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Sample records for region reveals somatic

  1. Myeloma Ig heavy chain V region sequences reveal prior antigenic selection and marked somatic mutation but no intraclonal diversity

    SciTech Connect

    Vescio, R.A.; Cao, J.; Hong, C.H.

    1995-09-01

    The IgV{sub H} region sequence in 48 patients with multiple myeloma (MM) was analyzed to characterize the malignant cell of origin. The sequences were obtained after amplification of bone marrow cDNA by using V{sub H} family-specific and C{sub H} primers, then compared with either directly sequenced patient germ-line or published V{sub H} gene sequences to assay for somatic mutation. Because somatic hypermutation of the V{sub H} gene occurs late in B cell development, its presence has been helpful in determining the cell of origin in other B cell malignancies. Overall, a median of 8.2% of the nucleotides had evidence of substitution within each V{sub H} gene sequence (range = 2.7% to 16.5%), which is more prevalent than in any other reported tumor type. Strong evidence of prior antigenic selection pressure was also evident. The ratio of nucleotide substitutions that resulted in amino acid replacement was significantly higher in the complementarity-determining region than in the framework region (3.25 vs. 1.56, respectively; p < 0.00005). No V{sub H} gene intraclonal diversity was noted, despite sequencing multiple clones (3-16) from each patient, nor was there evidence of further V{sub H} gene somatic mutation over the course of three patients` disease. These findings strongly imply that the malignant clone in MM evolves from a cell late in B cell development. 63 refs., 4 figs., 2 tabs.

  2. Copy number and targeted mutational analysis reveals novel somatic events in metastatic prostate tumors.

    PubMed

    Robbins, Christiane M; Tembe, Waibov A; Baker, Angela; Sinari, Shripad; Moses, Tracy Y; Beckstrom-Sternberg, Stephen; Beckstrom-Sternberg, James; Barrett, Michael; Long, James; Chinnaiyan, Arul; Lowey, James; Suh, Edward; Pearson, John V; Craig, David W; Agus, David B; Pienta, Kenneth J; Carpten, John D

    2011-01-01

    Advanced prostate cancer can progress to systemic metastatic tumors, which are generally androgen insensitive and ultimately lethal. Here, we report a comprehensive genomic survey for somatic events in systemic metastatic prostate tumors using both high-resolution copy number analysis and targeted mutational survey of 3508 exons from 577 cancer-related genes using next generation sequencing. Focal homozygous deletions were detected at 8p22, 10q23.31, 13q13.1, 13q14.11, and 13q14.12. Key genes mapping within these deleted regions include PTEN, BRCA2, C13ORF15, and SIAH3. Focal high-level amplifications were detected at 5p13.2-p12, 14q21.1, 7q22.1, and Xq12. Key amplified genes mapping within these regions include SKP2, FOXA1, and AR. Furthermore, targeted mutational analysis of normal-tumor pairs has identified somatic mutations in genes known to be associated with prostate cancer including AR and TP53, but has also revealed novel somatic point mutations in genes including MTOR, BRCA2, ARHGEF12, and CHD5. Finally, in one patient where multiple independent metastatic tumors were available, we show common and divergent somatic alterations that occur at both the copy number and point mutation level, supporting a model for a common clonal progenitor with metastatic tumor-specific divergence. Our study represents a deep genomic analysis of advanced metastatic prostate tumors and has revealed candidate somatic alterations, possibly contributing to lethal prostate cancer. PMID:21147910

  3. Copy number and targeted mutational analysis reveals novel somatic events in metastatic prostate tumors

    PubMed Central

    Robbins, Christiane M.; Tembe, Waibov A.; Baker, Angela; Sinari, Shripad; Moses, Tracy Y.; Beckstrom-Sternberg, Stephen; Beckstrom-Sternberg, James; Barrett, Michael; Long, James; Chinnaiyan, Arul; Lowey, James; Suh, Edward; Pearson, John V.; Craig, David W.; Agus, David B.; Pienta, Kenneth J.; Carpten, John D.

    2011-01-01

    Advanced prostate cancer can progress to systemic metastatic tumors, which are generally androgen insensitive and ultimately lethal. Here, we report a comprehensive genomic survey for somatic events in systemic metastatic prostate tumors using both high-resolution copy number analysis and targeted mutational survey of 3508 exons from 577 cancer-related genes using next generation sequencing. Focal homozygous deletions were detected at 8p22, 10q23.31, 13q13.1, 13q14.11, and 13q14.12. Key genes mapping within these deleted regions include PTEN, BRCA2, C13ORF15, and SIAH3. Focal high-level amplifications were detected at 5p13.2-p12, 14q21.1, 7q22.1, and Xq12. Key amplified genes mapping within these regions include SKP2, FOXA1, and AR. Furthermore, targeted mutational analysis of normal-tumor pairs has identified somatic mutations in genes known to be associated with prostate cancer including AR and TP53, but has also revealed novel somatic point mutations in genes including MTOR, BRCA2, ARHGEF12, and CHD5. Finally, in one patient where multiple independent metastatic tumors were available, we show common and divergent somatic alterations that occur at both the copy number and point mutation level, supporting a model for a common clonal progenitor with metastatic tumor-specific divergence. Our study represents a deep genomic analysis of advanced metastatic prostate tumors and has revealed candidate somatic alterations, possibly contributing to lethal prostate cancer. PMID:21147910

  4. [Somatic polyploidy associated metabolic changes revealed by modular biology].

    PubMed

    Anatskaia, O V; Vinogradov, A E

    2010-01-01

    Excessive somatic polyploidy usually accompanies physiologic and pathologic overload and it is generally accepted as a symptom of pathology. At the same time, polyploidy cells exist in most fungal, plant, mollusk, fish, bird and mammalian tissues confirming their great evolutionary success. The secret of this success remains enigmatic. Since transcriptome rearrangements usually start with metabolic flux redistribution, we decided to investigate firstly the effects of polyploidy on cell metabolism. Using multitest approach of modular biology and databases Entrez Gene, RefSeq, GNF SymAtlas, Gene Ontology, KEGG, BioCarta; MsigDb, Reactome, GenMAPP, and HumanCyc, we performed detailed comparison of metabolic genes expression in human and mouse organs with reciprocal pattern of polyploidy (i. e. in the heart and in the liver). Pairwise criss-cross comparison of diploid vs. polyploid organs allowed removing species- and tissue-specific effects. From our results, polyploidy is associated with rearrangements of main metabolic pathways. We found deep depression of mitochondrial processes, features of autophagia, and increased carbohydrate degradation and lipid biosynthesis. Taken together, these changes pointed to the energy and oxygen deprivation. We also found clear indications of enhanced oxidative stress protection. The major of them are triggering of pentose-phosphate pathway, depression of mitochondria-cytoplasm electron shuttles, and impartment of electron flows across 1 (NADH dehydrogenase) and IV (cytochrome c-oxydase) breath complexes. We suggest that all these changes are necessary for the increase in metabolic plasticity and for the protection of replicating DNA from oxidative damage. PMID:20302017

  5. Targeted Deep Sequencing Reveals No Definitive Evidence for Somatic Mosaicism in Atrial Fibrillation

    PubMed Central

    Roberts, Jason D.; Longoria, James; Poon, Annie; Gollob, Michael H.; Dewland, Thomas A.; Kwok, Pui-Yan; Olgin, Jeffrey E.; Deo, Rahul C.; Marcus, Gregory M.

    2015-01-01

    Background Studies of ≤15 atrial fibrillation (AF) patients have identified atrial-specific mutations within connexin genes, suggesting that somatic mutations may account for sporadic cases of the arrhythmia. We sought to identify atrial somatic mutations among patients with and without AF using targeted deep next-generation sequencing of 560 genes, including genetic culprits implicated in AF, the Mendelian cardiomyopathies and channelopathies, and all ion channels within the genome. Methods and Results Targeted gene capture and next generation sequencing were performed on DNA from lymphocytes and left atrial appendages of 34 patients (25 with AF). Twenty AF patients had undergone cardiac surgery exclusively for pulmonary vein isolation, and 17 had no structural heart disease. Sequence alignment and variant calling were performed for each atrial-lymphocyte pair using the Burrows-Wheeler Aligner, the Genome Analysis Toolkit, and MuTect packages. Next generation sequencing yielded a median 265-fold coverage depth (IQR 164–369). Comparison of the 3 million base pairs from each atrial-lymphocyte pair revealed a single potential somatic missense mutation in 3 AF patients and 2 in a single control (12 vs. 11%; p=1). All potential discordant variants had low allelic fractions (range: 2.3–7.3%) and none were detected with conventional sequencing. Conclusions Using high-depth next generation sequencing and state-of-the art somatic mutation calling approaches, no pathogenic atrial somatic mutations could be confirmed among 25 AF patients in a comprehensive cardiac arrhythmia genetic panel. These findings indicate that atrial specific mutations are rare and that somatic mosaicism is unlikely to exert a prominent role in AF pathogenesis. PMID:25406240

  6. 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. PMID:24622213

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

    PubMed Central

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

    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. PMID:24622213

  8. 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.

  9. Epigenetic transgenerational inheritance of somatic transcriptomes and epigenetic control regions

    PubMed Central

    2012-01-01

    Background Environmentally induced epigenetic transgenerational inheritance of adult onset disease involves a variety of phenotypic changes, suggesting a general alteration in genome activity. Results Investigation of different tissue transcriptomes in male and female F3 generation vinclozolin versus control lineage rats demonstrated all tissues examined had transgenerational transcriptomes. The microarrays from 11 different tissues were compared with a gene bionetwork analysis. Although each tissue transgenerational transcriptome was unique, common cellular pathways and processes were identified between the tissues. A cluster analysis identified gene modules with coordinated gene expression and each had unique gene networks regulating tissue-specific gene expression and function. A large number of statistically significant over-represented clusters of genes were identified in the genome for both males and females. These gene clusters ranged from 2-5 megabases in size, and a number of them corresponded to the epimutations previously identified in sperm that transmit the epigenetic transgenerational inheritance of disease phenotypes. Conclusions Combined observations demonstrate that all tissues derived from the epigenetically altered germ line develop transgenerational transcriptomes unique to the tissue, but common epigenetic control regions in the genome may coordinately regulate these tissue-specific transcriptomes. This systems biology approach provides insight into the molecular mechanisms involved in the epigenetic transgenerational inheritance of a variety of adult onset disease phenotypes. PMID:23034163

  10. GENOMIC ANALYSIS OF CANCER TISSUE REVEALS THAT SOMATIC MUTATIONS COMMONLY OCCUR IN A SPECIFIC MOTIF

    PubMed Central

    Makridakis, Nick M; Ferraz, Lúcio Fábio Caldas; Reichardt, Juergen KV

    2009-01-01

    Somatic mutations are hallmarks of cancer progression. We sequenced 26 matched human prostate tumor and constitutional DNA samples for somatic alterations in the SRD5A2, HPRT, and HSD3B2 genes, and identified 71 nucleotide substitutions. 79% (56/71) of these substitutions occur within a WKVnRRRnVWK sequence (THEMIS motif; W= A/T, K= G/T, V= G/A/C, R= purine (A/G) and n= any nucleotide), with one mismatch allowed. Literature searches identified this motif with one mismatch allowed in 66% (37/ 56) of the somatic prostate cancer mutations and in 74% (90/ 122) of the somatic breast cancer mutations found in all human genes analyzed. We also found the THEMIS motif with one allowed mismatch in 88% (23/26) of the ras1 gene somatic mutations formed in the SENCAR (SENsitive to skin CARcinogenesis) mouse model, after induction of error-prone DNA repair following mutagenic treatment. The high prevalence of the motif in each of the above mentioned cases cannot be explained by chance (p < 0.046). We further identified 27 somatic mutations in the error-prone DNA polymerase genes pol η, pol κ and pol β in these prostate cancer patients. The data suggest that most somatic nucleotide substitutions in human cancer may occur in sites that conform to the THEMIS motif. These mutations may be caused by “mutator” mutations in error-prone DNA polymerase genes. PMID:18623241

  11. Genomic profiling reveals extensive heterogeneity in somatic DNA copy number aberrations of canine hemangiosarcoma.

    PubMed

    Thomas, Rachael; Borst, Luke; Rotroff, Daniel; Motsinger-Reif, Alison; Lindblad-Toh, Kerstin; Modiano, Jaime F; Breen, Matthew

    2014-09-01

    Canine hemangiosarcoma is a highly aggressive vascular neoplasm associated with extensive clinical and anatomical heterogeneity and a grave prognosis. Comprehensive molecular characterization of hemangiosarcoma may identify novel therapeutic targets and advanced clinical management strategies, but there are no published reports of tumor-associated genome instability and disrupted gene dosage in this cancer. We performed genome-wide microarray-based somatic DNA copy number profiling of 75 primary intra-abdominal hemangiosarcomas from five popular dog breeds that are highly predisposed to this disease. The cohort exhibited limited global genomic instability, compared to other canine sarcomas studied to date, and DNA copy number aberrations (CNAs) were predominantly of low amplitude. Recurrent imbalances of several key cancer-associated genes were evident; however, the global penetrance of any single CNA was low and no distinct hallmark aberrations were evident. Copy number gains of dog chromosomes 13, 24, and 31, and loss of chromosome 16, were the most recurrent CNAs involving large chromosome regions, but their relative distribution within and between cases suggests they most likely represent passenger aberrations. CNAs involving CDKN2A, VEGFA, and the SKI oncogene were identified as potential driver aberrations of hemangiosarcoma development, highlighting potential targets for therapeutic modulation. CNA profiles were broadly conserved between the five breeds, although subregional variation was evident, including a near twofold lower incidence of VEGFA gain in Golden Retrievers versus other breeds (22 versus 40 %). These observations support prior transcriptional studies suggesting that the clinical heterogeneity of this cancer may reflect the existence of multiple, molecularly distinct subtypes of canine hemangiosarcoma. PMID:24599718

  12. 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

  13. 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

    2016-01-01

    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

  14. 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. PMID:23160490

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

    PubMed Central

    Abyzov, Alexej; Mariani, Jessica; Palejev, Dean; Zhang, Ying; Haney, Michael Seamus; Tomasini, Livia; Ferrandino, Anthony; Belmaker, Lior A. Rosenberg; 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.

    2012-01-01

    Reprogramming human somatic cells into induced pluripotent stem cells (iPSCs) has been suspected of causing de novo copy number variations (CNVs)1-4. To explore this issue, we performed a whole-genome and transcriptome analysis of 20 human iPSC lines derived from primary skin fibroblasts of 7 individuals using next-generation sequencing. We find that, on average, an iPSC line manifests two CNVs not apparent in the fibroblasts from which the iPSC was derived. Using qPCR, PCR, and digital droplet PCR (ddPCR), we show that at least 50% of those CNVs are present as low frequency somatic genomic variants in parental fibroblasts (i.e. the fibroblasts from which each corresponding hiPSC line is derived) and are manifested in iPSC colonies due to the colonies’ clonal origin. Hence, reprogramming does not necessarily lead to de novo CNVs in iPSC, since most of 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. PMID:23160490

  16. 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

    2014-01-01

    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

  17. 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

  18. Next-generation sequencing reveals somatic mutations that confer exceptional response to everolimus

    PubMed Central

    Kim, Sangwoo; Kim, Sora; Ali, Siraj M.; Greenbowe, Joel R.; Yang, In Seok; Kwon, Nak-Jung; Lee, Jae Lyun; Ryu, Min-Hee; Ahn, Jin-Hee; Lee, Jeeyun; Lee, Min Goo; Kim, Hyo Song; Kim, Hyunki; Kim, Hye Ryun; Moon, Yong Wha; Chung, Hyun Cheol; Kim, Joo-Hang; Kang, Yoon-Koo; Cho, Byoung Chul

    2016-01-01

    Background Given the modest responses to everolimus, a mTOR inhibitor, in multiple tumor types, there is a pressing need to identify predictive biomarkers for this drug. Using targeted ultra-deep sequencing, we aimed to explore genomic alterations that confer extreme sensitivity to everolimus. Results We collected formalin-fixed paraffin-embedded tumor/normal pairs from 39 patients (22 with exceptional clinical benefit, 17 with no clinical benefit) who were treated with everolimus across various tumor types (13 gastric cancers, 15 renal cell carcinomas, 2 thyroid cancers, 2 head and neck cancer, and 7 sarcomas). Ion AmpliSeqTM Comprehensive Cancer Panel was used to identify alterations across all exons of 409 target genes. Tumors were sequenced to a median coverage of 552x. Cancer genomes are characterized by 219 somatic single-nucleotide variants (181 missense, 9 nonsense, 7 splice-site) and 22 frameshift insertions/deletions, with a median of 2.1 mutations per Mb (0 to 12.4 mutations per Mb). Overall, genomic alterations with activating effect on mTOR signaling were identified in 10 of 22 (45%) patients with clinical benefit and these include MTOR, TSC1, TSC2, NF1, PIK3CA and PIK3CG mutations. Recurrently mutated genes in chromatin remodeling genes (BAP1; n = 2, 12%) and receptor tyrosine kinase signaling (FGFR4; n = 2, 12%) were noted only in patients without clinical benefit. Conclusions Regardless of different cancer types, mTOR-pathway-activating mutations confer sensitivity to everolimus. Targeted sequencing of mTOR pathway genes facilitates identification of potential candidates for mTOR inhibitors. PMID:26859683

  19. Exome sequencing of lymphomas from three dog breeds reveals somatic mutation patterns reflecting genetic background

    PubMed Central

    Elvers, Ingegerd; Turner-Maier, Jason; Swofford, Ross; Koltookian, Michele; Johnson, Jeremy; Stewart, Chip; Zhang, Cheng-Zhong; Schumacher, Steven E.; Beroukhim, Rameen; Rosenberg, Mara; Thomas, Rachael; Mauceli, Evan; Getz, Gad; Palma, Federica Di; Modiano, Jaime F.; Breen, Matthew; Lindblad-Toh, Kerstin; Alföldi, Jessica

    2015-01-01

    Lymphoma is the most common hematological malignancy in developed countries. Outcome is strongly determined by molecular subtype, reflecting a need for new and improved treatment options. Dogs spontaneously develop lymphoma, and the predisposition of certain breeds indicates genetic risk factors. Using the dog breed structure, we selected three lymphoma predisposed breeds developing primarily T-cell (boxer), primarily B-cell (cocker spaniel), and with equal distribution of B- and T-cell lymphoma (golden retriever), respectively. We investigated the somatic mutations in B- and T-cell lymphomas from these breeds by exome sequencing of tumor and normal pairs. Strong similarities were evident between B-cell lymphomas from golden retrievers and cocker spaniels, with recurrent mutations in TRAF3-MAP3K14 (28% of all cases), FBXW7 (25%), and POT1 (17%). The FBXW7 mutations recurrently occur in a specific codon; the corresponding codon is recurrently mutated in human cancer. In contrast, T-cell lymphomas from the predisposed breeds, boxers and golden retrievers, show little overlap in their mutation pattern, sharing only one of their 15 most recurrently mutated genes. Boxers, which develop aggressive T-cell lymphomas, are typically mutated in the PTEN-mTOR pathway. T-cell lymphomas in golden retrievers are often less aggressive, and their tumors typically showed mutations in genes involved in cellular metabolism. We identify genes with known involvement in human lymphoma and leukemia, genes implicated in other human cancers, as well as novel genes that could allow new therapeutic options. PMID:26377837

  20. A somatic cell hybrid panel for pig regional gene mapping characterized by molecular cytogenetics.

    PubMed

    Yerle, M; Echard, G; Robic, A; Mairal, A; Dubut-Fontana, C; Riquet, J; Pinton, P; Milan, D; Lahbib-Mansais, Y; Gellin, J

    1996-01-01

    A panel of 27 pig x rodent somatic cell hybrids was produced and characterized cytogenetically. The first step of this study consisted of hybridizing a SINE probe to GTG-banded metaphases of each hybrid clone in order to count and identify the normal pig chromosomes and to detect rearranged ones. The second step consisted of using the DNA of each clone as a probe after pIRS-PCR (porcine interspersed repetitive sequence-polymerase chain reaction) amplification to highly enrich it in pig sequences. These probes, hybridized to normal pig metaphase chromosomes, enabled the identification of the complete porcine complement in the hybrid lines. Whole chromosomes and fragments were characterized quickly and precisely, and results were compared. In addition to this cytogenetic characterization, molecular verification was also carried out by using primers specific to six microsatellites and to one gene previously mapped to pig chromosomes. The results obtained allow us to conclude that we have produced a panel that is informative for all porcine chromosomes. This panel constitutes a highly efficient tool to establish not only assignments of genes and markers but also regional localizations on pig chromosomes. PMID:8697807

  1. 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

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

    PubMed

    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

    2016-04-19

    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

  3. 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

  4. [Micronuclear index of somatic cells in the population of Chernivtsi region and its ecological conditionality].

    PubMed

    Rudenko, S S; Morozova, T V; Kostyshyn, S S; Bezrukov, V F; Gorova, A I

    2002-01-01

    Large-scale estimation of micronuclear index in the population of different physical-geographic regions near Chernivtsi was performed for the first time. The authors managed to reveal the correlation between the rate of genetic changes in children from Bukovyna and the level of soil and water contamination with heavy metals and aluminum in settlements examined. PMID:12379013

  5. Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine

    PubMed Central

    2011-01-01

    Background Globally, gastric cancer is the second most common cause of cancer-related death, with the majority of the health burden borne by economically less-developed countries. Methods Here, we report a genetic characterization of 50 gastric adenocarcinoma samples, using affymetrix SNP arrays and Illumina mRNA expression arrays as well as Illumina sequencing of the coding regions of 384 genes belonging to various pathways known to be altered in other cancers. Results Genetic alterations were observed in the WNT, Hedgehog, cell cycle, DNA damage and epithelial-to-mesenchymal-transition pathways. Conclusions The data suggests targeted therapies approved or in clinical development for gastric carcinoma would be of benefit to ~22% of the patients studied. In addition, the novel mutations detected here, are likely to influence clinical response and suggest new targets for drug discovery. PMID:21781349

  6. De novo genetic variation revealed in somatic sectors of single Arabidopsis plants

    PubMed Central

    Hopkins, Marianne T; Khalid, Aaron M; Chang, Pei-Chun; Vanderhoek, Karen C; Lai, Dulcie; Doerr, Meghan D; Lolle, Susan J

    2013-01-01

    Concern over the tremendous loss of genetic diversity among many of our most important crops has prompted major efforts to preserve seed stocks derived from cultivated species and their wild relatives.  Arabidopsis thaliana propagates mainly by self-fertilizing, and therefore, like many crop plants, theoretically has a limited potential for producing genetically diverse offspring. Despite this, inbreeding has persisted in Arabidopsis for over a million years suggesting that some underlying adaptive mechanism buffers the deleterious consequences of this reproductive strategy. Using presence-absence molecular markers we demonstrate that single Arabidopsis plants can have multiple genotypes. Sequence analyses reveal single nucleotide changes, loss of sequences and, surprisingly, acquisition of unique genomic insertions. Estimates based on quantitative analyses suggest that these genetically discordant sectors are very small but can have a complex genetic makeup. In ruling out more trivial explanations for these data, our findings raise the possibility that intrinsic drivers of genetic variation are responsible for the targeted sequence changes we detect. Given the evolutionary advantage afforded to populations with greater genetic diversity, we hypothesize that organisms that primarily self-fertilize or propagate clonally counteract the genetic cost of such reproductive strategies by leveraging a cryptic reserve of extra-genomic information. PMID:24555023

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

    PubMed

    Kretzmer, Helene; Bernhart, Stephan H; Wang, Wei; Haake, Andrea; Weniger, Marc A; Bergmann, Anke K; 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; Hummel, Michael; Karsch, Dennis; Kerstens, Hinrik H D; Klapper, Wolfram; Kreuz, Markus; Lawerenz, Chris; Lenze, Dido; Loeffler, Markus; López, Cristina; MacLeod, Roderick A F; Martens, Joost H A; Kulis, Marta; Martín-Subero, José Ignacio; Möller, Peter; Nagel, 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

    2015-11-01

    Although Burkitt lymphomas and follicular lymphomas both have features of germinal center B cells, they are biologically and clinically quite distinct. Here we performed whole-genome bisulfite, genome and transcriptome sequencing in 13 IG-MYC translocation-positive Burkitt lymphoma, nine BCL2 translocation-positive follicular lymphoma and four normal germinal center B cell samples. Comparison of Burkitt and follicular lymphoma samples showed differential methylation of intragenic regions that strongly correlated with expression of associated genes, for example, genes active in germinal center dark-zone and light-zone B cells. Integrative pathway analyses of regions differentially methylated in Burkitt and follicular lymphomas implicated DNA methylation as cooperating 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 in Burkitt lymphoma and other germinal center B cell lymphomas. PMID:26437030

  8. Analysis of a four generation family reveals the widespread sequence-dependent maintenance of allelic DNA methylation in somatic and germ cells

    PubMed Central

    Tang, Aifa; Huang, Yi; Li, Zesong; Wan, Shengqing; Mou, Lisha; Yin, Guangliang; Li, Ning; Xie, Jun; Xia, Yudong; Li, Xianxin; Luo, Liya; Zhang, Junwen; Chen, Shen; Wu, Song; Sun, Jihua; Sun, Xiaojuan; Jiang, Zhimao; Chen, Jing; Li, Yingrui; Wang, Jian; Wang, Jun; Cai, Zhiming; Gui, Yaoting

    2016-01-01

    Differential methylation of the homologous chromosomes, a well-known mechanism leading to genomic imprinting and X-chromosome inactivation, is widely reported at the non-imprinted regions on autosomes. To evaluate the transgenerational DNA methylation patterns in human, we analyzed the DNA methylomes of somatic and germ cells in a four-generation family. We found that allelic asymmetry of DNA methylation was pervasive at the non-imprinted loci and was likely regulated by cis-acting genetic variants. We also observed that the allelic methylation patterns for the vast majority of the cis-regulated loci were shared between the somatic and germ cells from the same individual. These results demonstrated the interaction between genetic and epigenetic variations and suggested the possibility of widespread sequence-dependent transmission of DNA methylation during spermatogenesis. PMID:26758766

  9. Constitutional and somatic deletions of the Williams-Beuren syndrome critical region in non-Hodgkin lymphoma.

    PubMed

    Guenat, David; Quentin, Samuel; Rizzari, Carmelo; Lundin, Catarina; Coliva, Tiziana; Edery, Patrick; Fryssira, Helen; Bermont, Laurent; Ferrand, Christophe; Soulier, Jean; Borg, Christophe; Rohrlich, Pierre-Simon

    2014-01-01

    Here, we report and investigate the genomic alterations of two novel cases of Non-Hodgkin Lymphoma (NHL) in children with Williams-Beuren syndrome (WBS), a multisystem disorder caused by 7q11.23 hemizygous deletion. Additionally, we report the case of a child with NHL and a somatic 7q11.23 deletion. Although the WBS critical region has not yet been identified as a susceptibility locus in NHL, it harbors a number of genes involved in DNA repair. The high proportion of pediatric NHL reported in WBS is intriguing. Therefore, the role of haploinsufficiency of genes located at 7q11.23 in lymphomagenesis deserves to be investigated. PMID:25388916

  10. 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

    2014-01-01

    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. PMID:24777035

  11. Mitochondrial Physiology and Gene Expression Analyses Reveal Metabolic and Translational Dysregulation in Oocyte-Induced Somatic Nuclear Reprogramming

    PubMed Central

    Esteves, Telma C.; Psathaki, Olympia E.; Pfeiffer, Martin J.; Balbach, Sebastian T.; Zeuschner, Dagmar; Shitara, Hiroshi; Yonekawa, Hiromichi; Siatkowski, Marcin; Fuellen, Georg; Boiani, Michele

    2012-01-01

    While reprogramming a foreign nucleus after somatic cell nuclear transfer (SCNT), the enucleated oocyte (ooplasm) must signal that biomass and cellular requirements changed compared to the nucleus donor cell. Using cells expressing nuclear-encoded but mitochondria-targeted EGFP, a strategy was developed to directly distinguish maternal and embryonic products, testing ooplasm demands on transcriptional and post-transcriptional activity during reprogramming. Specifically, we compared transcript and protein levels for EGFP and other products in pre-implantation SCNT embryos, side-by-side to fertilized controls (embryos produced from the same oocyte pool, by intracytoplasmic injection of sperm containing the EGFP transgene). We observed that while EGFP transcript abundance is not different, protein levels are significantly lower in SCNT compared to fertilized blastocysts. This was not observed for Gapdh and Actb, whose protein reflected mRNA. This transcript-protein relationship indicates that the somatic nucleus can keep up with ooplasm transcript demands, whilst transcription and translation mismatch occurs after SCNT for certain mRNAs. We further detected metabolic disturbances after SCNT, suggesting a place among forces regulating post-transcriptional changes during reprogramming. Our observations ascribe oocyte-induced reprogramming with previously unsuspected regulatory dimensions, in that presence of functional proteins may no longer be inferred from mRNA, but rather depend on post-transcriptional regulation possibly modulated through metabolism. PMID:22693623

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

    PubMed Central

    Zhuang, Jiali; Weng, Zhiping

    2015-01-01

    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. PMID:26283183

  13. Human Immunoglobulin (Ig)M+IgD+ Peripheral Blood B Cells Expressing the CD27 Cell Surface Antigen Carry Somatically Mutated Variable Region Genes: CD27 as a General Marker for Somatically Mutated (Memory) B Cells

    PubMed Central

    Klein, Ulf; Rajewsky, Klaus; Küppers, Ralf

    1998-01-01

    Immunoglobulin (Ig)M+IgD+ B cells are generally assumed to represent antigen-inexperienced, naive B cells expressing variable (V) region genes without somatic mutations. We report here that human IgM+IgD+ peripheral blood (PB) B cells expressing the CD27 cell surface antigen carry mutated V genes, in contrast to CD27-negative IgM+IgD+ B cells. IgM+IgD+CD27+ B cells resemble class-switched and IgM-only memory cells in terms of cell phenotype, and comprise ∼15% of PB B lymphocytes in healthy adults. Moreover, a very small population (<1% of PB B cells) of highly mutated IgD-only B cells was detected, which likely represent the PB counterpart of IgD-only tonsillar germinal center and plasma cells. Overall, the B cell pool in the PB of adults consists of ∼40% mutated memory B cells and 60% unmutated, naive IgD+CD27− B cells (including CD5+ B cells). In the somatically mutated B cells, VH region genes carry a two- to threefold higher load of somatic mutation than rearranged Vκ genes. This might be due to an intrinsically lower mutation rate in κ light chain genes compared with heavy chain genes and/or result from κ light chain gene rearrangements in GC B cells. A common feature of the somatically mutated B cell subsets is the expression of the CD27 cell surface antigen which therefore may represent a general marker for memory B cells in humans. PMID:9802980

  14. Polymorphisms in the promoter region of the bovine lactoferrin gene influence milk somatic cell score and milk production traits in Chinese Holstein cows.

    PubMed

    Mao, Yongjiang; Zhu, Xiaorui; Xing, Shiyu; Zhang, Meirong; Zhang, Huimin; Wang, Xiaolong; Karrow, Niel; Yang, Liguo; Yang, Zhangping

    2015-12-01

    Lactoferrin is an iron-binding protein found in cow's milk that plays an important role in preventing mastitis caused by intramammary infection. In this study, 20 Chinese Holstein cows were selected randomly for PCR amplification and sequencing of the bovine lactoferrin gene promoter region and used for SNP discovery in the region between nucleotide positions -461 to -132. Three SNPs (-270T>C, -190G>A and -156A>G) were identified in bovine lactoferrin, then Chinese Holstein cows (n=866) were genotyped using Sequenom MassARRAY (Sequenom Inc., San Diego, CA) based on the previous SNP information in this study, and the associations between SNPs or haplotype and milk somatic cell score (SCS) and production traits were analyzed by the least squares method in the GLM procedure of SAS. SNPs -270T>C and -156A>G showed close linkage disequilibrium (r(2)=0.76). The SNP -190G>A showed a significant association with SCS, and individuals with genotype GG had higher SCS than genotypes AG and AA. Associations were found between the SNPs -270T>C and -190G>A with SCS and the milk composition. The software MatInspector revealed that these SNPs were located within several potential transcription factor binding sites, including NF-κB p50, KLF7 and SP1, and may alter gene expression, but further investigation will be required to elucidate the biological and practical relevance of these SNPs. PMID:26679804

  15. Comparative analysis of somatic copy-number alterations across different human cancer types reveals two distinct classes of breakpoint hotspots

    PubMed Central

    Li, Yudong; Zhang, Li; Ball, Robyn L.; Liang, Xinle; Li, Jianrong; Lin, Zhenguo; Liang, Han

    2012-01-01

    Somatic copy-number alterations (SCNAs) play a crucial role in the development of human cancer. However, it is not well understood what evolutionary mechanisms contribute to the global patterns of SCNAs in cancer genomes. Taking advantage of data recently available through The Cancer Genome Atlas, we performed a systematic analysis on genome-wide SCNA breakpoint data for eight cancer types. First, we observed a high degree of overall similarity among the SCNA breakpoint landscapes of different cancer types. Then, we compiled 19 genomic features and evaluated their effects on the observed SCNA patterns. We found that evolutionary indel and substitution rates between species (i.e. humans and chimpanzees) consistently show the strongest correlations with breakpoint frequency among all the surveyed features; whereas the effects of some features are quite cancer-type dependent. Focusing on SCNA breakpoint hotspots, we found that cancer-type-specific breakpoint hotspots and common hotspots show distinct patterns. Cancer-type-specific hotspots are enriched with known cancer genes but are poorly predicted from genomic features; whereas common hotspots show the opposite patterns. This contrast suggests that explaining high-frequency SCNAs in cancer may require different evolutionary models: positive selection driven by cancer genes, and non-adaptive evolution related to an intrinsically unstable genomic context. Our results not only present a systematic view of the effects of genetic factors on genome-wide SCNA patterns, but also provide deep insights into the evolutionary process of SCNAs in cancer. PMID:22899649

  16. 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. PMID:19395009

  17. 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

  18. 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. PMID:27152024

  19. Polymorphisms in the 5' upstream region of the CXCR1 chemokine receptor gene, and their association with somatic cell score in Holstein cattle in Canada.

    PubMed

    Leyva-Baca, I; Schenkel, F; Martin, J; Karrow, N A

    2008-01-01

    Identification of regulatory elements in 5' regions of chemokine genes is fundamental for understanding chemokine gene expression in response to infection diseases. The CXCR1 receptor is expressed on the surface of neutrophils and interacts primarily with CXCL8 (IL-8), the most potent chemoattractant for neutrophils. The aim of this study was to characterize the 5' upstream region (2.1 kb) of the bovine CXCR1 chemokine receptor gene for polymorphism content and to identify in silico potential transcription-factor binding sites. The 5' flanking region was found by mining the NCBI GenBank (www.ncbi.nlm.nih.gov/). A DNA sequence from the whole genome shotgun sequence project with reference number AC150887.4 contained the CXCR1 5' flanking sequence. Computer analysis revealed potential binding sites for the transcription factors nuclear factor kappaB (NF-kappaB), binding factor GATA-1, barbiturate inducible element (Barbie), nuclear factor of activated T-cells, and activator protein 1. Polymorphism discovery in this region was conducted by constructing an inclusive DNA pool including 2 phenotypic extreme groups, 20 bulls with high estimated breeding values (EBV) for somatic cell score (SCS), and 20 bulls with low EBV for SCS. Independent amplicons along the 5' flanking region of bovine CXCR1 were generated for polymorphism discovery by sequencing. Three novel single nucleotide polymorphisms (SNP), CXCR1c.-344T>C, CXCR1c.-1768T>A, and CXCR1c.-1830A>G, and a previously identified SNP in the coding region, CXCR1c.777G>C, were identified. The 4 SNP were genotyped in Canadian Holstein bulls (n = 338) using tetra-primer amplification refractory mutation system (ARMS)-PCR. Average allele substitution effects were estimated to investigate associations between the 4 SNP and EBV for SCS in first, second, and third and later lactations. Multiple trait analysis revealed that the SNP CXCR1c.-1768T>A was associated with EBV for SCS in the first and second lactations and over all 3

  20. 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.

  1. 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.

  2. 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.

  3. Somatic complaints in frontotemporal dementia

    PubMed Central

    Landqvist Waldö, Maria; Santillo, Alexander Frizell; Gustafson, Lars; Englund, Elisabet; Passant, Ulla

    2014-01-01

    Frontotemporal dementia (FTD) is associated with a broad spectrum of clinical characteristics. The objective of this study was to analyze the prevalence of unexplained somatic complaints in neuropathologically verified FTD. We also examined whether the somatic presentations correlated with protein pathology or regional brain pathology and if the patients with these somatic features showed more depressive traits. Ninety-seven consecutively neuropathologically verified FTLD patients were selected. All 97 patients were part of a longitudinal study of FTD and all medical records were systematically reviewed. The somatic complaints focused on were headache, musculoskeletal, gastro/urogenital and abnormal pain response. Symptoms of somatic character (either somatic complaints and/or abnormal pain response) were found in 40.2%. These patients did not differ from the total group with regard to gender, age at onset or duration. Six patients showed exaggerated reactions to sensory stimuli, whereas three patients showed reduced response to pain. Depressive traits were present in 38% and did not correlate with somatic complaints. Suicidal behavior was present in 17 patients, in 10 of these suicidal behavior was concurrent with somatic complaints. No clear correlation between somatic complaints and brain protein pathology, regional pathology or asymmetric hemispherical atrophy was found. Our results show that many FTD patients suffer from unexplained somatic complaints before and/or during dementia where no clear correlation can be found with protein pathology or regional degeneration. Somatic complaints are not covered by current diagnostic criteria for FTD, but need to be considered in diagnostics and care. The need for prospective studies with neuropathological follow up must be stressed as these phenomena remain unexplained, misinterpreted, bizarre and, in many cases, excruciating. PMID:25232513

  4. Ultra-fast local-haplotype variant calling using paired-end DNA-sequencing data reveals somatic mosaicism in tumor and normal blood samples

    PubMed Central

    Sengupta, Subhajit; Gulukota, Kamalakar; Zhu, Yitan; Ober, Carole; Naughton, Katherine; Wentworth-Sheilds, William; Ji, Yuan

    2016-01-01

    Somatic mosaicism refers to the existence of somatic mutations in a fraction of somatic cells in a single biological sample. Its importance has mainly been discussed in theory although experimental work has started to emerge linking somatic mosaicism to disease diagnosis. Through novel statistical modeling of paired-end DNA-sequencing data using blood-derived DNA from healthy donors as well as DNA from tumor samples, we present an ultra-fast computational pipeline, LocHap that searches for multiple single nucleotide variants (SNVs) that are scaffolded by the same reads. We refer to scaffolded SNVs as local haplotypes (LH). When an LH exhibits more than two genotypes, we call it a local haplotype variant (LHV). The presence of LHVs is considered evidence of somatic mosaicism because a genetically homogeneous cell population will not harbor LHVs. Applying LocHap to whole-genome and whole-exome sequence data in DNA from normal blood and tumor samples, we find wide-spread LHVs across the genome. Importantly, we find more LHVs in tumor samples than in normal samples, and more in older adults than in younger ones. We confirm the existence of LHVs and somatic mosaicism by validation studies in normal blood samples. LocHap is publicly available at http://www.compgenome.org/lochap. PMID:26420835

  5. 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

  6. Spring-block model reveals region-like structures.

    PubMed

    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

  7. Regional localisation of 19 brain expressed sequence tags to human chromosome 11 using PCR amplification of somatic cell hybrid DNAs.

    PubMed

    Slorach, E M; Polymeropoulos, M H; Evans, K L; Seawright, A; Fletcher, J M; Porteous, D J; Brookes, A J

    1995-01-01

    Expressed sequence tags (ESTs) provide an efficient route to the identification of genes involved in normal development and in disease. PCR amplification of somatic cell hybrid DNAs was used to localise 22 brain-derived ESTs to subregions of human chromosome 11. Problems encountered with the standardised PCR conditions were overcome by optimising the annealing temperatures and the use of "touchdown" PCR. Amplification of the correct target sequence allowed the mapping of 19 ESTs, 8 to the short arm and 11 to the long arm of chromosome 11. No definitive localisation could be determined for the three remaining ESTs. PMID:7736794

  8. Whole-exome sequencing of polycythemia vera revealed novel driver genes and somatic mutation shared by T-cells and granulocytes

    PubMed Central

    Wang, Linghua; Swierczek, Sabina I.; Drummond, Jennifer; Hickman, Kimberly; Walker, Kimberly; Doddapaneni, Harshavardhan; Muzny, Donna M.; Gibbs, Richard A.; Wheeler, David A.; Prchal, Josef T.

    2015-01-01

    To better understand the underlying molecular basis of polycythemia vera (PV), we performed whole-exome sequencing and DNA copy-number analysis of 31 JAK2V617F-positive patients and further investigated the evolution of somatic mutations using longitudinal samples. In addition to JAK2V617F and 9pUPD, we identified frequent recurrent somatic mutation in ASXL1, TET2, DNMT3A, SF3B1 and NF1. Forty two percent of patients had a somatic mutation in at least one epigenetic modifier gene. In 4 of 31 patients, variant allele abundance suggested mutation of JAK2V617F was preceded by other somatic mutations including ASXL1, DNMT3A and SF3B1. Strikingly, in 7 patients, apparent germline variants were detected at COSMIC codons in one or more PV-related genes in which we had also discovered somatic mutations across the cohort, suggesting that some pre-JAK2V617F mutations contribute to substantial T-lymphocyte progeny. This study contributes to novel understanding of the complexity of PV pathogenesis. PMID:24413320

  9. Mice deficient in carbonic anhydrase type 8 exhibit motor dysfunctions and abnormal calcium dynamics in the somatic region of cerebellar granule cells.

    PubMed

    Lamont, Matthew G; Weber, John T

    2015-06-01

    The waddles (wdl) mouse is characterized by a namesake "side-to-side" waddling gait due to a homozygous mutation of the Car8 gene. This mutation results in non-functional copies of the protein carbonic anhydrase type 8. Rota-rod testing was conducted to characterize the wdl mutations' effect on motor output. Results indicated that younger homozygotes outperformed their older cohorts, an effect not seen in previous studies. Heterozygotes, which were thought to be free of motor impairment, displayed motor learning deficiencies when compared with wild type performance. Acute cerebellar slices were then utilized for fluorescent calcium imaging experiments, which revealed significant alterations in cerebellar granule cell somatic calcium signaling when exposed to glutamate. The contribution of GABAergic signaling to these alterations was also verified using bath application of bicuculline. Changes in somatic calcium signals were found to be applicable to an in vivo scenario by comparing group responses to electrical stimulation of afferent mossy fiber projections. Finally, intracellular calcium store function was also found to be altered by the wdl mutation when slices were treated with thapsigargin. These findings, taken together with previous work on the wdl mouse, indicate a widespread disruption in cerebellar circuitry hampering proper neuronal communication. PMID:25721739

  10. 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

  11. Pyrosequencing reveals regional differences in fruit-associated fungal communities.

    PubMed

    Taylor, Michael W; Tsai, Peter; Anfang, Nicole; Ross, Howard A; Goddard, Matthew R

    2014-09-01

    We know relatively little of the distribution of microbial communities generally. Significant work has examined a range of bacterial communities, but the distribution of microbial eukaryotes is less well characterized. Humans have an ancient association with grape vines (Vitis vinifera) and have been making wine since the dawn of civilization, and fungi drive this natural process. While the molecular biology of certain fungi naturally associated with vines and wines is well characterized, complementary investigations into the ecology of fungi associated with fruiting plants is largely lacking. DNA sequencing technologies allow the direct estimation of microbial diversity from a given sample, avoiding culture-based biases. Here, we use deep community pyrosequencing approaches, targeted at the 26S rRNA gene, to examine the richness and composition of fungal communities associated with grapevines and test for geographical community structure among four major regions in New Zealand (NZ). We find over 200 taxa using this approach, which is 10-fold more than previously recovered using culture-based methods. Our analyses allow us to reject the null hypothesis of homogeneity in fungal species richness and community composition across NZ and reveal significant differences between major areas. PMID:24650123

  12. Attachment in romantic relationships and somatization.

    PubMed

    Neumann, Eva; Sattel, Heribert; Gündel, Harald; Henningsen, Peter; Kruse, Johannes

    2015-02-01

    Adult attachment representations have been considered to play a role in the development and treatment of somatizing behavior. In this study, the associations between the two attachment dimensions avoidance and anxiety and dimensions of psychopathology (somatization, depression, and general anxiety) were explored. The sample consists of 202 outpatients diagnosed with a somatoform disorder. Data were collected via self-report measures. A path analysis shows that the two attachment dimensions are not directly associated with somatization. There are, however, significant indirect associations between attachment and somatization mediated by depression and general anxiety, which are more pronounced for attachment anxiety than for attachment avoidance. The findings reveal that a low level of attachment security in romantic relationships, especially an anxious stance toward the partner, comes along with poor mental health, which in turn is related to a preoccupation with somatic complaints. Implications for the treatment of somatizing patients are discussed. PMID:25594785

  13. RNA-Seq Profiling of Intact and Enucleated Oocyte SCNT Embryos Reveals the Role of Pig Oocyte Nucleus in Somatic Reprogramming.

    PubMed

    Bai, Lin; Li, Mengqi; Sun, Junli; Yang, Xiaogan; Lu, Yangqing; Lu, Shengsheng; Lu, Kehuan

    2016-01-01

    The specific molecular mechanisms involved in somatic reprogramming remain unidentified. Removal of the oocyte genome is one of the primary causes of developmental failure in cloned embryos, whereas intact oocyte shows stronger reprogramming capability than enucleated oocyte. To identify the reason for the low efficiency of cloning and elucidate the mechanisms involved in somatic reprogramming by the oocyte nucleus, we injected pig cumulus cells into 539 intact MII oocytes and 461 enucleated MII oocytes. Following activation, 260 polyploidy embryos developed to the blastocyst stage whereas only 93 traditionally cloned embryos (48.2% vs. 20.2%, P < 0.01) reached blastocyst stage. Blastocysts generated from intact oocytes also had more cells than those generated from enucleated oocytes (60.70 vs. 46.65, P < 0.01). To identify the genes that contribute to this phenomenon, two early embryos in 2-cell and 4-cell stages were collected for single-cell RNA sequencing. The two kinds of embryos were found to have dramatically different transcriptome profiles. Intact oocyte nuclear transfer embryos showed 1,738 transcripts that were up-regulated relative to enucleated cloned embryos at the 2-cell stage and 728 transcripts that were down-regulated (|log2Ratio| ≥ 5). They showed 2,941 transcripts that were up-regulated during the 4-cell stage and 1,682 that were down-regulated (|log2Ratio| ≥ 5). The most significantly enriched gene ontology categories were those involved in the regulation of binding, catalytic activity, and molecular transducer activity. Other genes that were notably up-regulated and expressed in intact oocyte nuclear transfer embryos were metabolic process. This study provides a comprehensive profile of the differences in gene expression between intact oocyte nuclear transfer embryos and traditional nuclear transfer embryos. This work thus paves the way for further research on the mechanisms underlying somatic reprogramming by oocytes. PMID:27070804

  14. RNA-Seq Profiling of Intact and Enucleated Oocyte SCNT Embryos Reveals the Role of Pig Oocyte Nucleus in Somatic Reprogramming

    PubMed Central

    Bai, Lin; Li, Mengqi; Sun, Junli; Yang, Xiaogan; Lu, Yangqing; Lu, Shengsheng; Lu, Kehuan

    2016-01-01

    The specific molecular mechanisms involved in somatic reprogramming remain unidentified. Removal of the oocyte genome is one of the primary causes of developmental failure in cloned embryos, whereas intact oocyte shows stronger reprogramming capability than enucleated oocyte. To identify the reason for the low efficiency of cloning and elucidate the mechanisms involved in somatic reprogramming by the oocyte nucleus, we injected pig cumulus cells into 539 intact MII oocytes and 461 enucleated MII oocytes. Following activation, 260 polyploidy embryos developed to the blastocyst stage whereas only 93 traditionally cloned embryos (48.2% vs. 20.2%, P < 0.01) reached blastocyst stage. Blastocysts generated from intact oocytes also had more cells than those generated from enucleated oocytes (60.70 vs. 46.65, P < 0.01). To identify the genes that contribute to this phenomenon, two early embryos in 2-cell and 4-cell stages were collected for single-cell RNA sequencing. The two kinds of embryos were found to have dramatically different transcriptome profiles. Intact oocyte nuclear transfer embryos showed 1,738 transcripts that were up-regulated relative to enucleated cloned embryos at the 2-cell stage and 728 transcripts that were down-regulated (|log2Ratio| ≥ 5). They showed 2,941 transcripts that were up-regulated during the 4-cell stage and 1,682 that were down-regulated (|log2Ratio| ≥ 5). The most significantly enriched gene ontology categories were those involved in the regulation of binding, catalytic activity, and molecular transducer activity. Other genes that were notably up-regulated and expressed in intact oocyte nuclear transfer embryos were metabolic process. This study provides a comprehensive profile of the differences in gene expression between intact oocyte nuclear transfer embryos and traditional nuclear transfer embryos. This work thus paves the way for further research on the mechanisms underlying somatic reprogramming by oocytes. PMID:27070804

  15. DNA polymerases β and λ do not directly affect Ig variable region somatic hypermutation although their absence reduces the frequency of mutations

    PubMed Central

    Schrader, Carol E.; Linehan, Erin K.; Ucher, Anna J.; Bertocci, Barbara; Stavnezer, Janet

    2014-01-01

    During somatic hypermutation (SHM) of antibody variable (V) region genes, activation-induced cytidine deaminase (AID) converts dC to dU, and dUs can either be excised by uracil DNA glycosylase (UNG), by mismatch repair, or replicated over. If UNG excises the dU, the abasic site could be cleaved by AP-endonuclease (APE), introducing the single-strand DNA breaks (SSBs) required for generating mutations at A:T bp, which are known to depend upon mismatch repair and DNA Pol η. DNA Pol β or λ could instead repair the lesion correctly. To assess the involvement of Pols β and λ in SHM of antibody genes, we analyzed mutations in the VDJh4 3′ flanking region in Peyer’s patch germinal center (GC) B cells from polβ−/−polλ−/−, polλ−/−, and polβ−/− mice. We find that deficiency of either or both polymerases results in a modest but significant decrease in V region SHM, with Pol β having a greater effect, but there is no effect on mutation specificity, suggesting they have no direct role in SHM. Instead, the effect on SHM appears to be due to a role for these enzymes in GC B cell proliferation or viability. The results suggest that the BER pathway is not important during V region SHM for generating mutations at A:T bp. Furthermore, this implies that most of the SSBs required for Pol η to enter and create A:T mutations are likely generated during replication instead. These results contrast with the inhibitory effect of Pol β on mutations at the Ig Sμ locus, Sμ DSBs and class switch recombination (CSR) reported previously. We show here that B cells deficient in Pol λ or both Pol β and λ proliferate normally in culture and undergo slightly elevated CSR, as shown previously for Pol β-deficient B cells. PMID:24084171

  16. First Membrane Proximal External Region-Specific Anti-HIV1 Broadly Neutralizing Monoclonal IgA1 Presenting Short CDRH3 and Low Somatic Mutations.

    PubMed

    Benjelloun, Fahd; Oruc, Zeliha; Thielens, Nicole; Verrier, Bernard; Champier, Gael; Vincent, Nadine; Rochereau, Nicolas; Girard, Alexandre; Jospin, Fabienne; Chanut, Blandine; Genin, Christian; Cogné, Michel; Paul, Stephane

    2016-09-01

    Mucosal HIV-1-specific IgA have been described as being able to neutralize HIV-1 and to block viral transcytosis. In serum and saliva, the anti-HIV IgA response is predominantly raised against the envelope of HIV-1. In this work, we describe the in vivo generation of gp41-specific IgA1 in humanized α1KI mice to produce chimeric IgA1. Mice were immunized with a conformational immunogenic gp41-transfected cell line. Among 2300 clones screened by immunofluorescence microscopy, six different gp41-specific IgA with strong recognition of gp41 were identified. Two of them have strong neutralizing activity against primary HIV-1 tier 1, 2, and 3 strains and present a low rate of somatic mutations and autoreactivity, unlike what was described for classical gp41-specific IgG. Epitopes were identified and located in the hepted repeat 2/membrane proximal external region. These Abs could be of interest in prophylactic treatment to block HIV-1 penetration in mucosa or in chronically infected patients in combination with antiretroviral therapy to reduce viral load and reservoir. PMID:27481846

  17. 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

  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. 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

  1. Highly ionized region surrounding SN Refsdal revealed by MUSE

    NASA Astrophysics Data System (ADS)

    Karman, W.; Grillo, C.; Balestra, I.; Rosati, P.; Caputi, K. I.; Di Teodoro, E.; Fraternali, F.; Gavazzi, R.; Mercurio, A.; Prochaska, J. X.; Rodney, S.; Treu, T.

    2016-01-01

    Supernova (SN) Refsdal is the first multiply imaged, highly magnified, and spatially resolved SN ever observed. The SN exploded in a highly magnified spiral galaxy at z = 1.49 behind the Frontier Fields cluster MACS1149, and provides a unique opportunity to study the environment of SNe at high z. We exploit the time delay between multiple images to determine the properties of the SN and its environment before, during, and after the SN exploded. We use the integral-field spectrograph MUSE on the VLT to simultaneously target all observed and model-predicted positions of SN Refsdal. We find Mg II emission at all positions of SN Refsdal, accompanied by weak Fe II* emission at two positions. The measured ratios of [O II] to Mg II emission of 10-20 indicate a high degree of ionization with low metallicity. Because the same high degree of ionization is found in all images, and our spatial resolution is too coarse to resolve the region of influence of SN Refsdal, we conclude that this high degree of ionization has been produced by previous SNe or a young and hot stellar population. We find no variability of the [O II] line over a period of 57 days. This suggests that there is no variation in the [O II] luminosity of the SN over this period, or that the SN has a small contribution to the integrated [O II] emission over the scale resolved by our observations.

  2. Somatic symptom disorder

    MedlinePlus

    ... disorder References American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders . 5th ed. Arlington, VA: American Psychiatric Publishing, 2013. Ferri F. Somatization disorder. In: Ferri FF, ...

  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. 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…

  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. 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.

  7. Somatic Embryogenesis and Plant Regeneration in Sapindus mukorossi Gaertn. from Leaf-Derived Callus Induced with 6-Benzylaminopurine.

    PubMed

    Singh, Reetika; Rai, Manoj Kumar; Kumari, Nishi

    2015-09-01

    A somatic embryogenesis system was developed for Sapindus mukorossi Gaertn. from leaf explants obtained from fresh flushes of a mature tree. Callus was induced from the midrib region of leaf explants on Murashige and Skoog (MS) medium containing different concentrations of 2,4-dichlorophenoxyacetic acid or 6-benzylaminopurine. Callus induction and somatic embryogenesis was significantly influenced by the size, physiological age, and orientation of leaf explants on the culture medium and plant growth regulators. Adaxial-side-up orientation of leaf explants significantly promoted embryogenesis in comparison with abaxial-side-up orientation. Maximum number of somatic embryos was induced on MS medium supplemented with 8.88 μM 6-benzylaminopurine. Scanning electron microscopy of embryogenic callus revealed somatic embryo origin and the development of globular-, heart-, and cotyledonary-stage somatic embryos. The frequency of maturation as well as germination of somatic embryos was higher on MS medium containing 8.88 μM 6-benzylaminopurine than on medium without 6-benzylaminopurine. Plantlets which developed from somatic embryos were acclimatized successfully with 90 % survival. PMID:26208689

  8. 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)

  9. Somatic symptom disorder

    MedlinePlus

    ... disorders; Somatization disorder; Somatiform disorders; Briquet syndrome; Illness anxiety disorder ... and emotionally sensitive to pain and other sensations Family ... to illness anxiety disorder . This is when a person is overly ...

  10. Somatic symptoms in depression

    PubMed Central

    Kapfhammer, Hans-Peter

    2006-01-01

    Both painful and nonpainful somatic symptoms essentially characterize clinical states of depressive mood. So far, this well-established psychopathological knowledge has been appreciated only insufficiently by the official diagnostic sys-terms of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IVTR) and the ICD-10 Classification of Mental and Behavioral Disorders. Clinical Descriptions and Diagnostic Guidelines (ICD-10). From a perspective of primary care services, this unmet diagnostic need is deplorable, as the main mode of presenting a depression is by reporting somatic symptoms. This somatic form of presentation, however, significantly contributes to low rates of recognition in primary care. A diagnostic challenge may be seen in the differentiation of a depression with prevailing somatic symptoms from anxiety, somatoform disorders, and medical conditions. When somatic symptoms, particularly painful physical conditions, accompany the already debilitating psychiatric and behavioral symptoms of depression, the course of the illness may be more severe, implying a higher risk of early relapse, chronicity suicide, or mortality due to other natural causes, the economic burden increases considerably, the functional status may be hampered heavily, and health-related quality of life may be lowered dramatically. The neurobiological underpinnings of somatic symptoms in depression may guide more promising treatment approaches. PMID:16889108

  11. Genetic and epigenetic profiling of CLL disease progression reveals limited somatic evolution and suggests a relationship to memory-cell development

    PubMed Central

    Smith, E N; Ghia, E M; DeBoever, C M; Rassenti, L Z; Jepsen, K; Yoon, K-A; Matsui, H; Rozenzhak, S; Alakus, H; Shepard, P J; Dai, Y; Khosroheidari, M; Bina, M; Gunderson, K L; Messer, K; Muthuswamy, L; Hudson, T J; Harismendy, O; Barrett, C L; Jamieson, C H M; Carson, D A; Kipps, T J; Frazer, K A

    2015-01-01

    We examined genetic and epigenetic changes that occur during disease progression from indolent to aggressive forms of chronic lymphocytic leukemia (CLL) using serial samples from 27 patients. Analysis of DNA mutations grouped the leukemia cases into three categories: evolving (26%), expanding (26%) and static (47%). Thus, approximately three-quarters of the CLL cases had little to no genetic subclonal evolution. However, we identified significant recurrent DNA methylation changes during progression at 4752 CpGs enriched for regions near Polycomb 2 repressive complex (PRC2) targets. Progression-associated CpGs near the PRC2 targets undergo methylation changes in the same direction during disease progression as during normal development from naive to memory B cells. Our study shows that CLL progression does not typically occur via subclonal evolution, but that certain CpG sites undergo recurrent methylation changes. Our results suggest CLL progression may involve developmental processes shared in common with the generation of normal memory B cells. PMID:25860294

  12. 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

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

    PubMed

    Huang, Tianming; Zhao, Zhiyong; 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

  14. Repression of somatic cell fate in the germline.

    PubMed

    Robert, Valérie J; Garvis, Steve; Palladino, Francesca

    2015-10-01

    Germ cells must transmit genetic information across generations, and produce gametes while also maintaining the potential to form all cell types after fertilization. Preventing the activation of somatic programs is, therefore, crucial to the maintenance of germ cell identity. Studies in Caenorhabditis elegans, Drosophila melanogaster, and mouse have revealed both similarities and differences in how somatic gene expression is repressed in germ cells, thereby preventing their conversion into somatic tissues. This review will focus on recent developments in our understanding of how global or gene-specific transcriptional repression, chromatin regulation, and translational repression operate in the germline to maintain germ cell identity and repress somatic differentiation programs. PMID:26043973

  15. Risk factors for bulk milk somatic cell counts and total bacterial counts in smallholder dairy farms in the 10th region of Chile.

    PubMed

    van Schaik, G; Green, L E; Guzmán, D; Esparza, H; Tadich, N

    2005-01-01

    We investigated the principal management factors that influenced bulk milk somatic cell count (BMSCC) and total bacterial count (TBC) of smallholder dairy farms in the 10th region of Chile. One hundred and fifty smallholder milk producers were selected randomly from 42 milk collection centres (MCCs). In April and May of 2002, all farms were visited and a detailed interview questionnaire on dairy-cow management related to milk quality was conducted. In addition, the BMSCC and TBC results from the previous 2 months' fortnightly tests were obtained from the MCCs. The mean BMSCC and TBC were used as the dependent variables in the analyses and were normalised by a natural-logarithm transformation (LN). All independent management variables were categorised into binary outcomes and present (=1) was compared with absent (=0). Biserial correlations were calculated between the LNBMSCC or LNTBC and the management factors of the smallholder farms. Management factors with correlations with P0.05) factors. A random MCC effect was included in the models to investigate the importance of clustering of herds within MCC. In the null model for mean LNTBC, the random effect of MCCs was highly significant. It was explained by: milk collected once a day or less compared with collection twice a day, not cleaning the bucket after milking mastitic cows versus cleaning the bucket and cooling milk in a vat of water versus not cooling milk or using ice or a bulk tank to cool milk. Other factors that increased the LNTBC were a waiting yard with a soil or gravel floor versus concrete, use of plastic buckets for milking instead of metal, not feeding California mastitis test (CMT)-positive milk to calves and cows of dual-purpose breed. The final model explained 35% of the variance. The model predicted that a herd that complied with all the management practices had a mean

  16. Somatic mutations in the variable regions of a human IgG anti-double-stranded DNA autoantibody suggest a role for antigen in the induction of systemic lupus erythematosus.

    PubMed

    van Es, J H; Gmelig Meyling, F H; van de Akker, W R; Aanstoot, H; Derksen, R H; Logtenberg, T

    1991-02-01

    The processes that govern the generation of pathogenic anti-DNA autoantibodies in human systemic lupus erythematosus (SLE) are largely unknown. Autoantibodies may arise as a consequence of polyclonal B cell activation and/or antigen-driven B cell activation and selection. The role of these processes in humoral autoimmunity may be studied by molecular genetic analysis of immunoglobulin (Ig) variable (V) regions of antibodies that are characteristic of SLE. We have analyzed the gene elements that encode a high affinity, IgG anti-double-stranded DNA autoantibody secreted by a monoclonal Epstein-Barr virus (EBV)-transformed cell line derived from a patient with active SLE. In addition, we have identified, cloned, and sequenced the germline counterparts of the VH and VL genes expressed in this autoantibody. The comparison of both sets of gene elements shows that the autoantibody VH and VL regions harbor numerous somatic mutations characteristic of an antigen-driven immune response. The light chain expressed in this autoantibody is a somatically mutated variant of the kv325 germline gene that is frequently associated with paraproteins having autoantibody activity and with Ig molecules produced by malignant B cells that express the CD5 antigen. Furthermore, the utilized DH segment has been repeatedly found in multireactive, low affinity IgM anti-DNA autoantibodies from SLE patients and healthy individuals. These results suggest that pathogenic IgG anti-DNA autoantibodies in human SLE may arise through antigen-driven selection of somatic mutations in the gene elements that frequently encode multireactive IgM autoantibodies. PMID:1899104

  17. Somatization, paranoia, and language.

    PubMed

    Oxman, T E; Rosenberg, S D; Schnurr, P P; Tucker, G J

    1988-02-01

    Somatization and paranoia are circumscribed distortions of reality that are impervious to the normative process of consensual validation. These distortions are often postulated as a means of bolstering lowered self-esteem. We used computerized content analysis of the free speech of patients with these disorders in order to identify and compare dimensions of self-concept reflected in their lexical choices. Interestingly, patients with these disorders differed in the themes prominent in their speech. The higher frequency categories used by the somatization disorder group conveyed an overwhelming sense of negativism, distress, and a preoccupation with an uncertain self-identity. In contrast, the categories used by the paranoid patients portrayed an artificially positive, grandiose self-image and a defensive abstractness. Our exploratory analysis suggests that circumscribed distortions of reality in somatization and paranoid disorders are not associated with the same common defensive style attempting to bolster self-esteem. PMID:3343385

  18. 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. PMID:22979962

  19. 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…

  20. Multiple region whole-exome sequencing reveals dramatically evolving intratumor genomic heterogeneity in esophageal squamous cell carcinoma

    PubMed Central

    Cao, W; Wu, W; Yan, M; Tian, F; Ma, C; Zhang, Q; Li, X; Han, P; Liu, Z; Gu, J; Biddle, F G

    2015-01-01

    Cancer is a disease of genome instability and genomic alterations; now, genomic heterogeneity is rapidly emerging as a defining feature of cancer, both within and between tumors. Motivation for our pilot study of tumor heterogeneity in esophageal squamous cell carcinoma (ESCC) is that it is not well studied, but the highest incidences of esophageal cancers are found in China and ESCC is the most common type. We profiled the mutations and changes in copy number that were identified by whole-exome sequencing and array-based comparative genomic hybridization in multiple regions within an ESCC from two patients. The average mutational heterogeneity rate was 90% in all regions of the individual tumors in each patient; most somatic point mutations were nonsynonymous substitutions, small Indels occurred in untranslated regions of genes, and copy number alterations varied among multiple regions of a tumor. Independent Sanger sequencing technology confirmed selected gene mutations with more than 88% concordance. Phylogenetic analysis of the somatic mutation frequency demonstrated that multiple, genomically heterogeneous divergent clones evolve and co-exist within a primary ESCC and metastatic subclones result from the dispersal and adaptation of an initially non-metastatic parental clone. Therefore, a single-region sampling will not reflect the evolving architecture of a genomically heterogeneous landscape of mutations in ESCC tumors and the divergent complexity of this genomic heterogeneity among patients will complicate any promise of a simple genetic or epigenetic diagnostic signature in ESCC. We conclude that any potential for informative biomarker discovery in ESCC and targeted personalized therapies will require a deeper understanding of the functional biology of the ontogeny and phylogeny of the tumor heterogeneity. PMID:26619400

  1. Somatization disorders in dermatology.

    PubMed

    Gupta, Madhulika A

    2006-02-01

    This paper reviews a wide range of somatization-related symptoms that are encountered in dermatology. These include the unexplained cutaneous sensory syndromes especially the cutaneous dysesthesias associated with pain, numbness and pruritus; traumatic memories in post-traumatic stress disorder (PTSD) which are experienced on a sensory level as 'body memories' and may present as local or generalized pruritic states, urticaria and angioedema; and unexplained flushing reactions and profuse perspiration, in addition to unexplained exacerbations of stress-reactive dermatoses such as psoriasis and atopic eczema secondary to the autonomic hyperarousal in PTSD; classic 'pseudoneurologic' symptoms associated with dissociation including unexplained loss of touch or pain, in addition to the self-induced dermatoses such as dermatitis artefacta and trichotillomania that are encountered with dissociative states; and body dysmorphic disorder where the patient often presents with a somatic preoccupation involving the skin or hair. PMID:16451879

  2. AID AND SOMATIC HYPERMUTATION

    PubMed Central

    Maul, Robert W.; Gearhart, Patricia J.

    2010-01-01

    In response to an assault by foreign organisms, peripheral B cells can change their antibody affinity and isotype by somatically mutating their genomic DNA. The ability of a cell to modify its DNA is exceptional in light of the potential consequences of genetic alterations to cause human disease and cancer. Thus, as expected, this mechanism of antibody diversity is tightly regulated and coordinated through one protein, activation induced deaminase (AID). AID produces diversity by converting cytosine to uracil within the immunoglobulin loci. The deoxyuracil residue is mutagenic when paired with deoxyguanosine, since it mimics thymidine during DNA replication. Additionally, B cells can manipulate the DNA repair pathways so that deoxyuracils are not faithfully repaired. Therefore, an intricate balance exists which is regulated at multiple stages to promote mutation of immunoglobulin genes, while retaining integrity of the rest of the genome. Here we discuss and summarize the current understanding of how AID functions to cause somatic hypermutation. PMID:20510733

  3. 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. PMID:22917226

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

    PubMed

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

    2016-06-01

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

  5. 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

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

    PubMed

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

    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

  7. 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

  8. 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.; Schenk, Paul M.; Smith, David E.; Solomon, Sean C.; Zuber, Maria T.

    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.

  9. Direct somatic lineage conversion.

    PubMed

    Tanabe, Koji; Haag, Daniel; Wernig, Marius

    2015-10-19

    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

  10. mtDNA and the origin of Caucasians: identification of ancient Caucasian-specific haplogroups, one of which is prone to a recurrent somatic duplication in the D-loop region.

    PubMed Central

    Torroni, A.; Lott, M. T.; Cabell, M. F.; Chen, Y. S.; Lavergne, L.; Wallace, D. C.

    1994-01-01

    mtDNA sequence variation was examined in 175 Caucasians from the United States and Canada by PCR amplification and high-resolution restriction-endonuclease analysis. The majority of the Caucasian mtDNAs were subsumed within four mtDNA lineages (haplogroups) defined by mutations that are rarely seen in Africans and Mongoloids. The sequence divergence of these haplogroups indicates that they arose early in Caucasian radiation and gave raise to modern European mtDNAs. Although ancient, none of these haplogroups is old enough to be compatible with a Neanderthal origin, suggesting that Homo sapiens sapiens displaced H. s. neanderthaliensis, rather than mixed with it. The mtDNAs of one of these haplogroups have a unique homoplasmic insertion between nucleotide pair (np) 573 and np 574, within the D-loop control region. This insertion makes these mtDNAs prone to a somatic mutation that duplicates a 270-bp portion of the D-loop region between np 309 and np 572. This finding suggests that certain nonpathogenic mtDNA mutations could predispose individuals to mtDNA rearrangements. Images Figure 3 Figure 4 PMID:7942855

  11. Identification of Chronic Stress Activated Regions Reveals a Potential Recruited Circuit in Rat Brain

    PubMed Central

    Flak, Jonathan N.; Solomon, Matia B.; Jankord, Ryan; Krause, Eric G.; Herman, James P.

    2015-01-01

    Chronic stress induces pre-synaptic and post-synaptic modifications in the paraventricular nucleus of the hypothalamus (PVN) that are consistent with enhanced excitatory hypothalamo-pituitary-adrenocortical (HPA) axis drive. The brain regions mediating these molecular modifications are not known. We hypothesized that chronic variable stress (CVS) tonically activates stress-excitatory regions that interact with the PVN, culminating in stress facilitation. In order to identify chronically activated brain regions, ΔFosB, a documented marker of tonic neuronal activation, was assessed in known stress regulatory limbic and brainstem sites. Four experimental groups were included: CVS, repeated restraint (RR) (control for HPA habituation), animals weight-matched (WM) to CVS animals (control for changes in circulating metabolic factors due to reduced weight gain), and non-handled controls. CVS, but not RR or WM, induced adrenal hypertrophy, indicating that sustained HPA axis drive only occurred in the CVS group. CVS (but not RR or WM) selectively increased the number of FosB/ΔFosB nuclei in the nucleus of the solitary tract, posterior hypothalamic nucleus, and both the infralimbic and prelimbic divisions of the medial prefrontal cortex, indicating an involvement of these regions in chronic drive of the HPA axis. Increases in FosB/ΔFosB-immunoreactive cells were observed following both RR and CVS in the other regions (e.g., the dorsomedial hypothalamus), suggesting activation by both habituating and non-habituating stress conditions. The data suggest that unpredictable stress uniquely activates interconnected cortical, hypothalamic, and brainstem nuclei, potentially revealing the existence of a recruited circuitry mediating chronic drive of brain stress effector systems. PMID:22789020

  12. The source regions of the solar wind revealed by UV/EUV spectroscopic observations

    NASA Astrophysics Data System (ADS)

    Xia, L.

    2012-06-01

    The heating of the solar corona and the origin and acceleration of the solar wind are among the important unsolved problems of space plasma and solar physics. During the SOHO era, coronal holes as source regions of the fast solar wind have been investigated by using UV/EUV spectroscopic data observed with high-resolution spectrometers. At the base of the coronal hole, a detailed picture concerning the origin of the fast solar wind was first obtained by SUMER observations. For example, the Dopplergram deduced from the line profile of Ne VIII and other transition-region lines showed strong evidence that the wind originates in the chromospheric network and starts flowing out of the corona in magnetic funnels. Solar wind mass is suggested to be supplied through supergranule-scale magnetoconvection in the chromosphere and transition region. However, the spectral lines used in these studies are mainly obtained in the transition region and the behaviours of the nascent solar wind at higher temperatures have not yet been understood. Recent spectroscopic and imaging observations with instruments on Hinode and SDO provide further information about the coronal holes seen in EUV lines formed in the solar corona. Some interesting results, e.g., ubiquitous episodic outflow (jets) and enhanced emission in the blue wing of coronal line profiles, are found from the new observations. The purpose of this presentation is to review recent research progress on solar-wind source regions revealed by UV/EUV spectroscopic and imaging observations. Such observational studies and further interpretations of the data may provide crucial constraints and implications for future studies on both observations and theoretical models concerning coronal heating and acceleration of the nascent solar wind.

  13. Somatic embryogenesis in Hedychium bousigonianum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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. Context Differences Reveal Insulator and Activator Functions of a Su(Hw) Binding Region

    PubMed Central

    Wehling, Misty D.; Geyer, Pamela K.

    2008-01-01

    Insulators are DNA elements that divide chromosomes into independent transcriptional domains. The Drosophila genome contains hundreds of binding sites for the Suppressor of Hairy-wing [Su(Hw)] insulator protein, corresponding to locations of the retroviral gypsy insulator and non-gypsy binding regions (BRs). The first non-gypsy BR identified, 1A-2, resides in cytological region 1A. Using a quantitative transgene system, we show that 1A-2 is a composite insulator containing enhancer blocking and facilitator elements. We discovered that 1A-2 separates the yellow (y) gene from a previously unannotated, non-coding RNA gene, named yar for y-achaete (ac) intergenic RNA. The role of 1A-2 was elucidated using homologous recombination to excise these sequences from the natural location, representing the first deletion of any Su(Hw) BR in the genome. Loss of 1A-2 reduced yar RNA accumulation, without affecting mRNA levels from the neighboring y and ac genes. These data indicate that within the 1A region, 1A-2 acts an activator of yar transcription. Taken together, these studies reveal that the properties of 1A-2 are context-dependent, as this element has both insulator and enhancer activities. These findings imply that the function of non-gypsy Su(Hw) BRs depends on the genomic environment, predicting that Su(Hw) BRs represent a diverse collection of genomic regulatory elements. PMID:18704163

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

    NASA Astrophysics Data System (ADS)

    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.; Schenk, Paul M.; Smith, David E.; Solomon, Sean C.; Zuber, Maria T.

    2014-10-01

    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 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.

  16. 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

    2014-10-01

    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 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. PMID:25279919

  17. Somatic mosaicism and variable expressivity.

    PubMed

    Gottlieb, B; Beitel, L K; Trifiro, M A

    2001-02-01

    For more than 50 years geneticists have assumed that variations in phenotypic expression are caused by alterations in genotype. Recent evidence shows that 'simple' mendelian disorders or monogenic traits are often far from simple, exhibiting phenotypic variation (variable expressivity) that cannot be explained entirely by a gene or allelic alteration. In certain cases of androgen insensitivity syndrome caused by identical mutations in the androgen receptor gene, phenotypic variability is caused by somatic mosaicism, that is, somatic mutations that occur only in certain androgen-sensitive cells. Recently, more than 30 other genetic conditions that exhibit variable expressivity have been linked to somatic mosaicism. Somatic mutations have also been identified in diseases such as prostate and colorectal cancer. Therefore, the concept of somatic mutations and mosaicism is likely to have far reaching consequences for genetics, in particular in areas such as genetic counseling. PMID:11173116

  18. 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.

  19. Deletion mapping of the potyviral helper component-proteinase reveals two regions involved in RNA binding.

    PubMed

    Urcuqui-Inchima, S; Maia, I G; Arruda, P; Haenni, A L; Bernardi, F

    2000-03-01

    The Potyvirus helper component-proteinase (HC-Pro) binds nonspecifically to single-stranded nucleic acids with a preference for RNA. To delineate the regions of the protein responsible for RNA binding, deletions were introduced into the full-length Potato potyvirus Y HC-Pro gene carried by an Escherichia coli expression vector. The corresponding proteins were expressed as fusions with the maltose-binding protein, purified, and assayed for their RNA-binding capacity. The results obtained by UV cross-linking and Northwestern blot assays demonstrated that the N- and C-terminal regions of HC-Pro are dispensable for RNA binding. They also revealed the presence of two independent RNA-binding domains (designated A and B) located in the central part of HC-Pro. Domain B appears to contain a ribonucleoprotein (RNP) motif typical of a large family of RNA-binding proteins involved in several cellular processes. The possibility that domain B consists of an RNP domain is discussed and suggests that HC-Pro could constitute the first example of a plant viral protein belonging to the RNP-containing family of proteins. PMID:10683332

  20. 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

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

    PubMed Central

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

    2016-01-01

    Allen Brain Atlas (ABA) provides a valuable resource of spatial/temporal gene expressions in mammalian brains. Despite rich information extracted from this database, current analyses suffer from several limitations. First, most studies are either gene-centric or region-centric, thus are inadequate to capture the superposition of multiple spatial-temporal patterns. Second, standard tools of expression analysis such as matrix factorization can capture those patterns but do not explicitly 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. PMID:26786896

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

    DOE PAGESBeta

    Nik-Zainal, Serena; Davies, Helen; Staaf, Johan; Ramakrishna, Manasa; Glodzik, Dominik; Zou, Xueqing; Martincorena, Inigo; Alexandrov, Ludmil B.; Martin, Sancha; Wedge, David C.; et al

    2016-06-02

    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

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

    PubMed

    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 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; 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

    2016-06-01

    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. 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. PMID:27135926

  4. 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.

  5. 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

  6. 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.

  7. The Brain-to-Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions.

    PubMed

    Rosario, Wilfredo; Singh, Inderroop; Wautlet, Arnaud; Patterson, Christa; Flak, Jonathan; Becker, Thomas C; Ali, Almas; Tamarina, Natalia; Philipson, Louis H; Enquist, Lynn W; Myers, Martin G; Rhodes, Christopher J

    2016-09-01

    The brain influences glucose homeostasis, partly by supplemental control over insulin and glucagon secretion. Without this central regulation, diabetes and its complications can ensue. Yet, the neuronal network linking to pancreatic islets has never been fully mapped. Here, we refine this map using pseudorabies virus (PRV) retrograde tracing, indicating that the pancreatic islets are innervated by efferent circuits that emanate from the hypothalamus. We found that the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMN), and lateral hypothalamic area (LHA) significantly overlap PRV and the physiological glucose-sensing enzyme glucokinase. Then, experimentally lowering glucose sensing, specifically in the ARC, resulted in glucose intolerance due to deficient insulin secretion and no significant effect in the VMN, but in the LHA it resulted in a lowering of the glucose threshold that improved glucose tolerance and/or improved insulin sensitivity, with an exaggerated counter-regulatory response for glucagon secretion. No significant effect on insulin sensitivity or metabolic homeostasis was noted. Thus, these data reveal novel direct neuronal effects on pancreatic islets and also render a functional validation of the brain-to-islet neuronal map. They also demonstrate that distinct regions of the hypothalamus differentially control insulin and glucagon secretion, potentially in partnership to help maintain glucose homeostasis and guard against hypoglycemia. PMID:27207534

  8. 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

  9. Genetic architecture of trout from Albania as revealed by mtDNA control region variation

    PubMed Central

    2009-01-01

    To determine the genetic architecture of trout in Albania, 87 individuals were collected from 19 riverine and lacustrine sites in Albania, FYROM and Greece. All individuals were analyzed for sequence variation in the mtDNA control region. Among fourteen haplotypes detected, four previously unpublished haplotypes, bearing a close relationship to haplotypes of the Adriatic and marmoratus lineages of Salmo trutta, were revealed. Ten previously described haplotypes, characteristic of S. ohridanus, S. letnica and the Adriatic and Mediterranean lineages of S. trutta, were also detected. Haplotypes detected in this study were placed in a well supported branch of S. ohridanus, and a cluster of Mediterranean – Adriatic – marmoratus haplotypes, which were further delimited into three subdivisions of Mediterranean, marmoratus, and a previously non-described formation of four Adriatic haplotypes (Balkan cluster). Haplotypes of the Balkan cluster and the other Adriatic haplotypes, do not represent a contiguous haplotype lineage and appear not to be closely related, indicating independent arrivals into the Adriatic drainage and suggesting successive colonization events. Despite the presence of marmoratus haplotypes in Albania, no marbled phenotype was found, confirming previously reported findings that there is no association between this phenotype and marmoratus haplotypes. PMID:19284692

  10. 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

  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. 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. PMID:18975127

  13. 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

  14. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  16. 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

  17. 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

  18. 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 ...

  19. 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. PMID:20336522

  20. [Somatic trends in Moscow children].

    PubMed

    Fedotova, T K

    2008-01-01

    Somatic trends was considered in Moscow children in a wide age range of 3 to 17 years, by attracting several series of data since the 1990s. To have the greater informative value in data analyses, investigators use the normalized rather than absolute values of various anthropometric signs in the considered data series versus the 2005 data in the age range of 3 to 7 years and versus the 1980s data in the range of 8 to 17 years. The overall somatic tendency in Moscow children aged 3 to 17 years in past decades is towards a transverse body development and some dolichomorphism with a continuous increase in longitudinal skeletal sizes. These processes are most pronounced in girls than in boys and preschool children than in school ones. The stronger somatic trend in preschool children can be associated with that they are, as compared with schoolchildren, neophytes in the compact anthropogenic space and have been, in the past decades, involved in the neurogenic growth stimulators world (a computer and computer games, unlimited TV seeing, inevitable intensive preparation for new-generation schools--increased intellectual-load lyceums and colleges). The decreased transverse body development and overall constitution asthenization seem to result from somatic muscular component abatement with no clear trends in adipopexis in schoolchildren and with an increase in subcutaneous fat deposition in preschool children. PMID:18507175

  1. Ozone variations over the northern subtropical region revealed by ozonesonde observations in Hanoi

    NASA Astrophysics Data System (ADS)

    Ogino, S.-Y.; Fujiwara, M.; Shiotani, M.; Hasebe, F.; Matsumoto, J.; Hoang, Thuy Ha T.; Nguyen, Tan Thanh T.

    2013-04-01

    Seasonal and subseasonal variations in the ozone mixing ratio (OMR) are investigated by using continuous 7 year ozonesonde data from Hanoi (21°N, 106°E), Vietnam. The mean seasonal variations for the 7 years show large amplitude at the upper troposphere and lower stratosphere (UTLS) region (10-18 km) and at the lower troposphere (around 3 km) with standard deviations normalized by the annual mean value of about 30% for both regions. In the UTLS region, the seasonal variation in the OMR shows a minimum in winter and a maximum in spring to summer. The variation seems to be caused by the seasonal change in horizontal transport. Low OMR air masses are transported from the equatorial troposphere in winter by the anticyclonic flow associated with the equatorial convections, and high OMR air masses are transported from the midlatitude stratosphere in summer possibly due to Rossby wave breakings in the UT region and anticyclonic circulation associated with the Tibetan High in the LS region. In the lower troposphere, a spring maximum is found at 3 km height. Biomass burning and tropopause foldings are suggested as possible causes of this maximum. Subseasonal variations in the OMR show large amplitude in the UTLS region (at around 15 km) and in the boundary layer (below 1 km) with the standard deviations normalized by the annual mean larger than 40%. The OMR variations in the winter UTLS region have a negative correlation with the meridional wind. This relation indicates that the low OMRs observed at Hanoi has been transported from the equatorial region.

  2. GRACE storage-streamflow hystereses reveal the dynamics of regional watersheds

    NASA Astrophysics Data System (ADS)

    Sproles, E. A.; Leibowitz, S. G.; Reager, J. T.; Wigington, P. J., Jr.; Famiglietti, J. S.; Patil, S. D.

    2014-10-01

    We characterize how regional watersheds function as simple, dynamic systems through a series of hysteresis loops. These loops illustrate the temporal relationship between runoff and terrestrial water storage using measurements from NASA's Gravity Recovery and Climate Experiment (GRACE) satellites in three regional-scale watersheds (>150 000 km2) of the Columbia River Basin, USA and Canada. The direction of the hystereses for the GRACE signal move in opposite directions from the isolated groundwater hystereses, suggesting that regional scale watersheds require soil water storage to reach a certain threshold before groundwater recharge and peak runoff occur. While the physical processes underlying these hystereses are inherently complex, the vertical integration of terrestrial water in the GRACE signal encapsulates the processes that govern the non-linear function of regional-scale watersheds. We use this process-based understanding to test how GRACE data can be applied prognostically to predict seasonal runoff (mean R2 of 0.91) and monthly runoff (mean R2 of 0.77) in all three watersheds. The global nature of GRACE data allows this same methodology to be applied in other regional-scale studies, and could be particularly useful in regions with minimal data and in trans-boundary watersheds.

  3. Patterns of Activity Revealed by a Time Lag Analysis of a Model Active Region

    NASA Astrophysics Data System (ADS)

    Bradshaw, Stephen; Viall, Nicholeen

    2016-05-01

    We investigate the global activity patterns predicted from a model active region heated by distributions of nanoflares that have a range of average frequencies. The activity patterns are manifested in time lag maps of narrow-band instrument channel pairs. We combine an extrapolated magnetic skeleton with hydrodynamic and forward modeling codes to create a model active region, and apply the time lag method to synthetic observations. Our aim is to recover some typical properties and patterns of activity observed in active regions. Our key findings are: 1. Cooling dominates the time lag signature and the time lags between the channel pairs are generally consistent with observed values. 2. Shorter coronal loops in the core cool more quickly than longer loops at the periphery. 3. All channel pairs show zero time lag when the line-of-sight passes through coronal loop foot-points. 4. There is strong evidence that plasma must be re-energized on a time scale comparable to the cooling timescale to reproduce the observed coronal activity, but it is likely that a relatively broad spectrum of heating frequencies operates across active regions. 5. Due to their highly dynamic nature, we find nanoflare trains produce zero time lags along entire flux tubes in our model active region that are seen between the same channel pairs in observed active regions.

  4. 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. PMID:26096084

  5. GRACE storage-runoff hystereses reveal the dynamics of regional watersheds

    NASA Astrophysics Data System (ADS)

    Sproles, E. A.; Leibowitz, S. G.; Reager, J. T.; Wigington, P. J., Jr.; Famiglietti, J. S.; Patil, S. D.

    2015-07-01

    We characterize how regional watersheds function as simple, dynamic systems through a series of hysteresis loops using measurements from NASA's Gravity Recovery and Climate Experiment (GRACE) satellites. These loops illustrate the temporal relationship between runoff and terrestrial water storage in three regional-scale watersheds (> 150 000 km2) of the Columbia River Basin, USA and Canada. The shape and size of the hysteresis loops are controlled by the climate, topography, and geology of the watershed. The direction of the hystereses for the GRACE signals moves in opposite directions from the isolated groundwater hystereses. The subsurface water (soil moisture and groundwater) hystereses more closely resemble the storage-runoff relationship of a soil matrix. While the physical processes underlying these hystereses are inherently complex, the vertical integration of terrestrial water in the GRACE signal encapsulates the processes that govern the non-linear function of regional-scale watersheds. We use this process-based understanding to test how GRACE data can be applied prognostically to predict seasonal runoff (mean Nash-Sutcliffe Efficiency of 0.91) and monthly runoff during the low flow/high demand month of August (mean Nash-Sutcliffe Efficiency of 0.77) in all three watersheds. The global nature of GRACE data allows this same methodology to be applied in other regional-scale studies, and could be particularly useful in regions with minimal data and in trans-boundary watersheds.

  6. Auditory sequence processing reveals evolutionarily conserved regions of frontal cortex in macaques and humans.

    PubMed

    Wilson, Benjamin; Kikuchi, Yukiko; Sun, Li; Hunter, David; Dick, Frederic; Smith, Kenny; Thiele, Alexander; Griffiths, Timothy D; Marslen-Wilson, William D; Petkov, Christopher I

    2015-01-01

    An evolutionary account of human language as a neurobiological system must distinguish between human-unique neurocognitive processes supporting language and evolutionarily conserved, domain-general processes that can be traced back to our primate ancestors. Neuroimaging studies across species may determine whether candidate neural processes are supported by homologous, functionally conserved brain areas or by different neurobiological substrates. Here we use functional magnetic resonance imaging in Rhesus macaques and humans to examine the brain regions involved in processing the ordering relationships between auditory nonsense words in rule-based sequences. We find that key regions in the human ventral frontal and opercular cortex have functional counterparts in the monkey brain. These regions are also known to be associated with initial stages of human syntactic processing. This study raises the possibility that certain ventral frontal neural systems, which play a significant role in language function in modern humans, originally evolved to support domain-general abilities involved in sequence processing. PMID:26573340

  7. Auditory sequence processing reveals evolutionarily conserved regions of frontal cortex in macaques and humans

    PubMed Central

    Wilson, Benjamin; Kikuchi, Yukiko; Sun, Li; Hunter, David; Dick, Frederic; Smith, Kenny; Thiele, Alexander; Griffiths, Timothy D.; Marslen-Wilson, William D.; Petkov, Christopher I.

    2015-01-01

    An evolutionary account of human language as a neurobiological system must distinguish between human-unique neurocognitive processes supporting language and evolutionarily conserved, domain-general processes that can be traced back to our primate ancestors. Neuroimaging studies across species may determine whether candidate neural processes are supported by homologous, functionally conserved brain areas or by different neurobiological substrates. Here we use functional magnetic resonance imaging in Rhesus macaques and humans to examine the brain regions involved in processing the ordering relationships between auditory nonsense words in rule-based sequences. We find that key regions in the human ventral frontal and opercular cortex have functional counterparts in the monkey brain. These regions are also known to be associated with initial stages of human syntactic processing. This study raises the possibility that certain ventral frontal neural systems, which play a significant role in language function in modern humans, originally evolved to support domain-general abilities involved in sequence processing. PMID:26573340

  8. Hybrid reuteransucrase enzymes reveal regions important for glucosidic linkage specificity and the transglucosylation/hydrolysis ratio.

    PubMed

    Kralj, Slavko; van Leeuwen, Sander S; Valk, Vincent; Eeuwema, Wieger; Kamerling, Johannis P; Dijkhuizen, Lubbert

    2008-12-01

    The reuteransucrase enzymes of Lactobacillus reuteri strain 121 (GTFA) and L. reuteri strain ATCC 55730 (GTFO) convert sucrose into alpha-d-glucans (labelled reuterans) with mainly alpha-(1-->4) glucosidic linkages (50% and 70%, respectively), plus alpha-(1-->6) linkages. In the present study, we report a detailed analysis of various hybrid GTFA/O enzymes, resulting in the identification of specific regions in the N-termini of the catalytic domains of these proteins as the main determinants of glucosidic linkage specificity. These regions were divided into three equal parts (A1-3; O1-3), and used to construct six additional GTFA/O hybrids. All hybrid enzymes were able to synthesize alpha-glucans from sucrose, and oligosaccharides from sucrose plus maltose or isomaltose as acceptor substrates. Interestingly, not only the A2/O2 regions, with the three catalytic residues, affect glucosidic linkage specificity, but also the upstream A1/O1 regions make a strong contribution. Some GTFO derived hybrid/mutant enzymes displayed strongly increased transglucosylation/hydrolysis activity ratios. The reduced sucrose hydrolysis allowed the much improved conversion of sucrose into oligo- and polysaccharide products. Thus, the glucosidic linkage specificity and transglucosylation/hydrolysis ratios of reuteransucrase enzymes can be manipulated in a relatively simple manner. This engineering approach has yielded clear changes in oligosaccharide product profiles, as well as a range of novel reuteran products differing in alpha-(1-->4) and alpha-(1-->6) linkage ratios. PMID:19016850

  9. 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. PMID:26667091

  10. 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

  11. 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.

  12. 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

  13. 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. PMID:20682340

  14. 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

  15. 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. PMID:25691860

  16. 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. PMID:23192671

  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. The 2007 Sumatra seismic sequence revealed by a regional seismic network in Indonesia

    NASA Astrophysics Data System (ADS)

    Nakano, M.; Inoue, H.; Kumagai, H.; Yamashina, T.; Sunarjo; Fauzi; Suhardjono

    2007-12-01

    distributed in a region extending about 300 km along the subduction zone of the Indo-Australian Plate. The depths of aftershocks range from 15 to 60 km. In the off-Bengkulu region, the earthquakes with M8 or above occurred in 1381, 1608 and 1833, approximately every 230 years. Now 174 years have been passed since the last event in 1833. We did not experience M8 class earthquakes during the last 210 years in the off-Padang region, which is to the north of off-Bengkulu. The off-Padang region corresponds to a seismic gap between the source regions of the 2007 Sumatra seismic sequence and M8.7 Nias earthquake on March 2005. The sequence of the M8.4, M8.0, and M6.8 earthquakes moving towards the northwest from off-Bengkulu in the 2007 seismic activity suggests the imminency of a large earthquake off Padang. We have been deploying broadband seismograph networks in Indonesia, including JISNET, by an international cooperation among Indonesia, Germany, China, and Japan, aiming at improving the capabilities to monitor seismic activity and tsunami generation in Indonesia. The seismic networks are now in operation, and totally 150 seismic stations will be installed by the end of 2008. Seismic monitoring based on these regional networks would contribute to early notification of a large earthquake anticipated to occur in the off-Padang region.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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). PMID:25846994

  5. A High-Density SNP and SSR Consensus Map Reveals Segregation Distortion Regions in Wheat

    PubMed Central

    Li, Chunlian; Bai, Guihua; Chao, Shiaoman; Wang, Zhonghua

    2015-01-01

    Segregation distortion is a widespread phenomenon in plant and animal genomes and significantly affects linkage map construction and identification of quantitative trait loci (QTLs). To study segregation distortion in wheat, a high-density consensus map was constructed using single nucleotide polymorphism (SNP) and simple sequence repeat (SSR) markers by merging two genetic maps developed from two recombinant-inbred line (RIL) populations, Ning7840 × Clark and Heyne × Lakin. Chromosome regions with obvious segregation distortion were identified in the map. A total of 3541 SNPs and 145 SSRs were mapped, and the map covered 3258.7 cM in genetic distance with an average interval of 0.88 cM. The number of markers that showed distorted segregation was 490 (18.5%) in the Ning7840 × Clark population and 225 (10.4%) in the Heyne × Lakin population. Most of the distorted markers (630) were mapped in the consensus map, which accounted for 17.1% of mapped markers. The majority of the distorted markers clustered in the segregation distortion regions (SDRs) on chromosomes 1B, 2A, 2B, 3A, 3B, 4B, 5A, 5B, 5D, 6B, 7A, and 7D. All of the markers in a given SDR skewed toward one of the parents, suggesting that gametophytic competition during zygote formation was most likely one of the causes for segregation distortion in the populations. PMID:26601111

  6. Single cell lineage tracing reveals that oriented cell division contributes to trabecular morphogenesis and regional specification

    PubMed Central

    Li, Jingjing; Miao, Lianjie; Shieh, David; Spiotto, Ernest; Li, Jian; Zhou, Bin; Paul, Antoni; Schwartz, Robert J.; Firulli, Anthony B.; Singer, Harold A.; Huang, Guoying; Wu, Mingfu

    2016-01-01

    Summary The cardiac trabeculae are sheet-like structures extending from the myocardium that function to increase surface area. A lack of trabeculation causes embryonic lethality due to compromised cardiac function. To understand the cellular and molecular mechanisms of trabecular formation, we genetically labeled individual cardiomyocytes prior to trabeculation via the brainbow multicolor system, and traced and analyzed the labeled cells during trabeculation by whole-embryo clearing and imaging. The clones derived from labeled single cells displayed four different geometric patterns that are derived from different patterns of oriented cell division (OCD) and migration. Of the four types of clones, the inner, transmural, and mixed clones contributed to trabecular cardiomyocytes. Further studies showed that perpendicular OCD is an extrinsic asymmetric cell division that putatively contributes to trabecular regional specification. Furthermore, N-Cadherin deletion in labeled clones disrupted the clonal patterns. In summary, our data demonstrate that OCD contributes to trabecular morphogenesis and specification. PMID:27052172

  7. Transmembrane Signaling by the Aspartate Receptor: Engineered Disulfides Reveal Static Regions of the Subunit Interface†

    PubMed Central

    Chervitz, Stephen A.; Lin, Christina M.; Falke, Joseph J.

    2010-01-01

    Ligand binding to the periplasmic domain of the transmembrane aspartate receptor generates an intramolecular conformational change which spans the bilayer and ultimately signals the cytoplasmic CheA histidine kinase, thereby triggering chemotaxis. The receptor is a homodimer stabilized by the interface between its two identical subunits: the present study investigates the role of the periplasmic and transmembrane regions of this interface in the mechanism of transmembrane signaling. Free cysteines and disulfide bonds are engineered into selected interfacial positions, and the resulting effects on the transmembrane signal are assayed by monitoring in vitro regulation of kinase activity. Three of the 14 engineered cysteine pairs examined, as well as six of the 14 engineered disulfides, cause perturbations of the interface structure which essentially destroy transmembrane regulation of the kinase. The remaining 11 cysteine pairs, and eight engineered disulfides covalently linking the two subunits at locations spanning positions 18–75, are observed to retain significant transmembrane kinase regulation. The eight functional disulfides positively identify adjacent faces of the two N-terminal helices in the native receptor dimer and indicate that large regions of the periplasmic and transmembrane subunit interface remain effectively static during the transmembrane signal. The results are consistent with a model in which the subunit interface plays a structural role, while the second membrane-spanning helix transmits the ligand-induced signal across the bilayer to the kinase binding domain. The effects of engineered cysteines and disulfides on receptor methylation in vitro are also measured, enabling direct comparison of the in vitro methylation and phosphorylation assays. PMID:7626643

  8. 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

  9. 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. PMID:27012723

  10. 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

  11. 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. PMID:15789206

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

    PubMed

    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

  13. Fine mapping of type 1 diabetes regions Idd9.1 and Idd9.2 reveals genetic complexity.

    PubMed

    Hamilton-Williams, Emma E; Rainbow, Daniel B; Cheung, Jocelyn; Christensen, Mikkel; Lyons, Paul A; Peterson, Laurence B; Steward, Charles A; Sherman, Linda A; Wicker, Linda S

    2013-10-01

    Nonobese diabetic (NOD) mice congenic for C57BL/10 (B10)-derived genes in the Idd9 region of chromosome 4 are highly protected from type 1 diabetes (T1D). Idd9 has been divided into three protective subregions (Idd9.1, 9.2, and 9.3), each of which partially prevents disease. In this study we have fine-mapped the Idd9.1 and Idd9.2 regions, revealing further genetic complexity with at least two additional subregions contributing to protection from T1D. Using the NOD sequence from bacterial artificial chromosome clones of the Idd9.1 and Idd9.2 regions as well as whole-genome sequence data recently made available, sequence polymorphisms within the regions highlight a high degree of polymorphism between the NOD and B10 strains in the Idd9 regions. Among numerous candidate genes are several with immunological importance. The Idd9.1 region has been separated into Idd9.1 and Idd9.4, with Lck remaining a candidate gene within Idd9.1. One of the Idd9.2 regions contains the candidate genes Masp2 (encoding mannan-binding lectin serine peptidase 2) and Mtor (encoding mammalian target of rapamycin). From mRNA expression analyses, we have also identified several other differentially expressed candidate genes within the Idd9.1 and Idd9.2 regions. These findings highlight that multiple, relatively small genetic effects combine and interact to produce significant changes in immune tolerance and diabetes onset. PMID:23934554

  14. Statistical diffusion tensor histology reveals regional dysmyelination effects in the shiverer mouse mutant.

    PubMed

    Tyszka, J Michael; Readhead, Carol; Bearer, Elaine L; Pautler, Robia G; Jacobs, Russell E

    2006-02-15

    Shiverer is an important model of central nervous system dysmyelination characterized by a deletion in the gene encoding myelin basic protein with relevance to human dysmyelinating and demyelinating diseases. Perfusion fixed brains from shiverer mutant (C3Fe.SWV Mbp(shi)/Mbp(shi)n = 6) and background control (C3HeB.FeJ, n = 6) mice were compared using contrast enhanced volumetric diffusion tensor magnetic resonance microscopy with a nominal isotropic spatial resolution of 80 mum. Images were accurately coregistered using non-linear warping allowing voxel-wise statistical parametric mapping of tensor invariant differences between control and shiverer groups. Highly significant differences in the tensor trace and both the axial and radial diffusivity were observed within the major white matter tracts and in the thalamus, midbrain, brainstem and cerebellar white matter, consistent with a high density of myelinated axons within these regions. The fractional anisotropy was found to be much less sensitive than the trace and eigenvalues to dysmyelination and associated microanatomic changes. PMID:16213163

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

    PubMed Central

    Kadakkuzha, Beena M.; Liu, Xin-An; McCrate, Jennifer; Shankar, Gautam; Rizzo, Valerio; Afinogenova, Alina; Young, Brandon; Fallahi, Mohammad; Carvalloza, Anthony C.; Raveendra, Bindu; Puthanveettil, Sathyanarayanan V.

    2015-01-01

    Despite the importance of the long non-coding RNAs (lncRNAs) in regulating biological functions, the expression profiles of lncRNAs in the sub-regions of the mammalian brain and neuronal populations remain largely uncharacterized. By analyzing RNASeq datasets, we demonstrate region specific enrichment of populations of lncRNAs and mRNAs in the mouse hippocampus and pre-frontal cortex (PFC), the two major regions of the brain involved in memory storage and neuropsychiatric disorders. We identified 2759 lncRNAs and 17,859 mRNAs in the hippocampus and 2561 lncRNAs and 17,464 mRNAs expressed in the PFC. The lncRNAs identified correspond to ~14% of the transcriptome of the hippocampus and PFC and ~70% of the lncRNAs annotated in the mouse genome (NCBIM37) and are localized along the chromosomes as varying numbers of clusters. Importantly, we also found that a few of the tested lncRNA-mRNA pairs that share a genomic locus display specific co-expression in a region-specific manner. Furthermore, we find that sub-regions of the brain and specific neuronal populations have characteristic lncRNA expression signatures. These results reveal an unexpected complexity of the lncRNA expression in the mouse brain. PMID:25798087

  16. 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.

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

    PubMed

    Cheloufi, Sihem; Elling, Ulrich; Hopfgartner, Barbara; Jung, Youngsook L; Murn, Jernej; Ninova, Maria; Hubmann, Maria; Badeaux, Aimee I; Euong Ang, Cheen; 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 J; Penninger, Josef M; Zuber, Johannes; Hochedlinger, Konrad

    2015-12-10

    Cellular differentiation involves profound remodelling 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 RNA interference (RNAi) screens targeting chromatin factors during transcription-factor-mediated reprogramming of mouse fibroblasts to induced pluripotent stem cells (iPS cells). Subunits of the chromatin assembly factor-1 (CAF-1) complex, including Chaf1a and Chaf1b, 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 iPS cell 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 to be 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

  18. 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

  19. 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

  20. 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. PMID:27528660

  1. Whole-exome sequencing identifies a somatic missense mutation of NBN in clear cell sarcoma of the salivary gland.

    PubMed

    Zhang, Lei; Jia, Zhen; Mao, Fengbiao; Shi, Yueyi; Bu, Rong Fa; Zhang, Baorong

    2016-06-01

    Clear cell sarcoma (CCS) is a rare, low-grade carcinoma commonly located in the distal extremities of young adults involving tendons and aponeuroses. CCS is characterized by its poor prognosis due to late diagnosis, multiple local recurrence, propensity to late metastases, and a high rate of tumor-related mortality. The genetic cause for CCS is thought to be EWSR1 gene translocation. However, CCS lacking a translocation may have other, as yet uncharacterized, genetic mutations that can cause the same pathological effect. A combination of whole‑exome sequencing and Sanger sequencing of cancer tissue and venous blood from a patient diagnosed with CCS of the salivary gland revealed a somatic missense mutation, c.1061C>T (p.P354L), in exon 9 of the Nibrin gene (NBN). This somatic missense mutation led to the conversion of proline to leucine (p.P354L), resulting in deleterious effects for the NBN protein. Multiple-sequence alignments showed that codon 354, where the mutation (c.1061C>T) occurs, is located within a phylogenetically conserved region. In conclusion, we here report a somatic missense mutation c.1061C>T (p.P354L) in the NBN gene in a patient with CCS lacking an EWSR1-ATF1 fusion. Our findings broaden the genotypic spectrum of CCS and provide new molecular insight that should prove useful in the future clinical genetic diagnosis of CCS. PMID:27109316

  2. Rapid regional surface uplift of the northern Altiplano plateau revealed by multiproxy paleoclimate reconstruction

    NASA Astrophysics Data System (ADS)

    Kar, Nandini; Garzione, Carmala N.; Jaramillo, Carlos; Shanahan, Timothy; Carlotto, Victor; Pullen, Alex; Moreno, Federico; Anderson, Veronica; Moreno, Enrique; Eiler, John

    2016-08-01

    The central Altiplano is inferred to have experienced ∼ 2.5 ± 1km surface uplift between ∼10 and 6 Ma, while the southern Altiplano experienced a similar magnitude of surface uplift that began earlier, between ∼16 and 9 Ma. To properly constrain the along strike timing of the Altiplano plateau surface uplift, it is necessary to know how and when the northernmost part of the Altiplano plateau evolved. We reconstruct the paleoclimate and infer the corresponding paleoelevation from the Miocene-Pliocene deposits of the Descanso-Yauri basin (14-15°S) in the northernmost part of the Altiplano plateau using 4 different proxies, including carbonate clumped isotope composition (i.e., Δ47 values), carbonate δ18Oc, leaf wax δDwax and pollen assemblages from paleosol, lacustrine and palustrine carbonates and organic-rich sediments. The isotopic signatures reflect past climate conditions of mean annual air temperature (Δ47) and meteoric water isotope values (δ18Oc, δDwax). Our results show that the northernmost plateau remained at low elevation (0.9 ± 0.8 to 2.1 ± 0.9km) until late Miocene time (∼9 Ma) characterized by ∼15 °C warmer than modern temperature (mean annual air temperature of 23 ± 4 °C, 2σ), low elevation vegetation and precipitation signature with reconstructed □ δ18Omw (VSMOW) of - 8.3 ± 2.0 ‰ (2 σ) from carbonate (δ18Oc) and - 8.6 ± 1.8 ‰ (2 σ) from leaf wax (δDwax). Modern elevations of 4 km were not reached until 5.4 ± 1.0Ma, as indicated by a negative shift in δDwax (VSMOW) from - 143.4 ± 12.8 ‰ (2 σ) to - 209.2 ± 21.1 ‰ (2 σ) between 9.1 ± 0.7 and 5.4 ± 1.0Ma. The timing of surface uplift of the northernmost Altiplano is consistent with the evidence for late Miocene surface uplift of the central Altiplano (16-19°S) between 10 and 6 Ma, and indicates that regional scale uplift in the northern-central plateau significantly postdates the onset of surface uplift in the southern Altiplano (19-22°S) between ∼16

  3. 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

  4. Clarifying the latent structure and correlates of somatic symptom distress: A bifactor model approach.

    PubMed

    Witthöft, Michael; Fischer, Susanne; Jasper, Fabian; Rist, Fred; Nater, Urs M

    2016-01-01

    Distressing somatic symptoms are ubiquitous both in mental disorders and medical diseases. From a psychometric perspective, the structure of somatic symptom distress is unclear, and little is known about the strengths of associations to related constructs, such as health anxiety and somatosensory amplification. To clarify the structure of somatic symptom distress and to explore associations to health anxiety, somatosensory amplification, and functional somatic syndromes, data sets of 2 samples of college students from Germany (N = 1,520) and Switzerland (N = 3,053) were investigated with confirmatory factor analysis with robust estimation. A bifactor model (with 1 general and 4 orthogonal specific symptom factors-gastrointestinal, fatigue, cardio-pulmonary, and pain symptoms) revealed the best model fit. Medium-sized associations were found among latent factors of general somatic symptom distress, health anxiety, and depression. First evidence for the construct validity of the latent variables within the proposed bifactor structure was gained by observing (a) strong associations between the general somatic symptom distress factor and somatosensory amplification and (b) significant associations between both the general somatic symptom factor as well as the symptom-specific factors with functional somatic syndromes. The results offer a theoretically and psychometrically plausible model for the structure of somatic symptom distress and suggest a distinction between cognitive-affective and sensory aspects of symptom perception. The findings are compatible with current cognitive psychological and neuropsychological approaches to symptom perception and imply that somatic symptom distress is a multidimensional phenomenon that is both strongly linked to but also clearly separable from related constructs. PMID:26029944

  5. Coseismic and Postseismic Deformations From Great 2006-2007 Kuril Earthquakes Revealed by Regional GPS Observations

    NASA Astrophysics Data System (ADS)

    Steblov, G. M.; Kogan, M. G.; Levin, B. V.; Vasilenko, N. F.; Prytkov, A. S.; Frolov, D. I.

    2007-12-01

    The 1200-km long Kuril arc is the last subduction zone never previously explored by space geodetic methods. In 2006, we installed the continuous GPS network (CGPS) over the whole arc and added several survey-mode stations (SGPS). In 2006-2007, the paired great earthquakes near the central Kurils happened several months after we installed the network: Mw 8.3, Nov. 15, 2006 underthrusting event, and Mw 8.1, Jan. 13, 2007 tensional outer-rise event. Although the earthquakes have prevented us from estimating reliable interseismic surface velocities for most of the Kuril arc, it has given us the chance to examine great earthquakes and their transient response in the region that was a seismic gap for a century. Two SGPS stations nearest to the hypocenters captured the largest observed offsets of about 0.6 m reflecting the superposed effect of both events. These offsets are mostly attributed to the Nov. 2006 event. More distant stations captured coseismic offsets caused by each event ranging from several mm to 60 mm. Significant transient signals associated with rapid postseismic afterslip in the rupture or with the relaxation in the viscous mantle were noticed for the Nov. 2006 event but not for the Jan. 2007 event. Large amount of afterslip was observed in the first 12 hours following the Nov. 2006 main shock. For both events, we inverted observed GPS offsets to evaluate the size and rake of the coseismic slip. In forward modeling, the PREM layered model of the spherical Earth was adopted (the method of F. Pollitz). The rupture dimensions and geometry were constrained by the spatial distribution of aftershocks, shallow seismicity, plate tectonics considerations, and CMT solutions. In case of the Jan. 2007 event, plate tectonic constraints are inapplicable. To ensure correct estimation of the Nov. 2006 coseismic offsets, we modeled postseismic transients by the logarithmic approximation in agreement with the rate-strengthening friction. For the Nov. 2006 event, our

  6. Photodynamic inactivation of somatic frog nerve ex vivo

    NASA Astrophysics Data System (ADS)

    Akchurin, Garif G.; Seliverstov, George A.; Akchurin, George G.; Kudryashova, Svetlana Y.

    2004-06-01

    New techniques research mechanisms of photdynamic reactions at somatic frog nerve was approved. Dosimetry PDT with minimum time resolution ~1ms determined by changing the amplitude of compound action potential of somatic frog nerve. Light-induced inactivation of dynamic response of somatic frog nerve on electrical pulsed excitation was study ex vivo. The light-sensitive dyes: methylene blue (Mb), Indocianin green and eryhtrocin-B has been used on photodynamic induced inactivation of the processes generation nerve pulses. Inactivation of consequence action potential of somatic frog nerve using excitation of electical pulsed was achieved by irradiation with He-Ne laser light in a red spectral region (λ=633 nm, power level 2-20 mW), diode laser (λ=805 nm, P<0.1-1 W/cm2) in the case of Indocianin green and YAG:Nd laser (λ=532 nm, P~1mW) for eryhtrocin-B. It was discovered that methylene blue, Indocainine green and erytrocin-B decrease of the amplitude compound action potential of the ensemble neurons. The possible cell death mechanism was connected with damage of the sodium potassium adenosine triphosphatase (K-Na ATP) active transport which decrease of amplitude of compound action potential and decrease lifetime ionic channel of membrane nerve.

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

    NASA Astrophysics Data System (ADS)

    Vourlidas, A.; Sanchez Andrade-Nuño, B.; Landi, E.; Patsourakos, S.; Teriaca, L.; Schühle, U.; Korendyke, C. M.; Nestoras, I.

    2010-01-01

    The Very high Angular resolution ULtraviolet Telescope (VAULT) is a sounding rocket payload built to study the crucial interface between the solar chromosphere and the corona by observing the strongest line in the solar spectrum, the Ly α line at 1216 Å. In two flights, VAULT succeeded in obtaining the first ever subarcsecond ( 0.5^'' ) images of this region with high sensitivity and cadence. Detailed analyses of those observations contributed significantly to new ideas about the nature of the transition region. Here, we present a broad overview of the Ly α atmosphere as revealed by the VAULT observations and bring together past results and new analyses from the second VAULT flight to create a synthesis of our current knowledge of the high-resolution Ly α Sun. We hope that this work will serve as a good reference for the design of upcoming Ly α telescopes and observing plans.

  8. Revealing the flexoelectricity in the mixed-phase regions of epitaxial BiFeO3 thin films

    PubMed Central

    Cheng, Cheng-En; Liu, Heng-Jui; Dinelli, Franco; Chen, Yi-Chun; Chang, Chen-Shiung; Chien, Forest Shih-Sen; Chu, Ying-Hao

    2015-01-01

    Understanding the elastic response on the nanoscale phase boundaries of multiferroics is an essential issue in order to explain their exotic behaviour. Mixed-phase BiFeO3 films, epitaxially grown on LaAlO3 (001) substrates, have been investigated by means of scanning probe microscopy to characterize the elastic and piezoelectric responses in the mixed-phase region of rhombohedral-like monoclinic (MI) and tilted tetragonal-like monoclinic (MII,tilt) phases. Ultrasonic force microscopy reveal that the regions with low/high stiffness values topologically coincide with the MI/MII,tilt phases. X-ray diffraction strain analysis confirms that the MI phase is more compliant than the MII,tilt one. Significantly, the correlation between elastic modulation and piezoresponse across the mixed-phase regions manifests that the flexoelectric effect results in the enhancement of the piezoresponse at the phase boundaries and in the MI regions. This accounts for the giant electromechanical effect in strained mixed-phase BiFeO3 films. PMID:25627445

  9. Revealing the flexoelectricity in the mixed-phase regions of epitaxial BiFeO3 thin films.

    PubMed

    Cheng, Cheng-En; Liu, Heng-Jui; Dinelli, Franco; Chen, Yi-Chun; Chang, Chen-Shiung; Chien, Forest Shih-Sen; Chu, Ying-Hao

    2015-01-01

    Understanding the elastic response on the nanoscale phase boundaries of multiferroics is an essential issue in order to explain their exotic behaviour. Mixed-phase BiFeO3 films, epitaxially grown on LaAlO3 (001) substrates, have been investigated by means of scanning probe microscopy to characterize the elastic and piezoelectric responses in the mixed-phase region of rhombohedral-like monoclinic (MI) and tilted tetragonal-like monoclinic (MII,tilt) phases. Ultrasonic force microscopy reveal that the regions with low/high stiffness values topologically coincide with the MI/MII,tilt phases. X-ray diffraction strain analysis confirms that the MI phase is more compliant than the MII,tilt one. Significantly, the correlation between elastic modulation and piezoresponse across the mixed-phase regions manifests that the flexoelectric effect results in the enhancement of the piezoresponse at the phase boundaries and in the MI regions. This accounts for the giant electromechanical effect in strained mixed-phase BiFeO3 films. PMID:25627445

  10. Molecular characterization of a Cyrtochilum loxense Somatic Embryogenesis Receptor-like Kinase (SERK) gene expressed during somatic embryogenesis.

    PubMed

    Cueva, Augusta; Concia, Lorenzo; Cella, Rino

    2012-06-01

    Somatic embryogenesis is crucial for the propagation of endangered Ecuadorian orchid species, among them Cyrtochilum loxense, in view of the fact that their number in nature or in collections is quite reduced. One of the genes expressed during somatic and zygotic embryogenesis is Somatic Embryogenesis Receptor-like Kinase (SERK). Despite the development of somatic embryogenesis protocols for orchids, no SERK genes have been isolated from this family. This is the first report on the isolation of a full-length orchid SERK sequence, namely that of Cyrtochilum loxense (ClSERK). The identity of ClSERK was inferred by the presence of all domains typical of SERK proteins: a signal peptide, a leucine zipper domain, five LRRs, a serine proline-rich domain, a transmembrane domain, a kinase domain, and the C-terminal region. We have observed that the ClSERK gene is highly expressed in embryogenic calluses generated from protocorms at the time of appearance of embryonic morphological features. At later stages when embryos become well visible on calluses, ClSERK gene expression decreases. Compared to early stages of embryo formation on calluses, the expression detected in leaf tissue is far lower, thus suggesting a role of this gene during development. PMID:22350407

  11. The Nucleotide Targets of Somatic Mutation and the Role of Selection in Immunoglobulin Heavy Chains of a Teleost Fish

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sequence analysis of H chain cDNA derived from the spleen of an individual catfish has shown that somatic mutation occurs within both the VH- and JH-encoded regions. Somatic mutation preferentially targets G and C nucleotides with approximately balanced frequencies, resulting in the predominant accu...

  12. Crustal S-wave structure beneath Eastern Black Sea Region revealed by Rayleigh-wave group velocities

    NASA Astrophysics Data System (ADS)

    Çınar, Hakan; Alkan, Hamdi

    2016-01-01

    In this study, the crustal S-wave structure beneath the Eastern Black Sea Region (including the Eastern Black Sea Basin (EBSB) and Eastern Pontides (EP)) has been revealed using inversion of single-station, fundamental-mode Rayleigh-wave group velocities in the period range of 4-40 seconds. We used digital broadband recordings of 13 regional earthquakes that recently occurred in the easternmost EBSB recorded at stations of the Kandilli Observatory and Earthquake Research Institute (KOERI). The average group-velocity-dispersion curves were generated from 26 paths for the EBSB, and 16 paths for the EP, and they were inverted to determine the average 1-D shear-wave structure of the region. We have created a pseudo-section, roughly depicting the crustal structure of the region based on the group velocity inversion results of all station-earthquake paths. The thickness of the sedimentary layer reaches 12 km in the center of EBSB (Vs = 2.5-3.1 km/s) and decreases 4 km in the EP. There is a thin sedimentary layer in the EP (Vs = 2.7 km/s). A consolidated thin crust that exists in the EBSB possesses a high seismic velocity (Vs = 3.8 km/s). While a thin (∼26 km) and transitional crust exists beneath the EBSB, a thick (about 42 km) continental crust exists beneath the EP where the Conrad is clearly seen at about a 24 km depth. Thick continental crust in the EP region is clearly distinguished from a gradational velocity change (Vs = 3.4-3.8 km/s). The Moho dips approximately southwards, and the Vs velocity (4.25-4.15 km/s) beneath the Moho discontinuity decreases from the EBSB to the EP in the N-S direction. This may be an indication of a southward subduction.

  13. Cortical processing of visceral and somatic stimulation: differentiating pain intensity from unpleasantness.

    PubMed

    Dunckley, P; Wise, R G; Aziz, Q; Painter, D; Brooks, J; Tracey, I; Chang, L

    2005-01-01

    Visceral and somatic pain perception differs in several aspects: poor localization of visceral pain and the ability of visceral pain to be referred to somatic structures. The perception of pain intensity and affect in visceral and somatic pain syndromes is often different, with visceral pain reported as more unpleasant. To determine whether these behavioral differences are due to differences in the central processing of visceral and somatic pain, non-invasive imaging tools are required to examine the neural correlates of visceral and somatic events when the behavior has been isolated and matched for either unpleasantness or pain intensity. In this study we matched the unpleasantness of somatic and visceral sensations and imaged the neural representation of this perception using functional magnetic resonance imaging in 10 healthy right-handed subjects. Each subject received noxious thermal stimuli to the left foot and midline lower back and balloon distension of the rectum while being scanned. Stimuli were matched to the same unpleasantness rating, producing mild-moderate pain intensity for somatic stimuli but an intensity below the pain threshold for the visceral stimuli. Visceral stimuli induced deactivation of the perigenual cingulate bilaterally with a relatively greater activation of the right anterior insula-i.e. regions encoding affect. Somatic pain induced left dorso-lateral pre-frontal cortex and bilateral inferior parietal cortex activation i.e. regions encoding spatial orientation and assessing perceptual valence of the stimulus. We believe that the observed patterns of activation represent the differences in cortical process of interoceptive (visceral) and exteroceptive (somatic) stimuli when matched for unpleasantness. PMID:15896917

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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. PMID:8786141

  19. 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.

  20. 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…

  1. 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

  2. Somatic Cell Counts in Bovine Milk

    PubMed Central

    Dohoo, I. R.; Meek, A. H.

    1982-01-01

    Factors which influence somatic cell counts in bovine milk are reviewed and guidelines for their interpretation are presented. It is suggested that the thresholds of 300 000 and 250 000 cells/mL be used to identify infected quarters and cows respectively. However, it is stressed that somatic cell counts are general indicators of udder health which are subject to the influence of many factors. Therefore the evaluation of several successive counts is preferable to the interpretation of an individual count. Relationships between somatic cell counts and both milk production and milk composition are discussed. Subclinical mastitis reduces milk quality and decreases yield although the relationship between production loss and somatic cell count requires clarification. Finally the availability of somatic cell counting programs in Canada is presented. PMID:17422127

  3. 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. PMID:26922778

  4. 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.

  5. 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

  6. Whole-genome sequencing reveals small genomic regions of introgression in an introduced crater lake population of threespine stickleback.

    PubMed

    Yoshida, Kohta; Miyagi, Ryutaro; Mori, Seiichi; Takahashi, Aya; Makino, Takashi; Toyoda, Atsushi; Fujiyama, Asao; Kitano, Jun

    2016-04-01

    Invasive species pose a major threat to biological diversity. Although introduced populations often experience population bottlenecks, some invasive species are thought to be originated from hybridization between multiple populations or species, which can contribute to the maintenance of high genetic diversity. Recent advances in genome sequencing enable us to trace the evolutionary history of invasive species even at whole-genome level and may help to identify the history of past hybridization that may be overlooked by traditional marker-based analysis. Here, we conducted whole-genome sequencing of eight threespine stickleback (Gasterosteus aculeatus) individuals, four from a recently introduced crater lake population and four of the putative source population. We found that both populations have several small genomic regions with high genetic diversity, which resulted from introgression from a closely related species (Gasterosteus nipponicus). The sizes of the regions were too small to be detected with traditional marker-based analysis or even some reduced-representation sequencing methods. Further amplicon sequencing revealed linkage disequilibrium around an introgression site, which suggests the possibility of selective sweep at the introgression site. Thus, interspecies introgression might predate introduction and increase genetic variation in the source population. Whole-genome sequencing of even a small number of individuals can therefore provide higher resolution inference of history of introduced populations. PMID:27069575

  7. 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

    2015-01-01

    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

  8. Voice-sensitive regions in the dog and human brain are revealed by comparative fMRI.

    PubMed

    Andics, Attila; Gácsi, Márta; Faragó, Tamás; Kis, Anna; Miklósi, Adám

    2014-03-01

    During the approximately 18-32 thousand years of domestication, dogs and humans have shared a similar social environment. Dog and human vocalizations are thus familiar and relevant to both species, although they belong to evolutionarily distant taxa, as their lineages split approximately 90-100 million years ago. In this first comparative neuroimaging study of a nonprimate and a primate species, we made use of this special combination of shared environment and evolutionary distance. We presented dogs and humans with the same set of vocal and nonvocal stimuli to search for functionally analogous voice-sensitive cortical regions. We demonstrate that voice areas exist in dogs and that they show a similar pattern to anterior temporal voice areas in humans. Our findings also reveal that sensitivity to vocal emotional valence cues engages similarly located nonprimary auditory regions in dogs and humans. Although parallel evolution cannot be excluded, our findings suggest that voice areas may have a more ancient evolutionary origin than previously known. PMID:24560578

  9. Deep sequencing of the tobacco mitochondrial transcriptome reveals expressed ORFs and numerous editing sites outside coding regions

    PubMed Central

    2014-01-01

    Background The purpose of this study was to sequence and assemble the tobacco mitochondrial transcriptome and obtain a genomic-level view of steady-state RNA abundance. Plant mitochondrial genomes have a small number of protein coding genes with large and variably sized intergenic spaces. In the tobacco mitogenome these intergenic spaces contain numerous open reading frames (ORFs) with no clear function. Results The assembled transcriptome revealed distinct monocistronic and polycistronic transcripts along with large intergenic spaces with little to no detectable RNA. Eighteen of the 117 ORFs were found to have steady-state RNA amounts above background in both deep-sequencing and qRT-PCR experiments and ten of those were found to be polysome associated. In addition, the assembled transcriptome enabled a full mitogenome screen of RNA C→U editing sites. Six hundred and thirty five potential edits were found with 557 occurring within protein-coding genes, five in tRNA genes, and 73 in non-coding regions. These sites were found in every protein-coding transcript in the tobacco mitogenome. Conclusion These results suggest that a small number of the ORFs within the tobacco mitogenome may produce functional proteins and that RNA editing occurs in coding and non-coding regions of mitochondrial transcripts. PMID:24433288

  10. 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

  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. PMID:27207135

  12. Unexplained in-vitro fertilization failure: implication of acrosomes with a small reacting region, as revealed by a monoclonal antibody.

    PubMed

    Albert, M; Gallo, J M; Escalier, D; Parseghian, N; Jouannet, P; Schrevel, J; David, G

    1992-10-01

    To determine the acrosomal characteristics related to in-vitro fertilization (IVF) outcome, spermatozoa from 50 men whose wives had resorted to IVF have been studied by indirect immunofluorescence microscopy with anti-human pro-acrosin monoclonal antibody 4D4 (mAb 4D4), prior to and after incubation in a capacitating medium. The antibody labelled only the acrosomal principal region (APR), revealing its shape (i.e. normal, small or amorphous) and its status (i.e. unreacted, partially or totally reacted). The IVF outcome distinguished: (i) spermatozoa which were able to fertilize at least one oocyte in vitro (group I; n = 25) and (ii) spermatozoa which failed to fertilize any oocyte in vitro (group II; n = 25). The semen characteristics of the two sperm groups, including the acrosome morphology, were similar according to conventional analysis. The mAb 4D4 detected in both the whole and the swim-up sperm cell fractions a lower percentage of normal APR in group II (< 50% for 10 patients in group II versus one patient from group I), which was related to a higher percentage of small APR. Moreover, after 21 h incubation, group II had a lower acrosomal loss index. The spermatozoa of five patients of this infertile group II did not undergo acrosomal modification whereas spermatozoa of all group I patients underwent the acrosomal reaction. The data showed that the relationship between acrosomal anomalies and IVF failure is mainly due to an increased incidence of acrosomes with a reduced size of the region involved in the acrosome reaction. Immunodiagnosis of this acrosomal region by means of mAb 4D4 is informative for IVF outcome. PMID:1479007

  13. Hypothesis: Somatic Mosaicism and Parkinson Disease

    PubMed Central

    Kim, Han-Joon

    2014-01-01

    Mutations causing genetic disorders can occur during mitotic cell division after fertilization, which is called somatic mutations. This leads to somatic mosaicism, where two or more genetically distinct cells are present in one individual. Somatic mutations are the most well studied in cancer where it plays an important role and also have been associated with some neurodegenerative disorders. The study of somatic mosaicism in Parkinson disease (PD) is only in its infancy, and a case with somatic mutation has not yet been described. However, we can speculate that a somatic mutation affecting cells in the central nervous system including substantia nigra dopaminergic neurons could lead to the development of PD through the same pathomechanisms of genetic PD even in the absence of a germ-line mutation. Theoretically, a number of genes could be candidates for genetic analysis for the presence of somatic mosaicism. Among them, SNCA and PARK2 could be the best candidates to analyze. Because analyzing brain tissues in living patients is impossible, alternative tissues could be used to indicate the genetic status of the brain. Performance of the technology is another factor to consider when analyzing the tissues. PMID:25548528

  14. 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

  15. [Somatization disorder - an overdiagnosed but underestimated illness].

    PubMed

    Karvonen, Juha T; Läksy, Kristian; Räsänen, Sami

    2016-01-01

    Physical symptoms often occur in the absence of physical illness. This is termed somatization when the symptoms are caused by psychic factors. When abundant symptoms affect the functional capacity and cause subjective harm and seeking healthcare services, a psychic disorder may be in question. Somatization may be associated with numerous psychic disorders. It may, however, also be a question of a somatoform disorder having a physical symptom picture. Somatization disorder is one of the somatoform disorders. Recognition of the disorder is often the problem in its treatment. Establishing a long-term treatment relationship actually forms the basis for therapy. PMID:26951025

  16. 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

  17. 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

  18. 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. PMID:26825265

  19. Direct Transcriptional Consequences of Somatic Mutation in Breast Cancer.

    PubMed

    Shlien, Adam; Raine, Keiran; Fuligni, Fabio; Arnold, Roland; Nik-Zainal, Serena; Dronov, Serge; Mamanova, Lira; Rosic, Andrej; Ju, Young Seok; Cooke, Susanna L; Ramakrishna, Manasa; Papaemmanuil, Elli; Davies, Helen R; Tarpey, Patrick S; Van Loo, Peter; Wedge, David C; Jones, David R; Martin, Sancha; Marshall, John; Anderson, Elizabeth; Hardy, Claire; Barbashina, Violetta; Aparicio, Samuel A J R; Sauer, Torill; Garred, Øystein; Vincent-Salomon, Anne; Mariani, Odette; Boyault, Sandrine; Fatima, Aquila; Langerød, Anita; Borg, Åke; Thomas, Gilles; Richardson, Andrea L; Børresen-Dale, Anne-Lise; Polyak, Kornelia; Stratton, Michael R; Campbell, Peter J

    2016-08-16

    Disordered transcriptomes of cancer encompass direct effects of somatic mutation on transcription, coordinated secondary pathway alterations, and increased transcriptional noise. To catalog the rules governing how somatic mutation exerts direct transcriptional effects, we developed an exhaustive pipeline for analyzing RNA sequencing data, which we integrated with whole genomes from 23 breast cancers. Using X-inactivation analyses, we found that cancer cells are more transcriptionally active than intermixed stromal cells. This is especially true in estrogen receptor (ER)-negative tumors. Overall, 59% of substitutions were expressed. Nonsense mutations showed lower expression levels than expected, with patterns characteristic of nonsense-mediated decay. 14% of 4,234 rearrangements caused transcriptional abnormalities, including exon skips, exon reusage, fusions, and premature polyadenylation. We found productive, stable transcription from sense-to-antisense gene fusions and gene-to-intergenic rearrangements, suggesting that these mutation classes drive more transcriptional disruption than previously suspected. Systematic integration of transcriptome with genome data reveals the rules by which transcriptional machinery interprets somatic mutation. PMID:27498871

  20. Ca2+-Dependent Enhancement of Release by Subthreshold Somatic Depolarization

    PubMed Central

    Christie, Jason M.; Chiu, Delia N.; Jahr, Craig E.

    2010-01-01

    Summary In many neurons, subthreshold somatic depolarization can spread electrotonically into the axon and modulate subsequent spike-evoked transmission. Although release probability is regulated by intracellular Ca2+, the Ca2+-dependence of this modulatory mechanism has been debated. Using paired recordings from synaptically connected molecular-layer interneurons (MLIs) of the rat cerebellum, we observed Ca2+-mediated strengthening of release following brief subthreshold depolarization of the soma. Two-photon microscopy revealed that, at the axon, somatic depolarization evoked Ca2+ influx through voltage-sensitive Ca2+ channels (VSCCs) and facilitated spike-evoked Ca2+ entry. Exogenous Ca2+ buffering diminished these Ca2+ transients and eliminated the strengthening of release. Axonal Ca2+ entry elicited by subthreshold somatic depolarization also triggered asynchronous transmission that may deplete vesicle availability and thereby temper release strengthening. In this cerebellar circuit, activity-dependent presynaptic plasticity depends on Ca2+ elevations resulting from both sub- and suprathreshold electrical activity initiated at the soma. PMID:21170054

  1. 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

  2. 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

  3. Somatic Complaints in Anxious Youth

    PubMed Central

    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.

    2013-01-01

    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) PMID:24129543

  4. 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

  5. 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. PMID:25328542

  6. 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

  7. 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

  8. Processed pseudogenes acquired somatically during cancer development.

    PubMed

    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

    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

  9. Somatic Embryogenesis in Lisianthus (Eustoma russellianum Griseb.).

    PubMed

    Ruffoni, Barbara; Bassolino, Laura

    2016-01-01

    Somatic embryogenesis is, for the main floricultural crops, a promising system for commercial scale-up, providing cloned material to be traded as seedlings. Somatic embryos, having the contemporary presence of root apical meristem and shoot apical meristem, can be readily acclimatized. For Lisianthus it is possible to induce embryogenic callus from leaf fragments of selected genotypes and to obtain embryos either in agarized substrate or in liquid suspension culture. The production of somatic embryos in liquid medium is high and can be modulated in order to synchronize the cycle and the size of the neoformed structures. The possibility to use the liquid substrate with high propagation rates reduces labor costs and could support the costs of eventual automation. In this paper we report a stepwise protocol for somatic embryogenesis in the species Eustoma russellianum. PMID:26619872

  10. 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

  11. Stress and Somatic Complaints in Low-Income Urban Adolescents.

    ERIC Educational Resources Information Center

    Reynolds, Linda K.; O'Koon, Jeffrey H.; Papademetriou, Eros; Szczygiel, Sylvia; Grant, Kathryn E.

    2001-01-01

    Studied rates of somatic complaints and the association between stress and somatic complaints for 1,030 low-income urban adolescents in grades 6 through 8. For both boys and girls, somatization was the most commonly reported internalizing symptom, and heightened rates of urban stress predicted heightened rates of somatic complaints. (SLD)

  12. (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.

  13. Somatic focus/awareness: Relationship to negative affect and pain in chronic pain patients

    PubMed Central

    O’Brien, Erin M.; Atchison, James W.; Gremillion, Henry A.; Waxenberg, Lori B.; Robinson, Michael E.

    2009-01-01

    Somatic focus refers to the tendency to notice and report physical symptoms, and has been investigated in relation to chronically painful conditions. This study investigated the relationship between somatic focus, as measured by the Pennebaker Inventory of Limbic Languidness (PILL), negative affect and pain. A secondary purpose of the present study was to examine sex differences in these relationships. Participants included 280 chronic pain patients (69.6% females, 88.9% Caucasian), who completed a battery of self-report measures on somatic focus, pain, negative affect, coping, and dysfunction. Results for the overall sample revealed that the PILL shares considerable variance with measures of negative affect, particularly with the physiological components of anxiety and depression. When the results were analyzed separately for male and female patients, it was found that several components of negative affect and cognitive factors play a stronger role in predicting somatic focus among men compared to women. Additional analyses then examined whether somatic focus was predictive of male and female patients’ pain reports. Results indicated that somatic focus explained a small, but unique amount of variance in female patients’ pain reports, which differed from the relationship observed among male patients. PMID:17524684

  14. Bovine ooplasm partially remodels primate somatic nuclei following somatic cell nuclear transfer.

    PubMed

    Wang, Kai; Beyhan, Zeki; Rodriguez, Ramon M; Ross, Pablo J; Iager, Amy E; Kaiser, German G; Chen, Ying; Cibelli, Jose B

    2009-03-01

    Interspecies somatic cell nuclear transfer (iSCNT) has the potential to become a useful tool to address basic questions about the nucleus-cytoplasm interactions between species. It has also been proposed as an alternative for the preservation of endangered species and to derive autologous embryonic stem cells. Using chimpanzee/ bovine iSCNT as our experimental model we studied the early epigenetic events that take place soon after cell fusion until embryonic genome activation (EGA). Our analysis suggested partial EGA in iSCNT embryos at the eight-cell stage, as indicated by Br-UTP incorporation and expression of chimpanzee embryonic genes. Oct4, Stella, Crabp1, CCNE2, CXCL6, PTGER4, H2AFZ, c-MYC, KLF4, and GAPDH transcripts were expressed, while Nanog, Glut1, DSC2, USF2, Adrbk1, and Lin28 failed to be activated. Although development of iSCNT embryos did not progress beyond the 8- to 16-cell stage, chromatin remodeling events, monitored by H3K27 methylation, H4K5 acetylation, and global DNA methylation, were similar in both intra- and interspecies SCNT embryos. However, bisulfite sequencing indicated incomplete demethylation of Oct4 and Nanog promoters in eight-cell iSCNT embryos. ATP production levels were significantly higher in bovine SCNT embryos than in iSCNT embryos, TUNEL assays did not reveal any difference in the apoptotic status of the nuclei from both types of embryos. Collectively, our results suggest that bovine ooplasm can partially remodel chimpanzee somatic nuclei, and provides insight into some of the current barriers iSCNT must overcome if further embryonic development is to be expected. PMID:19196039

  15. 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

    2016-06-01

    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. PMID:27251275

  16. 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.

  17. Revealing the Nature of Faint X-Ray Sources in the Giant Star-Forming Region NGC 3603

    NASA Astrophysics Data System (ADS)

    Poteet, C.; Marchenko, S.; Corcoran, M.; Andersen, M.

    2004-12-01

    NGC 3603, an open cluster embedded in the largest Galactic H II region, contains some of the most luminous, massive stars known in the Galaxy. It may serve as a good analog of star-forming regions in external starburst galaxies. The recent deep (50 Ksec) {Chandra} imaging of NGC 3603 revealed that its X-Ray emission is dominated by the bright Wolf-Rayet and O stars in the cluster core. However, there are hundreds of extremely weak point-like X-ray sources surrounding the central region. They tend to concentrate towards the cluster's center, suggestive of real cluster membership. Studying this population, we find that absolute majority of the weak sources does not belong to the lists of known OB and WR cluster members. Practically all the 263 weak X-ray sources have faint near-IR counterparts in the deep J,H,K images obtained by the ISAAC instrument on the VLT. Around 50% of the X-ray sources can be considered as visual binaries, an additional ˜ 20% as multiple systems (up to six stars in a r=1.5" ˜ 3σ circle). The composite spectrum of these sources is quite hard (kT ˜ 6 keV) and fairly absorbed (NH ˜ 1022). There is no obvious line emission, in particular, no strong Fe XXV line, so presently we cannot distinguish between thermal and non-thermal emission. The JHK colour-colour and colour-magnitude diagrams of the X-ray selected sources indicate that the X-ray data are very efficient in discriminating between field stars and cluster members. The X-ray sources have similar near-infrared properties as the whole near-infrared sample of the known cluster members. Hence, the discovered population of weak X-ray sources provide an effective means to obtain a "clean" sample of pre-main sequence stars down to 1 M⊙ assuming the cluster is 1 Myr old.

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

    PubMed Central

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

    2014-01-01

    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. DOI: http://dx.doi.org/10.7554/eLife.04094.001 PMID:25259795

  19. 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. PMID:26579095

  20. 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

  1. 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

  2. Multicellularity makes somatic differentiation evolutionarily stable.

    PubMed

    Wahl, Mary E; Murray, Andrew W

    2016-07-26

    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

  3. Biallelic BRCA2 Mutations Shape the Somatic Mutational Landscape of Aggressive Prostate Tumors.

    PubMed

    Decker, Brennan; Karyadi, Danielle M; Davis, Brian W; Karlins, Eric; Tillmans, Lori S; Stanford, Janet L; Thibodeau, Stephen N; Ostrander, Elaine A

    2016-05-01

    To identify clinically important molecular subtypes of prostate cancer (PCa), we characterized the somatic landscape of aggressive tumors via deep, whole-genome sequencing. In our discovery set of ten tumor/normal subject pairs with Gleason scores of 8-10 at diagnosis, coordinated analysis of germline and somatic variants, including single-nucleotide variants, indels, and structural variants, revealed biallelic BRCA2 disruptions in a subset of samples. Compared to the other samples, the PCa BRCA2-deficient tumors exhibited a complex and highly specific mutation signature, featuring a 2.88-fold increased somatic mutation rate, depletion of context-specific C>T substitutions, and an enrichment for deletions, especially those longer than 10 bp. We next performed a BRCA2 deficiency-targeted reanalysis of 150 metastatic PCa tumors, and each of the 18 BRCA2-mutated samples recapitulated the BRCA2 deficiency-associated mutation signature, underscoring the potent influence of these lesions on somatic mutagenesis and tumor evolution. Among all 21 individuals with BRCA2-deficient tumors, only about half carried deleterious germline alleles. Importantly, the somatic mutation signature in tumors with one germline and one somatic risk allele was indistinguishable from those with purely somatic mutations. Our observations clearly demonstrate that BRCA2-disrupted tumors represent a unique and clinically relevant molecular subtype of aggressive PCa, highlighting both the promise and utility of this mutation signature as a prognostic and treatment-selection biomarker. Further, any test designed to leverage BRCA2 status as a biomarker for PCa must consider both germline and somatic mutations and all types of deleterious mutations. PMID:27087322

  4. V-region mutation in vitro, in vivo, and in silico reveal the importance of the enzymatic properties of AID and the sequence environment

    PubMed Central

    MacCarthy, Thomas; Kalis, Susan L.; Roa, Sergio; Pham, Phuong; Goodman, Myron F.; Scharff, Matthew D.; Bergman, Aviv

    2009-01-01

    The somatic hypermutation of Ig variable regions requires the activity of activation-induced cytidine deaminase (AID) which has previously been shown to preferentially deaminate WRC (W = A/T, R = A/G) motif hot spots in in vivo and in vitro assays. We compared mutation profiles of in vitro assays for the 3′ flanking intron of VhJ558-Jh4 region to previously reported in vivo profiles for the same region in the Msh2−/−Ung−/− mice that lack base excision and mismatch repair. We found that the in vitro and in vivo mutation profiles were highly correlated for the top (nontranscribed) strand, while for the bottom (transcribed) strand the correlation is far lower. We used an in silico model of AID activity to elucidate the relative importance of motif targeting in vivo. We found that the mutation process entails substantial complexity beyond motif targeting, a large part of which is captured in vitro. To elucidate the contribution of the sequence environment to the observed differences between the top and bottom strands, we analyzed intermutational distances. The bottom strand shows an approximately exponential distribution of distances in vivo and in vitro, as expected from a null model. However, the top strand deviates strongly from this distribution in that mutations approximately 50 nucleotides apart are greatly reduced, again both in vivo and in vitro, illustrating an important strand asymmetry. While we have confirmed that AID targeting of hot and cold spots is a key part of the mutation process, our results suggest that the sequence environment plays an equally important role. PMID:19443686

  5. Somatic mutation profiling of follicular thyroid cancer by next generation sequencing.

    PubMed

    Swierniak, Michal; Pfeifer, Aleksandra; Stokowy, Tomasz; Rusinek, Dagmara; Chekan, Mykola; Lange, Dariusz; Krajewska, Jolanta; Oczko-Wojciechowska, Małgorzata; Czarniecka, Agnieszka; Jarzab, Michal; Jarzab, Barbara; Wojtas, Bartosz

    2016-09-15

    The molecular etiology of follicular thyroid tumors is largely unknown, rendering the diagnostics of these tumors challenging. The somatic alterations present in these tumors apart from RAS gene mutations and PAX8/PPARG translocations are not well described. To evaluate the profile of somatic alteration in follicular thyroid tumors, a total of 82 thyroid tissue samples derived from 48 patients were subjected to targeted Illumina HiSeq next generation sequencing of 372 cancer-related genes. New somatic alterations were identified in oncogenes (MDM2, FLI1), transcription factors and repressors (MITF, FLI1, ZNF331), epigenetic enzymes (KMT2A, NSD1, NCOA1, NCOA2), and protein kinases (JAK3, CHEK2, ALK). Single nucleotide and large structural variants were most and least frequently identified, respectively. A novel translocation in DERL/COX6C was detected. Many somatic alterations in non-coding gene regions with high penetrance were observed. Thus, follicular thyroid tumor somatic alterations exhibit complex patterns. Most tumors contained distinct somatic alterations, suggesting previously unreported heterogeneity. PMID:27283500

  6. 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

  7. Possible involvement of abscisic acid in the induction of secondary somatic embryogenesis on seed-coat-derived carrot somatic embryos.

    PubMed

    Ogata, Yumiko; Iizuka, Misato; Nakayama, Daisuke; Ikeda, Miho; Kamada, Hiroshi; Koshiba, Tomokazu

    2005-06-01

    When seed coats (pericarps) were picked from 14-day-old carrot (Daucus carota) seedlings and cultured on agar plates, embryogenic cell clusters were produced very rapidly at a high frequency on the open side edge. Embryo induction progressed without auxin treatment; indeed treatment caused the formation of non-embryogenic callus. The embryogenic tissues (primary embryos) developed normally until the torpedo stage; however, after this a number of secondary somatic embryos were produced in the hypocotyl and root regions. "Tertiary" embryos were formed on some of the secondary embryos, but many developed into normal plantlets. The primary embryos contained significantly higher levels of abscisic acid (ABA) than the hypocotyl-derived normal and seed-coat-derived secondary embryos. Fluridone inhibited the induction of secondary embryogenesis, while exogenously supplied ABA induced not only "tertiary" embryogenesis on the seed-coat-derived secondary embryos, but also secondary embryos on the hypocotyl-derived normal somatic embryos. These results indicate that ABA is one of the important endogenous factors for the induction of secondary embryogenesis on carrot somatic embryos. Higher levels of indole-3-acetic acid (IAA) in primary embryos also suggest the presence of some concerted effect of ABA and IAA on the induction of secondary embryogenesis in primary embryos. PMID:15770487

  8. Somatic presentation of psychiatric morbidity in general practice.

    PubMed Central

    Weich, S; Lewis, G; Donmall, R; Mann, A

    1995-01-01

    BACKGROUND. Twenty per cent of new illnesses in general practice, and 3% of consecutive attenders, are incident cases of 'pure' somatization. AIM. This study set out to estimate the prevalence of consultations by patients with psychiatric morbidity who present only somatic symptoms (somatic presentation), and to compare this with the likely prevalence of pure somatization. METHOD. A cross-sectional survey of consecutive general practice attenders was carried out. Psychiatric morbidity was measured using the general health questionnaire. Pure somatization was defined as medical consultation for somatic symptoms that were judged by a psychiatrist during an interview to be aetiologically attributable to an underlying psychiatric disorder but which were not recognized as such by the patient. RESULTS. Of attenders 25% were identified as somatic presenters. Of the somatic presenters interviewed one in six were estimated to be pure somatizers, which would extrapolate to 4% of attenders. Though all somatic presenters were probable cases of psychiatric disorder, subjects in this group had lower scores on the general health questionnaire than those who presented with psychological symptoms. General practitioner recognition of psychiatric morbidity was significantly lower among somatic presenters than for other subjects with psychiatric morbidity. CONCLUSION. General practitioner recognition of psychiatric morbidity could be improved for all types of somatic presentation, regardless of the aetiology of patients' somatic symptoms. There is a danger that concentrating attention on pure somatization may mean that psychiatric morbidity in the more common undifferentiated form of somatic presentation will be overlooked. PMID:7772392

  9. 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

  10. Molecular requirements for immunoglobulin heavy chain constant region gene switch-recombination revealed with switch-substrate retroviruses.

    PubMed

    Ott, D E; Marcu, K B

    1989-01-01

    We have employed a retroviral vector, ZN(Smu/S gamma 2b)tk1, as a means of introducing immunoglobulin heavy chain (IgH) switch (S) region sequences into B cell lines to directly measure their switch-recombinase activities. In an earlier study, we demonstrated that retrovector Smu-S gamma 2b recombination events occurred in two thymidine kinase (tk)-negative murine pre-B cell lines (18-8 and 38B9) upon selection in bromodeoxyuridine (BUdR) media for the loss of an Htk gene inserted in between the vector's Smu and S gamma 2b sequences. Here we have used this assay system to show that the 300-18 murine pre-B cell line possesses a very high level of switch-recombinase activity (greater than 1 event in 2500 cells/generation) while a terminally differentiated, antibody-secreting hybridoma line (A39R 1.1) has no detectable recombinase activity. Both S mu and S gamma 2b segments are required for switch region-mediated deletions. Retrovectors harboring only an Smu segment or an Smu segment and a portion of the murine c-myc gene in place of S gamma 2b sequences were both non-recombinagenic in this assay system. Nucleotide sequence analysis of six retrovector S segment recombinants, recovered from ZN(Smu/S gamma 2b) tk1-infected 18-8 and 39B9 pre-B lines, did not reveal homology at their sites of recombination. We conclude that: (1) S segment repetitive sequences play an essential but indirect role in IgCH gene switch-recombination, which occurs by an illegitimate, non-homologous mechanism; (2) the c-myc gene is not a significant target for switch-recombination; and (3) since endogenous Smu and S gamma 2b rearrangements were not observed in populations and clones of pre-B cells expressing a high level of switch-recombinase activity, multiple factors (presumably contributed in part by the degree of S segment accessibility) in addition to S recombinase activity are required for CH class switching. PMID:2489045

  11. Sequencing the GRHL3 Coding Region Reveals Rare Truncating Mutations and a Common Susceptibility Variant for Nonsyndromic Cleft Palate.

    PubMed

    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

    2016-04-01

    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

  12. Genetic variability among Schistosoma japonicum isolates from different endemic regions in China revealed by sequences of three mitochondrial DNA genes.

    PubMed

    Zhao, G H; Mo, X H; Zou, F C; Li, J; Weng, Y B; Lin, R Q; Xia, C M; Zhu, X Q

    2009-05-26

    The present study examined sequence variation in three mitochondrial DNA (mtDNA) regions, namely cytochrome c oxidase subunit 3 (cox3), NADH dehydrogenase subunits 4 and 5 (nad4 and nad5), among Schistosoma japonicum isolates from different endemic regions in China, and their phylogenetic relationships were re-constructed. A portion of the cox3 gene (pcox3), a portion of the nad4 and nad5 genes (pnad4 and pnad5) were amplified separately from individual trematodes by polymerase chain reaction (PCR) and the amplicons were subjected to direct sequencing. In the mountainous areas, sequence variations between parasites from Yunnan and those from Sichuan were 0.3% for pcox3, 0.0-0.1% for pnad4, and 0.0-0.2% for pnad5. In the lake/marshland areas, sequence variations between male and female parasites among different geographical locations were 0.0-0.3% for pcox3, 0.0-0.7% for pnad4, and 0.0-1.6% for pnad5. Sequence variations between S. japonicum from mountainous areas and those from lake/marshland areas were 0.0-0.5% for pcox3, 0.0-0.7% for pnad4, and 0.0-1.6% for pnad5. Phylogenetic analyses based on the combined sequences of pcox3, pnad4 and pnad5 revealed that S. japonicum isolates from mountainous areas (Yunnan and Sichuan provinces) clustered together. For isolates from the lake/marshland areas, isolates from Anhui and Jiangsu provinces clustered together and was sister to samples from Jiangxi province, while isolates from Hubei and Zhejiang province clustered together. However, isolates from different geographical locations in Hunan province were in different clades. These findings demonstrated the usefulness and attributes of the three mtDNA sequences for population genetic studies of S. japonicum, and have implications for studying population biology, molecular epidemiology, and genetic structure of S. japonicum, as well as for the effective control of schistosomiasis. PMID:19303214

  13. 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

  14. 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. PMID:26197980

  15. MASP-1, a promiscuous complement protease: structure of its catalytic region reveals the basis of its broad specificity.

    PubMed

    Dobó, József; Harmat, Veronika; Beinrohr, László; Sebestyén, Edina; Závodszky, Péter; Gál, Péter

    2009-07-15

    Mannose-binding lectin (MBL)-associated serine protease (MASP)-1 is an abundant component of the lectin pathway of complement. The related enzyme, MASP-2 is capable of activating the complement cascade alone. Though the concentration of MASP-1 far exceeds that of MASP-2, only a supporting role of MASP-1 has been identified regarding lectin pathway activation. Several non-complement substrates, like fibrinogen and factor XIII, have also been reported. MASP-1 belongs to the C1r/C1s/MASP family of modular serine proteases; however, its serine protease domain is evolutionary different. We have determined the crystal structure of the catalytic region of active MASP-1 and refined it to 2.55 A resolution. Unusual features of the structure are an internal salt bridge (similar to one in factor D) between the S1 Asp189 and Arg224, and a very long 60-loop. The functional and evolutionary differences between MASP-1 and the other members of the C1r/C1s/MASP family are reflected in the crystal structure. Structural comparison of the protease domains revealed that the substrate binding groove of MASP-1 is wide and resembles that of trypsin rather than early complement proteases explaining its relaxed specificity. Also, MASP-1's multifunctional behavior as both a complement and a coagulation enzyme is in accordance with our observation that antithrombin in the presence of heparin is a more potent inhibitor of MASP-1 than C1 inhibitor. Overall, MASP-1 behaves as a promiscuous protease. The structure shows that its substrate binding groove is accessible; however, its reactivity could be modulated by an unusually large 60-loop and an internal salt bridge involving the S1 Asp. PMID:19564340

  16. Somatic amplifications and deletions in genome of papillary thyroid carcinomas.

    PubMed

    Passon, Nadia; Bregant, Elisa; Sponziello, Marialuisa; Dima, Maria; Rosignolo, Francesca; Durante, Cosimo; Celano, Marilena; Russo, Diego; Filetti, Sebastiano; Damante, Giuseppe

    2015-11-01

    Somatic gene copy number variation contributes to tumor progression. Using comparative genomic hybridization (CGH) array, the presence of genomic imbalances was evaluated in a series of 27 papillary thyroid carcinomas (PTCs). To detect only somatic imbalances, for each sample, the reference DNA was from normal thyroid tissue of the same patient. The presence of the BRAF V600E mutation was also evaluated. Both amplifications and deletions showed an uneven distribution along the entire PTC cohort; amplifications were more frequent than deletions (mean values of 17.5 and 7.2, respectively). Number of aberration events was not even among samples, the majority of them occurring only in a small fraction of PTCs. Most frequent amplifications were detected at regions 2q35, 4q26, and 4q34.1, containing FN1, PDE5A, and GALNTL6 genes, respectively. Most frequent deletions occurred at regions 6q25.2, containing OPMR1 and IPCEF1 genes and 7q14.2, containing AOAH and ELMO1 genes. Amplification of FN1 and PDE5A genomic regions was confirmed by quantitative PCR. Frequency of amplifications and deletions was in relationship with clinical features and BRAF mutation status of tumor. In fact, according to the American Joint Committee on Cancer stage and American Thyroid Association (ATA) risk classification, amplifications are more frequent in higher risk samples, while deletions tend to prevail in the lower risk tumors. Analysis of single aberrations according to the ATA risk grouping shows that amplifications containing PDE5A, GALNTL6, DHRS3, and DOCK9 genes are significantly more frequent in the intermediate/high risk group than in the low risk group. Thus, our data would indicate that analysis of somatic genome aberrations by CGH array can be useful to identify additional prognostic variables. PMID:25863487

  17. Somatic markers, working memory, and decision making.

    PubMed

    Hinson, John M; Jameson, Tina L; Whitney, Paul

    2002-12-01

    The somatic marker hypothesis formulated by Damasio (e.g., 1994; Damasio, Tranel, & Damasio, 1991) argues that affective reactions ordinarily guide and simplify decision making. Although originally intended to explain decision-making deficits in people with specific frontal lobe damage, the hypothesis also applies to decision-making problems in populations without brain injury. Subsequently, the gambling task was developed by Bechara (Bechara, Damasio, Damasio, & Anderson, 1994) as a diagnostic test of decision-making deficit in neurological populations. More recently, the gambling task has been used to explore implications of the somatic marker hypothesis, as well as to study suboptimal decision making in a variety of domains. We examined relations among gambling task decision making, working memory (WM) load, and somatic markers in a modified version of the gambling task. Increased WM load produced by secondary tasks led to poorer gambling performance. Declines in gambling performance were associated with the absence of the affective reactions that anticipate choice outcomes and guide future decision making. Our experiments provide evidence that WM processes contribute to the development of somatic markers. If WM functioning is taxed, somatic markers may not develop, and decision making may thereby suffer. PMID:12641178

  18. 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. PMID:24441368

  19. Effects of VDT monitor placement and single versus bifocal glasses on somatic discomfort and postural profiles in data entry tasks.

    PubMed

    Basrai, Faisal; Aghazadeh, Fereydoun

    2004-12-01

    A study was conducted to determine the effects of VDT monitor positions and the use of single vision versus bifocal glasses on somatic elements in the data entry task. Eight male subjects performed data entry using a word processor in eight half-hour sessions with the four different monitor placements, i.e. "eye-level", "shoulder-level-front", "shoulder-level-side", and "sunken-level", wearing the two types of glasses. A subjective discomfort rating questionnaire covering 12 somatic elements was completed by the subject after each session. The head inclination and angle of gaze to the monitor were measured with a goniometer. The results revealed that the somatic elements which were affected significantly by the placement of the VDT monitor and the type of glasses were discomfort in the neck and back regions and eyestrain, respectively. The neck-back discomfort scores were highest at the "eye-level", lowest at the "sunken-level", and intermediate at the "shoulder-level-side" position. The "shoulder-level-front" position was not significantly different in the discomfort from other three positions. The eyestrain was significantly greater with the bifocal than with the single vision glasses. The lower the monitor was placed, the more forward was the head and gaze inclined. The head was inclined less forward, or even more backward, and the gaze was inclined more forward, with the bifocal than with the single vision glasses. As a conclusion, the VDT operators were advised to avoid the "eye-level" and "shoulder-level-side" positions and to prefer the "sunken-level" and "shoulder-level-front" positions as the first and second best choices, respectively. The preference becomes more critical for the wearers of bifocal glasses that suffer from postural constraints in viewing. PMID:17402506

  20. Atomic Force Microscopy Reveals Regional Variations in the Micromechanical Properties of the Pericellular and Extracellular Matrices of the Meniscus

    PubMed Central

    Sanchez-Adams, Johannah; Wilusz, Rebecca E.; Guilak, Farshid

    2014-01-01

    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. PMID:23568545

  1. Origin of somatic embryos from repetitively embryogenic cultures of walnut (Juglans regia L.): Implications forAgrobacterium-mediated transformation.

    PubMed

    Polito, V S; McGranahan, G; Pinney, K; Leslie, C

    1989-04-01

    Early stages of somatic embryo development from embryogenic cultures ofJuglans regia (Persian or English walnut) are described. Histological examination reveals that secondary somatic embryos arise from cotyledons and hypocotyls of primary embryos cultured in the dark. The embryos originate by transverse to oblique divisions of surface cells. Single-cell origin of the secondary embryos confirms the potential of the repetitive embryogenesis system forAgrobacterium-mediated transformation and regeneration of non-chimeric, transgenic walnut plants. PMID:24233141

  2. 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

  3. 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

  4. Somatic hypermutation of TCR γ V genes in the sandbar shark.

    PubMed

    Chen, Hao; Bernstein, Harris; Ranganathan, Parvathi; Schluter, Samuel F

    2012-05-01

    In a recent publication we demonstrated that somatic hypermutation occurs in the V region of the TCR γ gene of the sandbar shark (Carcharhinus plumbeus). We hypothesize that similar mechanisms are used to generate somatic mutations in both immunoglobulin and TCR γ genes of the sharks. Two distinct patterns of mutation occur, single nucleotide mutations (point mutations) and mutations comprising 2-5 consecutive bases (tandem mutations). Our data indicates that point mutations occur by a mechanism similar to that of somatic hypermutation in immunoglobulin genes of mammals, whereas tandem mutations may be generated by an error-prone DNA polymerase with terminal deoxynucleotidyl transferase (TdT)-like activity. Shark hotspot motifs identical to those of higher vertebrates were identified. We confirm that, as in immunoglobulin of sharks and higher vertebrates, highly significant targeting of AID activity to the classical DGYW/WRCH motif occurs in somatic hypermutation of sandbar shark TCR γ V genes. Our analysis suggests that the purpose of somatic mutations in shark TCR γ V-regions is to generate a more diverse repertoire in γ/δ receptors, rather than receptors with higher affinity. PMID:21925537

  5. 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

  6. Cellular mechanisms of somatic stem cell aging.

    PubMed

    Jung, Yunjoon; Brack, Andrew S

    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

  7. Somatic Mutation Favors the Evolution of Diploidy

    PubMed Central

    Orr, H. A.

    1995-01-01

    Explanations of diploidy have focused on advantages gained from masking deleterious mutations that are inherited. Recent theory has shown that these explanations are flawed. Indeed, we still lack any satisfactory explanation of diploidy in species that are asexual or that recombine only rarely. Here I consider a possibility first suggested by EFROIMSON in 1932, by MULLER in 1964 and by CROW and KIMURA in 1965: diploidy may provide protection against somatic, not inherited, mutations. I both compare the mean fitness of haploid and diploid populations that are asexual and investigate the invasion of ``diploidy'' alleles in sexual populations. When deleterious mutations are partially recessive and somatic mutation is sufficiently common, somatic mutation provides a clear advantage to diploidy in both asexual and sexual species. PMID:7768451

  8. Latent Variable Analysis of Coping, Anxiety/Depression, and Somatic Symptoms in Adolescents with Chronic Pain

    ERIC Educational Resources Information Center

    Compas, Bruce E.; Boyer, Margaret C.; Stanger, Catherine; Colletti, Richard B.; Thomsen, Alexandra H.; Dufton, Lynette M.; Cole, David A.

    2006-01-01

    Reports of adolescents' coping with recurrent pain, symptoms of anxiety/depression, and somatic complaints were obtained from a sample of 164 adolescents with recurrent abdominal pain and their parents. Confirmatory factor analysis revealed that coping consisted of 3 nonorthogonal factors: Primary Control Engagement Coping (problem solving,…

  9. Somatic heterogeneity of the CTG repeat in myotonic dystrophy is age and size dependent.

    PubMed Central

    Wong, L J; Ashizawa, T; Monckton, D G; Caskey, C T; Richards, C S

    1995-01-01

    The most common form of adult muscular dystrophy, myotonic dystrophy (DM), is caused by the abnormal expansion of the CTG repeat, located in the 3' UTR of the DM gene. The expanded-CTG allele often presents as a diffused band on Southern blot analysis, suggesting somatic mosaicism. In order to study the somatic instability of the CTG repeat, we have investigated the dynamics of the size heterogeneity of the CTG expansion. Size heterogeneity is shown as a smear on Southern blot and is measured by the midpeak-width ratio of the expanded allele to the normal sized allele. The ratio is also corrected for compression in the higher-molecular-weight region. It is found that the size heterogeneity of the expanded-CTG repeats, of 173 DM patients, correlates well with the age of the patient (r = .81, P << .001). The older patients show larger size variation. This correlation is independent of the sex of either the patient or the transmitting parent. The size heterogeneity of the expansion, based on age groups, is also dependent on the size of the expanded trinucleotide repeat. However, obvious size heterogeneity is not observed in congenital cases, regardless of the size of expansion. Comparison of individual patient samples collected at two different times has confirmed that the degree of size heterogeneity increases with age and has revealed a subtle but definite upward shift in the size of the expanded-CTG allele. The progression of the CTG repeat toward larger expansion with age is further confirmed by small-pool PCR assay that resolved the heterogeneous fragments into discrete bands.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1 Figure 4 Figure 5 PMID:7825566

  10. Somatic Embryogenesis in Crocus sativus L.

    PubMed

    Sevindik, Basar; Mendi, Yesim Yalcin

    2016-01-01

    Saffron (Crocus sativus L.) is one of the most important species in Crocus genus because of its effective usage. It is not only a very expensive spice, but it has also a big ornamental plant potential. Crocus species are propagated by corm and seed, and male sterility is the most important problem of this species. Hence, somatic embryogenesis can be regarded as a strategic tool for the multiplication of saffron plants. In this chapter, the production of saffron corms via somatic embryogenesis is described. PMID:26619871

  11. Consistently dated records from three Greenland ice cores reveal regional millennial-scale isotope gradients with possible Heinrich Event imprint

    NASA Astrophysics Data System (ADS)

    Seierstad, Inger K.; Rasmussen, Sune O.

    2014-05-01

    We here present records from the NGRIP, GRIP and GISP2 ice cores tied to the same chronology for the past 104 ka at an unprecedented time resolution. The three ice cores have been linked by matching distinct peaks in volcanic proxy records and other impurity records from the three ice cores, assuming that these layers of elevated impurity content represent the same, instantaneous event in the past at all three sites. In total there are more than 900 identified marker horizons between the three cores including previously published match points, of which we introduce a minor revision. Our matching is independently confirmed by new and existing volcanic ash layers (tephra). The depth-depth relationship from the detailed matching is used to transfer the most recent and widely used Greenland ice core chronology, the GICC05modelext timescale, to the two Summit cores, GRIP and GISP2. Furthermore, we provide gas chronologies for the Summit cores that are consistent with the GICC05modelext timescale by utilizing both existing and new unpublished gas data. A comparison of the GICC05modelext and the former GISP2 timescale reveals major discrepancies in short time intervals during the glacial section. We detect a pronounced change in the relative annual layer thickness between the two Summit sites and NGRIP across the Last Glacial termination and early-to-mid Holocene, which can be explained by a relative accumulation increase at NGRIP compared to the Summit region as response to the onset of the Holocene and the climatic optimum. Between stadials and interstadials we infer that the accumulation contrast typically was nearly 10% greater at Summit compared to at NGRIP. The δ18O temperature-proxy records from NGRIP, GRIP and GISP2 are generally very similar and display a synchronous behavior at climate transitions, but the δ18O differences between Summit and NGRIP is slowly changing over the last glacial-interglacial cycle superimposed by abrupt millennial-to centennial scale

  12. 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.

  13. Germline BAP1 mutations misreported as somatic based on tumor-only testing.

    PubMed

    Abdel-Rahman, Mohamed H; Rai, Karan; Pilarski, Robert; Davidorf, Frederick H; Cebulla, Colleen M

    2016-04-01

    We present three unrelated patients with germline mutations in BAP1 misreported as somatic mutations. All had strong family histories of cancer. One of these patients presented with an invasive breast cancer with the tumor tissue showing partial loss of the mutant rather than the wild type allele, suggesting that the germline BAP1 mutation didn't contribute to breast cancer development in this patient. This data highlights the importance of sequencing matching germline and tumor DNA for proper assessment of somatic versus germline mutation status. In patients with somatic mutations reported from laboratories carrying out tumor-only genomic testing, the possibility that a variant may be a germline mutation should be considered, especially if the personal and/or family history suggests hereditary cancer predisposition. Since tumor-only testing can reveal germline mutations, ethical issues for patients being tested should be considered including proper consent and genetic counseling. PMID:26748926

  14. Relationship between ploidy variation of citrus calli and competence for somatic embryogenesis.

    PubMed

    Zhang, Jun-E; Guo, Wen-Wu; Deng, Xiu-Xin

    2006-07-01

    This study focuses on the relationship between the genetic variation of calli and the competence for somatic embryogenesis in citrus. The DNA content of 35 citrus calli of different genotypes was measured three times by flow cytometry during a period of four years. The results showed that 71.4 % of the genotypes had a progressive increase of varied cells, while those of Page tangelo, Shamouti sweet orange, Russ navel orange and Cleopatra decreased; significant difference in the variation degree (percentages) existed among genotypes. Studies carried out on the induction of somatic embryogenesis revealed that 9 out of the 35 genotypes had still kept the competence of somatic embryogenesis, and the rest 26 had lost the competence. Correlation analysis indicated that there was no significant relationship between the variation degree and the embryogenesis competence r = -0.10 (P < 0.01), neither for the relationship between the subculture duration and the regeneration capacity. PMID:16875323

  15. Plant regeneration through somatic embryogenesis from callus induced on immature embryos of Alstroemeria spp. L.

    PubMed

    Van Schaik, C E; Posthuma, A; De Jeu, M J; Jacobsen, E

    1996-01-01

    The plant regeneration ability of callus obtained from zygotic embryos of the monocot Alstroemeria spp. was studied. The best explants for somatic embryogenesis were immature zygotic embryos in half-ovules when the endosperm was still soft and white. For 2 genotypes embryogenic callus was induced on callus induction medium with a success rate of 54%. The best callus induction period was 10 weeks. The morphology of embryogenic callus was nodular. Somatic embryos were formed after transfer of the callus to regeneration medium. These somatic embryos revealed later on the typical features of zygotic Alstroemeria embryos. The total duration of the plant regeneration protocol, from inoculation till rooted plantlets ready for transfer to the greenhouse, was 28 weeks. PMID:24178361

  16. Genomic footprinting of a yeast tRNA gene reveals stable complexes over the 5'-flanking region.

    PubMed Central

    Huibregtse, J M; Engelke, D R

    1989-01-01

    We have shown by genomic footprinting that the 5'-flanking region of the Saccharomyces cerevisiae tRNASUP53 gene is protected from DNase I digestion. The protected region has a 5' boundary at -40 (relative to the transcription initiation site) and extends into the coding region of the gene, with a 3' boundary at approximately +15. Although the DNase I protection over this region was much greater than at the A- and B-box internal promoters, point mutations within the A or B box that reduced transcription in vitro eliminated the upstream DNase I protection. This implies that formation of a stable complex over the 5'-flanking region is dependent on interaction of the gene with transcription factor IIIC but that stability of the complex may not require continued interaction with this factor. The DNase I protection under varied growth conditions further suggested that the upstream complex is composed of two or more components. The region over the transcription initiation site (approximately +15 to -10) was less protected in stationary-phase cultures, whereas the more upstream region (approximately -10 to -40) was protected in both exponential- and stationary-phase cultures. Images PMID:2677668

  17. Somatic Cell Count in Milk of Goats Enrolled in Dairy Herd Improvement Program in 2007

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of breed, parity, stage of lactation (month), herd size, and regions/states on somatic cell count (SCC) and production of milk from dairy goats enrolled in the Dairy Herd Improvement (DHI) program in the United States in 2007 were investigated to monitor the current status of SCC and to ...

  18. 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. PMID:24945569

  19. Somatic Symptoms in Traumatized Children and Adolescents

    ERIC Educational Resources Information Center

    Kugler, Brittany B.; Bloom, Marlene; Kaercher, Lauren B.; Truax, Tatyana V.; Storch, Eric A.

    2012-01-01

    Childhood exposure to trauma has been associated with increased rates of somatic symptoms (SS), which may contribute to diminished daily functioning. One hundred and sixty-one children residing at a residential treatment home who had experienced neglect and/or abuse were administered the Trauma Symptom Checklist for Children (TSCC), the…

  20. Studies for Somatic Embryogenesis in Sweet Potato

    NASA Technical Reports Server (NTRS)

    Bennett, J. Rasheed; Prakash, C. S.

    1997-01-01

    The purpose of this study was to improve the somatic embryo (SE) system for plant production of sweet potato (Ipomoea batatas L(Lam)). Explants isolated from SE-derived sweet potato plants were compared with control (non SE-derived) plants for their competency for SE production. Leaf explants were cultured on Murashige-Skoog (MS) medium with 2,4-dichlorophenoxy acetic acid (0.2 mg/L) and 6-benzylaminopurine (2.5 mg/L) for 2 weeks in darkness and transferred to MS medium with abscisic acid (2.5 mg/L). Explants isolated from those plants developed through somatic embryogenesis produced new somatic embryos rapidly and in higher frequency than those isolated from control plants They also appeared to grow faster in tissue culture than the control plants. Current studies in the laboratory are examining whether plants derived from a cyclical embryogenesis system (five cycles) would have any further positive impact on the rapidity and frequency of somatic embryo development. More detailed studies using electron microscopy are expected to show the point of origin of the embryos and to allow determination of their quality throughout the cyclical process. This study may facilitate improved plant micropropagation, gene transfer and germplasm conservation in sweet potato.

  1. Sexual Abuse: Somatic and Emotional Reactions.

    ERIC Educational Resources Information Center

    Rimza, Mary Ellen; And Others

    1988-01-01

    Chart reviews and telephone interviews with 72 sexual abuse victims found that 48 of the children had symptoms similar to the "rape trauma" syndrome. Two-thirds of victims commonly had somatic complaints (such as abdominal pain) and emotional/behavioral problems (runaway behavior, suicide attempts). (DB)

  2. Somatic cell nuclear transfer in zebrafish.

    PubMed

    Siripattarapravat, Kannika; Pinmee, Boonya; Venta, Patrick J; Chang, Chia-Cheng; Cibelli, Jose B

    2009-10-01

    We developed a method for somatic cell nuclear transfer in zebrafish using laser-ablated metaphase II eggs as recipients, the micropyle for transfer of the nucleus and an egg activation protocol after nuclear reconstruction. We produced clones from cells of both embryonic and adult origins, although the latter did not give rise to live adult clones. PMID:19718031

  3. Somatic Disorders of Childhood and Adolescence.

    ERIC Educational Resources Information Center

    Siegel, Lawrence J.

    1990-01-01

    Briefly reviews number of theories which address role of psychological factors in etiology of somatic disorders. Focuses on psychological treatment approaches that have been used to alleviate or reduce symptomatic behaviors associated with eating disorders, elimination disorders, and headaches in children. Discusses role of school psychologists in…

  4. Autophagy SEPArates germline and somatic cells.

    PubMed

    Baehrecke, Eric H

    2009-01-23

    Cellular determinants of the germline selectively accumulate in germ cell precursors and influence cell fate during early development in many organisms. Zhang et al. (2009) now report that targeted autophagy mediated by the SEPA-1 protein depletes germplasm proteins from somatic cells during early development of the nematode. PMID:19167322

  5. Studies on Somatic Embryogenesis in Sweetpotato

    NASA Technical Reports Server (NTRS)

    Bennett, J. Rasheed; Prakash, C. S.

    1997-01-01

    The purpose of this study was to improve the somatic embryo (SE) system for plant production of sweetpotato Ipomoea batatas L.(Lam)l. Explants isolated from SE-derived sweet potato plants were compared with control (non SE-derived) plants for their competency for SE production. Leaf explants were cultured on Murashige-Skoog (MS) medium with 2,4-dichlorophenoxy acetic acid (0.2 mg/L) and 6-benzylaminopurine (2.5 mg/L) for 2 weeks in darkness and transferred to MS medium with abscisic acid (2.5 Explants isolated from those plants developed through somatic embryo-genesis produced new somatic embryos rapidly and in higher frequency than those isolated from control plants. They also appeared to grow faster in tissue culture than the control plants. Current studies in the laboratory are examining whether plants derived from a cyclical embryogenesis system (five cycles) would have any further positive impact on the rapidity and frequency of somatic embryo development. More detailed studies using electron microscopy are expected to show the point of origin of the embryos and to allow determination of their quality throughout the cyclical process. This study may facilitate improved plant micropropagation, gene transfer and germplasm conservation in sweet potato.

  6. 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

    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

    2008-06-01

    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

  7. Somatic embryogenesis of a wild passion fruit species Passiflora cincinnata Masters: histocytological and histochemical evidences.

    PubMed

    Rocha, Diego Ismael; Vieira, Lorena Melo; Tanaka, Francisco André Ossamu; da Silva, Luzimar Campos; Otoni, Wagner Campos

    2012-07-01

    The characterization of cellular changes that occur during somatic embryogenesis is essential for understanding the factors involved in the transition of somatic cells into embryogenically competent cells and determination of cells and/or tissues involved. The present study describes the anatomical and ultrastructural events that lead to the formation of somatic embryos in the model system of the wild passion fruit (Passiflora cincinnata). Mature zygotic embryos were inoculated in Murashige and Skoog induction media supplemented with 2,4-dichlorophenoxyacetic acid and 6-benzyladenine. Zygotic embryo explants at different development stages were collected and processed by conventional methods for studies using light, scanning, and transmission electron microscopy (TEM). Histochemical tests were used to examine the mobilization of reserves. The differentiation of the somatic embryos began in the abaxial side of the cotyledon region. Protuberances were formed from the meristematic proliferation of the epidermal and mesophyll cells. These cells had large nuclei, dense cytoplasm with a predominance of mitochondria, and a few reserve compounds. The protuberances extended throughout the abaxial surface of the cotyledons. The ongoing differentiation of peripheral cells of these structures led to the formation of proembryogenic zones, which, in turn, dedifferentiated into somatic embryos of multicellular origin. In the initial stages of embryogenesis, the epidermal and mesophyll cells showed starch grains and less lipids and protein reserves than the starting explant. These results provide detailed information on anatomical and ultrastructural changes involved in the acquisition of embryogenic competence and embryo differentiation that has been lacking so far in Passiflora. PMID:21927886

  8. The Mechanism of Fibril Formation of a Non-inhibitory Serpin Ovalbumin Revealed by the Identification of Amyloidogenic Core Regions*

    PubMed Central

    Tanaka, Naoki; Morimoto, Yumi; Noguchi, Yurika; Tada, Tomoko; Waku, Tomonori; Kunugi, Shigeru; Morii, Takashi; Lee, Yin-Fai; Konno, Takashi; Takahashi, Nobuyuki

    2011-01-01

    Ovalbumin (OVA), a non-inhibitory member of the serpin superfamily, forms fibrillar aggregates upon heat-induced denaturation. Recent studies suggested that OVA fibrils are generated by a mechanism similar to that of amyloid fibril formation, which is distinct from polymerization mechanisms proposed for other serpins. In this study, we provide new insights into the mechanism of OVA fibril formation through identification of amyloidogenic core regions using synthetic peptide fragments, site-directed mutagenesis, and limited proteolysis. OVA possesses a single disulfide bond between Cys73 and Cys120 in the N-terminal helical region of the protein. Heat treatment of disulfide-reduced OVA resulted in the formation of long straight fibrils that are distinct from the semiflexible fibrils formed from OVA with an intact disulfide. Computer predictions suggest that helix B (hB) of the N-terminal region, strand 3A, and strands 4–5B are highly β-aggregation-prone regions. These predictions were confirmed by the fact that synthetic peptides corresponding to these regions formed amyloid fibrils. Site-directed mutagenesis of OVA indicated that V41A substitution in hB interfered with the formation of fibrils. Co-incubation of a soluble peptide fragment of hB with the disulfide-intact full-length OVA consistently promoted formation of long straight fibrils. In addition, the N-terminal helical region of the heat-induced fibril of OVA was protected from limited proteolysis. These results indicate that the heat-induced fibril formation of OVA occurs by a mechanism involving transformation of the N-terminal helical region of the protein to β-strands, thereby forming sequential intermolecular linkages. PMID:21156792

  9. Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells.

    PubMed

    Ghildiyal, Megha; Seitz, Hervé; Horwich, Michael D; Li, Chengjian; Du, Tingting; Lee, Soohyun; Xu, Jia; Kittler, Ellen L W; Zapp, Maria L; Weng, Zhiping; Zamore, Phillip D

    2008-05-23

    Small interfering RNAs (siRNAs) direct RNA interference (RNAi) in eukaryotes. In flies, somatic cells produce siRNAs from exogenous double-stranded RNA (dsRNA) as a defense against viral infection. We identified endogenous siRNAs (endo-siRNAs), 21 nucleotides in length, that correspond to transposons and heterochromatic sequences in the somatic cells of Drosophila melanogaster. We also detected endo-siRNAs complementary to messenger RNAs (mRNAs); these siRNAs disproportionately mapped to the complementary regions of overlapping mRNAs predicted to form double-stranded RNA in vivo. Normal accumulation of somatic endo-siRNAs requires the siRNA-generating ribonuclease Dicer-2 and the RNAi effector protein Argonaute2 (Ago2). We propose that endo-siRNAs generated by the fly RNAi pathway silence selfish genetic elements in the soma, much as Piwi-interacting RNAs do in the germ line. PMID:18403677

  10. Metagenome Sequencing Revealed 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

  11. Episodic nature of earthquake activity in stable continental regions revealed by palaeoseismicity studies of Australian and North American Quaternary faults

    USGS Publications Warehouse

    Crone, A.J.; Machette, M.N.; Bowman, J.R.

    1997-01-01

    Palaeoseismic investigations of recent faulting in stable continental regions of Australia, North America and India show that these faults typically have a long-term behaviour characterised by episodes of activity separated by quiescent intervals of at least 10 000 and commonly 100 000 years or more. Long recurrence intervals such as these are well documented by detailed studies of the faults that ruptured during the 1986 Marryat Creek, South Australia and 1988 Tennant Creek, Northern Territory earthquakes. Thus, neotectonic features associated with stable continental region faults such as scarps and grabens commonly have subtle geomorphic expression and may be poorly preserved. Many potentially hazardous faults in stable continental regions are aseismic, which is one reason why the inventory of these faults is incomplete. Although they may be currently aseismic, faults in stable continental regions that are favourably oriented for movement in the current stress field could produce damaging earthquakes, often in unexpected places. Comprehensive palaeoseismic investigations of modern and prehistoric faulting events in stable continental regions are needed to understand the long-term behaviour of these faults, and thereby, improve seismic-hazard assessments.

  12. Quantitative gene expression profiling of mouse brain regions reveals differential transcripts conserved in human and affected in disease models.

    PubMed

    Brochier, Camille; Gaillard, Marie-Claude; Diguet, Elsa; Caudy, Nicolas; Dossat, Carole; Ségurens, Béatrice; Wincker, Patrick; Roze, Emmanuel; Caboche, Jocelyne; Hantraye, Philippe; Brouillet, Emmanuel; Elalouf, Jean-Marc; de Chaldée, Michel

    2008-04-22

    Using serial analysis of gene expression, we collected quantitative transcriptome data in 11 regions of the adult wild-type mouse brain: the orbital, prelimbic, cingulate, motor, somatosensory, and entorhinal cortices, the caudate-putamen, the nucleus accumbens, the thalamus, the substantia nigra, and the ventral tegmental area. With >1.2 million cDNA tags sequenced, this database is a powerful resource to explore brain functions and disorders. As an illustration, we performed interregional comparisons and found 315 differential transcripts. Most of them are poorly characterized and 20% lack functional annotation. For 78 differential transcripts, we provide independent expression level measurements in mouse brain regions by real-time quantitative RT-PCR. We also show examples where we used in situ hybridization to achieve infrastructural resolution. For 30 transcripts, we next demonstrated that regional enrichment is conserved in the human brain. We then quantified the expression levels of region-enriched transcripts in the R6/2 mouse model of Huntington disease and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson disease and observed significant alterations in the striatum, cerebral cortex, thalamus and substantia nigra of R6/2 mice and in the striatum of MPTP-treated mice. These results show that the gene expression data provided here for the mouse brain can be used to explore pathophysiological models and disclose transcripts differentially expressed in human brain regions. PMID:18252803

  13. 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. PMID:18393309

  14. MAGNETIC FIELDS IN LARGE-DIAMETER H II REGIONS REVEALED BY THE FARADAY ROTATION OF COMPACT EXTRAGALACTIC RADIO SOURCES

    SciTech Connect

    Harvey-Smith, L.; Madsen, G. J.; Gaensler, B. M.

    2011-08-01

    We present a study of the line-of-sight magnetic fields in five large-diameter Galactic H II regions. Using the Faraday rotation of background polarized radio sources, as well as dust-corrected H{alpha} surface brightness as a probe of electron density, we estimated the strength and orientation of the magnetic field along 93 individual sight lines through the H II regions. Each of the H II regions displayed a coherent magnetic field. The magnetic field strength (line-of-sight component) in the regions ranges from 2 to 6 {mu}G, which is similar to the typical magnetic field strength in the diffuse interstellar medium. We investigated the relationship between magnetic field strength and electron density in the five H II regions. The slope of magnetic field versus density in the low-density regime (0.8 cm{sup -3} < n{sub e} <30 cm{sup -3}) is very slightly above zero. We also calculated the ratio of thermal to magnetic pressure, {beta}{sub th}, for each data point, which fell in the range 1.01 < {beta}{sub th} < 25. Finally, we studied the orientation of the magnetic field in the solar neighborhood (d < 1.1 kpc) using our data from five H II regions along with existing measurements of the line-of-sight magnetic field strength from polarized pulsars whose distances have been determined from their annual parallax. We identify a net direction for the magnetic field in the solar neighborhood, but find no evidence for a preferred vertical direction of the magnetic field above or below the Galactic plane.

  15. 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

  16. GPCRs Direct Germline Development and Somatic Gonad Function in Planarians

    PubMed Central

    Saberi, Amir; Beets, Isabel; Schoofs, Liliane; Newmark, Phillip A.

    2016-01-01

    Planarians display remarkable plasticity in maintenance of their germline, with the ability to develop or dismantle reproductive tissues in response to systemic and environmental cues. Here, we investigated the role of G protein-coupled receptors (GPCRs) in this dynamic germline regulation. By genome-enabled receptor mining, we identified 566 putative planarian GPCRs and classified them into conserved and phylum-specific subfamilies. We performed a functional screen to identify NPYR-1 as the cognate receptor for NPY-8, a neuropeptide required for sexual maturation and germ cell differentiation. Similar to NPY-8, knockdown of this receptor results in loss of differentiated germ cells and sexual maturity. NPYR-1 is expressed in neuroendocrine cells of the central nervous system and can be activated specifically by NPY-8 in cell-based assays. Additionally, we screened the complement of GPCRs with expression enriched in sexually reproducing planarians, and identified an orphan chemoreceptor family member, ophis, that controls differentiation of germline stem cells (GSCs). ophis is expressed in somatic cells of male and female gonads, as well as in accessory reproductive tissues. We have previously shown that somatic gonadal cells are required for male GSC specification and maintenance in planarians. However, ophis is not essential for GSC specification or maintenance and, therefore, defines a secondary role for planarian gonadal niche cells in promoting GSC differentiation. Our studies uncover the complement of planarian GPCRs and reveal previously unappreciated roles for these receptors in systemic and local (i.e., niche) regulation of germ cell development. PMID:27163480

  17. Genomic determinants of somatic copy number alterations across human cancers.

    PubMed

    Zhang, Yanping; Xu, Hongen; Frishman, Dmitrij

    2016-03-01

    Somatic copy number alterations (SCNAs) play an important role in carcinogenesis. However, the impact of genomic architecture on the global patterns of SCNAs in cancer genomes remains elusive. In this work, we conducted multiple linear regression (MLR) analyses of the pooled SCNA data from The Cancer Genome Atlas (TCGA) Pan-Cancer project. We performed MLR analyses for 11 individual cancer types and three different kinds of SCNAs-amplifications and deletions, telomere-bound and interstitial SCNAs and local SCNAs. Our MLR model explains >30% of the pooled SCNA breakpoint variation, with the explanatory power ranging from 13 to 32% for different cancer types and SCNA types. In addition to confirming previously identified features [e.g. long interspersed element-1 (L1) and short interspersed nuclear elements], we also identified several novel informative features, including distance to telomere, distance to centromere and low-complexity repeats. The results of the MLR analyses were additionally confirmed on an independent SCNA data set obtained from the catalogue of somatic mutations in cancer database. Using a rare-event logistic regression model and an extremely randomized tree classifier, we revealed that genomic features are informative for defining common SCNA breakpoint hotspots. Our findings shed light on the molecular mechanisms of SCNA generation in cancer. PMID:26732428

  18. GPCRs Direct Germline Development and Somatic Gonad Function in Planarians.

    PubMed

    Saberi, Amir; Jamal, Ayana; Beets, Isabel; Schoofs, Liliane; Newmark, Phillip A

    2016-05-01

    Planarians display remarkable plasticity in maintenance of their germline, with the ability to develop or dismantle reproductive tissues in response to systemic and environmental cues. Here, we investigated the role of G protein-coupled receptors (GPCRs) in this dynamic germline regulation. By genome-enabled receptor mining, we identified 566 putative planarian GPCRs and classified them into conserved and phylum-specific subfamilies. We performed a functional screen to identify NPYR-1 as the cognate receptor for NPY-8, a neuropeptide required for sexual maturation and germ cell differentiation. Similar to NPY-8, knockdown of this receptor results in loss of differentiated germ cells and sexual maturity. NPYR-1 is expressed in neuroendocrine cells of the central nervous system and can be activated specifically by NPY-8 in cell-based assays. Additionally, we screened the complement of GPCRs with expression enriched in sexually reproducing planarians, and identified an orphan chemoreceptor family member, ophis, that controls differentiation of germline stem cells (GSCs). ophis is expressed in somatic cells of male and female gonads, as well as in accessory reproductive tissues. We have previously shown that somatic gonadal cells are required for male GSC specification and maintenance in planarians. However, ophis is not essential for GSC specification or maintenance and, therefore, defines a secondary role for planarian gonadal niche cells in promoting GSC differentiation. Our studies uncover the complement of planarian GPCRs and reveal previously unappreciated roles for these receptors in systemic and local (i.e., niche) regulation of germ cell development. PMID:27163480

  19. Population Genomic Analysis of 962 Whole Genome Sequences of Humans Reveals Natural Selection in Non-Coding Regions

    PubMed Central

    Gazave, Elodie; Chang, Diana; Raj, Srilakshmi; Hunter-Zinck, Haley; Blekhman, Ran; Arbiza, Leonardo; Van Hout, Cris; Morrison, Alanna; Johnson, Andrew D.; Bis, Joshua; Cupples, L. Adrienne; Psaty, Bruce M.; Muzny, Donna; Yu, Jin; Gibbs, Richard A.; Keinan, Alon; Clark, Andrew G.; Boerwinkle, Eric

    2015-01-01

    Whole genome analysis in large samples from a single population is needed to provide adequate power to assess relative strengths of natural selection across different functional components of the genome. In this study, we analyzed next-generation sequencing data from 962 European Americans, and found that as expected approximately 60% of the top 1% of positive selection signals lie in intergenic regions, 33% in intronic regions, and slightly over 1% in coding regions. Several detailed functional annotation categories in intergenic regions showed statistically significant enrichment in positively selected loci when compared to the null distribution of the genomic span of ENCODE categories. There was a significant enrichment of purifying selection signals detected in enhancers, transcription factor binding sites, microRNAs and target sites, but not on lincRNA or piRNAs, suggesting different evolutionary constraints for these domains. Loci in “repressed or low activity regions” and loci near or overlapping the transcription start site were the most significantly over-represented annotations among the top 1% of signals for positive selection. PMID:25807536

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  1. 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

  2. Analysis of Genomic Regions Associated With Coronary Artery Disease Reveals Continent-Specific Single Nucleotide Polymorphisms in North African Populations

    PubMed Central

    Zanetti, Daniela; Via, Marc; Carreras-Torres, Robert; Esteban, Esther; Chaabani, Hassen; Anaibar, Fatima; Harich, Nourdin; Habbal, Rachida; Ghalim, Noreddine; Moral, Pedro

    2016-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:26780859

  3. 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…

  4. 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

  5. Regional Coherence Alterations Revealed by Resting-State fMRI in Post-Stroke Patients with Cognitive Dysfunction

    PubMed Central

    Peng, Cheng-Yu; Chen, Yu-Chen; Cui, Ying; Zhao, Deng-Ling; Jiao, Yun; Tang, Tian-Yu; Ju, Shenghong; Teng, Gao-Jun

    2016-01-01

    Objectives Post-stroke cognitive dysfunction greatly influences patients’ quality of life after stroke. However, its neurophysiological basis remains unknown. This study utilized resting-state functional magnetic resonance imaging (fMRI) to investigate the alterations in regional coherence in patients after subcortical stroke. Methods Resting-state fMRI measurements were acquired from 16 post-stroke patients with poor cognitive function (PSPC), 16 post-stroke patients with good cognitive function (PSGC) and 30 well-matched healthy controls (HC). Regional homogeneity (ReHo) was used to detect alterations in regional coherence. Abnormalities in regional coherence correlated with scores on neuropsychological scales. Results Compared to the HC and the PSGC, the PSPC showed remarkably decreased ReHo in the bilateral anterior cingulate cortex and the left posterior cingulate cortex/precuneus. ReHo in the bilateral anterior cingulate cortex positively correlated with the scores on the Symbol Digit Modalities Test (r = 0.399, P = 0.036) and the Complex Figure Test-delayed recall subtest (r = 0.397, P = 0.036) in all post-stroke patients. Moreover, ReHo in the left posterior cingulate cortex/precuneus positively correlated with the scores on the Forward Digit Span Test (r = 0.485, P = 0.009) in all post-stroke patients. Conclusions Aberrant regional coherence was observed in the anterior and posterior cingulate cortices in post-stroke patients with cognitive dysfunction. ReHo could represent a promising indicator of neurobiological deficiencies in post-stroke patients. PMID:27454170

  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 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

  7. Genetic analysis of historic western Great Lakes region wolf samples reveals early Canis lupus/lycaon hybridization

    PubMed Central

    Wheeldon, Tyler; White, Bradley N.

    2008-01-01

    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. PMID:18940770

  8. Somatic growth dynamics of West Atlantic hawksbill sea turtles: a spatio-temporal perspective

    USGS Publications Warehouse

    Bjorndal, Karen A.; Chaloupka, Milani; Saba, Vincent S.; Diez, Carlos E.; van Dam, Robert P.; Krueger, Barry H.; Horrocks, Julia A.; Santos, Armando J. B.; Bellini, Cláudio; Marcovaldi, Maria A. G.; Nava, Mabel; Willis, Sue; Godley, Brendan J.; Gore, Shannon; Hawkes, Lucy A.; McGowan, Andrew; Witt, Matthew J.; Stringell, Thomas B.; Sanghera, Amdeep; Richardson, Peter B.; Broderick, Annette C.; Phillips, Quinton; Calosso, Marta C.; Claydon, John A. B.; Blumenthal, Janice; Moncada, Felix; Nodarse, Gonzalo; Medina, Yosvani; Dunbar, Stephen G.; Wood, Lawrence D.; Lagueux, Cynthia J.; Campbell, Cathi L.; Meylan, Anne B.; Meylan, Peter A.; Burns Perez, Virginia R.; Coleman, Robin A.; Strindberg, Samantha; Guzmán-H, Vicente; Hart, Kristen M.; Cherkiss, Michael S.; Hillis-Starr, Zandy; Lundgren, Ian; Boulon, Ralf H., Jr.; Connett, Stephen; Outerbridge, Mark E.; Bolten, Alan B.

    2016-01-01

    Somatic growth dynamics are an integrated response to environmental conditions. Hawksbill sea turtles (Eretmochelys imbricata) are long-lived, major consumers in coral reef habitats that move over broad geographic areas (hundreds to thousands of kilometers). We evaluated spatio-temporal effects on hawksbill growth dynamics over a 33-yr period and 24 study sites throughout the West Atlantic and explored relationships between growth dynamics and climate indices. We compiled the largest ever data set on somatic growth rates for hawksbills – 3541 growth increments from 1980 to 2013. Using generalized additive mixed model analyses, we evaluated 10 covariates, including spatial and temporal variation, that could affect growth rates. Growth rates throughout the region responded similarly over space and time. The lack of a spatial effect or spatio-temporal interaction and the very strong temporal effect reveal that growth rates in West Atlantic hawksbills are likely driven by region-wide forces. Between 1997 and 2013, mean growth rates declined significantly and steadily by 18%. Regional climate indices have significant relationships with annual growth rates with 0- or 1-yr lags: positive with the Multivariate El Niño Southern Oscillation Index (correlation = 0.99) and negative with Caribbean sea surface temperature (correlation = −0.85). Declines in growth rates between 1997 and 2013 throughout the West Atlantic most likely resulted from warming waters through indirect negative effects on foraging resources of hawksbills. These climatic influences are complex. With increasing temperatures, trajectories of decline of coral cover and availability in reef habitats of major prey species of hawksbills are not parallel. Knowledge of how choice of foraging habitats, prey selection, and prey abundance are affected by warming water temperatures is needed to understand how climate change will affect productivity of consumers that live in association with coral reefs. Main

  9. Cloning mammary cell cDNAs from 17q12-q23 using interspecific somatic cell hybrids and subtractive hybridization

    SciTech Connect

    Cerosaletti, K.M.; Shapero, M.H.; Fournier, R.E.K.

    1995-01-01

    We have cloned human genes that are encoded in the region 17q12-q23 and expressed in breast tissue using interspecific somatic cell hybrids and subtractive hybridization. Two mouse microcell hybrids containing fragments of human chromosome 17 with a nonoverlap region at 17q12-q23 were generated by microcell transfer. Radiolabeled cDNA was synthesized from the hybrid cell containing the 17q12-q23 interval and was subtracted with an excess of RNA from the hybrid cell lacking the interval. Resulting cDNA probes enriched for sequences from 17q12-q23 were used to screen a human premenopausal breast cDNA library, and 60 cDNAs were identified. Three of these cDNAs mapped to the hybrid cell nonoverlap region. These cDNAs were expressed in mammary epithelial cell hybrids, although none appeared to be breast-specific. Sequence analysis of the cDNAs revealed that clone 93A represents a previously unidentified gene, clone 98C has homology to an expressed sequence tag from goat mammary tissue, and clone 200A is identical to the human homologue of the Drosophila melanogaster flightless-I gene. These genes map outside a 1-cM region linked to early onset familial breast cancer but may be useful genetic markers in the 17q12-q23 region. 47 refs., 6 figs.

  10. 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

  11. 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. PMID:25551761

  12. 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.

  13. 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. PMID:23919308

  14. fMRI reveals distinct CNS processing during symptomatic and recovered complex regional pain syndrome in children.

    PubMed

    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

    2008-07-01

    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 investigation of mechanisms underlying pain and other symptoms of CRPS. We used fMRI to evaluate CNS activation in paediatric patients (9-18 years) with CRPS affecting the lower extremity. Each patient underwent two scanning sessions: once during an active period of pain (CRPS(+)), and once after symptomatic recovery (CRPS(-)). In each session, mechanical (brush) and thermal (cold) stimuli were applied to the affected region of the involved limb and the corresponding mirror region of the unaffected limb. Two fundamental fMRI analyses were performed: (i) within-group analysis for CRPS(+) state and CRPS(-) state for brush and cold for the affected and unaffected limbs in each case; (ii) between-group (contrast) analysis for activations in affected and unaffected limbs in CRPS or post-CRPS states. We found: (i) in the CRPS(+) state, stimuli that evoked mechanical or cold allodynia produced patterns of CNS activation similar to those reported in adult CRPS; (ii) in the CRPS(+) state, stimuli that evoked mechanical or cold allodynia produced significant decreases in BOLD signal, suggesting pain-induced activation of endogenous pain modulatory systems; (iii) cold- or brush-induced activations in regions such as the basal ganglia and parietal lobe may explain some CNS-related symptoms in CRPS, including movement disorders and hemineglect/inattention; (iv) in the CRPS(-) state, significant activation differences persisted despite nearly complete elimination of evoked pain; (v) although non-noxious stimuli to the unaffected limb were perceived as equivalent in CRPS(+) and CRPS(-) states, the same stimulus produced different

  15. Fine fracture structures in the geothermal region of Hakone volcano, revealed by well-resolved earthquake hypocenters and focal mechanisms

    NASA Astrophysics Data System (ADS)

    Yukutake, Y.; Tanada, T.; Honda, R.; Harada, M.; Ito, H.; Yoshida, A.

    2009-12-01

    Occurrence of swarm earthquake in volcanically or geothermally active regions has been thought to be caused by the migration of the magmatic and/or hydrothermal fluid (e.g. Hill, 1977; Sibson, 1996; Spicak and Horalek, 2001; Hensch et al., 2008). It has been suggested that the fault-related fracture systems are responsible for the migration of fluid flow (e.g. Hill, 1977; Sibson, 1987; Sibson, 1996). For example, Sibson (1987) and Curewitz and Karson (1997) supposed that high permeable fracture system is mainly developed by the interaction between active faults at a pull- apart region (dilational fault jogs). However, it has not been shown that the fracture system is actually related to clustering of earthquakes in swarm activities. We investigated precise hypocentral distribution and mechanisms of small earthquakes in the geothermal region of Hakone volcano, near Tokyo Metropolitan Area central Japan, where swarm activities have been frequently observed. Hakone volcano is located in the northern boundary zone of the Izu-Mariana volcanic arc. The surface traces of the Hirayama and Tanna Fault are also located at the northern and southern part of Hakone volcano, respectively. The precise hypocenter determination is decisively important to elucidate occurrence mechanism of swarm earthquakes as well as to mitigate volcanic hazard at a world-famous sight-seeing spot near Tokyo Metropolitan Area, Japan. We first determined initial hypocenters, using the station corrections and one-dimensional velocity structures estimated by the joint hypocenter determination method (Kissling et al., 1994). Then, we applied the double-difference method (Waldhauser and Ellsworth, 2000) to relocate the initial hypocenters using the differential arrival time obtained by both manual picking and waveform cross-correlation analysis. Subsequently, we determined the focal mechanisms from the absolute P- and SH-wave amplitudes by adding the P-wave polarities. We found that most swarm earthquakes

  16. Analysis of the Tyrosine Kinome in Melanoma Reveals Recurrent Mutations in ERBB4

    PubMed Central

    Prickett, Todd D.; Agrawal, Neena S.; Wei, Xiaomu; Yates, Kristin E.; Lin, Jimmy C.; Wunderlich, John; Cronin, Julia C.; Cruz, Pedro; Rosenberg, Steven A.; Samuels, Yardena

    2010-01-01

    Tyrosine phosphorylation is important in signaling pathways underlying tumorigenesis. A mutational analysis of the Protein Tyrosine Kinase (PTK) gene family in cutaneous metastatic melanoma identified 30 somatic mutations in the kinase domain of 19 PTKs. The whole of the coding region of these 19 PTKs was further evaluated for somatic mutations in a total of 79 melanoma samples. This analysis revealed novel ERBB4 mutations in 19% of melanoma patients and that an additional two kinases (FLT1 and PTK2B) are mutated in 10% of melanomas. Seven missense mutations in the most commonly altered PTK (ERBB4) were examined and found to increase kinase activity and transformation ability. Melanoma cells expressing mutant ERBB4 had reduced cell growth after shRNA–mediated knockdown of ERBB4 or treatment with the ERBB inhibitor lapatinib. These studies might lead to personalized therapeutics specifically targeting the kinases that are mutationally altered in individual melanomas. PMID:19718025

  17. Somatic Cell Nuclear Transfer in the Mouse

    NASA Astrophysics Data System (ADS)

    Kishigami, Satoshi; Wakayama, Teruhiko

    Somatic cell nuclear transfer (SCNT) has become a unique and powerful tool for epigenetic reprogramming research and gene manipulation in animals since “Dolly,” the first animal cloned from an adult cell was reported in 1997. Although the success rates of somatic cloning have been inefficient and the mechanism of reprogramming is still largely unknown, this technique has been proven to work in more than 10 mammalian species. Among them, the mouse provides the best model for both basic and applied research of somatic cloning because of its abounding genetic resources, rapid sexual maturity and propagation, minimal requirements for housing, etc. This chapter describes a basic protocol for mouse cloning using cumulus cells, the most popular cell type for NT, in which donor nuclei are directly injected into the oocyte using a piezo-actuated micromanipulator. In particular, we focus on a new, more efficient mouse cloning protocol using trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, which increases both in vitro and in vivo developmental rates from twofold to fivefold. This new method including TSA will be helpful to establish mouse cloning in many laboratories.

  18. Reprogrammed pluripotent stem cells from somatic cells.

    PubMed

    Kim, Jong Soo; Choi, Hyun Woo; Choi, Sol; Do, Jeong Tae

    2011-06-01

    Pluripotent stem cells, such as embryonic stem (ES) cells, can differentiate into all cell types. So, these cells can be a biological resource for regenerative medicine. However, ES cells known as standard pluripotent cells have problem to be used for cell therapy because of ethical issue of the origin and immune response on the graft. Hence, recently reprogrammed pluripotent cells have been suggested as an alternative source for regenerative medicine. Somatic cells can acquire the ES cell-like pluripotency by transferring somatic cell nuclei into oocytes, by cell fusion with pluripotent cells. Retroviral-mediated introduction of four factors, Oct4, Sox2, Klf4 and c-Myc can successfully reprogram somatic cells into ES cell-like pluripotent stem cells, known as induced pluripotent stem (iPS) cells. These cells closely resemble ES cells in gene expression pattern, cell biologic and phenotypic characteristics. However, to reach the eventual goal of clinical application, it is necessary to overcome the major drawbacks such as low reprogramming efficiency and genomic alterations due to viral integration. In this review, we discuss the current reprogramming techniques and mechanisms of nuclear reprogramming induced by transcription factor transduction. PMID:24298328

  19. Somatic Embryogenesis and Genetic Modification of Vitis.

    PubMed

    Dhekney, Sadanand A; Li, Zhijian T; Grant, Trudi N L; Gray, Dennis J

    2016-01-01

    Grapevine embryogenic cultures are ideal target tissues for inserting desired traits of interest and improving existing cultivars via precision breeding (PB). PB is a new approach that, like conventional breeding, utilizes only DNA fragments obtained from sexually compatible grapevine plants. Embryogenic culture induction occurs by placing leaves or stamens and pistils on induction medium with a dark/light photoperiod cycle for 12-16 weeks. Resulting cultures produce sectors of embryogenic and non-embryogenic callus, which can be identified on the basis of callus morphology and color. Somatic embryo development occurs following transfer of embryogenic callus to development medium and cultures can be maintained for extended periods of time by transfer of the proliferating proembryonic masses to fresh medium at 4-6-week intervals. To demonstrate plant recovery via PB, somatic embryos at the mid-cotyledonary stage are cocultivated with Agrobacterium containing the desired gene of interest along with a, non-PB, enhanced green fluorescent protein/neomycin phosphotransferase II (egfp/nptII) fusion gene. Modified cultures are grown on proliferation and development medium to produce uniformly modified somatic embryos via secondary embryogenesis. Modified embryos identified on the basis of green fluorescence and kanamycin resistance are transferred to germination medium for plant development. The resulting plants are considered to prototype examples of the PB approach, since they contain egfp/nptII, a non-grapevine-derived fusion gene. Uniform green fluorescent protein (GFP) fluorescence can be observed in all tissues of regenerated plants. PMID:26619866

  20. Somatic cell nuclear transfer in the mouse.

    PubMed

    Kishigami, Satoshi; Wakayama, Teruhiko

    2009-01-01

    Somatic cell nuclear transfer (SCNT) has become a unique and powerful tool for epigenetic reprogramming research and gene manipulation in animals since "Dolly," the first animal cloned from an adult cell was reported in 1997. Although the success rates of somatic cloning have been inefficient and the mechanism of reprogramming is still largely unknown, this technique has been proven to work in more than 10 mammalian species. Among them, the mouse provides the best model for both basic and applied research of somatic cloning because of its abounding genetic resources, rapid sexual maturity and propagation, minimal requirements for housing, etc. This chapter describes a basic protocol for mouse cloning using cumulus cells, the most popular cell type for NT, in which donor nuclei are directly injected into the oocyte using a piezo-actuated micromanipulator. In particular, we focus on a new, more efficient mouse cloning protocol using trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, which increases both in vitro and in vivo developmental rates from twofold to fivefold. This new method including TSA will be helpful to establish mouse cloning in many laboratories. PMID:19085136

  1. Sequence analysis of the internal transcribed spacer (ITS) region reveals a novel clade of Ichthyophonus sp. from rainbow trout

    USGS Publications Warehouse

    Rasmussen, C.; Purcell, M.K.; Gregg, J.L.; LaPatra, S.E.; Winton, J.R.; Hershberger, P.K.

    2010-01-01

    The mesomycetozoean parasite Ichthyophonus hoferi is most commonly associated with marine fish hosts but also occurs in some components of the freshwater rainbow trout Oncorhynchus mykiss aquaculture industry in Idaho, USA. It is not certain how the parasite was introduced into rainbow trout culture, but it might have been associated with the historical practice of feeding raw, ground common carp Cyprinus carpio that were caught by commercial fisherman. Here, we report a major genetic division between west coast freshwater and marine isolates of Ichthyophonus hoferi. Sequence differences were not detected in 2 regions of the highly conserved small subunit (18S) rDNA gene; however, nucleotide variation was seen in internal transcribed spacer loci (ITS1 and ITS2), both within and among the isolates. Intra-isolate variation ranged from 2.4 to 7.6 nucleotides over a region consisting of ~740 bp. Majority consensus sequences from marine/anadromous hosts differed in only 0 to 3 nucleotides (99.6 to 100% nucleotide identity), while those derived from freshwater rainbow trout had no nucleotide substitutions relative to each other. However, the consensus sequences between isolates from freshwater rainbow trout and those from marine/anadromous hosts differed in 13 to 16 nucleotides (97.8 to 98.2% nucleotide identity).

  2. Non-Linear and Flexible Regions of the Human Notch1 Extracellular Domain Revealed by High-Resolution Structural Studies

    PubMed Central

    Weisshuhn, Philip C.; Sheppard, Devon; Taylor, Paul; Whiteman, Pat; Lea, Susan M.; Handford, Penny A.; Redfield, Christina

    2016-01-01

    Summary The Notch receptor is a key component of a core metazoan signaling pathway activated by Delta/Serrate/Lag-2 ligands expressed on an adjacent cell. This results in a short-range signal with profound effects on cell-fate determination, cell proliferation, and cell death. Key to understanding receptor function is structural knowledge of the large extracellular portion of Notch which contains multiple repeats of epidermal growth factor (EGF)-like domains. Here we investigate the EGF4-13 region of human Notch1 (hN1) using a multidisciplinary approach. Ca2+-binding measurements, X-ray crystallography, {1H}-15N heteronuclear nuclear Overhauser effects, and residual dipolar couplings support a non-linear organization for the EGF4-13 region with a rigid, bent conformation for EGF4-7 and a single flexible linkage between EGF9 and EGF10. These data allow us to construct an informed model for EGF10-13 which, in conjunction with comparative binding studies, demonstrates that EGF10 has an important role in determining Notch receptor sensitivity to Dll-4. PMID:26996961

  3. Genome-Wide Profiling of PARP1 Reveals an Interplay with Gene Regulatory Regions and DNA Methylation

    PubMed Central

    Nalabothula, Narasimharao; Al-jumaily, Taha; Eteleeb, Abdallah M.; Flight, Robert M.; Xiaorong, Shao; Moseley, Hunter; Rouchka, Eric C.; Fondufe-Mittendorf, Yvonne N.

    2015-01-01

    Poly (ADP-ribose) polymerase-1 (PARP1) is a nuclear enzyme involved in DNA repair, chromatin remodeling and gene expression. PARP1 interactions with chromatin architectural multi-protein complexes (i.e. nucleosomes) alter chromatin structure resulting in changes in gene expression. Chromatin structure impacts gene regulatory processes including transcription, splicing, DNA repair, replication and recombination. It is important to delineate whether PARP1 randomly associates with nucleosomes or is present at specific nucleosome regions throughout the cell genome. We performed genome-wide association studies in breast cancer cell lines to address these questions. Our studies show that PARP1 associates with epigenetic regulatory elements genome-wide, such as active histone marks, CTCF and DNase hypersensitive sites. Additionally, the binding of PARP1 to chromatin genome-wide is mutually exclusive with DNA methylation pattern suggesting a functional interplay between PARP1 and DNA methylation. Indeed, inhibition of PARylation results in genome-wide changes in DNA methylation patterns. Our results suggest that PARP1 controls the fidelity of gene transcription and marks actively transcribed gene regions by selectively binding to transcriptionally active chromatin. These studies provide a platform for developing our understanding of PARP1’s role in gene regulation. PMID:26305327

  4. Diet of a piscivorous seabird reveals spatiotemporal variation in abundance of forage fishes in the Monterey Bay region

    NASA Astrophysics Data System (ADS)

    Webb, Lisa A.; Harvey, James T.

    2015-06-01

    Brandt's Cormorant (Phalacrocorax penicillatus) diet was investigated using regurgitated pellets (n = 285) collected on 19 sampling days at three locations during the 2006-07 and 2007-08 nonbreeding seasons in the Monterey Bay region. The efficacy of using nested sieves and the all-structure technique to facilitate prey detection in the pellets was evaluated, but this method did not increase prey enumeration and greatly decreased efficiency. Although 29 prey species were consumed, northern anchovy (Engraulis mordax) dominated and speckled sanddab (Citharichthys stigmaeus) also was important in the diet. Few rockfishes (Sebastes spp.) and market squid (Doryteuthis opalescens) were consumed compared with great prevalence in previous studies during the 1970s. El Niño and La Niña during the study provided a unique opportunity to examine predator response to variation in prey availability. Patterns of prey number and diversity were not consistent among locations. Greatest number and diversity of prey occurred at locations within Monterey Bay during La Niña, results not evident at the outer coast location. Short-term specialization occurred but mean prey diversity indicated a generalist feeding mode. This study demonstrated the importance of periodic sampling at multiple locations within a region to detect spatiotemporal variability in the diet of opportunistic generalists.

  5. Conditional cell ablation via diphtheria toxin reveals distinct requirements for the basal plate in the regional identity of diencephalic subpopulations.

    PubMed

    Lee, Bumwhee; Lam, Duc Tri; Baek, Kwanghee; Yoon, Jaeseung; Jeong, Yongsu

    2015-06-01

    The mammalian diencephalon is the caudal derivative of the embryonic forebrain. Early events in diencephalic regionalization include its subdivision along the dorsoventral and anteroposterior axes. The prosomeric model by Puelles and Rubenstein (1993) suggests that the alar plate of the posterior diencephalon is partitioned into three different prosomeres (designated p1-p3), which develop into the pretectum, thalamus, and prethalamus, respectively. Here, we report the developmental consequences of genetic ablation of cell populations from the diencephalic basal plate. The strategy for conditionally regulated cell ablation is based on the targeted expression of the diphtheria toxin gene (DTA) to the diencephalic basal plate via tamoxifen- induced, Cre-mediated recombination of the ROSA(DTA) allele. We show that activation of DTA leads to specific cell loss in the basal plate of the posterior diencephalon, and disrupted early regionalization of distinct alar territories. In the basal plate-deficient embryos, the p1 alar plate exhibited reduced expression of subtype-specific markers in the pretectum, whereas p2 alar plate failed to further subdivide into two discrete thalamic subpopulations. We also show that these defects lead to abnormal nuclear organization at later developmental stages. Our data have implications for increased understanding of the interactive roles between discrete diencephalic compartments. PMID:25950659

  6. Functional analysis of the C-terminal region of human adenovirus E1A reveals a misidentified nuclear localization signal

    SciTech Connect

    Cohen, Michael J.; King, Cason R.; Dikeakos, Jimmy D.; Mymryk, Joe S.

    2014-11-15

    The immortalizing function of the human adenovirus 5 E1A oncoprotein requires efficient localization to the nucleus. In 1987, a consensus monopartite nuclear localization sequence (NLS) was identified at the C-terminus of E1A. Since that time, various experiments have suggested that other regions of E1A influence nuclear import. In addition, a novel bipartite NLS was recently predicted at the C-terminal region of E1A in silico. In this study, we used immunofluorescence microscopy and co-immunoprecipitation analysis with importin-α to verify that full nuclear localization of E1A requires the well characterized NLS spanning residues 285–289, as well as a second basic patch situated between residues 258 and 263 ({sup 258}RVGGRRQAVECIEDLLNEPGQPLDLSCKRPRP{sup 289}). Thus, the originally described NLS located at the C-terminus of E1A is actually a bipartite signal, which had been misidentified in the existing literature as a monopartite signal, altering our understanding of one of the oldest documented NLSs. - Highlights: • Human adenovirus E1A is localized to the nucleus. • The C-terminus of E1A contains a bipartite nuclear localization signal (NLS). • This signal was previously misidentified to be a monopartite NLS. • Key basic amino acid residues within this sequence are highly conserved.

  7. Comparative Genomic Hybridizations Reveal Genetic Regions within the Mycobacterium avium Complex That Are Divergent from Mycobacterium avium subsp. paratuberculosis Isolates†

    PubMed Central

    Paustian, Michael L.; Kapur, Vivek; Bannantine, John P.

    2005-01-01

    Mycobacterium avium subsp. paratuberculosis is genetically similar to other members of the Mycobacterium avium complex (MAC), some of which are nonpathogenic and widespread in the environment. We have utilized an M. avium subsp. paratuberculosis whole-genome microarray representing over 95% of the predicted coding sequences to examine the genetic conservation among 10 M. avium subsp. paratuberculosis isolates, two isolates each of Mycobacterium avium subsp. silvaticum and Mycobacterium avium subsp. avium, and a single isolate each of both Mycobacterium intracellulare and Mycobacterium smegmatis. Genomic DNA from each isolate was competitively hybridized with DNA from M. avium subsp. paratuberculosis K10, and open reading frames (ORFs) were classified as present, divergent, or intermediate. None of the M. avium subsp. paratuberculosis isolates had ORFs classified as divergent. The two M. avium subsp. avium isolates had 210 and 135 divergent ORFs, while the two M. avium subsp. silvaticum isolates examined had 77 and 103 divergent ORFs. Similarly, 130 divergent ORFs were identified in M. intracellulare. A set of 97 ORFs were classified as divergent or intermediate in all of the nonparatuberculosis MAC isolates tested. Many of these ORFs are clustered together on the genome in regions with relatively low average GC content compared with the entire genome and contain mobile genetic elements. One of these regions of sequence divergence contained genes homologous to a mammalian cell entry (mce) operon. Our results indicate that closely related MAC mycobacteria can be distinguished from M. avium subsp. paratuberculosis by multiple clusters of divergent ORFs. PMID:15774884

  8. Control of somatic membrane potential in nociceptive neurons and its implications for peripheral nociceptive transmission.

    PubMed

    Du, Xiaona; Hao, Han; Gigout, Sylvain; Huang, Dongyang; Yang, Yuehui; Li, Li; Wang, Caixue; Sundt, Danielle; Jaffe, David B; Zhang, Hailin; Gamper, Nikita

    2014-11-01

    Peripheral sensory ganglia contain somata of afferent fibres conveying somatosensory inputs to the central nervous system. Growing evidence suggests that the somatic/perisomatic region of sensory neurons can influence peripheral sensory transmission. Control of resting membrane potential (Erest) is an important mechanism regulating excitability, but surprisingly little is known about how Erest is regulated in sensory neuron somata or how changes in somatic/perisomatic Erest affect peripheral sensory transmission. We first evaluated the influence of several major ion channels on Erest in cultured small-diameter, mostly capsaicin-sensitive (presumed nociceptive) dorsal root ganglion (DRG) neurons. The strongest and most prevalent effect on Erest was achieved by modulating M channels, K2P and 4-aminopiridine-sensitive KV channels, while hyperpolarization-activated cyclic nucleotide-gated, voltage-gated Na(+), and T-type Ca(2+) channels to a lesser extent also contributed to Erest. Second, we investigated how varying somatic/perisomatic membrane potential, by manipulating ion channels of sensory neurons within the DRG, affected peripheral nociceptive transmission in vivo. Acute focal application of M or KATP channel enhancers or a hyperpolarization-activated cyclic nucleotide-gated channel blocker to L5 DRG in vivo significantly alleviated pain induced by hind paw injection of bradykinin. Finally, we show with computational modelling how somatic/perisomatic hyperpolarization, in concert with the low-pass filtering properties of the t-junction within the DRG, can interfere with action potential propagation. Our study deciphers a complement of ion channels that sets the somatic Erest of nociceptive neurons and provides strong evidence for a robust filtering role of the somatic and perisomatic compartments of peripheral nociceptive neuron. PMID:25168672

  9. Control of somatic membrane potential in nociceptive neurons and its implications for peripheral nociceptive transmission

    PubMed Central

    Du, Xiaona; Hao, Han; Gigout, Sylvain; Huang, Dongyang; Yang, Yuehui; Li, Li; Wang, Caixue; Sundt, Danielle; Jaffe, David B.; Zhang, Hailin; Gamper, Nikita

    2014-01-01

    Peripheral sensory ganglia contain somata of afferent fibres conveying somatosensory inputs to the central nervous system. Growing evidence suggests that the somatic/perisomatic region of sensory neurons can influence peripheral sensory transmission. Control of resting membrane potential (Erest) is an important mechanism regulating excitability, but surprisingly little is known about how Erest is regulated in sensory neuron somata or how changes in somatic/perisomatic Erest affect peripheral sensory transmission. We first evaluated the influence of several major ion channels on Erest in cultured small-diameter, mostly capsaicin-sensitive (presumed nociceptive) dorsal root ganglion (DRG) neurons. The strongest and most prevalent effect on Erest was achieved by modulating M channels, K2P and 4-aminopiridine-sensitive KV channels, while hyperpolarization-activated cyclic nucleotide-gated, voltage-gated Na+, and T-type Ca2+ channels to a lesser extent also contributed to Erest. Second, we investigated how varying somatic/perisomatic membrane potential, by manipulating ion channels of sensory neurons within the DRG, affected peripheral nociceptive transmission in vivo. Acute focal application of M or KATP channel enhancers or a hyperpolarization-activated cyclic nucleotide-gated channel blocker to L5 DRG in vivo significantly alleviated pain induced by hind paw injection of bradykinin. Finally, we show with computational modelling how somatic/perisomatic hyperpolarization, in concert with the low-pass filtering properties of the t-junction within the DRG, can interfere with action potential propagation. Our study deciphers a complement of ion channels that sets the somatic Erest of nociceptive neurons and provides strong evidence for a robust filtering role of the somatic and perisomatic compartments of peripheral nociceptive neuron. PMID:25168672

  10. Influences of climate change on California and Nevada regions revealed by a high-resolution dynamical downscaling study

    NASA Astrophysics Data System (ADS)

    Pan, Lin-Lin; Chen, Shu-Hua; Cayan, Dan; Lin, Mei-Ying; Hart, Quinn; Zhang, Ming-Hua; Liu, Yubao; Wang, Jianzhong

    2011-11-01

    In this study, the influence of climate change to California and Nevada regions was investigated through high-resolution (4-km grid spacing) dynamical downscaling using the WRF (Weather Research & Forecasting) model. The dynamical downscaling was performed to both the GFS (Global forecast model) reanalysis (called GFS-WRF runs) from 2000-2006 and PCM (Parallel Climate Model) simulations (called PCM-WRF runs) from 1997-2006 and 2047-2056. The downscaling results were first validated by comparing current model outputs with the observational analysis PRISM (Parameter-elevation Regressions on Independent Slopes Model) dataset. In general, the dominant features from GFS-WRF runs and PCM-WRF runs were consistent with each other, as well as with PRISM results. The influences of climate change on the California and Nevada regions can be inferred from the model future runs. The averaged temperature showed a positive trend in the future, as in other studies. The temperature increases by around 1-2°C under the assumption of business as usual over 50 years. This leads to an upward shifting of the freezing level (the contour line of 0°C temperature) and more rain instead of snow in winter (December, January, and February). More hot days (>32.2°C or 90°F) and extreme hot days (>37.8°C or 100°F) are predicted in the Sacramento Valley and the southern parts of California and Nevada during summer (June, July, and August). More precipitation is predicted in northern California but not in southern California. Rainfall frequency slightly increases in the coast regions, but not in the inland area. No obvious trend of the surface wind was indicated. The probability distribution functions (PDF) of daily temperature, wind and precipitation for California and Nevada showed no significant change in shape in either winter or summer. The spatial distributions of precipitation frequency from GFS-WRF and PCM-WRF were highly correlated (r = 0.83). However, overall positive shifts were seen

  11. Analysis of prepro-alpha-lytic protease expression in Escherichia coli reveals that the pro region is required for activity.

    PubMed Central

    Silen, J L; Frank, D; Fujishige, A; Bone, R; Agard, D A

    1989-01-01

    The alpha-lytic protease of Lysobacter enzymogenes was successfully expressed in Escherichia coli by fusing the promoter and signal sequence of the E. coli phoA gene to the proenzyme portion of the alpha-lytic protease gene. Following induction, active enzyme was found both within cells and in the extracellular medium, where it slowly accumulated to high levels. Use of a similar gene fusion to express the protease domain alone produced inactive enzyme, indicating that the large amino-terminal pro region is necessary for activity. The implications for protein folding are discussed. Furthermore, inactivation of the protease by mutation of the catalytic serine residue resulted in the production of a higher-molecular-weight form of the alpha-lytic protease, suggesting that the enzyme is self-processing in E. coli. Images PMID:2646278

  12. Single Molecule Analysis of Replicated DNA Reveals the Usage of Multiple KSHV Genome Regions for Latent Replication

    PubMed Central

    Verma, Subhash C.; Lu, Jie; Cai, Qiliang; Kosiyatrakul, Settapong; McDowell, Maria E.; Schildkraut, Carl L.; Robertson, Erle S.

    2011-01-01

    Kaposi's sarcoma associated herpesvirus (KSHV), an etiologic agent of Kaposi's sarcoma, Body Cavity Based Lymphoma and Multicentric Castleman's Disease, establishes lifelong latency in infected cells. The KSHV genome tethers to the host chromosome with the help of a latency associated nuclear antigen (LANA). Additionally, LANA supports replication of the latent origins within the terminal repeats by recruiting cellular factors. Our previous studies identified and characterized another latent origin, which supported the replication of plasmids ex-vivo without LANA expression in trans. Therefore identification of an additional origin site prompted us to analyze the entire KSHV genome for replication initiation sites using single molecule analysis of replicated DNA (SMARD). Our results showed that replication of DNA can initiate throughout the KSHV genome and the usage of these regions is not conserved in two different KSHV strains investigated. SMARD also showed that the utilization of multiple replication initiation sites occurs across large regions of the genome rather than a specified sequence. The replication origin of the terminal repeats showed only a slight preference for their usage indicating that LANA dependent origin at the terminal repeats (TR) plays only a limited role in genome duplication. Furthermore, we performed chromatin immunoprecipitation for ORC2 and MCM3, which are part of the pre-replication initiation complex to determine the genomic sites where these proteins accumulate, to provide further characterization of potential replication initiation sites on the KSHV genome. The ChIP data confirmed accumulation of these pre-RC proteins at multiple genomic sites in a cell cycle dependent manner. Our data also show that both the frequency and the sites of replication initiation vary within the two KSHV genomes studied here, suggesting that initiation of replication is likely to be affected by the genomic context rather than the DNA sequences. PMID

  13. A comparative antibody analysis of pannexin1 expression in four rat brain regions reveals varying subcellular localizations.

    PubMed

    Cone, Angela C; Ambrosi, Cinzia; Scemes, Eliana; Martone, Maryann E; Sosinsky, Gina E

    2013-01-01

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

  14. Charcoal records reveal past occurrences of disturbances in the forests of the Kisangani region, Democratic Republic of the Congo

    NASA Astrophysics Data System (ADS)

    Tshibamba Mukendi, John; Hubau, Wannes; Ntahobavuka, Honorine; Boyemba Bosela, Faustin; De Cannière, Charles; Beeckman, Hans

    2014-05-01

    Past disturbances have modified local density, structure and floristic composition of Central African rainforests. As such, these perturbations represent a driving force for forest dynamics and they were presumably at the origin of present-day forest mosaics. One of the most prominent disturbances within the forest is fire, leaving behind charcoal as a witness of past forest dynamics. Quantification and identification of ancient charcoal fragments found in soil layers (= pedoanthracology) allows a detailed reconstruction of forest history, including the possible occurrence of past perturbations. The primary objective of this study is to present palaeoenvironmental evidence for the existence of past disturbances in the forests of the Kisangani region (Democratic Republic of the Congo) using a pedoanthracological approach. We quantified and identified charcoal fragments from pedoanthracological excavations in the Yangambi, Yoko, Masako and Kole forest regions. Charcoal sampling was conducted in pit intervals of 10 cm, whereby pottery fragments were also registered and quantified. Floristic identifications were conducted using former protocols based on wood anatomy, which is largely preserved after charcoalification. 14 excavations were conducted and charcoal was found in most pit intervals. Specifically, 52 out of 56 sampled intervals from the Yangambi forest contained charcoal, along with 47 pit intervals from the Yoko forest reserve, 34 pit intervals from the Masako forest and 16 from the Kole forest. Highest specific anthracomasses were recorded in Yoko (167 mg charcoal per kg soil), followed by Yangambi (133 mg/kg), Masako (71,89 mg/kg) and finally Kole (42,4 mg/kg). Charcoal identifications point at a manifest presence of the family of Fabaceae (Caesalpinioideae). This family is characteristic for the tropical humid rainforest. The presence of charcoal fragments from these taxa, associated with pottery sherds on different depths within the profiles, suggests

  15. Screening the 3{prime} region of the polycystic kidney disease 1 (PKD1) gene reveals six novel mutations

    SciTech Connect

    Peral, B.; San Millan, J.L.; Ong, A.C.M.

    1996-01-01

    Recently, the gene for the most common form of autosomal dominant polycystic kidney disease (ADPKD), PKD1 (polycystic kidney disease 1), has been fully characterized and shown to encode an integral membrane protein, polycystin, involved in cell-cell and/or cell-matrix interactions. Study of the PKD1 gene has been complicated because most of the gene lies in a genomic region reiterated several times elsewhere on the same chromosome, and consequently only seven mutations have been described so far. Here we report a systematic screen covering {approximately}80% of the {approximately}-2.75 kb of translated transcript that is encoded by single-copy DNA. We have identified and characterized six novel mutations that, together with the previously described changes, amount to a detection rate of 10%-15% in the population studied. The newly described mutations are two deletions, an insertion of a T-nucleotide causing a frameshift, two single-base-pair substitutions resulting in premature stop codons, and a G{yields}C transversion that may be a missense mutation. These results have important implications for genetic diagnosis of PKD1 because they indicate that the majority of mutations lie within the duplicated area, which is difficult to study. The regions of polycystin removed in each mutation so far described are assessed for their functional significance; an area disrupted by two new small in-frame changes is highlighted. PKD1 mutations are contrasted with those in the PKD1/TSC2 contiguous-gene syndrome, and the likely mutational mechanism in PKD1 is considered. 36 refs., 6 figs., 2 tabs.

  16. A Comparative Antibody Analysis of Pannexin1 Expression in Four Rat Brain Regions Reveals Varying Subcellular Localizations

    PubMed Central

    Cone, Angela C.; Ambrosi, Cinzia; Scemes, Eliana; Martone, Maryann E.; Sosinsky, Gina E.

    2012-01-01

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

  17. Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility

    SciTech Connect

    Pancera, Marie; Majeed, Shahzad; Ban, Yih-En Andrew; Chen, Lei; Huang, Chih-chin; Kong, Leopold; Kwon, Young Do; Stuckey, Jonathan; Zhou, Tongqing; Robinson, James E.; Schief, William R.; Sodroski, Joseph; Wyatt, Richard; Kwong, Peter D.

    2010-04-15

    The viral spike of HIV-1 is composed of three gp120 envelope glycoproteins attached noncovalently to three gp41 transmembrane molecules. Viral entry is initiated by binding to the CD4 receptor on the cell surface, which induces large conformational changes in gp120. These changes not only provide a model for receptor-triggered entry, but affect spike sensitivity to drug- and antibody-mediated neutralization. Although some of the details of the CD4-induced conformational change have been visualized by crystal structures and cryoelectron tomograms, the critical gp41-interactive region of gp120 was missing from previous atomic-level characterizations. Here we determine the crystal structure of an HIV-1 gp120 core with intact gp41-interactive region in its CD4-bound state, compare this structure to unliganded and antibody-bound forms to identify structurally invariant and plastic components, and use ligand-oriented cryoelectron tomograms to define component mobility in the viral spike context. Newly defined gp120 elements proximal to the gp41 interface complete a 7-stranded {beta}-sandwich, which appeared invariant in conformation. Loop excursions emanating from the sandwich form three topologically separate - and structurally plastic - layers, topped off by the highly glycosylated gp120 outer domain. Crystal structures, cryoelectron tomograms, and interlayer chemistry were consistent with a mechanism in which the layers act as a shape-changing spacer, facilitating movement between outer domain and gp41-associated {beta}-sandwich and providing for conformational diversity used in immune evasion. A 'layered' gp120 architecture thus allows movement among alternative glycoprotein conformations required for virus entry and immune evasion, whereas a {beta}-sandwich clamp maintains gp120-gp41 interaction and regulates gp41 transitions.

  18. Magnitude and extent of land subsidence in central Mexico revealed by regional InSAR ALOS time-series survey

    NASA Astrophysics Data System (ADS)

    Chaussard, Estelle; Amelung, Falk; Wdowinski, Shimon; Cabral-Cano, Enrique

    2013-04-01

    The societal impacts of land subsidence are colossal, both in terms of decrease in water resources and in threat to human life due to buildings damages and increase in flood risk from rivers. Most subsidence surveys in Mexico focus on Mexico City, known to subside since the 1950s, while a few studies have documented the occurrence of land subsidence in other medium to large-seized cities of central Mexico. However, because most works target one single city, they fail to reveal the bigger picture. Here we use Interferometric Synthetic Aperture Radar (InSAR) time-series analysis of ALOS L-band SAR data to resolve land subsidence in an area of 200,000 km2 in central Mexico. We processed over 600 SAR images acquired between 2007-2011 and produced over 3000 interferograms. The data reveal significant subsidence in seventeen cities, including sixteen with over 100, 000 inhabitants and allow mapping of subsidence with high spatial and temporal resolutions. Land subsidence is detected, from east to west, in Puebla (population of 2.5 million), Mexico city (population of 21 million), Toluca de Lerdo (population of 427K), Queretaro (population of 825K), San Luis de la Paz (population of 101K), Celaya (population of 266K), San Luis Potosi (population of 936K), Morelia (population of 537K), Salamanca (population of 144K), Irapuato (population of 317K), Silao (population of 147K), Leon (population of 1.4 million), Aguascalientes (population of 735K), Zamora de Hidalgo (population of 186K), Guadalajara (population of 3.8 million), Ahuacatlan (population of 6.5K), and Tepic (population of 261K). We additionally identify subsidence in 3 agricultural areas outside major urban centers: 20 km southwest of the city of San Luis de la Paz, south of Villa de Reyes (40 km south of San Luis Potosi), and west of villa de Arista (50 km north of San Luis Potosi). The time-series suggest nearly constant rates of subsidence at most the locations over the 2-years period spanned by the SAR

  19. Somatic mutation and CDR3 lengths of immunoglobulin kappa light chains expressed in patients with rheumatoid arthritis and in normal individuals.

    PubMed Central

    Bridges, S L; Lee, S K; Johnson, M L; Lavelle, J C; Fowler, P G; Koopman, W J; Schroeder, H W

    1995-01-01

    Immunoglobulin secretion by plasma cells infiltrating synovial membranes is a prominent feature of RA. Previous analyses of a cDNA library generated from synovium of RA patient BC revealed immunoglobulin kappa light chain transcripts with extensive somatic mutation, frequent N region addition, and unexpected variation in the lengths of CDR3 regions which form the center of the antigen binding site. To determine if these characteristics are present in other individuals, we performed reverse transcription-polymerase chain reaction amplification and sequenced > or = 10 V kappa-containing amplicons from nine tissue samples: synovia of three individuals with long-standing RA (including patient BC), PBLs of two of these individuals, and PBLs or splenocytes of four normal individuals. Increased levels of somatic mutation in PBLs appeared to correlate with increased age, which may reflect accumulation of circulating memory cells and/or decreased bone marrow production of naive B lymphocytes. Two of three RA synovial samples and both RA PBL samples exhibited increased proportions of clones with unusual CDR3 lengths. Enrichment for these antibody binding sites could be due to abnormal regulation of the emerging repertoire or to selection for B lymphocytes bearing antibodies of unusual specificity, and may play a role in the pathogenesis of RA. Images PMID:7635977

  20. Physical Connectivity Mapping by Circular Permutation of Human Telomerase RNA Reveals New Regions Critical for Activity and Processivity.

    PubMed

    Mefford, Melissa A; Zappulla, David C

    2015-01-01

    Telomerase is a specialized ribonucleoprotein complex that extends the 3' ends of chromosomes to counteract telomere shortening. However, increased telomerase activity is associated with ∼90% of human cancers. The telomerase enzyme minimally requires an RNA (hTR) and a specialized reverse transcriptase protein (TERT) for activity in vitro. Understanding the structure-function relationships within hTR has important implications for human disease. For the first time, we have tested the physical-connectivity requirements in the 451-nucleotide hTR RNA using circular permutations, which reposition the 5' and 3' ends. Our extensive in vitro analysis identified three classes of hTR circular permutants with altered function. First, circularly permuting 3' of the template causes specific defects in repeat-addition processivity, revealing that the template recognition element found in ciliates is conserved in human telomerase RNA. Second, seven circular permutations residing within the catalytically important core and CR4/5 domains completely abolish telomerase activity, unveiling mechanistically critical portions of these domains. Third, several circular permutations between the core and CR4/5 significantly increase telomerase activity. Our extensive circular permutation results provide insights into the architecture and coordination of human telomerase RNA and highlight where the RNA could be targeted for the development of antiaging and anticancer therapeutics. PMID:26503788

  1. Isolation of the human chromosomal band Xq28 within somatic cell hybrids by fragile X site breakage.

    PubMed Central

    Warren, S T; Knight, S J; Peters, J F; Stayton, C L; Consalez, G G; Zhang, F P

    1990-01-01

    The chromosomal fragile-site mapping to Xq27.3 is associated with a frequent form of mental retardation and is prone to breakage after induced deoxyribonucleotide pool perturbation. The human hypoxanthine phosphoribosyltransferase (HPRT) and glucose-6-phosphate dehydrogenase (G6PD) genes flank the fragile X chromosome site and can be used to monitor integrity of the site in human-hamster somatic cell hybrids deficient in the rodent forms of these activities. After induction of the fragile X site, negative selection for HPRT and positive enrichment for G6PD resulted in 31 independent colonies of HPRT-,G6PD+ phenotype. Southern blot analysis demonstrated the loss of all tested markers proximal to the fragile X site with retention of all tested human Xq28 loci in a majority of the hybrids. In situ hybridization with a human-specific probe demonstrated the translocation of a small amount of human DNA to rodent chromosomes in these hybrids, suggesting chromosome breakage at the fragile X site and the subsequent translocation of Xq28. Southern blot hybridization of hybrid-cell DNA, resolved by pulsed-field gel electrophoresis, for human-specific repetitive sequences revealed abundant CpG-islands within Xq28, consistent with its known gene density. The electrophoretic banding patterns of human DNA among the hybrids were remarkably consistent, suggesting that fragile X site breakage is limited to a relatively small region in Xq27-28. These somatic cell hybrids, containing Xq27.3-qter as the sole human DNA, will aid the search for DNA associated with the fragile X site and will augment the high resolution genomic analysis of Xq28, including the identification of candidate genes for genetic-disease loci mapping to this region. Images PMID:2339126

  2. Offshore double-planed shallow seismic zone in the NE Japan forearc region revealed by sP depth phases recorded by regional networks

    NASA Astrophysics Data System (ADS)

    Gamage, Shantha S. N.; Umino, Norihito; Hasegawa, Akira; Kirby, Stephen H.

    2009-07-01

    We detected the sP depth phase at small epicentral distances of about 150 km or more in the seismograms of shallow earthquakes in the NE Japan forearc region. The focal depths of 1078 M > 3 earthquakes that occurred from 2000 to 2006 were precisely determined using the time delay of the sP phase from the initial P-wave arrival. The distribution of relocated hypocentres clearly shows the configuration of a double-planed shallow seismic zone beneath the Pacific Ocean. The upper plane has a low dip angle near the Japan Trench, increasing gradually to ~30° at approximately 100 km landward of the Japan Trench. The lower plane is approximately parallel to the upper plane, and appears to be the near-trench counterpart of the lower plane of the double-planed deep seismic zone beneath the land area. The distance between the upper and lower planes is 28-32 km, which is approximately the same as or slightly smaller than that of the double-planed deep seismic zone beneath the land area. Focal mechanism solutions of the relocated earthquakes are determined from P-wave initial motion data. Although P-wave initial motion data for these offshore events are not ideally distributed on the focal sphere, we found that the upper-plane events that occur near the Japan Trench are characterized by normal faulting, whereas lower-plane events are characterized by thrust faulting. This focal mechanism distribution is the opposite to that of the double-planed deep seismic zone beneath the land area. The characteristics of these focal mechanisms for the shallow and deep doubled-planed seismic zones can be explained by a bending-unbending model of the subducting Pacific plate. Some of relocated earthquakes took place in the source area of the 1933 Mw8.4 Sanriku earthquake at depths of 10-23 km. The available focal mechanisms for these events are characterized by normal faulting. Given that the 1933 event was a large normal-fault event that occurred along a fault plane dipping landward, the

  3. Offshore double-planed shallow seismic zone in the NE Japan forearc region revealed by sP depth phases recorded by regional networks

    USGS Publications Warehouse

    Gamage, S.S.N.; Umino, N.; Hasegawa, A.; Kirby, S.H.

    2009-01-01

    We detected the sP depth phase at small epicentral distances of about 150 km or more in the seismograms of shallow earthquakes in the NE Japan forearc region. The focal depths of 1078 M > 3 earthquakes that occurred from 2000 to 2006 were precisely determined using the time delay of the sP phase from the initial P-wave arrival. The distribution of relocated hypocentres clearly shows the configuration of a double-planed shallow seismic zone beneath the Pacific Ocean. The upper plane has a low dip angle near the Japan Trench, increasing gradually to ???30?? at approximately 100 km landward of the Japan Trench. The lower plane is approximately parallel to the upper plane, and appears to be the near-trench counterpart of the lower plane of the double-planed deep seismic zone beneath the land area. The distance between the upper and lower planes is 28-32 km, which is approximately the same as or slightly smaller than that of the double-planed deep seismic zone beneath the land area. Focal mechanism solutions of the relocated earthquakes are determined from P-wave initial motion data. Although P-wave initial motion data for these offshore events are not ideally distributed on the focal sphere, we found that the upper-plane events that occur near the Japan Trench are characterized by normal faulting, whereas lower-plane events are characterized by thrust faulting. This focal mechanism distribution is the opposite to that of the double-planed deep seismic zone beneath the land area. The characteristics of these focal mechanisms for the shallow and deep doubled-planed seismic zones can be explained by a bending-unbending model of the subducting Pacific plate. Some of relocated earthquakes took place in the source area of the 1933 Mw8.4 Sanriku earthquake at depths of 10-23 km. The available focal mechanisms for these events are characterized by normal faulting. Given that the 1933 event was a large normal-fault event that occurred along a fault plane dipping landward, the

  4. Partial lateral forcing experiments reveal how multi-scale processes induce devastating rainfall: a new application of regional modeling

    NASA Astrophysics Data System (ADS)

    Yang, Hongwei; Wang, Bin

    2015-09-01

    rainfall but significant reduction of the rainfall in South China. The IS forcing has dominant contributions to the seasonal-mean rainfall anomalies over all three sub-regions of China (North China, the YRB, and South China). The IA forcing mainly enhances the rainfall in South China but reduces the precipitation in the YRB slightly. This study portends a promising application of regional climate models to identify key factors causing extreme climate events. The PLF methodology can be used to study a broad range of climate phenomena and to understand the effects of variety of dynamic and physical processes in climate variability and predictability.

  5. The somatic genomic landscape of chromophobe renal cell carcinoma

    PubMed Central

    Davis, Caleb F.; Ricketts, Christopher; Wang, Min; Yang, Lixing; Cherniack, Andrew D.; Shen, Hui; Buhay, Christian; Kang, Hyojin; Kim, Sang Cheol; Fahey, Catherine C.; Hacker, Kathryn E.; Bhanot, Gyan; Gordenin, Dmitry A.; Chu, Andy; Gunaratne, Preethi H.; Biehl, Michael; Seth, Sahil; Kaipparettu, Benny A.; Bristow, Christopher A.; Donehower, Lawrence A.; Wallen, Eric M.; Smith, Angela B.; Tickoo, Satish K.; Tamboli, Pheroze; Reuter, Victor; Schmidt, Laura S.; Hsieh, James J.; Choueiri, Toni K.; Hakimi, A. Ari; Chin, Lynda; Meyerson, Matthew; Kucherlapati, Raju; Park, Woong-Yang; Robertson, A. Gordon; Laird, Peter W.; Henske, Elizabeth P.; Kwiatkowski, David J.; Park, Peter J.; Morgan, Margaret; Shuch, Brian; Muzny, Donna; Wheeler, David A.; Linehan, W. Marston; Gibbs, Richard A.; Rathmell, W. Kimryn; Creighton, Chad J.

    2014-01-01

    Summary We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) based on multidimensional and comprehensive characterization, including mitochondrial DNA (mtDNA) and whole genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared to other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT up-regulation in cancer distinct from previously-observed amplifications and point mutations. PMID:25155756

  6. Activation Domain-dependent Degradation of Somatic Wee1 Kinase*

    PubMed Central

    Owens, Laura; Simanski, Scott; Squire, Christopher; Smith, Anthony; Cartzendafner, Jeff; Cavett, Valerie; Caldwell Busby, Jennifer; Sato, Trey; Ayad, Nagi G.

    2010-01-01

    Cell cycle progression is dependent upon coordinate regulation of kinase and proteolytic pathways. Inhibitors of cell cycle transitions are degraded to allow progression into the subsequent cell cycle phase. For example, the tyrosine kinase and Cdk1 inhibitor Wee1 is degraded during G2 and mitosis to allow mitotic progression. Previous studies suggested that the N terminus of Wee1 directs Wee1 destruction. Using a chemical mutagenesis strategy, we report that multiple regions of Wee1 control its destruction. Most notably, we find that the activation domain of the Wee1 kinase is also required for its degradation. Mutations in this domain inhibit Wee1 degradation in somatic cell extracts and in cells without affecting the overall Wee1 structure or kinase activity. More broadly, these findings suggest that kinase activation domains may be previously unappreciated sites of recognition by the ubiquitin proteasome pathway. PMID:20038582

  7. The somatic genomic landscape of chromophobe renal cell carcinoma.

    PubMed

    Davis, Caleb F; Ricketts, Christopher J; Wang, Min; Yang, Lixing; Cherniack, Andrew D; Shen, Hui; Buhay, Christian; Kang, Hyojin; Kim, Sang Cheol; Fahey, Catherine C; Hacker, Kathryn E; Bhanot, Gyan; Gordenin, Dmitry A; Chu, Andy; Gunaratne, Preethi H; Biehl, Michael; Seth, Sahil; Kaipparettu, Benny A; Bristow, Christopher A; Donehower, Lawrence A; Wallen, Eric M; Smith, Angela B; Tickoo, Satish K; Tamboli, Pheroze; Reuter, Victor; Schmidt, Laura S; Hsieh, James J; Choueiri, Toni K; Hakimi, A Ari; Chin, Lynda; Meyerson, Matthew; Kucherlapati, Raju; Park, Woong-Yang; Robertson, A Gordon; Laird, Peter W; Henske, Elizabeth P; Kwiatkowski, David J; Park, Peter J; Morgan, Margaret; Shuch, Brian; Muzny, Donna; Wheeler, David A; Linehan, W Marston; Gibbs, Richard A; Rathmell, W Kimryn; Creighton, Chad J

    2014-09-01

    We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared with other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT upregulation in cancer distinct from previously observed amplifications and point mutations. PMID:25155756

  8. Somatic IDH1 mutation in a pituitary adenoma of a patient with Maffucci syndrome.

    PubMed

    Hao, Shuyu; Hong, Christopher S; Feng, Jie; Yang, Chunzhang; Chittiboina, Prashant; Zhang, Junting; Zhuang, Zhengping

    2016-06-01

    Maffucci syndrome is a rare disease characterized by multiple enchondromas and soft-tissue hemangiomas. Additionally, neuroendocrine tumors including pituitary adenomas have been described in these patients. The underlying genetic etiology lies in somatic mosaicism of mutations in isocitrate dehydrogenase 1 (IDH1) or isocitrate dehydrogenase 2 (IDH2). This report describes a patient with Maffucci syndrome who presented with intracranial tumors of the skull base and suprasellar region. The patient underwent resection of both intracranial tumors, revealing histopathological diagnoses of chondrosarcoma and pituitary adenoma. DNA sequencing of the tumors was performed to identify common IDH1/2 mutations. Clinical, radiological, and biochemical assessments were performed. Genotypic studies used standard Sanger sequencing in conjunction with a target-specific peptide nucleic acid to detect IDH1 mutations in tumor tissues. DNA sequencing demonstrated identical IDH1 mutations (c.394C > T) in both tumors. To the authors' knowledge, this report provides the first genetic evidence for the inclusion of pituitary adenomas among tumors characterizing Maffucci syndrome. In patients who are newly diagnosed with Maffucci syndrome, it is appropriate to monitor for development of pituitary pathology and neuroendocrine dysfunction. PMID:26473790

  9. Transcriptomic Features of Bovine Blastocysts Derived by Somatic Cell Nuclear Transfer

    PubMed Central

    Min, Byungkuk; Cho, Sunwha; Park, Jung Sun; Lee, Yun-Gyeong; Kim, Namshin; Kang, Yong-Kook

    2015-01-01

    Reprogramming incompletely occurs in most somatic cell nuclear transfer (SCNT) embryos, which results in misregulation of developmentally important genes and subsequent embryonic malfunction and lethality. Here we examined transcriptome profiles in single bovine blastocysts derived by in vitro fertilization (IVF) and SCNT. Different types of donor cells, cumulus cell and ear-skin fibroblast, were used to derive cSCNT and fSCNT blastocysts, respectively. SCNT blastocysts expressed 13,606 genes on average, similar to IVF (13,542). Correlation analysis found that both cSCNT and fSCNT blastocyst groups had transcriptomic features distinctive from the IVF group, with the cSCNT transcriptomes closer to the IVF ones than the fSCNT. Gene expression analysis identified 56 underrepresented and 78 overrepresented differentially expressed genes in both SCNT groups. A 400-kb locus harboring zinc-finger protein family genes in chromosome 18 were found coordinately down-regulated in fSCNT blastocysts, showing a feature of reprogramming-resistant regions. Probing into different categories of genes important for blastocyst development revealed that genes involved in trophectoderm development frequently were underrepresented, and those encoding epigenetic modifiers tended to be overrepresented in SCNT blastocysts. Our effort to identify reprogramming-resistant, differentially expressed genes can help map reprogramming error-prone loci onto the genome and elucidate how to handle the stochastic events of reprogramming to improve cloning efficiency. PMID:26342001

  10. Transcriptomic Features of Bovine Blastocysts Derived by Somatic Cell Nuclear Transfer.

    PubMed

    Min, Byungkuk; Cho, Sunwha; Park, Jung Sun; Lee, Yun-Gyeong; Kim, Namshin; Kang, Yong-Kook

    2015-12-01

    Reprogramming incompletely occurs in most somatic cell nuclear transfer (SCNT) embryos, which results in misregulation of developmentally important genes and subsequent embryonic malfunction and lethality. Here we examined transcriptome profiles in single bovine blastocysts derived by in vitro fertilization (IVF) and SCNT. Different types of donor cells, cumulus cell and ear-skin fibroblast, were used to derive cSCNT and fSCNT blastocysts, respectively. SCNT blastocysts expressed 13,606 genes on average, similar to IVF (13,542). Correlation analysis found that both cSCNT and fSCNT blastocyst groups had transcriptomic features distinctive from the IVF group, with the cSCNT transcriptomes closer to the IVF ones than the fSCNT. Gene expression analysis identified 56 underrepresented and 78 overrepresented differentially expressed genes in both SCNT groups. A 400-kb locus harboring zinc-finger protein family genes in chromosome 18 were found coordinately down-regulated in fSCNT blastocysts, showing a feature of reprogramming-resistant regions. Probing into different categories of genes important for blastocyst development revealed that genes involved in trophectoderm development frequently were underrepresented, and those encoding epigenetic modifiers tended to be overrepresented in SCNT blastocysts. Our effort to identify reprogramming-resistant, differentially expressed genes can help map reprogramming error-prone loci onto the genome and elucidate how to handle the stochastic events of reprogramming to improve cloning efficiency. PMID:26342001

  11. Morphology and Kinematics of Warm Molecular Gas in the Nuclear Region of Arp 220 as Revealed by ALMA

    NASA Astrophysics Data System (ADS)

    Rangwala, Naseem; Maloney, Philip R.; Wilson, Christine D.; Glenn, Jason; Kamenetzky, Julia; Spinoglio, Luigi

    2015-06-01

    We present Atacama Large Millimeter Array (ALMA) Cycle-0 observations of the CO J = 6-5 line in the advanced galaxy merger Arp 220. This line traces warm molecular gas, which dominates the total CO luminosity. The CO emission from the two nuclei is well resolved by the 0\\buildrel{\\prime\\prime}\\over{.} 39× 0\\buildrel{\\prime\\prime}\\over{.} 22 beam and the exceptional sensitivity and spatial/spectral resolution reveal new complex features in the morphology and kinematics of the warm gas. The line profiles are asymmetric between the red and blue sides of the nuclear disks and the peak of the line emission is offset from the peak of the continuum emission in both nuclei by about 100 pc in the same direction. CO self-absorption is detected at the centers of both nuclei but it is much deeper in the eastern nucleus. We also clearly detect strong, highly redshifted CO absorption located near the southwest side of each nucleus. For the eastern nucleus, we reproduce the major line profile features with a simple kinematic model of a highly turbulent, rotating disk with a substantial line center optical depth and a large gradient in the excitation temperature. The red/blue asymmetries and line-to-continuum offset are likely produced by absorption of the blue (SW) sides of the two nuclei by blueshifted, foreground molecular gas; the mass of the absorber is comparable to the nuclear warm gas mass (˜{{10}8} {{M}⊙ }). We measure an unusually high {{L}CO}/{{L}FIR} ratio in the eastern nucleus, suggesting there is an additional energy source, such as mechanical energy from shocks, present in this nucleus.

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

    PubMed

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

    2015-01-01

    Considerable progress has been made in the treatment of hearing loss with auditory implants. However, there are still many implanted patients that experience hearing deficiencies, such as limited speech understanding or vanishing perception with continuous stimulation (i.e., abnormal loudness adaptation). The present study aims to identify specific patterns of cerebral cortex activity involved with such deficiencies. We performed O-15-water positron emission tomography (PET) in patients implanted with electrodes within the cochlea, brainstem, or midbrain to investigate the pattern of cortical activation in response to speech or continuous multi-tone stimuli directly inputted into the implant processor that then delivered electrical patterns through those electrodes. Statistical parametric mapping was performed on a single subject basis. Better speech understanding was correlated with a larger extent of bilateral auditory cortex activation. In contrast to speech, the continuous multi-tone stimulus elicited mainly unilateral auditory cortical activity in which greater loudness adaptation corresponded to weaker activation and even deactivation. Interestingly, greater loudness adaptation was correlated with stronger activity within the ventral prefrontal cortex, which could be up-regulated to suppress the irrelevant or aberrant signals into the auditory cortex. The ability to detect these specific cortical patterns and differences across patients and stimuli demonstrates the potential for using PET to diagnose auditory function or dysfunction in implant patients, which in turn could guide the development of appropriate stimulation strategies for improving hearing rehabilitation. Beyond hearing restoration, our study also reveals a potential role of the frontal cortex in suppressing irrelevant or aberrant activity within the auditory cortex, and thus may be relevant for understanding and treating tinnitus. PMID:26046763

  13. Worldwide HLA-E nucleotide and haplotype variability reveals a conserved gene for coding and 3' untranslated regions.

    PubMed

    Felício, L P; Porto, I O P; Mendes-Junior, C T; Veiga-Castelli, L C; Santos, K E; Vianello-Brondani, R P; Sabbagh, A; Moreau, P; Donadi, E A; Castelli, E C

    2014-02-01

    The human leukocyte antigen-E (HLA-E) locus is a human major histocompatibility complex (MHC) gene associated with immune-modulation and suppression of the immune response by the interaction with specific natural killer (NK) and T cell receptors (TCRs). It is considered one of the most conserved genes of the human MHC; however, this low nucleotide variability seems to be a consequence of the scarce number of studies focusing on this subject. In this manuscript we assessed the nucleotide variability at the HLA-E coding and 3' untranslated regions (3'UTRs) in Brazil and in the populations from the 1000Genomes Consortium. Twenty-eight variable sites arranged into 33 haplotypes were detected and most of these haplotypes (98.2%) are encoding one of the two HLA-E molecules found worldwide, E*01:01 and E*01:03. Moreover, three worldwide spread haplotypes, associated with the coding alleles E*01:01:01, E*01:03:01 and E*01:03:02, account for 85% of all HLA-E haplotypes, suggesting that they arose early before human speciation. In addition, the low nucleotide diversity found for the HLA-E coding and 3'UTR in worldwide populations suggests that the HLA-E gene is in fact a conserved gene, which might be a consequence of its key role in the modulation of the immune system. PMID:24400773

  14. Mitogenomics reveals phylogeny and repeated motifs in control regions of the deep-sea family Siboglinidae (Annelida).

    PubMed

    Li, Yuanning; Kocot, Kevin M; Schander, Christoffer; Santos, Scott R; Thornhill, Daniel J; Halanych, Kenneth M

    2015-04-01

    Deep-sea tubeworms in the annelid family Siboglinidae have drawn considerable interest regarding their ecology and evolutionary biology. As adults, they lack a digestive tract and rely on endosymbionts for nutrition. Moreover, they are important members of chemosynthetic environments including hydrothermal vents, cold seeps, muddy sediments, and whale bones. Evolution and diversification of siboglinids has been associated with host-symbiont relationships and reducing habitats. Despite their importance, the taxonomy and phylogenetics of this clade are debated due to conflicting results. In this study, 10 complete and 2 partial mitochondrial genomes and one transcriptome were sequenced and analyzed to address siboglinid evolution. Notably, repeated nucleotide motifs were found in control regions of these mt genomes, which may explain previous challenges of sequencing siboglinid mt genomes. Phylogenetic analyses of amino acid and nucleotide datasets were conducted in order to infer evolutionary history. Both analyses generally had strong nodal support and suggest Osedax is most closely related to the Vestimentifera+Sclerolinum clade, rather than Frenulata, as recently reported. These results imply Osedax, the only siboglinid lineage with heterotrophic endosymbionts, evolved from a lineage utilizing chemoautotrophic symbionts. PMID:25721539

  15. Aberrant regional neural fluctuations and functional connectivity in generalized anxiety disorder revealed by resting-state functional magnetic resonance imaging.

    PubMed

    Wang, Wei; Hou, Jingming; Qian, Shaowen; Liu, Kai; Li, Bo; Li, Min; Peng, Zhaohui; Xin, Kuolin; Sun, Gang

    2016-06-15

    The purpose of this study was to investigate the neural activity and functional connectivity in generalized anxiety disorder (GAD) during resting state, and how these alterations correlate to patients' symptoms. Twenty-eight GAD patients and 28 matched healthy controls underwent resting-state functional magnetic resonance (fMRI) scans. Amplitude of low-frequency fluctuation (ALFF) and seed-based resting-state functional connectivity (RSFC) were computed to explore regional activity and functional integration, and were compared between the two groups using the voxel-based two-sample t test. Pearson's correlation analyses were performed to examine the neural relationships with demographics and clinical symptoms scores. Compared to controls, GAD patients showed functional abnormalities: higher ALFF in the bilateral dorsomedial prefrontal cortex, bilateral dorsolateral prefrontal cortex and left precuneus/posterior cingulate cortex; lower connectivity in prefrontal gyrus; lower in prefrontal-limbic and cingulate RSFC and higher prefrontal-hippocampus RSFC were correlated with clinical symptoms severity, but these associations were unable to withstand correction for multiple testing. These findings may help facilitate further understanding of the potential neural substrate of GAD. PMID:27163197

  16. Targeted mutagenesis of intergenic regions in the Neisseria gonorrhoeae gonococcal genetic island reveals multiple regulatory mechanisms controlling type IV secretion.

    PubMed

    Ramsey, Meghan E; Bender, Tobias; Klimowicz, Amy K; Hackett, Kathleen T; Yamamoto, Ami; Jolicoeur, Adrienne; Callaghan, Melanie M; Wassarman, Karen M; van der Does, Chris; Dillard, Joseph P

    2015-09-01

    Gonococci secrete chromosomal DNA into the extracellular environment using a type IV secretion system (T4SS). The secreted DNA acts in natural transformation and initiates biofilm development. Although the DNA and its effects are detectable, structural components of the T4SS are present at very low levels, suggestive of uncharacterized regulatory control. We sought to better characterize the expression and regulation of T4SS genes and found that the four operons containing T4SS genes are transcribed at very different levels. Increasing transcription of two of the operons through targeted promoter mutagenesis did not increase DNA secretion. The stability and steady-state levels of two T4SS structural proteins were affected by a homolog of tail-specific protease. An RNA switch was also identified that regulates translation of a third T4SS operon. The switch mechanism relies on two putative stem-loop structures contained within the 5' untranslated region of the transcript, one of which occludes the ribosome binding site and start codon. Mutational analysis of these stem loops supports a model in which induction of an alternative structure relieves repression. Taken together, these results identify multiple layers of regulation, including transcriptional, translational and post-translational mechanisms controlling T4SS gene expression and DNA secretion. PMID:26076069

  17. Expression profile analysis of aorta-gonad-mesonephros region-derived stromal cells reveals genes that regulate hematopoiesis

    SciTech Connect

    Nagao, Kenji; Ohta, Takayuki; Hinohara, Atsushi; Tahara, Tomoyuki; Hagiwara, Tetsuya; Maeda, Yoshitake; Yoneya, Takashi; Sohma, Yoshiaki; Heike, Toshio; Nakahata, Tatsutoshi; Inagaki, Yoshimasa Nishikawa, Mitsuo

    2008-12-05

    The aorta-gonad-mesonephros (AGM) region is involved in the generation and maintenance of the first definitive hematopoietic stem cells (HSCs). A mouse AGM-derived cell line, AGM-S3, was shown to support the development of HSCs. To elucidate the molecular mechanisms regulating early hematopoiesis, we obtained subclones from AGM-S3, one of which was hematopoiesis supportive (S3-A9) and the other one of which was non-supportive (S3-A7), and we analyzed their gene expression profiles by gene chip analysis. In the present study, we found that Glypican-1 (GPC1) was highly expressed in the supportive subclone AGM-S3-A9. Over-expression of GPC1 in non-supportive cells led to the proliferation of progenitor cells in human cord blood when cocultured with the transfected-stromal cells. Thus, GPC1 may have an important role in the establishment of a microenvironment that supports early events in hematopoiesis.

  18. Region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues

    PubMed Central

    Scheller, Erica L.; Doucette, Casey R.; Learman, Brian S.; Cawthorn, William P.; Khandaker, Shaima; Schell, Benjamin; Wu, Brent; Ding, Shi-Ying; Bredella, Miriam A.; Fazeli, Pouneh K.; Khoury, Basma; Jepsen, Karl J.; Pilch, Paul F.; Klibanski, Anne; Rosen, Clifford J.; MacDougald, Ormond A.

    2015-01-01

    Marrow adipose tissue (MAT) accumulates in diverse clinical conditions but remains poorly understood. Here we show region-specific variation in MAT adipocyte development, regulation, size, lipid composition, gene expression, and genetic determinants. Early MAT formation in mice is conserved, while later development is strain dependent. Proximal, but not distal, MAT is lost with 21-day cold exposure. Rat MAT adipocytes from distal sites have an increased proportion of monounsaturated fatty acids and expression of Scd1/Scd2, Cebpa and Cebpb. Humans also have increased distal marrow fat unsaturation. We define proximal ‘regulated’ MAT (rMAT) as single adipocytes interspersed with active hematopoiesis, whereas distal ‘constitutive’ MAT (cMAT) has low hematopoiesis, contains larger adipocytes, develops earlier, and remains preserved upon systemic challenges. Loss of rMAT occurs in mice with congenital generalized lipodystrophy type 4, whereas both rMAT and cMAT are preserved in mice with congenital generalized lipodystrophy type 3. Consideration of these MAT subpopulations may be important for future studies linking MAT to bone biology, hematopoiesis and whole-body metabolism. PMID:26245716

  19. Molecular evolution analysis of WUSCHEL-related homeobox transcription factor family reveals functional divergence among clades in the homeobox region.

    PubMed

    Segatto, Ana Lúcia A; Thompson, Claudia E; Freitas, Loreta B

    2016-07-01

    Gene families have been shown to play important roles in plant evolution and are associated with diversification and speciation. Genes of WUSCHEL-related homeobox family of transcription factors have important functions in plant development and are correlated with the appearance of evolutionary novelties. There are several published studies related to this family, but little is known about the relationships among the main clades in the phylogeny and the molecular evolution of the family. In this study, we obtained a well-resolved Bayesian phylogenetic tree establishing the relationships among the main clades and determining the position of Selaginella moellendorffii WOX genes. Moreover, a correlation was identified between the number of genes in the genomes and the events of whole-genome duplications. The intron-exon structure is more consistent across the modern clade, which appeared more recently in the WOX evolutionary history, and coincides with the development of higher complexity in plant species. No positive selection was detected among sites through the branches in the tree. However, with regard to the main clades, functional divergence among certain amino acids in the homeodomain region was found. Relaxed purifying selection could be the main driving force in the evolution of these genes and in agreement with some genes have been demonstrated to be functionally redundant. PMID:27150824

  20. Widely Extended [O III] 88μm Line Emission around the 30 Doradus Region Revealed with AKARI FIS-FTS

    NASA Astrophysics Data System (ADS)

    Kawada, Mitsunobu; Takahashi, Ai; Yasuda, Akiko; Kiriyama, Yuichi; Mori, Tatsuya; Mouri, Akio; Kaneda, Hidehiro; Okada, Yoko; Takahashi, Hidenori; Murakami, Noriko

    2011-08-01

    We present a distribution map of the far-infrared [O II] 88 μm line emission around the 30 Doradus (30 Dor) region in the Large Magellanic Cloud obtained with the Fourier Transform Spectrometer of the Far-Infrared Surveyor on board AKARI. The map reveals that the [O III] emission is widely distributed by more than 10' around the super star cluster R 136, implying that the 30 Dor region is affluent with interstellar radiation field that is hard enough to ionize O2+. The observed [O III] line intensities are as high as (1-2) × 10-6 W m-2 sr-1 on the peripheral regions 4'-5' away from the center of 30 Dor, which requires gas densities of 60-100 cm-3. However, the observed size of the distribution of the [O III] emission is too large to be explained by massive stars in the 30 Dor region enshrouded by clouds with a constant gas density of 102 cm-3. Therefore, the surrounding structure is likely to be highly clumpy. We also find a global correlation between the [O III] and the far-infrared continuum emission, suggesting that the gas and dust are well mixed in the highly ionized region where the dust survives in clumpy dense clouds shielded from energetic photons.

  1. Proterozoic structure, cambrian rifting, and younger faulting as revealed by a regional seismic reflection network in the Southern Illinois Basin

    USGS Publications Warehouse

    Potter, C.J.; Drahovzal, J.A.; Sargent, M.L.; McBride, J.H.

    1997-01-01

    Four high-quality seismic reflection profiles through the southern Illinois Basin, totaling 245 km in length, provide an excellent regional subsurface stratigraphic and structural framework for evaluation of seismic risk, hydrocarbon occurrence, and other regional geologic studies. These data provide extensive subsurface information on the geometry of the intersection of the Cambrian Reelfoot and Rough Creek rifts, on extensive Proterozoic reflection sequences, and on structures (including the Fluorspar Area Fault Complex and Hicks Dome) that underlie a transitional area between the well-defined New Madrid seismic zone (to the southwest) and a more diffuse area of seismicity in the southern Illinois Basin. Our principal interpretations from these data are listed here in order of geologic age, from oldest to youngest: 1. Prominent Proterozoic layering, possibly equivalent to Proterozoic (???1 Ga) Middle Run Formation clastic strata and underlying (1.3-1.5 Ga) volcanic rocks of the East Continent rift basin, has been strongly deformed, probably as part of the Grenville foreland fold and thrust belt. 2. A well-defined angular unconformity is seen in many places between Proterozoic and Cambrian strata; a post-Grenville Proterozoic sequence is also apparent locally, directly beneath the base of the Cambrian. 3. We infer a major reversal in Cambrian rift polarity (accommodation zone) in the Rough Creek Graben in western Kentucky. 4. Seismic facies analysis suggests the presence of basin-floor fan complexes at and near the base of the Cambrian interval and within parts of a Proterozoic post-Grenville sequence in several parts of the Rough Creek Graben. 5. There is an abrupt pinchout of the Mount Simon Sandstone against crystalline basement beneath the Dale Dome (near the Texaco no. 1 Cuppy well, Hamilton County) in southeastern Illinois, and a more gradual Mount Simon pinchout to the southeast. 6. Where crossed by the seismic reflection line in southeast Illinois, some

  2. Genome-wide analysis of glucocorticoid receptor binding regions in adipocytes reveal gene network involved in triglyceride homeostasis.

    PubMed

    Yu, Chi-Yi; Mayba, Oleg; Lee, Joyce V; Tran, Joanna; Harris, Charlie; Speed, Terence P; Wang, Jen-Chywan

    2010-01-01

    Glucocorticoids play important roles in the regulation of distinct aspects of adipocyte biology. Excess glucocorticoids in adipocytes are associated with metabolic disorders, including central obesity, insulin resistance and dyslipidemia. To understand the mechanisms underlying the glucocorticoid action in adipocytes, we used chromatin immunoprecipitation sequencing to isolate genome-wide glucocorticoid receptor (GR) binding regions (GBRs) in 3T3-L1 adipocytes. Furthermore, gene expression analyses were used to identify genes that were regulated by glucocorticoids. Overall, 274 glucocorticoid-regulated genes contain or locate nearby GBR. We found that many GBRs were located in or nearby genes involved in triglyceride (TG) synthesis (Scd-1, 2, 3, GPAT3, GPAT4, Agpat2, Lpin1), lipolysis (Lipe, Mgll), lipid transport (Cd36, Lrp-1, Vldlr, Slc27a2) and storage (S3-12). Gene expression analysis showed that except for Scd-3, the other 13 genes were induced in mouse inguinal fat upon 4-day glucocorticoid treatment. Reporter gene assays showed that except Agpat2, the other 12 glucocorticoid-regulated genes contain at least one GBR that can mediate hormone response. In agreement with the fact that glucocorticoids activated genes in both TG biosynthetic and lipolytic pathways, we confirmed that 4-day glucocorticoid treatment increased TG synthesis and lipolysis concomitantly in inguinal fat. Notably, we found that 9 of these 12 genes were induced in transgenic mice that have constant elevated plasma glucocorticoid levels. These results suggested that a similar mechanism was used to regulate TG homeostasis during chronic glucocorticoid treatment. In summary, our studies have identified molecular components in a glucocorticoid-controlled gene network involved in the regulation of TG homeostasis in adipocytes. Understanding the regulation of this gene network should provide important insight for future therapeutic developments for metabolic diseases. PMID:21187916

  3. Tissue-specific insulator function at H19/Igf2 revealed by deletions at the imprinting control region.

    PubMed

    Ideraabdullah, Folami Y; Thorvaldsen, Joanne L; Myers, Jennifer A; Bartolomei, Marisa S

    2014-12-01

    Parent-of-origin-specific expression at imprinted genes is regulated by allele-specific DNA methylation at imprinting control regions (ICRs). This mechanism of gene regulation, where one element controls allelic expression of multiple genes, is not fully understood. Furthermore, the mechanism of gene dysregulation through ICR epimutations, such as loss or gain of DNA methylation, remains a mystery. We have used genetic mouse models to dissect ICR-mediated genetic and epigenetic regulation of imprinted gene expression. The H19/insulin-like growth factor 2 (Igf2) ICR has a multifunctional role including insulation, activation and repression. Microdeletions at the human H19/IGF2 ICR (IC1) are proposed to be responsible for IC1 epimutations associated with imprinting disorders such as Beckwith-Wiedemann syndrome (BWS). Here, we have generated and characterized a mouse model that mimics BWS microdeletions to define the role of the deleted sequence in establishing and maintaining epigenetic marks and imprinted expression at the H19/IGF2 locus. These mice carry a 1.3 kb deletion at the H19/Igf2 ICR [Δ2,3] removing two of four CCCTC-binding factor (CTCF) sites and the intervening sequence, ∼75% of the ICR. Surprisingly, the Δ2,3 deletion does not perturb DNA methylation at the ICR; however, it does disrupt imprinted expression. While repressive functions of the ICR are compromised by the deletion regardless of tissue type, insulator function is only disrupted in tissues of mesodermal origin where a significant amount of CTCF is poly(ADP-ribosyl)ated. These findings suggest that insulator activity of the H19/Igf2 ICR varies by cell type and may depend on cell-specific enhancers as well as posttranslational modifications of the insulator protein CTCF. PMID:24990148

  4. The Variable Regions of Lactobacillus rhamnosus Genomes Reveal the Dynamic Evolution of Metabolic and Host-Adaptation Repertoires

    PubMed Central

    Ceapa, Corina; Davids, Mark; Ritari, Jarmo; Lambert, Jolanda; Wels, Michiel; Douillard, François P.; Smokvina, Tamara; de Vos, Willem M.; Knol, Jan; Kleerebezem, Michiel

    2016-01-01

    Lactobacillus rhamnosus is a diverse Gram-positive species with strains isolated from different ecological niches. Here, we report the genome sequence analysis of 40 diverse strains of L. rhamnosus and their genomic comparison, with a focus on the variable genome. Genomic comparison of 40 L. rhamnosus strains discriminated the conserved genes (core genome) and regions of plasticity involving frequent rearrangements and horizontal transfer (variome). The L. rhamnosus core genome encompasses 2,164 genes, out of 4,711 genes in total (the pan-genome). The accessory genome is dominated by genes encoding carbohydrate transport and metabolism, extracellular polysaccharides (EPS) biosynthesis, bacteriocin production, pili production, the cas system, and the associated clustered regularly interspaced short palindromic repeat (CRISPR) loci, and more than 100 transporter functions and mobile genetic elements like phages, plasmid genes, and transposons. A clade distribution based on amino acid differences between core (shared) proteins matched with the clade distribution obtained from the presence–absence of variable genes. The phylogenetic and variome tree overlap indicated that frequent events of gene acquisition and loss dominated the evolutionary segregation of the strains within this species, which is paralleled by evolutionary diversification of core gene functions. The CRISPR-Cas system could have contributed to this evolutionary segregation. Lactobacillus rhamnosus strains contain the genetic and metabolic machinery with strain-specific gene functions required to adapt to a large range of environments. A remarkable congruency of the evolutionary relatedness of the strains’ core and variome functions, possibly favoring interspecies genetic exchanges, underlines the importance of gene-acquisition and loss within the L. rhamnosus strain diversification. PMID:27358423

  5. The Variable Regions of Lactobacillus rhamnosus Genomes Reveal the Dynamic Evolution of Metabolic and Host-Adaptation Repertoires.

    PubMed

    Ceapa, Corina; Davids, Mark; Ritari, Jarmo; Lambert, Jolanda; Wels, Michiel; Douillard, François P; Smokvina, Tamara; de Vos, Willem M; Knol, Jan; Kleerebezem, Michiel

    2016-01-01

    Lactobacillus rhamnosus is a diverse Gram-positive species with strains isolated from different ecological niches. Here, we report the genome sequence analysis of 40 diverse strains of L. rhamnosus and their genomic comparison, with a focus on the variable genome. Genomic comparison of 40 L. rhamnosus strains discriminated the conserved genes (core genome) and regions of plasticity involving frequent rearrangements and horizontal transfer (variome). The L. rhamnosus core genome encompasses 2,164 genes, out of 4,711 genes in total (the pan-genome). The accessory genome is dominated by genes encoding carbohydrate transport and metabolism, extracellular polysaccharides (EPS) biosynthesis, bacteriocin production, pili production, the cas system, and the associated clustered regularly interspaced short palindromic repeat (CRISPR) loci, and more than 100 transporter functions and mobile genetic elements like phages, plasmid genes, and transposons. A clade distribution based on amino acid differences between core (shared) proteins matched with the clade distribution obtained from the presence-absence of variable genes. The phylogenetic and variome tree overlap indicated that frequent events of gene acquisition and loss dominated the evolutionary segregation of the strains within this species, which is paralleled by evolutionary diversification of core gene functions. The CRISPR-Cas system could have contributed to this evolutionary segregation. Lactobacillus rhamnosus strains contain the genetic and metabolic machinery with strain-specific gene functions required to adapt to a large range of environments. A remarkable congruency of the evolutionary relatedness of the strains' core and variome functions, possibly favoring interspecies genetic exchanges, underlines the importance of gene-acquisition and loss within the L. rhamnosus strain diversification. PMID:27358423

  6. Tracking wild sockeye salmon smolts to the ocean reveals distinct regions of nocturnal movement and high mortality.

    PubMed

    Clark, Timothy D; Furey, Nathan B; Rechisky, Erin L; Gale, Marika K; Jeffries, Ken M; Porter, Aswea D; Casselman, Matthew T; Lotto, Andrew G; Patterson, David A; Cooke, Steven J; Farrell, Anthony P; Welch, David W; Hinch, Scott G

    2016-06-01

    Few estimates of migration rates or descriptions of behavior or survival exist for wild populations of out-migrating Pacific salmon smolts from natal freshwater rearing areas to the ocean. Using acoustic transmitters and fixed receiver arrays across four years (2010-2013), we tracked the migration of > 1850 wild sockeye salmon (Oncorhynchus nerka) smolts from Chilko Lake, British Columbia, to the coastal Pacific Ocean (> 1000 km distance). Cumulative survival to the ocean ranged 3-10% among years, although this may be slightly underestimated due to technical limitations at the final receiver array. Distinct spatial patterns in both behavior and survival were observed through all years. In small, clear, upper-river reaches, downstream migration largely occurred at night at speeds up to 50 km/d and coincided with poor survival. Among years, only 57-78% of smolts survived the first 80 km. Parallel laboratory experiments revealed excellent short-term survival and unhindered swimming performance of dummy-tagged smolts, suggesting that predators rather than tagging effects were responsible for the initial high mortality of acoustic-tagged smolts. Migration speeds increased in the Fraser River mainstem (~220 km/d in some years), diel movement patterns ceased, and smolt survival generally exceeded 90% in this segment. Marine movement rates and survival were variable across years, with among-year segment-specific survival being the most variable and lowest (19-61%) during the final (and longest, 240 km) marine migration segment. Osmoregulatory preparedness was not expected to influence marine survival, as smolts could maintain normal levels of plasma chloride when experimentally exposed to saltwater (30 ppt) immediately upon commencing their migration from Chilko Lake. Transportation of smolts downstream generally increased survival to the farthest marine array. The act of tagging may have affected smolts in the marine environment in some years as dummy-tagged fish had

  7. Isolation of putative glycoprotein gene from early somatic embryo of carrot and its possible involvement in somatic embryo development.

    PubMed

    Takahata, Kiminori; Takeuchi, Miyuki; Fujita, Minoru; Azuma, Junichi; Kamada, Hiroshi; Sato, Fumihiko

    2004-11-01

    Somatic embryogenesis is a unique process in plant cells. For example, embryogenic cells (EC) of carrot (Daucus carota) maintained in a medium containing 2,4-dichlorophenoxyacetic acid (2,4-D) regenerate whole plants via somatic embryogenesis after the depletion of 2,4-D. Although some genes such as C-ABI3 and C-LEC1 have been found to be involved in somatic embryogenesis, the critical molecular and cellular mechanisms for somatic embryogenesis are unknown. To characterize the early mechanism in the induction of somatic embryogenesis, we isolated genes expressed during the early stage of somatic embryogenesis after 2,4-D depletion. Subtractive hybridization screening and subsequent RNA gel blot analysis suggested a candidate gene, Carrot Early Somatic Embryogenesis 1 (C-ESE1). C-ESE1 encodes a protein that has agglutinin and S-locus-glycoprotein domains and its expression is highly specific to primordial cells of somatic embryo. Transgenic carrot cells with reduced expression of C-ESE1 had wide intercellular space and decreased polysaccharides on the cell surface and showed delayed development in somatic embryogenesis. The importance of cell-to-cell attachment in somatic embryogenesis is discussed. PMID:15574842

  8. Indirect somatic embryogenesis in cassava for genetic modification purposes.

    PubMed

    Raemakers, Krit; Pereira, Isolde; van Putten, Herma Koehorst; Visser, Richard

    2006-01-01

    In cassava both direct and indirect somatic embryogenesis is described. Direct somatic embryogenesis starts with the culture of leaf explants on Murashige and Skoog (MS) medium supplemented with auxins. Somatic embryos undergo secondary somatic embryogenesis when cultured on the same medium. Indirect somatic embryogenesis is initiated by subculture of directly induced embryogenic tissue on auxin-supplemented medium with Gresshoff and Doy salts and vitamins. A very fine friable embryogenic callus (FEC) is formed after a few rounds of subculture and stringent selection. This FEC is maintained by subculture on auxin supplemented medium. Lowering of the auxin concentration allows the FEC to form mature somatic embryos that develop into plants when transferred to a cytokinin-supplemented medium. PMID:16673909

  9. Human somatic mutation assays as biomarkers of carcinogenesis

    SciTech Connect

    Compton, P.J.E.; Smith, M.T. ); Hooper, K. )

    1991-08-01

    This paper describes four assays that detect somatic gene mutations in humans: the hypoxanthine-guanine phosphoribosyl transferase assay, the glycophorin A assay, the HLA-A assay, and the sickle cell hemoglobin assay. Somatic gene mutations can be considered a biomarker of carcinogenesis, and assays for somatic mutation may assist epidemiologists in studies that attempt to identify factors associated with increased risks of cancer. Practical aspects of the use of these assays are discussed.

  10. Related Mechanisms of Antibody Somatic Hypermutation and Class Switch Recombination

    PubMed Central

    HWANG, JOYCE K.; ALT, FREDERICK W.; YEAP, LENG-SIEW

    2015-01-01

    The primary antibody repertoire is generated by mechanisms involving the assembly of the exons that encode the antigen-binding variable regions of immunoglobulin heavy (IgH) and light (IgL) chains during the early development of B lymphocytes. After antigen-dependent activation, mature B lymphocytes can further alter their IgH and IgL variable region exons by the process of somatic hypermutation (SHM), which allows the selection of B cells in which SHMs resulted in the production of antibodies with increased antigen affinity. In addition, during antigen-dependent activation, B cells can also change the constant region of their IgH chain through a DNA double-strand-break (DSB) dependent process referred to as IgH class switch recombination (CSR), which generates B cell progeny that produce antibodies with different IgH constant region effector functions that are best suited for a elimination of a particular pathogen or in a particular setting. Both the mutations that underlie SHM and the DSBs that underlie CSR are initiated in target genes by activation-induced cytidine deaminase (AID). This review describes in depth the processes of SHM and CSR with a focus on mechanisms that direct AID cytidine deamination in activated B cells and mechanisms that promote the differential outcomes of such cytidine deamination. PMID:26104555

  11. [Stress theories and the somatization process].

    PubMed

    Dantzer, R

    1995-12-01

    Stress theories aim at understanding pathophysiology of psychosomatic disorders. The first stress theories have been inspired by the principles of homeostasis. They view the response to stressors as a quasi reflex reaction which aims at normalizing disturbed homeostasis. More modern stress theories emphasize the intermediate role of cognitive and behavioural processes in the determinism of neuroendocrine and neurovegetative responses to stressors. Active attempts to control the situation are associated with activation of the sympathetic and adrenal medullary system whereas loss of control is associated with activation of the hypothalamic-pituitary-adrenal axis. Since the functional consequences of the activation of each of these physiological systems are not the same, the risk factors corresponding to each coping strategy are not the same. Whatever their details, physiological and psychobiological stress theories all emphasize the influence of psychic factors on bodily functions. However, mental states do not function independently of bodily functions. In the case of the influences of stress on immunity for instance, it has been shown that these influences represent the counterpart of feedback regulatory mechanisms in which the ability of the brain to regulate immune responses depends on the capacity of the immune system to influence brain functions. Activation of the immune system during infection or inflammation is accompanied by profound metabolic, neuroendocrine and behavioural changes which are mediated by the effects of immune products known as cytokines on brain cell targets. In view of the reciprocal relationships between peripheral organic systems and the brain, a purely psychosomatic view, from the psyche to the soma, is therefore no longer tenable. In addition, biological accounts of somatization processes run into the risk of minimizing the importance of perception and representation of somatic symptoms. Amplification of somatic symptoms is a common

  12. Mechanisms and models of somatic cell reprogramming

    PubMed Central

    Buganim, Yosef; Faddah, Dina A.; Jaenisch, Rudolf

    2014-01-01

    Conversion of somatic cells to pluripotency by defined factors is a long and complex process that yields embryonic stem cell-like cells that vary in their developmental potential. To improve the quality of resulting induced pluripotent stem cells (iPSCs), which is important for potential therapeutic applications, and to address fundamental questions about control of cell identity, molecular mechanisms of the reprogramming process must be understood. Here we discuss recent discoveries regarding the role of reprogramming factors in remodeling the genome, including new insights into the function of c-Myc, and describe the different phases, markers and emerging models of reprogramming. PMID:23681063

  13. Somatic memory and gain increase as preconditions for tinnitus: Insights from congenital deafness.

    PubMed

    Eggermont, Jos J; Kral, Andrej

    2016-03-01

    Tinnitus is the conscious perception of sound heard in the absence of physical sound sources internal or external to the body. The characterization of tinnitus by its spectrum reflects the missing frequencies originally represented in the hearing loss, i.e., partially or completely deafferented, region. The tinnitus percept, despite a total hearing loss, may thus be dependent on the persisting existence of a somatic memory for the "lost" frequencies. Somatic memory in this context is the reference for phantom sensations attributed to missing sensory surfaces or parts thereof. This raises the question whether tinnitus can exist in congenital deafness, were somatic representations have not been formed. We review the development of tonotopic maps in altricial and precocial animals evidence for a lack of tinnitus in congenital deafness and the effects of cochlear implants on the formation of tonotopic maps in the congenitally deaf. The latter relates to the emergence of tinnitus in these subjects. The reviewed material is consistent with the hypothesis that tinnitus requires an established and actively used somatotopic map that leads to a corresponding somatic memory. The absence of such experience explains the absence of tinnitus in congenital bilateral and unilateral deafness. PMID:26719143

  14. Signatures of accelerated somatic evolution in gene promoters in multiple cancer types

    PubMed Central

    Smith, Kyle S.; Yadav, Vinod K.; Pedersen, Brent S.; Shaknovich, Rita; Geraci, Mark W.; Pollard, Katherine S.; De, Subhajyoti

    2015-01-01

    Cancer-associated somatic mutations outside protein-coding regions remain largely unexplored. Analyses of the TERT locus have indicated that non-coding regulatory mutations can be more frequent than previously suspected and play important roles in oncogenesis. Using a computational method called SASE-hunter, developed here, we identified a novel signature of accelerated somatic evolution (SASE) marked by a significant excess of somatic mutations localized in a genomic locus, and prioritized those loci that carried the signature in multiple cancer patients. Interestingly, even when an affected locus carried the signature in multiple individuals, the mutations contributing to SASE themselves were rarely recurrent at the base-pair resolution. In a pan-cancer analysis of 906 samples from 12 tumor types, we detected SASE in the promoters of several genes, including known cancer genes such as MYC, BCL2, RBM5 and WWOX. Nucleotide substitution patterns consistent with oxidative DNA damage and local somatic hypermutation appeared to contribute to this signature in selected gene promoters (e.g. MYC). SASEs in selected cancer gene promoters were associated with over-expression, and also correlated with the age of onset of cancer, aggressiveness of the disease and survival. Taken together, our work detects a hitherto under-appreciated and clinically important class of regulatory changes in cancer genomes. PMID:25934800

  15. Values of somatic traits and of body proportion indices in male and female newborns of Lublin.

    PubMed

    Zatorska, M

    1992-01-01

    Between December 1984 and May 1985, anthropometric measurements were applied to 455 full-term and healthy newborns (225 boys and 230 girls). The purpose of the investigation was to learn about somatic development and body proportions of Lublin newborns. It has been found that although the studied somatic traits show bigger differences between newborns of the same sex, rather than between newborns of the opposite sexes, sexual dimorphism of morphological traits apparently starts already at birth. Out of the analysed somatic traits and calculated body proportion indices, the following ones have significantly bigger values on boys: body mass and length, length of trunk with head and neck, length of trunk alone, hip width, shoulder width, width of distal femoral epiphysis, head length, width and circumference, and Quetelet index. In girls, in turn, thickness of three skin folds and shoulder-hip index are statistically more prominent. Mean values of somatic traits and body proportion indices may serve the purposes of regional standards for the evaluation of newborns in Lublin itself as well as in other towns of similar characteristics. PMID:1344736

  16. Induction of direct somatic embryogenesis in garlic (Allium sativum).

    PubMed

    Sata, S J; Bagatharia, S B; Thaker, V S

    2000-01-01

    An efficient novel method of direct somatic embryogenesis from basal tissue of garlic clove was developed. The influence of plant growth regulators, basal medium and explant type on somatic embryo induction was examined. The best plant growth regulator combination was, 2,4-D and kinetin at 1.0 mg/L and 0.5 mg/L respectively, inducing direct somatic embryogenesis in 60% of explants. White's medium was used as basal medium and somatic embryos developed on explants after six weeks. The technique has potential applicability for problems associated with plant regeneration and virus elimination in garlic. PMID:11549942

  17. Confidence-based somatic mutation evaluation and prioritization.

    PubMed

    Löwer, Martin; Renard, Bernhard Y; de Graaf, Jos; Wagner, Meike; Paret, Claudia; Kneip, Christoph; Türeci, Ozlem; Diken, Mustafa; Britten, Cedrik; Kreiter, Sebastian; Koslowski, Michael; Castle, John C; Sahin, Ugur

    2012-01-01

    Next generation sequencing (NGS) has enabled high throughput discovery of somatic mutations. Detection depends on experimental design, lab platforms, parameters and analysis algorithms. However, NGS-based somatic mutation detection is prone to erroneous calls, with reported validation rates near 54% and congruence between algorithms less than 50%. Here, we developed an algorithm to assign a single statistic, a false discovery rate (FDR), to each somatic mutation identified by NGS. This FDR confidence value accurately discriminates true mutations from erroneous calls. Using sequencing data generated from triplicate exome profiling of C57BL/6 mice and B16-F10 melanoma cells, we used the existing algorithms GATK, SAMtools and SomaticSNiPer to identify somatic mutations. For each identified mutation, our algorithm assigned an FDR. We selected 139 mutations for validation, including 50 somatic mutations assigned a low FDR (high confidence) and 44 mutations assigned a high FDR (low confidence). All of the high confidence somatic mutations validated (50 of 50), none of the 44 low confidence somatic mutations validated, and 15 of 45 mutations with an intermediate FDR validated. Furthermore, the assignment of a single FDR to individual mutations enables statistical comparisons of lab and computation methodologies, including ROC curves and AUC metrics. Using the HiSeq 2000, single end 50 nt reads from replicates generate the highest confidence somatic mutation call set. PMID:23028300

  18. Confidence-based Somatic Mutation Evaluation and Prioritization

    PubMed Central

    de Graaf, Jos; Wagner, Meike; Paret, Claudia; Kneip, Christoph; Türeci, Özlem; Diken, Mustafa; Britten, Cedrik; Kreiter, Sebastian; Koslowski, Michael; Castle, John C.; Sahin, Ugur

    2012-01-01

    Next generation sequencing (NGS) has enabled high throughput discovery of somatic mutations. Detection depends on experimental design, lab platforms, parameters and analysis algorithms. However, NGS-based somatic mutation detection is prone to erroneous calls, with reported validation rates near 54% and congruence between algorithms less than 50%. Here, we developed an algorithm to assign a single statistic, a false discovery rate (FDR), to each somatic mutation identified by NGS. This FDR confidence value accurately discriminates true mutations from erroneous calls. Using sequencing data generated from triplicate exome profiling of C57BL/6 mice and B16-F10 melanoma cells, we used the existing algorithms GATK, SAMtools and SomaticSNiPer to identify somatic mutations. For each identified mutation, our algorithm assigned an FDR. We selected 139 mutations for validation, including 50 somatic mutations assigned a low FDR (high confidence) and 44 mutations assigned a high FDR (low confidence). All of the high confidence somatic mutations validated (50 of 50), none of the 44 low confidence somatic mutations validated, and 15 of 45 mutations with an intermediate FDR validated. Furthermore, the assignment of a single FDR to individual mutations enables statistical comparisons of lab and computation methodologies, including ROC curves and AUC metrics. Using the HiSeq 2000, single end 50 nt reads from replicates generate the highest confidence somatic mutation call set. PMID:23028300

  19. Multilocus phylogeography of a widespread savanna-woodland-adapted rodent reveals the influence of Pleistocene geomorphology and climate change in Africa's Zambezi region.

    PubMed

    McDonough, Molly M; Šumbera, Radim; Mazoch, Vladimír; Ferguson, Adam W; Phillips, Caleb D; Bryja, Josef

    2015-10-01

    Understanding historical influences of climate and physiographic barriers in shaping patterns of biodiversity remains limited for many regions of the world. For mammals of continental Africa, phylogeographic studies, particularly for West African lineages, implicate both geographic barriers and climate oscillations in shaping small mammal diversity. In contrast, studies for southern African species have revealed conflicting phylogenetic patterns for how mammalian lineages respond to both climate change and geologic events such as river formation, especially during the Pleistocene. However, these studies were often biased by limited geographic sampling or exclusively focused on large-bodied taxa. We exploited the broad southern African distribution of a savanna-woodland-adapted African rodent, Gerbilliscus leucogaster (bushveld gerbil) and generated mitochondrial, autosomal and sex chromosome data to quantify regional signatures of climatic and vicariant biogeographic phenomena. Results indicate the most recent common ancestor for all G. leucogaster lineages occurred during the early Pleistocene. We documented six divergent mitochondrial lineages that diverged ~0.270-0.100 mya, each of which was geographically isolated during periods characterized by alterations to the course of the Zambezi River and its tributaries as well as regional 'megadroughts'. Results demonstrate the presence of a widespread lineage exhibiting demographic expansion ~0.065-0.035 mya, a time that coincides with savanna-woodland expansion across southern Africa. A multilocus autosomal perspective revealed the influence of the Kafue River as a current barrier to gene flow and regions of secondary contact among divergent mitochondrial lineages. Our results demonstrate the importance of both climatic fluctuations and physiographic vicariance in shaping the distribution of southern African biodiversity. PMID:26340076

  20. Solution structure of the lymphocyte receptor Nkrp1a reveals a distinct conformation of the long loop region as compared to in the crystal structure.

    PubMed

    Rozbeský, Daniel; Adámek, David; Pospíšilová, Eliška; Novák, Petr; Chmelík, Josef

    2016-09-01

    Mouse Nkrp1a receptor is a C-type lectin-like receptor expressed on the surface of natural killer cells that play an important role against virally infected and tumor cells. The recently solved crystal structure of Nkrp1a raises questions about a long loop region which was uniquely extended from the central region in the crystal. To understand the functional significance of the loop, the solution structure of Nkrp1a using nuclear magnetic resonance (NMR) spectroscopy was determined. A notable difference between the crystal and NMR structure of Nkrp1a appears in the conformation of the long loop region. While the extended loop points away from the central core and mediates formation of a domain swapped dimer in the crystal, the solution structure is monomeric with the loop tightly anchored to the central region. The findings described the first solution structure in the Nkrp1 family and revealed intriguing similarities and differences to the crystal structure. Proteins 2016; 84:1304-1311. © 2016 Wiley Periodicals, Inc. PMID:27238500

  1. Genomewide Analysis of Rat Periaqueductal Gray-Dorsal Horn Reveals Time-, Region- and Frequency-Specific mRNA Expression Changes in Response to Electroacupuncture Stimulation

    PubMed Central

    Wang, Ke; Xiang, Xiao-Hui; Qiao, Nan; Qi, Jun-Yi; Lin, Li-Bo; Zhang, Rong; Shou, Xiao-jing; Ping, Xing-Jie; Han, Ji-Sheng; Han, Jing-Dong; Zhao, Guo-Ping; Cui, Cai-Lian

    2014-01-01

    Electroacupuncture (EA) has been widely applied for illness prevention, treatment or rehabilitation in the clinic, especially for pain management. However, the molecular events that induce these changes remain largely uncharacterized. The periaqueductal gray (PAG) and the spinal dorsal horn (DH) have been verified as two critical regions in the response to EA stimulation in EA analgesia. In this study, a genetic screen was conducted to delineate the gene expression profile in the PAG-DH regions of rats to explore the molecular events of the analgesic effect induced by low-frequency (2-Hz) and high-frequency (100-Hz) EAs. Microarray analysis at two different time points after EA stimulation revealed time-, region- and frequency-specific gene expression changes. These expression differences suggested that modulation of neural-immune interaction in the central nervous system played an important role during EA analgesia. Furthermore, low-frequency EA could regulate gene expression to a greater degree than high-frequency EA. Altogether, the present study offers, for the first time, a characterized transcriptional response pattern in the PAG-DH regions followed by EA stimulation and, thus, provides a solid experimental framework for future in-depth analysis of the mechanisms underlying EA-induced effects. PMID:25346229

  2. Monitoring exposure to atomic bomb radiation by somatic mutation

    SciTech Connect

    Akiyama, Mitoshi; Kyoizumi, Seishi; Kusunoki, Yoichiro

    1996-05-01

    Atomic bomb survivors are a population suitable for studying the relationship between somatic mutation and cancer risk because their exposure doses are relatively well known and their dose responses in terms of cancer risk have also been thoroughly studied. An analysis has been made of erythrocyte glycophorin A (GPA) gene mutations in 1,226 atomic bomb survivors in Hiroshima and Nagasaki. The GPA mutation frequency (Mf) increased slightly but significantly with age at the time of measurement and with the number of cigarettes smoked. After adjustment for the effect of smoking, the Mf was significantly higher in males than in females and higher in Hiroshima than in Nagasaki. All of these characteristics of the background GPA Mf were in accord with those of solid tumor incidence obtained from an earlier epidemiological study of A-bomb survivors. Analysis of the dose effect on Mf revealed the doubling dose to be about 1.20 Sv and the minimum dose for detection of a significant increase to be about 0.24 Sv. No significant dose effect for difference in sex, city, or age at the time of bombing was observed. Interestingly, the doubling dose for the GPA Mf approximated that for solid cancer incidence (1.59 Sv). And the minimum dose for detection was not inconsistent with the data for solid cancer incidence. The dose effect was significantly higher in those diagnosed with cancer before or after measurement than in those without a history of cancer. These findings are consistent with the hypothesis that somatic mutations are the main cause of excess cancer risk from radiation exposure. 27 refs., 2 figs.

  3. Monitoring exposure to atomic bomb radiation by somatic mutation.

    PubMed

    Akiyama, M; Kyoizumi, S; Kusunoki, Y; Hirai, Y; Tanabe, K; Cologne, J B

    1996-05-01

    Atomic bomb survivors are a population suitable for studying the relationship between somatic mutation and cancer risk because their exposure doses are relatively well known and their dose responses in terms of cancer risk have also been thoroughly studied. An analysis has been made of erythrocyte glycophorin A (GPA) gene mutations in 1,226 atomic bomb survivors in Hiroshima and Nagasaki. The GPA mutation frequency (Mf) increased slightly but significantly with age at the time of measurement and with the number of cigarettes smoked. After adjustment for the effect of smoking, the Mf was significantly higher in males than in females and higher in Hiroshima than in Nagasaki. All of these characteristics of the background GPA Mf were in accord with those of solid tumor incidence obtained from an earlier epidemiological study of A-bomb survivors. Analysis of the dose effect on Mf revealed the doubling dose to be about 1.20 Sv and the minimum dose for detection of a significant increase to be about 0.24 Sv. No significant dose effect for difference in sex, city, or age at the time of bombing was observed. Interestingly, the doubling dose for the GPA Mf approximated that for solid cancer incidence (1.59 Sv). And the minimum dose for detection was not inconsistent with the data for solid cancer incidence. The dose effect was significantly higher in those diagnosed with cancer before or after measurement than in those without a history of cancer. These findings are consistent with the hypothesis that somatic mutations are the main cause of excess cancer risk from radiation exposure. PMID:8781371

  4. Gnotobiotic Miniature Pig Interbreed Somatic Cell Nuclear Transfer for Xenotransplantation.

    PubMed

    Hwang, Jeong Ho; Kim, Sang Eun; Gupta, Mukesh Kumar; Lee, HoonTaek

    2016-08-01

    Transgenic animal producing technology has improved consistently over the last couple of decades. Among the available methods, somatic cell nuclear transfer (SCNT) technology was officially the most popular. However, SCNT has low efficiency and requires a highly skilled individual. Additionally, the allo-SCNT nuclear reprogramming mechanism is poorly understood in the gnotobiotic miniature pig, which is a candidate for xenotransplantation, making sampling in oocytes very difficult compared to commercial hybrid pigs. Therefore, interbreed SCNT (ibSCNT), which is a combination of miniature pig and commercial pig (Landrace based), was analyzed and was found to be similar to SCNT in terms of the rate of blastocyst formation (12.6% ± 2.9% vs. 15.5% ± 2.2%; p > 0.05). However, a significantly lower fusion rate was observed in the ibSCNT compared to normal SCNT with Landrace pig somatic cells (29.6% ± 0.8% vs. 65.0% ± 4.9%). Thus, the optimization of fusion parameters was necessary for efficient SCNT. Our results further revealed that ibSCNT by the whole-cell intracytoplasmic injection (WCICI) method had a significantly higher blastocyst forming efficiency than the electrofusion method (31.1 ± 8.5 vs. 15.5% ± 2.2%). The nuclear remodeling and the pattern of changes in acetylation at H3K9 residue were similar in both SCNT and ibSCNT embryos. PMID:27459580

  5. Somatic mutations found in the healthy blood compartment of a 115-yr-old woman demonstrate oligoclonal hematopoiesis

    PubMed Central

    Holstege, Henne; Pfeiffer, Wayne; Sie, Daoud; Hulsman, Marc; Nicholas, Thomas J.; Lee, Clarence C.; Ross, Tristen; Lin, Jue; Miller, Mark A.; Ylstra, Bauke; Meijers-Heijboer, Hanne; Brugman, Martijn H.; Staal, Frank J.T.; Holstege, Gert; Reinders, Marcel J.T.; Harkins, Timothy T.; Levy, Samuel; Sistermans, Erik A.

    2014-01-01

    The somatic mutation burden in healthy white blood cells (WBCs) is not well known. Based on deep whole-genome sequencing, we estimate that approximately 450 somatic mutations accumulated in the nonrepetitive genome within the healthy blood compartment of a 115-yr-old woman. The detected mutations appear to have been harmless passenger mutations: They were enriched in noncoding, AT-rich regions that are not evolutionarily conserved, and they were depleted for genomic elements where mutations might have favorable or adverse effects on cellular fitness, such as regions with actively transcribed genes. The distribution of variant allele frequencies of these mutations suggests that the majority of the peripheral white blood cells were offspring of two related hematopoietic stem cell (HSC) clones. Moreover, telomere lengths of the WBCs were significantly shorter than telomere lengths from other tissues. Together, this suggests that the finite lifespan of HSCs, rather than somatic mutation effects, may lead to hematopoietic clonal evolution at extreme ages. PMID:24760347

  6. Are Early Somatic Embryos of the Norway Spruce (Picea abies (L.) Karst.) Organised?

    PubMed Central

    Petrek, Jiri; Zitka, Ondrej; Adam, Vojtech; Bartusek, Karel; Anjum, Naser A.; Pereira, Eduarda; Havel, Ladislav; Kizek, Rene

    2015-01-01

    Background Somatic embryogenesis in conifer species has great potential for the forestry industry. Hence, a number of methods have been developed for their efficient and rapid propagation through somatic embryogenesis. Although information is available regarding the previous process-mediated generation of embryogenic cells to form somatic embryos, there is a dearth of information in the literature on the detailed structure of these clusters. Methodology/Principal Findings The main aim of this study was to provide a more detailed structure of the embryogenic tissue clusters obtained through the in vitro propagation of the Norway spruce (Picea abies (L.) Karst.). We primarily focused on the growth of early somatic embryos (ESEs). The data on ESE growth suggested that there may be clear distinctions between their inner and outer regions. Therefore, we selected ESEs collected on the 56th day after sub-cultivation to dissect the homogeneity of the ESE clusters. Two colourimetric assays (acetocarmine and fluorescein diacetate/propidium iodide staining) and one metabolic assay based on the use of 2,3,5-triphenyltetrazolium chloride uncovered large differences in the metabolic activity inside the cluster. Next, we performed nuclear magnetic resonance measurements. The ESE cluster seemed to be compactly aggregated during the first four weeks of cultivation; thereafter, the difference between the 1H nuclei concentration in the inner and outer clusters was more evident. There were clear differences in the visual appearance of embryos from the outer and inner regions. Finally, a cluster was divided into six parts (three each from the inner and the outer regions of the embryo) to determine their growth and viability. The innermost embryos (centripetally towards the cluster centre) could grow after sub-cultivation but exhibited the slowest rate and required the longest time to reach the common growth rate. To confirm our hypothesis on the organisation of the ESE cluster, we

  7. AID to overcome the limitations of genomic information by introducing somatic DNA alterations

    PubMed Central

    Honjo, Tasuku; Muramatsu, Masamichi; Nagaoka, Hitoshi; Kinoshita, Kazuo; Shinkura, Reiko

    2006-01-01

    The immune system has adopted somatic DNA alterations to overcome the limitations of the genomic information. Activation induced cytidine deaminase (AID) is an essential enzyme to regulate class switch recombination (CSR), somatic hypermutation (SHM) and gene conversion (GC) of the immunoglobulin gene. AID is known to be required for DNA cleavage of S regions in CSR and V regions in SHM. However, its molecular mechanism is a focus of extensive debate. RNA editing hypothesis postulates that AID edits yet unknown mRNA, to generate specific endonucleases for CSR and SHM. By contrast, DNA deamination hypothesis assumes that AID deaminates cytosine in DNA, followed by DNA cleavage by base excision repair enzymes. We summarize the basic knowledge for molecular mechanisms for CSR and SHM and then discuss the importance of AID not only in the immune regulation but also in the genome instability. PMID:25873751

  8. Evaluation of Nine Somatic Variant Callers for Detection of Somatic Mutations in Exome and Targeted Deep Sequencing Data

    PubMed Central

    Krøigård, Anne Bruun; Thomassen, Mads; Lænkholm, Anne-Vibeke; Kruse, Torben A.; Larsen, Martin Jakob

    2016-01-01

    Next generation sequencing is extensively applied to catalogue somatic mutations in cancer, in research settings and increasingly in clinical settings for molecular diagnostics, guiding therapy decisions. Somatic variant callers perform paired comparisons of sequencing data from cancer tissue and matched normal tissue in order to detect somatic mutations. The advent of many new somatic variant callers creates a need for comparison and validation of the tools, as no de facto standard for detection of somatic mutations exists and only limited comparisons have been reported. We have performed a comprehensive evaluation using exome sequencing and targeted deep sequencing data of paired tumor-normal samples from five breast cancer patients to evaluate the performance of nine publicly available somatic variant callers: EBCall, Mutect, Seurat, Shimmer, Indelocator, Somatic Sniper, Strelka, VarScan 2 and Virmid for the detection of single nucleotide mutations and small deletions and insertions. We report a large variation in the number of calls from the nine somatic variant callers on the same sequencing data and highly variable agreement. Sequencing depth had markedly diverse impact on individual callers, as for some callers, increased sequencing depth highly improved sensitivity. For SNV calling, we report EBCall, Mutect, Virmid and Strelka to be the most reliable somatic variant callers for both exome sequencing and targeted deep sequencing. For indel calling, EBCall is superior due to high sensitivity and robustness to changes in sequencing depths. PMID:27002637

  9. Germline and somatic mutations in meningiomas.

    PubMed

    Smith, Miriam J

    2015-04-01

    Meningiomas arise from the arachnoid layer of the meninges that surround the brain and spine. They account for over one third of all primary central nervous system tumors in adults and confer a significant risk of location-dependent morbidity due to compression or displacement. A significant increase in risk of meningiomas is associated with neurofibromatosis type 2 (NF2) disease through mutation of the NF2 gene. In addition, approximately 5% of individuals with schwannomatosis disease develop meningiomas, through mutation of the SWI/SNF chromatin remodeling complex subunit, SMARCB1. Recently, a second SWI/SNF complex subunit, SMARCE1, was identified as a cause of clear cell meningiomas, indicating a wider role for this complex in meningioma disease. The sonic hedgehog (SHH)-GLI1 signaling pathway gene, SUFU, has also been identified as the cause of hereditary multiple meningiomas in a large Finnish family. The recent identification of somatic mutations in components of the SHH-GLI1 and AKT1-MTOR signaling pathways indicates the potential for cross talk of these pathways in the development of meningiomas. This review describes the known meningioma predisposition genes and their links to the recently identified somatic mutations. PMID:25857641

  10. [Behavioral somatic disorders in hospitalized children].

    PubMed

    Guasco, G; Gugliada, D; Gamalero, G

    1989-01-01

    The research has investigated the occurrence of somatic and behavioural disorders in 100 hospitalised children. A hundred subjects, 55 males & 45 females, aged between 6 and 14 years were asked to fill in questionnaires. These, which were of a completely new type, related to 12 situations in a typical day. The results showed statistically significant differences between the two sexes. Girls manifested a much higher percentage of disorders than did boys. Further, young children and especially pre-adolescents (subjects aged 10-11) manifested more disturbances than did those in the adolescent category. Of the subjects 32% showed a number of disorders below the norm; 36% of the cases were within normal values, 17% were above the norm and the remaining 15% of the subjects were considered to be of particular interest. The most frequent somatic disorders were in heart-rate variations, abnormal sweating (especially of the hands when being orally tested at school), abdominal-aches and headaches. Of the behavioural disorders the most frequent were in the inability to stand still and nail-biting. Also worthy of note, though less frequent, were disorders in eating and in sleeping. It was especially at the end of the day ("before going to sleep") that all these problems occurred. They were also frequent, however, during the periods "at school", "during oral tests" and "watching television". The results obtained in parallel research on 125 primary school children confirm all of the above findings. PMID:2636381

  11. Somatic embryogenesis in Picea suspension cultures.

    PubMed

    Stasolla, Claudio

    2006-01-01

    Generation of somatic embryos in spruce is achieved through the execution of five steps designated as: (1) induction of embryogenic tissue, (2) maintenance of embryogenic tissue, (3) embryo development, (4) embryo maturation, and (5) conversion into plants. Depending on species and genotypes within the same species, each step must be optimized for obtaining maximum results. In general, embryogenic tissue is generated from immature and mature zygotic embryos and maintained in either liquid or solid conditions in the presence of plant growth regulators auxin and cytokinin. Initiation of embryo development in suspension cultured is induced by removal of plant growth regulators, whereas continuation of development and completion of maturation require applications of abscisic acid and imposition of a desiccation period. Both treatments are needed for conferring morphological and physiological maturation to the embryos. Mature somatic embryos are germinated in the absence of plant regulators and embryo conversion (i.e., formation of a functional shoot and root, occurs after a few weeks in culture). PMID:16673908

  12. Reprogramming of human somatic cells by bacteria.

    PubMed

    Ito, Naofumi; Ohta, Kunimasa

    2015-05-01

    In general, it had been believed that the cell fate restriction of terminally differentiated somatic cells was irreversible. In 1952, somatic cell nuclear transfer (SCNT) was introduced to study early embryonic development in frogs. So far, various mammalian species have been successfully cloned using the SCNT technique, though its efficiency is very low. Embryonic stem (ES) cells were the first pluripotent cells to be isolated from an embryo and have a powerful potential to differentiate into more than 260 types of cells. The generation of induced pluripotent stem (iPS) cells was a breakthrough in stem cell research, and the use of these iPS cells has solved problems such as low efficiency and cell fate restriction. These cells have since been used for clinical application, disease investigation, and drug selection. As it is widely accepted that the endosymbiosis of Archaea into eukaryotic ancestors resulted in the generation of eukaryotic cells, we examined whether bacterial infection could alter host cell fate. We previously showed that when human dermal fibroblast (HDF) cells were incorporated with lactic acid bacteria (LAB), the LAB-incorporated HDF cells formed clusters and expressed a subset of common pluripotent markers. Moreover, LAB-incorporated cell clusters could differentiate into cells derived from each of the three germinal layers both in vivo and in vitro, indicating successful reprogramming of host HDF cells by LAB. In the current review, we introduce the existing examples of cellular reprogramming by bacteria and discuss their nuclear reprogramming mechanisms. PMID:25866152

  13. Aneuploidy in mammalian somatic cells in vivo.

    PubMed

    Cimino, M C; Tice, R R; Liang, J C

    1986-01-01

    Aneuploidy is an important potential source of human disease and of reproductive failure. Nevertheless, the ability of chemical agents to induce aneuploidy has been investigated only sporadically in intact (whole-animal) mammalian systems. A search of the available literature from the EMCT Aneuploidy File (for years 1970-1983) provided 112 papers that dealt with aneuploidy in mammalian somatic cells in vivo. 59 of these papers did not meet minimal criteria for analysis and were rejected from subsequent review. Of the remaining 53 papers that dealt with aneuploidy induction by chemical agents in mammalian somatic cells in vivo, only 3 (6%) contained data that were considered to be supported conclusively by adequate study designs, execution, and reporting. These 3 papers dealt with 2 chemicals, one of which, mercury, was negative for aneuploidy induction in humans, and the other, pyrimethamine, was positive in an experimental rodent study. The majority of papers (94%) were considered inconclusive for a variety of reasons. The most common reasons for calling a study inconclusive were (a) combining data on hyperploidy with those on hypoploidy and/or polyploidy, (b) an inadequate or unspecified number of animals and/or cells per animal scored per treatment group, and (c) poor data presentation such that animal-to-animal variability could not be assessed. Suggestions for protocol development are made, and the future directions of research into aneuploidy induction are discussed. PMID:3941670

  14. Transcription Driven Somatic DNA Methylation within the Imprinted Gnas Cluster

    PubMed Central

    Mehta, Stuti; Williamson, Christine M.; Ball, Simon; Tibbit, Charlotte; Beechey, Colin; Fray, Martin; Peters, Jo

    2015-01-01

    Differential marking of genes in female and male gametes by DNA methylation is essential to genomic imprinting. In female gametes transcription traversing differentially methylated regions (DMRs) is a common requirement for de novo methylation at DMRs. At the imprinted Gnas cluster oocyte specific transcription of a protein-coding transcript, Nesp, is needed for methylation of two DMRs intragenic to Nesp, namely the Nespas-Gnasxl DMR and the Exon1A DMR, thereby enabling expression of the Gnas transcript and repression of the Gnasxl transcript. On the paternal allele, Nesp is repressed, the germline DMRs are unmethylated, Gnas is repressed and Gnasxl is expressed. Using mutant mouse models, we show that on the paternal allele, ectopic transcription of Nesp traversing the intragenic Exon1A DMR (which regulates Gnas expression) results in de novo methylation of the Exon1A DMR and de-repression of Gnas just as on the maternal allele. However, unlike the maternal allele, methylation on the mutant paternal allele occurs post-fertilisation, i.e. in somatic cells. This, to our knowledge is the first example of transcript/transcription driven DNA methylation of an intragenic CpG island, in somatic tissues, suggesting that transcription driven de novo methylation is not restricted to the germline in the mouse. Additionally, Gnasxl is repressed on a paternal chromosome on which Nesp is ectopically expressed. Thus, a paternally inherited Gnas cluster showing ectopic expression of Nesp is “maternalised” in terms of Gnasxl and Gnas expression. We show that these mice have a phenotype similar to mutants with two expressed doses of Gnas and none of Gnasxl. PMID:25659103

  15. Loss of CMD2-mediated resistance to cassava mosaic disease in plants regenerated through somatic embryogenesis.

    PubMed

    Beyene, Getu; Chauhan, Raj Deepika; Wagaba, Henry; Moll, Theodore; Alicai, Titus; Miano, Douglas; Carrington, James C; Taylor, Nigel J

    2016-09-01

    Cassava mosaic disease (CMD) and cassava brown streak disease (CBSD) are the two most important viral diseases affecting cassava production in Africa. Three sources of resistance are employed to combat CMD: polygenic recessive resistance, termed CMD1, the dominant monogenic type, named CMD2, and the recently characterized CMD3. The farmer-preferred cultivar TME 204 carries inherent resistance to CMD mediated by CMD2, but is highly susceptible to CBSD. Selected plants of TME 204 produced for RNA interference (RNAi)-mediated resistance to CBSD were regenerated via somatic embryogenesis and tested in confined field trials in East Africa. Although micropropagated, wild-type TME 204 plants exhibited the expected levels of resistance, all plants regenerated via somatic embryogenesis were found to be highly susceptible to CMD. Glasshouse studies using infectious clones of East African cassava mosaic virus conclusively demonstrated that the process of somatic embryogenesis used to regenerate cassava caused the resulting plants to become susceptible to CMD. This phenomenon could be replicated in the two additional CMD2-type varieties TME 3 and TME 7, but the CMD1-type cultivar TMS 30572 and the CMD3-type cultivar TMS 98/0505 maintained resistance to CMD after passage through somatic embryogenesis. Data are presented to define the specific tissue culture step at which the loss of CMD resistance occurs and to show that the loss of CMD2-mediated resistance is maintained across vegetative generations. These findings reveal new aspects of the widely used technique of somatic embryogenesis, and the stability of field-level resistance in CMD2-type cultivars presently grown by farmers in East Africa, where CMD pressure is high. PMID:26662210

  16. Psychosomatic or allergic symptoms? High levels for somatization in patients with drug intolerance.

    PubMed

    Hassel, Jessica C; Danner, Daniel; Hassel, Alexander J

    2011-10-01

    Patients with dermatological diseases often have associated psychological problems. For patients with allergic diseases, only a few publications have focused on psychological aspects. The objective of this study was to assess the psychometric profile, including somatization, depression, anxiety and health-related quality of life (HRQoL), of patients suffering from drug intolerance or hymenoptera venom allergies. In a prospective cohort study design, patients who were admitted to hospital for a challenge test for an alternative drug (n = 49, 24.5% men) or for induction of desensitization therapy with hymenoptera venom (n = 58, 37.9% men) were included. Psychometric screening questionnaires focusing on somatization (Symptom Check List), depression and anxiety (Hospital Anxiety Depression Scale), and also on HRQoL (Short Form questionnaire) were assessed. The scores were compared with population scores and between the two groups. Both groups had significantly higher somatization scores (P ≤ 0.003) than the normal population, and the challenge-test group had lower HRQoL than the normal population. Between-group analysis revealed significantly higher somatization scores in the challenge-test group (P = 0.011) and more impaired HRQoL (physical health domain P < 0.001). Anxiety/depression scores were not significantly different from those of the normal population, or between groups, although abnormally high scores for anxiety were frequent (18% and 12% for the challenge-test and allergy groups, respectively). Somatization, reduced HRQoL and anxiety seem to be part of the symptoms of patients with allergic diseases, especially for patients with drug intolerance. Standardized questionnaires could help to discover patients who may need psychological support. This may help to improve the patients' symptoms and quality of life. PMID:21767296

  17. A new crystal form of human tear lipocalin reveals high flexibility in the loop region and induced fit in the ligand cavity

    SciTech Connect

    Breustedt, Daniel A.; Chatwell, Lorenz; Skerra, Arne

    2009-10-01

    The crystal structure of tear lipocalin determined in space group P2{sub 1} revealed large structural deviations from the previously solved X-ray structure in space group C2, especially in the loop region and adjoining parts of the β-barrel which give rise to the ligand-binding site. These findings illustrate a novel mechanism for promiscuity in ligand recognition by the lipocalin protein family. Tear lipocalin (TLC) with the bound artificial ligand 1,4-butanediol has been crystallized in space group P2{sub 1} with four protein molecules in the asymmetric unit and its X-ray structure has been solved at 2.6 Å resolution. TLC is a member of the lipocalin family that binds ligands with diverse chemical structures, such as fatty acids, phospholipids and cholesterol as well as microbial siderophores and the antibiotic rifampin. Previous X-ray structural analysis of apo TLC crystallized in space group C2 revealed a rather large bifurcated ligand pocket and a partially disordered loop region at the entrace to the cavity. Analysis of the P2{sub 1} crystal form uncovered major conformational changes (i) in β-strands B, C and D, (ii) in loops 1, 2 and 4 at the open end of the β-barrel and (iii) in the extended C-terminal segment, which is attached to the β-barrel via a disulfide bridge. The structural comparison indicates high conformational plasticity of the loop region as well as of deeper parts of the ligand pocket, thus allowing adaptation to ligands that differ vastly in size and shape. This illustrates a mechanism for promiscuity in ligand recognition which may also be relevant for some other physiologically important members of the lipocalin protein family.

  18. Localization of 5S and 25S rRNA genes on somatic and meiotic chromosomes in Capsicum species of chili pepper.

    PubMed

    Kwon, Jin-Kyung; Kim, Byung-Dong

    2009-02-28

    The loci of the 5S and 45S rRNA genes were localized on chromosomes in five species of Capsicum, namely, annuum, chacoense, frutescens, baccatum, and chinense by FISH. The 5S rDNA was localized to the distal region of one chromosome in all species observed. The number of 45S rDNA loci varied among species; one in annuum, two in chacoense, frutescens, and chinense, and four in baccatum, with the exceptions that 'CM334' of annuum had three loci and 'tabasco' of frutescens had one locus. 'CM334'-derived BAC clones, 384B09 and 365P05, were screened with 5S rDNA as a probe, and BACs 278M03 and 262A23 were screened with 25S rDNA as a probe. Both ends of these BAC clones were sequenced. FISH with these BAC probes on pachytenes from 'CM334' plant showed one 5S rDNA locus and three 45S rDNA loci, consistent with the patterns on the somatic chromosomes. The 5S rDNA probe was also applied on extended DNA fibers to reveal that its coverage measured as long as 0.439 Mb in the pepper genome. FISH techniques applied on somatic and meiotic chromosomes and fibers have been established for chili to provide valuable information about the copy number variation of 45S rDNA and the actual physical size of the 5S rDNA in chili. PMID:19277503

  19. The somatic marker theory in the context of addiction: contributions to understanding development and maintenance.

    PubMed

    Olsen, Vegard V; Lugo, Ricardo G; Sütterlin, Stefan

    2015-01-01

    Recent theoretical accounts of addiction have acknowledged that addiction to substances and behaviors share inherent similarities (eg, insensitivity to future consequences and self-regulatory deficits). This recognition is corroborated by inquiries into the neurobiological correlates of addiction, which has indicated that different manifestations of addictive pathology share common neural mechanisms. This review of the literature will explore the feasibility of the somatic marker hypothesis as a unifying explanatory framework of the decision-making deficits that are believed to be involved in addiction development and maintenance. The somatic marker hypothesis provides a neuroanatomical and cognitive framework of decision making, which posits that decisional processes are biased toward long-term prospects by emotional marker signals engendered by a neuronal architecture comprising both cortical and subcortical circuits. Addicts display markedly impulsive and compulsive behavioral patterns that might be understood as manifestations of decision-making processes that fail to take into account the long-term consequences of actions. Evidence demonstrates that substance dependence, pathological gambling, and Internet addiction are characterized by structural and functional abnormalities in neural regions, as outlined by the somatic marker hypothesis. Furthermore, both substance dependents and behavioral addicts show similar impairments on a measure of decision making that is sensitive to somatic marker functioning. The decision-making deficits that characterize addiction might exist a priori to addiction development; however, they may be worsened by ingestion of substances with neurotoxic properties. It is concluded that the somatic marker model of addiction contributes a plausible account of the underlying neurobiology of decision-making deficits in addictive disorders that is supported by the current neuroimaging and behavioral evidence. Implications for future

  20. The somatic marker theory in the context of addiction: contributions to understanding development and maintenance

    PubMed Central

    Olsen, Vegard V; Lugo, Ricardo G; Sütterlin, Stefan

    2015-01-01

    Recent theoretical accounts of addiction have acknowledged that addiction to substances and behaviors share inherent similarities (eg, insensitivity to future consequences and self-regulatory deficits). This recognition is corroborated by inquiries into the neurobiological correlates of addiction, which has indicated that different manifestations of addictive pathology share common neural mechanisms. This review of the literature will explore the feasibility of the somatic marker hypothesis as a unifying explanatory framework of the decision-making deficits that are believed to be involved in addiction development and maintenance. The somatic marker hypothesis provides a neuroanatomical and cognitive framework of decision making, which posits that decisional processes are biased toward long-term prospects by emotional marker signals engendered by a neuronal architecture comprising both cortical and subcortical circuits. Addicts display markedly impulsive and compulsive behavioral patterns that might be understood as manifestations of decision-making processes that fail to take into account the long-term consequences of actions. Evidence demonstrates that substance dependence, pathological gambling, and Internet addiction are characterized by structural and functional abnormalities in neural regions, as outlined by the somatic marker hypothesis. Furthermore, both substance dependents and behavioral addicts show similar impairments on a measure of decision making that is sensitive to somatic marker functioning. The decision-making deficits that characterize addiction might exist a priori to addiction development; however, they may be worsened by ingestion of substances with neurotoxic properties. It is concluded that the somatic marker model of addiction contributes a plausible account of the underlying neurobiology of decision-making deficits in addictive disorders that is supported by the current neuroimaging and behavioral evidence. Implications for future

  1. Crystal structures of the F and pSLT plasmid TraJ N-terminal regions reveal similar homodimeric PAS folds with functional interchangeability

    SciTech Connect

    Lu, Jun; Wu, Ruiying; Adkins, Joshua N.; Joachimiak, Andrzej; Glover, Mark

    2014-09-16

    In the F-family of conjugative plasmids, TraJ is an essential transcriptional activator of the tra operon that encodes most of the proteins required for conjugation. Here we report for the first time the X-ray crystal structures of the TraJ N-terminal regions from the prototypic F plasmid (TraJF11-130) and from the Salmonella virulence plasmid pSLT (TraJpSLT 1-128). Both proteins form similar homodimeric Per-ARNT-Sim (PAS) fold structures. Mutational analysis reveals that the observed dimeric interface is critical for TraJF transcriptional activation, indicating that dimerization of TraJ is required for its in vivo function. An artificial ligand (oxidized dithiothreitol) occupies a cavity in the TraJF dimer interface, while a smaller cavity in corresponding region of the TraJpSLT structure lacks a ligand. Gas chromatography/mass spectrometry-electron ionization analysis of dithiothreitol-free TraJF suggests indole may be the natural TraJ ligand; however, disruption of the indole biosynthetic pathway does not affect TraJF function. Heterologous PAS domains from pSLT and R100 TraJ can functionally replace the TraJF PAS domain, suggesting that TraJ allelic specificity is mediated by the region C-terminal to the PAS domain.

  2. Slow Narrow Spectral Width E Region Echoes Observed During the March 17-2015 Storm and What They Reveal About the Disturbed Ionosphere.

    NASA Astrophysics Data System (ADS)

    St-Maurice, J. P.; Chau, J. L.

    2015-12-01

    As auroral-type disturbances moved equatorward during the March 17-2015 storm, coherent E region echoes were observed simultaneously with three radar links separated by 40 km each in the east-west direction in northern Germany. One radar operated at 36.2, and the other two at 32.55 MHz. One of the latter operated in a bistatic configuration. On each radar site five separate antennas were used to locate the echoes using interferometry. The unique configuration provided an unsurpassed opportunity to study the origin and evolution of ionospheric structures in a wide field of view during a strong storm. A most noticeable feature was that over a few time intervals, several minutes in duration each, very narrow spectra were observed, with Doppler shifts roughly 1/2 the ion-acoustic speed (often called "type III" echoes in the past). The inferred location indicated that the echoes came from below 100 km altitude. Echoes moving at the nominal ion-acoustic speed came from higher up and/or different flow angles. In one particularly clear instance the "Type III" echo region came from a region 50 to 75 km in extent drifting at roughly 1.5 km/s, while moving at some small (but non-zero) flow angle with respect to the line-of-sight. In view of the observations, a reevaluation of existing theories indicates that the echoes cannot be related to ion cyclotron waves. Instead, their low altitude and flow angle dependence reveal that they are the by-product of the ion Pedersen instability, which has been investigated by a few groups in relation to a non-isothermal treatment of the Farley-Buneman instability. In our present treatment of the problem, nonlinear effects are invoked to compute the final Doppler shift of the resulting structures. We find that the stronger the electric field is, the closer the region of slow echoes has to be to the ExB direction. In our most dramatic example of Type III structures, the size of the echo region pointed to a region of high energy precipitation

  3. Somatic Symptoms in Children from Three Ethnic Groups.

    ERIC Educational Resources Information Center

    Canino, Glorisa; Gonzalez, Gloria; Ramirez, Rafael

    A study compared the rates of somatic symptoms associated with anxiety disorder in African Americans, Hispanics residing in Puerto Rico, and European American children. A total of 1,285 children were interviewed, along with their primary caretakers. Headaches were the most frequently endorsed somatic symptom, with half of the total sample…

  4. Human somatic cell nuclear transfer is alive and well.

    PubMed

    Cibelli, Jose B

    2014-06-01

    In this issue, Chung et al. (2014) generate human embryonic stem cells by fusing an adult somatic cell to a previously enucleated human oocyte, in agreement with recent reports by the Mitalipov and Egli groups. We can now safely say that human somatic cell nuclear transfer is alive and well. PMID:24905159

  5. Expressive Writing Intervention for Adolescents' Somatic Symptoms and Mood

    ERIC Educational Resources Information Center

    Soliday, Elizabeth; Garofalo, John P.; Rogers, Debra

    2004-01-01

    The effects of a widely used expressive writing intervention on adolescents' somatic symptoms, distress, and positive psychological functioning were evaluated. Eighth-grade (n = 106) students were randomly assigned to write about either an emotional or a neutral topic for 3 consecutive days. Students completed measures of somatic symptoms, medical…

  6. Development of the Ghent Multidimensional Somatic Complaints Scale

    ERIC Educational Resources Information Center

    Beirens, Koen; Fontaine, Johnny R. J.

    2010-01-01

    The present study aimed at developing a new scale that operationalizes a hierarchical model of somatic complaints. First, 63 items representing a wide range of symptoms and sensations were compiled from somatic complaints scales and emotion literature. These complaints were rated by Belgian students (n = 307) and Belgian adults (n = 603).…

  7. Changes in somatic cell structure during senescence of Volvox carteri.

    PubMed

    Pommerville, J C; Kochert, G D

    1981-06-01

    Senescence of the terminally differentiated somatic cells of the green alga, Volvox carteri f. weismannia, was investigated by light, fluorescence, and electron microscopy. Viability of the somatic cell population, as determined by trypan blue or erythrosin B exclusion, showed a sharp reduction beginning 144 h after the somatic cells had lost the ability to divide. This increased mortality rate was correlated at the light microscopic level with a retraction of the somatic cell cytoplasm, a reduction in chloroplast autofluorescence (and total chlorophyll content), and a decline in the number of vacuoles which could be localized with 9-aminoacridine fluorescence microscopy. Nuclear fluorescence with acridine orange remained unaffected during this time. Lipid bodies increased in older cells, and total lipid analysis showed a sharp increase beginning 96 h after the somatic cells had stopped dividing. Electron microscopic comparison between young (48--72 h) and old (168 h) somatic cells showed a disorganization of chloroplast structure, a decline in the number of cytoplasmic ribosomes, and, substantiating the light microscopy, and accumulation of lipid bodies in the cytoplasm of the older cells. The results demonstrate progressive changes in somatic cell structure with age and are suggestive of cells under nutrient stress even though they are in nutrient medium. Therefore senescence and death of the V. carteri somatic cells may be caused, in part, by an inability to take up or utilize nutrients present in the culture medium. PMID:7285941

  8. Somatics in the Dance Studio: Embodying Feminist/Democratic Pedagogy

    ERIC Educational Resources Information Center

    Burnidge, Anne

    2012-01-01

    Since the 1970s, somatics have increasingly become a part of the dance training landscape. Although the psychophysical benefits seem sufficient in themselves to warrant inclusion in dance, this article explores another possible outcome of embracing somatic pedagogical principles, a change that affects not "what" is taught in a dance class, but…

  9. Depression, Health, and Somatic Complaints in Older Adults.

    ERIC Educational Resources Information Center

    Mahurin, Kathleen A.; Gatz, Margaret

    Although depression is considered to be common in the elderly, reliable rates of prevalence are lacking. Studies have shown that age differences on measures of depressive symptomatology can be attributed to higher levels of somatic complaints. In order to examine whether the association between somatic and depressive symptoms varies as a function…

  10. Residues of a proposed gate region in type I ATP-binding cassette import systems are crucial for function as revealed by mutational analysis.

    PubMed

    Weidlich, Daniela; Wiesemann, Nicole; Heuveling, Johanna; Wardelmann, Kristina; Landmesser, Heidi; Sani, Katayoun Behnam; Worth, Catherine L; Preissner, Robert; Schneider, Erwin

    2013-09-01

    The type I ATP-binding cassette (ABC) importer for positively charged amino acids of the thermophilic bacterium Geobacillus stearothermophilus consists of the extracellular solute binding protein, ArtJ, and a homodimer each of the transmembrane subunit, ArtM, and the nucleotide-binding and -hydrolyzing subunit, ArtP. We have investigated the functional consequences of mutations affecting conserved residues from two peptide regions in ArtM, recently proposed to form a 'gate' by which access of a substrate to the translocation path is controlled (Hollenstein et al., 2007 [14]). Transporter variants were reconstituted into proteoliposomes and assayed for ArtJ/arginine-stimulated ATPase activity. Replacement of residues from region 1 (Arg-63, Pro-66) caused no or only moderate reduction in ATPase activity. In contrast, mutating residues from gate region 2 (Lys-159, Leu-163) resulted in a substantial increase in ATPase activity which, however, as demonstrated for variants ArtM(K159I) and ArtM(K159E), is not coupled to transport. Replacing homologous residues in the closely related histidine transporter of Salmonella enterica serovar Typhimurium (HisJ-QMP2) caused different phenotypes. Mutation to isoleucine of HisQ(K163) or HisM(H172), both homologous to ArtM(K159), abolished ATPase activity. The mutations most likely caused a structural change as revealed by limited proteolysis. In contrast, substantial, albeit reduced, enzymatic activity was observed with variants of HisQ(L167→G) or HisM(L176→G), both homologous to ArtM(L163). Our study provides the first experimental evidence in favor of a crucial role of residues from the proposed gate region in type I ABC importer function. PMID:23747295

  11. Links among emotional awareness, somatic awareness and autonomic homeostatic processing.

    PubMed

    Kanbara, Kenji; Fukunaga, Mikihiko

    2016-01-01

    Emotional awareness and somatic interoceptive awareness are essential processes for human psychosomatic health. A typical trait of lacking emotional awareness related to psychosomatic symptoms is alexithymia. In contrast, alexisomia refers to the trait of lacking somatic awareness. Links between emotional and somatic awareness and homeostatic processing are also significant for the psychosomatic health. The purpose of the present paper is to review the links among emotional awareness, somatic interoceptive awareness and autonomic homeostatic processing. On the basis of the collected evidence, the following arguments were presented(1): (1) The main subcortical neural substrates for these processes are limbic-related systems, which are also responsible for autonomic functions for optimization of homeostatic efficiency. (2) Considerable studies have shown that autonomic activity and/or reactivity to stress correlate with both emotional and interoceptive awareness. A hypothesis was advocated about the links between the two types of awareness and autonomic function: Autonomic dysfunction, especially high sympathetic tone at baseline and/or attenuated reactivity or variability to stress, appears to be involved in disturbance of emotional and interoceptive awareness. (3) Several studies suggest that a link or a cooperative relationship exists between emotional and somatic awareness, and that somatic awareness is the more fundamental of the two types of awareness. Emotional awareness, somatic awareness and autonomic homeostatic processing generally occur in parallel or concurrently. However, some complex features of pathologies include coexistence of reduced interoceptive awareness and somatosensory amplification. The autonomic homeostatic process is fundamentally involved in emotional and somatic awareness. Investigation of these types of awareness with both neuroimaging evaluations and estimation of peripheral autonomic function are required as next steps for exploration

  12. Calcineurin-NFAT Signaling Controls Somatic Cell Reprogramming in a Stage-Dependent Manner.

    PubMed

    Sun, Ming; Liao, Bing; Tao, Yu; Chen, Hao; Xiao, Feng; Gu, Junjie; Gao, Shaorong; Jin, Ying

    2016-05-01

    Calcineurin-NFAT signaling is critical for early lineage specification of mouse embryonic stem cells and early embryos. However, its roles in somatic cell reprogramming remain unknown. Here, we report that calcineurin-NFAT signaling has a dynamic activity and plays diverse roles at different stages of reprogramming. At the early stage, calcineurin-NFAT signaling is transiently activated and its activation is required for successful reprogramming. However, at the late stage of reprogramming, activation of calcineurin-NFAT signaling becomes a barrier for reprogramming and its inactivation is critical for successful induction of pluripotency. Mechanistically, calcineurin-NFAT signaling contributes to the reprogramming through regulating multiple early events during reprogramming, including mesenchymal to epithelial transition (MET), cell adhesion and emergence of SSEA1(+) intermediate cells. Collectively, this study reveals for the first time the important roles of calcineurin-NFAT signaling during somatic cell reprogramming and provides new insights into the molecular regulation of reprogramming. PMID:26448199

  13. Systematic analysis of somatic mutations impacting gene expression in 12 tumour types

    PubMed Central

    Ding, Jiarui; McConechy, Melissa K.; Horlings, Hugo M.; Ha, Gavin; Chun Chan, Fong; Funnell, Tyler; Mullaly, Sarah C.; Reimand, Jüri; Bashashati, Ali; Bader, Gary D.; Huntsman, David; Aparicio, Samuel; Condon, Anne; Shah, Sohrab P.

    2015-01-01

    We present a novel hierarchical Bayes statistical model, xseq, to systematically quantify the impact of somatic mutations on expression profiles. We establish the theoretical framework and robust inference characteristics of the method using computational benchmarking. We then use xseq to analyse thousands of tumour data sets available through The Cancer Genome Atlas, to systematically quantify somatic mutations impacting expression profiles. We identify 30 novel cis-effect tumour suppressor gene candidates, enriched in loss-of-function mutations and biallelic inactivation. Analysis of trans-effects of mutations and copy number alterations with xseq identifies mutations in 150 genes impacting expression networks, with 89 novel predictions. We reveal two important novel characteristics of mutation impact on expression: (1) patients harbouring known driver mutations exhibit different downstream gene expression consequences; (2) expression patterns for some mutations are stable across tumour types. These results have critical implications for identification and interpretation of mutations with consequent impact on transcription in cancer. PMID:26436532

  14. Somatic cell genetic approaches to Down's syndrome.

    PubMed

    Patterson, D; Jones, C; Scoggin, C; Miller, Y E; Graw, S

    1982-01-01

    Somatic cell genetic analysis of mutants of Chinese hamster ovary cells with deficient purine synthesis and of hybrids between these mutants and human cells is described. Data are presented substantiating that two genes for enzymes of purine synthesis, AdeC and AdeG, can be coordinately regulated in mammalian cells. Analysis of a human-hamster hybrid cell, Ade C/21, which contains a normal complement of hamster chromosomes and human chromosome 21 as its only human genetic component recognizable by electrophoretic and immunogenetic techniques demonstrates that genes associated with the presence of human chromosome 21 and required for the synthesis of specific polypeptides and specific human lethal cell surface antigens can be detected in these hybrids. PMID:6217778

  15. The Somatic Genomic Landscape of Glioblastoma

    PubMed Central

    Brennan, Cameron W.; Verhaak, Roel G.W.; McKenna, Aaron; Campos, Benito; Noushmehr, Houtan; Salama, Sofie R.; Zheng, Siyuan; Chakravarty, Debyani; Sanborn, J. Zachary; Berman, Samuel H.; Beroukhim, Rameen; Bernard, Brady; Wu, Chang-Jiun; Genovese, Giannicola; Shmulevich, Ilya; Barnholtz-Sloan, Jill; Zou, Lihua; Vegesna, Rahulsimham; Shukla, Sachet A.; Ciriello, Giovanni; Yung, WK; Zhang, Wei; Sougnez, Carrie; Mikkelsen, Tom; Aldape, Kenneth; Bigner, Darell D.; Van Meir, Erwin G.; Prados, Michael; Sloan, Andrew; Black, Keith L.; Eschbacher, Jennifer; Finocchiaro, Gaetano; Friedman, William; Andrews, David W.; Guha, Abhijit; Iacocca, Mary; O’Neill, Brian P.; Foltz, Greg; Myers, Jerome; Weisenberger, Daniel J.; Penny, Robert; Kucherlapati, Raju; Perou, Charles M.; Hayes, D. Neil; Gibbs, Richard; Marra, Marco; Mills, Gordon B.; Lander, Eric; Spellman, Paul; Wilson, Richard; Sander, Chris; Weinstein, John; Meyerson, Matthew; Gabriel, Stacey; Laird, Peter W.; Haussler, David; Getz, Gad; Chin, Lynda

    2013-01-01

    We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer. PMID:24120142

  16. How Somatic Adult Tissues Develop Organizer Activity.

    PubMed

    Vogg, Matthias C; Wenger, Yvan; Galliot, Brigitte

    2016-01-01

    The growth and patterning of anatomical structures from specific cellular fields in developing organisms relies on organizing centers that instruct surrounding cells to modify their behavior, namely migration, proliferation, and differentiation. We discuss here how organizers can form in adult organisms, a process of utmost interest for regenerative medicine. Animals like Hydra and planarians, which maintain their shape and fitness thanks to a highly dynamic homeostasis, offer a useful paradigm to study adult organizers in steady-state conditions. Beside the homeostatic context, these model systems also offer the possibility to study how organizers form de novo from somatic adult tissues. Both extracellular matrix remodeling and caspase activation play a key role in this transition, acting as promoters of organizer formation in the vicinity of the wound. Their respective roles and the crosstalk between them just start to be deciphered. PMID:26970630

  17. Peculiar high energy cosmic ray stratospheric event reveals a heavy primary origin particle above the knee region of the cosmic ray spectrum

    SciTech Connect

    Kopenkin, V.; Fujimoto, Y.

    2005-01-15

    We wish to put forward an explanation for a peculiar cosmic ray event with energy {sigma}E{sub {gamma}}{>=}2x10{sup 15} eV detected in 1975 by the balloon borne emulsion chamber experiment performed in the stratosphere, at the altitude {>=}30 km above sea level. For almost 30 years the event has been described as unusual, invoking new exotic mechanisms or models. In our opinion there is no need for an extraordinary explanation. Contrary to the widespread belief, the event gives us an example of 'unrecognized standard physics'. At the same time this event revealed a variety of features which are of considerable interest for cosmic rays, nuclear physics, and astrophysics. Here we show that the observed family is most likely to be a result of a heavy nucleus interaction with an air nucleus. In this case a primary particle would originally have been in the energy region above 'the knee' of the cosmic ray spectrum.

  18. Effect of ploidy increase on transgene expression: example from Citrus diploid cybrid and allotetraploid somatic hybrid expressing the EGFP gene.

    PubMed

    Xu, Shi-Xiao; Cai, Xiao-Dong; Tan, Bin; Li, Ding-Li; Guo, Wen-Wu

    2011-07-01

    Polyploidization is an important speciation mechanism for all eukaryotes, and it has profound impacts on biodiversity dynamics and ecosystem functioning. Green fluorescent protein (GFP) has been used as an effective marker to visually screen somatic hybrids at an early stage in protoplast fusion. We have previously reported that the intensity of GFP fluorescence of regenerated embryoids was also an early indicator of ploidy level. However, little is known concerning the effects of ploidy increase on the GFP expression in citrus somatic hybrids at the plant level. Herein, allotetraploid and diploid cybrid plants with enhanced GFP (EGFP) expression were regenerated from the fusion of embryogenic callus protoplasts from 'Murcott' tangor (Citrus reticulata Blanco × Citrus sinensis (L.) Osbeck) and mesophyll protoplasts from transgenic 'Valencia' orange (C. sinensis (L.) Osbeck) expressing the EGFP gene, via electrofusion. Subsequent simple sequence repeat (SSR), chloroplast simple sequence repeat and cleaved amplified polymorphic sequence analysis revealed that the two regenerated tetraploid plants were true allotetraploid somatic hybrids possessing nuclear genomic DNA of both parents and cytoplasmic DNA from the callus parent, while the five regenerated diploid plants were cybrids containing nuclear DNA of the leaf parent and with complex segregation of cytoplasmic DNA. Furthermore, EGFP expression was compared in cells and protoplasts from mature leaves of these diploid cybrids and allotetraploid somatic hybrids. Results showed that the intensity of GFP fluorescence per cell or protoplast in diploid was generally brighter than in allotetraploid. Moreover, same hybridization signal was detected on allotetraploid and diploid plants by Southern blot analysis. By real-time RT-PCR and Western blot analysis, GFP expression level of the diploid cybrid was revealed significantly higher than that of the allotetraploid somatic hybrid. These results suggest that ploidy

  19. Fault structure and kinematics of the Long Valley Caldera region, California, revealed by high-accuracy earthquake hypocenters and focal mechanism stress inversions

    USGS Publications Warehouse

    Prejean, S.; Ellsworth, W.; Zoback, M.; Waldhauser, F.

    2002-01-01

    We have determined high-resolution hypocenters for 45,000+ earthquakes that occurred between 1980 and 2000 in the Long Valley caldera area using a double-difference earthquake location algorithm and routinely determined arrival times. The locations reveal numerous discrete fault planes in the southern caldera and adjacent Sierra Nevada block (SNB). Intracaldera faults include a series of east/west-striking right-lateral strike-slip faults beneath the caldera's south moat and a series of more northerly striking strike-slip/normal faults beneath the caldera's resurgent dome. Seismicity in the SNB south of the caldera is confined to a crustal block bounded on the west by an east-dipping oblique normal fault and on the east by the Hilton Creek fault. Two NE-striking left-lateral strike-slip faults are responsible for most seismicity within this block. To understand better the stresses driving seismicity, we performed stress inversions using focal mechanisms with 50 or more first motions. This analysis reveals that the least principal stress direction systematically rotates across the studied region, from NE to SW in the caldera's south moat to WNW-ESE in Round Valley, 25 km to the SE. Because WNW-ESE extension is characteristic of the western boundary of the Basin and Range province, caldera area stresses appear to be locally perturbed. This stress perturbation does not seem to result from magma chamber inflation but may be related to the significant (???20 km) left step in the locus of extension along the Sierra Nevada/Basin and Range province boundary. This implies that regional-scale tectonic processes are driving seismic deformation in the Long Valley caldera.

  20. Evidence of canonical somatic hypermutation in hairy cell leukemia

    PubMed Central

    Arons, Evgeny; Roth, Laura; Sapolsky, Jeffrey; Suntum, Tara; Stetler-Stevenson, Maryalice

    2011-01-01

    To compare hairy cell leukemia (HCL) with chronic lymphocytic leukemia (CLL) and normal B cells with respect to their B-cell receptors, somatic hypermutation (SHM) features in HCL were examined in a series of 130 immunoglobulin gene heavy chain rearrangements, including 102 from 100 classic (HCLc) and 28 from 26 variant (HCLv) patients. The frequency of unmutated rearrangements in HCLc was much lower than that in HCLv (17% vs 54%, P < .001) or historically in CLL (17% vs 46%, P < .001), but HCLv and CLL were similar (P = .45). As previously reported for CLL, evidence of canonical SHM was observed in HCLc rearrangements, including: (1) a higher ratio of replacement to silent mutations in the complementarity determining regions than in the framework regions (2.83 vs 1.41, P < .001), (2) higher transition to transversion ratio than would be expected if mutations were random (1.49 vs 0.5, P < .001), and (3) higher than expected concentration of mutations within RGYW hot spots (13.92% vs 3.33%, P < .001). HCLv met these 3 criteria of canonical SHM to a lesser extent. These data suggest that, whereas HCLc cells may recognize antigen-like CLL and normal B cells before malignant transformation, HCLv cells from some patients may originate differently, possibly without undergoing antigen recognition. PMID:21368287

  1. Meta-analysis of the TNFAIP3 region in psoriasis reveals a risk haplotype that is distinct from other autoimmune diseases.

    PubMed

    Nititham, J; Taylor, K E; Gupta, R; Chen, H; Ahn, R; Liu, J; Seielstad, M; Ma, A; Bowcock, A M; Criswell, L A; Stahle, M; Liao, W

    2015-03-01

    Tumor necrosis factor alpha-inducible protein 3 (TNFAIP3) encodes a ubiquitin-modifying protein, A20, that is a critical regulator of inflammatory responses. TNFAIP3 polymorphisms are associated with the susceptibility to multiple autoimmune diseases (AIDs) including psoriasis, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis and celiac disease. In order to refine the TNFAIP3 association signal in psoriasis and identify candidate causal variants, we performed imputation and meta-analysis of the TNFAIP3 region in five European ancestry cohorts totaling 4704 psoriasis cases and 7805 controls. We identified 49 variants whose significance exceeded a corrected Bonferroni threshold, with the top variant being rs582757 (P = 6.07 × 10(-12), odds ratio (OR) = 1.23). Conditional analysis revealed a suggestive independent association at rs6918329 (P(cond) = 7.22 × 10(-5), OR = 1.15). Functional annotation of the top variants identified several with a strong evidence of regulatory potential and several within long noncoding RNAs. Analysis of TNFAIP3 haplotypes revealed that the psoriasis risk haplotype is distinct from other AIDs. Overall, our findings identify novel candidate causal variants of TNFAIP3 in psoriasis and highlight the complex genetic architecture of this locus in autoimmune susceptibility. PMID:25521225

  2. Meta-Analysis of the TNFAIP3 Region in Psoriasis Reveals a Risk Haplotype that is Distinct from Other Autoimmune Diseases

    PubMed Central

    Nititham, Joanne; Taylor, Kimberly E.; Gupta, Rashmi; Chen, Haoyan; Ahn, Richard; Liu, Jianjun; Seielstad, Mark; Ma, Averil; Bowcock, Anne M.; Criswell, Lindsey A.; Stahle, Mona; Liao, Wilson

    2014-01-01

    TNFAIP3 encodes aubiquitin-modifying protein, A20, that is a critical regulator of inflammatory responses. TNFAIP3 polymorphisms are associated with susceptibility to multiple autoimmune diseases including psoriasis, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, and celiac disease. In order to refine the TNFAIP3 association signal in psoriasis and identify candidate causal variants, we performed imputation and meta-analysis of the TNFAIP3 region in five European ancestry cohorts totaling 4,704 psoriasis cases and 7,805 controls. We identified 49 variants whose significance exceeded a corrected Bonferroni threshold, with the top variant being rs582757 (P = 6.07 × 10−12, OR = 1.23). Conditional analysis revealed a suggestive independent association at rs6918329 (Pcond = 7.22 × 10−5, OR=1.15). Functional annotation of the top variants identified several with strong evidence of regulatory potential and several within long non-coding RNAs. Analysis of TNFAIP3 haplotypes revealed that the psoriasis risk haplotype is distinct from other autoimmune diseases. Overall, our findings identify novel candidate causal variants of TNFAIP3 in psoriasis and highlight the complex genetic architecture of this locus in autoimmune susceptibility. PMID:25521225

  3. Analysis of protein coding mutations in hiPSCs and their possible role during somatic cell reprogramming

    PubMed Central

    Ruiz, Sergio; Gore, Athurva; Li, Zhe; Panopoulos, Athanasia D.; Montserrat, Nuria; Fung, Ho-Lim; Giorgetti, Alessandra; Bilic, Josipa; Batchelder, Erika M.; Zaehres, Holm; Schöler, Hans R.; Zhang, Kun; Belmonte, Juan Carlos Izpisua

    2013-01-01

    Recent studies indicate that human induced pluripotent stem cells (hiPSCs) contain genomic structural variations and point mutations in coding regions. However, these studies have focused on fibroblast-derived hiPSCs, and it is currently unknown whether the use of alternative somatic cell sources with varying reprogramming efficiencies would result in different levels of genetic alterations. Here we characterize the genomic integrity of eight hiPSC lines derived from five different non-fibroblast somatic cell types. We show that protein-coding mutations are a general feature of the hiPSC state and are independent of somatic cell source. Furthermore, we analyze a total of 17 point mutations found in hiPSCs and demonstrate that they do not generally facilitate the acquisition of pluripotency and thus are not likely to provide a selective advantage for reprogramming. PMID:23340422

  4. Phylogenetic relationships within the genus Aspidisca (Protozoa, Ciliophora, Euplotida) revealed by ITS1-5.8S-ITS2 region sequences

    NASA Astrophysics Data System (ADS)

    Huang, Jie; Yi, Zhenzhen; Miao, Miao; Al-Rasheid, Khaled A. S.; Song, Weibo

    2011-03-01

    The internal transcribed spacer regions (ITS1 and ITS2) and 5.8S rRNA genes were sequenced in six populations of four Aspidisca species, namely A. leptaspis, A. orthopogon, A. magna and A. aculeata. Phylogenetic trees were constructed by means of Bayesian inference (BI), Maximum Parsimony (MP), Neighbor-Joining (NJ), and Maximum Likelihood (ML) to assess the inter- and intra-species relationships within the genus Aspidisca. All trees show similar topologies with stable supports and indicate that: (1) four well known groups, i.e., Oligotrichia, Stichotrichia, Choreotrichia and Hypotrichia, are distinctly outlined within the class Spirotrichea, and all are monophyletic other than Hypotrichia; (2) members of Aspidisca can be distinguished well, based on the ITS1-5.8S-ITS2 region sequences, and A. leptaspis and A. magna shared a closer relationship than other species; (3) Aspidisca and Euplotes branch early in the subclass Hypotrichia. To compare the phylogenetic relationships based on different genes, SSU rRNA trees were also constructed with nearly the same species inclusion, which revealed different topologies of inter-species, inter-genera and inter-subclasses.

  5. A physically anchored genetic map and linkage to avirulence reveals recombination suppression over the proximal region of Hessian fly chromosome A2.

    PubMed Central

    Behura, Susanta K; Valicente, Fernando H; Rider, S Dean; Shun-Chen, Ming; Jackson, Scott; Stuart, Jeffrey J

    2004-01-01

    Resistance in wheat (Triticum aestivum) to the Hessian fly (Mayetiola destructor), a major insect pest of wheat, is based on a gene-for-gene interaction. Close linkage (3 +/- 2 cM) was discovered between Hessian fly avirulence genes vH3 and vH5. Bulked segregant analysis revealed two DNA markers (28-178 and 23-201) within 10 cM of these loci and only 3 +/- 2 cM apart. However, 28-178 was located in the middle of the short arm of Hessian fly chromosome A2 whereas 23-201 was located in the middle of the long arm of chromosome A2, suggesting the presence of severe recombination suppression over its proximal region. To further test that possibility, an AFLP-based genetic map of the Hessian fly genome was constructed. Fluorescence in situ hybridization of 20 markers on the genetic map to the polytene chromosomes of the Hessian fly indicated good correspondence between the linkage groups and the four Hessian fly chromosomes. The physically anchored genetic map is the first of any gall midge species. The proximal region of mitotic chromosome A2 makes up 30% of its length but corresponded to <3% of the chromosome A2 genetic map. PMID:15166159

  6. A new crystal form of human tear lipocalin reveals high flexibility in the loop region and induced fit in the ligand cavity

    PubMed Central

    Breustedt, Daniel A.; Chatwell, Lorenz; Skerra, Arne

    2009-01-01

    Tear lipocalin (TLC) with the bound artificial ligand 1,4-butanediol has been crystallized in space group P21 with four protein molecules in the asymmetric unit and its X-ray structure has been solved at 2.6 Å resolution. TLC is a member of the lipocalin family that binds ligands with diverse chemical structures, such as fatty acids, phospholipids and cholesterol as well as microbial siderophores and the antibiotic rifampin. Previous X-ray structural analysis of apo TLC crystallized in space group C2 revealed a rather large bifurcated ligand pocket and a partially disordered loop region at the entrace to the cavity. Analysis of the P21 crystal form uncovered major conformational changes (i) in β-strands B, C and D, (ii) in loops 1, 2 and 4 at the open end of the β-­barrel and (iii) in the extended C-terminal segment, which is attached to the β-­barrel via a disulfide bridge. The structural comparison indicates high conformational plasticity of the loop region as well as of deeper parts of the ligand pocket, thus allowing adaptation to ligands that differ vastly in size and shape. This illustrates a mechanism for promiscuity in ligand recognition which may also be relevant for some other physiologically important members of the lipocalin protein family. PMID:19770509

  7. Quantitative meta-analysis of fMRI and PET studies reveals consistent activation in fronto-striatal-parietal regions and cerebellum during antisaccades and prosaccades

    PubMed Central

    Jamadar, Sharna D.; Fielding, Joanne; Egan, Gary F.

    2013-01-01

    The antisaccade task is a classic task of oculomotor control that requires participants to inhibit a saccade to a target and instead make a voluntary saccade to the mirror opposite location. By comparison, the prosaccade task requires participants to make a visually-guided saccade to the target. These tasks have been studied extensively using behavioral oculomotor, electrophysiological, and neuroimaging in both non-human primates and humans. In humans, the antisaccade task is under active investigation as a potential endophenotype or biomarker for multiple psychiatric and neurological disorders. A large and growing body of literature has used functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) to study the neural correlates of the antisaccade and prosaccade tasks. We present a quantitative meta-analysis of all published voxel-wise fMRI and PET studies (18) of the antisaccade task and show that consistent activation for antisaccades and prosaccades is obtained in a fronto-subcortical-parietal network encompassing frontal and supplementary eye fields (SEFs), thalamus, striatum, and intraparietal cortex. This network is strongly linked to oculomotor control and was activated to a greater extent for antisaccade than prosaccade trials. Antisaccade but not prosaccade trials additionally activated dorsolateral and ventrolateral prefrontal cortices. We also found that a number of additional regions not classically linked to oculomotor control were activated to a greater extent for antisaccade vs. prosaccade trials; these regions are often reported in antisaccade studies but rarely commented upon. While the number of studies eligible to be included in this meta-analysis was small, the results of this systematic review reveal that antisaccade and prosaccade trials consistently activate a distributed network of regions both within and outside the classic definition of the oculomotor network. PMID:24137150

  8. Electromobility Shift Assay Reveals Evidence in Favor of Allele-Specific Binding of RUNX1 to the 5' Hypersensitive Site 4-Locus Control Region.

    PubMed

    Dehghani, Hossein; Ghobakhloo, Sepideh; Neishabury, Maryam

    2016-08-01

    In our previous studies on the Iranian β-thalassemia (β-thal) patients, we identified an association between the severity of the β-thal phenotype and the polymorphic palindromic site at the 5' hypersensitive site 4-locus control region (5'HS4-LCR) of the β-globin gene cluster. Furthermore, a linkage disequilibrium was observed between this region and XmnI-HBG2 in the patient population. Based on this data, it was suggested that the well-recognized phenotype-ameliorating role assigned to positive XmnI could be associated with its linked elements in the LCR. To investigate the functional significance of polymorphisms at the 5'HS4-LCR, we studied its influence on binding of transcription factors. Web-based predictions of transcription factor binding revealed a binding site for runt-related transcription factor 1 (RUNX1), when the allele at the center of the palindrome (TGGGG(A/G)CCCCA) was A but not when it was G. Furthermore, electromobility shift assay (EMSA) presented evidence in support of allele-specific binding of RUNX1 to 5'HS4. Considering that RUNX1 is a well-known regulator of hematopoiesis, these preliminary data suggest the importance of further studies to confirm this interaction and consequently investigate its functional and phenotypical relevance. These studies could help us to understand the molecular mechanism behind the phenotype modifying role of the 5'HS4-LCR polymorphic palindromic region (rs16912979), which has been observed in previous studies. PMID:27492765

  9. SomamiR 2.0: a database of cancer somatic mutations altering microRNA-ceRNA interactions.

    PubMed

    Bhattacharya, Anindya; Cui, Yan

    2016-01-01

    SomamiR 2.0 (http://compbio.uthsc.edu/SomamiR) is a database of cancer somatic mutations in microRNAs (miRNA) and their target sites that potentially alter the interactions between miRNAs and competing endogenous RNAs (ceRNA) including mRNAs, circular RNAs (circRNA) and long noncoding RNAs (lncRNA). Here, we describe the recent major updates to the SomamiR database. We expanded the scope of the database by including somatic mutations that impact the interactions between miRNAs and two classes of non-coding RNAs, circRNAs and lncRNAs. Recently, a large number of miRNA target sites have been discovered by newly emerged high-throughput technologies for mapping the miRNA interactome. We have mapped 388 247 somatic mutations to the experimentally identified miRNA target sites. The updated database also includes a list of somatic mutations in the miRNA seed regions, which contain the most important guiding information for miRNA target recognition. A recently developed webserver, miR2GO, was integrated with the database to provide a seamless pipeline for assessing functional impacts of somatic mutations in miRNA seed regions. Data and functions from multiple sources including biological pathways and genome-wide association studies were updated and integrated with SomamiR 2.0 to make it a better platform for functional analysis of somatic mutations altering miRNA-ceRNA interactions. PMID:26578591

  10. Peer emotion socialization and somatic complaints in adolescents.

    PubMed

    Parr, Naomi J; Zeman, Janice; Braunstein, Kara; Price, Natalee

    2016-07-01

    Somatic symptoms tend to increase during early adolescence and although youth's social environments and emotional functioning play a role in somatic symptoms, few studies have examined mechanisms through which social interaction could influence youth's somatic wellbeing. Participants were 132 youth (61.6% girls, Mage = 12.61 years, 84.7% Caucasian) and their mothers. Reciprocated best-friend dyads participated in a video-taped problem discussion task to assess peer emotion socialization responses. Two supportive friend responses (i.e., emotion-focused, problem-focused) and two unsupportive responses (i.e., punitive, neglect) were examined. Mothers reported on their child's somatic complaints. Friends who provided emotion-focused, problem-focused, punitive, and neglect responses to their close friend's emotional disclosures had significantly fewer somatic symptoms. However, youth who received punitive responses to their emotional disclosures from their close friends had more somatic complaints. These findings provide initial evidence of a link between emotion socialization responses within close friendships and somatic complaints in early adolescence. PMID:27176784

  11. Somatic mutations in disorders with disrupted brain connectivity

    PubMed Central

    Lee, Jeong Ho

    2016-01-01

    Mutations occur during cell division in all somatic lineages. Because neurogenesis persists throughout human life, somatic mutations in the brain arise during development and accumulate with the aging process. The human brain consists of 100 billion neurons that form an extraordinarily intricate network of connections to achieve higher level cognitive functions. Due to this network architecture, perturbed neuronal functions are rarely restricted to a focal area; instead, they are often spread via the neuronal network to affect other connected areas. Although somatic diversity is an evident feature of the brain, the extent to which somatic mutations affect the neuronal structure and function and their contribution to neurological disorders associated with disrupted brain connectivity remain largely unexplored. Notably, recent reports indicate that brain somatic mutations can indeed play a critical role that leads to the structural and functional abnormalities of the brain observed in several neurodevelopmental disorders. Here, I review the extent and significance of brain somatic mutations and provide my perspective regarding these mutations as potential molecular lesions underlying relatively common conditions with disrupted brain connectivity. Moreover, I discuss emerging technical platforms that will facilitate the detection of low-frequency somatic mutations and validate the biological functions of the identified mutations in the context of brain connectivity. PMID:27282107

  12. Somatic mutations in disorders with disrupted brain connectivity.

    PubMed

    Lee, Jeong Ho

    2016-01-01

    Mutations occur during cell division in all somatic lineages. Because neurogenesis persists throughout human life, somatic mutations in the brain arise during development and accumulate with the aging process. The human brain consists of 100 billion neurons that form an extraordinarily intricate network of connections to achieve higher level cognitive functions. Due to this network architecture, perturbed neuronal functions are rarely restricted to a focal area; instead, they are often spread via the neuronal network to affect other connected areas. Although somatic diversity is an evident feature of the brain, the extent to which somatic mutations affect the neuronal structure and function and their contribution to neurological disorders associated with disrupted brain connectivity remain largely unexplored. Notably, recent reports indicate that brain somatic mutations can indeed play a critical role that leads to the structural and functional abnormalities of the brain observed in several neurodevelopmental disorders. Here, I review the extent and significance of brain somatic mutations and provide my perspective regarding these mutations as potential molecular lesions underlying relatively common conditions with disrupted brain connectivity. Moreover, I discuss emerging technical platforms that will facilitate the detection of low-frequency somatic mutations and validate the biological functions of the identified mutations in the context of brain connectivity. PMID:27282107

  13. Advances in Conifer Somatic Embryogenesis Since Year 2000.

    PubMed

    Klimaszewska, Krystyna; Hargreaves, Catherine; Lelu-Walter, Marie-Anne; Trontin, Jean-François

    2016-01-01

    This review compiles research results published over the last 14 years on conifer somatic embryogenesis (SE). Emphasis is placed on the newest findings that affect the response of seed embryos (typical explants) and shoot primordia (rare explants) to the induction of SE and long-term culture of early somatic embryos. Much research in recent years has focused on maturation of somatic embryos, with respect to both yield and quality, as an important stage for the production of a large number of vigorous somatic seedlings. Attempts to scale up somatic embryo production numbers and handling have resulted in a few bioreactor designs, the utility of which may prove beneficial for an industrial application. A few simplified cryopreservation methods for embryonal masses (EM) were developed as a means to ensure cost-efficient long-term storage of genotypes during clonal field testing. Finally, recent long-term studies on the growth of somatic trees in the field, including seed production yield and comparison of seed parameters produced by somatic versus seed-derived trees, are described. PMID:26619862

  14. Cognitive Mechanisms Reciprocally Transmit Vulnerability between Depressive and Somatic Symptoms

    PubMed Central

    Harding, Kaitlin A.; Murphy, Karly M.

    2015-01-01

    Despite high comorbidity between depressive and somatic symptoms, cognitive mechanisms that transmit vulnerability between symptom clusters are largely unknown. Dampening, positive rumination, and brooding are three cognitive predictors of depression, with rumination theoretically indicated as a transdiagnostic vulnerability through amplifying and diminishing affect in response to events. Specifically, the excess negative affect and lack of positive affect characteristic of depressive symptoms and underlying somatic symptoms may cause and be caused by cognitive responses to events. Therefore, the current study examined whether comorbidity between depressive and somatic symptoms may be explained by the cognitive mechanisms of dampening and positive rumination in response to positive events and brooding in response to negative events among adults (N = 321) across eight weeks of assessment. We hypothesized that greater dampening and brooding would reciprocally predict greater depressive and somatic symptoms, while greater positive rumination would reciprocally predict fewer depressive and somatic symptoms. Mediation analyses in AMOS 22 indicated that dampening and brooding mediated reciprocal pathways between depressive and somatic symptoms, but positive rumination did not. Findings propose dampening and brooding as mechanisms of the reciprocal relationship between depressive and somatic symptoms through diminishing positive affect and amplifying negative affect in response to positive and negative events. PMID:26783455

  15. Somatic hypermutations and isotype restricted exceptionally long CDR3H contribute to antibody diversification in cattle.

    PubMed

    Kaushik, Azad K; Kehrli, Marcus E; Kurtz, A; Ng, S; Koti, M; Shojaei, F; Saini, Surinder S

    2009-01-15

    Antibody diversification in IgM and IgG antibodies was analyzed in an 18-month old bovine (Bos taurus) suffering from naturally occurring chronic and recurrent infections due to bovine leukocyte adhesion deficiency (BLAD). The BLAD, involving impaired leukocyte beta2 integrin expression on leukocytes, develops due to a single point mutation in conserved region of the CD18 gene resulting in substitution of aspartic acid128 with glycine (D128G). Twenty four VDJCmu and 25 VDJCgamma recombinations from randomly constructed cDNA libraries, originating from peripheral blood lymphocytes, were examined for the variable-region structural characteristics in IgM and IgG antibody isotypes. These analyses led to conclude that: (a) expression of exceptionally long CDR3H is isotype restricted to cattle IgM antibody; (b) VDJ recombinations encoding IgM with exceptionally long CDR3H undergo clonal selection and affinity maturation via somatic mutations similar to conventional antibodies; (c) somatic mutations contribute significantly to both IgM and IgG antibody diversification but significant differences exist in the patterns of 'hot spot' in the FR1, FR3 and CDR1H and, also, position-dependant amino acid diversity; and (d) transition nucleotide substitutions predominate over transversions in both VDJCmu and VDJCgamma recombinations consistent with the evolutionary conservation of somatic mutation machinery. Overall, these studies suggest that both somatic mutations and exceptional CDR3H size generation contribute to IgM and IgG antibody diversification in cattle during the development of immune response to naturally occurring chronic and multiple microbial infections. PMID:19012969

  16. Steroidal glycoalkaloid content of potato, tomato and their somatic hybrids.

    PubMed

    Roddick, J G; Melchers, G

    1985-09-01

    Analyses of leaves and 'tubers' from somatic hybrids of potato and tomato ('pomato' with plastids of potato, 'topato' with plastids of tomato) produced by fusion of protoplasts from liquid cultures of dihaploid potato and mesophyll of tomato revealed the presence of the two major potato glycoalkaloids (α-solanine and α-chaconine) as well as the tomato glycoalkaloid (αtomatine). The total alkaloid content of leaves was greater than that of 'tubers' and similar to levels in the foliage of parent plants. However, glycoalkaloids were more abundant in hybrid 'tubers' than in normal potato tubers by a factor of 5-15. In hybrid foliage, approximately 98% of the alkaloid present was of potato origin whereas in 'tubers' the reverse was the case, with tomatine comprising 60-70% of the total alkaloid. The similarities in alkaloid content and ratios between the pomato and the topato lines indicate that plastomes do not influence the biosynthesis and distribution of these alkaloids. The results indicate that major secondary metabolites may prove useful for assessing the hybrid nature of such plants. PMID:24253124

  17. Imaging Mass Spectrometry Reveals Acyl-Chain- and Region-Specific Sphingolipid Metabolism in the Kidneys of Sphingomyelin Synthase 2-Deficient Mice

    PubMed Central

    Sugimoto, Masayuki; Wakabayashi, Masato; Shimizu, Yoichi; Yoshioka, Takeshi; Higashino, Kenichi; Numata, Yoshito; Okuda, Tomohiko; Zhao, Songji; Sakai, Shota; Igarashi, Yasuyuki; Kuge, Yuji

    2016-01-01

    Obesity was reported to cause kidney injury by excessive accumulation of sphingolipids such as sphingomyelin and ceramide. Sphingomyelin synthase 2 (SMS2) is an important enzyme for hepatic sphingolipid homeostasis and its dysfunction is considered to result in fatty liver disease. The expression of SMS2 is also high in the kidneys. However, the contribution of SMS2 on renal sphingolipid metabolism remains unclear. Imaging mass spectrometry is a powerful tool to visualize the distribution and provide quantitative data on lipids in tissue sections. Thus, in this study, we analyzed the effects of SMS2 deficiency on the distribution and concentration of sphingomyelins in the liver and kidneys of mice fed with a normal-diet or a high-fat-diet using imaging mass spectrometry and liquid chromatography/electrospray ionization-tandem mass spectrometry. Our study revealed that high-fat-diet increased C18–C22 sphingomyelins, but decreased C24-sphingomyelins, in the liver and kidneys of wild-type mice. By contrast, SMS2 deficiency decreased C18–C24 sphingomyelins in the liver. Although a similar trend was observed in the whole-kidneys, the effects were minor. Interestingly, imaging mass spectrometry revealed that sphingomyelin localization was specific to each acyl-chain length in the kidneys. Further, SMS2 deficiency mainly decreased C22-sphingomyelin in the renal medulla and C24-sphingomyelins in the renal cortex. Thus, imaging mass spectrometry can provide visual assessment of the contribution of SMS2 on acyl-chain- and region-specific sphingomyelin metabolism in the kidneys. PMID:27010944

  18. Somatic mutations of DICER1 and KMT2D are frequent in intraocular medulloepitheliomas.

    PubMed

    Sahm, Felix; Jakobiec, Frederick A; Meyer, Jochen; Schrimpf, Daniel; Eberhart, Charles G; Hovestadt, Volker; Capper, David; Lambo, Sander; Ryzhova, Marina; Schüller, Ulrich; Zheludkova, Olga; Kumirova, Ella; Lichter, Peter; von Deimling, Andreas; Jones, David T W; Pfister, Stefan M; Kool, Marcel; Korshunov, Andrey

    2016-05-01

    Intraocular medulloepithelioma (IO-MEPL) is an uncommon embryonal neuroepithelial neoplasm of the eye. Little is known about the cytogenetics, molecular biology, and pathogenesis of this tumor. In the present study we investigated the mutational landscape of 19 IO-MEPL using targeted next-generation sequencing. Routinely prepared paraffin-embedded samples were assessed with high-coverage genome sequencing on the Illumina NextSeq 500 platform using a customized gene panel set covering the coding region of 130 genes. This revealed several notable genomic alterations, including mutations of DICER1 (6 tumors) and KMT2D (also known as MLL2; 5 tumors)-which are frequently recurrent and mutually exclusive molecular events for IO-MEPL. Non-recurrent mutations in the cancer-associated genes BRCA2, BRCA1, NOTCH2, CDH1, and GSE1 were also identified. IO-MEPL samples harboring a DICER1 mutation disclosed few chromosomal alterations and formed a separate DNA methylation cluster, indicating potential differences in genetic and epigenetic events arising perhaps from the presence of this aberration in the tumor genome. The high proportion of recurrent somatic DICER1 and KMT2D mutations in this series of sporadic IO-MEPL points to their likely important roles in the molecular pathogenesis of these rare embryonal tumors, and perhaps suggests the existence of distinct molecular variants of IO-MEPL. Although the precise role of these recurrent mutations in the development of IO-MEPL, and their relationship to pro-oncogenic molecular mechanisms, have yet to be determined, unraveling their roles could eventually be exploited for nonsurgical therapies of these neoplasms. PMID:26841698

  19. Reprogramming somatic cells into iPS cells activates LINE-1 retroelement mobility

    PubMed Central

    Wissing, Silke; Muñoz-Lopez, Martin; Macia, Angela; Yang, Zhiyuan; Montano, Mauricio; Collins, William; Garcia-Perez, Jose Luis; Moran, John V.; Greene, Warner C.

    2012-01-01

    Long interspersed element-1 (LINE-1 or L1) retrotransposons account for nearly 17% of human genomic DNA and represent a major evolutionary force that has reshaped the structure and function of the human genome. However, questions remain concerning both the frequency and the developmental timing of L1 retrotransposition in vivo and whether the mobility of these retroelements commonly results in insertional and post-insertional mechanisms of genomic injury. Cells exhibiting high rates of L1 retrotransposition might be especially at risk for such injury. We assessed L1 mRNA expression and L1 retrotransposition in two biologically relevant cell types, human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), as well as in control parental human dermal fibroblasts (HDFs). Full-length L1 mRNA and the L1 open reading frame 1-encoded protein (ORF1p) were readily detected in hESCs and iPSCs, but not in HDFs. Sequencing analysis proved the expression of human-specific L1 element mRNAs in iPSCs. Bisulfite sequencing revealed that the increased L1 expression observed in iPSCs correlates with an overall decrease in CpG methylation in the L1 promoter region. Finally, retrotransposition of an engineered human L1 element was ∼10-fold more efficient in iPSCs than in parental HDFs. These findings indicate that somatic cell reprogramming is associated with marked increases in L1 expression and perhaps increases in endogenous L1 retrotransposition, which could potentially impact the genomic integrity of the resultant iPSCs. PMID:21989055

  20. Screening for somatic mutations of the neurofibromatosis genes in nervous system and other solid tumors

    SciTech Connect

    Rangaratnam, S.; Narod, S.; Ruttledge, M.

    1994-09-01

    Von Recklinghausen neurofibromatosis (NF1) and neurofibromatosis type 2 (NF2) are autosomal dominant inherited disorders which predispose carriers to various benign and malignant tumors. Both genes are thought to act as tumor suppressors with inactivation of both alleles resulting in abnormal cell growth. By inference from other hereditary cancer syndromes, it has been hypothesized that somatic mutation at the NF1 and NF2 loci is involved in the development of sporadic tumors of the types found with increased prevalence in these disorders. In addition to other malignancies, individuals with NF1 are at increased risk to develop astrocytomas and rhabdomyosarcomas. We have therefore screened 40 astrocytomas for LOH using three NF1-derived cDNA probes, and have found no abnormalities. Single-strand conformation polymorphism (SSCP) analysis of exons of the NF1 GAP-related domain has also failed to show any variants in a total of 70 astrocytomas and 14 rhabdomyosarcomas (7 each of embryonal and alveolar types). LOH of chromosome 22 markers is known to occur in meningioma, malignant melanoma, breast cancer, and ependymoma. SSCP of all 17 exons of the NF2 gene in 27 melanoma cell lines, 42 breast cancers, and 27 pendymomas revealed no alterations. In a screen of 151 menigiomas, 26 new variants have been found, bringing our total to 50 variants in this sample. These represent inactivating mutations (frameshift, splice-site, and nonsense), determined by direct sequencing. Since the majority of these changes occur in tumors previously shown to have LOH at chromosome 22 markers flanking NF2, our results support a tumor sequence role for this gene in meningiomas. In addition, given that 40% of our tumors do not show LOH over this region, we propose that other genes are involved in the development of this latter subset of meningiomas.

  1. Congenital Anomalies and Rhabdoid Tumor Associated with 22q11 Germline Deletion and Somatic Inactivation of the SMARCB1 Tumor Suppressor

    PubMed Central

    Toth, George; Zraly, Claudia B.; Thomson, Tricia L.; Jones, Carolyn; Lapetino, Shawn; Muraskas, Jonathan; Zhang, Jiwang; Dingwall, Andrew K.

    2011-01-01

    The most common microdeletion in humans involves the 22q11 region. Congenital anomalies associated with 22q11 loss include cardiac and facial defects. Less frequent is the co-presentation of malignant rhabdoid tumors that are highly aggressive childhood malignancies typically found in renal or extra-renal soft tissues and central nervous system. A newborn patient presented with multiple congenital anomalies consistent with 22q11 deletion syndrome including cleft lip and palate, ear tags and ventricular septal defects co-presenting with an axillary rhabdoid tumor. Comparative genomic hybridization revealed a 2.8 Mb germline deletion in the 22q11.2 region containing genes required for normal fetal development and the SMARCB1 tumor suppressor gene. Analysis of tumor DNA revealed a somatic deletion of exon 7 in the second allele of SMARCB1. Expression of SMARCB1 was absent, while tumor markers including MYC, GFAP and CLAUDIN-6 were upregulated. The presence of tandem oriented BCRL modules located within interspersed low copy repeat elements throughout the 22q11 distal region may predispose this area for microdeletions through nonalleleic homologous recombination. PMID:21412926

  2. Phenotypes of Aging Postovulatory Oocytes After Somatic Cell Nuclear Transfer in Mice.

    PubMed

    Lee, Ah Reum; Shimoike, Takashi; Wakayama, Teruhiko; Kishigami, Satoshi

    2016-06-01

    Oocytes rapidly lose their developmental potential after ovulation, termed postovulatory oocyte aging, and often exhibit characteristic phenotypes, such as cytofragmentation, abnormal spindle shapes, and chromosome misalignments. Here, we reconstructed mouse oocytes using somatic cell nuclear transfer (SCNT) to reveal the effect of somatic cell-derived nuclei on oocyte physiology during aging. Normal oocytes started undergoing cytofragmentation 24 hours after oocyte collection; however, this occurred earlier in SCNT oocytes and was more severe at 48 hours, suggesting that the transferred somatic cell nuclei affected oocyte physiology. We found no difference in the status of acetylated α-tubulin (Ac-Tub) and α-tubulin (Tub) between normal and SCNT aging oocytes, but unlike normal oocytes, aging SCNT oocytes did not have astral microtubules. Interestingly, aging SCNT oocytes displayed more severely scattered chromosomes or irregularly shaped spindles. Observations of the microfilaments showed that, in normal oocytes, there was a clear actin ring beneath the plasma membrane and condensed microfilaments around the spindle (the actin cap) at 0 hours, and the actin filaments started degenerating at 1 hour, becoming completely disrupted and distributed to the cytoplasm at 24 hours. By contrast, in SCNT oocytes, an actin cap formed around the transplanted nuclei within 1 hour of SCNT, which was still present at 24 hours. Thus, SCNT oocytes age in a similar but distinct way, suggesting that they not only contain nuclei with abnormal epigenetics but are also physiologically different. PMID:27253626

  3. Similar GABAA receptor subunit composition in somatic and axon initial segment synapses of hippocampal pyramidal cells

    PubMed Central

    Kerti-Szigeti, Katalin; Nusser, Zoltan

    2016-01-01

    Hippocampal pyramidal cells (PCs) express many GABAAR subunit types and receive GABAergic inputs from distinct interneurons. Previous experiments revealed input-specific differences in α1 and α2 subunit densities in perisomatic synapses, suggesting distinct IPSC decay kinetics. However, IPSC decays evoked by axo-axonic, parvalbumin- or cholecystokinin-expressing basket cells were found to be similar. Using replica immunogold labeling, here we show that all CA1 PC somatic and AIS synapses contain the α1, α2, β1, β2, β3 and γ2 subunits. In CA3 PCs, 90% of the perisomatic synapses are immunopositive for the α1 subunit and all synapses are positive for the remaining five subunits. Somatic synapses form unimodal distributions based on their immunoreactivity for these subunits. The α2 subunit densities in somatic synapses facing Cav2.1 (i.e. parvalbumin) or Cav2.2 (cholecystokinin) positive presynaptic active zones are comparable. We conclude that perisomatic synapses made by three distinct interneuron types have similar GABAA receptor subunit content. DOI: http://dx.doi.org/10.7554/eLife.18426.001 PMID:27537197

  4. Genetic and epigenetic changes in somatic hybrid introgression lines between wheat and tall wheatgrass.

    PubMed

    Liu, Shuwei; Li, Fei; Kong, Lina; Sun, Yang; Qin, Lumin; Chen, Suiyun; Cui, Haifeng; Huang, Yinghua; Xia, Guangmin

    2015-04-01

    Broad phenotypic variations were induced in derivatives of an asymmetric somatic hybridization of bread wheat (Triticum aestivum) and tall wheatgrass (Thinopyrum ponticum Podp); however, how these variations occurred was unknown. We explored the nature of these variations by cytogenetic assays and DNA profiling techniques to characterize six genetically stable somatic introgression lines. Karyotyping results show the six lines similar to their wheat parent, but GISH analysis identified the presence of a number of short introgressed tall wheatgrass chromatin segments. DNA profiling revealed many genetic and epigenetic differences, including sequences deletions, altered regulation of gene expression, changed patterns of cytosine methylation, and the reactivation of retrotransposons. Phenotypic variations appear to result from altered repetitive sequences combined with the epigenetic regulation of gene expression and/or retrotransposon transposition. The extent of genetic and epigenetic variation due to the maintenance of parent wheat cells in tissue culture was assessed and shown to be considerably lower than had been induced in the introgression lines. Asymmetric somatic hybridization provides appropriate material to explore the nature of the genetic and epigenetic variations induced by genomic shock. PMID:25670745

  5. Ecosensitivity and genetic polymorphism of somatic traits in the perinatal development of twins.

    PubMed

    Waszak, Małgorzata; Cieślik, Krystyna; Skrzypczak-Zielińska, Marzena; Szalata, Marlena; Wielgus, Karolina; Kempiak, Joanna; Bręborowicz, Grzegorz; Słomski, Ryszard

    2016-04-01

    In view of criticism regarding the usefulness of heritability coefficients, the aim of this study was to analyze separately the information on genetic and environmental variability. Such an approach, based on the normalization of trait's variability for its value, is determined by the coefficients of genetic polymorphism (Pg) and ecosensitivity (De). The studied material included 1263 twin pairs of both sexes (among them 424 pairs of monozygotic twins and 839 pairs of dizygotic twins) born between the 22nd and 41st week of gestation. Variability of six somatic traits was analyzed. The zygosity of same-sex twins was determined based on the polymorphism of DNA from lymphocytes of the umbilical cord blood, obtained at birth. The coefficients of genetic polymorphism and ecosensitivity for analyzed traits of male and female twins born at various months of gestation were calculated. Our study revealed that a contribution of the genetic component predominated over that of the environmental component in determining the phenotypic variability of somatic traits of newborns from twin pregnancies. The genetically determined phenotypic variability in male twins was greater than in the females. The genetic polymorphism and ecosensitivity of somatic traits were relatively stable during the period of fetal ontogeny analyzed in this study. Only in the case of body weight, a slight increase in the genetic contribution of polygenes to the phenotypic variance could be observed with gestational age, along with a slight decrease in the influence of environmental factors. PMID:26619791

  6. Genetic and Epigenetic Changes in Somatic Hybrid Introgression Lines Between Wheat and Tall Wheatgrass

    PubMed Central

    Liu, Shuwei; Li, Fei; Kong, Lina; Sun, Yang; Qin, Lumin; Chen, Suiyun; Cui, Haifeng; Huang, Yinghua; Xia, Guangmin

    2015-01-01

    Broad phenotypic variations were induced in derivatives of an asymmetric somatic hybridization of bread wheat (Triticum aestivum) and tall wheatgrass (Thinopyrum ponticum Podp); however, how these variations occurred was unknown. We explored the nature of these variations by cytogenetic assays and DNA profiling techniques to characterize six genetically stable somatic introgression lines. Karyotyping results show the six lines similar to their wheat parent, but GISH analysis identified the presence of a number of short introgressed tall wheatgrass chromatin segments. DNA profiling revealed many genetic and epigenetic differences, including sequences deletions, altered regulation of gene expression, changed patterns of cytosine methylation, and the reactivation of retrotransposons. Phenotypic variations appear to result from altered repetitive sequences combined with the epigenetic regulation of gene expression and/or retrotransposon transposition. The extent of genetic and epigenetic variation due to the maintenance of parent wheat cells in tissue culture was assessed and shown to be considerably lower than had been induced in the introgression lines. Asymmetric somatic hybridization provides appropriate material to explore the nature of the genetic and epigenetic variations induced by genomic shock. PMID:25670745

  7. Similar GABAA receptor subunit composition in somatic and axon initial segment synapses of hippocampal pyramidal cells.

    PubMed

    Kerti-Szigeti, Katalin; Nusser, Zoltan

    2016-01-01

    Hippocampal pyramidal cells (PCs) express many GABAAR subunit types and receive GABAergic inputs from distinct interneurons. Previous experiments revealed input-specific differences in α1 and α2 subunit densities in perisomatic synapses, suggesting distinct IPSC decay kinetics. However, IPSC decays evoked by axo-axonic, parvalbumin- or cholecystokinin-expressing basket cells were found to be similar. Using replica immunogold labeling, here we show that all CA1 PC somatic and AIS synapses contain the α1, α2, β1, β2, β3 and γ2 subunits. In CA3 PCs, 90% of the perisomatic synapses are immunopositive for the α1 subunit and all synapses are positive for the remaining five subunits. Somatic synapses form unimodal distributions based on their immunoreactivity for these subunits. The α2 subunit densities in somatic synapses facing Cav2.1 (i.e. parvalbumin) or Cav2.2 (cholecystokinin) positive presynaptic active zones are comparable. We conclude that perisomatic synapses made by three distinct interneuron types have similar GABAA receptor subunit content. PMID:27537197

  8. Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia

    PubMed Central

    Rajala, Hanna L. M.; Eldfors, Samuli; Kuusanmäki, Heikki; van Adrichem, Arjan J.; Olson, Thomas; Lagström, Sonja; Andersson, Emma I.; Jerez, Andres; Clemente, Michael J.; Yan, Yiyi; Zhang, Dan; Awwad, Andy; Ellonen, Pekka; Kallioniemi, Olli; Wennerberg, Krister; Porkka, Kimmo; Maciejewski, Jaroslaw P.; Loughran, Thomas P.; Heckman, Caroline

    2013-01-01

    Large granular lymphocytic (LGL) leukemia is characterized by clonal expansion of cytotoxic T cells or natural killer cells. Recently, somatic mutations in the signal transducer and activator of transcription 3 (STAT3) gene were discovered in 28% to 40% of LGL leukemia patients. By exome and transcriptome sequencing of 2 STAT3 mutation-negative LGL leukemia patients, we identified a recurrent, somatic missense mutation (Y665F) in the Src-like homology 2 domain of the STAT5b gene. Targeted amplicon sequencing of 211 LGL leukemia patients revealed 2 additional patients with STAT5b mutations (N642H), resulting in a total frequency of 2% (4 of 211) of STAT5b mutations across all patients. The Y665F and N642H mutant constructs increased the transcriptional activity of STAT5 and tyrosine (Y694) phosphorylation, which was also observed in patient samples. The clinical course of the disease in patients with the N642H mutation was aggressive and fatal, clearly different from typical LGL leukemia with a relatively favorable outcome. This is the first time somatic STAT5 mutations are discovered in human cancer and further emphasizes the role of STAT family genes in the pathogenesis of LGL leukemia. PMID:23596048

  9. Detection of somatic BRCA1/2 mutations in ovarian cancer - next-generation sequencing analysis of 100 cases.

    PubMed

    Koczkowska, Magdalena; Zuk, Monika; Gorczynski, Adam; Ratajska, Magdalena; Lewandowska, Marzena; Biernat, Wojciech; Limon, Janusz; Wasag, Bartosz

    2016-07-01

    The overall prevalence of germline BRCA1/2 mutations is estimated between 11% and 15% of all ovarian cancers. Individuals with germline BRCA1/2 alterations treated with the PARP1 inhibitors (iPARP1) tend to respond better than patients with wild-type BRCA1/2. Additionally, also somatic BRCA1/2 alterations induce the sensitivity to iPARP1. Therefore, the detection of both germline and somatic BRCA1/2 mutations is required for effective iPARP1 treatment. The aim of this study was to identify the frequency and spectrum of germline and somatic BRCA1/2 alterations in a group of Polish patients with ovarian serous carcinoma. In total, 100 formalin-fixed paraffin-embedded (FFPE) ovarian serous carcinoma tissues were enrolled to the study. Mutational analysis of BRCA1/2 genes was performed by using next-generation sequencing. The presence of pathogenic variants was confirmed by Sanger sequencing. In addition, to confirm the germline or somatic status of the mutation, the nonneoplastic tissue was analyzed by bidirectional Sanger sequencing. In total, 27 (28% of patient samples) mutations (20 in BRCA1 and 7 in BRCA2) were identified. For 22 of 27 patients, nonneoplastic cells were available and sequencing revealed the somatic character of two BRCA1 (2/16; 12.5%) and two BRCA2 (2/6; 33%) mutations. Notably, we identified six novel frameshift or nonsense BRCA1/2 mutations. The heterogeneity of the detected mutations confirms the necessity of simultaneous analysis of BRCA1/2 genes in all patients diagnosed with serous ovarian carcinoma. Moreover, the use of tumor tissue for mutational analysis allowed the detection of both somatic and germline BRCA1/2 mutations. PMID:27167707

  10. High regional genetic diversity and lack of host-specificity in Ostrinia nubilalis (Lepidoptera: Crambidae) as revealed by mtDNA variation.

    PubMed

    Piwczyński, M; Pabijan, M; Grzywacz, A; Glinkowski, W; Bereś, P K; Buszko, J

    2016-08-01

    The European corn borer (Ostrinia nubilalis) infests a wide array of host plants and is considered one of the most serious pests of maize in Europe. Recent studies suggest that individuals feeding on maize in Europe should be referred to O. nubilalis (sensu nov.), while those infesting dicots as Ostrinia scapulalis (sensu nov.). We test if the clear genetic distinctiveness among individuals of O. nubilalis living on maize vs. dicots is tracked by mitochondrial DNA (mtDNA). We used fragments of COI and COII genes of 32 individuals traditionally recognized as O. nubilalis collected on three host plants, maize, mugwort and hop, growing in different parts of Poland. In addition, we reconstructed the mtDNA phylogeny of Ostrinia species based on our data and sequences retrieved from GenBank to assess host and/or biogeographic patterns. We also compared haplotype variation found in Poland (east-central Europe) with other regions (Anatolia, Eastern Europe, Balkans, Far East, North America). Our study showed high mtDNA diversity of O. nubilalis in Poland in comparison with other regions and revealed rare haplotypes likely of Asian origin. We did not find distinct mtDNA haplotypes in larvae feeding on maize vs. dicotyledonous plants. Phylogenetic analyses showed an apparent lack of mtDNA divergence among putatively distinct lineages belonging to the O. nubilalis group as identical haplotypes are shared by Asian and European individuals. We argue that human-mediated dispersal, hybridization and sporadic host jumps are likely responsible for the lack of a geographic pattern in mtDNA variation. PMID:27019346

  11. Chronic lead and brain development: intraocular brain grafts as a method to reveal regional and temporal effects in the central nervous system

    SciTech Connect

    Bjoerklund, H.; Olson, L.; Seiger, A.; Hoffer, B.

    1980-06-01

    A model is presented for selective studies of regional and temporal effects of chronic lead exposure on brain development, based on intraocular brain tissue grafting. Adult rat recipients were given lead acetate (1 to 2%) in their drinking water. Controls received sodium acetate in the drinking water or tap water. One week later, developing brain tissues obtained prenatally from different regions of the central nervous system were homologously grafted to the anterior chamber of the eye. Survival, vascularization, and growth were followed in oculo by repeated measurements of graft size. Growth curves were thus obtained for grafts from isolated selected brain areas, grafted at different stages of development to recipients on different concentrations of lead. Lead treatment (1%) caused a significant and pronounced delay of growth of the substantia nigra area during the second and third week postgrafting, approximately corresponding to the first 2 weeks after birth. Grafts of the hippocampal formation showed a slight impairment of growth following lead treatment while there were no detectable effects on size of cerebellar grafts. Grafts of the developing parietal cerebral cortex were inhibited in their growth in host animals given 2% lead while there was a small but significant increase in size following 1% lead. These results demonstrate the applicability of the grafting technique for studies of chronic low level lead intoxication. The method has revealed highly significant effects of lead on growth of certain selected brain areas and will be used for further histological, biochemical, and electrophysiological analysis of chronic lead effects on development of defined brain areas.

  12. Visualization of actin filaments and monomers in somatic cell nuclei.

    PubMed

    Belin, Brittany J; Cimini, Beth A; Blackburn, Elizabeth H; Mullins, R Dyche

    2013-04-01

    In addition to its long-studied presence in the cytoplasm, actin is also found in the nuclei of eukaryotic cells. The function and form (monomer, filament, or noncanonical oligomer) of nuclear actin are hotly debated, and its localization and dynamics are largely unknown. To determine the distribution of nuclear actin in live somatic cells and evaluate its potential functions, we constructed and validated fluorescent nuclear actin probes. Monomeric actin probes concentrate in nuclear speckles, suggesting an interaction of monomers with RNA-processing factors. Filamentous actin probes recognize discrete structures with submicron lengths that are excluded from chromatin-rich regions. In time-lapse movies, these actin filament structures exhibit one of two types of mobility: 1) diffusive, with an average diffusion coefficient of 0.06-0.08 μm(2)/s, or (2) subdiffusive, with a mobility coefficient of 0.015 μm(2)/s. Individual filament trajectories exhibit features of particles moving within a viscoelastic mesh. The small size of nuclear actin filaments is inconsistent with a role in micron-scale intranuclear transport, and their localization suggests that they do not participate directly in chromatin-based processes. Our results instead suggest that actin filaments form part of a large, viscoelastic structure in the nucleoplasm and may act as scaffolds that help organize nuclear contents. PMID:23447706

  13. Constitutive heterochromatin reorganization during somatic cell reprogramming

    PubMed Central

    Fussner, Eden; Djuric, Ugljesa; Strauss, Mike; Hotta, Akitsu; Perez-Iratxeta, Carolina; Lanner, Fredrik; Dilworth, F Jeffrey; Ellis, James; Bazett-Jones, David P

    2011-01-01

    Induced pluripotent stem (iPS) cell reprogramming is a gradual epigenetic process that reactivates the pluripotent transcriptional network by erasing and establishing repressive epigenetic marks. In contrast to loci-specific epigenetic changes, heterochromatin domains undergo epigenetic resetting during the reprogramming process, but the effect on the heterochromatin ultrastructure is not known. Here, we characterize the physical structure of heterochromatin domains in full and partial mouse iPS cells by correlative electron spectroscopic imaging. In somatic and partial iPS cells, constitutive heterochromatin marked by H3K9me3 is highly compartmentalized into chromocentre structures of densely packed chromatin fibres. In contrast, chromocentre boundaries are poorly defined in pluripotent embryonic stem and full iPS cells, and are characterized by unusually dispersed 10 nm heterochromatin fibres in high Nanog-expressing cells, including pluripotent cells of the mouse blastocyst before differentiation. This heterochromatin reorganization accompanies retroviral silencing during conversion of partial iPS cells by MEK/GSK3 2i inhibitor treatment. Thus, constitutive heterochromatin is compacted in partial iPS cells but reorganizes into dispersed 10 nm chromatin fibres as the fully reprogrammed iPS cell state is acquired. PMID:21468033

  14. Dysphoria and somatization in Iranian culture.

    PubMed Central

    Pliskin, K L

    1992-01-01

    Iranians express dysphoria through an undifferentiated term called narahati, meaning depressed, ill at ease, nervous, inconvenienced, or anxious. People try masking this emotion or express it in specific ways nonverbally, such as sulking or not eating. Two other dysphoric affects, sadness and anger, are not masked. Because of the social conception of persons being emotionally sensitive, the expression of narahati is guarded: expressing it not only could show that one is socially vulnerable, it could also make another sensitive empathic person narahat. The body is also sensitive, but to the physical world. Physical health is maintained by balancing a diet of "hot" and "cold" foods and avoiding exposure to cold and moisture. With the social and cultural problems brought on by revolution, war, immigration, and accommodation to a new society, Iranian refugees experience changes in family, role, status, finances, language, and other sociocultural ways of being that cause them to feel narahat and to express it verbally, nonverbally, or through somatization. Understanding Iranian conceptions of emotional and physical sensitivity will help clinicians in treating Iranian patients. PMID:1413773

  15. Somatic Embryogenesis of Abies cephalonica Loud.

    PubMed

    Krajňáková, Jana; Häggman, Hely

    2016-01-01

    Greek fir (Abies cephalonica Loudon) belongs to the Mediterranean fir species and is widely distributed in the mountains of Central and Southern Greece. Considering a climatic scenario, infestation by pathogens or insects and fire episodes, it has been proposed that Mediterranean firs could be in danger in some parts of their present range but, on the other hand, could also replace other species in more northern zones with temperate humid climates (e.g., silver fir, Abies alba Mill.). As fir species are generally highly productive and therefore important for commercial forestry, they have traditionally been involved in conventional tree improvement programs. A lot of effort has been put into the development of vegetative propagation methods for firs, in order to rapidly gain the benefits of traditional breeding to be utilized in reforestation. The present paper provides up to date information on protocols for somatic embryogenesis (i.e., the most promising in vitro method for vegetative propagation) of Greek fir. Moreover, the protocols for cryopreservation and long-term storage of embryogenic material are described as well. PMID:26619877

  16. Spaceflight reduces somatic embryogenesis in orchardgrass (Poaceae)

    NASA Technical Reports Server (NTRS)

    Conger, B. V.; Tomaszewski, Z. Jr; McDaniel, J. K.; Vasilenko, A.

    1998-01-01

    Somatic embryos initiate and develop from single mesophyll cells in in vitro cultured leaf segments of orchard-grass (Dactylis glomerata L.). Segments were plated at time periods ranging from 21 to 0.9 d (21 h) prior to launch on an 11 d spaceflight (STS-64). Using a paired t-test, there was no significant difference in embryogenesis from preplating periods of 14 d and 21 d. However, embryogenesis was reduced by 70% in segments plated 21 h before launch and this treatment was significant at P=0.0001. The initial cell divisions leading to embryo formation would be taking place during flight in this treatment. A higher ratio of anticlinal:periclinal first cell divisions observed in the flight compared to the control tissue suggests that microgravity affects axis determination and embryo polarity at a very early stage. A similar reduction in zygotic embryogenesis would reduce seed formation and have important implications for long-term space flight or colonization where seeds would be needed either for direct consumption or to grow another generation of plants.

  17. Specification of the somatic musculature in Drosophila†

    PubMed Central

    Dobi, Krista C.; Schulman, Victoria K.; Baylies, Mary K.

    2015-01-01

    The somatic muscle system formed during Drosophila embryogenesis is required for larvae to hatch, feed, and crawl. This system is replaced in the pupa by a new adult muscle set, responsible for activities such as feeding, walking, and flight. Both the larval and adult muscle systems are comprised of distinct muscle fibers to serve these specific motor functions. In this way, the Drosophila musculature is a valuable model for patterning within a single tissue: while all muscle cells share properties such as the contractile apparatus, properties such as size, position, and number of nuclei are unique for a particular muscle. In the embryo, diversification of muscle fibers relies first on signaling cascades that pattern the mesoderm. Subsequently, the combinatorial expression of specific transcription factors leads muscle fibers to adopt particular sizes, shapes, and orientations. Adult muscle precursors (AMPs), set aside during embryonic development, proliferate during the larval phases and seed the formation of the abdominal, leg, and flight muscles in the adult fly. Adult muscle fibers may either be formed de novo from the fusion of the AMPs, or are created by the binding of AMPs to an existing larval muscle. While less is known about adult muscle specification compared to the larva, expression of specific transcription factors is also important for its diversification. Increasingly, the mechanisms required for the diversification of fly muscle have found parallels in vertebrate systems and mark Drosophila as a robust model system to examine questions about how diverse cell types are generated within an organism. PMID:25728002

  18. Cytogenetic analysis of human somatic cell haploidization.

    PubMed

    Galat, V; Ozen, S; Rechitsky, S; Kuliev, A; Verlinsky, Y

    2005-02-01

    Despite recent interest in the derivation of female and male gametes through somatic cell nuclear transfer, there is still insufficient data on chromosomal analysis of these gametes resulting from haploidization, especially involving a human nuclear donor and recipient oocytes. The objective of this study was to investigate the fidelity of chromosomal separation during haploidization of human cumulus cells by in-vitro matured human enucleated MII oocytes. A total of 129 oocytes were tested 4-7, 8-14, or 15-21 h after nuclear transfer (NT) followed by electro-stimulation, resulting in 71.3% activation efficiency on average. Haploidization was documented by the formation of two separate groups of chromosomes, originating from either polar body/pronucleus (PB/PN), or only 2PN, which were tested by 5-colour FISH, or DNA analysis for copy number of chromosomes 13, 16, 18, 21, 22 and X. Two PN were formed more frequently than PB/PN, irrespective of incubation time. In agreement with recent reports on mouse oocytes, as many as 90.2% of the resulting haploid sets tested showed abnormal chromosome segregation, suggesting unsuitability of the resulting artificial gametes for practical application at the present time. PMID:15823223

  19. Characterization of Somatically-Eliminated Genes During Development of the Sea Lamprey (Petromyzon marinus).

    PubMed

    Bryant, Stephanie A; Herdy, Joseph R; Amemiya, Chris T; Smith, Jeramiah J

    2016-09-01

    The sea lamprey (Petromyzon marinus) is a basal vertebrate that undergoes developmentally programmed genome rearrangements (PGRs) during early development. These events facilitate the elimination of ∼20% of the genome from the somatic cell lineage, resulting in distinct somatic and germline genomes. Thus far only a handful of germline-specific genes have been definitively identified within the estimated 500 Mb of DNA that is deleted during PGR, although a few thousand germline-specific genes are thought to exist. To improve our understanding of the evolutionary/developmental logic of PGR, we generated computational predictions to identify candidate germline-specific genes within a new transcriptomic dataset derived from adult germline and the early embryonic stages during which PGR occurs. Follow-up validation studies identified 44 germline-specific genes and further characterized patterns of transcription and DNA loss during early embryogenesis. Expression analyses reveal that many of these genes are differentially expressed during early embryogenesis and presumably function in the early development of the germline. Ontology analyses indicate that many of these germline-specific genes play known roles in germline development, pluripotency, and oncogenesis (when misexpressed). These studies provide support for the theory that PGR serves to segregate molecular functions related to germline development/pluripotency in order to prevent their potential misexpression in somatic cells. This larger set of eliminated genes also allows us to extend the evolutionary/developmental breadth of this theory, as some deleted genes (or their gnathostome homologs) appear to be associated with the early development of somatic lineages, perhaps through the evolution of novel functions within gnathostome lineages. PMID:27288344

  20. Knockout of exogenous EGFP gene in porcine somatic cells using zinc-finger nucleases

    SciTech Connect

    Watanabe, Masahito; Umeyama, Kazuhiro; Matsunari, Hitomi; Takayanagi, Shuko; Haruyama, Erika; Nakano, Kazuaki; Fujiwara, Tsukasa; Ikezawa, Yuka; Nakauchi, Hiromitsu; and others

    2010-11-05

    Research highlights: {yields} EGFP gene integrated in porcine somatic cells could be knocked out using the ZFN-KO system. {yields} ZFNs induced targeted mutations in porcine primary cultured cells. {yields} Complete absence of EGFP fluorescence was confirmed in ZFN-treated cells. -- Abstract: Zinc-finger nucleases (ZFNs) are expected as a powerful tool for generating gene knockouts in laboratory and domestic animals. Currently, it is unclear whether this technology can be utilized for knocking-out genes in pigs. Here, we investigated whether knockout (KO) events in which ZFNs recognize and cleave a target sequence occur in porcine primary cultured somatic cells that harbor the exogenous enhanced green fluorescent protein (EGFP) gene. ZFN-encoding mRNA designed to target the EGFP gene was introduced by electroporation into the cell. Using the Surveyor nuclease assay and flow cytometric analysis, we confirmed ZFN-induced cleavage of the target sequence and the disappearance of EGFP fluorescence expression in ZFN-treated cells. In addition, sequence analysis revealed that ZFN-induced mutations such as base substitution, deletion, or insertion were generated in the ZFN cleavage site of EGFP-expression negative cells that were cloned from ZFN-treated cells, thereby showing it was possible to disrupt (i.e., knock out) the function of the EGFP gene in porcine somatic cells. To our knowledge, this study provides the first evidence that the ZFN-KO system can be applied to pigs. These findings may open a new avenue to the creation of gene KO pigs using ZFN-treated cells and somatic cell nuclear transfer.

  1. Effect of Hypoxia on Ldh-c Expression in Somatic Cells of Plateau Pika.

    PubMed

    Wei, Dengbang; Wei, Linna; Li, Xiao; Wang, Yang; Wei, Lian

    2016-01-01

    Sperm specific lactate dehydrogenases (LDH-C₄) is a lactate dehydrogenase that catalyzes the conversion of pyruvate to lactate. In mammals, Ldh-c was originally thought to be expressed only in testes and spermatozoa. Plateau pika (Ochotona curzoniae), which belongs to the genus Ochotona of the Ochotonidea family, is a hypoxia-tolerant mammal living 3000-5000 m above sea level on the Qinghai-Tibet Plateau, an environment which is strongly hypoxic. Ldh-c is expressed not only in testes and sperm, but also in the somatic tissues of plateau pika. To reveal the effect of hypoxia on pika Ldh-c expression, we investigated the mRNA and protein level of Ldh-c as well as the biochemical index of anaerobic glycolysis in pika somatic tissues at the altitudes of 2200 m, 3200 m and 3900 m. Our results showed that mRNA and protein expression levels of Ldh-c in the tissues of pika's heart, liver, brain and skeletal muscle were increased significantly from 2200 m to 3200 m, but had no difference from 3200 m to 3900 m; the activities of LDH and the contents of lactate showed no difference from 2200 m to 3200 m, but were increased significantly from 3200 m to 3900 m. Hypoxia up-regulated and maintained the expression levels of Ldh-c in the pika somatic cells. Under the hypoxia condition, plateau pikas increased anaerobic glycolysis in somatic cells by LDH-C₄, and that may have reduced their dependence on oxygen and enhanced their adaptation to the hypoxic environment. PMID:27490559

  2. Reprogrammed Transcriptome in Rhesus-Bovine Interspecies Somatic Cell Nuclear Transfer Embryos

    PubMed Central

    Wang, Kai; Otu, Hasan H.; Chen, Ying; Lee, Young; Latham, Keith; Cibelli, Jose B.

    2011-01-01

    Background Global activation of the embryonic genome (EGA), one of the most critical steps in early mammalian embryo development, is recognized as the time when interspecies somatic cell nuclear transfer (iSCNT) embryos fail to thrive. Methodology/Principal Findings In this study, we analyzed the EGA-related transcriptome of rhesus-bovine iSCNT 8- to 16-cell embryos and dissected the reprogramming process in terms of embryonic gene activation, somatic gene silencing, and maternal RNA degradation. Compared with fibroblast donor cells, two thousand and seven genes were activated in iSCNT embryos, one quarter of them reaching expression levels comparable to those found in in vitro fertilized (IVF) rhesus embryos. This suggested that EGA in iSCNT embryos had partially recapitulated rhesus embryonic development. Eight hundred and sixty somatic genes were not silenced properly and continued to be expressed in iSCNT embryos, which indicated incomplete nuclear reprogramming. We compared maternal RNA degradation in bovine oocytes between bovine-bovine SCNT and iSCNT embryos. While maternal RNA degradation occurred in both SCNT and iSCNT embryos, we saw more limited overall degradation of maternal RNA in iSCNT embryos than in SCNT embryos. Several important maternal RNAs, like GPF9, were not properly processed in SCNT embryos. Conclusions/Significance Our data suggested that iSCNT embryos are capable of triggering EGA, while a portion of somatic cell-associated genes maintain their expression. Maternal RNA degradation seems to be impaired in iSCNT embryos. Further understanding of the biological roles of these genes, networks, and pathways revealed by iSCNT may expand our knowledge about cell reprogramming, pluripotency, and differentiation. PMID:21799794

  3. Effect of Hypoxia on Ldh-c Expression in Somatic Cells of Plateau Pika

    PubMed Central

    Wei, Dengbang; Wei, Linna; Li, Xiao; Wang, Yang; Wei, Lian

    2016-01-01

    Sperm specific lactate dehydrogenases (LDH-C4) is a lactate dehydrogenase that catalyzes the conversion of pyruvate to lactate. In mammals, Ldh-c was originally thought to be expressed only in testes and spermatozoa. Plateau pika (Ochotona curzoniae), which belongs to the genus Ochotona of the Ochotonidea family, is a hypoxia-tolerant mammal living 3000–5000 m above sea level on the Qinghai-Tibet Plateau, an environment which is strongly hypoxic. Ldh-c is expressed not only in testes and sperm, but also in the somatic tissues of plateau pika. To reveal the effect of hypoxia on pika Ldh-c expression, we investigated the mRNA and protein level of Ldh-c as well as the biochemical index of anaerobic glycolysis in pika somatic tissues at the altitudes of 2200 m, 3200 m and 3900 m. Our results showed that mRNA and protein expression levels of Ldh-c in the tissues of pika’s heart, liver, brain and skeletal muscle were increased significantly from 2200 m to 3200 m, but had no difference from 3200 m to 3900 m; the activities of LDH and the contents of lactate showed no difference from 2200 m to 3200 m, but were increased significantly from 3200 m to 3900 m. Hypoxia up-regulated and maintained the expression levels of Ldh-c in the pika somatic cells. Under the hypoxia condition, plateau pikas increased anaerobic glycolysis in somatic cells by LDH-C4, and that may have reduced their dependence on oxygen and enhanced their adaptation to the hypoxic environment. PMID:27490559

  4. Screening for the Most Suitable Reference Genes for Gene Expression Studies in Equine Milk Somatic Cells.

    PubMed

    Cieslak, Jakub; Mackowski, Mariusz; Czyzak-Runowska, Grazyna; Wojtowski, Jacek; Puppel, Kamila; Kuczynska, Beata; Pawlak, Piotr

    2015-01-01

    Apart from the well-known role of somatic cell count as a parameter reflecting the inflammatory status of the mammary gland, the composition of cells isolated from milk is considered as a valuable material for gene expression studies in mammals. Due to its unique composition, in recent years an increasing interest in mare's milk consumption has been observed. Thus, investigating the genetic background of horse's milk variability presents and interesting study model. Relying on 39 milk samples collected from mares representing three breeds (Polish Primitive Horse, Polish Cold-blooded Horse, Polish Warmblood Horse) we aimed to investigate the utility of equine milk somatic cells as a source of mRNA and to screen the best reference genes for RT-qPCR using geNorm and NormFinder algorithms. The results showed that despite relatively low somatic cell counts in mare's milk, the amount and the quality of the extracted RNA are sufficient for gene expression studies. The analysis of the utility of 7 potential reference genes for RT-qPCR experiments for the normalization of equine milk somatic cells revealed some differences between the outcomes of the applied algorithms, although in both cases the KRT8 and TOP2B genes were pointed as the most stable. Analysis by geNorm showed that the combination of 4 reference genes (ACTB, GAPDH, TOP2B and KRT8) is required for apropriate RT-qPCR experiments normalization, whereas NormFinder algorithm pointed the combination of KRT8 and RPS9 genes as the most suitable. The trial study of the relative transcript abundance of the beta-casein gene with the use of various types and numbers of internal control genes confirmed once again that the selection of proper reference gene combinations is crucial for the final results of each real-time PCR experiment. PMID:26437076

  5. Screening for the Most Suitable Reference Genes for Gene Expression Studies in Equine Milk Somatic Cells

    PubMed Central

    Cieslak, Jakub; Mackowski, Mariusz; Czyzak-Runowska, Grazyna; Wojtowski, Jacek; Puppel, Kamila; Kuczynska, Beata; Pawlak, Piotr

    2015-01-01

    Apart from the well-known role of somatic cell count as a parameter reflecting the inflammatory status of the mammary gland, the composition of cells isolated from milk is considered as a valuable material for gene expression studies in mammals. Due to its unique composition, in recent years an increasing interest in mare's milk consumption has been observed. Thus, investigating the genetic background of horse’s milk variability presents and interesting study model. Relying on 39 milk samples collected from mares representing three breeds (Polish Primitive Horse, Polish Cold-blooded Horse, Polish Warmblood Horse) we aimed to investigate the utility of equine milk somatic cells as a source of mRNA and to screen the best reference genes for RT-qPCR using geNorm and NormFinder algorithms. The results showed that despite relatively low somatic cell counts in mare's milk, the amount and the quality of the extracted RNA are sufficient for gene expression studies. The analysis of the utility of 7 potential reference genes for RT-qPCR experiments for the normalization of equine milk somatic cells revealed some differences between the outcomes of the applied algorithms, although in both cases the KRT8 and TOP2B genes were pointed as the most stable. Analysis by geNorm showed that the combination of 4 reference genes (ACTB, GAPDH, TOP2B and KRT8) is required for apropriate RT-qPCR experiments normalization, whereas NormFinder algorithm pointed the combination of KRT8 and RPS9 genes as the most suitable. The trial study of the relative transcript abundance of the beta-casein gene with the use of various types and numbers of internal control genes confirmed once again that the selection of proper reference gene combinations is crucial for the final results of each real-time PCR experiment. PMID:26437076

  6. High-throughput Phenotyping of Lung Cancer Somatic Mutations.

    PubMed

    Berger, Alice H; Brooks, Angela N; Wu, Xiaoyun; Shrestha, Yashaswi; Chouinard, Candace; Piccioni, Federica; Bagul, Mukta; Kamburov, Atanas; Imielinski, Marcin; Hogstrom, Larson; Zhu, Cong; Yang, Xiaoping; Pantel, Sasha; Sakai, Ryo; Watson, Jacqueline; Kaplan, Nathan; Campbell, Joshua D; Singh, Shantanu; Root, David E; Narayan, Rajiv; Natoli, Ted; Lahr, David L; Tirosh, Itay; Tamayo, Pablo; Getz, Gad; Wong, Bang; Doench, John; Subramanian, Aravind; Golub, Todd R; Meyerson, Matthew; Boehm, Jesse S

    2016-08-01

    Recent genome sequencing efforts have identified millions of somatic mutations in cancer. However, the functional impact of most variants is poorly understood. Here we characterize 194 somatic mutations identified in primary lung adenocarcinomas. We present an expression-based variant-impact phenotyping (eVIP) method that uses gene expression changes to distinguish impactful from neutral somatic mutations. eVIP identified 69% of mutations analyzed as impactful and 31% as functionally neutral. A subset of the impactful mutations induces xenograft tumor formation in mice and/or confers resistance to cellular EGFR inhibition. Among these impactful variants are rare somatic, clinically actionable variants including EGFR S645C, ARAF S214C and S214F, ERBB2 S418T, and multiple BRAF variants, demonstrating that rare mutations can be functionally important in cancer. PMID:27478040

  7. Somatic treatments excluding psychopharmacology in obsessive- compulsive disorder: a review.

    PubMed

    Atmaca, Murad

    2013-06-01

    Somatic treatments other than psychotropic drugs are increasingly used in the patients with obsessive compulsive disorder (OCD), however there has been little systematic review of them. Therefore, the present review deals with a variety of somatic treatment methods excluding psychotropic drugs. A literature search was performed on the PubMed database from the beginning of 1980, to September 2012, for published English, Turkish and French-language articles of somatic treatment approaches (excluding psychopharmacological agents) in the treatment of OCD. The search was carried out by using some terms in detail. Afterwards, the obtained investigations on electroconvusive therapy (ECT), deep brain stimulation (DBS), neurosurgical methods and transcranial magnetic stimulation (TMS) were presented. Although psychopharmacological treatment and psychotherapeutic approaches are primary treatment modalities in the management of OCD, other somatic treatment options seem to be used as alternatives, especially for patients with treatmentresistant OCD. PMID:24032546

  8. Human Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer

    PubMed Central

    Tachibana, Masahito; Amato, Paula; Sparman, Michelle; Gutierrez, Nuria Marti; Tippner-Hedges, Rebecca; Ma, Hong; Kang, Eunju; Fulati, Alimujiang; Lee, Hyo-Sang; Sritanaudomchai, Hathaitip; Masterson, Keith; Larson, Janine; Eaton, Deborah; Sadler-Fredd, Karen; Battaglia, David; Lee, David; Wu, Diana; Jensen, Jeffrey; Patton, Phillip; Gokhale, Sumita; Stouffer, Richard L.; Wolf, Don; Mitalipov, Shoukhrat

    2013-01-01

    SUMMARY Reprogramming somatic cells into pluripotent embryonic stem cells (ESCs) by somatic cell nuclear transfer (SCNT) has been envisioned as an approach for generating patient-matched nuclear transfer (NT)-ESCs for studies of disease mechanisms and for developing specific therapies. Past attempts to produce human NT-ESCs have failed secondary to early embryonic arrest of SCNT embryos. Here, we identified premature exit from meiosis in human oocytes and suboptimal activation as key factors that are responsible for these outcomes. Optimized SCNT approaches designed to circumvent these limitations allowed derivation of human NT-ESCs. When applied to premium quality human oocytes, NT-ESC lines were derived from as few as two oocytes. NT-ESCs displayed normal diploid karyotypes and inherited their nuclear genome exclusively from parental somatic cells. Gene expression and differentiation profiles in human NT-ESCs were similar to embryo-derived ESCs, suggesting efficient reprogramming of somatic cells to a pluripotent state. PMID:23683578

  9. Two susceptibility loci to Takayasu arteritis reveal a synergistic role of the IL12B and HLA-B regions in a Japanese population.

    PubMed

    Terao, Chikashi; Yoshifuji, Hajime; Kimura, Akinori; Matsumura, Takayoshi; Ohmura, Koichiro; Takahashi, Meiko; Shimizu, Masakazu; Kawaguchi, Takahisa; Chen, Zhiyong; Naruse, Taeko K; Sato-Otsubo, Aiko; Ebana, Yusuke; Maejima, Yasuhiro; Kinoshita, Hideyuki; Murakami, Kosaku; Kawabata, Daisuke; Wada, Yoko; Narita, Ichiei; Tazaki, Junichi; Kawaguchi, Yasushi; Yamanaka, Hisashi; Yurugi, Kimiko; Miura, Yasuo; Maekawa, Taira; Ogawa, Seishi; Komuro, Issei; Nagai, Ryozo; Yamada, Ryo; Tabara, Yasuharu; Isobe, Mitsuaki; Mimori, Tsuneyo; Matsuda, Fumihiko

    2013-08-01

    Takayasu arteritis (TAK) is an autoimmune systemic vasculitis of unknown etiology. Although previous studies have revealed that HLA-B*52:01 has an effect on TAK susceptibility, no other genetic determinants have been established so far. Here, we performed genome scanning of 167 TAK cases and 663 healthy controls via Illumina Infinium Human Exome BeadChip arrays, followed by a replication study consisting of 212 TAK cases and 1,322 controls. As a result, we found that the IL12B region on chromosome 5 (rs6871626, overall p = 1.7 × 10(-13), OR = 1.75, 95% CI 1.42-2.16) and the MLX region on chromosome 17 (rs665268, overall p = 5.2 × 10(-7), OR = 1.50, 95% CI 1.28-1.76) as well as the HLA-B region (rs9263739, a proxy of HLA-B*52:01, overall p = 2.8 × 10(-21), OR = 2.44, 95% CI 2.03-2.93) exhibited significant associations. A significant synergistic effect of rs6871626 and rs9263739 was found with a relative excess risk of 3.45, attributable proportion of 0.58, and synergy index of 3.24 (p ≤ 0.00028) in addition to a suggestive synergistic effect between rs665268 and rs926379 (p ≤ 0.027). We also found that rs6871626 showed a significant association with clinical manifestations of TAK, including increased risk and severity of aortic regurgitation, a representative severe complication of TAK. Detection of these susceptibility loci will provide new insights to the basic mechanisms of TAK pathogenesis. Our findings indicate that IL12B plays a fundamental role on the pathophysiology of TAK in combination with HLA-B(∗)52:01 and that common autoimmune mechanisms underlie the pathology of TAK and other autoimmune disorders such as psoriasis and inflammatory bowel diseases in which IL12B is involved as a genetic predisposing factor. PMID:23830516

  10. Forensic STR loci reveal common genetic ancestry of the Thai-Malay Muslims and Thai Buddhists in the deep Southern region of Thailand.

    PubMed

    Kutanan, Wibhu; Kitpipit, Thitika; Phetpeng, Sukanya; Thanakiatkrai, Phuvadol

    2014-12-01

    Among the people living in the five deep Southern Thai provinces, Thai-Malay Muslims (MUS) constitute the majority, while the remaining are Thai Buddhists (BUD). Cultural, linguistic and religious differences between these two populations have been previously reported. However, their biological relationship has never been investigated. In this study, we aimed to reveal the genetic structure and genetic affinity between MUS and BUD by analyzing 15 autosomal short tandem repeats. Both distance and model-based clustering methods showed significant genetic homogeneity between these two populations, suggesting a common biological ancestry. After Islamization in this region during the fourteenth century AD, gradual albeit nonstatistically significant genetic changes occurred within these two populations. Cultural barriers possibly influenced these genetic changes. MUS have closer admixture to Malaysian-Malay Muslims than BUD countrywide. Admixture proportions also support certain degree of genetic dissimilarity between the two studied populations, as shown by the unequal genetic contribution from Malaysian-Malay Muslims. Cultural transformation and recent minor genetic admixture are the likely processes that shaped the genetic structure of both MUS and BUD. PMID:25339232

  11. Characterization of the Group A Streptococcus Mga virulence regulator reveals a role for the C-terminal region in oligomerization and transcriptional activation.

    PubMed

    Hondorp, Elise R; Hou, Sherry C; Hempstead, Andrew D; Hause, Lara L; Beckett, Dorothy M; McIver, Kevin S

    2012-03-01

    The Group A Streptococcus (GAS) is a strict human pathogen that causes a broad spectrum of illnesses. One of the key regulators of virulence in GAS is the transcriptional activator Mga, which co-ordinates the early stages of infection. Although the targets of Mga have been well characterized, basic biochemical analyses have been limited due to difficulties in obtaining purified protein. In this study, high-level purification of soluble Mga was achieved, enabling the first detailed characterization of the protein. Fluorescence titrations coupled with filter-binding assays indicate that Mga binds cognate DNA with nanomolar affinity. Gel filtration analyses, analytical ultracentrifugation and co-immunoprecipitation experiments demonstrate that Mga forms oligomers in solution.Moreover, the ability of the protein to oligomerize in solution was found to correlate with transcriptional activation; DNA binding appears to be necessary but insufficient for full activity. Truncation analyses reveal that the uncharacterized C-terminal region of Mga, possessing similarity to phosphotransferase system EIIB proteins, plays a critical role in oligomerization and in vivo activity. Mga from a divergent serotype was found to behave similarly, suggesting that this study describes a general mechanism for Mga regulation of target virulence genes within GAS and provides insight into related regulators in other Gram-positive pathogens. PMID:22468267

  12. PacBio SMRT assembly of a complex multi-replicon genome reveals chlorocatechol degradative operon in a region of genome plasticity.

    PubMed

    Ricker, N; Shen, S Y; Goordial, J; Jin, S; Fulthorpe, R R

    2016-07-25

    We have sequenced a Burkholderia genome that contains multiple replicons and large repetitive elements that would make it inherently difficult to assemble by short read sequencing technologies. We illustrate how the integrated long read correction algorithms implemented through the PacBio Single Molecule Real-Time (SMRT) sequencing technology successfully provided a de novo assembly that is a reasonable estimate of both the gene content and genome organization without making any further modifications. This assembly is comparable to related organisms assembled by more labour intensive methods. Our assembled genome revealed regions of genome plasticity for further investigation, one of which harbours a chlorocatechol degradative operon highly homologous to those previously identified on globally ubiquitous plasmids. In an ideal world, this assembly would still require experimental validation to confirm gene order and copy number of repeated elements. However, we submit that particularly in instances where a polished genome is not the primary goal of the sequencing project, PacBio SMRT sequencing provides a financially viable option for generating a biologically relevant genome estimate that can be utilized by other researchers for comparative studies. PMID:27063562

  13. Wild Termitomyces Species Collected from Ondo and Ekiti States Are More Related to African Species as Revealed by ITS Region of rDNA

    PubMed Central

    Oyetayo, Victor Olusegun

    2012-01-01

    Molecular identification of eighteen Termitomyces species collected from two states, Ondo and Ekiti in Nigeria was carried out using the internal transcribed spacer (ITS) region. The amplicons obtained from rDNA of Termitomyces species were compared with existing sequences in the NCBI GenBank. The results of the ITS sequence analysis discriminated between all the Termitomyces species (obtained from Ondo and Ekiti States) and Termitomyces sp. sequences obtained from NCBI GenBank. The degree of similarity of T1 to T18 to gene of Termitomyces sp. obtained from NCBI ranges between 82 and 99 percent. Termitomyces species from Garbon with ascension number AF321374 was the closest relative of T1 to T18 except T12 that has T. eurhizus and T. striatus as the closet relative. Phylogenetic tree generated with ITS sequences obtained from NCBI GenBank data revealed that T1 to T18 are more related to Termitomyces species indigenous to African countries such as Senegal, Congo, and Gabon. PMID:22649309

  14. Seasonal and regional diversity of maple sap microbiota revealed using community PCR fingerprinting and 16S rRNA gene clone libraries.

    PubMed

    Filteau, Marie; Lagacé, Luc; LaPointe, Gisèle; Roy, Denis

    2010-04-01

    An arbitrary primed community PCR fingerprinting technique based on capillary electrophoresis was developed to study maple sap microbial community characteristics among 19 production sites in Québec over the tapping season. Presumptive fragment identification was made with corresponding fingerprint profiles of bacterial isolate cultures. Maple sap microbial communities were subsequently compared using a representative subset of 13 16S rRNA gene clone libraries followed by gene sequence analysis. Results from both methods indicated that all maple sap production sites and flow periods shared common microbiota members, but distinctive features also existed. Changes over the season in relative abundance of predominant populations showed evidence of a common pattern. Pseudomonas (64%) and Rahnella (8%) were the most abundantly and frequently represented genera of the 2239 sequences analyzed. Janthinobacterium, Leuconostoc, Lactococcus, Weissella, Epilithonimonas and Sphingomonas were revealed as occasional contaminants in maple sap. Maple sap microbiota showed a low level of deep diversity along with a high variation of similar 16S rRNA gene sequences within the Pseudomonas genus. Predominance of Pseudomonas is suggested as a typical feature of maple sap microbiota across geographical regions, production sites, and sap flow periods. PMID:20202776

  15. Structure of the iSH2 domain of Human phosphatidylinositol 3-kinase p85 beta Subunit Reveals Conformational Plasticity in the Interhelical Turn Region

    SciTech Connect

    C Schauder; L Ma; R Krug; G Montelione; R Guan

    2011-12-31

    Phosphatidylinositol 3-kinase (PI3K) proteins actively trigger signaling pathways leading to cell growth, proliferation and survival. These proteins have multiple isoforms and consist of a catalytic p110 subunit and a regulatory p85 subunit. The iSH2 domain of the p85 {beta} isoform has been implicated in the binding of nonstructural protein 1 (NS1) of influenza A viruses. Here, the crystal structure of human p85 {beta} iSH2 determined to 3.3 {angstrom} resolution is reported. The structure reveals that this domain mainly consists of a coiled-coil motif. Comparison with the published structure of the bovine p85 {beta} iSH2 domain bound to the influenza A virus nonstructural protein 1 indicates that little or no structural change occurs upon complex formation. By comparing this human p85 {beta} iSH2 structure with the bovine p85 {beta} iSH2 domain, which shares 99% sequence identity, and by comparing the multiple conformations observed within the asymmetric unit of the bovine iSH2 structure, it was found that this coiled-coil domain exhibits a certain degree of conformational variability or 'plasticity' in the interhelical turn region. It is speculated that this plasticity of p85 {beta} iSH2 may play a role in regulating its functional and molecular-recognition properties.

  16. Linkage and regional association analysis reveal two new tightly-linked major-QTLs for pod number and seed number per pod in rapeseed (Brassica napus L.).

    PubMed

    Shi, Jiaqin; Zhan, Jiepeng; Yang, Yuhua; Ye, Jiang; Huang, Shunmou; Li, Ruiyuan; Wang, Xinfa; Liu, Guihua; Wang, Hanzhong

    2015-01-01

    To facilitate the pseudochromosomes assembly and gene cloning in rapeseed, we developed a reference genetic population/map (named BnaZNF2) from two sequenced cultivars, Zhongshuang11 and No.73290, those exhibit significant differences in many traits, particularly yield components. The BnaZNF2 genetic map exhibited perfect collinearity with the physical map of B. napus, indicating its high quality. Comparative mapping revealed several genomic rearrangements between B. napus and B. rapa or B. oleracea. A total of eight and 16 QTLs were identified for pod number and seed number per pod, respectively, and of which three and five QTLs are identical to previously identified ones, whereas the other five and 11 are novel. Two new major QTL respectively for pod number and seed number per pod, qPN.A06-1 and qSN.A06-1 (R(2 )= 22.8% and 32.1%), were colocalised with opposite effects, and only qPN.A06-1 was confirmed and narrowed by regional association analysis to 180 kb including only 33 annotated genes. Conditional QTL analysis and subsequent NILs test indicated that tight linkage, rather than pleiotropy, was the genetic causation of their colocalisation. Our study demonstrates potential of this reference genetic population/map for precise QTL mapping and as a base for positional gene cloning in rapeseed. PMID:26434411

  17. Biophysical Studies on BEX3, the p75NTR-Associated Cell Death Executor, Reveal a High-Order Oligomer with Partially Folded Regions

    PubMed Central

    Sampaio, Laura A. G.; Johanson, Laizes; Hill, Luis Fernando; Almeida, Fabio C. L.; Cordeiro, Yraima; Almeida, Marcius S.

    2015-01-01

    BEX3 (Brain Expressed X–linked protein 3) is a member of a mammal-specific placental protein family. Several studies have found the BEX proteins to be associated with neurodegeneration, the cell cycle and cancer. BEX3 has been predicted to be intrinsically disordered and also to represent an intracellular hub for cell signaling. The pro-apoptotic activity of BEX3 in association with a number of additional proteins has been widely supported; however, to the best of our knowledge, very limited data are available on the conformation of any of the members of the BEX family. In this study, we structurally characterized BEX3 using biophysical experimental data. Small angle X-ray scattering and atomic force microscopy revealed that BEX3 forms a specific higher-order oligomer that is consistent with a globular molecule. Solution nuclear magnetic resonance, partial proteinase K digestion, circular dichroism spectroscopy, and fluorescence techniques that were performed on the recombinant protein indicated that the structure of BEX3 is composed of approximately 31% α-helix and 20% β-strand, contains partially folded regions near the N- and C-termini, and a core which is proteolysis-resistant around residues 55–120. The self-oligomerization of BEX3 has been previously reported in cell culture and is consistent with our in vitro data. PMID:26383250

  18. Biophysical Studies on BEX3, the p75NTR-Associated Cell Death Executor, Reveal a High-Order Oligomer with Partially Folded Regions.

    PubMed

    Cabral, Katia M S; Raymundo, Diana P; Silva, Viviane S; Sampaio, Laura A G; Johanson, Laizes; Hill, Luis Fernando; Almeida, Fabio C L; Cordeiro, Yraima; Almeida, Marcius S

    2015-01-01

    BEX3 (Brain Expressed X-linked protein 3) is a member of a mammal-specific placental protein family. Several studies have found the BEX proteins to be associated with neurodegeneration, the cell cycle and cancer. BEX3 has been predicted to be intrinsically disordered and also to represent an intracellular hub for cell signaling. The pro-apoptotic activity of BEX3 in association with a number of additional proteins has been widely supported; however, to the best of our knowledge, very limited data are available on the conformation of any of the members of the BEX family. In this study, we structurally characterized BEX3 using biophysical experimental data. Small angle X-ray scattering and atomic force microscopy revealed that BEX3 forms a specific higher-order oligomer that is consistent with a globular molecule. Solution nuclear magnetic resonance, partial proteinase K digestion, circular dichroism spectroscopy, and fluorescence techniques that were performed on the recombinant protein indicated that the structure of BEX3 is composed of approximately 31% α-helix and 20% β-strand, contains partially folded regions near the N- and C-termini, and a core which is proteolysis-resistant around residues 55-120. The self-oligomerization of BEX3 has been previously reported in cell culture and is consistent with our in vitro data. PMID:26383250

  19. Linkage and regional association analysis reveal two new tightly-linked major-QTLs for pod number and seed number per pod in rapeseed (Brassica napus L.)

    PubMed Central

    Shi, Jiaqin; Zhan, Jiepeng; Yang, Yuhua; Ye, Jiang; Huang, Shunmou; Li, Ruiyuan; Wang, Xinfa; Liu, Guihua; Wang, Hanzhong

    2015-01-01

    To facilitate the pseudochromosomes assembly and gene cloning in rapeseed, we developed a reference genetic population/map (named BnaZNF2) from two sequenced cultivars, Zhongshuang11 and No.73290, those exhibit significant differences in many traits, particularly yield components. The BnaZNF2 genetic map exhibited perfect collinearity with the physical map of B. napus, indicating its high quality. Comparative mapping revealed several genomic rearrangements between B. napus and B. rapa or B. oleracea. A total of eight and 16 QTLs were identified for pod number and seed number per pod, respectively, and of which three and five QTLs are identical to previously identified ones, whereas the other five and 11 are novel. Two new major QTL respectively for pod number and seed number per pod, qPN.A06-1 and qSN.A06-1 (R2 = 22.8% and 32.1%), were colocalised with opposite effects, and only qPN.A06-1 was confirmed and narrowed by regional association analysis to 180 kb including only 33 annotated genes. Conditional QTL analysis and subsequent NILs test indicated that tight linkage, rather than pleiotropy, was the genetic causation of their colocalisation. Our study demonstrates potential of this reference genetic population/map for precise QTL mapping and as a base for positional gene cloning in rapeseed. PMID:26434411

  20. Snake venomics of Micrurus alleni and Micrurus mosquitensis from the Caribbean region of Costa Rica reveals two divergent compositional patterns in New World elapids.

    PubMed

    Fernández, Julián; Vargas-Vargas, Nancy; Pla, Davinia; Sasa, Mahmood; Rey-Suárez, Paola; Sanz, Libia; Gutiérrez, José María; Calvete, Juan J; Lomonte, Bruno

    2015-12-01

    Protein composition, toxicity, and neutralization of the venoms of Micrurus alleni and Micrurus mosquitensis, two sympatric monadal coral snakes found in humid environments of the Caribbean region of Costa Rica, were studied. Proteomic profiling revealed that these venoms display highly divergent compositions: the former dominated by three-finger toxins (3FTx) and the latter by phospholipases A2 (PLA2). Protein family abundances correlated with enzymatic and toxic characteristics of the venoms. Selective inhibition experiments showed that PLA2s play only a marginal role in the lethal effect of M. alleni venom, but have a major role in M. mosquitensis venom. Proteomic data gathered from other Micrurus species evidenced that the two divergent venom phenotypes are recurrent, and may constitute a general trend across New World elapids. Further, M. mosquitensis, but not M. alleni, venom contains PLA2-like/Kunitz-type inhibitor complex(es) that resemble the ASIC1a/2-activating MitTx heterodimeric toxin isolated from Micrurus tener venom. The evolutionary origin and adaptive relevance of the puzzling phenotypic variability of Micrurus venoms remain to be understood. An antivenom against the PLA2-predominant Micrurus nigrocinctus venom strongly cross-recognized and neutralized M. mosquitensis venom, but only weakly M. alleni venom. PMID:26325292