but not CaHal3, acts as a

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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…

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

    International Nuclear Information System (INIS)

    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 11C-N-methylspiperone (11C-NMSP) to assess the availability of D2/5-HT2A receptors and with 18F-fluoro-D-glucose (18F-FDG) to assess regional brain glucose metabolism, a marker of brain function. 11C-NMSP and 18F-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. (orig.)

  11. 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.)

  12. Unexpected tolerance of glycosylation by UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferase revealed by electron capture dissociation mass spectrometry: carbohydrate as potential protective groups.

    Science.gov (United States)

    Yoshimura, Yayoi; Matsushita, Takahiko; Fujitani, Naoki; Takegawa, Yasuhiro; Fujihira, Haruhiko; Naruchi, Kentarou; Gao, Xiao-Dong; Manri, Naomi; Sakamoto, Takeshi; Kato, Kentaro; Hinou, Hiroshi; Nishimura, Shin-Ichiro

    2010-07-20

    UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases (ppGalNAcTs, EC 2.4.1.41), a family of key enzymes that initiate posttranslational modification with O-glycans in mucin synthesis by introduction of alpha-GalNAc residues, are structurally composed of a catalytic domain and a lectin domain. It has been known that multiple Ser/Thr residues are assigned in common mucin glycoproteins as potential O-glycosylation sites and more than 20 distinct isoforms of this enzyme family contribute to produce densely O-glycosylated mucin glycoproteins. However, it seems that the functional role of the lectin domain of ppGalNAcTs remains unclear. We considered that electron capture dissociation mass spectrometry (ECD-MS), a promising method for highly selective fragmentation at peptide linkages of glycopeptides to generate unique c and z series of ions, should allow for precise structural characterization to uncover the mechanism in O-glycosylation of mucin peptides by ppGalNAcTs. In the present study, it was demonstrated that a system composed of an electrospray source, a linear RFQ ion trap that isolates precursor ions, the ECD device, and a TOF mass spectrometer is a nice tool to identify the preferential O-glycosylation sites without any decomposition of the carbohydrate moiety. It should be noted that electrons used for ECD are accelerated within a range from 1.75 to 9.75 eV depending on the structures of glycopeptides of interest. We revealed for the first time that additional installation of a alpha-GalNAc residue at potential glycosylation sites by ppGalNAcT2 proceeds smoothly in various unnatural glycopeptides having alpha-Man, alpha-Fuc, and beta-Gal residues as well as alpha-GalNAc residues. The results may suggest that ppGalNAcT2 did not differentiate totally presubstituted sugar residues in terms of configuration of functional groups, d-, l-configuration, and even alpha-, beta-stereochemistry at an anomeric carbon atom when relatively short synthetic

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

    Science.gov (United States)

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

    2016-03-01

    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. PMID:26941317

  14. Hidden Stages of Cognition Revealed in Patterns of Brain Activation.

    Science.gov (United States)

    Anderson, John R; Pyke, Aryn A; Fincham, Jon M

    2016-09-01

    To advance cognitive theory, researchers must be able to parse the performance of a task into its significant mental stages. In this article, we describe a new method that uses functional MRI brain activation to identify when participants are engaged in different cognitive stages on individual trials. The method combines multivoxel pattern analysis to identify cognitive stages and hidden semi-Markov models to identify their durations. This method, applied to a problem-solving task, identified four distinct stages: encoding, planning, solving, and responding. We examined whether these stages corresponded to their ascribed functions by testing whether they are affected by appropriate factors. Planning-stage duration increased as the method for solving the problem became less obvious, whereas solving-stage duration increased as the number of calculations to produce the answer increased. Responding-stage duration increased with the difficulty of the motor actions required to produce the answer. PMID:27440808

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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.

  17. 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. PMID:26257697

  18. 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. PMID:27129758

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Hemispheric Asymmetry of Human Brain Anatomical Network Revealed by Diffusion Tensor Tractography

    Directory of Open Access Journals (Sweden)

    Ni Shu

    2015-01-01

    Full Text Available The topological architecture of the cerebral anatomical network reflects the structural organization of the human brain. Recently, topological measures based on graph theory have provided new approaches for quantifying large-scale anatomical networks. However, few studies have investigated the hemispheric asymmetries of the human brain from the perspective of the network model, and little is known about the asymmetries of the connection patterns of brain regions, which may reflect the functional integration and interaction between different regions. Here, we utilized diffusion tensor imaging to construct binary anatomical networks for 72 right-handed healthy adult subjects. We established the existence of structural connections between any pair of the 90 cortical and subcortical regions using deterministic tractography. To investigate the hemispheric asymmetries of the brain, statistical analyses were performed to reveal the brain regions with significant differences between bilateral topological properties, such as degree of connectivity, characteristic path length, and betweenness centrality. Furthermore, local structural connections were also investigated to examine the local asymmetries of some specific white matter tracts. From the perspective of both the global and local connection patterns, we identified the brain regions with hemispheric asymmetries. Combined with the previous studies, we suggested that the topological asymmetries in the anatomical network may reflect the functional lateralization of the human brain.

  1. Hemispheric Asymmetry of Human Brain Anatomical Network Revealed by Diffusion Tensor Tractography.

    Science.gov (United States)

    Shu, Ni; Liu, Yaou; Duan, Yunyun; Li, Kuncheng

    2015-01-01

    The topological architecture of the cerebral anatomical network reflects the structural organization of the human brain. Recently, topological measures based on graph theory have provided new approaches for quantifying large-scale anatomical networks. However, few studies have investigated the hemispheric asymmetries of the human brain from the perspective of the network model, and little is known about the asymmetries of the connection patterns of brain regions, which may reflect the functional integration and interaction between different regions. Here, we utilized diffusion tensor imaging to construct binary anatomical networks for 72 right-handed healthy adult subjects. We established the existence of structural connections between any pair of the 90 cortical and subcortical regions using deterministic tractography. To investigate the hemispheric asymmetries of the brain, statistical analyses were performed to reveal the brain regions with significant differences between bilateral topological properties, such as degree of connectivity, characteristic path length, and betweenness centrality. Furthermore, local structural connections were also investigated to examine the local asymmetries of some specific white matter tracts. From the perspective of both the global and local connection patterns, we identified the brain regions with hemispheric asymmetries. Combined with the previous studies, we suggested that the topological asymmetries in the anatomical network may reflect the functional lateralization of the human brain.

  2. 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. PMID:27339989

  3. 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.

  4. Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility.

    Science.gov (United States)

    Bagot, Rosemary C; Cates, Hannah M; Purushothaman, Immanuel; Lorsch, Zachary S; Walker, Deena M; Wang, Junshi; Huang, Xiaojie; Schlüter, Oliver M; Maze, Ian; Peña, Catherine J; Heller, Elizabeth A; Issler, Orna; Wang, Minghui; Song, Won-Min; Stein, Jason L; Liu, Xiaochuan; Doyle, Marie A; Scobie, Kimberly N; Sun, Hao Sheng; Neve, Rachael L; Geschwind, Daniel; Dong, Yan; Shen, Li; Zhang, Bin; Nestler, Eric J

    2016-06-01

    Depression is a complex, heterogeneous disorder and a leading contributor to the global burden of disease. Most previous research has focused on individual brain regions and genes contributing to depression. However, emerging evidence in humans and animal models suggests that dysregulated circuit function and gene expression across multiple brain regions drive depressive phenotypes. Here, we performed RNA sequencing on four brain regions from control animals and those susceptible or resilient to chronic social defeat stress at multiple time points. We employed an integrative network biology approach to identify transcriptional networks and key driver genes that regulate susceptibility to depressive-like symptoms. Further, we validated in vivo several key drivers and their associated transcriptional networks that regulate depression susceptibility and confirmed their functional significance at the levels of gene transcription, synaptic regulation, and behavior. Our study reveals novel transcriptional networks that control stress susceptibility and offers fundamentally new leads for antidepressant drug discovery. PMID:27181059

  5. Whole-brain circuit dissection in free-moving animals reveals cell-specific mesocorticolimbic networks

    Science.gov (United States)

    Michaelides, Michael; Anderson, Sarah Ann R.; Ananth, Mala; Smirnov, Denis; Thanos, Panayotis K.; Neumaier, John F.; Wang, Gene-Jack; Volkow, Nora D.; Hurd, Yasmin L.

    2013-01-01

    The ability to map the functional connectivity of discrete cell types in the intact mammalian brain during behavior is crucial for advancing our understanding of brain function in normal and disease states. We combined designer receptor exclusively activated by designer drug (DREADD) technology and behavioral imaging with μPET and [18F]fluorodeoxyglucose (FDG) to generate whole-brain metabolic maps of cell-specific functional circuits during the awake, freely moving state. We have termed this approach DREADD-assisted metabolic mapping (DREAMM) and documented its ability in rats to map whole-brain functional anatomy. We applied this strategy to evaluating changes in the brain associated with inhibition of prodynorphin-expressing (Pdyn-expressing) and of proenkephalin-expressing (Penk-expressing) medium spiny neurons (MSNs) of the nucleus accumbens shell (NAcSh), which have been implicated in neuropsychiatric disorders. DREAMM revealed discrete behavioral manifestations and concurrent engagement of distinct corticolimbic networks associated with dysregulation of Pdyn and Penk in MSNs of the NAcSh. Furthermore, distinct neuronal networks were recruited in awake versus anesthetized conditions. These data demonstrate that DREAMM is a highly sensitive, molecular, high-resolution quantitative imaging approach. PMID:24231358

  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. Novel aspects of brain metabolism as revealed by magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    Full text: The techniques of Magnetic Resonance Spectroscopy (MRS) and Imaging (MRI) are outlined, and compared with Positron Emission Tomography (PET). Invasive PET techniques using 19F-fluorodeoxyglucose (FDG) and 18O2 form the main basis of brain activation studies, and with 19F-fluoroDOPA, make major contributions to studies on neurological disorders such as stroke, Alzheimer's disease and Parkinson's disease. However the technique has no chemical specificity so can provide no knowledge of intermediary metabolism. Non-invasive MRI is also being applied to brain activation studies but also has no chemical specificity. On the other hand MRS has superb chemical specificity, although it suffers from low sensitivity. A most interesting example of this is the use of 13C-MRS. If glucose is labelled on the no. 1 or no. 2 positions with 13C, the passage of the label through different neuronal and glial metabolic pathways can be followed. If acetate is similarly labelled, metabolic routes through specifically glial pathways can be monitored, since acetate is taken up only by glia. These studies contributed to knowledge on metabolic trafficking, in that glia produce alanine, citrate and lactate in addition to the previously characterised production of glutamine. Studies on the hypoxic brain revealed increased production of alanine, lactate and glycerol 3-phosphate, providing further understanding of the role of the NADH redox state. 'Isotopomer analysis' of 13C resonances provides more information on metabolic pathways, because the chemical shift of a 13C atom is specifically affected by a neighbouring 13C within the same molecule. This approach was used to demonstrate that neurotransmitter γ-aminobutyrate (GABA) is partly derived from glial glutamine. Analogous 13C MRS studies are now providing novel information on metabolic flux rates within the human brain, and the most exciting developments are to follow changes in these rates on brain activation which can be

  8. From Amazonia to the Atlantic forest: molecular phylogeny of Phyzelaphryninae frogs reveals unexpected diversity and a striking biogeographic pattern emphasizing conservation challenges.

    Science.gov (United States)

    Fouquet, Antoine; Loebmann, Daniel; Castroviejo-Fisher, Santiago; Padial, José M; Orrico, Victor G D; Lyra, Mariana L; Roberto, Igor Joventino; Kok, Philippe J R; Haddad, Célio F B; Rodrigues, Miguel T

    2012-11-01

    Documenting the Neotropical amphibian diversity has become a major challenge facing the threat of global climate change and the pace of environmental alteration. Recent molecular phylogenetic studies have revealed that the actual number of species in South American tropical forests is largely underestimated, but also that many lineages are millions of years old. The genera Phyzelaphryne (1 sp.) and Adelophryne (6 spp.), which compose the subfamily Phyzelaphryninae, include poorly documented, secretive, and minute frogs with an unusual distribution pattern that encompasses the biotic disjunction between Amazonia and the Atlantic forest. We generated >5.8 kb sequence data from six markers for all seven nominal species of the subfamily as well as for newly discovered populations in order to (1) test the monophyly of Phyzelaphryninae, Adelophryne and Phyzelaphryne, (2) estimate species diversity within the subfamily, and (3) investigate their historical biogeography and diversification. Phylogenetic reconstruction confirmed the monophyly of each group and revealed deep subdivisions within Adelophryne and Phyzelaphryne, with three major clades in Adelophryne located in northern Amazonia, northern Atlantic forest and southern Atlantic forest. Our results suggest that the actual number of species in Phyzelaphryninae is, at least, twice the currently recognized species diversity, with almost every geographically isolated population representing an anciently divergent candidate species. Such results highlight the challenges for conservation, especially in the northern Atlantic forest where it is still degraded at a fast pace. Molecular dating revealed that Phyzelaphryninae originated in Amazonia and dispersed during early Miocene to the Atlantic forest. The two Atlantic forest clades of Adelophryne started to diversify some 7 Ma minimum, while the northern Amazonian Adelophryne diversified much earlier, some 13 Ma minimum. This striking biogeographic pattern coincides with

  9. 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.

  10. BRAIN DYSFUNCTION OF PATIENTS WITH QIGONG INDUCED MENTAL DISORDER REVEALED BY EVOKED POTENTIALS RECORDING

    Institute of Scientific and Technical Information of China (English)

    LU Yingzhi; ZONG Wenbin; CHEN Xingshi

    2003-01-01

    Objective: In order to investigate the brain function of patients with Qigong induced mental disorder (QIMD), this study was carried out. Methods: Four kinds of evoked potentials, including contingent negative variation (CNV), auditory evoked potentials (AEP), visual evoked potentials (VEP), and somatosensory evoked potentials (SEP), were recorded from 12 patients with Qigong induced mental disorder.Comparison of their evoked potentials with the data from some normal controls was made. Results: The results revealed that there were 3 kinds of abnormal changes in evoked potentials of patients with QIMD that is latency prolongation, amplitude increase and amplitude decrease, as compared with normal controls. Conclusion: Brain dysfunction of patients with QIMD was confirmed. Its biological mechanism needs further studying.

  11. Computerized three-dimensional reconstruction reveals cerebrovascular regulatory subregions in rat brain stem.

    Science.gov (United States)

    Underwood, M D; Arango, V; Smith, R W; Bakalian, M J; Mann, J J

    1993-09-01

    Three-dimensional wireframe reconstructions were used to examine the relationship between the anatomical localization of electrode sites and the cerebrovascular response which was elicited by electrical stimulation of the dorsal raphe nucleus (DRN). Reconstructions of the rat brain and DRN were done from atlas plates and from Nissl-stained coronal sections (100-micron increments). Data points were entered and three-dimensional reconstructions were performed using commercially available software and a personal computer. Display of the entire brain yielded views which obscured visualization of the DRN. The data file was edited to reduce the number of contours without affecting the display resolution of the DRN. Selective display of the DRN and electronic rotation from the coronal to a sagittal view revealed a functional organization of the cerebral blood flow responses which was not apparent in two-dimensional coronal sections.

  12. Intact-Brain Analyses Reveal Distinct Information Carried by SNc Dopamine Subcircuits.

    Science.gov (United States)

    Lerner, Talia N; Shilyansky, Carrie; Davidson, Thomas J; Evans, Kathryn E; Beier, Kevin T; Zalocusky, Kelly A; Crow, Ailey K; Malenka, Robert C; Luo, Liqun; Tomer, Raju; Deisseroth, Karl

    2015-07-30

    Recent progress in understanding the diversity of midbrain dopamine neurons has highlighted the importance--and the challenges--of defining mammalian neuronal cell types. Although neurons may be best categorized using inclusive criteria spanning biophysical properties, wiring of inputs, wiring of outputs, and activity during behavior, linking all of these measurements to cell types within the intact brains of living mammals has been difficult. Here, using an array of intact-brain circuit interrogation tools, including CLARITY, COLM, optogenetics, viral tracing, and fiber photometry, we explore the diversity of dopamine neurons within the substantia nigra pars compacta (SNc). We identify two parallel nigrostriatal dopamine neuron subpopulations differing in biophysical properties, input wiring, output wiring to dorsomedial striatum (DMS) versus dorsolateral striatum (DLS), and natural activity patterns during free behavior. Our results reveal independently operating nigrostriatal information streams, with implications for understanding the logic of dopaminergic feedback circuits and the diversity of mammalian neuronal cell types.

  13. Risk factors for small-vessel disease revealed by magnetic resonance imaging of the brain

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-02-01

    In total, 133 patients with asymptomatic or symptomatic cerebral infarction were randomly selected for the study (64 males, 69 females). Among them 91 patients had a history of symptomatic cerebral infarction, 46 patients of hypertension, and 28 patients of diabetes mellitus. The MRI scans were reviewed for areas with increased signal intensity on T2-weighted images. The grade of periventricular lesions, and the number of small infarctions in the subcortical white matter, basal ganglia and brain stem increased significantly with advancing age. It was thus reconfirmed that age is an important risk for demonstrating small-vessel disease on brain MRI. In addition, the degree of small-vessel disease on brain MRI was more extensive in patients with symptomatic cerebral infarction than with asymptomatic cerebral infarction. The detailed results suggest that small-vessel disease on brain MRI in patients with asymptomatic cerebral infarction might represent preclinical lesions for symptomatic cerebral infarction. The numbers of small infarctions in both the subcortical white matter and basal ganglia associated with advancing age, and histories of cerebrovascular accident and hypertension, suggest that common underlying mechanisms may exist in small-vessel disease in both the medullary arteries, which arise from cortical arteries, and perforating arteries. In the subcortical white matter, the number of patchy lesions was more strongly correlated with histories of hypertension and diabetes mellitus than was the number of spotty lesions, suggesting that the risk factors differed depending on the size of the lesions. The present study revealed that the degree of small-vessel disease on brain MRI was not correlated with the serum concentration of total cholesterol, triglyceride or HDL-cholesterol. The data thus indicate that the risk factors for small-vessel disease are distinct from those for large-vessel disease. (J.P.N.)

  14. Risk factors for small-vessel disease revealed by magnetic resonance imaging of the brain

    International Nuclear Information System (INIS)

    In total, 133 patients with asymptomatic or symptomatic cerebral infarction were randomly selected for the study (64 males, 69 females). Among them 91 patients had a history of symptomatic cerebral infarction, 46 patients of hypertension, and 28 patients of diabetes mellitus. The MRI scans were reviewed for areas with increased signal intensity on T2-weighted images. The grade of periventricular lesions, and the number of small infarctions in the subcortical white matter, basal ganglia and brain stem increased significantly with advancing age. It was thus reconfirmed that age is an important risk for demonstrating small-vessel disease on brain MRI. In addition, the degree of small-vessel disease on brain MRI was more extensive in patients with symptomatic cerebral infarction than with asymptomatic cerebral infarction. The detailed results suggest that small-vessel disease on brain MRI in patients with asymptomatic cerebral infarction might represent preclinical lesions for symptomatic cerebral infarction. The numbers of small infarctions in both the subcortical white matter and basal ganglia associated with advancing age, and histories of cerebrovascular accident and hypertension, suggest that common underlying mechanisms may exist in small-vessel disease in both the medullary arteries, which arise from cortical arteries, and perforating arteries. In the subcortical white matter, the number of patchy lesions was more strongly correlated with histories of hypertension and diabetes mellitus than was the number of spotty lesions, suggesting that the risk factors differed depending on the size of the lesions. The present study revealed that the degree of small-vessel disease on brain MRI was not correlated with the serum concentration of total cholesterol, triglyceride or HDL-cholesterol. The data thus indicate that the risk factors for small-vessel disease are distinct from those for large-vessel disease. (J.P.N.)

  15. Severe Left Ventricular Hypertrophy, Small Pericardial Effusion, and Diffuse Late Gadolinium Enhancement by Cardiac Magnetic Resonance Suspecting Cardiac Amyloidosis: Endomyocardial Biopsy Reveals an Unexpected Diagnosis

    Directory of Open Access Journals (Sweden)

    Nina P. Hofmann

    2016-01-01

    Full Text Available Left ventricular (LV hypertrophy can be related to a multitude of cardiac disorders, such as hypertrophic cardiomyopathy (HCM, cardiac amyloidosis, and hypertensive heart disease. Although the presence of LV hypertrophy is generally associated with poorer cardiac outcomes, the early differentiation between these pathologies is crucial due to the presence of specific treatment options. The diagnostic process with LV hypertrophy requires the integration of clinical evaluation, electrocardiography (ECG, echocardiography, biochemical markers, and if required CMR and endomyocardial biopsy in order to reach the correct diagnosis. Here, we present a case of a patient with severe LV hypertrophy (septal wall thickness of 23 mm, LV mass of 264 g, and LV mass index of 147 g/m2, severely impaired longitudinal function, and preserved radial contractility (ejection fraction = 55%, accompanied by small pericardial effusion and diffuse late gadolinium enhancement (LGE by cardiac magnetic resonance (CMR. Due to the imaging findings, an infiltrative cardiomyopathy, such as cardiac amyloidosis, was suspected. However, amyloid accumulation was excluded by endomyocardial biopsy, which revealed the presence of diffuse myocardial fibrosis in an advanced hypertensive heart disease.

  16. 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.

  17. Laterality of brain areas associated with arithmetic calculations revealed by functional magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yun-ting; ZHANG Quan; ZHANG Jing; LI Wei

    2005-01-01

    Background Asymmetry of bilateral cerebral function, i.e. laterality, is an important phenomenon in many brain actions: arithmetic calculation may be one of these phenomena. In this study, first, laterality of brain areas associated with arithmetic calculations was revealed by functional magnetic resonance imaging (fMRI). Second, the relationship among laterality, handedness, and types of arithmetic task was assessed. Third, we postulate possible reasons for laterality.Methods Using a block-designed experiment, twenty-five right-handed and seven left-handed healthy volunteers carried out simple calculations, complex calculations and proximity judgments. T1WI and GRE-EPI fMRI were performed with a GE 1.5T whole body MRI scanner. Statistical parametric mapping (SPM99) was used to process data and localize functional areas. Numbers of activated voxels were recorded to calculate laterality index for evaluating the laterality of functional brain areas.Results For both groups, the activation of functional areas in the frontal lobe showed a tendency towards the nonpredominant hand side, but the functional areas in the inferior parietal lobule had left laterality. During simple and complex calculations, the laterality indices of the prefrontal cortex and premotor area were higher in the right-handed group than that in the left-handed group, whereas the laterality of the inferior parietal lobule had no such significant difference. In both groups, when the difficulty of the task increased, the laterality of the prefrontal cortex, premotor area, and inferior parietal lobule decreased, but the laterality of posterior part of the inferior frontal gyrus increased.Conclusions The laterality of the functional brain areas associated with arithmetic calculations can be detected with fMRI. The laterality of the functional areas was related to handedness and task difficulty.

  18. 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

    2016-01-01

    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. PMID:27271458

  19. Recent adaptive events in human brain revealed by meta-analysis of positively selected genes.

    Directory of Open Access Journals (Sweden)

    Yue Huang

    Full Text Available BACKGROUND AND OBJECTIVES: Analysis of positively-selected genes can help us understand how human evolved, especially the evolution of highly developed cognitive functions. However, previous works have reached conflicting conclusions regarding whether human neuronal genes are over-represented among genes under positive selection. METHODS AND RESULTS: We divided positively-selected genes into four groups according to the identification approaches, compiling a comprehensive list from 27 previous studies. We showed that genes that are highly expressed in the central nervous system are enriched in recent positive selection events in human history identified by intra-species genomic scan, especially in brain regions related to cognitive functions. This pattern holds when different datasets, parameters and analysis pipelines were used. Functional category enrichment analysis supported these findings, showing that synapse-related functions are enriched in genes under recent positive selection. In contrast, immune-related functions, for instance, are enriched in genes under ancient positive selection revealed by inter-species coding region comparison. We further demonstrated that most of these patterns still hold even after controlling for genomic characteristics that might bias genome-wide identification of positively-selected genes including gene length, gene density, GC composition, and intensity of negative selection. CONCLUSION: Our rigorous analysis resolved previous conflicting conclusions and revealed recent adaptation of human brain functions.

  20. 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...

  1. K-shell decomposition reveals hierarchical cortical organization of the human brain

    Science.gov (United States)

    Lahav, Nir; Ksherim, Baruch; Ben-Simon, Eti; Maron-Katz, Adi; Cohen, Reuven; Havlin, Shlomo

    2016-08-01

    In recent years numerous attempts to understand the human brain were undertaken from a network point of view. A network framework takes into account the relationships between the different parts of the system and enables to examine how global and complex functions might emerge from network topology. Previous work revealed that the human brain features ‘small world’ characteristics and that cortical hubs tend to interconnect among themselves. However, in order to fully understand the topological structure of hubs, and how their profile reflect the brain’s global functional organization, one needs to go beyond the properties of a specific hub and examine the various structural layers that make up the network. To address this topic further, we applied an analysis known in statistical physics and network theory as k-shell decomposition analysis. The analysis was applied on a human cortical network, derived from MRI\\DSI data of six participants. Such analysis enables us to portray a detailed account of cortical connectivity focusing on different neighborhoods of inter-connected layers across the cortex. Our findings reveal that the human cortex is highly connected and efficient, and unlike the internet network contains no isolated nodes. The cortical network is comprised of a nucleus alongside shells of increasing connectivity that formed one connected giant component, revealing the human brain’s global functional organization. All these components were further categorized into three hierarchies in accordance with their connectivity profile, with each hierarchy reflecting different functional roles. Such a model may explain an efficient flow of information from the lowest hierarchy to the highest one, with each step enabling increased data integration. At the top, the highest hierarchy (the nucleus) serves as a global interconnected collective and demonstrates high correlation with consciousness related regions, suggesting that the nucleus might serve as a

  2. Pain facilitation brain regions activated by nalbuphine are revealed by pharmacological fMRI.

    Directory of Open Access Journals (Sweden)

    Robert Gear

    Full Text Available Nalbuphine, an agonist-antagonist kappa-opioid, produces brief analgesia followed by enhanced pain/hyperalgesia in male postsurgical patients. However, it produces profound analgesia without pain enhancement when co-administration with low dose naloxone. To examine the effect of nalbuphine or nalbuphine plus naloxone on activity in brain regions that may explain these differences, we employed pharmacological magnetic resonance imaging (phMRI in a double blind cross-over study with 13 healthy male volunteers. In separate imaging sessions subjects were administered nalbuphine (5 mg/70 kg preceded by either saline (Sal-Nalb or naloxone 0.4 mg (Nalox-Nalb. Blood oxygen level-dependent (BOLD activation maps followed by contrast and connectivity analyses revealed marked differences. Sal-Nalb produced significantly increased activity in 60 brain regions and decreased activity in 9; in contrast, Nalox-Nalb activated only 14 regions and deactivated only 3. Nalbuphine, like morphine in a previous study, attenuated activity in the inferior orbital cortex, and, like noxious stimulation, increased activity in temporal cortex, insula, pulvinar, caudate, and pons. Co-administration/pretreatment of naloxone selectively blocked activity in pulvinar, pons and posterior insula. Nalbuphine induced functional connectivity between caudate and regions in the frontal, occipital, temporal, insular, middle cingulate cortices, and putamen; naloxone co-admistration reduced all connectivity to non-significant levels, and, like phMRI measures of morphine, increased activation in other areas (e.g., putamen. Naloxone pretreatment to nalbuphine produced changes in brain activity possess characteristics of both analgesia and algesia; naloxone selectively blocks activity in areas associated with algesia. Given these findings, we suggest that nalbuphine interacts with a pain salience system, which can modulate perceived pain intensity.

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    Elisabeth Fonteneau

    Full Text Available BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.

  5. 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.

  6. Glycogen distribution in the microwave-fixed mouse brain reveals heterogeneous astrocytic patterns.

    Science.gov (United States)

    Oe, Yuki; Baba, Otto; Ashida, Hitoshi; Nakamura, Kouichi C; Hirase, Hajime

    2016-09-01

    In the brain, glycogen metabolism has been implied in synaptic plasticity and learning, yet the distribution of this molecule has not been fully described. We investigated cerebral glycogen of the mouse by immunohistochemistry (IHC) using two monoclonal antibodies that have different affinities depending on the glycogen size. The use of focused microwave irradiation yielded well-defined glycogen immunoreactive signals compared with the conventional periodic acid-Schiff method. The IHC signals displayed a punctate distribution localized predominantly in astrocytic processes. Glycogen immunoreactivity (IR) was high in the hippocampus, striatum, cortex, and cerebellar molecular layer, whereas it was low in the white matter and most of the subcortical structures. Additionally, glycogen distribution in the hippocampal CA3-CA1 and striatum had a 'patchy' appearance with glycogen-rich and glycogen-poor astrocytes appearing in alternation. The glycogen patches were more evident with large-molecule glycogen in young adult mice but they were hardly observable in aged mice (1-2 years old). Our results reveal brain region-dependent glycogen accumulation and possibly metabolic heterogeneity of astrocytes. GLIA 2016;64:1532-1545. PMID:27353480

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

    International Nuclear Information System (INIS)

    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

  8. 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. PMID:26969865

  9. 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.

  10. 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 <7d; n = 18) were compared to age-matched controls (n = 16) from the Glasgow TBI archive. We also examined 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

  11. Brain

    Science.gov (United States)

    ... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

  12. Unexpected Angiography Findings and Effects on Management.

    Science.gov (United States)

    Neill, Matthew; Charles, Hearns W; Gross, Jonathan S; Farquharson, Sean; Deipolyi, Amy R

    2016-01-01

    Despite progress in noninvasive imaging with computed tomography and magnetic resonance imaging, conventional angiography still contributes to the diagnostic workup of oncologic and other diseases. Arteriography can reveal tumors not evident on cross-sectional imaging, in addition to defining aberrant or unexpected arterial supply to targeted lesions. This additional and potentially unanticipated information can alter management decisions during interventional procedures. PMID:27688932

  13. Interspecies avian brain chimeras reveal that large brain size differences are influenced by cell-interdependent processes.

    Science.gov (United States)

    Chen, Chun-Chun; Balaban, Evan; Jarvis, Erich D

    2012-01-01

    Like humans, birds that exhibit vocal learning have relatively delayed telencephalon maturation, resulting in a disproportionately smaller brain prenatally but enlarged telencephalon in adulthood relative to vocal non-learning birds. To determine if this size difference results from evolutionary changes in cell-autonomous or cell-interdependent developmental processes, we transplanted telencephala from zebra finch donors (a vocal-learning species) into Japanese quail hosts (a vocal non-learning species) during the early neural tube stage (day 2 of incubation), and harvested the chimeras at later embryonic stages (between 9-12 days of incubation). The donor and host tissues fused well with each other, with known major fiber pathways connecting the zebra finch and quail parts of the brain. However, the overall sizes of chimeric finch telencephala were larger than non-transplanted finch telencephala at the same developmental stages, even though the proportional sizes of telencephalic subregions and fiber tracts were similar to normal finches. There were no significant changes in the size of chimeric quail host midbrains, even though they were innervated by the physically smaller zebra finch brain, including the smaller retinae of the finch eyes. Chimeric zebra finch telencephala had a decreased cell density relative to normal finches. However, cell nucleus size differences between each species were maintained as in normal birds. These results suggest that telencephalic size development is partially cell-interdependent, and that the mechanisms controlling the size of different brain regions may be functionally independent. PMID:22860132

  14. Interspecies avian brain chimeras reveal that large brain size differences are influenced by cell-interdependent processes.

    Directory of Open Access Journals (Sweden)

    Chun-Chun Chen

    Full Text Available Like humans, birds that exhibit vocal learning have relatively delayed telencephalon maturation, resulting in a disproportionately smaller brain prenatally but enlarged telencephalon in adulthood relative to vocal non-learning birds. To determine if this size difference results from evolutionary changes in cell-autonomous or cell-interdependent developmental processes, we transplanted telencephala from zebra finch donors (a vocal-learning species into Japanese quail hosts (a vocal non-learning species during the early neural tube stage (day 2 of incubation, and harvested the chimeras at later embryonic stages (between 9-12 days of incubation. The donor and host tissues fused well with each other, with known major fiber pathways connecting the zebra finch and quail parts of the brain. However, the overall sizes of chimeric finch telencephala were larger than non-transplanted finch telencephala at the same developmental stages, even though the proportional sizes of telencephalic subregions and fiber tracts were similar to normal finches. There were no significant changes in the size of chimeric quail host midbrains, even though they were innervated by the physically smaller zebra finch brain, including the smaller retinae of the finch eyes. Chimeric zebra finch telencephala had a decreased cell density relative to normal finches. However, cell nucleus size differences between each species were maintained as in normal birds. These results suggest that telencephalic size development is partially cell-interdependent, and that the mechanisms controlling the size of different brain regions may be functionally independent.

  15. Microfiberoptic fluorescence photobleaching reveals size-dependent macromolecule diffusion in extracellular space deep in brain.

    Science.gov (United States)

    Zador, Zsolt; Magzoub, Mazin; Jin, Songwan; Manley, Geoffrey T; Papadopoulos, Marios C; Verkman, A S

    2008-03-01

    Diffusion in brain extracellular space (ECS) is important for nonsynaptic intercellular communication, extracellular ionic buffering, and delivery of drugs and metabolites. We measured macromolecular diffusion in normally light-inaccessible regions of mouse brain by microfiberoptic epifluorescence photobleaching, in which a fiberoptic with a micron-size tip is introduced deep in brain tissue. In brain cortex, the diffusion of a noninteracting molecule [fluorescein isothiocyanate (FITC)-dextran, 70 kDa] was slowed 4.5 +/- 0.5-fold compared with its diffusion in water (D(o)/D), and was depth-independent down to 800 microm from the brain surface. Diffusion was significantly accelerated (D(o)/D of 2.9+/-0.3) in mice lacking the glial water channel aquaporin-4. FITC-dextran diffusion varied greatly in different regions of brain, with D(o)/D of 3.5 +/- 0.3 in hippocampus and 7.4 +/- 0.3 in thalamus. Remarkably, D(o)/D in deep brain was strongly dependent on solute size, whereas diffusion in cortex changed little with solute size. Mathematical modeling of ECS diffusion required nonuniform ECS dimensions in deep brain, which we call "heterometricity," to account for the size-dependent diffusion. Our results provide the first data on molecular diffusion in ECS deep in brain in vivo and demonstrate previously unrecognized hindrance and heterometricity for diffusion of large macromolecules in deep brain.

  16. Transcriptional profiling of human brain endothelial cells reveals key properties crucial for predictive in vitro blood-brain barrier models.

    Directory of Open Access Journals (Sweden)

    Eduard Urich

    Full Text Available Brain microvascular endothelial cells (BEC constitute the blood-brain barrier (BBB which forms a dynamic interface between the blood and the central nervous system (CNS. This highly specialized interface restricts paracellular diffusion of fluids and solutes including chemicals, toxins and drugs from entering the brain. In this study we compared the transcriptome profiles of the human immortalized brain endothelial cell line hCMEC/D3 and human primary BEC. We identified transcriptional differences in immune response genes which are directly related to the immortalization procedure of the hCMEC/D3 cells. Interestingly, astrocytic co-culturing reduced cell adhesion and migration molecules in both BECs, which possibly could be related to regulation of immune surveillance of the CNS controlled by astrocytic cells within the neurovascular unit. By matching the transcriptome data from these two cell lines with published transcriptional data from freshly isolated mouse BECs, we discovered striking differences that could explain some of the limitations of using cultured BECs to study BBB properties. Key protein classes such as tight junction proteins, transporters and cell surface receptors show differing expression profiles. For example, the claudin-5, occludin and JAM2 expression is dramatically reduced in the two human BEC lines, which likely explains their low transcellular electric resistance and paracellular leakiness. In addition, the human BEC lines express low levels of unique brain endothelial transporters such as Glut1 and Pgp. Cell surface receptors such as LRP1, RAGE and the insulin receptor that are involved in receptor-mediated transport are also expressed at very low levels. Taken together, these data illustrate that BECs lose their unique protein expression pattern outside of their native environment and display a more generic endothelial cell phenotype. A collection of key genes that seems to be highly regulated by the local

  17. Brain network analysis reveals affected connectome structure in bipolar I disorder.

    Science.gov (United States)

    Collin, Guusje; van den Heuvel, Martijn P; Abramovic, Lucija; Vreeker, Annabel; de Reus, Marcel A; van Haren, Neeltje E M; Boks, Marco P M; Ophoff, Roel A; Kahn, René S

    2016-01-01

    The notion that healthy brain function emerges from coordinated neural activity constrained by the brain's network of anatomical connections--i.e., the connectome--suggests that alterations in the connectome's wiring pattern may underlie brain disorders. Corroborating this hypothesis, studies in schizophrenia are indicative of altered connectome architecture including reduced communication efficiency, disruptions of central brain hubs, and affected "rich club" organization. Whether similar deficits are present in bipolar disorder is currently unknown. This study examines structural connectome topology in 216 bipolar I disorder patients as compared to 144 healthy controls, focusing in particular on central regions (i.e., brain hubs) and connections (i.e., rich club connections, interhemispheric connections) of the brain's network. We find that bipolar I disorder patients exhibit reduced global efficiency (-4.4%, P =0.002) and that this deficit relates (r = 0.56, P brain hub connections in general, or of connections spanning brain hubs (i.e., "rich club" connections) in particular (all P > 0.1). These findings highlight a role for aberrant brain network architecture in bipolar I disorder with reduced global efficiency in association with disruptions in interhemispheric connectivity, while the central "rich club" system appears not to be particularly affected.

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

    OpenAIRE

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

    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 li...

  19. Fossil skulls reveal that blood flow rate to the brain increased faster than brain volume during human evolution

    Science.gov (United States)

    Seymour, Roger S.; Bosiocic, Vanya; Snelling, Edward P.

    2016-08-01

    The evolution of human cognition has been inferred from anthropological discoveries and estimates of brain size from fossil skulls. A more direct measure of cognition would be cerebral metabolic rate, which is proportional to cerebral blood flow rate (perfusion). The hominin cerebrum is supplied almost exclusively by the internal carotid arteries. The sizes of the foramina that transmitted these vessels in life can be measured in hominin fossil skulls and used to calculate cerebral perfusion rate. Perfusion in 11 species of hominin ancestors, from Australopithecus to archaic Homo sapiens, increases disproportionately when scaled against brain volume (the allometric exponent is 1.41). The high exponent indicates an increase in the metabolic intensity of cerebral tissue in later Homo species, rather than remaining constant (1.0) as expected by a linear increase in neuron number, or decreasing according to Kleiber's Law (0.75). During 3 Myr of hominin evolution, cerebral tissue perfusion increased 1.7-fold, which, when multiplied by a 3.5-fold increase in brain size, indicates a 6.0-fold increase in total cerebral blood flow rate. This is probably associated with increased interneuron connectivity, synaptic activity and cognitive function, which all ultimately depend on cerebral metabolic rate.

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

    Science.gov (United States)

    Abe, Mitsunari; Fukuyama, Hidenao; Mima, Tatsuya

    2014-01-01

    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. PMID:24619090

  1. 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

  2. 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.

  3. Arborization pattern of engrailed-positive neural lineages reveal neuromere boundaries in the Drosophila brain neuropil.

    Science.gov (United States)

    Kumar, Abhilasha; Fung, S; Lichtneckert, Robert; Reichert, Heinrich; Hartenstein, Volker

    2009-11-01

    The Drosophila brain is a highly complex structure composed of thousands of neurons that are interconnected in numerous exquisitely organized neuropil structures such as the mushroom bodies, central complex, antennal lobes, and other specialized neuropils. While the neurons of the insect brain are known to derive in a lineage-specific fashion from a stereotyped set of segmentally organized neuroblasts, the developmental origin and neuromeric organization of the neuropil formed by these neurons is still unclear. In this study we used genetic labeling techniques to characterize the neuropil innervation pattern of engrailed-expressing brain lineages of known neuromeric origin. We show that the neurons of these lineages project to and form most arborizations, in particular all of their proximal branches, in the same brain neuropil compartments in embryonic, larval and adult stages. Moreover, we show that engrailed-positive neurons of differing neuromeric origin respect boundaries between neuromere-specific compartments in the brain. This is confirmed by an analysis of the arborization pattern of empty spiracles-expressing lineages. These findings indicate that arborizations of lineages deriving from different brain neuromeres innervate a nonoverlapping set of neuropil compartments. This supports a model for neuromere-specific brain neuropil, in which a given lineage forms its proximal arborizations predominantly in the compartments that correspond to its neuromere of origin. PMID:19711412

  4. Stepwise Connectivity of the Modal Cortex Reveals the Multimodal Organization of the Human Brain

    Science.gov (United States)

    Sepulcre, Jorge; Sabuncu, Mert R.; Yeo, Thomas B.; Liu, Hesheng; Johnson, Keith A.

    2012-01-01

    How human beings integrate information from external sources and internal cognition to produce a coherent experience is still not well understood. During the past decades, anatomical, neurophysiological and neuroimaging research in multimodal integration have stood out in the effort to understand the perceptual binding properties of the brain. Areas in the human lateral occipito-temporal, prefrontal and posterior parietal cortices have been associated with sensory multimodal processing. Even though this, rather patchy, organization of brain regions gives us a glimpse of the perceptual convergence, the articulation of the flow of information from modality-related to the more parallel cognitive processing systems remains elusive. Using a method called Stepwise Functional Connectivity analysis, the present study analyzes the functional connectome and transitions from primary sensory cortices to higher-order brain systems. We identify the large-scale multimodal integration network and essential connectivity axes for perceptual integration in the human brain. PMID:22855814

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

    OpenAIRE

    Wang, Chunmei; Zheng, Dong; Xu, Jie; Lam, Waiping; Yew, D. T.

    2013-01-01

    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 fi...

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

    OpenAIRE

    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...

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

    OpenAIRE

    Patrick eFissler; Iris-Tatjana eKolassa; Claudia eSchrader

    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...

  8. Prion Infection of Mouse Brain Reveals Multiple New Upregulated Genes Involved in Neuroinflammation or Signal Transduction

    OpenAIRE

    Carroll, James A.; Striebel, James F.; Race, Brent; Phillips, Katie; Chesebro, Bruce

    2014-01-01

    Gliosis is often a preclinical pathological finding in neurodegenerative diseases, including prion diseases, but the mechanisms facilitating gliosis and neuronal damage in these diseases are not understood. To expand our knowledge of the neuroinflammatory response in prion diseases, we assessed the expression of key genes and proteins involved in the inflammatory response and signal transduction in mouse brain at various times after scrapie infection. In brains of scrapie-infected mice at pre...

  9. A mu–delta opioid receptor brain atlas reveals neuronal co-occurrence in subcortical networks

    OpenAIRE

    Erbs, Eric; Faget, Lauren; Scherrer, Gregory; Matifas, Audrey; Filliol, Dominique; Vonesch, Jean-Luc; Koch, Marc; Kessler, Pascal; Hentsch, Didier; Birling, Marie-Christine; Koutsourakis, Manoussos; Vasseur, Laurent; Veinante, Pierre; Kieffer, Brigitte L.; Massotte, Dominique

    2014-01-01

    Opioid receptors are G protein-coupled receptors (GPCRs) that modulate brain function at all levels of neural integration, including autonomic, sensory, emotional and cognitive processing. Mu (MOR) and delta (DOR) opioid receptors functionally interact in vivo, but whether interactions occur at circuitry, cellular or molecular levels remains unsolved. To challenge the hypothesis of MOR/DOR heteromerization in the brain, we generated redMOR/greenDOR double knock-in mice and report dual recepto...

  10. Delay-correlation landscape reveals characteristic time delays of brain rhythms and heart interactions.

    Science.gov (United States)

    Lin, Aijing; Liu, Kang K L; Bartsch, Ronny P; Ivanov, Plamen Ch

    2016-05-13

    Within the framework of 'Network Physiology', we ask a fundamental question of how modulations in cardiac dynamics emerge from networked brain-heart interactions. We propose a generalized time-delay approach to identify and quantify dynamical interactions between physiologically relevant brain rhythms and the heart rate. We perform empirical analysis of synchronized continuous EEG and ECG recordings from 34 healthy subjects during night-time sleep. For each pair of brain rhythm and heart interaction, we construct a delay-correlation landscape (DCL) that characterizes how individual brain rhythms are coupled to the heart rate, and how modulations in brain and cardiac dynamics are coordinated in time. We uncover characteristic time delays and an ensemble of specific profiles for the probability distribution of time delays that underly brain-heart interactions. These profiles are consistently observed in all subjects, indicating a universal pattern. Tracking the evolution of DCL across different sleep stages, we find that the ensemble of time-delay profiles changes from one physiologic state to another, indicating a strong association with physiologic state and function. The reported observations provide new insights on neurophysiological regulation of cardiac dynamics, with potential for broad clinical applications. The presented approach allows one to simultaneously capture key elements of dynamic interactions, including characteristic time delays and their time evolution, and can be applied to a range of coupled dynamical systems. PMID:27044991

  11. 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.

  12. 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.

  13. Delay-correlation landscape reveals characteristic time delays of brain rhythms and heart interactions.

    Science.gov (United States)

    Lin, Aijing; Liu, Kang K L; Bartsch, Ronny P; Ivanov, Plamen Ch

    2016-05-13

    Within the framework of 'Network Physiology', we ask a fundamental question of how modulations in cardiac dynamics emerge from networked brain-heart interactions. We propose a generalized time-delay approach to identify and quantify dynamical interactions between physiologically relevant brain rhythms and the heart rate. We perform empirical analysis of synchronized continuous EEG and ECG recordings from 34 healthy subjects during night-time sleep. For each pair of brain rhythm and heart interaction, we construct a delay-correlation landscape (DCL) that characterizes how individual brain rhythms are coupled to the heart rate, and how modulations in brain and cardiac dynamics are coordinated in time. We uncover characteristic time delays and an ensemble of specific profiles for the probability distribution of time delays that underly brain-heart interactions. These profiles are consistently observed in all subjects, indicating a universal pattern. Tracking the evolution of DCL across different sleep stages, we find that the ensemble of time-delay profiles changes from one physiologic state to another, indicating a strong association with physiologic state and function. The reported observations provide new insights on neurophysiological regulation of cardiac dynamics, with potential for broad clinical applications. The presented approach allows one to simultaneously capture key elements of dynamic interactions, including characteristic time delays and their time evolution, and can be applied to a range of coupled dynamical systems.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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. 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.

  17. 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.

  18. Separation methods that are capable of revealing blood-brain barrier permeability.

    Science.gov (United States)

    Dash, Alekha K; Elmquist, William F

    2003-11-25

    The objective of this review is to emphasize the application of separation science in evaluating the blood-brain barrier (BBB) permeability to drugs and bioactive agents. Several techniques have been utilized to quantitate the BBB permeability. These methods can be classified into two major categories: in vitro or in vivo. The in vivo methods used include brain homogenization, cerebrospinal fluid (CSF) sampling, voltametry, autoradiography, nuclear magnetic resonance (NMR) spectroscopy, positron emission tomography (PET), intracerebral microdialysis, and brain uptake index (BUI) determination. The in vitro methods include tissue culture and immobilized artificial membrane (IAM) technology. Separation methods have always played an important role as adjunct methods to the methods outlined above for the quantitation of BBB permeability and have been utilized the most with brain homogenization, in situ brain perfusion, CSF sampling, intracerebral microdialysis, in vitro tissue culture and IAM chromatography. However, the literature published to date indicates that the separation method has been used the most in conjunction with intracerebral microdialysis and CSF sampling methods. The major advantages of microdialysis sampling in BBB permeability studies is the possibility of online separation and quantitation as well as the need for only a small sample volume for such an analysis. Separation methods are preferred over non-separation methods in BBB permeability evaluation for two main reasons. First, when the selectivity of a determination method is insufficient, interfering substances must be separated from the analyte of interest prior to determination. Secondly, when large number of analytes is to be detected and quantitated by a single analytical procedure, the mixture must be separated to each individual component prior to determination. Chiral separation in particular can be essential to evaluate the stereo-selective permeation and distribution of agents into the

  19. Separation methods that are capable of revealing blood-brain barrier permeability.

    Science.gov (United States)

    Dash, Alekha K; Elmquist, William F

    2003-11-25

    The objective of this review is to emphasize the application of separation science in evaluating the blood-brain barrier (BBB) permeability to drugs and bioactive agents. Several techniques have been utilized to quantitate the BBB permeability. These methods can be classified into two major categories: in vitro or in vivo. The in vivo methods used include brain homogenization, cerebrospinal fluid (CSF) sampling, voltametry, autoradiography, nuclear magnetic resonance (NMR) spectroscopy, positron emission tomography (PET), intracerebral microdialysis, and brain uptake index (BUI) determination. The in vitro methods include tissue culture and immobilized artificial membrane (IAM) technology. Separation methods have always played an important role as adjunct methods to the methods outlined above for the quantitation of BBB permeability and have been utilized the most with brain homogenization, in situ brain perfusion, CSF sampling, intracerebral microdialysis, in vitro tissue culture and IAM chromatography. However, the literature published to date indicates that the separation method has been used the most in conjunction with intracerebral microdialysis and CSF sampling methods. The major advantages of microdialysis sampling in BBB permeability studies is the possibility of online separation and quantitation as well as the need for only a small sample volume for such an analysis. Separation methods are preferred over non-separation methods in BBB permeability evaluation for two main reasons. First, when the selectivity of a determination method is insufficient, interfering substances must be separated from the analyte of interest prior to determination. Secondly, when large number of analytes is to be detected and quantitated by a single analytical procedure, the mixture must be separated to each individual component prior to determination. Chiral separation in particular can be essential to evaluate the stereo-selective permeation and distribution of agents into the

  20. Seeing Things That are Not There: Illusions Reveal How Our Brain Constructs What We See

    OpenAIRE

    Herrmann, Christoph S.; Murray, Micah M

    2013-01-01

    What we perceive is not always what our eyes see. Vision, and perception more generally, should not be thought of as a webcam that just takes pictures of the world. This is not a fault in how our brains work, but rather is exemplary of how the brain constructs perception and takes advantage of its massive inter-connectedness in ways that are highly similar to social networks. The construction of perception is not only based on the information the eyes capture, but also based on the informatio...

  1. 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.)

  2. 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…

  3. Event-Related Brain Potentials Reveal Anomalies in Temporal Processing of Faces in Autism Spectrum Disorder

    Science.gov (United States)

    McPartland, James; Dawson, Geraldine; Webb, Sara J.; Panagiotides, Heracles; Carver, Leslie J.

    2004-01-01

    Background: Individuals with autism exhibit impairments in face recognition, and neuroimaging studies have shown that individuals with autism exhibit abnormal patterns of brain activity during face processing. The current study examined the temporal characteristics of face processing in autism and their relation to behavior. Method: High-density…

  4. 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.

  5. 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

  6. Differential brain activity states during the perception and nonperception of illusory motion as revealed by magnetoencephalography

    OpenAIRE

    Crowe, David A.; Leuthold, Arthur C.; Georgopoulos, Apostolos P.

    2010-01-01

    We studied visual perception using an annular random-dot motion stimulus called the racetrack. We recorded neural activity using magnetoencephalography while subjects viewed variants of this stimulus that contained no inherent motion or various degrees of embedded motion. Subjects reported seeing rotary motion during viewing of all stimuli. We found that, in the absence of any motion signals, patterns of brain activity differed between states of motion perception and nonperception. Furthermor...

  7. Cell proliferation in the Drosophila adult brain revealed by clonal analysis and bromodeoxyuridine labelling

    OpenAIRE

    Brand Andrea H; Egger Boris; von Trotha Jakob W

    2009-01-01

    Abstract Background The production of new neurons during adulthood and their subsequent integration into a mature central nervous system have been shown to occur in all vertebrate species examined to date. However, the situation in insects is less clear and, in particular, it has been reported that there is no proliferation in the Drosophila adult brain. Results We report here, using clonal analysis and 5'-bromo-2'-deoxyuridine (BrdU) labelling, that cell proliferation does occur in the Droso...

  8. Diffusion tensor imaging of dolphin brains reveals direct auditory pathway to temporal lobe

    OpenAIRE

    Berns, Gregory S.; Cook, Peter F.; Foxley, Sean; Jbabdi, Saad; Miller, Karla L.; Marino, Lori

    2015-01-01

    The brains of odontocetes (toothed whales) look grossly different from their terrestrial relatives. Because of their adaptation to the aquatic environment and their reliance on echolocation, the odontocetes' auditory system is both unique and crucial to their survival. Yet, scant data exist about the functional organization of the cetacean auditory system. A predominant hypothesis is that the primary auditory cortex lies in the suprasylvian gyrus along the vertex of the hemispheres, with this...

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

    OpenAIRE

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

    2014-01-01

    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 learn...

  10. 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.

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

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    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.

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

    Science.gov (United States)

    Rayhan, Rakib U; Stevens, Benson W; Raksit, Megna P; Ripple, Joshua A; Timbol, Christian R; Adewuyi, Oluwatoyin; VanMeter, John W; Baraniuk, James N

    2013-01-01

    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.

  13. Statistical language learning in neonates revealed by event-related brain potentials

    Directory of Open Access Journals (Sweden)

    Näätänen Risto

    2009-03-01

    Full Text Available Abstract Background Statistical learning is a candidate for one of the basic prerequisites underlying the expeditious acquisition of spoken language. Infants from 8 months of age exhibit this form of learning to segment fluent speech into distinct words. To test the statistical learning skills at birth, we recorded event-related brain responses of sleeping neonates while they were listening to a stream of syllables containing statistical cues to word boundaries. Results We found evidence that sleeping neonates are able to automatically extract statistical properties of the speech input and thus detect the word boundaries in a continuous stream of syllables containing no morphological cues. Syllable-specific event-related brain responses found in two separate studies demonstrated that the neonatal brain treated the syllables differently according to their position within pseudowords. Conclusion These results demonstrate that neonates can efficiently learn transitional probabilities or frequencies of co-occurrence between different syllables, enabling them to detect word boundaries and in this way isolate single words out of fluent natural speech. The ability to adopt statistical structures from speech may play a fundamental role as one of the earliest prerequisites of language acquisition.

  14. Large-scale brain network abnormalities in Huntington's disease revealed by structural covariance.

    Science.gov (United States)

    Minkova, Lora; Eickhoff, Simon B; Abdulkadir, Ahmed; Kaller, Christoph P; Peter, Jessica; Scheller, Elisa; Lahr, Jacob; Roos, Raymund A; Durr, Alexandra; Leavitt, Blair R; Tabrizi, Sarah J; Klöppel, Stefan

    2016-01-01

    Huntington's disease (HD) is a progressive neurodegenerative disorder that can be diagnosed with certainty decades before symptom onset. Studies using structural MRI have identified grey matter (GM) loss predominantly in the striatum, but also involving various cortical areas. So far, voxel-based morphometric studies have examined each brain region in isolation and are thus unable to assess the changes in the interrelation of brain regions. Here, we examined the structural covariance in GM volumes in pre-specified motor, working memory, cognitive flexibility, and social-affective networks in 99 patients with manifest HD (mHD), 106 presymptomatic gene mutation carriers (pre-HD), and 108 healthy controls (HC). After correction for global differences in brain volume, we found that increased GM volume in one region was associated with increased GM volume in another. When statistically comparing the groups, no differences between HC and pre-HD were observed, but increased positive correlations were evident for mHD, relative to pre-HD and HC. These findings could be explained by a HD-related neuronal loss heterogeneously affecting the examined network at the pre-HD stage, which starts to dominate structural covariance globally at the manifest stage. Follow-up analyses identified structural connections between frontoparietal motor regions to be linearly modified by disease burden score (DBS). Moderator effects of disease load burden became significant at a DBS level typically associated with the onset of unequivocal HD motor signs. Together with existing findings from functional connectivity analyses, our data indicates a critical role of these frontoparietal regions for the onset of HD motor signs.

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

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    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.

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

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    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.

  17. Boomerang returns unexpectedly

    CERN Document Server

    White, M; Pierpaoli, E; White, Martin; Scott, Douglas; Pierpaol, Elena

    2000-01-01

    Experimental study of the anisotropy in the cosmic microwave background (CMB) is gathering momentum. The eagerly awaited Boomerang results have lived up to expectations. They provide convincing evidence in favor of the standard paradigm: the Universe is close to flat and with primordial fluctuations which are redolent of inflation. Further scrutiny reveals something even more exciting however -- two hints that there may be some unforeseen physical effects. Firstly the primary acoustic peak appears at slightly larger scales than expected. Although this may be explicable through a combination of mundane effects, we suggest it is also prudent to consider the possibility that the Universe might be marginally closed. The other hint is provided by a second peak which appears less prominent than expected. This may indicate one of a number of possibilities, including increased damping length or tilted initial conditions, but also breaking of coherence or features in the initial power spectrum. Further data should tes...

  18. 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.

  19. Gene Regulatory Network Analysis Reveals Differences in Site-specific Cell Fate Determination in Mammalian Brain

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    Gokhan eErtaylan

    2014-12-01

    Full Text Available Neurogenesis - the generation of new neurons - is an ongoing process that persists in the adult mammalian brain of several species, including humans. In this work we analyze two discrete brain regions: the subventricular zone (SVZ lining the walls of the lateral ventricles; and the subgranular zone (SGZ of the dentate gyrus of the hippocampus in mice and shed light on the SVZ and SGZ specific neurogenesis. We propose a computational model that relies on the construction and analysis of region specific gene regulatory networks from the publicly available data on these two regions. Using this model a number of putative factors involved in neuronal stem cell (NSC identity and maintenance were identified. We also demonstrate potential gender and niche-derived differences based on cell surface and nuclear receptors via Ar, Hif1a and Nr3c1.We have also conducted cell fate determinant analysis for SVZ NSC populations to Olfactory Bulb interneurons and SGZ NSC populations to the granule cells of the Granular Cell Layer. We report thirty-one candidate cell fate determinant gene pairs, ready to be validated. We focus on Ar - Pax6 in SVZ and Sox2 - Ncor1 in SGZ. Both pairs are expressed and localized in the suggested anatomical structures as shown by in situ hybridization and found to physically interact.Finally, we conclude that there are fundamental differences between SGZ and SVZ neurogenesis. We argue that these regulatory mechanisms are linked to the observed differential neurogenic potential of these regions. The presence of nuclear and cell surface receptors in the region specific regulatory circuits indicate the significance of niche derived extracellular factors, hormones and region specific factors such as the oxygen sensitivity, dictating SGZ and SVZ specific neurogenesis.

  20. Diffusion tensor imaging of dolphin brains reveals direct auditory pathway to temporal lobe.

    Science.gov (United States)

    Berns, Gregory S; Cook, Peter F; Foxley, Sean; Jbabdi, Saad; Miller, Karla L; Marino, Lori

    2015-07-22

    The brains of odontocetes (toothed whales) look grossly different from their terrestrial relatives. Because of their adaptation to the aquatic environment and their reliance on echolocation, the odontocetes' auditory system is both unique and crucial to their survival. Yet, scant data exist about the functional organization of the cetacean auditory system. A predominant hypothesis is that the primary auditory cortex lies in the suprasylvian gyrus along the vertex of the hemispheres, with this position induced by expansion of 'associative' regions in lateral and caudal directions. However, the precise location of the auditory cortex and its connections are still unknown. Here, we used a novel diffusion tensor imaging (DTI) sequence in archival post-mortem brains of a common dolphin (Delphinus delphis) and a pantropical dolphin (Stenella attenuata) to map their sensory and motor systems. Using thalamic parcellation based on traditionally defined regions for the primary visual (V1) and auditory cortex (A1), we found distinct regions of the thalamus connected to V1 and A1. But in addition to suprasylvian-A1, we report here, for the first time, the auditory cortex also exists in the temporal lobe, in a region near cetacean-A2 and possibly analogous to the primary auditory cortex in related terrestrial mammals (Artiodactyla). Using probabilistic tract tracing, we found a direct pathway from the inferior colliculus to the medial geniculate nucleus to the temporal lobe near the sylvian fissure. Our results demonstrate the feasibility of post-mortem DTI in archival specimens to answer basic questions in comparative neurobiology in a way that has not previously been possible and shows a link between the cetacean auditory system and those of terrestrial mammals. Given that fresh cetacean specimens are relatively rare, the ability to measure connectivity in archival specimens opens up a plethora of possibilities for investigating neuroanatomy in cetaceans and other species

  1. Boomerang Returns Unexpectedly

    Science.gov (United States)

    White, Martin; Scott, Douglas; Pierpaoli, Elena

    2000-12-01

    Experimental study of the anisotropy in the cosmic microwave background (CMB) is gathering momentum. The eagerly awaited Boomerang results have lived up to expectations. They provide convincing evidence in favor of the standard paradigm: the universe is close to flat and with primordial fluctuations that are redolent of inflation. Further scrutiny reveals something even more exciting, however-two hints that there may be some unforeseen physical effects. First, the primary acoustic peak appears at slightly larger scales than expected. Although this may be explicable through a combination of mundane effects, we suggest that it is also prudent to consider the possibility that the universe might be marginally closed. The other hint is provided by a second peak, which appears less prominent than expected. This may indicate one of a number of possibilities, including increased damping length or tilted initial conditions, but also breaking of coherence or features in the initial power spectrum. Further data should test whether the current concordance model needs only to be tweaked, or to be enhanced in some fundamental way. A paper about a boomerang by an Australian and his mates.

  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. Quantitative Proteomics of Sleep-Deprived Mouse Brains Reveals Global Changes in Mitochondrial Proteins

    Science.gov (United States)

    Li, Tie-Mei; Zhang, Ju-en; Lin, Rui; Chen, She; Luo, Minmin; Dong, Meng-Qiu

    2016-01-01

    Sleep is a ubiquitous, tightly regulated, and evolutionarily conserved behavior observed in almost all animals. Prolonged sleep deprivation can be fatal, indicating that sleep is a physiological necessity. However, little is known about its core function. To gain insight into this mystery, we used advanced quantitative proteomics technology to survey the global changes in brain protein abundance. Aiming to gain a comprehensive profile, our proteomics workflow included filter-aided sample preparation (FASP), which increased the coverage of membrane proteins; tandem mass tag (TMT) labeling, for relative quantitation; and high resolution, high mass accuracy, high throughput mass spectrometry (MS). In total, we obtained the relative abundance ratios of 9888 proteins encoded by 6070 genes. Interestingly, we observed significant enrichment for mitochondrial proteins among the differentially expressed proteins. This finding suggests that sleep deprivation strongly affects signaling pathways that govern either energy metabolism or responses to mitochondrial stress. Additionally, the differentially-expressed proteins are enriched in pathways implicated in age-dependent neurodegenerative diseases, including Parkinson’s, Huntington’s, and Alzheimer’s, hinting at possible connections between sleep loss, mitochondrial stress, and neurodegeneration. PMID:27684481

  4. The neural bases for devaluing radical political statements revealed by penetrating traumatic brain injury.

    Science.gov (United States)

    Cristofori, Irene; Viola, Vanda; Chau, Aileen; Zhong, Wanting; Krueger, Frank; Zamboni, Giovanna; Grafman, Jordan

    2015-08-01

    Given the determinant role of ventromedial prefrontal cortex (vmPFC) in valuation, we examined whether vmPFC lesions also modulate how people scale political beliefs. Patients with penetrating traumatic brain injury (pTBI; N = 102) and healthy controls (HCs; N = 31) were tested on the political belief task, where they rated 75 statements expressing political opinions concerned with welfare, economy, political involvement, civil rights, war and security. Each statement was rated for level of agreement and scaled along three dimensions: radicalism, individualism and conservatism. Voxel-based lesion-symptom mapping (VLSM) analysis showed that diminished scores for the radicalism dimension (i.e. statements were rated as less radical than the norms) were associated with lesions in bilateral vmPFC. After dividing the pTBI patients into three groups, according to lesion location (i.e. vmPFC, dorsolateral prefrontal cortex [dlPFC] and parietal cortex), we found that the vmPFC, but not the dlPFC, group had reduced radicalism scores compared with parietal and HC groups. These findings highlight the crucial role of the vmPFC in appropriately valuing political behaviors and may explain certain inappropriate social judgments observed in patients with vmPFC lesions.

  5. Tantalizing Thanatos: unexpected links in death pathways.

    Science.gov (United States)

    Cohen, Isabelle; Castedo, Maria; Kroemer, Guido

    2002-07-01

    Cell death is most frequently the result of apoptosis, an event that is often controlled by mitochondrial membrane permeabilization (MMP). Recent data reveal unexpected functional links between apoptosis and autophagic cell death, in the sense that MMP can trigger autophagy of damaged mitochondria. Conversely, one of the major signal-transducing molecules involved in the activation of autophagy during apoptosis--the so-called DAP kinase--can induce cell death through MMP. Connections are also emerging between apoptosis, autophagy, replicative senescence and cancer-specific metabolic changes. PMID:12185842

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

    Directory of Open Access Journals (Sweden)

    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

  7. Whole brain resting-state analysis reveals decreased functional connectivity in major depression

    Directory of Open Access Journals (Sweden)

    Ilya M. Veer

    2010-09-01

    Full Text Available Recently, both increases and decreases in resting-state functional connectivity have been found in major depression. However, these studies only assessed functional connectivity within a specific network or between a few regions of interest, while comorbidity and use of medication was not always controlled for. Therefore, the aim of the current study was to investigate whole-brain functional connectivity, unbiased by a priori definition of regions or networks of interest, in medication-free depressive patients without comorbidity. We analyzed resting-state fMRI data of 19 medication-free patients with a recent diagnosis of major depression (within six months before inclusion and no comorbidity, and 19 age- and gender-matched controls. Independent component analysis was employed on the concatenated data sets of all participants. Thirteen functionally relevant networks were identified, describing the entire study sample. Next, individual representations of the networks were created using a dual regression method. Statistical inference was subsequently done on these spatial maps using voxelwise permutation tests. Abnormal functional connectivity was found within three resting-state networks in depression: 1 decreased bilateral amygdala and left anterior insula connectivity in an affective network, 2 reduced connectivity of the left frontal pole in a network associated with attention and working memory, and 3 decreased bilateral lingual gyrus connectivity within ventromedial visual regions. None of these effects were associated with symptom severity or grey matter density. We found abnormal resting-state functional connectivity not previously associated with major depression, which might relate to abnormal affect regulation and mild cognitive deficits, both associated with the symptomatology of the disorder.

  8. 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. PMID:24110810

  9. 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

  10. Training to handle unexpected events

    International Nuclear Information System (INIS)

    The importance of conducting hands-on training to deal with complex situations is well recognized. Since most utilities now own or have ordered their own control room simulators, access to simulator training facilities has improved greatly. Most utilities now have a control room shift rotation that includes a dedicated training shift. The opportunities for practicing operational control over unexpected and off-normal events are just beginning to be recognized. Areas that are being enhanced include teamwork training, diagnostics training, expanded simulator training programs, improvements in simulator instructor training, emergency procedures training, and training on the use of probabilistic risk assessment studies. All these efforts are aimed at the goal of improving the plant staff's ability to cope with unexpected and off-normal events

  11. 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.

  12. Transcriptomic gene-network analysis of exposure to silver nanoparticle reveals potentially neurodegenerative progression in mouse brain neural cells.

    Science.gov (United States)

    Lin, Ho-Chen; Huang, Chin-Lin; Huang, Yuh-Jeen; Hsiao, I-Lun; Yang, Chung-Wei; Chuang, Chun-Yu

    2016-08-01

    Silver nanoparticles (AgNPs) are commonly used in daily living products. AgNPs can induce inflammatory response in neuronal cells, and potentially develop neurological disorders. The gene networks in response to AgNPs-induced neurodegenerative progression have not been clarified in various brain neural cells. This study found that 3-5nm AgNPs were detectable to enter the nuclei of mouse neuronal cells after 24-h of exposure. The differentially expressed genes in mouse brain neural cells exposure to AgNPs were further identified using Phalanx Mouse OneArray® chip, and permitted to explore the gene network pathway regulating in neurodegenerative progression according to Cytoscape analysis. In focal adhesion pathway of ALT astrocytes, AgNPs induced the gene expression of RasGRF1 and reduced its downstream BCL2 gene for apoptosis. In cytosolic DNA sensing pathway of microglial BV2 cells, AgNPs reduced the gene expression of TREX1 and decreased IRF7 to release pro-inflammatory cytokines for inflammation and cellular activation. In MAPK pathway of neuronal N2a cells, AgNPs elevated GADD45α gene expression, and attenuated its downstream PTPRR gene to interfere with neuron growth and differentiation. Moreover, AgNPs induced beta amyloid deposition in N2a cells, and decreased PSEN1 and PSEN2, which may disrupt calcium homeostasis and presynaptic dysfunction for Alzheimer's disease development. These findings suggested that AgNPs exposure reveals the potency to induce the progression of neurodegenerative disorder. PMID:27131904

  13. Unexpected bismuth concentration profiles in metal-organic vapor phase epitaxy-grown Ga(As1−xBix/GaAs superlattices revealed by Z-contrast scanning transmission electron microscopy imaging

    Directory of Open Access Journals (Sweden)

    A. W. Wood

    2015-03-01

    Full Text Available A set of GaAs1−xBix/GaAs multilayer quantum-well structures was deposited by metal-organic vapor phase epitaxy at 390 °C and 420 °C. The precursor fluxes were introduced with the intent of growing discrete and compositionally uniform GaAs1−xBix well and GaAs barrier layers in the epitaxial films. High-resolution high-angle annular-dark-field (or “Z-contrast” scanning transmission electron microscopy imaging revealed concentration profiles that were periodic in the growth direction, but far more complicated in shape than the intended square wave. The observed composition profiles could explain various reports of physical properties measurements that suggest compositional inhomogeneity in GaAs1−xBix alloys as they currently are grown.

  14. 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. PMID:25752905

  15. Three-dimensional brain atlas of pygmy squid, Idiosepius paradoxus, revealing the largest relative vertical lobe system volume among the cephalopods.

    Science.gov (United States)

    Koizumi, Motoki; Shigeno, Shuichi; Mizunami, Makoto; Tanaka, Nobuaki K

    2016-07-01

    Cephalopods have the largest and most complex nervous system of all invertebrates, and the brain-to-body weight ratio exceeds those of most fish and reptiles. The brain is composed of lobe units, the functions of which have been studied through surgical manipulation and electrical stimulation. However, how information is processed in each lobe for the animal to make a behavioral decision has rarely been investigated. To perform such functional analyses, it is necessary to precisely describe how brain lobes are spatially organized and mutually interconnected as a whole. We thus made three-dimensional digital brain atlases of both hatchling and juvenile pygmy squid, Idiosepius paradoxus. I. paradoxus is the smallest squid and has a brain small enough to scan as a whole region in the field-of-view of a low-magnification laser scan microscope objective. Precise analyses of the confocal images of the brains revealed one newly identified lobe and also that the relative volume of the vertical lobe system, the higher association center, in the pygmy squid represents the largest portion compared with the cephalopod species reported previously. In addition, principal component analyses of relative volumes of lobe complexes revealed that the organization of I. paradoxus brain is comparable to those of Decapodiformes species commonly used to analyze complex behaviors such as Sepia officinalis and Sepioteuthis sepioidea. These results suggest that the pygmy squid can be a good model to investigate the brain functions of coleoids utilizing physiological methods. J. Comp. Neurol. 524:2142-2157, 2016. © 2016 Wiley Periodicals, Inc. PMID:26663197

  16. Lazarillo expression reveals a subset of neurons contributing to the primary axon scaffold of the embryonic brain of the grasshopper Schistocerca gregaria.

    Science.gov (United States)

    Graf, S; Ludwig, P; Boyan, G

    2000-04-10

    The authors studied the contribution of seven clusters of Lazarillo-expressing cells to the primary axon scaffold of the brain in the grasshopper Schistocerca gregaria from 26% to 43% of embryogenesis. Each cluster, which was numbered according to when Lazarillo expression first appeared, was uniquely identifiable on the basis of its stereotypic position in the brain and the number of Lazarillo-expressing cells it contained. At no time during embryogenesis was Lazarillo expression found in brain neuroblasts: It was found only in progeny. For ease of analysis, axogenesis was followed in a cell cluster that contained only a single Lazarillo-expressing cell (the lateral cell) in the dorsal median domain of the brain midline. Bromodeoxyuridine incorporation revealed the presence of only a single midline precursor cell in this region during embryogenesis. Intracellular injection of Lucifer yellow into the lateral cell at various ages showed that there was no dye coupling to the midline precursor or to the nearby term-1-expressing primary commissure pioneers. The lateral cell is not related lineally to these cells and most likely differentiates directly from the neuroectoderm of the brain midline. Lazarillo expression appears at the onset of axogenesis as the lateral cell projects an axon laterally toward the next Lazarillo-expressing cell cluster. The cells of this target cluster direct axons into separate brain regions, thereby establishing an orthogonally organized scaffold that the lateral cell axon follows as it navigates away from the brain midline. The primary axon scaffold of the brain results from a stepwise interlinking of discrete brain regions, as exemplified by axons from neighboring Lazarillo-expressing cell clusters.

  17. Are rogue waves really unexpected?

    CERN Document Server

    Fedele, Francesco

    2015-01-01

    We present a third-order nonlinear model for the statistics of unexpected waves drawing on the work of Gemmrich & Garrett (2008). The model is verified by way of Monte Carlo simulations of Gaussian seas and comparisons to oceanic measurements. In particular, the analysis of oceanic data suggests that both skewness and kurtosis effects must be accounted for to obtain accurate predictions. As a specific application, the unexpectedness of the Andrea and WACSIS rogue wave events is examined in detail. Observations indicate that the crests of these waves have nearly the same amplitude ratio $h/H_s\\sim1.6$, where $H_s$ is the significant wave height. Both waves appeared without warning and they were nearly two-times larger than the surrounding $O(10)$ waves, and thus unexpected. The model developed here predicts that the two rogue waves are stochastically similar as they occur on average once every $10^{4}$ waves. Further, the maximum crest height actually observed is nearly the same as the threshold $h_{10^{6}...

  18. 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…

  19. 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.

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

    International Nuclear Information System (INIS)

    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)

  1. 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

  2. The arborization pattern of engrailed-positive neural lineages reveal neuromere boundaries in the Drosophila brain neuropile

    Science.gov (United States)

    Kumar, Abhilasha; Fung, S.; Lichtneckert, Robert; Reichert, Heinrich; Hartenstein, Volker

    2010-01-01

    The Drosophila brain is a highly complex structure composed of thousands of neurons that are interconnected in numerous exquisitely organized neuropile structures such as the mushroom bodies, central complex, antennal lobes, and other specialized neuropiles. While the neurons of the insect brain are known to derive in a lineage-specific fashion from a stereotyped set of segmentally organized neuroblasts, the developmental origin and neuromeric organization of the neuropile formed by these neurons is still unclear. In this report, we use genetic labeling techniques to characterize the neuropile innervation pattern of engrailed-expressing brain lineages of known neuromeric origin. We show that the neurons of these lineages project to and form most arborizations, in particular all of their proximal branches, in the same brain neuropile compartments in embryonic, larval and adult stages. Moreover, we show that engrailed-positive neurons of differing neuromeric origin respect boundaries between neuromere-specific compartments in the brain. This is confirmed by an analysis of the arborization pattern of empty spiracles-expressing lineages. These findings indicate that arborizations of lineages deriving from different brain neuromeres innervate a non-overlapping set of neuropile compartments. This supports a model for neuromere-specific brain neuropile, in which a given lineage forms its proximal arborizations predominantly in the compartments that correspond to its neuromere of origin. PMID:19711412

  3. Noninvasive monitoring of treatment response in a rabbit cyanide toxicity model reveals differences in brain and muscle metabolism

    Science.gov (United States)

    Kim, Jae G.; Lee, Jangwoen; Mahon, Sari B.; Mukai, David; Patterson, Steven E.; Boss, Gerry R.; Tromberg, Bruce J.; Brenner, Matthew

    2012-10-01

    Noninvasive near infrared spectroscopy measurements were performed to monitor cyanide (CN) poisoning and recovery in the brain region and in foreleg muscle simultaneously, and the effects of a novel CN antidote, sulfanegen sodium, on tissue hemoglobin oxygenation changes were compared using a sub-lethal rabbit model. The results demonstrated that the brain region is more susceptible to CN poisoning and slower in endogenous CN detoxification following exposure than peripheral muscles. However, sulfanegen sodium rapidly reversed CN toxicity, with brain region effects reversing more quickly than muscle. In vivo monitoring of multiple organs may provide important clinical information regarding the extent of CN toxicity and subsequent recovery, and facilitate antidote drug development.

  4. 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 a...

  5. Natural Minor Scale is More Natural to the Brain than Harmonic Minor Scale as Revealed by Magnetoencephalography

    Science.gov (United States)

    Ando, Hiromitsu; Nemoto, Iku; Oda, Shoichiro

    Minor mode is known to elicit stronger emotional responses than major mode in the brain. The present work focused on the minor scales and natural and harmonic minor scales were compared in automatic brain responses in an oddball paradigm. The standard stimulus was either the natural or harmonic minor scale, and a deviant stimulus lacked one scale tone of the corresponding complete minor scale. The brain responded to omission of every tone but omission of the tone B flat in the natural minor experiment elicited larger response than that of the other tones. In particular, the response was significantly larger than that to omission of B in the harmonic minor experiment. This result suggested that the brain felt the natural minor scale to be actually more natural than the harmonic minor scale.

  6. The arborization pattern of engrailed-positive neural lineages reveal neuromere boundaries in the Drosophila brain neuropile

    OpenAIRE

    Kumar, Abhilasha; S Fung; Lichtneckert, Robert; Reichert, Heinrich; Hartenstein, Volker

    2009-01-01

    The Drosophila brain is a highly complex structure composed of thousands of neurons that are interconnected in numerous exquisitely organized neuropile structures such as the mushroom bodies, central complex, antennal lobes, and other specialized neuropiles. While the neurons of the insect brain are known to derive in a lineage-specific fashion from a stereotyped set of segmentally organized neuroblasts, the developmental origin and neuromeric organization of the neuropile formed by these neu...

  7. Abnormalities in the brain of streptozotocin-induced type 1 diabetic rats revealed by diffusion tensor imaging ☆

    OpenAIRE

    Huang, Mingming; Gao, Lifeng; Yang, Liqin; Lin, Fuchun; Lei, Hao

    2012-01-01

    Diabetes mellitus affects the brain. Both type 1 and type 2 diabetic patients are associated with white matter (WM) damage observable to diffusion tensor imaging (DTI). The underlying histopathological mechanisms, however, are poorly understood. The objectives of this study are 1) to determine whether streptozotocin (STZ)-induced type 1 diabetes is associated with WM damage observable to DTI; and 2) to understand the pathophysiological aspects underlying STZ-induced brain injuries. Male Sprag...

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

    OpenAIRE

    Juha Marko Lahnakoski; Enrico eGlerean; Juha eSalmi; Jääskeläinen, Iiro P.; Mikko eSams; Riitta eHari; Lauri eNummenmaa

    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-selecte...

  9. Whole-brain, time-locked activation with simple tasks revealed using massive averaging and model-free analysis

    Science.gov (United States)

    Gonzalez-Castillo, Javier; Saad, Ziad S.; Handwerker, Daniel A.; Inati, Souheil J.; Brenowitz, Noah; Bandettini, Peter A.

    2012-01-01

    The brain is the body's largest energy consumer, even in the absence of demanding tasks. Electrophysiologists report on-going neuronal firing during stimulation or task in regions beyond those of primary relationship to the perturbation. Although the biological origin of consciousness remains elusive, it is argued that it emerges from complex, continuous whole-brain neuronal collaboration. Despite converging evidence suggesting the whole brain is continuously working and adapting to anticipate and actuate in response to the environment, over the last 20 y, task-based functional MRI (fMRI) have emphasized a localizationist view of brain function, with fMRI showing only a handful of activated regions in response to task/stimulation. Here, we challenge that view with evidence that under optimal noise conditions, fMRI activations extend well beyond areas of primary relationship to the task; and blood-oxygen level-dependent signal changes correlated with task-timing appear in over 95% of the brain for a simple visual stimulation plus attention control task. Moreover, we show that response shape varies substantially across regions, and that whole-brain parcellations based on those differences produce distributed clusters that are anatomically and functionally meaningful, symmetrical across hemispheres, and reproducible across subjects. These findings highlight the exquisite detail lying in fMRI signals beyond what is normally examined, and emphasize both the pervasiveness of false negatives, and how the sparseness of fMRI maps is not a result of localized brain function, but a consequence of high noise and overly strict predictive response models. PMID:22431587

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

    Science.gov (United States)

    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.

    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 detect structural brain alterations in adolescents and young adults with ADHD compared with healthy controls. We examined whether these alterations were also found in their unaffected siblings, using a uniquely large sample. Methods We performed voxel-based morphometry analyses on MRI scans of patients with ADHD, their unaffected siblings and typically developing controls. We identified brain areas that differed between participants with ADHD and controls and investigated whether these areas were different in unaffected siblings. Influences of medication use, age, sex and IQ were considered. Results Our sample included 307 patients with ADHD, 169 unaffected siblings and 196 typically developing controls (mean age 17.2 [range 8–30] yr). Compared with controls, participants with ADHD had significantly smaller grey matter volume in 5 clusters located in the precentral gyrus, medial and orbitofrontal cortex, and (para)cingulate cortices. Unaffected siblings showed intermediate volumes significantly different from controls in 4 of these clusters (all except the precentral gyrus). Medication use, age, sex and IQ did not have an undue influence on the results. Limitations Our sample was heterogeneous, most participants with ADHD were taking medication, and the comparison was cross-sectional. Conclusion Brain areas involved in decision making, motivation, cognitive control and motor functioning were smaller in participants with ADHD than in controls. Investigation of unaffected siblings indicated familiality of 4 of the structural brain differences, supporting their potential in molecular genetic analyses in ADHD research. PMID:26679925

  11. Altering blood flow does not reveal differences between nitrogen and helium kinetics in brain or in skeletal miracle in sheep.

    Science.gov (United States)

    Doolette, David J; Upton, Richard N; Grant, Cliff

    2015-03-01

    In underwater diving, decompression schedules are based on compartmental models of nitrogen and helium tissue kinetics. However, these models are not based on direct measurements of nitrogen and helium kinetics. In isoflurane-anesthetized sheep, nitrogen and helium kinetics in the hind limb (n = 5) and brain (n = 5) were determined during helium-oxygen breathing and after return to nitrogen-oxygen breathing. Nitrogen and helium concentrations in arterial, femoral vein, and sagittal sinus blood samples were determined using headspace gas chromatography, and venous blood flows were monitored continuously using ultrasonic Doppler. The experiment was repeated at different states of hind limb blood flow and cerebral blood flow. Using arterial blood gas concentrations and blood flows as input, parameters and model selection criteria of various compartmental models of hind limb and brain were estimated by fitting to the observed venous gas concentrations. In both the hind limb and brain, nitrogen and helium kinetics were best fit by models with multiexponential kinetics. In the brain, there were no differences in nitrogen and helium kinetics. Hind limb models fit separately to the two gases indicated that nitrogen kinetics were slightly faster than helium, but models with the same kinetics for both gases fit the data well. In the hind limb and brain, the blood:tissue exchange of nitrogen is similar to that of helium. On the basis of these results, it is inappropriate to assign substantially different time constants for nitrogen and helium in all compartments in decompression algorithms. PMID:25525213

  12. 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...

  13. Brain-based decoding of mentally imagined film clips and sounds reveals experience-based information patterns in film professionals.

    Science.gov (United States)

    de Borst, Aline W; Valente, Giancarlo; Jääskeläinen, Iiro P; Tikka, Pia

    2016-04-01

    In the perceptual domain, it has been shown that the human brain is strongly shaped through experience, leading to expertise in highly-skilled professionals. What has remained unclear is whether specialization also shapes brain networks underlying mental imagery. In our fMRI study, we aimed to uncover modality-specific mental imagery specialization of film experts. Using multi-voxel pattern analysis we decoded from brain activity of professional cinematographers and sound designers whether they were imagining sounds or images of particular film clips. In each expert group distinct multi-voxel patterns, specific for the modality of their expertise, were found during classification of imagery modality. These patterns were mainly localized in the occipito-temporal and parietal cortex for cinematographers and in the auditory cortex for sound designers. We also found generalized patterns across perception and imagery that were distinct for the two expert groups: they involved frontal cortex for the cinematographers and temporal cortex for the sound designers. Notably, the mental representations of film clips and sounds of cinematographers contained information that went beyond modality-specificity. We were able to successfully decode the implicit presence of film genre from brain activity during mental imagery in cinematographers. The results extend existing neuroimaging literature on expertise into the domain of mental imagery and show that experience in visual versus auditory imagery can alter the representation of information in modality-specific association cortices.

  14. 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.

  15. 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...

  16. Functional magnetic resonance imaging reveals abnormal brain connectivity in EGR3 gene transfected rat model of schizophrenia.

    Science.gov (United States)

    Song, Tianbin; Nie, Binbin; Ma, Ensen; Che, Jing; Sun, Shilong; Wang, Yuli; Shan, Baoci; Liu, Yawu; Luo, Senlin; Ma, Guolin; Li, Kefeng

    2015-05-01

    Schizophrenia is characterized by the disorder of "social brain". However, the alternation of connectivity density in brain areas of schizophrenia patients remains largely unknown. In this study, we successfully created a rat model of schizophrenia by the transfection of EGR3 gene into rat brain. We then investigated the connectivity density of schizophrenia susceptible regions in rat brain using functional magnetic resonance imaging (fMRI) in combination with multivariate Granger causality (GC) model. We found that the average signal strength in prefrontal lobe and hippocampus of schizophrenia model group was significantly higher than the control group. Bidirectional Granger causality connection was observed between hippocampus and thalamic in schizophrenia model group. Both connectivity density and Granger causality connection were changed in prefrontal lobe, hippocampus and thalamus after risperidone treatment. Our results indicated that fMRI in combination with GC connection analysis may be used as an important method in diagnosis of schizophrenia and evaluation the effect of antipsychotic treatment. These findings support the connectivity disorder hypothesis of schizophrenia and increase our understanding of the neural mechanisms of schizophrenia.

  17. Relationship between brain network pattern and cognitive performance of children revealed by MEG signals during free viewing of video.

    Science.gov (United States)

    Duan, Fang; Watanabe, Katsumi; Yoshimura, Yuko; Kikuchi, Mitsuru; Minabe, Yoshio; Aihara, Kazuyuki

    2014-04-01

    Application of graph theory to analysis of functional networks in the brain is an important research trend. Extensive research on the resting state has shown a "small-world" organization of the brain network as a whole. However, the small-worldness of children's brain networks in a working state has not yet been well characterized. In this paper, we used a custom-made, child-sized magnetoencephalography (MEG) device to collect data from children while they were watching cartoon videos. Network structures were analyzed and compared with scores on the Kaufman Assessment Battery for Children (K-ABC). The results of network analysis showed that (1) the small-world scalar showed a negative correlation with the simultaneous processing raw score, a measure of visual processing (Gv) ability, and (2) the children with higher simultaneous processing raw scores possessed network structures that can be more efficient for local information processing than children with lower scores. These results were compatible with previous studies on the adult working state. Additional results obtained from further analysis of the frontal and occipital lobes indicated that high cognitive performance could represent better local efficiency in task-related sub-networks. Under free viewing of cartoon videos, brain networks were no longer confined to their strongest small-world states; connections became clustered in local areas such as the frontal and occipital lobes, which might be a more useful configuration for handling visual processing tasks.

  18. Connectivity reveals relationship of brain areas for reward-guided learning and decision making in human and monkey frontal cortex

    NARCIS (Netherlands)

    Neubert, F.X.; Mars, R.B.; Sallet, J.; Rushworth, M.F.S.

    2015-01-01

    Reward-guided decision-making depends on a network of brain regions. Among these are the orbitofrontal and the anterior cingulate cortex. However, it is difficult to ascertain if these areas constitute anatomical and functional unities, and how these areas correspond between monkeys and humans. To a

  19. 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.

  20. Effects of Perfluorooctanoic Acid on Metabolic Profiles in Brain and Liver of Mouse Revealed by a High-throughput Targeted Metabolomics Approach

    Science.gov (United States)

    Yu, Nanyang; Wei, Si; Li, Meiying; Yang, Jingping; Li, Kan; Jin, Ling; Xie, Yuwei; Giesy, John P.; Zhang, Xiaowei; Yu, Hongxia

    2016-04-01

    Perfluorooctanoic acid (PFOA), a perfluoroalkyl acid, can result in hepatotoxicity and neurobehavioral effects in animals. The metabolome, which serves as a connection among transcriptome, proteome and toxic effects, provides pathway-based insights into effects of PFOA. Since understanding of changes in the metabolic profile during hepatotoxicity and neurotoxicity were still incomplete, a high-throughput targeted metabolomics approach (278 metabolites) was used to investigate effects of exposure to PFOA for 28 d on brain and liver of male Balb/c mice. Results of multivariate statistical analysis indicated that PFOA caused alterations in metabolic pathways in exposed individuals. Pathway analysis suggested that PFOA affected metabolism of amino acids, lipids, carbohydrates and energetics. Ten and 18 metabolites were identified as potential unique biomarkers of exposure to PFOA in brain and liver, respectively. In brain, PFOA affected concentrations of neurotransmitters, including serotonin, dopamine, norepinephrine, and glutamate in brain, which provides novel insights into mechanisms of PFOA-induced neurobehavioral effects. In liver, profiles of lipids revealed involvement of β-oxidation and biosynthesis of saturated and unsaturated fatty acids in PFOA-induced hepatotoxicity, while alterations in metabolism of arachidonic acid suggesting potential of PFOA to cause inflammation response in liver. These results provide insight into the mechanism and biomarkers for PFOA-induced effects.

  1. 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.

  2. 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. PMID:26855192

  3. Environmental changes in oxygen tension reveal ROS-dependent neurogenesis and regeneration in the adult newt brain.

    Science.gov (United States)

    Hameed, L Shahul; Berg, Daniel A; Belnoue, Laure; Jensen, Lasse D; Cao, Yihai; Simon, András

    2015-01-01

    Organisms need to adapt to the ecological constraints in their habitat. How specific processes reflect such adaptations are difficult to model experimentally. We tested whether environmental shifts in oxygen tension lead to events in the adult newt brain that share features with processes occurring during neuronal regeneration under normoxia. By experimental simulation of varying oxygen concentrations, we show that hypoxia followed by re-oxygenation lead to neuronal death and hallmarks of an injury response, including activation of neural stem cells ultimately leading to neurogenesis. Neural stem cells accumulate reactive oxygen species (ROS) during re-oxygenation and inhibition of ROS biosynthesis counteracts their proliferation as well as neurogenesis. Importantly, regeneration of dopamine neurons under normoxia also depends on ROS-production. These data demonstrate a role for ROS-production in neurogenesis in newts and suggest that this role may have been recruited to the capacity to replace lost neurons in the brain of an adult vertebrate. PMID:26485032

  4. RNA Sequence Analysis of Human Huntington Disease Brain Reveals an Extensive Increase in Inflammatory and Developmental Gene Expression

    OpenAIRE

    Labadorf, Adam; Hoss, Andrew G.; Lagomarsino, Valentina; Latourelle, Jeanne C.; Hadzi, Tiffany C.; Bregu, Joli; MacDonald, Marcy E.; Gusella, James F.; Chen, Jiang-Fan; Akbarian, Schahram; Weng, Zhiping; Myers, Richard H

    2015-01-01

    Huntington’s Disease (HD) is a devastating neurodegenerative disorder that is caused by an expanded CAG trinucleotide repeat in the Huntingtin (HTT) gene. Transcriptional dysregulation in the human HD brain has been documented but is incompletely understood. Here we present a genome-wide analysis of mRNA expression in human prefrontal cortex from 20 HD and 49 neuropathologically normal controls using next generation high-throughput sequencing. Surprisingly, 19% (5,480) of the 28,087 confident...

  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

    Science.gov (United States)

    Casanova, Ramon; Wang, Xinhui; Reyes, Jeanette; Akita, Yasuyuki; Serre, Marc L.; Vizuete, William; Chui, Helena C.; Driscoll, Ira; Resnick, Susan M.; Espeland, Mark A.; Chen, Jiu-Chiuan; Wassertheil-Smoller, Sylvia; Goodwin, Mimi; DeNise, Richard; Lipton, Michael; Hannigan, James; Carpini, Anthony; Noble, David; Guzman, Wilton; Kotchen, Jane Morley; Goveas, Joseph; Kerwin, Diana; Ulmer, John; Censky, Steve; Flinton, Troy; Matusewic, Tracy; Prost, Robert; Stefanick, Marcia L.; Swope, Sue; Sawyer-Glover, Anne Marie; Hartley, Susan; Jackson, Rebecca; Hallarn, Rose; Kennedy, Bonnie; Bolognone, Jill; Casimir, Lindsay; Kochis, Amanda; Robbins, John; Zaragoza, Sophia; Carter, Cameron; Ryan, John; Macias, Denise; Sonico, Jerry; Nathan, Lauren; Voigt, Barbara; Villablanca, Pablo; Nyborg, Glen; Godinez, Sergio; Perrymann, Adele; Limacher, Marian; Anderson, Sheila; Toombs, Mary Ellen; Bennett, Jeffrey; Jones, Kevin; Brum, Sandy; Chatfield, Shane; Vantrees, Kevin; Robinson, Jennifer; Wilson, Candy; Koch, Kevin; Hart, Suzette; Carroll, Jennifer; Cherrico, Mary; Ockene, Judith; Churchill, Linda; Fellows, Douglas; Serio, Anthony; Jackson, Sharon; Spavich, Deidre; Margolis, Karen; Bjerk, Cindy; Truwitt, Chip; Peitso, Margaret; Camcrena, Alexa; Grim, Richard; Levin, Julie; Perron, Mary; Brunner, Robert; Golding, Ross; Pansky, Leslie; Arguello, Sandie; Hammons, Jane; Peterson, Nikki; Murphy, Carol; Morgan, Maggie; Castillo, Mauricio; Beckman, Thomas; Huang, Benjamin; Kuller, Lewis; McHugh, Pat; Meltzer, Carolyn; Davis, Denise; Davis, Joyce; Kost, Piera; Lucas, Kim; Potter, Tom; Tarr, Lee; Shumaker, Sally; Espeland, Mark; Coker, Laura; Williamson, Jeff; Felton, Debbie; Gleiser, LeeAnn; Rapp, Steve; Legault, Claudine; Dailey, Maggie; Casanova, Ramon; Robertson, Julia; Hogan, Patricia; Gaussoin, Sarah; Nance, Pam; Summerville, Cheryl; Peral, Ricardo; Tan, Josh; Bryan, Nick; Davatzikos, Christos; Desiderio, Lisa; Buckholtz, Neil; Molchan, Susan; Resnick, Susan; Rossouw, Jacques; Pottern, Linda

    2016-01-01

    Objective: Exposure to ambient fine particulate matter (PM2.5: PM with aerodynamic diameters voxel-wise analyses, we examined whether PM2.5 exposure also affects brain structure. Methods: Brain MRI data were obtained from 1365 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 smaller WM volumes to PM2.5, 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. Quantitative proteomics reveals the novel co-expression signatures in early brain development for prognosis of glioblastoma multiforme

    OpenAIRE

    Yu, Xuexin; Feng, Lin; Liu, Dianming; Zhang, Lianfeng; Wu, Bo; Jiang, Wei; Han, Zujing; Cheng, Shujun

    2016-01-01

    Although several researches have explored the similarity across development and tumorigenesis in cellular behavior and underlying molecular mechanisms, not many have investigated the developmental characteristics at proteomic level and further extended to cancer clinical outcome. In this study, we used iTRAQ to quantify the protein expression changes during macaque rhesus brain development from fetuses at gestation 70 days to after born 5 years. Then, we performed weighted gene co-expression ...

  8. Functional genomics reveals dysregulation of cortical olfactory receptors in Parkinson disease: novel putative chemoreceptors in the human brain.

    Science.gov (United States)

    Garcia-Esparcia, Paula; Schlüter, Agatha; Carmona, Margarita; Moreno, Jesús; Ansoleaga, Belen; Torrejón-Escribano, Benjamín; Gustincich, Stefano; Pujol, Aurora; Ferrer, Isidre

    2013-06-01

    Parkinson disease (PD) is no longer considered a complex motor disorder but rather a systemic disease with variable nonmotor deficits that may include impaired olfaction, depression, mood and sleep disorders, and altered cortical function. Increasing evidence indicates that multiple metabolic defects occur in regions outside the substantia nigra, including the cerebral cortex, even at premotor stages of the disease. We investigated changes in gene expression in the frontal cortex in PD patient brains using a transcriptomics approach. Functional genomics analysis indicated that cortical olfactory receptors (ORs) and taste receptors (TASRs) are altered in PD patients. Olfactory receptors OR2L13, OR1E1, OR2J3, OR52L1, and OR11H1 and taste receptors TAS2R5 and TAS2R50 were downregulated, but TAS2R10 and TAS2R13 were upregulated at premotor and parkinsonian stages in the frontal cortex area 8 in PD patient brains. Furthermore, we present novel evidence that, in addition to the ORs, obligate downstream components of OR function adenylyl cyclase 3 and olfactory G protein (Gαolf), OR transporters, receptor transporter proteins 1 and 2 and receptor expression enhancing protein 1, and OR xenobiotic removing UDP-glucuronosyltransferase 1 family polypeptide A6 are widely expressed in neurons of the cerebral cortex and other regions of the adult human brain. Together, these findings support the concept that ORs and TASRs in the cerebral cortex may have novel physiologic functions that are affected in PD patients.

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

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    Shahabeddin Vahdat

    2015-06-01

    Full Text Available 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. Divergent whole-genome methylation maps of human and chimpanzee brains reveal epigenetic basis of human regulatory evolution.

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    Zeng, Jia; Konopka, Genevieve; Hunt, Brendan G; Preuss, Todd M; Geschwind, Dan; Yi, Soojin V

    2012-09-01

    DNA methylation is a pervasive epigenetic DNA modification that strongly affects chromatin regulation and gene expression. To date, it remains largely unknown how patterns of DNA methylation differ between closely related species and whether such differences contribute to species-specific phenotypes. To investigate these questions, we generated nucleotide-resolution whole-genome methylation maps of the prefrontal cortex of multiple humans and chimpanzees. Levels and patterns of DNA methylation vary across individuals within species according to the age and the sex of the individuals. We also found extensive species-level divergence in patterns of DNA methylation and that hundreds of genes exhibit significantly lower levels of promoter methylation in the human brain than in the chimpanzee brain. Furthermore, we investigated the functional consequences of methylation differences in humans and chimpanzees by integrating data on gene expression generated with next-generation sequencing methods, and we found a strong relationship between differential methylation and gene expression. Finally, we found that differentially methylated genes are strikingly enriched with loci associated with neurological disorders, psychological disorders, and cancers. Our results demonstrate that differential DNA methylation might be an important molecular mechanism driving gene-expression divergence between human and chimpanzee brains and might potentially contribute to the evolution of disease vulnerabilities. Thus, comparative studies of humans and chimpanzees stand to identify key epigenomic modifications underlying the evolution of human-specific traits. PMID:22922032

  11. Quantitative proteomics reveals the novel co-expression signatures in early brain development for prognosis of glioblastoma multiforme.

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    Yu, Xuexin; Feng, Lin; Liu, Dianming; Zhang, Lianfeng; Wu, Bo; Jiang, Wei; Han, Zujing; Cheng, Shujun

    2016-03-22

    Although several researches have explored the similarity across development and tumorigenesis in cellular behavior and underlying molecular mechanisms, not many have investigated the developmental characteristics at proteomic level and further extended to cancer clinical outcome. In this study, we used iTRAQ to quantify the protein expression changes during macaque rhesus brain development from fetuses at gestation 70 days to after born 5 years. Then, we performed weighted gene co-expression network analysis (WGCNA) on protein expression data of brain development to identify co-expressed modules that highly expressed on distinct development stages, including early stage, middle stage and late stage. Moreover, we used the univariate cox regression model to evaluate the prognostic potentials of these genes in two independent glioblastoma multiforme (GBM) datasets. The results showed that the modules highly expressed on early stage contained more reproducible prognostic genes, including ILF2, CCT7, CCT4, RPL10A, MSN, PRPS1, TFRC and APEX1. These genes were not only associated with clinical outcome, but also tended to influence chemoresponse. These signatures identified from embryonic brain development might contribute to precise prediction of GBM prognosis and identification of novel drug targets in GBM therapies. Thus, the development could become a viable reference model for researching cancers, including identifying novel prognostic markers and promoting new therapies. PMID:26895104

  12. Amish Lifestyle Brings Unexpected Benefit: Less Asthma

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_160228.html Amish Lifestyle Brings Unexpected Benefit: Less Asthma Finding suggests exposing ... are very similar genetically. They also share many lifestyle factors: low rates of childhood obesity, large family ...

  13. Immediate early gene expression reveals interactions between social and nicotine rewards on brain activity in adolescent male rats.

    Science.gov (United States)

    Bastle, Ryan M; Peartree, Natalie A; Goenaga, Julianna; Hatch, Kayla N; Henricks, Angela; Scott, Samantha; Hood, Lauren E; Neisewander, Janet L

    2016-10-15

    Smoking initiation predominantly occurs during adolescence, often in the presence of peers. Therefore, understanding the neural mechanisms underlying the rewarding effects of nicotine and social stimuli is vital. Using the conditioned place preference (CPP) procedure, we measured immediate early gene (IEG) expression in animals following exposure either to a reward-conditioned environment or to the unconditioned stimuli (US). Adolescent, male rats were assigned to the following CPP US conditions: (1) Saline+Isolated, (2) Nicotine+Isolated, (3) Saline+Social, or (4) Nicotine+Social. For Experiment 1, brain tissue was collected 90min following the CPP expression test and processed for Fos immunohistochemistry. We found that rats conditioned with nicotine with or without a social partner exhibited CPP; however, we found no group differences in Fos expression in any brain region analyzed, with the exception of the nucleus accumbens core that exhibited a social-induced attenuation in Fos expression. For Experiment 2, brain tissue was collected 90min following US exposure during the last conditioning session. We found social reward-induced increases in IEG expression in striatal and amydalar subregions. In contrast, nicotine reduced IEG expression in prefrontal and striatal subregions. Reward interactions were also found in the dorsolateral striatum, basolateral amygdala, and ventral tegmental area where nicotine alone attenuated IEG expression and social reward reversed this effect. These results suggest that in general social rewards enhance, whereas nicotine attenuates, activation of mesocorticolimbic regions; however, the rewards given together interact to enhance activation in some regions. The findings contribute to knowledge of how a social environment influences nicotine effects. PMID:27435419

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

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    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

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

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    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.

  16. Genome-wide RNAi screens in human brain tumor isolates reveal a novel viability requirement for PHF5A.

    Science.gov (United States)

    Hubert, Christopher G; Bradley, Robert K; Ding, Yu; Toledo, Chad M; Herman, Jacob; Skutt-Kakaria, Kyobi; Girard, Emily J; Davison, Jerry; Berndt, Jason; Corrin, Philip; Hardcastle, Justin; Basom, Ryan; Delrow, Jeffery J; Webb, Thomas; Pollard, Steven M; Lee, Jeongwu; Olson, James M; Paddison, Patrick J

    2013-05-01

    To identify key regulators of human brain tumor maintenance and initiation, we performed multiple genome-wide RNAi screens in patient-derived glioblastoma multiforme (GBM) stem cells (GSCs). These screens identified the plant homeodomain (PHD)-finger domain protein PHF5A as differentially required for GSC expansion, as compared with untransformed neural stem cells (NSCs) and fibroblasts. Given PHF5A's known involvement in facilitating interactions between the U2 snRNP complex and ATP-dependent helicases, we examined cancer-specific roles in RNA splicing. We found that in GSCs, but not untransformed controls, PHF5A facilitates recognition of exons with unusual C-rich 3' splice sites in thousands of essential genes. PHF5A knockdown in GSCs, but not untransformed NSCs, astrocytes, or fibroblasts, inhibited splicing of these genes, leading to cell cycle arrest and loss of viability. Notably, pharmacologic inhibition of U2 snRNP activity phenocopied PHF5A knockdown in GSCs and also in NSCs or fibroblasts overexpressing MYC. Furthermore, PHF5A inhibition compromised GSC tumor formation in vivo and inhibited growth of established GBM patient-derived xenograft tumors. Our results demonstrate a novel viability requirement for PHF5A to maintain proper exon recognition in brain tumor-initiating cells and may provide new inroads for novel anti-GBM therapeutic strategies. PMID:23651857

  17. Live imaging reveals a new role for the sigma-1 (σ1) receptor in allowing microglia to leave brain injuries.

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    Moritz, Christian; Berardi, Francesco; Abate, Carmen; Peri, Francesca

    2015-03-30

    Microglial cells are responsible for clearing and maintaining the central nervous system (CNS) microenvironment. Upon brain damage, they move toward injuries to clear the area by engulfing dying neurons. However, in the context of many neurological disorders chronic microglial responses are responsible for neurodegeneration. Therefore, it is important to understand how these cells can be "switched-off" and regain their ramified state. Current research suggests that microglial inflammatory responses can be inhibited by sigma (σ) receptor activation. Here, we take advantage of the optical transparency of the zebrafish embryo to study the role of σ1 receptor in microglia in an intact living brain. By combining chemical approaches with real time imaging we found that treatment with PB190, a σ1 agonist, blocks microglial migration toward injuries leaving cellular baseline motility and the engulfment of apoptotic neurons unaffected. Most importantly, by taking a reverse genetic approach, we discovered that the role of σ1in vivo is to "switch-off" microglia after they responded to an injury allowing for these cells to leave the site of damage. This indicates that pharmacological manipulation of σ1 receptor modulates microglial responses providing new approaches to reduce the devastating impact that microglia have in neurodegenerative diseases.

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

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    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.

  19. Pediatric Sudden Unexpected Death in Epilepsy: What Have we Learned from Animal and Human Studies, and Can we Prevent it?

    Science.gov (United States)

    Holt, Rebecca L; Arehart, Eric; Hunanyan, Arsen; Fainberg, Nina A; Mikati, Mohamad A

    2016-05-01

    Several factors, such as epilepsy syndrome, poor compliance, and increased seizure frequency increase the risks of sudden unexpected death in epilepsy (SUDEP). Animal models have revealed that the mechanisms of SUDEP involve initially a primary event, often a seizure of sufficient type and severity, that occurs in a brain, which is vulnerable to SUDEP due to either genetic or antecedent factors. This primary event initiates a cascade of secondary events starting, as some models indicate, with cortical spreading depolarization that propagates to the brainstem where it results in autonomic dysfunction. Intrinsic abnormalities in brainstem serotonin, adenosine, sodium-postassium ATPase, and respiratory-control systems are also important. The tertiary event, which results from the above dysfunction, consists of either lethal central apnea, pulmonary edema, or arrhythmia. Currently, it is necessary to (1) continue researching SUDEP mechanisms, (2) work on reducing SUDEP risk factors, and (3) address the major need to counsel families about SUDEP. PMID:27544469

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

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    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.

  1. 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

  2. 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. PMID:27014019

  3. 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. PMID:27014019

  4. Functionally Brain Network Connected to the Retrosplenial Cortex of Rats Revealed by 7T fMRI.

    Science.gov (United States)

    Wang, Jingjuan; Nie, Binbin; Duan, Shaofeng; Zhu, Haitao; Liu, Hua; Shan, Baoci

    2016-01-01

    Functional networks are regarded as important mechanisms for increasing our understanding of brain function in healthy and diseased states, and increased interest has been focused on extending the study of functional networks to animal models because such models provide a functional understanding of disease progression, therapy and repair. In rodents, the retrosplenial cortex (RSC) is an important cortical region because it has a large size and presents transitional patterns of lamination between the neocortex and archicortex. In addition, a number of invasive studies have highlighted the importance of the RSC for many functions. However, the network based on the RSC in rodents remains unclear. Based on the critical importance of the RSC, we defined the bilateral RSCs as two regions of interest and estimated the network based on the RSC. The results showed that the related regions include the parietal association cortex, hippocampus, thalamus nucleus, midbrain structures, and hypothalamic mammillary bodies. Our findings indicate two possible major networks: a sensory-cognitive network that has a hub in the RSCs and processes sensory information, spatial learning, and episodic memory; and a second network that is involved in the regulation of visceral functions and arousal. In addition, functional asymmetry between the bilateral RSCs was observed.

  5. Whole Exome Sequencing Reveals DYSF, FKTN, and ISPD Mutations in Congenital Muscular Dystrophy Without Brain or Eye Involvement

    Science.gov (United States)

    Ceyhan-Birsoy, Ozge; Talim, Beril; Swanson, Lindsay C.; Karakaya, Mert; Graff, Michelle A.; Beggs, Alan H.; Topaloglu, Haluk

    2015-01-01

    Background Congenital muscular dystrophies (CMDs) are a genetically and clinically heterogeneous group of neuromuscular disorders. Several genes encoding extracellular matrix, nuclear envelope, sarcolemmal proteins and glycosylation enzymes have been implicated in CMDs. The large overlap of clinical presentations due to mutations in different genes poses a challenge for clinicians in determining disease etiology for each patient. Objective We investigated the use of whole exome sequencing (WES) in identifying the genetic cause of disease in 5 CMD patients from 3 families who presented with highly similar clinical features, including early-onset rapidly progressive weakness without brain or eye abnormalities. Methods Whole exome sequencing was performed on DNA from affected individuals. Potential functional impacts of mutations were investigated by immunostaining on available muscle biopsies. Results Pathogenic mutations in 3 different genes, DYSF, FKTN, and ISPD were identified in each family. Mutation in DYSF led to absence of dysferlin protein in patient muscle. Mutations in ISPD led to impaired ISDP function, as demonstrated by deficiency of α-dystroglycan glycosylation in patient muscle. Conclusions This study highlights the benefit of unbiased genomic approaches in molecular diagnosis of neuromuscular disorders with high clinical heterogeneity, such as the phenotypes observed in our patients. Our results suggest that dysferlin deficiency should be in the differential diagnosis of congenital and rapidly progressive muscular dystrophy, and therefore dysferlin antibody should be in the standard immunohistochemistry panel for muscle biopsies in cases with suspected CMD. PMID:25821721

  6. Proteomic Analysis of Human Brain Microvascular Endothelial Cells Reveals Differential Protein Expression in Response to Enterovirus 71 Infection

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    Wenying Luo

    2015-01-01

    Full Text Available 2D DIGE technology was employed on proteins prepared from human brain microvascular endothelial cells (HBMEC, to study the differentially expressed proteins in cells at 0 h, 1 h, 16 h, and 24 h after infection. Proteins found to be differentially expressed were identified with matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry (MALDITOF/TOF MS analysis. We identified 43 spots showing changes of at least 2.5 fold up- or downregulated expressions in EV71-infected cells at different time when comparing to control, and 28 proteins could be successfully identified by MALDI TOF/TOF mass spectrometry analysis. 4 proteins were significantly upregulated, and 6 proteins were downregulated, another 18 proteins were different expression at different incubation time. We identified changes in the expression of 12 cellular metabolism-related proteins, 5 molecules involved in cytoskeleton, 3 molecules involved in energy metabolism, 2 molecules involved in signal transduction, 1 molecule involved in the ubiquitin-proteasome pathway, 1 molecule involved in cell cycle, 1 molecule involved in apoptosis-related protein, 1 molecular chaperone, and 2 unknown proteins. These findings build up a comprehensive profile of the HBMEC proteome and provide a useful basis for further analysis of the pathogenic mechanism that underlies EV71 infections to induce severe neural complications.

  7. 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.

  8. Sexually Dimorphic Gene Expression Associated with Growth and Reproduction of Tongue Sole (Cynoglossus semilaevis) Revealed by Brain Transcriptome Analysis.

    Science.gov (United States)

    Wang, Pingping; Zheng, Min; Liu, Jian; Liu, Yongzhuang; Lu, Jianguo; Sun, Xiaowen

    2016-01-01

    In this study, we performed a comprehensive analysis of the transcriptome of one- and two-year-old male and female brains of Cynoglossus semilaevis by high-throughput Illumina sequencing. A total of 77,066 transcripts, corresponding to 21,475 unigenes, were obtained with a N50 value of 4349 bp. Of these unigenes, 33 genes were found to have significant differential expression and potentially associated with growth, from which 18 genes were down-regulated and 12 genes were up-regulated in two-year-old males, most of these genes had no significant differences in expression among one-year-old males and females and two-year-old females. A similar analysis was conducted to look for genes associated with reproduction; 25 genes were identified, among them, five genes were found to be down regulated and 20 genes up regulated in two-year-old males, again, most of the genes had no significant expression differences among the other three. The performance of up regulated genes in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was significantly different between two-year-old males and females. Males had a high gene expression in genetic information processing, while female's highly expressed genes were mainly enriched on organismal systems. Our work identified a set of sex-biased genes potentially associated with growth and reproduction that might be the candidate factors affecting sexual dimorphism of tongue sole, laying the foundation to understand the complex process of sex determination of this economic valuable species. PMID:27571066

  9. 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

  10. 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

  11. 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.

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

    International Nuclear Information System (INIS)

    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 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.

  13. Orchestrating Proactive and Reactive Mechanisms for Filtering Distracting Information: Brain-Behavior Relationships Revealed by a Mixed-Design fMRI Study.

    Science.gov (United States)

    Marini, Francesco; Demeter, Elise; Roberts, Kenneth C; Chelazzi, Leonardo; Woldorff, Marty G

    2016-01-20

    Given the information overload often imparted to human cognitive-processing systems, suppression of irrelevant and distracting information is essential for successful behavior. Using a hybrid block/event-related fMRI design, we characterized proactive and reactive brain mechanisms for filtering distracting stimuli. Participants performed a flanker task, discriminating the direction of a target arrow in the presence versus absence of congruent or incongruent flanking distracting arrows during either Pure blocks (distracters always absent) or Mixed blocks (distracters on 80% of trials). Each Mixed block had either 20% or 60% incongruent trials. Activations in the dorsal frontoparietal attention network during Mixed versus Pure blocks evidenced proactive (blockwise) recruitment of a distraction-filtering mechanism. Sustained activations in right middle frontal gyrus during 60% Incongruent blocks correlated positively with behavioral indices of distraction-filtering (slowing when distracters might occur) and negatively with distraction-related behavioral costs (incongruent vs congruent trials), suggesting a role in coordinating proactive filtering of potential distracters. Event-related analyses showed that incongruent trials elicited greater reactive activations in 20% (vs 60%) Incongruent blocks for counteracting distraction and conflict, including in the insula and anterior cingulate. Context-related effects in occipitoparietal cortex consisted of greater target-evoked activations for distracter-absent trials (central-target-only) in Mixed versus Pure blocks, suggesting enhanced attentional engagement. Functional-localizer analyses in V1/V2/V3 revealed less distracter-processing activity in 60% (vs 20%) Incongruent blocks, presumably reflecting tonic suppression by proactive filtering mechanisms. These results delineate brain mechanisms underlying proactive and reactive filtering of distraction and conflict, and how they are orchestrated depending on distraction

  14. Orchestrating Proactive and Reactive Mechanisms for Filtering Distracting Information: Brain-Behavior Relationships Revealed by a Mixed-Design fMRI Study.

    Science.gov (United States)

    Marini, Francesco; Demeter, Elise; Roberts, Kenneth C; Chelazzi, Leonardo; Woldorff, Marty G

    2016-01-20

    Given the information overload often imparted to human cognitive-processing systems, suppression of irrelevant and distracting information is essential for successful behavior. Using a hybrid block/event-related fMRI design, we characterized proactive and reactive brain mechanisms for filtering distracting stimuli. Participants performed a flanker task, discriminating the direction of a target arrow in the presence versus absence of congruent or incongruent flanking distracting arrows during either Pure blocks (distracters always absent) or Mixed blocks (distracters on 80% of trials). Each Mixed block had either 20% or 60% incongruent trials. Activations in the dorsal frontoparietal attention network during Mixed versus Pure blocks evidenced proactive (blockwise) recruitment of a distraction-filtering mechanism. Sustained activations in right middle frontal gyrus during 60% Incongruent blocks correlated positively with behavioral indices of distraction-filtering (slowing when distracters might occur) and negatively with distraction-related behavioral costs (incongruent vs congruent trials), suggesting a role in coordinating proactive filtering of potential distracters. Event-related analyses showed that incongruent trials elicited greater reactive activations in 20% (vs 60%) Incongruent blocks for counteracting distraction and conflict, including in the insula and anterior cingulate. Context-related effects in occipitoparietal cortex consisted of greater target-evoked activations for distracter-absent trials (central-target-only) in Mixed versus Pure blocks, suggesting enhanced attentional engagement. Functional-localizer analyses in V1/V2/V3 revealed less distracter-processing activity in 60% (vs 20%) Incongruent blocks, presumably reflecting tonic suppression by proactive filtering mechanisms. These results delineate brain mechanisms underlying proactive and reactive filtering of distraction and conflict, and how they are orchestrated depending on distraction

  15. A Translational Murine Model of Sub-Lethal Intoxication with Shiga Toxin 2 Reveals Novel Ultrastructural Findings in the Brain Striatum

    Science.gov (United States)

    Tironi-Farinati, Carla; Geoghegan, Patricia A.; Cangelosi, Adriana; Pinto, Alipio; Loidl, C. Fabian; Goldstein, Jorge

    2013-01-01

    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. PMID:23383285

  16. Analysis of YFP(J16)-R6/2 reporter mice and postmortem brains reveals early pathology and increased vulnerability of callosal axons in Huntington's disease.

    Science.gov (United States)

    Gatto, Rodolfo G; Chu, Yaping; Ye, Allen Q; Price, Steven D; Tavassoli, Ehsan; Buenaventura, Andrea; Brady, Scott T; Magin, Richard L; Kordower, Jeffrey H; Morfini, Gerardo A

    2015-09-15

    Cumulative evidence indicates that the onset and severity of Huntington's disease (HD) symptoms correlate with connectivity deficits involving specific neuronal populations within cortical and basal ganglia circuits. Brain imaging studies and pathological reports further associated these deficits with alterations in cerebral white matter structure and axonal pathology. However, whether axonopathy represents an early pathogenic event or an epiphenomenon in HD remains unknown, nor is clear the identity of specific neuronal populations affected. To directly evaluate early axonal abnormalities in the context of HD in vivo, we bred transgenic YFP(J16) with R6/2 mice, a widely used HD model. Diffusion tensor imaging and fluorescence microscopy studies revealed a marked degeneration of callosal axons long before the onset of motor symptoms. Accordingly, a significant fraction of YFP-positive cortical neurons in YFP(J16) mice cortex were identified as callosal projection neurons. Callosal axon pathology progressively worsened with age and was influenced by polyglutamine tract length in mutant huntingtin (mhtt). Degenerating axons were dissociated from microscopically visible mhtt aggregates and did not result from loss of cortical neurons. Interestingly, other axonal populations were mildly or not affected, suggesting differential vulnerability to mhtt toxicity. Validating these results, increased vulnerability of callosal axons was documented in the brains of HD patients. Observations here provide a structural basis for the alterations in cerebral white matter structure widely reported in HD patients. Collectively, our data demonstrate a dying-back pattern of degeneration for cortical projection neurons affected in HD, suggesting that axons represent an early and potentially critical target for mhtt toxicity. PMID:26123489

  17. 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 ...... are SUDI, and the majority of these are caused by cardiac disease or SIDS. Autopsy is not always performed and valuable information is subsequently lost. Cause of Death registry data is not accurate in describing SIDS....

  18. Endometriosis: A Highly Unexpected Skin Lesion

    OpenAIRE

    Tolga Dinc

    2016-01-01

    Endometriosis: A highly unexpected skin lesion Endometriosis is the presence of functional endometrium in anywhere outside of uterin cavity. This clinical entity is relatively common, that 10-15% of fertile women and 6% of post-menopausal women are affected [1,2] . Cutaneous endometriosis is a form of endometriosis and it usually occurs in the incision scar, after gynecological surgeries, cesarean sections and episiotomies [3]. Cutaneous endometriosis is characterized with painful, bluish ...

  19. Metabolomics analysis reveals elevation of 3-indoxyl sulfate in plasma and brain during chemically-induced acute kidney injury in mice: Investigation of nicotinic acid receptor agonists

    International Nuclear Information System (INIS)

    An investigative renal toxicity study using metabolomics was conducted with a potent nicotinic acid receptor (NAR) agonist, SCH 900424. Liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) techniques were used to identify small molecule biomarkers of acute kidney injury (AKI) that could aid in a better mechanistic understanding of SCH 900424-induced AKI in mice. The metabolomics study revealed 3-indoxyl sulfate (3IS) as a more sensitive marker of SCH 900424-induced renal toxicity than creatinine or urea. An LC-MS assay for quantitative determination of 3IS in mouse matrices was also developed. Following treatment with SCH 900424, 3IS levels were markedly increased in murine plasma and brain, thereby potentially contributing to renal- and central nervous system (CNS)-related rapid onset of toxicities. Furthermore, significant decrease in urinary excretion of 3IS in those animals due to compromised renal function may be associated with the elevation of 3IS in plasma and brain. These data suggest that 3IS has a potential to be a marker of renal and CNS toxicities during chemically-induced AKI in mice. In addition, based on the metabolomic analysis other statistically significant plasma markers including p-cresol-sulfate and tryptophan catabolites (kynurenate, kynurenine, 3-indole-lactate) might be of toxicological importance but have not been studied in detail. This comprehensive approach that includes untargeted metabolomic and targeted bioanalytical sample analyses could be used to investigate toxicity of other compounds that pose preclinical or clinical development challenges in a pharmaceutical discovery and development. - Research highlights: → Nicotinic acid receptor agonist, SCH 900424, caused acute kidney injury in mice. → MS-based metabolomics was conducted to identify potential small molecule markers of renal toxicity. → 3-indoxyl-sulfate was found to be as a more sensitive marker of renal toxicity than

  20. Circadian variation in unexpected postoperative death

    DEFF Research Database (Denmark)

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

    1992-01-01

    Unexpected deaths still occur following major surgical procedures. The cause is often unknown but may be cardiac or thromboembolic in nature. Postoperative ischaemia, infarction and sudden cardiac death may be triggered by episodic or constant arterial hypoxaemia, which increases during the night...... 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.......Unexpected deaths still occur following major surgical procedures. The cause is often unknown but may be cardiac or thromboembolic in nature. Postoperative ischaemia, infarction and sudden cardiac death may be triggered by episodic or constant arterial hypoxaemia, which increases during the night....... 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...

  1. 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. PMID:16304941

  2. Immunohistochemical localization of the neuron-specific glutamate transporter EAAC1 (EAAT3) in rat brain and spinal cord revealed by a novel monoclonal antibody.

    Science.gov (United States)

    Shashidharan, P; Huntley, G W; Murray, J M; Buku, A; Moran, T; Walsh, M J; Morrison, J H; Plaitakis, A

    1997-10-31

    Neuronal regulation of glutamate homeostasis is mediated by high-affinity sodium-dependent and highly hydrophobic plasma membrane glycoproteins which maintain low levels of glutamate at central synapses. To further elucidate the molecular mechanisms that regulate glutamate metabolism and glutamate flux at central synapses, a monoclonal antibody was produced to a synthetic peptide corresponding to amino acid residues 161-177 of the deduced sequence of the human neuron-specific glutamate transporter III (EAAC1). Immunoblot analysis of human and rat brain total homogenates and isolated synaptosomes from frontal cortex revealed that the antibody immunoreacted with a protein band of apparent Mr approximately 70 kDa. Deglycosylation of immunoprecipitates obtained using the monoclonal antibody yielded a protein with a lower apparent Mr (approximately 65 kDa). These results are consistent with the molecular size of the human EAAC1 predicted from the cloned cDNA. Analysis of the transfected COS-1 cells by immunocytochemistry confirmed that the monoclonal antibody is specific for the neuron-specific glutamate transporter. Immunocytochemical studies of rat cerebral cortex, hippocampus, cerebellum, substantia nigra and spinal cord revealed intense labeling of neuronal somata, dendrites, fine-caliber fibers and puncta. Double-label immunofluorescence using antibody to glial fibrillary acidic protein as a marker for astrocytes demonstrated that astrocytes were not co-labeled for EAAC1. The localization of EAAC1 immunoreactivity in dendrites and particularly in cell somata suggests that this transporter may function in the regulation of other aspects of glutamate metabolism in addition to terminating the action of synaptically released glutamate at central synapses. PMID:9409715

  3. Spectrometric mixture analysis: An unexpected wrinkle

    Indian Academy of Sciences (India)

    Robert De Levie

    2009-09-01

    The spectrometric analysis of a mixture of two chemically and spectroscopically similar compounds is illustrated for the simultaneous spectrometric determination of caffeine and theobromine, the primary stimulants in coffee and tea, based on their ultraviolet absorbances. Their analysis indicates that such measurements may need an unexpectedly high precision to yield accurate answers, because of an artifact of inverse cancellation, in which a small noise or drift signal is misinterpreted in terms of a concentration difference. The computed sum of the concentrations is not affected.

  4. Spontaneous brain activity in chronic smokers revealed by fractional amplitude of low frequency fluctuation analysis: a resting state functional magnetic resonance imaging study

    Institute of Scientific and Technical Information of China (English)

    Chu Shuilian; Xiao Dan; Wang Shuangkun; Peng Peng; Xie Teng; He Yong; Wang Chen

    2014-01-01

    Background Nicotine is primarily rsponsible for the highly addictive properties of cigarettes.Similar to other substances,nicotine dependence is related to many important brain regions,particular in mesolimbic reward circuit.This study was to further reveal the alteration of brain function activity during resting state in chronic smokers by fractional amplitude of low frequency fluctuation (fALFF) based on functional magnetic resonance imaging (fMRI),in order to provide the evidence of neurobiological mechanism of smoking.Methods This case control study involved twenty healthy smokers and nineteen healthy nonsmokers recruited by advertisement.Sociodemographic,smoking related characteristics and fMRI images were collected and the data analyzed.Results Compared with nonsmokers,smokers showed fALFF increased significantly in the left middle occipital gyrus,left limbic lobe and left cerebellum posterior lobe but decreases in the right middle frontal gyrus,right superior temporal gyrus,right extra nuclear,left postcentral gyrus and left cerebellum anterior lobe (cluster size >100 voxels).Compared with light smokers (pack years ≤20),heavy smokers (pack years >20) showed fALFF increased significantly in the right superior temporal gyrus,right precentral gyrus,and right occipital lobe/cuneus but decreased in the right/left limbic lobe/cingulate gyrus,right/left frontal lobe/sub gyral,right/left cerebellum posterior lobe (cluster size >50 voxels).Compared with nonsevere nicotine dependent smokers (Fagerstr(o)m test for nicotine dependence,score ≤6),severe nicotine dependent smokers (score >6) showed fALFF increased significantly in the right/left middle frontal gyrus,right superior frontal gyrus and left inferior parietal lobule but decreased in the left limbic lobe/cingulate gyrus (duster size >25 voxels).Conclusions In smokers during rest,the activity of addiction related regions were increased and the activity of smoking feeling,memory,related regions were

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

    Directory of Open Access Journals (Sweden)

    Abu Bakar Ali Asad

    Full Text Available 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, p<0.02, n = 8, while no significant change was found after the vehicle application. The tail withdrawal behavioral study demonstrated a significant main effect of temperature and a trend towards capsaicin induced 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

  6. 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...

  7. Deep brain stimulation reveals a dissociation of consummatory and motivated behaviour in the medial and lateral nucleus accumbens shell of the rat.

    Science.gov (United States)

    van der Plasse, Geoffrey; Schrama, Regina; van Seters, Sebastiaan P; Vanderschuren, Louk J M J; Westenberg, Herman G M

    2012-01-01

    Following the successful application of deep brain stimulation (DBS) in the treatment of Parkinson's disease and promising results in clinical trials for obsessive compulsive disorder and major depression, DBS is currently being tested in small patient-populations with eating disorders and addiction. However, in spite of its potential use in a broad spectrum of disorders, the mechanisms of action of DBS remain largely unclear and optimal neural targets for stimulation in several disorders have yet to be established. Thus, there is a great need to examine site-specific effects of DBS on a behavioural level and to understand how DBS may modulate pathological behaviour. In view of the possible application of DBS in the treatment of disorders characterized by impaired processing of reward and motivation, like addiction and eating disorders, we examined the effect of DBS of the nucleus accumbens (NAcc) on food-directed behavior. Rats were implanted with bilateral stimulation electrodes in one of three anatomically and functionally distinct sub-areas of the NAcc: the core, lateral shell (lShell) and medial shell (mShell). Subsequently, we studied the effects of DBS on food consumption, and the motivational and appetitive properties of food. The data revealed a functional dissociation between the lShell and mShell. DBS of the lShell reduced motivation to respond for sucrose under a progressive ratio schedule of reinforcement, mShell DBS, however, profoundly and selectively increased the intake of chow. DBS of the NAcc core did not alter any form of food-directed behavior studied. DBS of neither structure affected sucrose preference. These data indicate that the intake of chow and the motivation to work for palatable food can independently be modulated by DBS of subregions of the NAcc shell. As such, these findings provide important leads for the possible future application of DBS as a treatment for eating disorders such as anorexia nervosa. PMID:22428054

  8. 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.

  9. Deep brain stimulation reveals a dissociation of consummatory and motivated behaviour in the medial and lateral nucleus accumbens shell of the rat.

    Directory of Open Access Journals (Sweden)

    Geoffrey van der Plasse

    Full Text Available Following the successful application of deep brain stimulation (DBS in the treatment of Parkinson's disease and promising results in clinical trials for obsessive compulsive disorder and major depression, DBS is currently being tested in small patient-populations with eating disorders and addiction. However, in spite of its potential use in a broad spectrum of disorders, the mechanisms of action of DBS remain largely unclear and optimal neural targets for stimulation in several disorders have yet to be established. Thus, there is a great need to examine site-specific effects of DBS on a behavioural level and to understand how DBS may modulate pathological behaviour. In view of the possible application of DBS in the treatment of disorders characterized by impaired processing of reward and motivation, like addiction and eating disorders, we examined the effect of DBS of the nucleus accumbens (NAcc on food-directed behavior. Rats were implanted with bilateral stimulation electrodes in one of three anatomically and functionally distinct sub-areas of the NAcc: the core, lateral shell (lShell and medial shell (mShell. Subsequently, we studied the effects of DBS on food consumption, and the motivational and appetitive properties of food. The data revealed a functional dissociation between the lShell and mShell. DBS of the lShell reduced motivation to respond for sucrose under a progressive ratio schedule of reinforcement, mShell DBS, however, profoundly and selectively increased the intake of chow. DBS of the NAcc core did not alter any form of food-directed behavior studied. DBS of neither structure affected sucrose preference. These data indicate that the intake of chow and the motivation to work for palatable food can independently be modulated by DBS of subregions of the NAcc shell. As such, these findings provide important leads for the possible future application of DBS as a treatment for eating disorders such as anorexia nervosa.

  10. The Consequential Problems of Unexpected Events for Human Element and Construction Organizations

    Directory of Open Access Journals (Sweden)

    Amir Khosravi

    2013-03-01

    Full Text Available 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, wicked messes and messes problems grew rapidly by high behavioral complexity of human affected environment and high dynamic complexity of interdependent systems in construction projects. We discovered human behavioral problems as wicked kind of problems for human element could lead to noticeable effects on project manager, such as irresponsibility and making a bizarre decision. Also, we identified wicked messes and messes problems, including loss of reputation and litigation, for construction organizations could terminate the viability of organizations and projects. Furthermore, we found out that three most important factors for responding successfully to the consequential problems of unexpected events were: 1 organizations’ structure and support, 2 competent project manager and 3 immediate actions. The findings of the study revealed that leadership, communication skills and hard-working were essential attributes of the competent project manager in responding to the consequential problems of unexpected events. Lastly, this research suggests the development of managerial reactive skills and control of behavioral responses through learning practice as key components of the required approach that need further investigations in future researches.

  11. Unexpected consequences of midwifery in the NHS.

    Science.gov (United States)

    Pollock, Jane

    2015-11-01

    This article presents information from the Caring for the carers conference held at George Eliot Hospital in July 2015. For many midwives, feelings of stress are an unexpected consequence of rising birth rates, low staffing levels and negative organisational cultures, so our aim was that delegates would take away skills for 'surviving' in maternity services. The conference was the catalyst to a project at George Eliot NHS Trust to improve the wellbeing of staff so that they can develop a positive outlook towards the care which they offer. As part of the project, a toolkit for survival was produced which helps to prompt maternity workers to remember their own wellbeing. This project is continuing to grow and the results will be available next year.

  12. In Vivo Microdialysis Reveals Age-Dependent Decrease of Brain Interstitial Fluid Tau Levels in P301S Human Tau Transgenic Mice

    OpenAIRE

    Yamada, Kaoru; Cirrito, John R.; Stewart, Floy R; Jiang, Hong; Finn, Mary Beth; Holmes, Brandon B.; Binder, Lester I.; Mandelkow, Eva-Maria; Diamond, Marc I.; Lee, Virginia M.-Y.; Holtzman, David M.

    2011-01-01

    Although tau is a cytoplasmic protein, it is also found in brain extracellular fluids, e.g., CSF. Recent findings suggest that aggregated tau can be transferred between cells and extracellular tau aggregates might mediate spread of tau pathology. Despite these data, details of whether tau is normally released into the brain interstitial fluid (ISF), its concentration in ISF in relation to CSF, and whether ISF tau is influenced by its aggregation are unknown. To address these issues, we develo...

  13. Analyses of resected human brain metastases of breast cancer reveal the association between up-regulation of hexokinase 2 and poor prognosis.

    Science.gov (United States)

    Palmieri, Diane; Fitzgerald, Daniel; Shreeve, S Martin; Hua, Emily; Bronder, Julie L; Weil, Robert J; Davis, Sean; Stark, Andreas M; Merino, Maria J; Kurek, Raffael; Mehdorn, H Maximilian; Davis, Gary; Steinberg, Seth M; Meltzer, Paul S; Aldape, Kenneth; Steeg, Patricia S

    2009-09-01

    Brain metastases of breast cancer seem to be increasingin incidence as systemic therapy improves. Metastatic disease in the brain is associated with high morbidity and mortality. We present the first gene expression analysis of laser-captured epithelial cells from resected human brain metastases of breast cancer compared with unlinked primary breast tumors. The tumors were matched for histology, tumor-node-metastasis stage, and hormone receptor status. Most differentially expressed genes were down-regulated in the brain metastases, which included, surprisingly, many genes associated with metastasis. Quantitative real-time PCR analysis confirmed statistically significant differences or strong trends in the expression of six genes: BMP1, PEDF, LAMgamma3, SIAH, STHMN3, and TSPD2. Hexokinase 2 (HK2) was also of interest because of its increased expression in brain metastases. HK2 is important in glucose metabolism and apoptosis. In agreement with our microarray results, HK2 levels (both mRNA and protein) were elevated in a brain metastatic derivative (231-BR) of the human breast carcinoma cell line MDA-MB-231 relative to the parental cell line (231-P) in vitro. Knockdown of HK2 expression in 231-BR cells using short hairpin RNA reduced cell proliferation when cultures were maintained in glucose-limiting conditions. Finally, HK2 expression was analyzed in a cohort of 123 resected brain metastases of breast cancer. High HK2 expression was significantly associated with poor patient survival after craniotomy (P = 0.028). The data suggest that HK2 overexpression is associated with metastasis to the brain in breast cancer and it may be a therapeutic target. PMID:19723875

  14. Unexpectedly ease surgery for a worrisome abdominal mass: Pedunculated GISTs☆

    Science.gov (United States)

    Baskiran, Adil; Otan, Emrah; Aydin, Cemalettin; Kayaalp, Cuneyt

    2013-01-01

    INTRODUCTION Discovery of abdominal masses often poses significant diagnostic difficulties. GISTs are mesenchymal masses, with specific histological features. Dimensions may vary from millimeters to giant tumours. We would like to present our case, which had an unexpectedly easy operative course which was easily handled with a simple surgical excision with a short operative duration. PRESENTATION OF CASE A 38 years old female patient was diagnosed to have an abdominal heterogen mass of 15 cm × 12 cm × 10 cm in dimension. Abdominal computed tomography revealed the solid mass between the stomach and pancreas corpus and tail, possibly orginating from the pancreas. With the preoperative diagnosis of locally invasive distal pancreas cancer the patient underwent laparotomy, following the dissection, the mass was observed to be originating from the posterior gastric Wall, extending exophytically with a peduncle of 5 cm in width, without any visual evidence for peritoneal invasion and metastasis. The tumour and the peduncle was resected with stapler device. Total operation time was 30 min. Postoperative course was uneventful. Pathologic diagnosis was gastrointestinal stromal tumour (GIST). DISCUSSION Pedunculated large GISTs are not frequent and they can enlarge as 15 cm in diameter and compress the neighbouring organs. When they were huge, it is difficult to differentiate the origin of the masses. GISTs should be considered in differential diagnosis of giant abdominal masses. CONCLUSION When GISTs are huge and pedunculated, it can be difficult to differentiate the origin of the masses. This case report presents unexpectedly ease surgery for a worrysome abdominal mass. PMID:23999120

  15. Sudden unexpected death in epilepsy: Evaluation of forensic autopsy cases.

    Science.gov (United States)

    Zhuo, Luo; Zhang, Yang; Zielke, H Ronald; Levine, Barry; Zhang, Xiang; Chang, Lin; Fowler, David; Li, Ling

    2012-11-30

    Epilepsy is a common chronic neurological disorder characterized by seizures. Mortality is significantly increased in patients with epilepsy. Sudden unexpected death in epilepsy (SUDEP) is the most common seizure-related category of death. A retrospective study of forensic autopsy cases from 2007 to 2009 at the Office of the Chief Medical Examiner (OCME) yielded a total of 104 sudden unexpected deaths directly or indirectly caused by an epilepsy/seizure disorder in the State of Maryland. Of these deaths, 74 cases met a general accepted definition of SUDEP. The age of SUDEP individuals ranged from 14 to 63 with the majority of subjects in the ages between 21 and 50 years (58 cases, 78.4%). Males were slightly more likely than females to die of SUDEP (male:female=1.5:1 based on the rate). The onset age of epilepsy was documented in 47.3% of cases (35/74) based on investigation and medical records. Of the 35 cases, 12 subjects had early onset epilepsy (onset ages 1-15 years) and 20 subjects had duration of epilepsy for more than 10 years. The majority of deaths (61 of the 74 cases, 82.4%) were unwitnessed. Death scene investigation showed that 71 deaths (95.9%) occurred inside their residence with 50 subjects (70.4%) found either in bed or on the bedroom floor near the bed. Forty-three out of 74 cases (58.1%) showed neuropathological lesions. Per history, 50 subjects were reported as being on anti-epileptic drugs (AEDs). However, postmortem toxicological analysis revealed that only 26 subjects (35.1%) had detectable AEDs. Of the 74 cases, seizure disorder or epilepsy was listed as primary cause of death in 66 cases and the term of SUDEP as official cause of death in only 8 cases. This report focuses on the characteristics of death scene investigation and postmortem examination findings of SUDEP cases.

  16. Postnatal pattern of ornithine decarboxylase activity reveals a disparity of rat brain regeneration capacity after prenatal X-ray or 5-azacytidine treatment

    International Nuclear Information System (INIS)

    Pregnant Wistar rats were treated on the 15th day of gestation either with 1.4 Gy X-radiation, or with 2 X 2.5 mg 5-azacytidine per kg body weight. X-irradiation caused negligible mortality among the offspring, despite of a 35% reduction of brain weights. The course of brain ornithine decarboxylase activity exhibited two breaches within 5 days after birth, each followed by recovery to control levels. After 5-azacytidine treatment brain weights were reduced by 16% only, but two thirds of the young died within a short time after birth. During three days following birth, the activity of ornithine decarboxylase in the brains of the young animals split into two ranges, a high one at control level and a low one at about one fifth of control level. As the ratio of brains with low to those with high enzyme activities correlated with the rate of postnatal mortality, the splitting of early postnatal enzyme activities was interpreted in terms of a nothing-or-all-law: beyond a certain amount of 5-azacytidine incorporated into brain DNA, gene expression was impaired to an extent not compatible with the survival of the animals

  17. Postnatal pattern of ornithine decarboxylase activity reveals a disparity of rat brain regeneration capacity after prenatal X-ray or 5-azacytidine treatment

    Energy Technology Data Exchange (ETDEWEB)

    Weber, L.W.; Schmahl, W.G.

    1987-05-01

    Pregnant Wistar rats were treated on the 15th day of gestation either with 1.4 Gy X-radiation, or with 2 X 2.5 mg 5-azacytidine per kg body weight. X-irradiation caused negligible mortality among the offspring, despite of a 35% reduction of brain weights. The course of brain ornithine decarboxylase activity exhibited two breaches within 5 days after birth, each followed by recovery to control levels. After 5-azacytidine treatment brain weights were reduced by 16% only, but two thirds of the young died within a short time after birth. During three days following birth, the activity of ornithine decarboxylase in the brains of the young animals split into two ranges, a high one at control level and a low one at about one fifth of control level. As the ratio of brains with low to those with high enzyme activities correlated with the rate of postnatal mortality, the splitting of early postnatal enzyme activities was interpreted in terms of a nothing-or-all-law: beyond a certain amount of 5-azacytidine incorporated into brain DNA, gene expression was impaired to an extent not compatible with the survival of the animals.

  18. 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.)

  19. Sudden unexpected death due to severe pulmonary and cardiac sarcoidosis.

    Science.gov (United States)

    Ginelliová, Alžbeta; Farkaš, Daniel; Farkašová Iannaccone, Silvia; Vyhnálková, Vlasta

    2016-09-01

    In this paper we report the autopsy findings of a 57 year old woman who died unexpectedly at home. She had been complaining of shortness of breath, episodes of dry coughing, and nausea. Her past medical and social history was unremarkable. She had no previous history of any viral or bacterial disease and no history of oncological disorders. Autopsy revealed multiple grayish-white nodular lesions in the pleura and epicardial fat and areas resembling fibrosis on the cut surface of the anterior and posterior wall of the left ventricle and interventricular septum. Histological examination of the lungs and heart revealed multiple well-formed noncaseating epithelioid cell granulomas with multinucleated giant cells. Death was attributed to myocardial ischemia due to vasculitis of intramural coronary artery branches associated with sarcoidosis. Sarcoidosis is a multisystemic disease of unknown etiology characterized by the formation of noncaseating epithelioid cell granulomas in the affected organs and tissues. The diagnosis of sarcoidosis in this case was established when other causes of granulomatous disease such as tuberculosis, berylliosis, hypersensitivity pneumonitis, and giant cell myocarditis had been reasonably excluded. PMID:27379608

  20. Sudden, unexpected death of a 15-year-old boy due to pancarditis

    Science.gov (United States)

    Osculati, Antonio; Visonà, Silvia Damiana; Ventura, Francesco; Castelli, Francesca; Andrello, Luisa

    2016-01-01

    Abstract Background: Generally, rheumatic heart disease is, today, sporadic in developed countries, even though it continues to be a major health hazard in the developing ones. It is also a very rare cause of sudden unexpected death. We report a case of a 15-year-old boy who suddenly died at home. Since 3 days he had presented fever and chest pain. The family physician had diagnosed bronchitis and treated the boy with amoxicillin. Methods: Seven hours after death, a forensic autopsy were performed . Before the autopsy, anamnesis and some circumstantial data were collected from the boy's parents. During the autopsy, samples for histological, toxicological and molecular examinations were collected. The samples for the histology (brain, hypophysis, heart and pericardium, lungs, spleen, liver, kidney, adrenal glands) were formalin fixed and paraffin embedded. Each section was stained with Hematoxylin-Eosin. Immunostaining was also performed, with anti-CD 68, anti-CD3, anti-CD 20, anti-myeloperoxidase. Microbiological cultures were performed on cardiac blood, myocardium, pericardial effusion and cerebrospinal fluid samples collected during autopsy. Blood specimens were also processed through PCR, in order to reveal the presence of Enteroviruses, Chickenpox virus, Epstein Barr virus. Also chemical-toxicological examinations for the detection of the main medications and drugs were performed on blood samples. Results: The anamnesis, collected before the autopsy, revealed an acute pharyngitis few weeks before. The autopsy, and the following histological and immunochemical examinations suggested an immunological etiology. The immunohistochemistry, showing a strong positivity of antiCD68 antibodies, integrated with clinical-anamnestic information, leads to hypothesize a rheumatic carditis. Conclusion: In light of this case, at least 3 main messages of great importance for the clinician can be deduced. First, an accurate anamnesis collected by the family physician could have

  1. Vicarious reinforcement: Expected and unexpected effects.

    Science.gov (United States)

    Ollendick, T H; Dailey, D; Shapiro, E S

    1983-01-01

    The primary purpose of this study was to examine the effects on one child of observing another child receive direct social reinforcement. In the first part of the study, pairs of same-sex children worked on puzzles for three sessions spaced 2 to 3 days apart. One child was praised on a continuous schedule for performance, whereas the other received no praise. Although children who observed other children being praised increased their performance initially (as predicted by vicarious reinforcement and social comparison hypotheses), their performance decreased over time, reaching levels below their own baseline rates. In the second part of the study, intermittent praise delivered to the observing child was examined as a potential strategy to reverse the unexpected effects obtained in the first part of the study. Intermittent praise was found to be effective in reducing these effects and in producing enhanced performance. Individual data, as well as group data, are presented. Results are discussed in light of theoretical and applied issues related to the use of vicarious reinforcement in applied settings. PMID:16795669

  2. The Unexpected 2012 Draconid Meteor Storm

    CERN Document Server

    Ye, Quanzhi; Brown, Peter G; Campbell-Brown, Margaret D; Weryk, Robert J

    2013-01-01

    An unexpected intense outburst of the Draconid meteor shower was detected by the Canadian Meteor Orbit Radar (CMOR) on October 8, 2012. The peak flux occurred at ~16:40 UT on October 8 with a maximum of 2.4 +/- 0.3 hr-1 km-2 (appropriate to meteoroid mass larger than 10-7 kg), equivalent to a ZHRmax = 9000 +/- 1000 using 5-minute intervals, using a mass distribution index of s = 1.88 +/- 0.01 as determined from the amplitude distribution of underdense Draconid echoes. This makes the out- burst among the strongest Draconid returns since 1946 and the highest flux shower since the 1966 Leonid meteor storm, assuming a constant power-law distribution holds from radar to visual meteoroid sizes. The weighted mean geocentric radiant in the time interval of 15-19h UT, Oct 8, 2012 was {\\alpha}g = 262.4 +/- 0.1 deg, {\\delta}g = 55.7 +/- 0.1 deg (epoch J2000.0). Visual observers also reported increased activity around the peak time, but with a much lower rate (ZHR 200), suggesting that the magnitude-cumulative num- ber r...

  3. Unexpected responses to EGFR inhibition in NSCLC

    Directory of Open Access Journals (Sweden)

    Giulia M. Stella

    2015-01-01

    Full Text Available The presence of activating mutations of the epidermal growth factor receptor (EGFR-gene identifies a distinct and clinically relevant molecular subset of non-small-cell lung cancer. It is now well demonstrated that EGFR tyrosine kinase inhibitors (TKIs gefitinib and erlotinib are superior to standard chemotherapy in this subset of tumors. Nevertheless, in many cases, responses are not durable and last for 6–12 months due to the occurrence of secondary or acquired resistance. Here we present three cases of EGFR-mutant lung adenocarcinomas (ADC, that showed an unexpected response to anti-EGFR small molecules. The first patient presented a continued 89 month-long response to erlotinib in a tumor recurred after surgery and conventional chemotherapy. In the other cases, subclinically persistent tumor in the lung tissue was documented histologically in lung resections performed after partial response to TKI treatment. The persistence of interstitial and endolymphatic tumor cells after TKI treatment might explain the common observation of tumor relapse after TKI discontinuation, and sustain the decision to continue treatment in responsive patients as in our first case.

  4. Unexpected responses to EGFR inhibition in NSCLC

    Science.gov (United States)

    Stella, Giulia M.; Valizia, Claudio; Zorzetto, Michele; Inghilleri, Simona; Valentini, Adele; Dore, Roberto; Colombo, Sara; Valentino, Francesco; Orlandoni, Giulio; Morbini, Patrizia

    2015-01-01

    The presence of activating mutations of the epidermal growth factor receptor (EGFR)-gene identifies a distinct and clinically relevant molecular subset of non-small-cell lung cancer. It is now well demonstrated that EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib are superior to standard chemotherapy in this subset of tumors. Nevertheless, in many cases, responses are not durable and last for 6–12 months due to the occurrence of secondary or acquired resistance. Here we present three cases of EGFR-mutant lung adenocarcinomas (ADC), that showed an unexpected response to anti-EGFR small molecules. The first patient presented a continued 89 month-long response to erlotinib in a tumor recurred after surgery and conventional chemotherapy. In the other cases, subclinically persistent tumor in the lung tissue was documented histologically in lung resections performed after partial response to TKI treatment. The persistence of interstitial and endolymphatic tumor cells after TKI treatment might explain the common observation of tumor relapse after TKI discontinuation, and sustain the decision to continue treatment in responsive patients as in our first case. PMID:26744648

  5. 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&...

  6. Diffusion tensor imaging reveals adolescent binge ethanol-induced brain structural integrity alterations in adult rats that correlate with behavioral dysfunction.

    Science.gov (United States)

    Vetreno, Ryan P; Yaxley, Richard; Paniagua, Beatriz; Crews, Fulton T

    2016-07-01

    Adolescence is characterized by considerable brain maturation that coincides with the development of adult behavior. Binge drinking is common during adolescence and can have deleterious effects on brain maturation because of the heightened neuroplasticity of the adolescent brain. Using an animal model of adolescent intermittent ethanol [AIE; 5.0 g/kg, intragastric, 20 percent EtOH w/v; 2 days on/2 days off from postnatal day (P)25 to P55], we assessed the adult brain structural volumes and integrity on P80 and P220 using diffusion tensor imaging (DTI). While we did not observe a long-term effect of AIE on structural volumes, AIE did reduce axial diffusivity (AD) in the cerebellum, hippocampus and neocortex. Radial diffusivity (RD) was reduced in the hippocampus and neocortex of AIE-treated animals. Prior AIE treatment did not affect fractional anisotropy (FA), but did lead to long-term reductions of mean diffusivity (MD) in both the cerebellum and corpus callosum. AIE resulted in increased anxiety-like behavior and diminished object recognition memory, the latter of which was positively correlated with DTI measures. Across aging, whole brain volumes increased, as did volumes of the corpus callosum and neocortex. This was accompanied by age-associated AD reductions in the cerebellum and neocortex as well as RD and MD reductions in the cerebellum. Further, we found that FA increased in both the cerebellum and corpus callosum as rats aged from P80 to P220. Thus, both age and AIE treatment caused long-term changes to brain structural integrity that could contribute to cognitive dysfunction. PMID:25678360

  7. 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...... (Bcl-2 and Bax) were analyzed in selected brain regions. CLPE showed significant improvement in survival compared with CLPV 18 h postinduction of sepsis (P ... induced by cecal ligation alters cerebral redox status and supports a proapoptotic phenotype. The free radical scavenger edavarone reduces mortality of septic mice and protects against sepsis-induced neuronal cell death....

  8. Brain MRI of diabetes Mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Araki, Yutaka; Tanaka, Hisashi; Ohtani, Masatoshi; Yamamoto, Hiroshi; Yamamoto, Tadashi; Tsukaguchi, Isao (Osaka Rosai Hospital, Sakai (Japan))

    1993-11-01

    One hundred and fifty-nine patients with diabetes mellitus (DM) and 2,566 patients without DM were studied on brain MRI. The results taught us that the incidence of cerebral atrophy was significantly higher in DM patients than in controls. Unexpectedly, the incidence of cerebral infarction showed no significant difference between the two groups. (author).

  9. Brain MRI of diabetes Mellitus

    International Nuclear Information System (INIS)

    One hundred and fifty-nine patients with diabetes mellitus (DM) and 2,566 patients without DM were studied on brain MRI. The results taught us that the incidence of cerebral atrophy was significantly higher in DM patients than in controls. Unexpectedly, the incidence of cerebral infarction showed no significant difference between the two groups. (author)

  10. Unexpected allergic reactions to food, a prospective study

    NARCIS (Netherlands)

    Michelsen-Huisman, A.D.; Os-Medendorp, H. van; Versluis, A.; Kruizinga, A.G.; Castenmiller, J.J.M.; Noteborn, H.P.J.M.; Houben, G.F.; Knulst, A.C.

    2013-01-01

    Unexpected reactions occur in patients with food allergy, but frequency data are scare. This prospective study investigates the frequency, severity and causes of unexpected allergic reactions to food in adults with a doctor's diagnosed food allergy. Participants complete an online questionnaire afte

  11. Discovering novel microRNAs and age-related nonlinear changes in rat brains using deep sequencing.

    Science.gov (United States)

    Yin, Lanxuan; Sun, Yubai; Wu, Jinfeng; Yan, Siyu; Deng, Zhenglu; Wang, Jun; Liao, Shenke; Yin, Dazhong; Li, Guolin

    2015-02-01

    Elucidating the molecular mechanisms of brain aging remains a significant challenge for biogerontologists. The discovery of gene regulation by microRNAs (miRNAs) has added a new dimension for examining this process; however, the full complement of miRNAs involved in brain aging is still not known. In this study, miRNA profiles of young, adult, and old rats were obtained to evaluate molecular changes during aging. High-throughput deep sequencing revealed 547 known and 171 candidate novel miRNAs that were differentially expressed among groups. Unexpectedly, miRNA expression did not decline progressively with advancing age; moreover, genes targeted by age-associated miRNAs were predicted to be involved in biological processes linked to aging and neurodegenerative diseases. These findings provide novel insight into the molecular mechanisms underlying brain aging and a resource for future studies on age-related brain disorders.

  12. 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....

  13. Genome-wide DNA methylation analyses in the brain reveal four differentially methylated regions between humans and non-human primates

    Directory of Open Access Journals (Sweden)

    Wang Jinkai

    2012-08-01

    Full Text Available Abstract Background The highly improved cognitive function is the most significant change in human evolutionary history. Recently, several large-scale studies reported the evolutionary roles of DNA methylation; however, the role of DNA methylation on brain evolution is largely unknown. Results To test if DNA methylation has contributed to the evolution of human brain, with the use of MeDIP-Chip and SEQUENOM MassARRAY, we conducted a genome-wide analysis to identify differentially methylated regions (DMRs in the brain between humans and rhesus macaques. We first identified a total of 150 candidate DMRs by the MeDIP-Chip method, among which 4 DMRs were confirmed by the MassARRAY analysis. All 4 DMRs are within or close to the CpG islands, and a MIR3 repeat element was identified in one DMR, but no repeat sequence was observed in the other 3 DMRs. For the 4 DMR genes, their proteins tend to be conserved and two genes have neural related functions. Bisulfite sequencing and phylogenetic comparison among human, chimpanzee, rhesus macaque and rat suggested several regions of lineage specific DNA methylation, including a human specific hypomethylated region in the promoter of K6IRS2 gene. Conclusions Our study provides a new angle of studying human brain evolution and understanding the evolutionary role of DNA methylation in the central nervous system. The results suggest that the patterns of DNA methylation in the brain are in general similar between humans and non-human primates, and only a few DMRs were identified.

  14. MaxiK channel interactome reveals its interaction with GABA transporter 3 and heat shock protein 60 in the mammalian brain.

    Science.gov (United States)

    Singh, H; Li, M; Hall, L; Chen, S; Sukur, S; Lu, R; Caputo, A; Meredith, A L; Stefani, E; Toro, L

    2016-03-11

    Large conductance voltage and calcium-activated potassium (MaxiK) channels are activated by membrane depolarization and elevated cytosolic Ca(2+). In the brain, they localize to neurons and astrocytes, where they play roles such as resetting the membrane potential during an action potential, neurotransmitter release, and neurovascular coupling. MaxiK channels are known to associate with several modulatory proteins and accessory subunits, and each of these interactions can have distinct physiological consequences. To uncover new players in MaxiK channel brain physiology, we applied a directed proteomic approach and obtained MaxiK channel pore-forming α subunit brain interactome using specific antibodies. Controls included immunoprecipitations with rabbit immunoglobulin G (IgG) and with anti-MaxiK antibodies in wild type and MaxiK channel knockout mice (Kcnma1(-/-)), respectively. We have found known and unreported interactive partners that localize to the plasma membrane, extracellular space, cytosol and intracellular organelles including mitochondria, nucleus, endoplasmic reticulum and Golgi apparatus. Localization of MaxiK channel to mitochondria was further confirmed using purified brain mitochondria colabeled with MitoTracker. Independent proof of MaxiK channel interaction with previously unidentified partners is given for GABA transporter 3 (GAT3) and heat shock protein 60 (HSP60). In human embryonic kidney 293 cells containing SV40 T-antigen (HEK293T) cells, both GAT3 and HSP60 coimmunoprecipitated and colocalized with MaxiK channel; colabeling was observed mainly at the cell periphery with GAT3 and intracellularly with HSP60 with protein proximity indices of ∼ 0.6 and ∼ 0.4, respectively. In rat primary hippocampal neurons, colocalization index was identical for GAT3 (∼ 0.6) and slightly higher for HSP60 (∼ 0.5) association with MaxiK channel. The results of this study provide a complete interactome of MaxiK channel the mouse brain, further establish

  15. MaxiK channel interactome reveals its interaction with GABA transporter 3 and heat shock protein 60 in the mammalian brain.

    Science.gov (United States)

    Singh, H; Li, M; Hall, L; Chen, S; Sukur, S; Lu, R; Caputo, A; Meredith, A L; Stefani, E; Toro, L

    2016-03-11

    Large conductance voltage and calcium-activated potassium (MaxiK) channels are activated by membrane depolarization and elevated cytosolic Ca(2+). In the brain, they localize to neurons and astrocytes, where they play roles such as resetting the membrane potential during an action potential, neurotransmitter release, and neurovascular coupling. MaxiK channels are known to associate with several modulatory proteins and accessory subunits, and each of these interactions can have distinct physiological consequences. To uncover new players in MaxiK channel brain physiology, we applied a directed proteomic approach and obtained MaxiK channel pore-forming α subunit brain interactome using specific antibodies. Controls included immunoprecipitations with rabbit immunoglobulin G (IgG) and with anti-MaxiK antibodies in wild type and MaxiK channel knockout mice (Kcnma1(-/-)), respectively. We have found known and unreported interactive partners that localize to the plasma membrane, extracellular space, cytosol and intracellular organelles including mitochondria, nucleus, endoplasmic reticulum and Golgi apparatus. Localization of MaxiK channel to mitochondria was further confirmed using purified brain mitochondria colabeled with MitoTracker. Independent proof of MaxiK channel interaction with previously unidentified partners is given for GABA transporter 3 (GAT3) and heat shock protein 60 (HSP60). In human embryonic kidney 293 cells containing SV40 T-antigen (HEK293T) cells, both GAT3 and HSP60 coimmunoprecipitated and colocalized with MaxiK channel; colabeling was observed mainly at the cell periphery with GAT3 and intracellularly with HSP60 with protein proximity indices of ∼ 0.6 and ∼ 0.4, respectively. In rat primary hippocampal neurons, colocalization index was identical for GAT3 (∼ 0.6) and slightly higher for HSP60 (∼ 0.5) association with MaxiK channel. The results of this study provide a complete interactome of MaxiK channel the mouse brain, further establish

  16. 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

    in dendrites. The in vivo roles of microRNAs in these processes are still uninvestigated, partly due to the lack of tools enabling stable in vivo delivery of microRNAs or microRNA inhibitors into neurons of the mammalian brain. Here we describe the construction and validation of a vector-based tool for stable...... 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...

  17. 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.

  18. Competition can lead to unexpected patterns in tropical ant communities

    Science.gov (United States)

    Ellwood, M. D. Farnon; Blüthgen, Nico; Fayle, Tom M.; Foster, William A.; Menzel, Florian

    2016-08-01

    Ecological communities are structured by competitive, predatory, mutualistic and parasitic interactions combined with chance events. Separating deterministic from stochastic processes is possible, but finding statistical evidence for specific biological interactions is challenging. We attempt to solve this problem for ant communities nesting in epiphytic bird's nest ferns (Asplenium nidus) in Borneo's lowland rainforest. By recording the frequencies with which each and every single ant species occurred together, we were able to test statistically for patterns associated with interspecific competition. We found evidence for competition, but the resulting co-occurrence pattern was the opposite of what we expected. Rather than detecting species segregation-the classical hallmark of competition-we found species aggregation. Moreover, our approach of testing individual pairwise interactions mostly revealed spatially positive rather than negative associations. Significant negative interactions were only detected among large ants, and among species of the subfamily Ponerinae. Remarkably, the results from this study, and from a corroborating analysis of ant communities known to be structured by competition, suggest that competition within the ants leads to species aggregation rather than segregation. We believe this unexpected result is linked with the displacement of species following asymmetric competition. We conclude that analysing co-occurrence frequencies across complete species assemblages, separately for each species, and for each unique pairwise combination of species, represents a subtle yet powerful way of detecting structure and compartmentalisation in ecological communities.

  19. Revealing Rembrandt

    Directory of Open Access Journals (Sweden)

    Andrew J Parker

    2014-04-01

    Full Text Available The power and significance of artwork in shaping human cognition is self-evident. The starting point for our empirical investigations is the view that the task of neuroscience is to integrate itself with other forms of knowledge, rather than to seek to supplant them. In our recent work, we examined a particular aspect of the appreciation of artwork using present-day functional magnetic resonance imaging (fMRI. Our results emphasised the continuity between viewing artwork and other human cognitive activities. We also showed that appreciation of a particular aspect of artwork, namely authenticity, depends upon the co-ordinated activity between the brain regions involved in multiple decision making and those responsible for processing visual information. The findings about brain function probably have no specific consequences for understanding how people respond to the art of Rembrandt in comparison with their response to other artworks. However, the use of images of Rembrandt’s portraits, his most intimate and personal works, clearly had a significant impact upon our viewers, even though they have been spatially confined to the interior of an MRI scanner at the time of viewing. Neuroscientific studies of humans viewing artwork have the capacity to reveal the diversity of human cognitive responses that may be induced by external advice or context as people view artwork in a variety of frameworks and settings.

  20. Deep brain stimulation reveals a dissociation of consummatory and motivated behaviour in the medial and lateral nucleus accumbens shell of the rat

    OpenAIRE

    Geoffrey van der Plasse; Regina Schrama; van Seters, Sebastiaan P.; Vanderschuren, Louk J. M. J.; Westenberg, Herman G. M.

    2012-01-01

    Following the successful application of deep brain stimulation (DBS) in the treatment of Parkinson's disease and promising results in clinical trials for obsessive compulsive disorder and major depression, DBS is currently being tested in small patient-populations with eating disorders and addiction. However, in spite of its potential use in a broad spectrum of disorders, the mechanisms of action of DBS remain largely unclear and optimal neural targets for stimulation in several disorders hav...

  1. Abnormal intrinsic brain activity in amnestic mild cognitive impairment revealed by amplitude of low-frequency fluctuation: a resting-state functional magnetic resonance imaging study

    Institute of Scientific and Technical Information of China (English)

    XI Qian; ZHAO Xiao-hu; WANG Pei-jun; GUO Qi-hao; HE Yong

    2013-01-01

    Background Previous studies have shown that brain functional activity in the resting state is impaired in Alzheimer's disease (AD) patients.However,alterations in intrinsic brain activity patterns in mild cognitive impairment (MCI) patients are poorly understood.This study aimed to explore the differences in regional intrinsic activities throughout the whole brain between aMCI patients and controls.Methods In the present study,resting-state functional magnetic resonance imaging (fMRI) was performed on 18 amnestic MCI (aMCI) patients,18 mild AD patients and 20 healthy elderly subjects.And amplitude of low-frequency fluctuation (ALFF) method was used.Results Compared with healthy elderly subjects,aMCI patients showed decreased ALFF in the right hippocampus and parahippocampal cortex,left lateral temporal cortex,and right ventral medial prefrontal cortex (vMPFC) and increased ALFF in the left temporal-parietal junction (TPJ) and inferior parietal Iobule (IPL).Mild AD patients showed decreased ALFF in the left TPJ,posterior IPL (plPL),and dorsolateral prefrontal cortex compared with aMCI patients.Mild AD patients also had decreased ALFF in the right posterior cingulate cortex,right vMPFC and bilateral dorsal MPFC (dMPFC) compared with healthy elderly subjects.Conclusions Decreased intrinsic activities in brain regions closely related to episodic memory were found in aMCI and AD patients.Increased TPJ and IPL activity may indicate compensatory mechanisms for loss of memory function in aMCI patients.These findings suggest that the fMRI based on ALFF analysis may provide a useful tool in the study of aMCI patients.

  2. Alteration of Cortical Functional Connectivity as a Result of Traumatic Brain Injury Revealed by Graph Theory, ICA, and sLORETA Analyses of EEG Signals

    OpenAIRE

    Cao, C.; Slobounov, S.

    2009-01-01

    In this paper, a novel approach to examine the cortical functional connectivity using multichannel electroen-cephalographic (EEG) signals is proposed. First we utilized independent component analysis (ICA) to transform multichannel EEG recordings into independent processes and then applied source reconstruction algorithm [i.e., standardize low resolution brain electromagnetic (sLORETA)] to identify the cortical regions of interest (ROIs). Second, we performed a graph theory analysis of the bi...

  3. Dynamic changes in glucose metabolism of living rat brain slices induced by hypoxia and neurotoxic chemical-loading revealed by positron autoradiography

    International Nuclear Information System (INIS)

    Fresh rat brain slices were incubated with 2-deoxy-2-[18F]-fluoro-D-glucose ([18F]FDG) in oxygenated Krebs-Ringer solution at 36 degree C, and serial two-dimensional time-resolved images of [18F]FDG uptake were obtained from these specimens on imaging plates. The fractional rate constant (= k3*) of [18F]FDG proportional to the cerebral glucose metabolic rate (CMRglc) was evaluated by applying the Gjedde-Patlak graphical method to the image data. With hypoxia loading (oxygen deprivation) or glucose metabolism inhibitors acting on oxidative phosphorylation, the k3* value increased dramatically suggesting enhanced glycolysis. After relieving hypoxia ≤10-min, the k3* value returned to the pre-loading level. In contrast, with ≥20-min hypoxia only partial or no recovery was observed, indicating that irreversible neuronal damage had been induced. However, after loading with tetrodotoxin (TTX), the k3* value also decreased but returned to the pre-loading level even after 70-min TTX-loading, reflecting a transient inhibition of neuronal activity. This technique provides a new means of quantifying dynamic changes in the regional CMRglc in living brain slices in response to various interventions such as hypoxia and neurotoxic chemical-loading as well as determining the viability and prognosis of brain tissues. (author)

  4. Alteration of cortical functional connectivity as a result of traumatic brain injury revealed by graph theory, ICA, and sLORETA analyses of EEG signals.

    Science.gov (United States)

    Cao, C; Slobounov, S

    2010-02-01

    In this paper, a novel approach to examine the cortical functional connectivity using multichannel electroencephalographic (EEG) signals is proposed. First we utilized independent component analysis (ICA) to transform multichannel EEG recordings into independent processes and then applied source reconstruction algorithm [i.e., standardize low resolution brain electromagnetic (sLORETA)] to identify the cortical regions of interest (ROIs). Second, we performed a graph theory analysis of the bipartite network composite of ROIs and independent processes to assess the connectivity between ROIs. We applied this proposed algorithm and compared the functional connectivity network properties under resting state condition using 29 student-athletes prior to and shortly after sport-related mild traumatic brain injury (MTBI). The major findings of interest are the following. There was 1) alterations in vertex degree at frontal and occipital regions in subjects suffering from MTBI, ( p world network configuration in MTBI subjects. These major findings are discussed in relation to current debates regarding the brain functional connectivity within and between local and distal regions both in normal controls in pathological subjects. PMID:20064767

  5. Audit of practice in sudden unexpected death in epilepsy (SUDEP) post mortems and neuropathological findings

    Science.gov (United States)

    Michalak, Zuzanna; Wright, Gabriella; Dawson, Timothy; Hilton, David; Joshi, Abhijit; Diehl, Beate; Koepp, Matthias; Lhatoo, Samden; Sander, Josemir W.; Sisodiya, Sanjay M.

    2015-01-01

    Aims Sudden unexpected death in epilepsy (SUDEP) is one of the leading causes of death in people with epilepsy. For classification of definite SUDEP, a post mortem (PM), including anatomical and toxicological examination, is mandatory to exclude other causes of death. We audited PM practice as well as the value of brain examination in SUDEP. Methods We reviewed 145 PM reports in SUDEP cases from four UK neuropathology centres. Data were extracted for clinical epilepsy details, circumstances of death and neuropathological findings. Results Macroscopic brain abnormalities were identified in 52% of cases. Mild brain swelling was present in 28%, and microscopic pathologies relevant to cause or effect of seizures were seen in 89%. Examination based on whole fixed brains (76.6% of all PMs), and systematic regional sampling was associated with higher detection rates of underlying pathology (P < 0.01). Information was more frequently recorded regarding circumstances of death and body position/location than clinical epilepsy history and investigations. Conclusion Our findings support the contribution of examination of the whole fixed brain in SUDEP, with high rates of detection of relevant pathology. Availability of full clinical epilepsy‐related information at the time of PM could potentially further improve detection through targeted tissue sampling. Apart from confirmation of SUDEP, complete neuropathological examination contributes to evaluation of risk factors as well as helping to direct future research into underlying causes. PMID:26300477

  6. Acute toxicity profile of cadmium revealed by proteomics in brain tissue of Paralichthys olivaceus: Potential role of transferrin in cadmium toxicity

    International Nuclear Information System (INIS)

    An analytical approach using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) separated proteins from the brain tissue of the fish Paralichthys olivaceus. Approximately 600 protein spots were detected from the brain sample when applying 600 μg protein to a 2D-PAGE gel in the pH range 3.5-10.0. Compared to a control sample, significant changes of 24 protein spots were observed in the fish tissue exposed to acute toxicity of seawater cadmium (SCAT) at 10 ppm for 24 h. Among these spots, nine were down-regulated, nine were up-regulated, two showed high expression, and four showed low expression. The collected spots were identified by peptide mass fingerprinting (PMF) and database search, and they were further classified by LOCtree, a hierarchical system of support vector machines which predict their sub-cellular localization. The amount of transferrin expression in brain cells decreased linearly with the increase of SCAT concentration in seawater. Among the 24 proteins identified on a 2D-PAGE gel, 9 demonstrated a synchronous response to acute cadmium, suggesting that they might represent a biomarker profile. Based on their variable levels and trends on the 2D-PAGE gel this protein (likely to be transferrin) suggesting they might be utilized as biomarkers to investigate cadmium pollution levels in seawater and halobios survival, as well as to evaluate the degree of risk of human fatalities. The results indicate that the application of multiple biomarkers has an advantage over a single biomarker for monitoring levels of environmental contamination

  7. Forward shift of feeding buzz components of dolphins and belugas during associative learning reveals a likely connection to reward expectation, pleasure and brain dopamine activation.

    Science.gov (United States)

    Ridgway, S H; Moore, P W; Carder, D A; Romano, T A

    2014-08-15

    For many years, we heard sounds associated with reward from dolphins and belugas. We named these pulsed sounds victory squeals (VS), as they remind us of a child's squeal of delight. Here we put these sounds in context with natural and learned behavior. Like bats, echolocating cetaceans produce feeding buzzes as they approach and catch prey. Unlike bats, cetaceans continue their feeding buzzes after prey capture and the after portion is what we call the VS. Prior to training (or conditioning), the VS comes after the fish reward; with repeated trials it moves to before the reward. During training, we use a whistle or other sound to signal a correct response by the animal. This sound signal, named a secondary reinforcer (SR), leads to the primary reinforcer, fish. Trainers usually name their whistle or other SR a bridge, as it bridges the time gap between the correct response and reward delivery. During learning, the SR becomes associated with reward and the VS comes after the SR rather than after the fish. By following the SR, the VS confirms that the animal expects a reward. Results of early brain stimulation work suggest to us that SR stimulates brain dopamine release, which leads to the VS. Although there are no direct studies of dopamine release in cetaceans, we found that the timing of our VS is consistent with a response after dopamine release. We compared trained vocal responses to auditory stimuli with VS responses to SR sounds. Auditory stimuli that did not signal reward resulted in faster responses by a mean of 151 ms for dolphins and 250 ms for belugas. In laboratory animals, there is a 100 to 200 ms delay for dopamine release. VS delay in our animals is similar and consistent with vocalization after dopamine release. Our novel observation suggests that the dopamine reward system is active in cetacean brains. PMID:25122919

  8. 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.

  9. 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......, the HGPS mutation results in organ-specific defects. For example, bone and skin are strongly affected by HGPS, while the brain appears to be unaffected. There are no definite explanations as to the variable sensitivity to progeria disease among different organs. In addition, low levels of progerin have...

  10. Causes and consequences of unexpected educational transitions in Switzerland

    OpenAIRE

    Neuenschwander, M P; Garrett, J L

    2008-01-01

    The present study examines transition patterns of Swiss secondary and tertiary school students. Switzerland's highly canalized education system allows us to test how tracking affects person-environment fit of students for students who choose a normative versus unexpected downward transition pattern. In addition, we investigate how self-efficacy expectations and personal values affect an unexpected transition choice. Results indicate that students with strong expectancies and personal values c...

  11. (Un)Expected Retirement and the Consumption Puzzle

    OpenAIRE

    Margherita Borella; Flavia Coda Moscarola; Mariacristina Rossi

    2011-01-01

    In this work we revisit the retirement consumption puzzle using Italian panel data. As emphasized in the literature, the observed consumption drop might be due to unexpected wealth shocks at retirement, which modify optimal consumption plans. Using an Euler equation approach, we test the impact of unexpected retirement on the consumption patterns of individuals around the age of retirement by using the panel component of the Survey of Household Income and Wealth (SHIW). This data set contains...

  12. Metabolomic Analyses of Brain Tissue in Sepsis Induced by Cecal Ligation Reveal Specific Redox Alterations--Protective Effects of the Oxygen Radical Scavenger Edaravone.

    Science.gov (United States)

    Hara, Naomi; Chijiiwa, Miyuki; Yara, Miki; Ishida, Yusuke; Ogiwara, Yukihiko; Inazu, Masato; Kuroda, Masahiko; Karlsson, Michael; Sjovall, Fredrik; Elmér, Eskil; Uchino, Hiroyuki

    2015-12-01

    The pathophysiology of sepsis-associated encephalopathy (SAE) is complex and remains incompletely elucidated. Dysregulated reactive oxygen species (ROS) production and mitochondrial-mediated necrotic-apoptotic pathway have been proposed as part of the pathogenesis. The present study aimed 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), and sham-operated (Sham). Mice in CLPV and CLPE were injected with saline or edaravone intraperitoneally at a dose of 10 mg/kg twice daily. The treatments were initiated 4 days prior to the surgical procedure. Mortality, histological changes, electron microscopy (EM), and expression of Bcl-2 family genes (Bcl-2 and Bax) were analyzed in selected brain regions. CLPE showed significant improvement in survival compared with CLPV 18 h postinduction of sepsis (P free radical scavenger edavarone reduces mortality of septic mice and protects against sepsis-induced neuronal cell death.

  13. Metabolomic Profiling of Post-Mortem Brain Reveals Changes in Amino Acid and Glucose Metabolism in Mental Illness Compared with Controls.

    Science.gov (United States)

    Zhang, Rong; Zhang, Tong; Ali, Ali Muhsen; Al Washih, Mohammed; Pickard, Benjamin; Watson, David G

    2016-01-01

    Metabolomic profiling was carried out on 53 post-mortem brain samples from subjects diagnosed with schizophrenia, depression, bipolar disorder (SDB), diabetes, and controls. Chromatography on a ZICpHILIC column was used with detection by Orbitrap mass spectrometry. Data extraction was carried out with m/z Mine 2.14 with metabolite searching against an in-house database. There was no clear discrimination between the controls and the SDB samples on the basis of a principal components analysis (PCA) model of 755 identified or putatively identified metabolites. Orthogonal partial least square discriminant analysis (OPLSDA) produced clear separation between 17 of the controls and 19 of the SDB samples (R2CUM 0.976, Q2 0.671, p-value of the cross-validated ANOVA score 0.0024). The most important metabolites producing discrimination were the lipophilic amino acids leucine/isoleucine, proline, methionine, phenylalanine, and tyrosine; the neurotransmitters GABA and NAAG and sugar metabolites sorbitol, gluconic acid, xylitol, ribitol, arabinotol, and erythritol. Eight samples from diabetic brains were analysed, six of which grouped with the SDB samples without compromising the model (R2 CUM 0.850, Q2 CUM 0.534, p-value for cross-validated ANOVA score 0.00087). There appears on the basis of this small sample set to be some commonality between metabolic perturbations resulting from diabetes and from SDB. PMID:27076878

  14. Performance of cumulant-based rank reduction estimator in presence of unexpected modeling errors

    Institute of Scientific and Technical Information of China (English)

    王鼎

    2015-01-01

    Compared with the rank reduction estimator (RARE) based on second-order statistics (called SOS-RARE), the RARE based on fourth-order cumulants (referred to as FOC-RARE) can handle more sources and restrain the negative impacts of the Gaussian colored noise. However, the unexpected modeling errors appearing in practice are known to significantly degrade the performance of the RARE. Therefore, the direction-of-arrival (DOA) estimation performance of the FOC-RARE is quantitatively derived. The explicit expression for direction-finding (DF) error is derived via the first-order perturbation analysis, and then the theoretical formula for the mean square error (MSE) is given. Simulation results demonstrate the validation of the theoretical analysis and reveal that the FOC-RARE is more robust to the unexpected modeling errors than the SOS-RARE.

  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. 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

  17. Brain Basics

    Medline Plus

    Full Text Available ... News 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 ...

  18. Brain Basics

    Science.gov (United States)

    ... News 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 ...

  19. 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 ...

  20. Spontaneous brain activity in type 2 diabetics revealed by amplitude of low-frequency fluctuations and its association with diabetic vascular disease: a resting-state FMRI study.

    Directory of Open Access Journals (Sweden)

    Chun-Xia Wang

    Full Text Available To investigate correlations between altered spontaneous brain activity, diabetic vascular disease, and cognitive function for patients with type 2 diabetes mellitus (T2DM using resting-state functional magnetic resonance imaging (rs-fMRI.Rs-fMRI was performed for T2DM patients (n = 26 and age-, gender-, and education-matched non-diabetic control subjects (n = 26. Amplitude of low frequency fluctuations (ALFF were computed from fMRI signals to measure spontaneous neuronal activity. Differences in the ALFF patterns between patients and controls, as well as their correlations with clinical variables, were evaluated.Compared with healthy controls, T2DM patients exhibited significantly decreased ALFF values mainly in the frontal and parietal lobes, the bilateral thalumi, the posterior lobe of the cerebellum, and increased ALFF values mainly in the visual cortices. Furthermore, lower ALFF values in the left subcallosal gyrus correlated with lower ankle-brachial index values (r = 0.481, p = 0.020, while lower ALFF values in the bilateral medial prefrontal gyri correlated with higher urinary albumin-creatinine ratio (r =  -0.418, p = 0.047. In addition, most of the regions with increased ALFF values in the visual cortices were found to negatively correlate with MoCA scores.These results confirm that ALFF are altered in many brain regions in T2DM patients, and this is associated with the presence of diabetic vascular disease and poor cognitive performance. These findings may provide additional insight into the neurophysiological mechanisms that mediate T2DM-related cognitive dysfunction, and may also serve as a reference for future research.

  1. 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

  2. Brains studying brains: look before you think in vision

    Science.gov (United States)

    Zhaoping, Li

    2016-06-01

    Using our own brains to study our brains is extraordinary. For example, in vision this makes us naturally blind to our own blindness, since our impression of seeing our world clearly is consistent with our ignorance of what we do not see. Our brain employs its ‘conscious’ part to reason and make logical deductions using familiar rules and past experience. However, human vision employs many ‘subconscious’ brain parts that follow rules alien to our intuition. Our blindness to our unknown unknowns and our presumptive intuitions easily lead us astray in asking and formulating theoretical questions, as witnessed in many unexpected and counter-intuitive difficulties and failures encountered by generations of scientists. We should therefore pay a more than usual amount of attention and respect to experimental data when studying our brain. I show that this can be productive by reviewing two vision theories that have provided testable predictions and surprising insights.

  3. Vigilance Task-Related Change in Brain Functional Connectivity as Revealed by Wavelet Phase Coherence Analysis of Near-Infrared Spectroscopy Signals.

    Science.gov (United States)

    Wang, Wei; Wang, Bitian; Bu, Lingguo; Xu, Liwei; Li, Zengyong; Fan, Yubo

    2016-01-01

    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 min (Task t1) and the second 10 min (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 (RT) 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 per 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. PMID:27547182

  4. 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.

  5. Vigilance Task-Related Change in Brain Functional Connectivity as Revealed by Wavelet Phase Coherence Analysis of Near-Infrared Spectroscopy Signals

    Science.gov (United States)

    Wang, Wei; Wang, Bitian; Bu, Lingguo; Xu, Liwei; Li, Zengyong; Fan, Yubo

    2016-01-01

    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 min (Task t1) and the second 10 min (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 (RT) 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 per 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. PMID:27547182

  6. The thermal properties of beeswaxes: unexpected findings.

    Science.gov (United States)

    Buchwald, Robert; Breed, Michael D; Greenberg, Alan R

    2008-01-01

    Standard melting point analyses only partially describe the thermal properties of eusocial beeswaxes. Differential scanning calorimetry (DSC) revealed that thermal phase changes in wax are initiated at substantially lower temperatures than visually observed melting points. Instead of a sharp, single endothermic peak at the published melting point of 64 degrees C, DSC analysis of Apis mellifera Linnaeus wax yielded a broad melting curve that showed the initiation of melting at approximately 40 degrees C. Although Apis beeswax retained a solid appearance at these temperatures, heat absorption and initiation of melting could affect the structural characteristics of the wax. Additionally, a more complete characterization of the thermal properties indicated that the onset of melting, melting range and heat of fusion of beeswaxes varied significantly among tribes of social bees (Bombini, Meliponini, Apini). Compared with other waxes examined, the relatively malleable wax of bumblebees (Bombini) had the lowest onset of melting and lowest heat of fusion but an intermediate melting temperature range. Stingless bee (Meliponini) wax was intermediate between bumblebee and honeybee wax (Apini) in heat of fusion, but had the highest onset of melting and the narrowest melting temperature range. The broad melting temperature range and high heat of fusion in the Apini may be associated with the use of wax comb as a free-hanging structural material, while the Bombini and Meliponini support their wax structures with exogenous materials. PMID:18083740

  7. 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 ...

  8. Heterogeneous intracellular trafficking dynamics of brain-derived neurotrophic factor complexes in the neuronal soma revealed by single quantum dot tracking.

    Directory of Open Access Journals (Sweden)

    Anke Vermehren-Schmaedick

    Full Text Available Accumulating evidence underscores the importance of ligand-receptor dynamics in shaping cellular signaling. In the nervous system, growth factor-activated Trk receptor trafficking serves to convey biochemical signaling that underlies fundamental neural functions. Focus has been placed on axonal trafficking but little is known about growth factor-activated Trk dynamics in the neuronal soma, particularly at the molecular scale, due in large part to technical hurdles in observing individual growth factor-Trk complexes for long periods of time inside live cells. Quantum dots (QDs are intensely fluorescent nanoparticles that have been used to study the dynamics of ligand-receptor complexes at the plasma membrane but the value of QDs for investigating ligand-receptor intracellular dynamics has not been well exploited. The current study establishes that QD conjugated brain-derived neurotrophic factor (QD-BDNF binds to TrkB receptors with high specificity, activates TrkB downstream signaling, and allows single QD tracking capability for long recording durations deep within the soma of live neurons. QD-BDNF complexes undergo internalization, recycling, and intracellular trafficking in the neuronal soma. These trafficking events exhibit little time-synchrony and diverse heterogeneity in underlying dynamics that include phases of sustained rapid motor transport without pause as well as immobility of surprisingly long-lasting duration (several minutes. Moreover, the trajectories formed by dynamic individual BDNF complexes show no apparent end destination; BDNF complexes can be found meandering over long distances of several microns throughout the expanse of the neuronal soma in a circuitous fashion. The complex, heterogeneous nature of neuronal soma trafficking dynamics contrasts the reported linear nature of axonal transport data and calls for models that surpass our generally limited notions of nuclear-directed transport in the soma. QD-ligand probes are

  9. Reading the dyslexic brain: multiple dysfunctional routes revealed by a new meta-analysis of PET and fMRI activation studies

    Directory of Open Access Journals (Sweden)

    Eraldo ePaulesu

    2014-11-01

    Full Text Available Developmental dyslexia has been the focus of much functional anatomical research. The main trust of this work is that typical developmental dyslexics have a dysfunction of the phonological and orthography to phonology conversion systems, in which the left occipito-temporal cortex has a crucial role. It remains to be seen whether there is a systematic co-occurrence of dysfunctional patterns of different functional systems perhaps converging on the same brain regions associated with the reading deficit. Such evidence would be relevant for theories like, for example, the magnocellular/attentional or the motor/cerebellar ones, which postulate a more basic and anatomically distributed disorder in dyslexia. We addressed this issue with a meta-analysis of all the imaging literature published until September 2013 using a combination of hierarchical clustering and activation likelihood estimates. The clustering analysis on 2360 peaks identified 193 clusters, 92 of which proved significant for spatial extent. Following binomial tests on the clusters, we found left hemispheric network specific for normal controls (i.d. of reduced involvement in dyslexics involving the left inferior frontal, premotor, supramarginal cortices and the left infero-temporal and fusiform region: these were specific for reading and the visual-to-phonology processes. There was also a more dorsal left fronto-parietal network: these clusters included peaks from tasks involving phonological manipulation, but also motoric or visuo-spatial perception/attention. No cluster was identified in area V5 for no task, nor in cerebellar clusters either.We conclude that the available literature demonstrates a specific lack of activation of the left occipitotemporal cortex in dyslexics that is specific for reading and reading-like behaviours and for visuo-phonological tasks. Additional deficits may be associated with altered functionality of dorsal fronto-parietal cortex.

  10. 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.

  11. 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.

  12. Sudden unexpected nocturnal death in Chiari type 1 malformation and potential role of opioid analgesics

    Directory of Open Access Journals (Sweden)

    Fereydoon Roohi

    2014-01-01

    Full Text Available Background: Chiari malformation type 1 (CM1 is a common congenital anomaly of the craniocervical junction. CM1 is reported to run a usually benign course and patients typically experience no symptoms or chronic, slowly progressive symptoms. However, recent reports indicate that a subset of patients with CM1 may present with acute deterioration and sudden unexpected death (SUD. We report a case of SUD during sleep in a young man with CM1, which we believe was related to the administration of common and therapeutic doses of narcotic analgesics for the management of pain. We will clarify the pathophysiology of acute deterioration and SUD in CM1 and the possibility that the adverse effects of opiate analgesics likely were the leading cause of death in our patient. Case Description: In this review, we present a 29-year-old male with worsening headache secondary to previously diagnosed CM1. The patient died suddenly and unexpectedly after administration of common and therapeutic doses of narcotic analgesics for the management of pain. Conclusion: The mechanism(s of acute neurological deterioration and sudden death in patients with CM1 remains poorly understood. We believe the rapid fatal deterioration in our patient following administration of opioids suggests that this category of medication may cause sudden unexpected "neurogenic" cardiac death in CM1 patients by inducing sleep-related breathing difficulties and associated hypercapnia. Hypercapnia by further increasing intracranial pressure can result in a sudden pressure-induced decompensation of the cardiopulmonary control centers in the brain stem and cause instantaneous cardiorespiratory arrest.

  13. Attentional gain and processing capacity limits predict the propensity to neglect unexpected visual stimuli.

    Science.gov (United States)

    Papera, Massimiliano; Richards, Anne

    2016-05-01

    Exogenous allocation of attentional resources allows the visual system to encode and maintain representations of stimuli in visual working memory (VWM). However, limits in the processing capacity to allocate resources can prevent unexpected visual stimuli from gaining access to VWM and thereby to consciousness. Using a novel approach to create unbiased stimuli of increasing saliency, we investigated visual processing during a visual search task in individuals who show a high or low propensity to neglect unexpected stimuli. When propensity to inattention is high, ERP recordings show a diminished amplification concomitantly with a decrease in theta band power during the N1 latency, followed by a poor target enhancement during the N2 latency. Furthermore, a later modulation in the P3 latency was also found in individuals showing propensity to visual neglect, suggesting that more effort is required for conscious maintenance of visual information in VWM. Effects during early stages of processing (N80 and P1) were also observed suggesting that sensitivity to contrasts and medium-to-high spatial frequencies may be modulated by low-level saliency (albeit no statistical group differences were found). In accordance with the Global Workplace Model, our data indicate that a lack of resources in low-level processors and visual attention may be responsible for the failure to "ignite" a state of high-level activity spread across several brain areas that is necessary for stimuli to access awareness. These findings may aid in the development of diagnostic tests and intervention to detect/reduce inattention propensity to visual neglect of unexpected stimuli.

  14. Unexpected pattern of beta-globin mutations in beta-thalassaemia patients from northern Portugal

    OpenAIRE

    Cabeda, J.; Correia, C.; Estevinho, A.; Simões, C.; Amorim, M; L. Pinho; Justiça, B

    1999-01-01

    We characterized the genetic nature of beta-thalassaemia in northern Portugal. Of the 164 patients studied three were beta-thalassaemia major cases (one IVS-1-6/beta degrees 39 and two homozygous IVS-1-110). The analysis of the frequency of each mutation in the families revealed that the codon 6(-A) mutation was unexpectedly frequent (40%) and associated with the beta-globin haplotype E, and not with the usual European and North African CD6(-A) haplotypes. In contrast, the frequency of IVS-1-...

  15. Unexpected involvement of staple leads to redesign of selective bicyclic peptide inhibitor of Grb7

    OpenAIRE

    Menachem J. Gunzburg; Ketav Kulkarni; Gabrielle M. Watson; Ambaye, Nigus D.; Del Borgo, Mark P.; Rebecca Brandt; Stephanie C. Pero; Patrick Perlmutter; Wilce, Matthew C. J.; Wilce, Jacqueline A

    2016-01-01

    The design of potent and specific peptide inhibitors to therapeutic targets is of enormous utility for both proof-of-concept studies and for the development of potential new therapeutics. Grb7 is a key signaling molecule in the progression of HER2 positive and triple negative breast cancers. Here we report the crystal structure of a stapled bicyclic peptide inhibitor G7-B1 in complex with the Grb7-SH2 domain. This revealed an unexpected binding mode of the peptide, in which the staple forms a...

  16. 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.

  17. Comparative Assessment of the Prognostic Value of Biomarkers in Traumatic Brain Injury Reveals an Independent Role for Serum Levels of Neurofilament Light.

    Directory of Open Access Journals (Sweden)

    Faiez Al Nimer

    Full Text Available Traumatic brain injury (TBI is a common cause of death and disability, worldwide. Early determination of injury severity is essential to improve care. Neurofilament light (NF-L has been introduced as a marker of neuroaxonal injury in neuroinflammatory/-degenerative diseases. In this study we determined the predictive power of serum (s- and cerebrospinal fluid (CSF- NF-L levels towards outcome, and explored their potential correlation to diffuse axonal injury (DAI. A total of 182 patients suffering from TBI admitted to the neurointensive care unit at a level 1 trauma center were included. S-NF-L levels were acquired, together with S100B and neuron-specific enolase (NSE. CSF-NF-L was measured in a subcohort (n = 84 with ventriculostomies. Clinical and neuro-radiological parameters, including computerized tomography (CT and magnetic resonance imaging, were included in the analyses. Outcome was assessed 6 to 12 months after injury using the Glasgow Outcome Score (1-5. In univariate proportional odds analyses mean s-NF-L, -S100B and -NSE levels presented a pseudo-R2 Nagelkerke of 0.062, 0.214 and 0.074 in correlation to outcome, respectively. In a multivariate analysis, in addition to a model including core parameters (pseudo-R2 0.33 towards outcome; Age, Glasgow Coma Scale, pupil response, Stockholm CT score, abbreviated injury severity score, S100B, S-NF-L yielded an extra 0.023 pseudo-R2 and a significantly better model (p = 0.006 No correlation between DAI or CT assessed-intracranial damage and NF-L was found. Our study thus demonstrates that S-NF-L correlates to TBI outcome, even if used in models with S100B, indicating an independent contribution to the prediction, perhaps by reflecting different pathophysiological processes, not possible to monitor using conventional neuroradiology. Although we did not find a predictive value of NF-L for DAI, this cannot be completely excluded. We suggest further studies, with volume quantification of axonal

  18. 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. PMID:26874256

  19. 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.H.

    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 suc

  20. Mitochondrial DNA assessment of Phytophthora infestans isolates from potato and tomato in Ethiopia reveals unexpected diversity.

    Science.gov (United States)

    Shimelash, Daniel; Hussien, Temam; Fininsa, Chemeda; Forbes, Greg; Yuen, Jonathan

    2016-08-01

    Mitochondrial DNA (mtDNA) haplotypes were determined using restriction fragment length polymorphism (RFLP) for P. infestans sampled from 513 foliar lesions of late blight found on potato and tomato in different regions of Ethiopia. Among the four reported mitochondrial haplotypes of Phytophthora infestans, Ia, Ib and IIb were detected in 93 % of the samples analyzed but the vast majority of these were Ia. The remaining 7 % represented a previously unreported haplotype. DNA sequencing of this new haplotype also confirmed a single base nucleotide substitution that resulted in loss of EcoRI restriction site and gain of two additional MspI sites in cox1 and atp1 genes, respectively. There were 28 polymorphic sites among all nucleotide sequences including five reference isolates. Sites with alignment gaps were observed in P4 with one nucleotide deletion in 11 Ethiopian isolates. None of the reference sequence produced frame-shifts, with the exception of the 3-nucleotide deletion in the P4 region by Phytophthora andina, a feature that can be used to distinguish the new Ethiopian isolates from P. andina. While a distinguishing molecular data presented here clearly separated them from P. infestans, 7 % of the isolates that share this feature formed an important component of the late blight pathogen causing disease on Solanum tuberosum in Ethiopia. Thus, these Ethiopian isolates could represent a novel Phytophthora species reported for the first time here. PMID:26873223

  1. Molecular phylogeny of the Astrophorida (Porifera, Demospongiae) reveals an unexpected high level of spicule homoplasy

    OpenAIRE

    Paco Cárdenas; Xavier, Joana R.; Julie Reveillaud; Christoffer Schander; Hans Tore Rapp

    2011-01-01

    BackgroundThe Astrophorida (Porifera, Demospongiaep) is geographically and bathymetrically widely distributed. Systema Porifera currently includes five families in this order: Ancorinidae, Calthropellidae, Geodiidae, Pachastrellidae and Thrombidae. To date, molecular phylogenetic studies including Astrophorida species are scarce and offer limited sampling. Phylogenetic relationships within this order are therefore for the most part unknown and hypotheses based on morphology largely untested. ...

  2. Unexpected Diversity of Chloroplast Noncoding RNAs as Revealed by Deep Sequencing of the Arabidopsis Transcriptome.

    Science.gov (United States)

    Hotto, Amber M; Schmitz, Robert J; Fei, Zhangjun; Ecker, Joseph R; Stern, David B

    2011-12-01

    Noncoding RNAs (ncRNA) are widely expressed in both prokaryotes and eukaryotes. Eukaryotic ncRNAs are commonly micro- and small-interfering RNAs (18-25 nt) involved in posttranscriptional gene silencing, whereas prokaryotic ncRNAs vary in size and are involved in various aspects of gene regulation. Given the prokaryotic origin of organelles, the presence of ncRNAs might be expected; however, the full spectrum of organellar ncRNAs has not been determined systematically. Here, strand-specific RNA-Seq analysis was used to identify 107 candidate ncRNAs from Arabidopsis thaliana chloroplasts, primarily encoded opposite protein-coding and tRNA genes. Forty-eight ncRNAs were shown to accumulate by RNA gel blot as discrete transcripts in wild-type (WT) plants and/or the pnp1-1 mutant, which lacks the chloroplast ribonuclease polynucleotide phosphorylase (cpPNPase). Ninety-eight percent of the ncRNAs detected by RNA gel blot had different transcript patterns between WT and pnp1-1, suggesting cpPNPase has a significant role in chloroplast ncRNA biogenesis and accumulation. Analysis of materials deficient for other major chloroplast ribonucleases, RNase R, RNase E, and RNase J, showed differential effects on ncRNA accumulation and/or form, suggesting specificity in RNase-ncRNA interactions. 5' end mapping demonstrates that some ncRNAs are transcribed from dedicated promoters, whereas others result from transcriptional read-through. Finally, correlations between accumulation of some ncRNAs and the symmetrically transcribed sense RNA are consistent with a role in RNA stability. Overall, our data suggest that this extensive population of ncRNAs has the potential to underpin a previously underappreciated regulatory mode in the chloroplast.

  3. Whole genome sequence analysis of Cryptococcus gattii from the Pacific Northwest reveals unexpected diversity.

    Directory of Open Access Journals (Sweden)

    John D Gillece

    Full Text Available A recent emergence of Cryptococcus gattii in the Pacific Northwest involves strains that fall into three primarily clonal molecular subtypes: VGIIa, VGIIb and VGIIc. Multilocus sequence typing (MLST and variable number tandem repeat analysis appear to identify little diversity within these molecular subtypes. Given the apparent expansion of these subtypes into new geographic areas and their ability to cause disease in immunocompetent individuals, differentiation of isolates belonging to these subtypes could be very important from a public health perspective. We used whole genome sequence typing (WGST to perform fine-scale phylogenetic analysis on 20 C. gattii isolates, 18 of which are from the VGII molecular type largely responsible for the Pacific Northwest emergence. Analysis both including and excluding (289,586 SNPs and 56,845 SNPs, respectively molecular types VGI and VGIII isolates resulted in phylogenetic reconstructions consistent, for the most part, with MLST analysis but with far greater resolution among isolates. The WGST analysis presented here resulted in identification of over 100 SNPs among eight VGIIc isolates as well as unique genotypes for each of the VGIIa, VGIIb and VGIIc isolates. Similar levels of genetic diversity were found within each of the molecular subtype isolates, despite the fact that the VGIIb clade is thought to have emerged much earlier. The analysis presented here is the first multi-genome WGST study to focus on the C. gattii molecular subtypes involved in the Pacific Northwest emergence and describes the tools that will further our understanding of this emerging pathogen.

  4. The transcriptome of Euglena gracilis reveals unexpected metabolic capabilities for carbohydrate and natural product biochemistry

    OpenAIRE

    O'Neill, EC; Trick, M.; L. Hill; Rejzek, M.; Dusi, RG; Hamilton, CJ; Zimba, PV; Henrissat, B; Field, RA

    2015-01-01

    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 molec...

  5. Drosophila Mutant Model of Parkinson's Disease Revealed an Unexpected Olfactory Performance: Morphofunctional Evidences

    Science.gov (United States)

    De Rose, Francescaelena; Corda, Valentina; Belcari, Antonio; Poddighe, Simone; Marrosu, Francesco

    2016-01-01

    Parkinson's disease (PD) is one of the most common neurodegenerative diseases characterized by the clinical triad: tremor, akinesia, and rigidity. Several studies have suggested that PD patients show disturbances in olfaction as one of the earliest, nonspecific nonmotor symptoms of disease onset. We sought to use the fruit fly Drosophila melanogaster as a model organism to explore olfactory function in LRRK loss-of-function mutants, which was previously demonstrated to be a useful model for PD. Surprisingly, our results showed that the LRRK mutant, compared to the wild flies, presents a dramatic increase in the amplitude of the electroantennogram responses and this is coupled with a higher number of olfactory sensilla. In spite of the above reported results, the behavioural response to olfactory stimuli in mutant flies is impaired compared to that obtained in wild type flies. Thus, behaviour modifications and morphofunctional changes in the olfaction of LRRK loss-of-function mutants might be used as an index to explore the progression of parkinsonism in this specific model, also with the aim of studying and developing new treatments. PMID:27648340

  6. Light echoes reveal an unexpectedly cool Eta Carinae during its 19th-century Great Eruption

    CERN Document Server

    Rest, A; Walborn, N R; Smith, N; Bianco, F B; Chornock, R; Welch, D L; Howell, D A; Huber, M E; Foley, R J; Fong, W; Sinnott, B; Bond, H E; Smith, R C; Toledo, I; Minniti, D; Mandel, K

    2011-01-01

    Eta Carinae (Eta Car) is one of the most massive binary stars in the Milky Way. It became the second-brightest star in the sky during its mid-19th century "Great Eruption," but then faded from view (with only naked-eye estimates of brightness). Its eruption is unique among known astronomical transients in that it exceeded the Eddington luminosity limit for 10 years. Because it is only 2.3 kpc away, spatially resolved studies of the nebula have constrained the ejected mass and velocity, indicating that in its 19th century eruption, Eta Car ejected more than 10 M_solar in an event that had 10% of the energy of a typical core-collapse supernova without destroying the star. Here we report the discovery of light echoes of Eta Carinae which appear to be from the 1838-1858 Great Eruption. Spectra of these light echoes show only absorption lines, which are blueshifted by -210 km/s, in good agreement with predicted expansion speeds. The light-echo spectra correlate best with those of G2-G5 supergiant spectra, which ha...

  7. Drosophila Mutant Model of Parkinson's Disease Revealed an Unexpected Olfactory Performance: Morphofunctional Evidences.

    Science.gov (United States)

    De Rose, Francescaelena; Corda, Valentina; Solari, Paolo; Sacchetti, Patrizia; Belcari, Antonio; Poddighe, Simone; Kasture, Sanjay; Solla, Paolo; Marrosu, Francesco; Liscia, Anna

    2016-01-01

    Parkinson's disease (PD) is one of the most common neurodegenerative diseases characterized by the clinical triad: tremor, akinesia, and rigidity. Several studies have suggested that PD patients show disturbances in olfaction as one of the earliest, nonspecific nonmotor symptoms of disease onset. We sought to use the fruit fly Drosophila melanogaster as a model organism to explore olfactory function in LRRK loss-of-function mutants, which was previously demonstrated to be a useful model for PD. Surprisingly, our results showed that the LRRK mutant, compared to the wild flies, presents a dramatic increase in the amplitude of the electroantennogram responses and this is coupled with a higher number of olfactory sensilla. In spite of the above reported results, the behavioural response to olfactory stimuli in mutant flies is impaired compared to that obtained in wild type flies. Thus, behaviour modifications and morphofunctional changes in the olfaction of LRRK loss-of-function mutants might be used as an index to explore the progression of parkinsonism in this specific model, also with the aim of studying and developing new treatments.

  8. Unexpected functional similarities between gatekeeper tumour suppressor genes and proto-oncogenes revealed by systems biology.

    Science.gov (United States)

    Zhao, Yongzhong; Epstein, Richard J

    2011-05-01

    Familial tumor suppressor genes comprise two subgroups: caretaker genes (CTs) that repair DNA, and gatekeeper genes (GKs) that trigger cell death. Since GKs may also induce cell cycle delay and thus enhance cell survival by facilitating DNA repair, we hypothesized that the prosurvival phenotype of GKs could be selected during cancer progression, and we used a multivariable systems biology approach to test this. We performed multidimensional data analysis, non-negative matrix factorization and logistic regression to compare the features of GKs with those of their putative antagonists, the proto-oncogenes (POs), as well as with control groups of CTs and functionally unrelated congenital heart disease genes (HDs). GKs and POs closely resemble each other, but not CTs or HDs, in terms of gene structure (P<0.001), expression level and breadth (P<0.01), DNA methylation signature (P<0.001) and evolutionary rate (P<0.001). The similar selection pressures and epigenetic trajectories of GKs and POs so implied suggest a common functional attribute that is strongly negatively selected-that is, a shared phenotype that enhances cell survival. The counterintuitive finding of similar evolutionary pressures affecting GKs and POs raises an intriguing possibility: namely, that cancer microevolution is accelerated by an epistatic cascade in which upstream suppressor gene defects subvert the normal bifunctionality of wild-type GKs by constitutively shifting the phenotype away from apoptosis towards survival. If correct, this interpretation would explain the hitherto unexplained phenomenon of frequent wild-type GK (for example, p53) overexpression in tumors.

  9. Amygdala activity can be modulated by unexpected chord functions during music listening.

    Science.gov (United States)

    Koelsch, Stefan; Fritz, Thomas; Schlaug, Gottfried

    2008-12-01

    Numerous earlier studies have investigated the cognitive processing of musical syntax with regular and irregular chord sequences. However, irregular sequences may also be perceived as unexpected, and therefore have a different emotional valence than regular sequences. We provide behavioral data showing that irregular chord functions presented in chord sequence paradigms are perceived as less pleasant than regular sequences. A reanalysis of functional MRI data showed increased blood oxygen level-dependent signal changes bilaterally in the amygdala in response to music-syntactically irregular (compared with regular) chord functions. The combined data indicate that music-syntactically irregular events elicit brain activity related to emotional processes, and that, in addition to intensely pleasurable music or highly unpleasant music, single chord functions can also modulate amygdala activity. PMID:19050462

  10. Regulation of neurogenesis by neurotrophins during adulthood: expected and unexpected roles

    Directory of Open Access Journals (Sweden)

    Marçal eVilar

    2016-02-01

    Full Text Available The subventricular zone (SVZ of the anterolateral ventricle and the subgranular zone (SGZ of the hippocampal dentate gyrus are the two main regions of the adult mammalian brain in which neurogenesis is maintained throughout life. Because alterations in adult neurogenesis appear to be a common hallmark of different neurodegenerative diseases, understanding the molecular mechanisms controlling adult neurogenesis is a focus of active research. Neurotrophic factors are a family of molecules that play critical roles in the survival and differentiation of neurons during development and in the control of neural plasticity in the adult. Several neurotrophins and neurotrophin receptors have been implicated in the regulation of adult neurogenesis at different levels. Here we review the current understanding of neurotrophin modulation of adult neurogenesis in both the SVZ and SGZ. We compile data supporting a variety of roles for neurotrophins/neurotrophin receptors in different scenarios, including both expected and unexpected functions.

  11. Regulation of Neurogenesis by Neurotrophins during Adulthood: Expected and Unexpected Roles.

    Science.gov (United States)

    Vilar, Marçal; Mira, Helena

    2016-01-01

    The subventricular zone (SVZ) of the anterolateral ventricle and the subgranular zone (SGZ) of the hippocampal dentate gyrus are the two main regions of the adult mammalian brain in which neurogenesis is maintained throughout life. Because alterations in adult neurogenesis appear to be a common hallmark of different neurodegenerative diseases, understanding the molecular mechanisms controlling adult neurogenesis is a focus of active research. Neurotrophic factors are a family of molecules that play critical roles in the survival and differentiation of neurons during development and in the control of neural plasticity in the adult. Several neurotrophins and neurotrophin receptors have been implicated in the regulation of adult neurogenesis at different levels. Here, we review the current understanding of neurotrophin modulation of adult neurogenesis in both the SVZ and SGZ. We compile data supporting a variety of roles for neurotrophins/neurotrophin receptors in different scenarios, including both expected and unexpected functions. PMID:26903794

  12. Liver Transplant From Unexpected Donation After Circulatory Determination of Death Donors: A Challenge in Perioperative Management.

    Science.gov (United States)

    Blasi, A; Hessheimer, A J; Beltrán, J; Pereira, A; Fernández, J; Balust, J; Martínez-Palli, G; Fuster, J; Navasa, M; García-Valdecasas, J C; Taurá, P; Fondevila, C

    2016-06-01

    Unexpected donation after circulatory determination of death (uDCD) liver transplantation is a complex procedure, in particular when it comes to perioperative recipient management. However, very little has been published to date regarding intraoperative and immediate postoperative care in this setting. Herein, we compare perioperative events in uDCD liver recipients with those of a matched group of donation after brain death liver recipients. We demonstrate that the former group of recipients suffers significantly greater hemodynamic instability and derangements in coagulation following graft reperfusion. Based on our experience, we recommend a proactive recipient management strategy in uDCD liver transplantation that involves early use of vasopressor support; maintaining adequate intraoperative levels of red cells, platelets, and fibrinogen; and routinely administering tranexamic acid before graft reperfusion. PMID:26601629

  13. 77 FR 42947 - Unexpected Urgent Refugee and Migration Needs

    Science.gov (United States)

    2012-07-20

    ... memorandum in the Federal Register. (Presidential Sig.) THE WHITE HOUSE, Washington, July 12, 2012 [FR Doc... Documents#0;#0; ] Presidential Determination No. 2012-12 of July 12, 2012 Unexpected Urgent Refugee and... Constitution and the laws of the United States, including section 2(c)(1) of the Migration and...

  14. 77 FR 21389 - Unexpected Urgent Refugee and Migration Needs

    Science.gov (United States)

    2012-04-10

    ..., Washington, April 3, 2012 [FR Doc. 2012-8674 Filed 4-9-12; 8:45 am] Billing code 4710-10-P ... Documents#0;#0; ] Presidential Determination No. 2012-06 of April 3, 2012 Unexpected Urgent Refugee and... Constitution and the laws of the United States, including section 2(c)(1) of the Migration and...

  15. 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.

  16. Thallium-201 accumulation in cerebral candidiasis: Unexpected finding on SPECT

    International Nuclear Information System (INIS)

    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

  17. Mapping brain function to brain anatomy

    International Nuclear Information System (INIS)

    In Imaging the human brain, MRI is commonly used to reveal anatomical structure, while PET is used to reveal tissue function. This paper presents a protocol for correlating data between these two imaging modalities; this correlation can provide in vivo regional measurements of brain function which are essential to our understanding of the human brain. The authors propose a general protocol to standardize the acquisition and analysis of functional image data. First, MR and PET images are collected to form three-dimensional volumes of structural and functional image data. Second, these volumes of image data are corrected for distortions inherent in each imaging modality. Third, the image volumes are correlated to provide correctly aligned structural and functional images. The functional images are then mapped onto the structural images in both two-dimensional and three-dimensional representations. Finally, morphometric techniques can be used to provide statistical measures of the structure and function of the human brain

  18. Aquaporin 9 in rat brain after severe traumatic brain injury

    OpenAIRE

    Hui Liu; Mei Yang; Guo-ping Qiu; Fei Zhuo; Wei-hua Yu; Shan-quan Sun; Yun Xiu

    2012-01-01

    OBJECTIVE: To reveal the expression and possible roles of aquaporin 9 (AQP9) in rat brain, after severe traumatic brain injury (TBI). METHODS: Brain water content (BWC), tetrazolium chloride staining, Evans blue staining, immunohistochemistry (IHC), immunofluorescence (IF), western blot, and real-time polymerase chain reaction were used. RESULTS: The BWC reached the first and second (highest) peaks at 6 and 72 hours, and the blood brain barrier (BBB) was severely destroyed at six hours after ...

  19. Understanding brain networks and brain organization

    Science.gov (United States)

    Pessoa, Luiz

    2014-09-01

    What is the relationship between brain and behavior? The answer to this question necessitates characterizing the mapping between structure and function. The aim of this paper is to discuss broad issues surrounding the link between structure and function in the brain that will motivate a network perspective to understanding this question. However, as others in the past, I argue that a network perspective should supplant the common strategy of understanding the brain in terms of individual regions. Whereas this perspective is needed for a fuller characterization of the mind-brain, it should not be viewed as panacea. For one, the challenges posed by the many-to-many mapping between regions and functions is not dissolved by the network perspective. Although the problem is ameliorated, one should not anticipate a one-to-one mapping when the network approach is adopted. Furthermore, decomposition of the brain network in terms of meaningful clusters of regions, such as the ones generated by community-finding algorithms, does not by itself reveal "true" subnetworks. Given the hierarchical and multi-relational relationship between regions, multiple decompositions will offer different "slices" of a broader landscape of networks within the brain. Finally, I described how the function of brain regions can be characterized in a multidimensional manner via the idea of diversity profiles. The concept can also be used to describe the way different brain regions participate in networks.

  20. Sudden unexpected death in epilepsy: Identifying risk and preventing mortality.

    Science.gov (United States)

    Lhatoo, Samden; Noebels, Jeffrey; Whittemore, Vicky

    2015-11-01

    Premature death among individuals with epilepsy is higher than in the general population, and sudden unexpected death is the most common cause of this mortality. A new multisite collaborative research consortium, the Center for sudden unexpected death in epilepsy (SUDEP) Research (CSR), has received major funding from the National Institutes of Health (NIH) to examine the possible biologic mechanisms underlying this potentially preventable comorbidity and develop predictive biomarkers for interventions that could lower SUDEP incidence. This inaugural report describes the structure of the CSR, its priorities for human and experimental research, and the strategic collaborations and advanced tools under development to reduce this catastrophic outcome of epilepsy. The CSR Partners Program will work closely with committed volunteer agencies, industry, and academic institutions to accelerate and communicate these advances to the professional and lay community.

  1. Origin of Unexpected Isotopic Trends in Synthesis of Superheavy Nuclei

    Institute of Scientific and Technical Information of China (English)

    LIU Zu-Hua; BAO Jing-Dong

    2007-01-01

    We investigate the dependence of the yield of superheavy nuclei with Z = 110, 112, 114 on the neutron excess of the projectile nucleus with a two-parameter Smoluchowski equation. It is confirmed that in some cases, the cold fusion reactions with less neutron excess are more favourable than those with more neutron excess. In order to probe the origin of these unexpected isotopic trends, we also investigate the probabilities of capture, fusion and survival in the cold fusion reactions in detail. It is found that the maximal ER cross sections of the superheavy nuclei exponentially increase as a function of Bf - Sn with Bf being the fission barrier and Sn being the neutron separation energy. Although the probabilities of capture and fusion have some influences, the unexpected isotopic trends mainly due to the dependence of the ER cross sections on the Bf - Sn value. Therefore, the reactions with larger Bf - Sn values should be more favourable for synthesis of superheavy nuclei.

  2. 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.

  3. Sudden unexpected death in epilepsy: Identifying risk and preventing mortality.

    Science.gov (United States)

    Lhatoo, Samden; Noebels, Jeffrey; Whittemore, Vicky

    2015-11-01

    Premature death among individuals with epilepsy is higher than in the general population, and sudden unexpected death is the most common cause of this mortality. A new multisite collaborative research consortium, the Center for sudden unexpected death in epilepsy (SUDEP) Research (CSR), has received major funding from the National Institutes of Health (NIH) to examine the possible biologic mechanisms underlying this potentially preventable comorbidity and develop predictive biomarkers for interventions that could lower SUDEP incidence. This inaugural report describes the structure of the CSR, its priorities for human and experimental research, and the strategic collaborations and advanced tools under development to reduce this catastrophic outcome of epilepsy. The CSR Partners Program will work closely with committed volunteer agencies, industry, and academic institutions to accelerate and communicate these advances to the professional and lay community. PMID:26494436

  4. Responding to Rapid and Unexpected Retail Innovations: Planning Retail Resilience

    Science.gov (United States)

    Rao, Fujie

    Retail areas within cities have traditionally not only satisfied the demands for various goods and services, but also promoted community sustainability and healthy lifestyles. Since the end of World War II (WWII), retail innovations have occurred rapidly and unexpectedly. In retail development, economic efficiency is highly prioritized over other functions, in opposition to sustainable development. In retail planning, a communicative approach frequently results in the public responses by "Not In My Back Yard" sentiments, contradicting the projected cooperation between different stakeholders. This research implements the resilience theory to tackle the shocks created by these rapid and unexpected retail changes, based on a comparative case of Edmonton (Alberta, Canada) and Portland (Oregon, USA). Primarily through interviews with senior planners in both cities, it is found that adaptive retail management, polycentric retail planning, a well-informed public, and the use of consensus building could better stimulates resilient retail outcomes.

  5. Brain Fingerprinting

    Directory of Open Access Journals (Sweden)

    Ravi Kumar

    2012-12-01

    Full Text Available Brain Fingerprinting is a scientific technique to determine whether or not specific information is stored in an individual's brain by measuring a electrical brain wave response to Word, phrases, or picture that are presented on computer screen. Brain Fingerprinting is a controversial forensic science technique that uses electroencephalography (EEG to determine whether specific information is stored in a subject's brain.

  6. Brain Fingerprinting

    Directory of Open Access Journals (Sweden)

    ravi kumar

    2012-12-01

    Full Text Available Brain Fingerprinting is a scientific technique to determine whether or not specific information is stored in an individual's brain by measuring a electrical brain wave response to Word, phrases, or picture that are presented on computer screen. Brain Fingerprinting is a controversial forensic science technique that uses electroencephalograph y (EEG to determine whether specific information is stored in a subject's brain

  7. 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 ...

  8. Using Event Studies to Assess the Impact of Unexpected Events

    OpenAIRE

    James V Koch; Robert N Fenili

    2013-01-01

    The quantitative assessment of the financial impact of unexpected events is the realm of the “event study.” We examine how CEOs, boards, and public policymakers can utilize event studies to inform and improve their decision making. The breadth of application of event studies is surprisingly broad and ranges from situations involving the death of a CEO to emergency product recalls. We present illustrative event studies for two Steve Jobs-related announcements concerning his health in order to ...

  9. Clinical, pathological and sonographic characteristics of unexpected gallbladder carcinoma

    OpenAIRE

    Jin-huan WANG; Liu, Bo-Ji; Xu, Hui-Xiong; Sun, Li-ping; Li, Dan-Dan; Guo, Le-Hang; Liu, Lin-Na; Xu, Xiao-Hong

    2015-01-01

    Objectives: To investigate the clinical, pathological, and sonographic characteristics of unexpected gallbladder carcinoma (UGC). Methods: Of 5424 patients who had undergone cholecystectomy from December 2006 to October 2013, 54 patients with primary gallbladder carcinomas confirmed by pathological diagnosis were identified. The patients were divided into two groups: diagnosed before operation (n=34) and UGC groups (n=20), of whom the clinical, pathological, and sonographic characteristics we...

  10. Sudden Unexpected Death in Fetal Life Through Early Childhood.

    Science.gov (United States)

    Goldstein, Richard D; Kinney, Hannah C; Willinger, Marian

    2016-06-01

    In March 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development held a workshop entitled "Sudden Unexpected Death in Fetal Life Through Early Childhood: New Opportunities." Its objective was to advance efforts to understand and ultimately prevent sudden deaths in early life, by considering their pathogenesis as a potential continuum with some commonalities in biological origins or pathways. A second objective of this meeting was to highlight current issues surrounding the classification of sudden infant death syndrome (SIDS), and the implications of variations in the use of the term "SIDS" in forensic practice, and pediatric care and research. The proceedings reflected the most current knowledge and understanding of the origins and biology of vulnerability to sudden unexpected death, and its environmental triggers. Participants were encouraged to consider the application of new technologies and "omics" approaches to accelerate research. The major advances in delineating the intrinsic vulnerabilities to sudden death in early life have come from epidemiologic, neural, cardiac, metabolic, genetic, and physiologic research, with some commonalities among cases of unexplained stillbirth, SIDS, and sudden unexplained death in childhood observed. It was emphasized that investigations of sudden unexpected death are inconsistent, varying by jurisdiction, as are the education, certification practices, and experience of death certifiers. In addition, there is no practical consensus on the use of "SIDS" as a determination in cause of death. Major clinical, forensic, and scientific areas are identified for future research. PMID:27230764

  11. Risk factors and consequences of unexpected trapping for ruptured anterior communicating artery aneurysms

    Directory of Open Access Journals (Sweden)

    Hitoshi Fukuda

    2014-01-01

    Full Text Available Background: While clipping cerebral aneurysms at the neck is optimal, in some cases this is not possible and other strategies are necessary. The purpose of this study was to describe the incidence, risk factors, and outcomes for inability to clip reconstruct ruptured anterior communicating artery (ACoA aneurysms. Methods: Of the 70 cases of ruptured ACoA aneurysms between January 2006 and December 2013, our institutional experience revealed four cases of small ACoA aneurysms that had been considered clippable prior to operation but required trapping. When a unilateral A2 segment of anterior cerebral artery (ACA was compromised by trapping, revascularization was performed by bypass surgery. Clinical presentation, angiographic characteristics, operative approach, intraoperative findings, and treatment outcomes were assessed. Results: Very small aneurysm under 3 mm was a risk factor for unexpected trapping. The reason for unexpected trapping was laceration of the aneurysmal neck in two cases, and lack of clippaple component due to disintegration of entire aneurysmal wall at the time of rupture in the others. Aneurysms with bilateral A1 were treated with sole trapping through pterional approach in two cases. The other two cases had hypoplastic unilateral A1 segment of ACA and were treated with combination of aneurysm trapping and revascularization of A2 segment of ACA through interhemispheric approach. No patients had new cerebral infarctions of cortical ACA territory from surgery. Cognitive dysfunction was observed in three cases, but all patients became independent at 12-month follow up. Conclusions: Unexpected trapping was performed when ruptured ACoA aneurysms were unclippable. Trapping with or without bypass can result in reasonable outcomes, with acceptable risk of cognitive dysfunction.

  12. Characterization of task-free and task-performance brain states via functional connectome patterns.

    Science.gov (United States)

    Zhang, Xin; Guo, Lei; Li, Xiang; Zhang, Tuo; Zhu, Dajiang; Li, Kaiming; Chen, Hanbo; Lv, Jinglei; Jin, Changfeng; Zhao, Qun; Li, Lingjiang; Liu, Tianming

    2013-12-01

    Both resting state fMRI (R-fMRI) and task-based fMRI (T-fMRI) have been widely used to study the functional activities of the human brain during task-free and task-performance periods, respectively. However, due to the difficulty in strictly controlling the participating subject's mental status and their cognitive behaviors during R-fMRI/T-fMRI scans, it has been challenging to ascertain whether or not an R-fMRI/T-fMRI scan truly reflects the participant's functional brain states during task-free/task-performance periods. This paper presents a novel computational approach to characterizing and differentiating the brain's functional status into task-free or task-performance states, by which the functional brain activities can be effectively understood and differentiated. Briefly, the brain's functional state is represented by a whole-brain quasi-stable connectome pattern (WQCP) of R-fMRI or T-fMRI data based on 358 consistent cortical landmarks across individuals, and then an effective sparse representation method was applied to learn the atomic connectome patterns (ACPs) of both task-free and task-performance states. Experimental results demonstrated that the learned ACPs for R-fMRI and T-fMRI datasets are substantially different, as expected. A certain portion of ACPs from R-fMRI and T-fMRI data were overlapped, suggesting some subjects with overlapping ACPs were not in the expected task-free/task-performance brain states. Besides, potential outliers in the T-fMRI dataset were further investigated via functional activation detections in different groups, and our results revealed unexpected task-performances of some subjects. This work offers novel insights into the functional architectures of the brain.

  13. Brain Basics

    Medline Plus

    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 ...

  14. 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 ...

  15. 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, ...

  16. Brain Basics

    Medline Plus

    Full Text Available ... Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, ... others live with symptoms of mental illness every day. They can be moderate, or serious and cause ...

  17. Brain Basics

    Medline Plus

    Full Text Available ... The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are the basic working unit of the ... distant nerve cells (via axons) to form brain circuits. These circuits control specific body functions such as ...

  18. Brain Basics

    Medline Plus

    Full Text Available ... Basics will introduce you to some of this science, such as: How the brain develops How genes and the environment affect the brain The basic structure of the brain How different parts of ...

  19. Brain Basics

    Medline Plus

    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 ...

  20. Tbx1 regulates brain vascularization.

    Science.gov (United States)

    Cioffi, Sara; Martucciello, Stefania; Fulcoli, Filomena Gabriella; Bilio, Marchesa; Ferrentino, Rosa; Nusco, Edoardo; Illingworth, Elizabeth

    2014-01-01

    The transcription factor TBX1 is the major gene involved in 22q11.2 deletion syndrome (22q11.2DS). Using mouse models of these diseases, we have previously shown that TBX1 activates VEGFR3 in endothelial cells (EC), and that this interaction is critical for the development of the lymphatic vasculature. In this study, we show that TBX1 regulates brain angiogenesis. Using loss-of-function genetics and molecular approaches, we show that TBX1 regulates the VEGFR3 and DLL4 genes in brain ECs. In mice, loss of TBX1 causes global brain vascular defects, comprising brain vessel hyperplasia, enhanced angiogenic sprouting and vessel network disorganization. This phenotype is recapitulated in EC-specific Tbx1 conditional mutants and in an EC-only 3-dimensional cell culture system (matrigel), indicating that the brain vascular phenotype is cell autonomous. Furthermore, EC-specific conditional Tbx1 mutants have poorly perfused brain vessels and brain hypoxia, indicating that the expanded vascular network is functionally impaired. In EC-matrigel cultures, a Notch1 agonist is able to partially rescue microtubule hyperbranching induced by TBX1 knockdown. Thus, we have identified a novel transcriptional regulator of angiogenesis that exerts its effect in brain by negatively regulating angiogenesis through the DLL4/Notch1-VEGFR3 regulatory axis. Given the similarity of the phenotypic consequences of TBX1 mutation in humans and mice, this unexpected role of TBX1 in murine brain vascularization should stimulate clinicians to search for brain microvascular anomalies in 22q11.2DS patients and to evaluate whether some of the anatomical and functional brain anomalies in patients may have a microvascular origin. PMID:23945394

  1. 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.

  2. Biallelic PPA2 Mutations Cause Sudden Unexpected Cardiac Arrest in Infancy.

    Science.gov (United States)

    Guimier, Anne; Gordon, Christopher T; Godard, François; Ravenscroft, Gianina; Oufadem, Myriam; Vasnier, Christelle; Rambaud, Caroline; Nitschke, Patrick; Bole-Feysot, Christine; Masson, Cécile; Dauger, Stéphane; Longman, Cheryl; Laing, Nigel G; Kugener, Béatrice; Bonnet, Damien; Bouvagnet, Patrice; Di Filippo, Sylvie; Probst, Vincent; Redon, Richard; Charron, Philippe; Rötig, Agnès; Lyonnet, Stanislas; Dautant, Alain; de Pontual, Loïc; di Rago, Jean-Paul; Delahodde, Agnès; Amiel, Jeanne

    2016-09-01

    Sudden unexpected death in infancy occurs in apparently healthy infants and remains largely unexplained despite thorough investigation. The vast majority of cases are sporadic. Here we report seven individuals from three families affected by sudden and unexpected cardiac arrest between 4 and 20 months of age. Whole-exome sequencing revealed compound heterozygous missense mutations in PPA2 in affected infants of each family. PPA2 encodes the mitochondrial pyrophosphatase, which hydrolyzes inorganic pyrophosphate into two phosphates. This is an essential activity for many biosynthetic reactions and for energy metabolism of the cell. We show that deletion of the orthologous gene in yeast (ppa2Δ) compromises cell viability due to the loss of mitochondria. Expression of wild-type human PPA2, but not PPA2 containing the mutations identified in affected individuals, preserves mitochondrial function in ppa2Δ yeast. Using a regulatable (doxycycline-repressible) gene expression system, we found that the pathogenic PPA2 mutations rapidly inactivate the mitochondrial energy transducing system and prevent the maintenance of a sufficient electrical potential across the inner membrane, which explains the subsequent disappearance of mitochondria from the mutant yeast cells. Altogether these data demonstrate that PPA2 is an essential gene in yeast and that biallelic mutations in PPA2 cause a mitochondrial disease leading to sudden cardiac arrest in infants. PMID:27523598

  3. Unexpected findings at imaging: Predicting frequency in various types of studies

    International Nuclear Information System (INIS)

    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.

  4. Attention Sharpens the Distinction between Expected and Unexpected Percepts in the Visual Brain

    OpenAIRE

    Jiang, J; Summerfield, C.; Egner, T.

    2013-01-01

    Attention, the prioritization of goal-relevant stimuli, and expectation, the modulation of stimulus processing by probabilistic context, represent the two main endogenous determinants of visual cognition. Neural selectivity in visual cortex is enhanced for both attended and expected stimuli, but the functional relationship between these mechanisms is poorly understood. Here, we adjudicated between two current hypotheses of how attention relates to predictive processing, namely, that attention...

  5. 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 bridges, for the first time, MuRF1's regulation of PPARα, cardiac hypertrophy, and hemostasis. PMID:26764147

  6. Alopecia associated with unexpected leakage from electron cone

    International Nuclear Information System (INIS)

    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

  7. Cutaneous anthrax on an unexpected area of body

    OpenAIRE

    Ertuğrul Güçlü; Nazan Tuna; Oğuz Karabay

    2012-01-01

    Anthrax is a zoonotic disease caused by Bacillus anthracis. Cutaneous anthrax is the most commonly seen form of anthrax.Skin lesions usually occur on the most exposed areas of the body, such as the face, neck, hand or upper extremity.The aim of this paper is to report a case of cutaneous anthrax form which was occurred on an unexpected area of thebody of a slaughter-house worker. J Microbiol Infect Dis 2012;2(4): 163-164Key words: Anthrax, Bacillus anthracis, cutaneous

  8. 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

  9. 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.

  10. Brain Basics

    Medline Plus

    Full Text Available ... Welcome. Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, ... highly developed area at the front of the brain that, in humans, plays a role in executive functions such as ...

  11. Brain Basics

    Medline Plus

    Full Text Available ... Research Modern research tools and techniques are giving scientists a more detailed understanding of the brain than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of the brain's structure, studies ...

  12. Leaning in and holding on: team support with unexpected death.

    Science.gov (United States)

    Kobler, Kathie

    2014-01-01

    Integral to the care of medically fragile infants and children is the sobering reality that not all will survive. Supporting children and families through the dying process requires knowledge, skill, compassion, and a willingness to be present to the suffering of others. As healthcare professionals journey with a dying child, they experience an ongoing dual nature of their own grief, shifting between focusing on the loss at hand or avoiding the loss and refocusing their attention elsewhere. This internal conflict may be potentiated with the sudden, unexpected death of a patient, which affords little time for caregivers to process their own experience of the loss. When an unanticipated death occurs, a palpable grief ripples through the entire unit, impacting caregivers, the bereaved parents, and other patients and families. Such an event holds the potential for either team disorganization or growth. This article presents a case study of one unit's response to the unexpected death of a long-term patient, which caused caregivers to lean in to support each other. Using a case study approach, the author identifies strategies to best guide teams when death arrives without warning, and provides ideas for cocreating ritual to honor relationship in the midst of tragedy. PMID:24445436

  13. Unexpected but Incidental Positive Outcomes Predict Real-World Gambling.

    Science.gov (United States)

    Otto, A Ross; Fleming, Stephen M; Glimcher, Paul W

    2016-03-01

    Positive mood can affect a person's tendency to gamble, possibly because positive mood fosters unrealistic optimism. At the same time, unexpected positive outcomes, often called prediction errors, influence mood. However, a linkage between positive prediction errors-the difference between expected and obtained outcomes-and consequent risk taking has yet to be demonstrated. Using a large data set of New York City lottery gambling and a model inspired by computational accounts of reward learning, we found that people gamble more when incidental outcomes in the environment (e.g., local sporting events and sunshine) are better than expected. When local sports teams performed better than expected, or a sunny day followed a streak of cloudy days, residents gambled more. The observed relationship between prediction errors and gambling was ubiquitous across the city's socioeconomically diverse neighborhoods and was specific to sports and weather events occurring locally in New York City. Our results suggest that unexpected but incidental positive outcomes influence risk taking. PMID:26796614

  14. Unexpected arousal modulates the influence of sensory noise on confidence

    Science.gov (United States)

    Allen, Micah; Frank, Darya; Schwarzkopf, D Samuel; Fardo, Francesca; Winston, Joel S; Hauser, Tobias U; Rees, Geraint

    2016-01-01

    Human perception is invariably accompanied by a graded feeling of confidence that guides metacognitive awareness and decision-making. It is often assumed that this arises solely from the feed-forward encoding of the strength or precision of sensory inputs. In contrast, interoceptive inference models suggest that confidence reflects a weighted integration of sensory precision and expectations about internal states, such as arousal. Here we test this hypothesis using a novel psychophysical paradigm, in which unseen disgust-cues induced unexpected, unconscious arousal just before participants discriminated motion signals of variable precision. Across measures of perceptual bias, uncertainty, and physiological arousal we found that arousing disgust cues modulated the encoding of sensory noise. Furthermore, the degree to which trial-by-trial pupil fluctuations encoded this nonlinear interaction correlated with trial level confidence. Our results suggest that unexpected arousal regulates perceptual precision, such that subjective confidence reflects the integration of both external sensory and internal, embodied states. DOI: http://dx.doi.org/10.7554/eLife.18103.001 PMID:27776633

  15. 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

    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......-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....

  16. Biopersistence and brain translocation of aluminum adjuvants of vaccines

    Directory of Open Access Journals (Sweden)

    Romain Kroum Gherardi

    2015-02-01

    Full Text Available Aluminum oxyhydroxide (alum is a crystaline compound widely used as an immunologic adjuvant of vaccines. Concerns linked to the use of alum particles emerged following recognition of their causative role in the so-called macrophagic myofasciitis (MMF lesion detected in patients with myalgic encephalomyelitis/chronic fatigue/syndrome. MMF revealed an unexpectedly long-lasting biopersistence of alum within immune cells in presumably susceptible individuals, stressing the previous fundamental misconception of its biodisposition. We previously showed that poorly biodegradable aluminum-coated particles injected into muscle are promptly phagocytozed in muscle and the draining lymph nodes, and can disseminate within phagocytic cells throughout the body and slowly accumulate in brain. This strongly suggests that long-term adjuvant biopersistence within phagocytic cells is a prerequisite for slow brain translocation and delayed neurotoxicity. The understanding of basic mechanisms of particle biopersistence and brain translocation represents a major health challenge, since it could help to define susceptibility factors to develop chronic neurotoxic damage. Biopersistence of alum may be linked to its lysosome-destabilizing effect, which is likely due to direct crystal-induced rupture of phagolysosomal membranes. Macrophages that continuously perceive foreign particles in their cytosol will likely reiterate, with variable interindividual efficiency, a dedicated form of autophagy (xenophagy until they dispose of alien materials. Successful compartmentalization of particles within double membrane autophagosomes and subsequent fusion with repaired and re-acidified lysosomes will expose alum to lysosomal acidic pH, the sole factor that can solubilize alum particles. Brain translocation of alum particles is linked to a Trojan horse mechanism previously described for infectious particles (HIV, HCV, that obeys to CCL2 signaling the major inflammatory monocyte

  17. In vivo 3D digital atlas database of the adult C57BL/6J mouse brain by magnetic resonance microscopy

    Directory of Open Access Journals (Sweden)

    Yu Ma

    2008-04-01

    Full Text Available In this study, a 3D digital atlas of the live mouse brain based on magnetic resonance microscopy (MRM is presented. C57BL/6J adult mouse brains were imaged in vivo on a 9.4 Tesla MR instrument at an isotropic spatial resolution of 100 μm. With sufficient signal-to-noise (SNR and contrast-to-noise ratio (CNR, 20 brain regions were identified. Several atlases were constructed including 12 individual brain atlases, an average atlas, a probabilistic atlas and average geometrical deformation maps. We also investigated the feasibility of using lower spatial resolution images to improve time efficiency for future morphological phenotyping. All of the new in vivo data were compared to previous published in vitro C57BL/6J mouse brain atlases and the morphological differences were characterized. Our analyses revealed significant volumetric as well as unexpected geometrical differences between the in vivo and in vitro brain groups which in some instances were predictable (e.g. collapsed and smaller ventricles in vitro but not in other instances. Based on these findings we conclude that although in vitro datasets, compared to in vivo images, offer higher spatial resolutions, superior SNR and CNR, leading to improved image segmentation, in vivo atlases are likely to be an overall better geometric match for in vivo studies, which are necessary for longitudinal examinations of the same animals and for functional brain activation studies. Thus the new in vivo mouse brain atlas dataset presented here is a valuable complement to the current mouse brain atlas collection and will be accessible to the neuroscience community on our public domain mouse brain atlas website.

  18. Brain iron homeostasis.

    Science.gov (United States)

    Moos, Torben

    2002-11-01

    [125I]transferrin in the brain. Some of the 59Fe was detected in CSF in a fraction less than 30 kDa (III). It was estimated that the iron-binding capacity of transferrin in CSF was exceeded, suggesting that iron is transported into the brain in a quantity that exceeds that of transferrin. Accordingly, it was concluded that the paramount iron transport across the BBB is the result of receptor-mediated endocytosis of iron-containing transferrin by capillary endothelial cells, followed by recycling of transferrin to the blood and transport of non-transferrin-bound iron into the brain. It was found that retrograde axonal transport in a cranial motor nerve is age-dependent, varying from almost negligible in the neonatal brain to high in the adult brain. The principle sources of extracellular transferrin in the brain are hepatocytes, oligodendrocytes, and the choroid plexus. As the passage of liver-derived transferrin into the brain is restricted due to the BBB, other candidates for binding iron in the interstitium should be considered. In vitro studies have revealed secretion of transferrin from the choroid plexus and oligodendrocytes. The second part of the thesis encompasses the circulation of iron in the extracellular fluids of the brain, i.e. the brain interstitial fluid and the CSF. As the latter receives drainage from the interstitial fluid, the CSF of the ventricles can be considered a mixture of these fluids, which may allow for analysis of CSF in matters that relate to the brain interstitial fluid. As the choroid plexus is known to synthesize transferrin, a key question is whether transferrin of the CSF might play a role for iron homeostasis by diffusing from the ventricles and subarachnoid space to the brain interstitium. Intracerebroventricular injection of [59Fe125I]transferrin led to a higher accumulation of 59Fe than of [125I]transferrin in the brain. Except for uptake and axonal transport by certain neurons with access to the ventricular CSF, both iron and

  19. Brain foods: the effects of nutrients on brain function

    OpenAIRE

    Gómez-Pinilla, Fernando

    2008-01-01

    It has long been suspected that the relative abundance of specific nutrients can affect cognitive processes and emotions. Newly described influences of dietary factors on neuronal function and synaptic plasticity have revealed some of the vital mechanisms that are responsible for the action of diet on brain health and mental function. Several gut hormones that can enter the brain, or that are produced in the brain itself, influence cognitive ability. In addition, well-established regulators o...

  20. 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.

  1. Expected and unexpected features of protein-binding RNA aptamers

    DEFF Research Database (Denmark)

    Bjerregaard, Nils; Andreasen, Peter A; Dupont, Daniel M

    2016-01-01

    RNA molecules with high affinity to specific proteins can be isolated from libraries of up to 10(16) different RNA sequences by systematic evolution of ligands by exponential enrichment (SELEX). These so-called protein-binding RNA aptamers are often interesting, e.g., as modulators of protein...... function for therapeutic use, for probing the conformations of proteins, for studies of basic aspects of nucleic acid-protein interactions, etc. Studies on the interactions between RNA aptamers and proteins display a number of expected and unexpected features, including the chemical nature of the...... interacting RNA-protein surfaces, the conformation of protein-bound aptamer versus free aptamer, the conformation of aptamer-bound protein versus free protein, and the effects of aptamers on protein function. Here, we review current insights into the details of RNA aptamer-protein interactions. For further...

  2. Unexpected radionuclide uptake due to calcification in muscles

    International Nuclear Information System (INIS)

    Full text: A male patient aged 27 years was injected with 1000 MBq of 99Tcm-MDP. The patient was an active man indulging in contact sport. He presented with lower back and pelvic pain. Spot pictures were made of the pelvis, lumbar spine and femurs. Unexpected active radionuclide uptake in the muscles was seen. In the delayed static images, there was focal accumulation of tracer uptake in the muscles overlying the mid-shaft of the left femur consistent with myositis ossificans. Myositis ossificans is a benign ossifying process that is generally solitary and well circumscribed. It is most commonly found in the muscles but it may occur in other connective tissues, especially tendons and subcutaneous fat. This was presumably associated with chronic muscular injuries contracted during sports activity

  3. Detecting the unexpected: a research framework for ocean acidification.

    Science.gov (United States)

    Pfister, Catherine A; Esbaugh, Andrew J; Frieder, Christina A; Baumann, Hannes; Bockmon, Emily E; White, Meredith M; Carter, Brendan R; Benway, Heather M; Blanchette, Carol A; Carrington, Emily; McClintock, James B; McCorkle, Daniel C; McGillis, Wade R; Mooney, T Aran; Ziveri, Patrizia

    2014-09-01

    The threat that ocean acidification (OA) poses to marine ecosystems is now recognized and U.S. funding agencies have designated specific funding for the study of OA. We present a research framework for studying OA that describes it as a biogeochemical event that impacts individual species and ecosystems in potentially unexpected ways. We draw upon specific lessons learned about ecosystem responses from research on acid rain, carbon dioxide enrichment in terrestrial plant communities, and nitrogen deposition. We further characterize the links between carbon chemistry changes and effects on individuals and ecosystems, and enumerate key hypotheses for testing. Finally, we quantify how U.S. research funding has been distributed among these linkages, concluding that there is an urgent need for research programs designed to anticipate how the effects of OA will reverberate throughout assemblages of species.

  4. Preparing for the unexpected - A psychologist's case for improved training

    Science.gov (United States)

    Foushee, H. C.

    1984-01-01

    In the procedures designed to minimize human errors that lead to aircraft incidents, the improved human factor engineering and automation approaches must be supplemented by new training methods. Changes are suggested in the preprogrammed training principles which are currently based almost exclusively on the procedures-oriented environment, with insufficient training for cognitive processing and awareness. Use of the Line-Oriented Flight Training procedure, in which a training simulator is supplemented by a highly structured script or scenario to simulate the total line operational environment for the purpose of simultaneously training the entire flight crew, offers one way of providing pilots and other crewmembers with the experience of dealing with unexpected or stressful events. Of primary importance is maximal coordination between the aircraft captain and other crewmembers during the flight, which puts emphasis on the importance of teamwork and personal relations among all other crewmembers. The current FARs governing training and proficiency will have to be modified to accommodate new training appoaches.

  5. Sudden unexpected death in epilepsy genetics: Molecular diagnostics and prevention.

    Science.gov (United States)

    Goldman, Alica M; Behr, Elijah R; Semsarian, Christopher; Bagnall, Richard D; Sisodiya, Sanjay; Cooper, Paul N

    2016-01-01

    Epidemiologic studies clearly document the public health burden of sudden unexpected death in epilepsy (SUDEP). Clinical and experimental studies have uncovered dynamic cardiorespiratory dysfunction, both interictally and at the time of sudden death due to epilepsy. Genetic analyses in humans and in model systems have facilitated our current molecular understanding of SUDEP. Many discoveries have been informed by progress in the field of sudden cardiac death and sudden infant death syndrome. It is becoming apparent that SUDEP genomic complexity parallels that of sudden cardiac death, and that there is a pauci1ty of analytically useful postmortem material. Because many challenges remain, future progress in SUDEP research, molecular diagnostics, and prevention rests in international, collaborative, and transdisciplinary dialogue in human and experimental translational research of sudden death.

  6. The Unexpected Awakening of Chaitén Volcano, Chile

    Science.gov (United States)

    Carn, Simon A.; Pallister, John S.; Lara, Luis; Ewert, John W.; Watt, Sebastian; Prata, Alfred J.; Thomas, Ronald J.; Villarosa, Gustavo

    2009-06-01

    On 2 May 2008, a large eruption began unexpectedly at the inconspicuous Chaitén volcano in Chile's southern volcanic zone. Ash columns abruptly jetted from the volcano into the stratosphere, followed by lava dome effusion and continuous low-altitude ash plumes [Lara, 2009]. Apocalyptic photographs of eruption plumes suffused with lightning were circulated globally. Effects of the eruption were extensive. Floods and lahars inundated the town of Chaitén, and its 4625 residents were evacuated. Widespread ashfall and drifting ash clouds closed regional airports and cancelled hundreds of domestic flights in Argentina and Chile and numerous international flights [Guffanti et al., 2008]. Ash heavily affected the aquaculture industry in the nearby Gulf of Corcovado, curtailed ecotourism, and closed regional nature preserves. To better prepare for future eruptions, the Chilean government has boosted support for monitoring and hazard mitigation at Chaitén and at 42 other highly hazardous, active volcanoes in Chile.

  7. Unexpected ST segment changes in children--a case report.

    Science.gov (United States)

    Alfirevic, Andrej; Mossad, Emad; Niezgoda, Julie

    2005-01-01

    In children, myocardial ischemic changes during anesthesia are a rare event unless there is underlying pathology. The patient in this case report was an apparently healthy child scheduled for adenoidectomy and bilateral tympanostomy. Occurrence of significant ST changes as well as intraoperative and postoperative hypoxemia required further diagnostic work-up. Postoperative echocardiographic findings were suspicious of intrapulmonary right to left shunting. The pulmonary arteriovenous fistula is probably the major pathophysiological factor for the development of hypoxemia and paradoxical air embolism especially during positive pressure ventilation in our patient. Unexpected ST segment changes might also occur in patients with anomalous origin of coronary arteries. Although diagnostic work-up was inconclusive, it is necessary to rule out any underlying pathological process. Further follow-up is also important in order to learn more about these disease states that often have subclinical, but potentially fatal presentation. PMID:15649167

  8. A search for unexpected bound states in 15B

    Science.gov (United States)

    Hoffman, Calem R.

    2014-09-01

    Bound states in 15B are to be populated through the one proton removal reaction from a 16C beam produced at the RCNP EN Course through 18O fragmentation. γ-decays from these states will be identified by an array of Compton-suppressed HPGe Clover detectors (CAGRA). The goals consist of i) identifying any previously unobserved and unexpected bound states in 15B and ii) to assign total angular momenta to known excited states for the first time. At present only two bound states have been observed in 15B, neither with firm spin or parity assignments. The present work to be discussed is aimed at determining whether an excited 3 /2- state, a state with identical spin-parity as the ground state, resides below the neutron separation energy in 15B. Such an excited 3 /2- state is not predicted to appear below the 15B Sn by shell-model calculations using various p- sd interactions. However, a robust systematic, probably related to the s-wave trends found in the single-neutron states in this region, has been observed for neutron-rich N=10 nuclei and it suggests that the state may appear lower in excitation energy than expected. Providing some measure of validation for the N=10 prediction is a similar trend noticed in the energy differences between ground (p)2 neutron states and excited (sd)2 neutron states in the N=8 neutron-rich isotones. In addition to a search for this unexpected state, additional spectroscopic information on 15B will better aid in the understanding of the N=10 isotones when transitioning from 16C into sparsely probed 14Be. Details of the experimental procedures and motivation will be presented and discussed. Bound states in 15B are to be populated through the one proton removal reaction from a 16C beam produced at the RCNP EN Course through 18O fragmentation. γ-decays from these states will be identified by an array of Compton-suppressed HPGe Clover detectors (CAGRA). The goals consist of i) identifying any previously unobserved and unexpected bound

  9. Brain Basics

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    Full Text Available ... all. She was happily married and successful in business. Then, after a serious setback at work, she ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses ...

  10. Brain Basics

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    Full Text Available ... the anatomy, physiology, and chemistry of the nervous system. When the brain cannot effectively coordinate the billions ... basic working unit of the brain and nervous system. These cells are highly specialized for the function ...

  11. Brain Basics

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    Full Text Available ... the brain cannot effectively coordinate the billions of cells in the body, the results can affect many ... unit of the brain and nervous system. These cells are highly specialized for the function of conducting ...

  12. Brain Basics

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    Full Text Available ... Trials — Participants Statistics Help for Mental Illnesses Outreach Research Priorities Funding Labs at NIMH News About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The ...

  13. Brain Basics

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    Full Text Available ... brain may play a role in disorders like schizophrenia or attention deficit hyperactivity disorder (ADHD) . Glutamate —the ... mental disorders, including autism , obsessive compulsive disorder (OCD) , schizophrenia , and depression . Brain Regions Just as many neurons ...

  14. Brain Basics

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    Full Text Available ... body, the results can affect many aspects of life. Scientists are continually learning more about how the brain grows and works in healthy people, and how normal brain development and function ...

  15. Brain Basics

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    Full Text Available ... Brain Basics will introduce you to some of this science, such as: How the brain develops How ... cell, and responds to signals from the environment; this all helps the cell maintain its balance with ...

  16. Brain Basics

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    Full Text Available ... How the brain develops How genes and the environment affect the brain The basic structure of the ... inside contents of the cell from its surrounding environment and controls what enters and leaves the cell, ...

  17. Brain Basics

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    Full Text Available ... affect many aspects of life. Scientists are continually learning more about how the brain grows and works ... early brain development. It may also assist in learning and memory. Problems in making or using glutamate ...

  18. Brain Basics

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    Full Text Available ... have been linked to many mental disorders, including autism , obsessive compulsive disorder (OCD) , schizophrenia , and depression . Brain ... studies show that brain growth in children with autism appears to peak early. And as they grow ...

  19. Brain Basics

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    Full Text Available ... may help improve treatments for anxiety disorders like phobias or post-traumatic stress disorder (PTSD) . Prefrontal cortex ( ... brain's structure, studies show that brain growth in children with autism appears to peak early. And as ...

  20. Brain Basics

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    Full Text Available ... body, the results can affect many aspects of life. Scientists are continually learning more about how the brain grows and works in healthy people, and how normal brain development ...

  1. Brain Basics

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    Full Text Available ... medications could reduce the amount of trial and error and frustration that many people with depression experience ... early brain development, and may also assist in learning and memory. hippocampus —A portion of the brain ...

  2. Brain Diseases

    Science.gov (United States)

    The brain is the control center of the body. It controls thoughts, memory, speech, and movement. It regulates the function of many organs. When the brain is healthy, it works quickly and automatically. However, ...

  3. Brain Basics

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    Full Text Available ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses ... depression experience when starting treatment. Gene Studies Advanced technologies are also making it faster, easier, and more ...

  4. Brain Basics

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    Full Text Available ... mainly involved in controlling movement and aiding the flow of information to the front of the brain, ... the neuron will fire. This enhances the electrical flow among brain cells required for normal function and ...

  5. Brain Basics

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    Full Text Available ... works in healthy people, and how normal brain development and function can go awry, leading to mental ... and are working to compare that with brain development in people mental disorders. Genes and environmental cues ...

  6. Brain Basics

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    Full Text Available ... and epigenetic changes can be passed on to future generations. Further understanding of genes and epigenetics may ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses ...

  7. Brain Basics

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    Full Text Available ... neurons, the most highly specialized cells of all, conduct messages. Every cell in our bodies contains a ... brain's structure, studies show that brain growth in children with autism appears to peak early. And as ...

  8. Brain Basics

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    Full Text Available ... can be related to changes in the anatomy, physiology, and chemistry of the nervous system. When the ... healthy people, and how normal brain development and function can go awry, leading to mental illnesses. Brain ...

  9. 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 ... blues" from time to time. In contrast, major depression is a serious disorder that lasts for weeks. ...

  10. Astroglial Contribution to Brain Energy Metabolism in Humans Revealed by 13C Nuclear Magnetic Resonance Spectroscopy: Elucidation of the Dominant Pathway for Neurotransmitter Glutamate Repletion and Measurement of Astrocytic Oxidative Metabolism

    OpenAIRE

    Lebon, Vincent; Petersen, Kitt F.; Cline, Gary W.; Shen, Jun; Mason, Graeme F.; Dufour, Sylvie; Behar, Kevin L.; Shulman, Gerald I.; Rothman, Douglas L.

    2002-01-01

    Increasing evidence supports a crucial role for glial metabolism in maintaining proper synaptic function and in the etiology of neurological disease. However, the study of glial metabolism in humans has been hampered by the lack of noninvasive methods. To specifically measure the contribution of astroglia to brain energy metabolism in humans, we used a novel noninvasive nuclear magnetic resonance spectroscopic approach. We measured carbon 13 incorporation into brain glutamate and glutamine in...

  11. Separate effects of sex hormones and sex chromosomes on brain structure and function revealed by high-resolution magnetic resonance imaging and spatial navigation assessment of the Four Core Genotype mouse model.

    Science.gov (United States)

    Corre, Christina; Friedel, Miriam; Vousden, Dulcie A; Metcalf, Ariane; Spring, Shoshana; Qiu, Lily R; Lerch, Jason P; Palmert, Mark R

    2016-03-01

    Males and females exhibit several differences in brain structure and function. To examine the basis for these sex differences, we investigated the influences of sex hormones and sex chromosomes on brain structure and function in mice. We used the Four Core Genotype (4CG) mice, which can generate both male and female mice with XX or XY sex chromosome complement, allowing the decoupling of sex chromosomes from hormonal milieu. To examine whole brain structure, high-resolution ex vivo MRI was performed, and to assess differences in cognitive function, mice were trained on a radial arm maze. Voxel-wise and volumetric analyses of MRI data uncovered a striking independence of hormonal versus chromosomal influences in 30 sexually dimorphic brain regions. For example, the bed nucleus of the stria terminalis and the parieto-temporal lobe of the cerebral cortex displayed steroid-dependence while the cerebellar cortex, corpus callosum, and olfactory bulbs were influenced by sex chromosomes. Spatial learning and memory demonstrated strict hormone-dependency with no apparent influence of sex chromosomes. Understanding the influences of chromosomes and hormones on brain structure and function is important for understanding sex differences in brain structure and function, an endeavor that has eventual implications for understanding sex biases observed in the prevalence of psychiatric disorders.

  12. Brain Basics

    Medline Plus

    Full Text Available ... pituitary-adrenal (HPA) axis. Brain Basics in Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah ... having trouble coping with the stresses in her life. She began to think of suicide because she ...

  13. Brain Basics

    Medline Plus

    Full Text Available ... Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a middle-aged woman ... new memories. hypothalmic-pituitary-adrenal (HPA) axis —A brain-body ... stress. impulse —An electrical communication signal sent between neurons ...

  14. Brain Aneurysm

    Science.gov (United States)

    A brain aneurysm is an abnormal bulge or "ballooning" in the wall of an artery in the brain. They are sometimes called berry aneurysms because they ... often the size of a small berry. Most brain aneurysms produce no symptoms until they become large, ...

  15. Seroprevalence of unexpected red blood cell antibodies among pregnant women in Uganda.

    Science.gov (United States)

    Eipl, K; Nakabiito, C; Bwogi, K; Motevalli, M; Roots, A; Blagg, L; Jackson, J B

    2012-01-01

    We conducted a population-based, cross-sectional study among pregnant women in Kampala, Uganda, to determine ABO and D blood types and to determine the percentage who have unexpected red blood cell (RBC) antibodies and their specificities. De-identified blood samples from routine testing of 1001 pregnant women at the Mulago Hospital antenatal clinics in Kampala were typed for ABO and D and screened for the presence of unexpected RBC antibodies with confirmation and subsequent antibody identification. Of the 1001 blood samples tested, 48.9 percent, 26.4 percent, 21.0 percent, and 3.8 percent tested positive for blood groups 0, A, B, and AB, respectively. Of these samples, 23 (2.3%)were negative forD, and 55 (5.5%) showed initial reactivity with at least one screening RBC. The RBC antibody screen was repeated on these 55 samples, and antibody identification was performed at the Johns Hopkins Hospital Blood Bank in Baltimore, Maryland. Twenty-one of the 55 samples were confirmed to have evidence of agglutination. Nine of the 21 samples demonstrated the presence of clinically significant RBC antibodies with anti-S being the most common, 8 samples demonstrated the presence of benign or naturally occurring antibodies, and 4 had only inconclusive reactivity. This study revealed a relatively high frequency of D and a low frequency of demonstrable clinically significant alloantibodies that may cause hemolytic disease of the newborn or hemolytic transfusion reactions among pregnant women in Kampala, with anti-S being the most frequent antibody specificity. PMID:23421539

  16. Unexpected finding of T-cell lymphoma in a previously healthy 16-year-old patient after a thorax trauma

    DEFF Research Database (Denmark)

    Bach Okholm-Hansen, Anna; Brorson, Stig

    2014-01-01

    of an excessive amount of pleural fluid, he developed severe respiratory distress. A chest tube was inserted and he was transferred to a level 1 trauma centre. Here, a computed tomography scan unexpectedly revealed significantly swollen mediastinal and retroperitoneal lymph nodes, and he was later diagnosed......INTRODUCTION: We describe the clinical course and emphasize the difficulties in diagnosing T-cell lymphoblastic lymphoma. The differential diagnostic difficulties have previously been described in regard to pneumonia, but to the best of the authors' knowledge this is the first case report...

  17. Illuminating odors: when optogenetics brings to light unexpected olfactory abilities.

    Science.gov (United States)

    Grimaud, Julien; Lledo, Pierre-Marie

    2016-06-01

    For hundreds of years, the sense of smell has generated great interest in the world literature, oenologists, and perfume makers but less of scientists. Only recently this sensory modality has gained new attraction in neuroscience when original tools issued from physiology, anatomy, or molecular biology were available to decipher how the brain makes sense of olfactory cues. However, this move was promptly dampened by the difficulties of developing quantitative approaches to study the relationship between the physical characteristics of stimuli and the sensations they create. An upswing of olfactory investigations occurred when genetic tools could be used in combination with devices borrowed from the physics of light (a hybrid technique called optogenetics) to scrutinize the olfactory system and to provide greater physiological precision for studying olfactory-driven behaviors. This review aims to present the most recent studies that have used light to activate components of the olfactory pathway, such as olfactory receptor neurons, or neurons located further downstream, while leaving intact others brain circuits. With the use of optogenetics to unravel the mystery of olfaction, scientists have begun to disentangle how the brain makes sense of smells. In this review, we shall discuss how the brain recognizes odors, how it memorizes them, and how animals make decisions based on odorants they are capable of sensing. Although this review deals with olfaction, the role of light will be central throughout. PMID:27194792

  18. Illuminating odors: when optogenetics brings to light unexpected olfactory abilities

    Science.gov (United States)

    Grimaud, Julien

    2016-01-01

    For hundreds of years, the sense of smell has generated great interest in the world literature, oenologists, and perfume makers but less of scientists. Only recently this sensory modality has gained new attraction in neuroscience when original tools issued from physiology, anatomy, or molecular biology were available to decipher how the brain makes sense of olfactory cues. However, this move was promptly dampened by the difficulties of developing quantitative approaches to study the relationship between the physical characteristics of stimuli and the sensations they create. An upswing of olfactory investigations occurred when genetic tools could be used in combination with devices borrowed from the physics of light (a hybrid technique called optogenetics) to scrutinize the olfactory system and to provide greater physiological precision for studying olfactory-driven behaviors. This review aims to present the most recent studies that have used light to activate components of the olfactory pathway, such as olfactory receptor neurons, or neurons located further downstream, while leaving intact others brain circuits. With the use of optogenetics to unravel the mystery of olfaction, scientists have begun to disentangle how the brain makes sense of smells. In this review, we shall discuss how the brain recognizes odors, how it memorizes them, and how animals make decisions based on odorants they are capable of sensing. Although this review deals with olfaction, the role of light will be central throughout. PMID:27194792

  19. Hematogenous Pasteurella multocida brain abscess

    International Nuclear Information System (INIS)

    A case of hematogenously acquired brain abscess caused by Pasteurella multocida is described. CT scans of the head revealed the lesions in a 67 year old man with mild alcoholic liver disease and severe chronic obstructive pulmonary disease. Ultrasound examinations of the abdomen and chest and an echocardiogram failed to reveal a source for the abscess. On autopsy examination three encapsulated brain abscesses were found. 34 references, 2 figures, 1 table

  20. An unexpected evolution of symptomatic mild middle cerebral artery (MCA stenosis: asymptomatic occlusion

    Directory of Open Access Journals (Sweden)

    Malferrari Giovanni

    2011-12-01

    occlusion. Neuroradiological imaging did not identify new lesions of the brain parenchyma and a repeated selective cerebral angiography confirmed the left M1 MCA occlusion. Conclusions Regardless of the role of metabolic and/or inflammatory factors on the aetiology of the intracranial stenosis in this case, the course of the vessel disease was unexpected and previously unreported in the literature at our knowledge.

  1. Radiography after unexpected death in infants and children compared to autopsy

    International Nuclear Information System (INIS)

    Postmortem radiography may reveal skeletal and soft-tissue abnormalities of importance for the diagnosis of cause of death. To review the radiographs of children under 3 years of age who had died suddenly and unexpectedly. To compare the radiological and autopsy findings evaluating possible differences in children dying of SIDS and of an explainable cause. A total of 110 consecutive skeletal surveys performed between 1998 and 2002 were reviewed. All but one were performed before autopsy and comprised AP views of the appendicular and axial skeleton and thorax/abdomen, lateral views of the axial skeleton and thorax, and two oblique views of the ribs. Radiography and autopsy findings were compared. Causes of death were classified as SIDS/borderline SIDS (n = 52) and non-SIDS (n = 58), with one case of abuse. In 102 infants there were 150 pathological findings, 88 involving the chest, 24 skeletal, and 38 miscellaneous findings. The radiological-pathological agreement was poor concerning pulmonary findings. Skeletal findings were sometimes important for the final diagnosis. Radiography revealed many skeletal and soft-tissue findings. Pulmonary pathology was most frequently found, but showed poor agreement with autopsy findings. Recognizing skeletal findings related to abuse is important, as these may escape recognition at autopsy. (orig.)

  2. Unexpected properties of interactions of high energy protons

    CERN Document Server

    Dremin, I M

    2016-01-01

    Experimental data on proton-proton interactions in high energy collisions show quite a special and unexpected behaviour of the proportion of elastic scattering compared to inelastic processes with increasing energy. It decreases at the beginning (at comparatively low energies) but then starts increasing. From Intersecting Storage Rings (ISR) energies of 23.5 - 62.5 GeV up to higher energies 7 - 13 TeV at the Large Hadron Collider (LHC) it increases by a factor more than 1.5! According to intuitive classical ideas we would expect a stable tendency with increasing proportion of the break-down of protons compared to their survival probability. One can assume that either the asymptotic freedom or the extremely short time of flight of high energy protons through each other are in charge of such a surprising effect. The unquestionable principle of unitarity combined with the available experimental data on elastic scattering is used to get new conclusions about the shape of the interaction region of colliding proton...

  3. Unexpected Molecular Sieving Properties of Zeolitic Imidazolate Framework-8

    KAUST Repository

    Zhang, Chen

    2012-08-16

    We studied molecular sieving properties of zeolitic imidazolate framework-8 (ZIF-8) by estimating the thermodynamically corrected diffusivities of probe molecules at 35 °C. From helium (2.6 Å) to iso-C 4H 10 (5.0 Å), the corrected diffusivity drops 14 orders of magnitude. Our results further suggest that the effective aperture size of ZIF-8 for molecular sieving is in the range of 4.0 to 4.2 Å, which is significantly larger than the XRD-derived value (3.4 Å) and between the well-known aperture size of zeolite 4A (3.8 Å) and 5A (4.3 Å). Interestingly, because of aperture flexibility, the studied C 4 hydrocarbon molecules that are larger than this effective aperture size still adsorb in the micropores of ZIF-8 with kinetic selectivities for iso-C 4H 8/iso-C 4H 10 of 180 and n-C 4H 10/iso-C 4H 10 of 2.5 × 10 6. These unexpected molecular sieving properties open up new opportunities for ZIF materials for separations that cannot be economically achieved by traditional microporous adsorbents such as synthetic zeolites. © 2012 American Chemical Society.

  4. Unexpectedly large charge radii of neutron-rich calcium isotopes

    CERN Document Server

    Garcia Ruiz, R F; Blaum, K; Ekström, A; Frömmgen, N; Hagen, G; Hammen, M; Hebeler, K; Holt, J D; Jansen, G R; Kowalska, M; Kreim, K; Nazarewicz, W; Neugart, R; Neyens, G; Nörtershäuser, W; Papenbrock, T; Papuga, J; Schwenk, A; Simonis, J; Wendt, K A; Yordanov, D T

    2016-01-01

    Despite being a complex many-body system, the atomic nucleus exhibits simple structures for certain ‘magic’ numbers of protons and neutrons. The calcium chain in particular is both unique and puzzling: evidence of doubly magic features are known in 40,48Ca, and recently suggested in two radioactive isotopes, 52,54Ca. Although many properties of experimentally known calcium isotopes have been successfully described by nuclear theory, it is still a challenge to predict the evolution of their charge radii. Here we present the first measurements of the charge radii of 49,51,52Ca, obtained from laser spectroscopy experiments at ISOLDE, CERN. The experimental results are complemented by state-of-the-art theoretical calculations. The large and unexpected increase of the size of the neutron-rich calcium isotopes beyond N = 28 challenges the doubly magic nature of 52Ca and opens new intriguing questions on the evolution of nuclear sizes away from stability, which are of importance for our understanding of neutron-...

  5. Unexpectedly large charge radii of neutron-rich calcium isotopes

    Science.gov (United States)

    Garcia Ruiz, R. F.; Bissell, M. L.; Blaum, K.; Ekström, A.; Frömmgen, N.; Hagen, G.; Hammen, M.; Hebeler, K.; Holt, J. D.; Jansen, G. R.; Kowalska, M.; Kreim, K.; Nazarewicz, W.; Neugart, R.; Neyens, G.; Nörtershäuser, W.; Papenbrock, T.; Papuga, J.; Schwenk, A.; Simonis, J.; Wendt, K. A.; Yordanov, D. T.

    2016-06-01

    Despite being a complex many-body system, the atomic nucleus exhibits simple structures for certain `magic’ numbers of protons and neutrons. The calcium chain in particular is both unique and puzzling: evidence of doubly magic features are known in 40,48Ca, and recently suggested in two radioactive isotopes, 52,54Ca. Although many properties of experimentally known calcium isotopes have been successfully described by nuclear theory, it is still a challenge to predict the evolution of their charge radii. Here we present the first measurements of the charge radii of 49,51,52Ca, obtained from laser spectroscopy experiments at ISOLDE, CERN. The experimental results are complemented by state-of-the-art theoretical calculations. The large and unexpected increase of the size of the neutron-rich calcium isotopes beyond N = 28 challenges the doubly magic nature of 52Ca and opens new intriguing questions on the evolution of nuclear sizes away from stability, which are of importance for our understanding of neutron-rich atomic nuclei.

  6. An unexpected ending: Noncanonical 3′ end processing mechanisms

    Science.gov (United States)

    Wilusz, Jeremy E.; Spector, David L.

    2010-01-01

    Proper 3′ end processing of a nascent transcript is critical for the functionality of the mature RNA. Although it has long been thought that virtually all long RNA polymerase II transcripts terminate in a poly(A) tail that is generated by endonucleolytic cleavage followed by polyadenylation, noncanonical 3′ end processing mechanisms have recently been identified at several gene loci. Unexpectedly, enzymes with well-characterized roles in other RNA processing events, such as tRNA biogenesis and pre-mRNA splicing, cleave these nascent transcripts to generate their mature 3′ ends despite the presence of nearby polyadenylation signals. In fact, the presence of multiple potential 3′ end cleavage sites is the norm at many human genes, and recent work suggests that the choice among sites is regulated during development and in response to cellular cues. It is, therefore, becoming increasing clear that the selection of a proper 3′ end cleavage site represents an important step in the regulation of gene expression and that the mature 3′ ends of RNA polymerase II transcripts can be generated via multiple mechanisms. PMID:20007330

  7. Unexpected gallbladder cancer: Surgical strategies and prognostic factors.

    Science.gov (United States)

    Clemente, Gennaro

    2016-08-27

    Gallbladder cancer is the most common tumor of the biliary tract and it is associated with a poor prognosis. Unexpected gallbladder cancer is a cancer incidentally discovered, as a surprise, at the histological examination after cholecystectomy for gallstones or other indications. It is a potentially curable disease, with an intermediate or good prognosis in most cases. An adequate surgical strategy is mandatory to improve the prognosis and an adjunctive radical resection may be required depending on the depth of invasion. If the cancer discovered after cholecystectomy is a pTis or a pT1a, a second surgical procedure is not mandatory. In the other cases (pT1b, pT2 and pT3 cancer) a re-resection (4b + 5 liver segmentectomy, lymphadenectomy and port-sites excision in some cases) is required to obtain a radical excision of the tumor and an accurate disease staging. The operative specimens of re-resection should be examined by the pathologist to find any "residual" tumor. The "residual disease" is the most important prognostic factor, significantly reducing median disease-free survival and disease-specific survival. The other factors include depth of parietal invasion, metastatic nodal disease, surgical margin status, cholecystectomy for acute cholecystitis, histological differentiation, lymphatic, vascular and peri-neural invasion and overall TNM-stage. PMID:27648157

  8. Unexpected levels and movement of radon in a large warehouse

    International Nuclear Information System (INIS)

    Alpha-track detectors, used in screening for radon, identified a large warehouse with levels of radon as high as 20 p Ci/l. This circumstance was unexpected because large bay doors were left open for much of the day to admit 1 8-wheeler trucks, and exhaust fans in the roof produced good ventilation. More detailed temporal and spatial investigations of radon and air-flow patterns were made with electret chambers, Lucas-cell flow chambers, tracer gas, smoke pencils and pressure sensing micrometers. An oval-dome shaped zone of radon (>4 p Ci/L) persisted in the central region of each of four separate bays composing the warehouse. Detailed studies of air movement in the bay with the highest levels of radon showed clockwise rotation of air near the outer walls with a central dead zone. Sub slab, radon-laden air ingresses the building through expansion joints between the floor slabs to produce the measured radon. The likely source of radon is air within porous, karst bedrock that underlies much of north-central Tennessee where the warehouse is situated

  9. Unexpected diagnosis for preauricular swelling - two case reports

    International Nuclear Information System (INIS)

    Background. Preauricular swelling in children may be associated with a wide range of pathology. The history, clinical presentation and imaging features of such swellings may be non-specific. Sometimes it can be caused by underlying bone lesion. Case reports. We report about two children who were admitted to the hospital with swelling in the preauricular region and an unexpected final diagnosis. We found aneurismal bone cyst and central giant cell granuloma, respectively. Conclusions. Awareness of such lesions is important to avoid diagnostic errors and a potential mismanagement. These lesions are often difficult to differentiate on the basis of their radiographic features alone. A high-resolution US enables an accurate analysis of soft tissue and helps in the differential diagnosis. It also enables an accurate location of the lesion, which helps to avoid a wrong interpretation based on the clinical finding only. The CT-scan performed afterwards provides necessary information for the assessment of location, structure and size of the lesion. (author)

  10. Sudden unexpected death in epilepsy: epidemiology, mechanisms, and prevention.

    Science.gov (United States)

    Devinsky, Orrin; Hesdorffer, Dale C; Thurman, David J; Lhatoo, Samden; Richerson, George

    2016-09-01

    Sudden unexpected death in epilepsy (SUDEP) can affect individuals of any age, but is most common in younger adults (aged 20-45 years). Generalised tonic-clonic seizures are the greatest risk factor for SUDEP; most often, SUDEP occurs after this type of seizure in bed during sleep hours and the person is found in a prone position. SUDEP excludes other forms of seizure-related sudden death that might be mechanistically related (eg, death after single febrile, unprovoked seizures, or status epilepticus). Typically, postictal apnoea and bradycardia progress to asystole and death. A crucial element of SUDEP is brainstem dysfunction, for which postictal generalised EEG suppression might be a biomarker. Dysfunction in serotonin and adenosine signalling systems, as well as genetic disorders affecting cardiac conduction and neuronal excitability, might also contribute. Because generalised tonic-clonic seizures precede most cases of SUDEP, patients must be better educated about prevention. The value of nocturnal monitoring to detect seizures and postictal stimulation is unproven but warrants further study. PMID:27571159

  11. Unexpected demography in the recovery of an endangered primate population.

    Science.gov (United States)

    Strier, Karen B; Ives, Anthony R

    2012-01-01

    Assessments of the status of endangered species have focused on population sizes, often without knowledge of demographic and behavioral processes underlying population recovery. We analyzed demographic data from a 28-year study of a critically endangered primate, the northern muriqui, to investigate possible changes in demographic rates as this population recovered from near extirpation. As the population increased from 60 to nearly 300 individuals, its growth rate declined due to increased mortality and male-biased birth sex ratios; the increased mortality was not uniform across ages and sexes, and there has been a recent increase in mortality of prime-aged males. If not for a concurrent increase in fertility rates, the population would have stabilized at 200 individuals instead of continuing to grow. The unexpected increase in fertility rates and in adult male mortality can be attributed to the muriquis' expansion of their habitat by spending more time on the ground. The demographic consequences of this behavioral shift must be incorporated into management tactics for this population and emphasize the importance of understanding demographic rates in the recovery of endangered species. PMID:23028534

  12. Unexpected demography in the recovery of an endangered primate population.

    Directory of Open Access Journals (Sweden)

    Karen B Strier

    Full Text Available Assessments of the status of endangered species have focused on population sizes, often without knowledge of demographic and behavioral processes underlying population recovery. We analyzed demographic data from a 28-year study of a critically endangered primate, the northern muriqui, to investigate possible changes in demographic rates as this population recovered from near extirpation. As the population increased from 60 to nearly 300 individuals, its growth rate declined due to increased mortality and male-biased birth sex ratios; the increased mortality was not uniform across ages and sexes, and there has been a recent increase in mortality of prime-aged males. If not for a concurrent increase in fertility rates, the population would have stabilized at 200 individuals instead of continuing to grow. The unexpected increase in fertility rates and in adult male mortality can be attributed to the muriquis' expansion of their habitat by spending more time on the ground. The demographic consequences of this behavioral shift must be incorporated into management tactics for this population and emphasize the importance of understanding demographic rates in the recovery of endangered species.

  13. Illuminating odors: when optogenetics brings to light unexpected olfactory abilities

    OpenAIRE

    Grimaud, Julien; Lledo, Pierre-Marie

    2016-01-01

    For hundreds of years, the sense of smell has generated great interest in the world literature, oenologists, and perfume makers but less of scientists. Only recently this sensory modality has gained new attraction in neuroscience when original tools issued from physiology, anatomy, or molecular biology were available to decipher how the brain makes sense of olfactory cues. However, this move was promptly dampened by the difficulties of developing quantitative approaches to study the relations...

  14. Asymptomatic brain tumor detected at brain check-up

    Energy Technology Data Exchange (ETDEWEB)

    Onizuka, Masanari; Suyama, Kazuhiko; Shibayama, Akira; Hiura, Tsuyoshi; Horie, Nobutaka; Miyazaki, Hisaya [Sankoukai Miyazaki Hospital, Isahaya, Nagasaki (Japan)

    2001-09-01

    Brain check-up was performed in 4000 healthy subjects who underwent medical and radiological examinations for possible brain diseases in our hospital from April 1996 to March 2000. Magnetic resonance imaging revealed 11 brain tumors which consisted of six meningiomas, three pituitary adenomas, one astrocytoma, and one epidermoid cyst. The detection rate of incidental brain tumor in our hospital was 0.3%. Nine patients underwent surgery, with one case of morbidity due to postoperative transient oculomotor nerve paresis. The widespread use of brain check-up may increasingly detect asymptomatic brain tumors. Surgical indications for such lesions remain unclear, and the strategy for treatment should be determined with consideration of the patient's wishes. (author)

  15. Mathematics revealed

    CERN Document Server

    Berman, Elizabeth

    1979-01-01

    Mathematics Revealed focuses on the principles, processes, operations, and exercises in mathematics.The book first offers information on whole numbers, fractions, and decimals and percents. Discussions focus on measuring length, percent, decimals, numbers as products, addition and subtraction of fractions, mixed numbers and ratios, division of fractions, addition, subtraction, multiplication, and division. The text then examines positive and negative numbers and powers and computation. Topics include division and averages, multiplication, ratios, and measurements, scientific notation and estim

  16. Revealed Attention

    OpenAIRE

    Masatlioglu, Yusufcan; NAKAJIMA, Daisuke; Ozbay, Erkut Y

    2012-01-01

    The standard revealed preference argument relies on an implicit assumption that a decision maker considers all feasible alternatives. The marketing and psychology literatures, however, provide wellestablished evidence that consumers do not consider all brands in a given market before making a purchase (Limited Attention). In this paper, we illustrate how one can deduce both the decision maker's preference and the alternatives to which she pays attention and inattention from the observed behav...

  17. Revealed Attention

    OpenAIRE

    Yusufcan Masatlioglu; Daisuke Nakajima; Ozbay, Erkut Y

    2012-01-01

    The standard revealed preference argument relies on an implicit assumption that a decision maker considers all feasible alternatives. The marketing and psychology literatures, however, provide well-established evidence that consumers do not consider all brands in a given market before making a purchase (Limited Attention). In this paper, we illustrate how one can deduce both the decision maker's preference and the alternatives to which she pays attention and inattention from the observed beha...

  18. Brain glycogen

    DEFF Research Database (Denmark)

    Obel, Linea Lykke Frimodt; Müller, Margit S; Walls, Anne B;

    2012-01-01

    Glycogen is a complex glucose polymer found in a variety of tissues, including brain, where it is localized primarily in astrocytes. The small quantity found in brain compared to e.g., liver has led to the understanding that brain glycogen is merely used during hypoglycemia or ischemia....... In this review evidence is brought forward highlighting what has been an emerging understanding in brain energy metabolism: that glycogen is more than just a convenient way to store energy for use in emergencies-it is a highly dynamic molecule with versatile implications in brain function, i.e., synaptic...... activity and memory formation. In line with the great spatiotemporal complexity of the brain and thereof derived focus on the basis for ensuring the availability of the right amount of energy at the right time and place, we here encourage a closer look into the molecular and subcellular mechanisms...

  19. Sinking Brain: Unusual Cause of Orthostatic Headache

    Directory of Open Access Journals (Sweden)

    Raina R

    2015-04-01

    Full Text Available We report a case presenting with an orthostatic headache. Brain magnetic resonance imaging (MRI revealed typical pachymeningeal enhancement. CT myelography revealed leakage at the thoracic level. Patient was successfully treated by lumbar epidural blood patch (EBP.

  20. Effects of tank color on melanin-concentrating hormone levels in the brain, pituitary gland, and plasma of the barfin flounder as revealed by a newly developed time-resolved fluoroimmunoassay.

    Science.gov (United States)

    Amiya, Noriko; Amano, Masafumi; Takahashi, Akiyoshi; Yamanome, Takeshi; Kawauchi, Hiroshi; Yamamori, Kunio

    2005-09-15

    A pleuronectiform fish, the barfin flounder Verasper moseri, reared in a white tank had a smaller ratio of pigmented area of the skin on non-eyed side, grew faster, and had greater melanin-concentrating hormone (MCH)-immunoreactive cell bodies and MCH gene expression in the brain than in the black tank, indicating that synthesis and release of MCH are higher in fish from a white tank. In the present study, a time-resolved fluoroimmunoassay for MCH was developed. MCH levels were assessed in the brain, pituitary gland, and plasma of barfin flounders reared in a white or black tank. A competitive assay using two antibodies was performed among secondary antibodies in the solid phase, MCH antibodies, samples, and europium-labeled MCH. Displacement curves of serially diluted extracts (brain, pituitary gland, and plasma) of the barfin flounder paralleled that of the MCH standard. MCH levels in the brain and plasma were higher in fish reared in the white tank for 5 months than in the black tank. These results suggest that synthesis and secretion of MCH are enhanced with the white background and that MCH is involved in both somatic growth and the skin pigmentation in the barfin flounder. PMID:15979616

  1. 3 CFR - Unexpected Urgent Refugee and Migration Needs Related to the Continuing Conflict in Pakistan

    Science.gov (United States)

    2010-01-01

    ... 3 The President 1 2010-01-01 2010-01-01 false Unexpected Urgent Refugee and Migration Needs... Presidential Determination No. 2009-16 of March 11, 2009 Unexpected Urgent Refugee and Migration Needs Related... Migration and Refugee Assistance Act of 1962 (the “Act”), as amended (22 U.S.C. 2601), I hereby...

  2. 78 FR 9569 - Unexpected Urgent Refugee and Migration Needs Relating to Syria

    Science.gov (United States)

    2013-02-08

    ... Register. (Presidential Sig.) THE WHITE HOUSE, Washington, January 29, 2013. [FR Doc. 2013-03108 Filed 2-7...--Unexpected Urgent Refugee and Migration Needs Relating to Syria Memorandum of January 31, 2013--Delegation of... Determination No. 2013-04 of January 29, 2013 Unexpected Urgent Refugee and Migration Needs Relating to...

  3. 3 CFR - Unexpected Urgent Refugee and Migration Needs Related to Gaza

    Science.gov (United States)

    2010-01-01

    ... 3 The President 1 2010-01-01 2010-01-01 false Unexpected Urgent Refugee and Migration Needs... of January 27, 2009 Unexpected Urgent Refugee and Migration Needs Related to Gaza Memorandum for the..., including section 2(c)(1) of the Migration and Refugee Assistance Act of 1962 (the “Act”), as amended (22...

  4. Unexpected Fatal Hypernatremia after Successful Cardiopulmonary Resuscitation with Therapeutic Hypothermia: A Case Report

    OpenAIRE

    Choi, Sang-Sik; Kim, Won Young; Kim, Won; Lim, Kyung-Su

    2012-01-01

    Central diabetes insipidus (DI), characterized by unexpected fatal hypernatremia, is a rare complication after successful cardiopulmonary resuscitation with therapeutic hypothermia, but may be potentially fatal if recognition is delayed. We describe here a patient who experienced cardiac arrest due to a pulmonary embolism, followed by successful resuscitation after induction of therapeutic hypothermia. The patient, however, suddenly developed unexpected hypernatremia with increased urine outp...

  5. Communication of Unexpected and Significant Findings on Chest Radiographs With an Automated PACS Alert System.

    LENUS (Irish Health Repository)

    Hayes, Sara A

    2014-08-01

    An integral part of realizing the enormous potential of imaging in patient care is close communication between radiologists and referring physicians. One key element of this process is the communication of unexpected significant findings. The authors examined the performance of a PACS-based alert system in the appropriate communication of reports containing unexpected significant findings to referring physicians.

  6. Male or female? Brains are intersex

    OpenAIRE

    Daphna eJoel

    2011-01-01

    The underlying assumption in popular and scientific publications on sex differences in the brain is that human brains can take one of two forms male or female, and that the differences between these two forms underlie differences between men and women in personality, cognition, emotion and behavior. Documented sex differences in brain structure are typically taken to support this dimorphic view of the brain. However, neuroanatomical data reveal that sex interacts with other factors in utero a...

  7. Male or Female? Brains are Intersex

    OpenAIRE

    Joel, Daphna

    2011-01-01

    The underlying assumption in popular and scientific publications on sex differences in the brain is that human brains can take one of two forms “male” or “female,” and that the differences between these two forms underlie differences between men and women in personality, cognition, emotion, and behavior. Documented sex differences in brain structure are typically taken to support this dimorphic view of the brain. However, neuroanatomical data reveal that sex interacts with other factors in ut...

  8. Unexpected variation in neuroanatomy among diverse nematode species

    Directory of Open Access Journals (Sweden)

    Ziduan eHan

    2016-01-01

    Full Text Available Nematodes are considered excellent models for understanding fundamental aspects of neuron function. However, nematodes are less frequently used as models for examining the evolution of nervous systems. While the habitats and behaviors of nematodes are diverse, the neuroanatomy of nematodes is often considered highly conserved. A small number of nematode species greatly influences our understanding of nematode neurobiology. The free-living species Caenorhabditis elegans and, to a lesser extent, the mammalian gastrointestinal parasite Ascaris suum are, historically, the primary sources of knowledge regarding nematode neurobiology. Despite differences in size and habitat, C. elegans and Ascaris suum share a surprisingly similar neuroanatomy. Here, we examined species across several clades in the phylum Nematoda and show that there is a surprising degree of neuroanatomical variation both within and among nematode clades when compared to C. elegans and Ascaris. We found variation in the numbers of neurons in the ventral nerve cord and dye-filling pattern of sensory neurons. For example, we found that Pristionchus pacificus, a bacterial feeding species used for comparative developmental research, had 20% fewer ventral cord neurons compared to C. elegans. Steinernema carpocapse, an insect-parasitic nematode capable of jumping behavior, had 40% more ventral cord neurons than C. elegans. Interestingly, the non-jumping congeneric nematode, S. glaseri showed an identical number of ventral cord neurons as S. carpocapsae. There was also variability in the timing of neurodevelopment of the ventral cord with two of five species that hatch as second-stage juveniles showing delayed neurodevelopment. We also found unexpected variation in the dye-filling of sensory neurons among examined species. Again, sensory neuron dye-filling pattern did not strictly correlate with phylogeny. Our results demonstrate that variation in nematode neuroanatomy is more prevalent

  9. Unexpected Variation in Neuroanatomy among Diverse Nematode Species.

    Science.gov (United States)

    Han, Ziduan; Boas, Stephanie; Schroeder, Nathan E

    2015-01-01

    Nematodes are considered excellent models for understanding fundamental aspects of neuron function. However, nematodes are less frequently used as models for examining the evolution of nervous systems. While the habitats and behaviors of nematodes are diverse, the neuroanatomy of nematodes is often considered highly conserved. A small number of nematode species greatly influences our understanding of nematode neurobiology. The free-living species Caenorhabditis elegans and, to a lesser extent, the mammalian gastrointestinal parasite Ascaris suum are, historically, the primary sources of knowledge regarding nematode neurobiology. Despite differences in size and habitat, C. elegans and A. suum share a surprisingly similar neuroanatomy. Here, we examined species across several clades in the phylum Nematoda and show that there is a surprising degree of neuroanatomical variation both within and among nematode clades when compared to C. elegans and Ascaris. We found variation in the numbers of neurons in the ventral nerve cord and dye-filling pattern of sensory neurons. For example, we found that Pristionchus pacificus, a bacterial feeding species used for comparative developmental research had 20% fewer ventral cord neurons compared to C. elegans. Steinernema carpocapsae, an insect-parasitic nematode capable of jumping behavior, had 40% more ventral cord neurons than C. elegans. Interestingly, the non-jumping congeneric nematode, S. glaseri showed an identical number of ventral cord neurons as S. carpocapsae. There was also variability in the timing of neurodevelopment of the ventral cord with two of five species that hatch as second-stage juveniles showing delayed neurodevelopment. We also found unexpected variation in the dye-filling of sensory neurons among examined species. Again, sensory neuron dye-filling pattern did not strictly correlate with phylogeny. Our results demonstrate that variation in nematode neuroanatomy is more prevalent than previously assumed and

  10. Unexpected Activity of a Novel Kunitz-type Inhibitor

    Science.gov (United States)

    Smith, David; Tikhonova, Irina G.; Jewhurst, Heather L.; Drysdale, Orla C.; Dvořák, Jan; Robinson, Mark W.; Cwiklinski, Krystyna; Dalton, John P.

    2016-01-01

    Kunitz-type (KT) protease inhibitors are low molecular weight proteins classically defined as serine protease inhibitors. We identified a novel secreted KT inhibitor associated with the gut and parenchymal tissues of the infective juvenile stage of Fasciola hepatica, a helminth parasite of medical and veterinary importance. Unexpectedly, recombinant KT inhibitor (rFhKT1) exhibited no inhibitory activity toward serine proteases but was a potent inhibitor of the major secreted cathepsin L cysteine proteases of F. hepatica, FhCL1 and FhCL2, and of human cathepsins L and K (Ki = 0.4-27 nm). FhKT1 prevented the auto-catalytic activation of FhCL1 and FhCL2 and formed stable complexes with the mature enzymes. Pulldown experiments from adult parasite culture medium showed that rFhKT1 interacts specifically with native secreted FhCL1, FhCL2, and FhCL5. Substitution of the unusual P1 Leu15 within the exposed reactive loop of FhKT1 for the more commonly found Arg (FhKT1Leu15/Arg15) had modest adverse effects on the cysteine protease inhibition but conferred potent activity against the serine protease trypsin (Ki = 1.5 nm). Computational docking and sequence analysis provided hypotheses for the exclusive binding of FhKT1 to cysteine proteases, the importance of the Leu15 in anchoring the inhibitor into the S2 active site pocket, and the inhibitor's selectivity toward FhCL1, FhCL2, and human cathepsins L and K. FhKT1 represents a novel evolutionary adaptation of KT protease inhibitors by F. hepatica, with its prime purpose likely in the regulation of the major parasite-secreted proteases and/or cathepsin L-like proteases of its host. PMID:27422822

  11. Telomere end processing: unexpected complexity at the end game

    OpenAIRE

    Lundblad, Victoria

    2012-01-01

    Lundblad provides perspective on the recent work by Wright and colleagues (this issue) that reveals a tightly choreographed sequence of events that occur during telomere replication and end processing.

  12. Brain Basics

    Medline Plus

    Full Text Available ... as they grow there are differences in brain development in children who develop bipolar disorder than children who do not. Studies comparing such children to those with normal brain development may help scientists to pinpoint when and where ...

  13. Brain Basics

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    Full Text Available ... PTSD) . Prefrontal cortex (PFC) —Seat of the brain's executive functions, such as judgment, decision making, and problem solving. ... brain that, in humans, plays a role in executive functions such as judgment, decision making and problem solving, ...

  14. Brain Basics

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    Full Text Available ... Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of ... to slow or stop them from progressing. Functional magnetic resonance imaging (fMRI) is another important research tool in understanding ...

  15. Brain Basics

    Medline Plus

    Full Text Available ... little dopamine or problems using dopamine in the thinking and feeling regions of the brain may play ... axis —A brain-body circuit which plays a critical role in the body's response to stress. impulse — ...

  16. Brain Basics

    Medline Plus

    Full Text Available ... Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take ... to slow or stop them from progressing. Functional magnetic resonance imaging (fMRI) is another important research tool in ...

  17. Brain Basics

    Medline Plus

    Full Text Available ... Basics in Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a middle-aged woman who seemed to have it all. She was happily married and successful in business. Then, after a serious setback at work, she lost interest ...

  18. Pharmacokinetics of sevoflurane uptake into the brain.

    Science.gov (United States)

    Turner, M J; McCulloch, T J; Kennedy, R R; Baker, A B

    2004-12-01

    Two recent studies have examined the pharmacokinetics of sevoflurane in adults. Lu et al.(Pharmacokinetics of sevoflurane uptake into the brain and body, Anaesthesia 2003; 58: 951-6) observed that jugular bulb sevoflurane concentration initially rose unexpectedly rapidly and then approached arterial concentrations unexpectedly slowly, suggesting that a blood-brain diffusion barrier exists. They also observed a large alveolar-arterial sevoflurane gradient, suggesting that an alveolar-arterial diffusion barrier exists. Nakamura et al. (Predicted sevoflurane partial pressure in the brain with an uptake and distribution model: Comparison with the measured value in internal jugular vein blood. Journal of Clinical Monitoring and Computing 1999; 15: 299-305) found no diffusion barriers. We used a computer model to analyse both data sets and show that the observations of Lu et al. can be explained by contamination of jugular samples with extracerebral blood. It is possible that the alveolar-arterial gradients observed by Lu et al. are due to discrepancies in conversions between blood concentrations and gas partial pressures. Our study suggests that there is no blood-brain diffusion barrier for sevoflurane and that the data of Lu et al. must be interpreted with caution.

  19. Brain peroxisomes.

    Science.gov (United States)

    Trompier, D; Vejux, A; Zarrouk, A; Gondcaille, C; Geillon, F; Nury, T; Savary, S; Lizard, G

    2014-03-01

    Peroxisomes are essential organelles in higher eukaryotes as they play a major role in numerous metabolic pathways and redox homeostasis. Some peroxisomal abnormalities, which are often not compatible with life or normal development, were identified in severe demyelinating and neurodegenerative brain diseases. The metabolic roles of peroxisomes, especially in the brain, are described and human brain peroxisomal disorders resulting from a peroxisome biogenesis or a single peroxisomal enzyme defect are listed. The brain abnormalities encountered in these disorders (demyelination, oxidative stress, inflammation, cell death, neuronal migration, differentiation) are described and their pathogenesis are discussed. Finally, the contribution of peroxisomal dysfunctions to the alterations of brain functions during aging and to the development of Alzheimer's disease is considered.

  20. Unexpected diversity and photoperiod dependence of the zebrafish melanopsin system.

    Directory of Open Access Journals (Sweden)

    Vanessa Matos-Cruz

    Full Text Available Animals have evolved specialized photoreceptors in the retina and in extraocular tissues that allow them to measure light changes in their environment. In mammals, the retina is the only structure that detects light and relays this information to the brain. The classical photoreceptors, rods and cones, are responsible for vision through activation of rhodopsin and cone opsins. Melanopsin, another photopigment first discovered in Xenopus melanophores (Opn4x, is expressed in a small subset of retinal ganglion cells (RGCs in the mammalian retina, where it mediates non-image forming functions such as circadian photoentrainment and sleep. While mammals have a single melanopsin gene (opn4, zebrafish show remarkable diversity with two opn4x-related and three opn4-related genes expressed in distinct patterns in multiple neuronal cell types of the developing retina, including bipolar interneurons. The intronless opn4.1 gene is transcribed in photoreceptors as well as in horizontal cells and produces functional photopigment. Four genes are also expressed in the zebrafish embryonic brain, but not in the photoreceptive pineal gland. We discovered that photoperiod length influences expression of two of the opn4-related genes in retinal layers involved in signaling light information to RGCs. Moreover, both genes are expressed in a robust diurnal rhythm but with different phases in relation to the light-dark cycle. The results suggest that melanopsin has an expanded role in modulating the retinal circuitry of fish.

  1. Costly hide and seek pays: unexpected consequences of deceit in a social dilemma

    International Nuclear Information System (INIS)

    Deliberate deceptiveness intended to gain an advantage is commonplace in human and animal societies. In a social dilemma, an individual may only pretend to be a cooperator to elicit cooperation from others, while in reality he is a defector. With this as motivation, we study a simple variant of the evolutionary prisoner's dilemma game entailing deceitful defectors and conditional cooperators that lifts the veil on the impact of such two-faced behavior. Defectors are able to hide their true intentions at a personal cost, while conditional cooperators are probabilistically successful at identifying defectors and act accordingly. By focusing on the evolutionary outcomes in structured populations, we observe a number of unexpected and counterintuitive phenomena. We show that deceitful behavior may fare better if it is costly, and that a higher success rate of identifying defectors does not necessarily favor cooperative behavior. These results are rooted in the spontaneous emergence of cycling dominance and spatial patterns that give rise to fascinating phase transitions, which in turn reveal the hidden complexity behind the evolution of deception. (paper)

  2. Crude oil as a microbial seed bank with unexpected functional potentials

    Science.gov (United States)

    Cai, Man; Nie, Yong; Chi, Chang-Qiao; Tang, Yue-Qin; Li, Yan; Wang, Xing-Biao; Liu, Ze-Shen; Yang, Yunfeng; Zhou, Jizhong; Wu, Xiao-Lei

    2015-11-01

    It was widely believed that oil is a harsh habitat for microbes because of its high toxicity and hydrophobicity. However, accumulating evidence has revealed the presence of live microbes in crude oil. Therefore, it’s of value to conduct an in-depth investigation on microbial communities in crude oil. To this end, microorganisms in oil and water phases were collected from four oil-well production mixtures in Qinghai Oilfield, China, and analyzed for their taxonomic and functional compositions via pyrosequencing and GeoChip, respectively. Hierarchical clustering of 16S rRNA gene sequences and functional genes clearly separated crude oil and water phases, suggestive of distinct taxonomic and functional gene compositions between crude oil and water phases. Unexpectedly, Pseudomonas dominated oil phase where diverse functional gene groups were identified, which significantly differed from those in the corresponding water phases. Meanwhile, most functional genes were significantly more abundant in oil phase, which was consistent with their important roles in facilitating survival of their host organisms in crude oil. These findings provide strong evidence that crude oil could be a “seed bank” of functional microorganisms with rich functional potentials. This offers novel insights for industrial applications of microbial-enhanced oil recovery and bioremediation of petroleum-polluted environments.

  3. Unexpected temporal evolution of atomic spectral lines of aluminum in a laser induced breakdown spectroscopy experiment

    Energy Technology Data Exchange (ETDEWEB)

    Saad, Rawad, E-mail: rawad.saad@cea.fr [CEA, DEN, DPC, SEARS, LANIE, 91191 Gif-sur-Yvette (France); L' Hermite, Daniel, E-mail: daniel.lhermite@cea.fr [CEA, DEN, DPC, SEARS, LANIE, 91191 Gif-sur-Yvette (France); Bousquet, Bruno, E-mail: bruno.bousquet@u-bordeaux1.fr [LOMA, Université de Bordeaux, CNRS, 351 Cours de la Libération, 33405 Talence Cedex (France)

    2014-11-01

    The temporal evolution of the laser induced breakdown (LIBS) signal of a pure aluminum sample was studied under nitrogen and air atmospheres. In addition to the usual decrease of signal due to plasma cooling, unexpected temporal evolutions were observed for a spectral lines of aluminum, which revealed the existence of collisional energy transfer effects. Furthermore, molecular bands of AlN and AlO were observed in the LIBS spectra, indicating recombination of aluminum with the ambient gas. Within the experimental conditions reported in this study, both collisional energy transfer and recombination processes occurred around 1.5 μs after the laser shot. This highlights the possible influence of collisional and chemical effects inside the plasma that can play a role on LIBS signals. - Highlights: • Persistence of two Al I lines related to the 61,844 cm{sup −1} energy level only under nitrogen atmosphere. • Collisional energy transfer effect exists between aluminum and nitrogen. • Observation of molecular band of AlN (under nitrogen) and AlO (under air) after a delay time of 1.5 µs. • 20% of oxygen in air is sufficient to annihilate both the collisional energy transfer effect and the AlN molecular formation.

  4. New hepatitis B virus of cranes that has an unexpected broad host range.

    Science.gov (United States)

    Prassolov, Alexej; Hohenberg, Heinz; Kalinina, Tatyana; Schneider, Carola; Cova, Lucyna; Krone, Oliver; Frölich, Kai; Will, Hans; Sirma, Hüseyin

    2003-02-01

    All hepadnaviruses known so far have a very limited host range, restricted to their natural hosts and a few closely related species. This is thought to be due mainly to sequence divergence in the large envelope protein and species-specific differences in host components essential for virus propagation. Here we report an infection of cranes with a novel hepadnavirus, designated CHBV, that has an unexpectedly broad host range and is only distantly evolutionarily related to avihepadnaviruses of related hosts. Direct DNA sequencing of amplified CHBV DNA as well a sequencing of cloned viral genomes revealed that CHBV is most closely related to, although distinct from, Ross' goose hepatitis B virus (RGHBV) and slightly less closely related to duck hepatitis B virus (DHBV). Phylogenetically, cranes are very distant from geese and ducks and are most closely related to herons and storks. Naturally occurring hepadnaviruses in the last two species are highly divergent in sequence from RGHBV and DHBV and do not infect ducks or do so only marginally. In contrast, CHBV from crane sera and recombinant CHBV produced from LMH cells infected primary duck hepatocytes almost as efficiently as DHBV did. This is the first report of a rather broad host range of an avihepadnavirus. Our data imply either usage of similar or identical entry pathways and receptors by DHBV and CHBV, unusual host and virus adaptation mechanisms, or divergent evolution of the host genomes and cellular components required for virus propagation.

  5. Malaria's contribution to World War One - the unexpected adversary.

    Science.gov (United States)

    Brabin, Bernard J

    2014-12-16

    Malaria in the First World War was an unexpected adversary. In 1914, the scientific community had access to new knowledge on transmission of malaria parasites and their control, but the military were unprepared, and underestimated the nature, magnitude and dispersion of this enemy. In summarizing available information for allied and axis military forces, this review contextualizes the challenge posed by malaria, because although data exist across historical, medical and military documents, descriptions are fragmented, often addressing context specific issues. Military malaria surveillance statistics have, therefore, been summarized for all theatres of the War, where available. These indicated that at least 1.5 million solders were infected, with case fatality ranging from 0.2 -5.0%. As more countries became engaged in the War, the problem grew in size, leading to major epidemics in Macedonia, Palestine, Mesopotamia and Italy. Trans-continental passages of parasites and human reservoirs of infection created ideal circumstances for parasite evolution. Details of these epidemics are reviewed, including major epidemics in England and Italy, which developed following home troop evacuations, and disruption of malaria control activities in Italy. Elsewhere, in sub-Saharan Africa many casualties resulted from high malaria exposure combined with minimal control efforts for soldiers considered semi-immune. Prevention activities eventually started but were initially poorly organized and dependent on local enthusiasm and initiative. Nets had to be designed for field use and were fundamental for personal protection. Multiple prevention approaches adopted in different settings and their relative utility are described. Clinical treatment primarily depended on quinine, although efficacy was poor as relapsing Plasmodium vivax and recrudescent Plasmodium falciparum infections were not distinguished and managed appropriately. Reasons for this are discussed and the clinical trial data

  6. Malaria's contribution to World War One - the unexpected adversary.

    Science.gov (United States)

    Brabin, Bernard J

    2014-01-01

    Malaria in the First World War was an unexpected adversary. In 1914, the scientific community had access to new knowledge on transmission of malaria parasites and their control, but the military were unprepared, and underestimated the nature, magnitude and dispersion of this enemy. In summarizing available information for allied and axis military forces, this review contextualizes the challenge posed by malaria, because although data exist across historical, medical and military documents, descriptions are fragmented, often addressing context specific issues. Military malaria surveillance statistics have, therefore, been summarized for all theatres of the War, where available. These indicated that at least 1.5 million solders were infected, with case fatality ranging from 0.2 -5.0%. As more countries became engaged in the War, the problem grew in size, leading to major epidemics in Macedonia, Palestine, Mesopotamia and Italy. Trans-continental passages of parasites and human reservoirs of infection created ideal circumstances for parasite evolution. Details of these epidemics are reviewed, including major epidemics in England and Italy, which developed following home troop evacuations, and disruption of malaria control activities in Italy. Elsewhere, in sub-Saharan Africa many casualties resulted from high malaria exposure combined with minimal control efforts for soldiers considered semi-immune. Prevention activities eventually started but were initially poorly organized and dependent on local enthusiasm and initiative. Nets had to be designed for field use and were fundamental for personal protection. Multiple prevention approaches adopted in different settings and their relative utility are described. Clinical treatment primarily depended on quinine, although efficacy was poor as relapsing Plasmodium vivax and recrudescent Plasmodium falciparum infections were not distinguished and managed appropriately. Reasons for this are discussed and the clinical trial data

  7. More 'mapping' in brain mapping: statistical comparison of effects

    DEFF Research Database (Denmark)

    Jernigan, Terry Lynne; Gamst, Anthony C.; Fennema-Notestine, Christine;

    2003-01-01

    The term 'mapping' in the context of brain imaging conveys to most the concept of localization; that is, a brain map is meant to reveal a relationship between some condition or parameter and specific sites within the brain. However, in reality, conventional voxel-based maps of brain function, or ...

  8. Pigmented Tumour of the Eyelid with Unexpected Findings

    Directory of Open Access Journals (Sweden)

    Anne C. Hunold

    2012-01-01

    Full Text Available A 63-year-old patient presented with a small painless nodular tumour of his left lower eyelid which had increased in size over the last few weeks. The tumour was excised by wedge resection and submitted for ophthalmopathologic examination. Histopathologic examination revealed a cystic lesion of apocrine origin with focal proliferations. The proliferative cells appeared pleomorphic and displayed marked atypia. Staining with Ki67 revealed a significant mitotic activity supporting the diagnosis of an apocrine adenocarcinoma of Moll. As the lesion displayed in most parts characteristics of a benign apocrine hidrocystoma, a thorough and critical histopathological examination is required in such cases to avoid missing an early malignant transformation.

  9. Polytypism and unexpected strong interlayer coupling in two-dimensional layered ReS2

    Science.gov (United States)

    Qiao, Xiao-Fen; Wu, Jiang-Bin; Zhou, Linwei; Qiao, Jingsi; Shi, Wei; Chen, Tao; Zhang, Xin; Zhang, Jun; Ji, Wei; Tan, Ping-Heng

    2016-04-01

    Anisotropic two-dimensional (2D) van der Waals (vdW) layered materials, with both scientific interest and application potential, offer one more dimension than isotropic 2D materials to tune their physical properties. Various physical properties of 2D multi-layer materials are modulated by varying their stacking orders owing to significant interlayer vdW coupling. Multilayer rhenium disulfide (ReS2), a representative anisotropic 2D material, was expected to be randomly stacked and lack interlayer coupling. Here, we demonstrate two stable stacking orders, namely isotropic-like (IS) and anisotropic-like (AI) N layer (NL, N > 1) ReS2 are revealed by ultralow- and high-frequency Raman spectroscopy, photoluminescence and first-principles density functional theory calculation. Two interlayer shear modes are observed in AI-NL-ReS2 while only one shear mode appears in IS-NL-ReS2, suggesting anisotropic- and isotropic-like stacking orders in IS- and AI-NL-ReS2, respectively. This explicit difference in the observed frequencies identifies an unexpected strong interlayer coupling in IS- and AI-NL-ReS2. Quantitatively, the force constants of them are found to be around 55-90% of those of multilayer MoS2. The revealed strong interlayer coupling and polytypism in multi-layer ReS2 may stimulate future studies on engineering physical properties of other anisotropic 2D materials by stacking orders.Anisotropic two-dimensional (2D) van der Waals (vdW) layered materials, with both scientific interest and application potential, offer one more dimension than isotropic 2D materials to tune their physical properties. Various physical properties of 2D multi-layer materials are modulated by varying their stacking orders owing to significant interlayer vdW coupling. Multilayer rhenium disulfide (ReS2), a representative anisotropic 2D material, was expected to be randomly stacked and lack interlayer coupling. Here, we demonstrate two stable stacking orders, namely isotropic-like (IS) and

  10. Cellular immune surveillance of central nervous system bypasses blood-brain barrier and blood-cerebrospinal-fluid barrier: revealed with the New Marburg cerebrospinal-fluid model in healthy humans.

    Science.gov (United States)

    Kleine, Tilmann O

    2015-03-01

    In healthy human brain/spinal cord, blood capillaries and venules are locked differently with junctions and basement membrane (blood-brain barrier, blood-venule barrier). In choroid plexus, epithelial tight junctions and basement membrane lock blood-cerebrospinal-fluid (CSF) barrier. Lymphocytic cell data, quantified with multicolour flow-cytometry or immuno-cytochemical methods in sample pairs of lumbar CSF, ventrictricular CSF and peripheral venous blood, are taken from references; similarly, data of thoracic duct chyle and blood sample pairs. Through three circumventricular organs (median eminence, organum vasculosum lamina terminalis, area postrema), 15-30 μl blood are pressed by blood pressure through fenestrated capillaries, matrix/basement membrane spaces and ependyma cell lacks into ventricular/suboccipital CSF to generate CD3(+) , CD4(+) , CD8(+) , CD3(+) HLA-DR(+) , CD16(+) 56(+) 3(-) NK, CD19(+) 3(-) B subsets; some B, few NK cells adhere in circumventricular organs. Into lumbar CSF, 10-15 μl thoracic chyle with five lymphocyte subsets (without CD3(+) HLA-DR(+) cells) reflux, when CSF drains out with to-and-fro movements of chyle/CSF along nerve roots. Lymphocytes in lumbar CSF represent a mixture of blood and lymph lymphocytic cells with similar HLA-DR(+) CD3(+) cell counts in ventricular and lumbar CSF, higher CD3(+) , CD4(+) , CD8(+) subsets in lumbar CSF, and few NK and B cells due to absorption in circumventricular organs. The Marburg CSF Model reflects origin and turnover of lymphatic cells in CSF realistically; the model differs from ligand-multistep processes of activated lymphocytes through blood-brain-, blood-venule-, and blood-CSF-barriers; because transfer of inactivated native lymphocytes through the barriers is not found with healthy humans, although described so in literature. PMID:25641944

  11. Unique Microstructural Changes in the Brain Associated with Urological Chronic Pelvic Pain Syndrome (UCPPS) Revealed by Diffusion Tensor MRI, Super-Resolution Track Density Imaging, and Statistical Parameter Mapping: A MAPP Network Neuroimaging Study.

    Science.gov (United States)

    Woodworth, Davis; Mayer, Emeran; Leu, Kevin; Ashe-McNalley, Cody; Naliboff, Bruce D; Labus, Jennifer S; Tillisch, Kirsten; Kutch, Jason J; Farmer, Melissa A; Apkarian, A Vania; Johnson, Kevin A; Mackey, Sean C; Ness, Timothy J; Landis, J Richard; Deutsch, Georg; Harris, Richard E; Clauw, Daniel J; Mullins, Chris; Ellingson, Benjamin M

    2015-01-01

    Studies have suggested chronic pain syndromes are associated with neural reorganization in specific regions associated with perception, processing, and integration of pain. Urological chronic pelvic pain syndrome (UCPPS) represents a collection of pain syndromes characterized by pelvic pain, namely Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) and Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS), that are both poorly understood in their pathophysiology, and treated ineffectively. We hypothesized patients with UCPPS may have microstructural differences in the brain compared with healthy control subjects (HCs), as well as patients with irritable bowel syndrome (IBS), a common gastrointestinal pain disorder. In the current study we performed population-based voxel-wise DTI and super-resolution track density imaging (TDI) in a large, two-center sample of phenotyped patients from the multicenter cohort with UCPPS (N = 45), IBS (N = 39), and HCs (N = 56) as part of the MAPP Research Network. Compared with HCs, UCPPS patients had lower fractional anisotropy (FA), lower generalized anisotropy (GA), lower track density, and higher mean diffusivity (MD) in brain regions commonly associated with perception and integration of pain information. Results also showed significant differences in specific anatomical regions in UCPPS patients when compared with IBS patients, consistent with microstructural alterations specific to UCPPS. While IBS patients showed clear sex related differences in FA, MD, GA, and track density consistent with previous reports, few such differences were observed in UCPPS patients. Heat maps illustrating the correlation between specific regions of interest and various pain and urinary symptom scores showed clustering of significant associations along the cortico-basal ganglia-thalamic-cortical loop associated with pain integration, modulation, and perception. Together, results suggest patients with UCPPS have extensive microstructural

  12. Brain tumor - primary - adults

    Science.gov (United States)

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  13. Brain radiation - discharge

    Science.gov (United States)

    Radiation - brain - discharge; Cancer-brain radiation; Lymphoma - brain radiation; Leukemia - brain radiation ... Decadron) while you are getting radiation to the brain. It may make you hungrier, cause leg swelling ...

  14. Brain and Addiction

    Science.gov (United States)

    ... Teens / Drug Facts / Brain and Addiction Brain and Addiction Print Your Brain Your brain is who you ... is taken over and over. What Is Drug Addiction? Addiction is a chronic brain disease that causes ...

  15. Brain Basics

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    Full Text Available ... related to changes in the anatomy, physiology, and chemistry of the nervous system. When the brain cannot ... who can diagnose mental disorders are psychologists or clinical social workers. The psychiatrist asked Sarah and her ...

  16. Brain Basics

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    Full Text Available ... begun to chart how the brain develops over time in healthy people and are working to compare ... listless, and had no appetite most of the time. Weeks later, Sarah realized she was having trouble ...

  17. Brain Basics

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    Full Text Available ... as in areas of the brain that control movement. When electrical signals are abnormal, they can cause ... normal mood functioning. Dopamine —mainly involved in controlling movement and aiding the flow of information to the ...

  18. Brain Basics

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    Full Text Available ... Statistics Help for Mental Illnesses Outreach Outreach Home Public Involvement Outreach Partners Alliance for Research Progress Coalition ... also linked to reward systems in the brain. Problems in producing dopamine can result in Parkinson's disease, ...

  19. Brain Basics

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    Full Text Available ... related to changes in the anatomy, physiology, and chemistry of the nervous system. When the brain cannot ... husband questions about Sarah's symptoms and family medical history. Epigenetic changes from stress or early-life experiences ...

  20. Brain Basics

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    Full Text Available ... at the front of the brain that, in humans, plays a role in executive functions such as ... to another. Share Science News Connectome Re-Maps Human Cortex ECT Lifts Depression, Sustains Remission in Older ...

  1. Brain Basics

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    Full Text Available ... treatments, and possibly prevention of such illnesses. The Working Brain Neurotransmitters Everything we do relies on neurons ... depression, can occur when this process does not work correctly. Communication between neurons can also be electrical, ...

  2. Brain Basics

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    Full Text Available ... in controlling movement, managing the release of various hormones, and aiding the flow of information to the ... at the front of the brain that, in humans, plays a role in executive functions such as ...

  3. Brain Basics

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    Full Text Available ... the understanding of how the brain grows and works and the effects of genes and environment on mental health. This knowledge is allowing scientists to make important discoveries that ...

  4. Brain Basics

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    Full Text Available ... may help improve treatments for anxiety disorders like phobias or post-traumatic stress disorder (PTSD) . Prefrontal cortex ( ... doctor, who ran some tests. After deciding her symptoms were not caused by a stroke, brain tumor, ...

  5. Brain Basics

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    Full Text Available ... related to changes in the anatomy, physiology, and chemistry of the nervous system. When the brain cannot ... NIMH Strategic Plan in 2016 August 31, 2016, 2:00-3:00 PM ET General Health Information ...

  6. Brain Basics

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    Full Text Available ... sends impulses and extends from cell bodies to meet and deliver impulses to another nerve cell. Axons ... in Real Life—How Depression affects the Brain Meet Sarah Sarah is a middle-aged woman who ...

  7. Brain Basics

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    Full Text Available ... Director’s Blog Budget Strategic Plan Offices and Divisions Careers@NIMH Advisory Boards and Groups Staff Directories Getting ... works in healthy people, and how normal brain development and function can go awry, leading to mental ...

  8. Brain Basics

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    Full Text Available ... little dopamine or problems using dopamine in the thinking and feeling regions of the brain may play ... but can still remember past events and learned skills, and carry on a conversation, all which rely ...

  9. Brain Basics

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    Full Text Available ... and plays an important role during early brain development. It may also assist in learning and memory. ... but can still remember past events and learned skills, and carry on a conversation, all which rely ...

  10. Brain Basics

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    Full Text Available ... These factors may act alone or together in complex ways, to change the way a gene is ... little dopamine or problems using dopamine in the thinking and feeling regions of the brain may play ...

  11. Brain Basics

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    Full Text Available ... the brain, which is linked to thought and emotion. It is also linked to reward systems in ... or-flight response and is also involved in emotions and memory. anterior cingulate cortex —Is involved in ...

  12. Brain Basics

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    Full Text Available ... or serious and cause severe disability. Through research, we know that mental disorders are brain disorders. Evidence ... many different types of cells in the body. We say that cells differentiate as the embryo develops, ...

  13. Brain Basics

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    Full Text Available ... These circuits control specific body functions such as sleep and speech. The brain continues maturing well into ... factors that can affect our bodies, such as sleep, diet, or stress. These factors may act alone ...

  14. Brain Health

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    ... Love Your Brain Stay Physically Active Adopt a Healthy Diet Stay Mentally and Socially Active We Can Help ... of any wellness plan. Learn More Adopt a Healthy Diet > Eat a heart-healthy diet that benefits both ...

  15. Brain Basics

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    Full Text Available ... for the function of conducting messages. A neuron has three basic parts: Cell body which includes the ... disorder (ADHD) . Glutamate —the most common neurotransmitter, glutamate has many roles throughout the brain and nervous system. ...

  16. Brain Basics

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    Full Text Available ... the brain, which is linked to thought and emotion. It is also linked to reward systems in ... stay focused on a task, and managing proper emotional reactions. Reduced ACC activity or damage to this ...

  17. Brain Basics

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    Full Text Available ... genes and epigenetics may one day lead to genetic testing for people at risk for mental disorders. ... brain. DNA —The "recipe of life," containing inherited genetic information that helps to define physical and some ...

  18. Brain Basics

    Medline Plus

    Full Text Available ... interconnections. neuron —A nerve cell that is the basic, working unit of the brain and nervous system, which processes and transmits information. neurotransmitter —A chemical produced by ...

  19. Brain Basics

    Medline Plus

    Full Text Available ... they can cause tremors or symptoms found in Parkinson's disease. Serotonin —helps control many functions, such as ... brain. Problems in producing dopamine can result in Parkinson's disease, a disorder that affects a person's ability ...

  20. Brain Basics

    Medline Plus

    Full Text Available ... as sleep and speech. The brain continues maturing well into a person's early 20s. Knowing how the ... as judgment, decision making and problem solving, as well as emotional control and memory. serotonin —A neurotransmitter ...

  1. Brain Basics

    Medline Plus

    Full Text Available ... mental disorder, or perhaps you have experienced one yourself at some point. Such disorders include depression , anxiety ... control specific body functions such as sleep and speech. The brain continues maturing well into a person's ...

  2. Brain Basics

    Medline Plus

    Full Text Available ... some point. Such disorders include depression , anxiety disorders , bipolar disorder , attention deficit hyperactivity disorder (ADHD) , and many others. ... differences in brain development in children who develop bipolar disorder than children who do not. Studies comparing such ...

  3. Brain Basics

    Medline Plus

    Full Text Available ... can diagnose mental disorders are psychologists or clinical social workers. The psychiatrist asked Sarah and her husband ... the understanding of how the brain grows and works and the effects of genes and environment on ...

  4. Inhibition of HMG CoA reductase reveals an unexpected role for cholesterol during PGC migration in the mouse

    Directory of Open Access Journals (Sweden)

    Ewing Andrew G

    2008-12-01

    Full Text Available Abstract Background Primordial germ cells (PGCs are the embryonic precursors of the sperm and eggs. Environmental or genetic defects that alter PGC development can impair fertility or cause formation of germ cell tumors. Results We demonstrate a novel role for cholesterol during germ cell migration in mice. Cholesterol was measured in living tissue dissected from mouse embryos and was found to accumulate within the developing gonads as germ cells migrate to colonize these structures. Cholesterol synthesis was blocked in culture by inhibiting the activity of HMG CoA reductase (HMGCR resulting in germ cell survival and migration defects. These defects were rescued by co-addition of isoprenoids and cholesterol, but neither compound alone was sufficient. In contrast, loss of the last or penultimate enzyme in cholesterol biosynthesis did not alter PGC numbers or position in vivo. However embryos that lack these enzymes do not exhibit cholesterol defects at the stage at which PGCs are migrating. This demonstrates that during gestation, the cholesterol required for PGC migration can be supplied maternally. Conclusion In the mouse, cholesterol is required for PGC survival and motility. It may act cell-autonomously by regulating clustering of growth factor receptors within PGCs or non cell-autonomously by controlling release of growth factors required for PGC guidance and survival.

  5. Novel and unexpected bacterial diversity in an arsenic-rich ecosystem revealed by culture-dependent approaches

    Directory of Open Access Journals (Sweden)

    Delavat François

    2012-09-01

    Full Text Available Abstract Background Acid Mine Drainages (AMDs are extreme environments characterized by very acid conditions and heavy metal contaminations. In these ecosystems, the bacterial diversity is considered to be low. Previous culture-independent approaches performed in the AMD of Carnoulès (France confirmed this low species richness. However, very little is known about the cultured bacteria in this ecosystem. The aims of the study were firstly to apply novel culture methods in order to access to the largest cultured bacterial diversity, and secondly to better define the robustness of the community for 3 important functions: As(III oxidation, cellulose degradation and cobalamine biosynthesis. Results Despite the oligotrophic and acidic conditions found in AMDs, the newly designed media covered a large range of nutrient concentrations and a pH range from 3.5 to 9.8, in order to target also non-acidophilic bacteria. These approaches generated 49 isolates representing 19 genera belonging to 4 different phyla. Importantly, overall diversity gained 16 extra genera never detected in Carnoulès. Among the 19 genera, 3 were previously uncultured, one of them being novel in databases. This strategy increased the overall diversity in the Carnoulès sediment by 70% when compared with previous culture-independent approaches, as specific phylogenetic groups (e.g. the subclass Actinobacteridae or the order Rhizobiales were only detected by culture. Cobalamin auxotrophy, cellulose degradation and As(III-oxidation are 3 crucial functions in this ecosystem, and a previous meta- and proteo-genomic work attributed each function to only one taxon. Here, we demonstrate that other members of this community can also assume these functions, thus increasing the overall community robustness. Conclusions This work highlights that bacterial diversity in AMDs is much higher than previously envisaged, thus pointing out that the AMD system is functionally more robust than expected. The isolated bacteria may be part of the rare biosphere which remained previously undetected due to molecular biases. No matter their current ecological relevance, the exploration of the full diversity remains crucial to decipher the function and dynamic of any community. This work also underlines the importance to associate culture-dependent and -independent approaches to gain an integrative view of the community function. Reviewers This paper was reviewed by Sándor Pongor, Eugene V. Koonin and Brett Baker (nominated by Purificacion Lopez-Garcia.

  6. Mapping enteroendocrine cell populations in transgenic mice reveals an unexpected degree of complexity in cellular differentiation within the gastrointestinal tract

    OpenAIRE

    1990-01-01

    The gastrointestinal tract is lined with a monolayer of cells that undergo perpetual and rapid renewal. Four principal, terminally differentiated cell types populate the monolayer, enterocytes, goblet cells, Paneth cells, and enteroendocrine cells. This epithelium exhibits complex patterns of regional differentiation, both from crypt- to-villus and from duodenum-to-colon. The "liver" fatty acid binding protein (L-FABP) gene represents a useful model for analyzing the molecular basis for intes...

  7. Molecular phylogeny of the Astrophorida (Porifera, Demospongiae(p reveals an unexpected high level of spicule homoplasy.

    Directory of Open Access Journals (Sweden)

    Paco Cárdenas

    Full Text Available BACKGROUND: The Astrophorida (Porifera, Demospongiae(p is geographically and bathymetrically widely distributed. Systema Porifera currently includes five families in this order: Ancorinidae, Calthropellidae, Geodiidae, Pachastrellidae and Thrombidae. To date, molecular phylogenetic studies including Astrophorida species are scarce and offer limited sampling. Phylogenetic relationships within this order are therefore for the most part unknown and hypotheses based on morphology largely untested. Astrophorida taxa have very diverse spicule sets that make them a model of choice to investigate spicule evolution. METHODOLOGY/PRINCIPAL FINDINGS: With a sampling of 153 specimens (9 families, 29 genera, 89 species covering the deep- and shallow-waters worldwide, this work presents the first comprehensive molecular phylogeny of the Astrophorida, using a cytochrome c oxidase subunit I (COI gene partial sequence and the 5' end terminal part of the 28S rDNA gene (C1-D2 domains. The resulting tree suggested that i the Astrophorida included some lithistid families and some Alectonidae species, ii the sub-orders Euastrophorida and Streptosclerophorida were both polyphyletic, iii the Geodiidae, the Ancorinidae and the Pachastrellidae were not monophyletic, iv the Calthropellidae was part of the Geodiidae clade (Calthropella at least, and finally that v many genera were polyphyletic (Ecionemia, Erylus, Poecillastra, Penares, Rhabdastrella, Stelletta and Vulcanella. CONCLUSION: The Astrophorida is a larger order than previously considered, comprising ca. 820 species. Based on these results, we propose new classifications for the Astrophorida using both the classical rank-based nomenclature (i.e., Linnaean classification and the phylogenetic nomenclature following the PhyloCode, independent of taxonomic rank. A key to the Astrophorida families, sub-families and genera incertae sedis is also included. Incongruences between our molecular tree and the current classification can be explained by the banality of convergent evolution and secondary loss in spicule evolution. These processes have taken place many times, in all the major clades, for megascleres and microscleres.

  8. Nuclear markers reveal unexpected genetic variation and a Congolese-Nilotic origin of the Lake Victoria cichlid species flock.

    OpenAIRE

    Seehausen, Ole; Koetsier, Egbert; Schneider, Maria Victoria; Chapman, Lauren J.; Colin A Chapman; Knight, Mairi E.; Turner, George F.; van Alphen, Jacques J.M; Bills, Roger

    2003-01-01

    Phylogenetic analyses based on mitochondrial (mt) DNA have indicated that the cichlid species flock of the Lake Victoria region is derived from a single ancestral species found in East African rivers, closely related to the ancestor of the Lake Malawi cichlid species flock. The Lake Victoria flock contains ten times less mtDNA variation than the Lake Malawi radiation, consistent with current estimates of the ages of the lakes. We present results of a phylogenetic investigation using nuclear (...

  9. Screening the expression of ABCB6 in erythrocytes reveals an unexpectedly high frequency of Lan mutations in healthy individuals.

    Directory of Open Access Journals (Sweden)

    Magdalena Koszarska

    Full Text Available Lan is a high-incidence blood group antigen expressed in more than 99.9% of the population. Identification of the human ABC transporter ABCB6 as the molecular basis of Lan has opened the way for studies assessing the relation of ABCB6 function and expression to health and disease. To date, 34 ABCB6 sequence variants have been described in association with reduced ABCB6 expression based on the genotyping of stored blood showing weak or no reactivity with anti-Lan antibodies. In the present study we examined the red blood cell (RBC surface expression of ABCB6 by quantitative flow cytometry in a cohort of 47 healthy individuals. Sequencing of the entire coding region of the ABCB6 gene in low RBC ABCB6 expressors identified a new allele (IVS9+1G>A, affecting a putative splice site at the boundary of exon 9 and two nonsynonymous SNPs listed in the SNP database (R192Q (rs150221689 and G588 S (rs145526996. The R192Q mutation showed co-segregation with reduced RBC ABCB6 expression in a family, and we found the G588 S mutation in a compound heterozygous individual with undetectable ABCB6 expression, suggesting that both mutations result in weak or no expression of ABCB6 on RBCs. Analysis of the intracellular expression pattern in HeLa cells by confocal microscopy indicated that these mutations do not compromise overall expression or the endolysosomal localization of ABCB6. Genotyping of two large cohorts, containing 235 and 1039 unrelated volunteers, confirmed the high allele frequency of Lan-mutations. Our results suggest that genetic variants linked to lower or absent cell surface expression of ABCB6/Langereis may be more common than previously thought.

  10. Phylogenetic analysis of glycerol 3-phosphate acyltransferases in opisthokonts reveals unexpected ancestral complexity and novel modern biosynthetic components.

    Directory of Open Access Journals (Sweden)

    Heather C Smart

    Full Text Available Glycerolipid synthesis represents a central metabolic process of all forms of life. In the last decade multiple genes coding for enzymes responsible for the first step of the pathway, catalyzed by glycerol 3-phosphate acyltransferase (GPAT, have been described, and characterized primarily in model organisms like Saccharomyces cerevisiae and mice. Notoriously, the fungal enzymes share low sequence identity with their known animal counterparts, and the nature of their homology is unclear. Furthermore, two mitochondrial GPAT isoforms have been described in animal cells, while no such enzymes have been identified in Fungi. In order to determine if the yeast and mammalian GPATs are representative of the set of enzymes present in their respective groups, and to test the hypothesis that metazoan orthologues are indeed absent from the fungal clade, a comparative genomic and phylogenetic analysis was performed including organisms spanning the breadth of the Opisthokonta supergroup. Surprisingly, our study unveiled the presence of 'fungal' orthologs in the basal taxa of the holozoa and 'animal' orthologues in the basal holomycetes. This includes a novel clade of fungal homologues, with putative peroxisomal targeting signals, of the mitochondrial/peroxisomal acyltransferases in Metazoa, thus potentially representing an undescribed metabolic capacity in the Fungi. The overall distribution of GPAT homologues is suggestive of high relative complexity in the ancestors of the opisthokont clade, followed by loss and sculpting of the complement in the descendent lineages. Divergence from a general versatile metabolic model, present in ancestrally deduced GPAT complements, points to distinctive contributions of each GPAT isoform to lipid metabolism and homeostasis in contemporary organisms like humans and their fungal pathogens.

  11. Rethinking the longitudinal stream temperature paradigm: region-wide comparison of thermal infrared imagery reveals unexpected complexity of river temperatures

    Science.gov (United States)

    Fullerton, Aimee H.; Torgersen, Christian; Lawler, Joshua J.; Faux, Russell N.; Steel, E. Ashley; Beechie, Timothy J.; Ebersole, Joseph L.; Leibowitz, Scott J.

    2015-01-01

    Prevailing theory suggests that stream temperature warms asymptotically in a downstream direction, beginning at the temperature of the source in the headwaters and leveling off downstream as it converges to match meteorological conditions. However, there have been few empirical examples of longitudinal patterns of temperature in large rivers due to a paucity of data. We constructed longitudinal thermal profiles (temperature versus distance) for 53 rivers in the Pacific Northwest (USA) using an extensive dataset of remotely sensed summertime river temperatures and classified each profile into one of five patterns of downstream warming: asymptotic (increasing then flattening), linear (increasing steadily), uniform (not changing), parabolic (increasing then decreasing), or complex (not fitting other classes). We evaluated (1) how frequently profiles warmed asymptotically downstream as expected, and (2) whether relationships between river temperature and common hydroclimatic variables differed by profile class. We found considerable diversity in profile shape, with 47% of rivers warming asymptotically, and 53% having alternative profile shapes. Water temperature did not warm substantially over the course of the river for coastal parabolic and uniform profiles, and for some linear and complex profiles. Profile classes showed no clear geographical trends. The degree of correlation between river temperature and hydroclimatic variables differed among profile classes, but there was overlap among classes. Water temperature in rivers with asymptotic or parabolic profiles was positively correlated with August air temperature, tributary temperature and velocity, and negatively correlated with elevation, August precipitation, gradient, and distance upstream. Conversely, associations were less apparent in rivers with linear, uniform, or complex profiles. Factors contributing to the unique shape of parabolic profiles differed for coastal and inland rivers, where downstream cooling was influenced locally by climate or cool water inputs, respectively. Potential drivers of shape for complex profiles were specific to each river. These thermal patterns indicate diverse thermal habitats that may promote resilience of aquatic biota to climate change. Without this spatial context, climate change models may incorrectly estimate loss of thermally suitable habitat.

  12. Nuclear markers reveal unexpected genetic variation and a Congolese-Nilotic origin of the Lake Victoria cichlid species flock.

    Science.gov (United States)

    Seehausen, Ole; Koetsier, Egbert; Schneider, Maria Victoria; Chapman, Lauren J; Chapman, Colin A; Knight, Mairi E; Turner, George F; van Alphen, Jacques J M; Bills, Roger

    2003-01-22

    Phylogenetic analyses based on mitochondrial (mt) DNA have indicated that the cichlid species flock of the Lake Victoria region is derived from a single ancestral species found in East African rivers, closely related to the ancestor of the Lake Malawi cichlid species flock. The Lake Victoria flock contains ten times less mtDNA variation than the Lake Malawi radiation, consistent with current estimates of the ages of the lakes. We present results of a phylogenetic investigation using nuclear (amplified fragment length polymorphism) markers and a wider coverage of riverine haplochromines. We demonstrate that the Lake Victoria-Edward flock is derived from the morphologically and ecologically diverse cichlid genus Thoracochromis from the Congo and Nile, rather than from the phenotypically conservative East African Astatotilapia. This implies that the ability to express much of the morphological diversity found in the species flock may by far pre-date the origin of the flock. Our data indicate that the nuclear diversity of the Lake Victoria-Edward species flock is similar to that of the Lake Malawi flock, indicating that the genetic diversity is considerably older than the 15 000 years that have passed since the lake began to refill. Most of this variation is manifested in trans-species polymorphisms, indicating very recent cladogenesis from a genetically very diverse founder stock. Our data do not confirm strict monophyly of either of the species flocks, but raise the possibility that these flocks have arisen from hybrid swarms. PMID:12590750

  13. The accrual anomaly - focus on changes in specific unexpected accruals results in new evidence

    DEFF Research Database (Denmark)

    Schøler, Finn

    it is demonstrated that different specific components of earnings have significantly different earnings persistence characteristics and that these differences are not fully reflected in share prices. In the analysis presented here the earnings persistence effect of two particular unexpected accrual components...... and unexpected accruals, estimated by the extended Jones model like in both some US-analyses and some international studies of the accrual anomaly phenomenon. It is found that the persistence of earnings is decreasing in the magnitude of the unexpected accrual components of earnings and that the persistence...... of current earnings performance is particularly decreasing in the magnitude of unexpected changes in inventory. The special accrual parts are related to the perceptions of earnings persistence implicit in the market prices, and it is found that the differences in earnings persistence are not rationally...

  14. Unexpected Antitumorigenic Effect of Fenbendazole when Combined with Supplementary Vitamins

    OpenAIRE

    Gao, Ping; Dang, Chi V.; Watson, Julie

    2008-01-01

    Diet containing the anthelminthic fenbendazole is used often to treat rodent pinworm infections because it is easy to use and has few reported adverse effects on research. However, during fenbendazole treatment at our institution, an established human lymphoma xenograft model in C.B-17/Icr-prkdcscid/Crl (SCID) mice failed to grow. Further investigation revealed that the fenbendazole had been incorporated into a sterilizable diet supplemented with additional vitamins to compensate for loss dur...

  15. Cardiac arrest due to intracranial hypotension following pseudohypoxic brain swelling induced by negative suction drainage in a cranioplasty patient: a case report

    OpenAIRE

    Moon, Hyun-Soo; Lee, Soo Kyung; Kim, Su Ryun; Kim, Seon Ju

    2016-01-01

    Pseudohypoxic brain swelling (PHBS) is known to be an uncommon event that may occur during and following an uneventful brain surgery, when negative suction drainage is used. The cerebrospinal fluid loss related to suction drainage can evoke intracranial hypotension that progress to PHBS. The main presentations of PHBS are sudden unexpected circulatory collapses, such as severe bradycardia, hypotension, cardiac arrest, consciousness deterioration and diffuse brain swelling as seen with brain c...

  16. Robust passive dynamics of the musculoskeletal system compensate for unexpected surface changes during human hopping

    OpenAIRE

    Krogt, van der, Mark; Graaf, de, M.; Farley, C T; Morits, C.T.; Casius, L.J.R.; Bobbert, M.F.

    2009-01-01

    When human hoppers are surprised by a change in surface stiffness, they adapt almost instantly by changing leg stiffness, implying that neural feedback is not necessary. The goal of this simulation study was first to investigate whether leg stiffness can change without neural control adjustment when landing on an unexpected hard or unexpected compliant (soft) surface, and second to determine what underlying mechanisms are responsible for this change in leg stiffness. The muscle stimulation pa...

  17. Unexpected game calculations in educational wargaming : Design flaw or beneficial to learning?

    OpenAIRE

    Frank, Anders

    2011-01-01

    This paper describes situations where learning games are not perceived by the player as being realistic. In educational wargaming this is seen when the game calculates battle-outcomes. Defined as unexpected game calculations, these incidents can cause players to adopt a Gamer Mode attitude, in which players reject the idea that the game accurately portrays warfare. In a study involving cadets playing a commercial strategic wargame as part of their course in war science, unexpected game calcul...

  18. Inside the Brain: Unraveling the Mystery of Alzheimer's Disease

    Medline Plus

    Full Text Available ... disease over time destroys memory and thinking skills. Scientific research has revealed some of the brain changes that ... Alzheimer's disease as the brain and body age? Scientific research is helping to unravel the mystery of Alzheimer's ...

  19. Inside the Brain: Unraveling the Mystery of Alzheimer's Disease

    Medline Plus

    Full Text Available ... over time destroys memory and thinking skills. Scientific research has revealed some of the brain changes that ... disease as the brain and body age? Scientific research is helping to unravel the mystery of Alzheimer's ...

  20. Carcinoid of the Appendix During Laparoscopic Cholecystectomy: Unexpected Benefits

    Science.gov (United States)

    Haluck, Randy; Cooney, Robert N.; Minnick, Kathleen E.; Ruggiero, Francesco; Smith, J. Stanley

    1999-01-01

    Carcinoid tumors of the midgut arise from the distal duodenum, jejunum, ileum, appendix, ascending and right transverse colon. The appendix and terminal ileum are the most common location. The majority of carcinoid tumors originate from neuroendocrine cells along the gastrointestinal tract, but they are also found in the lung, ovary, and biliary tracts. We report the first case of elective laparoscopic cholecystectomy in which we found a suspicious lesion at the tip of the appendix and proceeded to perform a laparoscopic appendectomy. The lesion revealed a carcinoid tumor of the appendix. PMID:10323177

  1. Unexpected Mesons X, Y, Z, ... (tetraquarks? hadron molecules? ...)

    CERN Document Server

    Azimov, Ya I

    2015-01-01

    This talk briefly discusses the set of meson resonances discovered in the latest decade. They are frequently treated in the literature as tetraquarks or hadron molecules. Our consideration (using the energy-time uncertainty relation) suggests, however, that the most reasonable description for each of them may be a two- (or more-) component Fock column, with one line being a conventional quark-antiquark pair, and the other line(s) corresponding to a charmed (or beauty) meson-antimeson pair near its threshold. Detailed investigation of decay properties might allow to reveal presence of several Fock components and separate their contributions.

  2. An Unexpected Gas-Phase Binding Motif for Metal Dication Complexation with Peptides: Irmpd Spectroscopic Structure Determination

    Science.gov (United States)

    Dunbar, Robert C.; Steill, Jeffrey; Polfer, Nicolas; Berden, Giel; Oomens, Jos

    2011-06-01

    The favorable orientation of the amide linkage and the aromatic side chain of N-terminal Phe or Trp leads to several favorable motifs for metal ion binding to dipeptides, having distinct characteristics in the IR spectrum. Infrared multiple photon photodissociation spectroscopy using the FELIX free electron laser has enabled clear resolution of these isomeric forms. The spectral patterns of complexes of small dications (Mg2+, Ni2+ and Co2+) reveal an unexpected new isomeric form, in which the metal ion displaces the amide hydrogen, forming a metal-nitrogen bond with covalent character which is unprecedented in such gas-phase complexes. Spectra of the ions were acquired by irradiating the cell of the Fourier-transform ion cyclotron resonance mass spectrometer with infrared light from the FELIX laser at wavelengths in the approximate range 500 to 1900 Cm-1.

  3. Carney complex--an unexpected finding during puerperium.

    Science.gov (United States)

    Schulz, S; Redlich, A; Köppe, I; Reschke, K; Weise, W

    2001-01-01

    Carney complex is an extremely rare, autosomal dominant, multi-system disorder characterized by multiple neoplasias and lentiginosis. The genetic defect responsible for this complex has been localized to the short arm of chromosome 2 (2p16). The most prevalent clinical manifestations in patients with Carney complex are spotty skin pigmentation, skin and cardiac myxomas, Cushing's syndrome and acromegaly. Here we report the case of a 31-year-old woman with a spontaneous pregnancy. At 32 weeks of gestation, she was admitted to our Department of Obstetrics with hypertension and severe back pain. In addition, she had unusual pigmentation and typical cushingoid features. One day after admission, the pregnancy was terminated by emergency cesarian section because of preeclampsia and pathological CTG. During the postoperative period the severe back pain persisted, and radiographic evaluation revealed a collapse of L(2)/L(3) with severe osteopenia. A CT scan showed a mass in the right suprarenal area. Histopathological examination revealed a primary pigmented nodular adrenocortical disease. After biochemical confirmation of the diagnosis of Cushing's syndrome, it was recognized that the patient met the diagnostic criteria for Carney complex. PMID:11306912

  4. Pictures as a neurological tool: lessons from enhanced and emergent artistry in brain disease.

    Science.gov (United States)

    Schott, G D

    2012-06-01

    Pictures created spontaneously by patients with brain disease often display impaired or diminished artistry, reflecting the patient's cerebral damage. This article explores the opposite: those pictures created in the face of brain disease that show enhanced or enduring artistry, and those that emerge for the first time in artistically naïve patients. After comments on background issues relating to the patient and the viewer, the paintings and drawings are considered in relation to the heterogeneous conditions in which this artistic creativity is seen. These conditions include various dementias-most notably frontotemporal lobar dementia, stroke, Parkinson's disease, autism and related disorders and psychiatric disease, epilepsy, migraine and trauma. In the discussion, it is argued that evidence of underlying brain dysfunction revealed by these pictures often rests on the abnormal context in which the pictures are created, or on changes in artistry demonstrated by a sequence of pictures. In the former, the compulsive element and sensory and emotional accompaniments are often important features; in the latter, evolving changes are evident, and have included depiction of increasing menace in portrayal of faces. The occurrence of synaesthesia, and its relation to creativity, are briefly discussed in respect of two unusual patients, followed by considering the role of the anterior and frontal lobes, mesolimbic connections and the right hemisphere. In at least some patients, impaired inhibition leading to paradoxical functional facilitation, with compensatory changes particularly in the right posterior hemisphere, is likely to be pivotal in enabling unusual artistry to emerge; preservation of language, however, is not a prerequisite. Many patients studied have been artists, and it appears possible that some of those with an artistic predisposition may be more likely to experience pathologically obsessive creativity. The discussion concludes that occasionally pictures

  5. Muerte súbita inesperada en la epilepsia (SUDEP Suden unexpected death in epilepsy

    Directory of Open Access Journals (Sweden)

    Luis Fernando Castro Vargas

    2012-03-01

    Full Text Available El SUDEP se refiere a la muerte súbita e inesperada con o sin testigos, no traumática, y no por ahogamientos en un paciente epiléptico, con o sin evidencia de que haya sufrido una crisis epiléptica al morir, en el que se haya descartado un estado convulsivo como causa de muerte y en el que la autopsia no proporcione evidencia alguna de una causa anatómica o tóxica de la muerte. Aunque SUDEP ha sido reconocida desde el siglo XIX, sólo en las últimas dos décadas se le ha dado la importancia que ésta requiere. La frecuencia de SUDEP depende de la severidad de la epilepsia pero en general el riesgo de muerte súbita es de 20 veces mayor que el de la población en general. El edema pulmonar neurógeno, la apnea central y la arritmia cardiaca, inducidos por una descarga α-adrenérgica de origen central, constituyen los tres mecanismos fisiopatogénicos más estrechamente relacionados con la SUDEP. Por lo anterior obliga al clínico a realizar una minuciosa autopsia la cual debería incluir un examen neuropatológico que documente los cambios cerebrales que subyacen a la epilepsia, toxicología y el examen del corazón, los pulmones y otros órganosThe SUDEP refers to the sudden and unexpected death with or without witnesses, non-traumatic, and not drowning in an epileptic patient, with or without evidence that he suffered a seizure at death, in which a state is ruled seizure as the cause of death in the autopsy did not provide evidence of a toxic or anatomic cause of death. Although SUDEP has been recognized since the nineteenth century, only in the last two decades has been given the importance it requires. SUDEP frequency depends on the severity of epilepsy but in general the risk of sudden death is 20 times higher than the general population. Neurogenic pulmonary edema, central apnea and cardiac arrhythmias induced by α-adrenergic shock of central origin, pathophysiologic mechanisms are the three most closely related to SUDEP. This

  6. Aluminum neurotoxicity in the rat brain

    International Nuclear Information System (INIS)

    To investigate the etiology of Alzheimer's disease, we administered aluminum to healthy rats and examined the aluminum uptake in the brain and isolated brain cell nuclei by particle-induced X-ray emission (PIXE) analysis. Ten days after the last injection, Al was detected in the rat brain and in isolated brain cell nuclei by PIXE analysis. Al was also demonstrated in the brain after 15 months of oral aluminum administration. Moreover, Al was detected in the brain and isolated brain cell nuclei from the patients with Alzheimer's disease. Silver impregnation studies revealed that spines attached to the dendritic processes of cortical nerve cells decreased remarkably after aluminum administration. Electron microscopy revealed characteristic inclusion bodies in the hippocampal nerve cells 75 days after the injection. These morphological changes in the rat brain after the aluminum administration were similar to those reportedly observed in the brain of Alzheimer's disease patients. Our results indicate that Alzheimer's disease is caused by irreversible accumulation of aluminum in the brain, as well as in the nuclei of brain cells. (author)

  7. Unexpected recovery from longterm renal failure in severe diffuse proliferative lupus nephritis

    Directory of Open Access Journals (Sweden)

    Ross Sophia

    2012-08-01

    Full Text Available Abstract Background Severe renal manifestation of systemic lupus erythematosus (SLE is not uncommon and is associated with an indeterminate prognosis. Complete remission can be obtained, however, at least in the young when chronic lesions are absent and adequate anti-inflammatory therapy is immediately initiated. Case presentation We report the unusual case of a 12-year-old girl who presented with severe oliguric renal failure, macrohematuria and skin rash. Renal biopsy revealed the diagnosis of severe diffuse proliferative glomerulonephritis (GN with cellular crescents in 15 out of 18 glomeruli and full-house pattern in immunofluorescence indicating lupus nephritis IVB according to WHO, IV-G(A according to ISN/RPS classification. The serological parameters confirmed the diagnosis of SLE and the patient was immediately treated with methylprednisolone, cyclophosphamide and immunoadsorption. Initially, despite rapid amelioration of her general condition, no substantial improvement of renal function could be achieved and the patient needed hemodialysis treatment for 12 weeks. Unexpectedly, in the further follow-up at first diuresis increased and thereafter also creatinine levels substantially declined so that hemodialysis could be discontinued. Today, 6 years after the initial presentation, the patient has normal renal function and a SLEDAI score of 0 under a continuous immunosuppressive therapy with Mycophenolate mofetil (MMF and low dose steroid. Conclusion Despite the severity of the initial renal injury and the unfavourable renal prognosis the kidney apparently has a tremendous capacity to recover in young patients when the damage is acute and adequate anti-inflammatory therapy is initiated without delay.

  8. Epigenetic modulation of brain gene networks for cocaine and alcohol abuse.

    Science.gov (United States)

    Farris, Sean P; Harris, Robert A; Ponomarev, Igor

    2015-01-01

    Cocaine and alcohol are two substances of abuse that prominently affect the central nervous system (CNS). Repeated exposure to cocaine and alcohol leads to longstanding changes in gene expression, and subsequent functional CNS plasticity, throughout multiple brain regions. Epigenetic modifications of histones are one proposed mechanism guiding these enduring changes to the transcriptome. Characterizing the large number of available biological relationships as network models can reveal unexpected biochemical relationships. Clustering analysis of variation from whole-genome sequencing of gene expression (RNA-Seq) and histone H3 lysine 4 trimethylation (H3K4me3) events (ChIP-Seq) revealed the underlying structure of the transcriptional and epigenomic landscape within hippocampal postmortem brain tissue of drug abusers and control cases. Distinct sets of interrelated networks for cocaine and alcohol abuse were determined for each abusive substance. The network approach identified subsets of functionally related genes that are regulated in agreement with H3K4me3 changes, suggesting cause and effect relationships between this epigenetic mark and gene expression. Gene expression networks consisted of recognized substrates for addiction, such as the dopamine- and cAMP-regulated neuronal phosphoprotein PPP1R1B/DARPP-32 and the vesicular glutamate transporter SLC17A7/VGLUT1 as well as potentially novel molecular targets for substance abuse. Through a systems biology based approach our results illustrate the utility of integrating epigenetic and transcript expression to establish relevant biological networks in the human brain for addiction. Future work with laboratory models may clarify the functional relevance of these gene networks for cocaine and alcohol, and provide a framework for the development of medications for the treatment of addiction. PMID:26041984

  9. Epigenetic Modulation of Brain Gene Networks for Cocaine and Alcohol Abuse

    Directory of Open Access Journals (Sweden)

    Sean P Farris

    2015-05-01

    Full Text Available Cocaine and alcohol are two substances of abuse that prominently affect the central nervous system (CNS. Repeated exposure to cocaine and alcohol leads to longstanding changes in gene expression, and subsequent functional CNS plasticity, throughout multiple brain regions. Epigenetic modifications of histones are one proposed mechanism guiding these enduring changes to the transcriptome. Characterizing the large number of available biological relationships as network models can reveal unexpected biochemical relationships. Clustering analysis of variation from whole-genome sequencing of gene expression (RNA-Seq and histone H3 lysine 4 trimethylation (H3K4me3 events (ChIP-Seq revealed the underlying structure of the transcriptional and epigenomic landscape within hippocampal postmortem brain tissue of drug abusers and control cases. Distinct sets of interrelated networks for cocaine and alcohol abuse were determined for each abusive substance. The network approach identified subsets of functionally related genes that are regulated in agreement with H3K4me3 changes, suggesting cause and effect relationships between this epigenetic mark and gene expression. Gene expression networks consisted of recognized substrates for addiction, such as the dopamine- and cAMP-regulated neuronal phosphoprotein PPP1R1B / DARPP-32 and the vesicular glutamate transporter SLC17A7 / VGLUT1 as well as potentially novel molecular targets for substance abuse. Through a systems biology based approach our results illustrate the utility of integrating epigenetic and transcript expression to establish relevant biological networks in the human brain for addiction. Future work with laboratory models may clarify the functional relevance of these gene networks for cocaine and alcohol, and provide a framework for the development of medications for the treatment of addiction.

  10. Controlling large malpractice claims: the unexpected impact of damage caps.

    Science.gov (United States)

    Gronfein, W P; Kinney, E D

    1991-01-01

    Indiana's comprehensive malpractice reforms, inaugurated in 1975, include a cap on damages, a mandated medical review before trial, and a state insurance fund to pay claims equal to or greater than $100,000. We have found that the amount of compensation going to claimants with such large malpractice claims in Indiana is, on average, substantially higher than in Michigan and Ohio. Indiana's mean claim severity between 1977 and 1988 was $404,832, while the means for Michigan and Ohio were $290,022 and $303,220, respectively, with the difference between these three means being highly significant. Although data on claim and claimant characteristics reveal considerable interstate variation, the results of regression analyses show that Indiana claim payment amounts are higher than Michigan or Ohio payments, independent of the effect of factors such as sex, age, severity of injury, allegations of negligence, and year of settlement.

  11. An unexpected side-effect of a commonly used drug.

    Science.gov (United States)

    Fernández González, Francisco; Miranda, Samayra; Santiago Casiano, Mónica; Nieves, José; Adorno, Edgardo; Fernández González, Ricardo

    2013-01-01

    We report a case of a 68 year-old-female patient with clinical features of drug-induced lupus erythematosus after five years of treatment with amiodarone. She presented generalized skin rash, arthralgia on upper and lower extremities, associated with difficulty to walk. Remarkable laboratory results revealed a positive antinuclear antibody test and a skin rash biopsy showing a superficial and deep perivascular infiltrate of lymphocytes, histiocytes, and eosinophils. Once the etiology of the patient's symptoms was identified, the culprit drug was removed and she had a complete remission of all signs and symptoms. Early diagnose should be recognized for prompt intervention and avoid further complications associated with this rare side-effect.

  12. [Features of brain oscillatory activity and cardiac defense in treatment arterial hypertensives].

    Science.gov (United States)

    Aftanas, L I; Brak, I V; Gilinskaia, O M; Pavlov, S V; Reva, N V

    2014-01-01

    Stress reactivity of the motivational system of defense can be assessed with the aid the cardiac defense response (CDR) - the reaction of the cardiovascular system to unexpected aversive unconditioned stimulus. The main objective of the study was revealing putative contribution of oscillatory systems of the brain into central pathogenic mechanisms of enhanced blood pressure (BP) stress-reactivity in naive patients with arterial hypertension (AH) of the 1st-2nd degrees (n = 17) and healthy control (n = 19) subjects. Using dynamic registration "beat-by-beat" arterial pressure, and oscillatory activity related EEG (64 channels) is estimated using the event-related synchronization/desynchronization (ERD/ERS). Along with abnormally high blood pressure in patients with hypertension background set significantly lower concentrations of serotonin blood platelets and increased tonic activation of the left hemisphere, reflected in the asymmetric reduction of delta- (2-4 Hz) and theta-1 (4-6 Hz) power in the central and parietal cortex in the hemisphere CDR of the patients are characterized by hyperactivity both short- and long-latency components of blood pressure. According to the dynamic analysis of the concomitant EEG, long-latency BP components may be accounted by, among other mechanisms, weakening of the descending ("top-down") inhibitory control, hypothetically implemented with the high-frequency EEG alpha (10-12 Hz) oscillations from the medial central-parietal cortex of both hemispheres of the brain. PMID:25464727

  13. Regional differences in gene expression and promoter usage in aged human brains

    KAUST Repository

    Pardo, Luba M.

    2013-02-19

    To characterize the promoterome of caudate and putamen regions (striatum), frontal and temporal cortices, and hippocampi from aged human brains, we used high-throughput cap analysis of gene expression to profile the transcription start sites and to quantify the differences in gene expression across the 5 brain regions. We also analyzed the extent to which methylation influenced the observed expression profiles. We sequenced more than 71 million cap analysis of gene expression tags corresponding to 70,202 promoter regions and 16,888 genes. More than 7000 transcripts were differentially expressed, mainly because of differential alternative promoter usage. Unexpectedly, 7% of differentially expressed genes were neurodevelopmental transcription factors. Functional pathway analysis on the differentially expressed genes revealed an overrepresentation of several signaling pathways (e.g., fibroblast growth factor and wnt signaling) in hippocampus and striatum. We also found that although 73% of methylation signals mapped within genes, the influence of methylation on the expression profile was small. Our study underscores alternative promoter usage as an important mechanism for determining the regional differences in gene expression at old age.

  14. Robot brains

    NARCIS (Netherlands)

    Babuska, R.

    2011-01-01

    The brain hosts complex networks of neurons that are responsible for behavior in humans and animals that we generally call intelligent. I is not easy to give an exact definition of intelligence – for the purpose of this talk it will suffice to say that we refer to intelligence as a collection of cap

  15. Brain Basics

    Medline Plus

    Full Text Available ... early brain development. It may also assist in learning and memory. Problems in making or using glutamate have been linked ... we see, and help us to solve a problem. Some of the regions most commonly ... also appears to be involved in learning to fear an event, such as touching a ...

  16. Brain Basics

    Medline Plus

    Full Text Available ... or post-traumatic stress disorder (PTSD) . Prefrontal cortex (PFC) —Seat of the brain's executive functions, such as ... making, and problem solving. Different parts of the PFC are involved in using short-term or "working" ...

  17. Brain Basics

    Medline Plus

    Full Text Available ... at the front of the brain that, in humans, plays a role in executive functions such as ... ClinicalTrials.gov : Federally and privately supported research using human volunteers PubMed Central: An archive of life sciences ...

  18. Brain Basics

    Medline Plus

    Full Text Available ... ADHD , schizophrenia , and depression . Hippocampus —Helps create and file new memories. When the hippocampus is damaged, a ... portion of the brain involved in creating and filing new memories. hypothalmic-pituitary-adrenal (HPA) axis —A ...

  19. The unexpected properties of alkali metal iron selenide superconductors

    Energy Technology Data Exchange (ETDEWEB)

    Dagotto, Elbio R [ORNL

    2013-01-01

    The iron-based superconductors that contain FeAs layers as the fundamental building block in the crystal structures have been rationalized in the past using ideas based on the Fermi surface nesting of hole and electron pockets when in the presence of weak Hubbard U interactions. This approach seemed appropriate considering the small values of the magnetic moments in the parent compounds and the clear evidence based on photoemission experiments of the required electron and hole pockets. However, recent results in the context of alkali metal iron selenides, with generic chemical composition AxFe2ySe2 (A alkali metal element), have challenged those previous ideas since at particular compositions y the low-temperature ground states are insulating and display antiferromagnetic order with large iron magnetic moments. Moreover, angle-resolved photoemission studies have revealed the absence of hole pockets at the Fermi level in these materials. The present status of this exciting area of research, with the potential to alter conceptually our understanding of the ironbased superconductors, is here reviewed, covering both experimental and theoretical investigations. Other recent related developments are also briefly reviewed, such as the study of selenide two-leg ladders and the discovery of superconductivity in a single layer of FeSe. The conceptual issues considered established for the alkali metal iron selenides, as well as several issues that still require further work, are discussed.

  20. Unexpected antitumorigenic effect of fenbendazole when combined with supplementary vitamins.

    Science.gov (United States)

    Gao, Ping; Dang, Chi V; Watson, Julie

    2008-11-01

    Diet containing the anthelminthic fenbendazole is used often to treat rodent pinworm infections because it is easy to use and has few reported adverse effects on research. However, during fenbendazole treatment at our institution, an established human lymphoma xenograft model in C.B-17/Icr-prkdcscid/Crl (SCID) mice failed to grow. Further investigation revealed that the fenbendazole had been incorporated into a sterilizable diet supplemented with additional vitamins to compensate for loss during autoclaving, but the diet had not been autoclaved. To assess the role of fenbendazole and supplementary vitamins on tumor suppression, 20 vendor-supplied 4-wk-old SCID mice were assigned to 4 treatment groups: standard diet, diet plus fenbendazole, diet plus vitamins, and diet plus both vitamins and fenbendazole. Diet treatment was initiated 2 wk before subcutaneous flank implantation with 3 x 107 lymphoma cells. Tumor size was measured by caliper at 4-d intervals until the largest tumors reached a calculated volume of 1500 mm3. Neither diet supplemented with vitamins alone nor fenbendazole alone caused altered tumor growth as compared with that of controls. However, the group supplemented with both vitamins and fenbendazole exhibited significant inhibition of tumor growth. The mechanism for this synergy is unknown and deserves further investigation. Fenbendazole should be used with caution during tumor studies because it may interact with other treatments and confound research results.