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Sample records for human brain transcriptome

  1. Analysis of a human brain transcriptome map

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    Greene Jonathan R

    2002-04-01

    Full Text Available Abstract Background Genome wide transcriptome maps can provide tools to identify candidate genes that are over-expressed or silenced in certain disease tissue and increase our understanding of the structure and organization of the genome. Expressed Sequence Tags (ESTs from the public dbEST and proprietary Incyte LifeSeq databases were used to derive a transcript map in conjunction with the working draft assembly of the human genome sequence. Results Examination of ESTs derived from brain tissues (excluding brain tumor tissues suggests that these genes are distributed on chromosomes in a non-random fashion. Some regions on the genome are dense with brain-enriched genes while some regions lack brain-enriched genes, suggesting a significant correlation between distribution of genes along the chromosome and tissue type. ESTs from brain tumor tissues have also been mapped to the human genome working draft. We reveal that some regions enriched in brain genes show a significant decrease in gene expression in brain tumors, and, conversely that some regions lacking in brain genes show an increased level of gene expression in brain tumors. Conclusions This report demonstrates a novel approach for tissue specific transcriptome mapping using EST-based quantitative assessment.

  2. Functional organization of the transcriptome in human brain

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    Oldham, Michael C; Konopka, Genevieve; Iwamoto, Kazuya; Langfelder, Peter; Kato, Tadafumi; Horvath, Steve; Geschwind, Daniel H

    2009-01-01

    The enormous complexity of the human brain ultimately derives from a finite set of molecular instructions encoded in the human genome. These instructions can be directly studied by exploring the organization of the brain’s transcriptome through systematic analysis of gene coexpression relationships. We analyzed gene coexpression relationships in microarray data generated from specific human brain regions and identified modules of coexpressed genes that correspond to neurons, oligodendrocytes, astrocytes and microglia. These modules provide an initial description of the transcriptional programs that distinguish the major cell classes of the human brain and indicate that cell type–specific information can be obtained from whole brain tissue without isolating homogeneous populations of cells. Other modules corresponded to additional cell types, organelles, synaptic function, gender differences and the subventricular neurogenic niche. We found that subventricular zone astrocytes, which are thought to function as neural stem cells in adults, have a distinct gene expression pattern relative to protoplasmic astrocytes. Our findings provide a new foundation for neurogenetic inquiries by revealing a robust and previously unrecognized organization to the human brain transcriptome. PMID:18849986

  3. mRNA Transcriptomics of Galectins Unveils Heterogeneous Organization in Mouse and Human Brain

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    Sebastian John

    2016-12-01

    Full Text Available Background: Galectins, a family of non-classically secreted, β-galactoside binding proteins is involved in several brain disorders; however no systematic knowledge on the normal neuroanatomical distribution and functions of galectins exits. Hence, the major purpose of this study was to understand spatial distribution and predict functions of galectins in brain and also compare the degree of conservation vs. divergence between mouse and human species. The latter objective was required to determine the relevance and appropriateness of studying galectins in mouse brain which may ultimately enable us to extrapolate the findings to human brain physiology and pathologies.Results: In order to fill this crucial gap in our understanding of brain galectins, we analyzed the in situ hybridization (ISH and microarray data of adult mouse and human brain respectively, from the Allen Brain Atlas, to resolve each galectin-subtype’s spatial distribution across brain distinct cytoarchitecture. Next, transcription factors (TFs that may regulate galectins were identified using TRANSFAC software and the list obtained was further curated to sort TFs on their confirmed transcript expression in the adult brain. Galectin-TF cluster analysis, gene-ontology annotations and co-expression networks were then extrapolated to predict distinct functional relevance of each galectin in the neuronal processes. Data shows that galectins have highly heterogeneous expression within and across brain sub-structures and are predicted to be the crucial targets of brain enriched TFs. Lgals9 had maximal spatial distribution across mouse brain with inferred predominant roles in neurogenesis while LGALS1 was ubiquitously expressed in human. Limbic region associated with learning, memory and emotions and substantia nigra associated with motor movements showed strikingly high expression of LGALS1 and LGALS8 in human vs. mouse brain. The overall expression profile of galectin-8 was most

  4. Transcriptome of E. coli K1 bound to human brain microvascular endothelial cells

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    Xie, Yi; Parthasarathy, Geetha; Di Cello, Francescopaolo; Teng, Ching-Hao; Paul-Satyaseela, Maneesh; Kim, Kwang Sik

    2007-01-01

    Escherichia coli K1 is the most common Gram-negative organism causing neonatal meningitis. Binding to human brain microvascdular endothelial cells (HBMEC) is an essential step for E. coli K1 traversal of the blood-brain barrier. In this study, we examined expression profiles of E. coli K1 strain RS218 during its binding to HBMEC. Comparison of HBMEC-bound E. coli K1 with collagen-bound E. coli revealed more than one hundred genes whose expression patterns were significantly changed in HBMEC-b...

  5. A transcriptome-based assessment of the astrocytic dystrophin-associated complex in the developing human brain.

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    Simon, Matthew J; Murchison, Charles; Iliff, Jeffrey J

    2018-02-01

    Astrocytes play a critical role in regulating the interface between the cerebral vasculature and the central nervous system. Contributing to this is the astrocytic endfoot domain, a specialized structure that ensheathes the entirety of the vasculature and mediates signaling between endothelial cells, pericytes, and neurons. The astrocytic endfoot has been implicated as a critical element of the glymphatic pathway, and changes in protein expression profiles in this cellular domain are linked to Alzheimer's disease pathology. Despite this, basic physiological properties of this structure remain poorly understood including the developmental timing of its formation, and the protein components that localize there to mediate its functions. Here we use human transcriptome data from male and female subjects across several developmental stages and brain regions to characterize the gene expression profile of the dystrophin-associated complex (DAC), a known structural component of the astrocytic endfoot that supports perivascular localization of the astroglial water channel aquaporin-4. Transcriptomic profiling is also used to define genes exhibiting parallel expression profiles to DAC elements, generating a pool of candidate genes that encode gene products that may contribute to the physiological function of the perivascular astrocytic endfoot domain. We found that several genes encoding transporter proteins are transcriptionally associated with DAC genes. © 2017 Wiley Periodicals, Inc.

  6. Brain transcriptome atlases : A computational perspective

    NARCIS (Netherlands)

    Mahfouz, A.M.E.T.A.; Huisman, S.M.H.; Lelieveldt, B.P.F.; Reinders, M.J.T.

    2017-01-01

    The immense complexity of the mammalian brain is largely reflected in the underlying molecular signatures of its billions of cells. Brain transcriptome atlases provide valuable insights into gene expression patterns across different brain areas throughout the course of development. Such atlases

  7. A MARKOV RANDOM FIELD-BASED APPROACH TO CHARACTERIZING HUMAN BRAIN DEVELOPMENT USING SPATIAL-TEMPORAL TRANSCRIPTOME DATA.

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    Lin, Zhixiang; Sanders, Stephan J; Li, Mingfeng; Sestan, Nenad; State, Matthew W; Zhao, Hongyu

    2015-03-01

    Human neurodevelopment is a highly regulated biological process. In this article, we study the dynamic changes of neurodevelopment through the analysis of human brain microarray data, sampled from 16 brain regions in 15 time periods of neurodevelopment. We develop a two-step inferential procedure to identify expressed and unexpressed genes and to detect differentially expressed genes between adjacent time periods. Markov Random Field (MRF) models are used to efficiently utilize the information embedded in brain region similarity and temporal dependency in our approach. We develop and implement a Monte Carlo expectation-maximization (MCEM) algorithm to estimate the model parameters. Simulation studies suggest that our approach achieves lower misclassification error and potential gain in power compared with models not incorporating spatial similarity and temporal dependency.

  8. The Human Transcriptome: An Unfinished Story

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    Mihaela Pertea

    2012-06-01

    Full Text Available Despite recent technological advances, the study of the human transcriptome is still in its early stages. Here we provide an overview of the complex human transcriptomic landscape, present the bioinformatics challenges posed by the vast quantities of transcriptomic data, and discuss some of the studies that have tried to determine how much of the human genome is transcribed. Recent evidence has suggested that more than 90% of the human genome is transcribed into RNA. However, this view has been strongly contested by groups of scientists who argued that many of the observed transcripts are simply the result of transcriptional noise. In this review, we conclude that the full extent of transcription remains an open question that will not be fully addressed until we decipher the complete range and biological diversity of the transcribed genomic sequences.

  9. Transgenerational epigenetic programming of the brain transcriptome and anxiety behavior.

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    Michael K Skinner

    Full Text Available Embryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination promotes an epigenetic reprogramming of the male germ-line that is associated with transgenerational adult onset disease states. Further analysis of this transgenerational phenotype on the brain demonstrated reproducible changes in the brain transcriptome three generations (F3 removed from the exposure. The transgenerational alterations in the male and female brain transcriptomes were distinct. In the males, the expression of 92 genes in the hippocampus and 276 genes in the amygdala were transgenerationally altered. In the females, the expression of 1,301 genes in the hippocampus and 172 genes in the amygdala were transgenerationally altered. Analysis of specific gene sets demonstrated that several brain signaling pathways were influenced including those involved in axon guidance and long-term potentiation. An investigation of behavior demonstrated that the vinclozolin F3 generation males had a decrease in anxiety-like behavior, while the females had an increase in anxiety-like behavior. These observations demonstrate that an embryonic exposure to an environmental compound appears to promote a reprogramming of brain development that correlates with transgenerational sex-specific alterations in the brain transcriptomes and behavior. Observations are discussed in regards to environmental and transgenerational influences on the etiology of brain disease.

  10. The human airway epithelial basal cell transcriptome.

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    Neil R Hackett

    2011-05-01

    Full Text Available The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population.Bronchial brushing was used to obtain airway epithelium from healthy nonsmokers. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium in comparison to the transcriptome of the differentiated airway epithelium. This analysis identified the "human airway basal cell signature" as 1,161 unique genes with >5-fold higher expression level in basal cells compared to differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels.The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of the stem/progenitor cells of the human airway epithelium.

  11. The Human Blood Metabolome-Transcriptome Interface

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    Schramm, Katharina; Adamski, Jerzy; Gieger, Christian; Herder, Christian; Carstensen, Maren; Peters, Annette; Rathmann, Wolfgang; Roden, Michael; Strauch, Konstantin; Suhre, Karsten; Kastenmüller, Gabi; Prokisch, Holger; Theis, Fabian J.

    2015-01-01

    Biological systems consist of multiple organizational levels all densely interacting with each other to ensure function and flexibility of the system. Simultaneous analysis of cross-sectional multi-omics data from large population studies is a powerful tool to comprehensively characterize the underlying molecular mechanisms on a physiological scale. In this study, we systematically analyzed the relationship between fasting serum metabolomics and whole blood transcriptomics data from 712 individuals of the German KORA F4 cohort. Correlation-based analysis identified 1,109 significant associations between 522 transcripts and 114 metabolites summarized in an integrated network, the ‘human blood metabolome-transcriptome interface’ (BMTI). Bidirectional causality analysis using Mendelian randomization did not yield any statistically significant causal associations between transcripts and metabolites. A knowledge-based interpretation and integration with a genome-scale human metabolic reconstruction revealed systematic signatures of signaling, transport and metabolic processes, i.e. metabolic reactions mainly belonging to lipid, energy and amino acid metabolism. Moreover, the construction of a network based on functional categories illustrated the cross-talk between the biological layers at a pathway level. Using a transcription factor binding site enrichment analysis, this pathway cross-talk was further confirmed at a regulatory level. Finally, we demonstrated how the constructed networks can be used to gain novel insights into molecular mechanisms associated to intermediate clinical traits. Overall, our results demonstrate the utility of a multi-omics integrative approach to understand the molecular mechanisms underlying both normal physiology and disease. PMID:26086077

  12. The Human Blood Metabolome-Transcriptome Interface.

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    Jörg Bartel

    2015-06-01

    Full Text Available Biological systems consist of multiple organizational levels all densely interacting with each other to ensure function and flexibility of the system. Simultaneous analysis of cross-sectional multi-omics data from large population studies is a powerful tool to comprehensively characterize the underlying molecular mechanisms on a physiological scale. In this study, we systematically analyzed the relationship between fasting serum metabolomics and whole blood transcriptomics data from 712 individuals of the German KORA F4 cohort. Correlation-based analysis identified 1,109 significant associations between 522 transcripts and 114 metabolites summarized in an integrated network, the 'human blood metabolome-transcriptome interface' (BMTI. Bidirectional causality analysis using Mendelian randomization did not yield any statistically significant causal associations between transcripts and metabolites. A knowledge-based interpretation and integration with a genome-scale human metabolic reconstruction revealed systematic signatures of signaling, transport and metabolic processes, i.e. metabolic reactions mainly belonging to lipid, energy and amino acid metabolism. Moreover, the construction of a network based on functional categories illustrated the cross-talk between the biological layers at a pathway level. Using a transcription factor binding site enrichment analysis, this pathway cross-talk was further confirmed at a regulatory level. Finally, we demonstrated how the constructed networks can be used to gain novel insights into molecular mechanisms associated to intermediate clinical traits. Overall, our results demonstrate the utility of a multi-omics integrative approach to understand the molecular mechanisms underlying both normal physiology and disease.

  13. A transcriptome anatomy of human colorectal cancers

    International Nuclear Information System (INIS)

    Lü, Bingjian; Xu, Jing; Lai, Maode; Zhang, Hao; Chen, Jian

    2006-01-01

    Accumulating databases in human genome research have enabled integrated genome-wide study on complicated diseases such as cancers. A practical approach is to mine a global transcriptome profile of disease from public database. New concepts of these diseases might emerge by landscaping this profile. In this study, we clustered human colorectal normal mucosa (N), inflammatory bowel disease (IBD), adenoma (A) and cancer (T) related expression sequence tags (EST) into UniGenes via an in-house GetUni software package and analyzed the transcriptome overview of these libraries by GOTree Machine (GOTM). Additionally, we downloaded UniGene based cDNA libraries of colon and analyzed them by Xprofiler to cross validate the efficiency of GetUni. Semi-quantitative RT-PCR was used to validate the expression of β-catenin and. 7 novel genes in colorectal cancers. The efficiency of GetUni was successfully validated by Xprofiler and RT-PCR. Genes in library N, IBD and A were all found in library T. A total of 14,879 genes were identified with 2,355 of them having at least 2 transcripts. Differences in gene enrichment among these libraries were statistically significant in 50 signal transduction pathways and Pfam protein domains by GOTM analysis P < 0.01 Hypergeometric Test). Genes in two metabolic pathways, ribosome and glycolysis, were more enriched in the expression profiles of A and IBD than in N and T. Seven transmembrane receptor superfamily genes were typically abundant in cancers. Colorectal cancers are genetically heterogeneous. Transcription variants are common in them. Aberrations of ribosome and glycolysis pathway might be early indicators of precursor lesions in colon cancers. The electronic gene expression profile could be used to highlight the integral molecular events in colorectal cancers

  14. Transcriptome

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    ... Also: Talking Glossary of Genetic Terms Definitions for genetic terms used on this page En Español: Transcriptoma Transcriptome What is a transcriptome? What can a transcriptome tell us? How can transcriptome data be used to explore gene function? What is ...

  15. Brain transcriptome perturbations in the Hfe(-/-) mouse model of genetic iron loading.

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    Johnstone, Daniel; Graham, Ross M; Trinder, Debbie; Delima, Roheeth D; Riveros, Carlos; Olynyk, John K; Scott, Rodney J; Moscato, Pablo; Milward, Elizabeth A

    2012-04-11

    Severe disruption of brain iron homeostasis can cause fatal neurodegenerative disease, however debate surrounds the neurologic effects of milder, more common iron loading disorders such as hereditary hemochromatosis, which is usually caused by loss-of-function polymorphisms in the HFE gene. There is evidence from both human and animal studies that HFE gene variants may affect brain function and modify risks of brain disease. To investigate how disruption of HFE influences brain transcript levels, we used microarray and real-time reverse transcription polymerase chain reaction to assess the brain transcriptome in Hfe(-/-) mice relative to wildtype AKR controls (age 10 weeks, n≥4/group). The Hfe(-/-) mouse brain showed numerous significant changes in transcript levels (pgenes relating to transcriptional regulation (FBJ osteosarcoma oncogene Fos, early growth response genes), neurotransmission (glutamate NMDA receptor Grin1, GABA receptor Gabbr1) and synaptic plasticity and memory (calcium/calmodulin-dependent protein kinase IIα Camk2a). As previously reported for dietary iron-supplemented mice, there were altered levels of transcripts for genes linked to neuronal ceroid lipofuscinosis, a disease characterized by excessive lipofuscin deposition. Labile iron is known to enhance lipofuscin generation which may accelerate brain aging. The findings provide evidence that iron loading disorders can considerably perturb levels of transcripts for genes essential for normal brain function and may help explain some of the neurologic signs and symptoms reported in hemochromatosis patients. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Chapter 4 genomics, transcriptomics, and epigenomics in traumatic brain injury research.

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    Puccio, Ava M; Alexander, Sheila

    2015-01-01

    The long-term effects and significant impact of the full spectrum of traumatic brain injury (TBI) has received increased attention in recent years. Despite increased research efforts, there has been little movement toward improving outcomes for the survivors of TBI. TBI is a heterogeneous condition with a complex biological response, and significant variability in human recovery contributes to the difficulty in identifying therapeutics that improve outcomes. Personalized medicine, identifying the best course of treatment for a given individual based on individual characteristics, has great potential to improve recovery for TBI survivors. The advances in medical genetics and genomics over the past 20 years have increased our understanding of many biological processes. A substantial amount of research has focused on the genomic, transcriptomic, and epigenomic profiles in many health and disease states, including recovery from TBI. The focus of this review chapter is to describe the current state of the science in genomic, transcriptomic, and epigenomic research in the TBI population. There have been some advancements toward understanding the genomic, transcriptomic, and epigenomic processes in humans, but much of this work remains at the preclinical stage. This current evidence does improve our understanding of TBI recovery, but also serves as an excellent platform upon which to build further study toward improved outcomes for this population.

  17. Transcriptomics resources of human tissues and organs

    DEFF Research Database (Denmark)

    Uhlén, Mathias; Hallström, Björn M.; Lindskog, Cecilia

    2016-01-01

    a framework for defining the molecular constituents of the human body as well as for generating comprehensive lists of proteins expressed across tissues or in a tissue-restricted manner. Here, we review publicly available human transcriptome resources and discuss body-wide data from independent genome......Quantifying the differential expression of genes in various human organs, tissues, and cell types is vital to understand human physiology and disease. Recently, several large-scale transcriptomics studies have analyzed the expression of protein-coding genes across tissues. These datasets provide...

  18. Brain Transcriptomic Response to Social Eavesdropping in Zebrafish (Danio rerio.

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    João Sollari Lopes

    Full Text Available Public information is widely available at low cost to animals living in social groups. For instance, bystanders may eavesdrop on signaling interactions between conspecifics and use it to adapt their subsequent behavior towards the observed individuals. This social eavesdropping ability is expected to require specialized mechanisms such as social attention, which selects social information available for learning. To begin exploring the genetic basis of social eavesdropping, we used a previously established attention paradigm in the lab to study the brain gene expression profile of male zebrafish (Danio rerio in relation to the attention they paid towards conspecifics involved or not involved in agonistic interactions. Microarray gene chips were used to characterize their brain transcriptomes based on differential expression of single genes and gene sets. These analyses were complemented by promoter region-based techniques. Using data from both approaches, we further drafted protein interaction networks. Our results suggest that attentiveness towards conspecifics, whether interacting or not, activates pathways linked to neuronal plasticity and memory formation. The network analyses suggested that fos and jun are key players on this response, and that npas4a, nr4a1 and egr4 may also play an important role. Furthermore, specifically observing fighting interactions further triggered pathways associated to a change in the alertness status (dnajb5 and to other genes related to memory formation (btg2, npas4b, which suggests that the acquisition of eavesdropped information about social relationships activates specific processes on top of those already activated just by observing conspecifics.

  19. Traumatic Brain Injury Induces Genome-Wide Transcriptomic, Methylomic, and Network Perturbations in Brain and Blood Predicting Neurological Disorders

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    Qingying Meng

    2017-02-01

    Full Text Available The complexity of the traumatic brain injury (TBI pathology, particularly concussive injury, is a serious obstacle for diagnosis, treatment, and long-term prognosis. Here we utilize modern systems biology in a rodent model of concussive injury to gain a thorough view of the impact of TBI on fundamental aspects of gene regulation, which have the potential to drive or alter the course of the TBI pathology. TBI perturbed epigenomic programming, transcriptional activities (expression level and alternative splicing, and the organization of genes in networks centered around genes such as Anax2, Ogn, and Fmod. Transcriptomic signatures in the hippocampus are involved in neuronal signaling, metabolism, inflammation, and blood function, and they overlap with those in leukocytes from peripheral blood. The homology between genomic signatures from blood and brain elicited by TBI provides proof of concept information for development of biomarkers of TBI based on composite genomic patterns. By intersecting with human genome-wide association studies, many TBI signature genes and network regulators identified in our rodent model were causally associated with brain disorders with relevant link to TBI. The overall results show that concussive brain injury reprograms genes which could lead to predisposition to neurological and psychiatric disorders, and that genomic information from peripheral leukocytes has the potential to predict TBI pathogenesis in the brain.

  20. Human brain imaging

    International Nuclear Information System (INIS)

    Kuhar, M.J.

    1987-01-01

    Just as there have been dramatic advances in the molecular biology of the human brain in recent years, there also have been remarkable advances in brain imaging. This paper reports on the development and broad application of microscopic imaging techniques which include the autoradiographic localization of receptors and the measurement of glucose utilization by autoradiography. These approaches provide great sensitivity and excellent anatomical resolution in exploring brain organization and function. The first noninvasive external imaging of receptor distributions in the living human brain was achieved by positron emission tomography (PET) scanning. Developments, techniques and applications continue to progress. Magnetic resonance imaging (MRI) is also becoming important. Its initial clinical applications were in examining the structure and anatomy of the brain. However, more recent uses, such as MRI spectroscopy, indicate the feasibility of exploring biochemical pathways in the brain, the metabolism of drugs in the brain, and also of examining some of these procedures at an anatomical resolution which is substantially greater than that obtainable by PET scanning. The issues will be discussed in greater detail

  1. Characterization of the Pathogenicity of Streptococcus intermedius TYG1620 Isolated from a Human Brain Abscess Based on the Complete Genome Sequence with Transcriptome Analysis and Transposon Mutagenesis in a Murine Subcutaneous Abscess Model.

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    Hasegawa, Noriko; Sekizuka, Tsuyoshi; Sugi, Yutaka; Kawakami, Nobuhiro; Ogasawara, Yumiko; Kato, Kengo; Yamashita, Akifumi; Takeuchi, Fumihiko; Kuroda, Makoto

    2017-02-01

    Streptococcus intermedius is known to cause periodontitis and pyogenic infections in the brain and liver. Here we report the complete genome sequence of strain TYG1620 (genome size, 2,006,877 bp; GC content, 37.6%; 2,020 predicted open reading frames [ORFs]) isolated from a brain abscess in an infant. Comparative analysis of S. intermedius genome sequences suggested that TYG1620 carries a notable type VII secretion system (T7SS), two long repeat regions, and 19 ORFs for cell wall-anchored proteins (CWAPs). To elucidate the genes responsible for the pathogenicity of TYG1620, transcriptome analysis was performed in a murine subcutaneous abscess model. The results suggest that the levels of expression of small hypothetical proteins similar to phenol-soluble modulin β1 (PSMβ1), a staphylococcal virulence factor, significantly increased in the abscess model. In addition, an experiment in a murine subcutaneous abscess model with random transposon (Tn) mutant attenuation suggested that Tn mutants with mutations in 212 ORFs in the Tn mutant library were attenuated in the murine abscess model (629 ORFs were disrupted in total); the 212 ORFs are putatively essential for abscess formation. Transcriptome analysis identified 37 ORFs, including paralogs of the T7SS and a putative glucan-binding CWAP in long repeat regions, to be upregulated and attenuated in vivo This study provides a comprehensive characterization of S. intermedius pathogenicity based on the complete genome sequence and a murine subcutaneous abscess model with transcriptome and Tn mutagenesis, leading to the identification of pivotal targets for vaccines or antimicrobial agents for the control of S. intermedius infections. Copyright © 2017 American Society for Microbiology.

  2. Transcriptome Profiling in Human Diseases: New Advances and Perspectives

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    Amelia Casamassimi

    2017-07-01

    Full Text Available In the last decades, transcriptome profiling has been one of the most utilized approaches to investigate human diseases at the molecular level. Through expression studies, many molecular biomarkers and therapeutic targets have been found for several human pathologies. This number is continuously increasing thanks to total RNA sequencing. Indeed, this new technology has completely revolutionized transcriptome analysis allowing the quantification of gene expression levels and allele-specific expression in a single experiment, as well as to identify novel genes, splice isoforms, fusion transcripts, and to investigate the world of non-coding RNA at an unprecedented level. RNA sequencing has also been employed in important projects, like ENCODE (Encyclopedia of the regulatory elements and TCGA (The Cancer Genome Atlas, to provide a snapshot of the transcriptome of dozens of cell lines and thousands of primary tumor specimens. Moreover, these studies have also paved the way to the development of data integration approaches in order to facilitate management and analysis of data and to identify novel disease markers and molecular targets to use in the clinics. In this scenario, several ongoing clinical trials utilize transcriptome profiling through RNA sequencing strategies as an important instrument in the diagnosis of numerous human pathologies.

  3. Transcriptome Profiling in Human Diseases: New Advances and Perspectives.

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    Casamassimi, Amelia; Federico, Antonio; Rienzo, Monica; Esposito, Sabrina; Ciccodicola, Alfredo

    2017-07-29

    In the last decades, transcriptome profiling has been one of the most utilized approaches to investigate human diseases at the molecular level. Through expression studies, many molecular biomarkers and therapeutic targets have been found for several human pathologies. This number is continuously increasing thanks to total RNA sequencing. Indeed, this new technology has completely revolutionized transcriptome analysis allowing the quantification of gene expression levels and allele-specific expression in a single experiment, as well as to identify novel genes, splice isoforms, fusion transcripts, and to investigate the world of non-coding RNA at an unprecedented level. RNA sequencing has also been employed in important projects, like ENCODE (Encyclopedia of the regulatory elements) and TCGA (The Cancer Genome Atlas), to provide a snapshot of the transcriptome of dozens of cell lines and thousands of primary tumor specimens. Moreover, these studies have also paved the way to the development of data integration approaches in order to facilitate management and analysis of data and to identify novel disease markers and molecular targets to use in the clinics. In this scenario, several ongoing clinical trials utilize transcriptome profiling through RNA sequencing strategies as an important instrument in the diagnosis of numerous human pathologies.

  4. Major differences between human atopic dermatitis and murine models as determined by global transcriptomic profiling

    DEFF Research Database (Denmark)

    Ewald, David Adrian; Noda, Shinji; Oliva, Margeaux

    2017-01-01

    , and a comparison of these models with the human AD transcriptomic fingerprint is lacking. We sought to evaluate the transcriptomic profiles of six common murine models and determine how they relate to human AD skin. Transcriptomic profiling was performed using microarrays and qRT-PCR on biopsies from NC/Nga, flaky...

  5. Evolution of the aging brain transcriptome and synaptic regulation.

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    Patrick M Loerch

    Full Text Available Alzheimer's disease and other neurodegenerative disorders of aging are characterized by clinical and pathological features that are relatively specific to humans. To obtain greater insight into how brain aging has evolved, we compared age-related gene expression changes in the cortex of humans, rhesus macaques, and mice on a genome-wide scale. A small subset of gene expression changes are conserved in all three species, including robust age-dependent upregulation of the neuroprotective gene apolipoprotein D (APOD and downregulation of the synaptic cAMP signaling gene calcium/calmodulin-dependent protein kinase IV (CAMK4. However, analysis of gene ontology and cell type localization shows that humans and rhesus macaques have diverged from mice due to a dramatic increase in age-dependent repression of neuronal genes. Many of these age-regulated neuronal genes are associated with synaptic function. Notably, genes associated with GABA-ergic inhibitory function are robustly age-downregulated in humans but not in mice at the level of both mRNA and protein. Gene downregulation was not associated with overall neuronal or synaptic loss. Thus, repression of neuronal gene expression is a prominent and recently evolved feature of brain aging in humans and rhesus macaques that may alter neural networks and contribute to age-related cognitive changes.

  6. Human Transcriptome and Chromatin Modifications: An ENCODE Perspective

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    Li Shen

    2013-06-01

    Full Text Available A decade-long project, led by several international research groups, called the Encyclopedia of DNA Elements (ENCODE, recently released an unprecedented amount of data. The ambitious project covers transcriptome, cistrome, epigenome, and interactome data from more than 1,600 sets of experiments in human. To make use of this valuable resource, it is important to understand the information it represents and the techniques that were used to generate these data. In this review, we introduce the data that ENCODE generated, summarize the observations from the data analysis, and revisit a computational approach that ENCODE used to predict gene expression, with a focus on the human transcriptome and its association with chromatin modifications.

  7. Chromosomal clustering of a human transcriptome reveals regulatory background

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    Purmann Antje

    2005-09-01

    Full Text Available Abstract Background There has been much evidence recently for a link between transcriptional regulation and chromosomal gene order, but the relationship between genomic organization, regulation and gene function in higher eukaryotes remains to be precisely defined. Results Here, we present evidence for organization of a large proportion of a human transcriptome into gene clusters throughout the genome, which are partly regulated by the same transcription factors, share biological functions and are characterized by non-housekeeping genes. This analysis was based on the cardiac transcriptome identified by our genome-wide array analysis of 55 human heart samples. We found 37% of these genes to be arranged mainly in adjacent pairs or triplets. A significant number of pairs of adjacent genes are putatively regulated by common transcription factors (p = 0.02. Furthermore, these gene pairs share a significant number of GO functional classification terms. We show that the human cardiac transcriptome is organized into many small clusters across the whole genome, rather than being concentrated in a few larger clusters. Conclusion Our findings suggest that genes expressed in concert are organized in a linear arrangement for coordinated regulation. Determining the relationship between gene arrangement, regulation and nuclear organization as well as gene function will have broad biological implications.

  8. Structural covariance of brain region volumes is associated with both structural connectivity and transcriptomic similarity.

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    Yee, Yohan; Fernandes, Darren J; French, Leon; Ellegood, Jacob; Cahill, Lindsay S; Vousden, Dulcie A; Spencer Noakes, Leigh; Scholz, Jan; van Eede, Matthijs C; Nieman, Brian J; Sled, John G; Lerch, Jason P

    2018-05-18

    An organizational pattern seen in the brain, termed structural covariance, is the statistical association of pairs of brain regions in their anatomical properties. These associations, measured across a population as covariances or correlations usually in cortical thickness or volume, are thought to reflect genetic and environmental underpinnings. Here, we examine the biological basis of structural volume covariance in the mouse brain. We first examined large scale associations between brain region volumes using an atlas-based approach that parcellated the entire mouse brain into 318 regions over which correlations in volume were assessed, for volumes obtained from 153 mouse brain images via high-resolution MRI. We then used a seed-based approach and determined, for 108 different seed regions across the brain and using mouse gene expression and connectivity data from the Allen Institute for Brain Science, the variation in structural covariance data that could be explained by distance to seed, transcriptomic similarity to seed, and connectivity to seed. We found that overall, correlations in structure volumes hierarchically clustered into distinct anatomical systems, similar to findings from other studies and similar to other types of networks in the brain, including structural connectivity and transcriptomic similarity networks. Across seeds, this structural covariance was significantly explained by distance (17% of the variation, up to a maximum of 49% for structural covariance to the visceral area of the cortex), transcriptomic similarity (13% of the variation, up to maximum of 28% for structural covariance to the primary visual area) and connectivity (15% of the variation, up to a maximum of 36% for structural covariance to the intermediate reticular nucleus in the medulla) of covarying structures. Together, distance, connectivity, and transcriptomic similarity explained 37% of structural covariance, up to a maximum of 63% for structural covariance to the

  9. Sensitive detection of viral transcripts in human tumor transcriptomes.

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    Sven-Eric Schelhorn

    Full Text Available In excess of 12% of human cancer incidents have a viral cofactor. Epidemiological studies of idiopathic human cancers indicate that additional tumor viruses remain to be discovered. Recent advances in sequencing technology have enabled systematic screenings of human tumor transcriptomes for viral transcripts. However, technical problems such as low abundances of viral transcripts in large volumes of sequencing data, viral sequence divergence, and homology between viral and human factors significantly confound identification of tumor viruses. We have developed a novel computational approach for detecting viral transcripts in human cancers that takes the aforementioned confounding factors into account and is applicable to a wide variety of viruses and tumors. We apply the approach to conducting the first systematic search for viruses in neuroblastoma, the most common cancer in infancy. The diverse clinical progression of this disease as well as related epidemiological and virological findings are highly suggestive of a pathogenic cofactor. However, a viral etiology of neuroblastoma is currently contested. We mapped 14 transcriptomes of neuroblastoma as well as positive and negative controls to the human and all known viral genomes in order to detect both known and unknown viruses. Analysis of controls, comparisons with related methods, and statistical estimates demonstrate the high sensitivity of our approach. Detailed investigation of putative viral transcripts within neuroblastoma samples did not provide evidence for the existence of any known human viruses. Likewise, de-novo assembly and analysis of chimeric transcripts did not result in expression signatures associated with novel human pathogens. While confounding factors such as sample dilution or viral clearance in progressed tumors may mask viral cofactors in the data, in principle, this is rendered less likely by the high sensitivity of our approach and the number of biological replicates

  10. Transcriptome sequencing from diverse human populations reveals differentiated regulatory architecture.

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    Alicia R Martin

    2014-08-01

    Full Text Available Large-scale sequencing efforts have documented extensive genetic variation within the human genome. However, our understanding of the origins, global distribution, and functional consequences of this variation is far from complete. While regulatory variation influencing gene expression has been studied within a handful of populations, the breadth of transcriptome differences across diverse human populations has not been systematically analyzed. To better understand the spectrum of gene expression variation, alternative splicing, and the population genetics of regulatory variation in humans, we have sequenced the genomes, exomes, and transcriptomes of EBV transformed lymphoblastoid cell lines derived from 45 individuals in the Human Genome Diversity Panel (HGDP. The populations sampled span the geographic breadth of human migration history and include Namibian San, Mbuti Pygmies of the Democratic Republic of Congo, Algerian Mozabites, Pathan of Pakistan, Cambodians of East Asia, Yakut of Siberia, and Mayans of Mexico. We discover that approximately 25.0% of the variation in gene expression found amongst individuals can be attributed to population differences. However, we find few genes that are systematically differentially expressed among populations. Of this population-specific variation, 75.5% is due to expression rather than splicing variability, and we find few genes with strong evidence for differential splicing across populations. Allelic expression analyses indicate that previously mapped common regulatory variants identified in eight populations from the International Haplotype Map Phase 3 project have similar effects in our seven sampled HGDP populations, suggesting that the cellular effects of common variants are shared across diverse populations. Together, these results provide a resource for studies analyzing functional differences across populations by estimating the degree of shared gene expression, alternative splicing, and

  11. The Drosophila surface glia transcriptome: evolutionary conserved blood-brain barrier processes.

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    Michael K DeSalvo

    2014-11-01

    Full Text Available AbstractCentral nervous system (CNS function is dependent on the stringent regulation of metabolites, drugs, cells, and pathogens exposed to the CNS space. Cellular blood-brain barrier (BBB structures are highly specific checkpoints governing entry and exit of all small molecules to and from the brain interstitial space, but the precise mechanisms that regulate the BBB are not well understood. In addition, the BBB has long been a challenging obstacle to the pharmacologic treatment of CNS diseases; thus model systems that can parse the functions of the BBB are highly desirable. In this study, we sought to define the transcriptome of the adult Drosophila melanogaster BBB by isolating the BBB surface glia with FACS and profiling their gene expression with microarrays. By comparing the transcriptome of these surface glia to that of all brain glia, brain neurons, and whole brains, we present a catalog of transcripts that are selectively enriched at the Drosophila BBB. We found that the fly surface glia show high expression of many ABC and SLC transporters, cell adhesion molecules, metabolic enzymes, signaling molecules, and components of xenobiotic metabolism pathways. Using gene sequence-based alignments, we compare the Drosophila and Murine BBB transcriptomes and discover many shared chemoprotective and small molecule control pathways, thus affirming the relevance of invertebrate models for studying evolutionary conserved BBB properties. The Drosophila BBB transcriptome is valuable to vertebrate and insect biologists alike as a resource for studying proteins underlying diffusion barrier development and maintenance, glial biology, and regulation of drug transport at tissue barriers.

  12. The Drosophila surface glia transcriptome: evolutionary conserved blood-brain barrier processes.

    Science.gov (United States)

    DeSalvo, Michael K; Hindle, Samantha J; Rusan, Zeid M; Orng, Souvinh; Eddison, Mark; Halliwill, Kyle; Bainton, Roland J

    2014-01-01

    Central nervous system (CNS) function is dependent on the stringent regulation of metabolites, drugs, cells, and pathogens exposed to the CNS space. Cellular blood-brain barrier (BBB) structures are highly specific checkpoints governing entry and exit of all small molecules to and from the brain interstitial space, but the precise mechanisms that regulate the BBB are not well understood. In addition, the BBB has long been a challenging obstacle to the pharmacologic treatment of CNS diseases; thus model systems that can parse the functions of the BBB are highly desirable. In this study, we sought to define the transcriptome of the adult Drosophila melanogaster BBB by isolating the BBB surface glia with fluorescence activated cell sorting (FACS) and profiling their gene expression with microarrays. By comparing the transcriptome of these surface glia to that of all brain glia, brain neurons, and whole brains, we present a catalog of transcripts that are selectively enriched at the Drosophila BBB. We found that the fly surface glia show high expression of many ATP-binding cassette (ABC) and solute carrier (SLC) transporters, cell adhesion molecules, metabolic enzymes, signaling molecules, and components of xenobiotic metabolism pathways. Using gene sequence-based alignments, we compare the Drosophila and Murine BBB transcriptomes and discover many shared chemoprotective and small molecule control pathways, thus affirming the relevance of invertebrate models for studying evolutionary conserved BBB properties. The Drosophila BBB transcriptome is valuable to vertebrate and insect biologists alike as a resource for studying proteins underlying diffusion barrier development and maintenance, glial biology, and regulation of drug transport at tissue barriers.

  13. Educating the Human Brain. Human Brain Development Series

    Science.gov (United States)

    Posner, Michael I.; Rothbart, Mary K.

    2006-01-01

    "Educating the Human Brain" is the product of a quarter century of research. This book provides an empirical account of the early development of attention and self regulation in infants and young children. It examines the brain areas involved in regulatory networks, their connectivity, and how their development is influenced by genes and…

  14. Transcriptomic analyses of tributyltin-induced sexual dimorphisms in rare minnow (Gobiocypris rarus) brains.

    Science.gov (United States)

    Zhang, Ji-Liang; Liu, Min; Zhang, Chun-Nuan; Li, Er-Chao; Fan, Ming-Zhen; Huang, Mao-Xian

    2018-07-30

    The brain of fish displays sexual dimorphisms and exhibits remarkable sexual plasticity throughout their life span. Although reproductive toxicity of tributyltin (TBT) in fish is well documented in fish, it remains unknown whether TBT interrupts sexual dimorphisms of fish brains. In this work, brain transcriptomic profiles of rare minnow (Gobiocypris rarus) was characterized and sex-biased genes were identified using RNA sequencing. Functional annotation and enrichment analysis were performed to reveal differences of gene products and pathways between the brains of male and female fish. Furthermore, transcriptomic responses of male and female brains to TBT at 10 ng/L were also investigated to understand effects of TBT on brain sexual dimorphisms. Only 345 male-biased and 273 female-biased genes were found in the brains. However, significant female-biased pathways of circadian rhythm and phototransduction were identified in the brains by enrichment analysis. Interestingly, following TBT exposure in the female fish, the circadian rhythm pathway was significantly disrupted based on enrichment analysis, while in the male fish, the phototransduction pathway was significantly disrupted. In the female fish, expression of genes (Per, Cry, Rev-Erb α, Ror, Dec and CK1δ/ε) in the circadian rhythm pathway was down-regulated after TBT exposure; while in the male fish, expression of genes (Rec, GNAT1_2, GNGT1, Rh/opsin, PDE and Arr) in the phototransduction pathway was up-regulated after TBT exposure. Overall, our results not only provide key data on the molecular basis of brain sexual dimorphisms in fish, but also offer valuable resources for investigating molecular mechanisms by which environmental chemicals might influence brain sexual plasticity. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Sex-specific differences in transcriptome profiles of brain and muscle tissue of the tropical gar.

    Science.gov (United States)

    Cribbin, Kayla M; Quackenbush, Corey R; Taylor, Kyle; Arias-Rodriguez, Lenin; Kelley, Joanna L

    2017-04-07

    The tropical gar (Atractosteus tropicus) is the southernmost species of the seven extant species of gar fishes in the world. In Mexico and Central America, the species is an important food source due to its nutritional quality and low price. Despite its regional importance and increasing concerns about overexploitation and habitat degradation, basic genetic information on the tropical gar is lacking. Determining genetic information on the tropical gar is important for the sustainable management of wild populations, implementation of best practices in aquaculture settings, evolutionary studies of ancient lineages, and an understanding of sex-specific gene expression. In this study, the transcriptome of the tropical gar was sequenced and assembled de novo using tissues from three males and three females using Illumina sequencing technology. Sex-specific and highly differentially expressed transcripts in brain and muscle tissues between adult males and females were subsequently identified. The transcriptome was assembled de novo resulting in 80,611 transcripts with a contig N50 of 3,355 base pairs and over 168 kilobases in total length. Male muscle, brain, and gonad as well as female muscle and brain were included in the assembly. The assembled transcriptome was annotated to identify the putative function of expressed transcripts using Trinotate and SwissProt, a database of well-annotated proteins. The brain and muscle datasets were then aligned to the assembled transcriptome to identify transcripts that were differentially expressed between males and females. The contrast between male and female brain identified 109 transcripts from 106 genes that were significantly differentially expressed. In the muscle comparison, 82 transcripts from 80 genes were identified with evidence for significant differential expression. Almost all genes identified as differentially expressed were sex-specific. The differentially expressed transcripts were enriched for genes involved in

  16. Legionella pneumophila transcriptome during intracellular multiplication in human macrophages

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    Sebastien P Faucher

    2011-04-01

    Full Text Available Legionella pneumophila is the causative agent of Legionnaires’ disease, an acute pulmonary infection. L. pneumophila is able to infect and multiply in both phagocytic protozoa, such as Acanthamoeba castellanii, and mammalian professional phagocytes. The best-known L. pneumophila virulence determinant is the Icm/Dot Type IVB secretion system (TFBSS, which is used to translocate more than 150 effector proteins to host cells. While the transcriptional response of Legionella to the intracellular environment of A. castellanii has been investigated, much less is known about the Legionella transcriptional response inside human macrophages. In this study, the transcriptome of L. pneumophila was monitored during exponential and post-exponential phase in rich AYE broth as well as during infection of human cultured macrophages. This was accomplished with microarrays and an RNA amplification procedure called SCOTS to detect small amounts of mRNA from low numbers of intracellular bacteria. Among the genes induced intracellularly are those involved in amino acid biosynthetic pathways leading to L-arginine, L-histidine and L-proline as well as many transport systems involved in amino acid and iron uptake. Gene involved in catabolism of glycerol is also induced during intracellular growth and could be used as a carbon source. The genes encoding the Icm/Dot system are not differentially expressed inside cells compared to control bacteria grown in rich broth, but the genes encoding several translocated effectors are strongly induced. Moreover, we used the transcriptome data to predict previously unrecognized Icm/Dot effector genes based on their expression pattern and confirmed translocation for three candidates. This study provides a comprehensive view of how L. pneumophila responds to the human macrophage intracellular environment.

  17. Intergenic and repeat transcription in human, chimpanzee and macaque brains measured by RNA-Seq.

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    Augix Guohua Xu

    Full Text Available Transcription is the first step connecting genetic information with an organism's phenotype. While expression of annotated genes in the human brain has been characterized extensively, our knowledge about the scope and the conservation of transcripts located outside of the known genes' boundaries is limited. Here, we use high-throughput transcriptome sequencing (RNA-Seq to characterize the total non-ribosomal transcriptome of human, chimpanzee, and rhesus macaque brain. In all species, only 20-28% of non-ribosomal transcripts correspond to annotated exons and 20-23% to introns. By contrast, transcripts originating within intronic and intergenic repetitive sequences constitute 40-48% of the total brain transcriptome. Notably, some repeat families show elevated transcription. In non-repetitive intergenic regions, we identify and characterize 1,093 distinct regions highly expressed in the human brain. These regions are conserved at the RNA expression level across primates studied and at the DNA sequence level across mammals. A large proportion of these transcripts (20% represents 3'UTR extensions of known genes and may play roles in alternative microRNA-directed regulation. Finally, we show that while transcriptome divergence between species increases with evolutionary time, intergenic transcripts show more expression differences among species and exons show less. Our results show that many yet uncharacterized evolutionary conserved transcripts exist in the human brain. Some of these transcripts may play roles in transcriptional regulation and contribute to evolution of human-specific phenotypic traits.

  18. A digital atlas to characterize the mouse brain transcriptome.

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    James P Carson

    2005-09-01

    Full Text Available Massive amounts of data are being generated in an effort to represent for the brain the expression of all genes at cellular resolution. Critical to exploiting this effort is the ability to place these data into a common frame of reference. Here we have developed a computational method for annotating gene expression patterns in the context of a digital atlas to facilitate custom user queries and comparisons of this type of data. This procedure has been applied to 200 genes in the postnatal mouse brain. As an illustration of utility, we identify candidate genes that may be related to Parkinson disease by using the expression of a dopamine transporter in the substantia nigra as a search query pattern. In addition, we discover that transcription factor Rorb is down-regulated in the barrelless mutant relative to control mice by quantitative comparison of expression patterns in layer IV somatosensory cortex. The semi-automated annotation method developed here is applicable to a broad spectrum of complex tissues and data modalities.

  19. Optimized Exon-Exon Junction Library and its Application on Rodents' Brain Transcriptome Analysis

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    Tong-Hai Dou

    2017-05-01

    Full Text Available ABSTRACT Background: Alternative splicing (AS, which plays an important role in gene expression and functional regulation, has been analyzed on genome-scale by various bioinformatic approaches based on RNA-seq data. Compared with the huge number of studies on mouse, the AS researches approaching the rat, whose genome is intermedia between mouse and human, were still limited. To enrich the knowledge on AS events in rodents' brain, we perfomed a comprehensive analysis on four transcriptome libraries (mouse cerebrum, mouse cerebellum, rat cerebrum, and rat cerebellum, recruiting high-throughput sequencing technology. An optimized exon-exon junction library approach was introduced to adapt the longer RNA-seq reads and to improve mapping efficiency. Results: In total, 7,106 mouse genes and 2,734 rat genes were differentially expressed between cerebrum and cerebellum, while 7,125 mouse genes and 1,795 rat genes exhibited varieties on transcript variant level. Only half of the differentially expressed exon-exon junctions could be reflected at gene expression level. Functional cluster analysis showed that 32 pathways in mouse and 9 pathways in rat were significantly enriched, and 6 of them were in both. Interestingly, some differentially expressed transcript variants did not show difference on gene expression level, such as PLCβ1 and Kcnma1. Conclusion: Our work provided a case study of a novel exon-exon junction strategy to analyze the expression of genes and isoforms, helping us understand which transcript contributes to the overall expression and further functional change.

  20. Brain transcriptome variation among behaviorally distinct strains of zebrafish (Danio rerio

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    Drew Robert E

    2012-07-01

    Full Text Available Abstract Background Domesticated animal populations often show profound reductions in predator avoidance and fear-related behavior compared to wild populations. These reductions are remarkably consistent and have been observed in a diverse array of taxa including fish, birds, and mammals. Experiments conducted in common environments indicate that these behavioral differences have a genetic basis. In this study, we quantified differences in fear-related behavior between wild and domesticated zebrafish strains and used microarray analysis to identify genes that may be associated with this variation. Results Compared to wild zebrafish, domesticated zebrafish spent more time near the water surface and were more likely to occupy the front of the aquarium nearest a human observer. Microarray analysis of the brain transcriptome identified high levels of population variation in gene expression, with 1,749 genes significantly differentially expressed among populations. Genes that varied among populations belonged to functional categories that included DNA repair, DNA photolyase activity, response to light stimulus, neuron development and axon guidance, cell death, iron-binding, chromatin reorganization, and homeobox genes. Comparatively fewer genes (112 differed between domesticated and wild strains with notable genes including gpr177 (wntless, selenoprotein P1a, synaptophysin and synaptoporin, and acyl-CoA binding domain containing proteins (acbd3 and acbd4. Conclusions Microarray analysis identified a large number of genes that differed among zebrafish populations and may underlie behavioral domestication. Comparisons with similar microarray studies of domestication in rainbow trout and canids identified sixteen evolutionarily or functionally related genes that may represent components of shared molecular mechanisms underlying convergent behavioral evolution during vertebrate domestication. However, this conclusion must be tempered by limitations

  1. Why did humans develop a large brain?

    OpenAIRE

    Muscat Baron, Yves

    2012-01-01

    "Of all animals, man has the largest brain in proportion to his size"- Aristotle. Dr Yves Muscat Baron shares his theory on how humans evolved large brains. The theory outlines how gravity could have helped humans develop a large brain- the author has named the theory 'The Gravitational Vascular Theory'. http://www.um.edu.mt/think/why-did-humans-develop-a-large-brain/

  2. Phosphatidylserine and the human brain.

    Science.gov (United States)

    Glade, Michael J; Smith, Kyl

    2015-06-01

    The aim of this study was to assess the roles and importance of phosphatidylserine (PS), an endogenous phospholipid and dietary nutrient, in human brain biochemistry, physiology, and function. A scientific literature search was conducted on MEDLINE for relevant articles regarding PS and the human brain published before June 2014. Additional publications were identified from references provided in original papers; 127 articles were selected for inclusion in this review. A large body of scientific evidence describes the interactions among PS, cognitive activity, cognitive aging, and retention of cognitive functioning ability. Phosphatidylserine is required for healthy nerve cell membranes and myelin. Aging of the human brain is associated with biochemical alterations and structural deterioration that impair neurotransmission. Exogenous PS (300-800 mg/d) is absorbed efficiently in humans, crosses the blood-brain barrier, and safely slows, halts, or reverses biochemical alterations and structural deterioration in nerve cells. It supports human cognitive functions, including the formation of short-term memory, the consolidation of long-term memory, the ability to create new memories, the ability to retrieve memories, the ability to learn and recall information, the ability to focus attention and concentrate, the ability to reason and solve problems, language skills, and the ability to communicate. It also supports locomotor functions, especially rapid reactions and reflexes. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Distribution of ADAT-Dependent Codons in the Human Transcriptome

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    Àlbert Rafels-Ybern

    2015-07-01

    Full Text Available Nucleotide modifications in the anticodons of transfer RNAs (tRNA play a central role in translation efficiency, fidelity, and regulation of translation, but, for most of these modifications, the details of their function remain unknown. The heterodimeric adenosine deaminases acting on tRNAs (ADAT2-ADAT3, or ADAT are enzymes present in eukaryotes that convert adenine (A to inosine (I in the first anticodon base (position 34 by hydrolytic deamination. To explore the influence of ADAT activity on mammalian translation, we have characterized the human transcriptome and proteome in terms of frequency and distribution of ADAT-related codons. Eight different tRNAs can be modified by ADAT and, once modified, these tRNAs will recognize NNC, NNU and NNA codons, but not NNG codons. We find that transcripts coding for proteins highly enriched in these eight amino acids (ADAT-aa are specifically enriched in NNC, NNU and NNA codons. We also show that the proteins most enriched in ADAT-aa are composed preferentially of threonine, alanine, proline, and serine (TAPS. We propose that the enrichment in ADAT-codons in these proteins is due to the similarities in the codons that correspond to TAPS.

  4. A comparative transcriptomic analysis of astrocytes differentiation from human neural progenitor cells.

    Science.gov (United States)

    Magistri, Marco; Khoury, Nathalie; Mazza, Emilia Maria Cristina; Velmeshev, Dmitry; Lee, Jae K; Bicciato, Silvio; Tsoulfas, Pantelis; Faghihi, Mohammad Ali

    2016-11-01

    Astrocytes are a morphologically and functionally heterogeneous population of cells that play critical roles in neurodevelopment and in the regulation of central nervous system homeostasis. Studies of human astrocytes have been hampered by the lack of specific molecular markers and by the difficulties associated with purifying and culturing astrocytes from adult human brains. Human neural progenitor cells (NPCs) with self-renewal and multipotent properties represent an appealing model system to gain insight into the developmental genetics and function of human astrocytes, but a comprehensive molecular characterization that confirms the validity of this cellular system is still missing. Here we used an unbiased transcriptomic analysis to characterize in vitro culture of human NPCs and to define the gene expression programs activated during the differentiation of these cells into astrocytes using FBS or the combination of CNTF and BMP4. Our results demonstrate that in vitro cultures of human NPCs isolated during the gliogenic phase of neurodevelopment mainly consist of radial glial cells (RGCs) and glia-restricted progenitor cells. In these cells the combination of CNTF and BMP4 activates the JAK/STAT and SMAD signaling cascades, leading to the inhibition of oligodendrocytes lineage commitment and activation of astrocytes differentiation. On the other hand, FBS-derived astrocytes have properties of reactive astrocytes. Our work suggests that in vitro culture of human NPCs represents a valuable cellular system to study human disorders characterized by impairment of astrocytes development and function. Our datasets represent an important resource for researchers studying human astrocytes development and might set the basis for the discovery of novel human-specific astrocyte markers. © 2016 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  5. Brain transcriptome sequencing and assembly of three songbird model systems for the study of social behavior

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    Christopher N. Balakrishnan

    2014-05-01

    Full Text Available Emberizid sparrows (emberizidae have played a prominent role in the study of avian vocal communication and social behavior. We present here brain transcriptomes for three emberizid model systems, song sparrow Melospiza melodia, white-throated sparrow Zonotrichia albicollis, and Gambel’s white-crowned sparrow Zonotrichia leucophrys gambelii. Each of the assemblies covered fully or in part, over 89% of the previously annotated protein coding genes in the zebra finch Taeniopygia guttata, with 16,846, 15,805, and 16,646 unique BLAST hits in song, white-throated and white-crowned sparrows, respectively. As in previous studies, we find tissue of origin (auditory forebrain versus hypothalamus and whole brain as an important determinant of overall expression profile. We also demonstrate the successful isolation of RNA and RNA-sequencing from post-mortem samples from building strikes and suggest that such an approach could be useful when traditional sampling opportunities are limited. These transcriptomes will be an important resource for the study of social behavior in birds and for data driven annotation of forthcoming whole genome sequences for these and other bird species.

  6. Functional annotation of the human retinal pigment epithelium transcriptome

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    Gorgels Theo GMF

    2009-04-01

    Full Text Available Abstract Background To determine level, variability and functional annotation of gene expression of the human retinal pigment epithelium (RPE, the key tissue involved in retinal diseases like age-related macular degeneration and retinitis pigmentosa. Macular RPE cells from six selected healthy human donor eyes (aged 63–78 years were laser dissected and used for 22k microarray studies (Agilent technologies. Data were analyzed with Rosetta Resolver, the web tool DAVID and Ingenuity software. Results In total, we identified 19,746 array entries with significant expression in the RPE. Gene expression was analyzed according to expression levels, interindividual variability and functionality. A group of highly (n = 2,194 expressed RPE genes showed an overrepresentation of genes of the oxidative phosphorylation, ATP synthesis and ribosome pathways. In the group of moderately expressed genes (n = 8,776 genes of the phosphatidylinositol signaling system and aminosugars metabolism were overrepresented. As expected, the top 10 percent (n = 2,194 of genes with the highest interindividual differences in expression showed functional overrepresentation of the complement cascade, essential in inflammation in age-related macular degeneration, and other signaling pathways. Surprisingly, this same category also includes the genes involved in Bruch's membrane (BM composition. Among the top 10 percent of genes with low interindividual differences, there was an overrepresentation of genes involved in local glycosaminoglycan turnover. Conclusion Our study expands current knowledge of the RPE transcriptome by assigning new genes, and adding data about expression level and interindividual variation. Functional annotation suggests that the RPE has high levels of protein synthesis, strong energy demands, and is exposed to high levels of oxidative stress and a variable degree of inflammation. Our data sheds new light on the molecular composition of BM, adjacent to the

  7. Transcriptomic configuration of mouse brain induced by adolescent exposure to 3,4-methylenedioxymethamphetamine

    International Nuclear Information System (INIS)

    Eun, Jung Woo; Kwack, Seung Jun; Noh, Ji Heon; Jung, Kwang Hwa; Kim, Jeong Kyu; Bae, Hyun Jin; Xie Hongjian; Ryu, Jae Chun; Ahn, Young Min; Min, Jin-Hye; Park, Won Sang; Lee, Jung Young; Rhee, Gyu Seek; Nam, Suk Woo

    2009-01-01

    The amphetamine derivative (±)-3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a synthetic amphetamine analogue used recreationally to obtain an enhanced affiliative emotional response. MDMA is a potent monoaminergic neurotoxin with the potential to damage brain serotonin and/or dopamine neurons. As the majority of MDMA users are young adults, the risk that users may expose the fetus to MDMA is a concern. However, the majority of studies on MDMA have investigated the effects on adult animals. Here, we investigated whether long-term exposure to MDMA, especially in adolescence, could induce comprehensive transcriptional changes in mouse brain. Transcriptomic analysis of mouse brain regions demonstrated significant gene expression changes in the cerebral cortex. Supervised analysis identified 1028 genes that were chronically dysregulated by long-term exposure to MDMA in adolescent mice. Functional categories most represented by this MDMA characteristic signature are intracellular molecular signaling pathways of neurotoxicity, such as, the MAPK signaling pathway, the Wnt signaling pathway, neuroactive ligand-receptor interaction, long-term potentiation, and the long-term depression signaling pathway. Although these resultant large-scale molecular changes remain to be studied associated with functional brain damage caused by MDMA, our observations delineate the possible neurotoxic effects of MDMA on brain function, and have therapeutic implications concerning neuro-pathological conditions associated with MDMA abuse.

  8. Distribution of cellular HSV-1 receptor expression in human brain.

    Science.gov (United States)

    Lathe, Richard; Haas, Juergen G

    2017-06-01

    Herpes simplex virus type 1 (HSV-1) is a neurotropic virus linked to a range of acute and chronic neurological disorders affecting distinct regions of the brain. Unusually, HSV-1 entry into cells requires the interaction of viral proteins glycoprotein D (gD) and glycoprotein B (gB) with distinct cellular receptor proteins. Several different gD and gB receptors have been identified, including TNFRSF14/HVEM and PVRL1/nectin 1 as gD receptors and PILRA, MAG, and MYH9 as gB receptors. We investigated the expression of these receptor molecules in different areas of the adult and developing human brain using online transcriptome databases. Whereas all HSV-1 receptors showed distinct expression patterns in different brain areas, the Allan Brain Atlas (ABA) reported increased expression of both gD and gB receptors in the hippocampus. Specifically, for PVRL1, TNFRFS14, and MYH9, the differential z scores for hippocampal expression, a measure of relative levels of increased expression, rose to 2.9, 2.9, and 2.5, respectively, comparable to the z score for the archetypical hippocampus-enriched mineralocorticoid receptor (NR3C2, z = 3.1). These data were confirmed at the Human Brain Transcriptome (HBT) database, but HBT data indicate that MAG expression is also enriched in hippocampus. The HBT database allowed the developmental pattern of expression to be investigated; we report that all HSV1 receptors markedly increase in expression levels between gestation and the postnatal/adult periods. These results suggest that differential receptor expression levels of several HSV-1 gD and gB receptors in the adult hippocampus are likely to underlie the susceptibility of this brain region to HSV-1 infection.

  9. Identification of Genes Related to Learning and Memory in the Brain Transcriptome of the Mollusc, "Hermissenda Crassicornis"

    Science.gov (United States)

    Tamvacakis, Arianna N.; Senatore, Adriano; Katz, Paul S.

    2015-01-01

    The sea slug "Hermissenda crassicornis" (Mollusca, Gastropoda, Nudibranchia) has been studied extensively in associative learning paradigms. However, lack of genetic information previously hindered molecular-level investigations. Here, the "Hermissenda" brain transcriptome was sequenced and assembled de novo, producing 165,743…

  10. Automatic registration of imaging mass spectrometry data to the Allen Brain Atlas transcriptome

    Science.gov (United States)

    Abdelmoula, Walid M.; Carreira, Ricardo J.; Shyti, Reinald; Balluff, Benjamin; Tolner, Else; van den Maagdenberg, Arn M. J. M.; Lelieveldt, B. P. F.; McDonnell, Liam; Dijkstra, Jouke

    2014-03-01

    Imaging Mass Spectrometry (IMS) is an emerging molecular imaging technology that provides spatially resolved information on biomolecular structures; each image pixel effectively represents a molecular mass spectrum. By combining the histological images and IMS-images, neuroanatomical structures can be distinguished based on their biomolecular features as opposed to morphological features. The combination of IMS data with spatially resolved gene expression maps of the mouse brain, as provided by the Allen Mouse Brain atlas, would enable comparative studies of spatial metabolic and gene expression patterns in life-sciences research and biomarker discovery. As such, it would be highly desirable to spatially register IMS slices to the Allen Brain Atlas (ABA). In this paper, we propose a multi-step automatic registration pipeline to register ABA histology to IMS- images. Key novelty of the method is the selection of the best reference section from the ABA, based on pre-processed histology sections. First, we extracted a hippocampus-specific geometrical feature from the given experimental histological section to initially localize it among the ABA sections. Then, feature-based linear registration is applied to the initially localized section and its two neighbors in the ABA to select the most similar reference section. A non-rigid registration yields a one-to-one mapping of the experimental IMS slice to the ABA. The pipeline was applied on 6 coronal sections from two mouse brains, showing high anatomical correspondence, demonstrating the feasibility of complementing biomolecule distributions from individual mice with the genome-wide ABA transcriptome.

  11. Linking Genes and Brain Development of Honeybee Workers: A Whole-Transcriptome Approach.

    Directory of Open Access Journals (Sweden)

    Christina Vleurinck

    Full Text Available Honeybees live in complex societies whose capabilities far exceed those of the sum of their single members. This social synergism is achieved mainly by the worker bees, which form a female caste. The worker bees display diverse collaborative behaviors and engage in different behavioral tasks, which are controlled by the central nervous system (CNS. The development of the worker brain is determined by the female sex and the worker caste determination signal. Here, we report on genes that are controlled by sex or by caste during differentiation of the worker's pupal brain. We sequenced and compared transcriptomes from the pupal brains of honeybee workers, queens and drones. We detected 333 genes that are differently expressed and 519 genes that are differentially spliced between the sexes, and 1760 genes that are differentially expressed and 692 genes that are differentially spliced between castes. We further found that 403 genes are differentially regulated by both the sex and caste signals, providing evidence of the integration of both signals through differential gene regulation. In this gene set, we found that the molecular processes of restructuring the cell shape and cell-to-cell signaling are overrepresented. Our approach identified candidate genes that may be involved in brain differentiation that ensures the various social worker behaviors.

  12. Rapid stress-induced transcriptomic changes in the brain depend on beta-adrenergic signaling.

    Science.gov (United States)

    Roszkowski, Martin; Manuella, Francesca; von Ziegler, Lukas; Durán-Pacheco, Gonzalo; Moreau, Jean-Luc; Mansuy, Isabelle M; Bohacek, Johannes

    2016-08-01

    Acute exposure to stressful experiences can rapidly increase anxiety and cause neuropsychiatric disorders. The effects of stress result in part from the release of neurotransmitters and hormones, which regulate gene expression in different brain regions. The fast neuroendocrine response to stress is largely mediated by norepinephrine (NE) and corticotropin releasing hormone (CRH), followed by a slower and more sustained release of corticosterone. While corticosterone is an important regulator of gene expression, it is not clear which stress-signals contribute to the rapid regulation of gene expression observed immediately after stress exposure. Here, we demonstrate in mice that 45 min after an acute swim stress challenge, large changes in gene expression occur across the transcriptome in the hippocampus, a region sensitive to the effects of stress. We identify multiple candidate genes that are rapidly and transiently altered in both males and females. Using a pharmacological approach, we show that most of these rapidly induced genes are regulated by NE through β-adrenergic receptor signaling. We find that CRH and corticosterone can also contribute to rapid changes in gene expression, although these effects appear to be restricted to fewer genes. These results newly reveal a widespread impact of NE on the transcriptome and identify novel genes associated with stress and adrenergic signaling. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. A pathology atlas of the human cancer transcriptome

    DEFF Research Database (Denmark)

    Uhlén, Mathias; Zhang, Xi-Cheng; Lee, Sunjae

    2017-01-01

    Cancer is one of the leading causes of death, and there is great interest in understanding the underlying molecular mechanisms involved in the pathogenesis and progression of individual tumors. We used systems-level approaches to analyze the genome-wide transcriptome of the protein-coding genes o...

  14. The contribution of 700,000 ORF sequence tags to the definition of the human transcriptome

    DEFF Research Database (Denmark)

    Camargo, A A; Samaia, H P; Dias-Neto, E

    2001-01-01

    ,095 full-length mRNAs as a means of assessing the efficiency of the strategy and its potential contribution to the definition of the human transcriptome. We estimate that ORESTES sampled over 80% of all highly and moderately expressed, and between 40% and 50% of rarely expressed, human genes. In our most...

  15. Sexual differences of human brain

    Directory of Open Access Journals (Sweden)

    Masoud Pezeshki Rad

    2014-04-01

    Full Text Available During the last decades there has been an increasing interest in studying the differences between males and females. These differences extend from behavioral to cognitive to micro- and macro- neuro-anatomical aspects of human biology. There have been many methods to evaluate these differences and explain their determinants. The most studied cause of this dimorphism is the prenatal sex hormones and their organizational effect on brain and behavior. However, there have been new and recent attentions to hormone's activational influences in puberty and also the effects of genomic imprinting. In this paper, we reviewed the sex differences of brain, the evidences for possible determinants of these differences and also the methods that have been used to discover them. We reviewed the most conspicuous findings with specific attention to macro-anatomical differences based on Magnetic Resonance Imaging (MRI data. We finally reviewed the findings and the many opportunities for future studies.

  16. Genome-wide binding and transcriptome analysis of human farnesoid X receptor in primary human hepatocytes.

    Directory of Open Access Journals (Sweden)

    Le Zhan

    Full Text Available Farnesoid X receptor (FXR, NR1H4 is a ligand-activated transcription factor, belonging to the nuclear receptor superfamily. FXR is highly expressed in the liver and is essential in regulating bile acid homeostasis. FXR deficiency is implicated in numerous liver diseases and mice with modulation of FXR have been used as animal models to study liver physiology and pathology. We have reported genome-wide binding of FXR in mice by chromatin immunoprecipitation - deep sequencing (ChIP-seq, with results indicating that FXR may be involved in regulating diverse pathways in liver. However, limited information exists for the functions of human FXR and the suitability of using murine models to study human FXR functions.In the current study, we performed ChIP-seq in primary human hepatocytes (PHHs treated with a synthetic FXR agonist, GW4064 or DMSO control. In parallel, RNA deep sequencing (RNA-seq and RNA microarray were performed for GW4064 or control treated PHHs and wild type mouse livers, respectively.ChIP-seq showed similar profiles of genome-wide FXR binding in humans and mice in terms of motif analysis and pathway prediction. However, RNA-seq and microarray showed more different transcriptome profiles between PHHs and mouse livers upon GW4064 treatment.In summary, we have established genome-wide human FXR binding and transcriptome profiles. These results will aid in determining the human FXR functions, as well as judging to what level the mouse models could be used to study human FXR functions.

  17. Brain Transcriptome Profiling Analysis of Nile Tilapia (Oreochromis niloticus Under Long-Term Hypersaline Stress

    Directory of Open Access Journals (Sweden)

    Yan Liu

    2018-03-01

    Full Text Available The fish brain plays an important role in controlling growth, development, reproduction, and adaptation to environmental change. However, few studies stem from the perspective of whole transcriptome change in a fish brain and its response to long-term hypersaline stress. This study compares the differential transcriptomic responses of juvenile Nile tilapia (Oreochromis niloticus maintained for 8 weeks in brackish water (16 practical salinity units, psu and in freshwater. Fish brains from each treatment were collected for RNA-seq analysis to identify potential genes and pathways responding to hypersaline stress. A total of 27,089 genes were annotated, and 391 genes were expressed differently in the salinity treatment. Ten pathways containing 40 differentially expressed genes were identified in the tilapia brain. Antigen processing and presentation and phagosome were the two principally affected pathways in the immune system. Thirty-one of 40 genes were involved in various expressions associated with environmental information processing pathways such as neuroactive ligand-receptor interaction, cytokine-cytokine receptor interaction, the Jak-STAT signaling pathway, cell adhesion molecules (CAMs, and the PI3K-Akt signaling pathway, which are the upstream pathways for modulation of immunity and osmoregulation. The most-changed genes (>5-fold were all down-regulated, including four growth hormone/prolactin gene families, i.e., prolactin precursor (−10.62, prolactin-1 (−11, somatotropin (−10.15, somatolactin-like (−6.18, and two other genes [thyrotropin subunit beta (−7.73 and gonadotropin subunit beta-2 (−5.06] that stimulated prolactin release in tilapia. The downregulation pattern of these genes corroborates the decrease in tilapia immunity with increasing salinity and reveals an adaptive mechanism of tilapia to long-term hypersaline stress. Ovarian steroidogenesis, isoquinoline alkaloid biosynthesis, and phenylalanine metabolism are the

  18. Cardiovascular risk protection from the Mediterranean diet and olive oil. A transcriptomic update in humans

    International Nuclear Information System (INIS)

    Carrion, S.; Torres, L.; Castañer, O.

    2016-01-01

    This review highlights the human studies that explore the benefits of the Mediterranean diet and olive oil, based on gene expression analysis. We summarized consistent human transcriptomic studies on cardiovascular risk, based on TMD and olive oil interventions, with real life doses and conditions. A literature review was carried out leading up to February 2016. The results show that the TMD, specially supplemented with virgin olive oil, produces beneficial changes in the transcriptomic response of relevant genes in cardiovascular risk such as CAT, GPX1 and SIRT2. p65 and MCP-1, IL1B, IL6, CXCL1, INF-γ, ARHGAP15 and IL7R, which are involved in inflammation; and ABCA1, SR-B1, PPARBP, PPARα, PPARγ, PPARδ, CD-36 and COX-1, which play an important role in cholesterol efflux. The available data illustrate a transcriptomic effect on atherosclerosis, inflammation and oxidative stress pathways as well as the mentioned genes. [es

  19. Cardiovascular risk protection from the Mediterranean diet and olive oil. A transcriptomic update in humans

    Directory of Open Access Journals (Sweden)

    S. Carrión

    2016-12-01

    Full Text Available This review highlights the human studies that explore the benefits of the Mediterranean diet and olive oil, based on gene expression analysis. We summarized consistent human transcriptomic studies on cardiovascular risk, based on TMD and olive oil interventions, with real life doses and conditions. A literature review was carried out leading up to February 2016. The results show that the TMD, specially supplemented with virgin olive oil, produces beneficial changes in the transcriptomic response of relevant genes in cardiovascular risk such as CAT, GPX1 and SIRT2. p65 and MCP-1, IL1B, IL6, CXCL1, INF-γ, ARHGAP15 and IL7R, which are involved in inflammation; and ABCA1, SR-B1, PPARBP, PPARα, PPARγ, PPARδ, CD-36 and COX-1, which play an important role in cholesterol efflux. The available data illustrate a transcriptomic effect on atherosclerosis, inflammation and oxidative stress pathways as well as the mentioned genes.

  20. Brain mechanisms underlying human communication

    Directory of Open Access Journals (Sweden)

    Matthijs L Noordzij

    2009-07-01

    Full Text Available Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the “mirror neurons system”. However, this view does not explain how these conventions could develop in the first place. Here we target the neglected but crucial issue of how people organize their non-verbal behavior to communicate a given intention without pre-established conventions. We have measured behavioral and brain responses in pairs of subjects during communicative exchanges occurring in a real, interactive, on-line social context. In two fMRI studies, we found robust evidence that planning new communicative actions (by a sender and recognizing the communicative intention of the same actions (by a receiver relied on spatially overlapping portions of their brains (the right posterior superior temporal sulcus. The response of this region was lateralized to the right hemisphere, modulated by the ambiguity in meaning of the communicative acts, but not by their sensorimotor complexity. These results indicate that the sender of a communicative signal uses his own intention recognition system to make a prediction of the intention recognition performed by the receiver. This finding supports the notion that our communicative abilities are distinct from both sensorimotor processes and language abilities.

  1. Brain mechanisms underlying human communication.

    Science.gov (United States)

    Noordzij, Matthijs L; Newman-Norlund, Sarah E; de Ruiter, Jan Peter; Hagoort, Peter; Levinson, Stephen C; Toni, Ivan

    2009-01-01

    Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the "mirror neurons system"). However, this view does not explain how these conventions could develop in the first place. Here we target the neglected but crucial issue of how people organize their non-verbal behavior to communicate a given intention without pre-established conventions. We have measured behavioral and brain responses in pairs of subjects during communicative exchanges occurring in a real, interactive, on-line social context. In two fMRI studies, we found robust evidence that planning new communicative actions (by a sender) and recognizing the communicative intention of the same actions (by a receiver) relied on spatially overlapping portions of their brains (the right posterior superior temporal sulcus). The response of this region was lateralized to the right hemisphere, modulated by the ambiguity in meaning of the communicative acts, but not by their sensorimotor complexity. These results indicate that the sender of a communicative signal uses his own intention recognition system to make a prediction of the intention recognition performed by the receiver. This finding supports the notion that our communicative abilities are distinct from both sensorimotor processes and language abilities.

  2. Mechanisms that determine the internal environment of the developing brain: a transcriptomic, functional and ultrastructural approach.

    Science.gov (United States)

    Liddelow, Shane A; Dziegielewska, Katarzyna M; Ek, C Joakim; Habgood, Mark D; Bauer, Hannelore; Bauer, Hans-Christian; Lindsay, Helen; Wakefield, Matthew J; Strazielle, Nathalie; Kratzer, Ingrid; Møllgård, Kjeld; Ghersi-Egea, Jean-François; Saunders, Norman R

    2013-01-01

    We provide comprehensive identification of embryonic (E15) and adult rat lateral ventricular choroid plexus transcriptome, with focus on junction-associated proteins, ionic influx transporters and channels. Additionally, these data are related to new structural and previously published permeability studies. Results reveal that most genes associated with intercellular junctions are expressed at similar levels at both ages. In total, 32 molecules known to be associated with brain barrier interfaces were identified. Nine claudins showed unaltered expression, while two claudins (6 and 8) were expressed at higher levels in the embryo. Expression levels for most cytoplasmic/regulatory adaptors (10 of 12) were similar at the two ages. A few junctional genes displayed lower expression in embryos, including 5 claudins, occludin and one junctional adhesion molecule. Three gap junction genes were enriched in the embryo. The functional effectiveness of these junctions was assessed using blood-delivered water-soluble tracers at both the light and electron microscopic level: embryo and adult junctions halted movement of both 286Da and 3kDa molecules into the cerebrospinal fluid (CSF). The molecular identities of many ion channel and transporter genes previously reported as important for CSF formation and secretion in the adult were demonstrated in the embryonic choroid plexus (and validated with immunohistochemistry of protein products), but with some major age-related differences in expression. In addition, a large number of previously unidentified ion channel and transporter genes were identified for the first time in plexus epithelium. These results, in addition to data obtained from electron microscopical and physiological permeability experiments in immature brains, indicate that exchange between blood and CSF is mainly transcellular, as well-formed tight junctions restrict movement of small water-soluble molecules from early in development. These data strongly indicate the

  3. Effect of Brain Tumor Presence During Radiation on Tissue Toxicity: Transcriptomic and Metabolic Changes.

    Science.gov (United States)

    Zawaski, Janice A; Sabek, Omaima M; Voicu, Horatiu; Eastwood Leung, Hon-Chiu; Gaber, M Waleed

    2017-11-15

    Radiation therapy (RT) causes functional and transcriptomic changes in the brain; however, most studies have been carried out in normal rodent brains. Here, the long-term effect of irradiation and tumor presence during radiation was investigated. Male Wistar rats ∼7 weeks old were divided into 3 groups: sham implant, RT+sham implant, and RT+tumor implant (C6 glioma). Hypofractionated irradiation (8 or 6 Gy/day for 5 days) was localized to a 1-cm strip of cranium starting 5 days after implantation, resulting in complete tumor regression and prolonged survival. Biopsy of tissue was performed in the implant area 65 days after implantation. RNA was hybridized to GeneChip Rat Exon 1.0 ST array. Data were analyzed using significant analysis of microarrays and ingenuity pathway analysis. 1 H magnetic resonance spectroscopy ( 1 H-MRS) imaging was performed in the implantation site 65 to 70 days after implantation using a 9.4 T Biospec magnetic resonance imaging scanner with a quadrature rat brain array. Immunohistochemical staining for astrogliosis, HMG-CoA synthase 2, γ-aminobutyric acid (GABA) and taurine was performed at ∼65 days after implantation. Eighty-four genes had a false discovery rate <3.5%. We compared RT+tumor implant with RT+sham implant animals. The tumor presence affected networks associated with cancer/cell morphology/tissue morphology. 1 H-MRS showed significant reduction in taurine levels (P<.04) at the implantation site in both groups. However, the RT+tumor group also showed significant increase in levels of neurotransmitter GABA (P=.02). Hippocampal taurine levels were only significantly reduced in the RT+tumor group (P=.03). HMG-CoA synthase 2, GABA and taurine levels were confirmed using staining. Glial fibrillary acidic protein staining demonstrated a significant increase in inflammation that was heightened in the RT+tumor group. Our data indicate that tumor presence during radiation significantly affects long-term functional

  4. Major differences between human atopic dermatitis and murine models, as determined by using global transcriptomic profiling

    DEFF Research Database (Denmark)

    Ewald, David A.; Noda, Shinji; Oliva, Margeaux

    2017-01-01

    , and a comparison of these models with the human AD transcriptomic fingerprint is lacking. Objective We sought to evaluate the transcriptomic profiles of 6 common murine models and determine how they relate to human AD skin. Methods Transcriptomic profiling was performed by using microarrays and quantitative RT......-PCR on biopsy specimens from NC/Nga, flaky tail, Flg-mutated, ovalbumin-challenged, oxazolone-challenged, and IL-23–injected mice. Gene expression data of patients with AD, psoriasis, and contact dermatitis were obtained from previous patient cohorts. Criteria of a fold change of 2 or greater and a false...... discovery rate of 0.05 or less were used for gene arrays. Results IL-23–injected, NC/Nga, and oxazolone-challenged mice show the largest homology with our human meta-analysis–derived AD transcriptome (37%, 18%, 17%, respectively). Similar to human AD, robust TH1, TH2, and also TH17 activation are seen in IL...

  5. High-protein and high-carbohydrate breakfasts differentially change the transcriptome of human blood cells

    NARCIS (Netherlands)

    Erk, M.J. van; Blom, W.A.M.; Ommen, B. van; Hendriks, H.F.J.

    2006-01-01

    Background: Application of transcriptomics technology in human nutrition intervention studies would allow for genome-wide screening of the effects of specific diets or nutrients and result in biomarker profiles. Objective: The aim was to evaluate the potential of gene expression profiling in blood

  6. Brain Evolution and Human Neuropsychology: The Inferential Brain Hypothesis

    Science.gov (United States)

    Koscik, Timothy R.; Tranel, Daniel

    2013-01-01

    Collaboration between human neuropsychology and comparative neuroscience has generated invaluable contributions to our understanding of human brain evolution and function. Further cross-talk between these disciplines has the potential to continue to revolutionize these fields. Modern neuroimaging methods could be applied in a comparative context, yielding exciting new data with the potential of providing insight into brain evolution. Conversely, incorporating an evolutionary base into the theoretical perspectives from which we approach human neuropsychology could lead to novel hypotheses and testable predictions. In the spirit of these objectives, we present here a new theoretical proposal, the Inferential Brain Hypothesis, whereby the human brain is thought to be characterized by a shift from perceptual processing to inferential computation, particularly within the social realm. This shift is believed to be a driving force for the evolution of the large human cortex. PMID:22459075

  7. Comparative Transcriptomic Profiling and Gene Expression for Myxomatous Mitral Valve Disease in the Dog and Human

    Directory of Open Access Journals (Sweden)

    Greg R. Markby

    2017-07-01

    Full Text Available Myxomatous mitral valve disease is the single most important mitral valve disease in both dogs and humans. In the case of the dog it is ubiquitous, such that all aged dogs will have some evidence of the disease, and for humans it is known as Barlow’s disease and affects up to 3% of the population, with an expected increase in prevalence as the population ages. Disease in the two species show many similarities and while both have the classic myxomatous degeneration only in humans is there extensive fibrosis. This dual pathology of the human disease markedly affects the valve transcriptome and the difference between the dog and human is dominated by changes in genes associated with fibrosis. This review will briefly examine the comparative valve pathology and then, in more detail, the transcriptomic profiling and gene expression reported so far for both species.

  8. Lipid transport and human brain development.

    Science.gov (United States)

    Betsholtz, Christer

    2015-07-01

    How the human brain rapidly builds up its lipid content during brain growth and maintains its lipids in adulthood has remained elusive. Two new studies show that inactivating mutations in MFSD2A, known to be expressed specifically at the blood-brain barrier, lead to microcephaly, thereby offering a simple and surprising solution to an old enigma.

  9. Transcriptomic responses in mouse brain exposed to chronic excess of the neurotransmitter glutamate

    Directory of Open Access Journals (Sweden)

    Pal Ranu

    2010-06-01

    Full Text Available Abstract Background Increases during aging in extracellular levels of glutamate (Glu, the major excitatory neurotransmitter in the brain, may be linked to chronic neurodegenerative diseases. Little is known about the molecular responses of neurons to chronic, moderate increases in Glu levels. Genome-wide gene expression in brain hippocampus was examined in a unique transgenic (Tg mouse model that exhibits moderate Glu hyperactivity throughout the lifespan, the neuronal Glutamate dehydrogenase (Glud1 mouse, and littermate 9 month-old wild type mice. Results Integrated bioinformatic analyses on transcriptomic data were used to identify bio-functions, pathways and gene networks underlying neuronal responses to increased Glu synaptic release. Bio-functions and pathways up-regulated in Tg mice were those associated with oxidative stress, cell injury, inflammation, nervous system development, neuronal growth, and synaptic transmission. Increased gene expression in these functions and pathways indicated apparent compensatory responses offering protection against stress, promoting growth of neuronal processes (neurites and re-establishment of synapses. The transcription of a key gene in the neurite growth network, the kinase Ptk2b, was significantly up-regulated in Tg mice as was the activated (phosphorylated form of the protein. In addition to genes related to neurite growth and synaptic development, those associated with neuronal vesicle trafficking in the Huntington's disease signalling pathway, were also up-regulated. Conclusions This is the first study attempting to define neuronal gene expression patterns in response to chronic, endogenous Glu hyperactivity at brain synapses. The patterns observed were characterized by a combination of responses to stress and stimulation of nerve growth, intracellular transport and recovery.

  10. Convergent transcriptional specializations in the brains of humans and song-learning birds

    DEFF Research Database (Denmark)

    Pfenning, Andreas R.; Hara, Erina; Whitney, Osceola

    2014-01-01

    Song-learning birds and humans share independently evolved similarities in brain pathways for vocal learning that are essential for song and speech and are not found in most other species. Comparisons of brain transcriptomes of song-learning birds and humans relative to vocal nonlearners identified...... convergent gene expression specializations in specific song and speech brain regions of avian vocal learners and humans. The strongest shared profiles relate bird motor and striatal song-learning nuclei, respectively, with human laryngeal motor cortex and parts of the striatum that control speech production...... and learning. Most of the associated genes function in motor control and brain connectivity. Thus, convergent behavior and neural connectivity for a complex trait are associated with convergent specialized expression of multiple genes....

  11. Transcriptome analyses of sex differential gene expression in brains of rare minnow (Gobiocypris rarus and effects of tributyltin exposure

    Directory of Open Access Journals (Sweden)

    Ji-liang Zhang

    2018-06-01

    Full Text Available RNA-sequencing was used to identify sex-biased gene expression in brains of rare minnow (Gobiocypris rarus by comparing transcriptomic profiles between females and males. Furthermore, transcriptomic responses to 10 ng/L tributyltin (TBT in both male and female brains were also investigated to understand whether TBT affects the identified sex-biased genes. Differentially expressed genes (DEGs were identified using the IDEG6 web tool. In this article, we presented male- and female-biased DEGs, and up-regulated and down-regulated DEGs after TBT exposure. The raw reads data supporting the present analyses has been deposited in NCBI Sequence Read Archive (SRA, http://www.ncbi.nlm.nih.gov/Traces/sra with accession number PRJNA376634. The data presented in this article are related to the research article entitled “Transcriptomic analyses of sexual dimorphism of rare minnow (G. rarus brains and effects of tributyltin exposure” (doi: 10.1016/j.ecoenv.2018.02.049.

  12. Transcriptomic analyses reveal novel genes with sexually dimorphic expression in the zebrafish gonad and brain.

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    Rajini Sreenivasan

    Full Text Available BACKGROUND: Our knowledge on zebrafish reproduction is very limited. We generated a gonad-derived cDNA microarray from zebrafish and used it to analyze large-scale gene expression profiles in adult gonads and other organs. METHODOLOGY/PRINCIPAL FINDINGS: We have identified 116638 gonad-derived zebrafish expressed sequence tags (ESTs, 21% of which were isolated in our lab. Following in silico normalization, we constructed a gonad-derived microarray comprising 6370 unique, full-length cDNAs from differentiating and adult gonads. Labeled targets from adult gonad, brain, kidney and 'rest-of-body' from both sexes were hybridized onto the microarray. Our analyses revealed 1366, 881 and 656 differentially expressed transcripts (34.7% novel that showed highest expression in ovary, testis and both gonads respectively. Hierarchical clustering showed correlation of the two gonadal transcriptomes and their similarities to those of the brains. In addition, we have identified 276 genes showing sexually dimorphic expression both between the brains and between the gonads. By in situ hybridization, we showed that the gonadal transcripts with the strongest array signal intensities were germline-expressed. We found that five members of the GTP-binding septin gene family, from which only one member (septin 4 has previously been implicated in reproduction in mice, were all strongly expressed in the gonads. CONCLUSIONS/SIGNIFICANCE: We have generated a gonad-derived zebrafish cDNA microarray and demonstrated its usefulness in identifying genes with sexually dimorphic co-expression in both the gonads and the brains. We have also provided the first evidence of large-scale differential gene expression between female and male brains of a teleost. Our microarray would be useful for studying gonad development, differentiation and function not only in zebrafish but also in related teleosts via cross-species hybridizations. Since several genes have been shown to play similar

  13. Brain Activity and Human Unilateral Chewing

    Science.gov (United States)

    Quintero, A.; Ichesco, E.; Myers, C.; Schutt, R.; Gerstner, G.E.

    2012-01-01

    Brain mechanisms underlying mastication have been studied in non-human mammals but less so in humans. We used functional magnetic resonance imaging (fMRI) to evaluate brain activity in humans during gum chewing. Chewing was associated with activations in the cerebellum, motor cortex and caudate, cingulate, and brainstem. We also divided the 25-second chew-blocks into 5 segments of equal 5-second durations and evaluated activations within and between each of the 5 segments. This analysis revealed activation clusters unique to the initial segment, which may indicate brain regions involved with initiating chewing. Several clusters were uniquely activated during the last segment as well, which may represent brain regions involved with anticipatory or motor events associated with the end of the chew-block. In conclusion, this study provided evidence for specific brain areas associated with chewing in humans and demonstrated that brain activation patterns may dynamically change over the course of chewing sequences. PMID:23103631

  14. The predictive nature of transcript expression levels on protein expression in adult human brain.

    Science.gov (United States)

    Bauernfeind, Amy L; Babbitt, Courtney C

    2017-04-24

    Next generation sequencing methods are the gold standard for evaluating expression of the transcriptome. When determining the biological implications of such studies, the assumption is often made that transcript expression levels correspond to protein levels in a meaningful way. However, the strength of the overall correlation between transcript and protein expression is inconsistent, particularly in brain samples. Following high-throughput transcriptomic (RNA-Seq) and proteomic (liquid chromatography coupled with tandem mass spectrometry) analyses of adult human brain samples, we compared the correlation in the expression of transcripts and proteins that support various biological processes, molecular functions, and that are located in different areas of the cell. Although most categories of transcripts have extremely weak predictive value for the expression of their associated proteins (R 2 values of < 10%), transcripts coding for protein kinases and membrane-associated proteins, including those that are part of receptors or ion transporters, are among those that are most predictive of downstream protein expression levels. The predictive value of transcript expression for corresponding proteins is variable in human brain samples, reflecting the complex regulation of protein expression. However, we found that transcriptomic analyses are appropriate for assessing the expression levels of certain classes of proteins, including those that modify proteins, such as kinases and phosphatases, regulate metabolic and synaptic activity, or are associated with a cellular membrane. These findings can be used to guide the interpretation of gene expression results from primate brain samples.

  15. Geographical, environmental and pathophysiological influences on the human blood transcriptome.

    Science.gov (United States)

    Tabassum, Rubina; Nath, Artika; Preininger, Marcela; Gibson, Greg

    2013-12-01

    Gene expression variation provides a read-out of both genetic and environmental influences on gene activity. Geographical, genomic and sociogenomic studies have highlighted how life circumstances of an individual modify the expression of hundreds and in some cases thousands of genes in a co-ordinated manner. This review places such results in the context of a conserved set of 90 transcripts known as Blood Informative Transcripts (BIT) that capture the major conserved components of variation in the peripheral blood transcriptome. Pathophysiological states are also shown to associate with the perturbation of transcript abundance along the major axes. Discussion of false negative rates leads us to argue that simple significance thresholds provide a biased perspective on assessment of differential expression that may cloud the interpretation of studies with small sample sizes.

  16. Brain anatomical networks in early human brain development.

    Science.gov (United States)

    Fan, Yong; Shi, Feng; Smith, Jeffrey Keith; Lin, Weili; Gilmore, John H; Shen, Dinggang

    2011-02-01

    Recent neuroimaging studies have demonstrated that human brain networks have economic small-world topology and modular organization, enabling efficient information transfer among brain regions. However, it remains largely unknown how the small-world topology and modular organization of human brain networks emerge and develop. Using longitudinal MRI data of 28 healthy pediatric subjects, collected at their ages of 1 month, 1 year, and 2 years, we analyzed development patterns of brain anatomical networks derived from morphological correlations of brain regional volumes. The results show that the brain network of 1-month-olds has the characteristically economic small-world topology and nonrandom modular organization. The network's cost efficiency increases with the brain development to 1 year and 2 years, so does the modularity, providing supportive evidence for the hypothesis that the small-world topology and the modular organization of brain networks are established during early brain development to support rapid synchronization and information transfer with minimal rewiring cost, as well as to balance between local processing and global integration of information. Copyright © 2010. Published by Elsevier Inc.

  17. Rate of evolution in brain-expressed genes in humans and other primates.

    Directory of Open Access Journals (Sweden)

    Hurng-Yi Wang

    2007-02-01

    Full Text Available Brain-expressed genes are known to evolve slowly in mammals. Nevertheless, since brains of higher primates have evolved rapidly, one might expect acceleration in DNA sequence evolution in their brain-expressed genes. In this study, we carried out full-length cDNA sequencing on the brain transcriptome of an Old World monkey (OWM and then conducted three-way comparisons among (i mouse, OWM, and human, and (ii OWM, chimpanzee, and human. Although brain-expressed genes indeed appear to evolve more rapidly in species with more advanced brains (apes > OWM > mouse, a similar lineage effect is observable for most other genes. The broad inclusion of genes in the reference set to represent the genomic average is therefore critical to this type of analysis. Calibrated against the genomic average, the rate of evolution among brain-expressed genes is probably lower (or at most equal in humans than in chimpanzee and OWM. Interestingly, the trend of slow evolution in coding sequence is no less pronounced among brain-specific genes, vis-à-vis brain-expressed genes in general. The human brain may thus differ from those of our close relatives in two opposite directions: (i faster evolution in gene expression, and (ii a likely slowdown in the evolution of protein sequences. Possible explanations and hypotheses are discussed.

  18. Computational Intelligence in a Human Brain Model

    Directory of Open Access Journals (Sweden)

    Viorel Gaftea

    2016-06-01

    Full Text Available This paper focuses on the current trends in brain research domain and the current stage of development of research for software and hardware solutions, communication capabilities between: human beings and machines, new technologies, nano-science and Internet of Things (IoT devices. The proposed model for Human Brain assumes main similitude between human intelligence and the chess game thinking process. Tactical & strategic reasoning and the need to follow the rules of the chess game, all are very similar with the activities of the human brain. The main objective for a living being and the chess game player are the same: securing a position, surviving and eliminating the adversaries. The brain resolves these goals, and more, the being movement, actions and speech are sustained by the vital five senses and equilibrium. The chess game strategy helps us understand the human brain better and easier replicate in the proposed ‘Software and Hardware’ SAH Model.

  19. Brain transcriptomes of harbor seals demonstrate gene expression patterns of animals undergoing a metabolic disease and a viral infection

    Directory of Open Access Journals (Sweden)

    Stephanie M. Rosales

    2016-12-01

    Full Text Available Diseases of marine mammals can be difficult to diagnose because of their life history and protected status. Stranded marine mammals have been a particularly useful resource to discover and comprehend the diseases that plague these top predators. Additionally, advancements in high-throughput sequencing (HTS has contributed to the discovery of novel pathogens in marine mammals. In this study, we use a combination of HTS and stranded harbor seals (Phoca vitulina to better understand a known and unknown brain disease. To do this, we used transcriptomics to evaluate brain tissues from seven neonatal harbor seals that expired from an unknown cause of death (UCD and compared them to four neonatal harbor seals that had confirmed phocine herpesvirus (PhV-1 infections in the brain. Comparing the two disease states we found that UCD animals showed a significant abundance of fatty acid metabolic transcripts in their brain tissue, thus we speculate that a fatty acid metabolic dysregulation contributed to the death of these animals. Furthermore, we were able to describe the response of four young harbor seals with PhV-1 infections in the brain. PhV-1 infected animals showed a significant ability to mount an innate and adaptive immune response, especially to combat viral infections. Our data also suggests that PhV-1 can hijack host pathways for DNA packaging and exocytosis. This is the first study to use transcriptomics in marine mammals to understand host and viral interactions and assess the death of stranded marine mammals with an unknown disease. Furthermore, we show the value of applying transcriptomics on stranded marine mammals for disease characterization.

  20. Male microchimerism in the human female brain.

    Directory of Open Access Journals (Sweden)

    William F N Chan

    Full Text Available In humans, naturally acquired microchimerism has been observed in many tissues and organs. Fetal microchimerism, however, has not been investigated in the human brain. Microchimerism of fetal as well as maternal origin has recently been reported in the mouse brain. In this study, we quantified male DNA in the human female brain as a marker for microchimerism of fetal origin (i.e. acquisition of male DNA by a woman while bearing a male fetus. Targeting the Y-chromosome-specific DYS14 gene, we performed real-time quantitative PCR in autopsied brain from women without clinical or pathologic evidence of neurologic disease (n=26, or women who had Alzheimer's disease (n=33. We report that 63% of the females (37 of 59 tested harbored male microchimerism in the brain. Male microchimerism was present in multiple brain regions. Results also suggested lower prevalence (p=0.03 and concentration (p=0.06 of male microchimerism in the brains of women with Alzheimer's disease than the brains of women without neurologic disease. In conclusion, male microchimerism is frequent and widely distributed in the human female brain.

  1. A SAGE based approach to human glomerular endothelium : defining the transcriptome, finding a novel molecule and highlighting endothelial diversity

    NARCIS (Netherlands)

    Sengoelge, Guerkan; Winnicki, Wolfgang; Kupczok, Anne; von Haeseler, Arndt; Schuster, Michael; Pfaller, Walter; Jennings, Paul; Weltermann, Ansgar; Blake, Sophia; Sunder-Plassmann, Gere

    2014-01-01

    BACKGROUND: Large scale transcript analysis of human glomerular microvascular endothelial cells (HGMEC) has never been accomplished. We designed this study to define the transcriptome of HGMEC and facilitate a better characterization of these endothelial cells with unique features. Serial analysis

  2. Transcriptome adaptation of group B Streptococcus to growth in human amniotic fluid.

    Directory of Open Access Journals (Sweden)

    Izabela Sitkiewicz

    Full Text Available BACKGROUND: Streptococcus agalactiae (group B Streptococcus is a bacterial pathogen that causes severe intrauterine infections leading to fetal morbidity and mortality. The pathogenesis of GBS infection in this environment is poorly understood, in part because we lack a detailed understanding of the adaptation of this pathogen to growth in amniotic fluid. To address this knowledge deficit, we characterized the transcriptome of GBS grown in human amniotic fluid (AF and compared it with the transcriptome in rich laboratory medium. METHODS: GBS was grown in Todd Hewitt-yeast extract medium and human AF. Bacteria were collected at mid-logarithmic, late-logarithmic and stationary growth phase. We performed global expression microarray analysis using a custom-made Affymetrix GeneChip. The normalized hybridization values derived from three biological replicates at each growth point were obtained. AF/THY transcript ratios representing greater than a 2-fold change and P-value exceeding 0.05 were considered to be statistically significant. PRINCIPAL FINDINGS: We have discovered that GBS significantly remodels its transcriptome in response to exposure to human amniotic fluid. GBS grew rapidly in human AF and did not exhibit a global stress response. The majority of changes in GBS transcripts in AF compared to THY medium were related to genes mediating metabolism of amino acids, carbohydrates, and nucleotides. The majority of the observed changes in transcripts affects genes involved in basic bacterial metabolism and is connected to AF composition and nutritional requirements of the bacterium. Importantly, the response to growth in human AF included significant changes in transcripts of multiple virulence genes such as adhesins, capsule, and hemolysin and IL-8 proteinase what might have consequences for the outcome of host-pathogen interactions. CONCLUSIONS/SIGNIFICANCE: Our work provides extensive new information about how the transcriptome of GBS responds

  3. Impact of traumatic brain injury on sleep structure, electrocorticographic activity and transcriptome in mice.

    Science.gov (United States)

    Sabir, Meriem; Gaudreault, Pierre-Olivier; Freyburger, Marlène; Massart, Renaud; Blanchet-Cohen, Alexis; Jaber, Manar; Gosselin, Nadia; Mongrain, Valérie

    2015-07-01

    findings reveal alterations in spectral signature across all vigilance states in the first days after mTBI, and show that sleep loss post-mTBI reprograms the transcriptome in a brain area-specific manner and in a way that could be deleterious to brain recovery. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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    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

  5. Protein phosphorylation systems in postmortem human brain

    International Nuclear Information System (INIS)

    Walaas, S.I.; Perdahl-Wallace, E.; Winblad, B.; Greengard, P.

    1989-01-01

    Protein phosphorylation systems regulated by cyclic adenosine 3',5'-monophosphate (cyclic AMP), or calcium in conjunction with calmodulin or phospholipid/diacylglycerol, have been studied by phosphorylation in vitro of particulate and soluble fractions from human postmortem brain samples. One-dimensional or two-dimensional gel electrophoretic protein separations were used for analysis. Protein phosphorylation catalyzed by cyclic AMP-dependent protein kinase was found to be highly active in both particulate and soluble preparations throughout the human CNS, with groups of both widely distributed and region-specific substrates being observed in different brain nuclei. Dopamine-innervated parts of the basal ganglia and cerebral cortex contained the phosphoproteins previously observed in rodent basal ganglia. In contrast, calcium/phospholipid-dependent and calcium/calmodulin-dependent protein phosphorylation systems were less prominent in human postmortem brain than in rodent brain, and only a few widely distributed substrates for these protein kinases were found. Protein staining indicated that postmortem proteolysis, particularly of high-molecular-mass proteins, was prominent in deeply located, subcortical regions in the human brain. Our results indicate that it is feasible to use human postmortem brain samples, when obtained under carefully controlled conditions, for qualitative studies on brain protein phosphorylation. Such studies should be of value in studies on human neurological and/or psychiatric disorders

  6. Transcranial magnetic stimulation and the human brain

    Science.gov (United States)

    Hallett, Mark

    2000-07-01

    Transcranial magnetic stimulation (TMS) is rapidly developing as a powerful, non-invasive tool for studying the human brain. A pulsed magnetic field creates current flow in the brain and can temporarily excite or inhibit specific areas. TMS of motor cortex can produce a muscle twitch or block movement; TMS of occipital cortex can produce visual phosphenes or scotomas. TMS can also alter the functioning of the brain beyond the time of stimulation, offering potential for therapy.

  7. Analysis of the Macaca mulatta transcriptome and the sequence divergence between Macaca and human.

    Science.gov (United States)

    Magness, Charles L; Fellin, P Campion; Thomas, Matthew J; Korth, Marcus J; Agy, Michael B; Proll, Sean C; Fitzgibbon, Matthew; Scherer, Christina A; Miner, Douglas G; Katze, Michael G; Iadonato, Shawn P

    2005-01-01

    We report the initial sequencing and comparative analysis of the Macaca mulatta transcriptome. Cloned sequences from 11 tissues, nine animals, and three species (M. mulatta, M. fascicularis, and M. nemestrina) were sampled, resulting in the generation of 48,642 sequence reads. These data represent an initial sampling of the putative rhesus orthologs for 6,216 human genes. Mean nucleotide diversity within M. mulatta and sequence divergence among M. fascicularis, M. nemestrina, and M. mulatta are also reported.

  8. An introduction to human brain anatomy

    NARCIS (Netherlands)

    Forstmann, B.U.; Keuken, M.C.; Alkemade, A.; Forstmann, B.U.; Wagenmakers, E.-J.

    2015-01-01

    This tutorial chapter provides an overview of the human brain anatomy. Knowledge of brain anatomy is fundamental to our understanding of cognitive processes in health and disease; moreover, anatomical constraints are vital for neurocomputational models and can be important for psychological

  9. Transcriptomic analysis of the effects of a fish oil enriched diet on murine brains.

    Directory of Open Access Journals (Sweden)

    Rasha Hammamieh

    Full Text Available The health benefits of fish oil enriched with high omega-3 polyunsaturated fatty acids (n-3 PUFA are widely documented. Fish oil as dietary supplements, however, show moderate clinical efficacy, highlighting an immediate scope of systematic in vitro feedback. Our transcriptomic study was designed to investigate the genomic shift of murine brains fed on fish oil enriched diets. A customized fish oil enriched diet (FD and standard lab diet (SD were separately administered to two randomly chosen populations of C57BL/6J mice from their weaning age until late adolescence. Statistical analysis mined 1,142 genes of interest (GOI differentially altered in the hemibrains collected from the FD- and SD-fed mice at the age of five months. The majority of identified GOI (∼ 40% encodes proteins located in the plasma membrane, suggesting that fish oil primarily facilitated the membrane-oriented biofunctions. FD potentially augmented the nervous system's development and functions by selectively stimulating the Src-mediated calcium-induced growth cascade and the downstream PI3K-AKT-PKC pathways. FD reduced the amyloidal burden, attenuated oxidative stress, and assisted in somatostatin activation-the signatures of attenuation of Alzheimer's disease, Parkinson's disease, and affective disorder. FD induced elevation of FKBP5 and suppression of BDNF, which are often linked with the improvement of anxiety disorder, depression, and post-traumatic stress disorder. Hence we anticipate efficacy of FD in treating illnesses such as depression that are typically triggered by the hypoactivities of dopaminergic, adrenergic, cholinergic, and GABAergic networks. Contrastingly, FD's efficacy could be compromised in treating illnesses such as bipolar disorder and schizophrenia, which are triggered by hyperactivities of the same set of neuromodulators. A more comprehensive investigation is recommended to elucidate the implications of fish oil on disease pathomechanisms, and the

  10. Tolerances of the human brain to concussion.

    Science.gov (United States)

    1971-03-01

    The report reviews the pertinent literature and adds additional evidence indicating that the human brain may be able to tolerate head impact forces in the range of 300 to 400 g's without evidence of concussion or other detectable neurologic sequelae,...

  11. Transcriptome tomography for brain analysis in the web-accessible anatomical space.

    Directory of Open Access Journals (Sweden)

    Yuko Okamura-Oho

    Full Text Available Increased information on the encoded mammalian genome is expected to facilitate an integrated understanding of complex anatomical structure and function based on the knowledge of gene products. Determination of gene expression-anatomy associations is crucial for this understanding. To elicit the association in the three-dimensional (3D space, we introduce a novel technique for comprehensive mapping of endogenous gene expression into a web-accessible standard space: Transcriptome Tomography. The technique is based on conjugation of sequential tissue-block sectioning, all fractions of which are used for molecular measurements of gene expression densities, and the block- face imaging, which are used for 3D reconstruction of the fractions. To generate a 3D map, tissues are serially sectioned in each of three orthogonal planes and the expression density data are mapped using a tomographic technique. This rapid and unbiased mapping technique using a relatively small number of original data points allows researchers to create their own expression maps in the broad anatomical context of the space. In the first instance we generated a dataset of 36,000 maps, reconstructed from data of 61 fractions measured with microarray, covering the whole mouse brain (ViBrism: http://vibrism.riken.jp/3dviewer/ex/index.html in one month. After computational estimation of the mapping accuracy we validated the dataset against existing data with respect to the expression location and density. To demonstrate the relevance of the framework, we showed disease related expression of Huntington's disease gene and Bdnf. Our tomographic approach is applicable to analysis of any biological molecules derived from frozen tissues, organs and whole embryos, and the maps are spatially isotropic and well suited to the analysis in the standard space (e.g. Waxholm Space for brain-atlas databases. This will facilitate research creating and using open-standards for a molecular

  12. Ionising radiation and the developing human brain

    International Nuclear Information System (INIS)

    Schull, W.J.

    1991-01-01

    This article reviews the effects of radiation exposure of the developing human brain. Much of the evidence has come from the prenatally exposed in Hiroshima and Nagasaki. The effects on development age, mental retardation, head size, neuromuscular performance, intelligence tests, school performance and the occurrence of convulsions are discussed. Other topics covered include the biological nature of the damage to the brain, risk estimates in human and problems in radiation protection. (UK)

  13. Transcriptome profiling of human pre-implantation development.

    Directory of Open Access Journals (Sweden)

    Pu Zhang

    Full Text Available BACKGROUND: Preimplantation development is a crucial step in early human development. However, the molecular basis of human preimplantation development is not well known. METHODOLOGY: By applying microarray on 397 human oocytes and embryos at six developmental stages, we studied the transcription dynamics during human preimplantation development. PRINCIPAL FINDINGS: We found that the preimplantation development consisted of two main transitions: from metaphase-II oocyte to 4-cell embryo where mainly the maternal genes were expressed, and from 8-cell embryo to blastocyst with down-regulation of the maternal genes and up-regulation of embryonic genes. Human preimplantation development proved relatively autonomous. Genes predominantly expressed in oocytes and embryos are well conserved during evolution. SIGNIFICANCE: Our database and findings provide fundamental resources for understanding

  14. Characterization of the Transcriptome and Gene Expression of Brain Tissue in Sevenband Grouper (Hyporthodus septemfasciatus in Response to NNV Infection

    Directory of Open Access Journals (Sweden)

    Jong-Oh Kim

    2017-01-01

    Full Text Available Grouper is one of the favorite sea food resources in Southeast Asia. However, the outbreaks of the viral nervous necrosis (VNN disease due to nervous necrosis virus (NNV infection have caused mass mortality of grouper larvae. Many aqua-farms have suffered substantial financial loss due to the occurrence of VNN. To better understand the infection mechanism of NNV, we performed the transcriptome analysis of sevenband grouper brain tissue, the main target of NNV infection. After artificial NNV challenge, transcriptome of brain tissues of sevenband grouper was subjected to next generation sequencing (NGS using an Illumina Hi-seq 2500 system. Both mRNAs from pooled samples of mock and NNV-infected sevenband grouper brains were sequenced. Clean reads of mock and NNV-infected samples were de novo assembled and obtained 104,348 unigenes. In addition, 628 differentially expressed genes (DEGs in response to NNV infection were identified. This result could provide critical information not only for the identification of genes involved in NNV infection, but for the understanding of the response of sevenband groupers to NNV infection.

  15. Simulated night shift work induces circadian misalignment of the human peripheral blood mononuclear cell transcriptome.

    Science.gov (United States)

    Kervezee, Laura; Cuesta, Marc; Cermakian, Nicolas; Boivin, Diane B

    2018-05-22

    Misalignment of the endogenous circadian timing system leads to disruption of physiological rhythms and may contribute to the development of the deleterious health effects associated with night shift work. However, the molecular underpinnings remain to be elucidated. Here, we investigated the effect of a 4-day simulated night shift work protocol on the circadian regulation of the human transcriptome. Repeated blood samples were collected over two 24-hour measurement periods from eight healthy subjects under highly controlled laboratory conditions before and 4 days after a 10-hour delay of their habitual sleep period. RNA was extracted from peripheral blood mononuclear cells to obtain transcriptomic data. Cosinor analysis revealed a marked reduction of significantly rhythmic transcripts in the night shift condition compared with baseline at group and individual levels. Subsequent analysis using a mixed-effects model selection approach indicated that this decrease is mainly due to dampened rhythms rather than to a complete loss of rhythmicity: 73% of transcripts rhythmically expressed at baseline remained rhythmic during the night shift condition with a similar phase relative to habitual bedtimes, but with lower amplitudes. Functional analysis revealed that key biological processes are affected by the night shift protocol, most notably the natural killer cell-mediated immune response and Jun/AP1 and STAT pathways. These results show that 4 days of simulated night shifts leads to a loss in temporal coordination between the human circadian transcriptome and the external environment and impacts biological processes related to the adverse health effects associated to night shift work.

  16. Genome-wide RNA-seq analysis of human and mouse platelet transcriptomes

    Science.gov (United States)

    Rowley, Jesse W.; Oler, Andrew J.; Tolley, Neal D.; Hunter, Benjamin N.; Low, Elizabeth N.; Nix, David A.; Yost, Christian C.; Zimmerman, Guy A.

    2011-01-01

    Inbred mice are a useful tool for studying the in vivo functions of platelets. Nonetheless, the mRNA signature of mouse platelets is not known. Here, we use paired-end next-generation RNA sequencing (RNA-seq) to characterize the polyadenylated transcriptomes of human and mouse platelets. We report that RNA-seq provides unprecedented resolution of mRNAs that are expressed across the entire human and mouse genomes. Transcript expression and abundance are often conserved between the 2 species. Several mRNAs, however, are differentially expressed in human and mouse platelets. Moreover, previously described functional disparities between mouse and human platelets are reflected in differences at the transcript level, including protease activated receptor-1, protease activated receptor-3, platelet activating factor receptor, and factor V. This suggests that RNA-seq is a useful tool for predicting differences in platelet function between mice and humans. Our next-generation sequencing analysis provides new insights into the human and murine platelet transcriptomes. The sequencing dataset will be useful in the design of mouse models of hemostasis and a catalyst for discovery of new functions of platelets. Access to the dataset is found in the “Introduction.” PMID:21596849

  17. The evolution of modern human brain shape.

    Science.gov (United States)

    Neubauer, Simon; Hublin, Jean-Jacques; Gunz, Philipp

    2018-01-01

    Modern humans have large and globular brains that distinguish them from their extinct Homo relatives. The characteristic globularity develops during a prenatal and early postnatal period of rapid brain growth critical for neural wiring and cognitive development. However, it remains unknown when and how brain globularity evolved and how it relates to evolutionary brain size increase. On the basis of computed tomographic scans and geometric morphometric analyses, we analyzed endocranial casts of Homo sapiens fossils ( N = 20) from different time periods. Our data show that, 300,000 years ago, brain size in early H. sapiens already fell within the range of present-day humans. Brain shape, however, evolved gradually within the H. sapiens lineage, reaching present-day human variation between about 100,000 and 35,000 years ago. This process started only after other key features of craniofacial morphology appeared modern and paralleled the emergence of behavioral modernity as seen from the archeological record. Our findings are consistent with important genetic changes affecting early brain development within the H. sapiens lineage since the origin of the species and before the transition to the Later Stone Age and the Upper Paleolithic that mark full behavioral modernity.

  18. The evolution of modern human brain shape

    Science.gov (United States)

    Neubauer, Simon; Hublin, Jean-Jacques; Gunz, Philipp

    2018-01-01

    Modern humans have large and globular brains that distinguish them from their extinct Homo relatives. The characteristic globularity develops during a prenatal and early postnatal period of rapid brain growth critical for neural wiring and cognitive development. However, it remains unknown when and how brain globularity evolved and how it relates to evolutionary brain size increase. On the basis of computed tomographic scans and geometric morphometric analyses, we analyzed endocranial casts of Homo sapiens fossils (N = 20) from different time periods. Our data show that, 300,000 years ago, brain size in early H. sapiens already fell within the range of present-day humans. Brain shape, however, evolved gradually within the H. sapiens lineage, reaching present-day human variation between about 100,000 and 35,000 years ago. This process started only after other key features of craniofacial morphology appeared modern and paralleled the emergence of behavioral modernity as seen from the archeological record. Our findings are consistent with important genetic changes affecting early brain development within the H. sapiens lineage since the origin of the species and before the transition to the Later Stone Age and the Upper Paleolithic that mark full behavioral modernity. PMID:29376123

  19. Early Transcriptomic Response to LDL and oxLDL in Human Vascular Smooth Muscle Cells.

    Directory of Open Access Journals (Sweden)

    Salvador Damián-Zamacona

    Full Text Available Although nowadays it is well known that the human transcriptome can importantly vary according to external or environmental condition, the reflection of this concept when studying oxidative stress and its direct relationship with gene expression profiling during the process of atherogenesis has not been thoroughly achieved.The ability to analyze genome-wide gene expression through transcriptomics has shown that the genome responds dynamically to diverse stimuli. Here, we describe the transcriptome of human vascular smooth muscle cells (hVSMC stimulated by native and oxidized low-density lipoprotein (nLDL and oxLDL respectively, with the aim of assessing the early molecular changes that induce a response in this cell type resulting in a transcriptomic transformation. This expression has been demonstrated in atherosclerotic plaques in vivo and in vitro, particularly in the light of the oxidative modification hypothesis of atherosclerosis.Total RNA was isolated with TRIzol reagent (Life Technologies and quality estimated using an Agilent 2100 bioanalyzer. The transcriptome of hVSMC under different experimental conditions (1,5 and 24 hours for nLDL and oxLDL was obtained using the GeneChip Human Gene 1.0 ST (Affymetrix designed to measure gene expression of 28,869 well-annotated genes. A fixed fold-change cut-off corresponding to ± 2 was used to identify genes exhibiting the most significant variation and statistical significance (P< 0.05, and 8 genes validated by qPCR using Taqman probes.10 molecular processes were significantly affected in hVSMC: Apoptosis and cell cycle, extracellular matrix remodeling, DNA repair, cholesterol efflux, cGMP biosynthesis, endocytic mechanisms, calcium homeostasis, redox balance, membrane trafficking and finally, the immune response to inflammation. The evidence we present supporting the hypothesis for the involvement of oxidative modification of several processes and metabolic pathways in atherosclerosis is

  20. Data of methylome and transcriptome derived from human dilated cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Bong-Seok Jo

    2016-12-01

    Full Text Available Alterations in DNA methylation and gene expression have been implicated in the development of human dilated cardiomyopathy (DCM. Differentially methylated probes (DMPs and differentially expressed genes (DEGs were identified between the left ventricle (LV, a pathological locus for DCM and the right ventricle (RV, a proxy for normal hearts. The data in this DiB are for supporting our report entitled “Methylome analysis reveals alterations in DNA methylation in the regulatory regions of left ventricle development genes in human dilated cardiomyopathy” (Bong-Seok Jo, In-Uk Koh, Jae-Bum Bae, Ho-Yeong Yu, Eun-Seok Jeon, Hae-Young Lee, Jae-Joong Kim, Murim Choi, Sun Shim Choi, 2016 [1].

  1. Molecular Aging of Human Liver: An Epigenetic/Transcriptomic Signature.

    Science.gov (United States)

    Bacalini, Maria Giulia; Franceschi, Claudio; Gentilini, Davide; Ravaioli, Francesco; Zhou, Xiaoyuan; Remondini, Daniel; Pirazzini, Chiara; Giuliani, Cristina; Marasco, Elena; Gensous, Noémie; Di Blasio, Anna Maria; Ellis, Ewa; Gramignoli, Roberto; Castellani, Gastone; Capri, Miriam; Strom, Stephen; Nardini, Christine; Cescon, Matteo; Grazi, Gian Luca; Garagnani, Paolo

    2018-03-15

    The feasibility of liver transplantation from old healthy donors suggests that this organ is able to preserve its functionality during aging. To explore the biological basis of this phenomenon, we characterized the epigenetic profile of liver biopsies collected from 45 healthy liver donors ranging from 13 to 90 years old using the Infinium HumanMethylation450 BeadChip. The analysis indicates that a large remodeling in DNA methylation patterns occurs, with 8823 age-associated differentially methylated CpG probes. Notably, these age-associated changes tended to level off after the age of 60, as confirmed by Horvath's clock. Using stringent selection criteria we further identified a DNA methylation signature of aging liver including 75 genomic regions. We demonstrated that this signature is specific for liver compared to other tissues and that it is able to detect biological age-acceleration effects associated with obesity. Finally we combined DNA methylation measurements with available expression data. Although the intersection between the two omic characterizations was low, both approaches suggested a previously unappreciated role of epithelial-mesenchymal transition and Wnt signaling pathways in the aging of human liver.

  2. The Brain Prize 2014: complex human functions.

    Science.gov (United States)

    Grigaityte, Kristina; Iacoboni, Marco

    2014-11-01

    Giacomo Rizzolatti, Stanislas Dehaene, and Trevor Robbins were recently awarded the 2014 Grete Lundbeck European Brain Research Prize for their 'pioneering research on higher brain mechanisms underpinning such complex human functions as literacy, numeracy, motivated behavior and social cognition, and for their effort to understand cognitive and behavioral disorders'. Why was their work highlighted? Is there anything that links together these seemingly disparate lines of research? Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Lactate fuels the human brain during exercise

    DEFF Research Database (Denmark)

    Quistorff, Bjørn; Secher, Niels H; Van Lieshout, Johannes J

    2008-01-01

    The human brain releases a small amount of lactate at rest, and even an increase in arterial blood lactate during anesthesia does not provoke a net cerebral lactate uptake. However, during cerebral activation associated with exercise involving a marked increase in plasma lactate, the brain takes up......)] from a resting value of 6 to exercise, cerebral activation associated with mental activity, or exposure to a stressful situation. The CMR decrease is prevented with combined beta(1)- and beta(2)-adrenergic receptor...

  4. Rhinovirus infection induces distinct transcriptome profiles in polarized human macrophages.

    Science.gov (United States)

    Rajput, Charu; Walsh, Megan P; Eder, Breanna N; Metitiri, Ediri E; Popova, Antonia P; Hershenson, Marc B

    2018-05-01

    Infections with rhinovirus (RV) cause asthma exacerbations. Recent studies suggest that macrophages play a role in asthmatic airway inflammation and the innate immune response to RV infection. Macrophages exhibit phenotypes based on surface markers and gene expression. We hypothesized that macrophage polarization state alters gene expression in response to RV infection. Cells were derived from human peripheral blood derived monocytes. M1 and M2 polarization was carried out by using IFN-γ and IL-4, respectively, and RNA was extracted for Affymetrix Human Gene ST2.1 exon arrays. Selected genes were validated by quantitative (q)PCR. Treatment of nonactivated (M0) macrophages with IFN-γ and IL-4 induced the expression of 252 and 153 distinct genes, respectively, including previously-identified M1 and M2 markers. RV infection of M0 macrophages induced upregulation of 232 genes; pathway analysis showed significant overrepresentation of genes involved in IFN-α/β signaling and cytokine signaling in the immune system. RV infection induced differential expression of 195 distinct genes in M1-like macrophages but only seven distinct genes in M2-like-polarized cells. In a secondary analysis, comparison between M0-, RV-infected, and M1-like-polarized, RV-infected macrophages revealed differential expression of 227 genes including those associated with asthma and its exacerbation. qPCR demonstrated increased expression of CCL8, CXCL10, TNFSF10, TNFSF18, IL6, NOD2, and GSDMD and reduced expression of VNN1, AGO1, and AGO2. Together, these data show that, in contrast to M2-like-polarized macrophages, gene expression of M1-like macrophages is highly regulated by RV.

  5. Brain mechanisms underlying human communication

    NARCIS (Netherlands)

    Noordzij, Matthijs Leendert; Newman-Norlund, Sarah E.; de Ruiter, Jan Peter; Hagoort, Peter; Levinson, Stephen C.; Toni, Ivan

    2009-01-01

    Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the “mirror neurons system”). However, this view does not explain how these conventions could develop in the first place. Here we

  6. Brain mechanisms underlying human communication

    NARCIS (Netherlands)

    Noordzij, M.L.; Newman-Norlund, S.E.; Ruiter, J.P.A. de; Hagoort, P.; Levinson, S.C.; Toni, I.

    2009-01-01

    Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the "mirror neurons system"). However, this view does not explain how these conventions could develop in the first place. Here we

  7. Novel theory of the human brain: information-commutation basis of architecture and principles of operation

    Directory of Open Access Journals (Sweden)

    Bryukhovetskiy AS

    2015-02-01

    Full Text Available Andrey S Bryukhovetskiy Center for Biomedical Technologies, Federal Research and Clinical Center for Specialized Types of Medical Assistance and Medical Technologies of the Federal Medical Biological Agency, NeuroVita Clinic of Interventional and Restorative Neurology and Therapy, Moscow, Russia Abstract: Based on the methodology of the informational approach and research of the genome, proteome, and complete transcriptome profiles of different cells in the nervous tissue of the human brain, the author proposes a new theory of information-commutation organization and architecture of the human brain which is an alternative to the conventional systemic connective morphofunctional paradigm of the brain framework. Informational principles of brain operation are defined: the modular principle, holographic principle, principle of systematicity of vertical commutative connection and complexity of horizontal commutative connection, regulatory principle, relay principle, modulation principle, “illumination” principle, principle of personalized memory and intellect, and principle of low energy consumption. The author demonstrates that the cortex functions only as a switchboard and router of information, while information is processed outside the nervous tissue of the brain in the intermeningeal space. The main structural element of information-commutation in the brain is not the neuron, but information-commutation modules that are subdivided into receiver modules, transmitter modules, and subscriber modules, forming a vertical architecture of nervous tissue in the brain as information lines and information channels, and a horizontal architecture as central, intermediate, and peripheral information-commutation platforms. Information in information-commutation modules is transferred by means of the carriers that are characteristic to the specific information level from inductome to genome, transcriptome, proteome, metabolome, secretome, and magnetome

  8. The Human Pancreas Proteome Defined by Transcriptomics and Antibody-Based Profiling

    Science.gov (United States)

    Fagerberg, Linn; Hallström, Björn M.; Schwenk, Jochen M.; Uhlén, Mathias; Korsgren, Olle; Lindskog, Cecilia

    2014-01-01

    The pancreas is composed of both exocrine glands and intermingled endocrine cells to execute its diverse functions, including enzyme production for digestion of nutrients and hormone secretion for regulation of blood glucose levels. To define the molecular constituents with elevated expression in the human pancreas, we employed a genome-wide RNA sequencing analysis of the human transcriptome to identify genes with elevated expression in the human pancreas. This quantitative transcriptomics data was combined with immunohistochemistry-based protein profiling to allow mapping of the corresponding proteins to different compartments and specific cell types within the pancreas down to the single cell level. Analysis of whole pancreas identified 146 genes with elevated expression levels, of which 47 revealed a particular higher expression as compared to the other analyzed tissue types, thus termed pancreas enriched. Extended analysis of in vitro isolated endocrine islets identified an additional set of 42 genes with elevated expression in these specialized cells. Although only 0.7% of all genes showed an elevated expression level in the pancreas, this fraction of transcripts, in most cases encoding secreted proteins, constituted 68% of the total mRNA in pancreas. This demonstrates the extreme specialization of the pancreas for production of secreted proteins. Among the elevated expression profiles, several previously not described proteins were identified, both in endocrine cells (CFC1, FAM159B, RBPJL and RGS9) and exocrine glandular cells (AQP12A, DPEP1, GATM and ERP27). In summary, we provide a global analysis of the pancreas transcriptome and proteome with a comprehensive list of genes and proteins with elevated expression in pancreas. This list represents an important starting point for further studies of the molecular repertoire of pancreatic cells and their relation to disease states or treatment effects. PMID:25546435

  9. Persistent Effects of Developmental Exposure to 17α-Ethinylestradiol on the Zebrafish (Danio rerio Brain Transcriptome and Behavior

    Directory of Open Access Journals (Sweden)

    Tove Porseryd

    2017-04-01

    Full Text Available The synthetic estrogen 17α-ethinylestradiol (EE2 is an endocrine disrupting compound of concern due to its persistence and widespread presence in the aquatic environment. Effects of developmental exposure to low concentrations of EE2 in fish on reproduction and behavior not only persisted to adulthood, but have also been observed to be transmitted to several generations of unexposed progeny. To investigate the possible biological mechanisms of the persistent anxiogenic phenotype, we exposed zebrafish embryos for 80 days post fertilization to 0, 3, and 10 ng/L EE2 (measured concentrations 2.14 and 7.34 ng/L. After discontinued exposure, the animals were allowed to recover for 120 days in clean water. Adult males and females were later tested for changes in stress response and shoal cohesion, and whole-brain gene expression was analyzed with RNA sequencing. The results show increased anxiety in the novel tank and scototaxis tests, and increased shoal cohesion in fish exposed during development to EE2. RNA sequencing revealed 34 coding genes differentially expressed in male brains and 62 in female brains as a result of EE2 exposure. Several differences were observed between males and females in differential gene expression, with only one gene, sv2b, coding for a synaptic vesicle protein, that was affected by EE2 in both sexes. Functional analyses showed that in female brains, EE2 had significant effects on pathways connected to the circadian rhythm, cytoskeleton and motor proteins and synaptic proteins. A large number of non-coding sequences including 19 novel miRNAs were also differentially expressed in the female brain. The largest treatment effect in male brains was observed in pathways related to cholesterol biosynthesis and synaptic proteins. Circadian rhythm and cholesterol biosynthesis, previously implicated in anxiety behavior, might represent possible candidate pathways connecting the transcriptome changes to the alterations to behavior

  10. Changes in the human transcriptome upon vitamin D supplementation.

    Science.gov (United States)

    Pasing, Yvonne; Fenton, Christopher Graham; Jorde, Rolf; Paulssen, Ruth Hracky

    2017-10-01

    Vitamin D is hydroxylated in the liver and kidneys to its active form, which can bind to the vitamin D receptor (VDR). The VDR is present in a wide variety of different cells types and tissues and acts as a transcription factor. Although activation of the VDR is estimated to regulate expression of up to 5% of the human genome, our study is the first analysing gene expression after supplementation in more than 10 subjects. Subjects of a randomized controlled trial (RCT) received either vitamin D 3 (n=47) in a weekly dose of 20,000 IU or placebo (n=47) for a period of three to five years. For this study, blood samples for preparation of RNA were drawn from the subjects and mRNA gene expression in blood was determined using microarray analysis. The two study groups were similar regarding gender, age, BMI and duration of supplementation, whereas the mean serum 25-hydroxyvitamin D (25(OH)D) level as expected was significantly higher in the vitamin D group (119 versus 63nmol/L). When analysing all subjects, nearly no significant differences in gene expression between the two groups were found. However, when analysing men and women separately, significant effects on gene expression were observed for women. Furthermore, when only including subjects with the highest and lowest serum 25(OH)D levels, additional vitamin D regulated genes were disclosed. Thus, a total of 99 genes (p≤0.05, log2 fold change ≥|0.2|) were found to be regulated, of which 72 have not been published before as influenced by vitamin D. These genes were particularly involved in the interleukin signaling pathway, oxidative stress response, apoptosis signaling pathway and gonadotropin releasing hormone receptor pathway. Thus, our results open the possibility for many future studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. The human brain. Prenatal development and structure

    International Nuclear Information System (INIS)

    Marin-Padilla, Miguel

    2011-01-01

    This book is unique among the current literature in that it systematically documents the prenatal structural development of the human brain. It is based on lifelong study using essentially a single staining procedure, the classic rapid Golgi procedure, which ensures an unusual and desirable uniformity in the observations. The book is amply illustrated with 81 large, high-quality color photomicrographs never previously reproduced. These photomicrographs, obtained at 6, 7, 11, 15, 18, 20, 25, 30, 35, and 40 weeks of gestation, offer a fascinating insight into the sequential prenatal development of neurons, blood vessels, and glia in the human brain. (orig.)

  12. The human brain. Prenatal development and structure

    Energy Technology Data Exchange (ETDEWEB)

    Marin-Padilla, Miguel

    2011-07-01

    This book is unique among the current literature in that it systematically documents the prenatal structural development of the human brain. It is based on lifelong study using essentially a single staining procedure, the classic rapid Golgi procedure, which ensures an unusual and desirable uniformity in the observations. The book is amply illustrated with 81 large, high-quality color photomicrographs never previously reproduced. These photomicrographs, obtained at 6, 7, 11, 15, 18, 20, 25, 30, 35, and 40 weeks of gestation, offer a fascinating insight into the sequential prenatal development of neurons, blood vessels, and glia in the human brain. (orig.)

  13. Revisiting Glycogen Content in the Human Brain.

    Science.gov (United States)

    Öz, Gülin; DiNuzzo, Mauro; Kumar, Anjali; Moheet, Amir; Seaquist, Elizabeth R

    2015-12-01

    Glycogen provides an important glucose reservoir in the brain since the concentration of glucosyl units stored in glycogen is several fold higher than free glucose available in brain tissue. We have previously reported 3-4 µmol/g brain glycogen content using in vivo (13)C magnetic resonance spectroscopy (MRS) in conjunction with [1-(13)C]glucose administration in healthy humans, while higher levels were reported in the rodent brain. Due to the slow turnover of bulk brain glycogen in humans, complete turnover of the glycogen pool, estimated to take 3-5 days, was not observed in these prior studies. In an attempt to reach complete turnover and thereby steady state (13)C labeling in glycogen, here we administered [1-(13)C]glucose to healthy volunteers for 80 h. To eliminate any net glycogen synthesis during this period and thereby achieve an accurate estimate of glycogen concentration, volunteers were maintained at euglycemic blood glucose levels during [1-(13)C]glucose administration and (13)C-glycogen levels in the occipital lobe were measured by (13)C MRS approximately every 12 h. Finally, we fitted the data with a biophysical model that was recently developed to take into account the tiered structure of the glycogen molecule and additionally incorporated blood glucose levels and isotopic enrichments as input function in the model. We obtained excellent fits of the model to the (13)C-glycogen data, and glycogen content in the healthy human brain tissue was found to be 7.8 ± 0.3 µmol/g, a value substantially higher than previous estimates of glycogen content in the human brain.

  14. Group B streptococcus activates transcriptomic pathways related to premature birth in human extraplacental membranes in vitro.

    Science.gov (United States)

    Park, Hae-Ryung; Harris, Sean M; Boldenow, Erica; McEachin, Richard C; Sartor, Maureen; Chames, Mark; Loch-Caruso, Rita

    2018-03-01

    Streptococcus agalactiae (group B streptococcus [GBS]) infection in pregnant women is the leading cause of infectious neonatal morbidity and mortality in the United States. Although inflammation during infection has been associated with preterm birth, the contribution of GBS to preterm birth is less certain. Moreover, the early mechanisms by which GBS interacts with the gestational tissue to affect adverse pregnancy outcomes are poorly understood. We hypothesized that short-term GBS inoculation activates pathways related to inflammation and premature birth in human extraplacental membranes. We tested this hypothesis using GBS-inoculated human extraplacental membranes in vitro. In agreement with our hypothesis, a microarray-based transcriptomics analysis of gene expression changes in GBS-inoculated membranes revealed that GBS activated pathways related to inflammation and preterm birth with significant gene expression changes occurring as early as 4 h postinoculation. In addition, pathways related to DNA replication and repair were downregulated with GBS treatment. Conclusions based on our transcriptomics data were further supported by responses of prostaglandin E2 (PGE2), and matrix metalloproteinases 1 (MMP1) and 3 (MMP3), all of which are known to be involved in parturition and premature rupture of membranes. These results support our initial hypothesis and provide new information on molecular targets of GBS infection in human extraplacental membranes.

  15. Dynamics of the transcriptome response of cultured human embryonic stem cells to ionizing radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Sokolov, Mykyta V., E-mail: sokolovm@mail.nih.gov [Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 (United States); Panyutin, Irina V., E-mail: ipanyutinv@mail.nih.gov [Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 (United States); Panyutin, Igor G., E-mail: igorp@helix.nih.gov [Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 (United States); Neumann, Ronald D., E-mail: rneumann@mail.nih.gov [Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 (United States)

    2011-05-10

    One of the key consequences of exposure of human cells to genotoxic agents is the activation of DNA damage responses (DDR). While the mechanisms underpinning DDR in fully differentiated somatic human cells have been studied extensively, molecular signaling events and pathways involved in DDR in pluripotent human embryonic stem cells (hESC) remain largely unexplored. We studied changes in the human genome-wide transcriptome of H9 hESC line following exposures to 1 Gy of gamma-radiation at 2 h and 16 h post-irradiation. Quantitative real-time PCR was performed to verify the expression data for a subset of genes. In parallel, the cell growth, DDR kinetics, and expression of pluripotency markers in irradiated hESC were monitored. The changes in gene expression in hESC after exposure to ionizing radiation (IR) are substantially different from those observed in somatic human cell lines. Gene expression patterns at 2 h post-IR showed almost an exclusively p53-dependent, predominantly pro-apoptotic, signature with a total of only 30 up-regulated genes. In contrast, the gene expression patterns at 16 h post-IR showed 354 differentially expressed genes, mostly involved in pro-survival pathways, such as increased expression of metallothioneins, ubiquitin cycle, and general metabolism signaling. Cell growth data paralleled trends in gene expression changes. DDR in hESC followed the kinetics reported for human somatic differentiated cells. The expression of pluripotency markers characteristic of undifferentiated hESC was not affected by exposure to IR during the time course of our analysis. Our data on dynamics of transcriptome response of irradiated hESCs may provide a valuable tool to screen for markers of IR exposure of human cells in their most naive state; thus unmasking the key elements of DDR; at the same time, avoiding the complexity of interpreting distinct cell type-dependent genotoxic stress responses of terminally differentiated cells.

  16. Dynamics of the transcriptome response of cultured human embryonic stem cells to ionizing radiation exposure

    International Nuclear Information System (INIS)

    Sokolov, Mykyta V.; Panyutin, Irina V.; Panyutin, Igor G.; Neumann, Ronald D.

    2011-01-01

    One of the key consequences of exposure of human cells to genotoxic agents is the activation of DNA damage responses (DDR). While the mechanisms underpinning DDR in fully differentiated somatic human cells have been studied extensively, molecular signaling events and pathways involved in DDR in pluripotent human embryonic stem cells (hESC) remain largely unexplored. We studied changes in the human genome-wide transcriptome of H9 hESC line following exposures to 1 Gy of gamma-radiation at 2 h and 16 h post-irradiation. Quantitative real-time PCR was performed to verify the expression data for a subset of genes. In parallel, the cell growth, DDR kinetics, and expression of pluripotency markers in irradiated hESC were monitored. The changes in gene expression in hESC after exposure to ionizing radiation (IR) are substantially different from those observed in somatic human cell lines. Gene expression patterns at 2 h post-IR showed almost an exclusively p53-dependent, predominantly pro-apoptotic, signature with a total of only 30 up-regulated genes. In contrast, the gene expression patterns at 16 h post-IR showed 354 differentially expressed genes, mostly involved in pro-survival pathways, such as increased expression of metallothioneins, ubiquitin cycle, and general metabolism signaling. Cell growth data paralleled trends in gene expression changes. DDR in hESC followed the kinetics reported for human somatic differentiated cells. The expression of pluripotency markers characteristic of undifferentiated hESC was not affected by exposure to IR during the time course of our analysis. Our data on dynamics of transcriptome response of irradiated hESCs may provide a valuable tool to screen for markers of IR exposure of human cells in their most naive state; thus unmasking the key elements of DDR; at the same time, avoiding the complexity of interpreting distinct cell type-dependent genotoxic stress responses of terminally differentiated cells.

  17. Transcriptomics and proteomics show that selenium affects inflammation, cytoskeleton, and cancer pathways in human rectal biopsies.

    Science.gov (United States)

    Méplan, Catherine; Johnson, Ian T; Polley, Abigael C J; Cockell, Simon; Bradburn, David M; Commane, Daniel M; Arasaradnam, Ramesh P; Mulholland, Francis; Zupanic, Anze; Mathers, John C; Hesketh, John

    2016-08-01

    Epidemiologic studies highlight the potential role of dietary selenium (Se) in colorectal cancer prevention. Our goal was to elucidate whether expression of factors crucial for colorectal homoeostasis is affected by physiologic differences in Se status. Using transcriptomics and proteomics followed by pathway analysis, we identified pathways affected by Se status in rectal biopsies from 22 healthy adults, including 11 controls with optimal status (mean plasma Se = 1.43 μM) and 11 subjects with suboptimal status (mean plasma Se = 0.86 μM). We observed that 254 genes and 26 proteins implicated in cancer (80%), immune function and inflammatory response (40%), cell growth and proliferation (70%), cellular movement, and cell death (50%) were differentially expressed between the 2 groups. Expression of 69 genes, including selenoproteins W1 and K, which are genes involved in cytoskeleton remodelling and transcription factor NFκB signaling, correlated significantly with Se status. Integrating proteomics and transcriptomics datasets revealed reduced inflammatory and immune responses and cytoskeleton remodelling in the suboptimal Se status group. This is the first study combining omics technologies to describe the impact of differences in Se status on colorectal expression patterns, revealing that suboptimal Se status could alter inflammatory signaling and cytoskeleton in human rectal mucosa and so influence cancer risk.-Méplan, C., Johnson, I. T., Polley, A. C. J., Cockell, S., Bradburn, D. M., Commane, D. M., Arasaradnam, R. P., Mulholland, F., Zupanic, A., Mathers, J. C., Hesketh, J. Transcriptomics and proteomics show that selenium affects inflammation, cytoskeleton, and cancer pathways in human rectal biopsies. © The Author(s).

  18. Evolutionary Divergence of Gene and Protein Expression in the Brains of Humans and Chimpanzees.

    Science.gov (United States)

    Bauernfeind, Amy L; Soderblom, Erik J; Turner, Meredith E; Moseley, M Arthur; Ely, John J; Hof, Patrick R; Sherwood, Chet C; Wray, Gregory A; Babbitt, Courtney C

    2015-07-10

    Although transcriptomic profiling has become the standard approach for exploring molecular differences in the primate brain, very little is known about how the expression levels of gene transcripts relate to downstream protein abundance. Moreover, it is unknown whether the relationship changes depending on the brain region or species under investigation. We performed high-throughput transcriptomic (RNA-Seq) and proteomic (liquid chromatography coupled with tandem mass spectrometry) analyses on two regions of the human and chimpanzee brain: The anterior cingulate cortex and caudate nucleus. In both brain regions, we found a lower correlation between mRNA and protein expression levels in humans and chimpanzees than has been reported for other tissues and cell types, suggesting that the brain may engage extensive tissue-specific regulation affecting protein abundance. In both species, only a few categories of biological function exhibited strong correlations between mRNA and protein expression levels. These categories included oxidative metabolism and protein synthesis and modification, indicating that the expression levels of mRNA transcripts supporting these biological functions are more predictive of protein expression compared with other functional categories. More generally, however, the two measures of molecular expression provided strikingly divergent perspectives into differential expression between human and chimpanzee brains: mRNA comparisons revealed significant differences in neuronal communication, ion transport, and regulatory processes, whereas protein comparisons indicated differences in perception and cognition, metabolic processes, and organization of the cytoskeleton. Our results highlight the importance of examining protein expression in evolutionary analyses and call for a more thorough understanding of tissue-specific protein expression levels. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular

  19. Brain activation during human male ejaculation

    NARCIS (Netherlands)

    Holstege, Ger; Georgiadis, Janniko R.; Paans, Anne M.J.; Meiners, Linda C.; Graaf, Ferdinand H.C.E. van der; Reinders, A.A.T.Simone

    2003-01-01

    Brain mechanisms that control human sexual behavior in general, and ejaculation in particular, are poorly understood. We used positron emission tomography to measure increases in regional cerebral blood flow (rCBF) during ejaculation compared with sexual stimulation in heterosexual male volunteers.

  20. The transcriptome of Legionella pneumophila-infected human monocyte-derived macrophages.

    Directory of Open Access Journals (Sweden)

    Christopher T D Price

    Full Text Available Legionella pneumophila is an intracellular bacterial pathogen that invades and replicates within alveolar macrophages through injection of ∼ 300 effector proteins by its Dot/Icm type IV translocation apparatus. The bona fide F-box protein, AnkB, is a nutritional virulence effector that triggers macrophages to generate a surplus of amino acids, which is essential for intravacuolar proliferation. Therefore, the ankB mutant represents a novel genetic tool to determine the transcriptional response of human monocyte-derived macrophages (hMDMs to actively replicating L. pneumophila.Here, we utilized total human gene microarrays to determine the global transcriptional response of hMDMs to infection by wild type or the ankB mutant of L. pneumophila. The transcriptomes of hMDMs infected with either actively proliferating wild type or non-replicative ankB mutant bacteria were remarkably similar. The transcriptome of infected hMDMs was predominated by up-regulation of inflammatory pathways (IL-10 anti-inflammatory, interferon signaling and amphoterin signaling, anti-apoptosis, and down-regulation of protein synthesis pathways. In addition, L. pneumophila modulated diverse metabolic pathways, particularly those associated with bio-active lipid metabolism, and SLC amino acid transporters expression.Taken together, the hMDM transcriptional response to L. pneumophila is independent of intra-vacuolar replication of the bacteria and primarily involves modulation of the immune response and metabolic as well as nutritional pathways.

  1. Transcriptomic comparisons between cultured human adipose tissue-derived pericytes and mesenchymal stromal cells

    Directory of Open Access Journals (Sweden)

    Lindolfo da Silva Meirelles

    2016-03-01

    Full Text Available Mesenchymal stromal cells (MSCs, sometimes called mesenchymal stem cells, are cultured cells able to give rise to mature mesenchymal cells such as adipocytes, osteoblasts, and chondrocytes, and to secrete a wide range of trophic and immunomodulatory molecules. Evidence indicates that pericytes, cells that surround and maintain physical connections with endothelial cells in blood vessels, can give rise to MSCs (da Silva Meirelles et al., 2008 [1]; Caplan and Correa, 2011 [2]. We have compared the transcriptomes of highly purified, human adipose tissue pericytes subjected to culture-expansion in pericyte medium or MSC medium, with that of human adipose tissue MSCs isolated with traditional methods to test the hypothesis that their transcriptomes are similar (da Silva Meirelles et al., 2015 [3]. Here, we provide further information and analyses of microarray data from three pericyte populations cultured in pericyte medium, three pericyte populations cultured in MSC medium, and three adipose tissue MSC populations deposited in the Gene Expression Omnibus under accession number GSE67747. Keywords: Mesenchymal stromal cells, Mesenchymal stem cells, Pericytes, Microarrays

  2. Imaging visual function of the human brain

    International Nuclear Information System (INIS)

    Marg, E.

    1988-01-01

    Imaging of human brain structure and activity with particular reference to visual function is reviewed along with methods of obtaining the data including computed tomographic (CT) scan, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and positron emission tomography (PET). The literature is reviewed and the potential for a new understanding of brain visual function is discussed. PET is reviewed from basic physical principles to the most recent visual brain findings with oxygen-15. It is shown that there is a potential for submillimeter localization of visual functions with sequentially different visual stimuli designed for the temporal separation of the responses. Single photon emission computed tomography (SPECT), a less expensive substitute for PET, is also discussed. MRS is covered from basic physical principles to the current state of the art of in vivo biochemical analysis. Future possible clinical applications are discussed. Improved understanding of the functional neural organization of vision and brain will open a window to maps and circuits of human brain function.119 references

  3. Novel mouse model recapitulates genome and transcriptome alterations in human colorectal carcinomas.

    Science.gov (United States)

    McNeil, Nicole E; Padilla-Nash, Hesed M; Buishand, Floryne O; Hue, Yue; Ried, Thomas

    2017-03-01

    Human colorectal carcinomas are defined by a nonrandom distribution of genomic imbalances that are characteristic for this disease. Often, these imbalances affect entire chromosomes. Understanding the role of these aneuploidies for carcinogenesis is of utmost importance. Currently, established transgenic mice do not recapitulate the pathognonomic genome aberration profile of human colorectal carcinomas. We have developed a novel model based on the spontaneous transformation of murine colon epithelial cells. During this process, cells progress through stages of pre-immortalization, immortalization and, finally, transformation, and result in tumors when injected into immunocompromised mice. We analyzed our model for genome and transcriptome alterations using ArrayCGH, spectral karyotyping (SKY), and array based gene expression profiling. ArrayCGH revealed a recurrent pattern of genomic imbalances. These results were confirmed by SKY. Comparing these imbalances with orthologous maps of human chromosomes revealed a remarkable overlap. We observed focal deletions of the tumor suppressor genes Trp53 and Cdkn2a/p16. High-level focal genomic amplification included the locus harboring the oncogene Mdm2, which was confirmed by FISH in the form of double minute chromosomes. Array-based global gene expression revealed distinct differences between the sequential steps of spontaneous transformation. Gene expression changes showed significant similarities with human colorectal carcinomas. Pathways most prominently affected included genes involved in chromosomal instability and in epithelial to mesenchymal transition. Our novel mouse model therefore recapitulates the most prominent genome and transcriptome alterations in human colorectal cancer, and might serve as a valuable tool for understanding the dynamic process of tumorigenesis, and for preclinical drug testing. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. [Evolution of human brain and intelligence].

    Science.gov (United States)

    Lakatos, László; Janka, Zoltán

    2008-07-30

    The biological evolution, including human evolution is mainly driven by environmental changes. Accidental genetic modifications and their innovative results make the successful adaptation possible. As we know the human evolution started 7-8 million years ago in the African savannah, where upright position and bipedalism were significantly advantageous. The main drive of improving manual actions and tool making could be to obtain more food. Our ancestor got more meat due to more successful hunting, resulting in more caloric intake, more protein and essential fatty acid in the meal. The nervous system uses disproportionally high level of energy, so better quality of food was a basic condition for the evolution of huge human brain. The size of human brain was tripled during 3.5 million years, it increased from the average of 450 cm3 of Australopithecinae to the average of 1350 cm3 of Homo sapiens. A genetic change in the system controlling gene expression could happen about 200 000 years ago, which influenced the development of nervous system, the sensorimotor function and learning ability for motor processes. The appearance and stabilisation of FOXP2 gene structure as feature of modern man coincided with the first presence and quick spread of Homo sapiens on the whole Earth. This genetic modification made opportunity for human language, as the basis of abrupt evolution of human intelligence. The brain region being responsible for human language is the left planum temporale, which is much larger in left hemisphere. This shows the most typical human brain asymmetry. In this case the anatomical asymmetry means a clearly defined functional asymmetry as well, where the brain hemispheres act differently. The preference in using hands, the lateralised using of tools resulted in the brain asymmetry, which is the precondition of human language and intelligence. However, it cannot be held anymore, that only humans make tools, because our closest relatives, the chimpanzees are

  5. Additive Effects of Millimeter Waves and 2-Deoxyglucose Co-Exposure on the Human Keratinocyte Transcriptome.

    Science.gov (United States)

    Soubere Mahamoud, Yonis; Aite, Meziane; Martin, Catherine; Zhadobov, Maxim; Sauleau, Ronan; Le Dréan, Yves; Habauzit, Denis

    2016-01-01

    Millimeter Waves (MMW) will be used in the next-generation of high-speed wireless technologies, especially in future Ultra-Broadband small cells in 5G cellular networks. Therefore, their biocompatibilities must be evaluated prior to their massive deployment. Using a microarray-based approach, we analyzed modifications to the whole genome of a human keratinocyte model that was exposed at 60.4 GHz-MMW at an incident power density (IPD) of 20 mW/cm2 for 3 hours in athermic conditions. No keratinocyte transcriptome modifications were observed. We tested the effects of MMWs on cell metabolism by co-treating MMW-exposed cells with a glycolysis inhibitor, 2-deoxyglucose (2dG, 20 mM for 3 hours), and whole genome expression was evaluated along with the ATP content. We found that the 2dG treatment decreased the cellular ATP content and induced a high modification in the transcriptome (632 coding genes). The affected genes were associated with transcriptional repression, cellular communication and endoplasmic reticulum homeostasis. The MMW/2dG co-treatment did not alter the keratinocyte ATP content, but it did slightly alter the transcriptome, which reflected the capacity of MMW to interfere with the bioenergetic stress response. The RT-PCR-based validation confirmed 6 MMW-sensitive genes (SOCS3, SPRY2, TRIB1, FAM46A, CSRNP1 and PPP1R15A) during the 2dG treatment. These 6 genes encoded transcription factors or inhibitors of cytokine pathways, which raised questions regarding the potential impact of long-term or chronic MMW exposure on metabolically stressed cells.

  6. Additive Effects of Millimeter Waves and 2-Deoxyglucose Co-Exposure on the Human Keratinocyte Transcriptome.

    Directory of Open Access Journals (Sweden)

    Yonis Soubere Mahamoud

    Full Text Available Millimeter Waves (MMW will be used in the next-generation of high-speed wireless technologies, especially in future Ultra-Broadband small cells in 5G cellular networks. Therefore, their biocompatibilities must be evaluated prior to their massive deployment. Using a microarray-based approach, we analyzed modifications to the whole genome of a human keratinocyte model that was exposed at 60.4 GHz-MMW at an incident power density (IPD of 20 mW/cm2 for 3 hours in athermic conditions. No keratinocyte transcriptome modifications were observed. We tested the effects of MMWs on cell metabolism by co-treating MMW-exposed cells with a glycolysis inhibitor, 2-deoxyglucose (2dG, 20 mM for 3 hours, and whole genome expression was evaluated along with the ATP content. We found that the 2dG treatment decreased the cellular ATP content and induced a high modification in the transcriptome (632 coding genes. The affected genes were associated with transcriptional repression, cellular communication and endoplasmic reticulum homeostasis. The MMW/2dG co-treatment did not alter the keratinocyte ATP content, but it did slightly alter the transcriptome, which reflected the capacity of MMW to interfere with the bioenergetic stress response. The RT-PCR-based validation confirmed 6 MMW-sensitive genes (SOCS3, SPRY2, TRIB1, FAM46A, CSRNP1 and PPP1R15A during the 2dG treatment. These 6 genes encoded transcription factors or inhibitors of cytokine pathways, which raised questions regarding the potential impact of long-term or chronic MMW exposure on metabolically stressed cells.

  7. Sequence comparison of prefrontal cortical brain transcriptome from a tame and an aggressive silver fox (Vulpes vulpes)

    Science.gov (United States)

    2011-01-01

    Background Two strains of the silver fox (Vulpes vulpes), with markedly different behavioral phenotypes, have been developed by long-term selection for behavior. Foxes from the tame strain exhibit friendly behavior towards humans, paralleling the sociability of canine puppies, whereas foxes from the aggressive strain are defensive and exhibit aggression to humans. To understand the genetic differences underlying these behavioral phenotypes fox-specific genomic resources are needed. Results cDNA from mRNA from pre-frontal cortex of a tame and an aggressive fox was sequenced using the Roche 454 FLX Titanium platform (> 2.5 million reads & 0.9 Gbase of tame fox sequence; >3.3 million reads & 1.2 Gbase of aggressive fox sequence). Over 80% of the fox reads were assembled into contigs. Mapping fox reads against the fox transcriptome assembly and the dog genome identified over 30,000 high confidence fox-specific SNPs. Fox transcripts for approximately 14,000 genes were identified using SwissProt and the dog RefSeq databases. An at least 2-fold expression difference between the two samples (p fox transcriptome. Conclusions Transcriptome sequencing significantly expanded genomic resources available for the fox, a species without a sequenced genome. In a very cost efficient manner this yielded a large number of fox-specific SNP markers for genetic studies and provided significant insights into the gene expression profile of the fox pre-frontal cortex; expression differences between the two fox samples; and a catalogue of potentially important gene-specific sequence variants. This result demonstrates the utility of this approach for developing genomic resources in species with limited genomic information. PMID:21967120

  8. Puberty and structural brain development in humans.

    Science.gov (United States)

    Herting, Megan M; Sowell, Elizabeth R

    2017-01-01

    Adolescence is a transitional period of physical and behavioral development between childhood and adulthood. Puberty is a distinct period of sexual maturation that occurs during adolescence. Since the advent of magnetic resonance imaging (MRI), human studies have largely examined neurodevelopment in the context of age. A breadth of animal findings suggest that sex hormones continue to influence the brain beyond the prenatal period, with both organizational and activational effects occurring during puberty. Given the animal evidence, human MRI research has also set out to determine how puberty may influence otherwise known patterns of age-related neurodevelopment. Here we review structural-based MRI studies and show that pubertal maturation is a key variable to consider in elucidating sex- and individual- based differences in patterns of human brain development. We also highlight the continuing challenges faced, as well as future considerations, for this vital avenue of research. Copyright © 2016. Published by Elsevier Inc.

  9. Connectome imaging for mapping human brain pathways.

    Science.gov (United States)

    Shi, Y; Toga, A W

    2017-09-01

    With the fast advance of connectome imaging techniques, we have the opportunity of mapping the human brain pathways in vivo at unprecedented resolution. In this article we review the current developments of diffusion magnetic resonance imaging (MRI) for the reconstruction of anatomical pathways in connectome studies. We first introduce the background of diffusion MRI with an emphasis on the technical advances and challenges in state-of-the-art multi-shell acquisition schemes used in the Human Connectome Project. Characterization of the microstructural environment in the human brain is discussed from the tensor model to the general fiber orientation distribution (FOD) models that can resolve crossing fibers in each voxel of the image. Using FOD-based tractography, we describe novel methods for fiber bundle reconstruction and graph-based connectivity analysis. Building upon these novel developments, there have already been successful applications of connectome imaging techniques in reconstructing challenging brain pathways. Examples including retinofugal and brainstem pathways will be reviewed. Finally, we discuss future directions in connectome imaging and its interaction with other aspects of brain imaging research.

  10. Increased expression of aquaporin-4 in human traumatic brain injury and brain tumors

    Institute of Scientific and Technical Information of China (English)

    HuaHu; Wei-PingZhang; LeiZhang; ZhongChen; Er-QingWei

    2004-01-01

    Aquaporin-4 (AQP4) is one of the aquaporins (AQPs), a water channel family. In the brain, AQP4 is expressed in astroeyte foot processes, and plays an important role in water homeostasis and in the formation of brain edema. In our study, AQP4 expression in human brain specimens from patients with traumatic brain injury or different brain tumors was detected

  11. RNA isolation for transcriptomics of human and mouse small skin biopsies

    Directory of Open Access Journals (Sweden)

    Breit Timo M

    2011-10-01

    Full Text Available Abstract Background Isolation of RNA from skin biopsies presents a challenge, due to the tough nature of skin tissue and a high presence of RNases. As we lacked the dedicated equipment, i.e. homogenizer or bead-beater, needed for the available RNA from skin isolation methods, we adapted and tested our zebrafish single-embryo RNA-isolation protocol for RNA isolation from skin punch biopsies. Findings We tested our new RNA-isolation protocol in two experiments: a large-scale study with 97 human skin samples, and a small study with 16 mouse skin samples. Human skin was sampled with 4.0 mm biopsy punches and for the mouse skin different punch diameter sizes were tested; 1.0, 1.5, 2.0, and 2.5 mm. The average RNA yield in human samples was 1.5 μg with an average RNA quality RIN value of 8.1. For the mouse biopsies, the average RNA yield was 2.4 μg with an average RIN value of 7.5. For 96% of the human biopsies and 100% of the mouse biopsies we obtained enough high-quality RNA. The RNA samples were successfully tested in a transcriptomics analysis using the Affymetrix and Roche NimbleGen platforms. Conclusions Using our new RNA-isolation protocol, we were able to consistently isolate high-quality RNA, which is apt for further transcriptomics analysis. Furthermore, this method is already useable on biopsy material obtained with a punch diameter as small as 1.5 mm.

  12. Defining the Human Macula Transcriptome and Candidate Retinal Disease Genes UsingEyeSAGE

    Science.gov (United States)

    Rickman, Catherine Bowes; Ebright, Jessica N.; Zavodni, Zachary J.; Yu, Ling; Wang, Tianyuan; Daiger, Stephen P.; Wistow, Graeme; Boon, Kathy; Hauser, Michael A.

    2009-01-01

    Purpose To develop large-scale, high-throughput annotation of the human macula transcriptome and to identify and prioritize candidate genes for inherited retinal dystrophies, based on ocular-expression profiles using serial analysis of gene expression (SAGE). Methods Two human retina and two retinal pigment epithelium (RPE)/choroid SAGE libraries made from matched macula or midperipheral retina and adjacent RPE/choroid of morphologically normal 28- to 66-year-old donors and a human central retina longSAGE library made from 41- to 66-year-old donors were generated. Their transcription profiles were entered into a relational database, EyeSAGE, including microarray expression profiles of retina and publicly available normal human tissue SAGE libraries. EyeSAGE was used to identify retina- and RPE-specific and -associated genes, and candidate genes for retina and RPE disease loci. Differential and/or cell-type specific expression was validated by quantitative and single-cell RT-PCR. Results Cone photoreceptor-associated gene expression was elevated in the macula transcription profiles. Analysis of the longSAGE retina tags enhanced tag-to-gene mapping and revealed alternatively spliced genes. Analysis of candidate gene expression tables for the identified Bardet-Biedl syndrome disease gene (BBS5) in the BBS5 disease region table yielded BBS5 as the top candidate. Compelling candidates for inherited retina diseases were identified. Conclusions The EyeSAGE database, combining three different gene-profiling platforms including the authors’ multidonor-derived retina/RPE SAGE libraries and existing single-donor retina/RPE libraries, is a powerful resource for definition of the retina and RPE transcriptomes. It can be used to identify retina-specific genes, including alternatively spliced transcripts and to prioritize candidate genes within mapped retinal disease regions. PMID:16723438

  13. Integrated Transcriptomic and Epigenomic Analysis of Primary Human Lung Epithelial Cell Differentiation

    Science.gov (United States)

    Marconett, Crystal N.; Zhou, Beiyun; Rieger, Megan E.; Selamat, Suhaida A.; Dubourd, Mickael; Fang, Xiaohui; Lynch, Sean K.; Stueve, Theresa Ryan; Siegmund, Kimberly D.; Berman, Benjamin P.

    2013-01-01

    Elucidation of the epigenetic basis for cell-type specific gene regulation is key to gaining a full understanding of how the distinct phenotypes of differentiated cells are achieved and maintained. Here we examined how epigenetic changes are integrated with transcriptional activation to determine cell phenotype during differentiation. We performed epigenomic profiling in conjunction with transcriptomic profiling using in vitro differentiation of human primary alveolar epithelial cells (AEC). This model recapitulates an in vivo process in which AEC transition from one differentiated cell type to another during regeneration following lung injury. Interrogation of histone marks over time revealed enrichment of specific transcription factor binding motifs within regions of changing chromatin structure. Cross-referencing of these motifs with pathways showing transcriptional changes revealed known regulatory pathways of distal alveolar differentiation, such as the WNT and transforming growth factor beta (TGFB) pathways, and putative novel regulators of adult AEC differentiation including hepatocyte nuclear factor 4 alpha (HNF4A), and the retinoid X receptor (RXR) signaling pathways. Inhibition of the RXR pathway confirmed its functional relevance for alveolar differentiation. Our incorporation of epigenetic data allowed specific identification of transcription factors that are potential direct upstream regulators of the differentiation process, demonstrating the power of this approach. Integration of epigenomic data with transcriptomic profiling has broad application for the identification of regulatory pathways in other models of differentiation. PMID:23818859

  14. Infrasounds and biorhythms of the human brain

    Science.gov (United States)

    Panuszka, Ryszard; Damijan, Zbigniew; Kasprzak, Cezary; McGlothlin, James

    2002-05-01

    Low Frequency Noise (LFN) and infrasound has begun a new public health hazard. Evaluations of annoyance of (LFN) on human occupational health were based on standards where reactions of human auditory system and vibrations of parts of human body were small. Significant sensitivity has been observed on the central nervous system from infrasonic waves especially below 10 Hz. Observed follow-up effects in the brain gives incentive to study the relationship between parameters of waves and reactions obtained of biorhythms (EEG) and heart action (EKG). New results show the impact of LFN on the electrical potentials of the brain are dependent on the pressure waves on the human body. Electrical activity of circulatory system was also affected. Signals recorded in industrial workplaces were duplicated by loudspeakers and used to record data from a typical LFN spectra with 5 and 7 Hz in a laboratory chamber. External noise, electromagnetic fields, temperature, dust, and other elements were controlled. Results show not only a follow-up effect in the brain but also a result similar to arrhythmia in the heart. Relaxations effects were observed of people impacted by waves generated from natural sources such as streams and waterfalls.

  15. Benchmarking Water Quality from Wastewater to Drinking Waters Using Reduced Transcriptome of Human Cells.

    Science.gov (United States)

    Xia, Pu; Zhang, Xiaowei; Zhang, Hanxin; Wang, Pingping; Tian, Mingming; Yu, Hongxia

    2017-08-15

    One of the major challenges in environmental science is monitoring and assessing the risk of complex environmental mixtures. In vitro bioassays with limited key toxicological end points have been shown to be suitable to evaluate mixtures of organic pollutants in wastewater and recycled water. Omics approaches such as transcriptomics can monitor biological effects at the genome scale. However, few studies have applied omics approach in the assessment of mixtures of organic micropollutants. Here, an omics approach was developed for profiling bioactivity of 10 water samples ranging from wastewater to drinking water in human cells by a reduced human transcriptome (RHT) approach and dose-response modeling. Transcriptional expression of 1200 selected genes were measured by an Ampliseq technology in two cell lines, HepG2 and MCF7, that were exposed to eight serial dilutions of each sample. Concentration-effect models were used to identify differentially expressed genes (DEGs) and to calculate effect concentrations (ECs) of DEGs, which could be ranked to investigate low dose response. Furthermore, molecular pathways disrupted by different samples were evaluated by Gene Ontology (GO) enrichment analysis. The ability of RHT for representing bioactivity utilizing both HepG2 and MCF7 was shown to be comparable to the results of previous in vitro bioassays. Finally, the relative potencies of the mixtures indicated by RHT analysis were consistent with the chemical profiles of the samples. RHT analysis with human cells provides an efficient and cost-effective approach to benchmarking mixture of micropollutants and may offer novel insight into the assessment of mixture toxicity in water.

  16. Imaging Monoamine Oxidase in the Human Brain

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, J. S.; Volkow, N. D.; Wang, G-J.; Logan, Jean

    1999-11-10

    Positron emission tomography (PET) studies mapping monoamine oxidase in the human brain have been used to measure the turnover rate for MAO B; to determine the minimum effective dose of a new MAO inhibitor drug lazabemide and to document MAO inhibition by cigarette smoke. These studies illustrate the power of PET and radiotracer chemistry to measure normal biochemical processes and to provide information on the effect of drug exposure on specific molecular targets.

  17. Imaging Monoamine Oxidase in the Human Brain

    International Nuclear Information System (INIS)

    Fowler, J. S.; Volkow, N. D.; Wang, G-J.; Logan, Jean

    1999-01-01

    Positron emission tomography (PET) studies mapping monoamine oxidase in the human brain have been used to measure the turnover rate for MAO B; to determine the minimum effective dose of a new MAO inhibitor drug lazabemide and to document MAO inhibition by cigarette smoke. These studies illustrate the power of PET and radiotracer chemistry to measure normal biochemical processes and to provide information on the effect of drug exposure on specific molecular targets

  18. Analysis of the cerebral transcriptome in mice subjected to traumatic brain injury: importance of IL-6

    DEFF Research Database (Denmark)

    Quintana, Albert; Giralt, Mercedes; Molinero, Amalia

    2007-01-01

    Traumatic brain injury is one of the leading causes of incapacity and death among young people. Injury to the brain elicits a potent inflammatory response, comprising recruitment of inflammatory cells, reactive astrogliosis and activation of brain macrophages. Under the influence of presumably...... such as microarrays. The combination of these modern techniques with the comparison of normal and genetically modified mice boosts the significance of the results obtained. With this approach, we have demonstrated that a cytokine such as interleukin-6 is one of the key players in the response of the brain to injury....

  19. Increased expression of aquaporin-4 in human traumatic brain injury and brain tumors

    Institute of Scientific and Technical Information of China (English)

    HU Hua; YAO Hong-tian; ZHANG Wei-ping; ZHANG LEI; DING Wei; ZHANG Shi-hong; CHEN Zhong; WEI Er-qing

    2005-01-01

    Objective: To characterize the expression of aquaporin-4 (AQP4), one of the aquaporins (AQPs), in human brain specimens from patients with traumatic brain injury or brain tumors. Methods: Nineteen human brain specimens were obtained from the patients with traumatic brain injury, brain tumors, benign meningioma or early stage hemorrhagic stroke. MRI or CT imaging was used to assess brain edema. Hematoxylin and eosin staining were used to evaluate cell damage. Immunohistochemistry was used to detect the AQP4 expression. Results: AQP4 expression was increased from 15h to at least 8 d after injury. AQP4immunoreactivity was strong around astrocytomas, ganglioglioma and metastatic adenocarcinoma. However, AQP4 immunoreactivity was only found in the centers of astrocytomas and ganglioglioma, but not in metastatic adenocarcinoma derived from lung.Conclusion: AQP4 expression increases in human brains after traumatic brain injury, within brain-derived tumors, and around brain tumors.

  20. Radiation effects on the developing human brain

    International Nuclear Information System (INIS)

    1993-01-01

    The developing human brain has been shown to be especially sensitive to ionizing radiation. Mental retardation has been observed in the survivors of the atomic bombings in Japan exposed in utero during sensitive periods, and clinical studies of pelvically irradiated pregnant women have demonstrated damaging effects on the fetus. In this annex the emphasis is on reviewing the results of the study of the survivors of the atomic bombings in Japan, although the results of other human epidemiological investigations and of pertinent experimental studies are also considered. Refs, 3 figs, 10 tabs

  1. Transcriptomic profiling of primary alveolar epithelial cell differentiation in human and rat

    Directory of Open Access Journals (Sweden)

    Crystal N. Marconett

    2014-12-01

    Full Text Available Cell-type specific gene regulation is a key to gaining a full understanding of how the distinct phenotypes of differentiated cells are achieved and maintained. Here we examined how changes in transcriptional activation during alveolar epithelial cell (AEC differentiation determine phenotype. We performed transcriptomic profiling using in vitro differentiation of human and rat primary AEC. This model recapitulates in vitro an in vivo process in which AEC transition from alveolar type 2 (AT2 cells to alveolar type 1 (AT1 cells during normal maintenance and regeneration following lung injury. Here we describe in detail the quality control, preprocessing, and normalization of microarray data presented within the associated study (Marconett et al., 2013. We also include R code for reproducibility of the referenced data and easily accessible processed data tables.

  2. Towards Developmental Connectomics of the Human Brain

    Directory of Open Access Journals (Sweden)

    Miao eCao

    2016-03-01

    Full Text Available Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying structural and functional connectivity patterns of the developing brain. Normal brain development is characterized by continuous and significant network evolution throughout infancy, childhood and adolescence, following specific maturational patterns. Disruption of these normal changes is associated with neuropsychiatric developmental disorders, such as autism spectrum disorders or attention-deficit hyperactivity disorder. In this review, we focused on the recent progresses regarding typical and atypical development of human brain networks from birth to early adulthood, using a connectomic approach. Specifically, by the time of birth, structural networks already exhibit adult-like organization, with global efficient small-world and modular structures, as well as hub regions and rich-clubs acting as communication backbones. During development, the structure networks are fine-tuned, with increased global integration and robustness and decreased local segregation, as well as the strengthening of the hubs. In parallel, functional networks undergo more dramatic changes during maturation, with both increased integration and segregation during development, as brain hubs shift from primary regions to high order functioning regions, and the organization of modules transitions from a local anatomical emphasis to a more distributed architecture. These findings suggest that structural networks develop earlier than functional networks; meanwhile functional networks demonstrate more dramatic maturational changes with the evolution of structural networks serving as the anatomical backbone. In this review, we also highlighted topologically disorganized characteristics in structural and functional brain networks in several major developmental neuropsychiatric disorders (e.g., autism spectrum disorders, attention-deficit hyperactivity disorder and

  3. Toward Developmental Connectomics of the Human Brain.

    Science.gov (United States)

    Cao, Miao; Huang, Hao; Peng, Yun; Dong, Qi; He, Yong

    2016-01-01

    Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying structural and functional connectivity patterns of the developing brain. Normal brain development is characterized by continuous and significant network evolution throughout infancy, childhood, and adolescence, following specific maturational patterns. Disruption of these normal changes is associated with neuropsychiatric developmental disorders, such as autism spectrum disorders or attention-deficit hyperactivity disorder. In this review, we focused on the recent progresses regarding typical and atypical development of human brain networks from birth to early adulthood, using a connectomic approach. Specifically, by the time of birth, structural networks already exhibit adult-like organization, with global efficient small-world and modular structures, as well as hub regions and rich-clubs acting as communication backbones. During development, the structure networks are fine-tuned, with increased global integration and robustness and decreased local segregation, as well as the strengthening of the hubs. In parallel, functional networks undergo more dramatic changes during maturation, with both increased integration and segregation during development, as brain hubs shift from primary regions to high order functioning regions, and the organization of modules transitions from a local anatomical emphasis to a more distributed architecture. These findings suggest that structural networks develop earlier than functional networks; meanwhile functional networks demonstrate more dramatic maturational changes with the evolution of structural networks serving as the anatomical backbone. In this review, we also highlighted topologically disorganized characteristics in structural and functional brain networks in several major developmental neuropsychiatric disorders (e.g., autism spectrum disorders, attention-deficit hyperactivity disorder and developmental

  4. Toward Developmental Connectomics of the Human Brain

    Science.gov (United States)

    Cao, Miao; Huang, Hao; Peng, Yun; Dong, Qi; He, Yong

    2016-01-01

    Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying structural and functional connectivity patterns of the developing brain. Normal brain development is characterized by continuous and significant network evolution throughout infancy, childhood, and adolescence, following specific maturational patterns. Disruption of these normal changes is associated with neuropsychiatric developmental disorders, such as autism spectrum disorders or attention-deficit hyperactivity disorder. In this review, we focused on the recent progresses regarding typical and atypical development of human brain networks from birth to early adulthood, using a connectomic approach. Specifically, by the time of birth, structural networks already exhibit adult-like organization, with global efficient small-world and modular structures, as well as hub regions and rich-clubs acting as communication backbones. During development, the structure networks are fine-tuned, with increased global integration and robustness and decreased local segregation, as well as the strengthening of the hubs. In parallel, functional networks undergo more dramatic changes during maturation, with both increased integration and segregation during development, as brain hubs shift from primary regions to high order functioning regions, and the organization of modules transitions from a local anatomical emphasis to a more distributed architecture. These findings suggest that structural networks develop earlier than functional networks; meanwhile functional networks demonstrate more dramatic maturational changes with the evolution of structural networks serving as the anatomical backbone. In this review, we also highlighted topologically disorganized characteristics in structural and functional brain networks in several major developmental neuropsychiatric disorders (e.g., autism spectrum disorders, attention-deficit hyperactivity disorder and developmental

  5. Brain Meta-Transcriptomics from Harbor Seals to Infer the Role of the Microbiome and Virome in a Stranding Event.

    Science.gov (United States)

    Rosales, Stephanie M; Thurber, Rebecca Vega

    2015-01-01

    Marine diseases are becoming more frequent, and tools for identifying pathogens and disease reservoirs are needed to help prevent and mitigate epizootics. Meta-transcriptomics provides insights into disease etiology by cataloguing and comparing sequences from suspected pathogens. This method is a powerful approach to simultaneously evaluate both the viral and bacterial communities, but few studies have applied this technique in marine systems. In 2009 seven harbor seals, Phoca vitulina, stranded along the California coast from a similar brain disease of unknown cause of death (UCD). We evaluated the differences between the virome and microbiome of UCDs and harbor seals with known causes of death. Here we determined that UCD stranded animals had no viruses in their brain tissue. However, in the bacterial community, we identified Burkholderia and Coxiella burnetii as important pathogens associated with this stranding event. Burkholderia were 100% prevalent and ~2.8 log2 fold more abundant in the UCD animals. Further, while C. burnetii was found in only 35.7% of all samples, it was highly abundant (~94% of the total microbial community) in a single individual. In this harbor seal, C. burnetii showed high transcription rates of invading and translation genes, implicating it in the pathogenesis of this animal. Based on these data we propose that Burkholderia taxa and C. burnetii are potentially important opportunistic neurotropic pathogens in UCD stranded harbor seals.

  6. Brain Meta-Transcriptomics from Harbor Seals to Infer the Role of the Microbiome and Virome in a Stranding Event.

    Directory of Open Access Journals (Sweden)

    Stephanie M Rosales

    Full Text Available Marine diseases are becoming more frequent, and tools for identifying pathogens and disease reservoirs are needed to help prevent and mitigate epizootics. Meta-transcriptomics provides insights into disease etiology by cataloguing and comparing sequences from suspected pathogens. This method is a powerful approach to simultaneously evaluate both the viral and bacterial communities, but few studies have applied this technique in marine systems. In 2009 seven harbor seals, Phoca vitulina, stranded along the California coast from a similar brain disease of unknown cause of death (UCD. We evaluated the differences between the virome and microbiome of UCDs and harbor seals with known causes of death. Here we determined that UCD stranded animals had no viruses in their brain tissue. However, in the bacterial community, we identified Burkholderia and Coxiella burnetii as important pathogens associated with this stranding event. Burkholderia were 100% prevalent and ~2.8 log2 fold more abundant in the UCD animals. Further, while C. burnetii was found in only 35.7% of all samples, it was highly abundant (~94% of the total microbial community in a single individual. In this harbor seal, C. burnetii showed high transcription rates of invading and translation genes, implicating it in the pathogenesis of this animal. Based on these data we propose that Burkholderia taxa and C. burnetii are potentially important opportunistic neurotropic pathogens in UCD stranded harbor seals.

  7. Identification of Human HK Genes and Gene Expression Regulation Study in Cancer from Transcriptomics Data Analysis

    Science.gov (United States)

    Zhang, Zhang; Liu, Jingxing; Wu, Jiayan; Yu, Jun

    2013-01-01

    The regulation of gene expression is essential for eukaryotes, as it drives the processes of cellular differentiation and morphogenesis, leading to the creation of different cell types in multicellular organisms. RNA-Sequencing (RNA-Seq) provides researchers with a powerful toolbox for characterization and quantification of transcriptome. Many different human tissue/cell transcriptome datasets coming from RNA-Seq technology are available on public data resource. The fundamental issue here is how to develop an effective analysis method to estimate expression pattern similarities between different tumor tissues and their corresponding normal tissues. We define the gene expression pattern from three directions: 1) expression breadth, which reflects gene expression on/off status, and mainly concerns ubiquitously expressed genes; 2) low/high or constant/variable expression genes, based on gene expression level and variation; and 3) the regulation of gene expression at the gene structure level. The cluster analysis indicates that gene expression pattern is higher related to physiological condition rather than tissue spatial distance. Two sets of human housekeeping (HK) genes are defined according to cell/tissue types, respectively. To characterize the gene expression pattern in gene expression level and variation, we firstly apply improved K-means algorithm and a gene expression variance model. We find that cancer-associated HK genes (a HK gene is specific in cancer group, while not in normal group) are expressed higher and more variable in cancer condition than in normal condition. Cancer-associated HK genes prefer to AT-rich genes, and they are enriched in cell cycle regulation related functions and constitute some cancer signatures. The expression of large genes is also avoided in cancer group. These studies will help us understand which cell type-specific patterns of gene expression differ among different cell types, and particularly for cancer. PMID:23382867

  8. Brain structures in the sciences and humanities.

    Science.gov (United States)

    Takeuchi, Hikaru; Taki, Yasuyuki; Sekiguchi, Atsushi; Nouchi, Rui; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos Makoto; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Sassa, Yuko; Kawashima, Ryuta

    2015-11-01

    The areas of academic interest (sciences or humanities) and area of study have been known to be associated with a number of factors associated with autistic traits. However, despite the vast amount of literature on the psychological and physiological characteristics associated with faculty membership, brain structural characteristics associated with faculty membership have never been investigated directly. In this study, we used voxel-based morphometry to investigate differences in regional gray matter volume (rGMV)/regional white matter volume (rWMV) between science and humanities students to test our hypotheses that brain structures previously robustly shown to be altered in autistic subjects are related to differences in faculty membership. We examined 312 science students (225 males and 87 females) and 179 humanities students (105 males and 74 females). Whole-brain analyses of covariance revealed that after controlling for age, sex, and total intracranial volume, the science students had significantly larger rGMV in an anatomical cluster around the medial prefrontal cortex and the frontopolar area, whereas the humanities students had significantly larger rWMV in an anatomical cluster mainly concentrated around the right hippocampus. These anatomical structures have been linked to autism in previous studies and may mediate cognitive functions that characterize differences in faculty membership. The present results may support the ideas that autistic traits and characteristics of the science students compared with the humanities students share certain characteristics from neuroimaging perspectives. This study improves our understanding of differences in faculty membership which is the link among cognition, biological factors, disorders, and education (academia).

  9. Dual Transcriptome Profiling of Leishmania-Infected Human Macrophages Reveals Distinct Reprogramming Signatures.

    Science.gov (United States)

    Fernandes, Maria Cecilia; Dillon, Laura A L; Belew, Ashton Trey; Bravo, Hector Corrada; Mosser, David M; El-Sayed, Najib M

    2016-05-10

    Macrophages are mononuclear phagocytes that constitute a first line of defense against pathogens. While lethal to many microbes, they are the primary host cells of Leishmania spp. parasites, the obligate intracellular pathogens that cause leishmaniasis. We conducted transcriptomic profiling of two Leishmania species and the human macrophage over the course of intracellular infection by using high-throughput RNA sequencing to characterize the global gene expression changes and reprogramming events that underlie the interactions between the pathogen and its host. A systematic exclusion of the generic effects of large-particle phagocytosis revealed a vigorous, parasite-specific response of the human macrophage early in the infection that was greatly tempered at later time points. An analogous temporal expression pattern was observed with the parasite, suggesting that much of the reprogramming that occurs as parasites transform into intracellular forms generally stabilizes shortly after entry. Following that, the parasite establishes an intracellular niche within macrophages, with minimal communication between the parasite and the host cell later during the infection. No significant difference was observed between parasite species transcriptomes or in the transcriptional response of macrophages infected with each species. Our comparative analysis of gene expression changes that occur as mouse and human macrophages are infected by Leishmania spp. points toward a general signature of the Leishmania-macrophage infectome. Little is known about the transcriptional changes that occur within mammalian cells harboring intracellular pathogens. This study characterizes the gene expression signatures of Leishmania spp. parasites and the coordinated response of infected human macrophages as the pathogen enters and persists within them. After accounting for the generic effects of large-particle phagocytosis, we observed a parasite-specific response of the human macrophages early in

  10. A SAGE based approach to human glomerular endothelium: defining the transcriptome, finding a novel molecule and highlighting endothelial diversity.

    Science.gov (United States)

    Sengoelge, Guerkan; Winnicki, Wolfgang; Kupczok, Anne; von Haeseler, Arndt; Schuster, Michael; Pfaller, Walter; Jennings, Paul; Weltermann, Ansgar; Blake, Sophia; Sunder-Plassmann, Gere

    2014-08-27

    Large scale transcript analysis of human glomerular microvascular endothelial cells (HGMEC) has never been accomplished. We designed this study to define the transcriptome of HGMEC and facilitate a better characterization of these endothelial cells with unique features. Serial analysis of gene expression (SAGE) was used for its unbiased approach to quantitative acquisition of transcripts. We generated a HGMEC SAGE library consisting of 68,987 transcript tags. Then taking advantage of large public databases and advanced bioinformatics we compared the HGMEC SAGE library with a SAGE library of non-cultured ex vivo human glomeruli (44,334 tags) which contained endothelial cells. The 823 tags common to both which would have the potential to be expressed in vivo were subsequently checked against 822,008 tags from 16 non-glomerular endothelial SAGE libraries. This resulted in 268 transcript tags differentially overexpressed in HGMEC compared to non-glomerular endothelia. These tags were filtered using a set of criteria: never before shown in kidney or any type of endothelial cell, absent in all nephron regions except the glomerulus, more highly expressed than statistically expected in HGMEC. Neurogranin, a direct target of thyroid hormone action which had been thought to be brain specific and never shown in endothelial cells before, fulfilled these criteria. Its expression in glomerular endothelium in vitro and in vivo was then verified by real-time-PCR, sequencing and immunohistochemistry. Our results represent an extensive molecular characterization of HGMEC beyond a mere database, underline the endothelial heterogeneity, and propose neurogranin as a potential link in the kidney-thyroid axis.

  11. Segmentation and Visualisation of Human Brain Structures

    Energy Technology Data Exchange (ETDEWEB)

    Hult, Roger

    2003-10-01

    In this thesis the focus is mainly on the development of segmentation techniques for human brain structures and of the visualisation of such structures. The images of the brain are both anatomical images (magnet resonance imaging (MRI) and autoradiography) and functional images that show blood flow (functional magnetic imaging (fMRI), positron emission tomography (PET), and single photon emission tomography (SPECT)). When working with anatomical images, the structures segmented are visible as different parts of the brain, e.g. the brain cortex, the hippocampus, or the amygdala. In functional images, the activity or the blood flow that be seen. Grey-level morphology methods are used in the segmentations to make tissue types in the images more homogenous and minimise difficulties with connections to outside tissue. A method for automatic histogram thresholding is also used. Furthermore, there are binary operations such as logic operation between masks and binary morphology operations. The visualisation of the segmented structures uses either surface rendering or volume rendering. For the visualisation of thin structures, surface rendering is the better choice since otherwise some voxels might be missed. It is possible to display activation from a functional image on the surface of a segmented cortex. A new method for autoradiographic images has been developed, which integrates registration, background compensation, and automatic thresholding to get faster and more reliable results than the standard techniques give.

  12. Segmentation and Visualisation of Human Brain Structures

    International Nuclear Information System (INIS)

    Hult, Roger

    2003-01-01

    In this thesis the focus is mainly on the development of segmentation techniques for human brain structures and of the visualisation of such structures. The images of the brain are both anatomical images (magnet resonance imaging (MRI) and autoradiography) and functional images that show blood flow (functional magnetic imaging (fMRI), positron emission tomography (PET), and single photon emission tomography (SPECT)). When working with anatomical images, the structures segmented are visible as different parts of the brain, e.g. the brain cortex, the hippocampus, or the amygdala. In functional images, the activity or the blood flow that be seen. Grey-level morphology methods are used in the segmentations to make tissue types in the images more homogenous and minimise difficulties with connections to outside tissue. A method for automatic histogram thresholding is also used. Furthermore, there are binary operations such as logic operation between masks and binary morphology operations. The visualisation of the segmented structures uses either surface rendering or volume rendering. For the visualisation of thin structures, surface rendering is the better choice since otherwise some voxels might be missed. It is possible to display activation from a functional image on the surface of a segmented cortex. A new method for autoradiographic images has been developed, which integrates registration, background compensation, and automatic thresholding to get faster and more reliable results than the standard techniques give

  13. The contribution of 700,000 ORF sequence tags to the definition of the human transcriptome

    Science.gov (United States)

    Camargo, Anamaria A.; Samaia, Helena P. B.; Dias-Neto, Emmanuel; Simão, Daniel F.; Migotto, Italo A.; Briones, Marcelo R. S.; Costa, Fernando F.; Aparecida Nagai, Maria; Verjovski-Almeida, Sergio; Zago, Marco A.; Andrade, Luis Eduardo C.; Carrer, Helaine; El-Dorry, Hamza F. A.; Espreafico, Enilza M.; Habr-Gama, Angelita; Giannella-Neto, Daniel; Goldman, Gustavo H.; Gruber, Arthur; Hackel, Christine; Kimura, Edna T.; Maciel, Rui M. B.; Marie, Suely K. N.; Martins, Elizabeth A. L.; Nóbrega, Marina P.; Paçó-Larson, Maria Luisa; Pardini, Maria Inês M. C.; Pereira, Gonçalo G.; Pesquero, João Bosco; Rodrigues, Vanderlei; Rogatto, Silvia R.; da Silva, Ismael D. C. G.; Sogayar, Mari C.; Sonati, Maria de Fátima; Tajara, Eloiza H.; Valentini, Sandro R.; Alberto, Fernando L.; Amaral, Maria Elisabete J.; Aneas, Ivy; Arnaldi, Liliane A. T.; de Assis, Angela M.; Bengtson, Mário Henrique; Bergamo, Nadia Aparecida; Bombonato, Vanessa; de Camargo, Maria E. R.; Canevari, Renata A.; Carraro, Dirce M.; Cerutti, Janete M.; Corrêa, Maria Lucia C.; Corrêa, Rosana F. R.; Costa, Maria Cristina R.; Curcio, Cyntia; Hokama, Paula O. M.; Ferreira, Ari J. S.; Furuzawa, Gilberto K.; Gushiken, Tsieko; Ho, Paulo L.; Kimura, Elza; Krieger, José E.; Leite, Luciana C. C.; Majumder, Paromita; Marins, Mozart; Marques, Everaldo R.; Melo, Analy S. A.; Melo, Monica; Mestriner, Carlos Alberto; Miracca, Elisabete C.; Miranda, Daniela C.; Nascimento, Ana Lucia T. O.; Nóbrega, Francisco G.; Ojopi, Élida P. B.; Pandolfi, José Rodrigo C.; Pessoa, Luciana G.; Prevedel, Aline C.; Rahal, Paula; Rainho, Claudia A.; Reis, Eduardo M. R.; Ribeiro, Marcelo L.; da Rós, Nancy; de Sá, Renata G.; Sales, Magaly M.; Sant'anna, Simone Cristina; dos Santos, Mariana L.; da Silva, Aline M.; da Silva, Neusa P.; Silva, Wilson A.; da Silveira, Rosana A.; Sousa, Josane F.; Stecconi, Daniella; Tsukumo, Fernando; Valente, Valéria; Soares, Fernando; Moreira, Eloisa S.; Nunes, Diana N.; Correa, Ricardo G.; Zalcberg, Heloisa; Carvalho, Alex F.; Reis, Luis F. L.; Brentani, Ricardo R.; Simpson, Andrew J. G.; de Souza, Sandro J.

    2001-01-01

    Open reading frame expressed sequences tags (ORESTES) differ from conventional ESTs by providing sequence data from the central protein coding portion of transcripts. We generated a total of 696,745 ORESTES sequences from 24 human tissues and used a subset of the data that correspond to a set of 15,095 full-length mRNAs as a means of assessing the efficiency of the strategy and its potential contribution to the definition of the human transcriptome. We estimate that ORESTES sampled over 80% of all highly and moderately expressed, and between 40% and 50% of rarely expressed, human genes. In our most thoroughly sequenced tissue, the breast, the 130,000 ORESTES generated are derived from transcripts from an estimated 70% of all genes expressed in that tissue, with an equally efficient representation of both highly and poorly expressed genes. In this respect, we find that the capacity of the ORESTES strategy both for gene discovery and shotgun transcript sequence generation significantly exceeds that of conventional ESTs. The distribution of ORESTES is such that many human transcripts are now represented by a scaffold of partial sequences distributed along the length of each gene product. The experimental joining of the scaffold components, by reverse transcription–PCR, represents a direct route to transcript finishing that may represent a useful alternative to full-length cDNA cloning. PMID:11593022

  14. The contribution of 700,000 ORF sequence tags to the definition of the human transcriptome.

    Science.gov (United States)

    Camargo, A A; Samaia, H P; Dias-Neto, E; Simão, D F; Migotto, I A; Briones, M R; Costa, F F; Nagai, M A; Verjovski-Almeida, S; Zago, M A; Andrade, L E; Carrer, H; El-Dorry, H F; Espreafico, E M; Habr-Gama, A; Giannella-Neto, D; Goldman, G H; Gruber, A; Hackel, C; Kimura, E T; Maciel, R M; Marie, S K; Martins, E A; Nobrega, M P; Paco-Larson, M L; Pardini, M I; Pereira, G G; Pesquero, J B; Rodrigues, V; Rogatto, S R; da Silva, I D; Sogayar, M C; Sonati, M F; Tajara, E H; Valentini, S R; Alberto, F L; Amaral, M E; Aneas, I; Arnaldi, L A; de Assis, A M; Bengtson, M H; Bergamo, N A; Bombonato, V; de Camargo, M E; Canevari, R A; Carraro, D M; Cerutti, J M; Correa, M L; Correa, R F; Costa, M C; Curcio, C; Hokama, P O; Ferreira, A J; Furuzawa, G K; Gushiken, T; Ho, P L; Kimura, E; Krieger, J E; Leite, L C; Majumder, P; Marins, M; Marques, E R; Melo, A S; Melo, M B; Mestriner, C A; Miracca, E C; Miranda, D C; Nascimento, A L; Nobrega, F G; Ojopi, E P; Pandolfi, J R; Pessoa, L G; Prevedel, A C; Rahal, P; Rainho, C A; Reis, E M; Ribeiro, M L; da Ros, N; de Sa, R G; Sales, M M; Sant'anna, S C; dos Santos, M L; da Silva, A M; da Silva, N P; Silva, W A; da Silveira, R A; Sousa, J F; Stecconi, D; Tsukumo, F; Valente, V; Soares, F; Moreira, E S; Nunes, D N; Correa, R G; Zalcberg, H; Carvalho, A F; Reis, L F; Brentani, R R; Simpson, A J; de Souza, S J; Melo, M

    2001-10-09

    Open reading frame expressed sequences tags (ORESTES) differ from conventional ESTs by providing sequence data from the central protein coding portion of transcripts. We generated a total of 696,745 ORESTES sequences from 24 human tissues and used a subset of the data that correspond to a set of 15,095 full-length mRNAs as a means of assessing the efficiency of the strategy and its potential contribution to the definition of the human transcriptome. We estimate that ORESTES sampled over 80% of all highly and moderately expressed, and between 40% and 50% of rarely expressed, human genes. In our most thoroughly sequenced tissue, the breast, the 130,000 ORESTES generated are derived from transcripts from an estimated 70% of all genes expressed in that tissue, with an equally efficient representation of both highly and poorly expressed genes. In this respect, we find that the capacity of the ORESTES strategy both for gene discovery and shotgun transcript sequence generation significantly exceeds that of conventional ESTs. The distribution of ORESTES is such that many human transcripts are now represented by a scaffold of partial sequences distributed along the length of each gene product. The experimental joining of the scaffold components, by reverse transcription-PCR, represents a direct route to transcript finishing that may represent a useful alternative to full-length cDNA cloning.

  15. Is human blood a good surrogate for brain tissue in transcriptional studies?

    Directory of Open Access Journals (Sweden)

    van den Berg Leonard H

    2010-10-01

    Full Text Available Abstract Background Since human brain tissue is often unavailable for transcriptional profiling studies, blood expression data is frequently used as a substitute. The underlying hypothesis in such studies is that genes expressed in brain tissue leave a transcriptional footprint in blood. We tested this hypothesis by relating three human brain expression data sets (from cortex, cerebellum and caudate nucleus to two large human blood expression data sets (comprised of 1463 individuals. Results We found mean expression levels were weakly correlated between the brain and blood data (r range: [0.24,0.32]. Further, we tested whether co-expression relationships were preserved between the three brain regions and blood. Only a handful of brain co-expression modules showed strong evidence of preservation and these modules could be combined into a single large blood module. We also identified highly connected intramodular "hub" genes inside preserved modules. These preserved intramodular hub genes had the following properties: first, their expression levels tended to be significantly more heritable than those from non-preserved intramodular hub genes (p -90; second, they had highly significant positive correlations with the following cluster of differentiation genes: CD58, CD47, CD48, CD53 and CD164; third, a significant number of them were known to be involved in infection mechanisms, post-transcriptional and post-translational modification and other basic processes. Conclusions Overall, we find transcriptome organization is poorly preserved between brain and blood. However, the subset of preserved co-expression relationships characterized here may aid future efforts to identify blood biomarkers for neurological and neuropsychiatric diseases when brain tissue samples are unavailable.

  16. Deconstructing Anger in the Human Brain.

    Science.gov (United States)

    Gilam, Gadi; Hendler, Talma

    2017-01-01

    Anger may be caused by a wide variety of triggers, and though it has negative consequences on health and well-being, it is also crucial in motivating to take action and approach rather than avoid a confrontation. While anger is considered a survival response inherent in all living creatures, humans are endowed with the mental flexibility that enables them to control and regulate their anger, and adapt it to socially accepted norms. Indeed, a profound interpersonal nature is apparent in most events which evoke anger among humans. Since anger consists of physiological, cognitive, subjective, and behavioral components, it is a contextualized multidimensional construct that poses theoretical and operational difficulties in defining it as a single psychobiological phenomenon. Although most neuroimaging studies have neglected the multidimensionality of anger and thus resulted in brain activations dispersed across the entire brain, there seems to be several reoccurring neural circuits subserving the subjective experience of human anger. Nevertheless, to capture the large variety in the forms and fashions in which anger is experienced, expressed, and regulated, and thus to better portray the related underlying neural substrates, neurobehavioral investigations of human anger should aim to further embed realistic social interactions within their anger induction paradigms.

  17. Differentiated neuroprogenitor cells incubated with human or canine adenovirus, or lentiviral vectors have distinct transcriptome profiles.

    Directory of Open Access Journals (Sweden)

    Stefania Piersanti

    Full Text Available Several studies have demonstrated the potential for vector-mediated gene transfer to the brain. Helper-dependent (HD human (HAd and canine (CAV-2 adenovirus, and VSV-G-pseudotyped self-inactivating HIV-1 vectors (LV effectively transduce human brain cells and their toxicity has been partly analysed. However, their effect on the brain homeostasis is far from fully defined, especially because of the complexity of the central nervous system (CNS. With the goal of dissecting the toxicogenomic signatures of the three vectors for human neurons, we transduced a bona fide human neuronal system with HD-HAd, HD-CAV-2 and LV. We analysed the transcriptional response of more than 47,000 transcripts using gene chips. Chip data showed that HD-CAV-2 and LV vectors activated the innate arm of the immune response, including Toll-like receptors and hyaluronan circuits. LV vector also induced an IFN response. Moreover, HD-CAV-2 and LV vectors affected DNA damage pathways--but in opposite directions--suggesting a differential response of the p53 and ATM pathways to the vector genomes. As a general response to the vectors, human neurons activated pro-survival genes and neuron morphogenesis, presumably with the goal of re-establishing homeostasis. These data are complementary to in vivo studies on brain vector toxicity and allow a better understanding of the impact of viral vectors on human neurons, and mechanistic approaches to improve the therapeutic impact of brain-directed gene transfer.

  18. Visualization of monoamine oxidase in human brain

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, J.S.; Volkow, N.D.; Wang, G.J.; Pappas, N.; Shea, C.; MacGregor, R.R.; Logan, J.

    1996-12-31

    Monoamine oxidase is a flavin enzyme which exists in two subtypes, MAO A and MAO B. In human brain MAO B predominates and is largely compartmentalized in cell bodies of serotonergic neurons and glia. Regional distribution of MAO B was determined by positron computed tomography with volunteers after the administration of deuterium substituted [11C]L-deprenyl. The basal ganglia and thalamus exhibited the greatest concentrations of MAO B with intermediate levels in the frontal cortex and cingulate gyrus while lowest levels were observed in the parietal and temporal cortices and cerebellum. We observed that brain MAO B increases with are in health normal subjects, however the increases were generally smaller than those revealed with post-mortem studies.

  19. The Drosophila surface glia transcriptome: evolutionary conserved blood-brain barrier processes

    OpenAIRE

    DeSalvo, Michael K.; Hindle, Samantha J.; Rusan, Zeid M.; Orng, Souvinh; Eddison, Mark; Halliwill, Kyle; Bainton, Roland J.

    2014-01-01

    Central nervous system (CNS) function is dependent on the stringent regulation of metabolites, drugs, cells, and pathogens exposed to the CNS space. Cellular blood-brain barrier (BBB) structures are highly specific checkpoints governing entry and exit of all small molecules to and from the brain interstitial space, but the precise mechanisms that regulate the BBB are not well understood. In addition, the BBB has long been a challenging obstacle to the pharmacologic treatment of CNS diseases; ...

  20. Human brain lesion-deficit inference remapped.

    Science.gov (United States)

    Mah, Yee-Haur; Husain, Masud; Rees, Geraint; Nachev, Parashkev

    2014-09-01

    Our knowledge of the anatomical organization of the human brain in health and disease draws heavily on the study of patients with focal brain lesions. Historically the first method of mapping brain function, it is still potentially the most powerful, establishing the necessity of any putative neural substrate for a given function or deficit. Great inferential power, however, carries a crucial vulnerability: without stronger alternatives any consistent error cannot be easily detected. A hitherto unexamined source of such error is the structure of the high-dimensional distribution of patterns of focal damage, especially in ischaemic injury-the commonest aetiology in lesion-deficit studies-where the anatomy is naturally shaped by the architecture of the vascular tree. This distribution is so complex that analysis of lesion data sets of conventional size cannot illuminate its structure, leaving us in the dark about the presence or absence of such error. To examine this crucial question we assembled the largest known set of focal brain lesions (n = 581), derived from unselected patients with acute ischaemic injury (mean age = 62.3 years, standard deviation = 17.8, male:female ratio = 0.547), visualized with diffusion-weighted magnetic resonance imaging, and processed with validated automated lesion segmentation routines. High-dimensional analysis of this data revealed a hidden bias within the multivariate patterns of damage that will consistently distort lesion-deficit maps, displacing inferred critical regions from their true locations, in a manner opaque to replication. Quantifying the size of this mislocalization demonstrates that past lesion-deficit relationships estimated with conventional inferential methodology are likely to be significantly displaced, by a magnitude dependent on the unknown underlying lesion-deficit relationship itself. Past studies therefore cannot be retrospectively corrected, except by new knowledge that would render them redundant

  1. Positive selection on gene expression in the human brain

    DEFF Research Database (Denmark)

    Khaitovich, Philipp; Tang, Kun; Franz, Henriette

    2006-01-01

    Recent work has shown that the expression levels of genes transcribed in the brains of humans and chimpanzees have changed less than those of genes transcribed in other tissues [1] . However, when gene expression changes are mapped onto the evolutionary lineage in which they occurred, the brain...... shows more changes than other tissues in the human lineage compared to the chimpanzee lineage [1] , [2] and [3] . There are two possible explanations for this: either positive selection drove more gene expression changes to fixation in the human brain than in the chimpanzee brain, or genes expressed...... in the brain experienced less purifying selection in humans than in chimpanzees, i.e. gene expression in the human brain is functionally less constrained. The first scenario would be supported if genes that changed their expression in the brain in the human lineage showed more selective sweeps than other genes...

  2. Sequence comparison of prefrontal cortical brain transcriptome from a tame and an aggressive silver fox (Vulpes vulpes

    Directory of Open Access Journals (Sweden)

    Sun Qi

    2011-10-01

    Full Text Available Abstract Background Two strains of the silver fox (Vulpes vulpes, with markedly different behavioral phenotypes, have been developed by long-term selection for behavior. Foxes from the tame strain exhibit friendly behavior towards humans, paralleling the sociability of canine puppies, whereas foxes from the aggressive strain are defensive and exhibit aggression to humans. To understand the genetic differences underlying these behavioral phenotypes fox-specific genomic resources are needed. Results cDNA from mRNA from pre-frontal cortex of a tame and an aggressive fox was sequenced using the Roche 454 FLX Titanium platform (> 2.5 million reads & 0.9 Gbase of tame fox sequence; >3.3 million reads & 1.2 Gbase of aggressive fox sequence. Over 80% of the fox reads were assembled into contigs. Mapping fox reads against the fox transcriptome assembly and the dog genome identified over 30,000 high confidence fox-specific SNPs. Fox transcripts for approximately 14,000 genes were identified using SwissProt and the dog RefSeq databases. An at least 2-fold expression difference between the two samples (p Conclusions Transcriptome sequencing significantly expanded genomic resources available for the fox, a species without a sequenced genome. In a very cost efficient manner this yielded a large number of fox-specific SNP markers for genetic studies and provided significant insights into the gene expression profile of the fox pre-frontal cortex; expression differences between the two fox samples; and a catalogue of potentially important gene-specific sequence variants. This result demonstrates the utility of this approach for developing genomic resources in species with limited genomic information.

  3. Transcriptomic Analysis and Meta-Analysis of Human Granulosa and Cumulus Cells.

    Directory of Open Access Journals (Sweden)

    Tanja Burnik Papler

    Full Text Available Specific gene expression in oocytes and its surrounding cumulus (CC and granulosa (GC cells is needed for successful folliculogenesis and oocyte maturation. The aim of the present study was to compare genome-wide gene expression and biological functions of human GC and CC. Individual GC and CC were derived from 37 women undergoing IVF procedures. Gene expression analysis was performed using microarrays, followed by a meta-analysis. Results were validated using quantitative real-time PCR. There were 6029 differentially expressed genes (q < 10-4; of which 650 genes had a log2 FC ≥ 2. After the meta-analysis there were 3156 genes differentially expressed. Among these there were genes that have previously not been reported in human somatic follicular cells, like prokineticin 2 (PROK2, higher expressed in GC, and pregnancy up-regulated nonubiquitous CaM kinase (PNCK, higher expressed in CC. Pathways like inflammatory response and angiogenesis were enriched in GC, whereas in CC, cell differentiation and multicellular organismal development were among enriched pathways. In conclusion, transcriptomes of GC and CC as well as biological functions, are distinctive for each cell subpopulation. By describing novel genes like PROK2 and PNCK, expressed in GC and CC, we upgraded the existing data on human follicular biology.

  4. Transcriptomic profiles of human foreskin fibroblast cells in response to orf virus.

    Science.gov (United States)

    Chen, Daxiang; Long, Mingjian; Xiao, Bin; Xiong, Yufeng; Chen, Huiqin; Chen, Yu; Kuang, Zhenzhan; Li, Ming; Wu, Yingsong; Rock, Daniel L; Gong, Daoyuan; Wang, Yong; He, Haijian; Liu, Fang; Luo, Shuhong; Hao, Wenbo

    2017-08-29

    Orf virus has been utilized as a safe and efficient viral vector against not only diverse infectious diseases, but also against tumors. However, the nature of the genes triggered by the vector in human cells is poorly characterized. Using RNA sequencing technology, we compared specific changes in the transcriptomic profiles in human foreskin fibroblast cells following infection by the orf virus. The results indicated that orf virus upregulates or downregulates expression of a variety of genes, including genes involved in antiviral immune response, apoptosis, cell cycle and a series of signaling pathways, such as the IFN and p53-signaling pathways. The orf virus stimulates or inhibits immune gene expression such as chemokines, chemokine receptors, cytokines, cytokine receptors, and molecules involved in antigen uptake and processing after infection. Expression of pro-apoptotic genes increased at 8 hours post-infection. The p53 signaling pathway was activated to induce apoptosis at the same time. However, the cell cycle program was promoted after infection, which may be due to the immunomodulatory genes of the orf virus. This presents the first description of transcription profile changes in human foreskin fibroblast cells after orf virus infection and provides an in-depth analysis of the interaction between the host and orf virus. These data offer new insights into the understanding of the mechanisms of infection by orf virus and identify potential targets for future studies.

  5. The dormant and the fully competent oocyte: comparing the transcriptome of human oocytes from primordial follicles and in metaphase II

    DEFF Research Database (Denmark)

    Grøndahl, Marie Louise; Borup, Rehannah; Vikeså, Jonas

    2013-01-01

    Oocytes become enclosed in primordial follicles during fetal life and remain dormant there until activation followed by growth and meiotic resumption. Current knowledge about the molecular pathways involved in oogenesis is incomplete. This study identifies the specific transcriptome of the human...... oocyte in the quiescent state and at the pinnacle of maturity at ovulation. In silico bioinformatic comparisons were made between the transcriptome of human oocytes from dormant primordial follicles and that of human metaphase II (MII) oocytes and granulosa cells and unique gene expression profiles were...... identified as well as functional and pathway enrichments associated with the oocytes from the two developmental hallmarks. A total of 729 genes were highly enriched in oocytes from primodial follicles and 1456 genes were highly enriched in MII oocytes (>10-fold, P...

  6. Physical biology of human brain development

    Directory of Open Access Journals (Sweden)

    Silvia eBudday

    2015-07-01

    Full Text Available Neurodevelopment is a complex, dynamic process that involves a precisely orchestrated sequence of genetic, environmental, biochemical, and physical events. Developmental biology and genetics have shaped our understanding of the molecular and cellular mechanisms during neurodevelopment. Recent studies suggest that physical forces play a central role in translating these cellular mechanisms into the complex surface morphology of the human brain. However, the precise impact of neuronal differentiation, migration, and connection on the physical forces during cortical folding remains unknown. Here we review the cellular mechanisms of neurodevelopment with a view towards surface morphogenesis, pattern selection, and evolution of shape. We revisit cortical folding as the instability problem of constrained differential growth in a multi-layered system. To identify the contributing factors of differential growth, we map out the timeline of neurodevelopment in humans and highlight the cellular events associated with extreme radial and tangential expansion. We demonstrate how computational modeling of differential growth can bridge the scales-from phenomena on the cellular level towards form and function on the organ level-to make quantitative, personalized predictions. Physics-based models can quantify cortical stresses, identify critical folding conditions, rationalize pattern selection, and predict gyral wavelengths and gyrification indices. We illustrate that physical forces can explain cortical malformations as emergent properties of developmental disorders. Combining biology and physics holds promise to advance our understanding of human brain development and enable early diagnostics of cortical malformations with the ultimate goal to improve treatment of neurodevelopmental disorders including epilepsy, autism spectrum disorders, and schizophrenia.

  7. Loss of Brain Aerobic Glycolysis in Normal Human Aging.

    Science.gov (United States)

    Goyal, Manu S; Vlassenko, Andrei G; Blazey, Tyler M; Su, Yi; Couture, Lars E; Durbin, Tony J; Bateman, Randall J; Benzinger, Tammie L-S; Morris, John C; Raichle, Marcus E

    2017-08-01

    The normal aging human brain experiences global decreases in metabolism, but whether this affects the topography of brain metabolism is unknown. Here we describe PET-based measurements of brain glucose uptake, oxygen utilization, and blood flow in cognitively normal adults from 20 to 82 years of age. Age-related decreases in brain glucose uptake exceed that of oxygen use, resulting in loss of brain aerobic glycolysis (AG). Whereas the topographies of total brain glucose uptake, oxygen utilization, and blood flow remain largely stable with age, brain AG topography changes significantly. Brain regions with high AG in young adults show the greatest change, as do regions with prolonged developmental transcriptional features (i.e., neoteny). The normal aging human brain thus undergoes characteristic metabolic changes, largely driven by global loss and topographic changes in brain AG. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Transcriptome variations among human embryonic stem cell lines are associated with their differentiation propensity.

    Directory of Open Access Journals (Sweden)

    Changbin Sun

    Full Text Available Human embryonic stem cells (hESCs have the potential to form any cell type in the body, making them attractive cell sources in drug screening, regenerative medicine, disease and developmental processes modeling. However, not all hESC lines have the equal potency to generate desired cell types in vitro. Significant variations have been observed for the differentiation efficiency of various human ESC lines. The precise underpinning molecular mechanisms are still unclear. In this work, we compared transcriptome variations of four hESC lines H7, HUES1, HUES8 and HUES9. We found that hESC lines have different gene expression profiles, and these differentially expressed genes (DEGs are significantly enriched in developmental processes, such as ectodermal, mesodermal and endodermal development. The enrichment difference between hESC lines was consistent with its lineage bias. Among these DEGs, some pluripotency factors and genes involved in signaling transduction showed great variations as well. The pleiotropic functions of these genes in controlling hESC identity and early lineage specification, implicated that different hESC lines may utilize distinct balance mechanisms to maintain pluripotent state. When the balance is broken in a certain environment, gene expression variation between them could impact on their different lineage specification behavior.

  9. Transcriptomic Profiles of Brain Provide Insights into Molecular Mechanism of Feed Conversion Efficiency in Crucian Carp (Carassius auratus)

    Science.gov (United States)

    Pang, Meixia; Luo, Weiwei; Yu, Xiaomu; Zhou, Ying; Tong, Jingou

    2018-01-01

    Feed efficiency is an economically crucial trait for cultured animals, however, progress has been scarcely made in the genetic analyses of feed conversion efficiency (FCE) in fish because of the difficulties in measurement of trait phenotypes. In the present investigation, we present the first application of RNA sequencing (RNA-Seq) combined with differentially expressed genes (DEGs) analysis for identification of functional determinants related to FCE at the gene level in an aquaculture fish, crucian carp (Carassius auratus). Brain tissues of six crucian carp with extreme FCE performances were subjected to transcriptome analysis. A total of 544,612 unigenes with a mean size of 644.38 bp were obtained from Low- and High-FCE groups, and 246 DEGs that may be involved in FCE traits were identified in these two groups. qPCR confirmed that genes previously identified as up- or down-regulated by RNA-Seq were effectively up- or down-regulated under the studied conditions. Thirteen key genes, whose functions are associated with metabolism (Dgkk, Mgst3 and Guk1b), signal transduction (Vdnccsa1b, Tgfα, Nr4a1 and Tacr2) and growth (Endog, Crebrtc2, Myh7, Myh1, Myh14 and Igfbp7) were identified according to GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) annotations. Our novel findings provide useful pathway information and candidate genes for future studies of genetic mechanisms underlying FCE in crucian carp. PMID:29538345

  10. Transcriptomic Profiles of Brain Provide Insights into Molecular Mechanism of Feed Conversion Efficiency in Crucian Carp (Carassius auratus

    Directory of Open Access Journals (Sweden)

    Meixia Pang

    2018-03-01

    Full Text Available Feed efficiency is an economically crucial trait for cultured animals, however, progress has been scarcely made in the genetic analyses of feed conversion efficiency (FCE in fish because of the difficulties in measurement of trait phenotypes. In the present investigation, we present the first application of RNA sequencing (RNA-Seq combined with differentially expressed genes (DEGs analysis for identification of functional determinants related to FCE at the gene level in an aquaculture fish, crucian carp (Carassius auratus. Brain tissues of six crucian carp with extreme FCE performances were subjected to transcriptome analysis. A total of 544,612 unigenes with a mean size of 644.38 bp were obtained from Low- and High-FCE groups, and 246 DEGs that may be involved in FCE traits were identified in these two groups. qPCR confirmed that genes previously identified as up- or down-regulated by RNA-Seq were effectively up- or down-regulated under the studied conditions. Thirteen key genes, whose functions are associated with metabolism (Dgkk, Mgst3 and Guk1b, signal transduction (Vdnccsa1b, Tgfα, Nr4a1 and Tacr2 and growth (Endog, Crebrtc2, Myh7, Myh1, Myh14 and Igfbp7 were identified according to GO (Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes annotations. Our novel findings provide useful pathway information and candidate genes for future studies of genetic mechanisms underlying FCE in crucian carp.

  11. Hierarchical modularity in human brain functional networks

    Directory of Open Access Journals (Sweden)

    David Meunier

    2009-10-01

    Full Text Available The idea that complex systems have a hierarchical modular organization originates in the early 1960s and has recently attracted fresh support from quantitative studies of large scale, real-life networks. Here we investigate the hierarchical modular (or “modules-within-modules” decomposition of human brain functional networks, measured using functional magnetic resonance imaging (fMRI in 18 healthy volunteers under no-task or resting conditions. We used a customized template to extract networks with more than 1800 regional nodes, and we applied a fast algorithm to identify nested modular structure at several hierarchical levels. We used mutual information, 0 < I < 1, to estimate the similarity of community structure of networks in different subjects, and to identify the individual network that is most representative of the group. Results show that human brain functional networks have a hierarchical modular organization with a fair degree of similarity between subjects, I=0.63. The largest 5 modules at the highest level of the hierarchy were medial occipital, lateral occipital, central, parieto-frontal and fronto-temporal systems; occipital modules demonstrated less sub-modular organization than modules comprising regions of multimodal association cortex. Connector nodes and hubs, with a key role in inter-modular connectivity, were also concentrated in association cortical areas. We conclude that methods are available for hierarchical modular decomposition of large numbers of high resolution brain functional networks using computationally expedient algorithms. This could enable future investigations of Simon's original hypothesis that hierarchy or near-decomposability of physical symbol systems is a critical design feature for their fast adaptivity to changing environmental conditions.

  12. Distribution of melatonin receptor in human fetal brain

    Institute of Scientific and Technical Information of China (English)

    WANG Guo-quan; SHAO Fu-yuan; ZHAO Ying; LIU Zhi-min

    2001-01-01

    Objective: To study the distribution of 2 kinds of melatonin receptor subtypes (mtl and MT2) in human fetal brain. Methods: The fetal brain tissues were sliced and the distribution ofmelatonin receptors in human fetal brain were detected using immunohistochemistry and in situ hybridization. Results: Melatonin receptor mtl existed in the cerebellun and hypothalamus, melatonin receptor MT2 exists in hypothalamus, occipital and medulla. Conclusion: Two kinds of melatonin receptors, mtl and MT2 exist in the membrane and cytosol of brain cells, indicating that human fetal brain is a target organ of melatonin.

  13. Transcriptomics and proteomics analyses of the PACAP38 influenced ischemic brain in permanent middle cerebral artery occlusion model mice

    Directory of Open Access Journals (Sweden)

    Hori Motohide

    2012-11-01

    Full Text Available Abstract Introduction The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP is considered to be a potential therapeutic agent for prevention of cerebral ischemia. Ischemia is a most common cause of death after heart attack and cancer causing major negative social and economic consequences. This study was designed to investigate the effect of PACAP38 injection intracerebroventrically in a mouse model of permanent middle cerebral artery occlusion (PMCAO along with corresponding SHAM control that used 0.9% saline injection. Methods Ischemic and non-ischemic brain tissues were sampled at 6 and 24 hours post-treatment. Following behavioral analyses to confirm whether the ischemia has occurred, we investigated the genome-wide changes in gene and protein expression using DNA microarray chip (4x44K, Agilent and two-dimensional gel electrophoresis (2-DGE coupled with matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS, respectively. Western blotting and immunofluorescent staining were also used to further examine the identified protein factor. Results Our results revealed numerous changes in the transcriptome of ischemic hemisphere (ipsilateral treated with PACAP38 compared to the saline-injected SHAM control hemisphere (contralateral. Previously known (such as the interleukin family and novel (Gabra6, Crtam genes were identified under PACAP influence. In parallel, 2-DGE analysis revealed a highly expressed protein spot in the ischemic hemisphere that was identified as dihydropyrimidinase-related protein 2 (DPYL2. The DPYL2, also known as Crmp2, is a marker for the axonal growth and nerve development. Interestingly, PACAP treatment slightly increased its abundance (by 2-DGE and immunostaining at 6 h but not at 24 h in the ischemic hemisphere, suggesting PACAP activates neuronal defense mechanism early on. Conclusions This study provides a detailed inventory of PACAP influenced gene expressions

  14. High-resolution temporal and regional mapping of MAPT expression and splicing in human brain development.

    Science.gov (United States)

    Hefti, Marco M; Farrell, Kurt; Kim, SoongHo; Bowles, Kathryn R; Fowkes, Mary E; Raj, Towfique; Crary, John F

    2018-01-01

    The microtubule associated protein tau plays a critical role in the pathogenesis of neurodegenerative disease. Recent studies suggest that tau also plays a role in disorders of neuronal connectivity, including epilepsy and post-traumatic stress disorder. Animal studies have shown that the MAPT gene, which codes for the tau protein, undergoes complex pre-mRNA alternative splicing to produce multiple isoforms during brain development. Human data, particularly on temporal and regional variation in tau splicing during development are however lacking. In this study, we present the first detailed examination of the temporal and regional sequence of MAPT alternative splicing in the developing human brain. We used a novel computational analysis of large transcriptomic datasets (total n = 502 patients), quantitative polymerase chain reaction (qPCR) and western blotting to examine tau expression and splicing in post-mortem human fetal, pediatric and adult brains. We found that MAPT exons 2 and 10 undergo abrupt shifts in expression during the perinatal period that are unique in the canonical human microtubule-associated protein family, while exon 3 showed small but significant temporal variation. Tau isoform expression may be a marker of neuronal maturation, temporally correlated with the onset of axonal growth. Immature brain regions such as the ganglionic eminence and rhombic lip had very low tau expression, but within more mature regions, there was little variation in tau expression or splicing. We thus demonstrate an abrupt, evolutionarily conserved shift in tau isoform expression during the human perinatal period that may be due to tau expression in maturing neurons. Alternative splicing of the MAPT pre-mRNA may play a vital role in normal brain development across multiple species and provides a basis for future investigations into the developmental and pathological functions of the tau protein.

  15. [Neuroethics: Ethical Endowments of Human Brain].

    Science.gov (United States)

    López Moratalla, Natalia

    2015-01-01

    The neurobiological processes underlying moral judgement have been the focus of Neuroethics. Neurosciences demonstrate which cerebral areas are active and inactive whilst people decide how to act when facing a moral dilemma; in this way we know the correlation between determined cerebral areas and our human acts. We can explain how the ″ethical endowments″ of each person, common to all human beings, is ″embedded″ in the dynamic of cerebral flows. Of central interest is whether emotions play a causal role in moral judgement, and, in parallel, how emotion related areas of the brain contribute to moral judgement. The outcome of man's natural inclinations is on one hand linked to instinctive systems of animal survival and to basic emotions, and on the other, to the life of each individual human uninhibited by automatism of the biological laws, because he is governed by the laws of freedom. The capacity to formulate an ethical judgement is an innate asset of the human mind.

  16. Linking Genes and Brain Development of Honeybee Workers: A Whole-Transcriptome Approach

    OpenAIRE

    Vleurinck, Christina; Raub, Stephan; Sturgill, David; Oliver, Brian; Beye, Martin

    2016-01-01

    Honeybees live in complex societies whose capabilities far exceed those of the sum of their single members. This social synergism is achieved mainly by the worker bees, which form a female caste. The worker bees display diverse collaborative behaviors and engage in different behavioral tasks, which are controlled by the central nervous system (CNS). The development of the worker brain is determined by the female sex and the worker caste determination signal. Here, we report on genes that are ...

  17. DNA microarray unravels rapid changes in transcriptome of MK-801 treated rat brain

    Science.gov (United States)

    Kobayashi, Yuka; Kulikova, Sofya P; Shibato, Junko; Rakwal, Randeep; Satoh, Hiroyuki; Pinault, Didier; Masuo, Yoshinori

    2015-01-01

    AIM: To investigate the impact of MK-801 on gene expression patterns genome wide in rat brain regions. METHODS: Rats were treated with an intraperitoneal injection of MK-801 [0.08 (low-dose) and 0.16 (high-dose) mg/kg] or NaCl (vehicle control). In a first series of experiment, the frontoparietal electrocorticogram was recorded 15 min before and 60 min after injection. In a second series of experiments, the whole brain of each animal was rapidly removed at 40 min post-injection, and different regions were separated: amygdala, cerebral cortex, hippocampus, hypothalamus, midbrain and ventral striatum on ice followed by DNA microarray (4 × 44 K whole rat genome chip) analysis. RESULTS: Spectral analysis revealed that a single systemic injection of MK-801 significantly and selectively augmented the power of baseline gamma frequency (30-80 Hz) oscillations in the frontoparietal electroencephalogram. DNA microarray analysis showed the largest number (up- and down- regulations) of gene expressions in the cerebral cortex (378), midbrain (376), hippocampus (375), ventral striatum (353), amygdala (301), and hypothalamus (201) under low-dose (0.08 mg/kg) of MK-801. Under high-dose (0.16 mg/kg), ventral striatum (811) showed the largest number of gene expression changes. Gene expression changes were functionally categorized to reveal expression of genes and function varies with each brain region. CONCLUSION: Acute MK-801 treatment increases synchrony of baseline gamma oscillations, and causes very early changes in gene expressions in six individual rat brain regions, a first report. PMID:26629322

  18. Comparative brain transcriptomic analyses of scouting across distinct behavioural and ecological contexts in honeybees

    Science.gov (United States)

    Liang, Zhengzheng S.; Mattila, Heather R.; Rodriguez-Zas, Sandra L.; Southey, Bruce R.; Seeley, Thomas D.; Robinson, Gene E.

    2014-01-01

    Individual differences in behaviour are often consistent across time and contexts, but it is not clear whether such consistency is reflected at the molecular level. We explored this issue by studying scouting in honeybees in two different behavioural and ecological contexts: finding new sources of floral food resources and finding a new nest site. Brain gene expression profiles in food-source and nest-site scouts showed a significant overlap, despite large expression differences associated with the two different contexts. Class prediction and ‘leave-one-out’ cross-validation analyses revealed that a bee's role as a scout in either context could be predicted with 92.5% success using 89 genes at minimum. We also found that genes related to four neurotransmitter systems were part of a shared brain molecular signature in both types of scouts, and the two types of scouts were more similar for genes related to glutamate and GABA than catecholamine or acetylcholine signalling. These results indicate that consistent behavioural tendencies across different ecological contexts involve a mixture of similarities and differences in brain gene expression. PMID:25355476

  19. Transcriptomic analysis of human polarized macrophages: more than one role of alternative activation?

    Directory of Open Access Journals (Sweden)

    Eleonora Derlindati

    Full Text Available Macrophages are a heterogeneous cell population which in response to the cytokine milieu polarize in either classically activated macrophages (M1 or alternatively activated macrophages (M2. This plasticity makes macrophages essential in regulating inflammation, immune response and tissue remodeling and a novel therapeutic target in inflammatory diseases such as atherosclerosis. The aim of the study was to describe the transcriptomic profiles of differently polarized human macrophages to generate new hypotheses on the biological function of the different macrophage subtypes.Polarization of circulating monocytes/macrophages of blood donors was induced in vitro by IFN-γ and LPS (M1, by IL-4 (M2a, and by IL-10 (M2c. Unstimulated cells (RM served as time controls. Gene expression profile of M1, M2a, M2c and RM was assessed at 6, 12 and 24h after polarization with Whole Human Genome Agilent Microarray technique. When compared to RM, M1 significantly upregulated pathways involved in immunity and inflammation, whereas M2a did the opposite. Conversely, decreased and increased expression of mitochondrial metabolism, consistent with insulin resistant and insulin sensitive patterns, was seen in M1 and M2a, respectively. The time sequence in the expression of some pathways appeared to have some specific bearing on M1 function. Finally, canonical and non-canonical Wnt genes and gene groups, promoting inflammation and tissue remodeling, were upregulated in M2a compared to RM.Our data in in vitro polarized human macrophages: 1. confirm and extend known inflammatory and anti-inflammatory gene expression patterns; 2. demonstrate changes in mitochondrial metabolism associated to insulin resistance and insulin sensitivity in M1 and M2a, respectively; 3. highlight the potential relevance of gene expression timing in M1 function; 4. unveil enhanced expression of Wnt pathways in M2a suggesting a potential dual (pro-inflammatory and anti-inflammatory role of M2a in

  20. Left Brain to Right Brain: Notes from the Human Laboratory.

    Science.gov (United States)

    Baumli, Francis

    1982-01-01

    Examines the implications of the left brain-right brain theory on communications styles in male-female relationships. The author contends that women tend to use the vagueness of their emotional responses manipulatively. Men need to apply rational approaches to increase clarity in communication. (AM)

  1. A systematically improved high quality genome and transcriptome of the human blood fluke Schistosoma mansoni.

    Directory of Open Access Journals (Sweden)

    Anna V Protasio

    2012-01-01

    Full Text Available Schistosomiasis is one of the most prevalent parasitic diseases, affecting millions of people in developing countries. Amongst the human-infective species, Schistosoma mansoni is also the most commonly used in the laboratory and here we present the systematic improvement of its draft genome. We used Sanger capillary and deep-coverage Illumina sequencing from clonal worms to upgrade the highly fragmented draft 380 Mb genome to one with only 885 scaffolds and more than 81% of the bases organised into chromosomes. We have also used transcriptome sequencing (RNA-seq from four time points in the parasite's life cycle to refine gene predictions and profile their expression. More than 45% of predicted genes have been extensively modified and the total number has been reduced from 11,807 to 10,852. Using the new version of the genome, we identified trans-splicing events occurring in at least 11% of genes and identified clear cases where it is used to resolve polycistronic transcripts. We have produced a high-resolution map of temporal changes in expression for 9,535 genes, covering an unprecedented dynamic range for this organism. All of these data have been consolidated into a searchable format within the GeneDB (www.genedb.org and SchistoDB (www.schistodb.net databases. With further transcriptional profiling and genome sequencing increasingly accessible, the upgraded genome will form a fundamental dataset to underpin further advances in schistosome research.

  2. The Peripheral Whole Blood Transcriptome of Acute Pyelonephritis in Human Pregnancy

    Science.gov (United States)

    Madan, Ichchha; Than, Nandor Gabor; Romero, Roberto; Chaemsaithong, Piya; Miranda, Jezid; Tarca, Adi L.; Bhatti, Gaurav; Draghici, Sorin; Yeo, Lami; Mazor, Moshe; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn

    2018-01-01

    Objective Human pregnancy is characterized by activation of the innate immune response and suppression of adaptive immunity. The former is thought to provide protection against infection to the mother, and the latter, tolerance against paternal antigens expressed in fetal cells. Acute pyelonephritis is associated with an increased risk of acute respiratory distress syndrome and sepsis in pregnant (vs. nonpregnant) women. The objective of this study was to describe the gene expression profile (transcriptome) of maternal whole blood in acute pyelonephritis. Method A case-control study was conducted to include pregnant women with acute pyelonephritis (n=15) and women with a normal pregnancy (n=34). Affymetrix HG-U133 Plus 2.0 arrays (Affymetrix, Santa Clara, CA, USA) were used for gene expression profiling. A linear model was used to test the association between the presence of pyelonephritis and gene expression levels while controlling for white blood cell count and gestational age. A fold change of 1.5 was considered significant at a false discovery rate of 0.1. A subset of differentially expressed genes (n=56) was tested with real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) (cases, n=19; controls, n=59). Gene ontology and pathway analysis were applied. Results A total of 983 genes were differentially expressed in acute pyelonephritis: 457 were up-regulated and 526 were down-regulated. Significant enrichment of 300 biological processes and 63 molecular functions was found in pyelonephritis. Significantly impacted pathways in pyelonephritis included a) cytokine-cytokine receptor interaction; b) T-cell receptor signaling; c) Jak-STAT signaling; and d) complement and coagulation cascades. Of 56 genes tested by qRT-PCR, 48 (85.7%) had confirmation of differential expression. Conclusion This is the first study of the transcriptomic signature of whole blood in pregnant women with acute pyelonephritis. Acute infection during pregnancy is

  3. Thresholding magnetic resonance images of human brain

    Institute of Scientific and Technical Information of China (English)

    Qing-mao HU; Wieslaw L NOWINSKI

    2005-01-01

    In this paper, methods are proposed and validated to determine low and high thresholds to segment out gray matter and white matter for MR images of different pulse sequences of human brain. First, a two-dimensional reference image is determined to represent the intensity characteristics of the original three-dimensional data. Then a region of interest of the reference image is determined where brain tissues are present. The non-supervised fuzzy c-means clustering is employed to determine: the threshold for obtaining head mask, the low threshold for T2-weighted and PD-weighted images, and the high threshold for T1-weighted, SPGR and FLAIR images. Supervised range-constrained thresholding is employed to determine the low threshold for T1-weighted, SPGR and FLAIR images. Thresholding based on pairs of boundary pixels is proposed to determine the high threshold for T2- and PD-weighted images. Quantification against public data sets with various noise and inhomogeneity levels shows that the proposed methods can yield segmentation robust to noise and intensity inhomogeneity. Qualitatively the proposed methods work well with real clinical data.

  4. Neocortical glial cell numbers in human brains

    DEFF Research Database (Denmark)

    Pelvig, D.P.; Pakkenberg, H.; Stark, A.K.

    2008-01-01

    Stereological cell counting was applied to post-mortem neocortices of human brains from 31 normal individuals, age 18-93 years, 18 females (average age 65 years, range 18-93) and 13 males (average age 57 years, range 19-87). The cells were differentiated in astrocytes, oligodendrocytes, microglia...... while the total astrocyte number is constant through life; finally males have a 28% higher number of neocortical glial cells and a 19% higher neocortical neuron number than females. The overall total number of neocortical neurons and glial cells was 49.3 billion in females and 65.2 billion in males...... and neurons and counting were done in each of the four lobes. The study showed that the different subpopulations of glial cells behave differently as a function of age; the number of oligodendrocytes showed a significant 27% decrease over adult life and a strong correlation to the total number of neurons...

  5. Transcriptome analysis of amoeboid and ramified microglia isolated from the corpus callosum of rat brain

    Directory of Open Access Journals (Sweden)

    Parakalan Rangarajan

    2012-06-01

    Full Text Available Abstract Background Microglia, the resident immune cells of the central nervous system (CNS, have two distinct phenotypes in the developing brain: amoeboid form, known to be amoeboid microglial cells (AMC and ramified form, known to be ramified microglial cells (RMC. The AMC are characterized by being proliferative, phagocytic and migratory whereas the RMC are quiescent and exhibit a slow turnover rate. The AMC transform into RMC with advancing age, and this transformation is indicative of the gradual shift in the microglial functions. Both AMC and RMC respond to CNS inflammation, and they become hypertrophic when activated by trauma, infection or neurodegenerative stimuli. The molecular mechanisms and functional significance of morphological transformation of microglia during normal development and in disease conditions is not clear. It is hypothesized that AMC and RMC are functionally regulated by a specific set of genes encoding various signaling molecules and transcription factors. Results To address this, we carried out cDNA microarray analysis using lectin-labeled AMC and RMC isolated from frozen tissue sections of the corpus callosum of 5-day and 4-week old rat brain respectively, by laser capture microdissection. The global gene expression profiles of both microglial phenotypes were compared and the differentially expressed genes in AMC and RMC were clustered based on their functional annotations. This genome wide comparative analysis identified genes that are specific to AMC and RMC. Conclusions The novel and specific molecules identified from the trancriptome explains the quiescent state functioning of microglia in its two distinct morphological states.

  6. "Messing with the Mind: Evolutionary Challenges to Human Brain Augmentation

    Directory of Open Access Journals (Sweden)

    ARTHUR eSANIOTIS

    2014-09-01

    Full Text Available The issue of brain augmentation has received considerable scientific attention over the last two decades. A key factor to brain augmentation that has been widely overlooked are the complex evolutionary processes which have taken place in evolving the human brain to its current state of functioning. Like other bodily organs, the human brain has been subject to the forces of biological adaptation. The structure and function of the brain, is very complex and only now we are beginning to understand some of the basic concepts of cognition. Therefore, this article proposes that brain-machine interfacing and nootropics are not going to produce augmented brains because we do not understand enough about how evolutionary pressures have informed the neural networks which support human cognitive faculties.

  7. From reverse transcription to human brain tumors

    Directory of Open Access Journals (Sweden)

    Dmitrenko V. V.

    2013-05-01

    Full Text Available Reverse transcriptase from avian myeloblastosis virus (AMV was the subject of the study, from which the investi- gations of the Department of biosynthesis of nucleic acids were started. Production of AMV in grams quantities and isolation of AMV reverse transcriptase were established in the laboratory during the seventies of the past cen- tury and this initiated research on the cDNA synthesis, cloning and investigation of the structure and functions of the eukaryotic genes. Structures of salmon insulin and insulin-like growth factor (IGF family genes and their transcripts were determined during long-term investigations. Results of two modern techniques, microarray-ba- sed hybridization and SAGE, were used for the identification of the genes differentially expressed in astrocytic gliomas and human normal brain. Comparison of SAGE results on the genes overexpressed in glioblastoma with the results of microarray analysis revealed a limited number of common genes. 105 differentially expressed genes, common to both methods, can be included in the list of candidates for the molecular typing of glioblastoma. The first experiments on the classification of glioblastomas based on the data of the 20 genes expression were conducted by using of artificial neural network analysis. The results of these experiments showed that the expression profiles of these genes in 224 glioblastoma samples and 74 normal brain samples could be according to the Koho- nen’s maps. The CHI3L1 and CHI3L2 genes of chitinase-like cartilage protein were revealed among the most overexpressed genes in glioblastoma, which could have prognostic and diagnostic potential. Results of in vitro experiments demonstrated that both proteins, CHI3L1 and CHI3L2, may initiate the phosphorylation of ERK1/ ERK2 and AKT kinases leading to the activation of MAPK/ERK1/2 and PI3K/AKT signaling cascades in human embryonic kidney 293 cells, human glioblastoma U87MG, and U373 cells. The new human cell line

  8. Transcriptomic analysis of human retinal detachment reveals both inflammatory response and photoreceptor death.

    Directory of Open Access Journals (Sweden)

    Marie-Noëlle Delyfer

    Full Text Available BACKGROUND: Retinal detachment often leads to a severe and permanent loss of vision and its therapeutic management remains to this day exclusively surgical. We have used surgical specimens to perform a differential analysis of the transcriptome of human retinal tissues following detachment in order to identify new potential pharmacological targets that could be used in combination with surgery to further improve final outcome. METHODOLOGY/PRINCIPAL FINDINGS: Statistical analysis reveals major involvement of the immune response in the disease. Interestingly, using a novel approach relying on coordinated expression, the interindividual variation was monitored to unravel a second crucial aspect of the pathological process: the death of photoreceptor cells. Within the genes identified, the expression of the major histocompatibility complex I gene HLA-C enables diagnosis of the disease, while PKD2L1 and SLCO4A1 -which are both down-regulated- act synergistically to provide an estimate of the duration of the retinal detachment process. Our analysis thus reveals the two complementary cellular and molecular aspects linked to retinal detachment: an immune response and the degeneration of photoreceptor cells. We also reveal that the human specimens have a higher clinical value as compared to artificial models that point to IL6 and oxidative stress, not implicated in the surgical specimens studied here. CONCLUSIONS/SIGNIFICANCE: This systematic analysis confirmed the occurrence of both neurodegeneration and inflammation during retinal detachment, and further identifies precisely the modification of expression of the different genes implicated in these two phenomena. Our data henceforth give a new insight into the disease process and provide a rationale for therapeutic strategies aimed at limiting inflammation and photoreceptor damage associated with retinal detachment and, in turn, improving visual prognosis after retinal surgery.

  9. 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

    2016-08-26

    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.

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

    Directory of Open Access Journals (Sweden)

    Pingping Wang

    2016-08-01

    Full Text Available 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.

  11. Sex differences in brain organization: implications for human communication.

    Science.gov (United States)

    Hanske-Petitpierre, V; Chen, A C

    1985-12-01

    This article reviews current knowledge in two major research domains: sex differences in neuropsychophysiology, and in human communication. An attempt was made to integrate knowledge from several areas of brain research with human communication and to clarify how such a cooperative effort may be beneficial to both fields of study. By combining findings from the area of brain research, a communication paradigm was developed which contends that brain-related sex differences may reside largely in the area of communication of emotion.

  12. Lipidomics of human brain aging and Alzheimer's disease pathology.

    Science.gov (United States)

    Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

    2015-01-01

    Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context. © 2015 Elsevier Inc. All rights reserved.

  13. Neocortical glial cell numbers in human brains.

    Science.gov (United States)

    Pelvig, D P; Pakkenberg, H; Stark, A K; Pakkenberg, B

    2008-11-01

    Stereological cell counting was applied to post-mortem neocortices of human brains from 31 normal individuals, age 18-93 years, 18 females (average age 65 years, range 18-93) and 13 males (average age 57 years, range 19-87). The cells were differentiated in astrocytes, oligodendrocytes, microglia and neurons and counting were done in each of the four lobes. The study showed that the different subpopulations of glial cells behave differently as a function of age; the number of oligodendrocytes showed a significant 27% decrease over adult life and a strong correlation to the total number of neurons while the total astrocyte number is constant through life; finally males have a 28% higher number of neocortical glial cells and a 19% higher neocortical neuron number than females. The overall total number of neocortical neurons and glial cells was 49.3 billion in females and 65.2 billion in males, a difference of 24% with a high biological variance. These numbers can serve as reference values in quantitative studies of the human neocortex.

  14. Macroscopic networks in the human brain: mapping connectivity in healthy and damaged brains

    NARCIS (Netherlands)

    Nijhuis, E.H.J.

    2013-01-01

    The human brain contains a network of interconnected neurons. Recent advances in functional and structural in-vivo magnetic resonance neuroimaging (MRI) techniques have provided opportunities to model the networks of the human brain on a macroscopic scale. This dissertation investigates the

  15. A Culture-Behavior-Brain Loop Model of Human Development.

    Science.gov (United States)

    Han, Shihui; Ma, Yina

    2015-11-01

    Increasing evidence suggests that cultural influences on brain activity are associated with multiple cognitive and affective processes. These findings prompt an integrative framework to account for dynamic interactions between culture, behavior, and the brain. We put forward a culture-behavior-brain (CBB) loop model of human development that proposes that culture shapes the brain by contextualizing behavior, and the brain fits and modifies culture via behavioral influences. Genes provide a fundamental basis for, and interact with, the CBB loop at both individual and population levels. The CBB loop model advances our understanding of the dynamic relationships between culture, behavior, and the brain, which are crucial for human phylogeny and ontogeny. Future brain changes due to cultural influences are discussed based on the CBB loop model. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Correspondence regarding "Effect of active smoking on the human bronchial epithelium transcriptome"

    Directory of Open Access Journals (Sweden)

    Zuyderduyn Scott D

    2009-02-01

    Full Text Available Abstract Background In the work of Chari et al. entitled "Effect of active smoking on the human bronchial epithelium transcriptome" the authors use SAGE to identify candidate gene expression changes in bronchial brushings from never, former, and current smokers. These gene expression changes are categorized into those that are reversible or irreversible upon smoking cessation. A subset of these identified genes is validated on an independent cohort using RT-PCR. The authors conclude that their results support the notion of gene expression changes in the lungs of smokers which persist even after an individual has quit. Results This correspondence raises questions about the validity of the approach used by the authors to analyze their data. The majority of the reported results suffer deficiencies due to the methods used. The most fundamental of these are explained in detail: biases introduced during data processing, lack of correction for multiple testing, and an incorrect use of clustering for gene discovery. A randomly generated "null" dataset is used to show the consequences of these shortcomings. Conclusion Most of Chari et al.'s findings are consistent with what would be expected by chance alone. Although there is clear evidence of reversible changes in gene expression, the majority of those identified appear to be false positives. However, contrary to the authors' claims, no irreversible changes were identified. There is a broad consensus that genetic change due to smoking persists once an individual has quit smoking; unfortunately, this study lacks sufficient scientific rigour to support or refute this hypothesis or identify any specific candidate genes. The pitfalls of large-scale analysis, as exemplified here, may not be unique to Chari et al.

  17. Lifetime stress cumulatively programs brain transcriptome and impedes stroke recovery: benefit of sensory stimulation.

    Directory of Open Access Journals (Sweden)

    Fabíola C R Zucchi

    Full Text Available Prenatal stress (PS represents a critical variable affecting lifetime health trajectories, metabolic and vascular functions. Beneficial experiences may attenuate the effects of PS and its programming of health outcomes in later life. Here we investigated in a rat model (1 if PS modulates recovery following cortical ischemia in adulthood; (2 if a second hit by adult stress (AS exaggerates stress responses and ischemic damage; and (3 if tactile stimulation (TS attenuates the cumulative effects of PS and AS. Prenatally stressed and non-stressed adult male rats underwent focal ischemic motor cortex lesion and were tested in skilled reaching and skilled walking tasks. Two groups of rats experienced recurrent restraint stress in adulthood and one of these groups also underwent daily TS therapy. Animals that experienced both PS and AS displayed the most severe motor disabilities after lesion. By contrast, TS promoted recovery from ischemic lesion and reduced hypothalamic-pituitary-adrenal axis activity. The data also showed that cumulative effects of adverse and beneficial lifespan experiences interact with disease outcomes and brain plasticity through the modulation of gene expression. Microarray analysis of the lesion motor cortex revealed that cumulative PS and AS interact with genes related to growth factors and transcription factors, which were not affected by PS or lesion alone. TS in PS+AS animals reverted these changes, suggesting a critical role for these factors in activity-dependent motor cortical reorganization after ischemic lesion. These findings suggest that beneficial experience later in life can moderate adverse consequences of early programming to improve cerebrovascular health.

  18. Human brain networks function in connectome-specific harmonic waves.

    Science.gov (United States)

    Atasoy, Selen; Donnelly, Isaac; Pearson, Joel

    2016-01-21

    A key characteristic of human brain activity is coherent, spatially distributed oscillations forming behaviour-dependent brain networks. However, a fundamental principle underlying these networks remains unknown. Here we report that functional networks of the human brain are predicted by harmonic patterns, ubiquitous throughout nature, steered by the anatomy of the human cerebral cortex, the human connectome. We introduce a new technique extending the Fourier basis to the human connectome. In this new frequency-specific representation of cortical activity, that we call 'connectome harmonics', oscillatory networks of the human brain at rest match harmonic wave patterns of certain frequencies. We demonstrate a neural mechanism behind the self-organization of connectome harmonics with a continuous neural field model of excitatory-inhibitory interactions on the connectome. Remarkably, the critical relation between the neural field patterns and the delicate excitation-inhibition balance fits the neurophysiological changes observed during the loss and recovery of consciousness.

  19. Mapping human whole-brain structural networks with diffusion MRI.

    Directory of Open Access Journals (Sweden)

    Patric Hagmann

    Full Text Available Understanding the large-scale structural network formed by neurons is a major challenge in system neuroscience. A detailed connectivity map covering the entire brain would therefore be of great value. Based on diffusion MRI, we propose an efficient methodology to generate large, comprehensive and individual white matter connectional datasets of the living or dead, human or animal brain. This non-invasive tool enables us to study the basic and potentially complex network properties of the entire brain. For two human subjects we find that their individual brain networks have an exponential node degree distribution and that their global organization is in the form of a small world.

  20. Analysis of brain CT on 120 patients of human cysticercosis

    International Nuclear Information System (INIS)

    Ma, J.; To, R.; Ri, T.; Ra, S.; Inomata, Taiten; Ogawa, Yasuhiro; Maeda, Tomoo.

    1990-01-01

    A study on brain CT was made in 120 patients of human cysticercosis, which is a rare disease in Japan and clinical symptoms and laboratory data for the diagnosis were also discussed. From the point of therapeutic view, we proposed a new differentiation on brain CT of human cysticercosis, which is divided into two groups according to the alve or dead parasite. Furthermore, we proposed a new type named multiple large and small cysts type on brain CT. The idea of diagnostic standard was made integrating brain CT image, clinical symptoms and labolatory data. (author)

  1. The progress of radiosensitive genes of human brain glioma

    International Nuclear Information System (INIS)

    Wang Xi; Liu Qiang

    2008-01-01

    Human gliomas are one of the most aggressive tumors in brain which grow infiltrativly. Surgery is the mainstay of treatment. But as the tumor could not be entirely cut off, it is easy to relapse. Radiotherapy plays an important role for patients with gliomas after surgery. The efficacy of radiotherapy is associated with radio sensitivity of human gliomas. This paper makes a summary of current situation and progress for radiosensitive genes of human brain gliomas. (authors)

  2. From Brain-Environment Connections to Temporal Dynamics and Social Interaction: Principles of Human Brain Function.

    Science.gov (United States)

    Hari, Riitta

    2017-06-07

    Experimental data about brain function accumulate faster than does our understanding of how the brain works. To tackle some general principles at the grain level of behavior, I start from the omnipresent brain-environment connection that forces regularities of the physical world to shape the brain. Based on top-down processing, added by sparse sensory information, people are able to form individual "caricature worlds," which are similar enough to be shared among other people and which allow quick and purposeful reactions to abrupt changes. Temporal dynamics and social interaction in natural environments serve as further essential organizing principles of human brain function. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Toward discovery science of human brain function

    DEFF Research Database (Denmark)

    Biswal, Bharat B; Mennes, Maarten; Zuo, Xi-Nian

    2010-01-01

    Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints...... individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain-behavior relationships...... in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/....

  4. Astrocyte calcium signal and gliotransmission in human brain tissue.

    Science.gov (United States)

    Navarrete, Marta; Perea, Gertrudis; Maglio, Laura; Pastor, Jesús; García de Sola, Rafael; Araque, Alfonso

    2013-05-01

    Brain function is recognized to rely on neuronal activity and signaling processes between neurons, whereas astrocytes are generally considered to play supportive roles for proper neuronal function. However, accumulating evidence indicates that astrocytes sense and control neuronal and synaptic activity, indicating that neuron and astrocytes reciprocally communicate. While this evidence has been obtained in experimental animal models, whether this bidirectional signaling between astrocytes and neurons occurs in human brain remains unknown. We have investigated the existence of astrocyte-neuron communication in human brain tissue, using electrophysiological and Ca(2+) imaging techniques in slices of the cortex and hippocampus obtained from biopsies from epileptic patients. Cortical and hippocampal human astrocytes displayed spontaneous Ca(2+) elevations that were independent of neuronal activity. Local application of transmitter receptor agonists or nerve electrical stimulation transiently elevated Ca(2+) in astrocytes, indicating that human astrocytes detect synaptic activity and respond to synaptically released neurotransmitters, suggesting the existence of neuron-to-astrocyte communication in human brain tissue. Electrophysiological recordings in neurons revealed the presence of slow inward currents (SICs) mediated by NMDA receptor activation. The frequency of SICs increased after local application of ATP that elevated astrocyte Ca(2+). Therefore, human astrocytes are able to release the gliotransmitter glutamate, which affect neuronal excitability through activation of NMDA receptors in neurons. These results reveal the existence of reciprocal signaling between neurons and astrocytes in human brain tissue, indicating that astrocytes are relevant in human neurophysiology and are involved in human brain function.

  5. Brain-Computer Interface Controlled Cyborg: Establishing a Functional Information Transfer Pathway from Human Brain to Cockroach Brain.

    Science.gov (United States)

    Li, Guangye; Zhang, Dingguo

    2016-01-01

    An all-chain-wireless brain-to-brain system (BTBS), which enabled motion control of a cyborg cockroach via human brain, was developed in this work. Steady-state visual evoked potential (SSVEP) based brain-computer interface (BCI) was used in this system for recognizing human motion intention and an optimization algorithm was proposed in SSVEP to improve online performance of the BCI. The cyborg cockroach was developed by surgically integrating a portable microstimulator that could generate invasive electrical nerve stimulation. Through Bluetooth communication, specific electrical pulse trains could be triggered from the microstimulator by BCI commands and were sent through the antenna nerve to stimulate the brain of cockroach. Serial experiments were designed and conducted to test overall performance of the BTBS with six human subjects and three cockroaches. The experimental results showed that the online classification accuracy of three-mode BCI increased from 72.86% to 78.56% by 5.70% using the optimization algorithm and the mean response accuracy of the cyborgs using this system reached 89.5%. Moreover, the results also showed that the cyborg could be navigated by the human brain to complete walking along an S-shape track with the success rate of about 20%, suggesting the proposed BTBS established a feasible functional information transfer pathway from the human brain to the cockroach brain.

  6. Toward Developmental Connectomics of the Human Brain

    OpenAIRE

    Cao, Miao; Huang, Hao; Peng, Yun; Dong, Qi; He, Yong

    2016-01-01

    Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying structural and functional connectivity patterns of the developing brain. Normal brain development is characterized by continuous and significant network evolution throughout infancy, childhood, and adolescence, following specific maturational patterns. Disruption of these normal changes is associated with neuropsychiatric developmental disorders, such as autism spectrum disorder...

  7. Towards Developmental Connectomics of the Human Brain

    OpenAIRE

    Miao eCao; Hao eHuang; Hao eHuang; Yun ePeng; Qi eDong; Yong eHe

    2016-01-01

    Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying structural and functional connectivity patterns of the developing brain. Normal brain development is characterized by continuous and significant network evolution throughout infancy, childhood and adolescence, following specific maturational patterns. Disruption of these normal changes is associated with neuropsychiatric developmental disorders, such as autism spectrum disorders...

  8. The Complex Functioning of the Human Brain: The Two Hemispheres

    Directory of Open Access Journals (Sweden)

    Iulia Cristina Timofti

    2010-04-01

    Full Text Available The present study reveals just a glimpse of the possible functions and reactions that the human brain can have. I considered as good examples different situations characteristic both of a normal person and a split-brain one. These situations prove that the brain, although divided in two, works as a unit, as an amazing computer that has data processing as a main goal.

  9. Neuroglobin and Cytoglobin expression in the human brain

    DEFF Research Database (Denmark)

    Hundahl, Christian Ansgar; Kelsen, Jesper; Hay-Schmidt, Anders

    2013-01-01

    Neuroglobin and Cytoglobin are new members of the heme-globin family. Both globins are primarily expressed in neurons of the brain and retina. Neuroglobin and Cytoglobin have been suggested as novel therapeutic targets in various neurodegenerative diseases based on their oxygen binding and cell...... protecting properties. However, findings in Neuroglobin-deficient mice question the endogenous neuroprotective properties. The expression pattern of Neuroglobin and Cytoglobin in the rodent brain is also in contradiction to a major role of neuronal protection. In a recent study, Neuroglobin was ubiquitously...... expressed and up-regulated following stroke in the human brain. The present study aimed at confirming our previous observations in rodents using two post-mortem human brains. The anatomical localization of Neuroglobin and Cytoglobin in the human brain is much like what has been described for the rodent...

  10. An in-depth comparison of the porcine, murine and human inflammasomes; lessons from the porcine genome and transcriptome.

    Science.gov (United States)

    Dawson, Harry D; Smith, Allen D; Chen, Celine; Urban, Joseph F

    2017-04-01

    Emerging evidence suggests that swine are a scientifically acceptable intermediate species between rodents and humans to model immune function relevant to humans. The swine genome has recently been sequenced and several preliminary structural and functional analysis of the porcine immunome have been published. Herein we provide an expanded in silico analysis using an improved assembly of the porcine transcriptome that provides an in depth analysis of genes that are related to inflammasomes, responses to Toll-like receptor ligands, and M1 macrophage polarization and Escherichia coli as a model organism. Comparisons of the expansion or contraction of orthologous gene families indicated more similar rates and classes of genes in humans and pigs than in mice; however several novel porcine or artiodactyl-specific paralogs or pseudogenes were identified. Conservation of homology and structural motifs of orthologs revealed that the overall similarity to human proteins was significantly higher for pigs compared to mouse. Despite these similarities, two out of four canonical inflammasome pathways, Absent in melanoma 2 (AIM2) and NLR family and CARD domain containing 4 (NLRC4), were found to be missing in pigs. Pig M1 Mφ polarization in response to interferon-γ (IFN-γ) and lipopolysaccharide (LPS) was assessed, via the transcriptome, using next generation sequencing. Our analysis revealed predominantly human-like responses however some, mouse-like responses were observed, as well as induction of numerous pig or artiodactyl-specific genes. This work supports using swine to model both human immunological and inflammatory responses to infection. However, caution must be exercised as pigs differ from humans in several fundamental pathways. Published by Elsevier B.V.

  11. Comparison of a teratogenic transcriptome-based predictive test based on human embryonic versus inducible pluripotent stem cells.

    Science.gov (United States)

    Shinde, Vaibhav; Perumal Srinivasan, Sureshkumar; Henry, Margit; Rotshteyn, Tamara; Hescheler, Jürgen; Rahnenführer, Jörg; Grinberg, Marianna; Meisig, Johannes; Blüthgen, Nils; Waldmann, Tanja; Leist, Marcel; Hengstler, Jan Georg; Sachinidis, Agapios

    2016-12-30

    Human embryonic stem cells (hESCs) partially recapitulate early embryonic three germ layer development, allowing testing of potential teratogenic hazards. Because use of hESCs is ethically debated, we investigated the potential for human induced pluripotent stem cells (hiPSCs) to replace hESCs in such tests. Three cell lines, comprising hiPSCs (foreskin and IMR90) and hESCs (H9) were differentiated for 14 days. Their transcriptome profiles were obtained on day 0 and day 14 and analyzed by comprehensive bioinformatics tools. The transcriptomes on day 14 showed that more than 70% of the "developmental genes" (regulated genes with > 2-fold change on day 14 compared to day 0) exhibited variability among cell lines. The developmental genes belonging to all three cell lines captured biological processes and KEGG pathways related to all three germ layer embryonic development. In addition, transcriptome profiles were obtained after 14 days of exposure to teratogenic valproic acid (VPA) during differentiation. Although the differentially regulated genes between treated and untreated samples showed more than 90% variability among cell lines, VPA clearly antagonized the expression of developmental genes in all cell lines: suppressing upregulated developmental genes, while inducing downregulated ones. To quantify VPA-disturbed development based on developmental genes, we estimated the "developmental potency" (D p ) and "developmental index" (D i ). Despite differences in genes deregulated by VPA, uniform D i values were obtained for all three cell lines. Given that the D i values for VPA were similar for hESCs and hiPSCs, D i can be used for robust hazard identification, irrespective of whether hESCs or hiPSCs are used in the test systems.

  12. Measurement of P-31 MR relaxation times and concentrations in human brain and brain tumors

    International Nuclear Information System (INIS)

    Roth, K.; Naruse, S.; Hubesch, B.; Gober, I.; Lawry, T.; Boska, M.; Matson, G.B.; Weiner, M.W.

    1987-01-01

    Measurements of high-energy phosphates and pH were made in human brain and brain tumors using P-31 MR imaging. Using a Philips Gyroscan 1.5-T MRMRS, MR images were used to select a cuboidal volume of interest and P-31 MR spectra were obtained from that volume using the ISIS technique. An external quantitation standard was used. T 1 s were measured by inversion recovery. Quantitative values for metabolites were calculated using B 1 field plot of the head coil. The results for normal brain phosphates are as follows; adenosine triphosphate, 2.2 mM; phosphocreatin, 5.3 mM; inorganic phosphate, 1.6 mM. Preliminary studies with human brain tumors show a decrease of all phosphate compounds. These experiments are the first to quantitate metabolites in human brain

  13. Common genetic variants influence human subcortical brain structures

    NARCIS (Netherlands)

    Hibar, D.P.; Stein, J.L.; Renteria, M.E.; Arias-Vasquez, A.; Desrivières, S.; Jahanshad, N.; Toro, R.; Wittfeld, K.; Abramovic, L.; Andersson, M.; Aribisala, B.S.; Armstrong, N.J.; Bernard, M.; Bohlken, M.M.; Biks, M.P.; Bralten, J.; Brown, A.A.; Chakravarty, M.M.; Chen, Q.; Ching, C.R.K.; Cuellar-Partida, G.; den Braber, A.; Giddaluru, S.; Goldman, A.L.; Grimm, O.; Guadalupe, T.; Hass, J.; Woldehawariat, G.; Holmes, A.J.; Hoogman, M.; Janowitz, D.; Jia, T.; Kim, S.; Klein, M.; Kraemer, B.; Lee, P.H.; Olde Loohuis, L.M.; Luciano, M.; Macare, C.; Mather, K.A.; Mattheisen, M.; Milaneschi, Y.; Nho, K.; Papmeyer, M.; Ramasamy, A.; Risacher, S.L.; Roiz-Santiañez, R.; Rose, E.J.; Salami, A.; Sämann, P.G.; Schmaal, L.; Schork, A.J.; Shin, J.; Strike, L.T.; Teumer, A.; Donkelaar, M.M.J.; van Eijk, K.R.; Walters, R.K.; Westlye, L.T.; Welan, C.D.; Winkler, A.M.; Zwiers, M.P.; Alhusaini, S.; Athanasiu, L.; Ehrlich, S.; Hakobjan, M.M.H.; Hartberg, C.B.; Haukvik, U.K.; Heister, A.J.G.A.M.; Hoehn, D.; Kasperaviciute, D.; Liewald, D.C.M.; Lopez, L.M.; Makkinje, R.R.; Matarin, M.; Naber, M.A.M.; Reese McKay, D.; Needham, M.; Nugent, A.C.; Pütz, B.; Royle, N.A.; Shen, L.; Sprooten, E.; Trabzuni, D.; van der Marel, S.S.L.; van Hulzen, K.J.E.; Walton, E.; Wolf, C.; Almasy, L.; Ames, D.; Arepalli, S.; Assareh, A.A.; Bastin, M.E.; Brodaty, H.; Bulayeva, K.B.; Carless, M.A.; Cichon, S.; Corvin, A.; Curran, J.E.; Czisch, M.; de Zubicaray, G.I.; Dillman, A.; Duggirala, R.; Dyer, T.D.; Erk, S.; Fedko, I.O.; Ferrucci, L.; Foroud, T.M.; Fox, P.T.; Fukunaga, M.; Gibbs, J.R.; Göring, H.H.H.; Green, R.C.; Guelfi, S.; Hansell, N.K.; Hartman, C.A.; Hegenscheid, K.; Heinz, A.; Hernandez, D.G.; Heslenfeld, D.J.; Hoekstra, P.J.; Holsboer, F.; Homuth, G.; Hottenga, J.J.; Ikeda, M.; Jack, C.R., Jr.; Jenkinson, M.; Johnson, R.; Kanai, R.; Keil, M.; Kent, J.W. Jr.; Kochunov, P.; Kwok, J.B.; Lawrie, S.M.; Liu, X.; Longo, D.L.; McMahon, K.L.; Meisenzahl, E.; Melle, I.; Mohnke, S.; Montgomery, G.W.; Mostert, J.C.; Mühleisen, T.W.; Nalls, M.A.; Nichols, T.E.; Nilsson, L.G.; Nöthen, M.M.; Ohi, K.; Olvera, R.L.; Perez-Iglesias, R.; Pike, G.B.; Potkin, S.G.; Reinvang, I.; Reppermund, S.; Rietschel, M.; Romanczuk-Seiferth, N.; Rosen, G.D.; Rujescu, D.; Schnell, K.; Schofield, P.R.; Smith, C.; Steen, V.M.; Sussmann, J.E.; Thalamuthu, A.; Toga, A.W.; Traynor, B.J.; Troncoso, J.; Turner, J.A.; Valdés Hernández, M.C.; van t Ent, D.; van der Brug, M.; van der Wee, N.J.A.; van Tol, M.J.; Veltman, D.J.; Wassink, T.H.; Westmann, E.; Zielke, R.H.; Zonderman, A.B.; Ashbrook, D.G.; Hager, R.; Lu, L.; McMahon, F.J.; Morris, D.W.; Williams, R.W.; Brunner, H.G.; Buckner, R.L.; Buitelaar, J.K.; Cahn, W.; Calhoun, V.D.; Cavalleri, G.L.; Crespo-Facorro, B.; Dale, A.M.; Davies, G.E.; Delanty, N.; Depondt, C.; Djurovic, S.; Drevets, W.C.; Espeseth, T.; Gollub, R.L.; Ho, B.C.; Hoffmann, W.; Hosten, N.; Kahn, R.S.; Le Hellard, S.; Meyer-Lindenberg, A.; Müller-Myhsok, B.; Nauck, M.; Nyberg, L.; Pandolfo, M.; Penninx, B.W.J.H.; Roffman, J.L.; Sisodiya, SM; Smoller, J.W.; van Bokhoven, H.; van Haren, N.E.M.; Völzke, H.; Walter, H.; Weiner, M.W.; Wen, W.; White, T.; Agartz, I.; Andreassen, O.A.; Blangero, J.; Boomsma, D.I.; Brouwer, R.M.; Cannon, D.M.; Cookson, M.R.; de Geus, E.J.C.; Deary, I.J.; Donohoe, G.; Fernandez, G.; Fisher, S.E.; Francks, C.; Glahn, D.C.; Grabe, H.J.; Gruber, O.; Hardy, J.; Hashimoto, R.; Hulshoff Pol, H.E.; Jönsson, E.G.; Kloszewska, I.; Lovestone, S.; Mattay, V.S.; Mecocci, P.; McDonald, C.; McIntosh, A.M.; Ophoff, R.A.; Paus, T.; Pausova, Z.; Ryten, M.; Sachdev, P.S.; Saykin, A.J.; Simmons, A.; Singleton, A.; Soininen, H.; Wardlaw, J.M.; Weale, M.E.; Weinberger, D.R.; Adams, H.H.H.; Launer, L.J.; Seiler, S.; Schmidt, R.; Chauhan, G.; Satizabal, C.L.; Becker, J.T.; Yanek, L.; van der Lee, S.J.; Ebling, M.; Fischl, B.; Longstreth, Jr. W.T.; Greve, D.; Schmidt, H.; Nyquist, P.; Vinke, L.N.; van Duijn, C.M.; Xue, L.; Mazoyer, B.; Bis, J.C.; Gudnason, V.; Seshadri, S.; Arfan Ikram, M.; Martin, N.G.; Wright, M.J.; Schumann, G.; Franke, B.; Thompson, P.M.; Medland, S.E.

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common

  14. Common genetic variants influence human subcortical brain structures

    NARCIS (Netherlands)

    D.P. Hibar (Derrek); J.L. Stein; M.E. Rentería (Miguel); A. Arias-Vásquez (Alejandro); S. Desrivières (Sylvane); N. Jahanshad (Neda); R. Toro (Roberto); K. Wittfeld (Katharina); L. Abramovic (Lucija); M. Andersson (Micael); B. Aribisala (Benjamin); N.J. Armstrong (Nicola J.); M. Bernard (Manon); M.M. Bohlken (Marc M.); M.P.M. Boks (Marco); L.B.C. Bralten (Linda); A.A. Brown (Andrew); M.M. Chakravarty (M. Mallar); Q. Chen (Qiang); C.R.K. Ching (Christopher); G. Cuellar-Partida (Gabriel); A. den Braber (Anouk); S. Giddaluru (Sudheer); A.L. Goldman (Aaron L.); O. Grimm (Oliver); T. Guadalupe (Tulio); J. Hass (Johanna); G. Woldehawariat (Girma); A.J. Holmes (Avram); M. Hoogman (Martine); D. Janowitz (Deborah); T. Jia (Tianye); S. Kim (Shinseog); M. Klein (Marieke); B. Kraemer (Bernd); P.H. Lee (Phil H.); L.M. Olde Loohuis (Loes M.); M. Luciano (Michelle); C. MacAre (Christine); R. Mather; M. Mattheisen (Manuel); Y. Milaneschi (Yuri); K. Nho (Kwangsik); M. Papmeyer (Martina); A. Ramasamy (Adaikalavan); S.L. Risacher (Shannon); R. Roiz-Santiañez (Roberto); E.J. Rose (Emma); A. Salami (Alireza); P.G. Sämann (Philipp); L. Schmaal (Lianne); N.J. Schork (Nicholas); J. Shin (Jean); L.T. Strike (Lachlan); A. Teumer (Alexander); M.M.J. Van Donkelaar (Marjolein M. J.); K.R. van Eijk (Kristel); R.K. Walters (Raymond); L.T. Westlye (Lars); C.D. Whelan (Christopher); A.M. Winkler (Anderson); M.P. Zwiers (Marcel); S. Alhusaini (Saud); L. Athanasiu (Lavinia); S.M. Ehrlich (Stefan); M. Hakobjan (Marina); C.B. Hartberg (Cecilie B.); U.K. Haukvik (Unn); A.J.G.A.M. Heister (Angelien J. G. A. M.); D. Hoehn (David); D. Kasperaviciute (Dalia); D.C. Liewald (David C.); L.M. Lopez (Lorna); R.R.R. Makkinje (Remco R. R.); M. Matarin (Mar); M.A.M. Naber (Marlies A. M.); D. Reese McKay; M. Needham (Margaret); A.C. Nugent (Allison); B. Pütz (Benno); N.A. Royle (Natalie); L. Shen (Li); R. Sprooten (Roy); D. Trabzuni (Danyah); S.S.L. Van Der Marel (Saskia S. L.); K.J.E. Van Hulzen (Kimm J. E.); E. Walton (Esther); A. Björnsson (Asgeir); L. Almasy (Laura); D.J. Ames (David); S. Arepalli (Sampath); A.A. Assareh; M.E. Bastin (Mark); H. Brodaty (Henry); K. Bulayeva (Kazima); M.A. Carless (Melanie); S. Cichon (Sven); A. Corvin (Aiden); J.E. Curran (Joanne); M. Czisch (Michael); G.I. de Zubicaray (Greig); A. Dillman (Allissa); A. Duggirala (Aparna); M.D. Dyer (Matthew); S. Erk; I. Fedko (Iryna); L. Ferrucci (Luigi); T. Foroud (Tatiana); P.T. Fox (Peter); M. Fukunaga (Masaki); J. Raphael Gibbs; H.H.H. Göring (Harald H.); R.C. Green (Robert C.); S. Guelfi (Sebastian); N.K. Hansell (Narelle); C.A. Hartman (Catharina); K. Hegenscheid (Katrin); J. Heinz (Judith); D.G. Hernandez (Dena); D.J. Heslenfeld (Dirk); P.J. Hoekstra (Pieter); F. Holsboer; G. Homuth (Georg); J.J. Hottenga (Jouke Jan); M. Ikeda (Masashi); C.R. Jack Jr. (Clifford); S. Jenkinson (Sarah); R. Johnson (Robert); R. Kanai (Ryota); M. Keil (Maria); J.W. Kent (Jack W.); P. Kochunov (Peter); J.B. Kwok (John B.); S. Lawrie (Stephen); X. Liu (Xinmin); D.L. Longo (Dan L.); K.L. Mcmahon (Katie); E. Meisenzahl (Eva); I. Melle (Ingrid); S. Mohnke (Sebastian); G.W. Montgomery (Grant); J.C. Mostert (Jeanette C.); T.W. Mühleisen (Thomas); M.A. Nalls (Michael); T.E. Nichols (Thomas); L.G. Nilsson; M.M. Nöthen (Markus); K. Ohi (Kazutaka); R.L. Olvera (Rene); R. Perez-Iglesias (Rocio); G. Bruce Pike; S.G. Potkin (Steven); I. Reinvang (Ivar); S. Reppermund; M. Rietschel (Marcella); N. Seiferth (Nina); G.D. Rosen (Glenn D.); D. Rujescu (Dan); K. Schnell (Kerry); C.J. Schofield (Christopher); C. Smith (Colin); V.M. Steen (Vidar); J. Sussmann (Jessika); A. Thalamuthu (Anbupalam); A.W. Toga (Arthur W.); B. Traynor (Bryan); J.C. Troncoso (Juan); J. Turner (Jessica); M.C. Valdés Hernández (Maria); D. van 't Ent (Dennis); M.P. van der Brug (Marcel); N.J. van der Wee (Nic); M.J.D. van Tol (Marie-José); D.J. Veltman (Dick); A.M.J. Wassink (Annemarie); E. Westman (Eric); R.H. Zielke (Ronald H.); A.B. Zonderman (Alan B.); D.G. Ashbrook (David G.); R. Hager (Reinmar); L. Lu (Lu); F.J. Mcmahon (Francis J); D.W. Morris (Derek W); R.W. Williams (Robert W.); H.G. Brunner; M. Buckner; J.K. Buitelaar (Jan K.); W. Cahn (Wiepke); V.D. Calhoun Vince D. (V.); G. Cavalleri (Gianpiero); B. Crespo-Facorro (Benedicto); A.M. Dale (Anders); G.E. Davies (Gareth); N. Delanty; C. Depondt (Chantal); S. Djurovic (Srdjan); D.A. Drevets (Douglas); T. Espeseth (Thomas); R.L. Gollub (Randy); B.C. Ho (Beng ); W. Hoffmann (Wolfgang); N. Hosten (Norbert); R. Kahn (René); S. Le Hellard (Stephanie); A. Meyer-Lindenberg; B. Müller-Myhsok (B.); M. Nauck (Matthias); L. Nyberg (Lars); M. Pandolfo (Massimo); B.W.J.H. Penninx (Brenda); J.L. Roffman (Joshua); S.M. Sisodiya (Sanjay); J.W. Smoller; H. van Bokhoven (Hans); N.E.M. van Haren (Neeltje E.); H. Völzke (Henry); H.J. Walter (Henrik); M.W. Weiner (Michael); W. Wen (Wei); T.J.H. White (Tonya); I. Agartz (Ingrid); O.A. Andreassen (Ole); J. Blangero (John); D.I. Boomsma (Dorret); R.M. Brouwer (Rachel); D.M. Cannon (Dara); M.R. Cookson (Mark); E.J.C. de Geus (Eco); I.J. Deary (Ian J.); D.J. Donohoe (Dennis); G. Fernandez (Guillén); S.E. Fisher (Simon); C. Francks (Clyde); D.C. Glahn (David); H.J. Grabe (Hans Jörgen); O. Gruber (Oliver); J. Hardy (John); R. Hashimoto (Ryota); H.E. Hulshoff Pol (Hilleke); E.G. Jönsson (Erik); I. Kloszewska (Iwona); S. Lovestone (Simon); V.S. Mattay (Venkata S.); P. Mecocci (Patrizia); C. McDonald (Colm); A.M. McIntosh (Andrew); R.A. Ophoff (Roel); T. Paus (Tomas); Z. Pausova (Zdenka); M. Ryten (Mina); P.S. Sachdev (Perminder); A.J. Saykin (Andrew); A. Simmons (Andrew); A. Singleton (Andrew); H. Soininen (H.); J.M. Wardlaw (J.); M.E. Weale (Michael); D.R. Weinberger (Daniel); H.H.H. Adams (Hieab); L.J. Launer (Lenore); S. Seiler (Stephan); R. Schmidt (Reinhold); G. Chauhan (Ganesh); C.L. Satizabal (Claudia L.); J.T. Becker (James); L.R. Yanek (Lisa); S.J. van der Lee (Sven); M. Ebling (Maritza); B. Fischl (Bruce); W.T. Longstreth Jr; D. Greve (Douglas); R. Schmidt (Reinhold); P. Nyquist (Paul); L.N. Vinke (Louis N.); C.M. van Duijn (Cornelia); L. Xue (Luting); B. Mazoyer (Bernard); J.C. Bis (Joshua); V. Gudnason (Vilmundur); S. Seshadri (Sudha); M.A. Ikram (Arfan); N.G. Martin (Nicholas); M.J. Wright (Margaret); G. Schumann (Gunter); B. Franke (Barbara); P.M. Thompson (Paul); S.E. Medland (Sarah Elizabeth)

    2015-01-01

    textabstractThe highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate

  15. Common genetic variants influence human subcortical brain structures

    NARCIS (Netherlands)

    Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivieres, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Loohuis, Loes M. Olde; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santianez, Roberto; Rose, Emma J.; Salami, Alireza; Saemann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Puetz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Goering, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzah, Eva; Melle, Ingrid; Mahnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Muehleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Noethen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdes Hernandez, Maria C.; van't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffman, Wolfgang; Hosten, Norbert; Kahn, Rene S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Mueller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Voelzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernandez, Guillen; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Pol, Hilleke E. Hulshoff; Joensson, Erik G.; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S.; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S.; Saykin, Andrew J.; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M.; Weale, Michael E.; Weinberger, Daniel R.; Adams, Hieab H. H.; Launer, Lenore J.; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L.; Becker, James T.; Yanek, Lisa; van der Lee, Sven J.; Ebling, Maritza; Fischl, Bruce; Longstreth, W. T.; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N.; van Duijn, Cornelia M.; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C.; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M. Arfan; Martin, Nicholas G.; Wright, Margaret J.; Schumann, Gunter; Franke, Barbara; Thompson, Paul M.; Medland, Sarah E.

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences(1). Subcortical brain regions form circuits with cortical areas to coordinate movement(2), learning, memory(3) and motivation(4), and altered circuits can lead to abnormal behaviour and disease(5). To

  16. Injury Response of Resected Human Brain Tissue In Vitro

    NARCIS (Netherlands)

    Verwer, Ronald W. H.; Sluiter, Arja A.; Balesar, Rawien A.; Baaijen, Johannes C.; de Witt Hamer, Philip C.; Speijer, Dave; Li, Yichen; Swaab, Dick F.

    2015-01-01

    Brain injury affects a significant number of people each year. Organotypic cultures from resected normal neocortical tissue provide unique opportunities to study the cellular and neuropathological consequences of severe injury of adult human brain tissue in vitro. The in vitro injuries caused by

  17. Neuronal substrates of sensory gating within the human brain.

    NARCIS (Netherlands)

    Grunwald, T.; Boutros, N.N.; Pezer, N.; Oertzen, J. von; Fernandez, G.S.E.; Schaller, C.; Elger, C.E.

    2003-01-01

    BACKGROUND: For the human brain, habituation to irrelevant sensory input is an important function whose failure is associated with behavioral disturbances. Sensory gating can be studied by recording the brain's electrical responses to repeated clicks: the P50 potential is normally reduced to the

  18. Quantitation of glial fibrillary acidic protein in human brain tumours

    DEFF Research Database (Denmark)

    Rasmussen, S; Bock, E; Warecka, K

    1980-01-01

    The glial fibrillary acidic protein (GFA) content of 58 human brain tumours was determined by quantitative immunoelectrophoresis, using monospecific antibody against GFA. Astrocytomas, glioblastomas, oligodendrogliomas, spongioblastomas, ependymomas and medulloblastomas contained relatively high...

  19. Sex beyond the genitalia: The human brain mosaic

    Science.gov (United States)

    Joel, Daphna; Berman, Zohar; Tavor, Ido; Wexler, Nadav; Gaber, Olga; Stein, Yaniv; Shefi, Nisan; Pool, Jared; Urchs, Sebastian; Margulies, Daniel S.; Liem, Franziskus; Hänggi, Jürgen; Jäncke, Lutz; Assaf, Yaniv

    2015-01-01

    Whereas a categorical difference in the genitals has always been acknowledged, the question of how far these categories extend into human biology is still not resolved. Documented sex/gender differences in the brain are often taken as support of a sexually dimorphic view of human brains (“female brain” or “male brain”). However, such a distinction would be possible only if sex/gender differences in brain features were highly dimorphic (i.e., little overlap between the forms of these features in males and females) and internally consistent (i.e., a brain has only “male” or only “female” features). Here, analysis of MRIs of more than 1,400 human brains from four datasets reveals extensive overlap between the distributions of females and males for all gray matter, white matter, and connections assessed. Moreover, analyses of internal consistency reveal that brains with features that are consistently at one end of the “maleness-femaleness” continuum are rare. Rather, most brains are comprised of unique “mosaics” of features, some more common in females compared with males, some more common in males compared with females, and some common in both females and males. Our findings are robust across sample, age, type of MRI, and method of analysis. These findings are corroborated by a similar analysis of personality traits, attitudes, interests, and behaviors of more than 5,500 individuals, which reveals that internal consistency is extremely rare. Our study demonstrates that, although there are sex/gender differences in the brain, human brains do not belong to one of two distinct categories: male brain/female brain. PMID:26621705

  20. Noninvasive Stimulation of the Human Brain

    DEFF Research Database (Denmark)

    Di Lazzaro, Vincenzo; Rothwell, John; Capogna, Marco

    2017-01-01

    Noninvasive brain stimulation methods, such as transcranial electric stimulation and transcranial magnetic stimulation are widely used tools for both basic research and clinical applications. However, the cortical circuits underlying their effects are poorly defined. Here we review the current...

  1. Short parietal lobe connections of the human and monkey brain

    DEFF Research Database (Denmark)

    Catani, Marco; Robertsson, Naianna; Beyh, Ahmad

    2017-01-01

    projections were reconstructed for both species and results compared to identify similarities or differences in tract anatomy (i.e., trajectories and cortical projections). In addition, post-mortem dissections were performed in a human brain. The largest tract identified in both human and monkey brains...... and angular gyri of the inferior parietal lobule in humans but only to the supramarginal gyrus in the monkey brain. The third tract connects the postcentral gyrus to the anterior region of the superior parietal lobule and is more prominent in monkeys compared to humans. Finally, short U-shaped fibres...... and monkeys with some differences for those areas that have cytoarchitectonically distinct features in humans. The overall pattern of intraparietal connectivity supports the special role of the inferior parietal lobule in cognitive functions characteristic of humans....

  2. New genes expressed in human brains: implications for annotating evolving genomes.

    Science.gov (United States)

    Zhang, Yong E; Landback, Patrick; Vibranovski, Maria; Long, Manyuan

    2012-11-01

    New genes have frequently formed and spread to fixation in a wide variety of organisms, constituting abundant sets of lineage-specific genes. It was recently reported that an excess of primate-specific and human-specific genes were upregulated in the brains of fetuses and infants, and especially in the prefrontal cortex, which is involved in cognition. These findings reveal the prevalent addition of new genetic components to the transcriptome of the human brain. More generally, these findings suggest that genomes are continually evolving in both sequence and content, eroding the conservation endowed by common ancestry. Despite increasing recognition of the importance of new genes, we highlight here that these genes are still seriously under-characterized in functional studies and that new gene annotation is inconsistent in current practice. We propose an integrative approach to annotate new genes, taking advantage of functional and evolutionary genomic methods. We finally discuss how the refinement of new gene annotation will be important for the detection of evolutionary forces governing new gene origination. Copyright © 2012 WILEY Periodicals, Inc.

  3. Optogenetic control of human neurons in organotypic brain cultures

    DEFF Research Database (Denmark)

    Andersson, My; Avaliani, Natalia; Svensson, Andreas

    2016-01-01

    Optogenetics is one of the most powerful tools in neuroscience, allowing for selective control of specific neuronal populations in the brain of experimental animals, including mammals. We report, for the first time, the application of optogenetic tools to human brain tissue providing a proof......-of-concept for the use of optogenetics in neuromodulation of human cortical and hippocampal neurons as a possible tool to explore network mechanisms and develop future therapeutic strategies....

  4. Default, Cognitive, and Affective Brain Networks in Human Tinnitus

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-13-1-0491 TITLE: Default, Cognitive, and Affective Brain Networks in Human Tinnitus PRINCIPAL INVESTIGATOR: Jennifer R...SUBTITLE 5a. CONTRACT NUMBER Default, Cognitive and Affective Brain Networks in Human Tinnitus 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Tinnitus is a major health problem among those currently and formerly in military

  5. Genetic contributions to human brain morphology and intelligence

    DEFF Research Database (Denmark)

    Hulshoff Pol, HE; Schnack, HG; Posthuma, D

    2006-01-01

    Variation in gray matter (GM) and white matter (WM) volume of the adult human brain is primarily genetically determined. Moreover, total brain volume is positively correlated with general intelligence, and both share a common genetic origin. However, although genetic effects on morphology...... of specific GM areas in the brain have been studied, the heritability of focal WM is unknown. Similarly, it is unresolved whether there is a common genetic origin of focal GM and WM structures with intelligence. We explored the genetic influence on focal GM and WM densities in magnetic resonance brain images...

  6. Outer brain barriers in rat and human development

    DEFF Research Database (Denmark)

    Brøchner, Christian B; Holst, Camilla Bjørnbak; Møllgård, Kjeld

    2015-01-01

    Complex barriers at the brain's surface, particularly in development, are poorly defined. In the adult, arachnoid blood-cerebrospinal fluid (CSF) barrier separates the fenestrated dural vessels from the CSF by means of a cell layer joined by tight junctions. Outer CSF-brain barrier provides...... diffusion restriction between brain and subarachnoid CSF through an initial radial glial end feet layer covered with a pial surface layer. To further characterize these interfaces we examined embryonic rat brains from E10 to P0 and forebrains from human embryos and fetuses (6-21st weeks post...

  7. Centrality of Social Interaction in Human Brain Function.

    Science.gov (United States)

    Hari, Riitta; Henriksson, Linda; Malinen, Sanna; Parkkonen, Lauri

    2015-10-07

    People are embedded in social interaction that shapes their brains throughout lifetime. Instead of emerging from lower-level cognitive functions, social interaction could be the default mode via which humans communicate with their environment. Should this hypothesis be true, it would have profound implications on how we think about brain functions and how we dissect and simulate them. We suggest that the research on the brain basis of social cognition and interaction should move from passive spectator science to studies including engaged participants and simultaneous recordings from the brains of the interacting persons. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Reflectance diffuse optical tomography. Its application to human brain mapping

    International Nuclear Information System (INIS)

    Ueda, Yukio; Yamanaka, Takeshi; Yamashita, Daisuke; Suzuki, Toshihiko; Ohmae, Etsuko; Oda, Motoki; Yamashita, Yutaka

    2005-01-01

    We report the successful application of reflectance diffuse optical tomography (DOT) using near-infrared light with the new reconstruction algorithm that we developed to the observation of regional hemodynamic changes in the brain under specific mental tasks. Our results reveal the heterogeneous distribution of oxyhemoglobin and deoxyhemoglobin in the brain, showing complementary images of oxyhemoglobin and deoxyhemoglobin changes in certain regions. We conclude that our reflectance DOT has practical potential for human brain mapping, as well as in the diagnostic imaging of brain diseases. (author)

  9. A curated transcriptome dataset collection to investigate the functional programming of human hematopoietic cells in early life.

    Science.gov (United States)

    Rahman, Mahbuba; Boughorbel, Sabri; Presnell, Scott; Quinn, Charlie; Cugno, Chiara; Chaussabel, Damien; Marr, Nico

    2016-01-01

    Compendia of large-scale datasets made available in public repositories provide an opportunity to identify and fill gaps in biomedical knowledge. But first, these data need to be made readily accessible to research investigators for interpretation. Here we make available a collection of transcriptome datasets to investigate the functional programming of human hematopoietic cells in early life. Thirty two datasets were retrieved from the NCBI Gene Expression Omnibus (GEO) and loaded in a custom web application called the Gene Expression Browser (GXB), which was designed for interactive query and visualization of integrated large-scale data. Quality control checks were performed. Multiple sample groupings and gene rank lists were created allowing users to reveal age-related differences in transcriptome profiles, changes in the gene expression of neonatal hematopoietic cells to a variety of immune stimulators and modulators, as well as during cell differentiation. Available demographic, clinical, and cell phenotypic information can be overlaid with the gene expression data and used to sort samples. Web links to customized graphical views can be generated and subsequently inserted in manuscripts to report novel findings. GXB also enables browsing of a single gene across projects, thereby providing new perspectives on age- and developmental stage-specific expression of a given gene across the human hematopoietic system. This dataset collection is available at: http://developmentalimmunology.gxbsidra.org/dm3/geneBrowser/list.

  10. Transcriptome profiling of whole blood cells identifies PLEK2 and C1QB in human melanoma.

    Directory of Open Access Journals (Sweden)

    Yuchun Luo

    Full Text Available Developing analytical methodologies to identify biomarkers in easily accessible body fluids is highly valuable for the early diagnosis and management of cancer patients. Peripheral whole blood is a "nucleic acid-rich" and "inflammatory cell-rich" information reservoir and represents systemic processes altered by the presence of cancer cells.We conducted transcriptome profiling of whole blood cells from melanoma patients. To overcome challenges associated with blood-based transcriptome analysis, we used a PAXgene™ tube and NuGEN Ovation™ globin reduction system. The combined use of these systems in microarray resulted in the identification of 78 unique genes differentially expressed in the blood of melanoma patients. Of these, 68 genes were further analyzed by quantitative reverse transcriptase PCR using blood samples from 45 newly diagnosed melanoma patients (stage I to IV and 50 healthy control individuals. Thirty-nine genes were verified to be differentially expressed in blood samples from melanoma patients. A stepwise logit analysis selected eighteen 2-gene signatures that distinguish melanoma from healthy controls. Of these, a 2-gene signature consisting of PLEK2 and C1QB led to the best result that correctly classified 93.3% melanoma patients and 90% healthy controls. Both genes were upregulated in blood samples of melanoma patients from all stages. Further analysis using blood fractionation showed that CD45(- and CD45(+ populations were responsible for the altered expression levels of PLEK2 and C1QB, respectively.The current study provides the first analysis of whole blood-based transcriptome biomarkers for malignant melanoma. The expression of PLEK2, the strongest gene to classify melanoma patients, in CD45(- subsets illustrates the importance of analyzing whole blood cells for biomarker studies. The study suggests that transcriptome profiling of blood cells could be used for both early detection of melanoma and monitoring of patients

  11. The immune response of the human brain to abdominal surgery

    DEFF Research Database (Denmark)

    Forsberg, Anton; Cervenka, Simon; Jonsson Fagerlund, Malin

    2017-01-01

    OBJECTIVE: Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans....... This study examines the short- and long-term impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function. METHODS: Eight males undergoing prostatectomy under general...... anesthesia were included. Prior to surgery (baseline), at postoperative days 3 to 4, and after 3 months, patients were examined using [11C]PBR28 brain PET imaging to assess brain immune cell activation. Concurrently, systemic inflammatory biomarkers, ex vivo blood tests on immunoreactivity...

  12. Do glutathione levels decline in aging human brain?

    Science.gov (United States)

    Tong, Junchao; Fitzmaurice, Paul S; Moszczynska, Anna; Mattina, Katie; Ang, Lee-Cyn; Boileau, Isabelle; Furukawa, Yoshiaki; Sailasuta, Napapon; Kish, Stephen J

    2016-04-01

    For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Effects of Sex Steroids in the Human Brain.

    Science.gov (United States)

    Nguyen, Tuong-Vi; Ducharme, Simon; Karama, Sherif

    2017-11-01

    Sex steroids are thought to play a critical developmental role in shaping both cortical and subcortical structures in the human brain. Periods of profound changes in sex steroids invariably coincide with the onset of sex differences in mental health vulnerability, highlighting the importance of sex steroids in determining sexual differentiation of the brain. Yet, most of the evidence for the central effects of sex steroids relies on non-human studies, as several challenges have limited our understanding of these effects in humans: the lack of systematic assessment of the human sex steroid metabolome, the different developmental trajectories of specific sex steroids, the impact of genetic variation and epigenetic changes, and the plethora of interactions between sex steroids, sex chromosomes, neurotransmitters, and other hormonal systems. Here we review how multimodal strategies may be employed to bridge the gap between the basic and clinical understanding of sex steroid-related changes in the human brain.

  14. Conscious brain-to-brain communication in humans using non-invasive technologies.

    Science.gov (United States)

    Grau, Carles; Ginhoux, Romuald; Riera, Alejandro; Nguyen, Thanh Lam; Chauvat, Hubert; Berg, Michel; Amengual, Julià L; Pascual-Leone, Alvaro; Ruffini, Giulio

    2014-01-01

    Human sensory and motor systems provide the natural means for the exchange of information between individuals, and, hence, the basis for human civilization. The recent development of brain-computer interfaces (BCI) has provided an important element for the creation of brain-to-brain communication systems, and precise brain stimulation techniques are now available for the realization of non-invasive computer-brain interfaces (CBI). These technologies, BCI and CBI, can be combined to realize the vision of non-invasive, computer-mediated brain-to-brain (B2B) communication between subjects (hyperinteraction). Here we demonstrate the conscious transmission of information between human brains through the intact scalp and without intervention of motor or peripheral sensory systems. Pseudo-random binary streams encoding words were transmitted between the minds of emitter and receiver subjects separated by great distances, representing the realization of the first human brain-to-brain interface. In a series of experiments, we established internet-mediated B2B communication by combining a BCI based on voluntary motor imagery-controlled electroencephalographic (EEG) changes with a CBI inducing the conscious perception of phosphenes (light flashes) through neuronavigated, robotized transcranial magnetic stimulation (TMS), with special care taken to block sensory (tactile, visual or auditory) cues. Our results provide a critical proof-of-principle demonstration for the development of conscious B2B communication technologies. More fully developed, related implementations will open new research venues in cognitive, social and clinical neuroscience and the scientific study of consciousness. We envision that hyperinteraction technologies will eventually have a profound impact on the social structure of our civilization and raise important ethical issues.

  15. Conscious brain-to-brain communication in humans using non-invasive technologies.

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    Carles Grau

    Full Text Available Human sensory and motor systems provide the natural means for the exchange of information between individuals, and, hence, the basis for human civilization. The recent development of brain-computer interfaces (BCI has provided an important element for the creation of brain-to-brain communication systems, and precise brain stimulation techniques are now available for the realization of non-invasive computer-brain interfaces (CBI. These technologies, BCI and CBI, can be combined to realize the vision of non-invasive, computer-mediated brain-to-brain (B2B communication between subjects (hyperinteraction. Here we demonstrate the conscious transmission of information between human brains through the intact scalp and without intervention of motor or peripheral sensory systems. Pseudo-random binary streams encoding words were transmitted between the minds of emitter and receiver subjects separated by great distances, representing the realization of the first human brain-to-brain interface. In a series of experiments, we established internet-mediated B2B communication by combining a BCI based on voluntary motor imagery-controlled electroencephalographic (EEG changes with a CBI inducing the conscious perception of phosphenes (light flashes through neuronavigated, robotized transcranial magnetic stimulation (TMS, with special care taken to block sensory (tactile, visual or auditory cues. Our results provide a critical proof-of-principle demonstration for the development of conscious B2B communication technologies. More fully developed, related implementations will open new research venues in cognitive, social and clinical neuroscience and the scientific study of consciousness. We envision that hyperinteraction technologies will eventually have a profound impact on the social structure of our civilization and raise important ethical issues.

  16. Deep mRNA sequencing of the Tritonia diomedea brain transcriptome provides access to gene homologues for neuronal excitability, synaptic transmission and peptidergic signalling.

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    Adriano Senatore

    Full Text Available The sea slug Tritonia diomedea (Mollusca, Gastropoda, Nudibranchia, has a simple and highly accessible nervous system, making it useful for studying neuronal and synaptic mechanisms underlying behavior. Although many important contributions have been made using Tritonia, until now, a lack of genetic information has impeded exploration at the molecular level.We performed Illumina sequencing of central nervous system mRNAs from Tritonia, generating 133.1 million 100 base pair, paired-end reads. De novo reconstruction of the RNA-Seq data yielded a total of 185,546 contigs, which partitioned into 123,154 non-redundant gene clusters (unigenes. BLAST comparison with RefSeq and Swiss-Prot protein databases, as well as mRNA data from other invertebrates (gastropod molluscs: Aplysia californica, Lymnaea stagnalis and Biomphalaria glabrata; cnidarian: Nematostella vectensis revealed that up to 76,292 unigenes in the Tritonia transcriptome have putative homologues in other databases, 18,246 of which are below a more stringent E-value cut-off of 1x10-6. In silico prediction of secreted proteins from the Tritonia transcriptome shotgun assembly (TSA produced a database of 579 unique sequences of secreted proteins, which also exhibited markedly higher expression levels compared to other genes in the TSA.Our efforts greatly expand the availability of gene sequences available for Tritonia diomedea. We were able to extract full length protein sequences for most queried genes, including those involved in electrical excitability, synaptic vesicle release and neurotransmission, thus confirming that the transcriptome will serve as a useful tool for probing the molecular correlates of behavior in this species. We also generated a neurosecretome database that will serve as a useful tool for probing peptidergic signalling systems in the Tritonia brain.

  17. Glioma cells on the run – the migratory transcriptome of 10 human glioma cell lines

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    Holz David

    2008-01-01

    Full Text Available Abstract Background Glioblastoma multiforme (GBM is the most common primary intracranial tumor and despite recent advances in treatment regimens, prognosis for affected patients remains poor. Active cell migration and invasion of GBM cells ultimately lead to ubiquitous tumor recurrence and patient death. To further understand the genetic mechanisms underlying the ability of glioma cells to migrate, we compared the matched transcriptional profiles of migratory and stationary populations of human glioma cells. Using a monolayer radial migration assay, motile and stationary cell populations from seven human long term glioma cell lines and three primary GBM cultures were isolated and prepared for expression analysis. Results Gene expression signatures of stationary and migratory populations across all cell lines were identified using a pattern recognition approach that integrates a priori knowledge with expression data. Principal component analysis (PCA revealed two discriminating patterns between migrating and stationary glioma cells: i global down-regulation and ii global up-regulation profiles that were used in a proband-based rule function implemented in GABRIEL to find subsets of genes having similar expression patterns. Genes with up-regulation pattern in migrating glioma cells were found to be overexpressed in 75% of human GBM biopsy specimens compared to normal brain. A 22 gene signature capable of classifying glioma cultures based on their migration rate was developed. Fidelity of this discovery algorithm was assessed by validation of the invasion candidate gene, connective tissue growth factor (CTGF. siRNA mediated knockdown yielded reduced in vitro migration and ex vivo invasion; immunohistochemistry on glioma invasion tissue microarray confirmed up-regulation of CTGF in invasive glioma cells. Conclusion Gene expression profiling of migratory glioma cells induced to disperse in vitro affords discovery of genomic signatures; selected

  18. RNA sequencing of the human milk fat layer transcriptome reveals distinct gene expression profiles at three stages of lactation.

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    Danielle G Lemay

    Full Text Available Aware of the important benefits of human milk, most U.S. women initiate breastfeeding but difficulties with milk supply lead some to quit earlier than intended. Yet, the contribution of maternal physiology to lactation difficulties remains poorly understood. Human milk fat globules, by enveloping cell contents during their secretion into milk, are a rich source of mammary cell RNA. Here, we pair this non-invasive mRNA source with RNA-sequencing to probe the milk fat layer transcriptome during three stages of lactation: colostral, transitional, and mature milk production. The resulting transcriptomes paint an exquisite portrait of human lactation. The resulting transcriptional profiles cluster not by postpartum day, but by milk Na:K ratio, indicating that women sampled during similar postpartum time frames could be at markedly different stages of gene expression. Each stage of lactation is characterized by a dynamic range (10(5-fold in transcript abundances not previously observed with microarray technology. We discovered that transcripts for isoferritins and cathepsins are strikingly abundant during colostrum production, highlighting the potential importance of these proteins for neonatal health. Two transcripts, encoding β-casein (CSN2 and α-lactalbumin (LALBA, make up 45% of the total pool of mRNA in mature lactation. Genes significantly expressed across all stages of lactation are associated with making, modifying, transporting, and packaging milk proteins. Stage-specific transcripts are associated with immune defense during the colostral stage, up-regulation of the machinery needed for milk protein synthesis during the transitional stage, and the production of lipids during mature lactation. We observed strong modulation of key genes involved in lactose synthesis and insulin signaling. In particular, protein tyrosine phosphatase, receptor type, F (PTPRF may serve as a biomarker linking insulin resistance with insufficient milk supply. This

  19. Cyto- and receptor architectonic mapping of the human brain.

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    Palomero-Gallagher, Nicola; Zilles, Karl

    2018-01-01

    Mapping of the human brain is more than the generation of an atlas-based parcellation of brain regions using histologic or histochemical criteria. It is the attempt to provide a topographically informed model of the structural and functional organization of the brain. To achieve this goal a multimodal atlas of the detailed microscopic and neurochemical structure of the brain must be registered to a stereotaxic reference space or brain, which also serves as reference for topographic assignment of functional data, e.g., functional magnet resonance imaging, electroencephalography, or magnetoencephalography, as well as metabolic imaging, e.g., positron emission tomography. Although classic maps remain pioneering steps, they do not match recent concepts of the functional organization in many regions, and suffer from methodic drawbacks. This chapter provides a summary of the recent status of human brain mapping, which is based on multimodal approaches integrating results of quantitative cyto- and receptor architectonic studies with focus on the cerebral cortex in a widely used reference brain. Descriptions of the methods for observer-independent and statistically testable cytoarchitectonic parcellations, quantitative multireceptor mapping, and registration to the reference brain, including the concept of probability maps and a toolbox for using the maps in functional neuroimaging studies, are provided. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. The intrinsic geometry of the human brain connectome.

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    Ye, Allen Q; Ajilore, Olusola A; Conte, Giorgio; GadElkarim, Johnson; Thomas-Ramos, Galen; Zhan, Liang; Yang, Shaolin; Kumar, Anand; Magin, Richard L; G Forbes, Angus; Leow, Alex D

    2015-12-01

    This paper describes novel methods for constructing the intrinsic geometry of the human brain connectome using dimensionality-reduction techniques. We posit that the high-dimensional, complex geometry that represents this intrinsic topology can be mathematically embedded into lower dimensions using coupling patterns encoded in the corresponding brain connectivity graphs. We tested both linear and nonlinear dimensionality-reduction techniques using the diffusion-weighted structural connectome data acquired from a sample of healthy subjects. Results supported the nonlinearity of brain connectivity data, as linear reduction techniques such as the multidimensional scaling yielded inferior lower-dimensional embeddings. To further validate our results, we demonstrated that for tractography-derived structural connectome more influential regions such as rich-club members of the brain are more centrally mapped or embedded. Further, abnormal brain connectivity can be visually understood by inspecting the altered geometry of these three-dimensional (3D) embeddings that represent the topology of the human brain, as illustrated using simulated lesion studies of both targeted and random removal. Last, in order to visualize brain's intrinsic topology we have developed software that is compatible with virtual reality technologies, thus allowing researchers to collaboratively and interactively explore and manipulate brain connectome data.

  1. Ecology of the aging human brain.

    Science.gov (United States)

    Sonnen, Joshua A; Santa Cruz, Karen; Hemmy, Laura S; Woltjer, Randall; Leverenz, James B; Montine, Kathleen S; Jack, Clifford R; Kaye, Jeffrey; Lim, Kelvin; Larson, Eric B; White, Lon; Montine, Thomas J

    2011-08-01

    Alzheimer disease, cerebral vascular brain injury, and isocortical Lewy body disease (LBD) are the major contributors to dementia in community- and population-based studies. To estimate the prevalence of clinically silent forms of these diseases in cognitively normal (CN) adults. Autopsy study. Community- and population based. A total of 1672 brain autopsies from the Adult Changes in Thought study, Honolulu-Asia Aging Study, Nun Study, and Oregon Brain Aging Study, of which 424 met the criteria for CN. Of these, 336 cases had a comprehensive neuropathologic examination of neuritic plaque density, Braak stage for neurofibrillary tangles, LB distribution, and number of cerebral microinfarcts. Forty-seven percent of CN cases had moderate or frequent neuritic plaque density; of these, 6% also had Braak stage V or VI for neurofibrillary tangles. Fifteen percent of CN cases had medullary LBD; 8% also had nigral and 4% isocortical LBD. The presence of any cerebral microinfarcts was identified in 33% and of high-level cerebral microinfarcts in 10% of CN individuals. Overall, the burden of lesions in each individual and their comorbidity varied widely within each study but were similar across studies. These data show an individually varying complex convergence of subclinical diseases in the brain of older CN adults. Appreciating this ecology should help guide future biomarker and neuroimaging studies and clinical trials that focus on community- and population-based cohorts.

  2. Insulin action in the human brain: evidence from neuroimaging studies.

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    Kullmann, S; Heni, M; Fritsche, A; Preissl, H

    2015-06-01

    Thus far, little is known about the action of insulin in the human brain. Nonetheless, recent advances in modern neuroimaging techniques, such as functional magnetic resonance imaging (fMRI) or magnetoencephalography (MEG), have made it possible to investigate the action of insulin in the brain in humans, providing new insights into the pathogenesis of brain insulin resistance and obesity. Using MEG, the clinical relevance of the action of insulin in the brain was first identified, linking cerebral insulin resistance with peripheral insulin resistance, genetic predisposition and weight loss success in obese adults. Although MEG is a suitable tool for measuring brain activity mainly in cortical areas, fMRI provides high spatial resolution for cortical as well as subcortical regions. Thus, the action of insulin can be detected within all eating behaviour relevant regions, which include regions deeply located within the brain, such as the hypothalamus, midbrain and brainstem, as well as regions within the striatum. In this review, we outline recent advances in the field of neuroimaging aiming to investigate the action of insulin in the human brain using different routes of insulin administration. fMRI studies have shown a significant insulin-induced attenuation predominantly in the occipital and prefrontal cortical regions and the hypothalamus, successfully localising insulin-sensitive brain regions in healthy, mostly normal-weight individuals. However, further studies are needed to localise brain areas affected by insulin resistance in obese individuals, which is an important prerequisite for selectively targeting brain insulin resistance in obesity. © 2015 British Society for Neuroendocrinology.

  3. Cognitive genomics: Linking genes to behavior in the human brain

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    Genevieve Konopka

    2017-02-01

    Full Text Available Correlations of genetic variation in DNA with functional brain activity have already provided a starting point for delving into human cognitive mechanisms. However, these analyses do not provide the specific genes driving the associations, which are complicated by intergenic localization as well as tissue-specific epigenetics and expression. The use of brain-derived expression datasets could build upon the foundation of these initial genetic insights and yield genes and molecular pathways for testing new hypotheses regarding the molecular bases of human brain development, cognition, and disease. Thus, coupling these human brain gene expression data with measurements of brain activity may provide genes with critical roles in brain function. However, these brain gene expression datasets have their own set of caveats, most notably a reliance on postmortem tissue. In this perspective, I summarize and examine the progress that has been made in this realm to date, and discuss the various frontiers remaining, such as the inclusion of cell-type-specific information, additional physiological measurements, and genomic data from patient cohorts.

  4. Genomic and transcriptome profiling identified both human and HBV genetic variations and their interactions in Chinese hepatocellular carcinoma

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    Hua Dong

    2015-12-01

    Full Text Available Interaction between HBV and host genome integrations in hepatocellular carcinoma (HCC development is a complex process and the mechanism is still unclear. Here we described in details the quality controls and data mining of aCGH and transcriptome sequencing data on 50 HCC samples from the Chinese patients, published by Dong et al. (2015 (GEO#: GSE65486. In additional to the HBV-MLL4 integration discovered, we also investigated the genetic aberrations of HBV and host genes as well as their genetic interactions. We reported human genome copy number changes and frequent transcriptome variations (e.g. TP53, CTNNB1 mutation, especially MLL family mutations in this cohort of the patients. For HBV genotype C, we identified a novel linkage disequilibrium region covering HBV replication regulatory elements, including basal core promoter, DR1, epsilon and poly-A regions, which is associated with HBV core antigen over-expression and almost exclusive to HBV-MLL4 integration.

  5. Coupled Transcriptome and Proteome Analysis of Human Lymphotropic Tumor Viruses: Insights on the Detection and Discovery of Viral Genes

    Energy Technology Data Exchange (ETDEWEB)

    Dresang, Lindsay R.; Teuton, Jeremy R.; Feng, Huichen; Jacobs, Jon M.; Camp, David G.; Purvine, Samuel O.; Gritsenko, Marina A.; Li, Zhihua; Smith, Richard D.; Sugden, Bill; Moore, Patrick S.; Chang, Yuan

    2011-12-20

    Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are related human tumor viruses that cause primary effusion lymphomas (PEL) and Burkitt's lymphomas (BL), respectively. Viral genes expressed in naturally-infected cancer cells contribute to disease pathogenesis; knowing which viral genes are expressed is critical in understanding how these viruses cause cancer. To evaluate the expression of viral genes, we used high-resolution separation and mass spectrometry coupled with custom tiling arrays to align the viral proteomes and transcriptomes of three PEL and two BL cell lines under latent and lytic culture conditions. Results The majority of viral genes were efficiently detected at the transcript and/or protein level on manipulating the viral life cycle. Overall the correlation of expressed viral proteins and transcripts was highly complementary in both validating and providing orthogonal data with latent/lytic viral gene expression. Our approach also identified novel viral genes in both KSHV and EBV, and extends viral genome annotation. Several previously uncharacterized genes were validated at both transcript and protein levels. Conclusions This systems biology approach coupling proteome and transcriptome measurements provides a comprehensive view of viral gene expression that could not have been attained using each methodology independently. Detection of viral proteins in combination with viral transcripts is a potentially powerful method for establishing virus-disease relationships.

  6. CLIP-seq analysis of multi-mapped reads discovers novel functional RNA regulatory sites in the human transcriptome.

    Science.gov (United States)

    Zhang, Zijun; Xing, Yi

    2017-09-19

    Crosslinking or RNA immunoprecipitation followed by sequencing (CLIP-seq or RIP-seq) allows transcriptome-wide discovery of RNA regulatory sites. As CLIP-seq/RIP-seq reads are short, existing computational tools focus on uniquely mapped reads, while reads mapped to multiple loci are discarded. We present CLAM (CLIP-seq Analysis of Multi-mapped reads). CLAM uses an expectation-maximization algorithm to assign multi-mapped reads and calls peaks combining uniquely and multi-mapped reads. To demonstrate the utility of CLAM, we applied it to a wide range of public CLIP-seq/RIP-seq datasets involving numerous splicing factors, microRNAs and m6A RNA methylation. CLAM recovered a large number of novel RNA regulatory sites inaccessible by uniquely mapped reads. The functional significance of these sites was demonstrated by consensus motif patterns and association with alternative splicing (splicing factors), transcript abundance (AGO2) and mRNA half-life (m6A). CLAM provides a useful tool to discover novel protein-RNA interactions and RNA modification sites from CLIP-seq and RIP-seq data, and reveals the significant contribution of repetitive elements to the RNA regulatory landscape of the human transcriptome. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  7. Sibling rivalry among paralogs promotes evolution of the human brain.

    Science.gov (United States)

    Tyler-Smith, Chris; Xue, Yali

    2012-05-11

    Geneticists have long sought to identify the genetic changes that made us human, but pinpointing the functionally relevant changes has been challenging. Two papers in this issue suggest that partial duplication of SRGAP2, producing an incomplete protein that antagonizes the original, contributed to human brain evolution. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Shortcomings of the Human Brain and Remedial Action by Religion

    Science.gov (United States)

    Reich, K. Helmut

    2010-01-01

    There is no consensus as to whether, and if so, in which regard and to what extent science and religion is needed for human survival. Here a circumscribed domain is taken up: the sovereignty and sufficiency of the human brain in this context. Several of its shortcomings are pointed out. Religion and other aspects of culture are needed for remedial…

  9. Gene expression in the aging human brain: an overview.

    Science.gov (United States)

    Mohan, Adith; Mather, Karen A; Thalamuthu, Anbupalam; Baune, Bernhard T; Sachdev, Perminder S

    2016-03-01

    The review aims to provide a summary of recent developments in the study of gene expression in the aging human brain. Profiling differentially expressed genes or 'transcripts' in the human brain over the course of normal aging has provided valuable insights into the biological pathways that appear activated or suppressed in late life. Genes mediating neuroinflammation and immune system activation in particular, show significant age-related upregulation creating a state of vulnerability to neurodegenerative and neuropsychiatric disease in the aging brain. Cellular ionic dyshomeostasis and age-related decline in a host of molecular influences on synaptic efficacy may underlie neurocognitive decline in later life. Critically, these investigations have also shed light on the mobilization of protective genetic responses within the aging human brain that help determine health and disease trajectories in older age. There is growing interest in the study of pre and posttranscriptional regulators of gene expression, and the role of noncoding RNAs in particular, as mediators of the phenotypic diversity that characterizes human brain aging. Gene expression studies in healthy brain aging offer an opportunity to unravel the intricately regulated cellular underpinnings of neurocognitive aging as well as disease risk and resiliency in late life. In doing so, new avenues for early intervention in age-related neurodegenerative disease could be investigated with potentially significant implications for the development of disease-modifying therapies.

  10. Development of human brain structural networks through infancy and childhood.

    Science.gov (United States)

    Huang, Hao; Shu, Ni; Mishra, Virendra; Jeon, Tina; Chalak, Lina; Wang, Zhiyue J; Rollins, Nancy; Gong, Gaolang; Cheng, Hua; Peng, Yun; Dong, Qi; He, Yong

    2015-05-01

    During human brain development through infancy and childhood, microstructural and macrostructural changes take place to reshape the brain's structural networks and better adapt them to sophisticated functional and cognitive requirements. However, structural topological configuration of the human brain during this specific development period is not well understood. In this study, diffusion magnetic resonance image (dMRI) of 25 neonates, 13 toddlers, and 25 preadolescents were acquired to characterize network dynamics at these 3 landmark cross-sectional ages during early childhood. dMRI tractography was used to construct human brain structural networks, and the underlying topological properties were quantified by graph-theory approaches. Modular organization and small-world attributes are evident at birth with several important topological metrics increasing monotonically during development. Most significant increases of regional nodes occur in the posterior cingulate cortex, which plays a pivotal role in the functional default mode network. Positive correlations exist between nodal efficiencies and fractional anisotropy of the white matter traced from these nodes, while correlation slopes vary among the brain regions. These results reveal substantial topological reorganization of human brain structural networks through infancy and childhood, which is likely to be the outcome of both heterogeneous strengthening of the major white matter tracts and pruning of other axonal fibers. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. Development of Human Brain Structural Networks Through Infancy and Childhood

    Science.gov (United States)

    Huang, Hao; Shu, Ni; Mishra, Virendra; Jeon, Tina; Chalak, Lina; Wang, Zhiyue J.; Rollins, Nancy; Gong, Gaolang; Cheng, Hua; Peng, Yun; Dong, Qi; He, Yong

    2015-01-01

    During human brain development through infancy and childhood, microstructural and macrostructural changes take place to reshape the brain's structural networks and better adapt them to sophisticated functional and cognitive requirements. However, structural topological configuration of the human brain during this specific development period is not well understood. In this study, diffusion magnetic resonance image (dMRI) of 25 neonates, 13 toddlers, and 25 preadolescents were acquired to characterize network dynamics at these 3 landmark cross-sectional ages during early childhood. dMRI tractography was used to construct human brain structural networks, and the underlying topological properties were quantified by graph-theory approaches. Modular organization and small-world attributes are evident at birth with several important topological metrics increasing monotonically during development. Most significant increases of regional nodes occur in the posterior cingulate cortex, which plays a pivotal role in the functional default mode network. Positive correlations exist between nodal efficiencies and fractional anisotropy of the white matter traced from these nodes, while correlation slopes vary among the brain regions. These results reveal substantial topological reorganization of human brain structural networks through infancy and childhood, which is likely to be the outcome of both heterogeneous strengthening of the major white matter tracts and pruning of other axonal fibers. PMID:24335033

  12. BrainNet Viewer: a network visualization tool for human brain connectomics.

    Science.gov (United States)

    Xia, Mingrui; Wang, Jinhui; He, Yong

    2013-01-01

    The human brain is a complex system whose topological organization can be represented using connectomics. Recent studies have shown that human connectomes can be constructed using various neuroimaging technologies and further characterized using sophisticated analytic strategies, such as graph theory. These methods reveal the intriguing topological architectures of human brain networks in healthy populations and explore the changes throughout normal development and aging and under various pathological conditions. However, given the huge complexity of this methodology, toolboxes for graph-based network visualization are still lacking. Here, using MATLAB with a graphical user interface (GUI), we developed a graph-theoretical network visualization toolbox, called BrainNet Viewer, to illustrate human connectomes as ball-and-stick models. Within this toolbox, several combinations of defined files with connectome information can be loaded to display different combinations of brain surface, nodes and edges. In addition, display properties, such as the color and size of network elements or the layout of the figure, can be adjusted within a comprehensive but easy-to-use settings panel. Moreover, BrainNet Viewer draws the brain surface, nodes and edges in sequence and displays brain networks in multiple views, as required by the user. The figure can be manipulated with certain interaction functions to display more detailed information. Furthermore, the figures can be exported as commonly used image file formats or demonstration video for further use. BrainNet Viewer helps researchers to visualize brain networks in an easy, flexible and quick manner, and this software is freely available on the NITRC website (www.nitrc.org/projects/bnv/).

  13. BrainNet Viewer: a network visualization tool for human brain connectomics.

    Directory of Open Access Journals (Sweden)

    Mingrui Xia

    Full Text Available The human brain is a complex system whose topological organization can be represented using connectomics. Recent studies have shown that human connectomes can be constructed using various neuroimaging technologies and further characterized using sophisticated analytic strategies, such as graph theory. These methods reveal the intriguing topological architectures of human brain networks in healthy populations and explore the changes throughout normal development and aging and under various pathological conditions. However, given the huge complexity of this methodology, toolboxes for graph-based network visualization are still lacking. Here, using MATLAB with a graphical user interface (GUI, we developed a graph-theoretical network visualization toolbox, called BrainNet Viewer, to illustrate human connectomes as ball-and-stick models. Within this toolbox, several combinations of defined files with connectome information can be loaded to display different combinations of brain surface, nodes and edges. In addition, display properties, such as the color and size of network elements or the layout of the figure, can be adjusted within a comprehensive but easy-to-use settings panel. Moreover, BrainNet Viewer draws the brain surface, nodes and edges in sequence and displays brain networks in multiple views, as required by the user. The figure can be manipulated with certain interaction functions to display more detailed information. Furthermore, the figures can be exported as commonly used image file formats or demonstration video for further use. BrainNet Viewer helps researchers to visualize brain networks in an easy, flexible and quick manner, and this software is freely available on the NITRC website (www.nitrc.org/projects/bnv/.

  14. Expression of iron-related genes in human brain and brain tumors

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    Britton Robert S

    2009-04-01

    Full Text Available Abstract Background Defective iron homeostasis may be involved in the development of some diseases within the central nervous system. Although the expression of genes involved in normal iron balance has been intensively studied in other tissues, little is known about their expression in the brain. We investigated the mRNA levels of hepcidin (HAMP, HFE, neogenin (NEO1, transferrin receptor 1 (TFRC, transferrin receptor 2 (TFR2, and hemojuvelin (HFE2 in normal human brain, brain tumors, and astrocytoma cell lines. The specimens included 5 normal brain tissue samples, 4 meningiomas, one medulloblastoma, 3 oligodendrocytic gliomas, 2 oligoastrocytic gliomas, 8 astrocytic gliomas, and 3 astrocytoma cell lines. Results Except for hemojuvelin, all genes studied had detectable levels of mRNA. In most tumor types, the pattern of gene expression was diverse. Notable findings include high expression of transferrin receptor 1 in the hippocampus and medulla oblongata compared to other brain regions, low expression of HFE in normal brain with elevated HFE expression in meningiomas, and absence of hepcidin mRNA in astrocytoma cell lines despite expression in normal brain and tumor specimens. Conclusion These results indicate that several iron-related genes are expressed in normal brain, and that their expression may be dysregulated in brain tumors.

  15. Electrical Guidance of Human Stem Cells in the Rat Brain

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    Jun-Feng Feng

    2017-07-01

    Full Text Available Limited migration of neural stem cells in adult brain is a roadblock for the use of stem cell therapies to treat brain diseases and injuries. Here, we report a strategy that mobilizes and guides migration of stem cells in the brain in vivo. We developed a safe stimulation paradigm to deliver directional currents in the brain. Tracking cells expressing GFP demonstrated electrical mobilization and guidance of migration of human neural stem cells, even against co-existing intrinsic cues in the rostral migration stream. Transplanted cells were observed at 3 weeks and 4 months after stimulation in areas guided by the stimulation currents, and with indications of differentiation. Electrical stimulation thus may provide a potential approach to facilitate brain stem cell therapies.

  16. Three-dimensional morphology of the human embryonic brain

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    N. Shiraishi

    2015-09-01

    Full Text Available The morphogenesis of the cerebral vesicles and ventricles was visualized in 3D movies using images derived from human embryo specimens between Carnegie stage 13 and 23 from the Kyoto Collection. These images were acquired with a magnetic resonance microscope equipped with a 2.35-T superconducting magnet. Three-dimensional images using the same scale demonstrated brain development and growth effectively. The non-uniform thickness of the brain tissue, which may indicate brain differentiation, was visualized with thickness-based surface color mapping. A closer view was obtained of the unique and complicated differentiation of the rhombencephalon, especially with regard to the internal view and thickening of the brain tissue. The present data contribute to a better understanding of brain and cerebral ventricle development.

  17. The maternal brain and its plasticity in humans

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    Kim, Pilyoung; Strathearn, Lane; Swain, James E.

    2015-01-01

    Early mother-infant relationships play important roles in infants’ optimal development. New mothers undergo neurobiological changes that support developing mother-infant relationships regardless of great individual differences in those relationships. In this article, we review the neural plasticity in human mothers’ brains based on functional magnetic resonance imaging (fMRI) studies. First, we review the neural circuits that are involved in establishing and maintaining mother-infant relationships. Second, we discuss early postpartum factors (e.g., birth and feeding methods, hormones, and parental sensitivity) that are associated with individual differences in maternal brain neuroplasticity. Third, we discuss abnormal changes in the maternal brain related to psychopathology (i.e., postpartum depression, posttraumatic stress disorder, substance abuse) and potential brain remodeling associated with interventions. Last, we highlight potentially important future research directions to better understand normative changes in the maternal brain and risks for abnormal changes that may disrupt early mother-infant relationships. PMID:26268151

  18. The bilingual brain: Flexibility and control in the human cortex

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    Buchweitz, Augusto; Prat, Chantel

    2013-12-01

    The goal of the present review is to discuss recent cognitive neuroscientific findings concerning bilingualism. Three interrelated questions about the bilingual brain are addressed: How are multiple languages represented in the brain? how are languages controlled in the brain? and what are the real-world implications of experience with multiple languages? The review is based on neuroimaging research findings about the nature of bilingual processing, namely, how the brain adapts to accommodate multiple languages in the bilingual brain and to control which language should be used, and when. We also address how this adaptation results in differences observed in the general cognition of bilingual individuals. General implications for models of human learning, plasticity, and cognitive control are discussed.

  19. Addiction Circuitry in the Human Brain*

    OpenAIRE

    Volkow, Nora D.; Wang, Gene-Jack; Fowler, Joanna S.; Tomasi, Dardo

    2011-01-01

    A major challenge in understanding substance-use disorders lies in uncovering why some individuals become addicted when exposed to drugs, whereas others do not. Although genetic, developmental, and environmental factors are recognized as major contributors to a person’s risk of becoming addicted, the neurobiological processes that underlie this vulnerability are still poorly understood. Imaging studies suggest that individual variations in key dopamine-modulated brain circuits, including circ...

  20. A family of hyperelastic models for human brain tissue

    Science.gov (United States)

    Mihai, L. Angela; Budday, Silvia; Holzapfel, Gerhard A.; Kuhl, Ellen; Goriely, Alain

    2017-09-01

    Experiments on brain samples under multiaxial loading have shown that human brain tissue is both extremely soft when compared to other biological tissues and characterized by a peculiar elastic response under combined shear and compression/tension: there is a significant increase in shear stress with increasing axial compression compared to a moderate increase with increasing axial tension. Recent studies have revealed that many widely used constitutive models for soft biological tissues fail to capture this characteristic response. Here, guided by experiments of human brain tissue, we develop a family of modeling approaches that capture the elasticity of brain tissue under varying simple shear superposed on varying axial stretch by exploiting key observations about the behavior of the nonlinear shear modulus, which can be obtained directly from the experimental data.

  1. Brain and Social Networks: Fundamental Building Blocks of Human Experience.

    Science.gov (United States)

    Falk, Emily B; Bassett, Danielle S

    2017-09-01

    How do brains shape social networks, and how do social ties shape the brain? Social networks are complex webs by which ideas spread among people. Brains comprise webs by which information is processed and transmitted among neural units. While brain activity and structure offer biological mechanisms for human behaviors, social networks offer external inducers or modulators of those behaviors. Together, these two axes represent fundamental contributors to human experience. Integrating foundational knowledge from social and developmental psychology and sociology on how individuals function within dyads, groups, and societies with recent advances in network neuroscience can offer new insights into both domains. Here, we use the example of how ideas and behaviors spread to illustrate the potential of multilayer network models. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Decade of the Brain 1990--2000: Maximizing human potential

    Energy Technology Data Exchange (ETDEWEB)

    1991-04-01

    The US Decade of the Brain offers scientists throughout the Federal Government a unique opportunity to advance and apply scientific knowledge about the brain and nervous system. During the next 10 years, scientists hope to maximize human potential through studies of human behavior, senses and communication, learning and memory, genetic/chemical alterations, and environmental interactions. Progress in these areas should lead to reductions in mortality from brain and nervous system disorders and to improvements in the quality of life. This report identifies nine research areas that could form the basis of an integrated program in the brain and behavioral sciences. A chart summarizing the Federal activities in these nine areas may be found at the back of the report. In addition, three areas that span the nine research areas -- basic research, technology and international activities -- are considered.

  3. Fundamental Dynamical Modes Underlying Human Brain Synchronization

    Directory of Open Access Journals (Sweden)

    Catalina Alvarado-Rojas

    2012-01-01

    Full Text Available Little is known about the long-term dynamics of widely interacting cortical and subcortical networks during the wake-sleep cycle. Using large-scale intracranial recordings of epileptic patients during seizure-free periods, we investigated local- and long-range synchronization between multiple brain regions over several days. For such high-dimensional data, summary information is required for understanding and modelling the underlying dynamics. Here, we suggest that a compact yet useful representation is given by a state space based on the first principal components. Using this representation, we report, with a remarkable similarity across the patients with different locations of electrode placement, that the seemingly complex patterns of brain synchrony during the wake-sleep cycle can be represented by a small number of characteristic dynamic modes. In this space, transitions between behavioral states occur through specific trajectories from one mode to another. These findings suggest that, at a coarse level of temporal resolution, the different brain states are correlated with several dominant synchrony patterns which are successively activated across wake-sleep states.

  4. Small-world human brain networks: Perspectives and challenges.

    Science.gov (United States)

    Liao, Xuhong; Vasilakos, Athanasios V; He, Yong

    2017-06-01

    Modelling the human brain as a complex network has provided a powerful mathematical framework to characterize the structural and functional architectures of the brain. In the past decade, the combination of non-invasive neuroimaging techniques and graph theoretical approaches enable us to map human structural and functional connectivity patterns (i.e., connectome) at the macroscopic level. One of the most influential findings is that human brain networks exhibit prominent small-world organization. Such a network architecture in the human brain facilitates efficient information segregation and integration at low wiring and energy costs, which presumably results from natural selection under the pressure of a cost-efficiency balance. Moreover, the small-world organization undergoes continuous changes during normal development and ageing and exhibits dramatic alterations in neurological and psychiatric disorders. In this review, we survey recent advances regarding the small-world architecture in human brain networks and highlight the potential implications and applications in multidisciplinary fields, including cognitive neuroscience, medicine and engineering. Finally, we highlight several challenging issues and areas for future research in this rapidly growing field. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Female Mimicry by Sneaker Males Has a Transcriptomic Signature in Both the Brain and the Gonad in a Sex-Changing Fish.

    Science.gov (United States)

    Todd, Erica V; Liu, Hui; Lamm, Melissa S; Thomas, Jodi T; Rutherford, Kim; Thompson, Kelly C; Godwin, John R; Gemmell, Neil J

    2018-01-01

    Phenotypic plasticity represents an elegant adaptive response of individuals to a change in their environment. Bluehead wrasses (Thalassoma bifasciatum) exhibit astonishing sexual plasticity, including female-to-male sex change and discrete male morphs that differ strikingly in behavior, morphology, and gonadal investment. Using RNA-seq transcriptome profiling, we examined the genes and physiological pathways underlying flexible behavioral and gonadal differences among female, dominant (bourgeois) male, and female-mimic (sneaker) male blueheads. For the first time in any organism, we find that female mimicry by sneaker males has a transcriptional signature in both the brain and the gonad. Sneaker males shared striking similarity in neural gene expression with females, supporting the idea that males with alternative reproductive phenotypes have "female-like brains." Sneaker males also overexpressed neuroplasticity genes, suggesting that their opportunistic reproductive strategy requires a heightened capacity for neuroplasticity. Bourgeois males overexpressed genes associated with socio-sexual behaviors (e.g., isotocin), but also neuroprotective genes and biomarkers of oxidative stress and aging, indicating a hitherto unexplored cost to these males of attaining the reproductively privileged position at the top of the social hierarchy. Our novel comparison of testicular transcriptomes in a fish with male sexual polymorphism associates greater gonadal investment by sneaker males with overexpression of genes involved in cell proliferation and sperm quality control. We propose that morphological female-mimicry by sneaker male teleosts entails pervasive downregulation of androgenesis genes, consistent with low androgen production in males lacking well-developed secondary sexual characters. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Temporal variation in brain transcriptome is associated with the expression of female mimicry as a sequential male alternative reproductive tactic in fish.

    Science.gov (United States)

    Cardoso, Sara D; Gonçalves, David; Goesmann, Alexander; Canário, Adelino V M; Oliveira, Rui F

    2018-02-01

    Distinct patterns of gene expression often underlie intra- and intersexual differences, and the study of this set of coregulated genes is essential to understand the emergence of complex behavioural phenotypes. Here, we describe the development of a de novo transcriptome and brain gene expression profiles of wild-caught peacock blenny, Salaria pavo, an intertidal fish with sex-role reversal in courtship behaviour (i.e., females are the courting sex) and sequential alternative reproductive tactics in males (i.e., larger and older nest-holder males and smaller and younger sneaker males occur). Sneakers mimic both female's courtship behaviour and nuptial coloration to get access to nests and sneak fertilizations, and later in life transition into nest-holder males. Thus, this species offers the unique opportunity to study how the regulation of gene expression can contribute to intersex phenotypes and to the sequential expression of male and female behavioural phenotypes by the same individual. We found that at the whole brain level, expression of the sneaker tactic was paralleled by broader and divergent gene expression when compared to either females or nest-holder males, which were more similar between themselves. When looking at sex-biased transcripts, sneaker males are intersex rather than being either nest-holder or female-like, and their transcriptome is simultaneously demasculinized for nest-holder-biased transcripts and feminized for female-biased transcripts. These results indicate that evolutionary changes in reproductive plasticity can be achieved through regulation of gene expression, and in particular by varying the magnitude of expression of sex-biased genes, throughout the lifetime of the same individual. © 2017 John Wiley & Sons Ltd.

  7. NMR relaxation times in human brain tumors (preliminary results)

    International Nuclear Information System (INIS)

    Benoist, L.; Certaines, J. de; Chatel, M.; Menault, F.

    1981-01-01

    Since the early work of Damadian in 1971, proton NMR studies of tumors has been well documented. Present study concerns the spin-lattice T 1 and spin-spin T 2 relaxation times of normal dog brain according to the histological differentiation and of 35 human benignant or malignant tumors. The results principally show T 2 important variations between white and gray substance in normal brain but no discrimination between malignant and benignant tumors [fr

  8. A psychology of the human brain-gut-microbiome axis.

    Science.gov (United States)

    Allen, Andrew P; Dinan, Timothy G; Clarke, Gerard; Cryan, John F

    2017-04-01

    In recent years, we have seen increasing research within neuroscience and biopsychology on the interactions between the brain, the gastrointestinal tract, the bacteria within the gastrointestinal tract, and the bidirectional relationship between these systems: the brain-gut-microbiome axis. Although research has demonstrated that the gut microbiota can impact upon cognition and a variety of stress-related behaviours, including those relevant to anxiety and depression, we still do not know how this occurs. A deeper understanding of how psychological development as well as social and cultural factors impact upon the brain-gut-microbiome axis will contextualise the role of the axis in humans and inform psychological interventions that improve health within the brain-gut-microbiome axis. Interventions ostensibly aimed at ameliorating disorders in one part of the brain-gut-microbiome axis (e.g., psychotherapy for depression) may nonetheless impact upon other parts of the axis (e.g., microbiome composition and function), and functional gastrointestinal disorders such as irritable bowel syndrome represent a disorder of the axis, rather than an isolated problem either of psychology or of gastrointestinal function. The discipline of psychology needs to be cognisant of these interactions and can help to inform the future research agenda in this emerging field of research. In this review, we outline the role psychology has to play in understanding the brain-gut-microbiome axis, with a focus on human psychology and the use of research in laboratory animals to model human psychology.

  9. Distribution of vesicular glutamate transporters in the human brain

    Directory of Open Access Journals (Sweden)

    Erika eVigneault

    2015-03-01

    Full Text Available Glutamate is the major excitatory transmitter in the brain. Vesicular glutamate transporters (VGLUT1-3 are responsible for uploading glutamate into synaptic vesicles. VGLUT1 and VGLUT2 are considered as specific markers of canonical glutamatergic neurons, while VGLUT3 is found in neurons previously shown to use other neurotransmitters than glutamate. Although there exists a rich literature on the localization of these glutamatergic markers in the rodent brain, little is currently known about the distribution of VGLUT1-3 in the human brain. In the present study, using subtype specific probes and antisera, we examined the localization of the three vesicular glutamate transporters in the human brain by in situ hybridization, immunoautoradiography and immunohistochemistry. We found that the VGLUT1 transcript was highly expressed in the cerebral cortex, hippocampus and cerebellum, whereas VGLUT2 mRNA was mainly found in the thalamus and brainstem. VGLUT3 mRNA was localized in scarce neurons within the cerebral cortex, hippocampus, striatum and raphe nuclei. Following immunoautoradiographic labeling, intense VGLUT1- and VGLUT2-immunoreactivities were observed in all regions investigated (cerebral cortex, hippocampus, caudate-putamen, cerebellum, thalamus, amygdala, substantia nigra, raphe while VGLUT3 was absent from the thalamus and cerebellum. This extensive mapping of VGLUT1-3 in human brain reveals distributions that correspond for the most part to those previously described in rodent brains.

  10. Regional distribution of serotonin transporter protein in postmortem human brain

    Energy Technology Data Exchange (ETDEWEB)

    Kish, Stephen J. [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada)]. E-mail: Stephen_Kish@CAMH.net; Furukawa, Yoshiaki [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Chang Lijan [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Tong Junchao [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Ginovart, Nathalie [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Wilson, Alan [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Houle, Sylvain [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Meyer, Jeffrey H. [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada)

    2005-02-01

    Introduction: The primary approach in assessing the status of brain serotonin neurons in human conditions such as major depression and exposure to the illicit drug ecstasy has been the use of neuroimaging procedures involving radiotracers that bind to the serotonin transporter (SERT). However, there has been no consistency in the selection of a 'SERT-free' reference region for the estimation of free and nonspecific binding, as occipital cortex, cerebellum and white matter have all been employed. Objective and Methods: To identify areas of human brain that might have very low SERT levels, we measured, by a semiquantitative Western blotting procedure, SERT protein immunoreactivity throughout the postmortem brain of seven normal adult subjects. Results: Serotonin transporter could be quantitated in all examined brain areas. However, the SERT concentration in cerebellar cortex and white matter were only at trace values, being approximately 20% of average cerebral cortex and 5% of average striatum values. Conclusion: Although none of the examined brain areas are completely free of SERT, human cerebellar cortex has low SERT binding as compared to other examined brain regions, with the exception of white matter. Since the cerebellar cortical SERT binding is not zero, this region will not be a suitable reference region for SERT radioligands with very low free and nonspecific binding. For SERT radioligands with reasonably high free and nonspecific binding, the cerebellar cortex should be a useful reference region, provided other necessary radioligand assumptions are met.

  11. Regional distribution of serotonin transporter protein in postmortem human brain

    International Nuclear Information System (INIS)

    Kish, Stephen J.; Furukawa, Yoshiaki; Chang Lijan; Tong Junchao; Ginovart, Nathalie; Wilson, Alan; Houle, Sylvain; Meyer, Jeffrey H.

    2005-01-01

    Introduction: The primary approach in assessing the status of brain serotonin neurons in human conditions such as major depression and exposure to the illicit drug ecstasy has been the use of neuroimaging procedures involving radiotracers that bind to the serotonin transporter (SERT). However, there has been no consistency in the selection of a 'SERT-free' reference region for the estimation of free and nonspecific binding, as occipital cortex, cerebellum and white matter have all been employed. Objective and Methods: To identify areas of human brain that might have very low SERT levels, we measured, by a semiquantitative Western blotting procedure, SERT protein immunoreactivity throughout the postmortem brain of seven normal adult subjects. Results: Serotonin transporter could be quantitated in all examined brain areas. However, the SERT concentration in cerebellar cortex and white matter were only at trace values, being approximately 20% of average cerebral cortex and 5% of average striatum values. Conclusion: Although none of the examined brain areas are completely free of SERT, human cerebellar cortex has low SERT binding as compared to other examined brain regions, with the exception of white matter. Since the cerebellar cortical SERT binding is not zero, this region will not be a suitable reference region for SERT radioligands with very low free and nonspecific binding. For SERT radioligands with reasonably high free and nonspecific binding, the cerebellar cortex should be a useful reference region, provided other necessary radioligand assumptions are met

  12. Brain Activation During Singing: "Clef de Sol Activation" Is the "Concert" of the Human Brain.

    Science.gov (United States)

    Mavridis, Ioannis N; Pyrgelis, Efstratios-Stylianos

    2016-03-01

    Humans are the most complex singers in nature, and the human voice is thought by many to be the most beautiful musical instrument. Aside from spoken language, singing represents a second mode of acoustic communication in humans. The purpose of this review article is to explore the functional anatomy of the "singing" brain. Methodologically, the existing literature regarding activation of the human brain during singing was carefully reviewed, with emphasis on the anatomic localization of such activation. Relevant human studies are mainly neuroimaging studies, namely functional magnetic resonance imaging and positron emission tomography studies. Singing necessitates activation of several cortical, subcortical, cerebellar, and brainstem areas, served and coordinated by multiple neural networks. Functionally vital cortical areas of the frontal, parietal, and temporal lobes bilaterally participate in the brain's activation process during singing, confirming the latter's role in human communication. Perisylvian cortical activity of the right hemisphere seems to be the most crucial component of this activation. This also explains why aphasic patients due to left hemispheric lesions are able to sing but not speak the same words. The term clef de sol activation is proposed for this crucial perisylvian cortical activation due to the clef de sol shape of the topographical distribution of these cortical areas around the sylvian fissure. Further research is needed to explore the connectivity and sequence of how the human brain activates to sing.

  13. A meta-analysis of human embryonic stem cells transcriptome integrated into a web-based expression atlas.

    Science.gov (United States)

    Assou, Said; Le Carrour, Tanguy; Tondeur, Sylvie; Ström, Susanne; Gabelle, Audrey; Marty, Sophie; Nadal, Laure; Pantesco, Véronique; Réme, Thierry; Hugnot, Jean-Philippe; Gasca, Stéphan; Hovatta, Outi; Hamamah, Samir; Klein, Bernard; De Vos, John

    2007-04-01

    Microarray technology provides a unique opportunity to examine gene expression patterns in human embryonic stem cells (hESCs). We performed a meta-analysis of 38 original studies reporting on the transcriptome of hESCs. We determined that 1,076 genes were found to be overexpressed in hESCs by at least three studies when compared to differentiated cell types, thus composing a "consensus hESC gene list." Only one gene was reported by all studies: the homeodomain transcription factor POU5F1/OCT3/4. The list comprised other genes critical for pluripotency such as the transcription factors NANOG and SOX2, and the growth factors TDGF1/CRIPTO and Galanin. We show that CD24 and SEMA6A, two cell surface protein-coding genes from the top of the consensus hESC gene list, display a strong and specific membrane protein expression on hESCs. Moreover, CD24 labeling permits the purification by flow cytometry of hESCs cocultured on human fibroblasts. The consensus hESC gene list also included the FZD7 WNT receptor, the G protein-coupled receptor GPR19, and the HELLS helicase, which could play an important role in hESCs biology. Conversely, we identified 783 genes downregulated in hESCs and reported in at least three studies. This "consensus differentiation gene list" included the IL6ST/GP130 LIF receptor. We created an online hESC expression atlas, http://amazonia.montp.inserm.fr, to provide an easy access to this public transcriptome dataset. Expression histograms comparing hESCs to a broad collection of fetal and adult tissues can be retrieved with this web tool for more than 15,000 genes.

  14. Multilayer modeling and analysis of human brain networks

    Science.gov (United States)

    2017-01-01

    Abstract Understanding how the human brain is structured, and how its architecture is related to function, is of paramount importance for a variety of applications, including but not limited to new ways to prevent, deal with, and cure brain diseases, such as Alzheimer’s or Parkinson’s, and psychiatric disorders, such as schizophrenia. The recent advances in structural and functional neuroimaging, together with the increasing attitude toward interdisciplinary approaches involving computer science, mathematics, and physics, are fostering interesting results from computational neuroscience that are quite often based on the analysis of complex network representation of the human brain. In recent years, this representation experienced a theoretical and computational revolution that is breaching neuroscience, allowing us to cope with the increasing complexity of the human brain across multiple scales and in multiple dimensions and to model structural and functional connectivity from new perspectives, often combined with each other. In this work, we will review the main achievements obtained from interdisciplinary research based on magnetic resonance imaging and establish de facto, the birth of multilayer network analysis and modeling of the human brain. PMID:28327916

  15. Human-like brain hemispheric dominance in birdsong learning.

    Science.gov (United States)

    Moorman, Sanne; Gobes, Sharon M H; Kuijpers, Maaike; Kerkhofs, Amber; Zandbergen, Matthijs A; Bolhuis, Johan J

    2012-07-31

    Unlike nonhuman primates, songbirds learn to vocalize very much like human infants acquire spoken language. In humans, Broca's area in the frontal lobe and Wernicke's area in the temporal lobe are crucially involved in speech production and perception, respectively. Songbirds have analogous brain regions that show a similar neural dissociation between vocal production and auditory perception and memory. In both humans and songbirds, there is evidence for lateralization of neural responsiveness in these brain regions. Human infants already show left-sided dominance in their brain activation when exposed to speech. Moreover, a memory-specific left-sided dominance in Wernicke's area for speech perception has been demonstrated in 2.5-mo-old babies. It is possible that auditory-vocal learning is associated with hemispheric dominance and that this association arose in songbirds and humans through convergent evolution. Therefore, we investigated whether there is similar song memory-related lateralization in the songbird brain. We exposed male zebra finches to tutor or unfamiliar song. We found left-sided dominance of neuronal activation in a Broca-like brain region (HVC, a letter-based name) of juvenile and adult zebra finch males, independent of the song stimulus presented. In addition, juvenile males showed left-sided dominance for tutor song but not for unfamiliar song in a Wernicke-like brain region (the caudomedial nidopallium). Thus, left-sided dominance in the caudomedial nidopallium was specific for the song-learning phase and was memory-related. These findings demonstrate a remarkable neural parallel between birdsong and human spoken language, and they have important consequences for our understanding of the evolution of auditory-vocal learning and its neural mechanisms.

  16. Data integration through brain atlasing: Human Brain Project tools and strategies.

    Science.gov (United States)

    Bjerke, Ingvild E; Øvsthus, Martin; Papp, Eszter A; Yates, Sharon C; Silvestri, Ludovico; Fiorilli, Julien; Pennartz, Cyriel M A; Pavone, Francesco S; Puchades, Maja A; Leergaard, Trygve B; Bjaalie, Jan G

    2018-04-01

    The Human Brain Project (HBP), an EU Flagship Initiative, is currently building an infrastructure that will allow integration of large amounts of heterogeneous neuroscience data. The ultimate goal of the project is to develop a unified multi-level understanding of the brain and its diseases, and beyond this to emulate the computational capabilities of the brain. Reference atlases of the brain are one of the key components in this infrastructure. Based on a new generation of three-dimensional (3D) reference atlases, new solutions for analyzing and integrating brain data are being developed. HBP will build services for spatial query and analysis of brain data comparable to current online services for geospatial data. The services will provide interactive access to a wide range of data types that have information about anatomical location tied to them. The 3D volumetric nature of the brain, however, introduces a new level of complexity that requires a range of tools for making use of and interacting with the atlases. With such new tools, neuroscience research groups will be able to connect their data to atlas space, share their data through online data systems, and search and find other relevant data through the same systems. This new approach partly replaces earlier attempts to organize research data based only on a set of semantic terminologies describing the brain and its subdivisions. Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

  17. Brain shape in human microcephalics and Homo floresiensis.

    Science.gov (United States)

    Falk, Dean; Hildebolt, Charles; Smith, Kirk; Morwood, M J; Sutikna, Thomas; Jatmiko; Saptomo, E Wayhu; Imhof, Herwig; Seidler, Horst; Prior, Fred

    2007-02-13

    Because the cranial capacity of LB1 (Homo floresiensis) is only 417 cm(3), some workers propose that it represents a microcephalic Homo sapiens rather than a new species. This hypothesis is difficult to assess, however, without a clear understanding of how brain shape of microcephalics compares with that of normal humans. We compare three-dimensional computed tomographic reconstructions of the internal braincases (virtual endocasts that reproduce details of external brain morphology, including cranial capacities and shape) from a sample of 9 microcephalic humans and 10 normal humans. Discriminant and canonical analyses are used to identify two variables that classify normal and microcephalic humans with 100% success. The classification functions classify the virtual endocast from LB1 with normal humans rather than microcephalics. On the other hand, our classification functions classify a pathological H. sapiens specimen that, like LB1, represents an approximately 3-foot-tall adult female and an adult Basuto microcephalic woman that is alleged to have an endocast similar to LB1's with the microcephalic humans. Although microcephaly is genetically and clinically variable, virtual endocasts from our highly heterogeneous sample share similarities in protruding and proportionately large cerebella and relatively narrow, flattened orbital surfaces compared with normal humans. These findings have relevance for hypotheses regarding the genetic substrates of hominin brain evolution and may have medical diagnostic value. Despite LB1's having brain shape features that sort it with normal humans rather than microcephalics, other shape features and its small brain size are consistent with its assignment to a separate species.

  18. Proposed link rates in the human brain.

    Science.gov (United States)

    van Putten, Michael J A M

    2003-07-15

    There is increasing experimental evidence that neuronal synchronization is necessary for the large-scale integration of distributed neuronal activity to realize various time-dependent coherent neuronal assemblies in the brain. Phase synchronization seems a promising candidate to quantify the time-dependent, frequency specific, synchrony between simultaneously recorded electroencephalogram (EEG) signals that may partially reflect this former process. We introduce a link rate (LR) as a measure of the spatial-temporal incidence of phase synchronization and phase de-synchronization. The concept is exemplified in its application to the analysis of spontaneous phase synchronization. To this end, three scalp EEG recordings are used: a normal control, a patient suffering from epileptic seizures and a patient with diffuse brain damage due to anoxia, showing a burst-suppression EEG. In addition, the method is applied to surrogate data (white noise). We find in the normal control that LR(control)=13.90+/-0.04 (mean+/-S.E.M.), which is different from the surrogate data, where we find that LR(surr)=15.36+/-0.05. In the two pathological conditions, the LR is significantly and strongly reduced to LR(burst)=4.52+/-0.05 and LR(seizure)=5.40+/-0.08. The derived LR seems a sensitive measure to relevant changes in synchronization, as these occur in the dynamic process of generating different spatial-temporal networks, both in physiological and pathological conditions.

  19. Message processing in the human brain. III

    Energy Technology Data Exchange (ETDEWEB)

    Gerke, P

    1983-10-07

    For pt.II see ibid., no.19, p.95-100 (1983). The general problem of the possibly achievable super brain is discussed, and subtle differences between various linkages leading to selective processes, creativity decision making and speculative assessments are pointed out and translated into possible approaches to the making of machine intelligence. Generally, associative sequences for processing of large data flows cannot be attempted without the provision of generally valid linkage rules. Such coordination steps are considered first, the brain-machine simulation being built-up vertically on 6 levels and horizontally as recognition stages in an event. These six levels are: repertoire (i.e. vocabulary); definition; scene; happenings; spatial linkages; temporal linkages. Event simulation proceeds from the descriptive to the cognitive situation. Speculative discussions continue with the gradual introduction of computer hardware and software concepts to be adapted for intelligence simulation; thus, the simplest associative process could start with an adder network and proceed to a virtual expert system, which would include teaching by example, autonomous control, non-procedural language, all these governed by schedules.

  20. Optimizing full-brain coverage in human brain MRI through population distributions of brain size

    NARCIS (Netherlands)

    Mennes, M.; Jenkinson, M.; Valabregue, R.; Buitelaar, J.K.; Beckmann, C.F.; Smith, S.

    2014-01-01

    When defining an MRI protocol, brain researchers need to set multiple interdependent parameters that define repetition time (TR), voxel size, field-of-view (FOV), etc. Typically, researchers aim to image the full brain, making the expected FOV an important parameter to consider. Especially in 2D-EPI

  1. Measuring dopamine release in the human brain with PET

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D. [Brookhaven National Lab., Upton, NY (United States)]|[State Univ. of New York at Stony Brook, Stony Brook, NY (United States). Dept. of Psychiatry; Fowler, J.S.; Logan, J.; Wang, G.J. [Brookhaven National Lab., Upton, NY (United States)

    1995-12-01

    The dopamine system is involved in the regulation of brain regions that subserve motor, cognitive and motivational behaviors. Disruptions of dopamine (DA) function have ben implicated in neurological and psychiatric illnesses including substance abuse as well as on some of the deficits associated with aging of the human brain. This has made the DA system an important topic in research in the neurosciences and neuroimaging as well as an important molecular target for drug development. Positron Emission Tomography (PET), was the first technology that enabled direct measurement of components of the DA system in the living human brain. Imaging studies of DA in the living brain have been indirect, relying on the development of radiotracers to label DA receptors, DA transporters, compounds which have specificity for the enzymes which degrade synaptic DA. Additionally, through the use of tracers that provide information on regional brain activity (ie brain glucose metabolism and cerebral blood flow) and of appropriate pharmacological interventions, it has been possible to assess the functional consequences of changes in brain DA activity. DA specific ligands have been useful in the evaluation of patients with neuropsychiatric illnesses as well as to investigate receptor blockade by antipsychotic drugs. A limitation of strategies that rely on the use of DA specific ligands is that the measures do not necessarily reflect the functional state of the dopaminergic system and that there use to study the effects of drugs is limited to the investigation of receptor or transporter occupancy. Newer strategies have been developed in an attempt to provide with information on dopamine release and on the functional responsivity of the DA system in the human brain. This in turn allows to investigate the effects of pharmacological agent in an analogous way to what is done with microdialysis techniques.

  2. Gender development and the human brain.

    Science.gov (United States)

    Hines, Melissa

    2011-01-01

    Convincing evidence indicates that prenatal exposure to the gonadal hormone, testosterone, influences the development of children's sex-typical toy and activity interests. In addition, growing evidence shows that testosterone exposure contributes similarly to the development of other human behaviors that show sex differences, including sexual orientation, core gender identity, and some, though not all, sex-related cognitive and personality characteristics. In addition to these prenatal hormonal influences, early infancy and puberty may provide additional critical periods when hormones influence human neurobehavioral organization. Sex-linked genes could also contribute to human gender development, and most sex-related characteristics are influenced by socialization and other aspects of postnatal experience, as well. Neural mechanisms underlying the influences of gonadal hormones on human behavior are beginning to be identified. Although the neural mechanisms underlying experiential influences remain largely uninvestigated, they could involve the same neural circuitry as that affected by hormones.

  3. Thrombin binding to human brain and spinal cord

    International Nuclear Information System (INIS)

    McKinney, M.; Snider, R.M.; Richelson, E.

    1983-01-01

    Thrombin, a serine protease that regulates hemostasis, has been shown to stimulate the formation of cGMP in murine neuroblastoma cells. The nervous system in vivo thus may be postulated to respond to this blood-borne factor after it breaches the blood-brain barrier, as in trauma. Human alpha-thrombin was radiolabeled with 125I and shown to bind rapidly, reversibly, and with high affinity to human brain and spinal cord. These findings indicate the presence of specific thrombin-binding sites in nervous tissue and may have important clinical implications

  4. Simplified detection system for neuroreceptor studies in the human brain

    International Nuclear Information System (INIS)

    Bice, A.N.; Wagner, H.N. Jr.; Frost, J.J.

    1986-01-01

    A simple, inexpensive dual-detector system has been developed for measurement of positronemitting receptor-binding drugs in the human brain. This high efficiency coincidence counting system requires that only a few hundred microcuries of labeled drug be administered to the subject, thereby allowing for multiple studies without an excessive radiation dose. Measurement of the binding of [11C]carfentanil, a high affinity synthetic opiate, to opiate receptors in the presence and in the absence of a competitive opiate antagonist indicates the potential utility of this system for estimating different degrees of receptor occupation in the human brain

  5. Mu opioid receptor binding sites in human brain

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  6. Glucose transporter of the human brain and blood-brain barrier

    International Nuclear Information System (INIS)

    Kalaria, R.N.; Gravina, S.A.; Schmidley, J.W.; Perry, G.; Harik, S.I.

    1988-01-01

    We identified and characterized the glucose transporter in the human cerebral cortex, cerebral microvessels, and choroid plexus by specific D-glucose-displaceable [3H]cytochalasin B binding. The binding was saturable, with a dissociation constant less than 1 microM. Maximal binding capacity was approximately 7 pmol/mg protein in the cerebral cortex, approximately 42 pmol/mg protein in brain microvessels, and approximately 27 pmol/mg protein in the choroid plexus. Several hexoses displaced specific [3H]cytochalasin B binding to microvessels in a rank-order that correlated well with their known ability to cross the blood-brain barrier; the only exception was 2-deoxy-D-glucose, which had much higher affinity for the glucose transporter than the natural substrate, D-glucose. Irreversible photoaffinity labeling of the glucose transporter of microvessels with [3H]cytochalasin B, followed by solubilization and polyacrylamide gel electrophoresis, labeled a protein band with an average molecular weight of approximately 55,000. Monoclonal and polyclonal antibodies specific to the human erythrocyte glucose transporter immunocytochemically stained brain blood vessels and the few trapped erythrocytes in situ, with minimal staining of the neuropil. In the choroid plexus, blood vessels did not stain, but the epithelium reacted positively. We conclude that human brain microvessels are richly endowed with a glucose transport moiety similar in molecular weight and antigenic characteristics to that of human erythrocytes and brain microvessels of other mammalian species

  7. Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders

    Science.gov (United States)

    Arloth, Janine; Bogdan, Ryan; Weber, Peter; Frishman, Goar; Menke, Andreas; Wagner, Klaus V.; Balsevich, Georgia; Schmidt, Mathias V.; Karbalai, Nazanin; Czamara, Darina; Altmann, Andre; Trümbach, Dietrich; Wurst, Wolfgang; Mehta, Divya; Uhr, Manfred; Klengel, Torsten; Erhardt, Angelika; Carey, Caitlin E.; Conley, Emily Drabant; Ripke, Stephan; Wray, Naomi R.; Lewis, Cathryn M.; Hamilton, Steven P.; Weissman, Myrna M.; Breen, Gerome; Byrne, Enda M.; Blackwood, Douglas H.R.; Boomsma, Dorret I.; Cichon, Sven; Heath, Andrew C.; Holsboer, Florian; Lucae, Susanne; Madden, Pamela A.F.; Martin, Nicholas G.; McGuffin, Peter; Muglia, Pierandrea; Noethen, Markus M.; Penninx, Brenda P.; Pergadia, Michele L.; Potash, James B.; Rietschel, Marcella; Lin, Danyu; Müller-Myhsok, Bertram; Shi, Jianxin; Steinberg, Stacy; Grabe, Hans J.; Lichtenstein, Paul; Magnusson, Patrik; Perlis, Roy H.; Preisig, Martin; Smoller, Jordan W.; Stefansson, Kari; Uher, Rudolf; Kutalik, Zoltan; Tansey, Katherine E.; Teumer, Alexander; Viktorin, Alexander; Barnes, Michael R.; Bettecken, Thomas; Binder, Elisabeth B.; Breuer, René; Castro, Victor M.; Churchill, Susanne E.; Coryell, William H.; Craddock, Nick; Craig, Ian W.; Czamara, Darina; De Geus, Eco J.; Degenhardt, Franziska; Farmer, Anne E.; Fava, Maurizio; Frank, Josef; Gainer, Vivian S.; Gallagher, Patience J.; Gordon, Scott D.; Goryachev, Sergey; Gross, Magdalena; Guipponi, Michel; Henders, Anjali K.; Herms, Stefan; Hickie, Ian B.; Hoefels, Susanne; Hoogendijk, Witte; Hottenga, Jouke Jan; Iosifescu, Dan V.; Ising, Marcus; Jones, Ian; Jones, Lisa; Jung-Ying, Tzeng; Knowles, James A.; Kohane, Isaac S.; Kohli, Martin A.; Korszun, Ania; Landen, Mikael; Lawson, William B.; Lewis, Glyn; MacIntyre, Donald; Maier, Wolfgang; Mattheisen, Manuel; McGrath, Patrick J.; McIntosh, Andrew; McLean, Alan; Middeldorp, Christel M.; Middleton, Lefkos; Montgomery, Grant M.; Murphy, Shawn N.; Nauck, Matthias; Nolen, Willem A.; Nyholt, Dale R.; O’Donovan, Michael; Oskarsson, Högni; Pedersen, Nancy; Scheftner, William A.; Schulz, Andrea; Schulze, Thomas G.; Shyn, Stanley I.; Sigurdsson, Engilbert; Slager, Susan L.; Smit, Johannes H.; Stefansson, Hreinn; Steffens, Michael; Thorgeirsson, Thorgeir; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; van den Oord, Edwin J.C.G.; Van Grootheest, Gerard; Völzke, Henry; Weilburg, Jeffrey B.; Willemsen, Gonneke; Zitman, Frans G.; Neale, Benjamin; Daly, Mark; Levinson, Douglas F.; Sullivan, Patrick F.; Ruepp, Andreas; Müller-Myhsok, Bertram; Hariri, Ahmad R.; Binder, Elisabeth B.

    2015-01-01

    Summary Depression risk is exacerbated by genetic factors and stress exposure; however, the biological mechanisms through which these factors interact to confer depression risk are poorly understood. One putative biological mechanism implicates variability in the ability of cortisol, released in response to stress, to trigger a cascade of adaptive genomic and non-genomic processes through glucocorticoid receptor (GR) activation. Here, we demonstrate that common genetic variants in long-range enhancer elements modulate the immediate transcriptional response to GR activation in human blood cells. These functional genetic variants increase risk for depression and co-heritable psychiatric disorders. Moreover, these risk variants are associated with inappropriate amygdala reactivity, a transdiagnostic psychiatric endophenotype and an important stress hormone response trigger. Network modeling and animal experiments suggest that these genetic differences in GR-induced transcriptional activation may mediate the risk for depression and other psychiatric disorders by altering a network of functionally related stress-sensitive genes in blood and brain. Video Abstract PMID:26050039

  8. Magnetic resonance elastography in normal human brain: preliminary study

    International Nuclear Information System (INIS)

    Xu Lei; Gao Peiyi; Lin Yan; Han Jiancheng; Xi Zhinong; Shen Hao

    2007-01-01

    Objective: To study the application of magnetic resonance elastography (MRE) in the human brain. Methods: An external force actuator was developed. The actuator was fixed to the head coil. During MRE scan, one side of the actuator was attached to the volunteers' head. Low frequency oscillation was produced by the actuator and generated shear waves propagating into brain tissue. The pulse sequence of MRE was designed. A modified gradient echo sequence was developed with motion sensitizing gradient (MSG) imposed along X, Y or Z direction. Cyclic displacement within brain tissue induced by shear waves caused a measurable phase shift in the received MR signal. From the measured phase shift, the displacement at each voxel could be calculated, and the shear waves within the brain were directly imaged. By adjusting the phase offset, the dynamic propagation of shear waves in a wave cycle was obtained. Phase images were processed with local frequency estimation (LFE) technique to obtain the elasticity images. Shear waves at 100 Hz, 150 Hz, and 200 Hz were applied. Results: The phase images of MRE directly imaged the propagating shear waves within the brain. The direction of the propagation was from surface of the brain to the center. The wavelength of shear waves varied with the change of actuating frequency. The change of wavelength of shear waves in gray and white matter of the brain was identified. The wavelength of shear waves in gray matter was shorter than that in white matter. The elasticity image of the brain revealed that the shear modulus of the white matter was higher than that of gray matter. Conclusion: The phase images of MRE can directly visualize the propagation of shear waves in the brain tissue. The elasticity image of the brain can demonstrate the change of elasticity between gray and white matter. (authors)

  9. Comprehensive analysis of RNA-Seq data reveals extensive RNA editing in a human transcriptome

    DEFF Research Database (Denmark)

    Peng, Zhiyu; Cheng, Yanbing; Tan, Bertrand Chin-Ming

    2012-01-01

    a computational pipeline that carefully controls for false positives while calling RNA editing events from genome and whole-transcriptome data of the same individual. We identified 22,688 RNA editing events in noncoding genes and introns, untranslated regions and coding sequences of protein-coding genes. Most......RNA editing is a post-transcriptional event that recodes hereditary information. Here we describe a comprehensive profile of the RNA editome of a male Han Chinese individual based on analysis of ∼767 million sequencing reads from poly(A)(+), poly(A)(-) and small RNA samples. We developed...... changes (∼93%) converted A to I(G), consistent with known editing mechanisms based on adenosine deaminase acting on RNA (ADAR). We also found evidence of other types of nucleotide changes; however, these were validated at lower rates. We found 44 editing sites in microRNAs (miRNAs), suggesting a potential...

  10. Measuring and Reconstructing the Brain at the Synaptic Scale: Towards a Biofidelic Human Brain in silico

    OpenAIRE

    NeuroData; CE, Priebe; Burns, R.; RJ, Vogelstein

    2015-01-01

    Vogelstein JT, Priebe CE, Burns R, Vogelstein RJ, Lichtman J. Measuring and Reconstructing the Brain at the Synaptic Scale: Towards a Biofidelic Human Brain in silico. DARPA Neural Engineering, Science and Technology Forum, 2010

  11. Neurospin Seminar: From the Proton to the Human Brain

    CERN Multimedia

    CERN. Geneva

    2016-01-01

    From the Proton to the Human Brain Speaker: Prof Denis Le Bihan Abstract: The understanding of the human brain is one of the main scientific challenges of the 21st century. In the early 2000s the French Atomic Energy Commission (CEA) launched a program to conceive and build a “human brain explorer”, the first human MRI scanner operating at 11.7T. This scanner was envisioned to be part of the ambitious Iseult project, bridging together industrial and academic partners to push the limits of molecular neuroimaging, from mouse to man, using Ultra-High Field (UHF) MRI. In this seminar a summary of the main features of this magnet, and the neuroscience and medical targets of NeuroSpin where this outstanding instrument will be installed in 2017 will be surveyed. The unprecedented resolution and the new contrasts allowed by such UHF magnets, in combination with innovative concepts in physics and neurobiology, will allow to explore the human brain at a mesoscale at which everything remains to d...

  12. Common genetic variants influence human subcortical brain structures.

    Science.gov (United States)

    Hibar, Derrek P; Stein, Jason L; Renteria, Miguel E; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S; Armstrong, Nicola J; Bernard, Manon; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brown, Andrew A; Chakravarty, M Mallar; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Olde Loohuis, Loes M; Luciano, Michelle; Macare, Christine; Mather, Karen A; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rose, Emma J; Salami, Alireza; Sämann, Philipp G; Schmaal, Lianne; Schork, Andrew J; Shin, Jean; Strike, Lachlan T; Teumer, Alexander; van Donkelaar, Marjolein M J; van Eijk, Kristel R; Walters, Raymond K; Westlye, Lars T; Whelan, Christopher D; Winkler, Anderson M; Zwiers, Marcel P; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M H; Hartberg, Cecilie B; Haukvik, Unn K; Heister, Angelien J G A M; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C M; Lopez, Lorna M; Makkinje, Remco R R; Matarin, Mar; Naber, Marlies A M; McKay, D Reese; Needham, Margaret; Nugent, Allison C; Pütz, Benno; Royle, Natalie A; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S L; van Hulzen, Kimm J E; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A; Bastin, Mark E; Brodaty, Henry; Bulayeva, Kazima B; Carless, Melanie A; Cichon, Sven; Corvin, Aiden; Curran, Joanne E; Czisch, Michael; de Zubicaray, Greig I; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Fedko, Iryna O; Ferrucci, Luigi; Foroud, Tatiana M; Fox, Peter T; Fukunaga, Masaki; Gibbs, J Raphael; Göring, Harald H H; Green, Robert C; Guelfi, Sebastian; Hansell, Narelle K; Hartman, Catharina A; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G; Heslenfeld, Dirk J; Hoekstra, Pieter J; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Liu, Xinmin; Longo, Dan L; McMahon, Katie L; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W; Mostert, Jeanette C; Mühleisen, Thomas W; Nalls, Michael A; Nichols, Thomas E; Nilsson, Lars G; Nöthen, Markus M; Ohi, Kazutaka; Olvera, Rene L; Perez-Iglesias, Rocio; Pike, G Bruce; Potkin, Steven G; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D; Rujescu, Dan; Schnell, Knut; Schofield, Peter R; Smith, Colin; Steen, Vidar M; Sussmann, Jessika E; Thalamuthu, Anbupalam; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Valdés Hernández, Maria C; van 't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J A; van Tol, Marie-Jose; Veltman, Dick J; Wassink, Thomas H; Westman, Eric; Zielke, Ronald H; Zonderman, Alan B; Ashbrook, David G; Hager, Reinmar; Lu, Lu; McMahon, Francis J; Morris, Derek W; Williams, Robert W; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Cahn, Wiepke; Calhoun, Vince D; Cavalleri, Gianpiero L; Crespo-Facorro, Benedicto; Dale, Anders M; Davies, Gareth E; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C; Espeseth, Thomas; Gollub, Randy L; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W J H; Roffman, Joshua L; Sisodiya, Sanjay M; Smoller, Jordan W; van Bokhoven, Hans; van Haren, Neeltje E M; Völzke, Henry; Walter, Henrik; Weiner, Michael W; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A; Blangero, John; Boomsma, Dorret I; Brouwer, Rachel M; Cannon, Dara M; Cookson, Mark R; de Geus, Eco J C; Deary, Ian J; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E; Francks, Clyde; Glahn, David C; Grabe, Hans J; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E; Jönsson, Erik G; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M; Ophoff, Roel A; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S; Saykin, Andrew J; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M; Weale, Michael E; Weinberger, Daniel R; Adams, Hieab H H; Launer, Lenore J; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L; Becker, James T; Yanek, Lisa; van der Lee, Sven J; Ebling, Maritza; Fischl, Bruce; Longstreth, W T; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N; van Duijn, Cornelia M; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M Arfan; Martin, Nicholas G; Wright, Margaret J; Schumann, Gunter; Franke, Barbara; Thompson, Paul M; Medland, Sarah E

    2015-04-09

    The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

  13. Human brain functional MRI and DTI visualization with virtual reality.

    Science.gov (United States)

    Chen, Bin; Moreland, John; Zhang, Jingyu

    2011-12-01

    Magnetic resonance diffusion tensor imaging (DTI) and functional MRI (fMRI) are two active research areas in neuroimaging. DTI is sensitive to the anisotropic diffusion of water exerted by its macromolecular environment and has been shown useful in characterizing structures of ordered tissues such as the brain white matter, myocardium, and cartilage. The diffusion tensor provides two new types of information of water diffusion: the magnitude and the spatial orientation of water diffusivity inside the tissue. This information has been used for white matter fiber tracking to review physical neuronal pathways inside the brain. Functional MRI measures brain activations using the hemodynamic response. The statistically derived activation map corresponds to human brain functional activities caused by neuronal activities. The combination of these two methods provides a new way to understand human brain from the anatomical neuronal fiber connectivity to functional activities between different brain regions. In this study, virtual reality (VR) based MR DTI and fMRI visualization with high resolution anatomical image segmentation and registration, ROI definition and neuronal white matter fiber tractography visualization and fMRI activation map integration is proposed. Rationale and methods for producing and distributing stereoscopic videos are also discussed.

  14. Mathematical logic in the human brain: syntax.

    Directory of Open Access Journals (Sweden)

    Roland Friedrich

    Full Text Available Theory predicts a close structural relation of formal languages with natural languages. Both share the aspect of an underlying grammar which either generates (hierarchically structured expressions or allows us to decide whether a sentence is syntactically correct or not. The advantage of rule-based communication is commonly believed to be its efficiency and effectiveness. A particularly important class of formal languages are those underlying the mathematical syntax. Here we provide brain-imaging evidence that the syntactic processing of abstract mathematical formulae, written in a first order language, is, indeed efficient and effective as a rule-based generation and decision process. However, it is remarkable, that the neural network involved, consisting of intraparietal and prefrontal regions, only involves Broca's area in a surprisingly selective way. This seems to imply that despite structural analogies of common and current formal languages, at the neural level, mathematics and natural language are processed differently, in principal.

  15. Addiction circuitry in the human brain (*).

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Wang, G.-J.; Fowler, J.S.; Tomasi, D.

    2011-09-27

    A major challenge in understanding substance-use disorders lies in uncovering why some individuals become addicted when exposed to drugs, whereas others do not. Although genetic, developmental, and environmental factors are recognized as major contributors to a person's risk of becoming addicted, the neurobiological processes that underlie this vulnerability are still poorly understood. Imaging studies suggest that individual variations in key dopamine-modulated brain circuits, including circuits involved in reward, memory, executive function, and motivation, contribute to some of the differences in addiction vulnerability. A better understanding of the main circuits affected by chronic drug use and the influence of social stressors, developmental trajectories, and genetic background on these circuits is bound to lead to a better understanding of addiction and to more effective strategies for the prevention and treatment of substance-use disorders.

  16. Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection

    Directory of Open Access Journals (Sweden)

    Erica L. McGrath

    2017-03-01

    Full Text Available Zika virus (ZIKV infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7, to infect primary human neural stem cells (hNSCs originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection.

  17. Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection.

    Science.gov (United States)

    McGrath, Erica L; Rossi, Shannan L; Gao, Junling; Widen, Steven G; Grant, Auston C; Dunn, Tiffany J; Azar, Sasha R; Roundy, Christopher M; Xiong, Ying; Prusak, Deborah J; Loucas, Bradford D; Wood, Thomas G; Yu, Yongjia; Fernández-Salas, Ildefonso; Weaver, Scott C; Vasilakis, Nikos; Wu, Ping

    2017-03-14

    Zika virus (ZIKV) infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7), to infect primary human neural stem cells (hNSCs) originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Quantifying anisotropy and fiber orientation in human brain histological sections

    Directory of Open Access Journals (Sweden)

    Matthew D Budde

    2013-02-01

    Full Text Available Diffusion weighted imaging (DWI has provided unparalleled insight into the microscopic structure and organization of the central nervous system. Diffusion tensor imaging (DTI and other models of the diffusion MRI signal extract microstructural properties of tissues with relevance to the normal and injured brain. Despite the prevalence of such techniques and applications, accurate and large-scale validation has proven difficult, particularly in the human brain. In this report, human brain sections obtained from a digital public brain bank were employed to quantify anisotropy and fiber orientation using structure tensor analysis. The derived maps depict the intricate complexity of white matter fibers at a resolution not attainable with current DWI experiments. Moreover, the effects of multiple fiber bundles (i.e. crossing fibers and intravoxel fiber dispersion were demonstrated. Examination of the cortex and hippocampal regions validated specific features of previous in vivo and ex vivo DTI studies of the human brain. Despite the limitation to two dimensions, the resulting images provide a unique depiction of white matter organization at resolutions currently unattainable with DWI. The method of analysis may be used to validate tissue properties derived from DTI and alternative models of the diffusion signal.

  19. Kisspeptin modulates sexual and emotional brain processing in humans.

    Science.gov (United States)

    Comninos, Alexander N; Wall, Matthew B; Demetriou, Lysia; Shah, Amar J; Clarke, Sophie A; Narayanaswamy, Shakunthala; Nesbitt, Alexander; Izzi-Engbeaya, Chioma; Prague, Julia K; Abbara, Ali; Ratnasabapathy, Risheka; Salem, Victoria; Nijher, Gurjinder M; Jayasena, Channa N; Tanner, Mark; Bassett, Paul; Mehta, Amrish; Rabiner, Eugenii A; Hönigsperger, Christoph; Silva, Meire Ribeiro; Brandtzaeg, Ole Kristian; Lundanes, Elsa; Wilson, Steven Ray; Brown, Rachel C; Thomas, Sarah A; Bloom, Stephen R; Dhillo, Waljit S

    2017-02-01

    Sex, emotion, and reproduction are fundamental and tightly entwined aspects of human behavior. At a population level in humans, both the desire for sexual stimulation and the desire to bond with a partner are important precursors to reproduction. However, the relationships between these processes are incompletely understood. The limbic brain system has key roles in sexual and emotional behaviors, and is a likely candidate system for the integration of behavior with the hormonal reproductive axis. We investigated the effects of kisspeptin, a recently identified key reproductive hormone, on limbic brain activity and behavior. Using a combination of functional neuroimaging and hormonal and psychometric analyses, we compared the effects of kisspeptin versus vehicle administration in 29 healthy heterosexual young men. We demonstrated that kisspeptin administration enhanced limbic brain activity specifically in response to sexual and couple-bonding stimuli. Furthermore, kisspeptin's enhancement of limbic brain structures correlated with psychometric measures of reward, drive, mood, and sexual aversion, providing functional significance. In addition, kisspeptin administration attenuated negative mood. Collectively, our data provide evidence of an undescribed role for kisspeptin in integrating sexual and emotional brain processing with reproduction in humans. These results have important implications for our understanding of reproductive biology and are highly relevant to the current pharmacological development of kisspeptin as a potential therapeutic agent for patients with common disorders of reproductive function. National Institute for Health Research (NIHR), Wellcome Trust (Ref 080268), and the Medical Research Council (MRC).

  20. Unveiling the mystery of visual information processing in human brain.

    Science.gov (United States)

    Diamant, Emanuel

    2008-08-15

    It is generally accepted that human vision is an extremely powerful information processing system that facilitates our interaction with the surrounding world. However, despite extended and extensive research efforts, which encompass many exploration fields, the underlying fundamentals and operational principles of visual information processing in human brain remain unknown. We still are unable to figure out where and how along the path from eyes to the cortex the sensory input perceived by the retina is converted into a meaningful object representation, which can be consciously manipulated by the brain. Studying the vast literature considering the various aspects of brain information processing, I was surprised to learn that the respected scholarly discussion is totally indifferent to the basic keynote question: "What is information?" in general or "What is visual information?" in particular. In the old days, it was assumed that any scientific research approach has first to define its basic departure points. Why was it overlooked in brain information processing research remains a conundrum. In this paper, I am trying to find a remedy for this bizarre situation. I propose an uncommon definition of "information", which can be derived from Kolmogorov's Complexity Theory and Chaitin's notion of Algorithmic Information. Embracing this new definition leads to an inevitable revision of traditional dogmas that shape the state of the art of brain information processing research. I hope this revision would better serve the challenging goal of human visual information processing modeling.

  1. Main-, minor- and trace elements distribution in human brain

    International Nuclear Information System (INIS)

    Zoeger, N.; Streli, C.; Wobrauschek, P.; Jokubonis, C.; Pepponi, G.; Roschger, P.; Bohic, S.; Osterode, W.

    2004-01-01

    Lead (Pb) is known to induce adverse health effects in humans. In fact, cognitive deficits are repeatedly described with Pb exposure, but little is known about the distribution of lead in brain. Measurements of the distribution of Pb in human brain and to study if Pb is associated with the distribution of other chemical elements such as zinc (Zn), iron (Fe) is of great interest and could reveal some hints about the metabolism of Pb in brain. To determine the local distribution of lead (Pb) and other trace elements x-ray fluorescence spectroscopy (XRF) measurements have been performed, using a microbeam setup and highest flux synchrotron radiation. Experiments have been carried out at ID-22, ESRF, Grenoble, France. The installed microprobe setup provides a monochromatic beam (17 keV) from an undulator station focused by Kirkpatrick-Baez x-ray optics to a spot size of 5 μm x 3μm. Brain slices (20 μm thickness, imbedded in paraffin and mounted on Kapton foils) from areas of the frontal cortex, thalamus and hippocampus have been investigated. Generally no significant increase in fluorescence intensities could be detected in one of the investigated brain compartments. However Pb and other (trace) elements (e.g. S, Ca, Fe, Cu, Zn, Br) could be detected in all samples and showed strong inhomogeneities across the analyzed areas. While S, Ca, Fe, Cu, Zn and Br could be clearly assigned to the investigated brain structures (vessels, etc.) Pb showed a very different behavior. In some cases (e.g. plexus choroidei) Pb was located at the walls of the vessel, whereas with other structures (e.g. blood vessel) this correlation was not found. Moreover, the detected Pb in different brain areas was individually correlated with various elements. The local distribution of the detected elements in various brain structures will be discussed in this work. (author)

  2. Uncovering intrinsic modular organization of spontaneous brain activity in humans.

    Directory of Open Access Journals (Sweden)

    Yong He

    Full Text Available The characterization of topological architecture of complex brain networks is one of the most challenging issues in neuroscience. Slow (<0.1 Hz, spontaneous fluctuations of the blood oxygen level dependent (BOLD signal in functional magnetic resonance imaging are thought to be potentially important for the reflection of spontaneous neuronal activity. Many studies have shown that these fluctuations are highly coherent within anatomically or functionally linked areas of the brain. However, the underlying topological mechanisms responsible for these coherent intrinsic or spontaneous fluctuations are still poorly understood. Here, we apply modern network analysis techniques to investigate how spontaneous neuronal activities in the human brain derived from the resting-state BOLD signals are topologically organized at both the temporal and spatial scales. We first show that the spontaneous brain functional networks have an intrinsically cohesive modular structure in which the connections between regions are much denser within modules than between them. These identified modules are found to be closely associated with several well known functionally interconnected subsystems such as the somatosensory/motor, auditory, attention, visual, subcortical, and the "default" system. Specifically, we demonstrate that the module-specific topological features can not be captured by means of computing the corresponding global network parameters, suggesting a unique organization within each module. Finally, we identify several pivotal network connectors and paths (predominantly associated with the association and limbic/paralimbic cortex regions that are vital for the global coordination of information flow over the whole network, and we find that their lesions (deletions critically affect the stability and robustness of the brain functional system. Together, our results demonstrate the highly organized modular architecture and associated topological properties in

  3. Consumption of seaweeds and the human brain

    DEFF Research Database (Denmark)

    Cornish, M. Lynn; Critchley, Alan T.; Mouritsen, Ole G.

    2017-01-01

    , and the impacts of anti-oxidant activities in neuroprotection. These elements have the capacity to help in the defense of human cognitive disorders, such as dementia, Alzheimer’s disease, depression, bipolar diseases, and adverse conditions characterized by progressive neurodegeneration. Psychological benefits...

  4. Visual dictionaries as intermediate features in the human brain

    Directory of Open Access Journals (Sweden)

    Kandan eRamakrishnan

    2015-01-01

    Full Text Available The human visual system is assumed to transform low level visual features to object and scene representations via features of intermediate complexity. How the brain computationally represents intermediate features is still unclear. To further elucidate this, we compared the biologically plausible HMAX model and Bag of Words (BoW model from computer vision. Both these computational models use visual dictionaries, candidate features of intermediate complexity, to represent visual scenes, and the models have been proven effective in automatic object and scene recognition. These models however differ in the computation of visual dictionaries and pooling techniques. We investigated where in the brain and to what extent human fMRI responses to short video can be accounted for by multiple hierarchical levels of the HMAX and BoW models. Brain activity of 20 subjects obtained while viewing a short video clip was analyzed voxel-wise using a distance-based variation partitioning method. Results revealed that both HMAX and BoW explain a significant amount of brain activity in early visual regions V1, V2 and V3. However BoW exhibits more consistency across subjects in accounting for brain activity compared to HMAX. Furthermore, visual dictionary representations by HMAX and BoW explain significantly some brain activity in higher areas which are believed to process intermediate features. Overall our results indicate that, although both HMAX and BoW account for activity in the human visual system, the BoW seems to more faithfully represent neural responses in low and intermediate level visual areas of the brain.

  5. Time-resolved transcriptome and proteome landscape of human regulatory T cell (Treg) differentiation reveals novel regulators of FOXP3

    KAUST Repository

    Schmidt, Angelika

    2018-04-27

    BackgroundRegulatory T cells (Tregs) expressing the transcription factor FOXP3 are crucial mediators of self-tolerance, preventing autoimmune diseases but possibly hampering tumor rejection. Clinical manipulation of Tregs is of great interest, and first-in-man trials of Treg transfer have achieved promising outcomes. Yet, the mechanisms governing induced Treg (iTreg) differentiation and the regulation of FOXP3 are incompletely understood.ResultsTo gain a comprehensive and unbiased molecular understanding of FOXP3 induction, we performed time-series RNA sequencing (RNA-Seq) and proteomics profiling on the same samples during human iTreg differentiation. To enable the broad analysis of universal FOXP3-inducing pathways, we used five differentiation protocols in parallel. Integrative analysis of the transcriptome and proteome confirmed involvement of specific molecular processes, as well as overlap of a novel iTreg subnetwork with known Treg regulators and autoimmunity-associated genes. Importantly, we propose 37 novel molecules putatively involved in iTreg differentiation. Their relevance was validated by a targeted shRNA screen confirming a functional role in FOXP3 induction, discriminant analyses classifying iTregs accordingly, and comparable expression in an independent novel iTreg RNA-Seq dataset.ConclusionThe data generated by this novel approach facilitates understanding of the molecular mechanisms underlying iTreg generation as well as of the concomitant changes in the transcriptome and proteome. Our results provide a reference map exploitable for future discovery of markers and drug candidates governing control of Tregs, which has important implications for the treatment of cancer, autoimmune, and inflammatory diseases.

  6. Simple instrument for biochemical studies of the living human brain

    International Nuclear Information System (INIS)

    Bice, A.N.; Wagner, H.N. Jr.; Lee, M.C.; Frost, J.J.

    1986-01-01

    A simple, relatively inexpensive radiation detection system was developed for measurement of positron-emitting receptor-binding drugs in the human brain. This high-efficiency coincidence counting system requires that only a few hundred microcuries of labeled drug be administered to the subject, thereby allowing for multiple studies without an excessive radiation dose. Measurement of the binding of [ 11 C]-carfentanil, a high-affinity synthetic opiate, to opiate receptors in the presence and in the absence of a competitive opiate antagonist exemplifies the use of this system for estimating different degrees of receptor binding of drugs in the human brain. The instrument has also been used for measurement of the transport into the brain of other positron-emitting radiotracers, such as large neutral amino acids

  7. Transcriptome patterns from primary cutaneous Leishmania braziliensis infections associate with eventual development of mucosal disease in humans.

    Directory of Open Access Journals (Sweden)

    Ana Claudia Maretti-Mira

    Full Text Available INTRODUCTION: Localized Cutaneous Leishmaniasis (LCL and Mucosal Leishmaniasis (ML are two extreme clinical forms of American Tegumentary Leishmaniasis that usually begin as solitary primary cutaneous lesions. Host and parasite factors that influence the progression of LCL to ML are not completely understood. In this manuscript, we compare the gene expression profiles of primary cutaneous lesions from patients who eventually developed ML to those that did not. METHODS: Using RNA-seq, we analyzed both the human and Leishmania transcriptomes in primary cutaneous lesions. RESULTS: Limited number of reads mapping to Leishmania transcripts were obtained. For human transcripts, compared to ML patients, lesions from LCL patients displayed a general multi-polarization of the adaptive immune response and showed up-regulation of genes involved in chemoattraction of innate immune cells and in antigen presentation. We also identified a potential transcriptional signature in the primary lesions that may predict long-term disease outcome. CONCLUSIONS: We were able to simultaneously sequence both human and Leishmania mRNA transcripts in primary cutaneous leishmaniasis lesions. Our results suggest an intrinsic difference in the immune capacity of LCL and ML patients. The findings correlate the complete cure of L. braziliensis infection with a controlled inflammatory response and a balanced activation of innate and adaptive immunity.

  8. Sodium MR imaging of human brain neoplasms

    International Nuclear Information System (INIS)

    Kobayashi, Shu; Yoshikawa, Kohki; Takakura, Kintomo; Iio, Masahiro

    1988-01-01

    We reported the experience of the sodium magnetic resonance imaging of 5 patients with brain tumors (4 astrocytomas and 1 craniopharyngioma), using a Siemens 1.5 Tesla superconductive magnet. We used two-dimensional Fourier imaging with a spin-echo scanning sequence (and with the repetition time of 140 msec and the echo time of 11 - 14 msec). The radiofrequency was maintained at 17 MHz. Sodium MR imaging was achieved with a 64 x 64 data acquisition (30 mm slice thickness) in 19.1 min. On the sodium MRI, all four astrocytomas, along with the eye balls and the cerebrospinal fluid spaces, appeared as high-intensity areas. Peritumoral edema is also visualized as highly intense, so that it is difficult to discriminate tumor extent from the surrounding edema. Our comparative studies with malignant glioma cases using the same equipment are needed to clarify the relationship between sodium signal intensities and the malignancy of gliomas, and to evaluate the potential clinical utility of sodium MRI. A craniopharyngioma than contained a yellowish cystic fluid with a sodium concentration as high as CSF was shown on sodium MRI as a mass with highly intense signals. The ability to differentiate extracellular from intracellular sodium, that has been studied by several investigators, would greatly augment the clinical specificity of MR imaging. (author)

  9. Patient specific 3D visualisation of human brain | Baichoo ...

    African Journals Online (AJOL)

    University of Mauritius Research Journal. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 15, No 1 (2009) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Patient specific 3D visualisation of human brain.

  10. Development of BOLD signal hemodynamic responses in the human brain

    NARCIS (Netherlands)

    Arichi, T.; Varela, M.; Melendez-Calderon, A.; Allievi, A.; Merchant, N.; Tusor, N.; Counsell, S.J.; Burdet, E.; Beckmann, Christian; Edwards, A.D.

    2012-01-01

    In the rodent brain the hemodynamic response to a brief external stimulus changes significantly during development. Analogous changes in human infants would complicate the determination and use of the hemodynamic response function (HRF) for functional magnetic resonance imaging (fMRI) in developing

  11. Using human brain activity to guide machine learning.

    Science.gov (United States)

    Fong, Ruth C; Scheirer, Walter J; Cox, David D

    2018-03-29

    Machine learning is a field of computer science that builds algorithms that learn. In many cases, machine learning algorithms are used to recreate a human ability like adding a caption to a photo, driving a car, or playing a game. While the human brain has long served as a source of inspiration for machine learning, little effort has been made to directly use data collected from working brains as a guide for machine learning algorithms. Here we demonstrate a new paradigm of "neurally-weighted" machine learning, which takes fMRI measurements of human brain activity from subjects viewing images, and infuses these data into the training process of an object recognition learning algorithm to make it more consistent with the human brain. After training, these neurally-weighted classifiers are able to classify images without requiring any additional neural data. We show that our neural-weighting approach can lead to large performance gains when used with traditional machine vision features, as well as to significant improvements with already high-performing convolutional neural network features. The effectiveness of this approach points to a path forward for a new class of hybrid machine learning algorithms which take both inspiration and direct constraints from neuronal data.

  12. Human brain evolution, theories of innovation, and lessons from the ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Biosciences; Volume 29; Issue 3. Human brain evolution, theories of innovation, and lessons from the history of technology. Alfred Gierer. Perspectives Volume 29 Issue 3 September 2004 pp 235-244. Fulltext. Click here to view fulltext PDF. Permanent link:

  13. Insights into Brain Glycogen Metabolism: THE STRUCTURE OF HUMAN BRAIN GLYCOGEN PHOSPHORYLASE.

    Science.gov (United States)

    Mathieu, Cécile; Li de la Sierra-Gallay, Ines; Duval, Romain; Xu, Ximing; Cocaign, Angélique; Léger, Thibaut; Woffendin, Gary; Camadro, Jean-Michel; Etchebest, Catherine; Haouz, Ahmed; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2016-08-26

    Brain glycogen metabolism plays a critical role in major brain functions such as learning or memory consolidation. However, alteration of glycogen metabolism and glycogen accumulation in the brain contributes to neurodegeneration as observed in Lafora disease. Glycogen phosphorylase (GP), a key enzyme in glycogen metabolism, catalyzes the rate-limiting step of glycogen mobilization. Moreover, the allosteric regulation of the three GP isozymes (muscle, liver, and brain) by metabolites and phosphorylation, in response to hormonal signaling, fine-tunes glycogenolysis to fulfill energetic and metabolic requirements. Whereas the structures of muscle and liver GPs have been known for decades, the structure of brain GP (bGP) has remained elusive despite its critical role in brain glycogen metabolism. Here, we report the crystal structure of human bGP in complex with PEG 400 (2.5 Å) and in complex with its allosteric activator AMP (3.4 Å). These structures demonstrate that bGP has a closer structural relationship with muscle GP, which is also activated by AMP, contrary to liver GP, which is not. Importantly, despite the structural similarities between human bGP and the two other mammalian isozymes, the bGP structures reveal molecular features unique to the brain isozyme that provide a deeper understanding of the differences in the activation properties of these allosteric enzymes by the allosteric effector AMP. Overall, our study further supports that the distinct structural and regulatory properties of GP isozymes contribute to the different functions of muscle, liver, and brain glycogen. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Human astrocytes: structure and functions in the healthy brain.

    Science.gov (United States)

    Vasile, Flora; Dossi, Elena; Rouach, Nathalie

    2017-07-01

    Data collected on astrocytes' physiology in the rodent have placed them as key regulators of synaptic, neuronal, network, and cognitive functions. While these findings proved highly valuable for our awareness and appreciation of non-neuronal cell significance in brain physiology, early structural and phylogenic investigations of human astrocytes hinted at potentially different astrocytic properties. This idea sparked interest to replicate rodent-based studies on human samples, which have revealed an analogous but enhanced involvement of astrocytes in neuronal function of the human brain. Such evidence pointed to a central role of human astrocytes in sustaining more complex information processing. Here, we review the current state of our knowledge of human astrocytes regarding their structure, gene profile, and functions, highlighting the differences with rodent astrocytes. This recent insight is essential for assessment of the relevance of findings using animal models and for comprehending the functional significance of species-specific properties of astrocytes. Moreover, since dysfunctional astrocytes have been described in many brain disorders, a more thorough understanding of human-specific astrocytic properties is crucial for better-adapted translational applications.

  15. Zika Virus Persistently Infects and Is Basolaterally Released from Primary Human Brain Microvascular Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Megan C. Mladinich

    2017-07-01

    Full Text Available Zika virus (ZIKV is a mosquito-borne Flavivirus that has emerged as the cause of encephalitis and fetal microencephaly in the Americas. ZIKV uniquely persists in human bodily fluids for up to 6 months, is sexually transmitted, and traverses the placenta and the blood-brain barrier (BBB to damage neurons. Cells that support persistent ZIKV replication and mechanisms by which ZIKV establishes persistence remain enigmatic but central to ZIKV entry into protected neuronal compartments. The endothelial cell (EC lining of capillaries normally constrains transplacental transmission and forms the BBB, which selectively restricts access of blood constituents to neurons. We found that ZIKV (strain PRVABC59 persistently infects and continuously replicates in primary human brain microvascular ECs (hBMECs, without cytopathology, for >9 days and following hBMEC passage. ZIKV did not permeabilize hBMECs but was released basolaterally from polarized hBMECs, suggesting a direct mechanism for ZIKV to cross the BBB. ZIKV-infected hBMECs were rapidly resistant to alpha interferon (IFN-α and transiently induced, but failed to secrete, IFN-β and IFN-λ. Global transcriptome analysis determined that ZIKV constitutively induced IFN regulatory factor 7 (IRF7, IRF9, and IFN-stimulated genes (ISGs 1 to 9 days postinfection, despite persistently replicating in hBMECs. ZIKV constitutively induced ISG15, HERC5, and USP18, which are linked to hepatitis C virus (HCV persistence and IFN regulation, chemokine CCL5, which is associated with immunopathogenesis, as well as cell survival factors. Our results reveal that hBMECs act as a reservoir of persistent ZIKV replication, suggest routes for ZIKV to cross hBMECs into neuronal compartments, and define novel mechanisms of ZIKV persistence that can be targeted to restrict ZIKV spread.

  16. Visualization of specific binding sites of benzodiazepine in human brain

    International Nuclear Information System (INIS)

    Shinotoh, H.; Yamasaki, T.; Inoue, O.; Itoh, T.; Suzuki, K.; Hashimoto, K.; Tateno, Y.; Ikehira, H.

    1986-01-01

    Using 11C-labeled Ro15-1788 and positron emission tomography, studies of benzodiazepine binding sites in the human brain were performed on four normal volunteers. Rapid and high accumulation of 11C activity was observed in the brain after i.v. injection of [11C]Ro15-1788, the maximum of which was within 12 min. Initial distribution of 11C activity in the brain was similar to the distribution of the normal cerebral blood flow. Ten minutes after injection, however, a high uptake of 11C activity was observed in the cerebral cortex and moderate uptake was seen in the cerebellar cortex, the basal ganglia, and the thalamus. The accumulation of 11C activity was low in the brain stem. This distribution of 11C activity was approximately parallel to the known distribution of benzodiazepine receptors. Saturation experiments were performed on four volunteers with oral administration of 0.3-1.8 mg/kg of cold Ro15-1788 prior to injection. Initial distribution of 11C activity following injection peaked within 2 min and then the accumulation of 11C activity decreased rapidly and remarkably throughout the brain. The results indicated that [11C] Ro15-1788 associates and dissociates to specific and nonspecific binding sites rapidly and has a high ratio of specific receptor binding to nonspecific binding in vivo. Carbon-11 Ro15-1788 is a suitable radioligand for the study of benzodiazepine receptors in vivo in humans

  17. Complex Trajectories of Brain Development in the Healthy Human Fetus.

    Science.gov (United States)

    Andescavage, Nickie N; du Plessis, Adre; McCarter, Robert; Serag, Ahmed; Evangelou, Iordanis; Vezina, Gilbert; Robertson, Richard; Limperopoulos, Catherine

    2017-11-01

    This study characterizes global and hemispheric brain growth in healthy human fetuses during the second half of pregnancy using three-dimensional MRI techniques. We studied 166 healthy fetuses that underwent MRI between 18 and 39 completed weeks gestation. We created three-dimensional high-resolution reconstructions of the brain and calculated volumes for left and right cortical gray matter (CGM), fetal white matter (FWM), deep subcortical structures (DSS), and the cerebellum. We calculated the rate of growth for each tissue class according to gestational age and described patterns of hemispheric growth. Each brain region demonstrated major increases in volume during the second half of gestation, the most pronounced being the cerebellum (34-fold), followed by FWM (22-fold), CGM (21-fold), and DSS (10-fold). The left cerebellar hemisphere, CGM, and DSS had larger volumes early in gestation, but these equalized by term. It has been increasingly recognized that brain asymmetry evolves throughout the human life span. Advanced quantitative MRI provides noninvasive measurements of early structural asymmetry between the left and right fetal brain that may inform functional and behavioral laterality differences seen in children and young adulthood. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Direct Electrical Stimulation in the Human Brain Disrupts Melody Processing.

    Science.gov (United States)

    Garcea, Frank E; Chernoff, Benjamin L; Diamond, Bram; Lewis, Wesley; Sims, Maxwell H; Tomlinson, Samuel B; Teghipco, Alexander; Belkhir, Raouf; Gannon, Sarah B; Erickson, Steve; Smith, Susan O; Stone, Jonathan; Liu, Lynn; Tollefson, Trenton; Langfitt, John; Marvin, Elizabeth; Pilcher, Webster H; Mahon, Bradford Z

    2017-09-11

    Prior research using functional magnetic resonance imaging (fMRI) [1-4] and behavioral studies of patients with acquired or congenital amusia [5-8] suggest that the right posterior superior temporal gyrus (STG) in the human brain is specialized for aspects of music processing (for review, see [9-12]). Intracranial electrical brain stimulation in awake neurosurgery patients is a powerful means to determine the computations supported by specific brain regions and networks [13-21] because it provides reversible causal evidence with high spatial resolution (for review, see [22, 23]). Prior intracranial stimulation or cortical cooling studies have investigated musical abilities related to reading music scores [13, 14] and singing familiar songs [24, 25]. However, individuals with amusia (congenitally, or from a brain injury) have difficulty humming melodies but can be spared for singing familiar songs with familiar lyrics [26]. Here we report a detailed study of a musician with a low-grade tumor in the right temporal lobe. Functional MRI was used pre-operatively to localize music processing to the right STG, and the patient subsequently underwent awake intraoperative mapping using direct electrical stimulation during a melody repetition task. Stimulation of the right STG induced "music arrest" and errors in pitch but did not affect language processing. These findings provide causal evidence for the functional segregation of music and language processing in the human brain and confirm a specific role of the right STG in melody processing. VIDEO ABSTRACT. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Ex-vivo MR Volumetry of Human Brain Hemispheres

    Science.gov (United States)

    Kotrotsou, Aikaterini; Bennett, David A.; Schneider, Julie A.; Dawe, Robert J.; Golak, Tom; Leurgans, Sue E.; Yu, Lei; Arfanakis, Konstantinos

    2013-01-01

    Purpose The aims of this work were to: a) develop an approach for ex-vivo MR volumetry of human brain hemispheres that does not contaminate the results of histopathological examination, b) longitudinally assess regional brain volumes postmortem, and c) investigate the relationship between MR volumetric measurements performed in-vivo and ex-vivo. Methods An approach for ex-vivo MR volumetry of human brain hemispheres was developed. Five hemispheres from elderly subjects were imaged ex-vivo longitudinally. All datasets were segmented. The longitudinal behavior of volumes measured ex-vivo was assessed. The relationship between in-vivo and ex-vivo volumetric measurements was investigated in seven elderly subjects imaged both ante-mortem and postmortem. Results The presented approach for ex-vivo MR volumetry did not contaminate the results of histopathological examination. For a period of 6 months postmortem, within-subject volume variation across time points was substantially smaller than inter-subject volume variation. A close linear correspondence was detected between in-vivo and ex-vivo volumetric measurements. Conclusion Regional brain volumes measured with the presented approach for ex-vivo MR volumetry remain relatively unchanged for a period of 6 months postmortem. Furthermore, the linear relationship between in-vivo and ex-vivo MR volumetric measurements suggests that the presented approach captures information linked to ante-mortem macrostructural brain characteristics. PMID:23440751

  20. Ex vivo MR volumetry of human brain hemispheres.

    Science.gov (United States)

    Kotrotsou, Aikaterini; Bennett, David A; Schneider, Julie A; Dawe, Robert J; Golak, Tom; Leurgans, Sue E; Yu, Lei; Arfanakis, Konstantinos

    2014-01-01

    The aims of this work were to (a) develop an approach for ex vivo MR volumetry of human brain hemispheres that does not contaminate the results of histopathological examination, (b) longitudinally assess regional brain volumes postmortem, and (c) investigate the relationship between MR volumetric measurements performed in vivo and ex vivo. An approach for ex vivo MR volumetry of human brain hemispheres was developed. Five hemispheres from elderly subjects were imaged ex vivo longitudinally. All datasets were segmented. The longitudinal behavior of volumes measured ex vivo was assessed. The relationship between in vivo and ex vivo volumetric measurements was investigated in seven elderly subjects imaged both antemortem and postmortem. This approach for ex vivo MR volumetry did not contaminate the results of histopathological examination. For a period of 6 months postmortem, within-subject volume variation across time points was substantially smaller than intersubject volume variation. A close linear correspondence was detected between in vivo and ex vivo volumetric measurements. Regional brain volumes measured with this approach for ex vivo MR volumetry remain relatively unchanged for a period of 6 months postmortem. Furthermore, the linear relationship between in vivo and ex vivo MR volumetric measurements suggests that this approach captures information linked to antemortem macrostructural brain characteristics. Copyright © 2013 Wiley Periodicals, Inc.

  1. A machine learning approach for the identification of key markers involved in brain development from single-cell transcriptomic data.

    Science.gov (United States)

    Hu, Yongli; Hase, Takeshi; Li, Hui Peng; Prabhakar, Shyam; Kitano, Hiroaki; Ng, See Kiong; Ghosh, Samik; Wee, Lawrence Jin Kiat

    2016-12-22

    The ability to sequence the transcriptomes of single cells using single-cell RNA-seq sequencing technologies presents a shift in the scientific paradigm where scientists, now, are able to concurrently investigate the complex biology of a heterogeneous population of cells, one at a time. However, till date, there has not been a suitable computational methodology for the analysis of such intricate deluge of data, in particular techniques which will aid the identification of the unique transcriptomic profiles difference between the different cellular subtypes. In this paper, we describe the novel methodology for the analysis of single-cell RNA-seq data, obtained from neocortical cells and neural progenitor cells, using machine learning algorithms (Support Vector machine (SVM) and Random Forest (RF)). Thirty-eight key transcripts were identified, using the SVM-based recursive feature elimination (SVM-RFE) method of feature selection, to best differentiate developing neocortical cells from neural progenitor cells in the SVM and RF classifiers built. Also, these genes possessed a higher discriminative power (enhanced prediction accuracy) as compared commonly used statistical techniques or geneset-based approaches. Further downstream network reconstruction analysis was carried out to unravel hidden general regulatory networks where novel interactions could be further validated in web-lab experimentation and be useful candidates to be targeted for the treatment of neuronal developmental diseases. This novel approach reported for is able to identify transcripts, with reported neuronal involvement, which optimally differentiate neocortical cells and neural progenitor cells. It is believed to be extensible and applicable to other single-cell RNA-seq expression profiles like that of the study of the cancer progression and treatment within a highly heterogeneous tumour.

  2. Common genetic variants influence human subcortical brain structures

    Science.gov (United States)

    Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Olde Loohuis, Loes M.; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rose, Emma J.; Salami, Alireza; Sämann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Pütz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Göring, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Mühleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Nöthen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdés Hernández, Maria C.; van ’t Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Völzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E.; Jönsson, Erik G.; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S.; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S.; Saykin, Andrew J.; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M.; Weale, Michael E.; Weinberger, Daniel R.; Adams, Hieab H. H.; Launer, Lenore J.; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L.; Becker, James T.; Yanek, Lisa; van der Lee, Sven J.; Ebling, Maritza; Fischl, Bruce; Longstreth, W. T.; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N.; van Duijn, Cornelia M.; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C.; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M. Arfan; Martin, Nicholas G.; Wright, Margaret J.; Schumann, Gunter; Franke, Barbara; Thompson, Paul M.; Medland, Sarah E.

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability inhuman brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. PMID:25607358

  3. Topological isomorphisms of human brain and financial market networks

    Directory of Open Access Journals (Sweden)

    Petra E Vértes

    2011-09-01

    Full Text Available Although metaphorical and conceptual connections between the human brain and the financial markets have often been drawn, rigorous physical or mathematical underpinnings of this analogy remain largely unexplored. Here, we apply a statistical and graph theoretic approach to the study of two datasets - the timeseries of 90 stocks from the New York Stock Exchange over a three-year period, and the fMRI-derived timeseries acquired from 90 brain regions over the course of a 10 min-long functional MRI scan of resting brain function in healthy volunteers. Despite the many obvious substantive differences between these two datasets, graphical analysis demonstrated striking commonalities in terms of global network topological properties. Both the human brain and the market networks were non-random, small-world, modular, hierarchical systems with fat-tailed degree distributions indicating the presence of highly connected hubs. These properties could not be trivially explained by the univariate time series statistics of stock price returns. This degree of topological isomorphism suggests that brains and markets can be regarded broadly as members of the same family of networks. The two systems, however, were not topologically identical. The financial market was more efficient and more modular - more highly optimised for information processing - than the brain networks; but also less robust to systemic disintegration as a result of hub deletion. We conclude that the conceptual connections between brains and markets are not merely metaphorical; rather these two information processing systems can be rigorously compared in the same mathematical language and turn out often to share important topological properties in common to some degree. There will be interesting scientific arbitrage opportunities in further work at the graph theoretically-mediated interface between systems neuroscience and the statistical physics of financial markets.

  4. Topological isomorphisms of human brain and financial market networks.

    Science.gov (United States)

    Vértes, Petra E; Nicol, Ruth M; Chapman, Sandra C; Watkins, Nicholas W; Robertson, Duncan A; Bullmore, Edward T

    2011-01-01

    Although metaphorical and conceptual connections between the human brain and the financial markets have often been drawn, rigorous physical or mathematical underpinnings of this analogy remain largely unexplored. Here, we apply a statistical and graph theoretic approach to the study of two datasets - the time series of 90 stocks from the New York stock exchange over a 3-year period, and the fMRI-derived time series acquired from 90 brain regions over the course of a 10-min-long functional MRI scan of resting brain function in healthy volunteers. Despite the many obvious substantive differences between these two datasets, graphical analysis demonstrated striking commonalities in terms of global network topological properties. Both the human brain and the market networks were non-random, small-world, modular, hierarchical systems with fat-tailed degree distributions indicating the presence of highly connected hubs. These properties could not be trivially explained by the univariate time series statistics of stock price returns. This degree of topological isomorphism suggests that brains and markets can be regarded broadly as members of the same family of networks. The two systems, however, were not topologically identical. The financial market was more efficient and more modular - more highly optimized for information processing - than the brain networks; but also less robust to systemic disintegration as a result of hub deletion. We conclude that the conceptual connections between brains and markets are not merely metaphorical; rather these two information processing systems can be rigorously compared in the same mathematical language and turn out often to share important topological properties in common to some degree. There will be interesting scientific arbitrage opportunities in further work at the graph-theoretically mediated interface between systems neuroscience and the statistical physics of financial markets.

  5. Brain lactate metabolism in humans with subarachnoid hemorrhage.

    Science.gov (United States)

    Oddo, Mauro; Levine, Joshua M; Frangos, Suzanne; Maloney-Wilensky, Eileen; Carrera, Emmanuel; Daniel, Roy T; Levivier, Marc; Magistretti, Pierre J; LeRoux, Peter D

    2012-05-01

    Lactate is central for the regulation of brain metabolism and is an alternative substrate to glucose after injury. Brain lactate metabolism in patients with subarachnoid hemorrhage has not been fully elucidated. Thirty-one subarachnoid hemorrhage patients monitored with cerebral microdialysis (CMD) and brain oxygen (PbtO(2)) were studied. Samples with elevated CMD lactate (>4 mmol/L) were matched to PbtO(2) and CMD pyruvate and categorized as hypoxic (PbtO(2) 119 μmol/L) versus nonhyperglycolytic. Median per patient samples with elevated CMD lactate was 54% (interquartile range, 11%-80%). Lactate elevations were more often attributable to cerebral hyperglycolysis (78%; interquartile range, 5%-98%) than brain hypoxia (11%; interquartile range, 4%-75%). Mortality was associated with increased percentage of samples with elevated lactate and brain hypoxia (28% [interquartile range 9%-95%] in nonsurvivors versus 9% [interquartile range 3%-17%] in survivors; P=0.02) and lower percentage of elevated lactate and cerebral hyperglycolysis (13% [interquartile range, 1%-87%] versus 88% [interquartile range, 27%-99%]; P=0.07). Cerebral hyperglycolytic lactate production predicted good 6-month outcome (odds ratio for modified Rankin Scale score, 0-3 1.49; CI, 1.08-2.05; P=0.016), whereas increased lactate with brain hypoxia was associated with a reduced likelihood of good outcome (OR, 0.78; CI, 0.59-1.03; P=0.08). Brain lactate is frequently elevated in subarachnoid hemorrhage patients, predominantly because of hyperglycolysis rather than hypoxia. A pattern of increased cerebral hyperglycolytic lactate was associated with good long-term recovery. Our data suggest that lactate may be used as an aerobic substrate by the injured human brain.

  6. Xanthine oxidase activity regulates human embryonic brain cells growth

    Directory of Open Access Journals (Sweden)

    Kevorkian G. A.

    2011-10-01

    Full Text Available Aim. Involvement of Xanthine Oxidase (XO; EC1.1.3.22 in cellular proliferation and differentiation has been suggested by the numerous investigations. We have proposed that XO might have undoubtedly important role during the development, maturation as well as the death of human embryos brain cells. Methods. Human abortion material was utilized for the cultivation of brain cells (E90. XO activity was measured by the formation of uric acid in tissue. Cell death was detected by the utility of Trypan Blue dye. Results. Allopurinol suppressed the XO activity in the brain tissue (0.12 ± 0.02; 0.20 ± 0.03 resp., p < 0.05. On day 12th the number of cells in the culture treated with the Allopurinol at the early stage of development was higher in comparison with the Control (2350.1 ± 199.0 vs 2123 ± 96 and higher in comparison with the late period of treatment (1479.6 ± 103.8, p < < 0.05. In all groups, the number of the dead cells was less than in Control, indicating the protective nature of Allopurinol as an inhibitor of XO. Conclusions. Allopurinol initiates cells proliferation in case of the early treatment of the human brain derived cell culture whereas at the late stages it has an opposite effect.

  7. Cross-hemispheric functional connectivity in the human fetal brain.

    Science.gov (United States)

    Thomason, Moriah E; Dassanayake, Maya T; Shen, Stephen; Katkuri, Yashwanth; Alexis, Mitchell; Anderson, Amy L; Yeo, Lami; Mody, Swati; Hernandez-Andrade, Edgar; Hassan, Sonia S; Studholme, Colin; Jeong, Jeong-Won; Romero, Roberto

    2013-02-20

    Compelling evidence indicates that psychiatric and developmental disorders are generally caused by disruptions in the functional connectivity (FC) of brain networks. Events occurring during development, and in particular during fetal life, have been implicated in the genesis of such disorders. However, the developmental timetable for the emergence of neural FC during human fetal life is unknown. We present the results of resting-state functional magnetic resonance imaging performed in 25 healthy human fetuses in the second and third trimesters of pregnancy (24 to 38 weeks of gestation). We report the presence of bilateral fetal brain FC and regional and age-related variation in FC. Significant bilateral connectivity was evident in half of the 42 areas tested, and the strength of FC between homologous cortical brain regions increased with advancing gestational age. We also observed medial to lateral gradients in fetal functional brain connectivity. These findings improve understanding of human fetal central nervous system development and provide a basis for examining the role of insults during fetal life in the subsequent development of disorders in neural FC.

  8. Dystrophic microglia in the aging human brain.

    Science.gov (United States)

    Streit, Wolfgang J; Sammons, Nicole W; Kuhns, Amanda J; Sparks, D Larry

    2004-01-15

    We have studied microglial morphology in the human cerebral cortex of two nondemented subjects using high-resolution LN-3 immunohistochemistry. Several abnormalities in microglial cytoplasmic structure, including deramification, spheroid formation, gnarling, and fragmentation of processes, were identified. These changes were determined to be different from the morphological changes that occur during microglial activation and they were designated collectively as microglial dystrophy. Quantitative evaluation of dystrophic changes in microglia revealed that these were much more prevalent in the older subject (68-year-old) than in the younger one (38-year-old). Thus, we conclude that microglial dystrophy is a sign of microglial cell senescence. We hypothesize that microglial senescence could be important for understanding age-related declines in cognitive function. Copyright 2003 Wiley-Liss, Inc.

  9. Mapping the calcitonin receptor in human brain stem

    DEFF Research Database (Denmark)

    Bower, Rebekah L; Eftekhari, Sajedeh; Waldvogel, Henry J

    2016-01-01

    understanding of these hormone systems by mapping CTR expression in the human brain stem, specifically the medulla oblongata. Widespread CTR-like immunoreactivity was observed throughout the medulla. Dense CTR staining was noted in several discrete nuclei, including the nucleus of the solitary tract...... receptors (AMY) are a heterodimer formed by the coexpression of CTR with receptor activity-modifying proteins (RAMPs). CTR with RAMP1 responds potently to both amylin and CGRP. The brain stem is a major site of action for circulating amylin and is a rich site of CGRP binding. This study aimed to enhance our...

  10. Comparative transcriptomic profiling of hydrogen peroxide signaling networks in zebrafish and human keratinocytes: Implications toward conservation, migration and wound healing.

    Science.gov (United States)

    Lisse, Thomas S; King, Benjamin L; Rieger, Sandra

    2016-02-05

    Skin wounds need to be repaired rapidly after injury to restore proper skin barrier function. Hydrogen peroxide (H2O2) is a conserved signaling factor that has been shown to promote a variety of skin wound repair processes, including immune cell migration, angiogenesis and sensory axon repair. Despite growing research on H2O2 functions in wound repair, the downstream signaling pathways activated by this reactive oxygen species in the context of injury remain largely unknown. The goal of this study was to provide a comprehensive analysis of gene expression changes in the epidermis upon exposure to H2O2 concentrations known to promote wound repair. Comparative transcriptome analysis using RNA-seq data from larval zebrafish and previously reported microarray data from a human epidermal keratinocyte line shows that H2O2 activates conserved cell migration, adhesion, cytoprotective and anti-apoptotic programs in both zebrafish and human keratinocytes. Further assessment of expression characteristics and signaling pathways revealed the activation of three major H2O2-dependent pathways, EGF, FOXO1, and IKKα. This study expands on our current understanding of the clinical potential of low-level H2O2 for the promotion of epidermal wound repair and provides potential candidates in the treatment of wound healing deficits.

  11. A human-specific de novo protein-coding gene associated with human brain functions.

    Directory of Open Access Journals (Sweden)

    Chuan-Yun Li

    2010-03-01

    Full Text Available To understand whether any human-specific new genes may be associated with human brain functions, we computationally screened the genetic vulnerable factors identified through Genome-Wide Association Studies and linkage analyses of nicotine addiction and found one human-specific de novo protein-coding gene, FLJ33706 (alternative gene symbol C20orf203. Cross-species analysis revealed interesting evolutionary paths of how this gene had originated from noncoding DNA sequences: insertion of repeat elements especially Alu contributed to the formation of the first coding exon and six standard splice junctions on the branch leading to humans and chimpanzees, and two subsequent substitutions in the human lineage escaped two stop codons and created an open reading frame of 194 amino acids. We experimentally verified FLJ33706's mRNA and protein expression in the brain. Real-Time PCR in multiple tissues demonstrated that FLJ33706 was most abundantly expressed in brain. Human polymorphism data suggested that FLJ33706 encodes a protein under purifying selection. A specifically designed antibody detected its protein expression across human cortex, cerebellum and midbrain. Immunohistochemistry study in normal human brain cortex revealed the localization of FLJ33706 protein in neurons. Elevated expressions of FLJ33706 were detected in Alzheimer's brain samples, suggesting the role of this novel gene in human-specific pathogenesis of Alzheimer's disease. FLJ33706 provided the strongest evidence so far that human-specific de novo genes can have protein-coding potential and differential protein expression, and be involved in human brain functions.

  12. Cells in human postmortem brain tissue slices remain alive for several weeks in culture

    NARCIS (Netherlands)

    Verwer, Ronald W. H.; Hermens, Wim T. J. M. C.; Dijkhuizen, PaulaA; ter Brake, Olivier; Baker, Robert E.; Salehi, Ahmad; Sluiter, Arja A.; Kok, Marloes J. M.; Muller, Linda J.; Verhaagen, Joost; Swaab, Dick F.

    2002-01-01

    Animal models for human neurological and psychiatric diseases only partially mimic the underlying pathogenic processes. Therefore, we investigated the potential use of cultured postmortem brain tissue from adult neurological patients and controls. The present study shows that human brain tissue

  13. Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq

    Science.gov (United States)

    Whitmore, S. Scott; Wagner, Alex H.; DeLuca, Adam P.; Drack, Arlene V.; Stone, Edwin M.; Tucker, Budd A.; Zeng, Shemin; Braun, Terry A.; Mullins, Robert F.; Scheetz, Todd E.

    2014-01-01

    Proper spatial differentiation of retinal cell types is necessary for normal human vision. Many retinal diseases, such as Best disease and male germ cell associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions of the retina. While much is known about the distribution of cell-types in the retina, the distribution of molecular components across the posterior pole of the eye has not been well-studied. To investigate regional difference in molecular composition of ocular tissues, we assessed differential gene expression across the temporal, macular, and nasal retina and retinal pigment epithelium (RPE)/choroid of human eyes using RNA-Seq. RNA from temporal, macular, and nasal retina and RPE/choroid from four human donor eyes was extracted, poly-A selected, fragmented, and sequenced as 100 bp read pairs. Digital read files were mapped to the human genome and analyzed for differential expression using the Tuxedo software suite. Retina and RPE/choroid samples were clearly distinguishable at the transcriptome level. Numerous transcription factors were differentially expressed between regions of the retina and RPE/choroid. Photoreceptor-specific genes were enriched in the peripheral samples, while ganglion cell and amacrine cell genes were enriched in the macula. Within the RPE/choroid, RPE-specific genes were upregulated at the periphery while endothelium associated genes were upregulated in the macula. Consistent with previous studies, BEST1 expression was lower in macular than extramacular regions. The MAK gene was expressed at lower levels in macula than in extramacular regions, but did not exhibit a significant difference between nasal and temporal retina. The regional molecular distinction is greatest between macula and periphery and decreases between different peripheral regions within a tissue. Datasets such as these can be used to prioritize candidate genes for possible involvement in retinal diseases with

  14. Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq.

    Science.gov (United States)

    Whitmore, S Scott; Wagner, Alex H; DeLuca, Adam P; Drack, Arlene V; Stone, Edwin M; Tucker, Budd A; Zeng, Shemin; Braun, Terry A; Mullins, Robert F; Scheetz, Todd E

    2014-12-01

    Proper spatial differentiation of retinal cell types is necessary for normal human vision. Many retinal diseases, such as Best disease and male germ cell associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions of the retina. While much is known about the distribution of cell types in the retina, the distribution of molecular components across the posterior pole of the eye has not been well-studied. To investigate regional difference in molecular composition of ocular tissues, we assessed differential gene expression across the temporal, macular, and nasal retina and retinal pigment epithelium (RPE)/choroid of human eyes using RNA-Seq. RNA from temporal, macular, and nasal retina and RPE/choroid from four human donor eyes was extracted, poly-A selected, fragmented, and sequenced as 100 bp read pairs. Digital read files were mapped to the human genome and analyzed for differential expression using the Tuxedo software suite. Retina and RPE/choroid samples were clearly distinguishable at the transcriptome level. Numerous transcription factors were differentially expressed between regions of the retina and RPE/choroid. Photoreceptor-specific genes were enriched in the peripheral samples, while ganglion cell and amacrine cell genes were enriched in the macula. Within the RPE/choroid, RPE-specific genes were upregulated at the periphery while endothelium associated genes were upregulated in the macula. Consistent with previous studies, BEST1 expression was lower in macular than extramacular regions. The MAK gene was expressed at lower levels in macula than in extramacular regions, but did not exhibit a significant difference between nasal and temporal retina. The regional molecular distinction is greatest between macula and periphery and decreases between different peripheral regions within a tissue. Datasets such as these can be used to prioritize candidate genes for possible involvement in retinal diseases with

  15. A subset of group A-like var genes encodes the malaria parasite ligands for binding to human brain endothelial cells

    DEFF Research Database (Denmark)

    Claessens, Antoine; Adams, Yvonne; Ghumra, Ashfaq

    2012-01-01

    Cerebral malaria is the most deadly manifestation of infection with Plasmodium falciparum. The pathology of cerebral malaria is characterized by the accumulation of infected erythrocytes (IEs) in the microvasculature of the brain caused by parasite adhesins on the surface of IEs binding to human...... receptors on microvascular endothelial cells. The parasite and host molecules involved in this interaction are unknown. We selected three P. falciparum strains (HB3, 3D7, and IT/FCR3) for binding to a human brain endothelial cell line (HBEC-5i). The whole transcriptome of isogenic pairs of selected.......029) but not by antibodies from controls with uncomplicated malaria (Mann-Whitney test, P = 0.58). This work describes a binding phenotype for virulence-associated group A P. falciparum erythrocyte membrane protein 1 variants and identifies targets for interventions to treat or prevent cerebral malaria....

  16. The neural encoding of guesses in the human brain.

    Science.gov (United States)

    Bode, Stefan; Bogler, Carsten; Soon, Chun Siong; Haynes, John-Dylan

    2012-01-16

    Human perception depends heavily on the quality of sensory information. When objects are hard to see we often believe ourselves to be purely guessing. Here we investigated whether such guesses use brain networks involved in perceptual decision making or independent networks. We used a combination of fMRI and pattern classification to test how visibility affects the signals, which determine choices. We found that decisions regarding clearly visible objects are predicted by signals in sensory brain regions, whereas different regions in parietal cortex became predictive when subjects were shown invisible objects and believed themselves to be purely guessing. This parietal network was highly overlapping with regions, which have previously been shown to encode free decisions. Thus, the brain might use a dedicated network for determining choices when insufficient sensory information is available. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Listening to humans walking together activates the social brain circuitry.

    Science.gov (United States)

    Saarela, Miiamaaria V; Hari, Riitta

    2008-01-01

    Human footsteps carry a vast amount of social information, which is often unconsciously noted. Using functional magnetic resonance imaging, we analyzed brain networks activated by footstep sounds of one or two persons walking. Listening to two persons walking together activated brain areas previously associated with affective states and social interaction, such as the subcallosal gyrus bilaterally, the right temporal pole, and the right amygdala. These areas seem to be involved in the analysis of persons' identity and complex social stimuli on the basis of auditory cues. Single footsteps activated only the biological motion area in the posterior STS region. Thus, hearing two persons walking together involved a more widespread brain network than did hearing footsteps from a single person.

  18. Brain-Computer Interfaces Revolutionizing Human-Computer Interaction

    CERN Document Server

    Graimann, Bernhard; Allison, Brendan

    2010-01-01

    A brain-computer interface (BCI) establishes a direct output channel between the human brain and external devices. BCIs infer user intent via direct measures of brain activity and thus enable communication and control without movement. This book, authored by experts in the field, provides an accessible introduction to the neurophysiological and signal-processing background required for BCI, presents state-of-the-art non-invasive and invasive approaches, gives an overview of current hardware and software solutions, and reviews the most interesting as well as new, emerging BCI applications. The book is intended not only for students and young researchers, but also for newcomers and other readers from diverse backgrounds keen to learn about this vital scientific endeavour.

  19. Interleukin-6 release from the human brain during prolonged exercise

    DEFF Research Database (Denmark)

    Nybo, Lars; Nielsen, Bodil; Pedersen, Bente Klarlund

    2002-01-01

    Interleukin (IL)-6 is a pleiotropic cytokine, which has a variety of physiological roles including functions within the central nervous system. Circulating IL-6 increases markedly during exercise, partly due to the release of IL-6 from the contracting skeletal muscles, and exercise-induced IL-6 m...... influence of hyperthermia. In conclusion, IL-6 is released from the brain during prolonged exercise in humans and it appears that the duration of the exercise rather than the increase in body temperature dictates the cerebral IL-6 response....... in the brain at rest or after 15 min of exercise, but a small release of IL-6 was observed after 60 min of exercise in the first bout (0.06 +/- 0.03 ng min(-1)). This release of IL-6 from the brain was five-fold greater at the end of the second bout (0.30 +/- 0.08 ng min(-1); P

  20. Endurance training enhances BDNF release from the human brain

    DEFF Research Database (Denmark)

    Seifert, Thomas; Brassard, Patrice; Wissenberg, Mads

    2010-01-01

    The circulating level of brain-derived neurotrophic factor (BDNF) is reduced in patients with major depression and type-2 diabetes. Because acute exercise increases BDNF production in the hippocampus and cerebral cortex, we hypothesized that endurance training would enhance the release of BDNF from...... the human brain as detected from arterial and internal jugular venous blood samples. In a randomized controlled study, 12 healthy sedentary males carried out 3 mo of endurance training (n = 7) or served as controls (n = 5). Before and after the intervention, blood samples were obtained at rest and during...... exercise. At baseline, the training group (58 + or - 106 ng x 100 g(-1) x min(-1), means + or - SD) and the control group (12 + or - 17 ng x 100 g(-1) x min(-1)) had a similar release of BDNF from the brain at rest. Three months of endurance training enhanced the resting release of BDNF to 206 + or - 108...

  1. Midsagittal Brain Variation among Non-Human Primates: Insights into Evolutionary Expansion of the Human Precuneus.

    Science.gov (United States)

    Pereira-Pedro, Ana Sofia; Rilling, James K; Chen, Xu; Preuss, Todd M; Bruner, Emiliano

    2017-01-01

    The precuneus is a major element of the superior parietal lobule, positioned on the medial side of the hemisphere and reaching the dorsal surface of the brain. It is a crucial functional region for visuospatial integration, visual imagery, and body coordination. Previously, we argued that the precuneus expanded in recent human evolution, based on a combination of paleontological, comparative, and intraspecific evidence from fossil and modern human endocasts as well as from human and chimpanzee brains. The longitudinal proportions of this region are a major source of anatomical variation among adult humans and, being much larger in Homo sapiens, is the main characteristic differentiating human midsagittal brain morphology from that of our closest living primate relative, the chimpanzee. In the current shape analysis, we examine precuneus variation in non-human primates through landmark-based models, to evaluate the general pattern of variability in non-human primates, and to test whether precuneus proportions are influenced by allometric effects of brain size. Results show that precuneus proportions do not covary with brain size, and that the main difference between monkeys and apes involves a vertical expansion of the frontal and occipital regions in apes. Such differences might reflect differences in brain proportions or differences in cranial architecture. In this sample, precuneus variation is apparently not influenced by phylogenetic or allometric factors, but does vary consistently within species, at least in chimpanzees and macaques. This result further supports the hypothesis that precuneus expansion in modern humans is not merely a consequence of increasing brain size or of allometric scaling, but rather represents a species-specific morphological change in our lineage. © 2017 S. Karger AG, Basel.

  2. Transcriptome signature of the adult mouse choroid plexus

    Directory of Open Access Journals (Sweden)

    Marques Fernanda

    2011-01-01

    Full Text Available Abstract Background Although the gene expression profile of several tissues in humans and in rodent animal models has been explored, analysis of the complete choroid plexus (CP transcriptome is still lacking. A better characterization of the CP transcriptome can provide key insights into its functions as one of the barriers that separate the brain from the periphery and in the production of cerebrospinal fluid. Methods This work extends further what is known about the mouse CP transcriptome through a microarray analysis of CP tissue from normal mice under physiological conditions. Results We found that the genes most highly expressed are those implicated in energy metabolism (oxidative phosphorylation, glycolysis/gluconeogenesis and in ribosomal function, which is in agreement with the secretory nature of the CP. On the other hand, genes encoding for immune mediators are among those with lower expression in basal conditions. In addition, we found genes known to be relevant during brain development, and not previously identified to be expressed in the CP, including those encoding for various axonal guidance and angiogenesis molecules and for growth factors. Some of these are known to influence the neural stem cell niche in the subventricular zone, highlighting the involvement of the CP as a likely modulator of neurogenesis. Interestingly, our observations confirm that the CP transcriptome is unique, displaying low homology with that of other tissues. Of note, we describe here that the closest similarity is with the transcriptome of the endothelial cells of the blood-brain barrier. Conclusions Based on the data presented here, it will now be possible to further explore the function of particular proteins of the CP secretome in health and in disease.

  3. Sigma and opioid receptors in human brain tumors

    International Nuclear Information System (INIS)

    Thomas, G.E.; Szuecs, M.; Mamone, J.Y.; Bem, W.T.; Rush, M.D.; Johnson, F.E.; Coscia, C.J.

    1990-01-01

    Human brain tumors and nude mouse-borne human neuroblastomas and gliomas were analyzed for sigma and opioid receptor content. Sigma binding was assessed using [ 3 H] 1, 3-di-o-tolylguanidine (DTG), whereas opioid receptor subtypes were measured with tritiated forms of the following: μ, [D-ala 2 , mePhe 4 , gly-ol 5 ] enkephalin (DAMGE); κ, ethylketocyclazocine (EKC) or U69,593; δ, [D-pen 2 , D-pen 5 ] enkephalin (DPDPE) or [D-ala 2 , D-leu 5 ] enkephalin (DADLE) with μ suppressor present. Binding parameters were estimated by homologous displacement assays followed by analysis using the LIGAND program. Sigma binding was detected in 15 of 16 tumors examined with very high levels found in a brain metastasis from an adenocarcinoma of lung and a human neuroblastoma (SK-N-MC) passaged in nude mice. κ opioid receptor binding was detected in 4 of 4 glioblastoma multiforme specimens and 2 of 2 human astrocytoma cell lines tested but not in the other brain tumors analyzed

  4. Sigma and opioid receptors in human brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, G.E.; Szuecs, M.; Mamone, J.Y.; Bem, W.T.; Rush, M.D.; Johnson, F.E.; Coscia, C.J. (St. Louis Univ. School of Medicine, MO (USA))

    1990-01-01

    Human brain tumors and nude mouse-borne human neuroblastomas and gliomas were analyzed for sigma and opioid receptor content. Sigma binding was assessed using ({sup 3}H) 1, 3-di-o-tolylguanidine (DTG), whereas opioid receptor subtypes were measured with tritiated forms of the following: {mu}, (D-ala{sup 2}, mePhe{sup 4}, gly-ol{sup 5}) enkephalin (DAMGE); {kappa}, ethylketocyclazocine (EKC) or U69,593; {delta}, (D-pen{sup 2}, D-pen{sup 5}) enkephalin (DPDPE) or (D-ala{sup 2}, D-leu{sup 5}) enkephalin (DADLE) with {mu} suppressor present. Binding parameters were estimated by homologous displacement assays followed by analysis using the LIGAND program. Sigma binding was detected in 15 of 16 tumors examined with very high levels found in a brain metastasis from an adenocarcinoma of lung and a human neuroblastoma (SK-N-MC) passaged in nude mice. {kappa} opioid receptor binding was detected in 4 of 4 glioblastoma multiforme specimens and 2 of 2 human astrocytoma cell lines tested but not in the other brain tumors analyzed.

  5. Is the social brain theory applicable to human individual differences? Relationship between sociability personality dimension and brain size.

    Science.gov (United States)

    Horváth, Klára; Martos, János; Mihalik, Béla; Bódizs, Róbert

    2011-06-17

    Our study intends to examine whether the social brain theory is applicable to human individual differences. According to the social brain theory primates have larger brains as it could be expected from their body sizes due to the adaptation to a more complex social life. Regarding humans there were few studies about the relationship between theory of mind and frontal and temporal brain lobes. We hypothesized that these brain lobes, as well as the whole cerebrum and neocortex are in connection with the Sociability personality dimension that is associated with individuals' social lives. Our findings support this hypothesis as Sociability correlated positively with the examined brain structures if we control the effects of body size differences and age. These results suggest that the social brain theory can be extended to human interindividual differences and they have some implications to personality psychology too.

  6. Sensitivity analysis of human brain structural network construction

    Directory of Open Access Journals (Sweden)

    Kuang Wei

    2017-12-01

    Full Text Available Network neuroscience leverages diffusion-weighted magnetic resonance imaging and tractography to quantify structural connectivity of the human brain. However, scientists and practitioners lack a clear understanding of the effects of varying tractography parameters on the constructed structural networks. With diffusion images from the Human Connectome Project (HCP, we characterize how structural networks are impacted by the spatial resolution of brain atlases, total number of tractography streamlines, and grey matter dilation with various graph metrics. We demonstrate how injudicious combinations of highly refined brain parcellations and low numbers of streamlines may inadvertently lead to disconnected network models with isolated nodes. Furthermore, we provide solutions to significantly reduce the likelihood of generating disconnected networks. In addition, for different tractography parameters, we investigate the distributions of values taken by various graph metrics across the population of HCP subjects. Analyzing the ranks of individual subjects within the graph metric distributions, we find that the ranks of individuals are affected differently by atlas scale changes. Our work serves as a guideline for researchers to optimize the selection of tractography parameters and illustrates how biological characteristics of the brain derived in network neuroscience studies can be affected by the choice of atlas parcellation schemes. Diffusion tractography has been proven to be a promising noninvasive technique to study the network properties of the human brain. However, how various tractography and network construction parameters affect network properties has not been studied using a large cohort of high-quality data. We utilize data provided by the Human Connectome Project to characterize the changes to network properties induced by varying the brain parcellation atlas scales, the number of reconstructed tractography tracks, and the degree of grey

  7. An xQTL map integrates the genetic architecture of the human brain's transcriptome and epigenome.

    Science.gov (United States)

    Ng, Bernard; White, Charles C; Klein, Hans-Ulrich; Sieberts, Solveig K; McCabe, Cristin; Patrick, Ellis; Xu, Jishu; Yu, Lei; Gaiteri, Chris; Bennett, David A; Mostafavi, Sara; De Jager, Philip L

    2017-10-01

    We report a multi-omic resource generated by applying quantitative trait locus (xQTL) analyses to RNA sequence, DNA methylation and histone acetylation data from the dorsolateral prefrontal cortex of 411 older adults who have all three data types. We identify SNPs significantly associated with gene expression, DNA methylation and histone modification levels. Many of these SNPs influence multiple molecular features, and we demonstrate that SNP effects on RNA expression are fully mediated by epigenetic features in 9% of these loci. Further, we illustrate the utility of our new resource, xQTL Serve, by using it to prioritize the cell type(s) most affected by an xQTL. We also reanalyze published genome wide association studies using an xQTL-weighted analysis approach and identify 18 new schizophrenia and 2 new bipolar susceptibility variants, which is more than double the number of loci that can be discovered with a larger blood-based expression eQTL resource.

  8. Sex differences in the structural connectome of the human brain.

    Science.gov (United States)

    Ingalhalikar, Madhura; Smith, Alex; Parker, Drew; Satterthwaite, Theodore D; Elliott, Mark A; Ruparel, Kosha; Hakonarson, Hakon; Gur, Raquel E; Gur, Ruben C; Verma, Ragini

    2014-01-14

    Sex differences in human behavior show adaptive complementarity: Males have better motor and spatial abilities, whereas females have superior memory and social cognition skills. Studies also show sex differences in human brains but do not explain this complementarity. In this work, we modeled the structural connectome using diffusion tensor imaging in a sample of 949 youths (aged 8-22 y, 428 males and 521 females) and discovered unique sex differences in brain connectivity during the course of development. Connection-wise statistical analysis, as well as analysis of regional and global network measures, presented a comprehensive description of network characteristics. In all supratentorial regions, males had greater within-hemispheric connectivity, as well as enhanced modularity and transitivity, whereas between-hemispheric connectivity and cross-module participation predominated in females. However, this effect was reversed in the cerebellar connections. Analysis of these changes developmentally demonstrated differences in trajectory between males and females mainly in adolescence and in adulthood. Overall, the results suggest that male brains are structured to facilitate connectivity between perception and coordinated action, whereas female brains are designed to facilitate communication between analytical and intuitive processing modes.

  9. Multiscale neural connectivity during human sensory processing in the brain

    Science.gov (United States)

    Maksimenko, Vladimir A.; Runnova, Anastasia E.; Frolov, Nikita S.; Makarov, Vladimir V.; Nedaivozov, Vladimir; Koronovskii, Alexey A.; Pisarchik, Alexander; Hramov, Alexander E.

    2018-05-01

    Stimulus-related brain activity is considered using wavelet-based analysis of neural interactions between occipital and parietal brain areas in alpha (8-12 Hz) and beta (15-30 Hz) frequency bands. We show that human sensory processing related to the visual stimuli perception induces brain response resulted in different ways of parieto-occipital interactions in these bands. In the alpha frequency band the parieto-occipital neuronal network is characterized by homogeneous increase of the interaction between all interconnected areas both within occipital and parietal lobes and between them. In the beta frequency band the occipital lobe starts to play a leading role in the dynamics of the occipital-parietal network: The perception of visual stimuli excites the visual center in the occipital area and then, due to the increase of parieto-occipital interactions, such excitation is transferred to the parietal area, where the attentional center takes place. In the case when stimuli are characterized by a high degree of ambiguity, we find greater increase of the interaction between interconnected areas in the parietal lobe due to the increase of human attention. Based on revealed mechanisms, we describe the complex response of the parieto-occipital brain neuronal network during the perception and primary processing of the visual stimuli. The results can serve as an essential complement to the existing theory of neural aspects of visual stimuli processing.

  10. In Vivo H MR spectroscopic imaging of human brain

    International Nuclear Information System (INIS)

    Choe, Bo Young; Suh, Tae Suk; Choi, Kyo Ho; Bahk, Yong Whee; Shinn, Kyung Sub

    1994-01-01

    To evaluate the spatial distribution of various proton metabolites in the human brain with use of water-suppressed in vivo H MR spectroscopic imaging (MRSI) technique. All of water-suppressed in vivo H MRSI were performed on 1.5 T whole-body MRI/MRS system using Stimulated Echo Acquisition Method (STEAM) Chemical Shift Imaging (CSI) pulse sequence. T1-weighted MR images were used for CSI field of view (FOV; 24 cm). Voxel size of 1.5 cm 3 was designated from the periphery of the brain which was divided by 1024 X 16 X 16 data points. Metabolite images of N-acetylaspartate (NAA), creatine/ phosphocreatine (Cr) + choline/phosphocholine (Cho), and complex of γ-aminobutyric acid (GABA) + glutamate (Glu) were obtained on the human brain. Our preliminary study suggests that in vivo H MRSI could provide the metabolite imaging to compensate for hypermetabolism on Positron Emission Tomography (PET) scans on the basis of the metabolic informations on brain tissues. The unique ability of in vivo H MRSI to offer noninvasive information about tissue biochemistry in disease states will stimulate on clinical research and disease diagnosis

  11. Drug delivery to the human brain via the cerebrospinal fluid

    Energy Technology Data Exchange (ETDEWEB)

    Howden, L.; Aroussi, A. [Univ. of Nottingham, School of Mechanical, Material, Manufacturing Engineering and Managements, Nottingham (United Kingdom)]. E-mail: eaxljh@nottingham.ac.uk; Vloeberghs, M. [Queens Medical Centre, Dept. of Child Health, Nottingham (United Kingdom)

    2003-07-01

    This Study investigates the flow of Cerebrospinal Fluid (CSF) inside the human ventricular system with particular emphasis on drug path flow for the purpose of medical drug injections. The investigation is conducted using the computational fluid dynamics package FLUENT. The role of the ventricular system is very important in protecting the brain from injury by cushioning it against the cranium during sudden movements. If for any reason the passage of CSF through the ventricular system is blocked (usually by stenosis) then a condition known as Hydrocephalus occurs, where by the blocked CSF causes the Intra Cranial Pressure (ICP) inside the brain to rise. If this is not treated then severe brain damage and death can occur. Previous work conducted by the authors on this subject has focused on the technique of ventriculostomy to treat hydrocephalus. The present study carries on from the previous work but focuses on delivering medical drugs to treat brain tumors that are conventionally not accessible and which require complicated surgical procedures to remove them. The study focuses on the possible paths for delivering drugs to tumors in the human nervous system through conventionally accessible locations without major surgery. The results of the investigation have shown that it is possible to reach over 95% of the ventricular system by injection of drugs however the results also show that there are many factors that can affect the drug flow paths through the ventricular system and thus the areas reachable, by these drugs. (author)

  12. Drug delivery to the human brain via the cerebrospinal fluid

    International Nuclear Information System (INIS)

    Howden, L.; Aroussi, A.; Vloeberghs, M.

    2003-01-01

    This Study investigates the flow of Cerebrospinal Fluid (CSF) inside the human ventricular system with particular emphasis on drug path flow for the purpose of medical drug injections. The investigation is conducted using the computational fluid dynamics package FLUENT. The role of the ventricular system is very important in protecting the brain from injury by cushioning it against the cranium during sudden movements. If for any reason the passage of CSF through the ventricular system is blocked (usually by stenosis) then a condition known as Hydrocephalus occurs, where by the blocked CSF causes the Intra Cranial Pressure (ICP) inside the brain to rise. If this is not treated then severe brain damage and death can occur. Previous work conducted by the authors on this subject has focused on the technique of ventriculostomy to treat hydrocephalus. The present study carries on from the previous work but focuses on delivering medical drugs to treat brain tumors that are conventionally not accessible and which require complicated surgical procedures to remove them. The study focuses on the possible paths for delivering drugs to tumors in the human nervous system through conventionally accessible locations without major surgery. The results of the investigation have shown that it is possible to reach over 95% of the ventricular system by injection of drugs however the results also show that there are many factors that can affect the drug flow paths through the ventricular system and thus the areas reachable, by these drugs. (author)

  13. The Speculative Neuroscience of the Future Human Brain

    Directory of Open Access Journals (Sweden)

    Robert A. Dielenberg

    2013-05-01

    Full Text Available The hallmark of our species is our ability to hybridize symbolic thinking with behavioral output. We began with the symmetrical hand axe around 1.7 mya and have progressed, slowly at first, then with greater rapidity, to producing increasingly more complex hybridized products. We now live in the age where our drive to hybridize has pushed us to the brink of a neuroscientific revolution, where for the first time we are in a position to willfully alter the brain and hence, our behavior and evolution. Nootropics, transcranial direct current stimulation (tDCS, transcranial magnetic stimulation (TMS, deep brain stimulation (DBS and invasive brain mind interface (BMI technology are allowing humans to treat previously inaccessible diseases as well as open up potential vistas for cognitive enhancement. In the future, the possibility exists for humans to hybridize with BMIs and mobile architectures. The notion of self is becoming increasingly extended. All of this to say: are we in control of our brains, or are they in control of us?

  14. Transcriptome Analysis Identifies Key Metabolic Changes in the Hooded Seal (Cystophora cristata Brain in Response to Hypoxia and Reoxygenation.

    Directory of Open Access Journals (Sweden)

    Mariana Leivas Müller Hoff

    Full Text Available The brain of diving mammals tolerates low oxygen conditions better than the brain of most terrestrial mammals. Previously, it has been demonstrated that the neurons in brain slices of the hooded seal (Cystophora cristata withstand hypoxia longer than those of mouse, and also tolerate reduced glucose supply and high lactate concentrations. This tolerance appears to be accompanied by a shift in the oxidative energy metabolism to the astrocytes in the seal while in terrestrial mammals the aerobic energy production mainly takes place in neurons. Here, we used RNA-Seq to compare the effect of hypoxia and reoxygenation in vitro on brain slices from the visual cortex of hooded seals. We saw no general reduction of gene expression, suggesting that the response to hypoxia and reoxygenation is an actively regulated process. The treatments caused the preferential upregulation of genes related to inflammation, as found before e.g. in stroke studies using mammalian models. Gene ontology and KEGG pathway analyses showed a downregulation of genes involved in ion transport and other neuronal processes, indicative for a neuronal shutdown in response to a shortage of O2 supply. These differences may be interpreted in terms of an energy saving strategy in the seal's brain. We specifically analyzed the regulation of genes involved in energy metabolism. Hypoxia and reoxygenation caused a similar response, with upregulation of genes involved in glucose metabolism and downregulation of the components of the pyruvate dehydrogenase complex. We also observed upregulation of the monocarboxylate transporter Mct4, suggesting increased lactate efflux. Together, these data indicate that the seal brain responds to the hypoxic challenge by a relative increase in the anaerobic energy metabolism.

  15. A Novel Human Body Area Network for Brain Diseases Analysis.

    Science.gov (United States)

    Lin, Kai; Xu, Tianlang

    2016-10-01

    Development of wireless sensor and mobile communication technology provide an unprecedented opportunity for realizing smart and interactive healthcare systems. Designing such systems aims to remotely monitor the health and diagnose the diseases for users. In this paper, we design a novel human body area network for brain diseases analysis, which is named BABDA. Considering the brain is one of the most complex organs in the human body, the BABDA system provides four function modules to ensure the high quality of the analysis result, which includes initial data collection, data correction, data transmission and comprehensive data analysis. The performance evaluation conducted in a realistic environment with several criteria shows the availability and practicability of the BABDA system.

  16. Editor's Highlight: Transcriptome Profiling Reveals Bisphenol A Alternatives Activate Estrogen Receptor Alpha in Human Breast Cancer Cells.

    Science.gov (United States)

    Mesnage, Robin; Phedonos, Alexia; Arno, Matthew; Balu, Sucharitha; Corton, J Christopher; Antoniou, Michael N

    2017-08-01

    Plasticizers with estrogenic activity, such as bisphenol A (BPA), have potential adverse health effects in humans. Due to mounting evidence of these health effects, BPA is being phased out and replaced by other bisphenol variants in "BPA-free" products. We have compared estrogenic activity of BPA with 6 bisphenol analogues [bisphenol S (BPS); bisphenol F (BPF); bisphenol AP (BPAP); bisphenol AF (BPAF); bisphenol Z (BPZ); bisphenol B (BPB)] in 3 human breast cancer cell lines. Estrogenicity was assessed (10-11-10-4 M) by cell growth in an estrogen receptor (ER)-mediated cell proliferation assay, and by the induction of estrogen response element-mediated transcription in a luciferase assay. BPAF was the most potent bisphenol, followed by BPB > BPZ ∼ BPA > BPF ∼ BPAP > BPS. The addition of ICI 182,780 antagonized the activation of ERs. Data mining of ToxCast high-throughput screening assays confirm our results but also show divergence in the sensitivities of the assays. Gene expression profiles were determined in MCF-7 cells by microarray analysis. The comparison of transcriptome profile alterations resulting from BPA alternatives with an ERα gene expression biomarker further indicates that all BPA alternatives act as ERα agonists in MCF-7 cells. These results were confirmed by Illumina-based RNA sequencing. In conclusion, BPA alternatives are not necessarily less estrogenic than BPA in human breast cancer cells. BPAF, BPB, and BPZ were more estrogenic than BPA. These findings point to the importance of better understanding the risk of adverse effects from exposure to BPA alternatives, including hormone-dependent breast cancer. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology.

  17. Molecular pathways undergoing dramatic transcriptomic changes during tumor development in the human colon

    Directory of Open Access Journals (Sweden)

    Maglietta Rosalia

    2012-12-01

    Full Text Available Abstract Background The malignant transformation of precancerous colorectal lesions involves progressive alterations at both the molecular and morphologic levels, the latter consisting of increases in size and in the degree of cellular atypia. Analyzing preinvasive tumors of different sizes can therefore shed light on the sequence of these alterations. Methods We used a molecular pathway-based approach to analyze transcriptomic profiles of 59 colorectal tumors representing early and late preinvasive stages and the invasive stage of tumorigenesis. Random set analysis was used to identify biological pathways enriched for genes differentially regulated in tumors (compared with 59 samples of normal mucosa. Results Of the 880 canonical pathways we investigated, 112 displayed significant tumor-related upregulation or downregulation at one or more stages of tumorigenesis. This allowed us to distinguish between pathways whose dysregulation is probably necessary throughout tumorigenesis and those whose involvement specifically drives progression from one stage to the next. We were also able to pinpoint specific changes within each gene set that seem to play key roles at each transition. The early preinvasive stage was characterized by cell-cycle checkpoint activation triggered by DNA replication stress and dramatic downregulation of basic transmembrane signaling processes that maintain epithelial/stromal homeostasis in the normal mucosa. In late preinvasive lesions, there was also downregulation of signal transduction pathways (e.g., those mediated by G proteins and nuclear hormone receptors involved in cell differentiation and upregulation of pathways governing nuclear envelope dynamics and the G2>M transition in the cell cycle. The main features of the invasive stage were activation of the G1>S transition in the cell cycle, upregulated expression of tumor-promoting microenvironmental factors, and profound dysregulation of metabolic pathways (e

  18. Transcriptomic changes in human breast cancer progression as determined by serial analysis of gene expression

    International Nuclear Information System (INIS)

    Abba, Martin C; Aldaz, C Marcelo; Drake, Jeffrey A; Hawkins, Kathleen A; Hu, Yuhui; Sun, Hongxia; Notcovich, Cintia; Gaddis, Sally; Sahin, Aysegul; Baggerly, Keith

    2004-01-01

    Genomic and transcriptomic alterations affecting key cellular processes such us cell proliferation, differentiation and genomic stability are considered crucial for the development and progression of cancer. Most invasive breast carcinomas are known to derive from precursor in situ lesions. It is proposed that major global expression abnormalities occur in the transition from normal to premalignant stages and further progression to invasive stages. Serial analysis of gene expression (SAGE) was employed to generate a comprehensive global gene expression profile of the major changes occurring during breast cancer malignant evolution. In the present study we combined various normal and tumor SAGE libraries available in the public domain with sets of breast cancer SAGE libraries recently generated and sequenced in our laboratory. A recently developed modified t test was used to detect the genes differentially expressed. We accumulated a total of approximately 1.7 million breast tissue-specific SAGE tags and monitored the behavior of more than 25,157 genes during early breast carcinogenesis. We detected 52 transcripts commonly deregulated across the board when comparing normal tissue with ductal carcinoma in situ, and 149 transcripts when comparing ductal carcinoma in situ with invasive ductal carcinoma (P < 0.01). A major novelty of our study was the use of a statistical method that correctly accounts for the intra-SAGE and inter-SAGE library sources of variation. The most useful result of applying this modified t statistics beta binomial test is the identification of genes and gene families commonly deregulated across samples within each specific stage in the transition from normal to preinvasive and invasive stages of breast cancer development. Most of the gene expression abnormalities detected at the in situ stage were related to specific genes in charge of regulating the proper homeostasis between cell death and cell proliferation. The comparison of in situ lesions

  19. A collection of annotated and harmonized human breast cancer transcriptome datasets, including immunologic classification [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Jessica Roelands

    2018-02-01

    Full Text Available The increased application of high-throughput approaches in translational research has expanded the number of publicly available data repositories. Gathering additional valuable information contained in the datasets represents a crucial opportunity in the biomedical field. To facilitate and stimulate utilization of these datasets, we have recently developed an interactive data browsing and visualization web application, the Gene Expression Browser (GXB. In this note, we describe a curated compendium of 13 public datasets on human breast cancer, representing a total of 2142 transcriptome profiles. We classified the samples according to different immune based classification systems and integrated this information into the datasets. Annotated and harmonized datasets were uploaded to GXB. Study samples were categorized in different groups based on their immunologic tumor response profiles, intrinsic molecular subtypes and multiple clinical parameters. Ranked gene lists were generated based on relevant group comparisons. In this data note, we demonstrate the utility of GXB to evaluate the expression of a gene of interest, find differential gene expression between groups and investigate potential associations between variables with a specific focus on immunologic classification in breast cancer. This interactive resource is publicly available online at: http://breastcancer.gxbsidra.org/dm3/geneBrowser/list.

  20. A curated compendium of monocyte transcriptome datasets of relevance to human monocyte immunobiology research [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Darawan Rinchai

    2016-04-01

    Full Text Available Systems-scale profiling approaches have become widely used in translational research settings. The resulting accumulation of large-scale datasets in public repositories represents a critical opportunity to promote insight and foster knowledge discovery. However, resources that can serve as an interface between biomedical researchers and such vast and heterogeneous dataset collections are needed in order to fulfill this potential. Recently, we have developed an interactive data browsing and visualization web application, the Gene Expression Browser (GXB. This tool can be used to overlay deep molecular phenotyping data with rich contextual information about analytes, samples and studies along with ancillary clinical or immunological profiling data. In this note, we describe a curated compendium of 93 public datasets generated in the context of human monocyte immunological studies, representing a total of 4,516 transcriptome profiles. Datasets were uploaded to an instance of GXB along with study description and sample annotations. Study samples were arranged in different groups. Ranked gene lists were generated based on relevant group comparisons. This resource is publicly available online at http://monocyte.gxbsidra.org/dm3/landing.gsp.

  1. Two distinct forms of functional lateralization in the human brain

    OpenAIRE

    Gotts, Stephen J.; Jo, Hang Joon; Wallace, Gregory L.; Saad, Ziad S.; Cox, Robert W.; Martin, Alex

    2013-01-01

    This study alters our fundamental understanding of the functional interactions between the cerebral hemispheres of the human brain by establishing that the left and right hemispheres have qualitatively different biases in how they dynamically interact with one another. Left-hemisphere regions are biased to interact more strongly within the same hemisphere, whereas right-hemisphere regions interact more strongly with both hemispheres. These two different patterns of interaction are associated ...

  2. Transcriptome Profiles in Normal Human Bronchial Epithelial Cells after Exposure to gamma-rays and different HZE particles

    Data.gov (United States)

    National Aeronautics and Space Administration — Distinct transcriptome profiles in response to low-LET and high-LET and different radiation qualities of HZE particles. Total RNA obtained from HBEC3KT cells after 1...

  3. Investigation of G72 (DAOA expression in the human brain

    Directory of Open Access Journals (Sweden)

    Hirsch Steven

    2008-12-01

    Full Text Available Abstract Background Polymorphisms at the G72/G30 locus on chromosome 13q have been associated with schizophrenia or bipolar disorder in more than ten independent studies. Even though the genetic findings are very robust, the physiological role of the predicted G72 protein has thus far not been resolved. Initial reports suggested G72 as an activator of D-amino acid oxidase (DAO, supporting the glutamate dysfunction hypothesis of schizophrenia. However, these findings have subsequently not been reproduced and reports of endogenous human G72 mRNA and protein expression are extremely limited. In order to better understand the function of this putative schizophrenia susceptibility gene, we attempted to demonstrate G72 mRNA and protein expression in relevant human brain regions. Methods The expression of G72 mRNA was studied by northern blotting and semi-quantitative SYBR-Green and Taqman RT-PCR. Protein expression in human tissue lysates was investigated by western blotting using two custom-made specific anti-G72 peptide antibodies. An in-depth in silico analysis of the G72/G30 locus was performed in order to try and identify motifs or regulatory elements that provide insight to G72 mRNA expression and transcript stability. Results Despite using highly sensitive techniques, we failed to identify significant levels of G72 mRNA in a variety of human tissues (e.g. adult brain, amygdala, caudate nucleus, fetal brain, spinal cord and testis human cell lines or schizophrenia/control post mortem BA10 samples. Furthermore, using western blotting in combination with sensitive detection methods, we were also unable to detect G72 protein in a number of human brain regions (including cerebellum and amygdala, spinal cord or testis. A detailed in silico analysis provides several lines of evidence that support the apparent low or absent expression of G72. Conclusion Our results suggest that native G72 protein is not normally present in the tissues that we analysed

  4. Evidence of sex-bias in gene expression in the brain transcriptome of two populations of rainbow trout (Oncorhynchus mykiss) with divergent life histories.

    Science.gov (United States)

    Hale, Matthew C; McKinney, Garrett J; Thrower, Frank P; Nichols, Krista M

    2018-01-01

    Sex-bias in gene expression is a mechanism that can generate phenotypic variance between the sexes, however, relatively little is known about how patterns of sex-bias vary during development, and how variable sex-bias is between different populations. To that end, we measured sex-bias in gene expression in the brain transcriptome of rainbow trout (Oncorhynchus mykiss) during the first two years of development. Our sampling included from the fry stage through to when O. mykiss either migrate to the ocean or remain resident and undergo sexual maturation. Samples came from two F1 lines: One from migratory steelhead trout and one from resident rainbow trout. All samples were reared in a common garden environment and RNA sequencing (RNA-seq) was used to estimate patterns of gene expression. A total of 1,716 (4.6% of total) genes showed evidence of sex-bias in gene expression in at least one time point. The majority (96.7%) of sex-biased genes were differentially expressed during the second year of development, indicating that patterns of sex-bias in expression are tied to key developmental events, such as migration and sexual maturation. Mapping of differentially expressed genes to the O. mykiss genome revealed that the X chromosome is enriched for female upregulated genes, and this may indicate a lack of dosage compensation in rainbow trout. There were many more sex-biased genes in the migratory line than the resident line suggesting differences in patterns of gene expression in the brain between populations subjected to different forces of selection. Overall, our results suggest that there is considerable variation in the extent and identity of genes exhibiting sex-bias during the first two years of life. These differentially expressed genes may be connected to developmental differences between the sexes, and/or between adopting a resident or migratory life history.

  5. “Messing with the mind”: evolutionary challenges to human brain augmentation

    OpenAIRE

    Saniotis, Arthur; Henneberg, Maciej; Kumaratilake, Jaliya; Grantham, James P.

    2014-01-01

    The issue of brain augmentation has received considerable scientific attention over the last two decades. A key factor to brain augmentation that has been widely overlooked are the complex evolutionary processes which have taken place in evolving the human brain to its current state of functioning. Like other bodily organs, the human brain has been subject to the forces of biological adaptation. The structure and function of the brain, is very complex and only now we are beginning to understa...

  6. Can transcriptomics provide insight into the underlying chemopreventive mechanisms of complex mixtures of phytochemicals in humans?

    NARCIS (Netherlands)

    Breda, van S.G.; Wilms, L.C.; Gaj, S.; Briedé, J.J.; Helsper, J.P.F.G.; Kleinjans, J.C.; Kok, de T.M.

    2014-01-01

    Blueberries contain relatively large amounts of different phytochemicals which are suggested to have chemopreventive properties, but little information is available on the underlying molecular modes of action. This study investigates whole genome gene expression changes in lymphocytes of 143 humans

  7. Hierarchy of transcriptomic specialization across human cortex captured by myelin map topography

    OpenAIRE

    Murray, John; Martin, William; Bernacchia, Alberto; Anticevic, Alan; Ji, Jie; Navejar, Natasha; Eckner, William; Demirtas, Murat; Burt, Joshua

    2017-01-01

    Hierarchy provides a unifying principle for the macroscale organization of anatomical and functional properties across primate cortex, yet the microscale bases of hierarchical specialization across human cortex are poorly understood. Anatomical hierarchy is conventionally informed by invasively measured laminar patterns of long-range cortico-cortical projections, creating the need for a principled proxy measure of hierarchy in humans. Moreover, cortex exhibits a transcriptional architecture c...

  8. Transcriptome dynamics of human pluripotent stem cell-derived contracting cardiomyocytes using an embryoid body model with fetal bovine serum.

    Science.gov (United States)

    Jung, Kwang Bo; Son, Ye Seul; Lee, Hana; Jung, Cho-Rok; Kim, Janghwan; Son, Mi-Young

    2017-07-25

    Cardiomyocyte (CM) differentiation techniques for generating adult-like mature CMs remain imperfect, and the plausible underlying mechanisms remain unclear; however, there are a number of current protocols available. Here, to explore the mechanisms controlling cardiac differentiation, we analyzed the genome-wide transcription dynamics occurring during the differentiation of human pluripotent stem cells (hPSCs) into CMs using embryoid body (EB) formation. We optimized and updated the protocol to efficiently generate contracting CMs from hPSCs by adding fetal bovine serum (FBS) as a medium supplement, which could have a significant impact on the efficiency of cardiac differentiation. To identify genes, biological processes, and pathways involved in the cardiac differentiation of hPSCs, integrative and comparative analyses of the transcriptome profiles of differentiated CMs from hPSCs and of control CMs of the adult human heart (CM-AHH) were performed using gene ontology, functional annotation clustering, and pathway analyses. Several genes commonly regulated in the differentiated CMs and CM-AHH were enriched in pathways related to cell cycle and nucleotide metabolism. Strikingly, we found that current differentiation protocols did not promote sufficient expression of genes involved in oxidative phosphorylation to differentiate CMs from hPSCs compared to the expression levels in CM-AHH. Therefore, to obtain mature CMs similar to CM-AHH, these deficient pathways in CM differentiation, such as energy-related pathways, must be augmented prior to use for in vitro and in vivo applications. This approach opens up new avenues for facilitating the utilization of hPSC-derived CMs in biomedical research, drug evaluation, and clinical applications for patients with cardiac failure.

  9. Single-Cell Transcriptomics Reveals a Population of Dormant Neural Stem Cells that Become Activated upon Brain Injury.

    Science.gov (United States)

    Llorens-Bobadilla, Enric; Zhao, Sheng; Baser, Avni; Saiz-Castro, Gonzalo; Zwadlo, Klara; Martin-Villalba, Ana

    2015-09-03

    Heterogeneous pools of adult neural stem cells (NSCs) contribute to brain maintenance and regeneration after injury. The balance of NSC activation and quiescence, as well as the induction of lineage-specific transcription factors, may contribute to diversity of neuronal and glial fates. To identify molecular hallmarks governing these characteristics, we performed single-cell sequencing of an unbiased pool of adult subventricular zone NSCs. This analysis identified a discrete, dormant NSC subpopulation that already expresses distinct combinations of lineage-specific transcription factors during homeostasis. Dormant NSCs enter a primed-quiescent state before activation, which is accompanied by downregulation of glycolytic metabolism, Notch, and BMP signaling and a concomitant upregulation of lineage-specific transcription factors and protein synthesis. In response to brain ischemia, interferon gamma signaling induces dormant NSC subpopulations to enter the primed-quiescent state. This study unveils general principles underlying NSC activation and lineage priming and opens potential avenues for regenerative medicine in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Human midsagittal brain shape variation: patterns, allometry and integration

    Science.gov (United States)

    Bruner, Emiliano; Martin-Loeches, Manuel; Colom, Roberto

    2010-01-01

    Midsagittal cerebral morphology provides a homologous geometrical reference for brain shape and cortical vs. subcortical spatial relationships. In this study, midsagittal brain shape variation is investigated in a sample of 102 humans, in order to describe and quantify the major patterns of correlation between morphological features, the effect of size and sex on general anatomy, and the degree of integration between different cortical and subcortical areas. The only evident pattern of covariation was associated with fronto-parietal cortical bulging. The allometric component was weak for the cortical profile, but more robust for the posterior subcortical areas. Apparent sex differences were evidenced in size but not in brain shape. Cortical and subcortical elements displayed scarcely integrated changes, suggesting a modular separation between these two areas. However, a certain correlation was found between posterior subcortical and parietal cortical variations. These results should be directly integrated with information ranging from functional craniology to wiring organization, and with hypotheses linking brain shape and the mechanical properties of neurons during morphogenesis. PMID:20345859

  11. A new microcontroller-based human brain hypothermia system.

    Science.gov (United States)

    Kapidere, Metin; Ahiska, Raşit; Güler, Inan

    2005-10-01

    Many studies show that artificial hypothermia of brain in conditions of anesthesia with the rectal temperature lowered down to 33 degrees C produces pronounced prophylactic effect protecting the brain from anoxia. Out of the methods employed now in clinical practice for reducing the oxygen consumption by the cerebral tissue, the most efficacious is craniocerebral hypothermia (CCH). It is finding even more extensive application in cardiovascular surgery, neurosurgery, neurorenimatology and many other fields of medical practice. In this study, a microcontroller-based designed human brain hypothermia system (HBHS) is designed and constructed. The system is intended for cooling and heating the brain. HBHS consists of a thermoelectric hypothermic helmet, a control and a power unit. Helmet temperature is controlled by 8-bit PIC16F877 microcontroller which is programmed using MPLAB editor. Temperature is converted to 10-bit digital and is controlled automatically by the preset values which have been already entered in the microcontroller. Calibration is controlled and the working range is tested. Temperature of helmet is controlled between -5 and +46 degrees C by microcontroller, with the accuracy of +/-0.5 degrees C.

  12. Insulin and C-peptide in human brain neurons (insulin/C-peptide/brain peptides/immunohistochemistry/radioimmunoassay)

    International Nuclear Information System (INIS)

    Dorn, A.; Bernstein, H.G.; Rinne, A.; Hahn, H.J.; Ziegler, M.

    1983-01-01

    The regional distribution and cellular localization of insulin and C-peptide immunoreactivities were studied in human cadaver brains using the indirect immunofluorescence method, the peroxidase-antiperoxidase technique, and radioimmunoassay. Products of the immune reactions to both polypeptides were observed in most nerve cells in all areas of the brain examined. Immunostaining was mainly restricted to the cell soma and proximal dendrites. Radioimmunoassay revealed that human brain contains insulin and C-peptide in concentrations much higher than the blood, the highest being in the hypothalamus. These findings support the hypothesis that the 'brain insulin' is - at least in part - produced in the CNS. (author)

  13. A transcript finishing initiative for closing gaps in the human transcriptome

    DEFF Research Database (Denmark)

    Sogayar, Mari Cleide; Camargo, Anamaria A; Bettoni, Fabiana

    2004-01-01

    We report the results of a transcript finishing initiative, undertaken for the purpose of identifying and characterizing novel human transcripts, in which RT-PCR was used to bridge gaps between paired EST clusters, mapped against the genomic sequence. Each pair of EST clusters selected...

  14. Transcriptome profiling reveals bisphenol A alternatives activate estrogen receptor alpha in human breast cancer cells

    Science.gov (United States)

    Plasticizers with estrogenic activity, such as bisphenol A (BPA), have potential adverse health effects in humans. Due to mounting evidence of these health effects, BPA is being phased out and replaced by other bisphenol variants in “BPA-free” products. We have compared estrogeni...

  15. Simplified data access on human skeletal muscle transcriptome responses to differentiated exercise

    DEFF Research Database (Denmark)

    Vissing, Kristian; Schjerling, Peter

    2014-01-01

    Few studies have investigated exercise-induced global gene expression responses in human skeletal muscle and these have typically focused at one specific mode of exercise and not implemented non-exercise control models. However, interpretation on effects of differentiated exercise necessitate dir...

  16. Memory-related brain lateralisation in birds and humans.

    Science.gov (United States)

    Moorman, Sanne; Nicol, Alister U

    2015-03-01

    Visual imprinting in chicks and song learning in songbirds are prominent model systems for the study of the neural mechanisms of memory. In both systems, neural lateralisation has been found to be involved in memory formation. Although many processes in the human brain are lateralised--spatial memory and musical processing involves mostly right hemisphere dominance, whilst language is mostly left hemisphere dominant--it is unclear what the function of lateralisation is. It might enhance brain capacity, make processing more efficient, or prevent occurrence of conflicting signals. In both avian paradigms we find memory-related lateralisation. We will discuss avian lateralisation findings and propose that birds provide a strong model for studying neural mechanisms of memory-related lateralisation. Copyright © 2014. Published by Elsevier Ltd.

  17. Two distinct forms of functional lateralization in the human brain

    Science.gov (United States)

    Gotts, Stephen J.; Jo, Hang Joon; Wallace, Gregory L.; Saad, Ziad S.; Cox, Robert W.; Martin, Alex

    2013-01-01

    The hemispheric lateralization of certain faculties in the human brain has long been held to be beneficial for functioning. However, quantitative relationships between the degree of lateralization in particular brain regions and the level of functioning have yet to be established. Here we demonstrate that two distinct forms of functional lateralization are present in the left vs. the right cerebral hemisphere, with the left hemisphere showing a preference to interact more exclusively with itself, particularly for cortical regions involved in language and fine motor coordination. In contrast, right-hemisphere cortical regions involved in visuospatial and attentional processing interact in a more integrative fashion with both hemispheres. The degree of lateralization present in these distinct systems selectively predicted behavioral measures of verbal and visuospatial ability, providing direct evidence that lateralization is associated with enhanced cognitive ability. PMID:23959883

  18. "Brain drain, brain gain. . . Brain sustain?" : Challenges in building Portuguese human research capacity

    NARCIS (Netherlands)

    Hasanefendic, Sandra

    2017-01-01

    This paper presents a systematic but essentially descriptive account of the policy measure of stimulating human research capacity development under the policy program "Commitment to Science" in Portugal in the period 2006-2009. It explores the conditions that contributed to the development of the

  19. [Isolation and identification of brain tumor stem cells from human brain neuroepithelial tumors].

    Science.gov (United States)

    Fang, Jia-sheng; Deng, Yong-wen; Li, Ming-chu; Chen, Feng-Hua; Wang, Yan-jin; Lu, Ming; Fang, Fang; Wu, Jun; Yang, Zhuan-yi; Zhou, Xang-yang; Wang, Fei; Chen, Cheng

    2007-01-30

    To establish a simplified culture system for the isolation of brain tumor stem cells (BTSCs) from the tumors of human neuroepithelial tissue, to observe the growth and differentiation pattern of BTSCs, and to investigate their expression of the specific markers. Twenty-six patients with brain neuroepithelial tumors underwent tumor resection. Two pieces of tumor tissues were taken from each tumor to be dissociated, triturated into single cells in sterile DMEM-F12 medium, and then filtered. The tumor cells were seeded at a concentration of 200,000 viable cells per mL into serum-free DMEM-F12 medium simply supplemented with B27, human basic fibroblast growth factor (20 microg/L), human epidermal growth factor (20 microg /L), insulin (4 U/L), L-glutamine, penicillin and streptomycin. After the primary brain tumor spheres (BTSs) were generated, they were triturated again and passed in fresh medium. Limiting dilution assay was performed to observe the monoclone formation. 5-bromodeoxyuridine (BrdU) incorporation test was performed to observe the proliferation of the BTS. The BTSCs were cultured in mitogen-free DMEM-F12 medium supplemented with 10% fetal bovine serum to observe their differentiation. Immunocytochemistry was used to examine the expression of CD133 and nestin, specific markers of BTSC, and the rate of CD133 positive cells. Only a minority of subsets of cells from the tumors of neuroepithelial tissue had the capacity to survive, proliferate, and generate free-floating neurosphere-like BTSs in the simplified serum-free medium. These cells attached to the poly-L-lysine coated coverslips in the serum-supplemented medium and differentiated. The BTSCs were CD133 and nestin positive. The rate of CD133 positive cells in the tumor specimens was (21 +/- 6.2)% - (38 +/- 7.0)%. A new simplified culture system for the isolation of BTSCs is established. The tumors of human neuroepithelial tissue contain CD133 and nestin positive tumor stem cells which can be isolated

  20. Social Rewards and Social Networks in the Human Brain.

    Science.gov (United States)

    Fareri, Dominic S; Delgado, Mauricio R

    2014-08-01

    The rapid development of social media and social networking sites in human society within the past decade has brought about an increased focus on the value of social relationships and being connected with others. Research suggests that we pursue socially valued or rewarding outcomes-approval, acceptance, reciprocity-as a means toward learning about others and fulfilling social needs of forming meaningful relationships. Focusing largely on recent advances in the human neuroimaging literature, we review findings highlighting the neural circuitry and processes that underlie pursuit of valued rewarding outcomes across non-social and social domains. We additionally discuss emerging human neuroimaging evidence supporting the idea that social rewards provide a gateway to establishing relationships and forming social networks. Characterizing the link between social network, brain, and behavior can potentially identify contributing factors to maladaptive influences on decision making within social situations. © The Author(s) 2014.

  1. Infection and upregulation of proinflammatory cytokines in human brain vascular pericytes by human cytomegalovirus

    Directory of Open Access Journals (Sweden)

    Alcendor Donald J

    2012-05-01

    Full Text Available Abstract Background Congenital human cytomegalovirus (HCMV infections can result in CNS abnormalities in newborn babies including vision loss, mental retardation, motor deficits, seizures, and hearing loss. Brain pericytes play an essential role in the development and function of the blood–brain barrier yet their unique role in HCMV dissemination and neuropathlogy has not been reported. Methods Primary human brain vascular pericytes were exposed to a primary clinical isolate of HCMV designated ‘SBCMV’. Infectivity was analyzed by microscopy, immunofluorescence, Western blot, and qRT-PCR. Microarrays were performed to identify proinflammatory cytokines upregulated after SBCMV exposure, and the results validated by real-time quantitative polymerase chain reaction (qPCR methodology. In situ cytokine expression of pericytes after exposure to HCMV was examined by ELISA and in vivo evidence of HCMV infection of brain pericytes was shown by dual-labeled immunohistochemistry. Results HCMV-infected human brain vascular pericytes as evidenced by several markers. Using a clinical isolate of HCMV (SBCMV, microscopy of infected pericytes showed virion production and typical cytomegalic cytopathology. This finding was confirmed by the expression of major immediate early and late virion proteins and by the presence of HCMV mRNA. Brain pericytes were fully permissive for CMV lytic replication after 72 to 96 hours in culture compared to human astrocytes or human brain microvascular endothelial cells (BMVEC. However, temporal transcriptional expression of pp65 virion protein after SBCMV infection was lower than that seen with the HCMV Towne laboratory strain. Using RT-PCR and dual-labeled immunofluorescence, proinflammatory cytokines CXCL8/IL-8, CXCL11/ITAC, and CCL5/Rantes were upregulated in SBCMV-infected cells, as were tumor necrosis factor-alpha (TNF-alpha, interleukin-1 beta (IL-1beta, and interleukin-6 (IL-6. Pericytes exposed to SBCMV elicited

  2. Transcriptomic and epigenetic responses to short-term nutrient-exercise stress in humans

    DEFF Research Database (Denmark)

    Laker, R C; Garde, C; Camera, D M

    2017-01-01

    of high fat feeding, we investigated the transcriptional and epigenetic response of human skeletal muscle to 9 days of a high-fat diet (HFD) alone (Sed-HFD) or in combination with resistance exercise (Ex-HFD), using genome-wide profiling of gene expression and DNA methylation. HFD markedly induced...... association between DNA methylation and gene expression changes were PYGM, which was epigenetically regulated in both groups, and ANGPTL4, which was regulated only following Ex. In conclusion, while short-term Ex did not prevent a HFD-induced inflammatory response, it provoked a genomic response that may...... protect skeletal muscle from atrophy. These epigenetic adaptations provide mechanistic insight into the gene-specific regulation of inflammatory and metabolic processes in human skeletal muscle....

  3. Brain transcriptomes of honey bees (Apis mellifera experimentally infected by two pathogens: Black queen cell virus and Nosema ceranae

    Directory of Open Access Journals (Sweden)

    Vincent Doublet

    2016-12-01

    Full Text Available Regulation of gene expression in the brain plays an important role in behavioral plasticity and decision making in response to external stimuli. However, both can be severely affected by environmental factors, such as parasites and pathogens. In honey bees, the emergence and re-emergence of pathogens and potential for pathogen co-infection and interaction have been suggested as major components that significantly impaired social behavior and survival. To understand how the honey bee is affected and responds to interacting pathogens, we co-infected workers with two prevalent pathogens of different nature, the positive single strand RNA virus Black queen cell virus (BQCV, and the Microsporidia Nosema ceranae, and explored gene expression changes in brains upon single infections and co-infections. Our data provide an important resource for research on honey bee diseases, and more generally on insect host-pathogen and pathogen-pathogen interactions. Raw and processed data are publicly available in the NCBI/GEO database: (http://www.ncbi.nlm.nih.gov/geo/ under accession number GSE81664.

  4. Transcriptome analysis of exosome-compromised human cells using high-density tiling arrays

    DEFF Research Database (Denmark)

    Jensen, Torben Heick

    The extent of RNA degradation in the nucleus has traditionally been underestimated. However, all major RNA species are synthesized, processed and can be degraded in this compartment and consequently an enormous amount of nucleosides are turned over and recycled. The RNA exosome, a multisubunit co......) tiling array that covers discrete regions from different chromosomes to represent a range of gene content and exonic/nonexonic conservation grades of the human genome....

  5. Landscape and variation of RNA secondary structure across the human transcriptome.

    OpenAIRE

    Wan, Y; Qu, K; Zhang, QC; Flynn, RA; Manor, O; Ouyang, Z; Zhang, J; Spitale, RC; Snyder, MP; Segal, E; Chang, HY

    2014-01-01

    In parallel to the genetic code for protein synthesis, a second layer of information is embedded in all RNA transcripts in the form of RNA structure. RNA structure influences practically every step in the gene expression program. However, the nature of most RNA structures or effects of sequence variation on structure are not known. Here we report the initial landscape and variation of RNA secondary structures (RSSs) in a human family trio (mother, father and their child). This provides a comp...

  6. The Dynamic Genome and Transcriptome of the Human Fungal Pathogen Blastomyces and Close Relative Emmonsia

    OpenAIRE

    Muñoz, José F.; Gauthier, Gregory M.; Desjardins, Christopher A.; Gallo, Juan E.; Holder, Jason; Sullivan, Thomas D.; Marty, Amber J.; Carmen, John C.; Chen, Zehua; Ding, Li; Gujja, Sharvari; Magrini, Vincent; Misas, Elizabeth; Mitreva, Makedonka; Priest, Margaret

    2015-01-01

    Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis and paracoccidioidomycosis. Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis, Blastomyces, and two species of the related genus Emmonsia, typically pathogens of small mammals. Compared to related species, Blastomyces genomes are highly expanded, with long, often sharply demarcated...

  7. Transcriptome association analysis identifies miR-375 as a major determinant of variable acetaminophen glucuronidation by human liver.

    Science.gov (United States)

    Papageorgiou, Ioannis; Freytsis, Marina; Court, Michael H

    2016-10-01

    Acetaminophen is the leading cause of acute liver failure (ALF) in many countries including the United States. Hepatic glucuronidation by UDP-glucuronosyltransferase (UGT) 1A subfamily enzymes is the major route of acetaminophen elimination. Reduced glucuronidation may predispose some individuals to acetaminophen-induced ALF, but mechanisms underlying reduced glucuronidation are poorly understood. We hypothesized that specific microRNAs (miRNAs) may reduce UGT1A activity by direct effects on the UGT1A 3'-UTR shared by all UGT1A enzyme transcripts, or by indirect effects on transcription factors regulating UGT1A expression. We performed an unbiased miRNA whole transcriptome association analysis using a bank of human livers with known acetaminophen glucuronidation activities. Of 754 miRNAs evaluated, 9 miRNAs were identified that were significantly overexpressed (p2-fold) in livers with low acetaminophen glucuronidation activities compared with those with high activities. miR-375 showed the highest difference (>10-fold), and was chosen for further mechanistic validation. We demonstrated using in silico analysis and luciferase reporter assays that miR-375 has a unique functional binding site in the 3'-UTR of the aryl hydrocarbon receptor (AhR) gene. Furthermore overexpression of miR-375 in LS180 cells demonstrated significant repression of endogenous AhR protein (by 40%) and mRNA (by 10%), as well as enzyme activity and/or mRNA of AhR regulated enzymes including UGT1A1, UGT1A6, and CYP1A2, without affecting UGT2B7, which is not regulated by AhR. Thus miR-375 is identified as a novel repressor of UGT1A-mediated hepatic acetaminophen glucuronidation through reduced AhR expression, which could predispose some individuals to increased risk for acetaminophen-induced ALF. Published by Elsevier Inc.

  8. Why our brains cherish humanity: Mirror neurons and colamus humanitatem

    Directory of Open Access Journals (Sweden)

    John R. Skoyles

    2008-06-01

    Full Text Available Commonsense says we are isolated. After all, our bodies are physically separate. But Seneca’s colamus humanitatem, and John Donne’s observation that “no man is an island” suggests we are neither entirely isolated nor separate. A recent discovery in neuroscience—that of mirror neurons—argues that the brain and the mind is neither built nor functions remote from what happens in other individuals. What are mirror neurons? They are brain cells that process both what happens to or is done by an individual, and, as it were, its perceived “refl ection,” when that same thing happens or is done by another individual. Thus, mirror neurons are both activated when an individual does a particular action, and when that individual perceives that same action done by another. The discovery of mirror neurons suggests we need to radically revise our notions of human nature since they offer a means by which we may not be so separated as we think. Humans unlike other apes are adapted to mirror interact nonverbally when together. Notably, our faces have been evolved to display agile and nimble movements. While this is usually explained as enabling nonverbal communication, a better description would be nonverbal commune based upon mirror neurons. I argue we cherish humanity, colamus humanitatem, because mirror neurons and our adapted mirror interpersonal interface blur the physical boundaries that separate us.

  9. Transcriptome analysis of Neisseria meningitidis in human whole blood and mutagenesis studies identify virulence factors involved in blood survival.

    Directory of Open Access Journals (Sweden)

    Hebert Echenique-Rivera

    2011-05-01

    Full Text Available During infection Neisseria meningitidis (Nm encounters multiple environments within the host, which makes rapid adaptation a crucial factor for meningococcal survival. Despite the importance of invasion into the bloodstream in the meningococcal disease process, little is known about how Nm adapts to permit survival and growth in blood. To address this, we performed a time-course transcriptome analysis using an ex vivo model of human whole blood infection. We observed that Nm alters the expression of ≈30% of ORFs of the genome and major dynamic changes were observed in the expression of transcriptional regulators, transport and binding proteins, energy metabolism, and surface-exposed virulence factors. In particular, we found that the gene encoding the regulator Fur, as well as all genes encoding iron uptake systems, were significantly up-regulated. Analysis of regulated genes encoding for surface-exposed proteins involved in Nm pathogenesis allowed us to better understand mechanisms used to circumvent host defenses. During blood infection, Nm activates genes encoding for the factor H binding proteins, fHbp and NspA, genes encoding for detoxifying enzymes such as SodC, Kat and AniA, as well as several less characterized surface-exposed proteins that might have a role in blood survival. Through mutagenesis studies of a subset of up-regulated genes we were able to identify new proteins important for survival in human blood and also to identify additional roles of previously known virulence factors in aiding survival in blood. Nm mutant strains lacking the genes encoding the hypothetical protein NMB1483 and the surface-exposed proteins NalP, Mip and NspA, the Fur regulator, the transferrin binding protein TbpB, and the L-lactate permease LctP were sensitive to killing by human blood. This increased knowledge of how Nm responds to adaptation in blood could also be helpful to develop diagnostic and therapeutic strategies to control the devastating

  10. Imaging neuroreceptors in the human brain in health and disease

    International Nuclear Information System (INIS)

    Wagner, H.N. Jr.; Dannals, R.F.; Frost, J.J.

    1985-01-01

    For nearly a century it has been known that chemical activity accompanies mental activity, but only recently has it been possible to begin to examine its exact nature. Positron-emitting radioactive tracers have made it possible to study the chemistry of the human brain in health and disease, using chiefly cyclotron-produced radionuclides, carbon-11, fluorine-18 and oxygen-15. It is now well established that measurable increases in regional cerebral blood flow, and glucose and oxygen metabolism accompany the mental functions of perception, cognition, emotion and motion. On 25 May 1983 the first imaging of a neuroreceptor in the human brain was accomplished with carbon-11 N-methyl spiperone, a ligand that binds preferentially to dopamine-2 receptors, 80% of which are located in the caudate nucleus and putamen. Quantitative imaging of serotonin-2, opiate, benzodiazapine and muscarinic cholinergic receptors has subsequently been accomplished. In studies of normal men and women, it has been found that dopamine and serotonin receptor activity decreases dramatically with age, such a decrease being more pronounced in men than in women and greater in the case of dopamine-2 receptors than in serotonin-2 receptors. Preliminary studies of patients with neuropsychiatric disorders suggest that dopamine-2 receptor activity is diminished in the caudate nucleus of patients with Huntington's disease. Positron tomography permits a quantitative assay of picomolar quantities of neuroreceptors within the living human brain. Studies of patients with Parkinson's disease, Alzheimer's disease, depression, anxiety, schizophrenia, acute and chronic pain states and drug addiction are now in progress. (author)

  11. Brain cDNA clone for human cholinesterase

    International Nuclear Information System (INIS)

    McTiernan, C.; Adkins, S.; Chatonnet, A.; Vaughan, T.A.; Bartels, C.F.; Kott, M.; Rosenberry, T.L.; La Du, B.N.; Lockridge, O.

    1987-01-01

    A cDNA library from human basal ganglia was screened with oligonucleotide probes corresponding to portions of the amino acid sequence of human serum cholinesterase. Five overlapping clones, representing 2.4 kilobases, were isolated. The sequenced cDNA contained 207 base pairs of coding sequence 5' to the amino terminus of the mature protein in which there were four ATG translation start sites in the same reading frame as the protein. Only the ATG coding for Met-(-28) lay within a favorable consensus sequence for functional initiators. There were 1722 base pairs of coding sequence corresponding to the protein found circulating in human serum. The amino acid sequence deduced from the cDNA exactly matched the 574 amino acid sequence of human serum cholinesterase, as previously determined by Edman degradation. Therefore, our clones represented cholinesterase rather than acetylcholinesterase. It was concluded that the amino acid sequences of cholinesterase from two different tissues, human brain and human serum, were identical. Hybridization of genomic DNA blots suggested that a single gene, or very few genes coded for cholinesterase

  12. Co-Transcriptomes of Initial Interactions In Vitro between Streptococcus Pneumoniae and Human Pleural Mesothelial Cells.

    Directory of Open Access Journals (Sweden)

    Claire J Heath

    Full Text Available Streptococcus pneumoniae (Spn is a major causative organism of empyema, an inflammatory condition occurring in the pleural sac. In this study, we used human and Spn cDNA microarrays to characterize the transcriptional responses occurring during initial contact between Spn and a human pleural mesothelial cell line (PMC in vitro. Using stringent filtering criteria, 42 and 23 Spn genes were up-and down-regulated respectively. In particular, genes encoding factors potentially involved in metabolic processes and Spn adherence to eukaryotic cells were up-regulated e.g. glnQ, glnA, aliA, psaB, lytB and nox. After Spn initial contact, 870 human genes were differentially regulated and the largest numbers of significant gene expression changes were found in canonical pathways for eukaryotic initiation factor 2 signaling (60 genes out of 171, oxidative phosphorylation (32/103, mitochondrial dysfunction (37/164, eIF4 and p70S6K signaling (28/142, mTOR signaling (27/182, NRF2-mediated oxidative stress response (20/177, epithelial adherens junction remodeling (11/66 and ubiquitination (22/254. The cellular response appeared to be directed towards host cell survival and defense. Spn did not activate NF-kB or phosphorylate p38 MAPK or induce cytokine production from PMC. Moreover, Spn infection of TNF-α pre-stimulated PMC inhibited production of IL-6 and IL-8 secretion by >50% (p<0.01. In summary, this descriptive study provides datasets and a platform for examining further the molecular mechanisms underlying the pathogenesis of empyema.

  13. The Lifespan and Turnover of Microglia in the Human Brain

    Directory of Open Access Journals (Sweden)

    Pedro Réu

    2017-07-01

    Full Text Available The hematopoietic system seeds the CNS with microglial progenitor cells during the fetal period, but the subsequent cell generation dynamics and maintenance of this population have been poorly understood. We report that microglia, unlike most other hematopoietic lineages, renew slowly at a median rate of 28% per year, and some microglia last for more than two decades. Furthermore, we find no evidence for the existence of a substantial population of quiescent long-lived cells, meaning that the microglia population in the human brain is sustained by continuous slow turnover throughout adult life.

  14. Landscape and variation of RNA secondary structure across the human transcriptome.

    Science.gov (United States)

    Wan, Yue; Qu, Kun; Zhang, Qiangfeng Cliff; Flynn, Ryan A; Manor, Ohad; Ouyang, Zhengqing; Zhang, Jiajing; Spitale, Robert C; Snyder, Michael P; Segal, Eran; Chang, Howard Y

    2014-01-30

    In parallel to the genetic code for protein synthesis, a second layer of information is embedded in all RNA transcripts in the form of RNA structure. RNA structure influences practically every step in the gene expression program. However, the nature of most RNA structures or effects of sequence variation on structure are not known. Here we report the initial landscape and variation of RNA secondary structures (RSSs) in a human family trio (mother, father and their child). This provides a comprehensive RSS map of human coding and non-coding RNAs. We identify unique RSS signatures that demarcate open reading frames and splicing junctions, and define authentic microRNA-binding sites. Comparison of native deproteinized RNA isolated from cells versus refolded purified RNA suggests that the majority of the RSS information is encoded within RNA sequence. Over 1,900 transcribed single nucleotide variants (approximately 15% of all transcribed single nucleotide variants) alter local RNA structure. We discover simple sequence and spacing rules that determine the ability of point mutations to impact RSSs. Selective depletion of 'riboSNitches' versus structurally synonymous variants at precise locations suggests selection for specific RNA shapes at thousands of sites, including 3' untranslated regions, binding sites of microRNAs and RNA-binding proteins genome-wide. These results highlight the potentially broad contribution of RNA structure and its variation to gene regulation.

  15. Accelerated evolution of the ASPM gene controlling brain size begins prior to human brain expansion.

    Directory of Open Access Journals (Sweden)

    Natalay Kouprina

    2004-05-01

    Full Text Available Primary microcephaly (MCPH is a neurodevelopmental disorder characterized by global reduction in cerebral cortical volume. The microcephalic brain has a volume comparable to that of early hominids, raising the possibility that some MCPH genes may have been evolutionary targets in the expansion of the cerebral cortex in mammals and especially primates. Mutations in ASPM, which encodes the human homologue of a fly protein essential for spindle function, are the most common known cause of MCPH. Here we have isolated large genomic clones containing the complete ASPM gene, including promoter regions and introns, from chimpanzee, gorilla, orangutan, and rhesus macaque by transformation-associated recombination cloning in yeast. We have sequenced these clones and show that whereas much of the sequence of ASPM is substantially conserved among primates, specific segments are subject to high Ka/Ks ratios (nonsynonymous/synonymous DNA changes consistent with strong positive selection for evolutionary change. The ASPM gene sequence shows accelerated evolution in the African hominoid clade, and this precedes hominid brain expansion by several million years. Gorilla and human lineages show particularly accelerated evolution in the IQ domain of ASPM. Moreover, ASPM regions under positive selection in primates are also the most highly diverged regions between primates and nonprimate mammals. We report the first direct application of TAR cloning technology to the study of human evolution. Our data suggest that evolutionary selection of specific segments of the ASPM sequence strongly relates to differences in cerebral cortical size.

  16. High resolution analysis of the human transcriptome: detection of extensive alternative splicing independent of transcriptional activity

    Directory of Open Access Journals (Sweden)

    Rouet Fabien

    2009-10-01

    Full Text Available Abstract Background Commercially available microarrays have been used in many settings to generate expression profiles for a variety of applications, including target selection for disease detection, classification, profiling for pharmacogenomic response to therapeutics, and potential disease staging. However, many commercially available microarray platforms fail to capture transcript diversity produced by alternative splicing, a major mechanism for driving proteomic diversity through transcript heterogeneity. Results The human Genome-Wide SpliceArray™ (GWSA, a novel microarray platform, utilizes an existing probe design concept to monitor such transcript diversity on a genome scale. The human GWSA allows the detection of alternatively spliced events within the human genome through the use of exon body and exon junction probes to provide a direct measure of each transcript, through simple calculations derived from expression data. This report focuses on the performance and validation of the array when measured against standards recently published by the Microarray Quality Control (MAQC Project. The array was shown to be highly quantitative, and displayed greater than 85% correlation with the HG-U133 Plus 2.0 array at the gene level while providing more extensive coverage of each gene. Almost 60% of splice events among genes demonstrating differential expression of greater than 3 fold also contained extensive splicing alterations. Importantly, almost 10% of splice events within the gene set displaying constant overall expression values had evidence of transcript diversity. Two examples illustrate the types of events identified: LIM domain 7 showed no differential expression at the gene level, but demonstrated deregulation of an exon skip event, while erythrocyte membrane protein band 4.1 -like 3 was differentially expressed and also displayed deregulation of a skipped exon isoform. Conclusion Significant changes were detected independent of

  17. Unmasking Language Lateralization in Human Brain Intrinsic Activity

    Science.gov (United States)

    McAvoy, Mark; Mitra, Anish; Coalson, Rebecca S.; d'Avossa, Giovanni; Keidel, James L.; Petersen, Steven E.; Raichle, Marcus E.

    2016-01-01

    Lateralization of function is a fundamental feature of the human brain as exemplified by the left hemisphere dominance of language. Despite the prominence of lateralization in the lesion, split-brain and task-based fMRI literature, surprisingly little asymmetry has been revealed in the increasingly popular functional imaging studies of spontaneous fluctuations in the fMRI BOLD signal (so-called resting-state fMRI). Here, we show the global signal, an often discarded component of the BOLD signal in resting-state studies, reveals a leftward asymmetry that maps onto regions preferential for semantic processing in left frontal and temporal cortex and the right cerebellum and a rightward asymmetry that maps onto putative attention-related regions in right frontal, temporoparietal, and parietal cortex. Hemispheric asymmetries in the global signal resulted from amplitude modulation of the spontaneous fluctuations. To confirm these findings obtained from normal, healthy, right-handed subjects in the resting-state, we had them perform 2 semantic processing tasks: synonym and numerical magnitude judgment and sentence comprehension. In addition to establishing a new technique for studying lateralization through functional imaging of the resting-state, our findings shed new light on the physiology of the global brain signal. PMID:25636911

  18. The structure of creative cognition in the human brain

    Directory of Open Access Journals (Sweden)

    Rex Eugene Jung

    2013-07-01

    Full Text Available Creativity is a vast construct, seemingly intractable to scientific inquiry – perhaps due to the vague concepts applied to the field of research. One attempt to limit the purview of creative cognition formulates the construct in terms of evolutionary constraints, namely that of blind variation and selective retention (BVSR. Behaviorally, one can limit the blind variation component to idea generation tests as manifested by measures of divergent thinking. The selective retention component can be represented by measures of convergent thinking, as represented by measures of remote associates. We summarize results from measures of creative cognition, correlated with structural neuroimaging measures including structural magnetic resonance imaging (sMRI, Diffusion Tensor Imaging (DTI, and proton magnetic resonance imaging (1H-MRS. We also review lesion studies, considered to be the gold standard of brain-behavioral studies. What emerges is a picture consistent with theories of disinhibitory brain features subserving creative cognition, as described previously (Martindale, 1981. We provide a perspective, involving aspects of the default mode network, which might provide a first approximation regarding how creative cognition might map on to the human brain.

  19. Mobile phone types and SAR characteristics of the human brain

    Science.gov (United States)

    Lee, Ae-Kyoung; Hong, Seon-Eui; Kwon, Jong-Hwa; Choi, Hyung-Do; Cardis, Elisabeth

    2017-04-01

    Mobile phones differ in terms of their operating frequency, outer shape, and form and location of the antennae, all of which affect the spatial distributions of their electromagnetic field and the level of electromagnetic absorption in the human head or brain. For this paper, the specific absorption rate (SAR) was calculated for four anatomical head models at different ages using 11 numerical phone models of different shapes and antenna configurations. The 11 models represent phone types accounting for around 86% of the approximately 1400 commercial phone models released into the Korean market since 2002. Seven of the phone models selected have an internal dual-band antenna, and the remaining four possess an external antenna. Each model was intended to generate an average absorption level equivalent to that of the same type of commercial phone model operating at the maximum available output power. The 1 g peak spatial SAR and ipsilateral and contralateral brain-averaged SARs were reported for all 11 phone models. The effects of the phone type, phone position, operating frequency, and age of head models on the brain SAR were comprehensively determined.

  20. Exceptional evolutionary divergence of human muscle and brain metabolomes parallels human cognitive and physical uniqueness

    DEFF Research Database (Denmark)

    Bozek, Katarzyna; Wei, Yuning; Yan, Zheng

    2014-01-01

    Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees,...

  1. Telomere length modulation in human astroglial brain tumors.

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    Domenico La Torre

    Full Text Available BACKGROUND: Telomeres alteration during carcinogenesis and tumor progression has been described in several cancer types. Telomeres length is stabilized by telomerase (h-TERT and controlled by several proteins that protect telomere integrity, such as the Telomere Repeat-binding Factor (TRF 1 and 2 and the tankyrase-poli-ADP-ribose polymerase (TANKs-PARP complex. OBJECTIVE: To investigate telomere dysfunction in astroglial brain tumors we analyzed telomeres length, telomerase activity and the expression of a panel of genes controlling the length and structure of telomeres in tissue samples obtained in vivo from astroglial brain tumors with different grade of malignancy. MATERIALS AND METHODS: Eight Low Grade Astrocytomas (LGA, 11 Anaplastic Astrocytomas (AA and 11 Glioblastoma Multiforme (GBM samples were analyzed. Three samples of normal brain tissue (NBT were used as controls. Telomeres length was assessed through Southern Blotting. Telomerase activity was evaluated by a telomere repeat amplification protocol (TRAP assay. The expression levels of TRF1, TRF2, h-TERT and TANKs-PARP complex were determined through Immunoblotting and RT-PCR. RESULTS: LGA were featured by an up-regulation of TRF1 and 2 and by shorter telomeres. Conversely, AA and GBM were featured by a down-regulation of TRF1 and 2 and an up-regulation of both telomerase and TANKs-PARP complex. CONCLUSIONS: In human astroglial brain tumours, up-regulation of TRF1 and TRF2 occurs in the early stages of carcinogenesis determining telomeres shortening and genomic instability. In a later stage, up-regulation of PARP-TANKs and telomerase activation may occur together with an ADP-ribosylation of TRF1, causing a reduced ability to bind telomeric DNA, telomeres elongation and tumor malignant progression.

  2. The brain's silent messenger: using selective attention to decode human thought for brain-based communication.

    Science.gov (United States)

    Naci, Lorina; Cusack, Rhodri; Jia, Vivian Z; Owen, Adrian M

    2013-05-29

    The interpretation of human thought from brain activity, without recourse to speech or action, is one of the most provoking and challenging frontiers of modern neuroscience. In particular, patients who are fully conscious and awake, yet, due to brain damage, are unable to show any behavioral responsivity, expose the limits of the neuromuscular system and the necessity for alternate forms of communication. Although it is well established that selective attention can significantly enhance the neural representation of attended sounds, it remains, thus far, untested as a response modality for brain-based communication. We asked whether its effect could be reliably used to decode answers to binary (yes/no) questions. Fifteen healthy volunteers answered questions (e.g., "Do you have brothers or sisters?") in the fMRI scanner, by selectively attending to the appropriate word ("yes" or "no"). Ninety percent of the answers were decoded correctly based on activity changes within the attention network. The majority of volunteers conveyed their answers with less than 3 min of scanning, suggesting that this technique is suited for communication in a reasonable amount of time. Formal comparison with the current best-established fMRI technique for binary communication revealed improved individual success rates and scanning times required to detect responses. This novel fMRI technique is intuitive, easy to use in untrained participants, and reliably robust within brief scanning times. Possible applications include communication with behaviorally nonresponsive patients.

  3. A microRNA activity map of human mesenchymal tumors: connections to oncogenic pathways; an integrative transcriptomic study

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    Fountzilas Elena

    2012-07-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are nucleic acid regulators of many human mRNAs, and are associated with many tumorigenic processes. miRNA expression levels have been used in profiling studies, but some evidence suggests that expression levels do not fully capture miRNA regulatory activity. In this study we integrate multiple gene expression datasets to determine miRNA activity patterns associated with cancer phenotypes and oncogenic pathways in mesenchymal tumors – a very heterogeneous class of malignancies. Results Using a computational method, we identified differentially activated miRNAs between 77 normal tissue specimens and 135 sarcomas and we validated many of these findings with microarray interrogation of an independent, paraffin-based cohort of 18 tumors. We also showed that miRNA activity is imperfectly correlated with miRNA expression levels. Using next-generation miRNA sequencing we identified potential base sequence alterations which may explain differential activity. We then analyzed miRNA activity changes related to the RAS-pathway and found 21 miRNAs that switch from silenced to activated status in parallel with RAS activation. Importantly, nearly half of these 21 miRNAs were predicted to regulate integral parts of the miRNA processing machinery, and our gene expression analysis revealed significant reductions of these transcripts in RAS-active tumors. These results suggest an association between RAS signaling and miRNA processing in which miRNAs may attenuate their own biogenesis. Conclusions Our study represents the first gene expression-based investigation of miRNA regulatory activity in human sarcomas, and our findings indicate that miRNA activity patterns derived from integrated transcriptomic data are reproducible and biologically informative in cancer. We identified an association between RAS signaling and miRNA processing, and demonstrated sequence alterations as plausible causes for differential miRNA activity

  4. Selectively altering belief formation in the human brain

    Science.gov (United States)

    Sharot, Tali; Kanai, Ryota; Marston, David; Korn, Christoph W.; Rees, Geraint; Dolan, Raymond J.

    2012-01-01

    Humans form beliefs asymmetrically; we tend to discount bad news but embrace good news. This reduced impact of unfavorable information on belief updating may have important societal implications, including the generation of financial market bubbles, ill preparedness in the face of natural disasters, and overly aggressive medical decisions. Here, we selectively improved people’s tendency to incorporate bad news into their beliefs by disrupting the function of the left (but not right) inferior frontal gyrus using transcranial magnetic stimulation, thereby eliminating the engrained “good news/bad news effect.” Our results provide an instance of how selective disruption of regional human brain function paradoxically enhances the ability to incorporate unfavorable information into beliefs of vulnerability. PMID:23011798

  5. Comparative and Experimental Studies on the Genes Altered by Chronic Hypoxia in Human Brain Microendothelial Cells

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    Eugenia Mata-Greenwood

    2017-05-01

    Full Text Available Background : Hypoxia inducible factor 1 alpha (HIF1A is a master regulator of acute hypoxia; however, with chronic hypoxia, HIF1A levels return to the normoxic levels. Importantly, the genes that are involved in the cell survival and viability under chronic hypoxia are not known. Therefore, we tested the hypothesis that chronic hypoxia leads to the upregulation of a core group of genes with associated changes in the promoter DNA methylation that mediates the cell survival under hypoxia.Results : We examined the effect of chronic hypoxia (3 days; 0.5% oxygen on human brain micro endothelial cells (HBMEC viability and apoptosis. Hypoxia caused a significant reduction in cell viability and an increase in apoptosis. Next, we examined chronic hypoxia associated changes in transcriptome and genome-wide promoter methylation. The data obtained was compared with 16 other microarray studies on chronic hypoxia. Nine genes were altered in response to chronic hypoxia in all 17 studies. Interestingly, HIF1A was not altered with chronic hypoxia in any of the studies. Furthermore, we compared our data to three other studies that identified HIF-responsive genes by various approaches. Only two genes were found to be HIF dependent. We silenced each of these 9 genes using CRISPR/Cas9 system. Downregulation of EGLN3 significantly increased the cell death under chronic hypoxia, whereas downregulation of ERO1L, ENO2, adrenomedullin, and spag4 reduced the cell death under hypoxia.Conclusions : We provide a core group of genes that regulates cellular acclimatization under chronic hypoxic stress, and most of them are HIF independent.

  6. The gene expression profile of non-cultured, highly purified human adipose tissue pericytes: Transcriptomic evidence that pericytes are stem cells in human adipose tissue

    Energy Technology Data Exchange (ETDEWEB)

    Silva Meirelles, Lindolfo da, E-mail: lindolfomeirelles@gmail.com [Center for Cell-Based Therapy (CEPID/FAPESP), Regional Center for Hemotherapy of Ribeirão Preto, University of São Paulo, Rua Tenente Catão Roxo 2501, 14051-140 Ribeirão Preto, SP (Brazil); Laboratory for Stem Cells and Tissue Engineering, PPGBioSaúde, Lutheran University of Brazil, Av. Farroupilha 8001, 92425-900 Canoas, RS (Brazil); Deus Wagatsuma, Virgínia Mara de; Malta, Tathiane Maistro; Bonini Palma, Patrícia Viana [Center for Cell-Based Therapy (CEPID/FAPESP), Regional Center for Hemotherapy of Ribeirão Preto, University of São Paulo, Rua Tenente Catão Roxo 2501, 14051-140 Ribeirão Preto, SP (Brazil); Araújo, Amélia Goes; Panepucci, Rodrigo Alexandre [Laboratory of Large-Scale Functional Biology (LLSFBio), Regional Center for Hemotherapy of Ribeirão Preto, University of São Paulo, Rua Tenente Catão Roxo 2501, 14051-140 Ribeirão Preto, SP (Brazil); and others

    2016-12-10

    Pericytes (PCs) are a subset of perivascular cells that can give rise to mesenchymal stromal cells (MSCs) when culture-expanded, and are postulated to give rise to MSC-like cells during tissue repair in vivo. PCs have been suggested to behave as stem cells (SCs) in situ in animal models, although evidence for this role in humans is lacking. Here, we analyzed the transcriptomes of highly purified, non-cultured adipose tissue (AT)-derived PCs (ATPCs) to detect gene expression changes that occur as they acquire MSC characteristics in vitro, and evaluated the hypothesis that human ATPCs exhibit a gene expression profile compatible with an AT SC phenotype. The results showed ATPCs are non-proliferative and express genes characteristic not only of PCs, but also of AT stem/progenitor cells. Additional analyses defined a gene expression signature for ATPCs, and revealed putative novel ATPC markers. Almost all AT stem/progenitor cell genes differentially expressed by ATPCs were not expressed by ATMSCs or culture-expanded ATPCs. Genes expressed by ATMSCs but not by ATPCs were also identified. These findings strengthen the hypothesis that PCs are SCs in vascularized tissues, highlight gene expression changes they undergo as they assume an MSC phenotype, and provide new insights into PC biology. - Highlights: • Non-cultured adipose tissue-derived human pericytes (ncATPCs) exhibit a distinctive gene expression signature. • ncATPCs express key adipose tissue stem cell genes previously described in vivo in mice. • ncATPCs express message for anti-proliferative and antiangiogenic molecules. • Most ncATPC-specific transcripts are absent in culture-expanded pericytes or ATMSCs • Gene expression changes ncATPCs undergo as they acquire a cultured ATMSC phenotype are pointed out.

  7. The gene expression profile of non-cultured, highly purified human adipose tissue pericytes: Transcriptomic evidence that pericytes are stem cells in human adipose tissue

    International Nuclear Information System (INIS)

    Silva Meirelles, Lindolfo da; Deus Wagatsuma, Virgínia Mara de; Malta, Tathiane Maistro; Bonini Palma, Patrícia Viana; Araújo, Amélia Goes; Panepucci, Rodrigo Alexandre

    2016-01-01

    Pericytes (PCs) are a subset of perivascular cells that can give rise to mesenchymal stromal cells (MSCs) when culture-expanded, and are postulated to give rise to MSC-like cells during tissue repair in vivo. PCs have been suggested to behave as stem cells (SCs) in situ in animal models, although evidence for this role in humans is lacking. Here, we analyzed the transcriptomes of highly purified, non-cultured adipose tissue (AT)-derived PCs (ATPCs) to detect gene expression changes that occur as they acquire MSC characteristics in vitro, and evaluated the hypothesis that human ATPCs exhibit a gene expression profile compatible with an AT SC phenotype. The results showed ATPCs are non-proliferative and express genes characteristic not only of PCs, but also of AT stem/progenitor cells. Additional analyses defined a gene expression signature for ATPCs, and revealed putative novel ATPC markers. Almost all AT stem/progenitor cell genes differentially expressed by ATPCs were not expressed by ATMSCs or culture-expanded ATPCs. Genes expressed by ATMSCs but not by ATPCs were also identified. These findings strengthen the hypothesis that PCs are SCs in vascularized tissues, highlight gene expression changes they undergo as they assume an MSC phenotype, and provide new insights into PC biology. - Highlights: • Non-cultured adipose tissue-derived human pericytes (ncATPCs) exhibit a distinctive gene expression signature. • ncATPCs express key adipose tissue stem cell genes previously described in vivo in mice. • ncATPCs express message for anti-proliferative and antiangiogenic molecules. • Most ncATPC-specific transcripts are absent in culture-expanded pericytes or ATMSCs • Gene expression changes ncATPCs undergo as they acquire a cultured ATMSC phenotype are pointed out.

  8. Hypnosis and imaging of the living human brain.

    Science.gov (United States)

    Landry, Mathieu; Raz, Amir

    2015-01-01

    Over more than two decades, studies using imaging techniques of the living human brain have begun to explore the neural correlates of hypnosis. The collective findings provide a gripping, albeit preliminary, account of the underlying neurobiological mechanisms involved in hypnotic phenomena. While substantial advances lend support to different hypotheses pertaining to hypnotic modulation of attention, control, and monitoring processes, the complex interactions among the many mediating variables largely hinder our ability to isolate robust commonalities across studies. The present account presents a critical integrative synthesis of neuroimaging studies targeting hypnosis as a function of suggestion. Specifically, hypnotic induction without task-specific suggestion is examined, as well as suggestions concerning sensation and perception, memory, and ideomotor response. The importance of carefully designed experiments is highlighted to better tease apart the neural correlates that subserve hypnotic phenomena. Moreover, converging findings intimate that hypnotic suggestions seem to induce specific neural patterns. These observations propose that suggestions may have the ability to target focal brain networks. Drawing on evidence spanning several technological modalities, neuroimaging studies of hypnosis pave the road to a more scientific understanding of a dramatic, yet largely evasive, domain of human behavior.

  9. Mapping human brain networks with cortico-cortical evoked potentials

    Science.gov (United States)

    Keller, Corey J.; Honey, Christopher J.; Mégevand, Pierre; Entz, Laszlo; Ulbert, Istvan; Mehta, Ashesh D.

    2014-01-01

    The cerebral cortex forms a sheet of neurons organized into a network of interconnected modules that is highly expanded in humans and presumably enables our most refined sensory and cognitive abilities. The links of this network form a fundamental aspect of its organization, and a great deal of research is focusing on understanding how information flows within and between different regions. However, an often-overlooked element of this connectivity regards a causal, hierarchical structure of regions, whereby certain nodes of the cortical network may exert greater influence over the others. While this is difficult to ascertain non-invasively, patients undergoing invasive electrode monitoring for epilepsy provide a unique window into this aspect of cortical organization. In this review, we highlight the potential for cortico-cortical evoked potential (CCEP) mapping to directly measure neuronal propagation across large-scale brain networks with spatio-temporal resolution that is superior to traditional neuroimaging methods. We first introduce effective connectivity and discuss the mechanisms underlying CCEP generation. Next, we highlight how CCEP mapping has begun to provide insight into the neural basis of non-invasive imaging signals. Finally, we present a novel approach to perturbing and measuring brain network function during cognitive processing. The direct measurement of CCEPs in response to electrical stimulation represents a potentially powerful clinical and basic science tool for probing the large-scale networks of the human cerebral cortex. PMID:25180306

  10. Endogenous neurogenesis in the human brain following cerebral infarction.

    Science.gov (United States)

    Minger, Stephen L; Ekonomou, Antigoni; Carta, Eloisa M; Chinoy, Amish; Perry, Robert H; Ballard, Clive G

    2007-01-01

    Increased endogenous neurogenesis has a significant regenerative role in many experimental models of cerebrovascular diseases, but there have been very few studies in humans. We therefore examined whether there was evidence of altered endogenous neurogenesis in an 84-year-old patient who suffered a cerebrovascular accident 1 week prior to death. Using antibodies that specifically label neural stem/neural progenitor cells, we examined the presence of immunopositive cells around and distant from the infarcted area, and compared this with a control, age-matched individual. Interestingly, a large number of neural stem cells, vascular endothelial growth factor-immunopositive cells and new blood vessels were observed only around the region of infarction, and none in the corresponding brain areas of the healthy control. In addition, an increased number of neural stem cells was observed in the neurogenic region of the lateral ventricle wall. Our results suggest increased endogenous neurogenesis associated with neovascularization and migration of newly-formed cells towards a region of cerebrovascular damage in the adult human brain and highlight possible mechanisms underlying this process.

  11. Flow distributions and spatial correlations in human brain capillary networks

    Science.gov (United States)

    Lorthois, Sylvie; Peyrounette, Myriam; Larue, Anne; Le Borgne, Tanguy

    2015-11-01

    The vascular system of the human brain cortex is composed of a space filling mesh-like capillary network connected upstream and downstream to branched quasi-fractal arterioles and venules. The distribution of blood flow rates in these networks may affect the efficiency of oxygen transfer processes. Here, we investigate the distribution and correlation properties of blood flow velocities from numerical simulations in large 3D human intra-cortical vascular network (10000 segments) obtained from an anatomical database. In each segment, flow is solved from a 1D non-linear model taking account of the complex rheological properties of blood flow in microcirculation to deduce blood pressure, blood flow and red blood cell volume fraction distributions throughout the network. The network structural complexity is found to impart broad and spatially correlated Lagrangian velocity distributions, leading to power law transit time distributions. The origins of this behavior (existence of velocity correlations in capillary networks, influence of the coupling with the feeding arterioles and draining veins, topological disorder, complex blood rheology) are studied by comparison with results obtained in various model capillary networks of controlled disorder. ERC BrainMicroFlow GA615102, ERC ReactiveFronts GA648377.

  12. Gaze-and-brain-controlled interfaces for human-computer and human-robot interaction

    Directory of Open Access Journals (Sweden)

    Shishkin S. L.

    2017-09-01

    Full Text Available Background. Human-machine interaction technology has greatly evolved during the last decades, but manual and speech modalities remain single output channels with their typical constraints imposed by the motor system’s information transfer limits. Will brain-computer interfaces (BCIs and gaze-based control be able to convey human commands or even intentions to machines in the near future? We provide an overview of basic approaches in this new area of applied cognitive research. Objective. We test the hypothesis that the use of communication paradigms and a combination of eye tracking with unobtrusive forms of registering brain activity can improve human-machine interaction. Methods and Results. Three groups of ongoing experiments at the Kurchatov Institute are reported. First, we discuss the communicative nature of human-robot interaction, and approaches to building a more e cient technology. Specifically, “communicative” patterns of interaction can be based on joint attention paradigms from developmental psychology, including a mutual “eye-to-eye” exchange of looks between human and robot. Further, we provide an example of “eye mouse” superiority over the computer mouse, here in emulating the task of selecting a moving robot from a swarm. Finally, we demonstrate a passive, noninvasive BCI that uses EEG correlates of expectation. This may become an important lter to separate intentional gaze dwells from non-intentional ones. Conclusion. The current noninvasive BCIs are not well suited for human-robot interaction, and their performance, when they are employed by healthy users, is critically dependent on the impact of the gaze on selection of spatial locations. The new approaches discussed show a high potential for creating alternative output pathways for the human brain. When support from passive BCIs becomes mature, the hybrid technology of the eye-brain-computer (EBCI interface will have a chance to enable natural, fluent, and the

  13. Diurnal variation of the human adipose transcriptome and the link to metabolic disease

    Directory of Open Access Journals (Sweden)

    Lamb John

    2009-02-01

    Full Text Available Abstract Background Circadian (diurnal rhythm is an integral part of the physiology of the body; specifically, sleep, feeding behavior and metabolism are tightly linked to the light-dark cycle dictated by earth's rotation. Methods The present study examines the effect of diurnal rhythm on gene expression in the subcutaneous adipose tissue of overweight to mildly obese, healthy individuals. In this well-controlled clinical study, adipose biopsies were taken in the morning, afternoon and evening from individuals in three study arms: treatment with the weight loss drug sibutramine/fasted, placebo/fed and placebo/fasted. Results The results indicated that diurnal rhythm was the most significant driver of gene expression variation in the human adipose tissue, with at least 25% of the genes having had significant changes in their expression levels during the course of the day. The mRNA expression levels of core clock genes at a specific time of day were consistent across multiple subjects on different days in all three arms, indicating robust diurnal regulation irrespective of potential confounding factors. The genes essential for energy metabolism and tissue physiology were part of the diurnal signature. We hypothesize that the diurnal transition of the expression of energy metabolism genes reflects the shift in the adipose tissue from an energy-expending state in the morning to an energy-storing state in the evening. Consistent with this hypothesis, the diurnal transition was delayed by fasting and treatment with sibutramine. Finally, an in silico comparison of the diurnal signature with data from the publicly-available Connectivity Map demonstrated a significant association with transcripts that were repressed by mTOR inhibitors, suggesting a possible link between mTOR signaling, diurnal gene expression and metabolic regulation. Conclusion Diurnal rhythm plays an important role in the physiology and regulation of energy metabolism in the adipose

  14. The Dynamic Genome and Transcriptome of the Human Fungal Pathogen Blastomyces and Close Relative Emmonsia.

    Directory of Open Access Journals (Sweden)

    José F Muñoz

    2015-10-01

    Full Text Available Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis and paracoccidioidomycosis. Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis, Blastomyces, and two species of the related genus Emmonsia, typically pathogens of small mammals. Compared to related species, Blastomyces genomes are highly expanded, with long, often sharply demarcated tracts of low GC-content sequence. These GC-poor isochore-like regions are enriched for gypsy elements, are variable in total size between isolates, and are least expanded in the avirulent B. dermatitidis strain ER-3 as compared with the virulent B. gilchristii strain SLH14081. The lack of similar regions in related species suggests these isochore-like regions originated recently in the ancestor of the Blastomyces lineage. While gene content is highly conserved between Blastomyces and related fungi, we identified changes in copy number of genes potentially involved in host interaction, including proteases and characterized antigens. In addition, we studied gene expression changes of B. dermatitidis during the interaction of the infectious yeast form with macrophages and in a mouse model. Both experiments highlight a strong antioxidant defense response in Blastomyces, and upregulation of dioxygenases in vivo suggests that dioxide produced by antioxidants may be further utilized for amino acid metabolism. We identify a number of functional categories upregulated exclusively in vivo, such as secreted proteins, zinc acquisition proteins, and cysteine and tryptophan metabolism, which may include critical virulence factors missed before in in vitro studies. Across the dimorphic fungi, loss of certain zinc acquisition genes and differences in amino acid metabolism suggest unique adaptations of Blastomyces to its host environment. These results reveal the dynamics

  15. The Dynamic Genome and Transcriptome of the Human Fungal Pathogen Blastomyces and Close Relative Emmonsia.

    Science.gov (United States)

    Muñoz, José F; Gauthier, Gregory M; Desjardins, Christopher A; Gallo, Juan E; Holder, Jason; Sullivan, Thomas D; Marty, Amber J; Carmen, John C; Chen, Zehua; Ding, Li; Gujja, Sharvari; Magrini, Vincent; Misas, Elizabeth; Mitreva, Makedonka; Priest, Margaret; Saif, Sakina; Whiston, Emily A; Young, Sarah; Zeng, Qiandong; Goldman, William E; Mardis, Elaine R; Taylor, John W; McEwen, Juan G; Clay, Oliver K; Klein, Bruce S; Cuomo, Christina A

    2015-10-01

    Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis and paracoccidioidomycosis. Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis, Blastomyces, and two species of the related genus Emmonsia, typically pathogens of small mammals. Compared to related species, Blastomyces genomes are highly expanded, with long, often sharply demarcated tracts of low GC-content sequence. These GC-poor isochore-like regions are enriched for gypsy elements, are variable in total size between isolates, and are least expanded in the avirulent B. dermatitidis strain ER-3 as compared with the virulent B. gilchristii strain SLH14081. The lack of similar regions in related species suggests these isochore-like regions originated recently in the ancestor of the Blastomyces lineage. While gene content is highly conserved between Blastomyces and related fungi, we identified changes in copy number of genes potentially involved in host interaction, including proteases and characterized antigens. In addition, we studied gene expression changes of B. dermatitidis during the interaction of the infectious yeast form with macrophages and in a mouse model. Both experiments highlight a strong antioxidant defense response in Blastomyces, and upregulation of dioxygenases in vivo suggests that dioxide produced by antioxidants may be further utilized for amino acid metabolism. We identify a number of functional categories upregulated exclusively in vivo, such as secreted proteins, zinc acquisition proteins, and cysteine and tryptophan metabolism, which may include critical virulence factors missed before in in vitro studies. Across the dimorphic fungi, loss of certain zinc acquisition genes and differences in amino acid metabolism suggest unique adaptations of Blastomyces to its host environment. These results reveal the dynamics of genome evolution

  16. Transcriptome dysregulation by anthrax lethal toxin plays a key role in induction of human endothelial cell cytotoxicity

    CSIR Research Space (South Africa)

    Rolando, M

    2010-07-01

    Full Text Available . They show that knock-down of cortactin and rhophilin-2 under conditions of calponin-1 expression defines the minimal set of genes regulated by LT for actin cable formation. Together their data establish that the modulation of the cell transcriptome by LT...

  17. Long distance communication in the human brain: timing constraints for inter-hemispheric synchrony and the origin of brain lateralization

    Directory of Open Access Journals (Sweden)

    FRANCISCO ABOITIZ

    2003-01-01

    Full Text Available Analysis of corpus callosum fiber composition reveals that inter-hemispheric transmission time may put constraints on the development of inter-hemispheric synchronic ensembles, especially in species with large brains like humans. In order to overcome this limitation, a subset of large-diameter callosal fibers are specialized for fast inter-hemispheric transmission, particularly in large-brained species. Nevertheless, the constraints on fast inter-hemispheric communication in large-brained species can somehow contribute to the development of ipsilateral, intrahemispheric networks, which might promote the development of brain lateralization.

  18. The role of positron emission tomography in neuropharmacology in the living human brain and drug development

    International Nuclear Information System (INIS)

    Yanai, Kazuhiko

    1999-01-01

    Neuroimaging is a powerful and innovative tool for studying the pathology of psychiatric and neurological diseases and, more recently, for studying the drugs used in their treatment. Technological advances in imaging have made it possible to noninvasively extract information from the human brain regarding a drug's mechanism and site of action. Until now, our understanding of human brain pharmacology has depended primarily on indirect assessments or models derived from animal studies. However, the advent of multiple techniques for human brain imaging allows researchers to focus directly on human pharmacology and brain function. In this review article, our PET studies on the histaminergic neuron system were presented as an example. We have developed and used the PET techniques for 10 years in order to examine the H 1 receptors in the living human brain. This review outlines available PET techniques and examine how these various methods have already been applied to the drug development process and neuropharmacology in the living human brain. (author)

  19. Differences in distribution and regulation of astrocytic aquaporin-4 in human and rat hydrocephalic brain

    DEFF Research Database (Denmark)

    Skjolding, Anders Daehli; Holst, Anders Vedel; Broholm, Helle

    2013-01-01

    findings to human pathophysiology. This study compares expression of aquaporin-4 in hydrocephalic human brain with human controls and hydrocephalic rat brain. Methods:  Cortical biopsies from patients with chronic hydrocephalus (n=29) were sampled secondary to planned surgical intervention. Aquaporin-4...

  20. A digital interactive human brain atlas based on Chinese visible human datasets for anatomy teaching.

    Science.gov (United States)

    Li, Qiyu; Ran, Xu; Zhang, Shaoxiang; Tan, Liwen; Qiu, Mingguo

    2014-01-01

    As we know, the human brain is one of the most complicated organs in the human body, which is the key and difficult point in neuroanatomy and sectional anatomy teaching. With the rapid development and extensive application of imaging technology in clinical diagnosis, doctors are facing higher and higher requirement on their anatomy knowledge. Thus, to cultivate medical students to meet the needs of medical development today and to improve their ability to read and understand radiographic images have become urgent challenges for the medical teachers. In this context, we developed a digital interactive human brain atlas based on the Chinese visible human datasets for anatomy teaching (available for free download from http://www.chinesevisiblehuman.com/down/DHBA.rar). The atlas simultaneously provides views in all 3 primary planes of section. The main structures of the human brain have been anatomically labeled in all 3 views. It is potentially useful for anatomy browsing, user self-testing, and automatic student assessment. In a word, it is interactive, 3D, user friendly, and free of charge, which can provide a new, intuitive means for anatomy teaching.

  1. Oligophrenin-1 (OPHN1, a gene involved in X-linked intellectual disability, undergoes RNA editing and alternative splicing during human brain development.

    Directory of Open Access Journals (Sweden)

    Sabina Barresi

    Full Text Available Oligophrenin-1 (OPHN1 encodes for a Rho-GTPase-activating protein, important for dendritic morphogenesis and synaptic function. Mutations in this gene have been identified in patients with X-linked intellectual disability associated with cerebellar hypoplasia. ADAR enzymes are responsible for A-to-I RNA editing, an essential post-transcriptional RNA modification contributing to transcriptome and proteome diversification. Specifically, ADAR2 activity is essential for brain development and function. Herein, we show that the OPHN1 transcript undergoes post-transcriptional modifications such as A-to-I RNA editing and alternative splicing in human brain and other tissues. We found that OPHN1 editing is detectable already at the 18th week of gestation in human brain with a boost of editing at weeks 20 to 33, concomitantly with OPHN1 expression increase and the appearance of a novel OPHN1 splicing isoform. Our results demonstrate that multiple post-transcriptional events occur on OPHN1, a gene playing an important role in brain function and development.

  2. Human Development XII: A Theory for the Structure and Function of the Human Brain

    Directory of Open Access Journals (Sweden)

    Søren Ventegodt

    2008-01-01

    Full Text Available The human brain is probably the most complicated single structure in the biological universe. The cerebral cortex that is traditionally connected with consciousness is extremely complex. The brain contains approximately 1,000,000 km of nerve fibers, indicating its enormous complexity and which makes it difficult for scientists to reveal the function of the brain. In this paper, we propose a new model for brain functions, i.e., information-guided self-organization of neural patterns, where information is provided from the abstract wholeness of the biophysical system of an organism (often called the true self, or the “soul””. We present a number of arguments in favor of this model that provide self-conscious control over the thought process or cognition. Our arguments arise from analyzing experimental data from different research fields: histology, anatomy, electroencephalography (EEG, cerebral blood flow, neuropsychology, evolutionary studies, and mathematics. We criticize the popular network theories as the consequence of a simplistic, mechanical interpretation of reality (philosophical materialism applied to the brain. We demonstrate how viewing brain functions as information-guided self-organization of neural patterns can explain the structure of conscious mentation; we seem to have a dual hierarchical representation in the cerebral cortex: one for sensation-perception and one for will-action. The model explains many of our unique mental abilities to think, memorize, associate, discriminate, and make abstractions. The presented model of the conscious brain also seems to be able to explain the function of the simpler brains, such as those of insects and hydra.

  3. Activation analysis study on subcellular distribution of trace elements in human brain tumor

    International Nuclear Information System (INIS)

    Zheng Jian; Zhuan Guisun; Wang Yongji; Dong Mo; Zhang Fulin

    1992-01-01

    The concentrations of up to 11 elements in subcellular fractions of human brain (normal and malignant tumor) have been determined by a combination of gradient centrifugation and INAA methods. Samples of human brain were homogenized in a glass homogenizer tube, the homogenate was separated into nuclei, mitochondrial, myelin, synaptosome fractions, and these fractions were then analyzed using the INAA method. The discussions of elemental subcelleular distributions in human brain malignant tumor are presented in this paper. (author) 11 refs.; 2 figs.; 4 tabs

  4. Deep brain stimulation, brain maps and personalized medicine: lessons from the human genome project.

    Science.gov (United States)

    Fins, Joseph J; Shapiro, Zachary E

    2014-01-01

    Although the appellation of personalized medicine is generally attributed to advanced therapeutics in molecular medicine, deep brain stimulation (DBS) can also be so categorized. Like its medical counterpart, DBS is a highly personalized intervention that needs to be tailored to a patient's individual anatomy. And because of this, DBS like more conventional personalized medicine, can be highly specific where the object of care is an N = 1. But that is where the similarities end. Besides their differing medical and surgical provenances, these two varieties of personalized medicine have had strikingly different impacts. The molecular variant, though of a more recent vintage has thrived and is experiencing explosive growth, while DBS still struggles to find a sustainable therapeutic niche. Despite its promise, and success as a vetted treatment for drug resistant Parkinson's Disease, DBS has lagged in broadening its development, often encountering regulatory hurdles and financial barriers necessary to mount an adequate number of quality trials. In this paper we will consider why DBS-or better yet neuromodulation-has encountered these challenges and contrast this experience with the more successful advance of personalized medicine. We will suggest that personalized medicine and DBS's differential performance can be explained as a matter of timing and complexity. We believe that DBS has struggled because it has been a journey of scientific exploration conducted without a map. In contrast to molecular personalized medicine which followed the mapping of the human genome and the Human Genome Project, DBS preceded plans for the mapping of the human brain. We believe that this sequence has given personalized medicine a distinct advantage and that the fullest potential of DBS will be realized both as a cartographical or electrophysiological probe and as a modality of personalized medicine.

  5. Abstract representations of associated emotions in the human brain.

    Science.gov (United States)

    Kim, Junsuk; Schultz, Johannes; Rohe, Tim; Wallraven, Christian; Lee, Seong-Whan; Bülthoff, Heinrich H

    2015-04-08

    Emotions can be aroused by various kinds of stimulus modalities. Recent neuroimaging studies indicate that several brain regions represent emotions at an abstract level, i.e., independently from the sensory cues from which they are perceived (e.g., face, body, or voice stimuli). If emotions are indeed represented at such an abstract level, then these abstract representations should also be activated by the memory of an emotional event. We tested this hypothesis by asking human participants to learn associations between emotional stimuli (videos of faces or bodies) and non-emotional stimuli (fractals). After successful learning, fMRI signals were recorded during the presentations of emotional stimuli and emotion-associated fractals. We tested whether emotions could be decoded from fMRI signals evoked by the fractal stimuli using a classifier trained on the responses to the emotional stimuli (and vice versa). This was implemented as a whole-brain searchlight, multivoxel activation pattern analysis, which revealed successful emotion decoding in four brain regions: posterior cingulate cortex (PCC), precuneus, MPFC, and angular gyrus. The same analysis run only on responses to emotional stimuli revealed clusters in PCC, precuneus, and MPFC. Multidimensional scaling analysis of the activation patterns revealed clear clustering of responses by emotion across stimulus types. Our results suggest that PCC, precuneus, and MPFC contain representations of emotions that can be evoked by stimuli that carry emotional information themselves or by stimuli that evoke memories of emotional stimuli, while angular gyrus is more likely to take part in emotional memory retrieval. Copyright © 2015 the authors 0270-6474/15/355655-09$15.00/0.

  6. The functional connectivity landscape of the human brain.

    Directory of Open Access Journals (Sweden)

    Bratislav Mišić

    Full Text Available Functional brain networks emerge and dissipate over a primarily static anatomical foundation. The dynamic basis of these networks is inter-regional communication involving local and distal regions. It is assumed that inter-regional distances play a pivotal role in modulating network dynamics. Using three different neuroimaging modalities, 6 datasets were evaluated to determine whether experimental manipulations asymmetrically affect functional relationships based on the distance between brain regions in human participants. Contrary to previous assumptions, here we show that short- and long-range connections are equally likely to strengthen or weaken in response to task demands. Additionally, connections between homotopic areas are the most stable and less likely to change compared to any other type of connection. Our results point to a functional connectivity landscape characterized by fluid transitions between local specialization and global integration. This ability to mediate functional properties irrespective of spatial distance may engender a diverse repertoire of cognitive processes when faced with a dynamic environment.

  7. Giovanni Aldini: from animal electricity to human brain stimulation.

    Science.gov (United States)

    Parent, André

    2004-11-01

    Two hundred years ago, Giovanni Aldini published a highly influential book that reported experiments in which the principles of Luigi Galvani (animal electricity) and Alessandro Volta (bimetallic electricity) were used together for the first time. Aldini was born in Bologna in 1762 and graduated in physics at the University of his native town in 1782. As nephew and assistant of Galvani, he actively participated in a series of crucial experiments with frog's muscles that led to the idea that electricity was the long-sought vital force coursing from brain to muscles. Aldini became professor of experimental physics at the University of Bologna in 1798. He traveled extensively throughout Europe, spending much time defending the concept of his discreet uncle against the incessant attacks of Volta, who did not believe in animal electricity. Aldini used Volta's bimetallic pile to apply electric current to dismembered bodies of animals and humans; these spectacular galvanic reanimation experiments made a strong and enduring impression on his contemporaries. Aldini also treated patients with personality disorders and reported complete rehabilitation following transcranial administration of electric current. Aldini's work laid the ground for the development of various forms of electrotherapy that were heavily used later in the 19th century. Even today, deep brain stimulation, a procedure currently employed to relieve patients with motor or behavioral disorders, owes much to Aldini and galvanism. In recognition of his merits, Aldini was made a knight of the Iron Crown and a councillor of state at Milan, where he died in 1834.

  8. Genetic contributions to human brain morphology and intelligence

    DEFF Research Database (Denmark)

    Hulshoff Pol, HE; Schnack, HG; Posthuma, D

    2006-01-01

    the focal GM and WM densities of each twin are correlated with the psychometric intelligence quotient of his/her cotwin. Genes influenced individual differences in left and right superior occipitofrontal fascicle (heritability up to 0.79 and 0.77), corpus callosum (0.82, 0.80), optic radiation (0.69, 0.......79), corticospinal tract (0.78, 0.79), medial frontal cortex (0.78, 0.83), superior frontal cortex (0.76, 0.80), superior temporal cortex (0.80, 0.77), left occipital cortex (0.85), left postcentral cortex (0.83), left posterior cingulate cortex (0.83), right parahippocampal cortex (0.69), and amygdala (0.80, 0......Variation in gray matter (GM) and white matter (WM) volume of the adult human brain is primarily genetically determined. Moreover, total brain volume is positively correlated with general intelligence, and both share a common genetic origin. However, although genetic effects on morphology...

  9. Brain Imaging of Human Sexual Response : Recent Developments and Future Directions

    NARCIS (Netherlands)

    Ruesink, Gerben B; Georgiadis, Janniko R

    2017-01-01

    Purpose of Review: The purpose of this study is to provide a comprehensive summary of the latest developments in the experimental brain study of human sexuality, focusing on brain connectivity during the sexual response. Recent Findings: Stable patterns of brain activation have been established for

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

    NARCIS (Netherlands)

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

    2017-01-01

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

  11. Exploring terra incognita of cognitive science: Lateralization of gene expression at the frontal pole of the human brain

    Directory of Open Access Journals (Sweden)

    Dolina I.A.

    2017-09-01

    Full Text Available Background. Rostral prefrontal cortex, or frontopolar cortex (FPC, also known as Brodmann area 10 (BA10, is the most anterior part of the human brain. It is one of the largest cytoarchitectonic areas of the human brain that has significantly increased its volume during evolution. Anatomically the le (BA10L and right (BA10R parts of FPC show slight asymmetries and they may have distinctive cognitive functions. Objective. In the present study, we investigated differential expression of the transcriptome in the le and right parts of BA10. Design. Postmortem samples of human brain tissue from fourteen donors (male/ female without history of psychiatric and neurological diseases, mean age 39.79±3.23 years old, mean postmortem interval 12.10±1.76 h were obtained using the resources of three institutions: the Partner Institute of Computational Biology of Chinese Academy of Sciences, the Max Planck Institute for Evolutionary Anthropology, and NIH Neuro-BioBank. Results. By using a standard RNA-sequencing followed by bioinformatic analysis, we identified 61 genes with differential expression in the le and right FPC. In general, gene expression was increased in BA10R relative to BA10L: 40 vs. 21 genes, respectively. According to gene ontology analysis, the majority of up-regulated genes in BA10R be- longed to the protein-coding category, whereas protein-coding and non-coding genes were equally up-expressed in BA10L. Most of the up-regulated genes in BA10R were involved in brain plasticity and activity-dependent mechanisms also known for their role in the hippocampus. 24 out of 30 mental disorder-related genes in the dataset were disrupted in schizophrenia. No such a wide association with other mental disorders was found. Conclusion. Discovered differences point at possible causes of hemispheric asymmetries in the human frontal lobes and at the molecular base of higher-order cognitive processes in health and disease.

  12. The addicted human brain viewed in the light of imaging studies: brain circuits and treatment strategies.

    Science.gov (United States)

    Volkow, Nora D; Fowler, Joanna S; Wang, Gene-Jack

    2004-01-01

    Imaging studies have provided evidence of how the human brain changes as an individual becomes addicted. Here, we integrate the findings from imaging studies to propose a model of drug addiction. The process of addiction is initiated in part by the fast and high increases in DA induced by drugs of abuse. We hypothesize that this supraphysiological effect of drugs trigger a series of adaptations in neuronal circuits involved in saliency/reward, motivation/drive, memory/conditioning, and control/disinhibition, resulting in an enhanced (and long lasting) saliency value for the drug and its associated cues at the expense of decreased sensitivity for salient events of everyday life (including natural reinforcers). Although acute drug intake increases DA neurotransmission, chronic drug consumption results in a marked decrease in DA activity, associated with, among others, dysregulation of the orbitofrontal cortex (region involved with salience attribution) and cingulate gyrus (region involved with inhibitory control). The ensuing increase in motivational drive for the drug, strengthened by conditioned responses and the decrease in inhibitory control favors emergence of compulsive drug taking. This view of how drugs of abuse affect the brain suggests strategies for intervention, which might include: (a) those that will decrease the reward value of the drug of choice; (b) interventions to increase the saliency value of non-drug reinforcers; (c) approaches to weaken conditioned drug behaviors; and (d) methods to strengthen frontal inhibitory and executive control. Though this model focuses mostly on findings from PET studies of the brain DA system it is evident that other neurotransmitters are involved and that a better understanding of their roles in addiction would expand the options for therapeutic targets.

  13. Brain-to-brain hyperclassification reveals action-specific motor mapping of observed actions in humans.

    Science.gov (United States)

    Smirnov, Dmitry; Lachat, Fanny; Peltola, Tomi; Lahnakoski, Juha M; Koistinen, Olli-Pekka; Glerean, Enrico; Vehtari, Aki; Hari, Riitta; Sams, Mikko; Nummenmaa, Lauri

    2017-01-01

    Seeing an action may activate the corresponding action motor code in the observer. It remains unresolved whether seeing and performing an action activates similar action-specific motor codes in the observer and the actor. We used novel hyperclassification approach to reveal shared brain activation signatures of action execution and observation in interacting human subjects. In the first experiment, two "actors" performed four types of hand actions while their haemodynamic brain activations were measured with 3-T functional magnetic resonance imaging (fMRI). The actions were videotaped and shown to 15 "observers" during a second fMRI experiment. Eleven observers saw the videos of one actor, and the remaining four observers saw the videos of the other actor. In a control fMRI experiment, one of the actors performed actions with closed eyes, and five new observers viewed these actions. Bayesian canonical correlation analysis was applied to functionally realign observers' and actors' fMRI data. Hyperclassification of the seen actions was performed with Bayesian logistic regression trained on actors' data and tested with observers' data. Without the functional realignment, between-subjects accuracy was at chance level. With the realignment, the accuracy increased on average by 15 percentage points, exceeding both the chance level and the accuracy without functional realignment. The highest accuracies were observed in occipital, parietal and premotor cortices. Hyperclassification exceeded chance level also when the actor did not see her own actions. We conclude that the functional brain activation signatures underlying action execution and observation are partly shared, yet these activation signatures may be anatomically misaligned across individuals.

  14. The power of love on the human brain.

    Science.gov (United States)

    Bianchi-Demicheli, Francesco; Grafton, Scott T; Ortigue, Stephanie

    2006-01-01

    Romantic love has been the source for some of the greatest achievements of mankind throughout the ages. The recent localization of romantic love within subcortico-cortical reward, motivation and emotion systems in the human brain has suggested that love is a goal-directed drive with predictable facilitation effects on cognitive behavior, rather than a pure emotion. Here we show that the subliminal exposure of a beloved's name (romantic prime) during a lexical decision task dramatically improves performance in women in love (Experiment 1), as the subliminal presentation of a passion's descriptive noun does (Experiment 2). The parallel between love and passion allows us to interpret these facilitation effects as corresponding to cognitive top-down processes within a motivation-enhanced neural network.

  15. Adrenergic receptors in frontal cortex in human brain.

    Science.gov (United States)

    Cash, R; Raisman, R; Ruberg, M; Agid, Y

    1985-02-05

    The binding of three adrenergic ligands ([3H]prazosin, [3H]clonidine, [3H]dihydroalprenolol) was studied in the frontal cortex of human brain. alpha 1-Receptors, labeled by [3H]prazosin, predominated. [3H]Clonidine bound to two classes of sites, one of high affinity and one of low affinity. Guanosine triphosphate appeared to lower the affinity of [3H]clonidine for its receptor. [3H]Dihydroalprenolol bound to three classes of sites: the beta 1-receptor, the beta 2-receptor and a receptor with low affinity which represented about 40% of the total binding, but which was probably a non-specific site; the beta 1/beta 2 ratio was 1/2.

  16. Exclusive neuronal expression of SUCLA2 in the human brain

    DEFF Research Database (Denmark)

    Dobolyi, Arpád; Ostergaard, Elsebet; Bagó, Attila G

    2015-01-01

    associated with SUCLA2 mutations, the precise localization of SUCLA2 protein has never been investigated. Here, we show that immunoreactivity of A-SUCL-β in surgical human cortical tissue samples was present exclusively in neurons, identified by their morphology and visualized by double labeling...... was absent in glial cells, identified by antibodies directed against the glial markers GFAP and S100. Furthermore, in situ hybridization histochemistry demonstrated that SUCLA2 mRNA was present in Nissl-labeled neurons but not glial cells labeled with S100. Immunoreactivity of the GTP-forming β subunit (G......-SUCL-β) encoded by SUCLG2, or in situ hybridization histochemistry for SUCLG2 mRNA could not be demonstrated in either neurons or astrocytes. Western blotting of post mortem brain samples revealed minor G-SUCL-β immunoreactivity that was, however, not upregulated in samples obtained from diabetic versus non...

  17. Role of synchronized oscillatory brain activity for human pain perception.

    Science.gov (United States)

    Hauck, Michael; Lorenz, Jürgen; Engel, Andreas K

    2008-01-01

    The understanding of cortical pain processing in humans has significantly improved since the development of modern neuroimaging techniques. Non-invasive electrophysiological approaches such as electro- and magnetoencephalography have proven to be helpful tools for the real-time investigation of neuronal signals and synchronous communication between cortical areas. In particular, time-frequency decomposition of signals recorded with these techniques seems to be a promising approach because different pain-related oscillatory changes can be observed within different frequency bands, which are likely to be linked to specific sensory and motor functions. In this review we discuss the latest evidence on pain-induced time-frequency signals and propose that changes in oscillatory activity reflect an essential communication mechanism in the brain that is modulated during pain processing. The importance of synchronization processes for normal and pathological pain processing, such as chronic pain states, is discussed.

  18. Implicit false-belief processing in the human brain.

    Science.gov (United States)

    Schneider, Dana; Slaughter, Virginia P; Becker, Stefanie I; Dux, Paul E

    2014-11-01

    Eye-movement patterns in 'Sally-Anne' tasks reflect humans' ability to implicitly process the mental states of others, particularly false-beliefs - a key theory of mind (ToM) operation. It has recently been proposed that an efficient ToM system, which operates in the absence of awareness (implicit ToM, iToM), subserves the analysis of belief-like states. This contrasts to consciously available belief processing, performed by the explicit ToM system (eToM). The frontal, temporal and parietal cortices are engaged when humans explicitly 'mentalize' about others' beliefs. However, the neural underpinnings of implicit false-belief processing and the extent to which they draw on networks involved in explicit general-belief processing are unknown. Here, participants watched 'Sally-Anne' movies while fMRI and eye-tracking measures were acquired simultaneously. Participants displayed eye-movements consistent with implicit false-belief processing. After independently localizing the brain areas involved in explicit general-belief processing, only the left anterior superior temporal sulcus and precuneus revealed greater blood-oxygen-level-dependent activity for false- relative to true-belief trials in our iToM paradigm. No such difference was found for the right temporal-parietal junction despite significant activity in this area. These findings fractionate brain regions that are associated with explicit general ToM reasoning and false-belief processing in the absence of awareness. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. The structural, connectomic and network covariance of the human brain.

    Science.gov (United States)

    Irimia, Andrei; Van Horn, John D

    2013-02-01

    Though it is widely appreciated that complex structural, functional and morphological relationships exist between distinct areas of the human cerebral cortex, the extent to which such relationships coincide remains insufficiently appreciated. Here we determine the extent to which correlations between brain regions are modulated by either structural, connectomic or network-theoretic properties using a structural neuroimaging data set of magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) volumes acquired from N=110 healthy human adults. To identify the linear relationships between all available pairs of regions, we use canonical correlation analysis to test whether a statistically significant correlation exists between each pair of cortical parcels as quantified via structural, connectomic or network-theoretic measures. In addition to this, we investigate (1) how each group of canonical variables (whether structural, connectomic or network-theoretic) contributes to the overall correlation and, additionally, (2) whether each individual variable makes a significant contribution to the test of the omnibus null hypothesis according to which no correlation between regions exists across subjects. We find that, although region-to-region correlations are extensively modulated by structural and connectomic measures, there are appreciable differences in how these two groups of measures drive inter-regional correlation patterns. Additionally, our results indicate that the network-theoretic properties of the cortex are strong modulators of region-to-region covariance. Our findings are useful for understanding the structural and connectomic relationship between various parts of the brain, and can inform theoretical and computational models of cortical information processing. Published by Elsevier Inc.

  20. A collaborative brain-computer interface for improving human performance.

    Directory of Open Access Journals (Sweden)

    Yijun Wang

    Full Text Available Electroencephalogram (EEG based brain-computer interfaces (BCI have been studied since the 1970s. Currently, the main focus of BCI research lies on the clinical use, which aims to provide a new communication channel to patients with motor disabilities to improve their quality of life. However, the BCI technology can also be used to improve human performance for normal healthy users. Although this application has been proposed for a long time, little progress has been made in real-world practices due to technical limits of EEG. To overcome the bottleneck of low single-user BCI performance, this study proposes a collaborative paradigm to improve overall BCI performance by integrating information from multiple users. To test the feasibility of a collaborative BCI, this study quantitatively compares the classification accuracies of collaborative and single-user BCI applied to the EEG data collected from 20 subjects in a movement-planning experiment. This study also explores three different methods for fusing and analyzing EEG data from multiple subjects: (1 Event-related potentials (ERP averaging, (2 Feature concatenating, and (3 Voting. In a demonstration system using the Voting method, the classification accuracy of predicting movement directions (reaching left vs. reaching right was enhanced substantially from 66% to 80%, 88%, 93%, and 95% as the numbers of subjects increased from 1 to 5, 10, 15, and 20, respectively. Furthermore, the decision of reaching direction could be made around 100-250 ms earlier than the subject's actual motor response by decoding the ERP activities arising mainly from the posterior parietal cortex (PPC, which are related to the processing of visuomotor transmission. Taken together, these results suggest that a collaborative BCI can effectively fuse brain activities of a group of people to improve the overall performance of natural human behavior.

  1. Single-cell analysis of targeted transcriptome predicts drug sensitivity of single cells within human myeloma tumors.

    Science.gov (United States)

    Mitra, A K; Mukherjee, U K; Harding, T; Jang, J S; Stessman, H; Li, Y; Abyzov, A; Jen, J; Kumar, S; Rajkumar, V; Van Ness, B

    2016-05-01

    Multiple myeloma (MM) is characterized by significant genetic diversity at subclonal levels that have a defining role in the heterogeneity of tumor progression, clinical aggressiveness and drug sensitivity. Although genome profiling studies have demonstrated heterogeneity in subclonal architecture that may ultimately lead to relapse, a gene expression-based prediction program that can identify, distinguish and quantify drug response in sub-populations within a bulk population of myeloma cells is lacking. In this study, we performed targeted transcriptome analysis on 528 pre-treatment single cells from 11 myeloma cell lines and 418 single cells from 8 drug-naïve MM patients, followed by intensive bioinformatics and statistical analysis for prediction of proteasome inhibitor sensitivity in individual cells. Using our previously reported drug response gene expression profile signature at the single-cell level, we developed an R Statistical analysis package available at https://github.com/bvnlabSCATTome, SCATTome (single-cell analysis of targeted transcriptome), that restructures the data obtained from Fluidigm single-cell quantitative real-time-PCR analysis run, filters missing data, performs scaling of filtered data, builds classification models and predicts drug response of individual cells based on targeted transcriptome using an assortment of machine learning methods. Application of SCATT should contribute to clinically relevant analysis of intratumor heterogeneity, and better inform drug choices based on subclonal cellular responses.

  2. Steady-state cerebral glucose concentrations and transport in the human brain

    OpenAIRE

    Gruetter, R.; Ugurbil, K.; Seaquist, E. R.

    1998-01-01

    Understanding the mechanism of brain glucose transport across the blood- brain barrier is of importance to understanding brain energy metabolism. The specific kinetics of glucose transport nave been generally described using standard Michaelis-Menten kinetics. These models predict that the steady- state glucose concentration approaches an upper limit in the human brain when the plasma glucose level is well above the Michaelis-Menten constant for half-maximal transport, K(t). In experiments wh...

  3. Variable ATP yields and uncoupling of oxygen consumption in human brain

    DEFF Research Database (Denmark)

    Gjedde, Albert; Aanerud, Joel; Peterson, Ericka

    2011-01-01

    normalized the metabolic rate to the population average of that region. Coefficients of variation ranged from 10 to 15% in the different regions of the human brain and the normalized regional metabolic rates ranged from 70% to 140% of the population average for each region, equal to a two-fold variation......The distribution of brain oxidative metabolism values among healthy humans is astoundingly wide for a measure that reflects normal brain function and is known to change very little with most changes of brain function. It is possible that the part of the oxygen consumption rate that is coupled...... to ATP turnover is the same in all healthy human brains, with different degrees of uncoupling explaining the variability of total oxygen consumption among people. To test the hypothesis that about 75% of the average total oxygen consumption of human brains is common to all individuals, we determined...

  4. TCW: transcriptome computational workbench.

    Science.gov (United States)

    Soderlund, Carol; Nelson, William; Willer, Mark; Gang, David R

    2013-01-01

    The analysis of transcriptome data involves many steps and various programs, along with organization of large amounts of data and results. Without a methodical approach for storage, analysis and query, the resulting ad hoc analysis can lead to human error, loss of data and results, inefficient use of time, and lack of verifiability, repeatability, and extensibility. The Transcriptome Computational Workbench (TCW) provides Java graphical interfaces for methodical analysis for both single and comparative transcriptome data without the use of a reference genome (e.g. for non-model organisms). The singleTCW interface steps the user through importing transcript sequences (e.g. Illumina) or assembling long sequences (e.g. Sanger, 454, transcripts), annotating the sequences, and performing differential expression analysis using published statistical programs in R. The data, metadata, and results are stored in a MySQL database. The multiTCW interface builds a comparison database by importing sequence and annotation from one or more single TCW databases, executes the ESTscan program to translate the sequences into proteins, and then incorporates one or more clusterings, where the clustering options are to execute the orthoMCL program, compute transitive closure, or import clusters. Both singleTCW and multiTCW allow extensive query and display of the results, where singleTCW displays the alignment of annotation hits to transcript sequences, and multiTCW displays multiple transcript alignments with MUSCLE or pairwise alignments. The query programs can be executed on the desktop for fastest analysis, or from the web for sharing the results. It is now affordable to buy a multi-processor machine, and easy to install Java and MySQL. By simply downloading the TCW, the user can interactively analyze, query and view their data. The TCW allows in-depth data mining of the results, which can lead to a better understanding of the transcriptome. TCW is freely available from www.agcol.arizona.edu/software/tcw.

  5. Temporal, Diagnostic, and Tissue-Specific Regulation of NRG3 Isoform Expression in Human Brain Development and Affective Disorders

    Science.gov (United States)

    Paterson, Clare; Wang, Yanhong; Hyde, Thomas M.; Weinberger, Daniel R.; Kleinman, Joel E.; Law, Amanda J.

    2018-01-01

    Objective Genes implicated in schizophrenia are enriched in networks differentially regulated during human CNS development. Neuregulin 3 (NRG3), a brain-enriched neurotrophin, undergoes alternative splicing and is implicated in several neurological disorders with developmental origins. Isoform-specific increases in NRG3 are observed in schizophrenia and associated with rs10748842, a NRG3 risk polymorphism, suggesting NRG3 transcriptional dysregulation as a molecular mechanism of risk. The authors quantitatively mapped the temporal trajectories of NRG3 isoforms (classes I–IV) in the neocortex throughout the human lifespan, examined whether tissue-specific regulation of NRG3 occurs in humans, and determined if abnormalities in NRG3 transcriptomics occur in mood disorders and are genetically determined. Method NRG3 isoform classes I–IV were quantified using quantitative real-time polymerase chain reaction in human postmortem dorsolateral prefrontal cortex from 286 nonpsychiatric control individuals, from gestational week 14 to 85 years old, and individuals diagnosed with either bipolar disorder (N=34) or major depressive disorder (N=69). Tissue-specific mapping was investigated in several human tissues. rs10748842 was genotyped in individuals with mood disorders, and association with NRG3 isoform expression examined. Results NRG3 classes displayed individually specific expression trajectories across human neocortical development and aging; classes I, II, and IV were significantly associated with developmental stage. NRG3 class I was increased in bipolar and major depressive disorder, consistent with observations in schizophrenia. NRG3 class II was increased in bipolar disorder, and class III was increased in major depression. The rs10748842 risk genotype predicted elevated class II and III expression, consistent with previous reports in the brain, with tissue-specific analyses suggesting that classes II and III are brain-specific isoforms of NRG3. Conclusions

  6. Quantitative proteomics and transcriptomics reveals metabolic differences in attracting and non-attracting human-in-mouse glioma stem cell xenografts and stromal cells

    Directory of Open Access Journals (Sweden)

    Norelle C. Wildburger

    2015-09-01

    Full Text Available Bone marrow-derived human mesenchymal stem cells (BM-hMSCs show promise as cell-based delivery vehicles for anti-glioma therapeutics, due to innate tropism for gliomas. However, in clinically relevant human-in-mouse glioma stem cell xenograft models, BM-hMSCs tropism is variable. We compared the proteomic profile of cancer and stromal cells in GSCXs that attract BM-hMSCs (“attractors” with those to do not (“non-attractors” to identify pathways that may modulate BM-hMSC homing, followed by targeted transcriptomics. The results provide the first link between fatty acid metabolism, glucose metabolism, ROS, and N-glycosylation patterns in attractors. Reciprocal expression of these pathways in the stromal cells suggests microenvironmental cross-talk.

  7. Exceptional evolutionary divergence of human muscle and brain metabolomes parallels human cognitive and physical uniqueness.

    Directory of Open Access Journals (Sweden)

    Katarzyna Bozek

    2014-05-01

    Full Text Available Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy metabolism pathways. These metabolic changes could not be attributed to environmental conditions and were confirmed against the expression of their corresponding enzymes. We further conducted muscle strength tests in humans, chimpanzees, and macaques. The results suggest that, while humans are characterized by superior cognition, their muscular performance might be markedly inferior to that of chimpanzees and macaque monkeys.

  8. Evidence of native α-synuclein conformers in the human brain.

    Science.gov (United States)

    Gould, Neal; Mor, Danielle E; Lightfoot, Richard; Malkus, Kristen; Giasson, Benoit; Ischiropoulos, Harry

    2014-03-14

    α-Synuclein aggregation is central to the pathogenesis of several brain disorders. However, the native conformations and functions of this protein in the human brain are not precisely known. The native state of α-synuclein was probed by gel filtration coupled with native gradient gel separation, an array of antibodies with non-overlapping epitopes, and mass spectrometry. The existence of metastable conformers and stable monomer was revealed in the human brain.

  9. Somatotopic Arrangement and Location of the Corticospinal Tract in the Brainstem of the Human Brain

    OpenAIRE

    Jang, Sung Ho

    2011-01-01

    The corticospinal tract (CST) is the most important motor pathway in the human brain. Detailed knowledge of CST somatotopy is important in terms of rehabilitative management and invasive procedures for patients with brain injuries. In this study, I conducted a review of nine previous studies of the somatotopical location and arrangement at the brainstem in the human brain. The results of this review indicated that the hand and leg somatotopies of the CST are arranged medio-laterally in the mi...

  10. Studying frequency processing of the brain to enhance long-term memory and develop a human brain protocol.

    Science.gov (United States)

    Friedrich, Wernher; Du, Shengzhi; Balt, Karlien

    2015-01-01

    The temporal lobe in conjunction with the hippocampus is responsible for memory processing. The gamma wave is involved with this process. To develop a human brain protocol, a better understanding of the relationship between gamma and long-term memory is vital. A more comprehensive understanding of the human brain and specific analogue waves it uses will support the development of a human brain protocol. Fifty-eight participants aged between 6 and 60 years participated in long-term memory experiments. It is envisaged that the brain could be stimulated through binaural beats (sound frequency) at 40 Hz (gamma) to enhance long-term memory capacity. EEG recordings have been transformed to sound and then to an information standard, namely ASCII. Statistical analysis showed a proportional relationship between long-term memory and gamma activity. Results from EEG recordings indicate a pattern. The pattern was obtained through the de-codification of an EEG recording to sound and then to ASCII. Stimulation of gamma should enhance long term memory capacity. More research is required to unlock the human brains' protocol key. This key will enable the processing of information directly to and from human memory via gamma, the hippocampus and the temporal lobe.

  11. Noninvasive quantification of human brain antioxidant concentrations after an intravenous bolus of vitamin C

    Science.gov (United States)

    Background: Until now, antioxidant based initiatives for preventing dementia have lacked a means to detect deficiency or measure pharmacologic effect in the human brain in situ. Objective: Our objective was to apply a novel method to measure key human brain antioxidant concentrations throughout the ...

  12. The human sexual response cycle : Brain imaging evidence linking sex to other pleasures

    NARCIS (Netherlands)

    Georgiadis, J. R.; Kringelbach, M. L.

    Sexual behavior is critical to species survival, yet comparatively little is known about the neural mechanisms in the human brain. Here we systematically review the existing human brain imaging literature on sexual behavior and show that the functional neuroanatomy of sexual behavior is comparable

  13. The future of neuroepigenetics in the human brain.

    Science.gov (United States)

    Mitchell, Amanda; Roussos, Panos; Peter, Cyril; Tsankova, Nadejda; Akbarian, Schahram

    2014-01-01

    Complex mechanisms shape the genome of brain cells into transcriptional units, clusters of condensed chromatin, and many other features that distinguish between various cell types and developmental stages sharing the same genetic material. Only a few years ago, the field's focus was almost entirely on a single mark, CpG methylation; the emerging complexity of neuronal and glial epigenomes now includes multiple types of DNA cytosine methylation, more than 100 residue-specific posttranslational histone modifications and histone variants, all of which superimposed by a dynamic and highly regulated three-dimensional organization of the chromosomal material inside the cell nucleus. Here, we provide an update on the most innovative approaches in neuroepigenetics and their potential contributions to approach cognitive functions and disorders unique to human. We propose that comprehensive, cell type-specific mappings of DNA and histone modifications, chromatin-associated RNAs, and chromosomal "loopings" and other determinants of three-dimensional genome organization will critically advance insight into the pathophysiology of the disease. For example, superimposing the epigenetic landscapes of neuronal and glial genomes onto genetic maps for complex disorders, ranging from Alzheimer's disease to schizophrenia, could provide important clues about neurological function for some of the risk-associated noncoding sequences in the human genome.

  14. Morphometry of medial gaps of human brain artery branches.

    Science.gov (United States)

    Canham, Peter B; Finlay, Helen M

    2004-05-01

    The bifurcation regions of the major human cerebral arteries are vulnerable to the formation of saccular aneurysms. A consistent feature of these bifurcations is a discontinuity of the tunica media at the apex of the flow divider. The objective was to measure the 3-dimensional geometry of these medial gaps or "medial defects." Nineteen bifurcations and 2 junctions of human cerebral arteries branches (from 4 male and 2 female subjects) were formalin-fixed at physiological pressure and processed for longitudinal serial sectioning. The apex and adjacent regions were examined and measurements were made from high-magnification photomicrographs, or projection microscope images, of the gap dimensions at multiple levels through the bifurcation. Plots were made of the width of the media as a function of distance from the apex. The media at each edge of the medial gap widened over a short distance, reaching the full width of the media of the contiguous daughter vessel. Medial gap dimensions were compared with the planar angle of the bifurcation, and a strong negative correlation was found, ie, the acute angled branches have the more prominent medial gaps. A discontinuity of the media at the apex was seen in all the bifurcations examined and was also found in the junction regions of brain arteries. We determined that the gap width is continuous with well-defined dimensions throughout its length and average length-to-width ratio of 6.9. The gaps were generally centered on the prominence of the apical ridge.

  15. Evidence for Functional Networks within the Human Brain's White Matter.

    Science.gov (United States)

    Peer, Michael; Nitzan, Mor; Bick, Atira S; Levin, Netta; Arzy, Shahar

    2017-07-05

    brain. However, most fMRI studies ignored a major part of the brain, the white-matter, discarding signals from it as arising from noise. Here we use resting-state fMRI data from 176 subjects to show that signals from the human white-matter contain meaningful information. We identify 12 functional networks composed of interacting long-distance white-matter tracts. Moreover, we show that these networks are highly correlated to resting-state gray-matter networks, highlighting their functional role. Our findings enable reinterpretation of many existing fMRI datasets, and suggest a new way to explore the white-matter role in cognition and its disturbances in neuropsychiatric disorders. Copyright © 2017 the authors 0270-6474/17/376394-14$15.00/0.

  16. Temperament, character and serotonin activity in the human brain

    DEFF Research Database (Denmark)

    Tuominen, L; Salo, J; Hirvonen, J

    2013-01-01

    The psychobiological model of personality by Cloninger and colleagues originally hypothesized that interindividual variability in the temperament dimension 'harm avoidance' (HA) is explained by differences in the activity of the brain serotonin system. We assessed brain serotonin transporter (5-HTT...

  17. Brain Imaging of Human Sexual Response: Recent Developments and Future Directions.

    Science.gov (United States)

    Ruesink, Gerben B; Georgiadis, Janniko R

    2017-01-01

    The purpose of this study is to provide a comprehensive summary of the latest developments in the experimental brain study of human sexuality, focusing on brain connectivity during the sexual response. Stable patterns of brain activation have been established for different phases of the sexual response, especially with regard to the wanting phase, and changes in these patterns can be linked to sexual response variations, including sexual dysfunctions. From this solid basis, connectivity studies of the human sexual response have begun to add a deeper understanding of the brain network function and structure involved. The study of "sexual" brain connectivity is still very young. Yet, by approaching the brain as a connected organ, the essence of brain function is captured much more accurately, increasing the likelihood of finding useful biomarkers and targets for intervention in sexual dysfunction.

  18. Impaired insulin action in the human brain: causes and metabolic consequences.

    Science.gov (United States)

    Heni, Martin; Kullmann, Stephanie; Preissl, Hubert; Fritsche, Andreas; Häring, Hans-Ulrich

    2015-12-01

    Over the past few years, evidence has accumulated that the human brain is an insulin-sensitive organ. Insulin regulates activity in a limited number of specific brain areas that are important for memory, reward, eating behaviour and the regulation of whole-body metabolism. Accordingly, insulin in the brain modulates cognition, food intake and body weight as well as whole-body glucose, energy and lipid metabolism. However, brain imaging studies have revealed that not everybody responds equally to insulin and that a substantial number of people are brain insulin resistant. In this Review, we provide an overview of the effects of insulin in the brain in humans and the relevance of the effects for physiology. We present emerging evidence for insulin resistance of the human brain. Factors associated with brain insulin resistance such as obesity and increasing age, as well as possible pathogenic factors such as visceral fat, saturated fatty acids, alterations at the blood-brain barrier and certain genetic polymorphisms, are reviewed. In particular, the metabolic consequences of brain insulin resistance are discussed and possible future approaches to overcome brain insulin resistance and thereby prevent or treat obesity and type 2 diabetes mellitus are outlined.

  19. Brain development in rodents and humans: Identifying benchmarks of maturation and vulnerability to injury across species

    Science.gov (United States)

    Semple, Bridgette D.; Blomgren, Klas; Gimlin, Kayleen; Ferriero, Donna M.; Noble-Haeusslein, Linda J.

    2013-01-01

    Hypoxic-ischemic and traumatic brain injuries are leading causes of long-term mortality and disability in infants and children. Although several preclinical models using rodents of different ages have been developed, species differences in the timing of key brain maturation events can render comparisons of vulnerability and regenerative capacities difficult to interpret. Traditional models of developmental brain injury have utilized rodents at postnatal day 7–10 as being