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Sample records for region reveals somatic

  1. Ultradeep sequencing of a human ultraconserved region reveals somatic and constitutional genomic instability.

    PubMed

    De Grassi, Anna; Segala, Cinzia; Iannelli, Fabio; Volorio, Sara; Bertario, Lucio; Radice, Paolo; Bernard, Loris; Ciccarelli, Francesca D

    2010-01-01

    Early detection of cancer-associated genomic instability is crucial, particularly in tumour types in which this instability represents the essential underlying mechanism of tumourigenesis. Currently used methods require the presence of already established neoplastic cells because they only detect clonal mutations. In principle, parallel sequencing of single DNA filaments could reveal the early phases of tumour initiation by detecting low-frequency mutations, provided an adequate depth of coverage and an effective control of the experimental error. We applied ultradeep sequencing to estimate the genomic instability of individuals with hereditary non-polyposis colorectal cancer (HNPCC). To overcome the experimental error, we used an ultraconserved region (UCR) of the human genome as an internal control. By comparing the mutability outside and inside the UCR, we observed a tendency of the ultraconserved element to accumulate significantly fewer mutations than the flanking segments in both neoplastic and nonneoplastic HNPCC samples. No difference between the two regions was detectable in cells from healthy donors, indicating that all three HNPCC samples have mutation rates higher than the healthy genome. This is the first, to our knowledge, direct evidence of an intrinsic genomic instability of individuals with heterozygous mutations in mismatch repair genes, and constitutes the proof of principle for the development of a more sensitive molecular assay of genomic instability.

  2. Next generation sequencing in sporadic retinoblastoma patients reveals somatic mosaicism.

    PubMed

    Amitrano, Sara; Marozza, Annabella; Somma, Serena; Imperatore, Valentina; Hadjistilianou, Theodora; De Francesco, Sonia; Toti, Paolo; Galimberti, Daniela; Meloni, Ilaria; Cetta, Francesco; Piu, Pietro; Di Marco, Chiara; Dosa, Laura; Lo Rizzo, Caterina; Carignani, Giulia; Mencarelli, Maria Antonietta; Mari, Francesca; Renieri, Alessandra; Ariani, Francesca

    2015-11-01

    In about 50% of sporadic cases of retinoblastoma, no constitutive RB1 mutations are detected by conventional methods. However, recent research suggests that, at least in some of these cases, there is somatic mosaicism with respect to RB1 normal and mutant alleles. The increased availability of next generation sequencing improves our ability to detect the exact percentage of patients with mosaicism. Using this technology, we re-tested a series of 40 patients with sporadic retinoblastoma: 10 of them had been previously classified as constitutional heterozygotes, whereas in 30 no RB1 mutations had been found in lymphocytes. In 3 of these 30 patients, we have now identified low-level mosaic variants, varying in frequency between 8 and 24%. In 7 out of the 10 cases previously classified as heterozygous from testing blood cells, we were able to test additional tissues (ocular tissues, urine and/or oral mucosa): in three of them, next generation sequencing has revealed mosaicism. Present results thus confirm that a significant fraction (6/40; 15%) of sporadic retinoblastoma cases are due to postzygotic events and that deep sequencing is an efficient method to unambiguously distinguish mosaics. Re-testing of retinoblastoma patients through next generation sequencing can thus provide new information that may have important implications with respect to genetic counseling and family care.

  3. Metabolite profiling reveals clear metabolic changes during somatic embryo development of Norway spruce (Picea abies).

    PubMed

    Businge, Edward; Brackmann, Klaus; Moritz, Thomas; Egertsdotter, Ulrika

    2012-02-01

    Progress on industrial-scale propagation of conifers by somatic embryogenesis has been hampered by the differences in developmental capabilities between cell lines, which are limiting the capture of genetic gains from breeding programs. In this study, we investigated the metabolic events occurring during somatic embryo development in Norway spruce to establish a better understanding of the fundamental metabolic events required for somatic embryo development. Three embryogenic cell lines of Norway spruce (Picea abies (L.) Karst) with different developmental capabilities were studied during somatic embryo development from proliferation of proembryogenic masses to mature somatic embryos. The three different cell lines displayed normal, aberrant and blocked somatic embryo development. Metabolite profiles from four development stages in each of the cell lines were obtained using combined gas chromatography-mass spectrometry. Multivariate discriminant analyses of the metabolic data revealed significant metabolites (P  ≤  0.05) for each development stage and transition. The results suggest that endogenous auxin and sugar signaling affects initial stages of somatic embryo development. Furthermore, the results highlight the importance of a timed stress response and the presence of stimulatory metabolites during late stages of embryo development.

  4. Developmental pathway of somatic embryogenesis in Picea abies as revealed by time-lapse tracking.

    PubMed

    Filonova, L H; Bozhkov, P V; von Arnold, S

    2000-02-01

    Several coniferous species can be propagated via somatic embryogenesis. This is a useful method for clonal propagation, but it can also be used for studying how embryo development is regulated in conifers. However, in conifers it is not known to what extent somatic and zygotic embryos develop similarly, because there has been little research on the origin and development of somatic embryos. A time-lapse tracking technique has been set up, and the development of more than 2000 single cells and few-celled aggregates isolated from embryogenic suspension cultures of Norway spruce (Picea abies L. Karst.) and embedded in thin layers of agarose has been traced. Experiments have shown that somatic embryos develop from proembryogenic masses which pass through a series of three characteristic stages distinguished by cellular organization and cell number (stages I, II and III) to transdifferentiate to somatic embryos. Microscopic inspection of different types of structures has revealed that proembryogenic masses are characterized by high interclonal variation of shape and cellular constitution. In contrast, somatic embryos are morphologically conservative structures, possessing a distinct protoderm-like cell layer as well as embryonal tube cells and suspensor. The lack of staining of the arabinogalactan protein epitope recognized by the monoclonal antibody JIM13 was shown to be an efficient marker for distinguishing proembryogenic masses from somatic embryos. The vast majority of cells in proembryogenic masses expressed this epitope and none of cells in the early somatic embryos. The conditions that promote cell proliferation (i.e. the presence of exogenous auxin and cytokinin), inhibit somatic embryo formation; instead, continuous multiplication of stage I proembryogenic masses by unequal division of embryogenic cells with dense cytoplasm is the prevailing process. Once somatic embryos have formed, their further development to mature forms requires abscisic acid and shares a

  5. L1-Associated Genomic Regions are Deleted in Somatic Cells of the Healthy Human Brain

    PubMed Central

    Erwin, Jennifer A.; Paquola, Apuã C.M.; Singer, Tatjana; Gallina, Iryna; Novotny, Mark; Quayle, Carolina; Bedrosian, Tracy; Ivanio, Francisco; Butcher, Cheyenne R.; Herdy, Joseph R.; Sarkar, Anindita; Lasken, Roger S.; Muotri, Alysson R.; Gage, Fred H.

    2016-01-01

    The healthy human brain is a mosaic of varied genomes. L1 retrotransposition is known to create mosaicism by inserting L1 sequences into new locations of somatic cell genomes. Using a machine learning-based, single-cell sequencing approach, we discovered that Somatic L1-Associated Variants (SLAVs) are actually composed of two classes: L1 retrotransposition insertions and retrotransposition-independent L1-associated variants. We demonstrate that a subset of SLAVs are, in fact, somatic deletions generated by L1 endonuclease cutting activity. Retrotransposition- independent rearrangements within inherited L1s resulted in the deletion of proximal genomic regions. These rearrangements were resolved by microhomology-mediated repair, which suggests that L1-associated genomic regions are hotspots for somatic copy number variants in the brain and therefore a heritable genetic contributor to somatic mosaicism. We demonstrate that SLAVs are present in crucial neural genes, such as DLG2/PSD93, and affect between 44–63% of cells of the cells in the healthy brain. PMID:27618310

  6. Somatic mutation in constant regions of mouse lambda 1 light chains.

    PubMed Central

    Motoyama, N; Okada, H; Azuma, T

    1991-01-01

    To study the distribution of somatic mutation, we determined nucleotide sequences of rearranged lambda 1-chain genomic DNA from four hybridomas obtained from C57BL/6 mice that had been immunized with (4-hydroxy-3-nitrophenyl)acetyl-conjugated chicken gamma globulin. In total, 114 nucleotide substitutions were observed, with neither insertion nor deletion. Sixty-one mutations occurred in the variable-joining region genes (V lambda 1-J lambda 1) and 49 in joining-constant (J lambda 1-C lambda 1) introns. Although frequency decreased with distance from the V lambda 1-J lambda 1 coding region, somatic mutations occurred in the entire J lambda 1-C lambda 1 intron and even in the C lambda 1 region. We found four nucleotide substitutions in C lambda 1 genes, all of which were replacement mutations. Therefore, the mechanism responsible for somatic mutation is operative into the C lambda 1 exons. Nucleotide sequences of rearranged but inactive lambda 2-chain genes from two hybridomas were also examined and compared with those of lambda 1-chain genes. The clustering of replacement mutations in complementarity-determining regions in the inactive lambda 2-chain genes similar to the active lambda 1-chain genes suggested a mechanism that induces somatic mutation preferentially in this region even in the absence of antigenic selection. PMID:1910169

  7. Regional gray matter volume and anxiety-related traits interact to predict somatic complaints in a non-clinical sample.

    PubMed

    Wei, Dongtao; Du, Xue; Li, Wenfu; Chen, Qunlin; Li, Haijiang; Hao, Xin; Zhang, Lei; Hitchman, Glenn; Zhang, Qinglin; Qiu, Jiang

    2015-01-01

    Somatic complaints can be important features of an individual's expression of anxiety. Anxiety-related traits are also risk factors for somatic symptoms. However, it is not known which neuroanatomical mechanisms may be responsible for this relationship. In this study, our first step was to use voxel-based morphometry (VBM) approaches to investigate the neuroanatomical basis underlying somatic complaints in a large sample of healthy subjects. We found a significant positive correlation between somatic complaints and parahippocampal gyrus (PHG) volume adjacent to the entorhinal cortex. Further analysis revealed that the interaction between PHG volume/entorhinal cortex and neuroticism-anxiety (N-Anx) predicted somatic complaints. Specifically, somatic complaints were associated with higher N-Anx for individuals with increased PHG volume. These findings suggest that increased PHG volume and higher trait anxiety can predict vulnerability to somatic complaints in the general population. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  8. Burkitt's lymphoma is a malignancy of mature B cells expressing somatically mutated V region genes.

    PubMed Central

    Klein, U.; Klein, G.; Ehlin-Henriksson, B.; Rajewsky, K.; Küppers, R.

    1995-01-01

    BACKGROUND: The developmental stage from which stems the malignant B cell population in Burkitt's lymphoma (BL) is unclear. An approach to answering this question is provided by the sequence analysis of rear-ranged immunoglobulin (Ig) variable region (V) genes from BL for evidence of somatic mutations, together with a phenotypic characterization. As somatic hypermutation of Ig V region genes occurs in germinal center B cells, somatically mutated Ig genes are found in germinal center B cells and their descendents. MATERIALS AND METHODS: Rearranged V kappa region genes from 10 kappa-expressing sporadic and endemic BL-derived cell lines (9 IgM and 1 IgG positive) and three kappa-expressing endemic BL biopsy specimens were amplified by polymerase chain reaction and sequenced. In addition, VH region gene sequences from these cell lines were determined. RESULTS: All BL cell lines and the three biopsy specimens carried somatically mutated V region genes. The average mutation frequency of rearranged V kappa genes from eight BL cell lines established from sporadic BL was 1.8%. A higher frequency (6%) was found in five endemic cases (three biopsy specimens and two BL cell lines). CONCLUSIONS: The detection of somatic mutations in the rearranged V region genes suggests that both sporadic and endemic BL represent a B-cell malignancy originating from germinal center B cells or their descendants. Interestingly, the mutation frequency detected in sporadic BL is in a range similar to that characteristic for IgM-expressing B cells in the human peripheral blood and for mu chain-expressing germinal center B cells, whereas the mutation frequency found in endemic BL is significantly higher. PMID:8529116

  9. Ultradeep analysis of tumor heterogeneity in regions of somatic hypermutation.

    PubMed

    Spence, Janice M; Spence, John P; Abumoussa, Andrew; Burack, W Richard

    2015-01-01

    Tumor heterogeneity is of growing importance in the treatment of cancers. Mutational hot spots are prime locations for determining number and proportions of low variant allele frequency (VAF) tumor subclones by next generation sequencing. Low VAF detection is complicated by poor mapping efficiency in regions with high mutation density. Our Deep-Drilling with iterative Mapping (DDiMAP) method retains variant allele patterns to aid in single nucleotide variation detection and generation of additional reference alleles, with remapping increasing coverage of highly mutated regions to capture data critical to heterogeneity analysis and enhancing sensitivity. DDiMAP outputs variant patterns with frequencies, enabling rapid phylogenetic analysis of ongoing mutation.

  10. Visceral and somatic pain modalities reveal NaV 1.7-independent visceral nociceptive pathways.

    PubMed

    Hockley, James R F; González-Cano, Rafael; McMurray, Sheridan; Tejada-Giraldez, Miguel A; McGuire, Cian; Torres, Antonio; Wilbrey, Anna L; Cibert-Goton, Vincent; Nieto, Francisco R; Pitcher, Thomas; Knowles, Charles H; Baeyens, José Manuel; Wood, John N; Winchester, Wendy J; Bulmer, David C; Cendán, Cruz Miguel; McMurray, Gordon

    2017-04-15

    Voltage-gated sodium channels play a fundamental role in determining neuronal excitability. Specifically, voltage-gated sodium channel subtype NaV 1.7 is required for sensing acute and inflammatory somatic pain in mice and humans but its significance in pain originating from the viscera is unknown. Using comparative behavioural models evoking somatic and visceral pain pathways, we identify the requirement for NaV 1.7 in regulating somatic (noxious heat pain threshold) but not in visceral pain signalling. These results enable us to better understand the mechanisms underlying the transduction of noxious stimuli from the viscera, suggest that the investigation of pain pathways should be undertaken in a modality-specific manner and help to direct drug discovery efforts towards novel visceral analgesics. Voltage-gated sodium channel NaV 1.7 is required for acute and inflammatory pain in mice and humans but its significance for visceral pain is unknown. Here we examine the role of NaV 1.7 in visceral pain processing and the development of referred hyperalgesia using a conditional nociceptor-specific NaV 1.7 knockout mouse (NaV 1.7(Nav1.8) ) and selective small-molecule NaV 1.7 antagonist PF-5198007. NaV 1.7(Nav1.8) mice showed normal nociceptive behaviours in response to intracolonic application of either capsaicin or mustard oil, stimuli known to evoke sustained nociceptor activity and sensitization following tissue damage, respectively. Normal responses following induction of cystitis by cyclophosphamide were also observed in both NaV 1.7(Nav1.8) and littermate controls. Loss, or blockade, of NaV 1.7 did not affect afferent responses to noxious mechanical and chemical stimuli in nerve-gut preparations in mouse, or following antagonism of NaV 1.7 in resected human appendix stimulated by noxious distending pressures. However, expression analysis of voltage-gated sodium channel α subunits revealed NaV 1.7 mRNA transcripts in nearly all retrogradely labelled colonic

  11. Characterization of conservative somatic instability of the CAG repeat region in Huntington`s disease

    SciTech Connect

    Schaefer, F.V.; Calikoglu, A.S.; Whetsell, L.H.

    1994-09-01

    Instability and enlargement of a CAG repeat region at the beginning of the huntingtin gene (IT-15) has been linked with Huntington`s disease. The CAG repeat size shows a highly significant correlation with age-of-onset of clinicial features in individuals with 40 or more repeats who have Huntington disease. The clinical status of nonsymptomatic individuals with 30 to 39 CAG repeats is considered ambiguous. In order to define more carefully the nature of the HD expansion instability, we examined patients in our HD population using a discriminating fluorescence-based PCR approach. The degree of somatic mutation increases with both earlier age of onset and the size of the inherited allele. A single prominent band one repeat larger than the index peak was typical in individuals with 40-41 CAG repeats. Three to four larger bands are typically discerned in individuals with 50 or more repeats. In an extreme example, an individual with approximately 95 repeats had at least 8 prominent bands. Plotting the degree of somatic mutation relative to the size of the HD allele shows somatic mutation activity increases with size. By this approach 40-60% of the alleles in a 40-41 CAG repeat HD loci is represented in the primary allele. In contrast, the primary allele represents a relatively minor proportion of the total alleles for expansions greater than 50 CAG repeats (10-20%). The limited range of somatic mutation suggest that the instability is restricted to very early stages of embryogenesis before tissue development diverges or that persistent somatic instability occurs at a slow rate. Therefore, the properties of somatic instability in Huntington`s disease have aspects that are both in common but also different from that found in other trinucleotide repeat expanding diseases such as myotonic muscular dystrophy and fragile X syndrome.

  12. Clustered somatic mutations are frequent in transcription factor binding motifs within proximal promoter regions in melanoma and other cutaneous malignancies

    PubMed Central

    Colebatch, Andrew J.; Di Stefano, Leon; Wong, Stephen Q.; Hannan, Ross D.; Waring, Paul M.; Dobrovic, Alexander

    2016-01-01

    Most cancer DNA sequencing studies have prioritized recurrent non-synonymous coding mutations in order to identify novel cancer-related mutations. Although attention is increasingly being paid to mutations in non-coding regions, standard approaches to identifying significant mutations may not be appropriate and there has been limited analysis of mutational clusters in functionally annotated non-coding regions. We sought to identify clustered somatic mutations (hotspot regions across samples) in functionally annotated regions in melanoma and other cutaneous malignancies (cutaneous squamous cell carcinoma, basal cell carcinoma and Merkel cell carcinoma). Sliding window analyses revealed numerous recurrent clustered hotspot mutations in proximal promoters, with some specific clusters present in up to 25% of cases. Mutations in melanoma were clustered within ETS and Sp1 transcription factor binding motifs, had a UV signature and were identified in other cutaneous malignancies. Clinicopathologic correlation and mutation analysis support a causal role for chronic UV irradiation generating somatic mutations in transcription factor binding motifs of proximal promoters. PMID:27611953

  13. Complex regional pain syndromes: the influence of cutaneous and deep somatic sympathetic innervation on pain.

    PubMed

    Schattschneider, Jörn; Binder, Andreas; Siebrecht, Dieter; Wasner, Gunnar; Baron, Ralf

    2006-01-01

    Complex regional pain syndromes (CRPS) can be relieved by sympathetic blockade. Different sympathetic efferent output channels innervate distinct effector organs (ie, cutaneous vasoconstrictor, muscle vasoconstrictor. and sudomotor neurons, as well as neurons innervating deep somatic tissues like bone, joints, and tendons). The aim of the present study was to elucidate in CRPS patients the sympathetically maintained pain (SMP) component that exclusively depends on cutaneous sympathetic activity compared with the SMP depending on the sympathetic innervation of deep somatic tissues. The sympathetic outflow to the painful skin was modulated selectively in awake humans. High and low cutaneous vasoconstrictor activity was produced in 12 CRPS type 1 patients by whole-body cooling and warming (thermal suit). Spontaneous pain was quantified during high and low cutaneous vasoconstrictor activity. By comparing the cutaneous SMP component with the change in pain that was achieved by modulation of the entire sympathetic outflow (sympathetic ganglion block), the SMP component originating in deep somatic structures was estimated. The relief of spontaneous pain after sympathetic blockade was more pronounced than changes in spontaneous pain that could be induced by selective sympathetic cutaneous modulation. The entire SMP component (cutaneous and deep) changes considerably over time. It is most prominent in the acute stages of CRPS. Sympathetic afferent coupling takes place in the skin and in the deep somatic tissues, but especially in the acute stages of CRPS, the pain component that is influenced by the sympathetic innervation of deep somatic structures is more important than the cutaneous activation. The entire sympathetic maintained pain component is not constant in the course of the disease but decreases over time.

  14. DNA-methylome analysis in Burkitt and follicular lymphomas identifies differentially methylated regions linked to somatic mutation and transcriptional control

    PubMed Central

    Betts, Matthew J.; Carrillo-de-Santa-Pau, Enrique; Doose, Gero; Gutwein, Jana; Richter, Julia; Hovestadt, Volker; Huang, Bingding; Rico, Daniel; Jühling, Frank; Kolarova, Julia; Lu, Qianhao; Otto, Christian; Wagener, Rabea; Arnolds, Judith; Burkhardt, Birgit; Claviez, Alexander; Drexler, Hans G.; Eberth, Sonja; Eils, Roland; Flicek, Paul; Haas, Siegfried; Humme, Michael; Karsch, Dennis; Kerstens, Hinrik H.D.; Klapper, Wolfram; Kreuz, Markus; Lawerenz, Chris; Lenzek, Dido; Loeffler, Markus; López, Cristina; MacLeod, Roderick A.F.; Martens, Joost H.A.; Kulis, Marta; Martín-Subero, José Ignacio; Möller, Peter; Nage, Inga; Picelli, Simone; Vater, Inga; Rohde, Marius; Rosenstiel, Philip; Rosolowski, Maciej; Russell, Robert B.; Schilhabel, Markus; Schlesner, Matthias; Stadler, Peter F.; Szczepanowski, Monika; Trümper, Lorenz; Stunnenberg, Hendrik G.; Küppers, Ralf; Ammerpohl, Ole; Lichter, Peter; Siebert, Reiner; Hoffmann, Steve; Radlwimmer, Bernhard

    2017-01-01

    In spite of both having features of germinal center B-cells, Burkitt lymphomas and follicular lymphomas are biologically and clinically quite diverse. We here performed whole genome bisulfite, genome and transcriptome sequencing from 13 IG-MYC-translocation positive Burkitt lymphoma, 9 BCL2-translocation positive follicular lymphoma and four normal germinal center B-cell samples. Comparison of Burkitt and follicular lymphoma samples revealed differential methylation of intragenic regions that strongly correlated with expression of associated genes, e.g. genes active in germinal center dark zone and light zone B-cells. Integrative pathway analyses of regions differentially methylated between Burkitt and follicular lymphoma implicated DNA methylation to cooperate with somatic mutation of sphingosine-phosphate signaling, as well as the TCF3/ID3 and SWI/SNF complexes in a large fraction of Burkitt lymphomas. Taken together, our results demonstrate a tight connection between somatic mutation, DNA methylation and transcriptional control in key B-cell pathways deregulated differentially between Burkitt and other germinal center B-cell lymphomas. PMID:26437030

  15. Some ethylene biosynthesis and AP2/ERF genes reveal a specific pattern of expression during somatic embryogenesis in Hevea brasiliensis

    PubMed Central

    2012-01-01

    Background Ethylene production and signalling play an important role in somatic embryogenesis, especially for species that are recalcitrant in in vitro culture. The AP2/ERF superfamily has been identified and classified in Hevea brasiliensis. This superfamily includes the ERFs involved in response to ethylene. The relative transcript abundance of ethylene biosynthesis genes and of AP2/ERF genes was analysed during somatic embryogenesis for callus lines with different regeneration potential, in order to identify genes regulated during that process. Results The analysis of relative transcript abundance was carried out by real-time RT-PCR for 142 genes. The transcripts of ERFs from group I, VII and VIII were abundant at all stages of the somatic embryogenesis process. Forty genetic expression markers for callus regeneration capacity were identified. Fourteen markers were found for proliferating calli and 35 markers for calli at the end of the embryogenesis induction phase. Sixteen markers discriminated between normal and abnormal embryos and, lastly, there were 36 markers of conversion into plantlets. A phylogenetic analysis comparing the sequences of the AP2 domains of Hevea and Arabidopsis genes enabled us to predict the function of 13 expression marker genes. Conclusions This first characterization of the AP2/ERF superfamily in Hevea revealed dramatic regulation of the expression of AP2/ERF genes during the somatic embryogenesis process. The gene expression markers of proliferating callus capacity to regenerate plants by somatic embryogenesis should make it possible to predict callus lines suitable to be used for multiplication. Further functional characterization of these markers opens up prospects for discovering specific AP2/ERF functions in the Hevea species for which somatic embryogenesis is difficult. PMID:23268714

  16. Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells.

    PubMed

    Abyzov, Alexej; Mariani, Jessica; Palejev, Dean; Zhang, Ying; Haney, Michael Seamus; Tomasini, Livia; Ferrandino, Anthony F; Rosenberg Belmaker, Lior A; Szekely, Anna; Wilson, Michael; Kocabas, Arif; Calixto, Nathaniel E; Grigorenko, Elena L; Huttner, Anita; Chawarska, Katarzyna; Weissman, Sherman; Urban, Alexander Eckehart; Gerstein, Mark; Vaccarino, Flora M

    2012-12-20

    Reprogramming somatic cells into induced pluripotent stem cells (iPSCs) has been suspected of causing de novo copy number variation. To explore this issue, here we perform a whole-genome and transcriptome analysis of 20 human iPSC lines derived from the primary skin fibroblasts of seven individuals using next-generation sequencing. We find that, on average, an iPSC line manifests two copy number variants (CNVs) not apparent in the fibroblasts from which the iPSC was derived. Using PCR and digital droplet PCR, we show that at least 50% of those CNVs are present as low-frequency somatic genomic variants in parental fibroblasts (that is, the fibroblasts from which each corresponding human iPSC line is derived), and are manifested in iPSC lines owing to their clonal origin. Hence, reprogramming does not necessarily lead to de novo CNVs in iPSCs, because most of the line-manifested CNVs reflect somatic mosaicism in the human skin. Moreover, our findings demonstrate that clonal expansion, and iPSC lines in particular, can be used as a discovery tool to reliably detect low-frequency CNVs in the tissue of origin. Overall, we estimate that approximately 30% of the fibroblast cells have somatic CNVs in their genomes, suggesting widespread somatic mosaicism in the human body. Our study paves the way to understanding the fundamental question of the extent to which cells of the human body normally acquire structural alterations in their DNA post-zygotically.

  17. Independent regulatory elements in the upstream region of the Drosophila beta 3 tubulin gene (beta Tub60D) guide expression in the dorsal vessel and the somatic muscles.

    PubMed

    Damm, C; Wolk, A; Buttgereit, D; Löher, K; Wagner, E; Lilly, B; Olson, E N; Hasenpusch-Theil, K; Renkawitz-Pohl, R

    1998-07-01

    The beta 3 tubulin gene (beta Tub60D) is a structural gene expressed during mesoderm development from the extended germ band stage onward. Expression within the individual mesodermal derivatives is guided by different control elements. The upstream regions allow expression in the dorsal vessel and the somatic mesoderm while enhancers localized in the first intron guide expression in the visceral mesoderm. Deletion analysis carried out in transgenic flies revealed independent regulatory elements for the dorsal vessel and the somatic mesoderm. For expression in the somatic mesoderm, a 279-bp region is absolutely essential. This region contains a binding site for the Drosophila myocyte-specific enhancer binding factor 2 (D-MEF2), a MADS-box transcription factor known to be essential for mesoderm development. Deletion or mutation of this D-MEF2 binding site strongly reduces transcription. This pattern is consistent with the strongly reduced expression of beta 3 tubulin in D-mef2 mutant embryos. This analysis furthermore reveals that the D-MEF2 binding site acts in concert with nearby cis regulatory elements. These data show that the upstream control region of the beta 3 tubulin gene is an early target of the D-MEF2 transcriptional activator.

  18. Decoding regulatory landscape of somatic embryogenesis reveals differential regulatory networks between japonica and indica rice subspecies

    PubMed Central

    Indoliya, Yuvraj; Tiwari, Poonam; Chauhan, Abhisekh Singh; Goel, Ridhi; Shri, Manju; Bag, Sumit Kumar; Chakrabarty, Debasis

    2016-01-01

    Somatic embryogenesis is a unique process in plants and has considerable interest for biotechnological application. Compare to japonica, indica rice has been less responsive to in vitro culture. We used Illumina Hiseq 2000 sequencing platform for comparative transcriptome analysis between two rice subspecies at six different developmental stages combined with a tag-based digital gene expression profiling. Global gene expression among different samples showed greater complexity in japonica rice compared to indica which may be due to polyphyletic origin of two rice subspecies. Expression pattern in initial stage indicate major differences in proembryogenic callus induction phase that may serve as key regulator to observe differences between both subspecies. Our data suggests that phytohormone signaling pathways consist of elaborate networks with frequent crosstalk, thereby allowing plants to regulate somatic embryogenesis pathway. However, this crosstalk varies between the two rice subspecies. Down regulation of positive regulators of meristem development (i.e. KNOX, OsARF5) and up regulation of its counterparts (OsRRs, MYB, GA20ox1/GA3ox2) in japonica may be responsible for its better regeneration and differentiation of somatic embryos. Comprehensive gene expression information in the present experiment may also facilitate to understand the monocot specific meristem regulation for dedifferentiation of somatic cell to embryogenic cells. PMID:26973288

  19. Decoding regulatory landscape of somatic embryogenesis reveals differential regulatory networks between japonica and indica rice subspecies.

    PubMed

    Indoliya, Yuvraj; Tiwari, Poonam; Chauhan, Abhisekh Singh; Goel, Ridhi; Shri, Manju; Bag, Sumit Kumar; Chakrabarty, Debasis

    2016-03-14

    Somatic embryogenesis is a unique process in plants and has considerable interest for biotechnological application. Compare to japonica, indica rice has been less responsive to in vitro culture. We used Illumina Hiseq 2000 sequencing platform for comparative transcriptome analysis between two rice subspecies at six different developmental stages combined with a tag-based digital gene expression profiling. Global gene expression among different samples showed greater complexity in japonica rice compared to indica which may be due to polyphyletic origin of two rice subspecies. Expression pattern in initial stage indicate major differences in proembryogenic callus induction phase that may serve as key regulator to observe differences between both subspecies. Our data suggests that phytohormone signaling pathways consist of elaborate networks with frequent crosstalk, thereby allowing plants to regulate somatic embryogenesis pathway. However, this crosstalk varies between the two rice subspecies. Down regulation of positive regulators of meristem development (i.e. KNOX, OsARF5) and up regulation of its counterparts (OsRRs, MYB, GA20ox1/GA3ox2) in japonica may be responsible for its better regeneration and differentiation of somatic embryos. Comprehensive gene expression information in the present experiment may also facilitate to understand the monocot specific meristem regulation for dedifferentiation of somatic cell to embryogenic cells.

  20. Clustering of Microarray Data Reveals Transcript Patterns Associated with Somatic Embryogenesis in Soybean1[w

    PubMed Central

    Thibaud-Nissen, Françoise; Shealy, Robin T.; Khanna, Anupama; Vodkin, Lila O.

    2003-01-01

    Globular somatic embryos can be induced from immature cotyledons of soybean (Glycine max L. Merr. cv Jack) placed on high levels of the auxin 2,4-dichlorophenoxyacetic acid (2,4-D). Somatic embryos develop from the adaxial side of the cotyledon, whereas the abaxial side evolves into a callus. Using a 9,280-cDNA clone array, we have compared steady-state RNA from the adaxial side from which embryos develop and from the abaxial callus at five time points over the course of the 4 weeks necessary for the development of globular embryos. In a second set of experiments, we have profiled the expression of each clone in the adaxial side during the same period. A total of 495 genes differentially expressed in at least one of these experiments were grouped according to the similarity of their expression profiles using a nonhierarchical clustering algorithm. Our results indicate that the appearance of somatic embryos is preceded by dedifferentiation of the cotyledon during the first 2 weeks on auxin. Changes in mRNA abundance of genes characteristic of oxidative stress and genes indicative of cell division in the adaxial side of the cotyledons suggest that the arrangement of the new cells into organized structures might depend on a genetically controlled balance between cell proliferation and cell death. Our data also suggest that the formation of somatic globular embryos is accompanied by the transcription of storage proteins and the synthesis of gibberellic acid. PMID:12746518

  1. Metabolic Profiling of Somatic Tissues from Monochamus alternatus (Coleoptera: Cerambycidae) Reveals Effects of Irradiation on Metabolism

    PubMed Central

    Qu, Liangjian; Wang, Lijuan; Wang, Qinghua; Wang, Yuzhu; Zhang, Yongan

    2014-01-01

    A high-level of sexual sterility is of importance for the sterile insect technique (SIT). However, the use of high-dose-intensity gamma radiation to induce sterility has negative impacts not only on reproductive cells but also on somatic cells. In this study, we investigated the metabolite differences in somatic tissues between non-irradiated, 20-Gy-irradiated, and 40-Gy-irradiated male Monochamus alternatus, an important vector of the pathogenic nematode, Bursaphelenchus xylophilus, which kills Asian pines. The results showed that metabolite levels changed moderately in the 20-Gy samples but were markedly altered in the 40-Gy samples compared with the non-irradiated samples. Twenty-six and 53 metabolites were disturbed by 20-Gy and 40-Gy radiation, respectively. Thirty-six metabolites were found to be markedly altered in the 40-Gy samples but were not changed significantly in the 20-Gy samples. The comprehensive metabolomic disorders induced by 40-Gy radiation dysregulated six metabolic pathways involved in the life process. The findings presented in this manuscript will contribute to our knowledge of the characteristic metabolic changes associated with gamma-radiation-induced damage to somatic cells and will allow for better exploration of the SIT for the control of this target pest. PMID:24937685

  2. Metabolic profiling of somatic tissues from Monochamus alternatus (Coleoptera: Cerambycidae) reveals effects of irradiation on metabolism.

    PubMed

    Qu, Liangjian; Wang, Lijuan; Wang, Qinghua; Wang, Yuzhu; Zhang, Yongan

    2014-06-16

    A high-level of sexual sterility is of importance for the sterile insect technique (SIT). However, the use of high-dose-intensity gamma radiation to induce sterility has negative impacts not only on reproductive cells but also on somatic cells. In this study, we investigated the metabolite differences in somatic tissues between non-irradiated, 20-Gy-irradiated, and 40-Gy-irradiated male Monochamus alternatus, an important vector of the pathogenic nematode, Bursaphelenchus xylophilus, which kills Asian pines. The results showed that metabolite levels changed moderately in the 20-Gy samples but were markedly altered in the 40-Gy samples compared with the non-irradiated samples. Twenty-six and 53 metabolites were disturbed by 20-Gy and 40-Gy radiation, respectively. Thirty-six metabolites were found to be markedly altered in the 40-Gy samples but were not changed significantly in the 20-Gy samples. The comprehensive metabolomic disorders induced by 40-Gy radiation dysregulated six metabolic pathways involved in the life process. The findings presented in this manuscript will contribute to our knowledge of the characteristic metabolic changes associated with gamma-radiation-induced damage to somatic cells and will allow for better exploration of the SIT for the control of this target pest.

  3. DNA methylation analysis on satellite I region in blastocysts obtained from somatic cell cloned cattle.

    PubMed

    Yamanaka, Ken-Ichi; Kaneda, Masahiro; Inaba, Yasushi; Saito, Koji; Kubota, Kaiyu; Sakatani, Miki; Sugimura, Satoshi; Imai, Kei; Watanabe, Shinya; Takahashi, Masashi

    2011-08-01

    Many observations have been made on cloned embryos and on adult clones by somatic cell nuclear transfer (SCNT), but it is still unclear whether the progeny of cloned animals is presenting normal epigenetic status. Here, in order to accumulate the information for evaluating the normality of cloned cattle, we analyzed the DNA methylation status on satellite I region in blastocysts obtained from cloned cattle. Embryos were produced by artificial insemination (AI) to non-cloned or cloned dams using semen from non-cloned or cloned sires. After 7 days of AI, embryos at blastocyst stage were collected by uterine flushing. The DNA methylation levels in embryos obtained by using semen and/or oocytes from cloned cattle were similar to those in in vivo embryos from non-cloned cattle. In contrast, the DNA methylation levels in SCNT embryos were significantly higher (P < 0.01) than those in in vivo embryos from non-cloned and cloned cattle, approximately similar to those in somatic cells used as donor cells. Thus, this study provides useful information that epigenetic status may be normal in the progeny of cloned cattle, suggesting the normality of germline cells in cloned cattle. 2011 The Authors. Animal Science Journal © 2011 Japanese Society of Animal Science.

  4. Regional localization of DNA sequences on chromosome 21 using somatic cell hybrids.

    PubMed Central

    Van Keuren, M L; Watkins, P C; Drabkin, H A; Jabs, E W; Gusella, J F; Patterson, D

    1986-01-01

    We have used a panel of Chinese hamster X human somatic cell hybrids, each containing various portions of chromosome 21 as the only detectable human chromosome component, for regional mapping of cloned, chromosome 21-derived DNA sequences. Thirty unique and very low-repeat sequences were mapped to the short arm and three sections of the long arm. Three unique sequences map to the proximal part of the terminal band 21q22.3, and five to the distal part of this band. Some of these may represent parts of gene sequences that may be relevant to the pathogenesis of Down syndrome, as 21q22 is the area required to be present in triplicate for the full clinical picture. Images Fig. 1 PMID:3014865

  5. Somatic mutation profiles of clear cell endometrial tumors revealed by whole exome and targeted gene sequencing.

    PubMed

    Le Gallo, Matthieu; Rudd, Meghan L; Urick, Mary Ellen; Hansen, Nancy F; Zhang, Suiyuan; Lozy, Fred; Sgroi, Dennis C; Vidal Bel, August; Matias-Guiu, Xavier; Broaddus, Russell R; Lu, Karen H; Levine, Douglas A; Mutch, David G; Goodfellow, Paul J; Salvesen, Helga B; Mullikin, James C; Bell, Daphne W

    2017-09-01

    The molecular pathogenesis of clear cell endometrial cancer (CCEC), a tumor type with a relatively unfavorable prognosis, is not well defined. We searched exome-wide for novel somatically mutated genes in CCEC and assessed the mutational spectrum of known and candidate driver genes in a large cohort of cases. We conducted whole exome sequencing of paired tumor-normal DNAs from 16 cases of CCEC (12 CCECs and the CCEC components of 4 mixed histology tumors). Twenty-two genes-of-interest were Sanger-sequenced from another 47 cases of CCEC. Microsatellite instability (MSI) and microsatellite stability (MSS) were determined by genotyping 5 mononucleotide repeats. Two tumor exomes had relatively high mutational loads and MSI. The other 14 tumor exomes were MSS and had 236 validated nonsynonymous or splice junction somatic mutations among 222 protein-encoding genes. Among the 63 cases of CCEC in this study, we identified frequent somatic mutations in TP53 (39.7%), PIK3CA (23.8%), PIK3R1 (15.9%), ARID1A (15.9%), PPP2R1A (15.9%), SPOP (14.3%), and TAF1 (9.5%), as well as MSI (11.3%). Five of 8 mutations in TAF1, a gene with no known role in CCEC, localized to the putative histone acetyltransferase domain and included 2 recurrently mutated residues. Based on patterns of MSI and mutations in 7 genes, CCEC subsets molecularly resembled serous endometrial cancer (SEC) or endometrioid endometrial cancer (EEC). Our findings demonstrate molecular similarities between CCEC and SEC and EEC and implicate TAF1 as a novel candidate CCEC driver gene. Cancer 2017;123:3261-8. © 2017 American Cancer Society. © 2017 American Cancer Society.

  6. Somatic mutations reveal asymmetric cellular dynamics in the early human embryo

    DOE PAGES

    Ju, Young Seok; Martincorena, Inigo; Gerstung, Moritz; ...

    2017-03-22

    Somatic cells acquire mutations throughout the course of an individual’s life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and theirmore » contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. As a result, this study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.« less

  7. Somatic mutations reveal asymmetric cellular dynamics in the early human embryo.

    PubMed

    Ju, Young Seok; Martincorena, Inigo; Gerstung, Moritz; Petljak, Mia; Alexandrov, Ludmil B; Rahbari, Raheleh; Wedge, David C; Davies, Helen R; Ramakrishna, Manasa; Fullam, Anthony; Martin, Sancha; Alder, Christopher; Patel, Nikita; Gamble, Steve; O'Meara, Sarah; Giri, Dilip D; Sauer, Torril; Pinder, Sarah E; Purdie, Colin A; Borg, Åke; Stunnenberg, Henk; van de Vijver, Marc; Tan, Benita K T; Caldas, Carlos; Tutt, Andrew; Ueno, Naoto T; van 't Veer, Laura J; Martens, John W M; Sotiriou, Christos; Knappskog, Stian; Span, Paul N; Lakhani, Sunil R; Eyfjörd, Jórunn Erla; Børresen-Dale, Anne-Lise; Richardson, Andrea; Thompson, Alastair M; Viari, Alain; Hurles, Matthew E; Nik-Zainal, Serena; Campbell, Peter J; Stratton, Michael R

    2017-03-30

    Somatic cells acquire mutations throughout the course of an individual's life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and their contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. This study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.

  8. Aldosterone-Producing Adenoma With a Somatic KCNJ5 Mutation Revealing APC-Dependent Familial Adenomatous Polyposis.

    PubMed

    Vouillarmet, Julien; Fernandes-Rosa, Fabio; Graeppi-Dulac, Julia; Lantelme, Pierre; Decaussin-Petrucci, Myriam; Thivolet, Charles; Peix, Jean-Louis; Boulkroun, Sheerazed; Clauser, Eric; Zennaro, Maria-Christina

    2016-11-01

    Recurrent somatic mutations in KCNJ5, CACNA1D, ATP1A1, and ATP2B3 have been identified in aldosterone-producing adenomas (APAs). The question as to whether they are responsible for both nodulation and aldosterone production is not solved. We describe the case of a young patient who was diagnosed with severe arterial hypertension due to primary aldosteronism at age 26 years, followed by hemorrhagic stroke 4 years later. Abdominal computed tomography showed bilateral macronodular adrenal hyperplasia. Identification of lateralized aldosterone secretion led to right adrenalectomy, followed by normalization of biochemical and hormonal parameters and amelioration of blood pressure. The resected adrenal showed three nodules, one of them expressing aldosterone synthase and harboring a somatic KNCJ5 mutation. A Weiss revisited index of 3 of the APA prompted us to perform a second 18F-2-fluoro-2-deoxy-D-glucose-positron emission tomography after surgery, which revealed abnormal rectal activity despite the absence of clinical symptoms. Gastrointestinal exploration showed multiple polyps with severe dysplasia, and the diagnosis of familial adenomatous polyposis was established in the presence of a germline heterozygous APC gene mutation. Sequencing of somatic DNA from the APA and a second adrenal nodule revealed biallelic APC inactivation due to loss of heterozygosity in both nodules. This case report underlines the need for establishing the frequency of germline APC variants in patients with primary aldosteronism and bilateral macronodular adrenal hyperplasia because their presence may predispose to APA development and severe hypertension well before the first familial adenomatous polyposis symptoms appear. From a mechanistic point of view, it supports a two-hit model for APA development, whereby the first hit drives increased cell proliferation whereas the second hit specifies the pattern of hormonal secretion.

  9. Somatic Cell Fusions Reveal Extensive Heterogeneity in Basal-like Breast Cancer.

    PubMed

    Su, Ying; Subedee, Ashim; Bloushtain-Qimron, Noga; Savova, Virginia; Krzystanek, Marcin; Li, Lewyn; Marusyk, Andriy; Tabassum, Doris P; Zak, Alexander; Flacker, Mary Jo; Li, Mei; Lin, Jessica J; Sukumar, Saraswati; Suzuki, Hiromu; Long, Henry; Szallasi, Zoltan; Gimelbrant, Alexander; Maruyama, Reo; Polyak, Kornelia

    2015-06-16

    Basal-like and luminal breast tumors have distinct clinical behavior and molecular profiles, yet the underlying mechanisms are poorly defined. To interrogate processes that determine these distinct phenotypes and their inheritance pattern, we generated somatic cell fusions and performed integrated genetic and epigenetic (DNA methylation and chromatin) profiling. We found that the basal-like trait is generally dominant and is largely defined by epigenetic repression of luminal transcription factors. Definition of super-enhancers highlighted a core program common in luminal cells but a high degree of heterogeneity in basal-like breast cancers that correlates with clinical outcome. We also found that protein extracts of basal-like cells are sufficient to induce a luminal-to-basal phenotypic switch, implying a trigger of basal-like autoregulatory circuits. We determined that KDM6A might be required for luminal-basal fusions, and we identified EN1, TBX18, and TCF4 as candidate transcriptional regulators of the luminal-to-basal switch. Our findings highlight the remarkable epigenetic plasticity of breast cancer cells.

  10. Mammary Stem Cell Based Somatic Mouse Models Reveal Breast Cancer Drivers Causing Cell Fate Dysregulation

    PubMed Central

    Zhang, Zheng; Christin, John R.; Wang, Chunhui; Ge, Kai; Oktay, Maja H.; Guo, Wenjun

    2016-01-01

    SUMMARY Cancer genomics have provided an unprecedented opportunity for understanding genetic causes of human cancer. However, distinguishing which mutations are functionally relevant to cancer pathogenesis remains a major challenge. We describe here a mammary stem cell (MaSC) organoid-based approach for rapid generation of somatic GEMMs (genetically engineered mouse models). By using RNAi and CRISPR-mediated genome engineering in MaSC-GEMMs, we have discovered that inactivation of Ptpn22 or Mll3, two genes mutated in human breast cancer, greatly accelerated PI3K-driven mammary tumorigenesis. Using these tumor models, we have also identified genetic alterations promoting tumor metastasis and causing resistance to PI3K-targeted therapy. Both Ptpn22 and Mll3 inactivation resulted in disruption of mammary gland differentiation and an increase in stem cell activity. Mechanistically, Mll3 deletion enhanced stem cell activity through activation of the HIF pathway. Thus, our study established a robust in vivo platform for functional cancer genomics and discovered functional breast cancer mutations. PMID:27653681

  11. Thin and thick primary cutaneous melanomas reveal distinct patterns of somatic copy number alterations

    PubMed Central

    Apollo, Alessandro; Pescucci, Chiara; Licastro, Danilo; Urso, Carmelo; Gerlini, Gianni; Borgognoni, Lorenzo; Luzzatto, Lucio; Stecca, Barbara

    2016-01-01

    Cutaneous melanoma is one of the most aggressive type of skin tumor. Early stage melanoma can be often cured by surgery; therefore current management guidelines dictate a different approach for thin (<1mm) versus thick (>4mm) melanomas. We have carried out whole-exome sequencing in 5 thin and 5 thick fresh-frozen primary cutaneous melanomas. Unsupervised hierarchical clustering analysis of somatic copy number alterations (SCNAs) identified two groups corresponding to thin and thick melanomas. The most striking difference between them was the much greater abundance of SCNAs in thick melanomas, whereas mutation frequency did not significantly change between the two groups. We found novel mutations and focal SCNAs in genes that are embryonic regulators of axon guidance, predominantly in thick melanomas. Analysis of publicly available microarray datasets provided further support for a potential role of Ephrin receptors in melanoma progression. In addition, we have identified a set of SCNAs, including amplification of BRAF and ofthe epigenetic modifier EZH2, that are specific for the group of thick melanomas that developed metastasis during the follow-up. Our data suggest that mutations occur early during melanoma development, whereas SCNAs might be involved in melanoma progression. PMID:27095580

  12. Gene Regulation by the AGL15 Transcription Factor Reveals Hormone Interactions in Somatic Embryogenesis1[OPEN

    PubMed Central

    Zheng, Qiaolin; Zheng, Yumei; Ji, Huihua; Burnie, Whitney

    2016-01-01

    The MADS box transcription factor Arabidopsis (Arabidopsis thaliana) AGAMOUS-LIKE15 (AGL15) and a putative ortholog from soybean (Glycine max), GmAGL15, are able to promote somatic embryogenesis (SE) in these plants when ectopically expressed. SE is an important means of plant regeneration, but many plants, or even particular cultivars, are recalcitrant for this process. Understanding how (Gm)AGL15 promotes SE by identifying and characterizing direct and indirect downstream regulated genes can provide means to improve regeneration by SE for crop improvement and to perform molecular tests of genes. Conserved transcription factors and the genes they regulate in common between species may provide the most promising avenue to identify targets for SE improvement. We show that (Gm)AGL15 negatively regulates auxin signaling in both Arabidopsis and soybean at many levels of the pathway, including the repression of AUXIN RESPONSE FACTOR6 (ARF6) and ARF8 and TRANSPORT INHIBITOR RESPONSE1 as well as the indirect control of components via direct expression of a microRNA-encoding gene. We demonstrate interaction between auxin and gibberellic acid in the promotion of SE and document an inverse correlation between bioactive gibberellic acid and SE in soybean, a difficult crop to transform. Finally, we relate hormone accumulation to transcript accumulation of important soybean embryo regulatory factors such as ABSCISIC ACID INSENSITIVE3 and FUSCA3 and provide a working model of hormone and transcription factor interaction in the control of SE. PMID:27794101

  13. Humanization of Antibodies Using Heavy Chain Complementarity-determining Region 3 Grafting Coupled with in Vitro Somatic Hypermutation*

    PubMed Central

    Bowers, Peter M.; Neben, Tamlyn Y.; Tomlinson, Geoffery L.; Dalton, Jennifer L.; Altobell, Larry; Zhang, Xue; Macomber, John L.; Wu, Betty F.; Toobian, Rachelle M.; McConnell, Audrey D.; Verdino, Petra; Chau, Betty; Horlick, Robert A.; King, David J.

    2013-01-01

    A method for simultaneous humanization and affinity maturation of monoclonal antibodies has been developed using heavy chain complementarity-determining region (CDR) 3 grafting combined with somatic hypermutation in vitro. To minimize the amount of murine antibody-derived antibody sequence used during humanization, only the CDR3 region from a murine antibody that recognizes the cytokine hβNGF was grafted into a nonhomologous human germ line V region. The resulting CDR3-grafted HC was paired with a CDR-grafted light chain, displayed on the surface of HEK293 cells, and matured using in vitro somatic hypermutation. A high affinity humanized antibody was derived that was considerably more potent than the parental antibody, possessed a low pm dissociation constant, and demonstrated potent inhibition of hβNGF activity in vitro. The resulting antibody contained half the heavy chain murine donor sequence compared with the same antibody humanized using traditional methods. PMID:23355464

  14. Analysis of the rolC promoter region involved in somatic embryogenesis-related activation in carrot cell cultures.

    PubMed Central

    Fujii, N; Yokoyama, R; Uchimiya, H

    1994-01-01

    In cell cultures of carrot (Daucus carota L.), somatic embryogenesis can be induced by transferring cells from a medium containing 2,4-dichlorophenoxyacetic acid (2,4-D) to one devoid of 2,4-D. Previous analysis of transgenic carrot cells containing the 5' non-coding sequence of the Ri plasmid rolC and a structural gene for bacterial beta-glucuronidase (uidA) has shown that the chimeric gene is actively expressed after induction of somatic embryogenesis. In this study, we demonstrate that activation of the rolC promoter is dependent on the process of embryo development but not on the duration of the cell culture in 2,4-D-free medium. We also analyzed the cis region of the rolC promoter that is responsible for somatic embryogenesis-related activation (SERA), namely relatively low beta-glucuronidase (GUS) activity in calli and proembryogenic masses (PEM) and high GUS activity in heart- and torpedo-stage embryos. When the -255-bp region of the rolC gene was used, SERA was retained. Internal deletions within this -255-bp region did not alter SERA by the rolC promoter. Furthermore, when a rolC promoter fragment (-848 to -94 bp) was fused to the cauliflower mosaic virus (CaMV) 35S core region (-90 to +6 bp), it conferred relatively low GUS activity in calli and PEM but high GUS activity in heart and torpedo embryos. When -848 to -255-bp or -255- to -94-bp fragments of the rolC promoter were fused to the same CaMV 35S core region, GUS activity patterns were not related to somatic embryogenesis. These results suggest that the combination of several regulatory regions in the rolC promoter may be required for SERA in carrot cell cultures. PMID:8016259

  15. Regional localization of the CCAAT displacement protein gene (CUTL1) to 7q22 by analysis of somatic cell hybrids

    SciTech Connect

    Scherer, S.W.; Tsui, L.C. The Hospital for Sick Children, Toronto, Ontario ); Neufeld, E.J.; Lievens, P.M.J. Dana Farber Cancer Inst., Cambridge, MA Harvard Medical School, Cambridge, MA ); Orkin, S.H. Dana Farber Cancer Inst., Cambridge, MA Harvard Medical School, Cambridge, MA Howard Hughes Medical Inst., Cambridge, MA ); Kim, J. )

    1993-03-01

    CCAAT displacement protein (CDP) is a putative repressor of tissue-specific gene expression, implicated in regulation of expression of the human myeloid-specific gene, gp91-phox. The cDNA sequence of the human gene predicts a polypeptide of 1506 amino acids, with a homeodomain and three repeated motifs closely homologous to cut, a protein known to specify the cell fate of peripheral neurons and other tissues during embryonic development of Drosophila. Therefore, the human gene locus for CDP has been named CUTL1, for cut-like 1. Preliminary data revealed that CUTL1 mapped to human chromosome 7 (E.J.N., P.M.-J.L., and S.H.O., unpublished results). Since diseases with abnormalities of myeloid differentitation often have aberrations of chromosome 7, especially in patients previously exposed to mutagenic agents or radiation therapy, the cell-type specificity of CDP makes it an attractive candidate for involvement in these conditions. As a first step in addressing this question, we have examined the regional localization of CUTL1 using a panel of rodent-human somatic cell hybrids containing various portions of chromosome 7. The results of our hybridization analysis are summarized. The regional localization of CUTL1 to 7q22 was based primarily on the negative hybridization signal with the human/hamster hybrid 1EF2/3/K017 (7cen-q21) and the positive result with 1CF2/5/K016 (7cen-q22). Since no hybridization signal was detected in GM1059Rag5 (a human-mouse hybrid carrying a single human chromosome 7 with an interstitial deletion 7pter-q22:q32-qter) and 2068Rag22-2 (7qter-q22), the regional assignment of CUTL1 could be narrowed to the distal boundary of 7q22.

  16. Somatic sex-specific transcriptome differences in Drosophila revealed by whole transcriptome sequencing

    PubMed Central

    2011-01-01

    Background Understanding animal development and physiology at a molecular-biological level has been advanced by the ability to determine at high resolution the repertoire of mRNA molecules by whole transcriptome resequencing. This includes the ability to detect and quantify rare abundance transcripts and isoform-specific mRNA variants produced from a gene. The sex hierarchy consists of a pre-mRNA splicing cascade that directs the production of sex-specific transcription factors that specify nearly all sexual dimorphism. We have used deep RNA sequencing to gain insight into how the Drosophila sex hierarchy generates somatic sex differences, by examining gene and transcript isoform expression differences between the sexes in adult head tissues. Results Here we find 1,381 genes that differ in overall expression levels and 1,370 isoform-specific transcripts that differ between males and females. Additionally, we find 512 genes not regulated downstream of transformer that are significantly more highly expressed in males than females. These 512 genes are enriched on the × chromosome and reside adjacent to dosage compensation complex entry sites, which taken together suggests that their residence on the × chromosome might be sufficient to confer male-biased expression. There are no transcription unit structural features, from a set of features, that are robustly significantly different in the genes with significant sex differences in the ratio of isoform-specific transcripts, as compared to random isoform-specific transcripts, suggesting that there is no single molecular mechanism that generates isoform-specific transcript differences between the sexes, even though the sex hierarchy is known to include three pre-mRNA splicing factors. Conclusions We identify thousands of genes that show sex-specific differences in overall gene expression levels, and identify hundreds of additional genes that have differences in the abundance of isoform-specific transcripts. No

  17. Exome and deep sequencing of clinically aggressive neuroblastoma reveal somatic mutations that affect key pathways involved in cancer progression

    PubMed Central

    Lasorsa, Vito Alessandro; Formicola, Daniela; Pignataro, Piero; Cimmino, Flora; Calabrese, Francesco Maria; Mora, Jaume; Esposito, Maria Rosaria; Pantile, Marcella; Zanon, Carlo; De Mariano, Marilena; Longo, Luca; Hogarty, Michael D.; de Torres, Carmen; Tonini, Gian Paolo; Iolascon, Achille; Capasso, Mario

    2016-01-01

    The spectrum of somatic mutation of the most aggressive forms of neuroblastoma is not completely determined. We sought to identify potential cancer drivers in clinically aggressive neuroblastoma. Whole exome sequencing was conducted on 17 germline and tumor DNA samples from high-risk patients with adverse events within 36 months from diagnosis (HR-Event3) to identify somatic mutations and deep targeted sequencing of 134 genes selected from the initial screening in additional 48 germline and tumor pairs (62.5% HR-Event3 and high-risk patients), 17 HR-Event3 tumors and 17 human-derived neuroblastoma cell lines. We revealed 22 significantly mutated genes, many of which implicated in cancer progression. Fifteen genes (68.2%) were highly expressed in neuroblastoma supporting their involvement in the disease. CHD9, a cancer driver gene, was the most significantly altered (4.0% of cases) after ALK. Other genes (PTK2, NAV3, NAV1, FZD1 and ATRX), expressed in neuroblastoma and involved in cell invasion and migration were mutated at frequency ranged from 4% to 2%. Focal adhesion and regulation of actin cytoskeleton pathways, were frequently disrupted (14.1% of cases) thus suggesting potential novel therapeutic strategies to prevent disease progression. Notably BARD1, CHEK2 and AXIN2 were enriched in rare, potentially pathogenic, germline variants. In summary, whole exome and deep targeted sequencing identified novel cancer genes of clinically aggressive neuroblastoma. Our analyses show pathway-level implications of infrequently mutated genes in leading neuroblastoma progression. PMID:27009842

  18. Transcript profiling reveals complex auxin signalling pathway and transcription regulation involved in dedifferentiation and redifferentiation during somatic embryogenesis in cotton

    PubMed Central

    2012-01-01

    Background Somatic embryogenesis (SE), by which somatic cells of higher plants can dedifferentiate and reorganize into new plants, is a notable illustration of cell totipotency. However, the precise molecular mechanisms regulating SE remain unclear. To characterize the molecular events of this unique process, transcriptome analysis, in combination with biochemical and histological approaches, were conducted in cotton, a typical plant species in SE. Genome-wide profiling of gene expression allowed the identification of novel molecular markers characteristic of this developmental process. Results RNA-Seq was used to identify 5,076 differentially expressed genes during cotton SE. Expression profile and functional assignments of these genes indicated significant transcriptional complexity during this process, associated with morphological, histological changes and endogenous indole-3-acetic acid (IAA) alteration. Bioinformatics analysis showed that the genes were enriched for basic processes such as metabolic pathways and biosynthesis of secondary metabolites. Unigenes were abundant for the functions of protein binding and hydrolase activity. Transcription factor–encoding genes were found to be differentially regulated during SE. The complex pathways of auxin abundance, transport and response with differentially regulated genes revealed that the auxin-related transcripts belonged to IAA biosynthesis, indole-3-butyric acid (IBA) metabolism, IAA conjugate metabolism, auxin transport, auxin-responsive protein/indoleacetic acid-induced protein (Aux/IAA), auxin response factor (ARF), small auxin-up RNA (SAUR), Aux/IAA degradation, and other auxin-related proteins, which allow an intricate system of auxin utilization to achieve multiple purposes in SE. Quantitative real-time PCR (qRT-PCR) was performed on selected genes with different expression patterns and functional assignments were made to demonstrate the utility of RNA-Seq for gene expression profiles during cotton SE

  19. Linking Regions between Helices in Bacteriorhodopsin Revealed

    PubMed Central

    Agard, David A.; Stroud, Robert M.

    1982-01-01

    Three-dimensional electron-microscopic structural analysis requires the combination of many different tilted views of the same specimen. The relative difficulty of tilting the sample to high angles >60° without introducing severe distortion due to different focal distances across the specimen entails that the observable range of electron diffraction data is often limited to this range of angles. Thus, it is generally not possible to observe the diffraction maxima that lie within the conical region of reciprocal space around the direction perpendicular to the electron microscope grid. The absence of data in this region leads to a predictable distortion in the object, and for ±60° tilting makes the resolution essentially twice as bad in the direction perpendicular to the grid as it is for the in-plane image. Constrained density map modification and refinement methods can significantly reduce these effects. A method has been developed, tested on model cases, and applied to the electron-microscopic structure determination of bacteriorhodopsin in order to visualize the location of linking regions between helices. Electron-microscopic structural analysis of bacteriorhodopsin (Henderson and Unwin. 1975 Nature [Lond.] 257:28-32.) showed that the molecule consists of seven rods of density each nearly spanning the lipid bilayer. Owing to the distortion introduced by the missing conical region of reciprocal space data, no density was visible for the polypeptide segments linking the α-helices. Density in the refined maps indicates the location of at least five of the extrahelical segments of the polypeptide. The total number of possible ways of interconnecting the helices is reduced from 7! (5,040) to the five most consistent possibilities without recourse to other considerations. In addition, the density for the helical regions is more uniform and cylindrical throughout their length, and the length of the helices increases from 35 to 45 Å, close to the membrane thickness

  20. Ultra-sensitive sequencing reveals an age-related increase in somatic mitochondrial mutations that are inconsistent with oxidative damage.

    PubMed

    Kennedy, Scott R; Salk, Jesse J; Schmitt, Michael W; Loeb, Lawrence A

    2013-01-01

    Mitochondrial DNA (mtDNA) is believed to be highly vulnerable to age-associated damage and mutagenesis by reactive oxygen species (ROS). However, somatic mtDNA mutations have historically been difficult to study because of technical limitations in accurately quantifying rare mtDNA mutations. We have applied the highly sensitive Duplex Sequencing methodology, which can detect a single mutation among >10(7) wild type molecules, to sequence mtDNA purified from human brain tissue from both young and old individuals with unprecedented accuracy. We find that the frequency of point mutations increases ~5-fold over the course of 80 years of life. Overall, the mutation spectra of both groups are comprised predominantly of transition mutations, consistent with misincorporation by DNA polymerase γ or deamination of cytidine and adenosine as the primary mutagenic events in mtDNA. Surprisingly, G → T mutations, considered the hallmark of oxidative damage to DNA, do not significantly increase with age. We observe a non-uniform, age-independent distribution of mutations in mtDNA, with the D-loop exhibiting a significantly higher mutation frequency than the rest of the genome. The coding regions, but not the D-loop, exhibit a pronounced asymmetric accumulation of mutations between the two strands, with G → A and T → C mutations occurring more often on the light strand than the heavy strand. The patterns and biases we observe in our data closely mirror the mutational spectrum which has been reported in studies of human populations and closely related species. Overall our results argue against oxidative damage being a major driver of aging and suggest that replication errors by DNA polymerase γ and/or spontaneous base hydrolysis are responsible for the bulk of accumulating point mutations in mtDNA.

  1. Conditional Inactivation of Upstream Binding Factor Reveals Its Epigenetic Functions and the Existence of a Somatic Nucleolar Precursor Body

    PubMed Central

    Hamdane, Nourdine; Stefanovsky, Victor Y.; Tremblay, Michel G.; Németh, Attila; Paquet, Eric; Lessard, Frédéric; Sanij, Elaine; Hannan, Ross; Moss, Tom

    2014-01-01

    Upstream Binding Factor (UBF) is a unique multi-HMGB-box protein first identified as a co-factor in RNA polymerase I (RPI/PolI) transcription. However, its poor DNA sequence selectivity and its ability to generate nucleosome-like nucleoprotein complexes suggest a more generalized role in chromatin structure. We previously showed that extensive depletion of UBF reduced the number of actively transcribed ribosomal RNA (rRNA) genes, but had little effect on rRNA synthesis rates or cell proliferation, leaving open the question of its requirement for RPI transcription. Using gene deletion in mouse, we now show that UBF is essential for embryo development beyond morula. Conditional deletion in cell cultures reveals that UBF is also essential for transcription of the rRNA genes and that it defines the active chromatin conformation of both gene and enhancer sequences. Loss of UBF prevents formation of the SL1/TIF1B pre-initiation complex and recruitment of the RPI-Rrn3/TIF1A complex. It is also accompanied by recruitment of H3K9me3, canonical histone H1 and HP1α, but not by de novo DNA methylation. Further, genes retain penta-acetyl H4 and H2A.Z, suggesting that even in the absence of UBF the rRNA genes can maintain a potentially active state. In contrast to canonical histone H1, binding of H1.4 is dependent on UBF, strongly suggesting that it plays a positive role in gene activity. Unexpectedly, arrest of rRNA synthesis does not suppress transcription of the 5S, tRNA or snRNA genes, nor expression of the several hundred mRNA genes implicated in ribosome biogenesis. Thus, rRNA gene activity does not coordinate global gene expression for ribosome biogenesis. Loss of UBF also unexpectedly induced the formation in cells of a large sub-nuclear structure resembling the nucleolar precursor body (NPB) of oocytes and early embryos. These somatic NPBs contain rRNA synthesis and processing factors but do not associate with the rRNA gene loci (NORs). PMID:25121932

  2. Tissue-specific signaling networks rewired by major somatic mutations in human cancer revealed by proteome-wide discovery.

    PubMed

    Zhao, Junfei; Cheng, Feixiong; Zhao, Zhongming

    2017-03-31

    Massive somatic mutations discovered by large cancer genome sequencing projects provide unprecedented opportunities in the development of precision oncology. However, deep understanding of functional consequences of somatic mutations and identifying actionable mutations and the related drug responses currently remain formidable challenges. Dysfunction of protein post-translational modification plays critical roles in tumorigenesis and drug responses. In this study, we proposed a novel computational oncoproteomics approach, named kinome-wide network module for cancer pharmacogenomics (KNMPx), for identifying actionable mutations that rewired signaling networks and further characterized tumorigenesis and anticancer drug responses. Specifically, we integrated 746,631 missense mutations in 4,997 tumor samples across 16 major cancer types/subtypes from The Cancer Genome Atlas into over 170,000 carefully curated non-redundant phosphorylation sites covering 18,610 proteins. We found 47 mutated proteins (e.g., ERBB2, TP53, and CTNNB1) that had enriched missense mutations at their phosphorylation sites in pan-cancer analysis. In addition, tissue-specific kinase-substrate interaction modules altered by somatic mutations identified by KNMPx were significantly associated with patient survival. We further reported a kinome-wide landscape of pharmacogenomic interactions by incorporating somatic mutation-rewired signaling networks in 1,001 cancer cell lines via KNMPx. Interestingly, we found that cell lines could highly reproduce oncogenic phosphorylation site mutations identified in primary tumors, supporting the confidence in their associations with sensitivity/resistance of inhibitors targeting EGF, MAPK, PI3K, mTOR, and Wnt signaling pathways. In summary, this systematic oncoproteomics analysis of kinome phosphorylation site mutations illustrates new capabilities to speed the development of precision oncology.

  3. Induced somatic sector analysis of cellulose synthase (CesA) promoter regions in woody stem tissues.

    PubMed

    Creux, Nicky M; Bossinger, Gerd; Myburg, Alexander A; Spokevicius, Antanas V

    2013-03-01

    The increasing focus on plantation forestry as a renewable source of cellulosic biomass has emphasized the need for tools to study the unique biology of woody genera such as Eucalyptus, Populus and Pinus. The domestication of these woody crops is hampered by long generation times, and breeders are now looking to molecular approaches such as marker-assisted breeding and genetic modification to accelerate tree improvement. Much of what is known about genes involved in the growth and development of plants has come from studies of herbaceous models such as Arabidopsis and rice. However, transferring this information to woody plants often proves difficult, especially for genes expressed in woody stems. Here we report the use of induced somatic sector analysis (ISSA) for characterization of promoter expression patterns directly in the stems of Populus and Eucalyptus trees. As a case study, we used previously characterized primary and secondary cell wall-related cellulose synthase (CesA) promoters cloned from Eucalyptus grandis. We show that ISSA can be used to elucidate the phloem and xylem expression patterns of the CesA genes in Eucalyptus and Populus stems and also show that the staining patterns differ in Eucalyptus and Populus stems. These findings show that ISSA is an efficient approach to investigate promoter function in the developmental context of woody plant tissues and raise questions about the suitability of heterologous promoters for genetic manipulation in plant species.

  4. Integrity of immunoglobulin variable region is supported by GANP during AID-induced somatic hypermutation in germinal center B cells.

    PubMed

    Eid, Mohammed Mansour Abbas; Shimoda, Mayuko; Singh, Shailendra Kumar; Almofty, Sarah Ameen; Pham, Phuong; Goodman, Myron F; Maeda, Kazuhiko; Sakaguchi, Nobuo

    2017-05-24

    Immunoglobulin (Ig) affinity maturation depends on somatic hypermutation (SHM) in variable (V) regions initiated by activation-induced cytidine deaminase (AID). AID induces transition mutations by C→U deamination on both strands, causing C:G→T:A. Error-prone repairs of U by base excision and mismatch repairs create transversion mutations at C/G and mutations at A/T sites. In Neuberger's model, it remained to clarify how transition/transversion repair is regulated. We investigate role of AID-interacting GANP (germinal-center associated nuclear protein) in IgV SHM profile. GANP enhances transition mutation of nontranscribed-strand G and reduces mutation at A, restricted to GYW of AID hotspot motif. It reduces DNA polymerase η hotspot mutations associated with mismatch repairs followed by uracil-DNA glycosylase. Mutation comparison between IgV complementary and framework regions by Statistical Bayesian estimation demonstrates GANP supports to preserve IgV framework region genomic sequences. GANP works to maintain antibody structure by reducing drastic changes in IgV framework region in affinity maturation. © The Author 2017. Published by Oxford University Press on behalf of The Japanese Society for Immunology.

  5. Whole Transcriptome Profiling of Maize during Early Somatic Embryogenesis Reveals Altered Expression of Stress Factors and Embryogenesis-Related Genes

    PubMed Central

    Salvo, Stella A. G. D.; Hirsch, Candice N.; Buell, C. Robin; Kaeppler, Shawn M.; Kaeppler, Heidi F.

    2014-01-01

    Embryogenic tissue culture systems are utilized in propagation and genetic engineering of crop plants, but applications are limited by genotype-dependent culture response. To date, few genes necessary for embryogenic callus formation have been identified or characterized. The goal of this research was to enhance our understanding of gene expression during maize embryogenic tissue culture initiation. In this study, we highlight the expression of candidate genes that have been previously regarded in the literature as having important roles in somatic embryogenesis. We utilized RNA based sequencing (RNA-seq) to characterize the transcriptome of immature embryo explants of the highly embryogenic and regenerable maize genotype A188 at 0, 24, 36, 48, and 72 hours after placement of explants on tissue culture initiation medium. Genes annotated as functioning in stress response, such as glutathione-S-transferases and germin-like proteins, and genes involved with hormone transport, such as PINFORMED, increased in expression over 8-fold in the study. Maize genes with high sequence similarity to genes previously described in the initiation of embryogenic cultures, such as transcription factors BABY BOOM, LEAFY COTYLEDON, and AGAMOUS, and important receptor-like kinases such as SOMATIC EMBRYOGENESIS RECEPTOR LIKE KINASES and CLAVATA, were also expressed in this time course study. By combining results from whole genome transcriptome analysis with an in depth review of key genes that play a role in the onset of embryogenesis, we propose a model of coordinated expression of somatic embryogenesis-related genes, providing an improved understanding of genomic factors involved in the early steps of embryogenic culture initiation in maize and other plant species. PMID:25356773

  6. Local sequence assembly reveals a high-resolution profile of somatic structural variations in 97 cancer genomes.

    PubMed

    Zhuang, Jiali; Weng, Zhiping

    2015-09-30

    Genomic structural variations (SVs) are pervasive in many types of cancers. Characterizing their underlying mechanisms and potential molecular consequences is crucial for understanding the basic biology of tumorigenesis. Here, we engineered a local assembly-based algorithm (laSV) that detects SVs with high accuracy from paired-end high-throughput genomic sequencing data and pinpoints their breakpoints at single base-pair resolution. By applying laSV to 97 tumor-normal paired genomic sequencing datasets across six cancer types produced by The Cancer Genome Atlas Research Network, we discovered that non-allelic homologous recombination is the primary mechanism for generating somatic SVs in acute myeloid leukemia. This finding contrasts with results for the other five types of solid tumors, in which non-homologous end joining and microhomology end joining are the predominant mechanisms. We also found that the genes recursively mutated by single nucleotide alterations differed from the genes recursively mutated by SVs, suggesting that these two types of genetic alterations play different roles during cancer progression. We further characterized how the gene structures of the oncogene JAK1 and the tumor suppressors KDM6A and RB1 are affected by somatic SVs and discussed the potential functional implications of intergenic SVs.

  7. Whole-genome sequencing of bladder cancers reveals somatic CDKN1A mutations and clinicopathological associations with mutation burden.

    PubMed

    Cazier, J-B; Rao, S R; McLean, C M; Walker, A K; Walker, A L; Wright, B J; Jaeger, E E M; Kartsonaki, C; Marsden, L; Yau, C; Camps, C; Kaisaki, P; Taylor, J; Catto, J W; Tomlinson, I P M; Kiltie, A E; Hamdy, F C

    2014-04-29

    Bladder cancers are a leading cause of death from malignancy. Molecular markers might predict disease progression and behaviour more accurately than the available prognostic factors. Here we use whole-genome sequencing to identify somatic mutations and chromosomal changes in 14 bladder cancers of different grades and stages. As well as detecting the known bladder cancer driver mutations, we report the identification of recurrent protein-inactivating mutations in CDKN1A and FAT1. The former are not mutually exclusive with TP53 mutations or MDM2 amplification, showing that CDKN1A dysfunction is not simply an alternative mechanism for p53 pathway inactivation. We find strong positive associations between higher tumour stage/grade and greater clonal diversity, the number of somatic mutations and the burden of copy number changes. In principle, the identification of sub-clones with greater diversity and/or mutation burden within early-stage or low-grade tumours could identify lesions with a high risk of invasive progression.

  8. Revealing of HII-regions in Galaxies with Panoramic Spectroscopy

    NASA Astrophysics Data System (ADS)

    Hakopian, S. A.; Balayan, S. K.

    2016-06-01

    Observations intended to investigation and revealing of nodes of processes of nuclear and starforming activity in galaxies were performed via panoramic spectroscopy. Data obtained on Mrk 1050 revealed evidence of starforming activity also outside the central engine of high surface brightness. Two small HII-regions, being likely a part of the chain, are located in the part of the spiral branch coming from the nucleus part.

  9. Somatic Point Mutations in mtDNA Control Region Are Influenced by Genetic Background and Associated with Healthy Aging: A GEHA Study

    PubMed Central

    Rose, Giuseppina; Romeo, Giuseppe; Dato, Serena; Crocco, Paolina; Bruni, Amalia C.; Hervonen, Antti; Majamaa, Kari; Sevini, Federica; Franceschi, Claudio; Passarino, Giuseppe

    2010-01-01

    Tissue specific somatic mutations occurring in the mtDNA control region have been proposed to provide a survival advantage. Data on twins and on relatives of long-lived subjects suggested that the occurrence/accumulation of these mutations may be genetically influenced. To further investigate control region somatic heteroplasmy in the elderly, we analyzed the segment surrounding the nt 150 position (previously reported as specific of Leukocytes) in various types of leukocytes obtained from 195 ultra-nonagenarians sib-pairs of Italian or Finnish origin collected in the frame of the GEHA Project. We found a significant correlation of the mtDNA control region heteroplasmy between sibs, confirming a genetic influence on this phenomenon. Furthermore, many subjects showed heteroplasmy due to mutations different from the C150T transition. In these cases heteroplasmy was correlated within sibpairs in Finnish and northern Italian samples, but not in southern Italians. This suggested that the genetic contribution to control region mutations may be population specific. Finally, we observed a possible correlation between heteroplasmy and Hand Grip strength, one of the best markers of physical performance and of mortality risk in the elderly. Our study provides new evidence on the relevance of mtDNA somatic mutations in aging and longevity and confirms that the occurrence of specific point mutations in the mtDNA control region may represent a strategy for the age-related remodelling of organismal functions. PMID:20976236

  10. Acquired somatic mutations in PNH reveal long-term maintenance of adaptive NK cells independent of HSPCs.

    PubMed

    Corat, Marcus A F; Schlums, Heinrich; Wu, Chuanfeng; Theorell, Jakob; Espinoza, Diego A; Sellers, Stephanie E; Townsley, Danielle M; Young, Neal S; Bryceson, Yenan T; Dunbar, Cynthia E; Winkler, Thomas

    2017-04-06

    Natural killer (NK) cells have long been considered short-lived effectors of innate immunity. However, recent animal models and human studies suggest that subsets of NK cells have adaptive features. We investigate clonal relationships of various NK-cell subsets, including the adaptive population, by taking advantage of naturally occurring X-linked somatic PIGA mutations in hematopoietic stem and progenitor cells (HSPCs) from patients with paroxysmal nocturnal hemoglobinuria (PNH). The affected HSPCs and their progeny lack expression of glycosylphosphatidylinositol (GPI) anchors on their cell surface, allowing quantification of PIGA-mutant (GPI-negative) HSPC-derived peripheral blood cell populations. The fraction of GPI-negative cells within the CD56(dim) NK cells was markedly lower than that of neutrophils and the CD56(bright) NK-cell compartments. This discrepancy was most prominent within the adaptive CD56(dim) NK-cell population lacking PLZF expression. The functional properties of these adaptive NK cells were similar in PNH patients and healthy individuals. Our findings support the existence of a long-lived, adaptive NK-cell population maintained independently from GPI(pos)CD56(dim).

  11. Somatic MED12 Nonsense Mutation Escapes mRNA Decay and Reveals a Motif Required for Nuclear Entry.

    PubMed

    Heikkinen, Tuomas; Kämpjärvi, Kati; Keskitalo, Salla; von Nandelstadh, Pernilla; Liu, Xiaonan; Rantanen, Ville; Pitkänen, Esa; Kinnunen, Matias; Kuusanmäki, Heikki; Kontro, Mika; Turunen, Mikko; Mäkinen, Netta; Taipale, Jussi; Heckman, Caroline; Lehti, Kaisa; Mustjoki, Satu; Varjosalo, Markku; Vahteristo, Pia

    2017-03-01

    MED12 is a key component of the transcription-regulating Mediator complex. Specific missense and in-frame insertion/deletion mutations in exons 1 and 2 have been identified in uterine leiomyomas, breast tumors, and chronic lymphocytic leukemia. Here, we characterize the first MED12 5' end nonsense mutation (c.97G>T, p.E33X) identified in acute lymphoblastic leukemia and show that it escapes nonsense-mediated mRNA decay (NMD) by using an alternative translation initiation site. The resulting N-terminally truncated protein is unable to enter the nucleus due to the lack of identified nuclear localization signal (NLS). The absence of NLS prevents the mutant MED12 protein to be recognized by importin-α and subsequent loading into the nuclear pore complex. Due to this mislocalization, all interactions between the MED12 mutant and other Mediator components are lost. Our findings provide new mechanistic insights into the MED12 functions and indicate that somatic nonsense mutations in early exons may avoid NMD.

  12. Collapse of germline piRNAs in the absence of Argonaute3 reveals somatic piRNAs in flies.

    PubMed

    Li, Chengjian; Vagin, Vasily V; Lee, Soohyun; Xu, Jia; Ma, Shengmei; Xi, Hualin; Seitz, Hervé; Horwich, Michael D; Syrzycka, Monika; Honda, Barry M; Kittler, Ellen L W; Zapp, Maria L; Klattenhoff, Carla; Schulz, Nadine; Theurkauf, William E; Weng, Zhiping; Zamore, Phillip D

    2009-05-01

    Piwi-interacting RNAs (piRNAs) silence transposons in animal germ cells. piRNAs are thought to derive from long transcripts spanning transposon-rich genomic loci and to direct an autoamplification loop in which an antisense piRNA, bound to Aubergine or Piwi protein, triggers production of a sense piRNA bound to the PIWI protein Argonaute3 (Ago3). In turn, the new piRNA is envisioned to produce a second antisense piRNA. Here, we describe strong loss-of-function mutations in ago3, allowing a direct genetic test of this model. We find that Ago3 acts to amplify piRNA pools and to enforce on them an antisense bias, increasing the number of piRNAs that can act to silence transposons. We also detect a second, Ago3-independent piRNA pathway centered on Piwi. Transposons targeted by this second pathway often reside in the flamenco locus, which is expressed in somatic ovarian follicle cells, suggesting a role for piRNAs beyond the germline.

  13. Characterization of a panel of somatic cell hybrids for regional mapping of the mouse X chromosome

    SciTech Connect

    Avner, P.; Arnaud, D.; Amar, L.; Cambrou, J.; Winking, H.; Russell, L.B.

    1987-08-01

    A panel of five hybrid cell lines containing mouse X chromosomes with various deletions has been obtained by fusing splenocytes from male mice carrying one of a series of reciprocal X-autosome translocations with the azaguanine-resistant Chinese hamster cell line CH3g. These hybrids have been extensively characterized by using the allozymes hypoxanthine/guanine phosphoribosyltransferase (encoded by the Hprt locus) and ..cap alpha..-galactosidase (Ags) and a series of 11 X-chromosome-specific DNA probes whose localization had been previously established by linkage studies. Such studies have established the genetic breakpoints of the T(X;12)13R1 and T(X;2)14R1 X-autosome translocations on the X chromosome and provided additional information as to the X-chromosome genetic breakpoints of the T(X;16)16H, T(X;4)7R1, and T(X;7)6R1 translocations. The data establish clearly that both the T(X;7)5RI and T(X;12)13R1 X-chromosome breakpoints are proximal to Hprt, the breakpoint of the former being more centromeric, lying as it does in the 9-centimorgan interval between the ornithine transcarbamoylase (Otc) and DXPas7 (M2C) loci. These five hybrid cell lines provide, with the previously characterized EBS4 hybrid cell line, a nested series of seven mapping intervals distributed along the length of the mouse X chromosome. Their characterization not only allows further correlation of the genetic and cytological X-chromosome maps but also should permit the rapid identification of DNA probes specific for particular regions of the mouse X chromosome.

  14. Diversity of somatic coliphages in coastal regions with different levels of anthropogenic activity in São Paulo State, Brazil.

    PubMed

    Burbano-Rosero, E M; Ueda-Ito, M; Kisielius, J J; Nagasse-Sugahara, T K; Almeida, B C; Souza, C P; Markman, C; Martins, G G; Albertini, L; Rivera, I N G

    2011-06-01

    Bacteriophages are the most abundant and genetically diverse viruses on Earth, with complex ecology in both quantitative and qualitative terms. Somatic coliphages (SC) have been reported to be good indicators of fecal pollution in seawater. This study focused on determining the concentration of SC and their diversity by electron microscopy of seawater, plankton, and bivalve samples collected at three coastal regions in São Paulo, Brazil. The SC counts varied from <1 to 3.4 × 10(3) PFU/100 ml in seawater (73 samples tested), from <1 to 4.7 × 10(2) PFU/g in plankton (46 samples tested), and from <1 to 2.2 × 10(1) PFU/g in bivalves (11 samples tested). In seawater samples, a relationship between the thermotolerant coliforms and Escherichia coli and SC was observed at the three regions (P = 0.0001) according to the anthropogenic activities present at each region. However, SC were found in plankton samples from three regions: Baixada Santista (17/20), Canal de São Sebastião (6/14), and Ubatuba (3/12). In seawater samples collected from Baixada Santista, four morphotypes were observed: A1 (4.5%), B1 (50%), C1 (36.4%), and D1 (9.1%). One coliphage, Siphoviridae type T1, had the longest tail: between 939 and 995 nm. In plankton samples, Siphoviridae (65.8%), Podoviridae (15.8%), Microviridae (15.8%), and Myoviridae (2.6%) were found. In bivalves, only the morphotype B1 was observed. These SC were associated with enteric hosts: enterobacteria, E. coli, Proteus, Salmonella, and Yersinia. Baixada Santista is an area containing a high level of fecal pollution compared to those in the Canal de São Sebastião and Ubatuba. This is the first report of coliphage diversity in seawater, plankton, and bivalve samples collected from São Paulo coastal regions. A better characterization of SC diversity in coastal environments will help with the management and evaluation of the microbiological risks for recreation, seafood cultivation, and consumption.

  15. Ultra-deep sequencing detects ovarian cancer cells in peritoneal fluid and reveals somatic TP53 mutations in noncancerous tissues.

    PubMed

    Krimmel, Jeffrey D; Schmitt, Michael W; Harrell, Maria I; Agnew, Kathy J; Kennedy, Scott R; Emond, Mary J; Loeb, Lawrence A; Swisher, Elizabeth M; Risques, Rosa Ana

    2016-05-24

    Current sequencing methods are error-prone, which precludes the identification of low frequency mutations for early cancer detection. Duplex sequencing is a sequencing technology that decreases errors by scoring mutations present only in both strands of DNA. Our aim was to determine whether duplex sequencing could detect extremely rare cancer cells present in peritoneal fluid from women with high-grade serous ovarian carcinomas (HGSOCs). These aggressive cancers are typically diagnosed at a late stage and are characterized by TP53 mutations and peritoneal dissemination. We used duplex sequencing to analyze TP53 mutations in 17 peritoneal fluid samples from women with HGSOC and 20 from women without cancer. The tumor TP53 mutation was detected in 94% (16/17) of peritoneal fluid samples from women with HGSOC (frequency as low as 1 mutant per 24,736 normal genomes). Additionally, we detected extremely low frequency TP53 mutations (median mutant fraction 1/13,139) in peritoneal fluid from nearly all patients with and without cancer (35/37). These mutations were mostly deleterious, clustered in hotspots, increased with age, and were more abundant in women with cancer than in controls. The total burden of TP53 mutations in peritoneal fluid distinguished cancers from controls with 82% sensitivity (14/17) and 90% specificity (18/20). Age-associated, low frequency TP53 mutations were also found in 100% of peripheral blood samples from 15 women with and without ovarian cancer (none with hematologic disorder). Our results demonstrate the ability of duplex sequencing to detect rare cancer cells and provide evidence of widespread, low frequency, age-associated somatic TP53 mutation in noncancerous tissue.

  16. Slowly inactivating component of Na+ current in peri-somatic region of hippocampal CA1 pyramidal neurons

    PubMed Central

    Park, Yul Young; Johnston, Daniel

    2013-01-01

    The properties of voltage-gated ion channels on the neuronal membrane shape electrical activity such as generation and backpropagation of action potentials, initiation of dendritic spikes, and integration of synaptic inputs. Subthreshold currents mediated by sodium channels are of interest because of their activation near rest, slow inactivation kinetics, and consequent effects on excitability. Modulation of these currents can also perturb physiological responses of a neuron that might underlie pathological states such as epilepsy. Using nucleated patches from the peri-somatic region of hippocampal CA1 neurons, we recorded a slowly inactivating component of the macroscopic Na+ current (which we have called INaS) that shared many biophysical properties with the persistent Na+ current, INaP, but showed distinctively faster inactivating kinetics. Ramp voltage commands with a velocity of 400 mV/s were found to elicit this component of Na+ current reliably. INaS also showed a more hyperpolarized I-V relationship and slower inactivation than those of the fast transient Na+ current (INaT) recorded in the same patches. The peak amplitude of INaS was proportional to the peak amplitude of INaT but was much smaller in amplitude. Hexanol, riluzole, and ranolazine, known Na+ channel blockers, were tested to compare their effects on both INaS and INaT. The peak conductance of INaS was preferentially blocked by hexanol and riluzole, but the shift of half-inactivation voltage (V1/2) was only observed in the presence of riluzole. Current-clamp measurements with hexanol suggested that INaS was involved in generation of an action potential and in upregulation of neuronal excitability. PMID:23236005

  17. Slowly inactivating component of Na+ current in peri-somatic region of hippocampal CA1 pyramidal neurons.

    PubMed

    Park, Yul Young; Johnston, Daniel; Gray, Richard

    2013-03-01

    The properties of voltage-gated ion channels on the neuronal membrane shape electrical activity such as generation and backpropagation of action potentials, initiation of dendritic spikes, and integration of synaptic inputs. Subthreshold currents mediated by sodium channels are of interest because of their activation near rest, slow inactivation kinetics, and consequent effects on excitability. Modulation of these currents can also perturb physiological responses of a neuron that might underlie pathological states such as epilepsy. Using nucleated patches from the peri-somatic region of hippocampal CA1 neurons, we recorded a slowly inactivating component of the macroscopic Na(+) current (which we have called INaS) that shared many biophysical properties with the persistent Na(+) current, INaP, but showed distinctively faster inactivating kinetics. Ramp voltage commands with a velocity of 400 mV/s were found to elicit this component of Na(+) current reliably. INaS also showed a more hyperpolarized I-V relationship and slower inactivation than those of the fast transient Na(+) current (INaT) recorded in the same patches. The peak amplitude of INaS was proportional to the peak amplitude of INaT but was much smaller in amplitude. Hexanol, riluzole, and ranolazine, known Na(+) channel blockers, were tested to compare their effects on both INaS and INaT. The peak conductance of INaS was preferentially blocked by hexanol and riluzole, but the shift of half-inactivation voltage (V1/2) was only observed in the presence of riluzole. Current-clamp measurements with hexanol suggested that INaS was involved in generation of an action potential and in upregulation of neuronal excitability.

  18. Somatic diversification in the heavy chain variable region genes expressed by human autoantibodies bearing a lupus-associated nephritogenic anti-DNA idiotype

    SciTech Connect

    Demaison, C.; Chastagner, P.; Theze, J.; Zouali, M. )

    1994-01-18

    Monoclonal anti-DNA antibodies bearing a lupus nephritis-associated idiotype were derived from five patients with systemic lupus erythematosus (SLE). Genes encoding their heavy (H)-chain variable (V[sub H]) regions were cloned and sequenced. When compared with their closest V[sub h] germ-line gene relatives, these sequences exhibit a number of silent (S) and replacement (R) substitutions. The ratios of R/S mutations were much higher in the complementarity-determining regions (CDRs) of the antibodies than in the framework regions. Molecular amplification of genomic V[sub H] genes and Southern hybridization with somatic CDR2-specific oligonucleotide probes showed that the configuration of the V[sub H] genes corresponding to V[sub H] sequences in the nephritogenic antibodies is not present in the patient's own germ-line DNA, implying that the B-cell clones underwent somatic mutation in vivo. These findings, together with the characteristics of the diversity and junctional gene elements utilized to form the antibody, indicate that these autoantibodies have been driven through somatic selection processes reminiscent of those that govern antibody responses triggered by exogenous stimuli.

  19. ISSR and isozyme characterization of androgenetic dihaploids reveals tetrasomic inheritance in tetraploid somatic hybrids between Solanum melongena and Solanum aethiopicum group Gilo.

    PubMed

    Toppino, Laura; Mennella, Giuseppe; Rizza, Fulvia; D'Alessandro, Antonietta; Sihachakr, Darasinh; Rotino, Giuseppe L

    2008-01-01

    Gene exchanges between Solanum melongena and its allied relative Solanum aethiopicum are a crucial prerequisite for introgression of useful traits from the allied species into the cultivated eggplant. In order to evaluate the extent of genetic recombination between the 2 species, biochemical and molecular markers were employed. A dihaploid population obtained through anther culture of the corresponding tetraploid somatic hybrids was genetically analyzed. The extent of disomic/tetrasomic inheritance and segregation ratios of 3 isozyme systems and intersimple sequence repeat (ISSR) markers were evaluated. The dihaploids, being derived from microspores, allowed for simple, complete, and accurate analyses. The segregation of 280 ISSR markers (110 aethiopicum-specific, 104 melongena-specific, and 66 monomorphic) were evaluated in 71 dihaploids. According to the genetic constitution (simplex/duplex/triplex), almost 64% of the fragments revealed the tetrasomic and/or disomic inheritance. With regard to the assigned species-specific fragments, 68% and 4% were unambiguously the result of tetrasomic and disomic inheritance, respectively. Twenty-four of the 66 monomorphic ISSRs were inherited according to random chromatid segregation. The phenotypes of glucose-6-phosphate dehydrogenase (G-6-PDH), 6-phosphogluconate dehydrogenase (6-PGDH), and shikimate dehydrogenase (SKDH) were studied in 70 dihaploids and inferences were made about the allelic state of their 5 loci. The isozyme markers segregated in the dihaploids in a distorted manner, their segregations did not fit in with any of the expected segregation ratios. However, tetrasomic inheritance might be suggested for G-6-PDH 2 and SKDH 1 loci. Our results demonstrated that gene exchanges occurred readily in the somatic hybrids between S. melongena and S. aethiopicum gr. Gilo.

  20. Spring-Block Model Reveals Region-Like Structures

    PubMed Central

    Máté, Gabriell; Néda, Zoltán; Benedek, József

    2011-01-01

    A mechanical spring-block model is used for realizing an objective space partition of settlements from a geographic territory in region-like structures. The method is based on the relaxation-dynamics of the spring-block system and reveals in a hierarchical manner region-like entities at different spatial scales. It takes into account in an elegant manner both the spatiality of the elements and the connectivity relations among them. Spatiality is taken into account by using the geographic coordinates of the settlements, and by detecting the neighbors with the help of a Delaunay triangulation. Connectivity between neighboring settlements are quantified using a Pearson-like correlation for the relative variation of a relevant socio-economic parameter (population size, GDP, tax payed per inhabitant, etc.). The method is implemented in an interactive JAVA application and it is applied with success for an artificially generated society and for the case of USA, Hungary and Transylvania. PMID:21346819

  1. A phosphorylation-wide sncRNA screen reveals Protein Functional Effector sncRNAs (pfeRNAs) in human lung somatic cells.

    PubMed

    Gable, Tyler; Wang, Yuyan; Clark, David; Kumari, Priti; Shetty, Amol Carl; Li, Mao; Mei, Yuping

    2017-06-28

    We recently reported that PIWI-interacting RNAs likes (piR-Ls) could regulate functions of the interacting phosphorylated proteins (p-Proteins). In addition, except for writers and erasers, functional efficacy of p-Proteins on their readers still remains unknown. We, therefore, reasoned there was a type of sncRNAs which could regulate functional efficacy of p-Proteins. Here, we profiled sncRNAs interacting with phosphorylated -Ser, -Thr and -Tyr residues in 3 HBE and 4 lung SCC cell lines, investigated effects and mechanisms of phosphorylated-residue-interacting sncRNAs. Our results demonstrated sncRNAs regulating functional efficacy of p-Proteins and we thus referred them as Protein Functional Effector sncRNAs (pfeRNAs). pfeRNAs were distributed among 26 to 50 nucleotides, shared some core sequences and showed distinctive expression patterns between HBE and SCC cells. Core sequences 417 (CS417), showing consistent upregulation in all 4 SCC cells, bound directly to p-Nucleolin (NCL), which was dependent on the key elements CGCG of CS417 and p-Ser619 of NCL. The CS417/p-NCL interaction was critical for functional efficacy of p-NCL in basic activities of lung normal and cancer cells. Thus, we revealed a novel type of pfeRNAs controlling functional efficacy of p-Proteins in lung somatic cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Proteomic analysis of stipe explants reveals differentially expressed proteins involved in early direct somatic embryogenesis of the tree fern Cyathea delgadii Sternb.

    PubMed

    Domżalska, Lucyna; Kędracka-Krok, Sylwia; Jankowska, Urszula; Grzyb, Małgorzata; Sobczak, Mirosław; Rybczyński, Jan J; Mikuła, Anna

    2017-05-01

    Using cyto-morphological analysis of somatic embryogenesis (SE) in the tree fern Cyathea delgadii as a guide, we performed a comparative proteomic analysis in stipe explants undergoing direct SE. Plant material was cultured on hormone-free medium supplemented with 2% sucrose. Phenol extracted proteins were separated using two-dimensional gel electrophoresis (2-DE) and mass spectrometry was performed for protein identification. A total number of 114 differentially regulated proteins was identified during early SE, i.e. when the first cell divisions started and several-cell pro-embryos were formed. Proteins were assigned to seven functional categories: carbohydrate metabolism, protein metabolism, cell organization, defense and stress responses, amino acid metabolism, purine metabolism, and fatty acid metabolism. Carbohydrate and protein metabolism were found to be the most sensitive SE functions with the greatest number of alterations in the intensity of spots in gel. Differences, especially in non-enzymatic and structural protein abundance, are indicative for cell organization, including cytoskeleton rearrangement and changes in cell wall components. The highest induced changes concern those enzymes related to fatty acid metabolism. Global analysis of the proteome reveals several proteins that can represent markers for the first 16days of SE induction and expression in fern. The findings of this research improve the understanding of molecular processes involved in direct SE in C. delgadii. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Germ cell regeneration-mediated, enhanced mutagenesis in the ascidian Ciona intestinalis reveals flexible germ cell formation from different somatic cells.

    PubMed

    Yoshida, Keita; Hozumi, Akiko; Treen, Nicholas; Sakuma, Tetsushi; Yamamoto, Takashi; Shirae-Kurabayashi, Maki; Sasakura, Yasunori

    2017-03-15

    The ascidian Ciona intestinalis has a high regeneration capacity that enables the regeneration of artificially removed primordial germ cells (PGCs) from somatic cells. We utilized PGC regeneration to establish efficient methods of germ line mutagenesis with transcription activator-like effector nucleases (TALENs). When PGCs were artificially removed from animals in which a TALEN pair was expressed, somatic cells harboring mutations in the target gene were converted into germ cells, this germ cell population exhibited higher mutation rates than animals not subjected to PGC removal. PGC regeneration enables us to use TALEN expression vectors of specific somatic tissues for germ cell mutagenesis. Unexpectedly, cis elements for epidermis, neural tissue and muscle could be used for germ cell mutagenesis, indicating there are multiple sources of regenerated PGCs, suggesting a flexibility of differentiated Ciona somatic cells to regain totipotency. Sperm and eggs of a single hermaphroditic, PGC regenerated animal typically have different mutations, suggesting they arise from different cells. PGCs can be generated from somatic cells even though the maternal PGCs are not removed, suggesting that the PGC regeneration is not solely an artificial event but could have an endogenous function in Ciona. This study provides a technical innovation in the genome-editing methods, including easy establishment of mutant lines. Moreover, this study suggests cellular mechanisms and the potential evolutionary significance of PGC regeneration in Ciona.

  4. Exome Sequencing in Classic Hairy Cell Leukaemia Reveals Widespread Variation in Acquired Somatic Mutations between Individual Tumours Apart from the Signature BRAF V(600)E Lesion

    PubMed Central

    Weston-Bell, Nicola J.; Tapper, Will; Gibson, Jane; Bryant, Dean; Moreno, Yurany; John, Melford; Ennis, Sarah; Kluin-Nelemans, Hanneke C.; Collins, Andrew R.; Sahota, Surinder S.

    2016-01-01

    In classic Hairy cell leukaemia (HCLc), a single case has thus far been interrogated by whole exome sequencing (WES) in a treatment naive patient, in which BRAF V(600)E was identified as an acquired somatic mutation and confirmed as occurring near-universally in this form of disease by conventional PCR-based cohort screens. It left open however the question whether other genome-wide mutations may also commonly occur at high frequency in presentation HCLc disease. To address this, we have carried out WES of 5 such typical HCLc cases, using highly purified splenic tumour cells paired with autologous T cells for germline. Apart from BRAF V(600)E, no other recurrent somatic mutation was identified in these HCLc exomes, thereby excluding additional acquired mutations as also prevalent at a near-universal frequency in this form of the disease. These data then place mutant BRAF at the centre of the neoplastic drive in HCLc. A comparison of our exome data with emerging genetic findings in HCL indicates that additional somatic mutations may however occur recurrently in smaller subsets of disease. As mutant BRAF alone is insufficient to drive malignant transformation in other histological cancers, it suggests that individual tumours utilise largely differing patterns of genetic somatic mutations to coalesce with BRAF V(600)E to drive pathogenesis of malignant HCLc disease. PMID:26871591

  5. Exome Sequencing in Classic Hairy Cell Leukaemia Reveals Widespread Variation in Acquired Somatic Mutations between Individual Tumours Apart from the Signature BRAF V(600)E Lesion.

    PubMed

    Weston-Bell, Nicola J; Tapper, Will; Gibson, Jane; Bryant, Dean; Moreno, Yurany; John, Melford; Ennis, Sarah; Kluin-Nelemans, Hanneke C; Collins, Andrew R; Sahota, Surinder S

    2016-01-01

    In classic Hairy cell leukaemia (HCLc), a single case has thus far been interrogated by whole exome sequencing (WES) in a treatment naive patient, in which BRAF V(600)E was identified as an acquired somatic mutation and confirmed as occurring near-universally in this form of disease by conventional PCR-based cohort screens. It left open however the question whether other genome-wide mutations may also commonly occur at high frequency in presentation HCLc disease. To address this, we have carried out WES of 5 such typical HCLc cases, using highly purified splenic tumour cells paired with autologous T cells for germline. Apart from BRAF V(600)E, no other recurrent somatic mutation was identified in these HCLc exomes, thereby excluding additional acquired mutations as also prevalent at a near-universal frequency in this form of the disease. These data then place mutant BRAF at the centre of the neoplastic drive in HCLc. A comparison of our exome data with emerging genetic findings in HCL indicates that additional somatic mutations may however occur recurrently in smaller subsets of disease. As mutant BRAF alone is insufficient to drive malignant transformation in other histological cancers, it suggests that individual tumours utilise largely differing patterns of genetic somatic mutations to coalesce with BRAF V(600)E to drive pathogenesis of malignant HCLc disease.

  6. Midazolam and Atropine Alter Theta Oscillations in the Hippocampal CA1 Region by Modulating Both the Somatic and Distal Dendritic Dipoles

    PubMed Central

    Balakrishnan, Shilpashree; Pearce, Robert A.

    2014-01-01

    Theta (4-12 Hz) oscillations in the hippocampus play an important role in learning and memory. They are altered by a wide variety of drugs that impair memory, and these effects may underlie or contribute to drug-induced amnesia. However, the network mechanisms linking drug actions with changes in memory formation remain poorly defined. Here, we used a multisite linear electrode array to measure local field potentials simultaneously across the CA1 layers of the hippocampus during active exploration, and employed current source density analysis and computational modeling to investigate how midazolam and atropine – two amnestic drugs that are used clinically and experimentally – change the relative timing and strength of the drivers of θ-oscillations. We found that two dipoles are present, with active inputs that are centered at the soma and the distal apical dendrite and passive return pathways that overlap in the mid-apical dendrite. Both drugs shifted the position of the phase reversal in the local field potential that occurred in the mid-apical dendritic region, but in opposite directions, by changing the strength of the dendritic pole, without altering the somatic pole or relative timing. Computational modeling showed that this constellation of changes, as well as an additional effect on a variably present mid-apical pole, could be produced by simultaneous changes in the active somatic and distal dendritic inputs. These network-level changes, produced by two amnestic drugs that target different types of receptors, may thus serve as a common basis for impaired memory encoding. PMID:24862458

  7. Midazolam and atropine alter theta oscillations in the hippocampal CA1 region by modulating both the somatic and distal dendritic dipoles.

    PubMed

    Balakrishnan, Shilpashree; Pearce, Robert A

    2014-10-01

    Theta (4-12 Hz) oscillations in the hippocampus play an important role in learning and memory. They are altered by a wide variety of drugs that impair memory, and these effects may underlie or contribute to drug-induced amnesia. However, the network mechanisms linking drug actions with changes in memory formation remain poorly defined. Here, we used a multisite linear electrode array to measure local field potentials simultaneously across the CA1 layers of the hippocampus during active exploration, and employed current source density analysis and computational modeling to investigate how midazolam and atropine-two amnestic drugs that are used clinically and experimentally-change the relative timing and strength of the drivers of θ-oscillations. We found that two dipoles are present, with active inputs that are centered at the soma and the distal apical dendrite and passive return pathways that overlap in the mid-apical dendrite. Both drugs shifted the position of the phase reversal in the local field potential that occurred in the mid-apical dendritic region, but in opposite directions, by changing the strength of the dendritic pole, without altering the somatic pole or relative timing. Computational modeling showed that this constellation of changes, as well as an additional effect on a variably present mid-apical pole, could be produced by simultaneous changes in the active somatic and distal dendritic inputs. These network-level changes, produced by two amnestic drugs that target different types of receptors, may thus serve as a common basis for impaired memory encoding.

  8. Genome-wide analysis reveals divergent patterns of gene expression during zygotic and somatic embryo maturation of Theobroma cacao L., the chocolate tree.

    PubMed

    Maximova, Siela N; Florez, Sergio; Shen, Xiangling; Niemenak, Nicolas; Zhang, Yufan; Curtis, Wayne; Guiltinan, Mark J

    2014-07-16

    Theobroma cacao L. is a tropical fruit tree, the seeds of which are used to create chocolate. In vitro somatic embryogenesis (SE) of cacao is a propagation system useful for rapid mass-multiplication to accelerate breeding programs and to provide plants directly to farmers. Two major limitations of cacao SE remain: the efficiency of embryo production is highly genotype dependent and the lack of full cotyledon development results in low embryo to plant conversion rates. With the goal to better understand SE development and to improve the efficiency of SE conversion we examined gene expression differences between zygotic and somatic embryos using a whole genome microarray. The expression of 28,752 genes was determined at 4 developmental time points during zygotic embryogenesis (ZE) and 2 time points during cacao somatic embryogenesis (SE). Within the ZE time course, 10,288 differentially expressed genes were enriched for functions related to responses to abiotic and biotic stimulus, metabolic and cellular processes. A comparison ZE and SE expression profiles identified 10,175 differentially expressed genes. Many TF genes, putatively involved in ethylene metabolism and response, were more strongly expressed in SEs as compared to ZEs. Expression levels of genes involved in fatty acid metabolism, flavonoid biosynthesis and seed storage protein genes were also differentially expressed in the two types of embryos. Large numbers of genes were differentially regulated during various stages of both ZE and SE development in cacao. The relatively higher expression of ethylene and flavonoid related genes during SE suggests that the developing tissues may be experiencing high levels of stress during SE maturation caused by the in vitro environment. The expression of genes involved in the synthesis of auxin, polyunsaturated fatty acids and secondary metabolites was higher in SEs relative to ZEs despite lack of lipid and metabolite accumulation. These differences in gene

  9. Genome-wide analysis reveals divergent patterns of gene expression during zygotic and somatic embryo maturation of Theobroma cacao L., the chocolate tree

    PubMed Central

    2014-01-01

    Background Theobroma cacao L. is a tropical fruit tree, the seeds of which are used to create chocolate. In vitro somatic embryogenesis (SE) of cacao is a propagation system useful for rapid mass-multiplication to accelerate breeding programs and to provide plants directly to farmers. Two major limitations of cacao SE remain: the efficiency of embryo production is highly genotype dependent and the lack of full cotyledon development results in low embryo to plant conversion rates. With the goal to better understand SE development and to improve the efficiency of SE conversion we examined gene expression differences between zygotic and somatic embryos using a whole genome microarray. Results The expression of 28,752 genes was determined at 4 developmental time points during zygotic embryogenesis (ZE) and 2 time points during cacao somatic embryogenesis (SE). Within the ZE time course, 10,288 differentially expressed genes were enriched for functions related to responses to abiotic and biotic stimulus, metabolic and cellular processes. A comparison ZE and SE expression profiles identified 10,175 differentially expressed genes. Many TF genes, putatively involved in ethylene metabolism and response, were more strongly expressed in SEs as compared to ZEs. Expression levels of genes involved in fatty acid metabolism, flavonoid biosynthesis and seed storage protein genes were also differentially expressed in the two types of embryos. Conclusions Large numbers of genes were differentially regulated during various stages of both ZE and SE development in cacao. The relatively higher expression of ethylene and flavonoid related genes during SE suggests that the developing tissues may be experiencing high levels of stress during SE maturation caused by the in vitro environment. The expression of genes involved in the synthesis of auxin, polyunsaturated fatty acids and secondary metabolites was higher in SEs relative to ZEs despite lack of lipid and metabolite accumulation

  10. An Algorithm for Defining Somatization in Children

    PubMed Central

    Postilnik, Inna; Eisman, Howard D.; Price, Rebecca; Fogel, Joshua

    2006-01-01

    Introduction Defining somatization in pediatric populations presents a unique challenge, because DSM-IV somatization criteria may be inadequate for identifying a child with somatization. Two approaches exist. Child somatization has frequently been rooted in a questionnaire model, focusing on child or parent responses to assess how well a child conforms to a specific mental health profile. Others use a medical diagnosis model, designating a child with somatization as those for whom a limited number of medical measures have failed to reveal a pathological source of symptoms. Method We incorporate concepts based upon a literature review from January 1994 to June 2005 of PubMed, PsycINFO, and CINAHL on classification and diagnosis of somatization in children ages 6 to 12. Our goal is to understand in depth the topic and suggest a way to better understand and classify somatization in children. Results We incorporate an integrative approach toward defining child somatization and propose an algorithm to step-by-step classify children with somatic symptoms into three distinct groups: sick, somatizers, and well. This approach includes information from self-report questionnaire, physician questionnaire, and the child’s medical chart. Conclusion This new algorithm suggests an approach for differentiating primary care pediatric clinic visitors into three distinct groups. Although used in clinical practice, empirical validation is necessary to further validate this algorithm. PMID:18392196

  11. Regional tomography reveals mantle traces of tectonic processes in the Circum-Arctic region

    NASA Astrophysics Data System (ADS)

    Koulakov, I.; Dobretsov, N. L.; Jakovlev, A.; Bushenkova, N.

    2012-04-01

    Studying the deep seismic structure beneath the Circum-Arctic region is important to understand the mechanisms of recent tectonic evolution. However, poor coverage of the region with seismic networks makes it difficult applying common tomography schemes. We propose using the travel time data from global seismological catalogues which correspond to seismicity located in the study region and recorded by worldwide stations at any epicentral distances. Another possibility to study "blank" areas is using travel times of PP rays having reflection points in the study area. Using more than 50 years of the ISC catalogue data, we have computed a seismic model in the upper mantle down to 700 km depth beneath the Arctic region. Based on this model, we confirm the existence of thick lithosphere (up to 300 km) beneath Greenland, Canadian and Baltic shield and the Siberian craton. The orogenic areas of Alaska, Chukotka and Yakutia coincide with low-velocity seismic anomalies which indicate the existence of relatively thin lithosphere that can be easily deformed due to tectonic displacements. In the oceanic segments corresponding to the Northern part of the Atlantic ocean and beneath Bering and Baffin seas we observe strong low-velocity anomalies indicating to the anomalously hot mantle. At the same time, beneath central basins of Arctic, the tomographic model does not reveal any significant perturbations. We propose that opening of the oceanic basins in Central Arctic is caused by passive rifting due to relative displacement of Eurasia and America. Beneath Chukotka, below 300 km depth we observe high-velocity anomaly whose origin is actively debated. It might be the trace of an old subduction zone which took place close to the Arctic coast of Chukotka. On the other hand, this positive anomaly might be a continuation of the Aleutian slab which moves horizontally along the transition zone between 410 km and 670 km depth. Besides the Arctic features we clearly observe well known

  12. Membrane Protein Profiling of Human Colon Reveals Distinct Regional Differences *

    PubMed Central

    van der Post, Sjoerd; Hansson, Gunnar C.

    2014-01-01

    The colonic epithelium is a highly dynamic system important for the regulation of ion and water homeostasis via absorption and secretion and for the maintenance of a protective barrier between the outer milieu and the inside of the body. These processes are known to gradually change along the length of the colon, although a complete characterization at the protein level is lacking. We therefore analyzed the membrane proteome of isolated human (n = 4) colonic epithelial cells from biopsies obtained via routine colonoscopy for four segments along the large intestine: ascending, transverse, descending, and sigmoid colon. Label-free quantitative proteomic analyses using high-resolution mass spectrometry were performed on enriched membrane proteins. The results showed a stable level for the majority of membrane proteins but a distinct decrease in proteins associated with bacterial sensing, cation transport, and O-glycosylation in the proximal to distal regions. In contrast, proteins involved in microbial defense and anion transport showed an opposing gradient and increased toward the distal end. The gradient of ion-transporter proteins could be directly related to previously observed ion transport activities. All individual glycosyltransferases required for the O-glycosylation of the major colonic mucin MUC2 were observed and correlated with the known glycosylation variation along the colon axis. This is the first comprehensive quantitative dataset of membrane protein abundance along the human colon and will add to the knowledge of the physiological function of the different regions of the colonic mucosa. Mass spectrometry data have been deposited to the ProteomeXchange with the identifier PXD000987. PMID:24889196

  13. MicroRNA genes and their target 3'-untranslated regions are infrequently somatically mutated in ovarian cancers.

    PubMed

    Ryland, Georgina L; Bearfoot, Jennifer L; Doyle, Maria A; Boyle, Samantha E; Choong, David Y H; Rowley, Simone M; Tothill, Richard W; Gorringe, Kylie L; Campbell, Ian G

    2012-01-01

    MicroRNAs are key regulators of gene expression and have been shown to have altered expression in a variety of cancer types, including epithelial ovarian cancer. MiRNA function is most often achieved through binding to the 3'-untranslated region of the target protein coding gene. Mutation screening using massively-parallel sequencing of 712 miRNA genes in 86 ovarian cancer cases identified only 5 mutated miRNA genes, each in a different case. One mutation was located in the mature miRNA, and three mutations were predicted to alter the secondary structure of the miRNA transcript. Screening of the 3'-untranslated region of 18 candidate cancer genes identified one mutation in each of AKT2, EGFR, ERRB2 and CTNNB1. The functional effect of these mutations is unclear, as expression data available for AKT2 and EGFR showed no increase in gene transcript. Mutations in miRNA genes and 3'-untranslated regions are thus uncommon in ovarian cancer.

  14. MicroRNA Genes and Their Target 3′-Untranslated Regions Are Infrequently Somatically Mutated in Ovarian Cancers

    PubMed Central

    Doyle, Maria A.; Boyle, Samantha E.; Choong, David Y. H.; Rowley, Simone M.; Tothill, Richard W.; Gorringe, Kylie L.; Campbell, Ian G.

    2012-01-01

    MicroRNAs are key regulators of gene expression and have been shown to have altered expression in a variety of cancer types, including epithelial ovarian cancer. MiRNA function is most often achieved through binding to the 3′-untranslated region of the target protein coding gene. Mutation screening using massively-parallel sequencing of 712 miRNA genes in 86 ovarian cancer cases identified only 5 mutated miRNA genes, each in a different case. One mutation was located in the mature miRNA, and three mutations were predicted to alter the secondary structure of the miRNA transcript. Screening of the 3′-untranslated region of 18 candidate cancer genes identified one mutation in each of AKT2, EGFR, ERRB2 and CTNNB1. The functional effect of these mutations is unclear, as expression data available for AKT2 and EGFR showed no increase in gene transcript. Mutations in miRNA genes and 3′-untranslated regions are thus uncommon in ovarian cancer. PMID:22536442

  15. VLBA Reveals Formation Region of Giant Cosmic Jet

    NASA Astrophysics Data System (ADS)

    1999-10-01

    Astronomers have gained their first glimpse of the mysterious region near a black hole at the heart of a distant galaxy, where a powerful stream of subatomic particles spewing outward at nearly the speed of light is formed into a beam, or jet, that then goes nearly straight for thousands of light-years. The astronomers used radio telescopes in Europe and the U.S., including the National Science Foundation's (NSF) Very Long Baseline Array (VLBA) to make the most detailed images ever of the center of the galaxy M87, some 50 million light-years away. "This is the first time anyone has seen the region in which a cosmic jet is formed into a narrow beam," said Bill Junor of the University of New Mexico, in Albuquerque. "We had always speculated that the jet had to be made by some mechanism relatively near the black hole, but as we looked closer and closer to the center, we kept seeing an already-formed beam. That was becoming embarrassing, because we were running out of places to put the formation mechanism that we knew had to be there." Junor, along with John Biretta and Mario Livio of the Space Telescope Science Institute, in Baltimore, MD, now have shown that M87's jet is formed within a few tenths of a light-year of the galaxy's core, presumed to be a black hole three billion times more massive than the sun. In the formation region, the jet is seen opening widely, at an angle of about 60 degrees, nearest the black hole, but is squeezed down to only 6 degrees a few light-years away. "The 60-degree angle of the inner part of M87's jet is the widest such angle yet seen in any jet in the universe," said Junor. "We found this by being able to see the jet to within a few hundredths of a light-year of the galaxy's core -- an unprecedented level of detail." The scientists reported their findings in the October 28 issue of the journal Nature. At the center of M87, material being drawn inward by the strong gravitation of the black hole is formed into a rapidly-spinning flat

  16. Impact of three THI levels on somatic cell count, milk yield and composition of multiparous Holstein cows in a subtropical region.

    PubMed

    Nasr, Mohammed A F; El-Tarabany, Mahmoud S

    2017-02-01

    In Egypt, cow's milk represents 52.11% of the total milk production. Climatic condition is mainly expected to impact the welfare and productive performance of livestock animals. Thus, we aimed to explore the impact of temperature-humidity index (THI) on somatic cell count (SCC), milk production and composition on daily milk test records (33600) of Holstein cows under subtropical Egyptian conditions with different levels of THI. Our results revealed that daily milk yield and composition (fat%, protein %, yielded fat, yielded protein and the percentage of lactose) were higher in low THI (31.91kg, 3.91%, 3.22%, 418kg, 349kg and 4.20%, respectively) when compared with high THI. SCC significantly increased 36% from low to high THI. In addition to, it was increased with advanced parities 231.11% from 2nd to 7th parities. At high THI level, SCC was negatively correlated with total MY (r=-0.12P<0.05), 305 MY (r=-0.16P<0.05), protein % (r=-0.15P<0.01), fat% (r=-0.14P<0.01) and lactose % (r=-0.26P<0.01). The current study concluded that dairy cows performance was better in most of the investigated parameters at low THI than those in high THI. Thus, indicating a detrimental effect of THI on both welfare and economic return.

  17. A somatically mutated human antiganglioside IgM antibody that induces experimental neuropathy in mice is encoded by the variable region heavy chain gene, V1-18.

    PubMed Central

    Willison, H J; O'Hanlon, G M; Paterson, G; Veitch, J; Wilson, G; Roberts, M; Tang, T; Vincent, A

    1996-01-01

    IgM paraproteins associated with autoimmune peripheral neuropathy and anti-Pr cold agglutinins react with sialic acid epitopes present on disialylated gangliosides including GD1b, GT1b, GQ1b, and GD3. A causal relationship between the paraprotein and the neuropathy has never been proven experimentally. From peripheral blood B cells of an affected patient, we have cloned a human hybridoma secreting an antidisialosyl IgM mAb, termed Ha1, that shows identical structural and functional characteristics to its serum counterpart. Variable region analysis shows Ha1 is encoded by the same VH1 family heavy chain gene, V1-18, as the only other known anti-Pr antibody sequence and is somatically mutated, suggesting that it [correction of is] arose in vivo in response to antigenic stimulation. In the rodent peripheral nervous system, Ha1 immunolocalizes to dorsal root ganglia, motor nerve terminals, muscle spindles, myelinated axons, and nodes of Ranvier. After intraperitoneal injection of affinity-purified antibody into mice for 10 d, electrophysiological recordings from the phrenic nerve-hemidiaphragm preparation demonstrated impairment of nerve excitability and a reduction in quantal release of neurotransmitter. These data unequivocally establish that an antidisialosyl antibody can exert pathophysiological effects on the peripheral nervous system and strongly support the view that the antibody contributes to the associated human disease. PMID:8636426

  18. Peak I of the human auditory brainstem response results from the somatic regions of type I spiral ganglion cells: Evidence from computer modeling

    PubMed Central

    Rattay, Frank; Danner, Simon M.

    2014-01-01

    Early neural responses to acoustic signals can be electrically recorded as a series of waves, termed the auditory brainstem response (ABR). The latencies of the ABR waves are important for clinical and neurophysiological evaluations. Using a biophysical model of transmembrane currents along spiral ganglion cells, we show that in human (i) the non-myelinated somatic regions of type I cells, which innervate inner hair cells, predominantly contribute to peak I, (ii) the supra-strong postsynaptic stimulating current (400 pA) and transmembrane currents of the myelinated peripheral axons of type I cells are an order smaller; such postsynaptic currents correspond to the short latencies of a small recordable ABR peak I’, (iii) the ABR signal involvement of the central axon of bipolar type I cells is more effective than their peripheral counterpart as the doubled diameter causes larger transmembrane currents and a larger spike dipole-length, (iv) non-myelinated fibers of type II cells which innervate the outer hair cells generate essentially larger transmembrane currents but their ABR contribution is small because of the small ratio type II/type I cells, low firing rates and a short dipole length of spikes propagating slowly in non-myelinated fibers. Using a finite element model of a simplified head, peaks In and II (where In is the negative peak after peak I) are found to be stationary potentials when volleys of spikes cross the external electrical conductivity barrier at the bone&dura/CSF and at the CSF/brainstem interface whereas peaks I’ and I may be generated by strong local transmembrane currents as postsynaptic events at the distal ending and the soma region of type I cells, respectively. All simulated human inter-peak times (I–I′, II–I, In–I) are close to published data. PMID:25019355

  19. Diversity of Somatic Coliphages in Coastal Regions with Different Levels of Anthropogenic Activity in São Paulo State, Brazil ▿

    PubMed Central

    Burbano-Rosero, E. M.; Ueda-Ito, M.; Kisielius, J. J.; Nagasse-Sugahara, T. K.; Almeida, B. C.; Souza, C. P.; Markman, C.; Martins, G. G.; Albertini, L.; Rivera, I. N. G.

    2011-01-01

    Bacteriophages are the most abundant and genetically diverse viruses on Earth, with complex ecology in both quantitative and qualitative terms. Somatic coliphages (SC) have been reported to be good indicators of fecal pollution in seawater. This study focused on determining the concentration of SC and their diversity by electron microscopy of seawater, plankton, and bivalve samples collected at three coastal regions in São Paulo, Brazil. The SC counts varied from <1 to 3.4 × 103 PFU/100 ml in seawater (73 samples tested), from <1 to 4.7 × 102 PFU/g in plankton (46 samples tested), and from <1 to 2.2 × 101 PFU/g in bivalves (11 samples tested). In seawater samples, a relationship between the thermotolerant coliforms and Escherichia coli and SC was observed at the three regions (P = 0.0001) according to the anthropogenic activities present at each region. However, SC were found in plankton samples from three regions: Baixada Santista (17/20), Canal de São Sebastião (6/14), and Ubatuba (3/12). In seawater samples collected from Baixada Santista, four morphotypes were observed: A1 (4.5%), B1 (50%), C1 (36.4%), and D1 (9.1%). One coliphage, Siphoviridae type T1, had the longest tail: between 939 and 995 nm. In plankton samples, Siphoviridae (65.8%), Podoviridae (15.8%), Microviridae (15.8%), and Myoviridae (2.6%) were found. In bivalves, only the morphotype B1 was observed. These SC were associated with enteric hosts: enterobacteria, E. coli, Proteus, Salmonella, and Yersinia. Baixada Santista is an area containing a high level of fecal pollution compared to those in the Canal de São Sebastião and Ubatuba. This is the first report of coliphage diversity in seawater, plankton, and bivalve samples collected from São Paulo coastal regions. A better characterization of SC diversity in coastal environments will help with the management and evaluation of the microbiological risks for recreation, seafood cultivation, and consumption. PMID:21531842

  20. Nuclear and cytoplasmic genome composition of Solanum bulbocastanum (+) S. tuberosum somatic hybrids.

    PubMed

    Iovene, Marina; Savarese, Salvatore; Cardi, Teodoro; Frusciante, Luigi; Scotti, Nunzia; Simon, Philipp W; Carputo, Domenico

    2007-05-01

    Somatic hybrids between the wild incongruent species Solanum bulbocastanum (2n = 2x = 24) and S. tuberosum haploids (2n = 2x = 24) have been characterized for their nuclear and cytoplasmic genome composition. Cytologic observations revealed the recovery of 8 (near-)tetraploid and 3 hexaploid somatic hybrids. Multicolor genomic in situ hybridization (GISH) analysis was carried out to study the genomic dosage of the parental species in 5 somatic hybrids with different ploidy. The GISH procedure used was effective in discriminating parental genomes in the hybrids; most chromosomes were unambiguously colored. Two (near-)tetraploid somatic hybrids showed the expected 2:2 cultivated-to-wild genomic dosage; 2 hexaploids revealed a 4:2 cultivated-to-wild genomic dosage, and 1 hexaploid had a 2:4 cultivated-to-wild genomic dosage. Characterization of hybrid cytoplasmic genomes was performed using gene-specific primers that detected polymorphisms between the fusion parents in the intergenic regions. The analysis showed that most of the somatic hybrids inherited the plastidial and mitochondrial DNA of the cultivated parent. A few hybrids, with a rearranged mitochondrial genome (showing fragments derived from both parents), were also identified. These results confirmed the potential of somatic hybridization in producing new variability for genetic studies and breeding.

  1. Response of the goat mammary gland to infection with Staphylococcus aureus revealed by gene expression profiling in milk somatic and white blood cells

    PubMed Central

    2012-01-01

    Background S. aureus is one of the main pathogens responsible for the intra-mammary infection in dairy ruminants. Although much work has been carried out to understand the complex physiological and cellular events that occur in the mammary gland in response to S. aureus, the protective mechanisms are still poorly understood. The objectives of the present study were to investigate gene expression during the early response of the goat mammary gland to an experimental challenge with S. aureus, in order to better understand the local and systemic response and to compare them in two divergent lines of goat selected for high and low milk somatic cell scores. Results No differences in gene expression were found between high and low SCS (Somatic Cells Score) selection lines. Analysing the two groups together, an expression of 300 genes were found to change from T0 before infection, and T4 at 24 hours and T5 at 30 hours following challenge. In blood derived white blood cells 8 genes showed increased expression between T0 and T5 and 1 gene has reduced expression. The genes showing the greatest increase in expression following challenge (5.65 to 3.16 fold change) play an important role in (i) immune and inflammatory response (NFKB1, TNFAIP6, BASP1, IRF1, PLEK, BATF3); (ii) the regulation of innate resistance to pathogens (PTX3); and (iii) the regulation of cell metabolism (CYTH4, SLC2A6, ARG2). The genes with reduced expression (−1.5 to −2.5 fold) included genes involved in (i) lipid metabolism (ABCG2, FASN), (ii) chemokine, cytokine and intracellular signalling (SPPI), and (iii) cell cytoskeleton and extracellular matrix (KRT19). Conclusions Analysis of genes with differential expression following infection showed an inverse relationship between immune response and lipid metabolism in the early response of the mammary gland to the S. aureus challenge. PTX3 showed a large change in expression in both milk and blood, and is therefore a candidate for further studies on

  2. Variable region gene analysis of B cell subsets derived from a 4-year- old child: somatically mutated memory B cells accumulate in the peripheral blood already at young age

    PubMed Central

    1994-01-01

    Tonsillar germinal center and immunoglobulin M+ (IgM+)IgD+ B cells as well as peripheral blood (PB) CD5+ and CD5- (conventional) B cells from a 4-yr-old child were isolated and nucleotide sequences of expressed Ig heavy chain variable regions encoded by VH4 gene family members were determined from amplified cDNA. Whereas both tonsillar IgM+IgD+ cells and the majority of IgM-expressing CD5+ and CD5- PB B cells showed no or little somatic mutation, tonsillar germinal center (GC) B cells and IgG-expressing PB B cells carried a high load of somatic mutations in their V region genes. This suggests that somatically mutated memory B cells which have switched isotype accumulate in the PB already at young age. Their frequency seems to increase with age. On the other hand, the antibody repertoire of tonsillar IgM+IgD+ B cells and the majority of IgM-expressing PB B cells is determined by germline-encoded specificities and by generation of variability in the complementary determining region III through VH-DH-JH recombination. A fraction of IgM-bearing PB B cells carries somatically mutated V region genes and probably represents GC-derived B cells which have left the GC at an early stage of the GC reaction without undergoing isotype switching. 10 VH4 germline genes were found to be expressed. Three gene segments were overrepresented in the sequence collection (35 of 50 clones): VH4.21 (30%), V71-4 (20%), and 3D279D (20%). It appears that most potentially functional VH4 germline genes are expressed in peripheral B cells. Some members of this VH gene family are clearly overrepresented over others. PMID:7931072

  3. Clinico-pathological features and somatic gene alterations in refractory ceramic fibre-induced murine mesothelioma reveal mineral fibre-induced mesothelioma identities

    PubMed Central

    Andujar, Pascal; Lecomte, Céline; Renier, Annie; Fleury-Feith, Jocelyne; Kheuang, Laurence; Daubriac, Julien; Janin, Anne; Jaurand, Marie-Claude

    2007-01-01

    Although human malignant mesothelioma (HMM) is mainly caused by asbestos exposure, refractory ceramic fibres (RCFs) have been classified as possibly carcinogenic to humans on the basis of their biological effects in rodents’ lung and pleura and in cultured cells. Hence, further investigations are needed to clarify the mechanism of fibre-induced carcinogenicity and to prevent use of harmful particles. In a previous study, mesotheliomas were found in hemizygous Nf2 (Nf2+/−) mice exposed to asbestos fibres, and showed similar alterations in genes at the Ink4 locus and in Trp53 as described in HMM. Here we found that Nf2+/− mice developed mesotheliomas after intra-peritoneal inoculation of a RCF sample (RCF1). Clinical features in exposed mice were similar to those observed in HMM, showing association between ascite and mesothelioma. Early passages of 12 mesothelioma cell cultures from ascites developed in RCF1-exposed Nf2+/− mice demonstrated frequent inactivation by deletion of genes at the Ink4 locus, and low rate of Trp53 point and insertion mutations. Nf2 gene was inactivated in all cultures. In most cases, co-inactivation of genes at the Ink4 locus and Nf2 was found and, at a lower rate, of Trp53 and Nf2. These results are the first to identify mutations in RCF-induced mesothelioma. They suggest that nf2 mutation is complementary of p15Ink4b, p16Ink4a and p19Arf or p53 mutations and show similar profile of gene alterations resulting from exposure to ceramic or asbestos fibres in Nf2+/− mice, also consistent with the one found in HMM. These somatic genetic changes define different pathways of mesothelial cell transformation. PMID:17272307

  4. Clinico-pathological features and somatic gene alterations in refractory ceramic fibre-induced murine mesothelioma reveal mineral fibre-induced mesothelioma identities.

    PubMed

    Andujar, Pascal; Lecomte, Céline; Renier, Annie; Fleury-Feith, Jocelyne; Kheuang, Laurence; Daubriac, Julien; Janin, Anne; Jaurand, Marie-Claude

    2007-07-01

    Although human malignant mesothelioma (HMM) is mainly caused by asbestos exposure, refractory ceramic fibres (RCFs) have been classified as possibly carcinogenic to humans on the basis of their biological effects in rodents' lung and pleura and in cultured cells. Hence, further investigations are needed to clarify the mechanism of fibre-induced carcinogenicity and to prevent use of harmful particles. In a previous study, mesotheliomas were found in hemizygous Nf2 (Nf2(+/-)) mice exposed to asbestos fibres, and showed similar alterations in genes at the Ink4 locus and in Trp53 as described in HMM. Here we found that Nf2(+/-) mice developed mesotheliomas after intra-peritoneal inoculation of a RCF sample (RCF1). Clinical features in exposed mice were similar to those observed in HMM, showing association between ascite and mesothelioma. Early passages of 12 mesothelioma cell cultures from ascites developed in RCF1-exposed Nf2(+/-) mice demonstrated frequent inactivation by deletion of genes at the Ink4 locus, and low rate of Trp53 point and insertion mutations. Nf2 gene was inactivated in all cultures. In most cases, co-inactivation of genes at the Ink4 locus and Nf2 was found and, at a lower rate, of Trp53 and Nf2. These results are the first to identify mutations in RCF-induced mesothelioma. They suggest that nf2 mutation is complementary of p15(Ink4b), p16(Ink4a) and p19(Arf) or p53 mutations and show similar profile of gene alterations resulting from exposure to ceramic or asbestos fibres in Nf2(+/-) mice, also consistent with the one found in HMM. These somatic genetic changes define different pathways of mesothelial cell transformation.

  5. SubClonal Hierarchy Inference from Somatic Mutations: Automatic Reconstruction of Cancer Evolutionary Trees from Multi-region Next Generation Sequencing

    PubMed Central

    Niknafs, Noushin; Beleva-Guthrie, Violeta; Naiman, Daniel Q.; Karchin, Rachel

    2015-01-01

    Recent improvements in next-generation sequencing of tumor samples and the ability to identify somatic mutations at low allelic fractions have opened the way for new approaches to model the evolution of individual cancers. The power and utility of these models is increased when tumor samples from multiple sites are sequenced. Temporal ordering of the samples may provide insight into the etiology of both primary and metastatic lesions and rationalizations for tumor recurrence and therapeutic failures. Additional insights may be provided by temporal ordering of evolving subclones—cellular subpopulations with unique mutational profiles. Current methods for subclone hierarchy inference tightly couple the problem of temporal ordering with that of estimating the fraction of cancer cells harboring each mutation. We present a new framework that includes a rigorous statistical hypothesis test and a collection of tools that make it possible to decouple these problems, which we believe will enable substantial progress in the field of subclone hierarchy inference. The methods presented here can be flexibly combined with methods developed by others addressing either of these problems. We provide tools to interpret hypothesis test results, which inform phylogenetic tree construction, and we introduce the first genetic algorithm designed for this purpose. The utility of our framework is systematically demonstrated in simulations. For most tested combinations of tumor purity, sequencing coverage, and tree complexity, good power (≥ 0.8) can be achieved and Type 1 error is well controlled when at least three tumor samples are available from a patient. Using data from three published multi-region tumor sequencing studies of (murine) small cell lung cancer, acute myeloid leukemia, and chronic lymphocytic leukemia, in which the authors reconstructed subclonal phylogenetic trees by manual expert curation, we show how different configurations of our tools can identify either a single

  6. Neural mechanisms underlying somatic tinnitus

    PubMed Central

    Shore, Susan; Zhou, Jianxun; Koehler, Seth

    2008-01-01

    Somatic tinnitus is clinically observed modulation of the pitch and loudness of tinnitus by somatic stimulation. This phenomenon and the association of tinnitus with somatic neural disorders indicate that neural connections between the somatosensory and auditory systems may play a role in tinnitus. Anatomical and physiological evidence supports these observations. The trigeminal and dorsal root ganglia relay afferent somatosensory information from the periphery to secondary sensory neurons in the brainstem, specifically, the spinal trigeminal nucleus and dorsal column nuclei, respectively. Each of these structures has been shown to send excitatory projections to the cochlear nucleus. Mossy fibers from the spinal trigeminal and dorsal column nuclei terminate in the granule cell domain while en passant boutons from the ganglia terminate in the granule cell domain and core region of the cochlear nucleus. Sources of these somatosensory–auditory projections are associated with proprioceptive and cutaneous, but not nociceptive, sensation. Single unit and evoked potential recordings in the dorsal cochlear nucleus indicate that these pathways are physiologically active. Stimulation of the dorsal column and the cervical dorsal root ganglia elicits short- and long-latency inhibition separated by a transient excitatory peak in DCN single units. Similarly, activation of the trigeminal ganglion elicits excitation in some DCN units and inhibition in others. Bimodal integration in the DCN is demonstrated by comparing responses to somatosensory and auditory stimulation alone with responses to paired somatosensory and auditory stimulation. The modulation of firing rate and synchrony in DCN neurons by somatatosensory input is physiological correlate of somatic tinnitus. PMID:17956776

  7. Somatic symptom disorder

    MedlinePlus

    ... disorders; Somatization disorder; Somatiform disorders; Briquet syndrome; Illness anxiety disorder ... a history of abuse. SSD is similar to anxiety disorder . This is when people are overly anxious ...

  8. Extinction of Oct-3/4 gene expression in embryonal carcinoma [times] fibroblast somatic cell hybrids is accompanied by changes in the methylation status, chromatin structure, and transcriptional activity of the Oct-3/4 upstream region

    SciTech Connect

    Ben-Shushan, E.; Pikarsky, E.; Klar, A.; Bergman, Y. )

    1993-02-01

    The OCT-3/4 gene provides an excellent model system with which to study the extinction phenomenon in somatic cell hybrids. The molecular mechanism that underlies the extinction of a tissue-specific transcription factor in somatic cell hybrides is evaluated and compared with its down-regulation in retinoic acid treated embryonal carcinoma cells. This study draws a connection between the shutdown of OCT-3/4 expression in retinoic acid (RA)-differentiated embryonal carcinoma (EC) cells and its extinction in hybrid cells. This repression of OCT-3/4 expression is achieved through changes in the methylation status, chromatin structure, and transcriptional activity of the OCT-3/4 upstream regulatory region. 59 refs.

  9. Landscape of somatic mutations in 560 breast cancer whole-genome sequences

    SciTech Connect

    Nik-Zainal, Serena; Davies, Helen; Staaf, Johan; Ramakrishna, Manasa; Glodzik, Dominik; Zou, Xueqing; Martincorena, Inigo; Alexandrov, Ludmil B.; Martin, Sancha; Wedge, David C.; Van Loo, Peter; Ju, Young Seok; Smid, Marcel; Brinkman, Arie B.; Morganella, Sandro; Aure, Miriam R.; Lingjærde, Ole Christian; Langerod, Anita; Ringner, Markus; Ahn, Sung -Min; Boyault, Sandrine; Brock, Jane E.; Broeks, Annegien; Butler, Adam; Desmedt, Christine; Dirix, Luc; Dronov, Serge; Fatima, Aquila; Foekens, John A.; Gerstung, Moritz; Hooijer, Gerrit K. J.; Jang, Se Jin; Jones, David R.; Kim, Hyung -Yong; King, Tari A.; Krishnamurthy, Savitri; Lee, Hee Jin; Lee, Jeong -Yeon; Li, Yilong; McLaren, Stuart; Menzies, Andrew; Mustonen, Ville; O’Meara, Sarah; Pauporte, Iris; Pivot, Xavier; Purdie, Colin A.; Raine, Keiran; Ramakrishnan, Kamna; Rodríguez-Gonzalez, F. German; Romieu, Gilles; Sieuwerts, Anieta M.; Simpson, Peter T.; Shepherd, Rebecca; Stebbings, Lucy; Stefansson, Olafur A.; Teague, Jon; Tommasi, Stefania; Treilleux, Isabelle; Van den Eynden, Gert G.; Vermeulen, Peter; Vincent-Salomon, Anne; Yates, Lucy; Caldas, Carlos; Veer, Laura van’t; Tutt, Andrew; Knappskog, Stian; Tan, Benita Kiat Tee; Jonkers, Jos; Borg, Ake; Ueno, Naoto T.; Sotiriou, Christos; Viari, Alain; Futreal, P. Andrew; Campbell, Peter J.; Span, Paul N.; Van Laere, Steven; Lakhani, Sunil R.; Eyfjord, Jorunn E.; Thompson, Alastair M.; Birney, Ewan; Stunnenberg, Hendrik G.; van de Vijver, Marc J.; Martens, John W. M.; Borresen-Dale, Anne -Lise; Richardson, Andrea L.; Kong, Gu; Thomas, Gilles; Stratton, Michael R.

    2016-05-02

    Here, we analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.

  10. Landscape of somatic mutations in 560 breast cancer whole-genome sequences

    SciTech Connect

    Nik-Zainal, Serena; Davies, Helen; Staaf, Johan; Ramakrishna, Manasa; Glodzik, Dominik; Zou, Xueqing; Martincorena, Inigo; Alexandrov, Ludmil B.; Martin, Sancha; Wedge, David C.; Van Loo, Peter; Ju, Young Seok; Smid, Marcel; Brinkman, Arie B.; Morganella, Sandro; Aure, Miriam R.; Lingjærde, Ole Christian; Langerod, Anita; Ringner, Markus; Ahn, Sung -Min; Boyault, Sandrine; Brock, Jane E.; Broeks, Annegien; Butler, Adam; Desmedt, Christine; Dirix, Luc; Dronov, Serge; Fatima, Aquila; Foekens, John A.; Gerstung, Moritz; Hooijer, Gerrit K. J.; Jang, Se Jin; Jones, David R.; Kim, Hyung -Yong; King, Tari A.; Krishnamurthy, Savitri; Lee, Hee Jin; Lee, Jeong -Yeon; Li, Yilong; McLaren, Stuart; Menzies, Andrew; Mustonen, Ville; O’Meara, Sarah; Pauporte, Iris; Pivot, Xavier; Purdie, Colin A.; Raine, Keiran; Ramakrishnan, Kamna; Rodríguez-Gonzalez, F. German; Romieu, Gilles; Sieuwerts, Anieta M.; Simpson, Peter T.; Shepherd, Rebecca; Stebbings, Lucy; Stefansson, Olafur A.; Teague, Jon; Tommasi, Stefania; Treilleux, Isabelle; Van den Eynden, Gert G.; Vermeulen, Peter; Vincent-Salomon, Anne; Yates, Lucy; Caldas, Carlos; Veer, Laura van’t; Tutt, Andrew; Knappskog, Stian; Tan, Benita Kiat Tee; Jonkers, Jos; Borg, Ake; Ueno, Naoto T.; Sotiriou, Christos; Viari, Alain; Futreal, P. Andrew; Campbell, Peter J.; Span, Paul N.; Van Laere, Steven; Lakhani, Sunil R.; Eyfjord, Jorunn E.; Thompson, Alastair M.; Birney, Ewan; Stunnenberg, Hendrik G.; van de Vijver, Marc J.; Martens, John W. M.; Borresen-Dale, Anne -Lise; Richardson, Andrea L.; Kong, Gu; Thomas, Gilles; Stratton, Michael R.

    2016-05-02

    Here, we analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.

  11. Landscape of somatic mutations in 560 breast cancer whole genome sequences

    PubMed Central

    Nik-Zainal, Serena; Davies, Helen; Staaf, Johan; Ramakrishna, Manasa; Glodzik, Dominik; Zou, Xueqing; Martincorena, Inigo; Alexandrov, Ludmil B.; Martin, Sancha; Wedge, David C.; Van Loo, Peter; Ju, Young Seok; Smid, Marcel; Brinkman, Arie B; Morganella, Sandro; Aure, Miriam R.; Lingjærde, Ole Christian; Langerød, Anita; Ringnér, Markus; Ahn, Sung-Min; Boyault, Sandrine; Brock, Jane E.; Broeks, Annegien; Butler, Adam; Desmedt, Christine; Dirix, Luc; Dronov, Serge; Fatima, Aquila; Foekens, John A.; Gerstung, Moritz; Hooijer, Gerrit KJ; Jang, Se Jin; Jones, David R.; Kim, Hyung-Yong; King, Tari A.; Krishnamurthy, Savitri; Lee, Hee Jin; Lee, Jeong-Yeon; Li, Yilong; McLaren, Stuart; Menzies, Andrew; Mustonen, Ville; O’Meara, Sarah; Pauporté, Iris; Pivot, Xavier; Purdie, Colin A.; Raine, Keiran; Ramakrishnan, Kamna; Rodríguez-González, F. Germán; Romieu, Gilles; Sieuwerts, Anieta M.; Simpson, Peter T; Shepherd, Rebecca; Stebbings, Lucy; Stefansson, Olafur A; Teague, Jon; Tommasi, Stefania; Treilleux, Isabelle; Van den Eynden, Gert G.; Vermeulen, Peter; Vincent-Salomon, Anne; Yates, Lucy; Caldas, Carlos; van’t Veer, Laura; Tutt, Andrew; Knappskog, Stian; Tan, Benita Kiat Tee; Jonkers, Jos; Borg, Åke; Ueno, Naoto T; Sotiriou, Christos; Viari, Alain; Futreal, P. Andrew; Campbell, Peter J; Span, Paul N.; Van Laere, Steven; Lakhani, Sunil R; Eyfjord, Jorunn E.; Thompson, Alastair M.; Birney, Ewan; Stunnenberg, Hendrik G; van de Vijver, Marc J; Martens, John W.M.; Børresen-Dale, Anne-Lise; Richardson, Andrea L.; Kong, Gu; Thomas, Gilles; Stratton, Michael R.

    2016-01-01

    We analysed whole genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. 93 protein-coding cancer genes carried likely driver mutations. Some non-coding regions exhibited high mutation frequencies but most have distinctive structural features probably causing elevated mutation rates and do not harbour driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed 12 base substitution and six rearrangement signatures. Three rearrangement signatures, characterised by tandem duplications or deletions, appear associated with defective homologous recombination based DNA repair: one with deficient BRCA1 function; another with deficient BRCA1 or BRCA2 function; the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operative, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer. PMID:27135926

  12. Combinatorial Library Cloning of Human Antibodies to Streptococcus pneumoniae Capsular Polysaccharides: Variable Region Primary Structures and Evidence for Somatic Mutation of Fab Fragments Specific for Capsular Serotypes 6B, 14, and 23F

    PubMed Central

    Lucas, Alexander H.; Moulton, Karen D.; Tang, Vanessa R.; Reason, Donald C.

    2001-01-01

    Antibodies specific for capsular polysaccharides play a central role in immunity to encapsulated Streptococcus pneumoniae, but little is known about their genetics or the variable (V) region polymorphisms that affect their protective function. To begin to address these issues, we used combinatorial library cloning to isolate pneumococcal polysaccharide (PPS)-specific Fab fragments from two vaccinated adults. We determined complete V region primary structures and performed antigen binding analyses of seven Fab fragments specific for PPS serotype 6B, 14, or 23F. Fabs were of the immunoglobulin G2 or A isotype. Several VHIII gene segments (HV 3-7, 3-15, 3-23, and 3-11) were identified. VL regions were encoded by several κ genes (KV 4-1, 3-15, 2-24, and 2D-29) and a λ gene (LV 1-51). Deviation of the VH and VL regions from their assigned germ line counterparts indicated that they were somatically mutated. Fabs of the same serotype specificity isolated from a single individual differed in affinity, and these differences could be accounted for either by the extent of mutation among clonal relatives or by usage of different V-region genes. Thus, functionally disparate anti-PPS antibodies can arise within individuals both by activation of independent clones and by intraclonal somatic mutation. For one pair of clonally related Fabs, the more extensively mutated VH was associated with lower affinity for PPS 14, a result suggesting that somatic mutation could lead to diminished protective efficacy. These findings indicate that the PPS repertoire in the adult derives from memory B-cell populations that have class switched and undergone extensive hypermutation. PMID:11159978

  13. Somatization, Paranoia, and Language.

    ERIC Educational Resources Information Center

    Oxman, Thomas E.; And Others

    1988-01-01

    Free speech of subjects with somatization and paranoia was analyzed to identify and compare self-concept dimensions reflected in their lexical choices. The somatization disorder group conveyed a sense of negativism, distress, and preoccupation with an uncertain self-identity. The paranoid patients portrayed an artificially positive, grandiose…

  14. Cognitive and somatic anxiety.

    PubMed

    Steptoe, A; Kearsley, N

    1990-01-01

    Three hundred and forty adults (including sports players, recreational exercisers, mediators and sedentary controls) completed three inventories purporting to measure cognitive and somatic aspects of anxiety. These were the Cognitive-Somatic Anxiety Questionnaire (CSAQ) devised by Schwartz, Davidson & Goleman (Psychosomatic Medicine, 40, 321-328, 1978), the Worry-Emotionality Scale (WES, Morris, Davis & Hutchens, Journal of Educational Psychology, 73, 541-555, 1981) and the Lehrer-Woolfolk (1982) Anxiety Symptom Questionnaire (LWASQ). Factor analysis of the CSAQ and WES identified distinct cognitive and somatic anxiety factors in both inventories. Higher somatic than cognitive ratings were recorded on the CSAQ and WES, while the pattern was reversed on the LWASQ. The CSAQ can tentatively be recommended as a useful measure of these two anxiety components. We were unable to confirm an observation made previously in the literature that practice of meditation is associated with reduced cognitive anxiety, or that exercise is linked with lower somatic anxiety.

  15. Altered Spontaneous Activity in Patients with Persistent Somatoform Pain Disorder Revealed by Regional Homogeneity

    PubMed Central

    Yan, Chao; Lu, Jing; Li, Xuzhou; Tang, Chaozheng; Fan, Mingxia; Luo, Yanli

    2016-01-01

    Persistent somatoform pain disorder (PSPD) is a mental disorder un-associated with any somatic injury and can cause severe somatosensory and emotional impairments in patients. However, so far, the neuro-pathophysiological mechanism of the functional impairments in PSPD is still unclear. The present study assesses the difference in regional spontaneous activity between PSPD and healthy controls (HC) during a resting state, in order to elucidate the neural mechanisms underlying PSPD. Resting-state functional Magnetic Resonance Imaging data were obtained from 13 PSPD patients and 23 age- and gender-matched HC subjects in this study. Kendall’s coefficient of concordance was used to measure regional homogeneity (ReHo), and a two-sample t-test was subsequently performed to investigate the ReHo difference between PSPD and HC. Additionally, the correlations between the mean ReHo of each survived area and the clinical assessments were further analyzed. Compared with the HC group, patients with PSPD exhibited decreased ReHo in the bilateral primary somatosensory cortex, posterior cerebellum, and occipital lobe, while increased ReHo in the prefrontal cortex (PFC) and default mode network (including the medial PFC, right inferior parietal lobe (IPL), and left supramarginal gyrus). In addition, significant positive correlations were found between the mean ReHo of both right IPL and left supramarginal gyrus and participants’ Self-Rating Anxiety Scale (SAS) scores, and between the mean ReHo of the left middle frontal gyrus and Visual Analogue Scale (VAS) scores. Our results suggest that abnormal spontaneous brain activity in specific brain regions during a resting state may be associated with the dysfunctions in pain, memory and emotional processing commonly observed in patients with PSPD. These findings help us to understand the neural mechanisms underlying PSPD and suggest that the ReHo metric could be used as a clinical marker for PSPD. PMID:26977802

  16. Brain perfusion asymmetry in patients with oral somatic delusions.

    PubMed

    Umezaki, Yojiro; Katagiri, Ayano; Watanabe, Motoko; Takenoshita, Miho; Sakuma, Tomomi; Sako, Emi; Sato, Yusuke; Toriihara, Akira; Uezato, Akihito; Shibuya, Hitoshi; Nishikawa, Toru; Motomura, Haruhiko; Toyofuku, Akira

    2013-06-01

    Oral cenesthopathy is a somatic delusion or hallucination involving the oral area and is categorized as a delusional disorder, somatic type. The pathophysiology of this intractable condition remains obscure. In this study, we clarified the pathophysiology of oral cenesthopathy by evaluating regional brain perfusion. We performed single photon emission computed tomography (SPECT) using (99m)Tc-ethylcysteinate dimer in 16 subjects (cenesthopathy:control = 8:8). The SPECT images were visually assessed qualitatively, and quantitative analyses were also performed using a three-dimensional stereotactic region-of-interest template. The visual assessment revealed a right > left perfusion asymmetry in broad areas of the brain among the patients. The quantitative analysis confirmed that the regional cerebral blood flow values on the right side were significantly larger than those on the left side for most areas of the brain in the patients. A comparison of the R/(R + L) ratios in both groups confirmed the significant brain perfusion asymmetry between the two sides in the callosomarginal, precentral, and temporal regions in the patients. Qualitative evaluation of the SPECT images revealed right > left brain perfusion asymmetry in broad regions of the brain. Moreover, the quantitative analyses confirmed the perfusion asymmetry between the two sides in the frontal and temporal areas. Those may provide the key for elucidation of the pathophysiology of oral cenesthopathy.

  17. Domain landscapes of somatic mutations in cancer

    PubMed Central

    2012-01-01

    Background Large-scale tumor sequencing projects are now underway to identify genetic mutations that drive tumor initiation and development. Most studies take a gene-based approach to identifying driver mutations, highlighting genes mutated in a large percentage of tumor samples as those likely to contain driver mutations. However, this gene-based approach usually does not consider the position of the mutation within the gene or the functional context the position of the mutation provides. Here we introduce a novel method for mapping mutations to distinct protein domains, not just individual genes, in which they occur, thus providing the functional context for how the mutation contributes to disease. Furthermore, aggregating mutations from all genes containing a specific protein domain enables the identification of mutations that are rare at the gene level, but that occur frequently within the specified domain. These highly mutated domains potentially reveal disruptions of protein function necessary for cancer development. Results We mapped somatic mutations from the protein coding regions of 100 colon adenocarcinoma tumor samples to the genes and protein domains in which they occurred, and constructed topographical maps to depict the “mutational landscapes” of gene and domain mutation frequencies. We found significant mutation frequency in a number of genes previously known to be somatically mutated in colon cancer patients including APC, TP53 and KRAS. In addition, we found significant mutation frequency within specific domains located in these genes, as well as within other domains contained in genes having low mutation frequencies. These domain “peaks” were enriched with functions important to cancer development including kinase activity, DNA binding and repair, and signal transduction. Conclusions Using our method to create the domain landscapes of mutations in colon cancer, we were able to identify somatic mutations with high potential to drive cancer

  18. Somatic Literacy. Bringing Somatic Education into Physical Education.

    ERIC Educational Resources Information Center

    Linden, Paul

    1994-01-01

    Examines the profession of physical education and what it could become if it embraced somatic work, explaining the basic concepts and processes of somatic education. Somatic education focuses on the interactions of posture, movement, emotion, thought, self-concept, and cultural values. A case study details somatic education in practice. (SM)

  19. The human blood DNA methylome displays a highly distinctive profile compared with other somatic tissues.

    PubMed

    Lowe, Robert; Slodkowicz, Greg; Goldman, Nick; Rakyan, Vardhman K

    2015-01-01

    In mammals, DNA methylation profiles vary substantially between tissues. Recent genome-scale studies report that blood displays a highly distinctive methylomic profile from other somatic tissues. In this study, we sought to understand why blood DNA methylation state is so different to the one found in other tissues. We found that whole blood contains approximately twice as many tissue-specific differentially methylated positions (tDMPs) than any other somatic tissue examined. Furthermore, a large subset of blood tDMPs showed much lower levels of methylation than tDMPs for other tissues. Surprisingly, these regions of low methylation in blood show no difference regarding genomic location, genomic content, evolutionary rates, or histone marks when compared to other tDMPs. Our results reveal why blood displays a distinctive methylation profile relative to other somatic tissues. In the future, it will be important to study how these blood specific tDMPs are mechanistically involved in blood-specific functions.

  20. A comprehensive catalogue of somatic mutations from a human cancer genome

    PubMed Central

    Pleasance, Erin D.; Cheetham, R. Keira; Stephens, Philip J.; McBride, David J.; Humphray, Sean J.; Greenman, Chris D.; Varela, Ignacio; Lin, Meng-Lay; Ordóñez, Gonzalo R.; Bignell, Graham R.; Ye, Kai; Alipaz, Julie; Bauer, Markus J.; Beare, David; Butler, Adam; Carter, Richard J.; Chen, Lina; Cox, Anthony J.; Edkins, Sarah; Kokko-Gonzales, Paula I.; Gormley, Niall A.; Grocock, Russell J.; Haudenschild, Christian D.; Hims, Matthew M.; James, Terena; Jia, Mingming; Kingsbury, Zoya; Leroy, Catherine; Marshall, John; Menzies, Andrew; Mudie, Laura J.; Ning, Zemin; Royce, Tom; Schulz-Trieglaff, Ole B.; Spiridou, Anastassia; Stebbings, Lucy A.; Szajkowski, Lukasz; Teague, Jon; Williamson, David; Chin, Lynda; Ross, Mark T.; Campbell, Peter J.; Bentley, David R.; Futreal, P. Andrew; Stratton, Michael R.

    2011-01-01

    All cancers carry somatic mutations. A subset of these somatic alterations, termed driver mutations, confer selective growth advantage and are implicated in cancer development, whereas the remainder are passengers. Here we have sequenced the genomes of a malignant melanoma and a lymphoblastoid cell line from the same person, providing the first comprehensive catalogue of somatic mutations from an individual cancer. The catalogue provides remarkable insights into the forces that have shaped this cancer genome. The dominant mutational signature reflects DNA damage due to ultraviolet light exposure, a known risk factor for malignant melanoma, whereas the uneven distribution of mutations across the genome, with a lower prevalence in gene footprints, indicates that DNA repair has been preferentially deployed towards transcribed regions. The results illustrate the power of a cancer genome sequence to reveal traces of the DNA damage, repair, mutation and selection processes that were operative years before the cancer became symptomatic. PMID:20016485

  1. Biogeography of Oenococcus oeni Reveals Distinctive but Nonspecific Populations in Wine-Producing Regions

    PubMed Central

    El Khoury, Mariette; Campbell-Sills, Hugo; Salin, Franck; Guichoux, Erwan; Claisse, Olivier

    2016-01-01

    ABSTRACT Understanding the mechanisms behind the typicity of regional wines inevitably brings attention to microorganisms associated with their production. Oenococcus oeni is the main bacterial species involved in wine and cider making. It develops after the yeast-driven alcoholic fermentation and performs the malolactic fermentation, which improves the taste and aromatic complexity of most wines. Here, we have evaluated the diversity and specificity of O. oeni strains in six regions. A total of 235 wines and ciders were collected during spontaneous malolactic fermentations and used to isolate 3,212 bacterial colonies. They were typed by multilocus variable analysis, which disclosed a total of 514 O. oeni strains. Their phylogenetic relationships were evaluated by a second typing method based on single nucleotide polymorphism (SNP) analysis. Taken together, the results indicate that each region holds a high diversity of strains that constitute a unique population. However, strains present in each region belong to diverse phylogenetic groups, and the same groups can be detected in different regions, indicating that strains are not genetically adapted to regions. In contrast, greater strain identity was seen for cider, white wine, or red wine of Burgundy, suggesting that genetic adaptation to these products occurred. IMPORTANCE This study reports the isolation, genotyping, and geographic distribution analysis of the largest collection of O. oeni strains performed to date. It reveals that there is very high diversity of strains in each region, the majority of them being detected in a single region. The study also reports the development of an SNP genotyping method that is useful for analyzing the distribution of O. oeni phylogroups. The results show that strains are not genetically adapted to regions but to specific types of wines. They reveal new phylogroups of strains, particularly two phylogroups associated with white wines and red wines of Burgundy. Taken together

  2. E2F1 somatic mutation within miRNA target site impairs gene regulation in colorectal cancer.

    PubMed

    Lopes-Ramos, Camila M; Barros, Bruna P; Koyama, Fernanda C; Carpinetti, Paola A; Pezuk, Julia; Doimo, Nayara T S; Habr-Gama, Angelita; Perez, Rodrigo O; Parmigiani, Raphael B

    2017-01-01

    Genetic studies have largely concentrated on the impact of somatic mutations found in coding regions, and have neglected mutations outside of these. However, 3' untranslated regions (3' UTR) mutations can also disrupt or create miRNA target sites, and trigger oncogene activation or tumor suppressor inactivation. We used next-generation sequencing to widely screen for genetic alterations within predicted miRNA target sites of oncogenes associated with colorectal cancer, and evaluated the functional impact of a new somatic mutation. Target sequencing of 47 genes was performed for 29 primary colorectal tumor samples. For 71 independent samples, Sanger methodology was used to screen for E2F1 mutations in miRNA predicted target sites, and the functional impact of these mutations was evaluated by luciferase reporter assays. We identified germline and somatic alterations in E2F1. Of the 100 samples evaluated, 3 had germline alterations at the MIR205-5p target site, while one had a somatic mutation at MIR136-5p target site. E2F1 gene expression was similar between normal and tumor tissues bearing the germline alteration; however, expression was increased 4-fold in tumor tissue that harbored a somatic mutation compared to that in normal tissue. Luciferase reporter assays revealed both germline and somatic alterations increased E2F1 activity relative to wild-type E2F1. We demonstrated that somatic mutation within E2F1:MIR136-5p target site impairs miRNA-mediated regulation and leads to increased gene activity. We conclude that somatic mutations that disrupt miRNA target sites have the potential to impact gene regulation, highlighting an important mechanism of oncogene activation.

  3. Antibody diversification by somatic mutation: from Burnet onwards.

    PubMed

    Neuberger, Michael S

    2008-02-01

    The clonal selection theory proposed by Burnet required a genetic process, for which there was then no precedent, which randomizes the region of the gene(s) responsible for the specification of gamma-globulin molecules. Work over the subsequent half-century substantiated Burnet's speculation, revealing two distinct novel genetic processes. During early development (when Burnet first thought the randomization took place) programmed gene segment rearrangement catalysed by the RAG1/RAG2 recombinase generates a substantial diversity of immunoglobulin molecules (the primary repertoire). Somatic hypermutation (triggered by the activation-induced deaminase (AID) DNA deaminase) then occurs following antigen encounter in man and mouse, yielding a secondary repertoire. This hypermutation allows both limitless diversification as well as maturation of the antibody response by a process of somatic evolution akin to that envisioned by Burnet in later formulations of the clonal selection theory. AID-triggered antigen receptor diversification probably arose earlier in evolution than RAG-mediated repertoire generation. Here I trace our insights into the molecular mechanism antibody somatic mutation from when it was first proposed through to our current understanding of how it is triggered by targeted deamination of deoxycytidine residues in immunoglobulin gene DNA.

  4. Domain regulation of imprinting cluster in Kip2/Lit1 subdomain on mouse chromosome 7F4/F5: large-scale DNA methylation analysis reveals that DMR-Lit1 is a putative imprinting control region.

    PubMed

    Yatsuki, Hitomi; Joh, Keiichiro; Higashimoto, Ken; Soejima, Hidenobu; Arai, Yuji; Wang, Youdong; Hatada, Izuho; Obata, Yayoi; Morisaki, Hiroko; Zhang, Zhongming; Nakagawachi, Tetsuji; Satoh, Yuji; Mukai, Tsunehiro

    2002-12-01

    Mouse chromosome 7F4/F5, where the imprinting domain is located, is syntenic to human 11p15.5, the locus for Beckwith-Wiedemann syndrome. The domain is thought to consist of the two subdomains Kip2 (p57(kip2))/Lit1 and Igf2/H19. Because DNA methylation is believed to be a key factor in genomic imprinting, we performed large-scale DNA methylation analysis to identify the cis-element crucial for the regulation of the Kip2/Lit1 subdomain. Ten CpG islands (CGIs) were found, and these were located at the promoter sites, upstream of genes, and within intergenic regions. Bisulphite sequencing revealed that CGIs 4, 5, 8, and 10 were differentially methylated regions (DMRs). CGIs 4, 5, and 10 were methylated paternally in somatic tissues but not in germ cells. CGI8 was methylated in oocyte and maternally in somatic tissues during development. Parental-specific DNase I hypersensitive sites (HSSs) were found near CGI8. These data indicate that CGI8, called DMR-Lit1, is not only the region for gametic methylation but might also be the imprinting control region (ICR) of the subdomain.

  5. Xyloglucan endotransglucosylase/hydrolase genes in cucumber (Cucumis sativus) - differential expression during somatic embryogenesis.

    PubMed

    Malinowski, Robert; Filipecki, Marcin; Tagashira, Norikazu; Wiśniewska, Anita; Gaj, Paweł; Plader, Wojciech; Malepszy, Stefan

    2004-04-01

    Defined changes in the cell wall directed by many proteins accompany every morphogenetic process in plants. Xyloglucan endotransglucosylase/hydrolase proteins (XTH; EC 2.4.1.207) have the potential to modify the hemicellulose matrix within the cell wall. Cs-XTH1 and Cs-XTH3 genes, which encode XTH proteins, were found among numerous genes that are differentially expressed after the induction of cucumber somatic embryogenesis. The expression of these genes increased during somatic embryogenesis. The Cs-XTH1 gene was localized on the second chromosome near the centromere region, whereas Cs-XTH3 was found in the middle of the fifth chromosome's longer arm. Northern blot hybridization showed that both genes were preferentially expressed in roots. We also observed higher accumulation of both transcripts in somatic embryos than in the proembryogenic mass. The localization of mRNA by in situ hybridization revealed that the Cs-XTH1 transcripts were largely accumulated in the presumptive cotyledon primordia of somatic embryos. The XTH gene family consists of a number of genes with a high degree of structural similarity. Screening a cucumber genomic library has identified other members of this gene family. The intron/exon structure, sequence similarities and the close chromosomal distance between some members suggest their common evolutionary origin. The involvement of XTH-related genes in somatic embryo formation is discussed.

  6. Circuit-wide transcriptional profiling reveals brain region-specific gene networks regulating depression susceptibility

    PubMed Central

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

    2016-01-01

    Summary Depression is a complex, heterogeneous disorder and a leading contributor to the global burden of disease. Most previous research has focused on individual brain regions and genes contributing to depression. However, emerging evidence in humans and animal models suggests that dysregulated circuit function and gene expression across multiple brain regions drive depressive phenotypes. Here we performed RNA-sequencing on 4 brain regions from control animals and those susceptible or resilient to chronic social defeat stress at multiple time points. We employed an integrative network biology approach to identify transcriptional networks and key driver genes that regulate susceptibility to depressive-like symptoms. Further, we validated in vivo several key drivers and their associated transcriptional networks that regulate depression susceptibility and confirmed their functional significance at the levels of gene transcription, synaptic regulation and behavior. Our study reveals novel transcriptional networks that control stress susceptibility and offers fundamentally new leads for antidepressant drug discovery. PMID:27181059

  7. Somatic mutations in the Ig variable region genes and expression of novel Cmu-germline transcripts in a B-lymphoma cell line ("Farage") not producing Ig polypeptide chains.

    PubMed

    Hochberg, M; Gabay, C; Laskov, R

    1998-08-01

    Non-Hodgkin's B-lymphomas (B-NHL) are a very heterogeneous group of B-cell neoplasias originating from the germinal centers of lymphatic follicles. Thus, they represent a suitable experimental model to study the molecular basis of certain key events which take place in the lymphatic follicles, including somatic hypermutation and heavy chain isotypic switch. An unusual B-NHL cell line ("Farage") not producing Ig polypeptide chains was previously shown to rearrange its IgH and Igkappa genes and transcribe seemingly normal size mu and kappa mRNAs. In an attempt to characterize the phenotype of Farage cells better and to elucidate the molecular basis of the failure of Farage cells to synthesize Ig chains, we sequenced its VH and Vkappa rearranged gene segments by PCR and RT-PCR. It was found that both V genes are somatically, heavily mutated compared to their germline counterparts. In addition, this rearranged VDJ gene of the heavy chain is not transcribed. Instead, the Farage cells express a low level of a new family of germline transcripts starting with a VH like sequence, continuing with a small segment of the 3'VH germline flanking region, and ending within the Cmu region. These transcripts lack D and J segments and do not contain the open reading frame of the full-length Cmu protein. Thus, Farage cells fail to produce mu heavy chains due to silencing of the expression of the conventional VDJCmu transcript and expression of unusual Cmu-germline transcripts. In contrast to the IgH genes, the rearranged VJ gene of Farage is transcribed and gives rise to a full-size kappa-mRNA. This transcript, however, is not translated to a full-length kappa-chain, as it contains a stop codon in its coding region. All the above show that Farage cells are unable to produce Ig polypeptide chains, due to somatic mutations altering the kappa-chain gene, and mutations and/or regulatory events that shutoff the transcription of the IgH gene. The heavily mutated Vkappa and Vkappa genes

  8. Biogeography of Oenococcus oeni Reveals Distinctive but Nonspecific Populations in Wine-Producing Regions.

    PubMed

    El Khoury, Mariette; Campbell-Sills, Hugo; Salin, Franck; Guichoux, Erwan; Claisse, Olivier; Lucas, Patrick M

    2017-02-01

    Understanding the mechanisms behind the typicity of regional wines inevitably brings attention to microorganisms associated with their production. Oenococcus oeni is the main bacterial species involved in wine and cider making. It develops after the yeast-driven alcoholic fermentation and performs the malolactic fermentation, which improves the taste and aromatic complexity of most wines. Here, we have evaluated the diversity and specificity of O. oeni strains in six regions. A total of 235 wines and ciders were collected during spontaneous malolactic fermentations and used to isolate 3,212 bacterial colonies. They were typed by multilocus variable analysis, which disclosed a total of 514 O. oeni strains. Their phylogenetic relationships were evaluated by a second typing method based on single nucleotide polymorphism (SNP) analysis. Taken together, the results indicate that each region holds a high diversity of strains that constitute a unique population. However, strains present in each region belong to diverse phylogenetic groups, and the same groups can be detected in different regions, indicating that strains are not genetically adapted to regions. In contrast, greater strain identity was seen for cider, white wine, or red wine of Burgundy, suggesting that genetic adaptation to these products occurred. This study reports the isolation, genotyping, and geographic distribution analysis of the largest collection of O. oeni strains performed to date. It reveals that there is very high diversity of strains in each region, the majority of them being detected in a single region. The study also reports the development of an SNP genotyping method that is useful for analyzing the distribution of O. oeni phylogroups. The results show that strains are not genetically adapted to regions but to specific types of wines. They reveal new phylogroups of strains, particularly two phylogroups associated with white wines and red wines of Burgundy. Taken together, the results shed

  9. Autoantibody-associated kappa light chain variable region gene expressed in chronic lymphocytic leukemia with little or no somatic mutation. Implications for etiology and immunotherapy

    PubMed Central

    1988-01-01

    Recently the minor B cell subpopulation that expresses the CD5 (Leu-1) antigen has been implicated as a source of IgM autoantibodies. Chronic lymphocytic leukemia (CLL), the most common leukemia in humans, represents a malignancy of small B lymphocytes that also express the CD5 antigen. However, little is known concerning the antibody variable region genes (V genes) that are used by these malignant CD5 B cells. We have found that a relatively high frequency of CLL patients have leukemic B cells with surface immunoglobulin (sIg) recognized by 17.109, a murine mAb specific for a kappa light chain associated crossreactive idiotype (CRI) associated with rheumatoid factor and other IgM autoantibodies. Flow cytometric analyses revealed that the relative expression of the 17.109-CRI by circulating leukemic B cells was directly proportional to the levels of sIg kappa light chain, indicating that there exists stable idiotype expression in the leukemic population. To examine this at the molecular level, the nucleic acid sequences encoding the Ig kappa light chains of two unrelated patients with CLL bearing sIg with the 17.109-CRI were determined. Analyses of multiple independent kappa light chain cDNA clones did not reveal any evidence for sequence heterogeneity in the CLL cell population. Furthermore, the nucleic acid sequences expressed by the leukemic cells of these two patients were identical or very homologous to a germline V kappa gene isolated from placental DNA, designated Humkv 325, or "V kappa RF" because of its association with IgM autoantibodies. This study suggests; (a) that the malignant CD5+ B lymphocytes in CLL use the same V kappa gene that has been highly associated with IgM autoantibodies and (b) that the expression of V genes is stable in CLL, in contrast to other B cell malignancies examined to date. We propose that many CLL cases represent malignancies of autoreactive CD5 B cells that use a restricted set of conserved V genes. This property may render

  10. Systems-Based Analyses of Brain Regions Functionally Impacted in Parkinson's Disease Reveals Underlying Causal Mechanisms

    PubMed Central

    Emig-Agius, Dorothea; Bessarabova, Marina; Ivliev, Alexander E.; Schüle, Birgit; Alexander, Jeff; Wallace, William; Halliday, Glenda M.; Langston, J. William; Braxton, Scott; Yednock, Ted; Shaler, Thomas; Johnston, Jennifer A.

    2014-01-01

    Detailed analysis of disease-affected tissue provides insight into molecular mechanisms contributing to pathogenesis. Substantia nigra, striatum, and cortex are functionally connected with increasing degrees of alpha-synuclein pathology in Parkinson's disease. We undertook functional and causal pathway analysis of gene expression and proteomic alterations in these three regions, and the data revealed pathways that correlated with disease progression. In addition, microarray and RNAseq experiments revealed previously unidentified causal changes related to oligodendrocyte function and synaptic vesicle release, and these and other changes were reflected across all brain regions. Importantly, subsets of these changes were replicated in Parkinson's disease blood; suggesting peripheral tissue may provide important avenues for understanding and measuring disease status and progression. Proteomic assessment revealed alterations in mitochondria and vesicular transport proteins that preceded gene expression changes indicating defects in translation and/or protein turnover. Our combined approach of proteomics, RNAseq and microarray analyses provides a comprehensive view of the molecular changes that accompany functional loss and alpha-synuclein pathology in Parkinson's disease, and may be instrumental to understand, diagnose and follow Parkinson's disease progression. PMID:25170892

  11. Shusterman on Somatic Experience

    ERIC Educational Resources Information Center

    Maattanen, Pentti

    2010-01-01

    Richard Shusterman's "Body Consciousness" aims at formulating a theory of somaesthetics and somatic experience. There has indeed been a growing interest in the role of the body in experience. Shusterman examines the arguments of six important writers who have been influential in this discussion. The emphasis on the body is natural for a…

  12. Shusterman on Somatic Experience

    ERIC Educational Resources Information Center

    Maattanen, Pentti

    2010-01-01

    Richard Shusterman's "Body Consciousness" aims at formulating a theory of somaesthetics and somatic experience. There has indeed been a growing interest in the role of the body in experience. Shusterman examines the arguments of six important writers who have been influential in this discussion. The emphasis on the body is natural for a…

  13. Reprogramming mammalian somatic cells.

    PubMed

    Rodriguez-Osorio, N; Urrego, R; Cibelli, J B; Eilertsen, K; Memili, E

    2012-12-01

    Somatic cell nuclear transfer (SCNT), the technique commonly known as cloning, permits transformation of a somatic cell into an undifferentiated zygote with the potential to develop into a newborn animal (i.e., a clone). In somatic cells, chromatin is programmed to repress most genes and express some, depending on the tissue. It is evident that the enucleated oocyte provides the environment in which embryonic genes in a somatic cell can be expressed. This process is controlled by a series of epigenetic modifications, generally referred to as "nuclear reprogramming," which are thought to involve the removal of reversible epigenetic changes acquired during cell differentiation. A similar process is thought to occur by overexpression of key transcription factors to generate induced pluripotent stem cells (iPSCs), bypassing the need for SCNT. Despite its obvious scientific and medical importance, and the great number of studies addressing the subject, the molecular basis of reprogramming in both reprogramming strategies is largely unknown. The present review focuses on the cellular and molecular events that occur during nuclear reprogramming in the context of SCNT and the various approaches currently being used to improve nuclear reprogramming. A better understanding of the reprogramming mechanism will have a direct impact on the efficiency of current SCNT procedures, as well as iPSC derivation.

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

    PubMed

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

    2014-07-01

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

  15. Awake fMRI reveals a specialized region in dog temporal cortex for face processing

    PubMed Central

    Dilks, Daniel D.; Cook, Peter; Weiller, Samuel K.; Berns, Helen P.; Spivak, Mark

    2015-01-01

    Recent behavioral evidence suggests that dogs, like humans and monkeys, are capable of visual face recognition. But do dogs also exhibit specialized cortical face regions similar to humans and monkeys? Using functional magnetic resonance imaging (fMRI) in six dogs trained to remain motionless during scanning without restraint or sedation, we found a region in the canine temporal lobe that responded significantly more to movies of human faces than to movies of everyday objects. Next, using a new stimulus set to investigate face selectivity in this predefined candidate dog face area, we found that this region responded similarly to images of human faces and dog faces, yet significantly more to both human and dog faces than to images of objects. Such face selectivity was not found in dog primary visual cortex. Taken together, these findings: (1) provide the first evidence for a face-selective region in the temporal cortex of dogs, which cannot be explained by simple low-level visual feature extraction; (2) reveal that neural machinery dedicated to face processing is not unique to primates; and (3) may help explain dogs’ exquisite sensitivity to human social cues. PMID:26290784

  16. Structure and Evolution of the Lunar Procellarum Region as Revealed by GRAIL Gravity Data

    NASA Technical Reports Server (NTRS)

    Andrews-Hanna, Jeffrey C.; Besserer, Jonathan; Head, James W., III; Howett, Carly J. A.; Kiefer, Walter S.; Lucey, Paul J.; McGovern, Patrick J.; Melosh, H. Jay; Neumann, Gregory A.; Phillips, Roger J.; hide

    2014-01-01

    The Procellarum region is a broad area on the nearside of the Moon that is characterized by low elevations, thin crust, and high surface concentrations of the heat-producing elements uranium, thorium, and potassium. The Procellarum region has been interpreted as an ancient impact basin approximately 3200 km in diameter, though supporting evidence at the surface would have been largely obscured as a result of the great antiquity and poor preservation of any diagnostic features. Here we use data from the Gravity Recovery and Interior Laboratory (GRAIL) mission to examine the subsurface structure of Procellarum. The Bouguer gravity anomalies and gravity gradients reveal a pattern of narrow linear anomalies that border the Procellarum region and are interpreted to be the frozen remnants of lava-filled rifts and the underlying feeder dikes that served as the magma plumbing system for much of the nearside mare volcanism. The discontinuous surface structures that were earlier interpreted as remnants of an impact basin rim are shown in GRAIL data to be a part of this continuous set of quasi-rectangular border structures with angular intersections, contrary to the expected circular or elliptical shape of an impact basin. The spatial pattern of magmatic-tectonic structures bounding Procellarum is consistent with their formation in response to thermal stresses produced by the differential cooling of the province relative to its surroundings, coupled with magmatic activity driven by the elevated heat flux in the region.

  17. Virtual screening on an α-helix to β-strand switchable region of the FGFR2 extracellular domain revealed positive and negative modulators.

    PubMed

    Diaz, Constantino; Corentin, Herbert; Thierry, Vermat; Chantal, Alcouffe; Tanguy, Bozec; David, Sibrac; Jean-Marc, Herbert; Pascual, Ferrara; Françoise, Bono; Edgardo, Ferran

    2014-11-01

    The secondary structure of some protein segments may vary between α-helix and β-strand. To predict these switchable segments, we have developed an algorithm, Switch-P, based solely on the protein sequence. This algorithm was used on the extracellular parts of FGF receptors. For FGFR2, it predicted that β4 and β5 strands of the third Ig-like domain were highly switchable. These two strands possess a high number of somatic mutations associated with cancer. Analysis of PDB structures of FGF receptors confirmed the switchability prediction for β5. We thus evaluated if compound-driven α-helix/β-strand switching of β5 could modulate FGFR2 signaling. We performed the virtual screening of a library containing 1.4 million of chemical compounds with two models of the third Ig-like domain of FGFR2 showing different secondary structures for β5, and we selected 32 compounds. Experimental testing using proliferation assays with FGF7-stimulated SNU-16 cells and a FGFR2-dependent Erk1/2 phosphorylation assay with FGFR2-transfected L6 cells, revealed activators and inhibitors of FGFR2. Our method for the identification of switchable proteinic regions, associated with our virtual screening approach, provides an opportunity to discover new generation of drugs with under-explored mechanism of action.

  18. Sequence analysis of mtDNA COI barcode region revealed three haplotypes within Culex pipiens assemblage.

    PubMed

    Koosha, Mona; Oshaghi, Mohammad Ali; Sedaghat, Mohammad Mehdi; Vatandoost, Hassan; Azari-Hamidian, Shahyad; Abai, Mohammad Reza; Hanafi-Bojd, Ahmad Ali; Mohtarami, Fatemeh

    2017-10-01

    Members of the Culex (Culex) pipiens assemblage are known vectors of deadly encephalitides, periodic filariasis, and West Nile virus throughout the world. However, members of this assemblage are morphologically indistinguishable or hard to distinguish and play distinct roles in transmission of the diseases. The current study aimed to provide further evidence on utility of the two most popular nuclear (ITS2-rDNA) and mitochondrial (COI barcode region) genetic markers to identify members of the assemblage. Culex pipiens assemblage specimens from different climate zones of Iran were collected and identified to species level based on morphological characteristics. Nucleotide sequences of the loci for the specimens plus available data in the GenBank were analyzed to find species specific genetic structures useful for diagnosis purposes. ITS2 region was highly divergent within species or populations suggesting lack of consistency as a reliable molecular marker. In contrast, sequence analysis of 710 bp of COI gene revealed three fixed haplotypes named here "C, T, H" within the assemblage which can be distinguished by HaeIII and AluI enzymes. There were a correlation between the haplotypes and the world climate regions, where the haplotypes H/T and C are present mainly in temperate and tropical regions of the world, respectively. In the New world, Australia, and Japan only haplotype H is found. In conjunction between tropical and temperate regions such Iran, China, and Turkey, a mix of C/H or C/H/T are present. Although, the haplotypes are not strictly species-specific, however, Cx. quinquefasciatus was mainly of haplotype C. Due to the lack of mating barrier and questionable taxonomic situation of the complex members, the mentioned haplotypes in combination with other morphological and molecular characters might be used to address the genetic structure of the studied populations. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Somatic reduction in cycads.

    PubMed

    Storey, W B

    1968-02-09

    Recurrent somatic reduction is a normal ontogenetic process in apogeotropic roots of cycads, which develop into dichotomously branching coralloid masses. The reduced cells make up part of a ring of differentiated cortical tissue lying midway between the pericycle and the epidermis; they serve as fillers among the large cells and become charged with slime. The differentiated tissue is colonized by a species of blue-green algae.

  20. Functional magnetic resonance imaging reveals brain regions mediating the response to resistive expiratory loads in humans.

    PubMed Central

    Gozal, D; Omidvar, O; Kirlew, K A; Hathout, G M; Lufkin, R B; Harper, R M

    1996-01-01

    Obstructive lung disease is the most common form of respiratory disturbance. However, the location of brain structures underlying the ventilatory response to resistive expiratory loads is unknown in humans. To study this issue, midsagittal magnetic resonance images were acquired in eight healthy volunteers before and after application of a moderate resistive expiratory load (30 cmH2O/liter/s), using functional magnetic resonance imaging (fMRI) strategies (1.5-T magnetic resonance; repetition time: 72 ms; echo time: 45 ms; flip angle: 30 degrees; field of view: 26 cm; slice thickness: 5 mm; 128 x 256 x 1 number of excitations). Digital image subtractions and region of interest analyses revealed significant increases in fMRI signal intensity in discrete areas of the ventral medulla, ventral and dorsal pontomedullary structures, basal forebrain, and cerebellum. Upon load withdrawal, a rapid fMRI signal off-transient occurred in all activated sites. Application of an identical load immediately after recovery from the initial stimulus resulted in smaller signal increases (P < 0.02). Prolongation of load duration was associated with progressive fMRI signal decrease across activated regions. In three additional subjects, the threshold for significant MRI signal increases was established at expiratory loads > or = 15 cmH2O/liter/s and was dose dependent with increasing loads. We conclude that resistive expiratory loads > or = 15 cmH2O/liter/s elicit regional activation of discrete brain locations in humans. PMID:8550849

  1. Structure and evolution of the lunar Procellarum region as revealed by GRAIL gravity data.

    PubMed

    Andrews-Hanna, Jeffrey C; Besserer, Jonathan; Head, James W; Howett, Carly J A; Kiefer, Walter S; Lucey, Paul J; McGovern, Patrick J; Melosh, H Jay; Neumann, Gregory A; Phillips, Roger J; Schenk, Paul M; Smith, David E; Solomon, Sean C; Zuber, Maria T

    2014-10-02

    The Procellarum region is a broad area on the nearside of the Moon that is characterized by low elevations, thin crust, and high surface concentrations of the heat-producing elements uranium, thorium, and potassium. The region has been interpreted as an ancient impact basin approximately 3,200 kilometres in diameter, although supporting evidence at the surface would have been largely obscured as a result of the great antiquity and poor preservation of any diagnostic features. Here we use data from the Gravity Recovery and Interior Laboratory (GRAIL) mission to examine the subsurface structure of Procellarum. The Bouguer gravity anomalies and gravity gradients reveal a pattern of narrow linear anomalies that border Procellarum and are interpreted to be the frozen remnants of lava-filled rifts and the underlying feeder dykes that served as the magma plumbing system for much of the nearside mare volcanism. The discontinuous surface structures that were earlier interpreted as remnants of an impact basin rim are shown in GRAIL data to be a part of this continuous set of border structures in a quasi-rectangular pattern with angular intersections, contrary to the expected circular or elliptical shape of an impact basin. The spatial pattern of magmatic-tectonic structures bounding Procellarum is consistent with their formation in response to thermal stresses produced by the differential cooling of the province relative to its surroundings, coupled with magmatic activity driven by the greater-than-average heat flux in the region.

  2. Human-mouse comparative genomics: successes and failures to reveal functional regions of the human genome

    SciTech Connect

    Pennacchio, Len A.; Baroukh, Nadine; Rubin, Edward M.

    2003-05-15

    Deciphering the genetic code embedded within the human genome remains a significant challenge despite the human genome consortium's recent success at defining its linear sequence (Lander et al. 2001; Venter et al. 2001). While useful strategies exist to identify a large percentage of protein encoding regions, efforts to accurately define functional sequences in the remaining {approx}97 percent of the genome lag. Our primary interest has been to utilize the evolutionary relationship and the universal nature of genomic sequence information in vertebrates to reveal functional elements in the human genome. This has been achieved through the combined use of vertebrate comparative genomics to pinpoint highly conserved sequences as candidates for biological activity and transgenic mouse studies to address the functionality of defined human DNA fragments. Accordingly, we describe strategies and insights into functional sequences in the human genome through the use of comparative genomics coupled wit h functional studies in the mouse.

  3. A vital region for human glycoprotein hormone trafficking revealed by an LHB mutation.

    PubMed

    Potorac, Iulia; Rivero-Müller, Adolfo; Trehan, Ashutosh; Kiełbus, Michał; Jozwiak, Krzysztof; Pralong, Francois; Hafidi, Aicha; Thiry, Albert; Ménagé, Jean-Jacques; Huhtaniemi, Ilpo; Beckers, Albert; Daly, Adrian F

    2016-12-01

    Glycoprotein hormones are complex hormonally active macromolecules. Luteinizing hormone (LH) is essential for the postnatal development and maturation of the male gonad. Inactivating Luteinizing hormone beta (LHB) gene mutations are exceptionally rare and lead to hypogonadism that is particularly severe in males. We describe a family with selective LH deficiency and hypogonadism in two brothers. DNA sequencing of LHB was performed and the effects of genetic variants on hormone function and secretion were characterized by mutagenesis studies, confocal microscopy and functional assays. A 20-year-old male from a consanguineous family had pubertal delay, hypogonadism and undetectable LH. A homozygous c.118_120del (p.Lys40del) mutation was identified in the patient and his brother, who subsequently had the same phenotype. Treatment with hCG led to pubertal development, increased circulating testosterone and spermatogenesis. Experiments in HeLa cells revealed that the mutant LH is retained intracellularly and showed diffuse cytoplasmic distribution. The mutated LHB heterodimerizes with the common alpha-subunit and can activate its receptor. Deletion of flanking glutamic acid residues at positions 39 and 41 impair LH to a similar extent as deletion of Lys40. This region is functionally important across all heterodimeric glycoprotein hormones, because deletion of the corresponding residues in hCG, follicle-stimulating hormone and thyroid-stimulating hormone beta-subunits also led to intracellular hormone retention. This novel LHB mutation results in hypogonadism due to intracellular sequestration of the hormone and reveals a discrete region in the protein that is crucial for normal secretion of all human glycoprotein hormones.

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

    PubMed

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

    2016-01-20

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

  5. Lithium Accumulates in Neurogenic Brain Regions as Revealed by High Resolution Ion Imaging

    PubMed Central

    Zanni, Giulia; Michno, Wojciech; Di Martino, Elena; Tjärnlund-Wolf, Anna; Pettersson, Jean; Mason, Charlotte Elizabeth; Hellspong, Gustaf; Blomgren, Klas; Hanrieder, Jörg

    2017-01-01

    Lithium (Li) is a potent mood stabilizer and displays neuroprotective and neurogenic properties. Despite extensive investigations, the mechanisms of action have not been fully elucidated, especially in the juvenile, developing brain. Here we characterized lithium distribution in the juvenile mouse brain during 28 days of continuous treatment that result in clinically relevant serum concentrations. By using Time-of-Flight Secondary Ion Mass Spectrometry- (ToF-SIMS) based imaging we were able to delineate temporospatial lithium profile throughout the brain and concurrent distribution of endogenous lipids with high chemical specificity and spatial resolution. We found that Li accumulated in neurogenic regions and investigated the effects on hippocampal neurogenesis. Lithium increased proliferation, as judged by Ki67-immunoreactivity, but did not alter the number of doublecortin-positive neuroblasts at the end of the treatment period. Moreover, ToF-SIMS revealed a steady depletion of sphingomyelin in white matter regions during 28d Li-treatment, particularly in the olfactory bulb. In contrast, cortical levels of cholesterol and choline increased over time in Li-treated mice. This is the first study describing ToF-SIMS imaging for probing the brain-wide accumulation of supplemented Li in situ. The findings demonstrate that this technique is a powerful approach for investigating the distribution and effects of neuroprotective agents in the brain. PMID:28098178

  6. Lithium Accumulates in Neurogenic Brain Regions as Revealed by High Resolution Ion Imaging.

    PubMed

    Zanni, Giulia; Michno, Wojciech; Di Martino, Elena; Tjärnlund-Wolf, Anna; Pettersson, Jean; Mason, Charlotte Elizabeth; Hellspong, Gustaf; Blomgren, Klas; Hanrieder, Jörg

    2017-01-18

    Lithium (Li) is a potent mood stabilizer and displays neuroprotective and neurogenic properties. Despite extensive investigations, the mechanisms of action have not been fully elucidated, especially in the juvenile, developing brain. Here we characterized lithium distribution in the juvenile mouse brain during 28 days of continuous treatment that result in clinically relevant serum concentrations. By using Time-of-Flight Secondary Ion Mass Spectrometry- (ToF-SIMS) based imaging we were able to delineate temporospatial lithium profile throughout the brain and concurrent distribution of endogenous lipids with high chemical specificity and spatial resolution. We found that Li accumulated in neurogenic regions and investigated the effects on hippocampal neurogenesis. Lithium increased proliferation, as judged by Ki67-immunoreactivity, but did not alter the number of doublecortin-positive neuroblasts at the end of the treatment period. Moreover, ToF-SIMS revealed a steady depletion of sphingomyelin in white matter regions during 28d Li-treatment, particularly in the olfactory bulb. In contrast, cortical levels of cholesterol and choline increased over time in Li-treated mice. This is the first study describing ToF-SIMS imaging for probing the brain-wide accumulation of supplemented Li in situ. The findings demonstrate that this technique is a powerful approach for investigating the distribution and effects of neuroprotective agents in the brain.

  7. Lateral and Medial Ventral Occipitotemporal Regions Interact During the Recognition of Images Revealed from Noise

    PubMed Central

    Nordhjem, Barbara; Ćurčić-Blake, Branislava; Meppelink, Anne Marthe; Renken, Remco J.; de Jong, Bauke M.; Leenders, Klaus L.; van Laar, Teus; Cornelissen, Frans W.

    2016-01-01

    Several studies suggest different functional roles for the medial and the lateral sections of the ventral visual cortex in object recognition. Texture and surface information is processed in medial sections, while shape information is processed in lateral sections. This begs the question whether and how these functionally specialized sections interact with each other and with early visual cortex to facilitate object recognition. In the current research, we set out to answer this question. In an fMRI study, 13 subjects viewed and recognized images of objects and animals that were gradually revealed from noise while their brains were being scanned. We applied dynamic causal modeling (DCM)—a method to characterize network interactions—to determine the modulatory effect of object recognition on a network comprising the primary visual cortex (V1), the lingual gyrus (LG) in medial ventral cortex and the lateral occipital cortex (LO). We found that object recognition modulated the bilateral connectivity between LG and LO. Moreover, the feed-forward connectivity from V1 to LG and LO was modulated, while there was no evidence for feedback from these regions to V1 during object recognition. In particular, the interaction between medial and lateral areas supports a framework in which visual recognition of objects is achieved by networked regions that integrate information on image statistics, scene content and shape—rather than by a single categorically specialized region—within the ventral visual cortex. PMID:26778997

  8. Upper crustal structure of the Mount Hood, Oregon, region as revealed by time term analysis.

    USGS Publications Warehouse

    Kohler, W.M.; Healy, J.H.; Wegener, S.S.

    1982-01-01

    Seismic refraction data with a dense areal distribution were collected to study the seismic structure of Mount Hood and the surrounding region. This area is typical of Cascade volcanoes and is geologically quite complex. The prime goals of this project were to search for velocity variations in the upper crustal rocks and to determine if the velocity of these rocks is anisotropic. A new system, including 100 remote recording units, was developed to facilitate the collection of data in this type of survey. The data collected in this study reveal a large variation in velocity and thickness of the uppermost crustal rocks that is probably typical of the High Cascade province. A regional structural pattern surrounding Mount Hood, where there is a marked thinning of low-velocity near-surface rocks, suggests that the present edifice of Mount Hood lies on top of a much larger structure, possibly the roof of a large batholith that was emplaced prior to the eruption of the volcanic rocks that form the modern mountain.-Authors

  9. Regional Atmospheric CO2 Inversion Reveals Seasonal and Geographic Differences in Amazon Net Biome Exchange

    NASA Technical Reports Server (NTRS)

    Alden, Caroline B.; Miller, John B.; Gatti, Luciana V.; Gloor, Manuel M.; Guan, Kaiyu; Michalak, Anna M.; van der Laan-Luijkx, Ingrid; Touma, Danielle; Andrews, Arlyn; Basso, Luana G.; hide

    2016-01-01

    Understanding tropical rainforest carbon exchange and its response to heat and drought is critical for quantifying the effects of climate change on tropical ecosystems, including global climate carbon feedbacks. Of particular importance for the global carbon budget is net biome exchange of CO2 with the atmosphere (NBE), which represents nonfire carbon fluxes into and out of biomass and soils. Subannual and sub-Basin Amazon NBE estimates have relied heavily on process-based biosphere models, despite lack of model agreement with plot-scale observations. We present a new analysis of airborne measurements that reveals monthly, regional-scale (Approx.1-8 x 10(exp -6) km2) NBE variations. We develop a regional atmospheric CO2 inversion that provides the first analysis of geographic and temporal variability in Amazon biosphere-atmosphere carbon exchange and that is minimally influenced by biosphere model-based first guesses of seasonal and annual mean fluxes. We find little evidence for a clear seasonal cycle in Amazon NBE but do find NBE sensitivity to aberrations from long-term mean climate. In particular, we observe increased NBE (more carbon emitted to the atmosphere) associated with heat and drought in 2010, and correlations between wet season NBE and precipitation (negative correlation) and temperature (positive correlation). In the eastern Amazon, pulses of increased NBE persisted through 2011, suggesting legacy effects of 2010 heat and drought. We also identify regional differences in postdrought NBE that appear related to long-term water availability. We examine satellite proxies and find evidence for higher gross primary productivity (GPP) during a pulse of increased carbon uptake in 2011, and lower GPP during a period of increased NBE in the 2010 dry season drought, but links between GPP and NBE changes are not conclusive. These results provide novel evidence of NBE sensitivity to short-term temperature and moisture extremes in the Amazon, where monthly and sub

  10. Numerical simulations and infrared spectro-interferometry reveal the wind collision region in γ2 Velorum

    NASA Astrophysics Data System (ADS)

    Lamberts, A.; Millour, F.; Liermann, A.; Dessart, L.; Driebe, T.; Duvert, G.; Finsterle, W.; Girault, V.; Massi, F.; Petrov, R. G.; Schmutz, W.; Weigelt, G.; Chesneau, O.

    2017-07-01

    Colliding stellar winds in massive binary systems have been studied through their radio, optical lines and strong X-ray emission for decades. More recently, near-infrared spectro-interferometric observations have become available in a few systems, but isolating the contribution from the individual stars and the wind collision region still remains a challenge. In this paper, we study the colliding wind binary γ2 Velorum and aim at identifying the wind collision zone from infrared interferometric data, which provide unique spatial information to determine the wind properties. Our analysis is based on multi-epoch Very Large Telescope Interferometer/Astronomical Multi-BEam Recombiner (VLTI/AMBER) data that allows us to separate the spectral components of both stars. First, we determine the astrometric solution of the binary and confirm previous distance measurements. We then analyse the spectra of the individual stars, showing that the O star spectrum is peculiar within its class. Then, we perform three-dimensional hydrodynamic simulations of the system from which we extract model images, visibility curves and closure phases that can be directly compared with the observed data. The hydrodynamic simulations reveal the 3D spiral structure of the wind collision region, which results in phase-dependent emission maps. Our model visibility curves and closure phases provide a good match when the wind collision region accounts for 3-10 per cent γ2 Vel's total flux in the near-infrared. The dialogue between hydrodynamic simulations, radiative transfer models and observations allows us to fully exploit the observations. Similar efforts will be crucial to study circumstellar environments with the new generation of VLTI instruments like GRAVITY and MATISSE.

  11. Regional atmospheric CO2 inversion reveals seasonal and geographic differences in Amazon net biome exchange.

    PubMed

    Alden, Caroline B; Miller, John B; Gatti, Luciana V; Gloor, Manuel M; Guan, Kaiyu; Michalak, Anna M; van der Laan-Luijkx, Ingrid T; Touma, Danielle; Andrews, Arlyn; Basso, Luana S; Correia, Caio S C; Domingues, Lucas G; Joiner, Joanna; Krol, Maarten C; Lyapustin, Alexei I; Peters, Wouter; Shiga, Yoichi P; Thoning, Kirk; van der Velde, Ivar R; van Leeuwen, Thijs T; Yadav, Vineet; Diffenbaugh, Noah S

    2016-10-01

    Understanding tropical rainforest carbon exchange and its response to heat and drought is critical for quantifying the effects of climate change on tropical ecosystems, including global climate-carbon feedbacks. Of particular importance for the global carbon budget is net biome exchange of CO2 with the atmosphere (NBE), which represents nonfire carbon fluxes into and out of biomass and soils. Subannual and sub-Basin Amazon NBE estimates have relied heavily on process-based biosphere models, despite lack of model agreement with plot-scale observations. We present a new analysis of airborne measurements that reveals monthly, regional-scale (~1-8 × 10(6)  km(2) ) NBE variations. We develop a regional atmospheric CO2 inversion that provides the first analysis of geographic and temporal variability in Amazon biosphere-atmosphere carbon exchange and that is minimally influenced by biosphere model-based first guesses of seasonal and annual mean fluxes. We find little evidence for a clear seasonal cycle in Amazon NBE but do find NBE sensitivity to aberrations from long-term mean climate. In particular, we observe increased NBE (more carbon emitted to the atmosphere) associated with heat and drought in 2010, and correlations between wet season NBE and precipitation (negative correlation) and temperature (positive correlation). In the eastern Amazon, pulses of increased NBE persisted through 2011, suggesting legacy effects of 2010 heat and drought. We also identify regional differences in postdrought NBE that appear related to long-term water availability. We examine satellite proxies and find evidence for higher gross primary productivity (GPP) during a pulse of increased carbon uptake in 2011, and lower GPP during a period of increased NBE in the 2010 dry season drought, but links between GPP and NBE changes are not conclusive. These results provide novel evidence of NBE sensitivity to short-term temperature and moisture extremes in the Amazon, where monthly and sub

  12. Small Retinoprotective Peptides Reveal a Receptor-binding Region on Pigment Epithelium-derived Factor*

    PubMed Central

    Kenealey, Jason; Subramanian, Preeti; Comitato, Antonella; Bullock, Jeanee; Keehan, Laura; Polato, Federica; Hoover, David; Marigo, Valeria; Becerra, S. Patricia

    2015-01-01

    The cytoprotective effects of pigment epithelium-derived factor (PEDF) require interactions between an as of a yet undefined region with a distinct ectodomain on the PEDF receptor (PEDF-R). Here we characterized the area in PEDF that interacts with PEDF-R to promote photoreceptor survival. Molecular docking studies suggested that the ligand binding site of PEDF-R interacts with the neurotrophic region of PEDF (44-mer, positions 78–121). Binding assays demonstrated that PEDF-R bound the 44-mer peptide. Moreover, peptide P1 from the PEDF-R ectodomain had affinity for the 44-mer and a shorter fragment within it, 17-mer (positions 98–114). Single residue substitutions to alanine along the 17-mer sequence were designed and tested for binding and biological activity. Altered 17-mer[R99A] did not bind to the P1 peptide, whereas 17-mer[H105A] had higher affinity than the unmodified 17-mer. Peptides 17-mer, 17-mer[H105A], and 44-mer exhibited cytoprotective effects in cultured retina R28 cells. Intravitreal injections of these peptides and PEDF in the rd1 mouse model of retinal degeneration decreased the numbers of dying photoreceptors, 17-mer[H105A] being most effective. The blocking peptide P1 hindered their protective effects both in retina cells and in vivo. Thus, in addition to demonstrating that the region composed of positions 98–114 of PEDF contains critical residues for PEDF-R interaction that mediates survival effects, the findings reveal distinct small PEDF fragments with neurotrophic effects on photoreceptors. PMID:26304116

  13. Age and sex differences in somatic complaints associated with depression.

    PubMed

    Berry, J M; Storandt, M; Coyne, A

    1984-07-01

    Following the procedure used by Zemore and Eames (1979) with the Beck Depression Inventory, the 20 items of the Zung Self-Rating Depression Scale were categorized as either somatic or psychological symptoms of depression. Scores of 179 college students and 462 community-dwelling older adults revealed significant, though small, age differences in somatic complaints. Somatic complaints were especially prominent in older women. Age differences in psychological symptoms of depression were not significant. Diagnosis of depression in later life, especially in women, may be confounded by the use of physical symptoms of depression that are comparable to physical changes that accompany the aging process.

  14. High rate of somatic point mutation in vitro in and near the variable-region segment of an immunoglobulin heavy chain gene.

    PubMed Central

    Meyer, J; Jäck, H M; Ellis, N; Wabl, M

    1986-01-01

    The "silent" allele at the immunoglobulin heavy-chain locus in the pre-B-lymphocyte line 18-81 contains a correctly assembled gene. However, an amber termination codon within the variable-region gene segment prematurely terminates translation into complete heavy chain. Revertants that do produce heavy chain are generated at a high rate, which is termed hypermutation. By DNA sequencing of subclones, we have confirmed that whenever mu chain is produced by the usually silent allele, a true reversion is found in the DNA. Mutations are not confined to the position of the amber termination codon but are also found at other sites in and near the variable-region gene segment. Images PMID:3092221

  15. Cerebral Cavernous Malformations: Somatic Mutations in Vascular Endothelial Cells

    PubMed Central

    Gault, Judith; Awad, Issam A.; Recksiek, Peter; Shenkar, Robert; Breeze, Robert; Handler, Michael; Kleinschmidt-DeMasters, Bette Kay

    2009-01-01

    OBJECTIVE Germline mutations in three genes have been found in familial cases of cerebral cavernous malformations (CCM). We previously discovered somatic and germline truncating mutations in the KRIT1 gene supporting the “two-hit” mechanism of CCM lesion formation in a single lesion. The purpose of this study was to screen for somatic, nonheritable, mutations in three more lesions from different patients and identify the cell type(s) in which somatic mutations occur. METHODS Somatic mutations were sought in DNA from three surgically excised, fresh-frozen CCM lesions by cloning and screening PCR products generated from KRIT1 or PDCD10 coding regions. Laser capture microdissection (LCM) was used to isolated endothelial and nonendothelial cells in order to determine if somatic mutations were found in endothelial cells. RESULTS A CCM lesion harbored somatic and germline KRIT1 mutations on different chromosomes and are therefore biallelic. Both mutations are predicted to truncate the protein. The KRIT1 somatic mutations (novel c.1800delG mutation and previously identified 34 nucleotide deletion) in CCMs from two different patients were only found in the vascular endothelial cells lining caverns. No obvious somatic mutations were identified in the two other lesions; however, the results were inconclusive possibly due to the technical limitations or the fact that these specimens had a small proportion of vascular endothelial cells lining pristine caverns. CONCLUSION The “two-hit” mechanism occurs in vascular endothelial cells lining CCM caverns from two patients with somatic and Hispanic-American KRIT1 germline mutations. Methods for somatic mutation detection should focus on vascular endothelial cells lining pristine caverns. PMID:19574835

  16. Direct somatic lineage conversion

    PubMed Central

    Tanabe, Koji; Haag, Daniel; Wernig, Marius

    2015-01-01

    The predominant view of embryonic development and cell differentiation has been that rigid and even irreversible epigenetic marks are laid down along the path of cell specialization ensuring the proper silencing of unrelated lineage programmes. This model made the prediction that specialized cell types are stable and cannot be redirected into other lineages. Accordingly, early attempts to change the identity of somatic cells had little success and was limited to conversions between closely related cell types. Nuclear transplantation experiments demonstrated, however, that specialized cells even from adult mammals can be reprogrammed into a totipotent state. The discovery that a small combination of transcription factors can reprogramme cells to pluripotency without the need of oocytes further supported the view that these epigenetic barriers can be overcome much easier than assumed, but the extent of this flexibility was still unclear. When we showed that a differentiated mesodermal cell can be directly converted to a differentiated ectodermal cell without a pluripotent intermediate, it was suggested that in principle any cell type could be converted into any other cell type. Indeed, the work of several groups in recent years has provided many more examples of direct somatic lineage conversions. Today, the question is not anymore whether a specific cell type can be generated by direct reprogramming but how it can be induced. PMID:26416679

  17. Reprogramming of somatic cells.

    PubMed

    Rajasingh, Johnson

    2012-01-01

    Reprogramming of adult somatic cells into pluripotent stem cells may provide an attractive source of stem cells for regenerative medicine. It has emerged as an invaluable method for generating patient-specific stem cells of any cell lineage without the use of embryonic stem cells. A revolutionary study in 2006 showed that it is possible to convert adult somatic cells directly into pluripotent stem cells by using a limited number of pluripotent transcription factors and is called as iPS cells. Currently, both genomic integrating viral and nonintegrating nonviral methods are used to generate iPS cells. However, the viral-based technology poses increased risk of safety, and more studies are now focused on nonviral-based technology to obtain autologous stem cells for clinical therapy. In this review, the pros and cons of the present iPS cell technology and the future direction for the successful translation of this technology into the clinic are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Identification of differentially methylated regions during vernalization revealed a role for RNA methyltransferases in bolting.

    PubMed

    Hébrard, Claire; Trap-Gentil, Marie-Véronique; Lafon-Placette, Clément; Delaunay, Alain; Joseph, Claude; Lefèbvre, Marc; Barnes, Steve; Maury, Stéphane

    2013-01-01

    Sugar beet (Beta vulgaris altissima) is a biennial root crop with an absolute requirement for cold exposure to bolt and flower, a process called vernalization. Global DNA methylation variations have been reported during vernalization in several plants. However, few genes targeted by DNA methylation during vernalization have been described. The objectives of this study were to identify differentially methylated regions and to study their involvement in bolting induction and tolerance. Restriction landmark genome scanning was applied to DNA from shoot apical meristems of sugar beet genotypes, providing a direct quantitative epigenetic assessment of several CG methylated genes without prior knowledge of gene sequence. Several differentially methylated regions exhibiting variations of gene-body DNA methylation and expression during cold exposure and/or between genotypes were identified, including an AROGENATE DEHYDRATASE and two RNA METHYLCYTOSINE TRANSFERASE sequences. One RNA METHYLCYTOSINE TRANSFERASE sequence displayed gene-body hypermethylation and activation of expression, while the other was hypomethylated and inhibited by cold exposure. Global RNA methylation and phenolic compound levels changed during cold exposure in a genotype-dependent way. The use of methyl RNA immunoprecipitation of total RNA and reverse transcription-PCR analysis revealed mRNA methylation in a vernalized bolting-resistant genotype for the FLOWERING LOCUS 1 gene, a repressor of flowering. Finally, Arabidopsis mutants for RNA METHYLCYTOSINE TRANSFERASE and AROGENATE DEHYDRATASE were shown to exhibit, under different environmental conditions, early or late bolting phenotypes, respectively. Overall, the data identified functional targets of DNA methylation during vernalization in sugar beet, and it is proposed that RNA methylation and phenolic compounds play a role in the floral transition.

  19. Dombrock genotyping in Brazilian blood donors reveals different regional frequencies of the HY allele

    PubMed Central

    Piassi, Fabiana Chagas Camargos; Santos, Silvana Maria Eloi; de Castilho, Lilian Maria; Baleotti Júnior, Wilson; Suzuki, Rodrigo Buzinaro; da Cunha, Débora Moura

    2013-01-01

    Background Dombrock blood group system genotyping has revealed various rearrangements of the Dombrock gene and identified new variant alleles in Brazil (i.e., DO*A-SH, DO*A-WL and DO*B-WL). Because of the high heterogeneity of the Brazilian population, interregional differences are expected during the investigation of Dombrock genotypes. Objective The present study aims to determine the frequencies of Dombrock genotypes in blood donors from Minas Gerais and compare the frequencies of the HY and JO alleles to those of another population in Brazil. Methods The frequencies of the DO alleles in Minas Gerais, a southeastern state of Brazil, were determined from the genotyping of 270 blood donors. Genotyping involved polymerase chain reaction and restriction fragment length polymorphism analysis to identify the 323G>T, 350C>T, 793A>G, and 898C>G mutations, which are related to the HY, JO, DO*A/DO*B, and DO*A-WL/DO*B-WL alleles, respectively. Moreover, the frequencies of rare HY and JO alleles were statistically compared using the chi-square test with data from another Brazilian region. Results The HY allele frequency in Minas Gerais (2.4%) was almost twice that of the JO allele (1.5%). The frequency of the HY allele was significantly higher (p-value = 0.001) than that in another Brazilian population and includes a rare homozygous donor with the Hy- phenotype. In addition, the DO*A-WL and DO*B-WL alleles, which were first identified in Brazil, were found in the state of Minas Gerais. Conclusions The data confirm that the frequencies of DO alleles differ between regions in Brazil. The population of Minas Gerais could be targeted in a screening strategy to identify the Hy- phenotype in order to develop a rare blood bank. PMID:24478605

  20. Migration of Frosts from High-Albedo Regions of Pluto: what New Horizons Reveals

    NASA Astrophysics Data System (ADS)

    Buratti, Bonnie J.; Stern, S. A.; Weaver, Hal A.; Young, Leslie A.; Olkin, Cathy B.; Ennico, Kimberly; Binzel, Richard P.; Zangari, Amanda; Earle, Alissa M.

    2015-11-01

    With its high eccentricity and obliquity, Pluto should exhibit seasonal volatile transport on its surface. Several lines of evidence support this transport: doubling of Pluto’s atmospheric pressure over the past two decades (Young et al., 2013, Ap. J. 766, L22; Olkin et al., 2015, Icarus 246, 230); changes in its historical rotational light curve, once all variations due to viewing geometry have been modelled (Buratti et al., 2015; Ap. J. 804, L6); and changes in HST albedo maps (Buie et al., 2010, Astron. J. 139, 1128). New Horizons LORRI images reveal that the region of greatest albedo change is not the polar cap(s) of Pluto, but the feature informally named Tombaugh Regio (TR). This feature has a normal reflectance as high as ~0.8 in some places, and it is superposed on older, lower-albedo pre-existing terrain with an albedo of only ~0.10. This contrast is larger than any other body in the Solar System, except for Iapetus. This albedo dichotomy leads to a complicated system of cold-trapping and thermal segregation, beyond the simple picture of seasonal volatile transport. Whatever the origin of TR, it initially acted as a cold trap, as the temperature differential between the high and low albedo regions could be enormous, possibly approaching 20K, based on their albedo differences and assuming their normalized phase curves are similar. This latter assumption will be refined as the full New Horizons data set is returned.Over six decades of ground-based photometry suggest that TR has been decreasing in albedo over the last 25 years. Possible causes include changing insolation angles, or sublimation from the edges where the high-albedo material impinges on a much warmer substrate.Funding by the NASA New Horizons Project acknowledged.

  1. Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations.

    PubMed

    Pugh, Trevor J; Weeraratne, Shyamal Dilhan; Archer, Tenley C; Pomeranz Krummel, Daniel A; Auclair, Daniel; Bochicchio, James; Carneiro, Mauricio O; Carter, Scott L; Cibulskis, Kristian; Erlich, Rachel L; Greulich, Heidi; Lawrence, Michael S; Lennon, Niall J; McKenna, Aaron; Meldrim, James; Ramos, Alex H; Ross, Michael G; Russ, Carsten; Shefler, Erica; Sivachenko, Andrey; Sogoloff, Brian; Stojanov, Petar; Tamayo, Pablo; Mesirov, Jill P; Amani, Vladimir; Teider, Natalia; Sengupta, Soma; Francois, Jessica Pierre; Northcott, Paul A; Taylor, Michael D; Yu, Furong; Crabtree, Gerald R; Kautzman, Amanda G; Gabriel, Stacey B; Getz, Gad; Jäger, Natalie; Jones, David T W; Lichter, Peter; Pfister, Stefan M; Roberts, Thomas M; Meyerson, Matthew; Pomeroy, Scott L; Cho, Yoon-Jae

    2012-08-02

    Medulloblastomas are the most common malignant brain tumours in children. Identifying and understanding the genetic events that drive these tumours is critical for the development of more effective diagnostic, prognostic and therapeutic strategies. Recently, our group and others described distinct molecular subtypes of medulloblastoma on the basis of transcriptional and copy number profiles. Here we use whole-exome hybrid capture and deep sequencing to identify somatic mutations across the coding regions of 92 primary medulloblastoma/normal pairs. Overall, medulloblastomas have low mutation rates consistent with other paediatric tumours, with a median of 0.35 non-silent mutations per megabase. We identified twelve genes mutated at statistically significant frequencies, including previously known mutated genes in medulloblastoma such as CTNNB1, PTCH1, MLL2, SMARCA4 and TP53. Recurrent somatic mutations were newly identified in an RNA helicase gene, DDX3X, often concurrent with CTNNB1 mutations, and in the nuclear co-repressor (N-CoR) complex genes GPS2, BCOR and LDB1. We show that mutant DDX3X potentiates transactivation of a TCF promoter and enhances cell viability in combination with mutant, but not wild-type, β-catenin. Together, our study reveals the alteration of WNT, hedgehog, histone methyltransferase and now N-CoR pathways across medulloblastomas and within specific subtypes of this disease, and nominates the RNA helicase DDX3X as a component of pathogenic β-catenin signalling in medulloblastoma.

  2. Seismotectonics of Marasesti region (Eastern Romania) revealed by earthquake relocations and moment tensor determinations

    NASA Astrophysics Data System (ADS)

    Borleanu, Felix; Rogozea, Maria; Placinta, Anca; Popa, Mihaela; Radulian, Mircea

    2017-04-01

    A large seismic sequence occurred between 22 November 2014 and 31 January 2015 in the Foredeep area of the South-Eastern Carpathians at a distance of about 10 km north-east relative to Marasesti city. The sequence was located in the lower crust, close to 40 km depth. Although the moment magnitude of the largest event was 5.4 according to Romplus (Romanian earthquakes catalog) the largest aftershock did not exceed 4.0 (Mw) and most of the aftershocks were weak (magnitude below 3). From a total of 230 well-located events, we relocated 178 using more than 17000 P and S differential travel times. The results show a NW-SE alignment consistent with the focal mechanism solution computed through the broadband seismic waveforms inversion. An important aspect of this sequence is the distribution in time of the seismic events, which reveals an aftershocks migration with an average velocity of about 3 km/day. This seismicity behavior might be due to the presence of the fluids. We interpret all these features in terms of the seismotectonics of the region.

  3. Abnormal Spontaneous Brain Activity in Women with Premenstrual Syndrome Revealed by Regional Homogeneity

    PubMed Central

    Liao, Hai; Pang, Yong; Liu, Peng; Liu, Huimei; Duan, Gaoxiong; Liu, Yanfei; Tang, Lijun; Tao, Jien; Wen, Danhong; Li, Shasha; Liang, Lingyan; Deng, Demao

    2017-01-01

    Background: Previous studies have revealed that the etiologies of premenstrual syndrome (PMS) refer to menstrual cycle related brain changes. However, its intrinsic neural mechanism is still unclear. The aim of the present study was to assess abnormal spontaneous brain activity and to explicate the intricate neural mechanism of PMS using resting state functional magnetic resonance imaging (RS-fMRI). Materials and Methods: The data of 20 PMS patients (PMS group) and 21 healthy controls (HC group) were analyzed by regional homogeneity (ReHo) method during the late luteal phase of menstrual cycle. In addition, all the participants were asked to complete a daily record of severity of problems (DRSP) questionnaire. Results: Compared with HC group, the results showed that PMS group had increased ReHo mainly in the bilateral precuneus, left inferior temporal cortex (ITC), right inferior frontal cortex (IFC) and left middle frontal cortex (MFC) and decreased ReHo in the right anterior cingulate cortex (ACC) at the luteal phase. Moreover, the PMS group had higher DRSP scores, and the DRSP scores positively correlated with ReHo in left MFC and negatively correlated with ReHo in the right ACC. Conclusion: Our results suggest that abnormal spontaneous brain activity is found in PMS patients and the severity of symptom is specifically related to the left MFC and right ACC. The present findings may be beneficial to explicate the intricate neural mechanism of PMS. PMID:28243196

  4. Rotating Snakes Illusion—Quantitative Analysis Reveals a Region in Luminance Space With Opposite Illusory Rotation

    PubMed Central

    Atala-Gérard, Lea

    2017-01-01

    The Rotating Snakes Illusion employs patterns with repetitive asymmetric luminance steps forming a “snake wheel.” In the underlying luminance sequence {black, dark grey, white, light grey}, coded as {0, g1, 100, g2}, we varied g1 and g2 and measured illusion strength via nulling: Saccades were performed next to a “snake wheel” that rotated physically; observers adjusted rotation until a stationary percept obtained. Observers performed the perceptual nulling of the seeming rotation reliably. Typical settings for (g1, g2), measured from images by Kitaoka, are around (20%, 60%). Indeed, we found a marked illusion in the region (g1≈{0%–25%}, g2≈{20%–75%}) with a rotation speed of ≈1°/s. Surprisingly, we detected a second “island” around (70%, 95%) with opposite direction of the illusory rotation and weaker illusion. Our quantitative measurements of illusion strength confirmed the optimal luminance choices of the standard snake wheel and, unexpectedly, revealed an opposite rotation illusion. PMID:28228928

  5. Transcriptome sequencing of purple petal spot region in tree peony reveals differentially expressed anthocyanin structural genes

    PubMed Central

    Zhang, Yanzhao; Cheng, Yanwei; Ya, Huiyuan; Xu, Shuzhen; Han, Jianming

    2015-01-01

    The pigmented cells in defined region of a petal constitute the petal spots. Petal spots attract pollinators and are found in many angiosperm families. Several cultivars of tree peony contain a single red or purple spot at the base of petal that makes the flower more attractive for the ornamental market. So far, the understanding of the molecular mechanism of spot formation is inadequate. In this study, we sequenced the transcriptome of the purple spot and the white non-spot of tree peony flower. We assembled and annotated 67,892 unigenes. Comparative analyses of the two transcriptomes showed 1,573 differentially expressed genes, among which 933 were up-regulated, and 640 were down-regulated in the purple spot. Subsequently, we examined four anthocyanin structural genes, including PsCHS, PsF3′H, PsDFR, and PsANS, which expressed at a significantly higher level in the purple spot than in the white non-spot. We further validated the digital expression data using quantitative real-time PCR. Our result uncovered transcriptome variance between the spot and non-spot of tree peony flower, and revealed that the co-expression of four anthocyanin structural genes was responsible for spot pigment in tree peony. The data will further help to unravel the genetic mechanism of peony flower spot formation. PMID:26583029

  6. Rotating Snakes Illusion-Quantitative Analysis Reveals a Region in Luminance Space With Opposite Illusory Rotation.

    PubMed

    Atala-Gérard, Lea; Bach, Michael

    2017-01-01

    The Rotating Snakes Illusion employs patterns with repetitive asymmetric luminance steps forming a "snake wheel." In the underlying luminance sequence {black, dark grey, white, light grey}, coded as {0, g1, 100, g2}, we varied g1 and g2 and measured illusion strength via nulling: Saccades were performed next to a "snake wheel" that rotated physically; observers adjusted rotation until a stationary percept obtained. Observers performed the perceptual nulling of the seeming rotation reliably. Typical settings for (g1, g2), measured from images by Kitaoka, are around (20%, 60%). Indeed, we found a marked illusion in the region (g1≈{0%-25%}, g2≈{20%-75%}) with a rotation speed of ≈1°/s. Surprisingly, we detected a second "island" around (70%, 95%) with opposite direction of the illusory rotation and weaker illusion. Our quantitative measurements of illusion strength confirmed the optimal luminance choices of the standard snake wheel and, unexpectedly, revealed an opposite rotation illusion.

  7. Seismic structure of the southern Apennines as revealed by waveform modelling of regional surface waves

    NASA Astrophysics Data System (ADS)

    Ökeler, Ahmet; Gu, Yu Jeffrey; Lerner-Lam, Arthur; Steckler, Michael S.

    2009-09-01

    We investigate the crust and upper-mantle structures beneath the southern Apennine mountain chain using three-component seismograms from the Calabria-Apennine-Tyrrhenian/Subduction-Collision-Accretion Network (CAT/SCAN) array. Surface wave waveforms from three moderate-sized (Mw > 5.0) regional earthquakes are modelled using multiple frequencies (0.03-0.06 and 0.05-0.2 Hz) and both forward and linearized-inversion algorithms. Our best-fitting shear velocity models clearly reflect the major tectonic units where, for example, the average seismic structure at depths above 50 km beneath Apulia is substantially faster than beneath the Apennine mountain chain. We identify a prominent low-velocity channel under the mountain belt at depths below ~25-30 km and a secondary low-velocity zone at 6-12 km depth near Mt Vulture (a once active volcano). Speed variations between Love and Rayleigh waves provide further constraints on the fabric and dynamic processes. Our analysis indicates that the crustal low-velocity zones are highly anisotropic (maximum 14 per cent) and allow transversely polarized shear waves to travel faster than vertically polarized shear waves. The upper crustal anomaly reveals a layer of highly deformed rocks caused by past collisions and by the active normal faults cutting across the thrust sheets, whereas hot mantle upwelling may be responsible for a high-temperature, partially molten lower crust beneath the southern Apennines.

  8. Rapid regional perturbations to the recent global geomagnetic decay revealed by a new Hawaiian record

    PubMed Central

    de Groot, L. V.; Biggin, A. J.; Dekkers, M. J.; Langereis, C. G.; Herrero-Bervera, E.

    2013-01-01

    The dominant dipolar component of the Earth’s magnetic field has been steadily weakening for at least the last 170 years. Prior to these direct measurements, archaeomagnetic records show short periods of significantly elevated geomagnetic intensity. These striking phenomena are not captured by current field models and their relationship to the recent dipole decay is highly unclear. Here we apply a novel multi-method archaeomagnetic approach to produce a new high-quality record of geomagnetic intensity variations for Hawaii, a crucial locality in the central Pacific. It reveals a short period of high intensity occurring ~1,000 years ago, qualitatively similar to behaviour observed 200 years earlier in Europe and 500 years later in Mesoamerica. We combine these records with one from Japan to produce a coherent picture that includes the dipole decaying steadily over the last millennium. Strong, regional, short-term intensity perturbations are superimposed on this global trend; their asynchronicity necessitates a highly non-dipolar nature. PMID:24177390

  9. Rapid regional perturbations to the recent global geomagnetic decay revealed by a new Hawaiian record

    NASA Astrophysics Data System (ADS)

    de Groot, L. V.; Biggin, A. J.; Dekkers, M. J.; Langereis, C. G.; Herrero-Bervera, E.

    2013-10-01

    The dominant dipolar component of the Earth’s magnetic field has been steadily weakening for at least the last 170 years. Prior to these direct measurements, archaeomagnetic records show short periods of significantly elevated geomagnetic intensity. These striking phenomena are not captured by current field models and their relationship to the recent dipole decay is highly unclear. Here we apply a novel multi-method archaeomagnetic approach to produce a new high-quality record of geomagnetic intensity variations for Hawaii, a crucial locality in the central Pacific. It reveals a short period of high intensity occurring ~1,000 years ago, qualitatively similar to behaviour observed 200 years earlier in Europe and 500 years later in Mesoamerica. We combine these records with one from Japan to produce a coherent picture that includes the dipole decaying steadily over the last millennium. Strong, regional, short-term intensity perturbations are superimposed on this global trend; their asynchronicity necessitates a highly non-dipolar nature.

  10. Genomic analysis of clonal eosinophils by CGH arrays reveals new genetic regions involved in chronic eosinophilia.

    PubMed

    Arefi, Maryam; Robledo, Cristina; Peñarrubia, María J; García de Coca, Alfonso; Cordero, Miguel; Hernández-Rivas, Jesús M; García, Juan Luis

    2014-11-01

    To assess the presence of genetic imbalances in patients with myeloproliferative neoplasms (MPNs), 38 patients with chronic eosinophilia were studied by array comparative genomic hybridization (aCGH): seven had chronic myelogenous leukaemia (CML), BCR-ABL1 positive, nine patients had myeloproliferative neoplasia Ph- (MPN-Ph-), three had a myeloid neoplasm associated with a PDGFRA rearrangement, and the remaining two cases were Lymphoproliferative T neoplasms associated with eosinophilia. In addition, 17 patients had a secondary eosinophilia and were used as controls. Eosinophilic enrichment was carried out in all cases. Genomic imbalances were found in 76% of all MPN patients. Losses on 20q were the most frequent genetic abnormality in MPNs (32%), affected the three types of MPN studied. This study also found losses at 11q13.3 in 26% of patients with MPN-Ph- and in 19p13.11 in two of the three patients with an MPN associated with a PDGFRA rearrangement. In addition, 29% of patients with CML had losses on 8q24. In summary, aCGH revealed clonality in eosinophils in most MPNs, suggesting that it could be a useful technique for defining clonality in these diseases. The presence of genetic losses in new regions could provide new insights into the knowledge of these MPN associated with eosinophilia. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. High temperature garnet growth in New England: regional temperature-time trends revealed

    NASA Astrophysics Data System (ADS)

    Sullivan, N.; Ostwald, C.; Chu, X.; Baxter, E. F.; Ague, J. J.; Eckert, J. O.

    2013-12-01

    A series of localized ultrahigh-temperature (UHT)/high-temperature (HT) granulite facies regions have been identified within the regional amphibolite facies metamorphic zone of the Central Maine Terrane stretching from north-central New Hampshire, through central Massachusetts, and into northeastern Connecticut. Here, we aim to constrain the age and peak temperature of metamorphism at three localities within this region: Bristol, NH, Phillipston, MA and Willington, CT. Garnet-forming reactions are linked directly to peak metamorphic temperatures through thermodynamic modeling and/or Zr-in-rutile thermometry. Precise garnet geochronology allows us to identify the timing of these peak temperatures, as well as the duration of garnet growth. Geochronologic and thermodynamic work was done on 12 samples collected throughout a ~5 km2 metamorphic 'hotspot' previously identified in Bristol, NH (Chamberlain and Rumble, 1988; Journal of Petrology). The highest temperature assemblage within this hotspot is characterized by the presence of garnet + sillimanite + K-feldspar + cordierite and reached temperatures >820οC. The lowest temperature periphery of the hotspot is characterized by sillimanite + muscovite + K-feldspar + minor garnet and reached a maximum temperature of 650οC. Bulk garnet ages from samples within the hotspot range significantly from at least 400.0 × 2.5 Ma to 352.7 × 1.8 Ma with the youngest ages associated with the lower temperature samples. This collection of ages indicates a prolonged period (~50 Ma) of >650οC temperatures interspersed by period(s) of garnet growth. Zoned garnet geochronology will help reveal whether garnet growth and related heating was continuous or episodic. Further south, in Phillipston, MA, zoned garnet geochronology performed on a 2.5 cm diameter garnet porphyroblast indicates garnet growth spanning 389 - 363 Ma, reaching peak temperatures at the end of that time span of 920-940οC, followed by a younger event recorded in

  12. Genomic profiling of multiple sequentially acquired tumor metastatic sites from an “exceptional responder” lung adenocarcinoma patient reveals extensive genomic heterogeneity and novel somatic variants driving treatment response. | Center for Cancer Research

    Cancer.gov

    Biswas et al. describe an “exceptional responder” lung adenocarcinoma patient who survived with metastatic lung adenocarcinoma for 7 years while undergoing single or combination ERBB2-directed therapies. Whole-genome, whole-exome, and high-coverage ion-torrent targeted sequencing were used to demonstrate extreme genomic heterogeneity between the lung and lymph node metastatic sites with only ∼1% similarity of somatic alterations between the lung and lymph node sites. However, one novel translocation, PLAG1-ACTA2, was present in both sites, and in all biopsies and autopsy samples.

  13. Somatic embryogenesis in Hedychium bousigonianum

    USDA-ARS?s Scientific Manuscript database

    An efficient primary somatic embryo (SE) and secondary somatic embryo (SSE) production system was developed for the ornamental ginger Hedychium bousigonianum Pierre ex Gagnepain. Addition of two ethylene inhibitors, salicylic acid (SA) and silver nitrate (AgNO3), to the culture media improved the sy...

  14. Interaction Landscape of Inherited Polymorphisms with Somatic Events in Cancer.

    PubMed

    Carter, Hannah; Marty, Rachel; Hofree, Matan; Gross, Andy; Jensen, James; Fisch, Kathleen M; Wu, Xingyu; DeBoever, Christopher; Van Nostrand, Eric L; Song, Yan; Wheeler, Emily; Kreisberg, Jason F; Lippman, Scott M; Yeo, Gene; Gutkind, J Silvio; Ideker, Trey

    2017-02-10

    Recent studies have characterized the extensive somatic alterations that arise during cancer. However, the somatic evolution of a tumor may be significantly affected by inherited polymorphisms carried in the germline. Here, we analyze genomic data for 5954 tumors to reveal and systematically validate 412 genetic interactions between germline polymorphisms and major somatic events, including tumor formation in specific tissues and alteration of specific cancer genes. Among germline-somatic interactions, we find germline variants in RBFOX1 that increase incidence of SF3B1 somatic mutation by eight-fold via functional alterations in RNA splicing. Similarly, 19p13.3 variants are associated with a four-fold increased likelihood of somatic mutations in PTEN. In support of this association, we find that PTEN knock-down sensitizes the MTOR pathway to high expression of the 19p13.3 gene GNA11. Finally, we observe that stratifying patients by germline polymorphisms exposes distinct somatic mutation landscapes, implicating new cancer genes. This study creates a validated resource of inherited variants that govern where and how cancer develops, opening avenues for prevention research.

  15. Use of Combined MSAP and NGS Techniques to Identify Differentially Methylated Regions in Somaclones: A Case Study of Two Stable Somatic Wheat Mutants

    PubMed Central

    Baránek, Miroslav; Čechová, Jana; Kovacs, Tamas; Eichmeier, Aleš; Wang, Shunli; Raddová, Jana; Nečas, Tomáš; Ye, Xingguo

    2016-01-01

    The appearance of somaclonal variability induced by in vitro cultivation is relatively frequent and can, in some cases, provide a valuable source of new genetic variation for crop improvement. The cause of this phenomenon remains unknown; however, there are a number of reports suggesting that epigenetics, including DNA methylations, are an important factor. In addition to the non-heritable DNA methylation changes caused by transient and reversible stress-responsive gene regulation, recent evidence supports the existence of mitotically and meiotically inherited changes. The induction of phenotypes via stable DNA methylation changes has occasionally great economical value; however, very little is known about the genetic or molecular basis of these phenotypes. We used a novel approach consisting of a standard MSAP analysis followed by deep amplicon sequencing to better understand this phenomenon. Our models included two wheat genotypes, and their somaclones induced using in vitro cultivation with a changed heritable phenotype (shortened stem height and silenced high molecular weight glutenin). Using this novel procedure, we obtained information on the dissimilarity of DNA methylation landscapes between the standard cultivar and its respective somaclones, and we extracted the sequences and genome regions that were differentially methylated between subjects. Transposable elements were identified as the most likely factor for producing changes in somaclone properties. In summary, the novel approach of combining MSAP and NGS is relatively easy and widely applicable, which is a rather unique feature compared with the currently available techniques in the epigenetics field. PMID:27792769

  16. Detection of somatic mosaicism in DMD using computer-assisted laser densitometry

    SciTech Connect

    Sutherland, J.E.; Allingham-Hawkins, D.J.; MacKenzie, J.

    1994-09-01

    Approximately two-thirds of Duchenne muscular dystrophy (DMD) patients have a deletion in the dystrophin gene located at Xp21.1. Two PCR-based multiplex systems have been developed which detect 98% of deletions in affected males. Diagnosis of carrier females requires densitometry of PCR products following gel electrophoresis to calculate dosage of specific exons. We have developed a system in which fluorescently labelled PCR products are analysed using a GENESCANNER automated fragment analyser (ABI). Dosage is determined using computer-assisted laser densitometry (CALD). Recently, we diagnosed somatic mosaicism in the mother of an affected boy using this method. PCR analysis showed that the patient had a deletion that included exons 47-51 of his dystrophin gene. CALD analysis on the patient`s 36-year-old mother revealed a 29-34% reduction in the intensity of the bands corresponding to the deleted region of the gene rather than the 50% reduction normally seen in carrier females. A skin biopsy was obtain and monoclonal fibroblast colonies were tested by CALD for the deletion. Four of the twenty colonies screened were found to be deleted while the remaining colonies had two intact copies of the gene. We conclude that this patient is a somatic mosaic for DMD and that the mutation was the result of a post-zygotic event. This is the only case of somatic mosaicism detected among 800 women from 400 DMD families tested using CALD in our laboratory. At least one other case of possible somatic mosaicism has been reported but not confirmed. Germinal mosaicism is thought to occur in approximately 10% of mothers of sporadic DMD patients. Our findings indicate that somatic mosaicism is a much rarer condition among DMD carriers, thus suggesting that mitotic mutations in the dystrophin gene are more likely to occur later in embryogenesis after differentiation of the germline.

  17. Piwi Is a Key Regulator of Both Somatic and Germline Stem Cells in the Drosophila Testis.

    PubMed

    Gonzalez, Jacob; Qi, Hongying; Liu, Na; Lin, Haifan

    2015-07-07

    The Piwi-piRNA pathway is well known for its germline function, yet its somatic role remains elusive. We show here that Piwi is required autonomously not only for germline stem cell (GSC) but also for somatic cyst stem cell (CySC) maintenance in the Drosophila testis. Reducing Piwi activity in the testis caused defects in CySC differentiation. Accompanying this, GSC daughters expanded beyond the vicinity of the hub but failed to differentiate further. Moreover, Piwi deficient in nuclear localization caused similar defects in somatic and germ cell differentiation, which was rescued by somatic Piwi expression. To explore the underlying molecular mechanism, we identified Piwi-bound piRNAs that uniquely map to a gene key for gonadal development, Fasciclin 3, and demonstrate that Piwi regulates its expression in somatic cyst cells. Our work reveals the cell-autonomous function of Piwi in both somatic and germline stem cell types, with somatic function possibly via its epigenetic mechanism.

  18. Genomic profiling of multiple sequentially acquired tumor metastatic sites from an “exceptional responder” lung adenocarcinoma patient reveals extensive genomic heterogeneity and novel somatic variants driving treatment response

    PubMed Central

    Biswas, Romi; Gao, Shaojian; Cultraro, Constance M.; Maity, Tapan K.; Venugopalan, Abhilash; Abdullaev, Zied; Shaytan, Alexey K.; Carter, Corey A.; Thomas, Anish; Rajan, Arun; Song, Young; Pitts, Stephanie; Chen, Kevin; Bass, Sara; Boland, Joseph; Hanada, Ken-Ichi; Chen, Jinqiu; Meltzer, Paul S.; Panchenko, Anna R.; Yang, James C.; Pack, Svetlana; Giaccone, Giuseppe; Schrump, David S.; Khan, Javed; Guha, Udayan

    2016-01-01

    We used next-generation sequencing to identify somatic alterations in multiple metastatic sites from an “exceptional responder” lung adenocarcinoma patient during his 7-yr course of ERBB2-directed therapies. The degree of heterogeneity was unprecedented, with ∼1% similarity between somatic alterations of the lung and lymph nodes. One novel translocation, PLAG1-ACTA2, present in both sites, up-regulated ACTA2 expression. ERBB2, the predominant driver oncogene, was amplified in both sites, more pronounced in the lung, and harbored an L869R mutation in the lymph node. Functional studies showed increased proliferation, migration, metastasis, and resistance to ERBB2-directed therapy because of L869R mutation and increased migration because of ACTA2 overexpression. Within the lung, a nonfunctional CDK12, due to a novel G879V mutation, correlated with down-regulation of DNA damage response genes, causing genomic instability, and sensitivity to chemotherapy. We propose a model whereby a subclone metastasized early from the primary site and evolved independently in lymph nodes. PMID:27900369

  19. The Nature of Genetic Variation for Complex Traits Revealed by GWAS and Regional Heritability Mapping Analyses

    PubMed Central

    Caballero, Armando; Tenesa, Albert; Keightley, Peter D.

    2015-01-01

    We use computer simulations to investigate the amount of genetic variation for complex traits that can be revealed by single-SNP genome-wide association studies (GWAS) or regional heritability mapping (RHM) analyses based on full genome sequence data or SNP chips. We model a large population subject to mutation, recombination, selection, and drift, assuming a pleiotropic model of mutations sampled from a bivariate distribution of effects of mutations on a quantitative trait and fitness. The pleiotropic model investigated, in contrast to previous models, implies that common mutations of large effect are responsible for most of the genetic variation for quantitative traits, except when the trait is fitness itself. We show that GWAS applied to the full sequence increases the number of QTL detected by as much as 50% compared to the number found with SNP chips but only modestly increases the amount of additive genetic variance explained. Even with full sequence data, the total amount of additive variance explained is generally below 50%. Using RHM on the full sequence data, a slightly larger number of QTL are detected than by GWAS if the same probability threshold is assumed, but these QTL explain a slightly smaller amount of genetic variance. Our results also suggest that most of the missing heritability is due to the inability to detect variants of moderate effect (∼0.03–0.3 phenotypic SDs) segregating at substantial frequencies. Very rare variants, which are more difficult to detect by GWAS, are expected to contribute little genetic variation, so their eventual detection is less relevant for resolving the missing heritability problem. PMID:26482794

  20. Analysis of plastome and chondriome genome types in potato somatic hybrids from Solanum tuberosum × Solanum etuberosum.

    PubMed

    Tiwari, Jagesh K; Chandel, Poonam; Singh, Bir Pal; Bhardwaj, Vinay

    2014-01-01

    Cytoplasm types of the potato somatic hybrids from Solanum tuberosum × Solanum etuberosum were analysed using chloroplast (cp) and mitochondrial (mt) organelle genomes-specific markers. Of the 29 markers (15 cpDNA and 14 mtDNA) amplified in the 26 genotypes, 5 cpDNA (H3, NTCP4, NTCP8, NTCP9, and ALC1/ALC3) and 13 mtDNA markers showed polymorphism. The cluster analysis based on the mtDNA markers detected higher diversity compared with the cpDNA markers. Presence of new mtDNA fragments of the markers, namely, T11-2, Nsm1, pumD, Nsm3, and Nsm4, were observed, while monomorphic loci revealed highly conserved genomic regions in the somatic hybrids. The study revealed that the somatic hybrids had diverse cytoplasm types consisting predominantly of T-, W-, and C-, with a few A- and S-type cp genomes; and α-, β-, and γ-type mt genomes. Somatic hybridization has unique potential to widen the cytoplasm types of the cultivated gene pools from wild species through introgression by breeding methods.

  1. Patterns of Somatic Mutations in Immunoglobulin Variable Genes

    PubMed Central

    Golding, G. Brian; Gearhart, Patricia J.; Glickman, Barry W.

    1987-01-01

    The mechanism responsible for somatic mutation in the variable genes of antibodies is unknown and may differ from previously described mechanisms that produce mutation in DNA. We have analyzed 421 somatic mutations from the rearranged immunoglobulin variable genes of mice to determine (1) if the nucleotide substitutions differ from those generated during meiosis and (2) if the presence of nearby direct and inverted repeated sequences could template mutations around the variable gene. The results reveal a difference in the pattern of substitutions obtained from somatic mutations vs. meiotic mutations. An increased frequency of T:A to C:G transitions and a decreased frequency of mutations involving a G in the somatic mutants compared to the meiotic mutants is indicated. This suggests that the mutational processes responsible for somatic mutation in antibody genes differs from that responsible for mutation during meiosis. An analysis of the local DNA sequences revealed many direct repeats and palindromic sequences that were capable of templating some of the known mutations. Although additional factors may be involved in targeting mutations to the variable gene, mistemplating by nearby repeats may provide a mechanism for the enhancement of somatic mutation. PMID:3557109

  2. Revealing an intermediate region between the collisional radiofrequency plasma bulk and its sheath

    NASA Astrophysics Data System (ADS)

    Beckers, J.; Trienekens, D. J. M.; Kroesen, G. M. W.

    2015-03-01

    Experimental evidence of the existence of an intermediate region between a capacitively coupled plasma and the collisional space-charge region at its borders is presented. This proof is generated by monitoring—in an airplane carrying out parabolic flights—the trajectory of plasma-confined microparticles. Based on only primary data and without the need for a sophisticated model, our analysis concludes a sharply marked transition from the sheath region into another region with a significantly lower—yet nonzero—space-charge density, i.e., a region which is often called the presheath.

  3. Revealing an intermediate region between the collisional radiofrequency plasma bulk and its sheath.

    PubMed

    Beckers, J; Trienekens, D J M; Kroesen, G M W

    2015-03-01

    Experimental evidence of the existence of an intermediate region between a capacitively coupled plasma and the collisional space-charge region at its borders is presented. This proof is generated by monitoring-in an airplane carrying out parabolic flights-the trajectory of plasma-confined microparticles. Based on only primary data and without the need for a sophisticated model, our analysis concludes a sharply marked transition from the sheath region into another region with a significantly lower-yet nonzero-space-charge density, i.e., a region which is often called the presheath.

  4. Landscape of somatic mutations in 560 breast cancer whole-genome sequences

    DOE PAGES

    Nik-Zainal, Serena; Davies, Helen; Staaf, Johan; ...

    2016-05-02

    Here, we analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, anothermore » with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.« less

  5. Pacific slab beneath northeast China revealed by regional and teleseismic waveform modeling

    NASA Astrophysics Data System (ADS)

    WANG, X.; Chen, Q. F.; Wei, S.

    2015-12-01

    Accurate velocity and geometry of the slab is essential for better understanding of the thermal, chemical structure of the mantle earth, as well as geodynamics. Recent tomography studies show similar morphology of the subducting Pacific slab beneath northeast China, which was stagnant in the mantle transition zone with thickness of more than 200km and an average velocity perturbation of ~1.5% [Fukao and Obayashi, 2013]. Meanwhile, waveform-modeling studies reveal that the Pacific slab beneath Japan and Kuril Island has velocity perturbation up to 5% and thickness up to 90km [Chen et al., 2007; Zhan et al., 2014]. These discrepancies are probably caused by the smoothing and limited data coverage in the tomographic inversions. Here we adopted 1D and 2D waveform modeling methods to study the fine structure of Pacific slab beneath northeast China using dense regional permanent and temporary broadband seismic records. The residual S- and P-wave travel time, difference between data and 1D synthetics, shows significant difference between the eastern and western stations. S-wave travel time residuals indicate 5-10s earlier arrivals for stations whose ray path lies within the slab, compared with those out of the slab. Teleseimic waveforms were used to rule out the major contribution of the possible low velocity structure above 200km. Furthermore, we use 2D finite-difference waveform modeling to confirm the velocity perturbation and geometry of the slab. Our result shows that the velocity perturbation in the slab is significantly higher than those reported in travel-time tomography studies. ReferencesChen, M., J. Tromp, D. Helmberger, and H. Kanamori (2007), Waveform modeling of the slab beneath Japan, J. Geophys. Res.-Solid Earth, 112(B2), 19, doi:10.1029/2006jb004394.Fukao, Y., and M. Obayashi (2013), Subducted slabs stagnant above, penetrating through, and trapped below the 660 km discontinuity, J. Geophys. Res.-Solid Earth, 118(11), 5920-5938, doi:10.1002/2013jb010466

  6. Polymorphism Analysis Reveals Reduced Negative Selection and Elevated Rate of Insertions and Deletions in Intrinsically Disordered Protein Regions.

    PubMed

    Khan, Tahsin; Douglas, Gavin M; Patel, Priyenbhai; Nguyen Ba, Alex N; Moses, Alan M

    2015-06-04

    Intrinsically disordered protein regions are abundant in eukaryotic proteins and lack stable tertiary structures and enzymatic functions. Previous studies of disordered region evolution based on interspecific alignments have revealed an increased propensity for indels and rapid rates of amino acid substitution. How disordered regions are maintained at high abundance in the proteome and across taxa, despite apparently weak evolutionary constraints, remains unclear. Here, we use single nucleotide and indel polymorphism data in yeast and human populations to survey the population variation within disordered regions. First, we show that single nucleotide polymorphisms in disordered regions are under weaker negative selection compared with more structured protein regions and have a higher proportion of neutral non-synonymous sites. We also confirm previous findings that nonframeshifting indels are much more abundant in disordered regions relative to structured regions. We find that the rate of nonframeshifting indel polymorphism in intrinsically disordered regions resembles that of noncoding DNA and pseudogenes, and that large indels segregate in disordered regions in the human population. Our survey of polymorphism confirms patterns of evolution in disordered regions inferred based on longer evolutionary comparisons.

  7. Polymorphism Analysis Reveals Reduced Negative Selection and Elevated Rate of Insertions and Deletions in Intrinsically Disordered Protein Regions

    PubMed Central

    Khan, Tahsin; Douglas, Gavin M.; Patel, Priyenbhai; Nguyen Ba, Alex N.; Moses, Alan M.

    2015-01-01

    Intrinsically disordered protein regions are abundant in eukaryotic proteins and lack stable tertiary structures and enzymatic functions. Previous studies of disordered region evolution based on interspecific alignments have revealed an increased propensity for indels and rapid rates of amino acid substitution. How disordered regions are maintained at high abundance in the proteome and across taxa, despite apparently weak evolutionary constraints, remains unclear. Here, we use single nucleotide and indel polymorphism data in yeast and human populations to survey the population variation within disordered regions. First, we show that single nucleotide polymorphisms in disordered regions are under weaker negative selection compared with more structured protein regions and have a higher proportion of neutral non-synonymous sites. We also confirm previous findings that nonframeshifting indels are much more abundant in disordered regions relative to structured regions. We find that the rate of nonframeshifting indel polymorphism in intrinsically disordered regions resembles that of noncoding DNA and pseudogenes, and that large indels segregate in disordered regions in the human population. Our survey of polymorphism confirms patterns of evolution in disordered regions inferred based on longer evolutionary comparisons. PMID:26047845

  8. Re-sequencing regions of the ovine Y chromosome in domestic and wild sheep reveals novel paternal haplotypes.

    PubMed

    Meadows, J R S; Kijas, J W

    2009-02-01

    The male-specific region of the ovine Y chromosome (MSY) remains poorly characterized, yet sequence variants from this region have the potential to reveal the wild progenitor of domestic sheep or examples of domestic and wild paternal introgression. The 5' promoter region of the sex-determining gene SRY was re-sequenced using a subset of wild sheep including bighorn (Ovis canadensis), thinhorn (Ovis dalli spp.), urial (Ovis vignei), argali (Ovis ammon), mouflon (Ovis musimon) and domestic sheep (Ovis aries). Seven novel SNPs (oY2-oY8) were revealed; these were polymorphic between but not within species. Re-sequencing and fragment analysis was applied to the MSY microsatellite SRYM18. It contains a complex compound repeat structure and sequencing of three novel size fragments revealed that a pentanucleotide element remained fixed, whilst a dinucleotide element displayed variability within species. Comparison of the sequence between species revealed that urial and argali sheep grouped more closely to the mouflon and domestic breeds than the pachyceriforms (bighorn and thinhorn). SNP and microsatellite data were combined to define six previously undetected haplotypes. Analysis revealed the mouflon as the only species to share a haplotype with domestic sheep, consistent with its status as a feral domesticate that has undergone male-mediated exchange with domestic animals. A comparison of the remaining wild species and domestic sheep revealed that O. aries is free from signatures of wild sheep introgression.

  9. Record keeping, genetic selection, educational experience and farm management effects on average milk yield per cow, milk fat percentage, bacterial score and bulk tank somatic cell count of dairy farms in the Central region of Thailand.

    PubMed

    Rhone, J A; Koonawootrittriron, S; Elzo, M A

    2008-12-01

    A study was conducted to estimate the record keeping, genetic selection, educational, and farm management effects on average milk yield per cow (AYC), milk fat percentage, bacterial score, and bulk tank somatic cell count (BTSCC) of dairy farms in the central region of Thailand. Farms were located in the provinces of Saraburi and Nakhon Ratchisima and were members of the Muaklek dairy cooperative. Records from individual animals were unavailable. Thus, farm records of milk yield, milk fat percentage, bacterial score, and BTCCC were collected from July 1, 2003 through June 30, 2006. Additional record keeping, genetic selection, education, and farm management information was collected through a questionnaire in May of 2006. Data from the Muaklek dairy cooperative and the questionnaire were then merged by a farm identification number. A single trait mixed model was used to analyze AYC, milk fat percentage, and BTSCC, while a log linear model was used to analyze bacterial score. Results showed that farms that kept records on individual animals had higher (P < 0.05) milk fat percentages and lower bacterial scores than farms that did not. Farms that used genetic information (EBV) and phenotypes when selecting sires were higher (P < 0.05) for milk fat percentage than farms that used only phenotypes and personal opinion. Farms milking cows with a single unit milking machine and by hand, had higher (P < 0.05) bacterial scores and BTSCC than farms using only a single or multi unit machine. Overall farms that kept individual animal records, used EBV when selecting sires, used a single method for collecting milk, and used family labor achieved higher performance from their herds than farms that did not.

  10. Middle Atmosphere Temperature and Dynamics as Revealed from D-region Observations

    NASA Technical Reports Server (NTRS)

    Danilov, A. D.

    1984-01-01

    The concept of so-called meteorological control of the ionospheric D-region is presently undergoing development. According to this concept the electron concentration in this region is governed not only by solar and geomagnetic parameters but strongly depends on the temperature and dynamical regime of the mesosphere and stratosphere. How this connection between D-region and meteorological parameters can be used to obtain some information about middle atmosphere temperature and dynamics is examined. The essential points of the meteorological control concept are reviewed and the influence of turbulence on nitric oxide distribution and thus the ion production rate is discussed.

  11. Diversity of Fusarium head blight populations and trichothecene toxin types reveals regional differences in pathogen composition and temporal dynamics

    USDA-ARS?s Scientific Manuscript database

    Analyses of genetic diversity, trichothecene genotype composition, and population structure were conducted using 4,086 Fusarium graminearum isolates collected from wheat in eight Canadian provinces over a three year period between 2005 and 2007. The results revealed substantial regional differences ...

  12. Regionality of Dust Haze Transport in the Mars Atmosphere Revealed by Ensemble Simulations

    NASA Astrophysics Data System (ADS)

    Ogohara, K.

    2017-06-01

    Regionality of dust haze transport in the Mars atmosphere is investigated by ensemble simulations using a GCM. It is turned out that processes of dust haze dispersion by advection are categorized into a few cases.

  13. Regional variation in celiac disease risk within Sweden revealed by the nationwide prospective incidence register.

    PubMed

    Olsson, Cecilia; Stenlund, Hans; Hörnell, Agneta; Hernell, Olle; Ivarsson, Anneli

    2009-02-01

    To determine if there is any regional celiac disease (CD) risk variation in the Swedish childhood population. Prospective nationwide Swedish incidence register of CD in children 0-15 years of age, with the present analysis covering the period from 1998 to 2003. ESPGHAN diagnostic criteria for CD were used. Regions were classified according to the Nomenclature of Territorial Units for Statistics. The incidence rate for each region, gender, age group and year of diagnosis was calculated. A regional variation in CD risk was demonstrated. The childhood populations in 'West Sweden' and 'Småland and the islands', situated in the southern part of the country, had a significantly higher incidence rate compared to in 'North Middle Sweden' and 'Stockholm', situated in the central part. This regional variation was not explained by variations in risk by gender, age at diagnosis or year of diagnosis. The Swedish regional variation in CD risk supports multifactorial disease aetiology. Continued efforts are warranted to define factors, besides gluten exposure, that modulate CD risk.

  14. Decomposing effects of time on task reveals an anteroposterior gradient of perceptual decision regions.

    PubMed

    Buchsbaum, Bradley R; Erickson, Drew T; Kayser, Andrew S

    2013-01-01

    In perceptual decision making, the selection of an appropriate action depends critically on an organism's ability to use sensory inputs to accumulate evidence for a decision. However, differentiating decision-related processes from effects of "time on task" can be difficult. Here we combine the response signal paradigm, in which the experimenter rather than the subject dictates the time of the response, and independent components analysis (ICA) to search for signatures consistent with time on task and decision making, respectively, throughout the brain. Using this novel approach, we identify two such independent components from BOLD activity related to a random dot motion task: one sensitive to the main effect of stimulus duration, and one to both the main effect of motion coherence and its interaction with duration. Furthermore, we demonstrate that these two components are expressed differently throughout the brain, with activity in occipital regions most reflective of the former, activity within intraparietal sulcus modulated by both factors, and more anterior regions including the anterior insula, pre-SMA, and inferior frontal sulcus driven almost exclusively by the latter. Consistent with these ICA findings, cluster analysis identifies a posterior-to-anterior gradient that differentiates regions sensitive to time on task from regions whose activity is strongly tied to motion coherence. Together, these findings demonstrate that progressively more anterior regions are likely to participate in progressively more proximate decision-related processes.

  15. Somatization and somatic symptom presentation in cancer: a neglected area.

    PubMed

    Grassi, Luigi; Caruso, Rosangela; Nanni, Maria Giulia

    2013-02-01

    Abstract The recognition of somatization process in cancer patients is a challenging and neglected area, for the extreme difficulty in differentiating and assessing the psycho(patho)logical components from those biologically determined and related to cancer and cancer treatment, as well as for the scarce usefulness of rigid categorical DSM criteria. However, several dimensions of somatization (and the interconnected concept of abnormal illness behaviour) have been shown to be diagnosable in cancer patients and to negatively influence coping and quality of life outcomes. An integration of the formal DSM-ICD nosology with a system specifically taking into account the patients' emotional responses to cancer and cancer treatment, such as the Diagnostic Criteria for Psychosomatic Research (DCPR), is suggested. More data on some specific symptom dimensions, including pain, fatigue and sexual disorders, are needed to examine their possible psychological components. More research is also needed regarding the association of somatization with personality traits (e.g. type D distressed personality, alexithymia), developmental dimensions (e.g. attachment), and cultural issues (e.g. culturally mediated attributional styles to somatic symptoms). Also, the impact and effectiveness of specific therapeutic intervention in 'somatizing' cancer patients is necessary.

  16. Temporal Regulation of Somatic Embryogenesis by Adjusting Cellular Polyamine Content in Eggplant1

    PubMed Central

    Singh Yadav, Jitender; Venkat Rajam, Manchikatla

    1998-01-01

    Four critical stages of embryogenesis, including callus induction, cellular acquisition of morphogenetic competence, expression of embryogenic program, and development and maturation of somatic embryos during somatic embryogenesis from leaf discs of eggplant (Solanum melongena L.), were identified by scanning electron microscopy. Temporal changes in arginine decarboxylase (ADC) activity and polyamines (PAs) during critical stages of embryogenesis revealed that high levels of PAs (especially putrescine [PUT]), due to higher ADC activity in discs from the apical region (with high embryogenic capacity) than from the basal region of the leaf (with poor embryogenic capacity), were correlated with differential embryogenesis response. Kinetic studies of the up- and down-regulation of embryogenesis revealed that PUT and difluoromethylarginine pretreatments were most effective before the onset of embryogenesis. Basal discs pretreated with PUT for 4 to 7 d showed improved embryogenesis that was comparable to apical discs. PA content at various critical steps in embryogenesis from basal discs were found to be comparable to that of apical discs following adjustments of cellular PA content by PUT. In contrast, pretreatment of apical discs with difluoromethylarginine for 3 d significantly reduced ADC activity, cellular PA content, and embryogenesis to levels that were comparable to basal discs. Discs from the basal region of leaves treated with PUT for 3 d during the identified stages of embryogenesis improved their embryogenic potential. PMID:9490762

  17. Genome-wide association study reveals regions associated with gestation length in two pig populations.

    PubMed

    Hidalgo, A M; Lopes, M S; Harlizius, B; Bastiaansen, J W M

    2016-04-01

    Reproduction traits, such as gestation length (GLE), play an important role in dam line breeding in pigs. The objective of our study was to identify single nucleotide polymorphisms (SNPs) that are associated with GLE in two pig populations. Genotypes and deregressed breeding values were available for 2081 Dutch Landrace-based (DL) and 2301 Large White-based (LW) pigs. We identified two QTL regions for GLE, one in each population. For DL, three associated SNPs were detected in one QTL region spanning 0.52 Mbp on Sus scrofa chromosome (SSC) 2. For LW, four associated SNPs were detected in one region of 0.14 Mbp on SSC5. The region on SSC2 contains the heparin-binding EGF-like growth factor (HBEGF) gene, which promotes embryo implantation and has been described to be involved in embryo survival throughout gestation. The associated SNP can be used for marker-assisted selection in the studied populations, and further studies of the HBEGF gene are warranted to investigate its role in GLE.

  18. Complex deformation in the Caucasus region revealed by ambient noise seismic tomography

    NASA Astrophysics Data System (ADS)

    Legendre, Cédric P.; Tseng, Tai-Lin; Chen, Ying-Nien; Huang, Tzu-Ying; Gung, Yuan-Cheng; Karakhanyan, Arkadiy; Huang, Bor-Shouh

    2017-08-01

    Cross-correlation of 3years of ambient seismic noise recorded at 35 seismic stations deployed in Caucasus region yields hundreds of short-period surface-wave phase-speed dispersion curves on inter-station paths. We inverted these measurements using two techniques to construct tomographic images of the principal geological units of Caucasus. High-resolution isotropic and azimuthally anisotropic phase-velocity maps (at periods between 5 and 20s) and shear-velocity tomographic maps between 5 and 30km are generated. The resulting maps show a velocity dichotomy between the Caucasus region and the surrounding that is interpreted in term of changes in crustal thickness. There is also a strong dichotomy in the anisotropic pattern between the eastern part and the western part of the Caucasus. This difference in both amplitudes and directions of the 2ψ anisotropy is linked to the tectonic regime changes in the region. These observations suggest a good correlation between the tomographic models and the geology of the region. It was also possible to identify the early stage of the indentation of the Arabian Plate into the Eurasian plate, as well as to detect the possible magma chamber responsible for the Javakheti highland.

  19. Altered spontaneous activity in antisocial personality disorder revealed by regional homogeneity.

    PubMed

    Tang, Yan; Liu, Wangyong; Chen, Jingang; Liao, Jian; Hu, Dewen; Wang, Wei

    2013-08-07

    There is increasing evidence that antisocial personality disorder (ASPD) stems from brain abnormalities. However, there are only a few studies investigating brain structure in ASPD. The aim of this study was to find regional coherence abnormalities in resting-state functional MRI of ASPD. Thirty-two ASPD individuals and 34 controls underwent a resting-state functional MRI scan. The regional homogeneity (ReHo) approach was used to examine whether ASPD was related to alterations in resting-state neural activity. Support vector machine discriminant analysis was used to evaluate the sensitivity/specificity characteristics of the ReHo index in discriminating between the ASPD individuals and controls. The results showed that, compared with controls, ASPD individuals show lower ReHo in the right cerebellum posterior lobe (Crus1) and the right middle frontal gyrus, as well as higher ReHo in the right middle occipital gyrus (BA 19), left inferior temporal gyrus (BA 37), and right inferior occipital gyrus (cuneus, BA 18). All alternation regions reported a predictive accuracy above 70%. To our knowledge, this study was the first to study the change in regional activity coherence in the resting brain of ASPD individuals. These results not only elucidated the pathological mechanism of ASPD from a resting-state functional viewpoint but also showed that these alterations in ReHo may serve as potential markers for the detection of ASPD.

  20. What the soil reveals: potential total ecosystem C stores of the Pacific Northwest region, USA.

    Treesearch

    Peter S. Homann; Mark Harmon; Suzanne Remillard; Erica A.H. Smithwick

    2005-01-01

    How much organic C can a region naturally store in its ecosystems? How can this be determined, when land management has altered the vegetation of the landscape substantially? The answers may lie in the soil: this study synthesized the spatial distribution of soil properties derived from the state soils geographic database with empirical measurements of old-growth...

  1. Genome-Wide Identification of Chromatin Transitional Regions Reveals Diverse Mechanisms Defining the Boundary of Facultative Heterochromatin

    PubMed Central

    Li, Guangyao; Zhou, Lei

    2013-01-01

    Due to the self-propagating nature of the heterochromatic modification H3K27me3, chromatin barrier activities are required to demarcate the boundary and prevent it from encroaching into euchromatic regions. Studies in Drosophila and vertebrate systems have revealed several important chromatin barrier elements and their respective binding factors. However, epigenomic data indicate that the binding of these factors are not exclusive to chromatin boundaries. To gain a comprehensive understanding of facultative heterochromatin boundaries, we developed a two-tiered method to identify the Chromatin Transitional Region (CTR), i.e. the nucleosomal region that shows the greatest transition rate of the H3K27me3 modification as revealed by ChIP-Seq. This approach was applied to identify CTRs in Drosophila S2 cells and human HeLa cells. Although many insulator proteins have been characterized in Drosophila, less than half of the CTRs in S2 cells are associated with known insulator proteins, indicating unknown mechanisms remain to be characterized. Our analysis also revealed that the peak binding of insulator proteins are usually 1–2 nucleosomes away from the CTR. Comparison of CTR-associated insulator protein binding sites vs. those in heterochromatic region revealed that boundary-associated binding sites are distinctively flanked by nucleosome destabilizing sequences, which correlates with significant decreased nucleosome density and increased binding intensities of co-factors. Interestingly, several subgroups of boundaries have enhanced H3.3 incorporation but reduced nucleosome turnover rate. Our genome-wide study reveals that diverse mechanisms are employed to define the boundaries of facultative heterochromatin. In both Drosophila and mammalian systems, only a small fraction of insulator protein binding sites co-localize with H3K27me3 boundaries. However, boundary-associated insulator binding sites are distinctively flanked by nucleosome destabilizing sequences, which

  2. Shyness as a Risk-Factor for Somatic Complaints among Norwegian Adolescents

    ERIC Educational Resources Information Center

    Henriksen, Roger E.; Murberg, Terje A.

    2009-01-01

    The associations between shyness, school-related stress, social support and somatic complaints, were assessed in a sample of 501 pupils from two secondary schools in Norway. The main finding from this cross-sectional study revealed a positive significant association between shyness and somatic complaints. Findings also showed a significant…

  3. Resolving the prevalence of somatic transposition in Drosophila

    PubMed Central

    Treiber, Christoph D; Waddell, Scott

    2017-01-01

    Somatic transposition in mammals and insects could increase cellular diversity and neural mobilization has been implicated in age-dependent decline. To understand the impact of transposition in somatic cells it is essential to reliably measure the frequency and map locations of new insertions. Here we identified thousands of putative somatic transposon insertions in neurons from individual Drosophila melanogaster using whole-genome sequencing. However, the number of de novo insertions did not correlate with transposon expression or fly age. Analysing our data with exons as ‘immobile genetic elements’ revealed a similar frequency of unexpected exon translocations. A new sequencing strategy that recovers transposon: chromosome junction information revealed most putative de novo transposon and exon insertions likely result from unavoidable chimeric artefacts. Reanalysis of other published data suggests similar artefacts are often mistaken for genuine somatic transposition. We conclude that somatic transposition is less prevalent in Drosophila than previously envisaged. DOI: http://dx.doi.org/10.7554/eLife.28297.001 PMID:28742021

  4. Meteorite source regions as revealed by the near-Earth object population

    NASA Astrophysics Data System (ADS)

    Binzel, R.; DeMeo, F.; Burt, B.; Polishook, D.; Burbine, T.; Bus, S.; Tokunaga, A.; Birlan, M.

    2014-07-01

    Spectroscopic and taxonomic information is now available for 1000 near-Earth objects, having been obtained through both targeted surveys (e.g. [1--3]) or resulting from all-sky surveys (e.g. [4]). We first evaluate these results within the framework of taxonomic types in the Bus-DeMeo system [5,6] and subsequently examine meteorite correlations based on spectral and mineralogical analysis (e.g. [7,8]). We correlate our spectral findings with the source region probabilities calculated using the methods of Bottke et al. [9]. The source regions evaluated are Mars Crossers, ν_6 resonance, 3:1 resonance, the Outer Belt, and Jupiter Family Comets. In terms of taxonomy, very clear sources are indicated: Q-, Sq-, and S-types most strongly associated with ordinary chondrite meteorites show clear source signatures through the innermost main-belt regions. V-types are relatively equally balanced between ν_6 and 3:1 resonance sources, consistent with the orbital dispersion of the Vesta family. Asteroid taxonomy classes interpreted as analogous to meteorites with primitive compositions, B- and C-types, show distinct source region preferences for the outer belt and for Jupiter family comets. Most strongly indicated is a Jupiter family comet source for the D-type near-Earth objects, implying a pronounced likelihood that these ''asteroidal'' bodies are extinct or dormant comets [10]. Similarly, near-Earth objects falling in the spectrally featureless ''X-type'' category also show a strong outer belt and Jupiter family comet source region preference; even though they lack albedo measurements, they may be interpreted as originating from among ''P-type'' primitive objects common in the outer belt. Finally the Xe-class of near-Earth objects, which most closely match the spectral properties of enstatite achondrite (aubrite) meteorites, show a source region preference consistent with a Hungaria origin (confirming [11]) by entering near-Earth space through the Mars crossing and ν_6

  5. Application of colour magnification technique for revealing skin microcirculation changes under regional anaesthetic input

    NASA Astrophysics Data System (ADS)

    Rubins, Uldis; Spigulis, Janis; Miscuks, Aleksejs

    2013-11-01

    In this work the colour magnification technique was applied for monitoring of palm skin microcirculation changes under peripheral (Plexus Brachialis with axiliary access) Regional Anaesthesia (RA). During the RA procedure 20 minute video of patient's forearm was taken at steady light conditions. Video content was processed offline by custom developed Matlab software with build-in colour magnification algorithm that performs temporal filtering of video sequence near-heartbeat frequency, spatial decomposition of video and amplification of pulsatile signal in every pixel of skin image. Using this method, we are able to visualize the subcutaneous microcirculation changes in high spatial resolution. The results showed different blood pulse amplitude dynamics over the skin regions of palm and forearm during the RA. The colour magnification technique could be used for real-time monitoring of RA effect.

  6. Early changes in the hypothalamic region in prodromal Huntington disease revealed by MRI analysis

    PubMed Central

    Soneson, Charlotte; Fontes, Magnus; Zhou, Yongxia; Denisov, Vladimir; Paulsen, Jane S.; Kirik, Deniz; Petersén, Åsa

    2010-01-01

    Huntington disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat. Its length can be used to estimate the time of clinical diagnosis, which is defined by overt motor symptoms. Non-motor symptoms begin before motor onset, and involve changes in hypothalamus-regulated functions such as sleep, emotion and metabolism. Therefore we hypothesized that hypothalamic changes occur already prior to the clinical diagnosis. We performed voxel-based morphometry and logistic regression analyses of cross-sectional MR images from 220 HD gene carriers and 75 controls in the Predict-HD study. We show that changes in the hypothalamic region are detectable before clinical diagnosis and that its grey matter contents alone is sufficient to distinguish HD gene carriers from control cases. In conclusion, our study shows, for the first time, that alterations in grey matter contents in the hypothalamic region occur at least a decade before clinical diagnosis in HD using MRI. PMID:20682340

  7. Revealing region-specific biofilm viscoelastic properties by means of a micro-rheological approach.

    PubMed

    Cao, Huayu; Habimana, Olivier; Safari, Ashkan; Heffernan, Rory; Dai, Yihong; Casey, Eoin

    2016-01-01

    Particle-tracking microrheology is an in situ technique that allows quantification of biofilm material properties. It overcomes the limitations of alternative techniques such as bulk rheology or force spectroscopy by providing data on region specific material properties at any required biofilm location and can be combined with confocal microscopy and associated structural analysis. This article describes single particle tracking microrheology combined with confocal laser scanning microscopy to resolve the biofilm structure in 3 dimensions and calculate the creep compliances locally. Samples were analysed from Pseudomonas fluorescens biofilms that were cultivated over two timescales (24 h and 48 h) and alternate ionic conditions (with and without calcium chloride supplementation). The region-based creep compliance analysis showed that the creep compliance of biofilm void zones is the primary contributor to biofilm mechanical properties, contributing to the overall viscoelastic character.

  8. Patterns of hypothalamic regionalization in amphibians and reptiles: common traits revealed by a genoarchitectonic approach

    PubMed Central

    Domínguez, Laura; González, Agustín; Moreno, Nerea

    2015-01-01

    Most studies in mammals and birds have demonstrated common patterns of hypothalamic development highlighted by the combination of developmental regulatory genes (genoarchitecture), supporting the notion of the hypothalamus as a component of the secondary prosencephalon, topologically rostral to the diencephalon. In our comparative analysis we have summarized the data on the expression patterns of different transcription factors and neuroactive substances, used as anatomical markers, in the developing hypothalamus of the amphibian Xenopus laevis and the juvenile turtle Pseudemys scripta. This analysis served to highlight the organization of the hypothalamus in the anamniote/amniotic transition. We have identified supraoptoparaventricular and the suprachiasmatic regions (SCs) in the alar part of the hypothalamus, and tuberal and mammillary regions in the basal hypothalamus. Shared features in the two species are: (1) The supraoptoparaventricular region (SPV) is defined by the expression of Otp and the lack of Nkx2.1/Isl1. It is subdivided into rostral, rich in Otp and Nkx2.2, and caudal, only Otp-positive, portions. (2) The suprachiasmatic area contains catecholaminergic cell groups and lacks Otp, and can be further divided into rostral (rich in Nkx2.1 and Nkx2.2) and a caudal (rich in Isl1 and devoid of Nkx2.1) portions. (3) Expression of Nkx2.1 and Isl1 define the tuberal hypothalamus and only the rostral portion expresses Otp. (4) Its caudal boundary is evident by the lack of Isl1 in the adjacent mammillary region, which expresses Nkx2.1 and Otp. Differences in the anamnio-amniote transition were noted since in the turtle, like in other amniotes, the boundary between the alar hypothalamus and the telencephalic preoptic area shows distinct Nkx2.2 and Otp expressions but not in the amphibian (anamniote), and the alar SPV is defined by the expression of Otp/Pax6, whereas in Xenopus only Otp is expressed. PMID:25691860

  9. Regional drivers of clutch loss reveal important trade-offs for beach-nesting birds

    PubMed Central

    Schlacher, Thomas A.; Weston, Michael A.; Huijbers, Chantal M.; Anderson, Chris; Gilby, Ben L.; Olds, Andrew D.; Connolly, Rod M.; Schoeman, David S.

    2016-01-01

    Coastal birds are critical ecosystem constituents on sandy shores, yet are threatened by depressed reproductive success resulting from direct and indirect anthropogenic and natural pressures. Few studies examine clutch fate across the wide range of environments experienced by birds; instead, most focus at the small site scale. We examine survival of model shorebird clutches as an index of true clutch survival at a regional scale (∼200 km), encompassing a variety of geomorphologies, predator communities, and human use regimes in southeast Queensland, Australia. Of the 132 model nests deployed and monitored with cameras, 45 (34%) survived the experimental exposure period. Thirty-five (27%) were lost to flooding, 32 (24%) were depredated, nine (7%) buried by sand, seven (5%) destroyed by people, three (2%) failed by unknown causes, and one (1%) was destroyed by a dog. Clutch fate differed substantially among regions, particularly with respect to losses from flooding and predation. ‘Topographic’ exposure was the main driver of mortality of nests placed close to the drift line near the base of dunes, which were lost to waves (particularly during storms) and to a lesser extent depredation. Predators determined the fate of clutches not lost to waves, with the depredation probability largely influenced by region. Depredation probability declined as nests were backed by higher dunes and were placed closer to vegetation. This study emphasizes the scale at which clutch fate and survival varies within a regional context, the prominence of corvids as egg predators, the significant role of flooding as a source of nest loss, and the multiple trade-offs faced by beach-nesting birds and those that manage them. PMID:27672510

  10. Regional drivers of clutch loss reveal important trade-offs for beach-nesting birds.

    PubMed

    Maslo, Brooke; Schlacher, Thomas A; Weston, Michael A; Huijbers, Chantal M; Anderson, Chris; Gilby, Ben L; Olds, Andrew D; Connolly, Rod M; Schoeman, David S

    2016-01-01

    Coastal birds are critical ecosystem constituents on sandy shores, yet are threatened by depressed reproductive success resulting from direct and indirect anthropogenic and natural pressures. Few studies examine clutch fate across the wide range of environments experienced by birds; instead, most focus at the small site scale. We examine survival of model shorebird clutches as an index of true clutch survival at a regional scale (∼200 km), encompassing a variety of geomorphologies, predator communities, and human use regimes in southeast Queensland, Australia. Of the 132 model nests deployed and monitored with cameras, 45 (34%) survived the experimental exposure period. Thirty-five (27%) were lost to flooding, 32 (24%) were depredated, nine (7%) buried by sand, seven (5%) destroyed by people, three (2%) failed by unknown causes, and one (1%) was destroyed by a dog. Clutch fate differed substantially among regions, particularly with respect to losses from flooding and predation. 'Topographic' exposure was the main driver of mortality of nests placed close to the drift line near the base of dunes, which were lost to waves (particularly during storms) and to a lesser extent depredation. Predators determined the fate of clutches not lost to waves, with the depredation probability largely influenced by region. Depredation probability declined as nests were backed by higher dunes and were placed closer to vegetation. This study emphasizes the scale at which clutch fate and survival varies within a regional context, the prominence of corvids as egg predators, the significant role of flooding as a source of nest loss, and the multiple trade-offs faced by beach-nesting birds and those that manage them.

  11. Two-dimensional correlation spectroscopy reveals coupled immunoglobulin regions of differential flexibility that influence stability.

    PubMed

    Kamerzell, Tim J; Middaugh, C Russell

    2007-08-28

    Despite the well-accepted importance of protein flexibility and dynamics in molecular recognition and conformational stability, our understanding of these relationships is incomplete. Immunoglobulin flexibility is essential for antigen binding and adaptation to diverse molecular shapes and sizes. The inherent flexibility of immunoglobulins also renders these molecules suitable for investigating the possible relationships between protein flexibility and stability. To better understand these inter-relationships, we employ generalized perturbation-based two-dimensional correlation FTIR spectroscopy to monitor the time evolution of H-D exchange of an IgG1 as a function of pH. The differential flexibility of various immunoglobulin regions is described in response to an external perturbation and shown to vary widely. The greatest number of regions with differential exchange rates and, thus differential flexibility, is seen at pH 6. Approximately seven, six, five, and four separate states that exchange with different rates were observed at pH 6, 8, 4, and 2, respectively. The overall distribution of exchange rates calculated from the decays of the integrated Amide I and Amide II areas provides further evidence of multiple regions with differential flexibility. The sequence of events at pH 4 determined from the asynchronous vibrational patterns is of significant interest and suggests protonation of Glu and Asp side chains occurs first and initiates changes in the conformation and flexibility of different sheet and turns structure. A complex inter-relationship between differential regional flexibility and conformational coupling (i.e., cooperativity) initiated by changes in pH influences the stability of this IgG.

  12. Patterns of hypothalamic regionalization in amphibians and reptiles: common traits revealed by a genoarchitectonic approach.

    PubMed

    Domínguez, Laura; González, Agustín; Moreno, Nerea

    2015-01-01

    Most studies in mammals and birds have demonstrated common patterns of hypothalamic development highlighted by the combination of developmental regulatory genes (genoarchitecture), supporting the notion of the hypothalamus as a component of the secondary prosencephalon, topologically rostral to the diencephalon. In our comparative analysis we have summarized the data on the expression patterns of different transcription factors and neuroactive substances, used as anatomical markers, in the developing hypothalamus of the amphibian Xenopus laevis and the juvenile turtle Pseudemys scripta. This analysis served to highlight the organization of the hypothalamus in the anamniote/amniotic transition. We have identified supraoptoparaventricular and the suprachiasmatic regions (SCs) in the alar part of the hypothalamus, and tuberal and mammillary regions in the basal hypothalamus. Shared features in the two species are: (1) The supraoptoparaventricular region (SPV) is defined by the expression of Otp and the lack of Nkx2.1/Isl1. It is subdivided into rostral, rich in Otp and Nkx2.2, and caudal, only Otp-positive, portions. (2) The suprachiasmatic area contains catecholaminergic cell groups and lacks Otp, and can be further divided into rostral (rich in Nkx2.1 and Nkx2.2) and a caudal (rich in Isl1 and devoid of Nkx2.1) portions. (3) Expression of Nkx2.1 and Isl1 define the tuberal hypothalamus and only the rostral portion expresses Otp. (4) Its caudal boundary is evident by the lack of Isl1 in the adjacent mammillary region, which expresses Nkx2.1 and Otp. Differences in the anamnio-amniote transition were noted since in the turtle, like in other amniotes, the boundary between the alar hypothalamus and the telencephalic preoptic area shows distinct Nkx2.2 and Otp expressions but not in the amphibian (anamniote), and the alar SPV is defined by the expression of Otp/Pax6, whereas in Xenopus only Otp is expressed.

  13. Metagenomic analysis reveals changes of the Drosophila suzukii microbiota in the newly colonised regions.

    PubMed

    Martinez-Sañudo, Isabel; Simonato, Mauro; Squartini, Andrea; Mori, Nicola; Marri, Laura; Mazzon, Luca

    2017-03-21

    The spotted wing drosophila, Drosophila suzukii (Matsumura) (Diptera: Drosophilidae) is a highly polyphagous pest of a wide variety of wild or cultivated berry and stone fruit. Originating from Southeast Asia, it has recently invaded a wide range of regions in Europe and North-America. It is well known that insect microbiotas may significantly influence several aspects of the host biology and play an important role in invasive species introduction into new areas. However, in spite of the great economic importance of D. suzukii, a limited attention has been given so far to its microbiota. In this study, we present the first in-depth characterization of gut bacterial diversity from field (native and invasive range) and lab-reared populations of this insect. The gut bacterial communities of field insects were dominated, regardless of their origin, by two families of the phylum Proteobacteria: Acetobacteraceae and Enterobacteriaceae, while Firmicutes, mainly represented by the family Staphylococcaceae, prevailed in lab-reared population. Locality was the most significant factor in shaping the microbiota of wild flies. Moreover, a negative correlation between diversity and abundance of Enterobacteriaceae and the time elapsed since the establishment of D. suzukii in a new region was observed. Altogether our results indicate that habitat, food resources as well as the colonization phase of a new region contribute to shape the bacterial communities of the invasive species which, in turn, by evolving more quickly, could influence host adaptation in a new environment. This article is protected by copyright. All rights reserved.

  14. Surface Response to Regional Uplift of Madagascar Reveals Short Wavelength Dynamic Topography

    NASA Astrophysics Data System (ADS)

    Stephenson, S.; White, N.

    2016-12-01

    The physiography of Madagascar is characterized by high elevation but low relief topography with 42% of the landscape at an elevation grgeater than 500 m. Eocene marine limestones crop out at an elevation of 400 m, extensive low relief erosion surfaces capped by laterites occur at elevations of up to 2 km, and longitudinal river profiles are disequilibrated. Together, these observations suggest that Madagascar underwent regional uplift in Neogene times. Inverse modeling of drainage networks suggests that regional uplift is diachronous and has occurred on wavelengths of 1000 km. The existence of deeply incised river channels together with low-temperature thermochronologic measurements (i.e. AFT, AHe) implies that erosion occurred in response to regional Neogene uplift. Admittance analysis of long wavelength free-air gravity and topography shows that admittance, Z = 45 ± 5 mGal/km. The history of Neogene volcanism and a lack of significant tectonic shortening both suggest that uplift is dynamically supported. Here we present a suite of U-Th dates of emergent coral reef deposits from northern Madagascar, whose margins are sometimes considered `stable'. Elevation of these coeval coral reefs decreases from 7.2 m at the northern tip of Madagascar to sea level 100 km to the south. The existence of a spatial gradient suggests that differential vertical motions occurred during Late Quaternary times. These results raise significant questions about the reliability both of emergent coral reefs as global sea-level markers and the length-scale of variations in dynamic topography.

  15. Genomic regions associated with the nitrogen limitation response revealed in a global wheat core collection.

    PubMed

    Bordes, Jacques; Ravel, C; Jaubertie, J P; Duperrier, B; Gardet, O; Heumez, E; Pissavy, A L; Charmet, G; Le Gouis, J; Balfourier, F

    2013-03-01

    Modern wheat (Triticum aestivum L.) varieties in Western Europe have mainly been bred, and selected in conditions where high levels of nitrogen-rich fertilizer are applied. However, high input crop management has greatly increased the risk of nitrates leaching into groundwater with negative impacts on the environment. To investigate wheat nitrogen tolerance characteristics that could be adapted to low input crop management, we supplied 196 accessions of a wheat core collection of old and modern cultivars with high or moderate amounts of nitrogen fertilizer in an experimental network consisting of three sites and 2 years. The main breeding traits were assessed including grain yield and grain protein content. The response to nitrogen level was estimated for grain yield and grain number per m(2) using both the difference and the ratio between performance at the two input levels and the slope of joint regression. A large variability was observed for all the traits studied and the response to nitrogen level. Whole genome association mapping was carried out using 899 molecular markers taking into account the five ancestral group structure of the collection. We identified 54 main regions involving almost all chromosomes that influence yield and its components, plant height, heading date and grain protein concentration. Twenty-three regions, including several genes, spread over 16 chromosomes were involved in the response to nitrogen level. These chromosomal regions may be good candidates to be used in breeding programs to improve the performance of wheat varieties at moderate nitrogen input levels.

  16. Three-Dimensional mRNA Measurements Reveal Minimal Regional Heterogeneity in Esophageal Squamous Cell Carcinoma

    PubMed Central

    Yan, Wusheng; Shih, Joanna; Rodriguez-Canales, Jaime; Tangrea, Michael A.; Player, Audrey; Diao, Lixia; Hu, Nan; Goldstein, Alisa M.; Wang, Jing; Taylor, Philip R.; Lippman, Scott M.; Wistuba, Ignacio I.; Emmert-Buck, Michael R.; Erickson, Heidi S.

    2014-01-01

    The classic tumor clonal evolution theory postulates that cancers change over time to produce unique molecular subclones within a parent neoplasm, presumably including regional differences in gene expression. More recently, however, this notion has been challenged by studies showing that tumors maintain a relatively stable transcript profile. To examine these competing hypotheses, we microdissected discrete subregions containing approximately 3000 to 8000 cells (500 to 1500 μm in diameter) from ex vivo esophageal squamous cell carcinoma (ESCC) specimens and analyzed transcriptomes throughout three-dimensional tumor space. Overall mRNA profiles were highly similar in all 59 intratumor comparisons, in distinct contrast to the markedly different global expression patterns observed in other dissected cell populations. For example, normal esophageal basal cells contained 1918 and 624 differentially expressed genes at a greater than twofold level (95% confidence level of <5% false positives), compared with normal differentiated esophageal cells and ESCC, respectively. In contrast, intratumor regions had only zero to four gene changes at a greater than twofold level, with most tumor comparisons showing none. The present data indicate that, when analyzed using a standard array-based method at this level of histological resolution, ESCC contains little regional mRNA heterogeneity. PMID:23219752

  17. Historical whaling records reveal major regional retreat of Antarctic sea ice

    NASA Astrophysics Data System (ADS)

    Cotté, Cédric; Guinet, Christophe

    2007-02-01

    Several studies have provided evidence of a reduction of the Antarctic sea ice extent. However, these studies were conducted either at a global scale or at a regional scale, and possible inter-regional differences were not analysed. Using the long-term whaling database we investigated circum-Antarctic changes in summer sea ice extent from 1931 to 1987. Accounting for bias inherent in the whaling method, this analysis provides new insight into the historical ice edge reconstruction and inter-regional differences. We highlight a reduction of the sea ice extent occurring in the 1960s, mainly in the Weddell sector where the change ranged from 3° to 7.9° latitude through summer. Although the whaling method may not be appropriate for detecting fine-scale change, these results provide evidence for a heterogeneous circumpolar change of the sea ice extent. The shift is temporally and spatially consistent with other environmental changes detected in the Weddell sector and also with a shift in the Southern Hemisphere annular mode. The large reduction of the sea ice extent has probably influenced the ecosystem of the Weddell Sea, particularly the krill biomass.

  18. Meteorite Source Regions as Revealed by the Near-Earth Object Population

    NASA Astrophysics Data System (ADS)

    Binzel, Richard P.; DeMeo, Francesca E.; Burt, Brian J.; Polishook, David; Burbine, Thomas H.; Bus, Schelte J.; Tokunaga, Alan; Birlan, Mirel

    2014-11-01

    Spectroscopic and taxonomic information is now available for 1000 near-Earth objects, having been obtained through both targeted surveys (e.g. [1], [2], [3]) or resulting from all-sky surveys (e.g. [4]). We determine their taxonomic types in the Bus-DeMeo system [5] [6] and subsequently examine meteorite correlations based on spectral analysis (e.g. [7],[8]). We correlate our spectral findings with the source region probabilities calculated using the methods of Bottke et al. [9]. In terms of taxonomy, very clear sources are indicated: Q-, Sq-, and S-types most strongly associated with ordinary chondrite meteorites show clear source signatures through the inner main-belt. V-types are relatively equally balanced between nu6 and 3:1 resonance sources, consistent with the orbital dispersion of the Vesta family. B- and C-types show distinct source region preferences for the outer belt and for Jupiter family comets. A Jupiter family comet source predominates for the D-type near-Earth objects, implying these "asteroidal" bodies may be extinct or dormant comets [10]. Similarly, near-Earth objects falling in the spectrally featureless "X-type" category also show a strong outer belt and Jupiter family comet source region preference. Finally the Xe-class near-Earth objects, which most closely match the spectral properties of enstatite achondrite (aubrite) meteorites seen in the Hungaria region[11], show a source region preference consistent with a Hungaria origin by entering near-Earth space through the Mars crossing and nu6 resonance pathways. This work supported by the National Science Foundation Grant 0907766 and NASA Grant NNX10AG27G.[1] Lazzarin, M. et al. (2004), Mem. S. A. It. Suppl. 5, 21. [2] Thomas, C. A. et al. (2014), Icarus 228, 217. [3] Tokunaga, A. et al. (2006) BAAS 38, 59.07. [4] Hasselmann, P. H., Carvano, J. M., Lazzaro, D. (2011) NASA PDS, EAR-A-I0035-5-SDSSTAX-V1.0. [5] Bus, S.J., Binzel, R.P. (2002). Icarus 158, 146. [6] DeMeo, F.E. et al. (2009), Icarus

  19. Automated 3D MRI volumetry reveals regional atrophy differences in Rasmussen encephalitis.

    PubMed

    Wagner, Jan; Schoene-Bake, Jan-Christoph; Bien, Christian G; Urbach, Horst; Elger, Christian E; Weber, Bernd

    2012-04-01

    Rasmussen encephalitis is a chronic immune-mediated disease leading to unilateral atrophy on magnetic resonance imaging (MRI) and progressive neurologic deficits. Until now, quantitative parameters describing the course of the disease on MRI require manual intervention and are, therefore, time-consuming and observer-dependent. Furthermore, regional atrophy differences cannot be evaluated with the previously published methods. In this study we present a fully automated volumetric approach applied to serial MRI scans of 12 patients with Rasmussen encephalitis. We retrospectively analyzed 12 patients with Rasmussen encephalitis with a disease onset between 2001 and 2008. All patients underwent a total of 66 serial MRI scans including a three-dimensional T(1) data set. The volumetric analysis was based on standard procedures of the freely available software FMRIB Software Library (FSL) and required about 45 min per scan. Furthermore, planimetric analyses were performed on 51 scans as described previously. The relative and absolute volume loss of the affected hemisphere was significantly higher compared to the unaffected hemisphere. Referring to regional atrophy differences our results show that the frontal lobe and the insula were preferentially involved in the atrophic process. The degree of hemispheric, parietal, and occipital atrophy was negatively correlated with the age at disease onset, indicating a more aggressive and outspread disease in young children compared to adolescents. Volumetric hemispheric ratio and planimetric hemispheric ratio correlated significantly, but planimetric hemispheric ratio underestimated the real degree of hemiatrophy, especially in patients with predominant affections outside the frontoinsular region. The volumetric analysis presented here offers a precise assessment of the disease progression in Rasmussen encephalitis in an observer-independent and time-efficient manner and gives an interesting insight into the course of the disease

  20. Functional somatotopy revealed across multiple cortical regions using a model of complex motor task

    PubMed Central

    Cunningham, David A.; Machado, Andre; Yue, Guang H.; Carey, Jim R.; Plow, Ela B.

    2014-01-01

    The primary motor cortex (M1) possesses a functional somatotopic structure -representations of adjacent within-limb joints overlap to facilitate coordination while maintaining discrete centers for individuated movement. We examined whether similar organization exists across other sensorimotor cortices. Twenty-four right-handed healthy subjects underwent functional Magnetic Resonance Imaging (fMRI) while tracking complex targets with flexion/extension at right finger, elbow and ankle separately. Activation related to each joint at false discovery rate of .005 served as its representation across multiple regions. Within each region, we identified the Center of Mass (COM) for each representation, and overlap between representations of within-limb (finger and elbow) and between-limb joints (finger and ankle). Somatosensory (S1) and premotor cortices (PMC) demonstrated greater distinction of COM and minimal overlap for within- and between-limb representations. Contrarily, M1 and supplementary motor area (SMA) showed more integrative somatotopy with higher sharing for within-limb representations. Superior and inferior parietal lobule (SPL and IPL) possessed both types of structure. Some clusters exhibited extensive overlap of within- and between-limb representations, while others showed discrete COMs for within-limb representations. Our results help infer hierarchy in motor control. Areas as S1 may be associated with individuated movements, while M1 may be more integrative for coordinated motion; parietal associative regions may allow switch between both modes of control. Such hierarchy creates redundant opportunities to exploit in stroke rehabilitation. Use of complex rather than traditionally used simple movements was integral to illustrating comprehensive somatotopic structure; complex tasks can potentially help understand cortical representation of skill and learning-related plasticity. PMID:23920009

  1. Earthquake swarms reveal submarine magma unrest induced by distant mega-earthquakes: Andaman Sea region

    NASA Astrophysics Data System (ADS)

    Špičák, Aleš; Vaněk, Jiří

    2016-02-01

    Little is known about earthquake-triggered magma intrusions or eruptions of submarine volcanoes. The analysis of teleseismic earthquake occurrence performed in this study offers a tool to address such enigmatic and inaccessible processes. In the past ten years, the Andaman Sea region repeatedly became a site of shallow earthquake swarms that followed distant mega-earthquakes by days to weeks. The MW 9.1 December 26, 2004 Sumatra-Andaman earthquake was followed by two earthquake swarms about 600 km northward in the Andaman Sea region, delayed by 30 and 35 days, respectively. Earthquakes of one of these seismic episodes, the extensive January 2005 earthquake swarm, migrated laterally at a rate of about 0.25 km per hour during the swarm evolution. The strong Indian Ocean MW 8.6 and 8.2 April 11, 2012 earthquake doublet west of Northern Sumatra was followed by an earthquake swarm approximately 800 km northward in the Andaman Sea region, delayed by 13 days. All the three swarms that followed the 2004 and 2012 mega-earthquakes occurred beneath distinct seamounts and seafloor ridges. Based on the observations of migration of earthquakes during the swarm and swarm occurrence beneath distinct highs at the seafloor, we conclude that these earthquake swarms probably resulted as a consequence of magma unrest induced by static and/or dynamic stress changes following the distant mega-earthquakes. Repeated occurrence of such a phenomenon suggests that the arc magma reservoirs beneath the Andaman Sea have recently reached some form of criticality and are vulnerable to even small stress changes. The Andaman seafloor could thus become a site of submarine volcanic eruptions in near future and deserves close attention of Earth scientists.

  2. Functional reorganization associated with outcome in hand function after stroke revealed by regional homogeneity.

    PubMed

    Yin, Dazhi; Luo, Yanli; Song, Fan; Xu, Dongrong; Peterson, Bradley S; Sun, Limin; Men, Weiwei; Yan, Xu; Fan, Mingxia

    2013-06-01

    Previous studies of task-based functional neuroimaging have shown that various patterns of functional reorganization underlie motor recovery following stroke. However, the mechanisms underlying functional reorganization that contribute to outcome differences in hand function after stroke have not been completely characterized. We, for the first time, investigate subgroups of stroke patients with different outcomes in hand function using a resting-state fMRI approach. We selected 24 patients with subcortical stroke and divided them into two subgroups: completely paralyzed hands (CPH, 12 patients) and partially paralyzed hands (PPH, 12 patients). Twenty-four healthy controls (HCs) matched for age and handedness were also recruited. We used regional homogeneity (ReHo) method to map regional spontaneous activity across the whole brain and performed a two-sample t test between each pair of the three diagnostic groups. Compared to HCs, we found increased ReHo in the ipsilesional hemisphere in PPH and, conversely, increased ReHo in the contralesional hemisphere in CPH. Moreover, we detected decreased ReHo in the ipsilesional primary sensorimotor cortex and superior temporal gyrus, in addition to increased ReHo in the contralesional premotor cortex and ipsilesional medial frontal gyrus in CPH compared to PPH. Additionally, the ReHo index of these regions significantly correlated with the Fugl-Meyer assessment scores (hand + wrist) across all stroke patients. Our study offers a new insight into relationships between functional reorganization and outcomes in hand function after subcortical stroke, and the ReHo method can provide an effective tool for evaluating the efficiency of rehabilitative therapies following stroke.

  3. Y chromosome analysis reveals a sharp genetic boundary in the Carpathian region.

    PubMed

    Stefan, M; Stefanescu, G; Gavrila, L; Terrenato, L; Jobling, M A; Malaspina, P; Novelletto, A

    2001-01-01

    Nine single nucleotide (SNP) or indel binary polymorphisms were used to determine the frequencies and phylogenetic relationships of 12 Y chromosomal haplogroups in 289 males from Romania and the Republic of Moldova. Our data indicated a low but not null rate of the homoplasic appearance of the DYZ3 (-) allelic state. All other markers confirmed the previously proposed phylogeny. Based on the affinities between populations in terms of haplogroup frequencies, this work identified the geographical region of the Carpathians as a break point in the gene geography of Eastern Central Europe, providing a finer definition of one of the possible sharp genetic changes between Western and Eastern Europe.

  4. The Thatcher illusion reveals orientation dependence in brain regions involved in processing facial expressions.

    PubMed

    Psalta, Lilia; Young, Andrew W; Thompson, Peter; Andrews, Timothy J

    2014-01-01

    Although the processing of facial identity is known to be sensitive to the orientation of the face, it is less clear whether orientation sensitivity extends to the processing of facial expressions. To address this issue, we used functional MRI (fMRI) to measure the neural response to the Thatcher illusion. This illusion involves a local inversion of the eyes and mouth in a smiling face-when the face is upright, the inverted features make it appear grotesque, but when the face is inverted, the inversion is no longer apparent. Using an fMRI-adaptation paradigm, we found a release from adaptation in the superior temporal sulcus-a region directly linked to the processing of facial expressions-when the images were upright and they changed from a normal to a Thatcherized configuration. However, this release from adaptation was not evident when the faces were inverted. These results show that regions involved in processing facial expressions display a pronounced orientation sensitivity.

  5. Molecular probe dynamics reveals suppression of ice-like regions in strongly confined supercooled water.

    PubMed

    Banerjee, Debamalya; Bhat, Shrivalli N; Bhat, Subray V; Leporini, Dino

    2012-01-01

    The structure of the hydrogen bond network is a key element for understanding water's thermodynamic and kinetic anomalies. While ambient water is strongly believed to be a uniform, continuous hydrogen-bonded liquid, there is growing consensus that supercooled water is better described in terms of distinct domains with either a low-density ice-like structure or a high-density disordered one. We evidenced two distinct rotational mobilities of probe molecules in interstitial supercooled water of polycrystalline ice [Banerjee D, et al. (2009) ESR evidence for 2 coexisting liquid phases in deeply supercooled bulk water. Proc Natl Acad Sci USA 106: 11448-11453]. Here we show that, by increasing the confinement of interstitial water, the mobility of probe molecules, surprisingly, increases. We argue that loose confinement allows the presence of ice-like regions in supercooled water, whereas a tighter confinement yields the suppression of this ordered fraction and leads to higher fluidity. Compelling evidence of the presence of ice-like regions is provided by the probe orientational entropy barrier which is set, through hydrogen bonding, by the configuration of the surrounding water molecules and yields a direct measure of the configurational entropy of the same. We find that, under loose confinement of supercooled water, the entropy barrier surmounted by the slower probe fraction exceeds that of equilibrium water by the melting entropy of ice, whereas no increase of the barrier is observed under stronger confinement. The lower limit of metastability of supercooled water is discussed.

  6. Molecular Probe Dynamics Reveals Suppression of Ice-Like Regions in Strongly Confined Supercooled Water

    PubMed Central

    Banerjee, Debamalya; Bhat, Shrivalli N.; Bhat, Subray V.; Leporini, Dino

    2012-01-01

    The structure of the hydrogen bond network is a key element for understanding water's thermodynamic and kinetic anomalies. While ambient water is strongly believed to be a uniform, continuous hydrogen-bonded liquid, there is growing consensus that supercooled water is better described in terms of distinct domains with either a low-density ice-like structure or a high-density disordered one. We evidenced two distinct rotational mobilities of probe molecules in interstitial supercooled water of polycrystalline ice [Banerjee D, et al. (2009) ESR evidence for 2 coexisting liquid phases in deeply supercooled bulk water. Proc Natl Acad Sci USA 106: 11448–11453]. Here we show that, by increasing the confinement of interstitial water, the mobility of probe molecules, surprisingly, increases. We argue that loose confinement allows the presence of ice-like regions in supercooled water, whereas a tighter confinement yields the suppression of this ordered fraction and leads to higher fluidity. Compelling evidence of the presence of ice-like regions is provided by the probe orientational entropy barrier which is set, through hydrogen bonding, by the configuration of the surrounding water molecules and yields a direct measure of the configurational entropy of the same. We find that, under loose confinement of supercooled water, the entropy barrier surmounted by the slower probe fraction exceeds that of equilibrium water by the melting entropy of ice, whereas no increase of the barrier is observed under stronger confinement. The lower limit of metastability of supercooled water is discussed. PMID:23049747

  7. Characterization of Multiple Light Damage Paradigms Reveals Regional Differences in Photoreceptor Loss

    PubMed Central

    Thomas, Jennifer L.; Nelson, Craig M.; Luo, Xixia; Hyde, David R.; Thummel, Ryan

    2012-01-01

    Zebrafish provide an attractive model to study the retinal response to photoreceptor apoptosis due to its remarkable ability to spontaneously regenerate retinal neurons following damage. There are currently two widely used light-induced retinal degeneration models to damage photoreceptors in the adult zebrafish. One model uses constant bright light, whereas the other uses a short exposure to extremely intense ultraviolet light. Although both models are currently used, it is unclear whether they differ in regard to the extent of photoreceptor damage or the subsequent regeneration response. Here we report a thorough analysis of the photoreceptor damage and subsequent proliferation response elicited by each individual treatment, as well as by the concomitant use of both treatments. We show a differential loss of rod and cone photoreceptors with each treatment. Additionally, we show that the extent of proliferation observed in the retina directly correlates with the severity of photoreceptor loss. We also demonstrate that both the ventral and posterior regions of the retina are partially protected from light damage. Finally, we show that combining a short ultraviolet exposure followed by a constant bright light treatment largely eliminates the neuroprotected regions, resulting in widespread loss of rod and cone photoreceptors and a robust regenerative response throughout the retina. PMID:22425727

  8. Post-radiotherapy prostate biopsies reveal heightened apex positivity relative to other prostate regions sampled

    PubMed Central

    Huang, Kris T.; Stoyanova, Radka; Walker, Gail; Sandler, Kiri; Studenski, Matthew T.; Dogan, Nesrin; Al-Saleem, Tahseen; Buyyounouski, Mark K.; Horwitz, Eric M.; Pollack, Alan

    2016-01-01

    Background and purpose Prostate biopsy positivity after radiotherapy (RT) is a significant determinant of eventual biochemical failure. We mapped pre- and post-treatment tumor locations to determine if residual disease is location-dependent. Materials and methods There were 303 patients treated on a randomized hypofractionation trial. Of these, 125 underwent prostate biopsy 2-years post-RT. Biopsy cores were mapped to a sextant template, and 86 patients with both pre-/post-treatment systematic sextant biopsies were analyzed. Results The pretreatment distribution of positive biopsy cores was not significantly related to prostate region (base, mid, apex; p = 0.723). Whereas all regions post-RT had reduced positive biopsies, the base was reduced to the greatest degree and the apex the least (p = 0.045). In 38 patients who had a positive post-treatment biopsy, there was change in the rate of apical positivity before and after treatment (76 vs. 71%; p = 0.774), while significant reductions were seen in the mid and base. Conclusion In our experience, persistence of prostate tumor cells after RT increases going from the base to apex. MRI was used in planning and image guidance was performed daily during treatment, so geographic miss of the apex is unlikely. Nonetheless, the pattern observed suggests that attention to apex dosimetry is a priority. PMID:25963053

  9. Gravity wave characteristics in the mesopause region revealed from OH airglow imager observations over Northern Colorado

    NASA Astrophysics Data System (ADS)

    Tang, Yihuan; Dou, Xiankang; Li, Tao; Nakamura, Takuji; Xue, Xianghui; Huang, Can; Manson, Alan; Meek, Chris; Thorsen, Denise; Avery, Susan

    2014-01-01

    Using 5 years of all-sky OH airglow imager data over Yucca Ridge Field Station, CO (40.7°N, 104.9°W), from September 2003 to September 2008, we extract and deduce quasi-monochromatic gravity wave (GW) characteristics in the mesopause region. The intrinsic periods are clustered between approximately 4 and 10 min, and many of them are unstable and evanescent. GW occurrence frequency exhibits a clear semiannual variation with equinoctial minima, which is likely related to the seasonal variation of background wind. The anomalous propagation direction in January 2006, with strong southward before major warming starting in 21 January and weak southward propagation afterward, was most likely affected by stratospheric sudden warming. The momentum fluxes show strongly anticorrelated with the tides, with ~180° out of phase in the zonal component. While in the meridional component, the easterly maximum occurred approximately 2-6 h after maximum easterly tidal wind. However, the anticorrelations are both weakest during the summer. The dissipating and breaking of small-scale and high-frequency GW's components could have a potential impact on the general circulation in the mesopause region.

  10. Regional movement patterns of a small-bodied shark revealed by stable-isotope analysis.

    PubMed

    Munroe, S E M; Heupel, M R; Fisk, A T; Logan, M; Simpfendorfer, C A

    2015-05-01

    This study used stable-isotope analysis to define the nearshore regional residency and movements of the small-bodied Australian sharpnose shark Rhizoprionodon taylori. Plasma and muscle δ(13) C and δ(15) N of R. taylori were collected from across five embayments and compared with values of seagrass and plankton from each bay. Linear distances between adjacent bays ranged from 30 to 150 km. There was a positive geographic correlation between R. taylori tissue and environmental δ(13) C values. Populations with the highest tissue δ(15) N were collected from bays that had the highest environmental δ(15) N values. These results suggest that R. taylori did not forage more than 100 km away from their capture location within 6 months to 1 year. The successful application of isotope analysis to define R. taylori movement demonstrates that this technique may be used in addition to traditional methods to study the movement of sharks, even within similar habitats across regionally small spatial scales (<100 km).

  11. Early changes in the hypothalamic region in prodromal Huntington disease revealed by MRI analysis.

    PubMed

    Soneson, Charlotte; Fontes, Magnus; Zhou, Yongxia; Denisov, Vladimir; Paulsen, Jane S; Kirik, Deniz; Petersén, Asa

    2010-12-01

    Huntington disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat. Its length can be used to estimate the time of clinical diagnosis, which is defined by overt motor symptoms. Non-motor symptoms begin before motor onset, and involve changes in hypothalamus-regulated functions such as sleep, emotion and metabolism. Therefore we hypothesized that hypothalamic changes occur already prior to the clinical diagnosis. We performed voxel-based morphometry and logistic regression analyses of cross-sectional MR images from 220 HD gene carriers and 75 controls in the Predict-HD study. We show that changes in the hypothalamic region are detectable before clinical diagnosis and that its grey matter contents alone are sufficient to distinguish HD gene carriers from control cases. In conclusion, our study shows, for the first time, that alterations in grey matter contents in the hypothalamic region occur at least a decade before clinical diagnosis in HD using MRI. Copyright © 2010 Elsevier Inc. All rights reserved.

  12. Transcriptome map of plant mitochondria reveals islands of unexpected transcribed regions

    PubMed Central

    2011-01-01

    Background Plant mitochondria contain a relatively large amount of genetic information, suggesting that their functional regulation may not be as straightforward as that of metazoans. We used a genomic tiling array to draw a transcriptomic atlas of Oryza sativa japonica (rice) mitochondria, which was predicted to be approximately 490-kb long. Results Whereas statistical analysis verified the transcription of all previously known functional genes such as the ones related to oxidative phosphorylation, a similar extent of RNA expression was frequently observed in the inter-genic regions where none of the previously annotated genes are located. The newly identified open reading frames (ORFs) predicted in these transcribed inter-genic regions were generally not conserved among flowering plant species, suggesting that these ORFs did not play a role in mitochondrial principal functions. We also identified two partial fragments of retrotransposon sequences as being transcribed in rice mitochondria. Conclusion The present study indicated the previously unexpected complexity of plant mitochondrial RNA metabolism. Our transcriptomic data (Oryza sativa Mitochondrial rna Expression Server: OsMES) is publicly accessible at [http://bioinf.mind.meiji.ac.jp/cgi-bin/gbrowse/OsMes/#search]. PMID:21627843

  13. Symbolic meanings of the body in Chinese culture and "somatization".

    PubMed

    Tung, M P

    1994-12-01

    It is proposed in this paper that the term "somatization" as applied to the Chinese requires further exploration. By way of a study of Chinese language usage employing body-related expressions, an indirect method of finding the "equivalence in meaning" is demonstrated. Results of the study reveal the scope and depth of the symbolic meanings of the body in Chinese culture.

  14. Phylogeographic patterns of Merodon hoverflies in the Eastern Mediterranean region: revealing connections and barriers.

    PubMed

    Ståhls, Gunilla; Vujić, Ante; Petanidou, Theodora; Cardoso, Pedro; Radenković, Snezana; Ačanski, Jelena; Pérez Bañón, Celeste; Rojo, Santos

    2016-04-01

    We investigated the phylogeographic patterns of Merodon species (Diptera, Syrphidae) in the Eastern Mediterranean. Ten species were sampled on five different islands and mainland sites as a minimum. All samples were screened for their mtDNA COI barcode haplotype diversity, and for some samples, we additionally generated genomic fingerprints. The recently established zoogeographic distribution categories classify these species as having (1) Balkan distribution; (2) Anatolian distribution; (3) continental areas and large islands distribution; and (4) with wide distribution. The ancestral haplotypes and their geographical localities were estimated with statistical parsimony (TCS). TCS networks identified as the ancestral haplotype samples that originated from localities situated within the distributional category of the species in question. Strong geographical haplotype structuring was detected for many Merodon species. We were particularly interested to test the relative importance of current (Aegean Sea) and past Mid-Aegean Trench) barriers to dispersal for Merodon flies in the Aegean. We employed phylogenetic β-diversity (Pβ total) and its partition in replacement (Pβ repl) and richness difference (Pβ rich) to test the importance of each explanatory variable (interisland distance, MAT, and island area) in interisland differences using partial Mantel tests and hierarchical partitioning of variation. β-Analyses confirmed the importance of both current and past barriers to dispersal on the evolution of group. Current interisland distance was particularly important to explain the replacement of haplotypes, while the MAT was driving differences in richness of haplotypes, revealing the MAT as a strong past barrier whose effects are still visible today in the phylogenetic history of the clade in the Aegean. These results support the hypothesis of a highly restricted dispersal and gene flow among Merodon populations between islands since late Pleistocene. Additionally

  15. Aeromagnetic and Gravity Data Reveal Crustal Structure and Tectonic History of the Central Transantarctic Mountains Region

    NASA Astrophysics Data System (ADS)

    Goodge, J.; Finn, C.; Damaske, D.; Abraham, J.; Moeller, H.; Anderson, E.; Roland, N.; Goldmann, F.; Braddock, P.; Rieser, M.

    2004-12-01

    Near complete coverage of the East Antarctic shield by ice hampers geological study of the crustal architecture important for understanding global tectonic and climate history. Limited exposures in the central Transantarctic Mountains, however, show that Archean and Proterozoic rocks of the shield as well as Neoproterozoic-lower Paleozoic sedimentary successions were deformed during oblique convergence associated with Gondwana amalgamation. Subsequently, the area was overprinted by Jurassic magmatism and Cenozoic uplift. To extend the known geology of the region to ice-covered areas, we conducted a draped aeromagnetic survey flown by helicopters over the Transantarctic Mountains and by fixed-wing aircraft over the adjacent polar plateau. We flew >32,000 line km covering an area of nearly 60,000 km2 at an average altitude of 600 m (average line spacing 2.5 km over most areas and 1.25 km over basement rocks exposed in the Miller and Geologists ranges). Additional lines flown to true north, south and west extended preliminary coverage and tied with existing surveys. Broad, moderate amplitude magnetic highs and lows over the ice-covered plateau resemble those inferred for Precambrian shield provinces to the north, suggesting a similar origin. Additionally, seismic tomographic models and a ground-based gravity profile show that the region is underlain by thick, cold lithosphere. Exposed high-grade metamorphic rocks, representing lower crust exhumed from ˜25-30 km depth during the Ross orogeny, show variable magnetic anomalies, with pronounced central highs and a linear, SE-trending corrugated fabric that correlates with ductile shear structures and regional folds. The magnetic highs correlate with retrogressed mafic eclogites in exposed layered gneiss and are in line with trends of high-amplitude magnetic highs and lows over the adjacent polar plateau. The parallelism of these anomaly trends with those farther to the west suggests that rock types exposed in the

  16. Clustering Regional Ozone Concentrations to Reveal Meteorological Regimes Influencing Air Quality in California's Central Valley

    NASA Astrophysics Data System (ADS)

    Jin, L.; Brown, N. J.; Harley, R. A.

    2008-12-01

    California's central valley suffers from serious ozone air pollution problems due to its unique geography as well as diverse emission sources from both local and upwind areas. The primary flows in the region are produced by the thermal contrast between the ocean and land, and between the valley and surrounding mountains. On typical summer days, westerly winds are funneled into the valley through gaps in the coastal range, along with the Bay area pollutants. During the day, the flow is directed up the Sierra Nevada Mountain slope, while at night it reverses and recirculates the local pollutants. Meteorological factors are important in governing the spatial distribution and variation of air pollutants in this region. Such knowledge is mainly obtained in previous studies using multi-year historical observations at limited measurement sites. There are concerns about spatial representativeness of these measurement locations, and confounding effects from changes in anthropogenic emissions over the analysis period. While modeling studies can control and minimize these limitations, the short simulation period usually makes temporally representative patterns difficult to discern. Our study simulates ozone formation in central California for the entire summer of 2000, with wide meteorological and air quality variations seen in both space and time, and thus provides a good opportunity to examine meteorological regimes that lead to different ozone production, transport, and accumulation in the Central valley. Using cluster analysis and principal component analysis, we determined distinctive meteorological regimes that are associated with different ozone spatial patterns in the Central Valley. In general, average ozone levels in the valley increase with temperature, while their spatial distribution depend on flow regimes, in particular, the strength of sea breezes and upslope flows. The regional meteorological effects are shown to explain the different ozone patterns in the

  17. Analysis of the genetics of boar taint reveals both single SNPs and regional effects.

    PubMed

    Rowe, Suzanne J; Karacaören, Burak; de Koning, Dirk-Jan; Lukic, Boris; Hastings-Clark, Nicola; Velander, Ingela; Haley, Chris S; Archibald, Alan L

    2014-06-03

    Boar taint is an offensive urine or faecal-like odour, affecting the smell and taste of cooked pork from some mature non-castrated male pigs. Androstenone and skatole in fat are the molecules responsible. In most pig production systems, males, which are not required for breeding, are castrated shortly after birth to reduce the risk of boar taint. There is evidence for genetic variation in the predisposition to boar taint.A genome-wide association study (GWAS) was performed to identify loci with effects on boar taint. Five hundred Danish Landrace boars with high levels of skatole in fat (>0.3 μg/g), were each matched with a litter mate with low levels of skatole and measured for androstenone. DNA from these 1,000 non-castrated boars was genotyped using the Illumina PorcineSNP60 Beadchip. After quality control, tests for SNPs associated with boar taint were performed on 938 phenotyped individuals and 44,648 SNPs. Empirical significance thresholds were set by permutation (100,000). For androstenone, a 'regional heritability approach' combining information from multiple SNPs was used to estimate the genetic variation attributable to individual autosomes. A highly significant association was found between variation in skatole levels and SNPs within the CYP2E1 gene on chromosome 14 (SSC14), which encodes an enzyme involved in degradation of skatole. Nominal significance was found for effects on skatole associated with 4 other SNPs including a region of SSC6 reported previously. Genome-wide significance was found for an association between SNPs on SSC5 and androstenone levels and nominal significance for associations with SNPs on SSC13 and SSC17. The regional analyses confirmed large effects on SSC5 for androstenone and suggest that SSC5 explains 23% of the genetic variation in androstenone. The autosomal heritability analyses also suggest that there is a large effect associated with androstenone on SSC2, not detected using GWAS. Significant SNP associations were found

  18. Genome-wide profiling of untranslated regions by paired-end ditag sequencing reveals unexpected transcriptome complexity in yeast.

    PubMed

    Kang, Ya-Ni; Lai, Deng-Pan; Ooi, Hong Sain; Shen, Ting-Ting; Kou, Yao; Tian, Jing; Czajkowsky, Daniel M; Shao, Zhifeng; Zhao, Xiaodong

    2015-02-01

    The identification of structural and functional elements encoded in a genome is a challenging task. Although the transcriptome of budding yeast has been extensively analyzed, the boundaries and untranslated regions of yeast genes remain elusive. To address this least-explored field of yeast genomics, we performed a transcript profiling analysis through paired-end ditag (PET) approach coupled with deep sequencing. With 562,133 PET sequences we accurately defined the boundaries and untranslated regions of 3,409 ORFs, suggesting many yeast genes have multiple transcription start sites (TSSs). We also identified 85 previously uncharacterized transcripts either in intergenic regions or from the opposite strand of reported genomic features. Furthermore, our data revealed the extensive 3' end heterogeneity of yeast genes and identified a novel putative motif for polyadenylation. Our results indicate the yeast transcriptome is more complex than expected. This study would serve as an invaluable resource for elucidating the regulation and evolution of yeast genes.

  19. Proteomic analysis of influenza haemagglutinin-specific antibodies following vaccination reveals convergent immunoglobulin variable region signatures.

    PubMed

    Adamson, Penelope J; Al Kindi, Mahmood A; Wang, Jing J; Colella, Alex D; Chataway, Timothy K; Petrovsky, Nikolai; Gordon, Tom P; Gordon, David L

    2017-10-09

    Analysis of the anti-haemagglutinin serum antibody proteome from six H1N1pdm09 influenza A vaccinated subjects demonstrated restricted IgG1 heavy chain species encoded by IGHV5-51 and IGHV3-7 gene families in 2 subjects and either IGHV5-51 or IGHV3-7 in 4 individuals. All subjects exhibited a dominant IGKV3-20 light chain, however 5 subjects also exhibited IGKV3-11 and IGKV4-1 families. Sequences were closely aligned with the matched germline sequence, with few shared mutations. This study illustrates the feasibility of using a proteomic approach to determine the expressed V region signatures of serum antibodies induced by vaccination. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Proteome profiling reveals regional protein alteration in cerebrum of common marmoset (Callithrix jacchus) exposed to methylmercury.

    PubMed

    Shao, Yueting; Yamamoto, Megumi; Figeys, Daniel; Ning, Zhibin; Chan, Hing Man

    2016-03-10

    Methylmercury (MeHg) is known to selectively damage the calcarine and precentral cortices along deep sulci and fissures in adult cases, but the detailed mechanism is still unclear. This study aims to identify and analyze the differential proteome expression in two regions of the cerebrum (the frontal lobe and the occipital lobe including the calcarine sulcus) of the common marmoset exposed to MeHg using a shot-gun proteomic approach. A total of 1045 and 1062 proteins were identified in the frontal lobe (FL) and occipital lobe (OL), of which, 62 and 89 proteins were found significantly changed with MeHg exposure. Functional enrichment/depletion analysis showed that the lipid metabolic process and proteolysis were affected in both two lobes. Functional changes in FL were characterized in cell cycle and cell division, sulfur compound metabolic process, microtubule-based process and glycerolipid metabolic process. In comparison, proteins were enriched in the functions of transport, carbohydrate metabolic process, chemical caused homeostasis and regulation of body fluid levels in OL. Pathway analysis predicted that vasopressin-regulated water reabsorption was disturbed in MeHg-treated FL. Our results showed that MeHg induced regional specific protein changes in FL and OL but with similar endpoint effects such as energy diminish and disruption of water transport. APOE and GPX1 were shown to be possible key proteins targeted by MeHg leading to multiple functional changes in OL. This is the first report of the whole proteome changes of primate cerebrum for MeHg neurotoxicity, and the results will contribute to the understanding of molecular basis of MeHg intoxication in humans.

  1. Immunological Testing Reveals Exposure to Malaria in the Hypoendemic Region of Iran.

    PubMed

    Obeidi, Narges; Rajasekariah, G-Halli; Nabipour, Iraj; Amirinejad, Roya; Dogcio, Diane; Emami, Habib

    2014-01-01

    Background. South eastern parts of Iran remain endemic for malaria infection. There is some concern that malaria infection may spread into Bushehr, which is located in the south western part bordering the Persian Gulf and at the periphery of the declared endemic region Hormozgan province due to frequency of visitors from eastern endemic areas and from neighboring malaria endemic countries. We investigated malaria prevalence in Bushehr. Methods and Results. Attempts were made to identify malaria active infection in blood smears and malaria specific antibody and antigens in serum samples. Traditional blood smears prepared from 1955 blood specimens yielded no definitive malaria positive case by microscopic technique. A total of 270 (13.8%) serum samples were positive for malaria antibodies. Using specific ELISA kits, presence of histidine rich proteins and lactate dehydrogenase antigens were investigated in serum samples. No histidine rich proteins specific for P. falciparum were detected amongst 270 antibody positive samples. However, six samples representing 0.3% of total population, were found to be positive for plasmodium pan specific lactate dehydrogenase antigens. This suggested the possibility of low level exposure to malaria in Bushehr community. Conclusions. Out of a total of 1955 samples tested, 270 (13.8%) were positive for malaria antibodies and six (0.3%) of these were positive for plasmodium-specific lactate dehydrogenase antigen suggesting a low level exposure to malaria in a hypoendemic region based on immunological testing. Since none of the 270 antibody samples were positive for histidine rich protein antigens, there is scope for further testing of blood samples by molecular methods such as polymerase chain reactions to confirm the plasmodium species and provide information valuable for future investigations. Our testing strategy for hypoemdemic malaria can be used as a template for investing malaria in 32 eliminating countries for testing ongoing

  2. Genome-Wide Analysis in Brazilians Reveals Highly Differentiated Native American Genome Regions.

    PubMed

    Mychaleckyj, Josyf C; Havt, Alexandre; Nayak, Uma; Pinkerton, Relana; Farber, Emily; Concannon, Patrick; Lima, Aldo A; Guerrant, Richard L

    2017-03-01

    Despite its population, geographic size, and emerging economic importance, disproportionately little genome-scale research exists into genetic factors that predispose Brazilians to disease, or the population genetics of risk. After identification of suitable proxy populations and careful analysis of tri-continental admixture in 1,538 North-Eastern Brazilians to estimate individual ancestry and ancestral allele frequencies, we computed 400,000 genome-wide locus-specific branch length (LSBL) Fst statistics of Brazilian Amerindian ancestry compared to European and African; and a similar set of differentiation statistics for their Amerindian component compared with the closest Asian 1000 Genomes population (surprisingly, Bengalis in Bangladesh). After ranking SNPs by these statistics, we identified the top 10 highly differentiated SNPs in five genome regions in the LSBL tests of Brazilian Amerindian ancestry compared to European and African; and the top 10 SNPs in eight regions comparing their Amerindian component to the closest Asian 1000 Genomes population. We found SNPs within or proximal to the genes CIITA (rs6498115), SMC6 (rs1834619), and KLHL29 (rs2288697) were most differentiated in the Amerindian-specific branch, while SNPs in the genes ADAMTS9 (rs7631391), DOCK2 (rs77594147), SLC28A1 (rs28649017), ARHGAP5 (rs7151991), and CIITA (rs45601437) were most highly differentiated in the Asian comparison. These genes are known to influence immune function, metabolic and anthropometry traits, and embryonic development. These analyses have identified candidate genes for selection within Amerindian ancestry, and by comparison of the two analyses, those for which the differentiation may have arisen during the migration from Asia to the Americas.

  3. GPS-seismograms reveal amplified shaking in California's San Joaquin Delta region

    NASA Astrophysics Data System (ADS)

    Johanson, I. A.

    2014-12-01

    The March 10, 2014, the Mw6.8 Ferndale earthquake occurred off the coast of Northern California, near the Mendocino Triple Junction. Aftershocks suggest a northeast striking fault plane for the strike-slip earthquake, oriented such that the California coast is roughly perpendicular to the rupture plane. Consequently, large amplitude Love waves were observed at seismic stations and continuous GPS stations throughout Northern California. While GPS is less sensitive then broadband instruments, in Northern California their station density is much higher, potentially providing valuable detail. A total of 269 GPS stations that have high-rate (1 sps) data available were used to generate GPS-seismograms. These include stations from the Bay Area Regional Deformation (BARD) network, the Plate Boundary Observatory (PBO, operated by UNAVCO), and the USGS, Menlo Park. The Track software package was used to generate relative displacements between pairs of stations, determined using Delaunay triangulation. This network-based approach allows for higher precision than absolute positioning, because common noise sources, in particular atmospheric noise, are cancelled out. A simple least-squares network adjustment with a stable centroid constraint is performed to transform the mesh of relative motions into absolute motions at individual GPS stations. This approach to generating GPS-seismograms is validated by the good agreement between time series records at 16 BARD stations that are co-located with broadband seismometers from the Berkeley Digital Seismic Network (BDSN). While the distribution of peak dynamic displacements is dominated in long periods by the radiation pattern, at shorter periods other patterns become visible. In particular, stations in the San Joaquin Delta (SJD) region show higher peak dynamic displacements than those in surrounding areas, as well as longer duration shaking. SJD stations also have higher dynamic displacements on the radial component than surrounding

  4. Genome-Wide Analysis in Brazilians Reveals Highly Differentiated Native American Genome Regions

    PubMed Central

    Havt, Alexandre; Nayak, Uma; Pinkerton, Relana; Farber, Emily; Concannon, Patrick; Lima, Aldo A.; Guerrant, Richard L.

    2017-01-01

    Despite its population, geographic size, and emerging economic importance, disproportionately little genome-scale research exists into genetic factors that predispose Brazilians to disease, or the population genetics of risk. After identification of suitable proxy populations and careful analysis of tri-continental admixture in 1,538 North-Eastern Brazilians to estimate individual ancestry and ancestral allele frequencies, we computed 400,000 genome-wide locus-specific branch length (LSBL) Fst statistics of Brazilian Amerindian ancestry compared to European and African; and a similar set of differentiation statistics for their Amerindian component compared with the closest Asian 1000 Genomes population (surprisingly, Bengalis in Bangladesh). After ranking SNPs by these statistics, we identified the top 10 highly differentiated SNPs in five genome regions in the LSBL tests of Brazilian Amerindian ancestry compared to European and African; and the top 10 SNPs in eight regions comparing their Amerindian component to the closest Asian 1000 Genomes population. We found SNPs within or proximal to the genes CIITA (rs6498115), SMC6 (rs1834619), and KLHL29 (rs2288697) were most differentiated in the Amerindian-specific branch, while SNPs in the genes ADAMTS9 (rs7631391), DOCK2 (rs77594147), SLC28A1 (rs28649017), ARHGAP5 (rs7151991), and CIITA (rs45601437) were most highly differentiated in the Asian comparison. These genes are known to influence immune function, metabolic and anthropometry traits, and embryonic development. These analyses have identified candidate genes for selection within Amerindian ancestry, and by comparison of the two analyses, those for which the differentiation may have arisen during the migration from Asia to the Americas. PMID:28100790

  5. Mutational analysis of Trypanosoma brucei RNA editing ligase reveals regions critical for interaction with KREPA2.

    PubMed

    Mehta, Vaibhav; Sen, Rajashree; Moshiri, Houtan; Salavati, Reza

    2015-01-01

    The Trypanosoma brucei parasite causes the vector-borne disease African sleeping sickness. Mitochondrial mRNAs of T. brucei undergo posttranscriptional RNA editing to make mature, functional mRNAs. The final step of this process is catalyzed by the essential ligase, T. brucei RNA Editing Ligase 1 (TbREL1) and the closely related T. brucei RNA Editing Ligase 2 (TbREL2). While other ligases such as T7 DNA ligase have both a catalytic and an oligonucleotide/oligosaccharide-binding (OB)-fold domain, T. brucei RNA editing ligases contain only the catalytic domain. The OB-fold domain, which is required for interaction with the substrate RNA, is provided in trans by KREPA2 (for TbREL1) and KREPA1 (for TbREL2). KREPA2 enhancement of TbREL1 ligase activity is presumed to occur via an OB-fold-mediated increase in substrate specificity and catalysis. We characterized the interaction between TbREL1 and KREPA2 in vitro using full-length, truncated, and point-mutated ligases. As previously shown, our data indicate strong, specific stimulation of TbREL1 catalytic activity by KREPA2. We narrowed the region of contact to the final 59 C-terminal residues of TbREL1. Specifically, the TbREL1 C-terminal KWKE (441-444) sequence appear to coordinate the KREPA2-mediated enhancement of TbREL1 activities. N-terminal residues F206, T264 and Y275 are crucial for the overall activity of TbREL1, particularly for F206, a mutation of this residue also disrupts KREPA2 interaction. Thus, we have identified the critical TbREL1 regions and amino acids that mediate the KREPA2 interaction.

  6. Immunological Testing Reveals Exposure to Malaria in the Hypoendemic Region of Iran

    PubMed Central

    Obeidi, Narges; Rajasekariah, G-Halli; Nabipour, Iraj; Amirinejad, Roya; Dogcio, Diane; Emami, Habib

    2014-01-01

    Background. South eastern parts of Iran remain endemic for malaria infection. There is some concern that malaria infection may spread into Bushehr, which is located in the south western part bordering the Persian Gulf and at the periphery of the declared endemic region Hormozgan province due to frequency of visitors from eastern endemic areas and from neighboring malaria endemic countries. We investigated malaria prevalence in Bushehr. Methods and Results. Attempts were made to identify malaria active infection in blood smears and malaria specific antibody and antigens in serum samples. Traditional blood smears prepared from 1955 blood specimens yielded no definitive malaria positive case by microscopic technique. A total of 270 (13.8%) serum samples were positive for malaria antibodies. Using specific ELISA kits, presence of histidine rich proteins and lactate dehydrogenase antigens were investigated in serum samples. No histidine rich proteins specific for P. falciparum were detected amongst 270 antibody positive samples. However, six samples representing 0.3% of total population, were found to be positive for plasmodium pan specific lactate dehydrogenase antigens. This suggested the possibility of low level exposure to malaria in Bushehr community. Conclusions. Out of a total of 1955 samples tested, 270 (13.8%) were positive for malaria antibodies and six (0.3%) of these were positive for plasmodium-specific lactate dehydrogenase antigen suggesting a low level exposure to malaria in a hypoendemic region based on immunological testing. Since none of the 270 antibody samples were positive for histidine rich protein antigens, there is scope for further testing of blood samples by molecular methods such as polymerase chain reactions to confirm the plasmodium species and provide information valuable for future investigations. Our testing strategy for hypoemdemic malaria can be used as a template for investing malaria in 32 eliminating countries for testing ongoing

  7. The lytic transcriptome of Kaposi's sarcoma-associated herpesvirus reveals extensive transcription of noncoding regions, including regions antisense to important genes.

    PubMed

    Chandriani, Sanjay; Xu, Yiyang; Ganem, Don

    2010-08-01

    Genomewide analyses of the mammalian transcriptome have revealed that large tracts of sequence previously annotated as noncoding are frequently transcribed and give rise to stable RNA. Although the transcription of individual genes of the Kaposi's sarcoma-associated herpesvirus (KSHV) has been well studied, little is known of the architecture of the viral transcriptome on a genomewide scale. Here we have employed a genomewide tiling array to examine the lytic transcriptome of the Kaposi's sarcoma-associated herpesvirus, KSHV. Our results reveal that during lytic growth (but not during latency), there is extensive transcription from noncoding regions, including both intergenic regions and, especially, noncoding regions antisense to known open reading frames (ORFs). Several of these transcripts have been characterized in more detail, including (i) a 10-kb RNA antisense to the major latency locus, including many of its microRNAs as well as its ORFs; (ii) a 17-kb RNA antisense to numerous ORFs at the left-hand end of the genome; and (iii) a 0.7-kb RNA antisense to the viral homolog of interleukin-6 (vIL-6). These studies indicate that the lytic herpesviral transcriptome resembles a microcosm of the host transcriptome and provides a useful system for the study of noncoding RNAs.

  8. Pedigree-based analysis of derivation of genome segments of an elite rice reveals key regions during its breeding.

    PubMed

    Zhou, Degui; Chen, Wei; Lin, Zechuan; Chen, Haodong; Wang, Chongrong; Li, Hong; Yu, Renbo; Zhang, Fengyun; Zhen, Gang; Yi, Junliang; Li, Kanghuo; Liu, Yaoguang; Terzaghi, William; Tang, Xiaoyan; He, Hang; Zhou, Shaochuan; Deng, Xing Wang

    2016-02-01

    Analyses of genome variations with high-throughput assays have improved our understanding of genetic basis of crop domestication and identified the selected genome regions, but little is known about that of modern breeding, which has limited the usefulness of massive elite cultivars in further breeding. Here we deploy pedigree-based analysis of an elite rice, Huanghuazhan, to exploit key genome regions during its breeding. The cultivars in the pedigree were resequenced with 7.6× depth on average, and 2.1 million high-quality single nucleotide polymorphisms (SNPs) were obtained. Tracing the derivation of genome blocks with pedigree and information on SNPs revealed the chromosomal recombination during breeding, which showed that 26.22% of Huanghuazhan genome are strictly conserved key regions. These major effect regions were further supported by a QTL mapping of 260 recombinant inbred lines derived from the cross of Huanghuazhan and a very dissimilar cultivar, Shuanggui 36, and by the genome profile of eight cultivars and 36 elite lines derived from Huanghuazhan. Hitting these regions with the cloned genes revealed they include numbers of key genes, which were then applied to demonstrate how Huanghuazhan were bred after 30 years of effort and to dissect the deficiency of artificial selection. We concluded the regions are helpful to the further breeding based on this pedigree and performing breeding by design. Our study provides genetic dissection of modern rice breeding and sheds new light on how to perform genomewide breeding by design. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  9. Somatic hypermutation as a generator of antinuclear antibodies in a murine model of systemic autoimmunity.

    PubMed

    Guo, Wenzhong; Smith, Diana; Aviszus, Katja; Detanico, Thiago; Heiser, Ryan A; Wysocki, Lawrence J

    2010-09-27

    Systemic lupus erythematosus (SLE) is characterized by high-avidity IgG antinuclear antibodies (ANAs) that are almost certainly products of T cell-dependent immune responses. Whether critical amino acids in the third complementarity-determining region (CDR3) of the ANA originate from V(D)J recombination or somatic hypermutation (SHM) is not known. We studied a mouse model of SLE in which all somatic mutations within ANA V regions, including those in CDR3, could be unequivocally identified. Mutation reversion analyses revealed that ANA arose predominantly from nonautoreactive B cells that diversified immunoglobulin genes via SHM. The resolution afforded by this model allowed us to demonstrate that one ANA clone was generated by SHM after a V(H) gene replacement event. Mutations producing arginine substitutions were frequent and arose largely (66%) from base changes in just two codons: AGC and AGT. These codons are abundant in the repertoires of mouse and human V genes. Our findings reveal the predominant role of SHM in the development of ANA and underscore the importance of self-tolerance checkpoints at the postmutational stage of B cell differentiation.

  10. Somatic uniparental disomy of Chromosome 16p in hemimegalencephaly.

    PubMed

    Griffin, Nicole G; Cronin, Kenneth D; Walley, Nicole M; Hulette, Christine M; Grant, Gerald A; Mikati, Mohamad A; LaBreche, Heather G; Rehder, Catherine W; Allen, Andrew S; Crino, Peter B; Heinzen, Erin L

    2017-09-01

    Hemimegalencephaly (HME) is a heterogeneous cortical malformation characterized by enlargement of one cerebral hemisphere. Somatic variants in mammalian target of rapamycin (mTOR) regulatory genes have been implicated in some HME cases; however, ∼70% have no identified genetic etiology. Here, we screened two HME patients to identify disease-causing somatic variants. DNA from leukocytes, buccal swabs, and surgically resected brain tissue from two HME patients were screened for somatic variants using genome-wide genotyping arrays or sequencing of the protein-coding regions of the genome. Functional studies were performed to evaluate the molecular consequences of candidate disease-causing variants. Both HME patients evaluated were found to have likely disease-causing variants in DNA extracted from brain tissue but not in buccal swab or leukocyte DNA, consistent with a somatic mutational mechanism. In the first case, a previously identified disease-causing somatic single nucleotide in MTOR was identified. In the second case, we detected an overrepresentation of the alleles inherited from the mother on Chromosome 16 in brain tissue DNA only, indicative of somatic uniparental disomy (UPD) of the p-arm of Chromosome 16. Using methylation analyses, an imprinted locus on 16p spanning ZNF597 was identified, which results in increased expression of ZNF597 mRNA and protein in the brain tissue of the second case. Enhanced mTOR signaling was observed in tissue specimens from both patients. We speculate that overexpression of maternally expressed ZNF597 led to aberrant hemispheric development in the patient with somatic UPD of Chromosome 16p possibly through modulation of mTOR signaling. © 2017 Griffin et al.; Published by Cold Spring Harbor Laboratory Press.

  11. Somatic uniparental disomy of Chromosome 16p in hemimegalencephaly

    PubMed Central

    Griffin, Nicole G.; Cronin, Kenneth D.; Walley, Nicole M.; Hulette, Christine M.; Grant, Gerald A.; Mikati, Mohamad A.; LaBreche, Heather G.; Rehder, Catherine W.; Allen, Andrew S.; Crino, Peter B.; Heinzen, Erin L.

    2017-01-01

    Hemimegalencephaly (HME) is a heterogeneous cortical malformation characterized by enlargement of one cerebral hemisphere. Somatic variants in mammalian target of rapamycin (mTOR) regulatory genes have been implicated in some HME cases; however, ∼70% have no identified genetic etiology. Here, we screened two HME patients to identify disease-causing somatic variants. DNA from leukocytes, buccal swabs, and surgically resected brain tissue from two HME patients were screened for somatic variants using genome-wide genotyping arrays or sequencing of the protein-coding regions of the genome. Functional studies were performed to evaluate the molecular consequences of candidate disease-causing variants. Both HME patients evaluated were found to have likely disease-causing variants in DNA extracted from brain tissue but not in buccal swab or leukocyte DNA, consistent with a somatic mutational mechanism. In the first case, a previously identified disease-causing somatic single nucleotide in MTOR was identified. In the second case, we detected an overrepresentation of the alleles inherited from the mother on Chromosome 16 in brain tissue DNA only, indicative of somatic uniparental disomy (UPD) of the p-arm of Chromosome 16. Using methylation analyses, an imprinted locus on 16p spanning ZNF597 was identified, which results in increased expression of ZNF597 mRNA and protein in the brain tissue of the second case. Enhanced mTOR signaling was observed in tissue specimens from both patients. We speculate that overexpression of maternally expressed ZNF597 led to aberrant hemispheric development in the patient with somatic UPD of Chromosome 16p possibly through modulation of mTOR signaling. PMID:28864461

  12. Autonomous Marine Robotic Technology Reveals an Expansive Benthic Bacterial Community Relevant to Regional Nitrogen Biogeochemistry.

    PubMed

    Valentine, David L; Fisher, G Burch; Pizarro, Oscar; Kaiser, Carl L; Yoerger, Dana; Breier, John A; Tarn, Jonathan

    2016-10-06

    Benthic accumulations of filamentous, mat-forming bacteria occur throughout the oceans where bisulfide mingles with oxygen or nitrate, providing key but poorly quantified linkages between elemental cycles of carbon, nitrogen and sulfur. Here we used the autonomous underwater vehicle Sentry to conduct a contiguous, 12.5 km photoimaging survey of sea-floor colonies of filamentous bacteria between 80 and 579 m water depth, spanning the continental shelf to the deep suboxic waters of the Santa Barbara Basin (SBB). The survey provided >31 000 images and revealed contiguous, white-colored bacterial colonization coating > ∼80% of the ocean floor and spanning over 1.6 km, between 487 and 523 m water depth. Based on their localization within the stratified waters of the SBB we hypothesize a dynamic and annular biogeochemical zonation by which the bacteria capitalize on periodic flushing events to accumulate and utilize nitrate. Oceanographic time series data bracket the imaging survey and indicate rapid and contemporaneous nitrate loss, while autonomous capture of microbial communities from the benthic boundary layer concurrent with imaging provides possible identities for the responsible bacteria. Based on these observations we explore the ecological context of such mats and their possible importance in the nitrogen cycle of the SBB.

  13. Genomic regions underlying agronomic traits in linseed (Linum usitatissimum L.) as revealed by association mapping‡

    PubMed Central

    Soto-Cerda, Braulio J; Duguid, Scott; Booker, Helen; Rowland, Gordon; Diederichsen, Axel; Cloutier, Sylvie

    2014-01-01

    The extreme climate of the Canadian Prairies poses a major challenge to improve yield. Although it is possible to breed for yield per se, focusing on yield-related traits could be advantageous because of their simpler genetic architecture. The Canadian flax core collection of 390 accessions was genotyped with 464 simple sequence repeat markers, and phenotypic data for nine agronomic traits including yield, bolls per area, 1,000 seed weight, seeds per boll, start of flowering, end of flowering, plant height, plant branching, and lodging collected from up to eight environments was used for association mapping. Based on a mixed model (principal component analysis (PCA) + kinship matrix (K)), 12 significant marker-trait associations for six agronomic traits were identified. Most of the associations were stable across environments as revealed by multivariate analyses. Statistical simulation for five markers associated with 1000 seed weight indicated that the favorable alleles have additive effects. None of the modern cultivars carried the five favorable alleles and the maximum number of four observed in any accessions was mostly in breeding lines. Our results confirmed the complex genetic architecture of yield-related traits and the inherent difficulties associated with their identification while illustrating the potential for improvement through marker-assisted selection. PMID:24138336

  14. Phylogenetic relationships of rat lungworm, Angiostrongylus cantonensis, isolated from different geographical regions revealed widespread multiple lineages.

    PubMed

    Tokiwa, Toshihiro; Harunari, Tsunehito; Tanikawa, Tsutomu; Komatsu, Noriyuki; Koizumi, Nobuo; Tung, Kwong-Chung; Suzuki, Jun; Kadosaka, Teruki; Takada, Nobuhiro; Kumagai, Takashi; Akao, Nobuaki; Ohta, Nobuo

    2012-09-01

    We conducted a pilot survey of genetic variation of A. cantonensis using small subunit (SSU) ribosomal (r) RNA and mitochondrial cytochrome c oxidase subunit I (coxI) gene sequences. Two distinct SSU genotypes (G1 and G2) were identified among 17 individual A. cantonensis worms from 17 different geographical localities in Japan, Mainland China, Taiwan, and Thailand. The partial coxI sequences were determined for 83 worms from 18 different geographical localities from Japan, Mainland China, Taiwan, and Thailand. Phylogenetic analysis showed eight distinct coxI haplotypes (ac1 to ac8). In 16 out of 18 localities, only a single coxI haplotype was found. However, in two localities, two coxI haplotypes coexisted. The common haplotypes found were: haplotype ac1 (Tokyo, Chiba, Kanagawa, Amamioshima Island, and Taichung), haplotype ac2 (Ishikawa, Shenzhen, and Lianjiang), haplotype ac5 (the Okinawa and the Ogasawara Islands), and haplotype ac7 (Miyagi, Aichi, and Kanagawa). Each of these regions is separated from the others by high mountain ranges or oceans. In addition, the lower genetic variation and particular geographical distribution of A. cantonensis in each location could indicate a founder effect, which may have resulted from multiple independent origins, and suggests that haplotypes migrated from endemic areas via human-related transportation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  15. Airborne methane remote measurements reveal heavy-tail flux distribution in Four Corners region.

    NASA Astrophysics Data System (ADS)

    Frankenberg, C.

    2016-12-01

    Methane (CH4) impacts climate as the second strongest anthropogenic greenhouse gas and air quality by influencing tropospheric ozone levels. Space-based observations have identified the Four Corners region in the Southwest United States as an area of large CH4 enhancements. We conducted an airborne campaign in Four Corners during April 2015 with the next-generation Airborne Visible/Infrared Imaging Spectrometer (near-infrared) and Hyperspectral Thermal Emission Spectrometer (thermal infrared) imaging spectrometers to better understand the source of methane by measuring methane plumes at 1- to 3-m spatial resolution. Our analysis detected more than 250 individual methane plumes from fossil fuel harvesting, processing, and distributing infrastructures, spanning an emission range from the detection limit ˜ 2 kg/h to 5 kg/h through ˜ 5,000 kg/h. Observed sources include gas processing facilities, storage tanks, pipeline leaks, natural seeps and well pads, as well as a coal mine venting shaft. Overall, plume enhancements and inferred fluxes follow a lognormal distribution, with the top 10% emitters contributing 49 to 66% to the inferred total point source flux of 0.23 Tg/y to 0.39 Tg/y. We will summarize the campaign results and provide an overview of how airborne remote sensing can be used to detect and infer methane fluxes over widespread geographic areas and how new instrumentation could be used to perform similar observations from space.

  16. Aboriginal mitogenomes reveal 50,000 years of regionalism in Australia.

    PubMed

    Tobler, Ray; Rohrlach, Adam; Soubrier, Julien; Bover, Pere; Llamas, Bastien; Tuke, Jonathan; Bean, Nigel; Abdullah-Highfold, Ali; Agius, Shane; O'Donoghue, Amy; O'Loughlin, Isabel; Sutton, Peter; Zilio, Fran; Walshe, Keryn; Williams, Alan N; Turney, Chris S M; Williams, Matthew; Richards, Stephen M; Mitchell, Robert J; Kowal, Emma; Stephen, John R; Williams, Lesley; Haak, Wolfgang; Cooper, Alan

    2017-03-08

    Aboriginal Australians represent one of the longest continuous cultural complexes known. Archaeological evidence indicates that Australia and New Guinea were initially settled approximately 50 thousand years ago (ka); however, little is known about the processes underlying the enormous linguistic and phenotypic diversity within Australia. Here we report 111 mitochondrial genomes (mitogenomes) from historical Aboriginal Australian hair samples, whose origins enable us to reconstruct Australian phylogeographic history before European settlement. Marked geographic patterns and deep splits across the major mitochondrial haplogroups imply that the settlement of Australia comprised a single, rapid migration along the east and west coasts that reached southern Australia by 49-45 ka. After continent-wide colonization, strong regional patterns developed and these have survived despite substantial climatic and cultural change during the late Pleistocene and Holocene epochs. Remarkably, we find evidence for the continuous presence of populations in discrete geographic areas dating back to around 50 ka, in agreement with the notable Aboriginal Australian cultural attachment to their country.

  17. A SOMATIC-MARKER THEORY OF ADDICTION

    PubMed Central

    Verdejo-García, Antonio; Bechara, Antoine

    2009-01-01

    Similar to patients with ventromedial prefrontal cortex (VMPC) lesions, substance abusers show altered decision-making, characterized by a tendency to choose the immediate reward, at the expense of negative future consequences. The somatic-marker model proposes that decision-making depends on neural substrates that regulate homeostasis, emotion and feeling. According to this model, there should be a link between alterations in processing emotions in substance abusers, and their impairments in decision-making. A growing evidence from neuroscientific studies indicate that core aspects of addiction may be explained in terms of abnormal emotional/homeostatic guidance of decision-making. Behavioural studies have revealed emotional processing and decision-making deficits in substance abusers. Neuroimaging studies have shown that altered decision-making in addiction is associated with abnormal functioning of a distributed neural network critical for the processing of emotional information, and the experience of “craving”, including the VMPC, the amygdala, the striatum, the anterior cingulate cortex, and the insular/somato-sensory cortices, as well as non-specific neurotransmitter systems that modulate activities of neural processes involved in decision-making. The aim of this paper is to review this growing evidence, and to examine the extent of which these studies support a somatic-marker theory of addiction. We conclude that there are at least two underlying types of dysfunctions where emotional signals (somatic-markers) turns in favor of immediate outcomes in addiction: (1) a hyperactivity in the amygdala or impulsive system, which exaggerates the rewarding impact of available incentives, and (2) hypoactivity in the prefrontal cortex or reflective system, which forecasts the long-term consequences of a given action. PMID:18722390

  18. Deciphering the spectrum of somatic mutations in the entire mitochondrial DNA genome.

    PubMed

    Chen, X Z; Fang, Y; Shi, Y H; Cui, J H; Li, L Y; Xu, Y C; Ling, B

    2015-04-30

    The mitochondrion is a crucial intracellular organelle responsible for regulating cellular energy metabolism, producing free radicals, initiating and executing the apoptotic pathways. Previous studies have shown that somatic mutations in mitochondrial DNA are associated with various tumors, which may be involved during carcinogenesis and tumor progression. To examine the mutation pattern in cancer, 625 reported somatic mutations in the mitochondrial DNA genome were analyzed. We found that, except for deletions and insertions, most somatic mutations were point mutations, accounting for 89.44% of somatic mutations. Transition was the predominant form of somatic mutation in the entire mitochondrial DNA genome, accounting for 87.12% of point mutations, most of which were homoplastic. Frequency statistics analysis of point mutations indicated that, except for 3 tRNA genes, the mutations were distributed on all resting genes and in the D-loop region, with the latter showing the highest frequency of somatic mutation (19.34%), followed by the tRNA leucine 2 gene and non-coding regions between base pairs 5892 and 5903, while 13 coding-region genes and 2 rRNA genes showed a relatively lower frequency of somatic point mutations. Nonsynonymous mutations and terminal amino acid changes were the primary point somatic mutations detected from 13 coding-region genes, which may cause mitochondrial dysfunction in cancer cells. We found that the somatic mutations may affect the mitochondrial DNA genome; the non-coding region should be examined to identify somatic mutations as potential diagnostic biomarkers for early detection of cancer.

  19. Application of Somatic Embryogenesis in Woody Plants.

    PubMed Central

    Guan, Yuan; Li, Shui-Gen; Fan, Xiao-Fen; Su, Zhen-Hong

    2016-01-01

    Somatic embryogenesis is a developmental process where a plant somatic cell can dedifferentiate to a totipotent embryonic stem cell that has the ability to give rise to an embryo under appropriate conditions. This new embryo can further develop into a whole plant. In woody plants, somatic embryogenesis plays a critical role in clonal propagation and is a powerful tool for synthetic seed production, germplasm conservation, and cryopreservation. A key step in somatic embryogenesis is the transition of cell fate from a somatic cell to embryo cell. Although somatic embryogenesis has already been widely used in a number of woody species, propagating adult woody plants remains difficult. In this review, we focus on molecular mechanisms of somatic embryogenesis and its practical applications in economic woody plants. Furthermore, we propose a strategy to improve the process of somatic embryogenesis using molecular means. PMID:27446166

  20. Diverse mechanisms of somatic structural variations in human cancer genomes

    PubMed Central

    Yang, Lixing; Luquette, Lovelace J.; Gehlenborg, Nils; Xi, Ruibin; Haseley, Psalm S.; Hsieh, Chih-Heng; Zhang, Chengsheng; Ren, Xiaojia; Protopopov, Alexei; Chin, Lynda; Kucherlapati, Raju; Lee, Charles; Park, Peter J.

    2013-01-01

    Summary Identification of somatic rearrangements in cancer genomes has accelerated through analysis of high-throughput sequencing data. However, characterization of complex structural alterations and their underlying mechanisms remains inadequate. Here, applying an algorithm to predict structural variations from short reads, we report a comprehensive catalog of somatic structural variations and the mechanisms generating them, using high-coverage whole-genome sequencing data from 140 patients across ten tumor types. We characterize the relative contributions of different types of rearrangements and their mutational mechanisms, find that ~20% of the somatic deletions are complex deletions formed by replication errors, and describe the differences between the mutational mechanisms in somatic and germline alterations. Importantly, we provide detailed reconstructions of the events responsible for loss of CDKN2A/B and gain of EGFR in glioblastoma, revealing that these alterations can result from multiple mechanisms even in a single genome and that both DNA double-strand breaks and replication errors drive somatic rearrangements. PMID:23663786

  1. Somatic Symptom and Related Disorders

    MedlinePlus

    ... and symptoms a person feels are related to psychological factors. These symptoms can’t be traced to a specific physical cause. In people who have a somatic symptom and related disorder, medical test results are either normal or don’t explain ...

  2. Bovine somatic cell nuclear transfer.

    PubMed

    Ross, Pablo J; Cibelli, Jose B

    2010-01-01

    Somatic cell nuclear transfer (SCNT) is a technique by which the nucleus of a differentiated cell is introduced into an oocyte from which its genetic material has been removed by a process called enucleation. In mammals, the reconstructed embryo is artificially induced to initiate embryonic development (activation). The oocyte turns the somatic cell nucleus into an embryonic nucleus. This process is called nuclear reprogramming and involves an important change of cell fate, by which the somatic cell nucleus becomes capable of generating all the cell types required for the formation of a new individual, including extraembryonic tissues. Therefore, after transfer of a cloned embryo to a surrogate mother, an offspring genetically identical to the animal from which the somatic cells where isolated, is born. Cloning by nuclear transfer has potential applications in agriculture and biomedicine, but is limited by low efficiency. Cattle were the second mammalian species to be cloned after Dolly the sheep, and it is probably the most widely used species for SCNT experiments. This is, in part due to the high availability of bovine oocytes and the relatively higher efficiency levels usually obtained in cattle. Given the wide utilization of this species for cloning, several alternatives to this basic protocol can be found in the literature. Here we describe a basic protocol for bovine SCNT currently being used in our laboratory, which is amenable for the use of the nuclear transplantation technique for research or commercial purposes.

  3. A temporary immersion system improves in vitro regeneration of peach palm through secondary somatic embryogenesis.

    PubMed

    Steinmacher, D A; Guerra, M P; Saare-Surminski, K; Lieberei, R

    2011-12-01

    Secondary somatic embryogenesis has been postulated to occur during induction of peach palm somatic embryogenesis. In the present study this morphogenetic pathway is described and a protocol for the establishment of cycling cultures using a temporary immersion system (TIS) is presented. Zygotic embryos were used as explants, and induction of somatic embryogenesis and plantlet growth were compared in TIS and solid culture medium. Light microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to describe in vitro morphogenesis and accompany morpho-histological alterations during culture. The development of secondary somatic embryos occurs early during the induction of primary somatic embryos. Secondary somatic embryos were observed to develop continually in culture, resulting in non-synchronized development of these somatic embryos. Using these somatic embryos as explants allowed development of cycling cultures. Somatic embryos had high embryogenic potential (65·8 ± 3·0 to 86·2 ± 5·0 %) over the period tested. The use of a TIS greatly improved the number of somatic embryos obtained, as well as subsequent plantlet growth. Histological analyses showed that starch accumulation precedes the development of somatic embryos, and that these cells presented high nucleus/cytoplasm ratios and high mitotic indices, as evidenced by DAPI staining. Morphological and SEM observations revealed clusters of somatic embryos on one part of the explants, while other parts grew further, resulting in callus tissue. A multicellular origin of the secondary somatic embryos is hypothesized. Cells in the vicinity of callus accumulated large amounts of phenolic substances in their vacuoles. TEM revealed that these cells are metabolically very active, with the presence of numerous mitochondria and Golgi apparatuses. Light microscopy and TEM of the embryogenic sector revealed cells with numerous amyloplasts, large nuclei and nucleoli, and numerous

  4. A temporary immersion system improves in vitro regeneration of peach palm through secondary somatic embryogenesis

    PubMed Central

    Steinmacher, D. A.; Guerra, M. P.; Saare-Surminski, K.; Lieberei, R.

    2011-01-01

    Background and Aims Secondary somatic embryogenesis has been postulated to occur during induction of peach palm somatic embryogenesis. In the present study this morphogenetic pathway is described and a protocol for the establishment of cycling cultures using a temporary immersion system (TIS) is presented. Methods Zygotic embryos were used as explants, and induction of somatic embryogenesis and plantlet growth were compared in TIS and solid culture medium. Light microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to describe in vitro morphogenesis and accompany morpho-histological alterations during culture. Key Results The development of secondary somatic embryos occurs early during the induction of primary somatic embryos. Secondary somatic embryos were observed to develop continually in culture, resulting in non-synchronized development of these somatic embryos. Using these somatic embryos as explants allowed development of cycling cultures. Somatic embryos had high embryogenic potential (65·8 ± 3·0 to 86·2 ± 5·0 %) over the period tested. The use of a TIS greatly improved the number of somatic embryos obtained, as well as subsequent plantlet growth. Histological analyses showed that starch accumulation precedes the development of somatic embryos, and that these cells presented high nucleus/cytoplasm ratios and high mitotic indices, as evidenced by DAPI staining. Morphological and SEM observations revealed clusters of somatic embryos on one part of the explants, while other parts grew further, resulting in callus tissue. A multicellular origin of the secondary somatic embryos is hypothesized. Cells in the vicinity of callus accumulated large amounts of phenolic substances in their vacuoles. TEM revealed that these cells are metabolically very active, with the presence of numerous mitochondria and Golgi apparatuses. Light microscopy and TEM of the embryogenic sector revealed cells with numerous amyloplasts

  5. Genetic map of the human pseudoautosomal region reveals a high rate of recombination in female meiosis at the Xp telomere

    SciTech Connect

    Henke, A.; Fischer, C.; Rappold, G.A. )

    1993-12-01

    This paper describes the genetic map of the pseudoautosomal region bounded by the telomere of the short arms of the X and Y chromosomes. In males, meiotic exchange on Xp/Yp is confined to this region, leading to highly elevated recombination rates. The map was constructed using 11 pseudoautosomal probes (six of which are new) and typing individuals from 38 CEPH families. All markers have been physically mapped, thus providing the opportunity to compare genetic distance to physical distance through all intervals of the map. This comparison reveals an unexpected high rate of recombination in female meiosis between loci DXYS20 and DXYS78, within 20-80 kb from the telomere. Within this telemore-adjacent region no differences in male and female recombination rates are seen. Furthermore, data from this genetic map support the hypothesis of a linear gradient of recombination across most of the region in male meiosis and provide densely spaced anchor points for linkage studies especially in the telomeric portion of the pseudoautosomal region. 34 refs., 4 figs., 4 tabs.

  6. Quantitative reconstructions of changes in regional openness in north-central Europe reveal new insights into old questions

    NASA Astrophysics Data System (ADS)

    Nielsen, Anne Birgitte; Giesecke, Thomas; Theuerkauf, Martin; Feeser, Ingo; Behre, Karl-Ernst; Beug, Hans-Jürgen; Chen, Su-Hwa; Christiansen, Jörg; Dörfler, Walter; Endtmann, Elisabeth; Jahns, Susanne; de Klerk, Pim; Kühl, Norbert; Latałowa, Małgorzata; Odgaard, Bent Vad; Rasmussen, Peter; Stockholm, Jette Raal; Voigt, Ricarda; Wiethold, Julian; Wolters, Steffen

    2012-07-01

    By applying the recently developed model REVEALS (Regional Estimates of VEgetation Abundance from Large Sites) (Sugita, 2007) to pollen data from a large number of sites across Northern Germany and Denmark, we construct maps of regional patterns in landscape openness and in cover abundance of key plant taxa in the cultural landscape of north-central Europe for selected time slices in the Holocene. The results indicate that the pattern of landscape openness across the regions of northern Germany and Denmark prior to the introduction of agriculture was affected by soil conditions and degree of continentality. The 8.2 ka climate event did not lead to a general decrease in tree cover, although some changes in species composition were observed. The early phases of agriculture also had little effect on landscape openness at the regional scale, but later human impact lead to large scale deforestation and development of arable areas, grasslands and of heathlands in the north-western part of the region. The timing and degree of deforestation, and the weight between arable and grazing areas varied in space, partly due to differences in natural conditions, partly due to differences in cultural impact.

  7. Cardiomyopathy mutations reveal variable region of myosin converter as major element of cross-bridge compliance.

    PubMed

    Seebohm, B; Matinmehr, F; Köhler, J; Francino, A; Navarro-Lopéz, F; Perrot, A; Ozcelik, C; McKenna, W J; Brenner, B; Kraft, T

    2009-08-05

    The ability of myosin to generate motile forces is based on elastic distortion of a structural element of the actomyosin complex (cross-bridge) that allows strain to develop before filament sliding. Addressing the question, which part of the actomyosin complex experiences main elastic distortion, we suggested previously that the converter domain might be the most compliant region of the myosin head domain. Here we test this proposal by studying functional effects of naturally occurring missense mutations in the beta-myosin heavy chain, 723Arg --> Gly (R723G) and 736Ile --> Thr (I736T), in comparison to 719Arg --> Trp (R719W). All three mutations are associated with hypertrophic cardiomyopathy and are located in the converter region of the myosin head domain. We determined several mechanical parameters of single skinned slow fibers isolated from Musculus soleus biopsies of hypertrophic cardiomyopathy patients and healthy controls. Major findings of this study for mutation R723G were i), a >40% increase in fiber stiffness in rigor with a 2.9-fold increase in stiffness per myosin head (S( *)(rigor R723G) = 0.84 pN/nm S( *)(rigor WT) = 0.29 pN/nm); and ii), a significant increase in force per head (F( *)(10 degrees C), 1.99 pN vs. 1.49 pN = 1.3-fold increase; F( *)(20 degrees C), 2.56 pN vs. 1.92 pN = 1.3-fold increase) as well as stiffness per head during isometric steady-state contraction (S( *)(active10 degrees C), 0.52 pN/nm vs. 0.28 pN/nm = 1.9-fold increase). Similar changes were found for mutation R719W (2.6-fold increase in S( *)(rigor); 1.8-fold increase in F( *)(10 degrees C), 1.6-fold in F( *)(20 degrees C); twofold increase in S( *)(active10 degrees C)). Changes in active cross-bridge cycling kinetics could not account for the increase in force and active stiffness. For the above estimates the previously determined fraction of mutated myosin in the biopsies was taken into account. Data for wild-type myosin of slow soleus muscle fibers support previous

  8. Metallothionein deficiency in the injured peripheral nerves of complex regional pain syndrome as revealed by proteomics.

    PubMed

    Oki, Gosuke; Wada, Takuro; Iba, Kosuke; Aiki, Hikono; Sasaki, Kouichi; Imai, Shin-ichi; Sohma, Hitoshi; Matsumoto, Kayo; Yamaguchi, Mami; Fujimiya, Mineko; Yamashita, Toshihiko; Kokai, Yasuo

    2012-03-01

    Complex regional pain syndrome (CRPS) is characterized by persistent and severe pain after trauma or surgery; however, its molecular mechanisms in the peripheral nervous system are poorly understood. Using proteomics, we investigated whether injured peripheral nerves of CRPS patients have altered protein profiles compared with control nerves. We obtained nerve samples from 3 patients with CRPS-2 who underwent resection of part of an injured peripheral nerve. Sural nerves from fresh cadavers with no history of trauma or neuropathic pain served as controls. Proteomic analysis showed that the number and functional distribution of proteins expressed in CRPS and control nerves was similar. Interestingly, metallothionein was absent in the injured nerves of CRPS-2, although it was readily detected in control nerves. Western blotting further confirmed the absence of metallothionein in CRPS-2 nerves, and immunohistochemistry corroborated the deficiency of metallothionein expression in injured nerves from 5 of 5 CRPS patients and 2 of 2 patients with painful neuromas. In contrast, all control nerves, including 5 sural nerves from fresh cadavers and 41 nerves obtained from surgically resected tumors, expressed MT. Furthermore, expression of S100 as a marker for Schwann cells, and neurofilament M as a marker of axons was comparable in both CRPS-2 and controls. Metallothioneins are zinc-binding proteins that are probably involved in protection against injury and subsequent regeneration after CNS damage. Their absence from the injured peripheral nerves of patients with CRPS-2 suggests a potential pathogenic role in generating pain in the damaged peripheral nerves. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  9. Comparative phylogeography reveals deep lineages and regional evolutionary hotspots in the Mojave and Sonoran Deserts

    USGS Publications Warehouse

    Wood, Dustin A.; Vandergast, Amy G.; Barr, Kelly R.; Inman, Richard D.; Esque, Todd C.; Nussear, Kenneth E.; Fisher, Robert N.

    2013-01-01

    Aim: We explored lineage diversification within desert-dwelling fauna. Our goals were (1) to determine whether phylogenetic lineages and population expansions were consistent with younger Pleistocene climate fluctuation hypotheses or much older events predicted by pre-Pleistocene vicariance hypotheses, (2) to assess concordance in spatial patterns of genetic divergence and diversity among species and (3) to identify regional evolutionary hotspots of divergence and diversity and assess their conservation status. Location: Mojave, Colorado, and Sonoran Deserts, USA. Methods: We analysed previously published gene sequence data for twelve species. We used Bayesian gene tree methods to estimate lineages and divergence times. Within each lineage, we tested for population expansion and age of expansion using coalescent approaches. We mapped interpopulation genetic divergence and intra-population genetic diversity in a GIS to identify hotspots of highest genetic divergence and diversity and to assess whether protected lands overlapped with evolutionary hotspots. Results: In seven of the 12 species, lineage divergence substantially predated the Pleistocene. Historical population expansion was found in eight species, but expansion events postdated the Last Glacial Maximum (LGM) in only four. For all species assessed, six hotspots of high genetic divergence and diversity were concentrated in the Colorado Desert, along the Colorado River and in the Mojave/Sonoran ecotone. At least some proportion of the land within each recovered hotspot was categorized as protected, yet four of the six also overlapped with major areas of human development. Main conclusions: Most of the species studied here diversified into distinct Mojave and Sonoran lineages prior to the LGM – supporting older diversification hypotheses. Several evolutionary hotspots were recovered but are not strategically paired with areas of protected land. Long-term preservation of species-level biodiversity would

  10. Airborne methane remote measurements reveal heavy-tail flux distribution in Four Corners region

    PubMed Central

    Thorpe, Andrew K.; Thompson, David R.; Hulley, Glynn; Kort, Eric Adam; Vance, Nick; Borchardt, Jakob; Krings, Thomas; Gerilowski, Konstantin; Sweeney, Colm; Conley, Stephen; Bue, Brian D.; Aubrey, Andrew D.; Hook, Simon; Green, Robert O.

    2016-01-01

    Methane (CH4) impacts climate as the second strongest anthropogenic greenhouse gas and air quality by influencing tropospheric ozone levels. Space-based observations have identified the Four Corners region in the Southwest United States as an area of large CH4 enhancements. We conducted an airborne campaign in Four Corners during April 2015 with the next-generation Airborne Visible/Infrared Imaging Spectrometer (near-infrared) and Hyperspectral Thermal Emission Spectrometer (thermal infrared) imaging spectrometers to better understand the source of methane by measuring methane plumes at 1- to 3-m spatial resolution. Our analysis detected more than 250 individual methane plumes from fossil fuel harvesting, processing, and distributing infrastructures, spanning an emission range from the detection limit ∼ 2 kg/h to 5 kg/h through ∼ 5,000 kg/h. Observed sources include gas processing facilities, storage tanks, pipeline leaks, and well pads, as well as a coal mine venting shaft. Overall, plume enhancements and inferred fluxes follow a lognormal distribution, with the top 10% emitters contributing 49 to 66% to the inferred total point source flux of 0.23 Tg/y to 0.39 Tg/y. With the observed confirmation of a lognormal emission distribution, this airborne observing strategy and its ability to locate previously unknown point sources in real time provides an efficient and effective method to identify and mitigate major emissions contributors over a wide geographic area. With improved instrumentation, this capability scales to spaceborne applications [Thompson DR, et al. (2016) Geophys Res Lett 43(12):6571–6578]. Further illustration of this potential is demonstrated with two detected, confirmed, and repaired pipeline leaks during the campaign. PMID:27528660

  11. Airborne methane remote measurements reveal heavy-tail flux distribution in Four Corners region.

    PubMed

    Frankenberg, Christian; Thorpe, Andrew K; Thompson, David R; Hulley, Glynn; Kort, Eric Adam; Vance, Nick; Borchardt, Jakob; Krings, Thomas; Gerilowski, Konstantin; Sweeney, Colm; Conley, Stephen; Bue, Brian D; Aubrey, Andrew D; Hook, Simon; Green, Robert O

    2016-08-30

    Methane (CH4) impacts climate as the second strongest anthropogenic greenhouse gas and air quality by influencing tropospheric ozone levels. Space-based observations have identified the Four Corners region in the Southwest United States as an area of large CH4 enhancements. We conducted an airborne campaign in Four Corners during April 2015 with the next-generation Airborne Visible/Infrared Imaging Spectrometer (near-infrared) and Hyperspectral Thermal Emission Spectrometer (thermal infrared) imaging spectrometers to better understand the source of methane by measuring methane plumes at 1- to 3-m spatial resolution. Our analysis detected more than 250 individual methane plumes from fossil fuel harvesting, processing, and distributing infrastructures, spanning an emission range from the detection limit [Formula: see text] 2 kg/h to 5 kg/h through [Formula: see text] 5,000 kg/h. Observed sources include gas processing facilities, storage tanks, pipeline leaks, and well pads, as well as a coal mine venting shaft. Overall, plume enhancements and inferred fluxes follow a lognormal distribution, with the top 10% emitters contributing 49 to 66% to the inferred total point source flux of 0.23 Tg/y to 0.39 Tg/y. With the observed confirmation of a lognormal emission distribution, this airborne observing strategy and its ability to locate previously unknown point sources in real time provides an efficient and effective method to identify and mitigate major emissions contributors over a wide geographic area. With improved instrumentation, this capability scales to spaceborne applications [Thompson DR, et al. (2016) Geophys Res Lett 43(12):6571-6578]. Further illustration of this potential is demonstrated with two detected, confirmed, and repaired pipeline leaks during the campaign.

  12. Contact investigation of melioidosis cases reveals regional endemicity in Puerto Rico.

    PubMed

    Doker, Thomas J; Sharp, Tyler M; Rivera-Garcia, Brenda; Perez-Padilla, Janice; Benoit, Tina J; Ellis, Esther M; Elrod, Mindy G; Gee, Jay E; Shieh, Wun-Ju; Beesley, Cari A; Ryff, Kyle R; Traxler, Rita M; Galloway, Renee L; Haberling, Dana L; Waller, Lance A; Shadomy, Sean V; Bower, William A; Hoffmaster, Alex R; Walke, Henry T; Blaney, David D

    2015-01-15

    Melioidosis results from infection with Burkholderia pseudomallei and is associated with case-fatality rates up to 40%. Early diagnosis and treatment with appropriate antimicrobials can improve survival rates. Fatal and nonfatal melioidosis cases were identified in Puerto Rico in 2010 and 2012, respectively, which prompted contact investigations to identify risk factors for infection and evaluate endemicity. Questionnaires were administered and serum specimens were collected from coworkers, neighborhood contacts within 250 m of both patients' residences, and injection drug user (IDU) contacts of the 2012 patient. Serum specimens were tested for evidence of prior exposure to B. pseudomallei by indirect hemagglutination assay. Neighborhood seropositivity results guided soil sampling to isolate B. pseudomallei. Serum specimens were collected from contacts of the 2010 (n = 51) and 2012 (n = 60) patients, respectively. No coworkers had detectable anti-B. pseudomallei antibody, whereas seropositive results among neighborhood contacts was 5% (n = 2) for the 2010 patient and 23% (n = 12) for the 2012 patient, as well as 2 of 3 IDU contacts for the 2012 case. Factors significantly associated with seropositivity were having skin wounds, sores, or ulcers (odds ratio [OR], 4.6; 95% confidence interval [CI], 1.2-17.8) and IDU (OR, 18.0; 95% CI, 1.6-194.0). Burkholderia pseudomallei was isolated from soil collected in the neighborhood of the 2012 patient. Taken together, isolation of B. pseudomallei from a soil sample and high seropositivity among patient contacts suggest at least regional endemicity of melioidosis in Puerto Rico. Increased awareness of melioidosis is needed to enable early case identification and early initiation of appropriate antimicrobial therapy. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  13. Environmental odours and somatic complaints.

    PubMed

    Steinheider, B

    1999-08-01

    Two field studies in two cities in Northrhine-Westfalia were carried out in order to characterize the degree of association between environmental odour-exposure, annoyance, and somatic symptoms. In both studies, odour effects were assessed through personal interviews by means of standardised questionnaires. In the first study, the odour source was a fertilizer plant for mushroom cultivation with particularly offensive odour emissions. The distance from the source was taken to characterize the intensity of odour exposure. 250 subjects were interviewed at close, medium or remote distance from the plant. Apart from an extremely high degree of annoyance, an increasing frequency of somatic symptoms was found with increasing proximity to the odour source. Somatic symptoms were directly linked to odour exposure and additionally mediated by annoyance. In the second study (n = 322), the odour source was a pig rearing facility, and the degree of odour exposure was assessed by measuring the frequency of odour-events by means of systematic field observations. Results showed that the degree of odour-annoyance as well as the frequency of somatic symptoms increased significantly with increasing odour-exposure, although their frequency was reduced relative to the first study, and mediated by annoyance. In both studies, perceived negative health was associated with increased symptom reports, however, results for old age were inconsistent. Response tendencies and biases were controlled. Environmental odours have been shown to be associated with somatic symptoms and, may, thus, be considered as a risk factor for health and wellbeing of exposed populations, especially for vulnerable subjects with perceived negative health.

  14. Integrating Somatic Learning into Everyday Life.

    ERIC Educational Resources Information Center

    Beaudoin, Charlotte

    1999-01-01

    Studied how proponents of somatic learning transfer their learning to the everyday life context by determining the experiences of six adults who had an average of six years experience with body-centered approaches to somatic education. Results show how subjects use their somatic learning in everyday situations of distress. (SLD)

  15. Gravity waves, Tides and Planetary wave characteristics revealed by network of MLT radars over Indian region

    NASA Astrophysics Data System (ADS)

    Venkat Ratnam, Madineni; Karanam, Kishore Kumar; Sunkara, Eswaraiah; Vijaya Bhaskara Rao, S.; Subrahmanyam, K. V.; Ramanjaneyulu, L.

    2016-07-01

    Mesosphere and Lower Thermosphere (MLT) mean winds, gravity waves, tidal and planetary wave characteristics are investigated using two years (2013-2015) of advanced meteor radar installed at Tirupathi (13.63oN, 79.4oE), India. The observations reveal the presence of high frequency gravity waves (30-120 minutes), atmospheric tides (diurnal, semi-diurnal and terr-diurnal) along with long period oscillations in both zonal and meridional winds. Background mean zonal winds show clear semi-annual oscillation in the mesosphere, whereas meridional winds are characterized by annual oscillation as expected. Diurnal tide amplitudes are significantly larger (60-80 m/s) than semi-diurnal (10-20 m/s) and terr-diurnal (5-8 m/s) tides and larger in meridional than zonal winds. The measured meridional components are in good agreement with Global Scale Wave Model (GSWM-09) predictions than zonal up to ~90 km in all the seasons, except fall equinox. Diurnal tidal phase matches well than the amplitudes between observations and model predictions. However, no similarity is being found in the semi-diurnal tides between observations and model. The measurements are further compared with nearby Thumba meteor radar (8.5oN, 77oE) observations. Some differences do exist between the measurements from Tirupati and Thumba meteor radar and model outputs at greater heights and the possible reasons are discussed. SVU meteor radar observations clearly showed the dominance of well-known ultra-fast kelvin waves (3.5 days), 5-8 day, 16 day, 27 day, and 30-40 day oscillations. Due to higher meteor count extending up to 110 km, we could investigate the variability of these PWs and oscillations covering wider range (70-110 km) for the first time. Significant change above 100 km is noticed in all the above mentioned PW activity and oscillations. We also used ERA-Interim reanalysis data sets available at 0.125x0.125 degree grids for investigating the characteristics of these PW right from surface to 1 h

  16. Local and Regional Diversity Reveals Dispersal Limitation and Drift as Drivers for Groundwater Bacterial Communities from a Fractured Granite Formation.

    PubMed

    Beaton, E D; Stevenson, Bradley S; King-Sharp, Karen J; Stamps, Blake W; Nunn, Heather S; Stuart, Marilyne

    2016-01-01

    Microorganisms found in terrestrial subsurface environments make up a large proportion of the Earth's biomass. Biogeochemical cycles catalyzed by subsurface microbes have the potential to influence the speciation and transport of radionuclides managed in geological repositories. To gain insight on factors that constrain microbial processes within a formation with restricted groundwater flow we performed a meta-community analysis on groundwater collected from multiple discrete fractures underlying the Chalk River Laboratories site (located in Ontario, Canada). Bacterial taxa were numerically dominant in the groundwater. Although these were mainly uncultured, the closest cultivated representatives were from the phenotypically diverse Betaproteobacteria, Deltaproteobacteria, Bacteroidetes, Actinobacteria, Nitrospirae, and Firmicutes. Hundreds of taxa were identified but only a few were found in abundance (>1%) across all assemblages. The remainder of the taxa were low abundance. Within an ecological framework of selection, dispersal and drift, the local and regional diversity revealed fewer taxa within each assemblage relative to the meta-community, but the taxa that were present were more related than predicted by chance. The combination of dispersion at one phylogenetic depth and clustering at another phylogenetic depth suggest both niche (dispersion) and filtering (clustering) as drivers of local assembly. Distance decay of similarity reveals apparent biogeography of 1.5 km. Beta diversity revealed greater influence of selection at shallow sampling locations while the influences of dispersal limitation and randomness were greater at deeper sampling locations. Although selection has shaped each assemblage, the spatial scale of groundwater sampling favored detection of neutral processes over selective processes. Dispersal limitation between assemblages combined with local selection means the meta-community is subject to drift, and therefore, likely reflects the

  17. Local and Regional Diversity Reveals Dispersal Limitation and Drift as Drivers for Groundwater Bacterial Communities from a Fractured Granite Formation

    PubMed Central

    Beaton, E. D.; Stevenson, Bradley S.; King-Sharp, Karen J.; Stamps, Blake W.; Nunn, Heather S.; Stuart, Marilyne

    2016-01-01

    Microorganisms found in terrestrial subsurface environments make up a large proportion of the Earth’s biomass. Biogeochemical cycles catalyzed by subsurface microbes have the potential to influence the speciation and transport of radionuclides managed in geological repositories. To gain insight on factors that constrain microbial processes within a formation with restricted groundwater flow we performed a meta-community analysis on groundwater collected from multiple discrete fractures underlying the Chalk River Laboratories site (located in Ontario, Canada). Bacterial taxa were numerically dominant in the groundwater. Although these were mainly uncultured, the closest cultivated representatives were from the phenotypically diverse Betaproteobacteria, Deltaproteobacteria, Bacteroidetes, Actinobacteria, Nitrospirae, and Firmicutes. Hundreds of taxa were identified but only a few were found in abundance (>1%) across all assemblages. The remainder of the taxa were low abundance. Within an ecological framework of selection, dispersal and drift, the local and regional diversity revealed fewer taxa within each assemblage relative to the meta-community, but the taxa that were present were more related than predicted by chance. The combination of dispersion at one phylogenetic depth and clustering at another phylogenetic depth suggest both niche (dispersion) and filtering (clustering) as drivers of local assembly. Distance decay of similarity reveals apparent biogeography of 1.5 km. Beta diversity revealed greater influence of selection at shallow sampling locations while the influences of dispersal limitation and randomness were greater at deeper sampling locations. Although selection has shaped each assemblage, the spatial scale of groundwater sampling favored detection of neutral processes over selective processes. Dispersal limitation between assemblages combined with local selection means the meta-community is subject to drift, and therefore, likely reflects the

  18. The Structure and Dynamics of the Upper Chromosphere and Lower Transition Region as Revealed by the Subarcsecond VAULT Observations

    DTIC Science & Technology

    2010-06-28

    Sailer , M.: 2006, Astron. Astrophys. 454, 1011. doi:10.1051/0004- 6361:20053918. Rutten, R.J., van Veelen, B., Sütterlin, P.: 2008, Solar Phys... Solar Physics DOI: 10.1007/•••••-•••-•••-••••-• The Structure and Dynamics of the Upper Chromosphere and Lower Transition Region as Revealed by the...the crucial interface between the solar chromosphere and the corona by observing the strongest line in the solar spectrum, the Lyα line at 1216Å. In

  19. Cognitive-affective neuroscience of somatization disorder and functional somatic syndromes: reconceptualizing the triad of depression-anxiety-somatic symptoms.

    PubMed

    Stein, Dan J; Muller, Jacqueline

    2008-05-01

    Somatization disorder is a somatoform disorder that overlaps with a number of functional somatic syndromes and has high comorbidity with major depression and anxiety disorders. Proposals have been made for revising the category of somatoform disorders, for simplifying the criteria for somatization disorder, and for emphasizing the unitary nature of the functional somatic syndromes in future classifications. A review of the cognitive-affective neuroscience of somatization disorder and related conditions suggests that overlapping psychobiological mechanisms mediate depression, anxiety, and somatization symptoms. Particular genes and environments may contribute to determining whether symptoms are predominantly depressive, anxious, or somatic, and there are perhaps also overlaps and distinctions in the distal evolutionary mechanisms that produce these symptoms.

  20. Monoamines tissue content analysis reveals restricted and site-specific correlations in brain regions involved in cognition.

    PubMed

    Fitoussi, A; Dellu-Hagedorn, F; De Deurwaerdère, P

    2013-01-01

    The dopamine (DA), noradrenalin (NA) and serotonin (5-HT) monoaminergic systems are deeply involved in cognitive processes via their influence on cortical and subcortical regions. The widespread distribution of these monoaminergic networks is one of the main difficulties in analyzing their functions and interactions. To address this complexity, we assessed whether inter-individual differences in monoamine tissue contents of various brain areas could provide information about their functional relationships. We used a sensitive biochemical approach to map endogenous monoamine tissue content in 20 rat brain areas involved in cognition, including 10 cortical areas and examined correlations within and between the monoaminergic systems. Whereas DA content and its respective metabolite largely varied across brain regions, the NA and 5-HT contents were relatively homogenous. As expected, the tissue content varied among individuals. Our analyses revealed a few specific relationships (10%) between the tissue content of each monoamine in paired brain regions and even between monoamines in paired brain regions. The tissue contents of NA, 5-HT and DA were inter-correlated with a high incidence when looking at a specific brain region. Most correlations found between cortical areas were positive while some cortico-subcortical relationships regarding the DA, NA and 5-HT tissue contents were negative, in particular for DA content. In conclusion, this work provides a useful database of the monoamine tissue content in numerous brain regions. It suggests that the regulation of these neuromodulatory systems is achieved mainly at the terminals, and that each of these systems contributes to the regulation of the other two. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Somatic Mutation, Genomic Variation, and Neurological Disease

    PubMed Central

    Poduri, Annapurna; Evrony, Gilad D.; Cai, Xuyu; Walsh, Christopher A.

    2014-01-01

    Genetic mutations causing human disease are conventionally thought to be inherited through the germ line from one’s parents and present in all somatic (body) cells, except for most cancer mutations, which arise somatically. Increasingly, somatic mutations are being identified in diseases other than cancer, including neurodevelopmental diseases. Somatic mutations can arise during the course of prenatal brain development and cause neurological disease—even when present at low levels of mosaicism, for example—resulting in brain malformations associated with epilepsy and intellectual disability. Novel, highly sensitive technologies will allow more accurate evaluation of somatic mutations in neurodevelopmental disorders and during normal brain development. PMID:23828942

  2. Physical and Chemical Properties of Jupiter's Polar Vortices and Regions of Auroral Influence Revealed Through High-Resolution Infrared Imaging

    NASA Astrophysics Data System (ADS)

    Fernandes, Josh; Orton, Glenn S.; Sinclair, James; Kasaba, Yasumasa; Sato, Takao M.; Fujiyoshi, Takuya; Momary, Thomas W.; Yanamandra-Fisher, Padma A.

    2016-10-01

    We report characterization of the physical and chemical properties of Jupiter's polar regions derived from mid-infrared imaging of Jupiter covering all longitudes at unprecedented spatial resolution using the COMICS instrument at the Subaru Telescope on the nights of January 24 and 25, 2016 (UT). Because of Jupiter's slight axial tilt of 3°, the low angular resolution and incomplete longitudinal coverage of previous mid-infrared observations, the physical and chemical properties of Jupiter's polar regions have been poorly characterized. In advance of the Juno mission's exploration of the polar regions, this study focuses on mapping the 3-dimensional structure of Jupiter's polar regions, specifically to characterize the polar vortices and compact regions of auroral influence. Using mid-infrared images taken in the 7.8 - 24.2 µm range, we determined the 3-dimensional temperature field, mapped the para-H2 fraction and aerosol opacity at 700 mbar and lower pressures, and constrained the distribution of gaseous NH3 in Jupiter's northern and southern polar regions. Retrievals of these atmospheric parameters was performed using NEMESIS, a radiative transfer forward model and retrieval code. Preliminary results indicate that there are vortices at both poles, each with very distinct low-latitude boundaries approximately 60° (planetocentric) from the equator, which can be defined by sharp thermal gradients extending at least from the upper troposphere (500 mbar) and into the stratosphere (0.1 mbar). These polar regions are characterized by lower temperatures, lower aerosol number densities, and lower NH3 volume mixing ratios, compared with the regions immediately outside the vortex boundaries. These images also provided the highest resolution of prominent auroral-related stratospheric heating to date, revealing a teardrop-shaped morphology in the north and a sharp-edged oval shape in the south. Both appear to be contained inside the locus of H3+ auroral emission detected

  3. Chronic functional somatic symptoms: a single syndrome?

    PubMed Central

    olde Hartman, Tim C; Lucassen, Peter L B J; van de Lisdonk, Eloy H; Bor, Hans H J; van Weel, Chris

    2004-01-01

    Background: Reliable longitudinal data of patients with functional somatic symptoms in general practice are lacking. Aims: To identify distinctive features in patients with chronic functional somatic symptoms, and to determine whether these symptoms support the hypothesis of the existence of specific somatic syndromes. Design of study: Observational study, with a comparison control group. Setting: Four primary care practices affiliated with the University of Nijmegen in the Netherlands. Method: One hundred and eighty-two patients diagnosed between 1998 and 2002 as having chronic functional somatic symptoms and 182 controls matched by age, sex, socioeconomic status, and practice were included. Data on comorbidity, referrals, diagnostic tests, and hospital admissions over a period of 10 years prior to the diagnosis were collected. Medication use and number of visits to the general practitioner (GP) were extracted from the moment computerised registration was started. Results: In the 10 years before the diagnosis of chronic functional somatic symptoms, significantly more patients than controls presented functional somatic symptoms in at least two body systems, and used more somatic and psychotropic drugs. They visited the GP twice as much, statistically had significantly more psychiatric morbidity, and were referred more often to mental health workers and somatic specialists. The number of patients undergoing diagnostic tests was higher for patients with chronic functional somatic symptoms than for controls, but hospital admissions rates were equal. Conclusion: Patients with chronic functional somatic symptoms have a great diversity of functional somatic symptoms. They use more somatic and psychotropic drugs than controls in the years before diagnosis. Moreover, they show high rates of referrals and psychiatric morbidity. The diversity of symptoms of patients with chronic functional somatic symptoms supports the concept that symptoms do not cluster in well defined

  4. Somatic and Depressive Symptoms in Female Japanese and American Students: A Preliminary Investigation

    PubMed Central

    Arnault, Denise Saint; Sakamoto, Shinji; Moriwaki, Aiko

    2007-01-01

    The present study examined the relationship between common somatic symptoms and depression in samples of Japanese and American college students. Fifty Japanese and 44 American women completed the Beck Depression Inventory (BDI) and rated 56 somatic-distress items for 7 days. Japanese had higher levels of somatic distress than Americans. ANOVA of somatic distress by BDI-level revealed that the High BDI Japanese group reported 26 somatic symptoms (including stomach ache, dizziness, and shoulder pain) with significantly higher means when compared with the low BDI group. High BDI Americans had a significantly higher mean for joint pain compared to the Low BDI group. The importance of the body in transcultural psychiatry is explored, and implications for primary and mental health care are discussed. PMID:16893876

  5. Identification of somatic TERT promoter mutations in familial nonmedullary thyroid carcinomas.

    PubMed

    Marques, Inês J; Moura, Margarida M; Cabrera, Rafael; Pinto, António E; Simões-Pereira, Joana; Santos, Catarina; Menezes, Francisco D; Montezuma, Diana; Henrique, Rui; Rodrigues Teixeira, Manuel; Leite, Valeriano; Cavaco, Branca M

    2017-10-01

    The genes causing familial nonmedullary thyroid carcinoma (FNMTC) identified to date are only involved in a small fraction of the families. Recently, somatic mutations in TERT promoter region and in EIF1AX gene were reported in thyroid tumours of undefined familial status. The aim of this study was to investigate the role of TERT and EIF1AX mutations in familial thyroid tumours. The promoter region of TERT was sequenced in leucocyte DNA of the probands from 75 FNMTC families. In thyroid tumours from 54 familial cases, we assessed somatic TERT promoter, RAS and BRAF hotspot mutations, and the whole EIF1AX gene. No potentially pathogenic germline variants were identified in TERT in the 75 FNMTC families' probands. In the 54 carcinomas, we identified five cases (9%) with hotspot somatic TERT promoter mutations. BRAF mutations were found in 41% of the tumours. All TERT-positive samples were also positive for BRAF p.Val600Glu, and this co-occurrence was found to be statistically significant (P=.008). RAS mutations were detected in four tumours wild-type for TERT (7%). Evaluation of tumour mutation data together with the patients' clinicopathological features revealed a significant correlation between TERT plus BRAF mutations and advanced tumour stage (T4) (P=.020). No mutations were identified in EIF1AX. The results of this study suggest that TERT promoter and EIF1AX mutations are not frequently involved in FNMTC aetiology. However, we show for the first time that TERT alterations are associated with familial thyroid tumour progression. Our data also suggest that TERT mutations are more often found in concomitance with BRAF mutations in advanced stages of FNMTC. © 2017 John Wiley & Sons Ltd.

  6. Comparative Genomic Analyses of the Human NPHP1 Locus Reveal Complex Genomic Architecture and Its Regional Evolution in Primates

    PubMed Central

    Yuan, Bo; Liu, Pengfei; Gupta, Aditya; Beck, Christine R.; Tejomurtula, Anusha; Campbell, Ian M.; Gambin, Tomasz; Simmons, Alexandra D.; Withers, Marjorie A.; Harris, R. Alan; Rogers, Jeffrey; Schwartz, David C.; Lupski, James R.

    2015-01-01

    Many loci in the human genome harbor complex genomic structures that can result in susceptibility to genomic rearrangements leading to various genomic disorders. Nephronophthisis 1 (NPHP1, MIM# 256100) is an autosomal recessive disorder that can be caused by defects of NPHP1; the gene maps within the human 2q13 region where low copy repeats (LCRs) are abundant. Loss of function of NPHP1 is responsible for approximately 85% of the NPHP1 cases—about 80% of such individuals carry a large recurrent homozygous NPHP1 deletion that occurs via nonallelic homologous recombination (NAHR) between two flanking directly oriented ~45 kb LCRs. Published data revealed a non-pathogenic inversion polymorphism involving the NPHP1 gene flanked by two inverted ~358 kb LCRs. Using optical mapping and array-comparative genomic hybridization, we identified three potential novel structural variant (SV) haplotypes at the NPHP1 locus that may protect a haploid genome from the NPHP1 deletion. Inter-species comparative genomic analyses among primate genomes revealed massive genomic changes during evolution. The aggregated data suggest that dynamic genomic rearrangements occurred historically within the NPHP1 locus and generated SV haplotypes observed in the human population today, which may confer differential susceptibility to genomic instability and the NPHP1 deletion within a personal genome. Our study documents diverse SV haplotypes at a complex LCR-laden human genomic region. Comparative analyses provide a model for how this complex region arose during primate evolution, and studies among humans suggest that intra-species polymorphism may potentially modulate an individual’s susceptibility to acquiring disease-associated alleles. PMID:26641089

  7. Unexpected diversity in the catfish Pseudancistrus brevispinis reveals dispersal routes in a Neotropical center of endemism: the Guyanas Region.

    PubMed

    Cardoso, Yamila P; Montoya-Burgos, Juan I

    2009-03-01

    Neotropical freshwater fishes have reached an unrivalled diversity, organized into several areas of endemism, yet the underlying processes are still largely unknown. The topographical and ecological characteristics of the Guyanas Region make it an ideal area of endemism in which to investigate the forces that have shaped this great diversity. This region is thought to be inhabited by species descending from Amazonian ancestors, which would have used two documented routes that, however, hardly explain the entrance of species adapted to running waters. Here, we investigate the evolutionary history of Pseudancistrus brevispinis, a catfish endemic to this region and exclusively found in running waters, thus making it an ideal model for investigating colonization routes and dispersal in such habitats. Our analyses, based on mitochondrial and nuclear markers, revealed an unexpected diversity consisting of six monophyletic lineages within P. brevispinis, showing a disjoint distribution pattern. The lineages endemic to Guyanas coastal rivers form a monophyletic group that originated via an ancestral colonization event from the Amazon basin. Evidence given favours a colonization pathway through river capture between an Amazonian tributary and the Upper Maroni River. Population genetic analyses of the most widespread species indicate that subsequent dispersal among Guyanas coastal rivers occurred principally by temporary connections between adjacent rivers during periods of lower sea level, yet instances of dispersal via interbasin river captures are not excluded. During high sea level intervals, the isolated populations would have diverged leading to the observed allopatric species. This evolutionary process is named the sea level fluctuation (SLF) hypothesis of diversification.

  8. Sequence analysis of the ERCC2 gene regions in human, mouse, and hamster reveals three linked genes.

    PubMed

    Lamerdin, J E; Stilwagen, S A; Ramirez, M H; Stubbs, L; Carrano, A V

    1996-06-15

    The ERCC2 (excision repair cross-complementing rodent repair group 2) gene product is involved in transcription-coupled repair as an integral member of the basal transcription factor BTF2/TFIIH complex. Defects in this gene can result in three distinct human disorders, namely the cancer-prone syndrome xeroderma pigmentosum complementation group D, trichothiodystrophy, and Cockayne syndrome. We report the comparative analysis of 91.6 kb of new sequence including 54.3 kb encompassing the human ERCC2 locus, the syntenic region in the mouse (32.6 kb), and a further 4.7 kb of sequence 3' of the previously reported ERCC2 region in the hamster. In addition to ERCC2, our analysis revealed the presence of two previously undescribed genes in all three species. The first is centromeric (in the human) to ERCC2 and is most similar to the kinesin light chain gene in sea urchin. The second gene is telomeric (in the human) to ERCC2 and contains a motif found in ankyrins, some cell cycle proteins, and transcription factors. Multiple EST matches to this putative new gene indicate that it is expressed in several human tissues, including breast. The identification and description of two new genes provides potential candidate genes for disorders mapping to this region of 19q13.2.

  9. Solution structure of the region 51–160 of human KIN17 reveals an atypical winged helix domain

    PubMed Central

    Carlier, Ludovic; Couprie, Joël; le Maire, Albane; Guilhaudis, Laure; Milazzo-Segalas, Isabelle; Courçon, Marie; Moutiez, Mireille; Gondry, Muriel; Davoust, Daniel; Gilquin, Bernard; Zinn-Justin, Sophie

    2007-01-01

    Human KIN17 is a 45-kDa eukaryotic DNA- and RNA-binding protein that plays an important role in nuclear metabolism and in particular in the general response to genotoxics. Its amino acids sequence contains a zinc finger motif (residues 28–50) within a 30-kDa N-terminal region conserved from yeast to human, and a 15-kDa C-terminal tandem of SH3-like subdomains (residues 268–393) only found in higher eukaryotes. Here we report the solution structure of the region 51–160 of human KIN17. We show that this fragment folds into a three-α-helix bundle packed against a three-stranded β-sheet. It belongs to the winged helix (WH) family. Structural comparison with analogous WH domains reveals that KIN17 WH module presents an additional and highly conserved 310-helix. Moreover, KIN17 WH helix H3 is not positively charged as in classical DNA-binding WH domains. Thus, human KIN17 region 51–160 might rather be involved in protein–protein interaction through its conserved surface centered on the 310-helix. PMID:18029424

  10. Sequence analysis of the ERCC2 gene regions in human, mouse, and hamster reveals three linked genes

    SciTech Connect

    Lamerdin, J.E.; Stilwagen, S.A.; Ramirez, M.H.

    1996-06-15

    The ERCC2 (excision repair cross-complementing rodent repair group 2) gene product is involved in transcription-coupled repair as an integral member of the basal transcription factor BTF2/TFIIH complex. Defects in this gene can result in three distinct human disorders, namely the cancer-prone syndrome xeroderma pigmentosum complementation group D, trichothiodystrophy, and Cockayne syndrome. We report the comparative analysis of 91.6 kb of new sequence including 54.3 kb encompassing the human ERCC2 locus, the syntenic region in the mouse (32.6 kb), and a further 4.7 kb of sequence 3{prime} of the previously reported ERCC2 region in the hamster. In addition to ERCC2, our analysis revealed the presence of two previously undescribed genes in all three species. The first is centromeric (in the human) to ERCC2 and is most similar to the kinesin light chain gene in sea urchin. The second gene is telomeric (in the human) to ERCC2 and contains a motif found in ankyrins, some cell proteins, and transcription factors. Multiple EST matches to this putative new gene indicate that it is expressed in several human tissues, including breast. The identification and description of two new genes provides potential candidate genes for disorders mapping to this region of 19q13.2. 42 refs., 6 figs., 3 tabs.

  11. Somatization and mental health: a comparative study of the idiom of distress hypothesis.

    PubMed

    Keyes, Corey L M; Ryff, Carol D

    2003-11-01

    Somatization is the expression of physical symptoms in the absence of medically explained physical illness. As a disproportionate response to psychosocial distress, somatization is usually correlated with depression. According to the idiom of distress hypothesis, the association of somatization and mental health is mitigated when somatizing indirectly expresses, and is understood by others as, emotional distress. Theory and data suggest that collectivistic societies such as South Korea (S.K.), unlike individualistic societies like the U.S. (U.S.), employ an idiom of distress. Multiple measures of physical and mental health were administered to a random sample of S.K. (n=220) and U.S. (n=215) adults. Measurement structures of physical health and mental health were comparable between samples. Individuals in both samples somatized the same number of symptoms, although the U.S. adults expressed those symptoms more frequently. Findings supported the idiom of distress hypothesis. Bivariate and multivariate analyses revealed that the relationship of somatization with mental health depends on culture. Also, the disparity in mental health was greatest and favored the U.S. adults at low levels of somatization, but the disparity in mental health between countries disappeared as somatization increased.

  12. Multilocus phylogenetic analysis of true morels (Morchella) reveals high levels of endemics in Turkey relative to other regions of Europe.

    PubMed

    Taskin, Hatira; Büyükalaca, Saadet; Hansen, Karen; O'Donnell, Kerry

    2012-01-01

    The present study was conducted to better understand how the phylogenetic diversity of true morels (Morchella) in Turkey compares with species found in other regions of the world. The current research builds on our recently published surveys of 10 Turkish provinces and the northern hemisphere in which DNA sequence data from 247 and 562 collections respectively were analyzed phylogenetically. Herein we report on phylogenetic analyses of 243 additional collections made in spring 2009 and 2010 from eight additional provinces in the Aegean, Black Sea, central Anatolia, eastern Anatolia and Marmara regions of Turkey. Our analysis revealed that five species within the Esculenta clade (yellow morels) and 15 species within the Elata clade (black morels) were present in Turkey. Our preliminary results also indicate that M. anatolica, recently described from a collection in Muğla province in the Aegean region of Turkey, is a closely related sister of M. rufobrunnea; these two species comprise a separate evolutionary lineage from the Esculenta and Elata clades. Nine species of Morchella currently are known only from Turkey, four species were present in Turkey and other European countries and seven species might have been introduced to Turkey anthropogenically. Three of the putatively exotic species in Turkey appear to be endemic to western North America; they are nested within a clade of fire-adapted morels that dates to the late Oligocene, 25 000 000 y ago. Our results indicate that there are roughly twice as many Morchella species in Turkey compared with the other regions of Europe sampled. Knowledge of Morchella species diversity and their biogeographic distribution are crucial for formulating informed conservation policies directed at preventing species loss and ensuring that annual morel harvests are sustainable and ecologically sound.

  13. Microarray analysis of 50 patients reveals the critical chromosomal regions responsible for 1p36 deletion syndrome-related complications.

    PubMed

    Shimada, Shino; Shimojima, Keiko; Okamoto, Nobuhiko; Sangu, Noriko; Hirasawa, Kyoko; Matsuo, Mari; Ikeuchi, Mayo; Shimakawa, Shuichi; Shimizu, Kenji; Mizuno, Seiji; Kubota, Masaya; Adachi, Masao; Saito, Yoshiaki; Tomiwa, Kiyotaka; Haginoya, Kazuhiro; Numabe, Hironao; Kako, Yuko; Hayashi, Ai; Sakamoto, Haruko; Hiraki, Yoko; Minami, Koichi; Takemoto, Kiyoshi; Watanabe, Kyoko; Miura, Kiyokuni; Chiyonobu, Tomohiro; Kumada, Tomohiro; Imai, Katsumi; Maegaki, Yoshihiro; Nagata, Satoru; Kosaki, Kenjiro; Izumi, Tatsuro; Nagai, Toshiro; Yamamoto, Toshiyuki

    2015-05-01

    Monosomy 1p36 syndrome is the most commonly observed subtelomeric deletion syndrome. Patients with this syndrome typically have common clinical features, such as intellectual disability, epilepsy, and characteristic craniofacial features. In cooperation with academic societies, we analyzed the genomic copy number aberrations using chromosomal microarray testing. Finally, the genotype-phenotype correlation among them was examined. We obtained clinical information of 86 patients who had been diagnosed with chromosomal deletions in the 1p36 region. Among them, blood samples were obtained from 50 patients (15 males and 35 females). The precise deletion regions were successfully genotyped. There were variable deletion patterns: pure terminal deletions in 38 patients (76%), including three cases of mosaicism; unbalanced translocations in seven (14%); and interstitial deletions in five (10%). Craniofacial/skeletal features, neurodevelopmental impairments, and cardiac anomalies were commonly observed in patients, with correlation to deletion sizes. The genotype-phenotype correlation analysis narrowed the region responsible for distinctive craniofacial features and intellectual disability into 1.8-2.1 and 1.8-2.2 Mb region, respectively. Patients with deletions larger than 6.2 Mb showed no ambulation, indicating that severe neurodevelopmental prognosis may be modified by haploinsufficiencies of KCNAB2 and CHD5, located at 6.2 Mb away from the telomere. Although the genotype-phenotype correlation for the cardiac abnormalities is unclear, PRDM16, PRKCZ, and RERE may be related to this complication. Our study also revealed that female patients who acquired ambulatory ability were likely to be at risk for obesity. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  14. Enhancement of American chestnut somatic seedling production.

    PubMed

    Andrade, G M; Merkle, S A

    2005-08-01

    Somatic embryogenesis holds promise for mass propagation of American chestnut trees bred or genetically engineered for resistance to chestnut blight. However, low germination frequency of chestnut somatic embryos has limited somatic seedling production for this forest tree. We tested the effects of culture regime (semi-solid versus liquid), cold treatment, AC and somatic embryo morphology (i.e., cotyledon number) on germination and conversion of the somatic embryos. Cold treatment for 12 weeks was critical for conversion of chestnut somatic embryos to somatic seedlings, raising conversion frequencies for one line to 47%, compared to 7% with no cold treatment. AC improved germination and conversion frequency for one line to 77% and 59%, respectively, and kept roots from darkening. For two lines that produced embryos with one, two or three-plus cotyledons, cotyledon number did not affect germination or conversion frequency. We also established embryogenic American chestnut suspension cultures and adapted a fractionation/plating system that allowed us to produce populations of relatively synchronous somatic embryos for multiple lines. Embryos derived from suspension cultures of two lines tested had higher conversion frequencies (46% and 48%) than those from cultures maintained on semi-solid medium (7% and 30%). The improvements in manipulation of American chestnut embryogenic cultures described in this study have allowed over a 100-fold increase in somatic seedling production efficiency over what we reported previously and thus constitute a substantial advance toward the application of somatic embryogenesis for mass clonal propagation of the tree.

  15. Comparative genomics reveals a functional thyroid-specific element in the far upstream region of the PAX8 gene

    PubMed Central

    2010-01-01

    Background The molecular mechanisms leading to a fully differentiated thyrocite are still object of intense study even if it is well known that thyroglobulin, thyroperoxidase, NIS and TSHr are the marker genes of thyroid differentiation. It is also well known that Pax8, TTF-1, Foxe1 and Hhex are the thyroid-enriched transcription factors responsible for the expression of the above genes, thus are responsible for the differentiated thyroid phenotype. In particular, the role of Pax8 in the fully developed thyroid gland was studied in depth and it was established that it plays a key role in thyroid development and differentiation. However, to date the bases for the thyroid-enriched expression of this transcription factor have not been unraveled yet. Here, we report the identification and characterization of a functional thyroid-specific enhancer element located far upstream of the Pax8 gene. Results We hypothesized that regulatory cis-acting elements are conserved among mammalian genes. Comparison of a genomic region extending for about 100 kb at the 5'-flanking region of the mouse and human Pax8 gene revealed several conserved regions that were tested for enhancer activity in thyroid and non-thyroid cells. Using this approach we identified one putative thyroid-specific regulatory element located 84.6 kb upstream of the Pax8 transcription start site. The in silico data were verified by promoter-reporter assays in thyroid and non-thyroid cells. Interestingly, the identified far upstream element manifested a very high transcriptional activity in the thyroid cell line PC Cl3, but showed no activity in HeLa cells. In addition, the data here reported indicate that the thyroid-enriched transcription factor TTF-1 is able to bind in vitro and in vivo the Pax8 far upstream element, and is capable to activate transcription from it. Conclusions Results of this study reveal the presence of a thyroid-specific regulatory element in the 5' upstream region of the Pax8 gene. The

  16. Complete gene sequence of spider attachment silk protein (PySp1) reveals novel linker regions and extreme repeat homogenization.

    PubMed

    Chaw, Ro Crystal; Saski, Christopher A; Hayashi, Cheryl Y

    2017-02-01

    Spiders use a myriad of silk types for daily survival, and each silk type has a unique suite of task-specific mechanical properties. Of all spider silk types, pyriform silk is distinct because it is a combination of a dry protein fiber and wet glue. Pyriform silk fibers are coated with wet cement and extruded into "attachment discs" that adhere silks to each other and to substrates. The mechanical properties of spider silk types are linked to the primary and higher-level structures of spider silk proteins (spidroins). Spidroins are often enormous molecules (>250 kDa) and have a lengthy repetitive region that is flanked by relatively short (∼100 amino acids), non-repetitive amino- and carboxyl-terminal regions. The amino acid sequence motifs in the repetitive region vary greatly between spidroin type, while motif length and number underlie the remarkable mechanical properties of spider silk fibers. Existing knowledge of pyriform spidroins is fragmented, making it difficult to define links between the structure and function of pyriform spidroins. Here, we present the full-length sequence of the gene encoding pyriform spidroin 1 (PySp1) from the silver garden spider Argiope argentata. The predicted protein is similar to previously reported PySp1 sequences but the A. argentata PySp1 has a uniquely long and repetitive "linker", which bridges the amino-terminal and repetitive regions. Predictions of the hydrophobicity and secondary structure of A. argentata PySp1 identify regions important to protein self-assembly. Analysis of the full complement of A. argentata PySp1 repeats reveals extreme intragenic homogenization, and comparison of A. argentata PySp1 repeats with other PySp1 sequences identifies variability in two sub-repetitive expansion regions. Overall, the full-length A. argentata PySp1 sequence provides new evidence for understanding how pyriform spidroins contribute to the properties of pyriform silk fibers. Copyright © 2017 The Authors. Published by

  17. Integrative analysis of somatic mutations altering microRNA targeting in cancer genomes.

    PubMed

    Ziebarth, Jesse D; Bhattacharya, Anindya; Cui, Yan

    2012-01-01

    Determining the functional impact of somatic mutations is crucial to understanding tumorigenesis and metastasis. Recent sequences of several cancers have provided comprehensive lists of somatic mutations across entire genomes, enabling investigation of the functional impact of somatic mutations in non-coding regions. Here, we study somatic mutations in 3'UTRs of genes that have been identified in four cancers and computationally predict how they may alter miRNA targeting, potentially resulting in dysregulation of the expression of the genes harboring these mutations. We find that somatic mutations create or disrupt putative miRNA target sites in the 3'UTRs of many genes, including several genes, such as MITF, EPHA3, TAL1, SCG3, and GSDMA, which have been previously associated with cancer. We also integrate the somatic mutations with germline mutations and results of association studies. Specifically, we identify putative miRNA target sites in the 3'UTRs of BMPR1B, KLK3, and SPRY4 that are disrupted by both somatic and germline mutations and, also, are in linkage disequilibrium blocks with high scoring markers from cancer association studies. The somatic mutation in BMPR1B is located in a target site of miR-125b; germline mutations in this target site have previously been both shown to disrupt regulation of BMPR1B by miR-125b and linked with cancer.

  18. High-throughput engineering of a mammalian genome reveals building principles of methylation states at CG rich regions.

    PubMed

    Krebs, Arnaud R; Dessus-Babus, Sophie; Burger, Lukas; Schübeler, Dirk

    2014-09-26

    The majority of mammalian promoters are CpG islands; regions of high CG density that require protection from DNA methylation to be functional. Importantly, how sequence architecture mediates this unmethylated state remains unclear. To address this question in a comprehensive manner, we developed a method to interrogate methylation states of hundreds of sequence variants inserted at the same genomic site in mouse embryonic stem cells. Using this assay, we were able to quantify the contribution of various sequence motifs towards the resulting DNA methylation state. Modeling of this comprehensive dataset revealed that CG density alone is a minor determinant of their unmethylated state. Instead, these data argue for a principal role for transcription factor binding sites, a prediction confirmed by testing synthetic mutant libraries. Taken together, these findings establish the hierarchy between the two cis-encoded mechanisms that define the DNA methylation state and thus the transcriptional competence of CpG islands.

  19. Genetic variation and evolutionary demography of Fenneropenaeus chinensis populations, as revealed by the analysis of mitochondrial control region sequences

    PubMed Central

    2010-01-01

    Genetic variation and evolutionary demography of the shrimp Fenneropenaeus chinensis were investigated using sequence data of the complete mitochondrial control region (CR). Fragments of 993 bp of the CR were sequenced for 93 individuals from five localities over most of the species' range in the Yellow Sea and the Bohai Sea. There were 84 variable sites defining 68 haplotypes. Haplotype diversity levels were very high (0.95 ± 0.03-0.99 ± 0.02) in F. chinensis populations, whereas those of nucleotide diversity were moderate to low (0.66 ± 0.36%-0.84 ± 0.46%). Analysis of molecular variance and conventional population statistics (FST ) revealed no significant genetic structure throughout the range of F. chinensis. Mismatch distribution, estimates of population parameters and neutrality tests revealed that the significant fluctuations and shallow coalescence of mtDNA genealogies observed were coincident with estimated demographic parameters and neutrality tests, in implying important past-population size fluctuations or range expansion. Isolation with Migration (IM) coalescence results suggest that F. chinensis, distributed along the coasts of northern China and the Korean Peninsula (about 1000 km apart), diverged recently, the estimated time-split being 12,800 (7,400-18,600) years ago. PMID:21637498

  20. Genome analysis of Excretory/Secretory proteins in Taenia solium reveals their Abundance of Antigenic Regions (AAR)

    PubMed Central

    Gomez, Sandra; Adalid-Peralta, Laura; Palafox-Fonseca, Hector; Cantu-Robles, Vito Adrian; Soberón, Xavier; Sciutto, Edda; Fragoso, Gladis; Bobes, Raúl J.; Laclette, Juan P.; Yauner, Luis del Pozo; Ochoa-Leyva, Adrián

    2015-01-01

    Excretory/Secretory (ES) proteins play an important role in the host-parasite interactions. Experimental identification of ES proteins is time-consuming and expensive. Alternative bioinformatics approaches are cost-effective and can be used to prioritize the experimental analysis of therapeutic targets for parasitic diseases. Here we predicted and functionally annotated the ES proteins in T. solium genome using an integration of bioinformatics tools. Additionally, we developed a novel measurement to evaluate the potential antigenicity of T. solium secretome using sequence length and number of antigenic regions of ES proteins. This measurement was formalized as the Abundance of Antigenic Regions (AAR) value. AAR value for secretome showed a similar value to that obtained for a set of experimentally determined antigenic proteins and was different to the calculated value for the non-ES proteins of T. solium genome. Furthermore, we calculated the AAR values for known helminth secretomes and they were similar to that obtained for T. solium. The results reveal the utility of AAR value as a novel genomic measurement to evaluate the potential antigenicity of secretomes. This comprehensive analysis of T. solium secretome provides functional information for future experimental studies, including the identification of novel ES proteins of therapeutic, diagnosis and immunological interest. PMID:25989346

  1. Use of Double Difference techniques to reveal seismicity and crustal structure patterns in the Galati region (SE part of Romania)

    NASA Astrophysics Data System (ADS)

    Borleanu, Felix; Rogozea, Maria; Liviu, Manea; Popa, Mihaela; Radulian, Mircea

    2017-04-01

    A large seismic swarm occurred between 15 August and 5 November 2013 in the outer side of the SE Carpathians at about 30 km north-west of Galati city. The National Institute for Earth Physics installed in the epicentral area 4 temporary stations to enhance the seismic monitoring and location capability. Although the magnitude of the events did not exceed 4.0 (according to seismic bulletins computed by the Romanian National Data Centre), their effects were unusually high, being felt by the population and creating panic throughout the duration of the swarm. Taking into account the large number of seismic events occurred during the swarm and the events sporadically produced in the same region after the swarm cessation until the present time, as well as the relatively dense seismic network monitoring the area, we applied Double Difference techniques to reveal the regional seismicity and crustal structure patterns. The results show alignments of the seismic events along the crustal faults orientated between Sf. Gheorghe and Peceneaga-Camena Faults and significant seismic velocity inhomogeneity from east to west for the upper part of the crust.

  2. Genome analysis of Excretory/Secretory proteins in Taenia solium reveals their Abundance of Antigenic Regions (AAR).

    PubMed

    Gomez, Sandra; Adalid-Peralta, Laura; Palafox-Fonseca, Hector; Cantu-Robles, Vito Adrian; Soberón, Xavier; Sciutto, Edda; Fragoso, Gladis; Bobes, Raúl J; Laclette, Juan P; Yauner, Luis del Pozo; Ochoa-Leyva, Adrián

    2015-05-19

    Excretory/Secretory (ES) proteins play an important role in the host-parasite interactions. Experimental identification of ES proteins is time-consuming and expensive. Alternative bioinformatics approaches are cost-effective and can be used to prioritize the experimental analysis of therapeutic targets for parasitic diseases. Here we predicted and functionally annotated the ES proteins in T. solium genome using an integration of bioinformatics tools. Additionally, we developed a novel measurement to evaluate the potential antigenicity of T. solium secretome using sequence length and number of antigenic regions of ES proteins. This measurement was formalized as the Abundance of Antigenic Regions (AAR) value. AAR value for secretome showed a similar value to that obtained for a set of experimentally determined antigenic proteins and was different to the calculated value for the non-ES proteins of T. solium genome. Furthermore, we calculated the AAR values for known helminth secretomes and they were similar to that obtained for T. solium. The results reveal the utility of AAR value as a novel genomic measurement to evaluate the potential antigenicity of secretomes. This comprehensive analysis of T. solium secretome provides functional information for future experimental studies, including the identification of novel ES proteins of therapeutic, diagnosis and immunological interest.

  3. Effects of age-associated regional changes in aortic stiffness on human hemodynamics revealed by computational modeling

    PubMed Central

    Cuomo, Federica; Roccabianca, Sara; Dillon-Murphy, Desmond; Xiao, Nan; Humphrey, Jay D.

    2017-01-01

    Although considered by many as the gold standard clinical measure of arterial stiffness, carotid-to-femoral pulse wave velocity (cf-PWV) averages material and geometric properties over a large portion of the central arterial tree. Given that such properties may evolve differentially as a function of region in cases of hypertension and aging, among other conditions, there is a need to evaluate the potential utility of cf-PWV as an early diagnostic of progressive vascular stiffening. In this paper, we introduce a data-driven fluid-solid-interaction computational model of the human aorta to simulate effects of aging-related changes in regional wall properties (e.g., biaxial material stiffness and wall thickness) and conduit geometry (e.g., vessel caliber, length, and tortuosity) on several metrics of arterial stiffness, including distensibility, augmented pulse pressure, and cyclic changes in stored elastic energy. Using the best available biomechanical data, our results for PWV compare well to findings reported for large population studies while rendering a higher resolution description of evolving local and global metrics of aortic stiffening. Our results reveal similar spatio-temporal trends between stiffness and its surrogate metrics, except PWV, thus indicating a complex dependency of the latter on geometry. Lastly, our analysis highlights the importance of the tethering exerted by external tissues, which was iteratively estimated until hemodynamic simulations recovered typical values of tissue properties, pulse pressure, and PWV for each age group. PMID:28253335

  4. Expression profiles of human epididymis epithelial cells reveal the functional diversity of caput, corpus and cauda regions

    PubMed Central

    Browne, James A.; Yang, Rui; Leir, Shih-Hsing; Eggener, Scott E.; Harris, Ann

    2016-01-01

    STUDY HYPOTHESIS Region-specific transcriptional profiling of tissues and cultured epithelial cells from the human epididymis will predict functional specialization along the duct. STUDY FINDING We identified the molecular signature driving functions of the caput, corpus and cauda epithelium, and determined how these differ to establish the regional differentiation of the organ. WHAT IS KNOWN ALREADY The epithelium lining the human male genital ducts has a critical role in fertility. In particular, it controls the luminal environment in the epididymis, which is required for normal sperm maturation and reproductive competence. Studies in many animal species have largely informed our understanding of the molecular basis of epididymis function. However, there are substantial differences between species. STUDY DESIGN, SAMPLES/MATERIALS, METHODS Using RNA sequencing on biological replicates, we described gene expression profiles for tissue from each region of the epididymis and cultured epithelial cells derived from these regions. Bioinformatic tools were then utilized to identify differentially expressed genes (DEGs) between tissues and cells from the caput, corpus and cauda. MAIN RESULTS AND THE ROLE OF CHANCE The data showed that the caput is functionally divergent from the corpus and cauda, which have very similar transcriptomes. Interrogation of DEGs using gene ontology process enrichment analyses showed that processes of ion transport, response to hormone stimulus and urogenital tract development are more evident in the caput, while defense response processes are more important in the corpus/cauda. Consistent with these regional differences in epididymis function, we observed differential expression of transcription factors in the caput and corpus/cauda. LIMITATIONS, REASONS FOR CAUTION Cultured caput, corpus and cauda cells may not faithfully represent the same cells in the intact organ, due to loss of hormonal signals from the testis and communication from other

  5. Expression profiles of human epididymis epithelial cells reveal the functional diversity of caput, corpus and cauda regions.

    PubMed

    Browne, James A; Yang, Rui; Leir, Shih-Hsing; Eggener, Scott E; Harris, Ann

    2016-02-01

    Region-specific transcriptional profiling of tissues and cultured epithelial cells from the human epididymis will predict functional specialization along the duct. We identified the molecular signature driving functions of the caput, corpus and cauda epithelium, and determined how these differ to establish the regional differentiation of the organ. The epithelium lining the human male genital ducts has a critical role in fertility. In particular, it controls the luminal environment in the epididymis, which is required for normal sperm maturation and reproductive competence. Studies in many animal species have largely informed our understanding of the molecular basis of epididymis function. However, there are substantial differences between species. Using RNA sequencing on biological replicates, we described gene expression profiles for tissue from each region of the epididymis and cultured epithelial cells derived from these regions. Bioinformatic tools were then utilized to identify differentially expressed genes (DEGs) between tissues and cells from the caput, corpus and cauda. The data showed that the caput is functionally divergent from the corpus and cauda, which have very similar transcriptomes. Interrogation of DEGs using gene ontology process enrichment analyses showed that processes of ion transport, response to hormone stimulus and urogenital tract development are more evident in the caput, while defense response processes are more important in the corpus/cauda. Consistent with these regional differences in epididymis function, we observed differential expression of transcription factors in the caput and corpus/cauda. Cultured caput, corpus and cauda cells may not faithfully represent the same cells in the intact organ, due to loss of hormonal signals from the testis and communication from other cell types. Our data provide a molecular characterization that will facilitate advances in understanding human epididymis epithelium biology in health and disease

  6. Late-onset psychosis with somatic delusions.

    PubMed

    Rockwell, E; Krull, A J; Dimsdale, J; Jeste, D V

    1994-01-01

    The authors studied 10 patients who had late-onset psychosis with somatic delusions and 2 comparison groups similar in age and education: 9 late-onset psychosis patients without somatic delusions and 10 normal control subjects. Demographic, clinical, and neuropsychological data were obtained. Brain magnetic resonance imaging was also done and compared. The patients with somatic delusions were somewhat more likely to be women, have been ill longer, and meet DSM-III-R criteria for delusional disorder, compared with late-onset psychotic patients without somatic delusions. Patients with somatic delusions also had lower scores on a full-scale IQ test, compared with the normal comparison subjects. The patients with somatic delusions rarely benefitted from and poorly complied with treatment with psychotropics. The study's limitations, such as small sample size and heterogeneity of diagnosis, as well as the possible clinical implications of these findings are also discussed.

  7. The histone chaperone CAF-1 safeguards somatic cell identity

    PubMed Central

    Cheloufi, Sihem; Elling, Ulrich; Hopfgartner, Barbara; Jung, Youngsook L; Murn, Jernej; Ninova, Maria; Hubmann, Maria; Badeaux, Aimee I; Ang, Cheen Euong; Tenen, Danielle; Wesche, Daniel J; Abazova, Nadezhda; Hogue, Max; Tasdemir, Nilgun; Brumbaugh, Justin; Rathert, Philipp; Jude, Julian; Ferrari, Francesco; Blanco, Andres; Fellner, Michaela; Wenzel, Daniel; Zinner, Marietta; Vidal, Simon E; Bell, Oliver; Stadtfeld, Matthias; Chang, Howard Y.; Almouzni, Genevieve; Lowe, Scott W; Rinn, John; Wernig, Marius; Aravin, Alexei; Shi, Yang; Park, Peter; Penninger, Josef M; Zuber, Johannes; Hochedlinger, Konrad

    2016-01-01

    Cellular differentiation involves profound remodeling of chromatic landscapes, yet the mechanisms by which somatic cell identity is subsequently maintained remain incompletely understood. To further elucidate regulatory pathways that safeguard the somatic state, we performed two comprehensive RNAi screens targeting chromatin factors during transcription factor-mediated reprogramming of mouse fibroblasts to induced pluripotent stem cells (iPSCs). Remarkably, subunits of the chromatin assembly factor-1 (CAF-1) complex emerged as the most prominent hits from both screens, followed by modulators of lysine sumoylation and heterochromatin maintenance. Optimal modulation of both CAF-1 and transcription factor levels increased reprogramming efficiency by several orders of magnitude and facilitated iPSC formation in as little as 4 days. Mechanistically, CAF-1 suppression led to a more accessible chromatin structure at enhancer elements early during reprogramming. These changes were accompanied by a decrease in somatic heterochromatin domains, increased binding of Sox2 to pluripotency-specific targets and activation of associated genes. Notably, suppression of CAF-1 also enhanced the direct conversion of B cells into macrophages and fibroblasts into neurons. Together, our findings reveal the histone chaperone CAF-1 as a novel regulator of somatic cell identity during transcription factor-induced cell fate transitions and provide a potential strategy to modulate cellular plasticity in a regenerative setting. PMID:26659182

  8. Somatic Variations in Cervical Cancers in Indian Patients

    PubMed Central

    Das, Poulami; Bansal, Akanksha; Rao, Sudha Narayan; Deodhar, Kedar; Mahantshetty, Umesh; Shrivastava, Shyam K.; Sivaraman, Karthikeyan; Mulherkar, Rita

    2016-01-01

    There are very few reports that describe the mutational landscape of cervical cancer, one of the leading cancers in Indian women. The aim of the present study was to investigate the somatic mutations that occur in cervical cancer. Whole exome sequencing of 10 treatment naïve tumour biopsies with matched blood samples, from a cohort of Indian patients with locally advanced disease, was performed. The data revealed missense mutations across 1282 genes, out of 1831 genes harbouring somatic mutations. These missense mutations (nonsynonymous + stop-gained) when compared with pre-existing mutations in the COSMIC database showed that 272 mutations in 250 genes were already reported although from cancers other than cervical cancer. More than 1000 novel somatic variations were obtained in matched tumour samples. Pathways / genes that are frequently mutated in various other cancers were found to be mutated in cervical cancers. A significant enrichment of somatic mutations in the MAPK pathway was observed, some of which could be potentially targetable. This is the first report of whole exome sequencing of well annotated cervical cancer samples from Indian women and helps identify trends in mutation profiles that are found in an Indian cohort of cervical cancer. PMID:27829003

  9. Mutagenesis of tGCN5 core region reveals two critical surface residues F90 and R140

    SciTech Connect

    Mehta, Kinjal Rajesh; Chan, Yan M.; Lee, Man X.; Yang, Ching Yao; Voloshchuk, Natalya; Montclare, Jin Kim

    2010-09-24

    Research highlights: {yields} Mutagenesis of the tGCN5 core region reveals two residues important for function. {yields} Developed a fluorescent lysate-based activity assay to assess mutants. {yields} Surface-exposed residues F90 and R140 of tGCN5 are critical for H3 acetylation. -- Abstract: Tetrahymena General Control Non-Derepressor 5 (tGCN5) is a critical regulator of gene transcription via acetylation of histones. Since the acetylation ability has been attributed to the 'core region', we perform mutagenesis of residues within the tGCN5 'core region' in order to identify those critical for function and stability. Residues that do not participate in catalysis are identified, mutated and characterized for activity, structure and thermodynamic stability. Variants I107V, Q114L, A121T and A130S maintain the acetylation function relative to wild-type tGCN5, while variants F90Y, F112R and R140H completely abolish function. Of the three non-functional variants, since F112 is mutated into a non-homologous charged residue, a loss in function is expected. However, the remaining two variants are mutated into homologous residues, suggesting that F90 and R140 are critical for the activity of tGCN5. While mutation to homologous residue maintains acetylation of histone H3 for the majority of the variants, the two surface-exposed residues, F90 and R140, appear to be essential for tGCN5 function, structure or stability.

  10. QTL identification of flowering time at three different latitudes reveals homeologous genomic regions that control flowering in soybean.

    PubMed

    Liu, Weixian; Kim, Moon Young; Kang, Yang Jae; Van, Kyujung; Lee, Yeong-Ho; Srinives, Peerasak; Yuan, Dong Lin; Lee, Suk-Ha

    2011-08-01

    Since the genetic control of flowering time is very important in photoperiod-sensitive soybean (Glycine max (L.) Merr.), genes affecting flowering under different environment conditions have been identified and described. The objectives were to identify quantitative trait loci (QTLs) for flowering time in different latitudinal and climatic regions, and to understand how chromosomal rearrangement and genome organization contribute to flowering time in soybean. Recombinant inbred lines from a cross between late-flowering 'Jinpumkong 2' and early-flowering 'SS2-2' were used to evaluate the phenotypic data for days to flowering (DF) collected from Kamphaeng Saen, Thailand (14°01'N), Suwon, Korea (37°15'N), and Longjing, China (42°46'N). A weakly positive phenotypic correlation (r = 0.36) was found between DF in Korea and Thailand; however, a strong correlation (r = 0.74) was shown between Korea and China. After 178 simple sequence repeat (SSR) markers were placed on a genetic map spanning 2,551.7 cM, four independent DF QTLs were identified on different chromosomes (Chrs). Among them, three QTLs on Chrs 9, 13 and 16 were either Thailand- or Korea-specific. The DF QTL on Chr 6 was identified in both Korea and China, suggesting it is less environment-sensitive. Comparative analysis of four DF QTL regions revealed a syntenic relationship between two QTLs on Chrs 6 and 13. All five duplicated gene pairs clustered in the homeologous genomic regions were found to be involved in the flowering. Identification and comparative analysis of multiple DF QTLs from different environments will facilitate the significant improvement in soybean breeding programs with respect to control of flowering time.

  11. Genetic variation between Schistosoma japonicum lineages from lake and mountainous regions in China revealed by resequencing whole genomes.

    PubMed

    Yin, Mingbo; Liu, Xiao; Xu, Bin; Huang, Jian; Zheng, Qi; Yang, Zhong; Feng, Zheng; Han, Ze-Guang; Hu, Wei

    2016-09-01

    Schistosoma infection is a major cause of morbidity and mortality worldwide. Schistosomiasis japonica is endemic in mainland China along the Yangtze River, typically distributed in two geographical categories of lake and mountainous regions. Study on schistosome genetic diversity is of interest in respect of understanding parasite biology and transmission, and formulating control strategy. Certain genetic variations may be associated with adaptations to different ecological habitats. The aim of this study is to gain insight into Schistosoma japonicum genetic variation, evolutionary origin and associated causes of different geographic lineages through examining homozygous Single Nucleotide Polymorphisms (SNPs) based on resequenced genome data. We collected S. japonicum samples from four sites, three in the lake regions (LR) of mid-east (Guichi and Tonglin in Anhui province, Laogang in Hunan province) and one in mountainous region (MR) (Xichang in Sichuan province) of south-west of China, resequenced their genomes using Next Generation Sequencing (NGS) technology, and made use of the available database of S. japonicum draft genomic sequence as a reference in genome mapping. A total of 14,575 SNPs from 2059 genes were identified in the four lineages. Phylogenetic analysis confirmed significant genetic variation exhibited between the different geographical lineages, and further revealed that the MR Xichang lineage is phylogenetically closer to LR Guich lineage than to other two LR lineages, and the MR lineage might be evolved from LR lineages. More than two thirds of detected SNPs were nonsynonymous; functional annotation of the SNP-containing genes showed that they are involved mainly in biological processes such as signaling and response to stimuli. Notably, unique nonsynonymous SNP variations were detected in 66 genes of MR lineage, inferring possible genetic adaption to mountainous ecological condition.

  12. Differential Responses to a Visual Self-Motion Signal in Human Medial Cortical Regions Revealed by Wide-View Stimulation

    PubMed Central

    Wada, Atsushi; Sakano, Yuichi; Ando, Hiroshi

    2016-01-01

    Vision is important for estimating self-motion, which is thought to involve optic-flow processing. Here, we investigated the fMRI response profiles in visual area V6, the precuneus motion area (PcM), and the cingulate sulcus visual area (CSv)—three medial brain regions recently shown to be sensitive to optic-flow. We used wide-view stereoscopic stimulation to induce robust self-motion processing. Stimuli included static, randomly moving, and coherently moving dots (simulating forward self-motion). We varied the stimulus size and the presence of stereoscopic information. A combination of univariate and multi-voxel pattern analyses (MVPA) revealed that fMRI responses in the three regions differed from each other. The univariate analysis identified optic-flow selectivity and an effect of stimulus size in V6, PcM, and CSv, among which only CSv showed a significantly lower response to random motion stimuli compared with static conditions. Furthermore, MVPA revealed an optic-flow specific multi-voxel pattern in the PcM and CSv, where the discrimination of coherent motion from both random motion and static conditions showed above-chance prediction accuracy, but that of random motion from static conditions did not. Additionally, while area V6 successfully classified different stimulus sizes regardless of motion pattern, this classification was only partial in PcM and was absent in CSv. This may reflect the known retinotopic representation in V6 and the absence of such clear visuospatial representation in CSv. We also found significant correlations between the strength of subjective self-motion and univariate activation in all examined regions except for primary visual cortex (V1). This neuro-perceptual correlation was significantly higher for V6, PcM, and CSv when compared with V1, and higher for CSv when compared with the visual motion area hMT+. Our convergent results suggest the significant involvement of CSv in self-motion processing, which may give rise to its

  13. Somatic Embryogenesis in Pinus spp.

    PubMed

    Montalbán, Itziar Aurora; García-Mendiguren, Olatz; Moncaleán, Paloma

    2016-01-01

    Somatic embryogenesis (SE) has been the most important development for plant tissue culture, not only for mass propagation but also for enabling the implementation of biotechnological tools that can be used to increase the productivity and wood quality of plantation forestry. Development of SE in forest trees started in 1985 and nowadays many studies are focused on the optimization of conifer SE system. However, these advances for many Pinus spp. are not sufficiently refined to be implemented commercially. In this chapter, a summary of the main systems used to achieve SE in Pinus spp. is reported.

  14. [Somatic consequences of cannabis use].

    PubMed

    Cottencin, Olivier; Bence, Camille; Rolland, Benjamin; Karila, Laurent

    2013-12-01

    Cannabis can have negative effects in its users, and a range of acute and chronic health problems associated with cannabis use has been dentified. Acute cannabis consumption is rarely lethal but it is associated with an increased risk of motor vehicle accident because of longer reaction time or impaired motor coordination. Chronic effects of cannabis use include generally cardiovascular and respiratory consequences but there are also oral, gastrointestinal, cutaneous and mucous, metabolic, gynecologic and obstetrical, sexual consequences, and cancer But associated tobacco smoking or other potential confounders may explain part of those somatic consequences.

  15. Nature of torture, PTSD, and somatic symptoms among political ex-prisoners.

    PubMed

    Punamäki, Raija-Leena; Qouta, Samir R; El Sarraj, Eyad

    2010-08-01

    The authors examined how different types of torture methods are associated with posttraumatic stress disorder (PTSD) and somatic symptoms among political ex-prisoners. Participants were 275 Palestinian men who reported their experiences in detention and imprisonment, PTSD (the Harvard Trauma Questionnaire), and somatic symptoms. A principal component analysis revealed physical torture, psychological torture, sensory discomfort and deprivation, and beatings as dimensions of exposure to torture. Both physical and psychological torture methods were associated with increased PTSD symptoms, especially when combined. Psychological torture was also associated with increased somatic symptoms. The results are discussed in relation to their contribution to the current debate on the nature and definition of torture.

  16. Activating Somatic FGFR2 Mutations in Breast Cancer

    PubMed Central

    Reintjes, Nadine; Li, Yun; Becker, Alexandra; Rohmann, Edyta; Schmutzler, Rita; Wollnik, Bernd

    2013-01-01

    It is known that FGFR2 gene variations confer a risk for breast cancer. FGFR2 and FGF10, the main ligand of FGFR2, are both overexpressed in 5–10% of breast tumors. In our study, we sequenced the most important coding regions of FGFR2 in somatic tumor tissue of 140 sporadic breast cancer patients and performed MLPA analysis to detect copy number variations in FGFR2 and FGF10. We identified one somatic heterozygous missense mutation, p.K660N (c.1980G>C), within the tyrosine kinase domain of FGFR2 in tumor tissue of a sporadic breast cancer patient, which is likely mediated by the FGFR2-IIIb isoform. The presence of wild type and mutated alleles in equal quantities suggests that the mutation has driven clonal amplification of mutant cells. We have analyzed the tyrosine kinase activity of p.K660N and another recently described somatic breast cancer mutation in FGFR2, p.R203C, after expression in HEK293 cells and demonstrated that the intrinsic tyrosine kinase activity of both mutant proteins is strongly increased resulting in elevated phosphorylation and activity of downstream effectors. To our knowledge, this is the first report of functional analysis of somatic breast cancer mutations in FGFR2 providing evidence for the activating nature of FGFR2-mediated signalling in the pathogenesis of breast cancer. PMID:23527311

  17. Multiscale imaging characterization of dopamine transporter knockout mice reveals regional alterations in spine density of medium spiny neurons.

    PubMed

    Berlanga, M L; Price, D L; Phung, B S; Giuly, R; Terada, M; Yamada, N; Cyr, M; Caron, M G; Laakso, A; Martone, M E; Ellisman, M H

    2011-05-16

    The dopamine transporter knockout (DAT KO) mouse is a model of chronic hyperdopaminergia used to study a wide range of neuropsychiatric disorders such as schizophrenia, attention deficit hyperactivity disorder (ADHD), drug abuse, depression, and Parkinson's disease (PD). Early studies characterizing this mouse model revealed a subtle, but significant, decrease in the anterior striatal volume of DAT KO mice accompanied by a decrease in neuronal cell body numbers (Cyr et al., 2005). The present studies were conducted to examine medium spiny neuron (MSN) morphology by extending these earlier reports to include multiscale imaging studies using correlated light microscopy (LM) and electron microscopy (EM) techniques. Specifically, we set out to determine if chronic hyperdopaminergia results in quantifiable or qualitative changes in DAT KO mouse MSNs relative to wild-type (WT) littermates. Using Neurolucida Explorer's morphometric analysis, we measured spine density, dendritic length and synapse number at ages that correspond with the previously reported changes in striatal volume and progressive cell loss. Light microscopic analysis using Neurolucida tracings of photoconverted striatal MSNs revealed a highly localized loss of dendritic spines on the proximal portion of the dendrite (30 μm from the soma) in the DAT KO group. Next, thick sections containing MSN dendritic segments located at a distance of 20-60 μm from the cell soma, a region of the dendrite where spine density is reported to be the highest, were analyzed using electron microscope tomography (EMT). Because of the resolution limits of LM, the EM analysis was an extra measure taken to assure that our analysis included nearly all spines. Spine density measurements collected from the EMT data revealed only a modest decrease in the DAT KO group (n=3 mice) compared to age-matched WT controls (n=3 mice), a trend that supports the LM findings. Finally, a synaptic quantification using unbiased stereology did not

  18. BINNING SOMATIC MUTATIONS BASED ON BIOLOGICAL KNOWLEDGE FOR PREDICTING SURVIVAL: AN APPLICATION IN RENAL CELL CARCINOMA

    PubMed Central

    Kim, Dokyoon; Li, Ruowang; Dudek, Scott M.; Wallace, John R.; Ritchie, Marylyn D.

    2014-01-01

    Enormous efforts of whole exome and genome sequencing from hundreds to thousands of patients have provided the landscape of somatic genomic alterations in many cancer types to distinguish between driver mutations and passenger mutations. Driver mutations show strong associations with cancer clinical outcomes such as survival. However, due to the heterogeneity of tumors, somatic mutation profiles are exceptionally sparse whereas other types of genomic data such as miRNA or gene expression contain much more complete data for all genomic features with quantitative values measured in each patient. To overcome the extreme sparseness of somatic mutation profiles and allow for the discovery of combinations of somatic mutations that may predict cancer clinical outcomes, here we propose a new approach for binning somatic mutations based on existing biological knowledge. Through the analysis using renal cell carcinoma dataset from The Cancer Genome Atlas (TCGA), we identified combinations of somatic mutation burden based on pathways, protein families, evolutionary conversed regions, and regulatory regions associated with survival. Due to the nature of heterogeneity in cancer, using a binning strategy for somatic mutation profiles based on biological knowledge will be valuable for improved prognostic biomarkers and potentially for tailoring therapeutic strategies by identifying combinations of driver mutations. PMID:25592572

  19. Transcriptional Control of Somatic Cell Reprogramming.

    PubMed

    Xu, Yan; Zhang, Meng; Li, Wenjuan; Zhu, Xihua; Bao, Xichen; Qin, Baoming; Hutchins, Andrew P; Esteban, Miguel A

    2016-04-01

    Somatic cells and pluripotent cells display remarkable differences in most aspects of cell function. Accordingly, somatic cell reprogramming by exogenous factors requires comprehensive changes in gene transcription to induce a forced pluripotent state, which is encompassed by a simultaneous transformation of the epigenome. Nevertheless, how the reprogramming factors and other endogenous regulators coordinate to suppress the somatic cell gene program and activate the pluripotency gene network, and why the conversion is multi-phased and lengthy, remain enigmatic. We summarize the current knowledge of transcriptional regulation in somatic cell reprogramming, and highlight new perspectives that may help to reshape existing paradigms.

  20. Childhood maltreatment in patients with somatization disorder.

    PubMed

    Spitzer, Carsten; Barnow, Sven; Gau, Kay; Freyberger, Harald J; Grabe, Hans Joergen

    2008-04-01

    There is converging evidence indicating a close association between trauma, particularly childhood trauma, and adult somatization, but studies using both structured interviews and self-report measures to assess childhood adversities in patients with somatization disorder are scarce. A total of 28 patients (82% women, mean age=41.7+/-10.1 years) meeting DSM-IV criteria for somatization disorder as confirmed by the Structured Clinical Interview for DSM-IV, Axis I (SCID-I) underwent the Structured Trauma Interview (STI) and the Childhood Trauma Questionnaire (CTQ). The comparison group consisted of 28 patients with major depression, but without a lifetime diagnosis of somatization disorder matched for gender and age. Univariate analyses of both the STI and the CTQ data showed that somatizing patients had been exposed to childhood sexual and physical abuse significantly more often than major depressive disorder (MDD) patients. In logistic regression analysis with somatization disorder as the dependent variable, sexual abuse emerged as the only significant predictor, and the odds of having been sexually abused were ninefold higher in patients with somatization disorders relative to MDD subjects (odds ratio=9.39; 95% confidence interval=1.73-50.96). There were no differences between somatizing and depressed participants with respect to other types of maltreatment. Childhood sexual abuse is an important factor in the multifactorial aetiopathogenesis of somatization disorder. Diagnostic and therapeutic implications are discussed.

  1. Somatic complaints in childhood tic disorders.

    PubMed

    Frank, M S; Sieg, K G; Gaffney, G R

    1991-01-01

    Twenty-six children diagnosed with chronic tic disorders (18 with Gilles de la Tourette syndrome and 8 with chronic motor tic disorder) were studied for unexplained physical complaints. Compared to normal controls, an excess of somatic complaints was found in the tic disorders group; this was similar to an excess of somatic complaints in a mixed psychiatric clinic group. Medication produced no significant effect on somatic complaints for patients in the tic and psychiatric clinic groups. Within the tic disorders group, no significant correlation was found between the increased somatic complaints and the severity of anxiety, dysphoria, or movement disorder.

  2. Germline and somatic DNA methylation and epigenetic regulation of KILLIN in renal cell carcinoma

    PubMed Central

    Bennett, Kristi L.; Campbell, Rebecca; Ganapathi, Shireen; Zhou, Ming; Rini, Brian; Ganapathi, Ram; Neumann, Hartmut P.H.; Eng, Charis

    2011-01-01

    We recently identified germline methylation of KILLIN, a novel p53-regulated tumor suppressor proximal to PTEN, in >1/3 Cowden or Cowden syndrome-like (CS/CSL) individuals who are PTEN mutation negative. Individuals with germline KILLIN methylation had increased risks of renal cell carcinoma (RCC) over those with PTEN mutations. Therefore, we tested the hypothesis that KILLIN may be a RCC susceptibility gene, silenced by germline methylation. We found germline hypermethylation by combined bisulfite restriction analysis (COBRA) in at least one of the four CpG-rich regions in 23/41 (56%) RCC patients compared to 0/50 controls (P<0.0001). Of the 23, 11 (48%) demonstrated methylation in the -598bp to -890bp region in respect to the KILLIN transcription start site. Furthermore, 19 of 20 advanced RCC showed somatic hypermethylation upstream of KILLIN, with the majority hypermethylated at more than one CpG island (13/19 vs 3/23 with germline methylation, p<0.0001). qRT-PCR revealed that methylation significantly downregulates KILLIN expression (P=0.05), and demethylation treatment by 5-aza-2’deoxycytidine significantly increased KILLIN expression in all RCC cell lines while only increasing PTEN expression in one line. Furthermore, targeted in vitro methylation revealed a significant decrease in KILLIN promoter activity only. These data reveal differential epigenetic regulation by DNA promoter methylation of this bidirectional promoter. In summary, we have identified KILLIN as a potential novel cancer predisposition gene for nonsyndromic ccRCC, and the epigenetic mechanism of KILLIN inactivation in both the germline and somatic setting suggests the potential for treatment with demethylating agents. PMID:21584899

  3. Alternative Polyadenylation Directs Tissue-Specific miRNA Targeting in Caenorhabditis elegans Somatic Tissues

    PubMed Central

    Blazie, Stephen M.; Geissel, Heather C.; Wilky, Henry; Joshi, Rajan; Newbern, Jason; Mangone, Marco

    2017-01-01

    mRNA expression dynamics promote and maintain the identity of somatic tissues in living organisms; however, their impact in post-transcriptional gene regulation in these processes is not fully understood. Here, we applied the PAT-Seq approach to systematically isolate, sequence, and map tissue-specific mRNA from five highly studied Caenorhabditis elegans somatic tissues: GABAergic and NMDA neurons, arcade and intestinal valve cells, seam cells, and hypodermal tissues, and studied their mRNA expression dynamics. The integration of these datasets with previously profiled transcriptomes of intestine, pharynx, and body muscle tissues, precisely assigns tissue-specific expression dynamics for 60% of all annotated C. elegans protein-coding genes, providing an important resource for the scientific community. The mapping of 15,956 unique high-quality tissue-specific polyA sites in all eight somatic tissues reveals extensive tissue-specific 3′untranslated region (3′UTR) isoform switching through alternative polyadenylation (APA) . Almost all ubiquitously transcribed genes use APA and harbor miRNA targets in their 3′UTRs, which are commonly lost in a tissue-specific manner, suggesting widespread usage of post-transcriptional gene regulation modulated through APA to fine tune tissue-specific protein expression. Within this pool, the human disease gene C. elegans orthologs rack-1 and tct-1 use APA to switch to shorter 3′UTR isoforms in order to evade miRNA regulation in the body muscle tissue, resulting in increased protein expression needed for proper body muscle function. Our results highlight a major positive regulatory role for APA, allowing genes to counteract miRNA regulation on a tissue-specific basis. PMID:28348061

  4. Alternative Polyadenylation Directs Tissue-Specific miRNA Targeting in Caenorhabditis elegans Somatic Tissues.

    PubMed

    Blazie, Stephen M; Geissel, Heather C; Wilky, Henry; Joshi, Rajan; Newbern, Jason; Mangone, Marco

    2017-06-01

    mRNA expression dynamics promote and maintain the identity of somatic tissues in living organisms; however, their impact in post-transcriptional gene regulation in these processes is not fully understood. Here, we applied the PAT-Seq approach to systematically isolate, sequence, and map tissue-specific mRNA from five highly studied Caenorhabditis elegans somatic tissues: GABAergic and NMDA neurons, arcade and intestinal valve cells, seam cells, and hypodermal tissues, and studied their mRNA expression dynamics. The integration of these datasets with previously profiled transcriptomes of intestine, pharynx, and body muscle tissues, precisely assigns tissue-specific expression dynamics for 60% of all annotated C. elegans protein-coding genes, providing an important resource for the scientific community. The mapping of 15,956 unique high-quality tissue-specific polyA sites in all eight somatic tissues reveals extensive tissue-specific 3'untranslated region (3'UTR) isoform switching through alternative polyadenylation (APA) . Almost all ubiquitously transcribed genes use APA and harbor miRNA targets in their 3'UTRs, which are commonly lost in a tissue-specific manner, suggesting widespread usage of post-transcriptional gene regulation modulated through APA to fine tune tissue-specific protein expression. Within this pool, the human disease gene C. elegans orthologs rack-1 and tct-1 use APA to switch to shorter 3'UTR isoforms in order to evade miRNA regulation in the body muscle tissue, resulting in increased protein expression needed for proper body muscle function. Our results highlight a major positive regulatory role for APA, allowing genes to counteract miRNA regulation on a tissue-specific basis. Copyright © 2017 Blazie et al.

  5. Diversity of Fusarium head blight populations and trichothecene toxin types reveals regional differences in pathogen composition and temporal dynamics.

    PubMed

    Kelly, Amy C; Clear, Randall M; O'Donnell, Kerry; McCormick, Susan; Turkington, T Kelly; Tekauz, Andy; Gilbert, Jeannie; Kistler, H Corby; Busman, Mark; Ward, Todd J

    2015-09-01

    Analyses of genetic diversity, trichothecene genotype composition, and population structure were conducted using 4086 Fusarium graminearum isolates collected from wheat in eight Canadian provinces over a three year period between 2005 and 2007. The results revealed substantial regional differences in Fusarium head blight pathogen composition and temporal population dynamics. The 3ADON trichothecene type consistently predominated in Maritime provinces (91%) over the sampled years, and increased significantly (P<0.05) between 2005 and 2007 in western Canada, accounting for 66% of the isolates in Manitoba by the end of the sampling period. In contrast, 3ADON frequency was lower (22%, P<0.001) in the eastern Canadian provinces of Ontario and Québec and did not change significantly between 2005 and 2007, resulting in two distinct longitudinal clines in 3ADON frequency across Canada. Overall, genetic structure was correlated with toxin type, as the endemic population (NA1) was dominated by 15ADON isolates (86%), whereas a second population (NA2) consisted largely of 3ADON isolates (88%). However, the percentage of isolates with trichothecene genotypes that were not predictive of their genetic population assignment (recombinant genotypes) increased from 10% in 2005 to 17% in 2007, indicating that trichothecene type became an increasingly unreliable marker of population identity over time. In addition, there were substantial regional differences in the composition of recombinant genotypes. In western and maritime provinces, NA2 isolates with 15ADON genotypes were significantly more common than NA1 isolates with 3ADON genotypes (P<0.001), and the reverse was true in the eastern provinces of Québec and Ontario. Temporal trends in recombinant genotype composition also varied regionally, as the percentage of 15ADON isolates with NA2 genetic backgrounds increased approximately three fold in western and Maritime provinces, while the opposite trends were observed in Québec and

  6. Somatic hybridization in higher plants.

    PubMed

    Constabel, F

    1976-11-01

    Somatic hybridization in higher plants has come into focus since methods have been established for protoplast fusion and uptake of foreign DNA and organelles by protoplasts. Polyethylene glycol (PEG) was an effective agent for inducing fusion. Treatment of protoplasts with PEG resulted in 5 to 30% heterospecific fusion products. Protoplasts of different species, genera and even families were compatible when fused. A number of protoplast combinations (soybean + corn, soybean + pea, soybean + tobacco, carrot + barley, etc.) provided fusion products which underwent cell division and callus formation. Fusion products initially were heterokaryocytes. In dividing heterokaryocytes, random distribution of mitotic nuclei was observed to be accompanied by multiple wall formation and to result in chimeral callus. Juxtaposition of mitotic nuclei suggested nuclear fusion and hybrid formation. Fusion of heterospecific interphase nuclei was demonstrated in soybean + pea and carrot + barley heterokaryons. Provided parental protoplasts carry suitable markers, the fusion products can be recognized. For the isolation and cloning of hybrid cells, fusion experiments must be supplemented with a selective system. Complementation of two non-allelic genes that prevent or inhibit growth under special culture conditions appears as the principle on which to base the selection of somatic hybrids. As protoplasts of some species have been induced to regenerate entire plants, the development of hybrid plants from protoplast fusion products is feasible and has already been demonstrated for tobacco.

  7. Geochronology of Zircon in Eclogite Reveals Imbrication of the Ultrahigh-Pressure Western Gneiss Region of Norway.

    NASA Astrophysics Data System (ADS)

    Young, D. J.; Kylander-Clark, A. R.; Root, D. B.

    2014-12-01

    Eclogite provides the only record of kinematic events at the deepest levels of orogens. Integrating the U-Pb geochronology and trace element chemistry of zircon in eclogite reveals the most complete view of the PTt history, yet low concentrations of uranium and zirconium and drier compositions that hinder zircon growth at peak conditions render it a challenging rocktype for this approach. The iconic Western Gneiss Region (WGR) in Norway is one of the largest terranes of deeply subducted continental rocks in the world, and contains many indicators of ultrahigh-pressure metamorphic conditions (P>2.8 GPa) that developed during the Siluro-Devonian Caledonian Orogeny. A metamorphic transition from amphibolite-facies to ultrahigh-pressure eclogite facies broadly coincides with a km-scale shear zone that underlies the majority of the WGR. A critical unknown is the timing of movement on this feature, which emplaced allochthonous units above the Baltica basement, but might also have accommodated late-orogenic exhumation of the WGR from mantle depths. We carried out laser ablation split-stream ICPMS (LASS) and selected multigrain TIMS analyses of zircons from eleven eclogites across the southern WGR, of which eight are located within or above the shear zone. LASS spots on polished grains mostly yield weakly discordant Proterozoic intrusive ages, and often minimal indication of a Caledonian (U)HP metamorphic overprint. Direct ablation into unpolished zircon reveals thin rims of Caledonian age in some cases. Overall, the dataset shows that all samples began zircon growth at approximately the same time (ca. 430-420 Ma). Eclogite from lower levels of the shear zone does not contain any dates younger than ca. 410 Ma, however, while eclogite from higher levels continued growth until ca. 400 Ma. We interpret this to result from thrusting of the WGR above cooler basement after 410 Ma, terminating new zircon crystallization within the shear zone but allowing limited further growth in

  8. Variations in a hotspot region of chloroplast DNAs among common wheat and Aegilops revealed by nucleotide sequence analysis.

    PubMed

    Guo, Chang-Hong; Terachi, Toru

    2005-08-01

    The second largest BamHI fragment (B2) of the chloroplast DNA in Triticum (wheat) and Aegilops contains a highly variable region (a hotspot), resulting in four types of B2 of different size, i.e. B2l (10.5kb), B2m (10.2kb), B2 (9.6kb) and B2s (9.4kb). In order to gain a better understanding of the molecular nature of the variations in length and explain unexpected identity among B2 of Ae. ovata, Ae. speltoides and common wheat (T. aestivum), the nucleotide sequence between a stop codon of rbcL and a HindIII site in cemA in the hotspot was determined for Ae. ovata, Ae. speltoides, Ae. caudata and Ae. mutica. The total number of nucleotides in the region was 2808, 2810, 3302, and 3594 bp, for Ae. speltoides, Ae. ovata, Ae. caudata and Ae. mutica, respectively, and the sequences were compared with the corresponding ones of Ae. crassa 4x, T. aestivum and Ae. squarrosa. Compared with the largest B2l fragment of Ae. mutica, a 791bp and a 793 bp deletion were found in Ae. speltoides and Ae. ovata, respectively, and the possible site of deletion in the two species is the same as that of T. aestivum. However, a deleted segment in Ae. ovata is 2 bp longer than that of Ae. speltoides (and T. aestivum), demonstrating that recurrent deletions had occurred in the chloroplast genomes of both species. Comparison of the sequences from Ae. caudata and Ae. crassa 4x with that of Ae. mutica revealed a 289 bp and a 61 bp deletion at the same site in Ae. caudata and Ae. crassa 4x, respectively. Sequence comparison using wild Aegilops plants showed that the large length variations in a hotspot are fixed to each species. A considerable number of polymorphisms are observed in a loop in the 3' of rbcL. The study reveals the relative importance of the large and small indels and minute inversions to account for variations in the chloroplast genomes among closely related species.

  9. Using GMD Data, AIRS Measurements, and the NASA Chemistry-Climate Model to Reveal Regional and Seasonal Variation of Methane

    NASA Astrophysics Data System (ADS)

    Steele, K. J.; Duncan, B. N.; Warner, J. X.; Nielsen, J. E.

    2010-12-01

    The concentration of methane (CH4) has more than doubled in the atmosphere since the preindustrial era due to a change in source-sink interactions. Many studies have aimed to quantify CH4 source contributions, but 1) the long tropospheric lifetime of CH4, resulting in a high background concentration, 2) along with sources often having overlapping distributions, and 3) the uncertainty in the chemical sink of CH4 with the hydroxyl radical makes it difficult to constrain inputs to the CH4 budget. The purpose of this study was to use a variety of observations in conjunction with the NASA GEOS-5 climate-chemistry model (CCM) to better understand regional and seasonal variation in atmospheric CH4. Seasonal variation in surface in situ data from the NOAA ESRL Global Monitoring Division (GMD) and data from the Japanese Airlines (JAL) in the upper troposphere (UT) were compared to satellite observations recorded by the Atmospheric Infrared Sounder (AIRS) on the EOS/Aqua satellite, which is most sensitive to CH4 in the UT. There was more variability in CH4 at the GMD sites than in the JAL data or AIRS because the GMD sites are closer to the source. As the CH4 is lofted into the UT, it mixes with the background CH4 so the seasonal variation is dampened. The JAL data followed the AIRS observations as expected. There was less variability in all measurements in the Southern Hemisphere and over oceans because these areas are farther away from sources. While the observations from AIRS, JAL flights, and the GMD sites provide valuable information regarding source locations and atmospheric CH4 concentration, it is important to understand which CH4 sources have the largest contribution to CH4 emissions in different regions of the world and the influence of these sources on the global CH4 cycle. Model output from the GEOS-5 CCM was used to monitor individual CH4 sources (e.g. from rice production, wetlands, biofuel use, etc.) as they are transported from the surface to the UT. The

  10. Site-directed mutagenesis reveals regions implicated in the stability and fiber formation of human λ3r light chains.

    PubMed

    Villalba, Miryam I; Canul-Tec, Juan C; Luna-Martínez, Oscar D; Sánchez-Alcalá, Rosalba; Olamendi-Portugal, Timoteo; Rudiño-Piñera, Enrique; Rojas, Sonia; Sánchez-López, Rosana; Fernández-Velasco, Daniel A; Becerril, Baltazar

    2015-01-30

    Light chain amyloidosis (AL) is a disease that affects vital organs by the fibrillar aggregation of monoclonal light chains. λ3r germ line is significantly implicated in this disease. In this work, we contrasted the thermodynamic stability and aggregation propensity of 3mJL2 (nonamyloidogenic) and 3rJL2 (amyloidogenic) λ3 germ lines. Because of an inherent limitation (extremely low expression), Cys at position 34 of the 3r germ line was replaced by Tyr reaching a good expression yield. A second substitution (W91A) was introduced in 3r to obtain a better template to incorporate additional mutations. Although the single mutant (C34Y) was not fibrillogenic, the second mutation located at CDR3 (W91A) induced fibrillogenesis. We propose, for the first time, that CDR3 (position 91) affects the stability and fiber formation of human λ3r light chains. Using the double mutant (3rJL2/YA) as template, other variants were constructed to evaluate the importance of those substitutions into the stability and aggregation propensity of λ3 light chains. A change in position 7 (P7D) boosted 3rJL2/YA fibrillogenic properties. Modification of position 48 (I48M) partially reverted 3rJL2/YA fibril aggregation. Finally, changes at positions 8 (P8S) or 40 (P40S) completely reverted fibril formation. These results confirm the influential roles of N-terminal region (positions 7 and 8) and the loop 40-60 (positions 40 and 48) on AL. X-ray crystallography revealed that the three-dimensional topology of the single and double λ3r mutants was not significantly altered. This mutagenic approach helped to identify key regions implicated in λ3 AL.

  11. Site-directed Mutagenesis Reveals Regions Implicated in the Stability and Fiber Formation of Human λ3r Light Chains*

    PubMed Central

    Villalba, Miryam I.; Canul-Tec, Juan C.; Luna-Martínez, Oscar D.; Sánchez-Alcalá, Rosalba; Olamendi-Portugal, Timoteo; Rudiño-Piñera, Enrique; Rojas, Sonia; Sánchez-López, Rosana; Fernández-Velasco, Daniel A.; Becerril, Baltazar

    2015-01-01

    Light chain amyloidosis (AL) is a disease that affects vital organs by the fibrillar aggregation of monoclonal light chains. λ3r germ line is significantly implicated in this disease. In this work, we contrasted the thermodynamic stability and aggregation propensity of 3mJL2 (nonamyloidogenic) and 3rJL2 (amyloidogenic) λ3 germ lines. Because of an inherent limitation (extremely low expression), Cys at position 34 of the 3r germ line was replaced by Tyr reaching a good expression yield. A second substitution (W91A) was introduced in 3r to obtain a better template to incorporate additional mutations. Although the single mutant (C34Y) was not fibrillogenic, the second mutation located at CDR3 (W91A) induced fibrillogenesis. We propose, for the first time, that CDR3 (position 91) affects the stability and fiber formation of human λ3r light chains. Using the double mutant (3rJL2/YA) as template, other variants were constructed to evaluate the importance of those substitutions into the stability and aggregation propensity of λ3 light chains. A change in position 7 (P7D) boosted 3rJL2/YA fibrillogenic properties. Modification of position 48 (I48M) partially reverted 3rJL2/YA fibril aggregation. Finally, changes at positions 8 (P8S) or 40 (P40S) completely reverted fibril formation. These results confirm the influential roles of N-terminal region (positions 7 and 8) and the loop 40–60 (positions 40 and 48) on AL. X-ray crystallography revealed that the three-dimensional topology of the single and double λ3r mutants was not significantly altered. This mutagenic approach helped to identify key regions implicated in λ3 AL. PMID:25505244

  12. Regional specificity of MRI contrast parameter changes in normal ageing revealed by voxel-based quantification (VBQ).

    PubMed

    Draganski, B; Ashburner, J; Hutton, C; Kherif, F; Frackowiak, R S J; Helms, G; Weiskopf, N

    2011-04-15

    Normal ageing is associated with characteristic changes in brain microstructure. Although in vivo neuroimaging captures spatial and temporal patterns of age-related changes of anatomy at the macroscopic scale, our knowledge of the underlying (patho)physiological processes at cellular and molecular levels is still limited. The aim of this study is to explore brain tissue properties in normal ageing using quantitative magnetic resonance imaging (MRI) alongside conventional morphological assessment. Using a whole-brain approach in a cohort of 26 adults, aged 18-85years, we performed voxel-based morphometric (VBM) analysis and voxel-based quantification (VBQ) of diffusion tensor, magnetization transfer (MT), R1, and R2* relaxation parameters. We found age-related reductions in cortical and subcortical grey matter volume paralleled by changes in fractional anisotropy (FA), mean diffusivity (MD), MT and R2*. The latter were regionally specific depending on their differential sensitivity to microscopic tissue properties. VBQ of white matter revealed distinct anatomical patterns of age-related change in microstructure. Widespread and profound reduction in MT contrasted with local FA decreases paralleled by MD increases. R1 reductions and R2* increases were observed to a smaller extent in overlapping occipito-parietal white matter regions. We interpret our findings, based on current biophysical models, as a fingerprint of age-dependent brain atrophy and underlying microstructural changes in myelin, iron deposits and water. The VBQ approach we present allows for systematic unbiased exploration of the interaction between imaging parameters and extends current methods for detection of neurodegenerative processes in the brain. The demonstrated parameter-specific distribution patterns offer insights into age-related brain structure changes in vivo and provide essential baseline data for studying disease against a background of healthy ageing.

  13. Site-directed Mutagenesis Reveals Regions Implicated in the Stability and Fiber Formation of Human λ3r Light Chains

    SciTech Connect

    Villalba, Miryam I.; Canul-Tec, Juan C.; Luna-Martínez, Oscar D.; Sánchez-Alcalá, Rosalba; Olamendi-Portugal, Timoteo; Rudiño-Piñera, Enrique; Rojas, Sonia; Sánchez-López, Rosana; Fernández-Velasco, Daniel A.; Becerril, Baltazar

    2014-12-11

    Light chain amyloidosis (AL) is a disease that affects vital organs by the fibrillar aggregation of monoclonal light chains. λ3r germ line is significantly implicated in this disease. In this paper, we contrasted the thermodynamic stability and aggregation propensity of 3mJL2 (nonamyloidogenic) and 3rJL2 (amyloidogenic) λ3 germ lines. Because of an inherent limitation (extremely low expression), Cys at position 34 of the 3r germ line was replaced by Tyr reaching a good expression yield. A second substitution (W91A) was introduced in 3r to obtain a better template to incorporate additional mutations. Although the single mutant (C34Y) was not fibrillogenic, the second mutation located at CDR3 (W91A) induced fibrillogenesis. We propose, for the first time, that CDR3 (position 91) affects the stability and fiber formation of human λ3r light chains. Using the double mutant (3rJL2/YA) as template, other variants were constructed to evaluate the importance of those substitutions into the stability and aggregation propensity of λ3 light chains. A change in position 7 (P7D) boosted 3rJL2/YA fibrillogenic properties. Modification of position 48 (I48M) partially reverted 3rJL2/YA fibril aggregation. Finally, changes at positions 8 (P8S) or 40 (P40S) completely reverted fibril formation. These results confirm the influential roles of N-terminal region (positions 7 and 8) and the loop 40–60 (positions 40 and 48) on AL. X-ray crystallography revealed that the three-dimensional topology of the single and double λ3r mutants was not significantly altered. Finally, this mutagenic approach helped to identify key regions implicated in λ3 AL.

  14. Site-directed Mutagenesis Reveals Regions Implicated in the Stability and Fiber Formation of Human λ3r Light Chains

    DOE PAGES

    Villalba, Miryam I.; Canul-Tec, Juan C.; Luna-Martínez, Oscar D.; ...

    2014-12-11

    Light chain amyloidosis (AL) is a disease that affects vital organs by the fibrillar aggregation of monoclonal light chains. λ3r germ line is significantly implicated in this disease. In this paper, we contrasted the thermodynamic stability and aggregation propensity of 3mJL2 (nonamyloidogenic) and 3rJL2 (amyloidogenic) λ3 germ lines. Because of an inherent limitation (extremely low expression), Cys at position 34 of the 3r germ line was replaced by Tyr reaching a good expression yield. A second substitution (W91A) was introduced in 3r to obtain a better template to incorporate additional mutations. Although the single mutant (C34Y) was not fibrillogenic, themore » second mutation located at CDR3 (W91A) induced fibrillogenesis. We propose, for the first time, that CDR3 (position 91) affects the stability and fiber formation of human λ3r light chains. Using the double mutant (3rJL2/YA) as template, other variants were constructed to evaluate the importance of those substitutions into the stability and aggregation propensity of λ3 light chains. A change in position 7 (P7D) boosted 3rJL2/YA fibrillogenic properties. Modification of position 48 (I48M) partially reverted 3rJL2/YA fibril aggregation. Finally, changes at positions 8 (P8S) or 40 (P40S) completely reverted fibril formation. These results confirm the influential roles of N-terminal region (positions 7 and 8) and the loop 40–60 (positions 40 and 48) on AL. X-ray crystallography revealed that the three-dimensional topology of the single and double λ3r mutants was not significantly altered. Finally, this mutagenic approach helped to identify key regions implicated in λ3 AL.« less

  15. Intra-areal and corticocortical circuits arising in the dysgranular zone of rat primary somatosensory cortex that processes deep somatic input.

    PubMed

    Kim, Uhnoh; Lee, Taehee

    2013-08-01

    Somesthesis-guided exploration of the external world requires cortical processing of both cutaneous and proprioceptive information and their integration into motor commands to guide further haptic movement. In the past, attention has been given mostly to the cortical circuits processing cutaneous information for somatic motor integration. By comparison, little has been examined about how cortical circuits are organized for higher order proprioceptive processing. Using the rat cortex as a model, we characterized the intrinsic and corticocortical circuits arising in the major proprioceptive region of the primary somatosensory cortex (SI) that is conventionally referred to as the dysgranular zone (DSZ). We made small injections of biotinylated dextran amine (BDA) as an anterograde tracer in various parts of the DSZ, revealing three distinct principles of its cortical circuit organization. First, its intrinsic circuits extend mainly along the major axis of DSZ to organize multiple patches of interconnections. Second, the central and peripheral regions of DSZ produce differential patterns of intra-areal and corticocortical circuits. Third, the projection fields of DSZ encompass only selective regions of the second somatic (SII), posterior parietal (PPC), and primary motor (MI) cortices. These projection fields are at least partially separated from those of SI cutaneous areas. We hypothesize, based on these observations, that the cortical circuits of DSZ facilitate a modular integration of proprioceptive information along its major axis and disseminate this information to only selective parts of higher order somatic and MI cortices in parallel with cutaneous information.

  16. Crystal Structure of the Core Region of Hantavirus Nucleocapsid Protein Reveals the Mechanism for Ribonucleoprotein Complex Formation

    PubMed Central

    Guo, Yu; Wang, Wenming; Sun, Yuna; Ma, Chao; Wang, Xu; Wang, Xin; Liu, Pi; Shen, Shu; Li, Baobin; Lin, Jianping; Deng, Fei

    2015-01-01

    ABSTRACT Hantaviruses, which belong to the genus Hantavirus in the family Bunyaviridae, infect mammals, including humans, causing either hemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS) in humans with high mortality. Hantavirus encodes a nucleocapsid protein (NP) to encapsidate the genome and form a ribonucleoprotein complex (RNP) together with viral polymerase. Here, we report the crystal structure of the core domains of NP (NPcore) encoded by Sin Nombre virus (SNV) and Andes virus (ANDV), which are two representative members that cause HCPS in the New World. The constructs of SNV and ANDV NPcore exclude the N- and C-terminal portions of full polypeptide to obtain stable proteins for crystallographic study. The structure features an N lobe and a C lobe to clamp RNA-binding crevice and exhibits two protruding extensions in both lobes. The positively charged residues located in the RNA-binding crevice play a key role in RNA binding and virus replication. We further demonstrated that the C-terminal helix and the linker region connecting the N-terminal coiled-coil domain and NPcore are essential for hantavirus NP oligomerization through contacts made with two adjacent protomers. Moreover, electron microscopy (EM) visualization of native RNPs extracted from the virions revealed that a monomer-sized NP-RNA complex is the building block of viral RNP. This work provides insight into the formation of hantavirus RNP and provides an understanding of the evolutionary connections that exist among bunyaviruses. IMPORTANCE Hantaviruses are distributed across a wide and increasing range of host reservoirs throughout the world. In particular, hantaviruses can be transmitted via aerosols of rodent excreta to humans or from human to human and cause HFRS and HCPS, with mortalities of 15% and 50%, respectively. Hantavirus is therefore listed as a category C pathogen. Hantavirus encodes an NP that plays essential roles both in RNP formation and

  17. Crystal Structure of the Core Region of Hantavirus Nucleocapsid Protein Reveals the Mechanism for Ribonucleoprotein Complex Formation.

    PubMed

    Guo, Yu; Wang, Wenming; Sun, Yuna; Ma, Chao; Wang, Xu; Wang, Xin; Liu, Pi; Shen, Shu; Li, Baobin; Lin, Jianping; Deng, Fei; Wang, Hualin; Lou, Zhiyong

    2015-11-11

    Hantaviruses, which belong to the genus Hantavirus in the family Bunyaviridae, infect mammals, including humans, causing either hemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS) in humans with high mortality. Hantavirus encodes a nucleocapsid protein (NP) to encapsidate the genome and form a ribonucleoprotein complex (RNP) together with viral polymerase. Here, we report the crystal structure of the core domains of NP (NPcore) encoded by Sin Nombre virus (SNV) and Andes virus (ANDV), which are two representative members that cause HCPS in the New World. The constructs of SNV and ANDV NPcore exclude the N- and C-terminal portions of full polypeptide to obtain stable proteins for crystallographic study. The structure features an N lobe and a C lobe to clamp RNA-binding crevice and exhibits two protruding extensions in both lobes. The positively charged residues located in the RNA-binding crevice play a key role in RNA binding and virus replication. We further demonstrated that the C-terminal helix and the linker region connecting the N-terminal coiled-coil domain and NPcore are essential for hantavirus NP oligomerization through contacts made with two adjacent protomers. Moreover, electron microscopy (EM) visualization of native RNPs extracted from the virions revealed that a monomer-sized NP-RNA complex is the building block of viral RNP. This work provides insight into the formation of hantavirus RNP and provides an understanding of the evolutionary connections that exist among bunyaviruses. Hantaviruses are distributed across a wide and increasing range of host reservoirs throughout the world. In particular, hantaviruses can be transmitted via aerosols of rodent excreta to humans or from human to human and cause HFRS and HCPS, with mortalities of 15% and 50%, respectively. Hantavirus is therefore listed as a category C pathogen. Hantavirus encodes an NP that plays essential roles both in RNP formation and in multiple

  18. Characterization of Somatic Mutations in Air Pollution-Related Lung Cancer

    PubMed Central

    Yu, Xian-Jun; Yang, Min-Jun; Zhou, Bo; Wang, Gui-Zhen; Huang, Yun-Chao; Wu, Li-Chuan; Cheng, Xin; Wen, Zhe-Sheng; Huang, Jin-Yan; Zhang, Yun-Dong; Gao, Xiao-Hong; Li, Gao-Feng; He, Shui-Wang; Gu, Zhao-Hui; Ma, Liang; Pan, Chun-Ming; Wang, Ping; Chen, Hao-Bin; Hong, Zhi-Peng; Wang, Xiao-Lu; Mao, Wen-Jing; Jin, Xiao-Long; Kang, Hui; Chen, Shu-Ting; Zhu, Yong-Qiang; Gu, Wen-Yi; Liu, Zi; Dong, Hui; Tian, Lin-Wei; Chen, Sai-Juan; Cao, Yi; Wang, Sheng-Yue; Zhou, Guang-Biao

    2015-01-01

    Air pollution has been classified as Group 1 carcinogenic to humans, but the underlying tumorigenesis remains unclear. In Xuanwei City of Yunnan Province, the lung cancer incidence is among the highest in China attributed to severe air pollution generated by combustion of smoky coal, providing a unique opportunity to dissect lung carcinogenesis of air pollution. Here we analyzed the somatic mutations of 164 non-small cell lung cancers (NSCLCs) from Xuanwei and control regions (CR) where smoky coal was not used. Whole genome sequencing revealed a mean of 289 somatic exonic mutations per tumor and the frequent C:G → A:T nucleotide substitutions in Xuanwei NSCLCs. Exome sequencing of 2010 genes showed that Xuanwei and CR NSCLCs had a mean of 68 and 22 mutated genes per tumor, respectively (p < 0.0001). We found 167 genes (including TP53, RYR2, KRAS, CACNA1E) which had significantly higher mutation frequencies in Xuanwei than CR patients, and mutations in most genes in Xuanwei NSCLCs differed from those in CR cases. The mutation rates of 70 genes (e.g., RYR2, MYH3, GPR144, CACNA1E) were associated with patients' lifetime benzo(a)pyrene exposure. This study uncovers the mutation spectrum of air pollution-related lung cancers, and provides evidence for pollution exposure–genomic mutation relationship at a large scale. PMID:26288819

  19. Characterization of Somatic Mutations in Air Pollution-Related Lung Cancer.

    PubMed

    Yu, Xian-Jun; Yang, Min-Jun; Zhou, Bo; Wang, Gui-Zhen; Huang, Yun-Chao; Wu, Li-Chuan; Cheng, Xin; Wen, Zhe-Sheng; Huang, Jin-Yan; Zhang, Yun-Dong; Gao, Xiao-Hong; Li, Gao-Feng; He, Shui-Wang; Gu, Zhao-Hui; Ma, Liang; Pan, Chun-Ming; Wang, Ping; Chen, Hao-Bin; Hong, Zhi-Peng; Wang, Xiao-Lu; Mao, Wen-Jing; Jin, Xiao-Long; Kang, Hui; Chen, Shu-Ting; Zhu, Yong-Qiang; Gu, Wen-Yi; Liu, Zi; Dong, Hui; Tian, Lin-Wei; Chen, Sai-Juan; Cao, Yi; Wang, Sheng-Yue; Zhou, Guang-Biao

    2015-06-01

    Air pollution has been classified as Group 1 carcinogenic to humans, but the underlying tumorigenesis remains unclear. In Xuanwei City of Yunnan Province, the lung cancer incidence is among the highest in China attributed to severe air pollution generated by combustion of smoky coal, providing a unique opportunity to dissect lung carcinogenesis of air pollution. Here we analyzed the somatic mutations of 164 non-small cell lung cancers (NSCLCs) from Xuanwei and control regions (CR) where smoky coal was not used. Whole genome sequencing revealed a mean of 289 somatic exonic mutations per tumor and the frequent C:G → A:T nucleotide substitutions in Xuanwei NSCLCs. Exome sequencing of 2010 genes showed that Xuanwei and CR NSCLCs had a mean of 68 and 22 mutated genes per tumor, respectively (p < 0.0001). We found 167 genes (including TP53, RYR2, KRAS, CACNA1E) which had significantly higher mutation frequencies in Xuanwei than CR patients, and mutations in most genes in Xuanwei NSCLCs differed from those in CR cases. The mutation rates of 70 genes (e.g., RYR2, MYH3, GPR144, CACNA1E) were associated with patients' lifetime benzo(a)pyrene exposure. This study uncovers the mutation spectrum of air pollution-related lung cancers, and provides evidence for pollution exposure-genomic mutation relationship at a large scale.

  20. Cortical processing of human somatic and visceral sensation.

    PubMed

    Aziz, Q; Thompson, D G; Ng, V W; Hamdy, S; Sarkar, S; Brammer, M J; Bullmore, E T; Hobson, A; Tracey, I; Gregory, L; Simmons, A; Williams, S C

    2000-04-01

    Somatic sensation can be localized precisely, whereas localization of visceral sensation is vague, possibly reflecting differences in the pattern of somatic and visceral input to the cerebral cortex. We used functional magnetic resonance imaging to study the cortical processing of sensation arising from the proximal (somatic) and distal (visceral) esophagus in six healthy male subjects. Esophageal stimulation was performed by phasic distension of a 2 cm balloon at 0.5 Hz. For each esophageal region, five separate 30 sec periods of nonpainful distension were alternated with five periods of similar duration without distension. Gradient echoplanar images depicting bold contrast were acquired using a 1.5 T GE scanner. Distension of the proximal esophagus was localized precisely to the upper chest and was represented in the trunk region of the left primary somatosensory cortex. In contrast, distension of the distal esophagus was perceived diffusely over the lower chest and was represented bilaterally at the junction of the primary and secondary somatosensory cortices. Different activation patterns were also observed in the anterior cingulate gyrus with the proximal esophagus being represented in the right midanterior cingulate cortex (BA 24) and the distal esophagus in the perigenual area (BA32). Differences in the activation of the dorsolateral prefrontal cortex and cerebellum were also observed for the two esophageal regions. These findings suggest that cortical specialization in the sensory-discriminative, affective, and cognitive areas of the cortex accounts for the perceptual differences observed between the two sensory modalities.

  1. Quantitative woody cover reconstructions from eastern continental Asia of the last 22 kyr reveal strong regional peculiarities

    NASA Astrophysics Data System (ADS)

    Tian, Fang; Cao, Xianyong; Dallmeyer, Anne; Ni, Jian; Zhao, Yan; Wang, Yongbo; Herzschuh, Ulrike

    2016-04-01

    We present a calibration-set based on modern pollen and satellite-based Advanced Very High Resolution Radiometer (AVHRR) observations of woody cover (including needleleaved, broadleaved and total tree cover) in eastern continental Asia, which shows good performance under cross-validation with the modern analogue technique (all the coefficients of determination between observed and predicted values are greater than 0.65). The calibration-set is used to reconstruct woody cover from a taxonomically harmonized and temporally standardized fossil pollen dataset (including 274 cores) with 500-year resolution over the last 22 kyr. The spatial range of forest has not noticeably changed in eastern continental Asia during the last 22 kyr, although woody cover has, especially at the margin of the eastern Tibetan Plateau and in the forest-steppe transition area of north-central China. Vegetation was sparse during the LGM in the present forested regions, but woody cover increased markedly at the beginning of the Bølling/Allerød period (B/A; ca. 14.5 ka BP) and again at the beginning of the Holocene (ca. 11.5 ka BP), and is related to the enhanced strength of the East Asian Summer Monsoon. Forest flourished in the mid-Holocene (ca. 8 ka BP) possibly due to favourable climatic conditions. In contrast, cover was stable in southern China (high cover) and arid central Asia (very low cover) throughout the investigated period. Forest cover increased in the north-eastern part of China during the Holocene. Comparisons of these regional pollen-based results with simulated forest cover from runs of a global climate model (for 9, 6 and 0 ka BP (ECHAM5/JSBACH ∼1.125° spatial resolution)) reveal many similarities in temporal change. The Holocene woody cover history of eastern continental Asia is different from that of other regions, likely controlled by different climatic variables, i.e. moisture in eastern continental Asia; temperature in northern Eurasia and North America.

  2. The effectiveness of somatic embryogenesis in eliminating the cocoa swollen shoot virus from infected cocoa trees.

    PubMed

    Quainoo, A K; Wetten, A C; Allainguillaume, J

    2008-04-01

    Investigations were undertaken on the use of somatic embryogenesis to generate cocoa swollen shoot virus (CSSV) disease free clonal propagules from infected trees. Polymerase chain reaction (PCR) capillary electrophoresis revealed the presence of CSSV in all the callus tissues induced from the CSSV-infected Amelonado cocoa trees (T1, T2 and T4). The virus was transmitted to primary somatic embryos induced from the infected callus tissues at the rate of 10 (19%), 18 (14%) and 16 (15%) for T1, T2 and T4, respectively. Virus free primary somatic embryos from the infected callus tissues converted into plantlets tested CSSV negative by PCR/capillary electrophoresis 2 years after weaning. Secondary somatic embryos induced from the CSSV-infected primary somatic embryos revealed the presence of viral fragments at the rate of 4 (4%) and 9 (9%) for T2 and T4, respectively. Real-time PCR revealed 23 of the 24 secondary somatic embryos contained no detectable virus. Based on these findings, it is proposed that progressive elimination of the CSSV in infected cocoa trees occurred from primary embryogenesis to secondary embryogenesis.

  3. Diversity and structure of soil bacterial communities in the Fildes Region (maritime Antarctica) as revealed by 454 pyrosequencing

    PubMed Central

    Wang, Neng Fei; Zhang, Tao; Zhang, Fang; Wang, En Tao; He, Jian Feng; Ding, Hui; Zhang, Bo Tao; Liu, Jie; Ran, Xiang Bin; Zang, Jia Ye

    2015-01-01

    This study assessed the diversity and composition of bacterial communities in four different soils (human-, penguin-, seal-colony impacted soils and pristine soil) in the Fildes Region (King George Island, Antarctica) using 454 pyrosequencing with bacterial-specific primers targeting the 16S rRNA gene. Proteobacteria, Actinobacteria, Acidobacteria, and Verrucomicrobia were abundant phyla in almost all the soil samples. The four types of soils were significantly different in geochemical properties and bacterial community structure. Thermotogae, Cyanobacteria, Fibrobacteres, Deinococcus-Thermus, and Chlorobi obviously varied in their abundance among the 4 soil types. Considering all the samples together, members of the genera Gaiella, Chloracidobacterium, Nitrospira, Polaromonas, Gemmatimonas, Sphingomonas, and Chthoniobacter were found to predominate, whereas members of the genera Chamaesiphon, Herbaspirillum, Hirschia, Nevskia, Nitrosococcus, Rhodococcus, Rhodomicrobium, and Xanthomonas varied obviously in their abundance among the four soil types. Distance-based redundancy analysis revealed that pH (p < 0.01), phosphate phosphorus (p < 0.01), organic carbon (p < 0.05), and organic nitrogen (p < 0.05) were the most significant factors that correlated with the community distribution of soil bacteria. To our knowledge, this is the first study to explore the soil bacterial communities in human-, penguin-, and seal- colony impacted soils from ice-free areas in maritime Antarctica using high-throughput pyrosequencing. PMID:26579095

  4. Barcoding Beetles: A Regional Survey of 1872 Species Reveals High Identification Success and Unusually Deep Interspecific Divergences

    PubMed Central

    Pentinsaari, Mikko; Hebert, Paul D. N.; Mutanen, Marko

    2014-01-01

    With 400 K described species, beetles (Insecta: Coleoptera) represent the most diverse order in the animal kingdom. Although the study of their diversity currently represents a major challenge, DNA barcodes may provide a functional, standardized tool for their identification. To evaluate this possibility, we performed the first comprehensive test of the effectiveness of DNA barcodes as a tool for beetle identification by sequencing the COI barcode region from 1872 North European species. We examined intraspecific divergences, identification success and the effects of sample size on variation observed within and between species. A high proportion (98.3%) of these species possessed distinctive barcode sequence arrays. Moreover, the sequence divergences between nearest neighbor species were considerably higher than those reported for the only other insect order, Lepidoptera, which has seen intensive analysis (11.99% vs up to 5.80% mean NN divergence). Although maximum intraspecific divergence increased and average divergence between nearest neighbors decreased with increasing sampling effort, these trends rarely hampered identification by DNA barcodes due to deep sequence divergences between most species. The Barcode Index Number system in BOLD coincided strongly with known species boundaries with perfect matches between species and BINs in 92.1% of all cases. In addition, DNA barcode analysis revealed the likely occurrence of about 20 overlooked species. The current results indicate that DNA barcodes distinguish species of beetles remarkably well, establishing their potential to provide an effective identification tool for this order and to accelerate the discovery of new beetle species. PMID:25255319

  5. Modified ribosome profiling reveals high abundance of ribosome protected mRNA fragments derived from 3′ untranslated regions

    PubMed Central

    Miettinen, Teemu P.; Björklund, Mikael

    2015-01-01

    Ribosome profiling identifies ribosome positions on translated mRNAs. A prominent feature of published datasets is the near complete absence of ribosomes in 3′ untranslated regions (3′UTR) although substantial ribosome density can be observed on non-coding RNAs. Here we perform ribosome profiling in cultured Drosophila and human cells and show that different features of translation are revealed depending on the nuclease and the digestion conditions used. Most importantly, we observe high abundance of ribosome protected fragments in 3′UTRs of thousands of genes without manipulation of translation termination. Affinity purification of ribosomes indicates that the 3′UTR reads originate from ribosome protected fragments. Association of ribosomes with the 3′UTR may be due to ribosome migration through the stop codon or 3′UTR mRNA binding to ribosomes on the coding sequence. This association depends primarily on the relative length of the 3′UTR and may be related to translational regulation or ribosome recycling, for which the efficiency is known to inversely correlate with 3′UTR length. Together our results indicate that ribosome profiling is highly dependent on digestion conditions and that ribosomes commonly associate with the 3′UTR, which may have a role in translational regulation. PMID:25550424

  6. A Gene-Oriented Haplotype Comparison Reveals Recently Selected Genomic Regions in Temperate and Tropical Maize Germplasm

    PubMed Central

    Zhang, Jie; Li, Yongxiang; Zheng, Jun; Zhang, Hongwei; Yang, Xiaohong; Wang, Jianhua; Wang, Guoying

    2017-01-01

    The extensive genetic variation present in maize (Zea mays) germplasm makes it possible to detect signatures of positive artificial selection that occurred during temperate and tropical maize improvement. Here we report an analysis of 532,815 polymorphisms from a maize association panel consisting of 368 diverse temperate and tropical inbred lines. We developed a gene-oriented approach adapting exonic polymorphisms to identify recently selected alleles by comparing haplotypes across the maize genome. This analysis revealed evidence of selection for more than 1100 genomic regions during recent improvement, and included regulatory genes and key genes with visible mutant phenotypes. We find that selected candidate target genes in temperate maize are enriched in biosynthetic processes, and further examination of these candidates highlights two cases, sucrose flux and oil storage, in which multiple genes in a common pathway can be cooperatively selected. Finally, based on available parallel gene expression data, we hypothesize that some genes were selected for regulatory variations, resulting in altered gene expression. PMID:28099470

  7. Diversity and structure of soil bacterial communities in the Fildes Region (maritime Antarctica) as revealed by 454 pyrosequencing.

    PubMed

    Wang, Neng Fei; Zhang, Tao; Zhang, Fang; Wang, En Tao; He, Jian Feng; Ding, Hui; Zhang, Bo Tao; Liu, Jie; Ran, Xiang Bin; Zang, Jia Ye

    2015-01-01

    This study assessed the diversity and composition of bacterial communities in four different soils (human-, penguin-, seal-colony impacted soils and pristine soil) in the Fildes Region (King George Island, Antarctica) using 454 pyrosequencing with bacterial-specific primers targeting the 16S rRNA gene. Proteobacteria, Actinobacteria, Acidobacteria, and Verrucomicrobia were abundant phyla in almost all the soil samples. The four types of soils were significantly different in geochemical properties and bacterial community structure. Thermotogae, Cyanobacteria, Fibrobacteres, Deinococcus-Thermus, and Chlorobi obviously varied in their abundance among the 4 soil types. Considering all the samples together, members of the genera Gaiella, Chloracidobacterium, Nitrospira, Polaromonas, Gemmatimonas, Sphingomonas, and Chthoniobacter were found to predominate, whereas members of the genera Chamaesiphon, Herbaspirillum, Hirschia, Nevskia, Nitrosococcus, Rhodococcus, Rhodomicrobium, and Xanthomonas varied obviously in their abundance among the four soil types. Distance-based redundancy analysis revealed that pH (p < 0.01), phosphate phosphorus (p < 0.01), organic carbon (p < 0.05), and organic nitrogen (p < 0.05) were the most significant factors that correlated with the community distribution of soil bacteria. To our knowledge, this is the first study to explore the soil bacterial communities in human-, penguin-, and seal- colony impacted soils from ice-free areas in maritime Antarctica using high-throughput pyrosequencing.

  8. Depression, Life Events and Somatic Symptoms.

    ERIC Educational Resources Information Center

    Rozzini, Renzo; And Others

    1988-01-01

    Investigated the relationship between somatic symptoms, depression, and life events (health status, function, social satisfaction, income) in a population of 1,201 elderly persons living at home. Found depression was the most important factor in the appearance of somatic complaints; however, life events were important cofactors in defining…

  9. Five classic articles in somatic cell reprogramming.

    PubMed

    Park, In-Hyun

    2010-09-01

    Research on somatic cell reprogramming has progressed significantly over the past few decades, from nuclear transfer into frogs' eggs in 1952 to the derivation of human-induced pluripotent stem (iPS) cells in the present day. In this article, I review five landmark papers that have laid the foundation for current efforts to apply somatic cell reprogramming in the clinic.

  10. Parental Somatic Mosaicism Is Underrecognized and Influences Recurrence Risk of Genomic Disorders

    PubMed Central

    Campbell, Ian M.; Yuan, Bo; Robberecht, Caroline; Pfundt, Rolph; Szafranski, Przemyslaw; McEntagart, Meriel E.; Nagamani, Sandesh C.S.; Erez, Ayelet; Bartnik, Magdalena; Wiśniowiecka-Kowalnik, Barbara; Plunkett, Katie S.; Pursley, Amber N.; Kang, Sung-Hae L.; Bi, Weimin; Lalani, Seema R.; Bacino, Carlos A.; Vast, Mala; Marks, Karen; Patton, Michael; Olofsson, Peter; Patel, Ankita; Veltman, Joris A.; Cheung, Sau Wai; Shaw, Chad A.; Vissers, Lisenka E.L.M.; Vermeesch, Joris R.; Lupski, James R.; Stankiewicz, Paweł

    2014-01-01

    New human mutations are thought to originate in germ cells, thus making a recurrence of the same mutation in a sibling exceedingly rare. However, increasing sensitivity of genomic technologies has anecdotally revealed mosaicism for mutations in somatic tissues of apparently healthy parents. Such somatically mosaic parents might also have germline mosaicism that can potentially cause unexpected intergenerational recurrences. Here, we show that somatic mosaicism for transmitted mutations among parents of children with simplex genetic disease is more common than currently appreciated. Using the sensitivity of individual-specific breakpoint PCR, we prospectively screened 100 families with children affected by genomic disorders due to rare deletion copy-number variants (CNVs) determined to be de novo by clinical analysis of parental DNA. Surprisingly, we identified four cases of low-level somatic mosaicism for the transmitted CNV in DNA isolated from parental blood. Integrated probabilistic modeling of gametogenesis developed in response to our observations predicts that mutations in parental blood increase recurrence risk substantially more than parental mutations confined to the germline. Moreover, despite the fact that maternally transmitted mutations are the minority of alleles, our model suggests that sexual dimorphisms in gametogenesis result in a greater proportion of somatically mosaic transmitting mothers who are thus at increased risk of recurrence. Therefore, somatic mosaicism together with sexual differences in gametogenesis might explain a considerable fraction of unexpected recurrences of X-linked recessive disease. Overall, our results underscore an important role for somatic mosaicism and mitotic replicative mutational mechanisms in transmission genetics. PMID:25087610

  11. Differential regulation of DNA damage response activation between somatic and germline cells in Caenorhabditis elegans

    PubMed Central

    Vermezovic, J; Stergiou, L; Hengartner, M O; d'Adda di Fagagna, F

    2012-01-01

    The germline of Caenorhabditis elegans is a well-established model for DNA damage response (DDR) studies. However, the molecular basis of the observed cell death resistance in the soma of these animals remains unknown. We established a set of techniques to study ionizing radiation-induced DNA damage generation and DDR activation in a whole intact worm. Our single-cell analyses reveal that, although germline and somatic cells show similar levels of inflicted DNA damage, somatic cells, differently from germline cells, do not activate the crucial apical DDR kinase ataxia-telengiectasia mutated (ATM). We also show that DDR signaling proteins are undetectable in all somatic cells and this is due to transcriptional repression. However, DNA repair genes are expressed and somatic cells retain the ability to efficiently repair DNA damage. Finally, we demonstrate that germline cells, when induced to transdifferentiate into somatic cells within the gonad, lose the ability to activate ATM. Overall, these observations provide a molecular mechanism for the known, but hitherto unexplained, resistance to DNA damage-induced cell death in C. elegans somatic cells. We propose that the observed lack of signaling and cell death but retention of DNA repair functions in the soma is a Caenorhabditis-specific evolutionary-selected strategy to cope with its lack of adult somatic stem cell pools and regenerative capacity. PMID:22705849

  12. Clonal reproduction with androgenesis and somatic recombination: the case of the ant Cardiocondyla kagutsuchi

    NASA Astrophysics Data System (ADS)

    Okita, Ichiro; Tsuchida, Koji

    2016-04-01

    In haplodiploid insects such as ants, male sexuals develop from unfertilised haploid eggs, while female sexuals and workers develop from fertilized diploid eggs. However, some ant species do not exchange their gene pool between sexes; both male and female sexuals are clonally produced, while workers are sexually produced. To date, three ant species, Wasmannia auropunctata, Vollenhovia emeryi, and Paratrechina longicornis, have been reported to reproduce using such reproductive systems. In this study, we reveal that in one lineage of the ant Cardiocondyla kagutsuchi, male and female sexuals are also clonally produced. In contrast to the abovementioned three species, the workers were not only sexually produced but had recombinant sequences in their nuclear internal transcribed spacer regions, although the recombinant sequences were not detected in male or female sexuals. These results suggest that the lineage likely possesses a mechanism to compensate for the reduction in genetic variation due to clonal reproduction with somatic recombination that occurs within the workers.

  13. Clonal reproduction with androgenesis and somatic recombination: the case of the ant Cardiocondyla kagutsuchi.

    PubMed

    Okita, Ichiro; Tsuchida, Koji

    2016-04-01

    In haplodiploid insects such as ants, male sexuals develop from unfertilised haploid eggs, while female sexuals and workers develop from fertilized diploid eggs. However, some ant species do not exchange their gene pool between sexes; both male and female sexuals are clonally produced, while workers are sexually produced. To date, three ant species, Wasmannia auropunctata, Vollenhovia emeryi, and Paratrechina longicornis, have been reported to reproduce using such reproductive systems. In this study, we reveal that in one lineage of the ant Cardiocondyla kagutsuchi, male and female sexuals are also clonally produced. In contrast to the abovementioned three species, the workers were not only sexually produced but had recombinant sequences in their nuclear internal transcribed spacer regions, although the recombinant sequences were not detected in male or female sexuals. These results suggest that the lineage likely possesses a mechanism to compensate for the reduction in genetic variation due to clonal reproduction with somatic recombination that occurs within the workers.

  14. Somatic Mosaicism in the Human Genome

    PubMed Central

    Freed, Donald; Stevens, Eric L.; Pevsner, Jonathan

    2014-01-01

    Somatic mosaicism refers to the occurrence of two genetically distinct populations of cells within an individual, derived from a postzygotic mutation. In contrast to inherited mutations, somatic mosaic mutations may affect only a portion of the body and are not transmitted to progeny. These mutations affect varying genomic sizes ranging from single nucleotides to entire chromosomes and have been implicated in disease, most prominently cancer. The phenotypic consequences of somatic mosaicism are dependent upon many factors including the developmental time at which the mutation occurs, the areas of the body that are affected, and the pathophysiological effect(s) of the mutation. The advent of second-generation sequencing technologies has augmented existing array-based and cytogenetic approaches for the identification of somatic mutations. We outline the strengths and weaknesses of these techniques and highlight recent insights into the role of somatic mosaicism in causing cancer, neurodegenerative, monogenic, and complex disease. PMID:25513881

  15. Somatic complaints in anxious youth.

    PubMed

    Crawley, Sarah A; Caporino, Nicole E; Birmaher, Boris; Ginsburg, Golda; Piacentini, John; Albano, Anne Marie; Sherrill, Joel; Sakolsky, Dara; Compton, Scott N; Rynn, Moira; McCracken, James; Gosch, Elizabeth; Keeton, Courtney; March, John; Walkup, John T; Kendall, Philip C

    2014-08-01

    This study examined (a) demographic and clinical characteristics associated with physical symptoms in anxiety-disordered youth and (b) the impact of cognitive-behavioral therapy (Coping Cat), medication (sertraline), their combination, and pill placebo on physical symptoms. Youth (N = 488, ages 7-17 years) with a principal diagnosis of generalized anxiety disorder, separation anxiety disorder, or social phobia participated as part of a multi-site, randomized controlled trial and received treatment delivered over 12 weeks. Diagnostic status, symptom severity, and impairment were assessed at baseline and week 12. The total number and severity of physical symptoms was associated with age, principal diagnosis, anxiety severity, impairment, and the presence of comorbid internalizing disorders. Common somatic complaints were headaches, stomachaches, head cold or sniffles, sleeplessness, and feeling drowsy or too sleepy. Physical symptoms decreased over the course of treatment, and were unrelated to treatment condition. Clinical implications and directions for future research are discussed (ClinicalTrials.gov number, NCT00052078).

  16. Somatic Treatments for Mood Disorders

    PubMed Central

    Rosa, Moacyr A; Lisanby, Sarah H

    2012-01-01

    Somatic treatments for mood disorders represent a class of interventions available either as a stand-alone option, or in combination with psychopharmacology and/or psychotherapy. Here, we review the currently available techniques, including those already in clinical use and those still under research. Techniques are grouped into the following categories: (1) seizure therapies, including electroconvulsive therapy and magnetic seizure therapy, (2) noninvasive techniques, including repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and cranial electric stimulation, (3) surgical approaches, including vagus nerve stimulation, epidural electrical stimulation, and deep brain stimulation, and (4) technologies on the horizon. Additionally, we discuss novel approaches to the optimization of each treatment, and new techniques that are under active investigation. PMID:21976043

  17. Minor tranquillizers in somatic disorders.

    PubMed Central

    Krogh, C.; McLean, W. M.; LaPierre, Y. D.

    1978-01-01

    Conclusive evidence of improved outcome due to adjunctive anxiolytic therapy in some somatic conditions is lacking. However, such therapy may facilitate patient management without being "curative". The resulting improved feeling of well-being may be of value in the management of gastrointestinal disorders, migraine and myocardial infarction. Negative effects may be observed in acute respiratory conditions, especially during acute exacerbations of chronic conditions, with the administration of benzodiazepines; hence they should be used with caution. The use of these agents in treating persons with hypertension seems to be of no value and may even be detrimental. Careful evaluation of each case is desirable, and treatment should be planned with its termination in mind. PMID:25708

  18. Magnitude and extent of land subsidence in central Mexico revealed by regional InSAR ALOS time-series survey

    NASA Astrophysics Data System (ADS)

    Chaussard, E.; Wdowinski, S.; Amelung, F.; Cabral-Cano, E.

    2013-05-01

    Massive groundwater extraction is very common in Mexico and is well known to result in land subsidence. However, most surveys dedicated to land subsidence focus on one single city, mainly Mexico City, and thus fail to provide a comprehensive picture of the problem. Here we use a space-based radar remote sensing technique, known as Interferometric Synthetic Aperture Radar (InSAR) to detect land subsidence in the entire central Mexico area. We used data from the Japanese satellite ALOS, processed over 600 SAR images acquired between 2007-2011 and produced over 3000 interferograms to cover and area of 200,000 km2 in central Mexico. We identify land subsidence in twenty-one areas, including seventeen cities, namely from east to west, Puebla, Mexico city, Toluca de Lerdo, Queretaro, San Luis de la Paz, south of San Luis de la Paz, Celaya, south of Villa de Reyes, San Luis Potosi, west of Villa de Arista, Morelia, Salamanca, Irapuato, Silao, Leon, Aguascalientes, north of Aguascalientes, Zamora de Hidalgo, Guadalajara, Ahuacatlan, and Tepic. Subsidence rates of 30 cm/yr are observed in Mexico City, while in the other locations typical rates of 5-10 cm/yr are noticed. Regional surveys of this type are necessary for the development of hazard mitigation plans and efficient use of ground-based monitoring. We additionally correlate subsidence with land use, surface geology, and faults distribution and suggest that groundwater extraction for agricultural, urban, and industrial uses are the main causes of land subsidence. We also reveal that the limits of the subsiding areas often correlate with existing faults, motion on these faults being driven by water extraction rather than by tectonic activity. In all the subsiding locations we observe high ground velocity gradients emphasizing the significant risks associated with land subsidence in central Mexico. Averaged 2007-2011 ground velocity map from ALOS InSAR time-series in central Mexico, revealing land subsidence in 21

  19. Extensive hydrothermal activity revealed by multi-tracer survey in the Wallis and Futuna region (SW Pacific)

    NASA Astrophysics Data System (ADS)

    Konn, C.; Fourré, E.; Jean-Baptiste, P.; Donval, J. P.; Guyader, V.; Birot, D.; Alix, A. S.; Gaillot, A.; Perez, F.; Dapoigny, A.; Pelleter, E.; Resing, J. A.; Charlou, J. L.; Fouquet, Y.

    2016-10-01

    The study area is close to the Wallis and Futuna Islands in the French EEZ. It exists on the western boundary of the fastest tectonic area in the world at the junction of the Lau and North-Fiji basins. At this place, the unstable back-arc accommodates the plate motion in three ways: (i) the north Fiji transform fault, (ii) numerous unstable spreading ridges, and (iii) large areas of recent volcanic activity. This instability creates bountiful opportunity for hydrothermal discharge to occur. Based on geochemical (CH4, TDM, 3He) and geophysical (nephelometry) tracer surveys: (1) no hydrothermal activity could be found on the Futuna Spreading Centre (FSC) which sets the western limit of hydrothermal activity; (2) four distinct hydrothermal active areas were identified: Kulo Lasi Caldera, Amanaki Volcano, Fatu Kapa and Tasi Tulo areas; (3) extensive and diverse hydrothermal manifestations were observed and especially a 2D distribution of the sources. At Kulo Lasi, our data and especially tracer ratios (CH4/3He 50×106 and CH4/TDM 4.5) reveal a transient CH4 input, with elevated levels of CH4 measured in 2010, that had vanished in 2011, most likely caused by an eruptive magmatic event. By contrast at Amanaki, vertical tracer profiles and tracer ratios point to typical seawater/basalt interactions. Fatu Kapa is characterised by a substantial spatial variability of the hydrothermal water column anomalies, most likely due to widespread focused and diffuse hydrothermal discharge in the area. In the Tasi Tulo zone, the hydrothermal signal is characterised by a total lack of turbidity, although other tracer anomalies are in the same range as in nearby Fatu Kapa. The background data set revealed the presence of a Mn and 3He chronic plume due to the extensive and cumulative venting over the entire area. To that respect, we believe that the joined domain composed of our active area and the nearby active area discovered in the East by Lupton et al. (2012) highly contribute to the

  20. Sequencing the GRHL3 Coding Region Reveals Rare Truncating Mutations and a Common Susceptibility Variant for Nonsyndromic Cleft Palate

    PubMed Central

    Mangold, Elisabeth; Böhmer, Anne C.; Ishorst, Nina; Hoebel, Ann-Kathrin; Gültepe, Pinar; Schuenke, Hannah; Klamt, Johanna; Hofmann, Andrea; Gölz, Lina; Raff, Ruth; Tessmann, Peter; Nowak, Stefanie; Reutter, Heiko; Hemprich, Alexander; Kreusch, Thomas; Kramer, Franz-Josef; Braumann, Bert; Reich, Rudolf; Schmidt, Gül; Jäger, Andreas; Reiter, Rudolf; Brosch, Sibylle; Stavusis, Janis; Ishida, Miho; Seselgyte, Rimante; Moore, Gudrun E.; Nöthen, Markus M.; Borck, Guntram; Aldhorae, Khalid A.; Lace, Baiba; Stanier, Philip; Knapp, Michael; Ludwig, Kerstin U.

    2016-01-01

    Nonsyndromic cleft lip with/without cleft palate (nsCL/P) and nonsyndromic cleft palate only (nsCPO) are the most frequent subphenotypes of orofacial clefts. A common syndromic form of orofacial clefting is Van der Woude syndrome (VWS) where individuals have CL/P or CPO, often but not always associated with lower lip pits. Recently, ∼5% of VWS-affected individuals were identified with mutations in the grainy head-like 3 gene (GRHL3). To investigate GRHL3 in nonsyndromic clefting, we sequenced its coding region in 576 Europeans with nsCL/P and 96 with nsCPO. Most strikingly, nsCPO-affected individuals had a higher minor allele frequency for rs41268753 (0.099) than control subjects (0.049; p = 1.24 × 10−2). This association was replicated in nsCPO/control cohorts from Latvia, Yemen, and the UK (pcombined = 2.63 × 10−5; ORallelic = 2.46 [95% CI 1.6–3.7]) and reached genome-wide significance in combination with imputed data from a GWAS in nsCPO triads (p = 2.73 × 10−9). Notably, rs41268753 is not associated with nsCL/P (p = 0.45). rs41268753 encodes the highly conserved p.Thr454Met (c.1361C>T) (GERP = 5.3), which prediction programs denote as deleterious, has a CADD score of 29.6, and increases protein binding capacity in silico. Sequencing also revealed four novel truncating GRHL3 mutations including two that were de novo in four families, where all nine individuals harboring mutations had nsCPO. This is important for genetic counseling: given that VWS is rare compared to nsCPO, our data suggest that dominant GRHL3 mutations are more likely to cause nonsyndromic than syndromic CPO. Thus, with rare dominant mutations and a common risk variant in the coding region, we have identified an important contribution for GRHL3 in nsCPO. PMID:27018475

  1. Breeding density, fine-scale tracking, and large-scale modeling reveal the regional distribution of four seabird species.

    PubMed

    Wakefield, Ewan D; Owen, Ellie; Baer, Julia; Carroll, Matthew J; Daunt, Francis; Dodd, Stephen G; Green, Jonathan A; Guilford, Tim; Mavor, Roddy A; Miller, Peter I; Newell, Mark A; Newton, Stephen F; Robertson, Gail S; Shoji, Akiko; Soanes, Louise M; Votier, Stephen C; Wanless, Sarah; Bolton, Mark

    2017-10-01

    Population-level estimates of species' distributions can reveal fundamental ecological processes and facilitate conservation. However, these may be difficult to obtain for mobile species, especially colonial central-place foragers (CCPFs; e.g., bats, corvids, social insects), because it is often impractical to determine the provenance of individuals observed beyond breeding sites. Moreover, some CCPFs, especially in the marine realm (e.g., pinnipeds, turtles, and seabirds) are difficult to observe because they range tens to ten thousands of kilometers from their colonies. It is hypothesized that the distribution of CCPFs depends largely on habitat availability and intraspecific competition. Modeling these effects may therefore allow distributions to be estimated from samples of individual spatial usage. Such data can be obtained for an increasing number of species using tracking technology. However, techniques for estimating population-level distributions using the telemetry data are poorly developed. This is of concern because many marine CCPFs, such as seabirds, are threatened by anthropogenic activities. Here, we aim to estimate the distribution at sea of four seabird species, foraging from approximately 5,500 breeding sites in Britain and Ireland. To do so, we GPS-tracked a sample of 230 European Shags Phalacrocorax aristotelis, 464 Black-legged Kittiwakes Rissa tridactyla, 178 Common Murres Uria aalge, and 281 Razorbills Alca torda from 13, 20, 12, and 14 colonies, respectively. Using Poisson point process habitat use models, we show that distribution at sea is dependent on (1) density-dependent competition among sympatric conspecifics (all species) and parapatric conspecifics (Kittiwakes and Murres); (2) habitat accessibility and coastal geometry, such that birds travel further from colonies with limited access to the sea; and (3) regional habitat availability. Using these models, we predict space use by birds from unobserved colonies and thereby map the

  2. Transcriptome analysis reveals regional and temporal differences in mucosal immune system development in the small intestine of neonatal calves.

    PubMed

    Liang, Guanxiang; Malmuthuge, Nilusha; Bao, Hua; Stothard, Paul; Griebel, Philip J; Guan, Le Luo

    2016-08-11

    Postnatal development of the mammalian mucosal immune system is crucial for responding to the rapid colonization by commensal bacteria and possible exposure to pathogens. This study analyzed expression patterns for mRNAs and their relationship with microRNAs (miRNAs) in the bovine small intestine during the critical neonatal period (0 to 42 days). This analysis revealed molecular mechanisms regulating the postnatal development of the intestinal mucosal immune system. Small intestine samples (jejunum and ileum) were collected from newborn male, Holstein calves immediately post-partum (n = 3) and at 7 (n = 5), 21 (n = 5), and 42 (n = 5) days of age and the transcriptomes were profiled using RNA-Seq. When analyzing all time points collectively, greater expression of genes encoding the complement functional pathway, as well as lower expression of genes encoding Toll-like receptors and NOD-like receptors were observed in the jejunum when compared to the ileum. In addition, significant changes in the expression of immune-related genes were detected within the first week post-partum in both jejunum and ileum. For example, increased expression of genes encoding tight junction proteins (claudin 1, claudin 4 and occludin), an antimicrobial peptide (Regenerating Islet-Derived 3-γ), NOD-like receptors (NACHT, LRR and PYD domain-containing protein 3), regulatory T cell marker (forkhead box P3), and both anti-inflammatory (interleukin 10) and pro-inflammatory (interleukin 8) cytokines was observed throughout the small intestine of 7-day-old calves when compared to newborn calves. Moreover, the expression of mucosal immune-related genes were either positively or negatively correlated with total bacterial population depending on both intestinal region and age. The integrated analysis of miRNAs and mRNAs supported the conclusion that miRNAs may regulate temporal changes in the expression of genes encoding tight junction proteins (miR-335), cytokines (miR-335) and

  3. A recurrent copy number variation of the NEB triplicate region: only revealed by the targeted nemaline myopathy CGH array.

    PubMed

    Kiiski, Kirsi; Lehtokari, Vilma-Lotta; Löytynoja, Ari; Ahlstén, Liina; Laitila, Jenni; Wallgren-Pettersson, Carina; Pelin, Katarina

    2016-04-01

    Recently, new large variants have been identified in the nebulin gene (NEB) causing nemaline myopathy (NM). NM constitutes a heterogeneous group of disorders among the congenital myopathies, and disease-causing variants in NEB are a main cause of the recessively inherited form of NM. NEB consists of 183 exons and it includes homologous sequences such as a 32-kb triplicate region (TRI), where eight exons are repeated three times (exons 82-89, 90-97, 98-105). In human, the normal copy number of NEB TRI is six (three copies in each allele). Recently, we described a custom NM-CGH microarray designed to detect copy number variations (CNVs) in the known NM genes. The array has now been updated to include all the currently known 10 NM genes. The NM-CGH array is superior in detecting CNVs, especially of the NEB TRI, that is not included in the exome capture kits. To date, we have studied 266 samples from 196 NM families using the NM-CGH microarray, and identified a novel recurrent NEB TRI variation in 13% (26/196) of the families and in 10% of the controls (6/60). An analysis of the breakpoints revealed adjacent repeat elements, which are known to predispose for rearrangements such as CNVs. The control CNV samples deviate only one copy from the normal six copies, whereas the NM samples include CNVs of up to four additional copies. Based on this study, NEB seems to tolerate deviations of one TRI copy, whereas addition of two or more copies might be pathogenic.

  4. A recurrent copy number variation of the NEB triplicate region: only revealed by the targeted nemaline myopathy CGH array

    PubMed Central

    Kiiski, Kirsi; Lehtokari, Vilma-Lotta; Löytynoja, Ari; Ahlstén, Liina; Laitila, Jenni; Wallgren-Pettersson, Carina; Pelin, Katarina

    2016-01-01

    Recently, new large variants have been identified in the nebulin gene (NEB) causing nemaline myopathy (NM). NM constitutes a heterogeneous group of disorders among the congenital myopathies, and disease-causing variants in NEB are a main cause of the recessively inherited form of NM. NEB consists of 183 exons and it includes homologous sequences such as a 32-kb triplicate region (TRI), where eight exons are repeated three times (exons 82–89, 90–97, 98–105). In human, the normal copy number of NEB TRI is six (three copies in each allele). Recently, we described a custom NM-CGH microarray designed to detect copy number variations (CNVs) in the known NM genes. The array has now been updated to include all the currently known 10 NM genes. The NM-CGH array is superior in detecting CNVs, especially of the NEB TRI, that is not included in the exome capture kits. To date, we have studied 266 samples from 196 NM families using the NM-CGH microarray, and identified a novel recurrent NEB TRI variation in 13% (26/196) of the families and in 10% of the controls (6/60). An analysis of the breakpoints revealed adjacent repeat elements, which are known to predispose for rearrangements such as CNVs. The control CNV samples deviate only one copy from the normal six copies, whereas the NM samples include CNVs of up to four additional copies. Based on this study, NEB seems to tolerate deviations of one TRI copy, whereas addition of two or more copies might be pathogenic. PMID:26197980

  5. Local-scale models reveal ecological niche variability in amphibian and reptile communities from two contrasting biogeographic regions

    PubMed Central

    Santos, Xavier; Felicísimo, Ángel M.

    2016-01-01

    Ecological Niche Models (ENMs) are widely used to describe how environmental factors influence species distribution. Modelling at a local scale, compared to a large scale within a high environmental gradient, can improve our understanding of ecological species niches. The main goal of this study is to assess and compare the contribution of environmental variables to amphibian and reptile ENMs in two Spanish national parks located in contrasting biogeographic regions, i.e., the Mediterranean and the Atlantic area. The ENMs were built with maximum entropy modelling using 11 environmental variables in each territory. The contributions of these variables to the models were analysed and classified using various statistical procedures (Mann–Whitney U tests, Principal Components Analysis and General Linear Models). Distance to the hydrological network was consistently the most relevant variable for both parks and taxonomic classes. Topographic variables (i.e., slope and altitude) were the second most predictive variables, followed by climatic variables. Differences in variable contribution were observed between parks and taxonomic classes. Variables related to water availability had the larger contribution to the models in the Mediterranean park, while topography variables were decisive in the Atlantic park. Specific response curves to environmental variables were in accordance with the biogeographic affinity of species (Mediterranean and non-Mediterranean species) and taxonomy (amphibians and reptiles). Interestingly, these results were observed for species located in both parks, particularly those situated at their range limits. Our findings show that ecological niche models built at local scale reveal differences in habitat preferences within a wide environmental gradient. Therefore, modelling at local scales rather than assuming large-scale models could be preferable for the establishment of conservation strategies for herptile species in natural parks. PMID

  6. Extensive Pyrosequencing Reveals Frequent Intra-Genomic Variations of Internal Transcribed Spacer Regions of Nuclear Ribosomal DNA

    PubMed Central

    Li, Dezhu; Sun, Yongzhen; Niu, Yunyun; Chen, Zhiduan; Luo, Hongmei; Pang, Xiaohui; Sun, Zhiying; Liu, Chang; Lv, Aiping; Deng, Youping; Larson-Rabin, Zachary; Wilkinson, Mike; Chen, Shilin

    2012-01-01

    Background Internal transcribed spacer of nuclear ribosomal DNA (nrDNA) is already one of the most popular phylogenetic and DNA barcoding markers. However, the existence of its multiple copies has complicated such usage and a detailed characterization of intra-genomic variations is critical to address such concerns. Methodology/Principal Findings In this study, we used sequence-tagged pyrosequencing and genome-wide analyses to characterize intra-genomic variations of internal transcribed spacer 2 (ITS2) regions from 178 plant species. We discovered that mutation of ITS2 is frequent, with a mean of 35 variants per species. And on average, three of the most abundant variants make up 91% of all ITS2 copies. Moreover, we found different congeneric species share identical variants in 13 genera. Interestingly, different species across different genera also share identical variants. In particular, one minor variant of ITS2 in Eleutherococcus giraldii was found identical to the ITS2 major variant of Panax ginseng, both from Araliaceae family. In addition, DNA barcoding gap analysis showed that the intra-genomic distances were markedly smaller than those of the intra-specific or inter-specific variants. When each of 5543 variants were examined for its species discrimination efficiency, a 97% success rate was obtained at the species level. Conclusions Identification of identical ITS2 variants across intra-generic or inter-generic species revealed complex species evolutionary history, possibly, horizontal gene transfer and ancestral hybridization. Although intra-genomic multiple variants are frequently found within each genome, the usage of the major variants alone is sufficient for phylogeny construction and species determination in most cases. Furthermore, the inclusion of minor variants further improves the resolution of species identification. PMID:22952830

  7. Genetic structure among sorghum landraces as revealed by morphological variation and microsatellite markers in three agroclimatic regions of Burkina Faso.

    PubMed

    Barro-Kondombo, Clarisse; Sagnard, Fabrice; Chantereau, Jacques; Deu, Monique; Vom Brocke, Kirsten; Durand, Patrick; Gozé, Eric; Zongo, Jean Didier

    2010-05-01

    Diversity among 124 sorghum landraces from 10 villages surveyed in 3 regions of Burkina Faso covering different agroecological zones was assessed by 28 agromorphological traits and 29 microsatellite markers. 94.4% of the landraces collected belonged to the botanical race guinea (consisting of 96.6% guinea gambicum and 3.4% guinea margaritiferum), 74.2% had white kernels, 13.7% had orange and 12.1% had red kernels. Compared to the "village nested within zone" factor, the "variety nested within village within zone" factor predominately contributed to the diversity pattern for all nine statistically analysed quantitative traits. The multivariate analyses performed on ten morphological traits identified five landrace groups, and of these, the red kernel sorghum types appeared the most homogenous. 2 to 17 alleles were detected per locus with a mean 4.9 alleles per locus and a gene diversity (He) of 0.37. Landraces from the sub-Sahelian zone had the highest gene diversity (He = 0.38). Cluster analysis revealed that the diversity was weakly stratified and could not be explained by any biophysical criteria. One homogenous guinea margaritiferum group was distinguished from other guinea landraces. The red kernel type appeared to be genetically distinct from all other guinea landraces. The kernel colour was the principal structuring factor. This is an example of a homogeneous group of varieties selected for a specific use (for local beer preparation), mainly grown around the households in compound fields, and presenting particular agromorphological and genetic traits. This is the most original feature of sorghum diversity in Burkina Faso and should be the focus of special conservation efforts.

  8. Aplastic anemia and clonal evolution: germ line and somatic genetics.

    PubMed

    Shimamura, Akiko

    2016-12-02

    Clonal progression to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) remains a dreaded complication for a subset of patients with bone marrow failure (BMF). Recognizing risk factors for the development of MDS or AML would inform individualized treatment decisions and identify patients who may benefit from early or upfront hematopoietic stem cell transplantation. Now that next-generation DNA sequencing is available in the clinical laboratory, research has focused on the implications of germ line and somatic mutations for diagnosing and monitoring patients with BMF. Most germ line genetic BMF disorders are characterized by a high propensity to develop MDS or AML. Many affected patients lack the physical stigmata traditionally associated with the inherited marrow failure syndromes. Although any single inherited marrow failure disorder is rare, multiplexed genetic sequencing that allows simultaneous evaluation of marrow failure genes en masse demonstrated that, as a group, these inherited disorders compose a significant subset (5% to 10%) of patients with BMF. Early diagnosis of a germ line genetic marrow failure disorder allows individualized monitoring and tailored therapy. Recent studies of somatic variants in marrow failure revealed a high frequency of clonal hematopoiesis with the acquisition of mutations in genes associated with MDS or AML. Investigation of somatic mutations in marrow failure revealed important insights into the mechanisms promoting clonal disease but also raised additional questions. This review will focus on the evaluation and implications of germ line and somatic mutations for the development of clonal disorders in patients with BMF. Challenges and limitations of clinical genetic testing will be explored. © 2016 by The American Society of Hematology. All rights reserved.

  9. Exploring the psychological and somatic impact of identity theft.

    PubMed

    Sharp, Tracy; Shreve-Neiger, Andrea; Fremouw, William; Kane, John; Hutton, Shawn

    2004-01-01

    Identity theft is a new and growing form of white-collar crime. This exploratory study examined the psychological and somatic impact of identity theft and coping methods utilized by victims. Thirty-seven victims of identity theft participated in regional victim focus groups. Participants completed a victim impact questionnaire designed by the authors and the Brief Symptom Inventory-18 (BSI-18). The majority of participants expressed an increase in maladaptive psychological and somatic symptoms post victimization. Results on the BSI indicated that identity theft victims with unresolved cases, in contrast to those with resolved cases, were more likely to have clinically elevated scores when compared with a normative sample. Relatively similar coping mechanisms were utilized across victims. The results from this study suggest that victims of identity theft do have increased psychological and physical distress, and for those whose cases remain unresolved, distress is maintained over time.

  10. Somatic embryogenesis in suspension cultures of Gossypium klotzschianum anderss.

    PubMed

    Price, H J; Smith, R H

    1979-01-01

    Somatic embryoids differentiated in suspension cultures of G. klotzschianum after 3-4 weeks of culture in a liquid medium containing glutamine (optimally, 10-15 mM). Embryogenesis occurred after a preculture of callus on a medium containing 10 mg/l of the cytokinin, 2iP. The embryoids had meristematic regions, a well formed epidermis, and formed roots and vestigial leaves. Asparagine was much less effective than glutamine in promoting embryoid differentiation. The presence of 2,4-D in the medium resulted in increased vigor of the suspension cultures and subsequently in the formation of many embryoids, but does not seem to be necessary for somatic embryogenesis in cotton.

  11. Somatic mutation in single human neurons tracks developmental and transcriptional history

    PubMed Central

    Evrony, Gilad D.; Mehta, Bhaven K.; Karger, Amir; Lee, Soohyun; Chittenden, Thomas W.; D’Gama, Alissa M.; Cai, Xuyu; Luquette, Lovelace J.; Lee, Eunjung; Park, Peter J.; Walsh, Christopher A.

    2015-01-01

    Neurons live for decades in a postmitotic state, their genomes susceptible to DNA damage. Here we survey the landscape of somatic single-nucleotide variants (SNVs) in the human brain. We identified thousands of somatic SNVs by single-cell sequencing of 36 neurons from the cerebral cortex of three normal individuals. Unlike germline and cancer SNVs, which are often caused by errors in DNA replication, neuronal mutations appear to reflect damage during active transcription. Somatic mutations create nested lineage trees, allowing them to be dated relative to developmental landmarks and revealing a polyclonal architecture of the human cerebral cortex. Thus, somatic mutations in the brain represent a durable and ongoing record of neuronal life history, from development through postmitotic function. PMID:26430121

  12. [Somatic mosaicism of expanded CAG trinucleotide repeat in spinal and bulbar muscular atrophy (SBMA)].

    PubMed

    Tanaka, F; Ito, Y; Sobue, G

    1999-04-01

    The CAG repeat in spinal and bulbar muscular atrophy (SBMA) is relatively stable in mitotic and meiotic processes as compared with other CAG repeat diseases. Previous reports indicate that SBMA does not manifest somatic mosaicism. However, detailed analysis in various tissues from 20 SBMA including 4 autopsied patients revealed the presence of the tissue-specific pattern of mosaicism. The prominent somatic mosaicism was observed in the cardiac and skeletal muscles, which are predominantly composed of postmitotic cells, and in the skin, prostate, and testis. The central nervous system (CNS) tissues, liver, and spleen showed smallest mosaicism. Such tissue-specific pattern of somatic mosaicism in SBMA is not explained by cell composition with different cell turnover rates. Other cell specific factors are likely more important for the somatic mosaicism in SBMA.

  13. HER2 somatic mutations are associated with poor survival in HER2-negative breast cancers.

    PubMed

    Wang, Tonghui; Xu, Ye; Sheng, Shuyan; Yuan, Hua; Ouyang, Tao; Li, Jinfeng; Wang, Tianfeng; Fan, Zhaoqing; Fan, Tie; Lin, Benyao; Xie, Yuntao

    2017-02-06

    It is well documented that HER2 overexpression/amplification is associated with the poor survival in breast cancer patients. However, it is largely unknown whether HER2 somatic mutations are associated with the survival in HER2-negative breast cancer patients. Here, we identified HER2 somatic mutations in tumors from 1,348 unselected breast cancer patients by sequencing the entire HER2 coding region. All these mutations were tested for in corresponding blood samples to determine whether they were somatic or germline mutations. We further investigated the associations between the HER2 somatic mutations and recurrence-free survival (RFS) and distant recurrence-free survival (DRFS) in this cohort of patients. We found that 27 of 1,348 (2.0%) of these patients carried a HER2 somatic mutation. In vitro experiments demonstrated that some of novel mutations and those with unknown functions increased HER2 activity. HER2 status was available for 1,306 patients, and the HER2 somatic mutation rates in HER2-positive (n=353) and HER2-negative breast cancers (n=953) were 1.4% and 2.3%, respectively. Among the HER2-negative patients, those with a HER2 somatic mutation had a significantly worse recurrence-free survival (unadjusted hazard ratio [HR] =2.67; 95% confidence interval [CI]: 1.25-5.72, P=0.002) and distant recurrence-free survival (unadjusted HR=2.50; 95% CI: 1.10-5.68, P=0.004) than those with wild-type HER2. Taken together, our findings suggested that HER2 somatic mutations occur at a higher frequency in HER2-negative breast cancer, and HER2-negative breast cancer patients with these mutations have poor survival. Therefore, HER2-negative patients with a HER2 somatic mutation are potentially good candidates for HER2-targeted therapy. This article is protected by copyright. All rights reserved.

  14. Atomic force microscopy reveals regional variations in the micromechanical properties of the pericellular and extracellular matrices of the meniscus.

    PubMed

    Sanchez-Adams, Johannah; Wilusz, Rebecca E; Guilak, Farshid

    2013-08-01

    Regional variations in the composition and architecture of the extracellular matrix (ECM) and pericellular matrix (PCM) of the knee meniscus play important roles in determining the local mechanical environment of meniscus cells. In this study, atomic force microscopy was used to spatially map the mechanical properties of matched ECM and perlecan-labeled PCM sites within the outer, middle, and inner porcine medial meniscus, and to evaluate the properties of the proximal surface of each region. The elastic modulus of the PCM was significantly higher in the outer region (151.4 ± 38.2 kPa) than the inner region (27.5 ± 8.8 kPa), and ECM moduli were consistently higher than region-matched PCM sites in both the outer (320.8 ± 92.5 kPa) and inner (66.1 ± 31.4 kPa) regions. These differences were associated with a higher proportion of aligned collagen fibers and lower glycosaminoglycan content in the outer region. Regional variations in the elastic moduli and some viscoelastic properties were observed on the proximal surface of the meniscus, with the inner region exhibiting the highest moduli overall. These results indicate that matrix architecture and composition play an important role in the regional micromechanical properties of the meniscus, suggesting that the local stress-strain environment of meniscal cells may vary significantly among the different regions.

  15. Somatic embryos from callus of Sequoia sempervirens.

    PubMed

    Bourgkard, F; Favre, J M

    1988-10-01

    Compact calli with a potential for somatic embryogenesis were obtained from complete or split mature zygotic embryos or from cotyledons and hypocotyls of in vitro grown seedlings of Sequoia sempervirens. Somatic embryos which showed a typical bipolar structure, were formed together with adventitious buds. When placed on filter paper supports they developed into complete plantlets. Of the various combinations tested, culture medium adapted from Murashige and Skoog mineral solution complemented with 6-benzylaminopurine (2 μM), kinetin (2 μM) and 2,4-dichlorophenoxyacetic acid (2.5 μM) was established as the optimal for somatic embryo production.

  16. The rich somatic life of Wolbachia.

    PubMed

    Pietri, Jose E; DeBruhl, Heather; Sullivan, William

    2016-12-01

    Wolbachia is an intracellular endosymbiont infecting most arthropod and some filarial nematode species that is vertically transmitted through the maternal lineage. Due to this primary mechanism of transmission, most studies have focused on Wolbachia interactions with the host germline. However, over the last decade many studies have emerged highlighting the prominence of Wolbachia in somatic tissues, implicating somatic tissue tropism as an important aspect of the life history of this endosymbiont. Here, we review our current understanding of Wolbachia-host interactions at both the cellular and organismal level, with a focus on Wolbachia in somatic tissues. © 2016 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  17. Temporal Fluctuation in North East Baltic Sea Region Cattle Population Revealed by Mitochondrial and Y-Chromosomal DNA Analyses

    PubMed Central

    Niemi, Marianna; Bläuer, Auli; Iso-Touru, Terhi; Harjula, Janne; Nyström Edmark, Veronica; Rannamäe, Eve; Lõugas, Lembi; Sajantila, Antti; Lidén, Kerstin; Taavitsainen, Jussi-Pekka

    2015-01-01

    Background Ancient DNA analysis offers a way to detect changes in populations over time. To date, most studies of ancient cattle have focused on their domestication in prehistory, while only a limited number of studies have analysed later periods. Conversely, the genetic structure of modern cattle populations is well known given the undertaking of several molecular and population genetic studies. Results Bones and teeth from ancient cattle populations from the North-East Baltic Sea region dated to the Prehistoric (Late Bronze and Iron Age, 5 samples), Medieval (14), and Post-Medieval (26) periods were investigated by sequencing 667 base pairs (bp) from the mitochondrial DNA (mtDNA) and 155 bp of intron 19 in the Y-chromosomal UTY gene. Comparison of maternal (mtDNA haplotypes) genetic diversity in ancient cattle (45 samples) with modern cattle populations in Europe and Asia (2094 samples) revealed 30 ancient mtDNA haplotypes, 24 of which were shared with modern breeds, while 6 were unique to the ancient samples. Of seven Y-chromosomal sequences determined from ancient samples, six were Y2 and one Y1 haplotype. Combined data including Swedish samples from the same periods (64 samples) was compared with the occurrence of Y-chromosomal haplotypes in modern cattle (1614 samples). Conclusions The diversity of haplogroups was highest in the Prehistoric samples, where many haplotypes were unique. The Medieval and Post-Medieval samples also show a high diversity with new haplotypes. Some of these haplotypes have become frequent in modern breeds in the Nordic Countries and North-Western Russia while other haplotypes have remained in only a few local breeds or seem to have been lost. A temporal shift in Y-chromosomal haplotypes from Y2 to Y1 was detected that corresponds with the appearance of new mtDNA haplotypes in the Medieval and Post-Medieval period. This suggests a replacement of the Prehistoric mtDNA and Y chromosomal haplotypes by new types of cattle. PMID:25992976

  18. Pilates, Mindfulness and Somatic Education

    PubMed Central

    Caldwell, Karen; Quin, Rebecca; Harrison, Mandy; Greeson, Jeffrey

    2014-01-01

    The Pilates Method is a form of somatic education with the potential to cultivate mindfulness – a mental quality associated with overall well-being. However, controlled studies are needed to determine whether changes in mindfulness are specific to the Pilates Method or also result from other forms of exercise. This quasi-experimental study compared Pilates Method mat classes and recreational exercise classes on measures of mindfulness and well-being at the beginning, middle and end of a 15 week semester. Total mindfulness scores increased overall for the Pilates Method group but not for the exercise control group, and these increases were directly related to end of semester ratings of self-regulatory self-efficacy, perceived stress and mood. Findings suggest that the Pilates Method specifically enhances mindfulness, and these increases are associated with other measures of wellness. The changes in mindfulness identified in this study support the role of the Pilates Method in the mental well-being of its practitioners and its potential to support dancers’ overall well-being. PMID:25328542

  19. Pilates, Mindfulness and Somatic Education.

    PubMed

    Caldwell, Karen; Adams, Marianne; Quin, Rebecca; Harrison, Mandy; Greeson, Jeffrey

    2013-12-01

    The Pilates Method is a form of somatic education with the potential to cultivate mindfulness - a mental quality associated with overall well-being. However, controlled studies are needed to determine whether changes in mindfulness are specific to the Pilates Method or also result from other forms of exercise. This quasi-experimental study compared Pilates Method mat classes and recreational exercise classes on measures of mindfulness and well-being at the beginning, middle and end of a 15 week semester. Total mindfulness scores increased overall for the Pilates Method group but not for the exercise control group, and these increases were directly related to end of semester ratings of self-regulatory self-efficacy, perceived stress and mood. Findings suggest that the Pilates Method specifically enhances mindfulness, and these increases are associated with other measures of wellness. The changes in mindfulness identified in this study support the role of the Pilates Method in the mental well-being of its practitioners and its potential to support dancers' overall well-being.

  20. Somatic mutations affect key pathways in lung adenocarcinoma

    PubMed Central

    Ding, Li; Getz, Gad; Wheeler, David A.; Mardis, Elaine R.; McLellan, Michael D.; Cibulskis, Kristian; Sougnez, Carrie; Greulich, Heidi; Muzny, Donna M.; Morgan, Margaret B.; Fulton, Lucinda; Fulton, Robert S.; Zhang, Qunyuan; Wendl, Michael C.; Lawrence, Michael S.; Larson, David E.; Chen, Ken; Dooling, David J.; Sabo, Aniko; Hawes, Alicia C.; Shen, Hua; Jhangiani, Shalini N.; Lewis, Lora R.; Hall, Otis; Zhu, Yiming; Mathew, Tittu; Ren, Yanru; Yao, Jiqiang; Scherer, Steven E.; Clerc, Kerstin; Metcalf, Ginger A.; Ng, Brian; Milosavljevic, Aleksandar; Gonzalez-Garay, Manuel L.; Osborne, John R.; Meyer, Rick; Shi, Xiaoqi; Tang, Yuzhu; Koboldt, Daniel C.; Lin, Ling; Abbott, Rachel; Miner, Tracie L.; Pohl, Craig; Fewell, Ginger; Haipek, Carrie; Schmidt, Heather; Dunford-Shore, Brian H.; Kraja, Aldi; Crosby, Seth D.; Sawyer, Christopher S.; Vickery, Tammi; Sander, Sacha; Robinson, Jody; Winckler, Wendy; Baldwin, Jennifer; Chirieac, Lucian R.; Dutt, Amit; Fennell, Tim; Hanna, Megan; Johnson, Bruce E.; Onofrio, Robert C.; Thomas, Roman K.; Tonon, Giovanni; Weir, Barbara A.; Zhao, Xiaojun; Ziaugra, Liuda; Zody, Michael C.; Giordano, Thomas; Orringer, Mark B.; Roth, Jack A.; Spitz, Margaret R.; Wistuba, Ignacio I.; Ozenberger, Bradley; Good, Peter J.; Chang, Andrew C.; Beer, David G.; Watson, Mark A.; Ladanyi, Marc; Broderick, Stephen; Yoshizawa, Akihiko; Travis, William D.; Pao, William; Province, Michael A.; Weinstock, George M.; Varmus, Harold E.; Gabriel, Stacey B.; Lander, Eric S.; Gibbs, Richard A.; Meyerson, Matthew; Wilson, Richard K.

    2009-01-01

    Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers—including NF1, APC, RB1 and ATM—and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment. PMID:18948947

  1. Somatic Symptoms Mediate the Relationship Between Trauma During the Arab Spring and Quality of Life Among Tunisians.

    PubMed

    Hiar, Soraya; Thomas, Charmaine L; Hinton, Devon E; Salles, Juliette; Goutaudier, Nelly; Olliac, Bertrand; Bui, Eric

    2016-02-01

    This study examined the relationship between peritraumatic reactions, posttraumatic stress disorder (PTSD) symptoms, somatic complaints, and quality of life in Tunisians exposed to the events of the Arab Spring. Participants (n = 60) completed an online survey 1 year after the events, assessing peritraumatic distress, peritraumatic dissociation, PTSD symptoms, somatic complaints, and physical and mental quality of life. Results showed that peritraumatic dissociation was independently associated with increased PTSD symptoms and somatic complaints 12 months after the events. Multiple mediator mediation analyses revealed that somatic complaints (not PTSD symptoms) were the only independent mediators of the relationships between peritraumatic dissociation and both physical and mental quality of life. Assessing peritraumatic dissociation soon after trauma exposure among the North African population might help identify individuals at risk for PTSD. Furthermore, the impact of trauma on quality of life may be better explained by somatic complaints than PTSD symptoms among North Africans.

  2. ECONOMIC STRESSORS AND ALCOHOL-RELATED OUTCOMES: EXPLORING GENDER DIFFERENCES IN THE MEDIATING ROLE OF SOMATIC COMPLAINTS

    PubMed Central

    BROWN, ROBYN LEWIS; RICHMAN, JUDITH A.; ROSPENDA, KATHLEEN M.

    2015-01-01

    This study examined processes linking economic stressors, somatic complaints, and two alcohol-related outcomes (past-month drinking and problematic drinking). Structural equation models of data from a national survey revealed that somatic complaints partly explain the association between economic stressors and problematic drinking. The associations of both economic stressors and somatic complaints with problematic drinking were significantly greater for men than women. However, the association between economic stressors and somatic complaints was greater for women. These findings clarify the circumstances in which gender matters most for the associations among economy-related stressors, somatic complaints, and drinking. They highlight the significance of difficult economic circumstances for physical health and, in turn, problematic drinking – particularly among men. PMID:25310370

  3. Processed pseudogenes acquired somatically during cancer development

    PubMed Central

    Cooke, Susanna L.; Shlien, Adam; Marshall, John; Pipinikas, Christodoulos P.; Martincorena, Inigo; Tubio, Jose M.C.; Li, Yilong; Menzies, Andrew; Mudie, Laura; Ramakrishna, Manasa; Yates, Lucy; Davies, Helen; Bolli, Niccolo; Bignell, Graham R.; Tarpey, Patrick S.; Behjati, Sam; Nik-Zainal, Serena; Papaemmanuil, Elli; Teixeira, Vitor H.; Raine, Keiran; O’Meara, Sarah; Dodoran, Maryam S.; Teague, Jon W.; Butler, Adam P.; Iacobuzio-Donahue, Christine; Santarius, Thomas; Grundy, Richard G.; Malkin, David; Greaves, Mel; Munshi, Nikhil; Flanagan, Adrienne M.; Bowtell, David; Martin, Sancha; Larsimont, Denis; Reis-Filho, Jorge S.; Boussioutas, Alex; Taylor, Jack A.; Hayes, Neil D.; Janes, Sam M.; Futreal, P. Andrew; Stratton, Michael R.; McDermott, Ultan; Campbell, Peter J.; Provenzano, Elena; van de Vijver, Marc; Richardson, Andrea L.; Purdie, Colin; Pinder, Sarah; Mac Grogan, Gaetan; Vincent-Salomon, Anne; Larsimont, Denis; Grabau, Dorthe; Sauer, Torill; Garred, Øystein; Ehinger, Anna; Van den Eynden, Gert G.; van Deurzen, C.H.M; Salgado, Roberto; Brock, Jane E.; Lakhani, Sunil R.; Giri, Dilip D.; Arnould, Laurent; Jacquemier, Jocelyne; Treilleux, Isabelle; Caldas, Carlos; Chin, Suet-Feung; Fatima, Aquila; Thompson, Alastair M.; Stenhouse, Alasdair; Foekens, John; Martens, John; Sieuwerts, Anieta; Brinkman, Arjen; Stunnenberg, Henk; Span, Paul N.; Sweep, Fred; Desmedt, Christine; Sotiriou, Christos; Thomas, Gilles; Broeks, Annegein; Langerod, Anita; Aparicio, Samuel; Simpson, Peter T.; van ’t Veer, Laura; Erla Eyfjörd, Jórunn; Hilmarsdottir, Holmfridur; Jonasson, Jon G.; Børresen-Dale, Anne-Lise; Lee, Ming Ta Michael; Wong, Bernice Huimin; Tan, Benita Kiat Tee; Hooijer, Gerrit K.J.

    2014-01-01

    Cancer evolves by mutation, with somatic reactivation of retrotransposons being one such mutational process. Germline retrotransposition can cause processed pseudogenes, but whether this occurs somatically has not been evaluated. Here we screen sequencing data from 660 cancer samples for somatically acquired pseudogenes. We find 42 events in 17 samples, especially non-small cell lung cancer (5/27) and colorectal cancer (2/11). Genomic features mirror those of germline LINE element retrotranspositions, with frequent target-site duplications (67%), consensus TTTTAA sites at insertion points, inverted rearrangements (21%), 5′ truncation (74%) and polyA tails (88%). Transcriptional consequences include expression of pseudogenes from UTRs or introns of target genes. In addition, a somatic pseudogene that integrated into the promoter and first exon of the tumour suppressor gene, MGA, abrogated expression from that allele. Thus, formation of processed pseudogenes represents a new class of mutation occurring during cancer development, with potentially diverse functional consequences depending on genomic context. PMID:24714652

  4. Review of somatic symptoms in post-traumatic stress disorder.

    PubMed

    Gupta, Madhulika A

    2013-02-01

    Post-traumatic stress disorder (PTSD) is associated with both (1) 'ill-defined' or 'medically unexplained' somatic syndromes, e.g. unexplained dizziness, tinnitus and blurry vision, and syndromes that can be classified as somatoform disorders (DSM-IV-TR); and (2) a range of medical conditions, with a preponderance of cardiovascular, respiratory, musculoskeletal, neurological, and gastrointestinal disorders, diabetes, chronic pain, sleep disorders and other immune-mediated disorders in various studies. Frequently reported medical co-morbidities with PTSD across various studies include cardiovascular disease, especially hypertension, and immune-mediated disorders. PTSD is associated with limbic instability and alterations in both the hypothalamic- pituitary-adrenal and sympatho-adrenal medullary axes, which affect neuroendocrine and immune functions, have central nervous system effects resulting in pseudo-neurological symptoms and disorders of sleep-wake regulation, and result in autonomic nervous system dysregulation. Hypervigilance, a central feature of PTSD, can lead to 'local sleep' or regional arousal states, when the patient is partially asleep and partially awake, and manifests as complex motor and/or verbal behaviours in a partially conscious state. The few studies of the effects of standard PTSD treatments (medications, CBT) on PTSD-associated somatic syndromes report a reduction in the severity of ill-defined and autonomically mediated somatic symptoms, self-reported physical health problems, and some chronic pain syndromes.

  5. Proteogenomics connects somatic mutations to signalling in breast cancer.

    PubMed

    Mertins, Philipp; Mani, D R; Ruggles, Kelly V; Gillette, Michael A; Clauser, Karl R; Wang, Pei; Wang, Xianlong; Qiao, Jana W; Cao, Song; Petralia, Francesca; Kawaler, Emily; Mundt, Filip; Krug, Karsten; Tu, Zhidong; Lei, Jonathan T; Gatza, Michael L; Wilkerson, Matthew; Perou, Charles M; Yellapantula, Venkata; Huang, Kuan-lin; Lin, Chenwei; McLellan, Michael D; Yan, Ping; Davies, Sherri R; Townsend, R Reid; Skates, Steven J; Wang, Jing; Zhang, Bing; Kinsinger, Christopher R; Mesri, Mehdi; Rodriguez, Henry; Ding, Li; Paulovich, Amanda G; Fenyö, David; Ellis, Matthew J; Carr, Steven A

    2016-06-02

    Somatic mutations have been extensively characterized in breast cancer, but the effects of these genetic alterations on the proteomic landscape remain poorly understood. Here we describe quantitative mass-spectrometry-based proteomic and phosphoproteomic analyses of 105 genomically annotated breast cancers, of which 77 provided high-quality data. Integrated analyses provided insights into the somatic cancer genome including the consequences of chromosomal loss, such as the 5q deletion characteristic of basal-like breast cancer. Interrogation of the 5q trans-effects against the Library of Integrated Network-based Cellular Signatures, connected loss of CETN3 and SKP1 to elevated expression of epidermal growth factor receptor (EGFR), and SKP1 loss also to increased SRC tyrosine kinase. Global proteomic data confirmed a stromal-enriched group of proteins in addition to basal and luminal clusters, and pathway analysis of the phosphoproteome identified a G-protein-coupled receptor cluster that was not readily identified at the mRNA level. In addition to ERBB2, other amplicon-associated highly phosphorylated kinases were identified, including CDK12, PAK1, PTK2, RIPK2 and TLK2. We demonstrate that proteogenomic analysis of breast cancer elucidates the functional consequences of somatic mutations, narrows candidate nominations for driver genes within large deletions and amplified regions, and identifies therapeutic targets.

  6. (Somatic mutations in nuclear and mitochondrial DNA)

    SciTech Connect

    Not Available

    1992-01-01

    The study is concerned the design of new assays that may detect rare somatic mutations in nuclear and mitochondrial DNA, which may increase upon exposure to mutagens, and thus become a marker of human exposure to such mutagens. Two assays for somatic mutation were presented, one for mitochondrial DNA deletions which was developed by the author, and one for deletions of the ADA gene which resides in the nucleus.

  7. Progress in the reprogramming of somatic cells.

    PubMed

    Ma, Tianhua; Xie, Min; Laurent, Timothy; Ding, Sheng

    2013-02-01

    Pluripotent stem cells can differentiate into nearly all types of cells in the body. This unique potential provides significant promise for cell-based therapies to restore tissues or organs destroyed by injuries, degenerative diseases, aging, or cancer. The discovery of induced pluripotent stem cell (iPSC) technology offers a possible strategy to generate patient-specific pluripotent stem cells. However, because of concerns about the specificity, efficiency, kinetics, and safety of iPSC reprogramming, improvements or fundamental changes in this process are required before their effective clinical use. A chemical approach is regarded as a promising strategy to improve and change the iPSC process. Dozens of small molecules have been identified that can functionally replace reprogramming factors and significantly improve iPSC reprogramming. In addition to the prospect of deriving patient-specific tissues and organs from iPSCs, another attractive strategy for regenerative medicine is transdifferentiation-the direct conversion of one somatic cell type to another. Recent studies revealed a new paradigm of transdifferentiation: using transcription factors used in iPSC generation to induce transdifferentiation or called iPSC transcription factor-based transdifferentiation. This type of transdifferentiation not only reveals and uses the developmentally plastic intermediates generated during iPSC reprogramming but also produces a wide range of cells, including expandable tissue-specific precursor cells. Here, we review recent progress of small molecule approaches in the generation of iPSCs. In addition, we summarize the new concept of iPSC transcription factor-based transdifferentiation and discuss its application in generating various lineage-specific cells, especially cardiovascular cells.

  8. Dance and Somatic Inquiry in Studios and Community Dance Programs.

    ERIC Educational Resources Information Center

    Eddy, Martha Hart

    2002-01-01

    Addresses pragmatic aspects of somatics in the public sector, investigating the fit of somatics within various institutions and settings, including universities, professional schools, and community programs. The article explores issues such as somatic movement approaches, certification, academic degrees in somatic study, confusions within the…

  9. Living in Movement: Development of Somatic Practices in Different Cultures.

    ERIC Educational Resources Information Center

    Fortin, Sylvie

    2002-01-01

    Provides a transcultural perspective on somatics, reflecting on the evolution of somatics in different dance communities around the world, noting shifts that have occurred within specific cultural contexts, and discussing the presence of somatics in academia with the challenge of conducting research that retains somatic integrity. The article…

  10. Delineation of a slow-twitch-myofiber-specific transcriptional element by using in vivo somatic gene transfer.

    PubMed Central

    Corin, S J; Levitt, L K; O'Mahoney, J V; Joya, J E; Hardeman, E C; Wade, R

    1995-01-01

    Contractile proteins are encoded by multigene families, most of whose members are differentially expressed in fast- versus slow-twitch myofibers. This fiber-type-specific gene regulation occurs by unknown mechanisms and does not occur within cultured myocytes. We have developed a transient, whole-animal assay using somatic gene transfer to study this phenomenon and have identified a fiber-type-specific regulatory element within the promoter region of a slow myofiber-specific gene. A plasmid-borne luciferase reporter gene fused to various muscle-specific contractile gene promoters was differentially expressed when injected into slow- versus fast-twitch rat muscle: the luciferase gene was preferentially expressed in slow muscle when fused to a slow troponin I promoter, and conversely, was preferentially expressed in fast muscle when fused to a fast troponin C promoter. In contrast, the luciferase gene was equally well expressed by both muscle types when fused to a nonfiber-type-specific skeletal actin promoter. Deletion analysis of the troponin I promoter region revealed that a 157-bp enhancer conferred slow-muscle-preferential activity upon a minimal thymidine kinase promoter. Transgenic analysis confirmed the role of this enhancer in restricting gene expression to slow-twitch myofibers. Hence, somatic gene transfer may be used to rapidly define elements that direct myofiber-type-specific gene expression prior to the generation of transgenic mice. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7597099

  11. Multicellularity makes somatic differentiation evolutionarily stable

    PubMed Central

    Wahl, Mary E.; Murray, Andrew W.

    2016-01-01

    Many multicellular organisms produce two cell lineages: germ cells, whose descendants produce the next generation, and somatic cells, which support, protect, and disperse the germ cells. This germ-soma demarcation has evolved independently in dozens of multicellular taxa but is absent in unicellular species. A common explanation holds that in these organisms, inefficient intercellular nutrient exchange compels the fitness cost of producing nonreproductive somatic cells to outweigh any potential benefits. We propose instead that the absence of unicellular, soma-producing populations reflects their susceptibility to invasion by nondifferentiating mutants that ultimately eradicate the soma-producing lineage. We argue that multicellularity can prevent the victory of such mutants by giving germ cells preferential access to the benefits conferred by somatic cells. The absence of natural unicellular, soma-producing species previously prevented these hypotheses from being directly tested in vivo: to overcome this obstacle, we engineered strains of the budding yeast Saccharomyces cerevisiae that differ only in the presence or absence of multicellularity and somatic differentiation, permitting direct comparisons between organisms with different lifestyles. Our strains implement the essential features of irreversible conversion from germ line to soma, reproductive division of labor, and clonal multicellularity while maintaining sufficient generality to permit broad extension of our conclusions. Our somatic cells can provide fitness benefits that exceed the reproductive costs of their production, even in unicellular strains. We find that nondifferentiating mutants overtake unicellular populations but are outcompeted by multicellular, soma-producing strains, suggesting that multicellularity confers evolutionary stability to somatic differentiation. PMID:27402737

  12. Amphetamine treatment during early postnatal development transiently restricts somatic growth

    PubMed Central

    Smith, Andrew M.; Chen, Wei-Jung A.

    2010-01-01

    Aims Restricted somatic growth during fetal or early postnatal periods has been suggested to serve as a predictive indicator for neuroanatomical changes and behavioral impairments during adulthood. Here, the effects of d-amphetamine sulphate (AMPH) exposure during the brain growth spurt period on this potential indicator were evaluated. Main Methods Rats received 0, 5, 15 or 25 mg/kg/day of AMPH via two daily intragastric intubations from PD4-9. Body weight data were collected every other day from PD1 to 21, and then weekly until PD59. On PD9, a subset of animals was terminated 90 min after the last amphetamine treatment and the weights of the cortex, cerebellum, and brainstem were collected. Weights of these brain regions from young adult rats were also assessed on PD68. Key Findings AMPH exposure during early postnatal development limited somatic growth in a dose-related manner, with significantly lower body weights in animals assigned to the AMPH 25 and AMPH 15 groups. However, this was transient in nature, with no significant difference in weight observed after pups were weaned on PD21. Further, no differences in brain weight were observed at either age as a result of AMPH exposure. Significance These findings support the idea that developmental AMPH exposure transiently restricts somatic growth. Moreover, the lack of effect on brain weight shows that AMPH differentially affects somatic and brain growth. The current findings suggest that in addition to the immediate effects on body weight, amphetamine may alter the rate of growth, and increase the risk for weight-related adult diseases. PMID:20153755

  13. Somatic embryogenesis from bud and leaf explants of date palm (Phoenix dactylifera L.) cv. Najda.

    PubMed

    Mazri, Mouaad Amine; Belkoura, Ilham; Meziani, Reda; Mokhless, Boutaïna; Nour, Souad

    2017-05-01

    An efficient regeneration system through somatic embryogenesis was developed for date palm cv. Najda. Adventitious bud and proximal leaf segments cultured on Murashige and Skoog (MS) medium supplemented with various combinations of auxins and cytokinins induced embryogenesis after at least 6 months of culture. Somatic embryogenesis induction seemed correlated with the type of the explant, the induction period and the auxin used. The highest rate of somatic embryogenesis (86.0%) was obtained on bud explants cultured on MS medium supplemented with 45.0 µM 2,4-dichlorophenoxyacetic acid (2,4-D), and 4.5 µM kinetin or 4.5 µM 6-(dimethylallylamino) purine (2iP). Whereas, low levels of embryogenesis were obtained on media supplemented with 1-naphthalene acetic acid (NAA) or 2-naphthoxyacetic acid (NOA). Proximal leaf segments showed somatic embryogenesis only when cultured on media supplemented with 2,4-D or picloram. Statistical analysis revealed significant effects of explant type and plant growth regulators (PGRs) combination on somatic embryogenesis. Somatic embryos were germinated successfully on PGR-free MS medium with or without activated charcoal (50.0-60.0 and 26.6-36.6%, respectively), and 80.0% of plantlets survived after transferring to a glasshouse for 6 months. Our results will be useful for large-scale propagation of date palm cv. Najda, characterized by high fruit quality and bayoud disease resistance.

  14. Fluid escape structures in the Graham Bank region (Sicily Channel, Central Mediterranean) revealing volcanic and neotectonic activity.

    NASA Astrophysics Data System (ADS)

    Spatola, Daniele; Pennino, Valentina; Basilone, Luca; Interbartolo, Francesco; Micallef, Aaron; Sulli, Attilio; Basilone, Walter

    2016-04-01

    morphometric analysis of these volcanoes has been conducted: they are up to about 115-160 m high and 500-1500 m wide. Most of them show very strongly inclined flanks with 30° of average slope. The SCV2 and SCV3 form the Graham Bank, 3.5X2.8 km wide, elongated in the NW-SE direction. At the top of SCV2 focused seepage plumes were observed in the entire water column, through the CHIRP data, where we calculated that they release, a volume of about 10950 m3 and 43960 m3of gases, respectively. In this work, we present the first results of a data collection that have got as main result the identification and mapping of the fluid escape structures revealing the relationship between the active tectonic with migration of fluids, to be used to assess the Submarine Geo-Hazard in the Sicily Channel. We identified two fluid escape fields whose genesis and evolution appear linked to the neotectonic and volcanic activities respectively, that represent the main controlling factors for the migration of fluid; considering the good correlation between pockmarks and the main identified fault systems. In conclusion, our results suggest that the degassing of fluids in this region is rooted at depth, and is mainly aligned with the NW-SE dip/strike slip fault systems, repeatedly reactivated, and linked to the volcanic activity.

  15. Modeling of region-specific fMRI BOLD neurovascular response functions in rat brain reveals residual differences that correlate with the differences in regional evoked potentials

    PubMed Central

    Pawela, Christopher P.; Hudetz, Anthony G.; Ward, B. Douglas; Schulte, Marie L.; Li, Rupeng; Kao, Dennis S.; Mauck, Matthew C.; Cho, Younghoon R.; Neitz, Jay; Hyde, James S.

    2008-01-01

    The response of the rat visual system to flashes of blue light has been studied by blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). The BOLD temporal response is dependent on the number of flashes presented and demonstrates a refractory period that depends on flash frequency. Activated brain regions included the primary and secondary visual cortex, superior colliculus (SC), dorsal Lateral Geniculate (DLG), and Lateral Posterior Nucleus (LP), which were found to exhibit differing temporal responses. To explain these differences, the BOLD neurovascular response function was modeled. A second order differential equation was developed and solved numerically to arrive at region-specific response functions. Included in the model are the light input from the diode (duty cycle), a refractory period, a transient response following onset and cessation of stimulus, and a slow adjustment to changes in the average level of the signal. Constants in the differential equation were evaluated for each region by fitting the model to the experimental BOLD response from a single flash, and the equation was then solved for multiple flashes. The simulation mimics the major features of the data; however, remaining differences in the frequency dependence of the response between the cortical and subcortical regions were unexplained. We hypothesized that these discrepancies were due to regional-specific differences in neuronal response to flash frequency. To test this hypothesis, cortical visual evoked potentials (VEPs) were recorded using the same stimulation protocol as the fMRI. Cortical VEPs were more suppressed than subcortical VEPs as flash frequency increased, supporting our hypothesis. This is the first report that regional differences in neuronal activation to the same stimulus lead to differential BOLD activation. PMID:18406628

  16. Kinematic mapping reveals different spatial distributions of center of pressure high-speed regions under somatosensory loss.

    PubMed

    Portela, Fellipe M; Ferreira, Arthur S

    2014-01-01

    The spatial distribution of center-of-pressure speed during postural tasks and its changes due to somatosensory constraint (temporary ischemic hypoxia on ankle/feet) were investigated in young, healthy subjects (n = 13). A single high-speed region in the central region of the statokinesigram was observed during postural tasks with full sensory information. A significant increase in the quantity of high-speed regions was observed during ischemia and somatosensory constraint, whereas a significant increase in the quantity of high-speed regions localized more distant to the center of center-of-pressure area occurred under somatosensory constraints, suggesting a redirection of center-of-pressure trajectory to adjust the position of the center of mass with respect to the egocentric reference of balance.

  17. Novel Variants of Oct-3/4 Gene Expressed in Mouse Somatic Cells*S⃞

    PubMed Central

    Mizuno, Nobuhiko; Kosaka, Mitsuko

    2008-01-01

    It has been suggested that Oct-3/4 may regulate self-renewal in somatic stem cells, as it does in embryonic stem cells. However, recent reports raise the possibility that detection of human Oct-3/4 expression by RT-PCR is prone to artifacts generated by pseudogene transcripts and argue against a role for Oct-3/4 in somatic cells. In this study, we clarified Oct-3/4 expression in mouse somatic tissues using designed PCR primers, which can exclude amplification of its pseudogenes. We found that novel alternative transcripts are indeed expressed in somatic tissues, rather than the normal length transcripts in germline and ES cells. The alternative transcripts indicate the expression of two kinds of truncated proteins. Furthermore, we determined novel promoter regions that are sufficient for the expression of Oct-3/4 transcript variants in somatic cells. These findings provide new insights into the postnatal role of Oct-3/4 in somatic tissues. PMID:18765667

  18. NMR-based metabolomics reveals brain region-specific metabolic alterations in streptozotocin-induced diabetic rats with cognitive dysfunction.

    PubMed

    Zheng, Hong; Lin, Qiuting; Wang, Dan; Xu, Pengtao; Zhao, Liangcai; Hu, Wenyi; Bai, Guanghui; Yan, Zhihan; Gao, Hongchang

    2017-04-01

    Diabetes mellitus (DM) can result in cognitive dysfunction, but its potential metabolic mechanisms remain unclear. In the present study, we analyzed the metabolite profiling in eight different brain regions of the normal rats and the streptozotocin (STZ)-induced diabetic rats accompanied by cognitive dysfunction using a (1)H NMR-based metabolomic approach. A mixed linear model analysis was performed to assess the effects of DM, brain region and their interaction on metabolic changes. We found that different brain regions in rats displayed significant metabolic differences. In addition, the hippocampus was more susceptible to DM compared with other brain regions in rats. More interestingly, significant interaction effects of DM and brain region were observed on alanine, creatine/creatine-phosphate, lactate, succinate, aspartate, glutamate, glutamine, γ-aminobutyric acid, glycine, choline, N-acetylaspartate, myo-inositol and taurine. Based on metabolic pathway analysis, we speculate that cognitive dysfunction in the STZ-induced diabetic rats may be associated with brain region-specific metabolic alterations involving energy metabolism, neurotransmitters, membrane metabolism and osmoregulation.

  19. Somatic Mutations in Cerebral Cortical Malformations

    PubMed Central

    Jamuar, Saumya S.; Lam, Anh-Thu N.; Kircher, Martin; D'Gama, Alissa M.; Wang, Jian; Barry, Brenda J.; Zhang, Xiaochang; Hill, Robert Sean; Partlow, Jennifer N.; Rozzo, Aldo; Servattalab, Sarah; Mehta, Bhaven K.; Topcu, Meral; Amrom, Dina; Andermann, Eva; Dan, Bernard; Parrini, Elena; Guerrini, Renzo; Scheffer, Ingrid E.; Berkovic, Samuel F.; Leventer, Richard J.; Shen, Yiping; Wu, Bai Lin; Barkovich, A. James; Sahin, Mustafa; Chang, Bernard S.; Bamshad, Michael; Nickerson, Deborah A.; Shendure, Jay; Poduri, Annapurna; Yu, Timothy W.; Walsh, Christopher A.

    2014-01-01

    BACKGROUND Although there is increasing recognition of the role of somatic mutations in genetic disorders, the prevalence of somatic mutations in neurodevelopmental disease and the optimal techniques to detect somatic mosaicism have not been systematically evaluated. METHODS Using a customized panel of known and candidate genes associated with brain malformations, we applied targeted high-coverage sequencing (depth, ≥200×) to leukocyte-derived DNA samples from 158 persons with brain malformations, including the double-cortex syndrome (subcortical band heterotopia, 30 persons), polymicrogyria with megalencephaly (20), periventricular nodular heterotopia (61), and pachygyria (47). We validated candidate mutations with the use of Sanger sequencing and, for variants present at unequal read depths, subcloning followed by colony sequencing. RESULTS Validated, causal mutations were found in 27 persons (17%; range, 10 to 30% for each phenotype). Mutations were somatic in 8 of the 27 (30%), predominantly in persons with the double-cortex syndrome (in whom we found mutations in DCX and LIS1), persons with periventricular nodular heterotopia (FLNA), and persons with pachygyria (TUBB2B). Of the somatic mutations we detected, 5 (63%) were undetectable with the use of traditional Sanger sequencing but were validated through subcloning and subsequent sequencing of the subcloned DNA. We found potentially causal mutations in the candidate genes DYNC1H1, KIF5C, and other kinesin genes in persons with pachygyria. CONCLUSIONS Targeted sequencing was found to be useful for detecting somatic mutations in patients with brain malformations. High-coverage sequencing panels provide an important complement to whole-exome and whole-genome sequencing in the evaluation of somatic mutations in neuropsychiatric disease. (Funded by the National Institute of Neurological Disorders and Stroke and others.) PMID:25140959

  20. Metagenome Sequencing Reveals Rhodococcus Dominance in Farpuk Cave, Mizoram, India, an Eastern Himalayan Biodiversity Hot Spot Region

    PubMed Central

    De Mandal, Surajit; Sanga, Zothan

    2015-01-01

    The present study employed 16S rRNA amplicon sequencing to survey the prokaryotic microbiota on Farpuk Cave, revealing a diverse bacterial community with 4,021 operational taxonomical units (OTUs), mainly dominated by the genus Rhodococcus. Moreover, 18.17% of the OTUs were unclassified at the phylum level, suggesting the existence of novel bacterial species. PMID:26067958

  1. Morphallactic regeneration as revealed by region-specific gene expression in the digestive tract of Enchytraeus japonensis (Oligochaeta, Annelida).

    PubMed

    Takeo, Makoto; Yoshida-Noro, Chikako; Tochinai, Shin

    2008-05-01

    Enchytraeus japonensis is a small oligochaete, which primarily reproduces asexually by fragmentation and regeneration. For precise analysis of the pattern formation during regeneration, we isolated three region-specific genes (EjTuba, mino, and horu) expressed in the digestive tract. In growing worms, the expression of EjTuba in the head and mino in the trunk region just posterior to the head were observed in defined body segments, while the expression areas of EjTuba in the trunk and horu were proportional to the total number of body segments. In the regeneration process, expression of these genes disappeared once and recovered to their original pattern by day 7. In abnormal regeneration such as a bipolar head, mino was still expressed in the region next to both the normal and the ectopic heads. These results suggest that there is morphallactic as well as epimorphic or inductive regulation of the body patterning during regeneration of E. japonensis.

  2. Regional TNFα mapping in the brain reveals the striatum as a neuroinflammatory target after ventricular fibrillation cardiac arrest in rats☆

    PubMed Central

    Janata, Andreas; Magnet, Ingrid A.M.; Uray, Thomas; Stezoski, Jason P.; Janesko-Feldman, Keri; Tisherman, Samuel A.; Kochanek, Patrick M.; Drabek, Tomas

    2014-01-01

    Cardiac arrest (CA) triggers neuroinflammation that could play a role in a delayed neuronal death. In our previously established rat model of ventricular fibrillation (VF) CA characterized by extensive neuronal death, we tested the hypothesis that individual brain regions have specific neuroinflammatory responses, as reflected by regional brain tissue levels of tumor necrosis factor (TNF)α and other cytokines. In a prospective study, rats were randomized to 6 min (CA6), 8 min (CA8) or 10 min (CA10) of VF CA, or sham group. Cortex, striatum, hippocampus and cerebellum were evaluated for TNFα and interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12 and interferon gamma at 3 h, 6 h or 14 d after CA by ELISA and Luminex. Immunohistochemistry was used to determine the cell source of TNFα. CA resulted in a selective TNFα response with significant regional and temporal differences. At 3 h after CA, TNFα-levels increased in all regions depending on the duration of the insult. The most pronounced increase was observed in striatum that showed 20-fold increase in CA10 vs. sham, and 3-fold increase vs. CA6 or CA8 group, respectively (p < 0.01). TNFα levels in striatum decreased between 3 h and 6 h, but increased in other regions between 3 h and 14 d. TNFα levels remained twofold higher in CA6 vs. shams across brain regions at 14 d (p < 0.01). In contrast to pronounced TNFα response, other cytokines showed only a minimal increase in CA6 and CA8 groups vs. sham in all brain regions with the exception that IL-1β increased twofold in cerebellum and striatum (p < 0.01). TNFα colocalized with neurons. In conclusion, CA produced a duration-dependent acute TNFα response, with dramatic increase in the striatum where TNFα colocalized with neurons. Increased TNFα levels persist for at least two weeks. This TNFα surge contrasts the lack of an acute increase in other cytokines in brain after CA. Given that striatum is a selectively vulnerable brain region, our data

  3. [Somatization Symptoms in Lung Cancer Patients and Correlative Analysis between Anxiety, Depression and Somatization Symptoms].

    PubMed

    Zhang, Xinyao; Zhang, Xiaoye

    2017-07-20

    Lung cancer is a serious threat to human health and its morbidity and mortality in recent years has always been ranked first in the country. Lung cancer patients are often associated with anxiety, depression and other emotional problems, and anxiety, depression and other emotional problems will further lead to a series of somatic symptoms. At present, we lack the clinical understanding of somatization symptoms in patients with lung cancer and related clinical studies are not too much. This research is to study the features of clinical manifestation of lung cancer patients with somatization symptoms and correlative analysis between anxiety, depression and somatization symptoms in medical oncology department of general hospital. Lung cancer patients who met somatization symptoms diagnostic standard were assessed with the self-constructed somatic symptoms investigation questionnaire, the Chinese version of the Patient Health Questionnaire-15 (PHQ-15) and anxiety and depression were recorded by the Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD). The detection rate of the anxiety, depression and the number of patients with different severity somatization symptoms were calculated, the relationship between the PHQ-15 scores and anxiety and/or depression and the distribution of the different frequency somatization symptoms were analyzed. There were 43 patients with anxiety and/or depression in the 50 lung cancer patients with somatization symptoms. Prevalence rates of anxiety, depression and anxiety combined with depression were 10%, 10% and 66% respectively. The more severity the somatization symptoms are, the higher detection rates of anxiety combined with depression are. Significant positive correlations were observed between PHQ-15 scores, PHQ-15 positive symptom numbers and HAMA scores (r=0.752, P<0.001; r=0.710, P<0.001), HAMD scores (r=0.648, P<0.001; r=0.618, P<0.001). The most common somatization symptoms were fatigue (96%), weakness (88

  4. Multilocus phylogenetic analysis of true morels (Morchella) reveals high levels of endemics in Turkey relative ot other regions of Europe

    USDA-ARS?s Scientific Manuscript database

    The present study was conducted to better understand how the phylogenetic diversity of true morels (Morchella) in Turkey compares with species found in other regions of the world. The current research builds on our recently published survey of 10 Turkish provinces and another of the world in which D...

  5. Analysis of Genomic Regions Associated With Coronary Artery Disease Reveals Continent-Specific Single Nucleotide Polymorphisms in North African Populations.

    PubMed

    Zanetti, Daniela; Via, Marc; Carreras-Torres, Robert; Esteban, Esther; Chaabani, Hassen; Anaibar, Fatima; Harich, Nourdin; Habbal, Rachida; Ghalim, Noreddine; Moral, Pedro

    2016-05-05

    In recent years, several genomic regions have been robustly associated with coronary artery disease (CAD) in different genome-wide association studies (GWASs) conducted mainly in people of European descent. These kinds of data are lacking in African populations, even though heart diseases are a major cause of premature death and disability. Here, 384 single nucleotide polymorphisms (SNPs) in the top four CAD risk regions (1p13, 1q41, 9p21, and 10q11) were genotyped in 274 case-control samples from Morocco and Tunisia, with the aim of analyzing for the first time if the associations found in European populations were transferable to North Africans. The results indicate that, as in Europe, these four genetic regions are also important for CAD risk in North Africa. However, the individual SNPs associated with CAD in Africa are different from those identified in Europe in most cases (1p13, 1q41, and 9p21). Moreover, the seven risk variants identified in North Africans are efficient in discriminating between cases and controls in North African populations, but not in European populations. This study indicates a disparity in markers associated to CAD susceptibility between North Africans and Europeans that may be related to population differences in the chromosomal architecture of these risk regions.

  6. fMRI Reveals Distinct CNS Processing during Symptomatic and Recovered Complex Regional Pain Syndrome in Children

    ERIC Educational Resources Information Center

    Lebel, A.; Becerra, L.; Wallin, D.; Moulton, E. A.; Morris, S.; Pendse, G.; Jasciewicz, J.; Stein, M.; Aiello-Lammens, M.; Grant, E.; Berde, C.; Borsook, D.

    2008-01-01

    Complex regional pain syndrome (CRPS) in paediatric patients is clinically distinct from the adult condition in which there is often complete resolution of its signs and symptoms within several months to a few years. The ability to compare the symptomatic and asymptomatic condition in the same individuals makes this population interesting for the…

  7. Employing 454 amplicon pyrosequencing to reveal intragenomic divergence in the internal transcribed spacer rDNA region in fungi

    Treesearch

    Daniel L. Lindner; Tor Carlsen; Henrik Nilsson; Marie Davey; Trond Schumacher; Havard. Kauserud

    2013-01-01

    The rDNA internal transcribed spacer (ITS) region has been accepted as a DNA barcoding marker for fungi and is widely used in phylogenetic studies; however, intragenomic ITS variability has been observed in a broad range of taxa, including prokaryotes, plants, animals, and fungi, and this variability has the potential to inflate species richness estimates in molecular...

  8. RNA sequencing reveals region-specific molecular mechanisms associated with epileptogenesis in a model of classical hippocampal sclerosis

    PubMed Central

    Vieira, A. S.; de Matos, A. H.; do Canto, A. M.; Rocha, C. S.; Carvalho, B. S.; Pascoal, V. D. B.; Norwood, B.; Bauer, S.; Rosenow, F.; Gilioli, R.; Cendes, F.; Lopes-Cendes, I.

    2016-01-01

    We report here the first complete transcriptome analysis of the dorsal (dDG) and ventral dentate gyrus (vDG) of a rat epilepsy model presenting a hippocampal lesion with a strict resemblance to classical hippocampal sclerosis (HS). We collected the dDG and vDG by laser microdissection 15 days after electrical stimulation and performed high-throughput RNA-sequencing. There were many differentially regulated genes, some of which were specific to either of the two sub-regions in stimulated animals. Gene ontology analysis indicated an enrichment of inflammation-related processes in both sub-regions and of axonal guidance and calcium signaling processes exclusively in the vDG. There was also a differential regulation of genes encoding molecules involved in synaptic function, neural electrical activity and neuropeptides in stimulated rats. The data presented here suggests, in the time point analyzed, a remarkable interaction among several molecular components which takes place in the damaged hippocampi. Furthermore, even though similar mechanisms may function in different regions of the DG, the molecular components involved seem to be region specific. PMID:26935982

  9. Employing 454 amplicon pyrosequencing to reveal intragenomic divergence in the internal transcribed spacer rDNA region in fungi.

    PubMed

    Lindner, Daniel L; Carlsen, Tor; Henrik Nilsson, R; Davey, Marie; Schumacher, Trond; Kauserud, Håvard

    2013-06-01

    The rDNA internal transcribed spacer (ITS) region has been accepted as a DNA barcoding marker for fungi and is widely used in phylogenetic studies; however, intragenomic ITS variability has been observed in a broad range of taxa, including prokaryotes, plants, animals, and fungi, and this variability has the potential to inflate species richness estimates in molecular investigations of environmental samples. In this study 454 amplicon pyrosequencing of the ITS1 region was applied to 99 phylogenetically diverse axenic single-spore cultures of fungi (Dikarya: Ascomycota and Basidiomycota) to investigate levels of intragenomic variation. Three species (one Basidiomycota and two Ascomycota), in addition to a positive control species known to contain ITS paralogs, displayed levels of molecular variation indicative of intragenomic variation; taxon inflation due to presumed intragenomic variation was ≈9%. Intragenomic variability in the ITS region appears to be widespread but relatively rare in fungi (≈3-5% of species investigated in this study), suggesting this problem may have minor impacts on species richness estimates relative to PCR and/or pyrosequencing errors. Our results indicate that 454 amplicon pyrosequencing represents a powerful tool for investigating levels of ITS intragenomic variability across taxa, which may be valuable for better understanding the fundamental mechanisms underlying concerted evolution of repetitive DNA regions.

  10. fMRI Reveals Distinct CNS Processing during Symptomatic and Recovered Complex Regional Pain Syndrome in Children

    ERIC Educational Resources Information Center

    Lebel, A.; Becerra, L.; Wallin, D.; Moulton, E. A.; Morris, S.; Pendse, G.; Jasciewicz, J.; Stein, M.; Aiello-Lammens, M.; Grant, E.; Berde, C.; Borsook, D.

    2008-01-01

    Complex regional pain syndrome (CRPS) in paediatric patients is clinically distinct from the adult condition in which there is often complete resolution of its signs and symptoms within several months to a few years. The ability to compare the symptomatic and asymptomatic condition in the same individuals makes this population interesting for the…

  11. Regional modeling reveals summer precipitation trend signals over the European Alps consistent with trends observed in recent decades

    NASA Astrophysics Data System (ADS)

    Giorgi, Filippo; Torma, Csaba; Coppola, Erika

    2015-04-01

    We analyze an ensemble of high resolution regional climate model (RCM) projections for the 21st century (RCP8.5 scenario) over the European Alps from the EURO-CORDEX and MED-CORDEX experiments. We find that, while the driving global models project a reduction in future summer precipitation over the region, the RCM ensemble project an increase in precipitation over the highest elevations of the Alpine chain. This positive precipitation change signal is associated with an increase of convective precipitation driven by increased potential instability induced by high elevation surface heating. An analysis of observed summer precipitation trends over the region during the historical period 1975-2004 shows a precipitation trend signal consistent with the late 21st century RCM projections and with the RCM-simulated late 20th century trends. These multiple lines of evidence challenge the picture of a decreasing summer precipitation change signal over the Alps found in most GCM projections and point to the added value of high resolution RCMs in providing future climate information over mountainous regions.

  12. High-resolution physical mapping in Pennisetum squamulatum reveals extensive chromosomal heteromorphism of the genomic region associated with apomixis.

    PubMed

    Akiyama, Yukio; Conner, Joann A; Goel, Shailendra; Morishige, Daryl T; Mullet, John E; Hanna, Wayne W; Ozias-Akins, Peggy

    2004-04-01

    Gametophytic apomixis is asexual reproduction as a consequence of parthenogenetic development of a chromosomally unreduced egg. The trait leads to the production of embryos with a maternal genotype, i.e. progeny are clones of the maternal plant. The application of the trait in agriculture could be a tremendous tool for crop improvement through conventional and nonconventional breeding methods. Unfortunately, there are no major crops that reproduce by apomixis, and interspecific hybridization with wild relatives has not yet resulted in commercially viable germplasm. Pennisetum squamulatum is an aposporous apomict from which the gene(s) for apomixis has been transferred to sexual pearl millet by backcrossing. Twelve molecular markers that are linked with apomixis coexist in a tight linkage block called the apospory-specific genomic region (ASGR), and several of these markers have been shown to be hemizygous in the polyploid genome of P. squamulatum. High resolution genetic mapping of these markers has not been possible because of low recombination in this region of the genome. We now show the physical arrangement of bacterial artificial chromosomes containing apomixis-linked molecular markers by high resolution fluorescence in situ hybridization on pachytene chromosomes. The size of the ASGR, currently defined as the entire hemizygous region that hybridizes with apomixis-linked bacterial artificial chromosomes, was estimated on pachytene and mitotic chromosomes to be approximately 50 Mbp (a quarter of the chromosome). The ASGR includes highly repetitive sequences from an Opie-2-like retrotransposon family that are particularly abundant in this region of the genome.

  13. Employing 454 amplicon pyrosequencing to reveal intragenomic divergence in the internal transcribed spacer rDNA region in fungi

    PubMed Central

    Lindner, Daniel L; Carlsen, Tor; Henrik Nilsson, R; Davey, Marie; Schumacher, Trond; Kauserud, Håvard

    2013-01-01

    The rDNA internal transcribed spacer (ITS) region has been accepted as a DNA barcoding marker for fungi and is widely used in phylogenetic studies; however, intragenomic ITS variability has been observed in a broad range of taxa, including prokaryotes, plants, animals, and fungi, and this variability has the potential to inflate species richness estimates in molecular investigations of environmental samples. In this study 454 amplicon pyrosequencing of the ITS1 region was applied to 99 phylogenetically diverse axenic single-spore cultures of fungi (Dikarya: Ascomycota and Basidiomycota) to investigate levels of intragenomic variation. Three species (one Basidiomycota and two Ascomycota), in addition to a positive control species known to contain ITS paralogs, displayed levels of molecular variation indicative of intragenomic variation; taxon inflation due to presumed intragenomic variation was ≈9%. Intragenomic variability in the ITS region appears to be widespread but relatively rare in fungi (≈3–5% of species investigated in this study), suggesting this problem may have minor impacts on species richness estimates relative to PCR and/or pyrosequencing errors. Our results indicate that 454 amplicon pyrosequencing represents a powerful tool for investigating levels of ITS intragenomic variability across taxa, which may be valuable for better understanding the fundamental mechanisms underlying concerted evolution of repetitive DNA regions. PMID:23789083

  14. Regional vegetation patterns at lake Son Kul reveal Holocene climatic variability in central Tien Shan (Kyrgyzstan, Central Asia)

    NASA Astrophysics Data System (ADS)

    Mathis, Marie; Sorrel, Philippe; Klotz, Stefan; Huang, Xiangtong; Oberhänsli, Hedi

    2014-04-01

    A multiproxy study was conducted on Holocene sediments from the alpine lake Son Kul (3010 m a.s.l, 41°48‧33N/75°07‧38E) in central Tien Shan (Kyrgyzstan). The combination of high-resolution pollen, palynofacies and magnetic susceptibility data allowed reconstruction of changes in sedimentary and vegetation dynamics regionally at Son Kul between 8350 and ca 2000 cal. BP. Using pollen data to quantify climatic parameters, a quantitative reconstruction of climatic conditions was performed using the "Modern Analogue Vegetation types" (MAV) method and a ranged index of seasonality. The most temperate (e.g. moister) climate conditions occurred between 8350 and 5000-4500 cal. BP when alpine meadow vegetation was enriched in plants requiring moister conditions and trees developed regionally. Conversely, more continental and arid conditions prevailed after 4500 cal. BP with the decline of arboreal vegetation (especially Juniperus) and the extension of an alpine steppe-meadow along with a regional decrease in Poaceae. This climate transition was associated with a change in seasonality as the continentality greatly intensified after 5000-4500 cal. BP. Our results are consistent with other records from the Tien Shan range and the Chinese Province Xinjiang showing that relatively wet conditions prevailed regionally before 5000 cal. BP, whereas reduced moisture conditions were established after that time. From a more global perspective, we highlight that regional rainfall in central Tien Shan and western Central Asia is likely to be predominantly controlled by the Eastern Mediterranean cyclonic system and North Atlantic climate, as based on the close correspondence between climatic archives from western Central Asia, the Levant, the Eastern Mediterranean and Caspian Sea regions. However, the effect of monsoonal dynamics on the regional climatic system in central Tien Shan still remains dubious, since recent modelling studies have shown that no dynamic link exists between

  15. Internal wave activity in the polar atmospheric regions during 2006 - 2009 revealed by COSMIC radio occultation data

    NASA Astrophysics Data System (ADS)

    Kirillovich, Ivan; Gubenko, Vladimir; Pavelyev, Alexander; Liou, Yuei-An

    The satellite mission Formosat-3/COSMIC (Constellation Observing System for Meteorology, Ionosphere and Climate) consists of six micro-satellites, and each of them has four GPS-antennas. It was launched in April 2006, orbiting around the Earth at approximately 800 km. The primary scientific goal of the mission is to demonstrate the value of near-real-time radio occultation (RO) observations in improving operational numerical weather predictions (NWP). The goal is readily shown by assimilating the measurements of atmospheric parameters into used NWP-models. These parameters include density, temperature, pressure and relative humidity fields in the atmosphere. An analysis of their geographic and seasonal distributions is necessary to the understanding of the energy and momentum transfer and the reaction of the polar atmosphere in response to global warming. This task is especially important as the Polar Regions are very sensitive to the change in global temperature and it may be a major cause of global sea level rising. In this work, a statistical analysis of the internal gravity wave (IGW) activity in polar atmospheric regions (latitudes more than 60º) using Formosat-3/COSMIC RO temperature data collected from July 2006 to March 2009 has been performed. Geographic and seasonal distributions of the IGW potential energy (wave activity indicator) in the altitude interval from 15 to 35 km have been determined and analyzed. The obtained results show that the wave activity in the polar atmosphere is strong in winter and spring. The potential energy of IGWs in spring is largest in Antarctic atmospheric region, while it is largest in winter in Arctic region. The wave potential energy increases with altitude up to 35 km in the atmosphere of both Earth’s hemispheres. In Antarctic region, internal waves with high potential energy occur in the atmosphere over the Antarctic Peninsula. In Arctic region, a high wave activity is mainly observed over North Atlantic Ocean (Iceland

  16. Integrative Gene Regulatory Network Analysis Reveals Light-Induced Regional Gene Expression Phase Shift Programs in the Mouse Suprachiasmatic Nucleus

    PubMed Central

    Zhu, Haisun; Vadigepalli, Rajanikanth; Rafferty, Rachel; Gonye, Gregory E.; Weaver, David R.; Schwaber, James S.

    2012-01-01

    We use the multigenic pattern of gene expression across suprachiasmatic nuclei (SCN) regions and time to understand the dynamics within the SCN in response to a circadian phase-resetting light pulse. Global gene expression studies of the SCN indicate that circadian functions like phase resetting are complex multigenic processes. While the molecular dynamics of phase resetting are not well understood, it is clear they involve a “functional gene expression program”, e.g., the coordinated behavior of functionally related genes in space and time. In the present study we selected a set of 89 of these functionally related genes in order to further understand this multigenic program. By use of high-throughput qPCR we studied 52 small samples taken by anatomically precise laser capture from within the core and shell SCN regions, and taken at time points with and without phase resetting light exposure. The results show striking regional differences in light response to be present in the mouse SCN. By using network-based analyses, we are able to establish a highly specific multigenic correlation between genes expressed in response to light at night and genes normally activated during the day. The light pulse triggers a complex and highly coordinated network of gene regulation. The largest differences marking neuroanatomical location are in transmitter receptors, and the largest time-dependent differences occur in clock-related genes. Nighttime phase resetting appears to recruit transcriptional regulatory processes normally active in the day. This program, or mechanism, causes the pattern of core region gene expression to transiently shift to become more like that of the shell region. PMID:22662235

  17. Solar Wind Heating as Revealed from the Variation of 3D Ion Velocity Distributions across the Magnetic Reconnection Exhaust Region

    NASA Astrophysics Data System (ADS)

    He, J.

    2015-12-01

    Magnetic reconnection within current sheet has been regarded as one of the crucial dissipation and heating processes of coherent structures in the solar wind turbulence. Counter-streaming of ions is an important phenomenon in the reconnection exhaust region ranged from the ion diffusion region to the extended outflow region. It has been suggested by theoretical and numerical models that the ions are going to be picked up by the ejecting magnetic field and show larger T_perpendicular than T_parallel, if the guide field is strong enough (in other word, the shear angle is relatively low). The pick-up behavior seems to favor the heating of heavy ions with high mass-to-charge ratio, since the high M/Q ions have larger gyro-period/transit-time and tend to be non-adiabatic more easily. The above statements from theoretical models have not been thoroughly testified in the solar wind observations, though the changes in total temperature and 1D reduced velocity distribution function had been studied. Until now, it remains unclear about the difference of full 3D velocity distribution for the proton and helium ions between the upstream and the exhaust regions. Here, we will analyze the plasma measurement data from WIND/3DP to explore and compare the parallel and perpendicular heating effect of different species of ions. As a preliminary result, the proton is found to show bi-directional streams in its velocity distribution in some reconnection exhaust regions. The thermalization of the counter-streaming protons will be presented. The relation between proton T_parallel/T_perpendicular and guide field strength (or shear angle) will be studied. The velocity distributions of helium ions will be illustrated, which shows the difference of heating effect between different M/Q ratios.

  18. Coupling of functional connectivity and regional cerebral blood flow reveals a physiological basis for network hubs of the human brain.

    PubMed

    Liang, Xia; Zou, Qihong; He, Yong; Yang, Yihong

    2013-01-29

    Human brain functional networks contain a few densely connected hubs that play a vital role in transferring information across regions during resting and task states. However, the relationship of these functional hubs to measures of brain physiology, such as regional cerebral blood flow (rCBF), remains incompletely understood. Here, we used functional MRI data of blood-oxygenation-level-dependent and arterial-spin-labeling perfusion contrasts to investigate the relationship between functional connectivity strength (FCS) and rCBF during resting and an N-back working-memory task. During resting state, functional brain hubs with higher FCS were identified, primarily in the default-mode, insula, and visual regions. The FCS showed a striking spatial correlation with rCBF, and the correlation was stronger in the default-mode network (DMN; including medial frontal-parietal cortices) and executive control network (ECN; including lateral frontal-parietal cortices) compared with visual and sensorimotor networks. Moreover, the relationship was connection-distance dependent; i.e., rCBF correlated stronger with long-range hubs than short-range ones. It is notable that several DMN and ECN regions exhibited higher rCBF per unit connectivity strength (rCBF/FCS ratio); whereas, this index was lower in posterior visual areas. During the working-memory experiment, both FCS-rCBF coupling and rCBF/FCS ratio were modulated by task load in the ECN and/or DMN regions. Finally, task-induced changes of FCS and rCBF in the lateral-parietal lobe positively correlated with behavioral performance. Together, our results indicate a tight coupling between blood supply and brain functional topology during rest and its modulation in response to task demands, which may shed light on the physiological basis of human brain functional connectome.

  19. Is there an Asian idiom of distress? Somatic Symptoms in Female Japanese and Korean Students

    PubMed Central

    Arnault, Denise Saint; Kim, Oksoo

    2007-01-01

    The term “idiom of distress” is used to describe culturally-specific experiences of suffering. Most of these studies have been conducted with small groups, making comparison of symptom profiles difficult. Female undergraduate and graduate students in Japan (N=50) and Korea (N=61) completed Beck Depression Inventory (BDI) and seven-day dairy reports of their experiences of 46 somatic symptoms. Between-culture comparisons revealed that BDI scores did not differ; however, Korean women had significantly higher somatic distress means than the Japanese women. Despite the higher Korean distress mean, regression analysis showed that somatic distress explained 30% of the variance of BDI score for the Japanese, but only 22% of the variance for the Koreans. Within-culture comparisons showed that both the High BDI Japanese and Koreans had 19 somatic distress symptoms with significantly higher means than their Low BDI counterparts; eleven somatic symptoms were shared by the two groups. Multidimensional Scaling matrices were used to compare symptom proximities and revealed cultural differences. The problems with using broad racial categories in clinical research, the clinical significance of these findings, and implications for psychiatric nursing assessment and practice are discussed. PMID:18207054

  20. Somatic mosaicism in a patient with neurofibromatosis type 1.

    PubMed Central

    Colman, S. D.; Rasmussen, S. A.; Ho, V. T.; Abernathy, C. R.; Wallace, M. R.

    1996-01-01

    Using loss of heterozygosity analysis, a method designed to detect moderate to large gene deletions, we have identified a new-mutation neurofibromatosis type 1 (NF1) patient who is somatically mosaic for a large maternally derived deletion in the NF1 gene region. The deletion extends at least from exon 4 near the 5' end of the gene to intron 39 near the 3' end. The gene-coding region is, therefore, mostly or entirely deleted, encompassing a loss of > or = 100 kb. We hypothesize that the deletion occurred at a relatively early developmental timepoint, since signs of NF1 in this patient are not confined to a specific body region, as seen in "segmental" NF, and since both mesodermally and ectodermally derived cells are affected. This report provides the first molecular evidence of somatic mosaicism in NF1 and, taken together with a recent report of germ-line mosaicism in NF1, adds credence to the concept that mosaicism plays an important role in phenotypic and genetic aspects of NF1 and may even be a relatively common phenomenon. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8644707

  1. Somatic mutations of CASP3 gene in human cancers.

    PubMed

    Soung, Young Hwa; Lee, Jong Woo; Kim, Su Young; Park, Won Sang; Nam, Suk Woo; Lee, Jung Young; Yoo, Nam Jin; Lee, Sug Hyung

    2004-07-01

    Failure of apoptosis is one of the hallmarks of cancer. As an execution-phase caspase, caspase-3 plays a crucial role during apoptosis. To explore the possibility that the genetic alterations of CASP3, which encodes caspase-3, might be involved in the development of human tumors, we analyzed the entire coding region and all splice sites of human CASP3 gene for the detection of somatic mutations in a series of 944 human tumors, including 165 stomach carcinomas, 95 colon carcinomas, 76 breast carcinomas, 80 hepatocellular carcinomas, 181 non-small cell lung cancers, 45 acute leukemias, 28 multiple myelomas, 12 medulloblastomas, 15 Wilms' tumors, 12 renal cell carcinomas, 40 esophagus carcinomas, 33 urinary bladder carcinomas, 33 laryngeal carcinomas, and 129 non-Hodgkin lymphomas. Overall, we detected 14 somatic mutations of the CASP3 gene, including six missense and four silent mutations, two mutations in the introns, one mutation in the 5'-untranslated region, and one mutation in the 3'-untranslated region. The mutations were observed in four of 98 colon carcinomas (4.1%), four of 181 non-small cell lung cancers (2.2%), two of 129 non-Hodgkin lymphomas (1.6%), two of 165 stomach carcinomas (1.2%), one of 80 hepatocellular carcinomas (1.3%), and one of 28 multiple myelomas (3.6%). This is the first report on CASP3 gene mutations in human tumors; these data indicate that the CASP3 gene is occasionally mutated in human tumors.

  2. Somatic mosaicism in a patient with neurofibromomatosis type 1

    SciTech Connect

    Colman, S.D.; Rasmussen, S.A.; Ho, V.T.

    1996-03-01

    Using loss of heterozygosity analysis, a method designed to detect moderate to large gene deletions, we have identified a new-mutation neurofibromatosis type 1 (NF1) patient who is somatically mosaic for a large maternally derived deletion in the NF1 gene region. The deletion extends at least from exon 4 near the 5{prime} end of the gene to intron 39 near the 3{prime} end. The gene-coding region is, therefore, mostly or entirely deleted, encompassing a loss of {>=}100 kb. We hypothesize that the deletion occurred at a relatively early developmental timepoint, since signs of NF in this patient are not confined to a specific body region, as seen in {open_quotes}segmental{close_quotes} NF, and since both mesodermally and ectodermally derived cells are affected. This report provides the first molecular evidence of somatic mosaicism in NF1 and, taken together with a recent report of germ-line mosaicism in NF1, adds credence to the concept that mosaicism plays an important role in phenotypic and genetic aspects of NF1 and may even be a relatively common phenomenon. 37 refs., 4 figs.

  3. Cryopreservation of Arachis pintoi (leguminosae) somatic embryos.

    PubMed

    Rey, H Y; Faloci, M; Medina, R; Dolce, N; Engelmann, F; Mroginski, L

    2013-01-01

    In this study, we successfully cryopreserved cotyledonary somatic embryos of diploid and triploid Arachis pintoi cytotypes using the encapsulation-dehydration technique. The highest survival rates were obtained when somatic embryos were encapsulated in calcium alginate beads and precultured in agitated (80 rpm) liquid establishment medium (EM) with daily increasing sucrose concentration (0.50, 0.75, and 1.0 M). The encapsulated somatic embryos were then dehydrated with silica gel for 5 h to 20% moisture content (fresh weight basis) and cooled either rapidly (direct immersion in liquid nitrogen, LN) or slowly (1 degree C per min from 25 degree C to -30 degree C followed by immersion in LN). Beads were kept in LN for a minimum of 1 h and then were rapidly rewarmed in a 30 degree C water-bath for 2 min. Finally, encapsulated somatic embryos were post-cultured in agitated (80 rpm) liquid EM with daily decreasing sucrose concentration (0.75 and 0.5 M) and transferred to solidified EM. Using this protocol, we obtained 26% and 30% plant regeneration from cryopreserved somatic embryos of diploid and triploid cytotypes. No morphological abnormalities were observed in any of the plants regenerated from cryopreserved embryos and their genetic stability was confirmed with 10 isozyme systems and nine RAPD profiles.

  4. [Panic attacks simulate presence of somatic illnesses].

    PubMed

    Latas, Milan; Soldatović, Ivan; Stamenović, Marko; Starcević, Vladan

    2009-01-01

    Panic attacks are characterized with sudden attacks of anxiety with numerous somatic symptoms, such as palpitations, tachycardia, tachypnea, nausea, vertigo. The objective of this study was to analyze symptoms of panic attacks in patients with panic disorder, especially, to determine the specific relationship of somatic and neurological symptoms of panic attacks in boundaries of somatic systems. The study sample consisted of 97 patients with primary diagnosis of panic disorder, without any acute, severe and unstable somatic illness. The presence and frequency of symptoms of panic attacks were estimated by the Panic Disorder Questionnaire. The study results indicate that the most frequent symptoms of panic attacks were cardiological signs (heart pounding or racing) and trembling, followed by unsteady and fainting feeling symptoms, sweating, respiratory symptoms and gastroenterological symptoms. The results of correlation analyses indicate that symptoms of panic attacks classified into cardiovascular, gastro-enterological, respiratory and neurootological systems show statistically significant correlations. The results of analyses of symptoms of panic attacks point to their intercorrelation. This specific association of the symptoms, if they are examined on their own in the patients, could lead to false clinical manifestation of some somatic illness. Therefore, it is necessary to analyze adequately and make the proper differential diagnosis of patients with panic disorder.

  5. Somatic Host Cell Alterations in HPV Carcinogenesis

    PubMed Central

    Litwin, Tamara R.; Clarke, Megan A.; Dean, Michael; Wentzensen, Nicolas

    2017-01-01

    High-risk human papilloma virus (HPV) infections cause cancers in different organ sites, most commonly cervical and head and neck cancers. While carcinogenesis is initiated by two viral oncoproteins, E6 and E7, increasing evidence shows the importance of specific somatic events in host cells for malignant transformation. HPV-driven cancers share characteristic somatic changes, including apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC)-driven mutations and genomic instability leading to copy number variations and large chromosomal rearrangements. HPV-associated cancers have recurrent somatic mutations in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and phosphatase and tensin homolog (PTEN), human leukocyte antigen A and B (HLA-A and HLA-B)-A/B, and the transforming growth factor beta (TGFβ) pathway, and rarely have mutations in the tumor protein p53 (TP53) and RB transcriptional corepressor 1 (RB1) tumor suppressor genes. There are some variations by tumor site, such as NOTCH1 mutations which are primarily found in head and neck cancers. Understanding the somatic events following HPV infection and persistence can aid the development of early detection biomarkers, particularly when mutations in precancers are characterized. Somatic mutations may also influence prognosis and treatment decisions. PMID:28771191

  6. Genetic structure and demographic history reveal migration of the diamondback moth Plutella xylostella (Lepidoptera: Plutellidae) from the southern to northern regions of China.

    PubMed

    Wei, Shu-Jun; Shi, Bao-Cai; Gong, Ya-Jun; Jin, Gui-Hua; Chen, Xue-Xin; Meng, Xiang-Feng

    2013-01-01

    The diamondback moth Plutella xylostella (Linnaeus) (Lepidoptera: Plutellidae) is one of the most destructive insect pests of cruciferous plants worldwide. Biological, ecological and genetic studies have indicated that this moth is migratory in many regions around the world. Although outbreaks of this pest occur annually in China and cause heavy damage, little is known concerning its migration. To better understand its migration pattern, we investigated the population genetic structure and demographic history of the diamondback moth by analyzing 27 geographical populations across China using four mitochondrial genes and nine microsatellite loci. The results showed that high haplotype diversity and low nucleotide diversity occurred in the diamondback moth populations, a finding that is typical for migratory species. No genetic differentiation among all populations and no correlation between genetic and geographical distance were found. However, pairwise analysis of the mitochondrial genes has indicated that populations from the southern region were more differentiated than those from the northern region. Gene flow analysis revealed that the effective number of migrants per generation into populations of the northern region is very high, whereas that into populations of the southern region is quite low. Neutrality testing, mismatch distribution and Bayesian Skyline Plot analyses based on mitochondrial genes all revealed that deviation from Hardy-Weinberg equilibrium and sudden expansion of the effective population size were present in populations from the northern region but not in those from the southern region. In conclusion, all our analyses strongly demonstrated that the diamondback moth migrates within China from the southern to northern regions with rare effective migration in the reverse direction. Our research provides a successful example of using population genetic approaches to resolve the seasonal migration of insects.

  7. Genetic Structure and Demographic History Reveal Migration of the Diamondback Moth Plutella xylostella (Lepidoptera: Plutellidae) from the Southern to Northern Regions of China

    PubMed Central

    Wei, Shu-Jun; Shi, Bao-Cai; Gong, Ya-Jun; Jin, Gui-Hua; Chen, Xue-Xin; Meng, Xiang-Feng

    2013-01-01

    The diamondback moth Plutella xylostella (Linnaeus) (Lepidoptera: Plutellidae) is one of the most destructive insect pests of cruciferous plants worldwide. Biological, ecological and genetic studies have indicated that this moth is migratory in many regions around the world. Although outbreaks of this pest occur annually in China and cause heavy damage, little is known concerning its migration. To better understand its migration pattern, we investigated the population genetic structure and demographic history of the diamondback moth by analyzing 27 geographical populations across China using four mitochondrial genes and nine microsatellite loci. The results showed that high haplotype diversity and low nucleotide diversity occurred in the diamondback moth populations, a finding that is typical for migratory species. No genetic differentiation among all populations and no correlation between genetic and geographical distance were found. However, pairwise analysis of the mitochondrial genes has indicated that populations from the southern region were more differentiated than those from the northern region. Gene flow analysis revealed that the effective number of migrants per generation into populations of the northern region is very high, whereas that into populations of the southern region is quite low. Neutrality testing, mismatch distribution and Bayesian Skyline Plot analyses based on mitochondrial genes all revealed that deviation from Hardy-Weinberg equilibrium and sudden expansion of the effective population size were present in populations from the northern region but not in those from the southern region. In conclusion, all our analyses strongly demonstrated that the diamondback moth migrates within China from the southern to northern regions with rare effective migration in the reverse direction. Our research provides a successful example of using population genetic approaches to resolve the seasonal migration of insects. PMID:23565158

  8. Mapping of PARK2 and PACRG overlapping regulatory region reveals LD structure and functional variants in association with leprosy in unrelated indian population groups.

    PubMed

    Chopra, Rupali; Ali, Shafat; Srivastava, Amit K; Aggarwal, Shweta; Kumar, Bhupender; Manvati, Siddharth; Kalaiarasan, Ponnusamy; Jena, Mamta; Garg, Vijay K; Bhattacharya, Sambit N; Bamezai, Rameshwar N K

    2013-01-01

    Leprosy is a chronic infectious disease caused by Mycobacterium Leprae, where the host genetic background plays an important role toward the disease pathogenesis. Various studies have identified a number of human genes in association with leprosy or its clinical forms. However, non-replication of results has hinted at the heterogeneity among associations between different population groups, which could be due to differently evolved LD structures and differential frequencies of SNPs within the studied regions of the genome. A need for systematic and saturated mapping of the associated regions with the disease is warranted to unravel the observed heterogeneity in different populations. Mapping of the PARK2 and PACRG gene regulatory region with 96 SNPs, with a resolution of 1 SNP per 1 Kb for PARK2 gene regulatory region in a North Indian population, showed an involvement of 11 SNPs in determining the susceptibility towards leprosy. The association was replicated in a geographically distinct and unrelated population from Orissa in eastern India. In vitro reporter assays revealed that the two significantly associated SNPs, located 63.8 kb upstream of PARK2 gene and represented in a single BIN of 8 SNPs, influenced the gene expression. A comparison of BINs between Indian and Vietnamese populations revealed differences in the BIN structures, explaining the heterogeneity and also the reason for non-replication of the associated genomic region in different populations.

  9. Mapping of PARK2 and PACRG Overlapping Regulatory Region Reveals LD Structure and Functional Variants in Association with Leprosy in Unrelated Indian Population Groups

    PubMed Central

    Chopra, Rupali; Aggarwal, Shweta; Kumar, Bhupender; Manvati, Siddharth; Kalaiarasan, Ponnusamy; Jena, Mamta; Garg, Vijay K.; Bhattacharya, Sambit N.; Bamezai, Rameshwar N. K.

    2013-01-01

    Leprosy is a chronic infectious disease caused by Mycobacterium Leprae, where the host genetic background plays an important role toward the disease pathogenesis. Various studies have identified a number of human genes in association with leprosy or its clinical forms. However, non-replication of results has hinted at the heterogeneity among associations between different population groups, which could be due to differently evolved LD structures and differential frequencies of SNPs within the studied regions of the genome. A need for systematic and saturated mapping of the associated regions with the disease is warranted to unravel the observed heterogeneity in different populations. Mapping of the PARK2 and PACRG gene regulatory region with 96 SNPs, with a resolution of 1 SNP per 1 Kb for PARK2 gene regulatory region in a North Indian population, showed an involvement of 11 SNPs in determining the susceptibility towards leprosy. The association was replicated in a geographically distinct and unrelated population from Orissa in eastern India. In vitro reporter assays revealed that the two significantly associated SNPs, located 63.8 kb upstream of PARK2 gene and represented in a single BIN of 8 SNPs, influenced the gene expression. A comparison of BINs between Indian and Vietnamese populations revealed differences in the BIN structures, explaining the heterogeneity and also the reason for non-replication of the associated genomic region in different populations. PMID:23861666

  10. Importance of the converter region for the motility of myosin as revealed by the studies on chimeric Chara myosins.

    PubMed

    Seki, Masaya; Kashiyama, Taku; Hachikubo, You; Ito, Kohji; Yamamoto, Keiichi

    2004-11-19

    A long alpha-helix in myosin head constitutes a lever arm together with light chains. It is known from X-ray crystallographic studies that the first three turns of this lever arm alpha-helix are inserted into the converter region of myosin. We previously showed that chimeric Chara myosin in which the motor domain of Chara myosin was connected to the lever arm alpha-helix of Dictyostelium myosin had motility far less than that expected for the motor domain of Chara myosin. Here, we replaced the inserted three turns of alpha-helix of Dictyostelium myosin with that of the Chara myosin and found that the replacement enhanced the motility 2.6-fold without changing the ATPase activity so much. The result clearly showed the importance of interaction between the converter region and the lever arm alpha-helix for the efficient motility of myosin.

  11. Single nucleotide polymorphisms typing of Mycobacterium leprae reveals focal transmission of leprosy in high endemic regions of India.

    PubMed

    Lavania, M; Jadhav, R S; Turankar, R P; Chaitanya, V S; Singh, M; Sengupta, U

    2013-11-01

    Earlier studies indicate that genotyping of Mycobaterium leprae based on single-nucleotide polymorphisms (SNPs) is useful for analysis of the global spread of leprosy. In the present study, we investigated the diversity of M. leprae at eight SNP loci using 180 clinical isolates obtained from patients with leprosy residing mainly in Delhi and Purulia (West Bengal) regions. It was observed that the frequency of SNP type 1 and subtype D was most predominant in the Indian population. Further, the SNP type 2 subtype E was noted only from East Delhi region and SNP type 2 subtype G was noted only from the nearby areas of Hoogly district of West Bengal. These results indicate the occurrence of focal transmission of M. leprae infection and demonstrate that analysis by SNP typing has great potential to help researchers in understanding the transmission of M. leprae infection in the community.

  12. Regional endemism and cryptic species revealed by molecular and morphological analysis of a widespread species of Neotropical catfish.

    PubMed

    Martin, A P; Bermingham, E

    2000-06-07

    The lower Central American landscape was fully emergent approximately three million years ago, an event which marked the beginning of the Great American biotic interchange. Freshwater fishes participated in the biotic interchange. Because primary freshwater fishes are restricted to freshwater, they provide an excellent system for investigating the interplay of historical and recent processes on the assembly, structure and diversity of the regions' aquatic ecosystems. We focused on examining the history of diversification for a species of catfish (Pimelodella chagresi) whose distribution spans multiple, isolated drainage basins across the Isthmian landscape and into north-western South America. Analysis of mitochondrial DNA haplotypes and morphological traits indicated that P. chagresi, as currently recognized, comprises a species complex. In addition, along the Pacific slope of Panama, repeated dispersion, diversification, extinction and possibly hybridization are thought to underlie a complex distribution of haplotypes. Overall, the results underscore the tremendous importance of historical processes on regional biodiversity.

  13. Genetic analysis of historic western Great Lakes region wolf samples reveals early Canis lupus/lycaon hybridization.

    PubMed

    Wheeldon, Tyler; White, Bradley N

    2009-02-23

    The genetic status of wolves in the western Great Lakes region has received increased attention following the decision to remove them from protection under the US Endangered Species Act. A recent study of mitochondrial DNA has suggested that the recovered wolf population is not genetically representative of the historic population. We present microsatellite genotype data on three historic samples and compare them with extant populations, and interpret published genetic data to show that the pre-recovery population was admixed over a century ago by eastern wolf (Canis lycaon) and grey wolf (Canis lupus) hybridization. The DNA profiles of the historic samples are similar to those of extant animals in the region, suggesting that the current Great Lakes wolves are representative of the historic population.

  14. Mangrove Habitat Use by Juvenile Reef Fish: Meta-Analysis Reveals that Tidal Regime Matters More than Biogeographic Region

    PubMed Central

    Igulu, Mathias M.; Nagelkerken, Ivan; Dorenbosch, Martijn; Grol, Monique G. G.; Harborne, Alastair R.; Kimirei, Ismael A.; Mumby, Peter J.; Olds, Andrew D.; Mgaya, Yunus D.

    2014-01-01

    Identification of critical life-stage habitats is key to successful conservation efforts. Juveniles of some species show great flexibility in habitat use while other species rely heavily on a restricted number of juvenile habitats for protection and food. Considering the rapid degradation of coastal marine habitats worldwide, it is important to evaluate which species are more susceptible to loss of juvenile nursery habitats and how this differs across large biogeographic regions. Here we used a meta-analysis approach to investigate habitat use by juvenile reef fish species in tropical coastal ecosystems across the globe. Densities of juvenile fish species were compared among mangrove, seagrass and coral reef habitats. In the Caribbean, the majority of species showed significantly higher juvenile densities in mangroves as compared to seagrass beds and coral reefs, while for the Indo-Pacific region seagrass beds harbored the highest overall densities. Further analysis indicated that differences in tidal amplitude, irrespective of biogeographic region, appeared to be the major driver for this phenomenon. In addition, juvenile reef fish use of mangroves increased with increasing water salinity. In the Caribbean, species of specific families (e.g. Lutjanidae, Haemulidae) showed a higher reliance on mangroves or seagrass beds as juvenile habitats than other species, whereas in the Indo-Pacific family-specific trends of juvenile habitat utilization were less apparent. The findings of this study highlight the importance of incorporating region-specific tidal inundation regimes into marine spatial conservation planning and ecosystem based management. Furthermore, the significant role of water salinity and tidal access as drivers of mangrove fish habitat use implies that changes in seawater level and rainfall due to climate change may have important effects on how juvenile reef fish use nearshore seascapes in the future. PMID:25551761

  15. Genomewide linkage analysis of stature in multiple populations reveals several regions with evidence of linkage to adult height.

    PubMed

    Hirschhorn, J N; Lindgren, C M; Daly, M J; Kirby, A; Schaffner, S F; Burtt, N P; Altshuler, D; Parker, A; Rioux, J D; Platko, J; Gaudet, D; Hudson, T J; Groop, L C; Lander, E S

    2001-07-01

    Genomewide linkage analysis has been extremely successful at identification of the genetic variation underlying single-gene disorders. However, linkage analysis has been less successful for common human diseases and other complex traits in which multiple genetic and environmental factors interact to influence disease risk. We hypothesized that a highly heritable complex trait, in which the contribution of environmental factors was relatively limited, might be more amenable to linkage analysis. We therefore chose to study stature (adult height), for which heritability is approximately 75%-90% (Phillips and Matheny 1990; Carmichael and McGue 1995; Preece 1996; Silventoinen et al. 2000). We reanalyzed genomewide scans from four populations for which genotype and height data were available, using a variance-components method implemented in GENEHUNTER 2.0 (Pratt et al. 2000). The populations consisted of 408 individuals in 58 families from the Botnia region of Finland, 753 individuals in 183 families from other parts of Finland, 746 individuals in 179 families from Southern Sweden, and 420 individuals in 63 families from the Saguenay-Lac-St.-Jean region of Quebec. Four regions showed evidence of linkage to stature: 6q24-25, multipoint LOD score 3.85 at marker D6S1007 in Botnia (genomewide P<.06), 7q31.3-36 (LOD 3.40 at marker D7S2195 in Sweden, P<.02), 12p11.2-q14 (LOD 3.35 at markers D12S10990-D12S398 in Finland, P<.05) and 13q32-33 (LOD 3.56 at markers D13S779-D13S797 in Finland, P<.05). In a companion article (Perola et al. 2001 [in this issue]), strong supporting evidence is obtained for linkage to the region on chromosome 7. These studies suggest that highly heritable complex traits such as stature may be genetically tractable and provide insight into the genetic architecture of complex traits.

  16. Genetic Dissection of a Genomic Region with Pleiotropic Effects on Domestication Traits in Maize Reveals Multiple Linked QTL

    PubMed Central

    Lemmon, Zachary H.; Doebley, John F.

    2014-01-01

    The domesticated crop maize and its wild progenitor, teosinte, have been used in numerous experiments to investigate the nature of divergent morphologies. This study examines a poorly understood region on the fifth chromosome of maize associated with a number of traits under selection during domestication, using a quantitative trait locus (QTL) mapping population specific to the fifth chromosome. In contrast with other major domestication loci in maize where large-effect, highly pleiotropic, single genes are responsible for phenotypic effects, our study found the region on chromosome five fractionates into multiple-QTL regions, none with singularly large effects. The smallest 1.5-LOD support interval for a QTL contained 54 genes, one of which was a MADS MIKCC transcription factor, a family of proteins implicated in many developmental programs. We also used simulated trait data sets to investigate the power of our mapping population to identify QTL for which there is a single underlying causal gene. This analysis showed that while QTL for traits controlled by single genes can be accurately mapped, our population design can detect no more than ∼4.5 QTL per trait even when there are 100 causal genes. Thus when a trait is controlled by ≥5 genes in the simulated data, the number of detected QTL can represent a simplification of the underlying causative factors. Our results show how a QTL region with effects on several domestication traits may be due to multiple linked QTL of small effect as opposed to a single gene with large and pleiotropic effects. PMID:24950893

  17. Mangrove habitat use by juvenile reef fish: meta-analysis reveals that tidal regime matters more than biogeographic region.

    PubMed

    Igulu, Mathias M; Nagelkerken, Ivan; Dorenbosch, Martijn; Grol, Monique G G; Harborne, Alastair R; Kimirei, Ismael A; Mumby, Peter J; Olds, Andrew D; Mgaya, Yunus D

    2014-01-01

    Identification of critical life-stage habitats is key to successful conservation efforts. Juveniles of some species show great flexibility in habitat use while other species rely heavily on a restricted number of juvenile habitats for protection and food. Considering the rapid degradation of coastal marine habitats worldwide, it is important to evaluate which species are more susceptible to loss of juvenile nursery habitats and how this differs across large biogeographic regions. Here we used a meta-analysis approach to investigate habitat use by juvenile reef fish species in tropical coastal ecosystems across the globe. Densities of juvenile fish species were compared among mangrove, seagrass and coral reef habitats. In the Caribbean, the majority of species showed significantly higher juvenile densities in mangroves as compared to seagrass beds and coral reefs, while for the Indo-Pacific region seagrass beds harbored the highest overall densities. Further analysis indicated that differences in tidal amplitude, irrespective of biogeographic region, appeared to be the major driver for this phenomenon. In addition, juvenile reef fish use of mangroves increased with increasing water salinity. In the Caribbean, species of specific families (e.g. Lutjanidae, Haemulidae) showed a higher reliance on mangroves or seagrass beds as juvenile habitats than other species, whereas in the Indo-Pacific family-specific trends of juvenile habitat utilization were less apparent. The findings of this study highlight the importance of incorporating region-specific tidal inundation regimes into marine spatial conservation planning and ecosystem based management. Furthermore, the significant role of water salinity and tidal access as drivers of mangrove fish habitat use implies that changes in seawater level and rainfall due to climate change may have important effects on how juvenile reef fish use nearshore seascapes in the future.

  18. Phylogenetic Footprinting Reveals Evolutionarily Conserved Regions of the Gonadotropin-Releasing Hormone Gene that Enhance Cell-Specific Expression

    PubMed Central

    GIVENS, MARJORY L.; KUROTANI, REIKO; RAVE-HAREL, NAAMA; MILLER, NICHOL L. G.; MELLON, PAMELA L.

    2010-01-01

    Reproductive function is controlled by the hypothalamic neuropeptide, GnRH, which serves as the central regulator of the hypothalamic-pituitary-gonadal axis. GnRH expression is limited to a small population of neurons in the hypothalamus. Targeting this minute population of neurons (as few as 800 in the mouse) requires regulatory elements upstream of the GnRH gene that remain to be fully characterized. Previously, we have identified an evolutionarily conserved promoter region (−173 to −1) and an enhancer (−1863 to −1571) in the rat gene that targets a subset of the GnRH neurons in vivo. In the present study, we used phylogenetic sequence comparison between human and rodents and analysis of the transcription factor clusters within conserved regions in an attempt to identify additional upstream regulatory elements. This approach led to the characterization of a new upstream enhancer that regulates expression of GnRH in a cell-specific manner. Within this upstream enhancer are nine binding sites for Octamer-binding transcription factor 1 (OCT1), known to be an important transcriptional regulator of GnRH gene expression. In addition, we have identified nuclear factor I (NF1) binding to multiple elements in the GnRH-regulatory regions, each in close proximity to OCT1. We show that OCT1 and NF1 physically and functionally interact. Moreover, the OCT1 and NF1 binding sites in the regulatory regions appear to be essential for appropriate GnRH gene expression. These findings indicate a role for this upstream enhancer and novel OCT1/NF1 complexes in neuron-restricted expression of the GnRH gene. PMID:15319450

  19. Molecular and epidemiologic study of Clostridium difficile reveals unusual heterogeneity in clinical strains circulating in different regions in Portugal.

    PubMed

    Santos, A; Isidro, J; Silva, C; Boaventura, L; Diogo, J; Faustino, A; Toscano, C; Oleastro, M

    2016-08-01

    Clostridium difficile infection (CDI) represents a great healthcare burden in developed countries. The emergence of the epidemic PCR ribotype (RT) 027 and its acquired fluoroquinolones resistance have accentuated the need for an active surveillance of CDI. Here we report the first countrywide study of CDI in Portugal with the characterization of 498 C. difficile clinical isolates from 20 hospitals in four regions in Portugal regarding RT, virulence factors and antimicrobial susceptibility. We identified 96 RTs with marked variations between and within regions, as only six RTs appeared in all four regions. RT027 was the most frequent RT overall (18.5%) and among healthcare facility-associated isolates (19.6%), while RT014 was the most common among community-associated isolates (12%). The north showed a high RT diversity among isolates and a low moxifloxacin (MXF) resistance rate (11.9%), being the only region in which RT027 was not predominant. In contrast, the isolates from the centre presented the highest RT027 frequency, and 53.4% were resistant to MXF. Overall, MXF resistance (33.2%) was associated (p <0.001) with the presence of binary toxin genes and mutations in tcdC regardless of the RT. Both traits appeared in almost 30% of the strains. RT027 showed a reduced susceptibility to metronidazole (p <0.01), and RT126 had higher minimum inhibitory concentrations to vancomycin (p = 0.03) compared to other RTs. The present study highlights an unusual heterogeneity of RTs in Portugal, with a high frequency of hypervirulent RTs and the emergence of virulence factors in non-027 RTs, emphasizing the need for a surveillance system for CDI in Portugal.

  20. Crystal structure of the plexin A3 intracellular region reveals an autoinhibited conformation through active site sequestration

    SciTech Connect

    He, Huawei; Yang, Taehong; Terman, Jonathan R.; Zhang, Xuewu

    2010-01-20

    Plexin cell surface receptors bind to semaphorin ligands and transduce signals for regulating neuronal axon guidance. The intracellular region of plexins is essential for signaling and contains a R-Ras/M-Ras GTPase activating protein (GAP) domain that is divided into two segments by a Rho GTPase-binding domain (RBD). The regulation mechanisms for plexin remain elusive, although it is known that activation requires both binding of semaphorin to the extracellular region and a Rho-family GTPase (Rac1 or Rnd1) to the RBD. Here we report the crystal structure of the plexin A3 intracellular region. The structure shows that the N- and C-terminal portions of the GAP homologous regions together form a GAP domain with an overall fold similar to other Ras GAPs. However, the plexin GAP domain adopts a closed conformation and cannot accommodate R-Ras/M-Ras in its substrate-binding site, providing a structural basis for the autoinhibited state of plexins. A comparison with the plexin B1 RBD/Rnd1 complex structure suggests that Rnd1 binding alone does not induce a conformational change in plexin, explaining the requirement of both semaphorin and a Rho GTPase for activation. The structure also identifies an N-terminal segment that is important for regulation. Both the N-terminal segment and the RBD make extensive interactions with the GAP domain, suggesting the presence of an allosteric network connecting these three domains that integrates semaphorin and Rho GTPase signals to activate the GAP. The importance of these interactions in plexin signaling is shown by both cell-based and in vivo axon guidance assays.

  1. Sedimentation rates in eastern North America reveal strong links between regional climate, depositional environments, and sediment accumulation

    NASA Astrophysics Data System (ADS)

    Goring, S. J.; McLachlan, J. S.; Jackson, S. T.; Blaauw, M.; Christen, J.; Marlon, J.; Blois, J.; Williams, J. W.

    2011-12-01

    PalEON is a multidisciplinary project that combines paleo and modern ecological data with state-of-the-art statistical and modelling tools to examine the interactions between climate, fire and vegetation during the past two millennia in the northeastern United States. A fundamental challenge for PalEON (and paleo research more broadly) is to improve age modelling to yield more accurate sediment-core chronologies. To address this challenge, we assessed sedimentation rates and their controls for 218 lakes and mires in the northeastern U.S. Sedimentation rates (yr/cm) were calculated from age-depth models, which were obtained from the Neotoma database (www.neotomadb.org) and other contributed pollen records. The age models were recalibrated to IntCal09 and augmented in some cases using biostratigraphic markers (Picea decline, 16 kcal BP - 10.5 kcal BP; Quercus rise, 12 - 9.1 kcal BP; and Alnus decline, 11.5 - 10.6 kcal BP) as described in Blois et al. (2011). Relationships between sedimentation rates and sediment age, site longitude, and depositional environment (lacustrine or mire) are significant but weak. There are clear and significant links between variations in the NGRIP record of δ18O and sedimentation in mires across the PalEON region, but no links to lacustrine sedimentation rates. This result indicates that super-regional climatic control of primary productivity, and thus autochthonic sediment deposition, dominates in mires while deposition in lacustrine basins may be driven primarily by local and regional factors including watershed size, surficial materials,and regional vegetation. The shape of the gamma probability functions that best describe sedimentation rate distributions are calculated and presented here for use as priors in Bayesian age modelling applications such as BACON (Blaauw and Christen, in press). Future applications of this research are also discussed.

  2. Genome-wide occupancy profile of mediator and the Srb8-11 module reveals interactions with coding regions.

    PubMed

    Zhu, Xuefeng; Wirén, Marianna; Sinha, Indranil; Rasmussen, Nina N; Linder, Tomas; Holmberg, Steen; Ekwall, Karl; Gustafsson, Claes M

    2006-04-21

    Mediator exists in a free form containing the Med12, Med13, CDK8, and CycC subunits (the Srb8-11 module) and a smaller form, which lacks these four subunits and associates with RNA polymerase II (Pol II), forming a holoenzyme. We use chromatin immunoprecipitation (ChIP) and DNA microarrays to investigate genome-wide localization of Mediator and the Srb8-11 module in fission yeast. Mediator and the Srb8-11 module display similar binding patterns, and interactions with promoters and upstream activating sequences correlate with increased transcription activity. Unexpectedly, Mediator also interacts with the downstream coding region of many genes. These interactions display a negative bias for positions closer to the 5' ends of open reading frames (ORFs) and appear functionally important, because downregulation of transcription in a temperature-sensitive med17 mutant strain correlates with increased Mediator occupancy in the coding region. We propose that Mediator coordinates transcription initiation with transcriptional events in the coding region of eukaryotic genes.

  3. Regional Variation of White Matter Development in the Cat Brain Revealed by Ex Vivo Diffusion MR Tractography

    PubMed Central

    Dai, Guangping; Das, Avilash; Hayashi, Emiko; Chen, Qin; Takahashi, Emi

    2016-01-01

    Three-dimensional reconstruction of developing fiber pathways is essential to assessing the developmental course of fiber pathways in the whole brain. We applied diffusion spectrum imaging (DSI) tractography to five juvenile ex vivo cat brains at postnatal day (P) 35, when the degree of myelination varies across brain regions. We quantified diffusion properties (fractional anisotropy [FA] and apparent diffusion coefficient [ADC]) and other measurements (number, volume, and voxel count) on reconstructed pathways for projection (cortico-spinal and thalamo-cortical), corpus callosal, limbic (cingulum and fornix), and association (cortico-cortical) pathways, and characterized regional differences in maturation patterns by assessing diffusion properties. FA values were significantly higher in cortico-cortical pathways within the right hemisphere compared to those within the left hemisphere, while the other measurements for the cortico-cortical pathways within the hemisphere did not show asymmetry. ADC values were not asymmetric in both types of pathways. Interestingly, tract count and volume were significantly larger in the left thalamo-cortical pathways compared to the right thalamo-cortical pathways. The bilateral thalamo-cortical pathways showed high FA values compared to the other fiber pathways. On the other hand, ADC values did not show any differences across pathways studied. These results demonstrate that DSI tractography successfully depicted regional variations of white matter tracts during development when myelination is incomplete. Low FA and high ADC values in the cingulum bundle suggest that the cingulum bundle is less mature than the others at this developmental stage. PMID:27568056

  4. Multivoxel patterns in face-sensitive temporal regions reveal an encoding schema based on detecting life in a face.

    PubMed

    Looser, Christine E; Guntupalli, Jyothi S; Wheatley, Thalia

    2013-10-01

    More than a decade of research has demonstrated that faces evoke prioritized processing in a 'core face network' of three brain regions. However, whether these regions prioritize the detection of global facial form (shared by humans and mannequins) or the detection of life in a face has remained unclear. Here, we dissociate form-based and animacy-based encoding of faces by using animate and inanimate faces with human form (humans, mannequins) and dog form (real dogs, toy dogs). We used multivariate pattern analysis of BOLD responses to uncover the representational similarity space for each area in the core face network. Here, we show that only responses in the inferior occipital gyrus are organized by global facial form alone (human vs dog) while animacy becomes an additional organizational priority in later face-processing regions: the lateral fusiform gyri (latFG) and right superior temporal sulcus. Additionally, patterns evoked by human faces were maximally distinct from all other face categories in the latFG and parts of the extended face perception system. These results suggest that once a face configuration is perceived, faces are further scrutinized for whether the face is alive and worthy of social cognitive resources.

  5. Mantle plumes beneath the South Pacific superswell revealed by finite frequency P tomography using regional seafloor and island data

    NASA Astrophysics Data System (ADS)

    Obayashi, M.; Yoshimitsu, J.; Sugioka, H.; Ito, A.; Isse, T.; Shiobara, H.; Reymond, D.; Suetsugu, D.

    2016-11-01

    We present a new tomographic image beneath the South Pacific superswell, using finite frequency P wave travel time tomography with global and regional data. The regional stations include broadband ocean-bottom seismograph stations. The tomographic image shows slow anomalies of 200-300 km in diameter beneath most hot spots in the studied region, extending continuously from the shallow upper mantle to 400 km depth. Narrow and weak slow anomalies are detected at depths of 500-1000 km, connecting the upper mantle slow anomalies with large-scale slow anomalies with lateral dimension of 1000-2000 km prevailing below 1000 km depth down to the core-mantle boundary. There are two slow anomalies around the Society hot spot at depths shallower than 400 km, which both emerge from the same slow anomaly at 500 km depth. One of them is located beneath the Society hot spot and the other underlies 500 km east of the Society hot spot, where no volcanism is observed.

  6. Methylome analysis reveals alterations in DNA methylation in the regulatory regions of left ventricle development genes in human dilated cardiomyopathy.

    PubMed

    Jo, Bong-Seok; Koh, In-Uk; Bae, Jae-Bum; Yu, Ho-Yeong; Jeon, Eun-Seok; Lee, Hae-Young; Kim, Jae-Joong; Choi, Murim; Choi, Sun Shim

    2016-08-01

    Dilated cardiomyopathy (DCM) is one of the main causes of heart failure (called cardiomyopathies) in adults. Alterations in epigenetic regulation (i.e., DNA methylation) have been implicated in the development of DCM. Here, we identified a total of 1828 differentially methylated probes (DMPs) using the Infinium 450K HumanMethylation Bead chip by comparing the methylomes between 18 left ventricles and 9 right ventricles. Alterations in DNA methylation levels were observed mainly in lowly methylated regions corresponding to promoter-proximal regions, which become hypermethylated in severely affected left ventricles. Subsequent mRNA microarray analysis showed that the effect of DNA methylation on gene expression regulation is not unidirectional but is controlled by the functional sub-network context. DMPs were significantly enriched in the transcription factor binding sites (TFBSs) we tested. Alterations in DNA methylation were specifically enriched in the cis-regulatory regions of cardiac development genes, the majority of which are involved in ventricular development (e.g., TBX5 and HAND1). Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Plant somatic hybrid cytoplasmic DNA characterization by single-strand conformation polymorphism.

    PubMed

    Olivares-Fuster, Oscar; Hernández-Garrido, María; Guerri, José; Navarro, Luis

    2007-06-01

    Unlike maternal inheritance in sexual hybridization, plant somatic hybridization allows transfer, mixing and recombination of cytoplasmic genomes. In addition to the use of somatic hybridization in plant breeding programs, application of this unique tool should lead to a better understanding of the roles played by the chloroplastic and mitochondrial genomes in determining agronomically important traits. The nucleotide sequences of cytoplasmic genomes are much more conserved than those of nuclear genomes. Cytoplasmic DNA composition in somatic hybrids is commonly elucidated either by length polymorphism analysis of restricted genome regions amplified with universal primers (PCR-RF) or by hybridization of total DNA using universal cytoplasmic probes. In this study, we demonstrate that single-stranded conformational polymorphism (SSCP) analysis is a powerful, quick and easy alternative method for cytoplasmic DNA characterization of somatic hybrids, especially for mitochondrial DNA. The technique allows detection of polymorphisms based on both size and sequence of amplified targets. Twenty-two species of the subfamily Aurantioideae were analyzed with eight universal primers (four from chloroplastic and four from mitochondrial regions). Differences in chloroplastic DNA composition were scored in 98% of all possible two-parent combinations, and different mitochondrial DNA profiles were found in 87% of them. Analysis by SSCP was also successfully used to characterize somatic hybrids and cybrids obtained by fusion of Citrus sinensis (L.) Osb. and C. excelsa Wester protoplasts.

  8. Characterization of field and vaccine infectious bursal disease viruses from Nigeria revealing possible virulence and regional markers in the VP2 minor hydrophilic peaks.

    PubMed

    Adamu, J; Owoade, A A; Abdu, P A; Kazeem, H M; Fatihu, M Y

    2013-01-01

    Outbreaks of infectious bursal disease in vaccinated chicken flocks are frequent in Nigeria. For the control of infectious bursal disease, live vaccines based on foreign infectious bursal disease virus (IBDV) strains are used. The present study investigated the phylogenetic relationship between field and vaccine IBDV strains from northwestern Nigeria. Thirty field IBDV strains and three commercial vaccines strains were characterized through sequencing the VP2 hypervariable region. In addition, the complete genome segment A coding region for two vaccines and two field strains was sequenced. The deduced amino acid sequences (position 212 to 331) of IBDV strains from Nigeria and other regions of the world were aligned and possible regional and virulence markers were identified associated with VP2 minor hydrophilic peaks. Reversion to virulence of a vaccine strain with a Q to L mutation at position 253 was observed. Phylogenetic analyses revealed a unique cluster of northwest Nigerian field IBDV strains alone or related to imported characterized classical and very virulent IBDV vaccines. The results suggest that when IBDV strains spread from their region of origin to a different region they mutate alongside indigenous field strains but may retain their identity on the VP2 region.

  9. Cellular Mechanisms of Somatic Stem Cell Aging

    PubMed Central

    Jung, Yunjoon

    2014-01-01

    Tissue homeostasis and regenerative capacity rely on rare populations of somatic stem cells endowed with the potential to self-renew and differentiate. During aging, many tissues show a decline in regenerative potential coupled with a loss of stem cell function. Cells including somatic stem cells have evolved a series of checks and balances to sense and repair cellular damage to maximize tissue function. However, during aging the mechanisms that protect normal cell function begin to fail. In this review, we will discuss how common cellular mechanisms that maintain tissue fidelity and organismal lifespan impact somatic stem cell function. We will highlight context-dependent changes and commonalities that define aging, by focusing on three age-sensitive stem cell compartments: blood, neural, and muscle. Understanding the interaction between extrinsic regulators and intrinsic effectors that operate within different stem cell compartments is likely to have important implications for identifying strategies to improve health span and treat age-related degenerative diseases. PMID:24439814

  10. [Revertant somatic mosaicism in primary immunodeficiency diseases].

    PubMed

    Wada, Taizo

    2014-01-01

    Revertant somatic mosaicism has been described in an increasing number of genetic disorders including primary immunodeficiency diseases. Both back mutations leading to restoration of wild-type sequences and second-site mutations resulting in compensatory changes have been demonstrated in mosaic individuals. Recent studies identifying revertant somatic mosaicism caused by multiple independent genetic changes further support its frequent occurrence in primary immunodeficiency diseases. Revertant mosaicism acquires a particular clinical relevance because it may lead to selective growth advantage of the corrected cells, resulting in improvement of disease symptoms or atypical clinical presentations. This phenomenon also provides us unique opportunities to evaluate the biological effects of restored gene expression in different cell lineages. Here we review the recent findings of revertant somatic mosaicism in primary immunodeficiency diseases and discuss its clinical implications.

  11. A simple consensus approach improves somatic mutation prediction accuracy

    PubMed Central

    2013-01-01

    Differentiating true somatic mutations from artifacts in massively parallel sequencing data is an immense challenge. To develop methods for optimal somatic mutation detection and to identify factors influencing somatic mutation prediction accuracy, we validated predictions from three somatic mutation detection algorithms, MuTect, JointSNVMix2 and SomaticSniper, by Sanger sequencing. Full consensus predictions had a validation rate of >98%, but some partial consensus predictions validated too. In cases of partial consensus, read depth and mapping quality data, along with additional prediction methods, aided in removing inaccurate predictions. Our consensus approach is fast, flexible and provides a high-confidence list of putative somatic mutations. PMID:24073752

  12. Coherent Somatic Mutation in Autoimmune Disease

    PubMed Central

    Ross, Kenneth Andrew

    2014-01-01

    Background Many aspects of autoimmune disease are not well understood, including the specificities of autoimmune targets, and patterns of co-morbidity and cross-heritability across diseases. Prior work has provided evidence that somatic mutation caused by gene conversion and deletion at segmentally duplicated loci is relevant to several diseases. Simple tandem repeat (STR) sequence is highly mutable, both somatically and in the germ-line, and somatic STR mutations are observed under inflammation. Results Protein-coding genes spanning STRs having markers of mutability, including germ-line variability, high total length, repeat count and/or repeat similarity, are evaluated in the context of autoimmunity. For the initiation of autoimmune disease, antigens whose autoantibodies are the first observed in a disease, termed primary autoantigens, are informative. Three primary autoantigens, thyroid peroxidase (TPO), phogrin (PTPRN2) and filaggrin (FLG), include STRs that are among the eleven longest STRs spanned by protein-coding genes. This association of primary autoantigens with long STR sequence is highly significant (). Long STRs occur within twenty genes that are associated with sixteen common autoimmune diseases and atherosclerosis. The repeat within the TTC34 gene is an outlier in terms of length and a link with systemic lupus erythematosus is proposed. Conclusions The results support the hypothesis that many autoimmune diseases are triggered by immune responses to proteins whose DNA sequence mutates somatically in a coherent, consistent fashion. Other autoimmune diseases may be caused by coherent somatic mutations in immune cells. The coherent somatic mutation hypothesis has the potential to be a c